CN103276398A

CN103276398A - Biological medical absorbable material and preparation method thereof

Info

Publication number: CN103276398A
Application number: CN2013102001907A
Authority: CN
Inventors: 张永君; 沈军; 夏兰梅; 贾书功; 董连军; 陶胜; 李爱红
Original assignee: South China University of Technology SCUT
Current assignee: South China University of Technology SCUT
Priority date: 2013-05-24
Filing date: 2013-05-24
Publication date: 2013-09-04
Anticipated expiration: 2033-05-24
Also published as: CN103276398B

Abstract

The invention discloses a biological medical absorbable material and a preparation method thereof. The preparation method of the material mainly comprises the following steps: 1) smelting and forming; 2 roughening by etching; 3) cathodic deposition; 4) heat treatment; and 5) coating. The material disclosed by the invention comprises a pure magnesium or magnesium alloy base and a functional film covered on the base surface with degradation protection and self-degradation characteristics; and the integral material has the characteristic of controllable all-degradable absorption, and satisfies the serious requirements for ideal characteristics of degradable biological materials. The invention provides a preferred scheme for solving the contradiction between biodegradable characteristic utilization and degradation rate control of the absorbable biological material, especially medical magnesium alloy; and the related material and technique are not only suitable for common medical appliance products, but also have competitive edges in manufacturing of high-end medical appliance products, such as implantation instruments, especially secondary-operation-free implantation substances.

Description

Bio-medical absorbable material and preparation method thereof

Technical field

The invention belongs to bio-medical novel material and medical device product manufacturing and applied technical field, relate in particular to a kind of bio-medical absorbable 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 disaster 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 integral 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 " sunrise 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 community and scientific and technological circle day by day, is successively listed in the crucial new material development plan of hi-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 metallic substance is because of its intensity and fracture toughness property 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, nickelalloy 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 widespread use at clinical medicine, its salient features defective comprises: (1) does not match owing to Young's modulus, 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 resorption 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 inflammatory diseases, and Al is combined with inorganic phosphorus, also can bring out senile dementia when causing lacking phosphorus; (3) because biological degradability is poor, and after damaged tissue/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 economical load.For these reasons, seek better novel material, the new technology of over-all properties 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) biological degradation sexual clorminance.The MAGNESIUM METAL chemical property is active, at aggressiveness physiological environment (Cl ^-, organic acid, protein, enzyme and cell etc.) effect under, the magnesium implant in-service can be by the progressively extremely last completely dissolve of biological degradation, 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) physiologically acceptable sexual clorminance.Magnesium is the non-dissident's composition of human body, is one of human body major element (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 positively charged ion; 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, ground substance of bone 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 lifeless matter 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 Young's modulus 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) biological activity 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 tenacity; the specific rigidity 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 aerospace; automobile; the IT electronics; communication; industrial sectors such as national defense and military, magnesium alloy cause in the world as the Application and Development of structured material shows great attention to.(6) resource and price advantage.Magnesium resource is very abundant on the earth, and magnesium relative content 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 titanium 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 starting 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 novel 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 novel material is especially based on the advanced composite material of magnesium or magnesium alloy, strongthener biological degradation controllability is (not only biodegradable, and degradation rate can be regulated as required) time, improve the biocompatibility of material even give its biological activity, to satisfy clinical medicine to the harsh requirement of material over-all properties, have very important meaning, become the important topic of bio-medical novel 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 compounding technology of conventional MAO, as the MAO/ organic coat, MAO/ electroless plating etc., (3) organic coat, (4) chemical conversion, (5) bionical passivation, (6) cathodic deposition, (7) anodically deposit, (8) IBAD(ion beam assisted depositing), (9) sol-gel method, (10) silane-modified, (11) ion implantation, (12) ion plating, (13) electrochemical polymerization, and (14) hydrothermal method, etc.Though above-mentioned technology and each the tool advantage of matrix material 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 tissue/organ is finished reconstruction---biological degradation 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 matrix material, owing to adopt conventional electrolysis liquid (as silicate, phosphoric acid salt and fluoride-based electrolytic solution), so gained MAO film main component is degradable or very poor silicate, phosphoric acid salt or the fluorochemical of degradation property 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 matrix material 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 subject matter that exists in existing bio-medical material and the utilisation technology thereof, a kind of bio-medical absorbable 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 absorbable 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) corrosion roughening: step a) resulting product matrix is immersed behind surface dressing in the group water solution of sodium chloride-containing 5.0-100.0g/L, hydrogenchloride 0-50.0g/L, carry out corrosion treatment, realize the purpose that the goods matrix is carried out surperficial roughening;

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) thermal 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 thermal treatment temp is 350-550 ℃, soaking 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 magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, with water, acetone, ethanol, propyl carbinol 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 magnesium oxide, 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 total 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-chlor described in the step b) with SODIUMNITRATE, sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, vitriolate of tartar, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, sal epsom or wherein two or more mixtures partly or entirely replace; Hydrogenchloride described in the step b) with nitric acid, sulfuric acid, acetic acid, citric acid or wherein two or more mixtures partly or entirely replace; Magnesium chloride described in the step c) partly or entirely replaces with magnesium nitrate, sal epsom 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 epoxy chloropropane, methylene dichloride or the chloroform, the B solvent be the A solvent with acetone, ethanol or propyl carbinol 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, particulate state, sheet, thread, banded, tubulose or whisker shape, and its open circuit potential in any equivalent environment medium is not higher than the open circuit potential 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 magnesium oxide, 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 total mass.

Step e-2) a kind of of scheme one described 1# solution and 2# solution replaces with 3# solution in; Step e-2) coating 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 solidification treatment, after treating this coating layer portion or solidifying fully, carry out the coating of follow-up coating again; When applying magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein behind the two or more mixtures, carrying out drying treatment.

A kind of bio-medical absorbable 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 magnesium oxide or magnesium oxide and magnesium hydroxide; Described surface layer comprises in No.1 coating and the No.2 coating at least a; Described No.1 coating for magnesium oxide, 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 magnesium oxide, 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 matrix material 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, particulate state, sheet, thread, banded, tubulose or whisker shape, and its open circuit potential in any equivalent environment medium is not higher than the open circuit potential 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 cutting out shapes, etc.The effect of melting is to obtain the high-quality melt (metal or alloy liquid) that chemical ingredients and inclusion (as oxide inclusion), 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 disposal requires.Surface dressing can any known or commercially available physics and/or chemical technology carry out, as sand paper/grinder buffing, polishing cloth polishing, organic solvent comprises dehydrated alcohol, acetone etc. directly or degreasing under outer field actions such as ultrasonic wave, alkali cleaning, pickling, washing, etc.

The technical spirit of corrosion roughening is the controlled corrosion of material in the material preparation method step b) of the present invention, its purpose is to utilize simple, economic corrosive nature to realize the surperficial roughening of body material is handled, thereby is that combining closely between coating/matrix established solid architecture basics.Sodium-chlor in the corrosion roughening liquid is basic etchant, and hydrogenchloride is corrosion promotor.Sodium chloride concentration is low excessively, and corrosion roughening speed is slow excessively, and excessive concentration, corrosion roughening effect do not take place obviously to improve thereupon, therefore, and should be with the scope of sodium chloride concentration control at 5.0-100.0g/L.Hydrogen cloride concentration is low excessively, and the corrosion promoter action is not obvious, excessive concentration, and roughening speed is too fast, and operation control difficulty strengthens, and easily causes excessive erosion.Hydrochloric acid, nitric acid, sulfuric acid, acetic acid or citric acid in the corrosion roughening liquid can other any known or commercially available inorganic or organic acidity compound or the replacement of its mixture.During the corrosion roughening, electrolyte temperature should be controlled at 5-95 ℃.The corrosion roughening treatment time is then relevant with concentration of electrolyte and the requirement of roughening degree etc.Generally speaking, concentration of electrolyte is more big, and the time that obtains same roughening effect needs is more short; When electrolytic solution is identical, require to improve with the roughening degree, the corrosion roughening treatment time is more long.

The purpose of cathodic deposition is that the matrix surface after the corrosion roughening prepares the prefilter layer of functional membrane bottom in the material preparation method step c) of the present invention.During cathodic deposition, counter electrode both can be used inert materials such as platinum, stainless steel and graphite, 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 electrolytic solution also can use the ethanol based solution of magnesium chloride, magnesium nitrate, sal epsom or its mixture to replace.Cathodic deposition electrical parameter master mode comprises constant current, constant voltage (permanent electropotential), or with electrokinetic potential linear time base sweep or the scan round in certain electropotential interval of certain scanning speed.During cathodic deposition, electrolyte temperature should be controlled at 2-60 ℃, and other concrete processing parameter such as the selection of current density, electropotential, scanning speed and action time etc. then require to determine according to performance index 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 nodulizing, thereby obtain the finer and close functional membrane bottom of structure.Magnesium hydroxide is 340 ℃ to the beginning temperature that magnesium oxide transforms (or decomposing generation magnesium oxide), and end temp is 490 ℃.Therefore, by in 350-550 ℃ of scope, regulating the thermal treatment temp level, just can realize that magnesium hydroxide is to the control of magnesium oxide transforming degree.As control thermal treatment temp in the time of 350-489 ℃, and the magnesium hydroxide part transforms to magnesium oxide, and the functional membrane bottom is made up of the mixture of magnesium oxide and magnesium hydroxide; Thermal treatment temp is in the time of 490-550 ℃, and magnesium hydroxide all is converted into magnesium oxide, and the functional membrane bottom only is made up of magnesium oxide.Thermal 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, thermal treatment can promote the thermooxidizing of goods top layer metal simultaneously to a certain extent, thereby further increases the thickness of functional membrane bottom.

After corrosion roughening, cathodic deposition and thermal treatment finish, processing such as material preferably cleans respectively, drying, comprise tap water and/or distilled water, rinsed with deionized water, hot blast or pressurized air dry up or the process furnace oven dry, or dry after the rinsings such as easy volatile organic solvent such as ethanol, acetone etc.Cleaning, dry purpose are to remove the non-target product that is adsorbed on workpiece surface, comprise corrosion roughening by product, corrosion roughening solution and cathodic deposition solution etc., avoid the solution crossed contamination and influence the subsequent disposal effect.

With the main purpose of various coated 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 dissolution rate, 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 soltion 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 homogeneity, porosity etc.).When magnesium oxide, 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 force of cohesion, obviously worsen with basal body binding force and degraded barrier propterty etc.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture 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 total 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 magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be carried out under agitation conditions such as mechanical, ultrasonic or pressurized air.When applying operation, the concrete coating number of times of every kind of coated material is then controlled according to needs such as coating structure, thickness.When using identical coated material repeatedly to apply, each solution that applies use can be identical, also can be different.For identical coating solution, the coat-thickness of acquisition and the positive correlation of coating number of times.

Technology generation such as the coating method of magnesium oxide of the present invention, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture can electrophoretic deposition, magnetron sputtering or ion beam assisted depositing are replaced.

It should be noted that in the material of the present invention and may have the autoxidation film between the cathodic deposition layer and matrix.Be that matrix and surrounding environment (comprise atmosphere, cleaning solution such as water, dehydrated alcohol, alkaline wash or pickle solution, corrosion roughening solution and cathodic deposition solution etc.) during contact its top layer by the rete of mainly being formed by oxide compound, oxyhydroxide (as magnesium oxide, magnesium hydroxide) or its mixture of matrix that natural oxidation 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 (nano level) usually can ignore substantially to the general usage Effect on Performance of material.In addition, a spot of corrosion product also may distribute between cathodic deposition layer and the matrix, namely corrode the material that deposition reaction generates takes place between the cathodic reaction product (hydroxide ion) and reaction product of anode (being generally magnesium ion) in the roughening process, its main component is magnesium hydroxide.

Used magnesium oxide, 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, particulate state, 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 open circuit potential of pure magnesium or magnesium alloy is not higher than the open circuit potential 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 magnesium oxide, 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 structure unit); The kind of macromolecular material and molecular weight thereof etc.), structure (as density, porosity, surfaceness 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 differing materials component units to realize the successful control to material monolithic over-all properties especially biological degradability, biocompatibility and coating/basal body binding force, coating force of cohesion 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, bonding force 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 protein, gelatin and chitosans, and other synthetic degradable high polymer 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) Magnuminium 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 behavior with regard to the functional membrane bottom part of material of the present invention, because its main component---the thermodynamic stability of magnesium oxide or magnesium hydroxide all is higher than atomic state magnesium, therefore, 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 magnesium oxide 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, magnesium oxide and magnesium hydroxide all 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 magnesium oxide, 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 degradation property; Wherein magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP not only possess biodegradability, and degraded product is the nutrient substance of needed by human body.On the other hand, magnesium oxide, 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 final product carbonic acid gas 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, magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP not only can improve the mechanical property of matrix to a certain extent, and can improve 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 specified phase 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 tissue/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 moiety 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 biological activity concurrently, and its degradation rate can be regulated and control by composition, microtexture optimization such as technology such as alloying, grain refining.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 differing materials, fully realizing of the advantage of different technologies and synergistic effect thereof, forming technique and process for modifying surface is organic compound, especially unite and utilize the corrosion roughening, cathodic deposition, thermal 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, when in the electrolytic solution that contains aggressiveness ion such as chlorion, nitrate ion or sulfate ion, carrying out corrosion treatment, because the ununiformity of composition, microtexture etc., matrix microcell dissolution process is inhomogeneous to carry out, and corrosive nature shows selectivity, be the optimum solvation of micro anode district, therefore, objectively, corrosion has certain roughening effect to matrix, can form micro-" anchor point " in a large number, thereby be that combining closely between cathodic deposition layer/matrix created condition.In addition, because corrosive fluid is cheap, corrosion operating procedure window is wide, and therefore corroding the roughening technology has high economy and practical value.Synthetic and the coating preparation integrated technique as coating, advantage such as that the electrochemistry cathodic deposition has is non-linear, cold operation and controllability are good, with low cost is one of desirable technique of material surface modifying.Cathode run can realize that the matrix surface magnesium hydroxide is that the original position of prefilter layer of functional membrane bottom is synthetic.Heat treatment process can realize that magnesium hydroxide to magnesian conversion and to having the sintering of rete, namely forms the functional membrane bottom.The formation of functional membrane bottom internally for the matrix one deck of putting on has protective film from degradation characteristic, externally relies on its microtexture coarse, porous to become at the bottom of the ideal basis of follow-up coating (functional membrane surface layer).When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP independently use as coated material, there is outstanding problems such as applying difficulty, bonding force 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 flow sheet in the embodiment;

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

Fig. 3 is material function surface layer film section structure synoptic 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-magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more mixture layers wherein, c-degradable high polymer material layer, d-with magnesium oxide, 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.

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 flow sheet of the present invention.The preparation method of bio-medical absorbable material of the present invention is made of melting, shaping → corrosion roughening → cathodic deposition → thermal treatment → coating five big key steps.The purpose of wherein melting, shaping is to obtain the goods matrix that material (chemistry and phase composite, microtexture, grain size etc.), shape and size etc. meet the demands; The main effect of corrosion roughening is to realize the surperficial roughening of goods matrix is handled; 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 synoptic diagram of the present invention.Bio-medical absorbable 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 material function film section structure synoptic diagram 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 soaking time 30min.Forming technique comprises permanent mold casting (high-purity magnesium and above-mentioned whole magnesium alloy), die casting (magnesium alloy AZ31), forges (magnesium alloy ZK60) and hot extrusion (magnesium alloy AZ31 and AZ91), wherein permanent mold casting condition: 710-720 ℃; Die casting condition: 660 ℃ of teeming temperatures, 220 ℃ of type temperature, injection ratio pressure 50MPa, injection speed 40m/s; Forging condition: be blank with cylindrical ingot casting, flat-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 → dehydrated alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → standby, wherein alkali cleaning condition: the combination solution of 40g/L sodium hydroxide, 10g/L sodium phosphate and 0.2g/L Sodium dodecylbenzene sulfonate, 95 ℃, 15min; Pickling condition: the combination solution of 20g/L nitric acid, 50g/L magnesium nitrate and 50g/L dehydrated alcohol, 25 ℃, 15sec; Washing condition: tap water and distilled water rinsing successively.

Embodiment 1

Be research object with the high-purity magnesium sample of permanent mold casting attitude.Be solvent with distilled water, preparation 50.0g/L sodium chloride solution is as corrosion roughening liquid.Sample is immersed in the above-mentioned solution of 50 ℃ of temperature controls, take out behind the 2h, after washing, the drying, find that obvious pit appears in specimen surface.To wash, dried corrosion roughening sample and stainless steel cylinder form electrode pair, sample connects the DC power cathode, the stainless steel cylinder connects the DC positive source, immerses with in the 50.0g/L magnesium chloride solution of deionized water preparation (sample places the cylinder geometric centre) 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 retort 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 uniform mixture of epoxy chloropropane and acetone (mixed volume than be 2:1), at first prepare 25g/LPLLA solution (liquid), add 10g/L magnesium hydroxide (solid dispersed phase) then, the acquisition suspension that stirs is labeled as S ₀₁By following standard washing, dried thermal treatment sample are carried out 3 and take turns dip-coating processing: sample is immersed solution S ₀₁, take out behind the 40sec, treat coating curing.The result obtains uniformly compound coating (functional membrane surface layer) by magnesium hydroxide/the PLLA composite coating successively is formed by stacking at specimen surface.

Be tested media (its composition and human plasma chemical ingredients contrast situation see Table 1) with HBSS, 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 to said sample.The result shows: sample matrix behind about 12d just begins to occur macroscopic erosion trace, compare and namely begin the result of corroding after check sample (namely only surface dressing and corrode the sample of roughening, cathodic deposition, thermal treatment and coating processing) immerses, its initial stage, anti-degradation capability obviously strengthened, and showed that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 31d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 185d, shows that material monolithic has high-fall solution characteristic.

Embodiment 2

Be research object with permanent mold casting attitude AZ31 magnesium alloy sample.Except the 5.0g/L sodium chloride solution that solution is changed into deionized water preparation, other condition control of corrosion roughening is with embodiment 1, and the pit 1 sparse than embodiment, that area is slightly little appears in specimen surface as a result.Except density of magnesium chloride is changed into the 0.5g/L, other condition control of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Be solvent with the chloroform, at first prepare totally 4 parts of 25g/LPLLA solution, add 5g/L magnesium oxide, pure magnesium (sphere, meta particle diameter d then respectively ₅₀=47 μ m), β-TCP and CPP(solid dispersed phase) and stir, obtain suspension, be labeled as solution S respectively ₀₁-1, S ₀₁-2, S ₀₁-3 and S ₀₁-4.By following standard washing, dried thermal treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₁Take out behind-1, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₁Take out behind-2, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₁Take out behind-3, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₁-4, treat coating curing.The result obtains uniform compound coating (functional membrane surface layer) at specimen surface, and this coating is by being that the PLLA matrix composite coating of wild phase successively is formed by stacking with magnesium oxide, pure magnesium, β-TCP and CPP respectively.With the performance test of 1 pair of said sample biodegrade of embodiment, the result shows: sample matrix behind about 24d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 45d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 97d, shows that material monolithic has high-fall solution characteristic.

Embodiment 3

Be research object with extruding attitude AZ31 magnesium alloy sample.Except the concentration with sodium-chlor changes into the 100.0g/L, other condition control of corrosion roughening is with embodiment 1, and the pit higher than embodiment 1 density, that area is bigger appears in specimen surface as a result.Except density of magnesium chloride is changed into the 150.0g/L, other condition control of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Be solvent with the methylene dichloride, at first compound concentration is respectively the PLLA solution of 75.0g/L and 0.2g/L, adds the corresponding 75g/LPLLA solution of 0.377g/L(then respectively) and the corresponding 0.2g/LPLLA solution of 0.133g/L() magnesium hydroxide, stir, obtain suspension, be labeled as solution S respectively ₀₁-5 and S ₀₁-6.By following standard washing, dried thermal treatment sample are carried out 10 and take turns dip-coating processing: sample is immersed solution S ₀₁Take out behind-5, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₁Take out behind-6, the 7sec, treat coating curing.The result obtains uniformly compound coating (functional membrane surface layer) by magnesium hydroxide/the PLLA composite coating successively superposes at specimen surface.With the performance test of 1 pair of said sample biodegrade of embodiment, the result shows: sample matrix behind about 42d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 75d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 185d, shows that material monolithic has high-fall solution characteristic.

Embodiment 4

Be research object with permanent mold casting attitude WE43 magnesium alloy sample.Be solvent with distilled water, preparation contains the corrosion roughening liquid of 50.0g/L sodium-chlor and 25.0g/L hydrogenchloride (namely adding 37% hydrochloric acid mother liquor 57.26ml/L).Sample is immersed in the above-mentioned solution of 20 ℃ of temperature controls, take out behind the 10sec, after washing, the drying, find that specimen surface presents uniform sand face effect.Except counter electrode (anode) is changed into the graphite flake, other condition control of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Except changing PLLA into PLGA, the 10.0g/L magnesium hydroxide is changed into outside magnesium hydroxide and each 5.0g/L of magnesium oxide, carry out solution S with embodiment 1 ₀₁Preparation.Be solvent with the uniform mixture of methylene dichloride and dehydrated alcohol (mixed volume than be 4:1), preparation 30.0g/LPLLA solution is labeled as solution S ₀₂Be dispersion agent (liquid) with the propyl carbinol, add 15.0g/L magnesium oxide (solid dispersed phase), stir, obtain suspension, be labeled as solution S ₀₃By following standard washing, dried thermal treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₁, take out behind the 3sec, treat behind the coating curing sample to be immersed solution S ₀₃, take out behind the 12sec, treat after the coating drying sample to be immersed solution S ₀₂, take out behind the 5sec, treat behind the coating curing sample to be immersed solution S ₀₁, take out behind the 5sec, treat behind the coating curing sample to be immersed solution S ₀₂, take out behind the 45sec, treat coating curing.The result obtains uniformly by 1 at specimen surface) be sandwich of layers with magnesium oxide, both sides are respectively the PLLA coating and are the coating and 2 of the PLGA matrix composite coating of wild phase with magnesium oxide and magnesium hydroxide) be that the PLGA based composites of wild phase is the compound coating (functional membrane surface layer) that the PLLA coating of sandwich of layers successively superposes with magnesium oxide and magnesium hydroxide.With the performance test of 1 pair of said sample biodegrade of embodiment, the result shows: sample matrix behind about 35d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 76d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 152d, shows that material monolithic has high-fall solution characteristic.

Embodiment 5

Be research object to forge attitude ZK60 magnesium alloy sample.Namely add 37% hydrochloric acid mother liquor 114.52ml/L except the concentration with hydrogenchloride changes 50.0g/L(into), the preparation of corrosion roughening liquid is with embodiment 4.Sample is immersed in the above-mentioned solution of 20 ℃ of temperature controls, take out behind the 3sec, after washing, the drying, find that the roughening effect is with embodiment 4.Forge the attitude ZK60 magnesium alloy sheet except counter electrode (anode) is changed into, the control of cathodic deposition condition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Be solvent with the chloroform, prepare 75.0g/L and 0.2g/LPLLA solution respectively, be labeled as solution S respectively ₀₂-1 and S ₀₂-2.Be dispersion agent (liquid) with distilled water and acetone, add 0.5g/L and 45.0g/L magnesium oxide (solid dispersed phase) respectively, the acquisition suspension that stirs is labeled as solution S respectively ₀₃-1 and S ₀₃-2.By following standard washing, dried thermal treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₂Take out behind-1, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₃Take out behind-1, the 15sec, treat after the coating drying sample to be immersed solution S ₀₂Take out behind-2, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₃Take out behind-2, the 15sec, treat after the coating drying sample to be immersed solution S ₀₂Take out behind-2, the 7sec, treat coating curing.The result obtains uniform compound coating (functional membrane surface layer) at specimen surface, and this coating structure unit is for being the PLLA coating of sandwich of layers with magnesium oxide.With the performance test of 1 pair of said sample biodegrade of embodiment, the result shows: sample matrix behind about 23d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 44d, 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 with extruding attitude AZ91 magnesium alloy sample.Except sodium-chlor is changed into respectively SODIUMNITRATE, sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, vitriolate of tartar, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate or the sal epsom, other condition control of corrosion roughening and result are with embodiment 4.Except the magnesium chloride in the electrolytic solution is changed into respectively magnesium nitrate or the sal epsom, 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 thermal treatment and result are with embodiment 1.Carry out solution S with embodiment 1 ₀₁Preparation.By following standard to washing, dried thermal treatment sample carries out spin coating, brushing and spray treatment respectively, treats that obtaining area density at specimen surface behind the coating curing is 1.23mg/cm ²Uniform magnesium hydroxide/PLLA composite coating.With the performance test of 1 pair of said sample biodegrade of embodiment, the result shows: sample matrix behind about 45d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve behind about 97d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 215d, shows that material monolithic has high-fall solution characteristic.

Embodiment 7

Be research object with die casting attitude AZ31 magnesium alloy sample.Except hydrogenchloride is changed into respectively nitric acid, sulfuric acid, acetic acid or the citric acid, other condition control of corrosion roughening and result are with embodiment 4.The control of cathodic deposition condition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 6.85.0gPLLA is heated to molten state and 210 ℃ of insulations, adds the 15.0g magnesium hydroxide, the acquisition suspension that stirs is labeled as solution S ₀₄By following standard to through washing, dried thermal treatment sample carries out dip-coating processing: sample is immersed solution S ₀₄, take out behind the 30sec, treat coating curing.The result obtains uniform magnesium hydroxide/PLLA composite coating at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind 29d just begins to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve behind 59d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 155d, shows that material monolithic has high-fall solution characteristic.

Embodiment 8

Be research object to forge attitude WE43 magnesium alloy sample.Corrosion roughening condition control and result are with embodiment 4.Carry out solution S with embodiment 4 ₀₃Preparation.The control of cathodic deposition condition and result are with embodiment 1.Except temperature being changed into 550 ℃, the time changes into outside the 1h, and other condition control of thermal treatment and result are with embodiment 1.PLLA is heated to molten state and 210 ℃ of insulations, is labeled as solution S ₀₅By following standard washing, dried thermal treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₅, take out behind the 10sec, treat behind the coating curing sample to be immersed solution S ₀₃, take out behind the 30sec, treat after the coating drying sample to be immersed solution S ₀₅, take out behind the 5sec, treat coating curing.It is the PLLA coating (functional membrane surface layer) of sandwich of layers with magnesium oxide 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 17d just begins to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve behind 36d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 135d, shows that material monolithic has high-fall solution characteristic.

Embodiment 9

Be research object with die casting attitude AZ91 magnesium alloy sample.Corrosion roughening condition control and result are with embodiment 4.The control of cathodic deposition condition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 8.Be solvent with the chloroform, preparation 10.0,15.0,20.0 and 25.0g/LPLLA solution are labeled as solution S respectively ₀₆-1, S ₀₆-2, S ₀₆-3 and S ₀₆-4; Be dispersion agent (liquid) with ethanol, add 10.0g/L magnesium hydroxide, pure magnesium (sphere, meta particle diameter d respectively ₅₀=47 μ m), β-TCP and CPP(solid dispersed phase), the acquisition suspension that stirs is labeled as solution S respectively ₀₇-1, S ₀₇-2, S ₀₇-3 and S ₀₇-4.By following standard washing, dried thermal treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₆Take out behind-1, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₇Take out behind-1, the 10sec, treat after the coating drying sample to be immersed solution S ₀₆Take out behind-2, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₇Take out behind-2, the 10sec, treat after the coating drying sample to be immersed solution S ₀₆Take out behind-3, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₇Take out behind-3, the 10sec, treat after the coating drying sample to be immersed solution S ₀₆Take out behind-4, the 7sec, treat behind the coating curing sample to be immersed solution S ₀₇Take out behind-4, the 10sec, treat after the coating drying sample to be immersed solution S ₀₆Take out behind-1, the 7sec, treat coating curing.It is the compound coating (functional membrane surface layer) that the PLLA coating of sandwich of layers successively is formed by stacking that the result obtains uniformly respectively with magnesium hydroxide, pure magnesium, β-TCP and CPP at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind 27d just begins to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve behind 58d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 174d, 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 physiologically acceptable 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 ingredients

Claims

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

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 magnesium oxide, 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, propyl carbinol 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;

2. the preparation method of bio-medical absorbable material according to claim 1 is characterized in that: sodium-chlor described in the step b) with SODIUMNITRATE, sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, vitriolate of tartar, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, sal epsom or wherein two or more mixtures partly or entirely replace; Hydrogenchloride described in the step b) with nitric acid, sulfuric acid, acetic acid, citric acid or wherein two or more mixtures partly or entirely replace; Magnesium chloride described in the step c) partly or entirely replaces with magnesium nitrate, sal epsom or its mixture.

3. the preparation method of bio-medical absorbable 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 epoxy chloropropane, methylene dichloride or the chloroform, the B solvent be the A solvent with acetone, ethanol or propyl carbinol 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, particulate state, sheet, thread, banded, tubulose or whisker shape, and its open circuit potential in any equivalent environment medium is not higher than the open circuit potential of pure magnesium in the goods matrix or magnesium alloy.

4. the preparation method of bio-medical absorbable 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 magnesium oxide, 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 total mass.

5. the preparation method of bio-medical absorbable 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) coating method described in comprises dip-coating, brushing, spin coating or spraying.

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

7. bio-medical absorbable 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 magnesium oxide or magnesium oxide and magnesium hydroxide; Described surface layer comprises in No.1 coating and the No.2 coating at least a; Described No.1 coating for magnesium oxide, 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 magnesium oxide, 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 matrix material quality; Degradable high polymer material in described No.1 coating and the No.2 coating is PLLA, PLGA or its mixture.

8. bio-medical absorbable 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 absorbable 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, particulate state, sheet, thread, banded, tubulose or whisker shape, and its open circuit potential in any equivalent environment medium is not higher than the open circuit potential of the pure magnesium of matrix or magnesium alloy.