CN103272285A - All-degradable biological material and preparation method thereof - Google Patents
All-degradable biological material and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an all-degradable biological material and a preparation method thereof. The preparation method of the all-degradable biological material comprises the following steps: 1) smelting and forming; 2) shot blasting; and 3) coating. The material disclosed by the invention comprises a pure magnesium or magnesium alloy base and a functional film covered on the base surface with degradation protection and self-degradation characteristics; and the integral material has the characteristic of controllable all-degradable absorption, and satisfies the serious requirements for ideal characteristics of degradable biological materials. The invention provides a preferred scheme for solving the contradiction between biodegradable characteristic utilization and degradation rate control of the absorbable biological material, especially medical magnesium alloy; and the related material and technique are not only suitable for common medical appliance products, but also have competitive edges in manufacturing of high-end medical appliance products, such as implantation instruments, especially secondary-operation-free implantation substances.
Description
Technical field
The invention belongs to bio-medical new material and medical device product manufacturing and applied technical field, but relate in particular to a kind of full-degradable biological 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---medical apparatus and instruments and ingredient, biomaterial are used for reparation, replacement or the function of the diagnosis of disease and treatment, histoorgan promotes, and a large amount of struggles are rehabilitated in sufferer residual, dead painful edge.In recent years, global medical apparatus industry high speed development, average annual growth rate be the same period increasing speed of national economy more than 2 times, be described as " rising industry ", become the very active new source of economic growth of 21 century.Be example with China, China medical apparatus and instruments market speedup in 2010 is up to 23%, and market scale breaks through 1,000 hundred million yuan of high point first, becomes the second-biggest-in-the-world medical apparatus and instruments market that is only second to the U.S., and expecting market scale in 2015 will be near 3,400 hundred million yuan.Just because of biomaterial huge social like this and economic worth, its R﹠D work is subjected to showing great attention to of countries in the world government, industrial circle and scientific and technological circle day by day, is successively listed in the crucial new material development plan of high-tech by U.S., moral, day, Australia and the Chinese government.
Biomaterial is of a great variety, and up to now, what be studied exceedes thousand kinds, and extensive medical also has nearly hundred kinds.Wherein metal material is because of its intensity and fracture toughness height, easily advantage such as shape, and becomes especially most widely used load embedded material in the orthopaedics (as backbone correcting, knochenbruch joint, skull repairing etc.) of present clinical medicine.Yet existing medical metal material such as ubiquitous problems such as rustless steel, cochrome, nickel alloy and titanium alloy are: except expensive, mechanical compatibility, biocompatibility and biological degradability are also not fully up to expectations.Be example with the titanium alloy that at present obtained extensive use at clinical medicine, its main performance defective comprises: (1) does not match owing to elastic modelling quantity, cause by the load conductive obstruction of implant to adjacent bone tissue, namely produce " stress shielding " effect, make its risk as implants (as suppressing knitting, cause osteoporosis, bone 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 disease, and Al is combined with Phos, also can bring out senile dementia when causing phosphorus deficiency; (3) because biological degradability is poor, and after damaged tissues/organ was finished reconstruction, implant must take out through second operation, therefore block the rehabilitation of patients process, additionally increased its body and mind misery and financial burden.For these reasons, seek better new material, the new technique of combination property under the prerequisite that guarantees safety, be emphasis and the focus place of biomaterial research always.Under this overall background, magnesium alloy leaps to the visual field of material supply section scholar, clinical medicine expert and medical equipment new high-tech enterprise with its many advantage just.
Magnesium alloy uses the inherent advantage with a series of uniquenesses as bio-medical material: (one) biodegradation sexual clorminance.The magnesium metal chemical property is active, at aggressivity physiological environment (Cl
-, organic acid, protein, enzyme and cell etc.) effect under, the magnesium implant in-service can be by the progressively extremely last complete obiteration of biodegradation, overcome metal body and in human body, retained the complication that causes for a long time, the Kucheng who makes the patient avoid second operation is possible, means simultaneously at same diseased region and can repeatedly get involved intervention.(2) bio-compatible sexual clorminance.Magnesium is the non-dissident's composition of human body, is one of human body macroelement (Mg
2+Be to be only second to Na in the human body
+, K
+And Ca
2+Occupy the 4th, be only second to K in the cell
+Occupy the 2nd cation; Human body per weight magnesium average content 0.3-0.4g/kg), participate in a series of metabolic processes, healthy closely related with the keeping of life, health, form at the biological phosphorus lime stone, bone matrix changes, osteocyte forms and in conjunction with, knitting, and very important role is all being played the part of in the normal performance aspect of functions such as nerve, muscle, heart.Therefore, the magnesium metal is inanimate object toxicity in essence, when using as biomaterial, as long as effectively control the rate of release of magnesium ion, then its degraded is to host useful and harmless (human body is to the daily demand of magnesium: baby 40-70mg/d, child 250mg/d, adult 300-700mg/d).(3) mechanical compatibility advantage.Young ' the s elastic modelling quantity of magnesium is the most approaching with the corresponding parameter (10-40GPa) of skeleton, is conducive to reduce even 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 strength; the specific stiffness height); " three is good " (casting and machinability; dimensional stability and recyclable property are good) and " top four " (electromagnetic shielding ability; damping noise reduction ability and heat conduction; conductive capability is strong) characteristics; therefore enjoy the good reputation of " 21 century green engineering material "; in various fields especially in " lightweight "; " environmental protectionization " etc. is significant or the field of special technical requirement arranged; as Aero-Space; automobile; the IT electronics; communication; industrial departments such as national defense and military, magnesium alloy cause in the world as the Application and Development of structural material shows great attention to.(6) resource and price advantage.Magnesium resource is very abundant on the earth, and magnesium relative amount 10.63% in the earth's crust metallic element is only second to aluminum (31.51%) and ferrum (22.02%) and occupies the 3rd, is 4.37 times of Ti content (2.43%).The magnesium that " inexhaustible " wherein only just arranged in the sea water---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 the raw material, the statistical result of latest domestic market quotes shows, at present, the average price of 99.95% primary magnesium ingot (about 17.0 yuan/kg) only be (about 160.0 yuan/kg) about 10% of TA0 titanium ingot.Based on above-mentioned many advantages, magnesium alloy is expected to become desirable bio-medical metal new material, be used for comprising orthopedic fixation device tools such as (1) hone lamella, nail and skeletal framework, (2) artificial bone, (3) intravascular stent and (4) tissue engineering bracket etc. are in the manufacturing of interior many high added value medical device product.
But the poor (E of magnesium self thermodynamic stability regrettably,
0=-2.37V NHE), surperficial autoxidation film thin (~ 10nm) loosen (because of PBR=0.80) and do not have " spontaneous recovery " 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 local pH value sharply soaring, and f) the local organization pneumatosis, etc.For these reasons, the development new material is especially based on the advanced composite material (ACM) of magnesium or magnesium alloy, reinforcing material biodegradation controllability is (not only biodegradable, and degradation rate can be regulated as required) time, improve the biocompatibility of material even give its biological activity, to satisfy clinical medicine to the harsh requirement of material combination property, have very important meaning, become the important topic of bio-medical new material and medical instruments field.
Up to now, be application background with the biomedicine, obtained great success based on the magnesium of surface modification and the exploitation of magnesium alloy composite technology of preparing.Relating to main process for modifying surface comprises: (1) conventional differential arc oxidation (MAO) technology (refers to Nondegradable or the MAO ceramic membrane that almost do not have a degradation capability is the MAO technology of preparation object, down together), (2) based on the complex technique of conventional MAO, as the MAO/ organic coat, MAO/ chemical deposition etc., (3) organic coat, (4) chemical conversion, (5) bionical passivation, (6) cathodic deposition, (7) anodic deposition, (8) IBAD(ion beam assisted depositing), (9) sol-gel process, (10) silane-modified, (11) ion implantation, (12) ion plating, (13) electrochemical polymerization, and (14) hydro-thermal method, etc.Though above-mentioned technology and each the tool advantage of composite that makes thereof, but also there is major defect: or be absorbed in the inhibition of matrix biological degradability and the improvement of biocompatibility, not only do not consider surface reforming layer " retiring from political life after winning tremendous successes " after damaged tissues/organ is finished reconstruction---biodegradation problem, on the contrary, be to improve modified effect, but routinely thinking synthesize/apply compactness, the Nondegradable modified layer is worked hard; Though or with respect to the biological degradability of modified layer, comprehensive usage performance is unsatisfactory.With regard to the former, to utilize the MAO to matrix to handle the example that is prepared as that realizes composite, owing to adopt conventional electrolysis liquid (as silicate, phosphate and fluoride-based electrolyte), so gained MAO film main component is degradable or very poor silicate, phosphate or the fluoride of degradability hardly.This is impeccable beyond doubt for non-medical magnesium alloy, but with the magnesium alloy bio-medical maximum bright spot---the utilization of biological degradability constitutes serious contradiction.In other words, when using as " exempting from second operation " implantation instrument or tubulose/chamber shape tissue/organ timbering material such as intravascular stent etc., even the environment lower substrate can progressively degrade, absorb according to expection under arms, Nondegradable housing (surface modification rete such as MAO film) or its are peeled off the long-term existence of fragment, all that has been achieved is spoiled also will to make all effort of exempting the permanent external source precursor reactant of body, even bringing on a disaster property consequence (as artery-clogging).With regard to the latter, apply the example that is prepared as that degradable high polymer material is realized composite in order to being used in matrix surface, have following subject matter: (1) does not consider the potential hazard of macromolecular material acid degradation product, cause the acidify 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 Nondegradable HA(hydroxyapatite) compound use, limited its modified effect and application category; (3) coating/basal body binding force is undesirable, etc.
Summary of the invention
The objective of the invention is to the subject matter that exists in existing bio-medical material and the application technology thereof, but a kind of full-degradable biological material and preparation method thereof is provided.
The present invention is achieved by the following technical programs:
But a kind of preparation method of full-degradable biological 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) shot-peening: step a) resulting product matrix is carried out bead behind surface dressing;
C) apply: comprise following key step:
C-1) preparation of solution:
1# solution: be the organic solvent based sols of PLLA, PLGA or its mixture, its concentration is 0.2-75.0g/L;
2# solution: for magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, with water, acetone, ethanol, n-butyl alcohol or wherein two or more mixture 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 mixture be solid dispersed phase, organic solvent based sols with PLLA, PLGA or its mixture is the suspension of liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass;
C-2) coating of coating: the goods matrix of handling through step b) is carried out coating processing, obtain to have concurrently the degraded protection and from the functional membrane of degradation characteristic, described coating processing adopts in following three kinds of schemes more than one to carry out:
Scheme one: unite and use c-1) step is joined 1# solution and 2# solution, follows first order with usefulness 2# solution reuse 1# solution behind the 1# solution, carries out taking turns above coating;
Scheme two: the independent c-1 that uses) step is joined 3# solution and is carried out taking turns above coating.
Scheme three: unite and use c-1) step is joined 1# solution, 2# solution and 3# solution, follows first order with usefulness 2# solution reuse 3# solution behind the 1# solution, carries out taking turns above coating.
The organic solvent of the solution of 1# step c-1) and 3# solution is a kind of in A solvent and the B solvent, wherein the A solvent is more than one in epoxychloropropane, dichloromethane or the chloroform, the B solvent be the A solvent with acetone, ethanol or n-butyl alcohol in more than one mixture that obtain after evenly mixing; Step c-1) the pure magnesium in the solution of 2# described in and the 3# solution and magnesium alloy are Powdered, graininess, lamellar, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of pure magnesium in the goods matrix or magnesium alloy.
Step c-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 c-1) solution of 3# described in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, mixture with molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is the suspension replacement of liquid, and the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass.
Step c-2) a kind of of scheme one described 1# solution and 2# solution replaces with 3# solution in; Step c-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.
Contain the coating of PLLA or PLGA when coating after, carry out spontaneous curing or artificial cured, 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 mixture, carrying out dried.
But a kind of full-degradable biological 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; Described functional membrane 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 mixture 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 mixture be the degradable high polymer material based composites layer of wild phase, the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality; Degradable high polymer material in described No.1 coating and the No.2 coating is PLLA, PLGA or its mixture.
Described No.1 coating and No.2 coating are respectively more than one deck, and the composition of different layers, structure and thickness are identical or different; Composition, structure and the thickness of the degradable high polymer material layer of sandwich of layers both sides are identical or different in the described No.1 coating; Sandwich of layers in the described No.1 coating replaces with the No.2 coating; One deck at least of the degradable high polymer material layer of sandwich of layers both sides replaces with the No.2 coating in the described No.1 coating.
Pure magnesium in described No.1 coating and the No.2 coating and magnesium alloy are Powdered, graininess, lamellar, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of the pure magnesium of matrix or magnesium alloy.
The melting of material preparation method step a) of the present invention and shaping can any known or commercially available technology be carried out, as: the melting under the protective atmosphere, casting, forging and pressing, extruding or shaping by stock removal, etc.The effect of melting is to obtain the high-quality melt (metal or alloy liquid) that chemical constituent and field trash (as oxide inclusions), air content control levels such as (as hydrogen) meet the demands; Shaping comprises and utilizes above-mentioned directly from melt formation (as casting) or be shaped indirectly (namely first make blank such as ingot casting with above-mentioned melt, blank is handled, as forging, extruding and cutting etc.) again.
The purpose of surface dressing is to remove the burr, dirt, oxide skin of goods remained on surface or generation during processing, accumulating etc. in the material preparation method step b) of the present invention, to obtain to satisfy the surface quality that subsequent treatment requires.Surface dressing can any known or commercially available physics and/or chemical technology carry out, as sand paper/grinder buffing, polishing cloth polishing, organic solvent comprises dehydrated alcohol, acetone etc. directly or defat under outer field actions such as ultrasound wave, alkali cleaning, pickling, washing, etc.
Shot-peening be with the high-speed shot blasting material as working media, surface of the work produce is impacted and shear action, make surface of the work obtain the method for specific cleannes and roughness." sandblast " is real with " shot-peening " to be the identical concept, and just used medium is different.In other words, broadly, " sandblast " belongs to the category of " shot-peening "." shot-peening " concept namely refers to sensu lato blasting technology described in the material preparation method step b) of the present invention, namely comprises " sandblast ".The main purpose of shot-peening is to realize cleaning surfaces and the roughening of workpiece are handled, and improves corrosion fatigue (especially stress corrosion fatigue) and spot corrosion (pitting) drag and mechanical strength and the wearability of material simultaneously to a certain extent.Bead can be carried out by any known or commercially available technology and equipment, as mechanic shot peening etc.When adopting the mechanic shot peening method, available devices comprises mechanical centrifugal compressed air shotblasting machine and pneumatic type compressed air shotblasting machine etc., and available shot-peening material comprises corundum (as brown corundum, white fused alumina and black corundum), carborundum (as black silicon carbide, green silicon carbide), glass bullet, ceramic bullet, shot (as rustless steel, cast steel and cast iron bullet) and polymer bullet etc.The particle diameter of shot-peening material, speed and flow concrete parameters such as (the bullet quality of ejection in the unit interval) then can be according to the actual needs of the especially surperficial roughening degree for the treatment of effect is controlled.
After bead finishes, processing such as material preferably cleans respectively, drying, comprise tap water and/or distilled water, rinsed with deionized water, hot blast or compressed air dry up or the heating furnace oven dry, or dry after the rinsings such as effumability organic solvent such as ethanol, acetone etc.Cleaning, dry purpose are to remove the non-target product that is adsorbed on surface of the work, comprise the chip of residual shot-peening material etc., avoid influencing the subsequent treatment effect.
With the main purpose of various coating material liquefaction (being mixed with solution or fusing use), be conveniently to apply and guarantee to obtain the coating effect of homogeneous in the material preparation method step c) of the present invention.The organic solvent of described PLLA, PLGA can be selected in A solvent, B solvent and other any known or commercially available solvent according to qualifications according to rate of dissolution, curing mode and specific requirements such as speed and coating porosity.When being mixed with the organic solvent based sols when using, the concentration of degradable high polymer material is low excessively, and then the thick coating that obtains of single application is spent thinly, and coating efficiency is low excessively; Excessive concentration, then solution viscosity is excessive, is unfavorable for that coating and coating uniformity are poor.The concrete concentration of degradable high polymer material then can require to control according to coating speed, coating quality (as uniformity, porosity etc.).When 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 cohesiveness, obviously worsen with basal body binding force and degraded barrier propterty etc.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture as 1) be the suspension of liquid with the organic solvent based sols of PLLA, PLGA or its mixture; or 2) be that the solid dispersed phase of the suspension of liquid is when using with the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA; at the 0.5%-40% that accounts for solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass, then be in order to ensure the composite coating that obtains to meet the demands with its quality control.During preparation 2# solution, control wherein that the concentration of solid dispersed phase is 0.5-45.0g/L, reason has two: one, concentration are low excessively, and then the thicknesses of layers that obtains of single application is thin excessively, and coating efficiency is low excessively; Its two, excessive concentration, then the homodisperse difficulty of solid dispersed phase strengthens and the stability of solution variation, be unfavorable for applying and film quality poor.For obtaining high-quality suspension, the dispersion of described magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be carried out under stirring conditions such as mechanical, ultrasonic or compressed air.When applying operation, the concrete coating number of times of every kind of coating material is then controlled according to needs such as coating structure, thickness.When using identical coating material repeatedly to apply, each solution that applies use can be identical, also can be different.For identical coating solution, the coating layer thickness of acquisition and coating number of times positive correlation.
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, may there be the autoxidation thin film between functional membrane and the matrix in the material of the present invention, be that matrix and surrounding (comprise atmosphere, cleaning solution such as water, dehydrated alcohol, alkali wash water or pickle, etc.) when contact its top layer by the rete of mainly being formed by oxide, hydroxide (as magnesium oxide, magnesium hydroxide) or its mixture of matrix that autoxidation generated.This " autoxidation thin film " is most of metals and the inevitable outcome of alloy under conventional manufacturing environment (corresponding is special manufacturing environments such as vacuum with it) thereof, but because its thickness very thin (nanoscale) usually can ignore substantially to the general usage Effect on Performance of material.
Used 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, graininess, lamellar, thread, banded, tubulose or whisker shape product especially.For the stability of pure magnesium and magnesium alloy in the enhancing coating, can carry out surface modification treatment to it by known or commercially available technology before using.The OCP of pure magnesium or magnesium alloy is not higher than the OCP of pure magnesium in the matrix or magnesium alloy in control preparation method and the coating that makes, purpose is to obtain required coating and guarantees that coating ingredients is not the degraded of accelerating matrix as the cathodic component under the service state, degrades but preferably have precedence over matrix (as sacrificial anode).
No.1 coating and No.2 coated designs are more than one deck in the material of the present invention, and the composition (as: consumption of 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 structural units); The kind of macromolecular material and molecular weight thereof etc.), structure (as density, porosity, surface roughness etc.) and thickness is identical or different, in addition, the composition of the polymer material layer of sandwich of layers both sides in the No.1 coating (kind and molecular weight thereof etc.), structure and thickness are identical or different, and its purpose all is to take full advantage of the characteristic of different materials component units to realize the successful control to material monolithic combination property especially biological degradability, biocompatibility and coating/basal body binding force, coating cohesiveness etc.The concrete thickness of sandwich of layers and both sides polymer material layer thereof can be controlled according to actual needs flexibly in No.2 coating and the No.1 coating.When carrying out the preparation of No.1 coating, adhesion for the polymer material layer that strengthens sandwich of layers and its both sides, the coating of sandwich of layers should be selected in to be carried out before first floor polymer material layer solidifies fully, or suitably control the porosity of the polymer material layer of sandwich of layers both sides, or finish the back at the coating coating procedure and heat-treat with suitable standard.
PLLA and PLGA can partly or entirely replace by any other known or commercially available macromolecular material with biodegradation character in material of the present invention and preparation method thereof, as natural degradable macromolecular materials such as collagen 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) magnesium base alloy of different-alloy constituent element and alloying level, 2) magnesium base composite material, and 3) magnesium alloy product and 4) contain the goods of magnesium alloy component (constituent element).
Compared with prior art, advantage of the present invention is many-sided, and outstanding behaviours is aspect following two:
(1) material integrates ideal characterisitics with regard to the functional membrane 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 degradability; Wherein magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP not only possess biodegradability, and catabolite is the nutrient of needed by human body.On the other hand, magnesium oxide, magnesium hydroxide, pure magnesium and magnesium alloy also have simultaneously with the acid degradation product of degradable high polymer material (as intermediate product lactic acid and end product carbon dioxide and the water of PLLA degraded) neutralization reaction take place, the outstanding role of its potential hazard of buffering/eliminate (as aseptic inflammation etc.).In addition, wild phase as the macromolecular material based composites, 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 moment such as effective effect passage of blocking corrosive medium in the environment of implantation initial stage; matrix is formed tight protection; again can be along with the reconstruction of damaged tissues/organ self controlled degradation gradually; the final matrix that exposes is in order to its natural degradation, absorption, and its degraded protective capacities reaches all can regulate and control by membranous layer ingredient, structure and thickness from degradation rate.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; Difficult degradation is got in functional membrane self constituent, and then it is more slow from degradation rate.With regard to 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, microstructure optimization such as technology such as alloying, grain refinement.Therefore, material monolithic of the present invention has remarkable advantages---and it is ubiquitous or damage biocompatibility or mechanical integrity because putting undue emphasis on biological degradability to be expected to thoroughly eliminate current material, or damage drawbacks such as biological degradability because putting undue emphasis on the degraded protective, thereby provide desirable solution for the contradiction between the control of the utilization of degradable biomaterial biodegradation character and degradation rate.
(2) technology synergy realizes that the optimization of material prepares material preparation method of the present invention based on to different materials, fully realizing of the advantage of different technologies and cooperative effect thereof, forming technique and process for modifying surface is organic compound, especially unite and utilize shot-peening 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, bead has significant roughening effect to matrix surface, can form micro-" anchor point " in a large number, thereby is that combining closely between coating/matrix creates conditions.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP independently use as coating material, there is outstanding problems such as applying difficulty, adhesion difference, and when its disperse phase (wild phase) as the sandwich of layers of organic coating or macromolecular material based composites used, the problems referred to above then were readily solved.Therefore, utilize technology provided by the invention, but can realize the optimization preparation of full-degradable biological material.
Description of drawings
Fig. 1 is material preparation method process chart in the embodiment;
Fig. 2 is material section structure sketch map in the embodiment;
Fig. 3 is material functional membrane section structure sketch map in the embodiment;
Among the figure: the 1-matrix, the 2-functional membrane, 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 mixture be the degradable high polymer material based composites layer of wild phase.
The specific embodiment
Below in conjunction with accompanying drawing and example concrete enforcement of the present invention is described further, but enforcement of the present invention and protection domain are not limited thereto.
As shown in Figure 1, be material preparation method process chart in the embodiment.But the preparation method of the present invention's full-degradable biological material is made of melting, shaping → shot-peening → coating three big key steps.The purpose of wherein melting, shaping is to obtain the goods matrix that material (chemistry and phase composition, microstructure, grain size etc.), shape and size etc. meet the demands; The main effect of shot-peening is to realize the surperficial roughening of goods matrix is handled; The effect that applies is to construct functional membrane at the goods matrix surface.
As shown in Figure 2, be material section structure sketch map in the embodiment.Biological medical degradable material of the present invention is constructed by pure magnesium or magnesium alloy substrate 1 and functional membrane 2 integral body that cover matrix 1 surface and is formed.
As shown in Figure 3, be material functional membrane section structure sketch map in the embodiment.Wherein a coating, b coating and c coating are superimposed, and belong to No.1 coating of the present invention, and the b coating belongs to the sandwich of layers of No.1 coating.Wherein the d coating belongs to No.2 coating of the present invention.
Below in conjunction with the preferred embodiments of the present invention, above-mentioned feature of the present invention is described in further detail.
Material therefor comprises high-purity magnesium (purity 99.9%), magnesium alloy AZ31, AZ91, WE43 and ZK60 among the embodiment.Carry out melting respectively according to material composition, be shaped, obtain test specimen.Wherein melting condition: temperature 750-760 ℃, 0.3vol%SF
6+ 50vol%CO
2With the Air mixing gas shield, melt temperature retention time 30min.Forming technique comprises permanent mold casting (high-purity magnesium and above-mentioned whole magnesium alloy), die casting (magnesium alloy AZ31 and AZ91), forges (magnesium alloy WE43 and ZK60) and hot extrusion (magnesium alloy AZ31 and AZ91), wherein permanent mold casting condition: 710-720 ℃; Die casting condition: 660 ℃ of pouring temperatures, 220 ℃ of type temperature, injection ratio pressure 50MPa, injection speed 40m/s; Forging condition: be blank with cylindrical ingot casting, open die forging, 400 ℃ of initial forging temperatures, 320 ℃ of final forging temperatures, forging ratio 1.87 is forged preceding 420 ℃ of insulation 2h at every turn; The hot extrusion condition: be blank with cylindrical ingot casting, 350 ℃ of extrusion temperatures, extrusion ratio 20, extruding rate 1.5m/min.Line cuts the test sample that above-mentioned test specimen obtains to be of a size of 20mm * 15mm * 2.5mm.By following standard sample is carried out surface dressing: alkali cleaning → washing → pickling → washing → silicon carbide paper polishing → washing → dehydrated alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → standby, wherein alkali cleaning condition: the combination solution of 40.0g/L sodium hydroxide, 10.0g/L sodium phosphate and 0.2g/L dodecylbenzene sodium sulfonate, 95 ℃, 15min; Pickling condition: the combination solution of 20.0g/L nitric acid, 50.0g/L magnesium nitrate and 50.0g/L dehydrated alcohol, 25 ℃, 15sec; Washing condition: tap water and distilled water rinsing successively.
Be object of study with the high-purity magnesium sample of permanent mold casting attitude.Select 100 purpose glass bullets, with the manual sandblasting machine of commercially available general pressure type (3 atmospheric pressure, 500kg/h emitted dose) sample is carried out the 30sec bead, obvious and uniform sand face effect appears in specimen surface as a result.Homogeneous mixture (mixed volume is than 2:1) with epoxychloropropane and acetone is that solvent is at first prepared 35.0g/LPLLA solution (liquid), adds 10.0g/L magnesium oxide (solid dispersed phase) then, and the acquisition suspension that stirs is labeled as solution S
01By following standard to through washing, dried shot-peening sample carries out 15 and takes turns dip-coating processing: sample is immersed solution S
01, take out behind the 15sec, treat coating curing.The result obtains uniform magnesium oxide/PLLA composite coating (functional membrane) at specimen surface.
Be tested media (its composition and human plasma chemical constituent 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 65d just begins to occur macroscopic erosion trace, compare and namely begin the result of corroding after blank sample (namely only surface dressing and do not carry out the sample of shot-peening and coating processing) immerses, its initial stage, anti-degradation capability obviously strengthened, and showed that functional membrane has good biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 112d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 265d, shows that material monolithic has high-fall solution characteristic.
Be object of study with permanent mold casting attitude AZ31 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Except changing the concentration of PLLA into 75.0g/L, magnesian concentration change into 0.377g/L(account for magnesium oxide, PLLA total content 0.5%), solvent changes into outside the chloroform, solution S
01Preparation with embodiment 1.By following standard washing, dried shot-peening sample are carried out 10 and take turns dip-coating processing: sample is immersed suspension S
01, take out behind the 30sec, treat coating curing.The result obtains uniform magnesium oxide/PLLA composite coating (functional membrane) at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 32d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 73d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 133d, shows that material monolithic has high-fall solution characteristic.
Embodiment 3
Be object of study with permanent mold casting attitude AZ91 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Except changing PLLA concentration into 0.2g/L, magnesium oxide concentration changes 0.133g/L into, and solvent changes into outside the dichloromethane, solution S
01Preparation with embodiment 1.By following standard washing, dried shot-peening sample are carried out 10 and take turns dip-coating processing: sample is immersed suspension S
01, take out behind the 7sec, treat coating curing.The result obtains uniform magnesium oxide/PLLA composite coating (functional membrane) at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 17d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 30d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 110d, shows that material monolithic has high-fall solution characteristic.
Embodiment 4
Be object of study with permanent mold casting attitude WE43 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Carry out solution S with embodiment 1
01Preparation.With brushing, spin coating or spraying method washing, dried shot-peening sample are applied respectively, treat that it is 1.57mg/cm in specimen surface acquisition surface density that coating is solidified the back
2Uniform magnesium oxide/PLLA composite coating.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 39d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 75d, 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 object of study with permanent mold casting attitude ZK60 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.195.0gPLLA is heated to molten condition and 210 ℃ of insulations, adds the 5.0g magnesium oxide, the acquisition suspension stirs.By following standard to through washing, dried shot-peening sample carries out dip-coating processing: sample is immersed suspension, takes out behind the 10sec, treat that coating solidifies.The result obtains uniform magnesium oxide/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 about 19d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 42d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 90d, shows that material monolithic has high-fall solution characteristic.
Embodiment 6
Be object of study to forge attitude WE43 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Except 35.0g/LPLLA is changed into the mixture of 10.0g/LPLLA and 25.0g/LPLGA, apply other process conditions control and result with embodiment 1.The result obtains uniform composite coating (functional membrane) at specimen surface, and the wild phase of this composite is magnesium oxide, and matrix is the mixture of PLLA and PLGA.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 57d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 95d, 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 7
Be object of study with extruding attitude AZ31 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Be solvent with the chloroform, at first prepare totally 4 parts of 30.0g/LPLLA solution, add 10.0g/L magnesium hydroxide, β-TCP, CPP and pure magnesium powder (sphere, meta particle diameter d then respectively
50=47 μ m), 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 shot-peening sample are carried out 3 and take turns dip-coating processing: sample is immersed solution S
01Take out behind-1, the 15sec, treat after coating is solidified sample to be immersed solution S
01Take out behind-2, the 15sec, treat after coating is solidified sample to be immersed solution S
01Take out behind-3, the 15sec, treat after coating is solidified sample to be immersed solution S
01Take out behind-4, the 15sec, treat coating curing.The result obtains uniformly by being the composite coating (functional membrane) that the PLLA matrix composite coating of wild phase is formed by stacking successively with magnesium hydroxide, β-TCP, CPP and pure magnesium respectively at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 35d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 79d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 194d, shows that material monolithic has high-fall solution characteristic.
Embodiment 8
Be object of study with die casting attitude AZ31 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Be solvent with the chloroform, preparation 25.0g/LPLLA solution is labeled as S
02Be dispersant (liquid) with the n-butyl alcohol, add 20.0g/L magnesium hydroxide (solid dispersed phase) and also stir, obtain suspension, be labeled as solution S
03By following standard to through washing, dried shot-peening sample carries out 10 and takes turns dip-coating processing: sample is immersed solution S
02, take out behind the 30sec, treat after coating is solidified sample to be immersed solution S
03, take out behind the 7sec, treat after the coating drying sample to be immersed solution S
02, take out behind the 5sec, treat coating curing.The result obtains uniform coating (functional membrane) at specimen surface, and the construction unit of this coating is for being the PLLA layer of sandwich of layers with magnesium hydroxide.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 32d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 70d, 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 9
Be object of study with die casting attitude AZ91 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Homogeneous mixture (mixed volume is than 3:1) with dichloromethane and acetone is solvent, prepares 75.0g/L and 0.2.0g/LPLLA solution respectively, is labeled as solution S
02-1 and S
02-2.Be dispersant (liquid) with the dehydrated alcohol, add 0.5.0g/L and 45.0g/L magnesium hydroxide (solid dispersed phase) respectively and stir, obtain suspension, be labeled as solution S
03-1 and S
03-2.By following standard washing, dried shot-peening sample are carried out 5 and take turns dip-coating processing: sample is immersed solution S
02Take out behind-1, the 7sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-1, the 3sec, treat after the coating drying sample to be immersed solution S
02Take out behind-2, the 15sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-2, the 3sec, treat after the coating drying sample to be immersed solution S
02-1, treat coating curing.The result obtains uniform composite coating (functional membrane) at specimen surface, and the construction unit of this coating is for being the PLLA layer of sandwich of layers with magnesium hydroxide.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 23d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 40d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 158d, shows that material monolithic has high-fall solution characteristic.
Embodiment 10
Be object of study with extruding attitude AZ91 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Except solvent is changed into the epoxychloropropane, carry out solution S with embodiment 8
02Preparation.Except changing magnesium hydroxide into magnesium oxide, β-TCP, CPP and pure magnesium powder (sphere, meta particle diameter d respectively
50=47 μ m), dispersant changes into outside the acetone, carries out solution S with embodiment 8
03Preparation, gained solution is labeled as S respectively
03-3, S
03-4, S
03-5 and S
03-6.By following standard washing, dried shot-peening sample are carried out dip-coating processing: sample is immersed solution S
02, take out behind the 45sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-3, the 15sec, treat after the coating drying sample to be immersed solution S
02, take out behind the 45sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-4, the 15sec, treat after the coating drying sample to be immersed solution S
02, take out behind the 45sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-5, the 15sec; Treat after the coating drying sample to be immersed solution S
02, take out behind the 45sec, treat after coating is solidified sample to be immersed solution S
03Take out behind-6, the 15sec, treat after the coating drying sample to be immersed solution S
02, take out behind the 45sec, treat the coating spontaneous curing.The result obtains the uniform composite coating (functional membrane) that is formed by stacking successively by the PLLA coating that with magnesium oxide, β-TCP, CPP and pure magnesium is sandwich of layers respectively at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 11d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 32d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 160d, shows that material monolithic has high-fall solution characteristic.
Embodiment 11
Be object of study to forge attitude ZK60 magnesium alloy sample.The control of shot-blast process condition and result are with embodiment 1.Carry out solution S with embodiment 1
01Preparation, carry out solution S with embodiment 8
02And S
03Preparation.By following standard to through washing, dried shot-peening sample carries out dip-coating processing: sample is at first immersed solution S
01, take out behind the 3sec, treat after coating is solidified 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 after coating is solidified sample to be immersed solution S
01, take out behind the 5sec, treat after coating is solidified 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 hydroxide, both sides are respectively the coating of PLLA coating and magnesium oxide/PLLA composite coating, and 2) be the composite coating (functional membrane) that the PLLA coating of sandwich of layers is formed by stacking with magnesium oxide/PLLA composite.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 20d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 45d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 122d, shows that material monolithic has high-fall solution characteristic.
Embodiment 12
Be object of study with the high-purity magnesium sample of permanent mold casting attitude.Except the stainless shot that bullet is changed into φ 0.2mm, other process conditions control of shot-peening and result are with embodiment 1.Carry out solution S with embodiment 8
03Preparation.PLLA is heated to molten condition and 210 ℃ of insulations, is labeled as solution S
04According to following standard washing, dried shot-peening sample are carried out dip-coating processing: sample is immersed solution S
04, take out behind the 60sec, after treating coating curing and being cooled to room temperature sample is immersed solution S
03, take out behind the 15sec, treat after the coating drying sample to be immersed solution S
04, 3sec treats the coating spontaneous curing.It is the PLLA coating of sandwich of layers with magnesium hydroxide uniformly that the result obtains at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 11d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 25d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 190d, shows that material monolithic has high-fall solution characteristic.
With further reference to medical apparatus and instruments biological assessment ISO 10993 standards, with the negative contrast of widely used titanium alloy ti6al4v on the clinical medicine, it is the bio-compatible property testing of representative that each sample in above-described embodiment 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 constituent
Claims (8)
1. but the preparation method of a full-degradable biological material is characterized in that comprising following key step:
A) melting and shaping: the pure magnesium of melting or magnesium alloy, and form manufacturing, obtain the goods matrix;
B) shot-peening: step a) resulting product matrix is carried out bead behind surface dressing;
C) apply: comprise following key step:
C-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 mixture are solid dispersed phase, with water, acetone, ethanol, n-butyl alcohol or wherein two or more mixture 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 mixture be solid dispersed phase, organic solvent based sols with PLLA, PLGA or its mixture is the suspension of liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass;
C-2) coating of coating: the goods matrix of handling through step b) is carried out coating processing, obtain to have concurrently the degraded protection and from the functional membrane of degradation characteristic, described coating processing adopts in following three kinds of schemes more than one to carry out:
Scheme one: unite and use c-1) step is joined 1# solution and 2# solution, follows first order with usefulness 2# solution reuse 1# solution behind the 1# solution, carries out taking turns above coating;
Scheme two: the independent c-1 that uses) step is joined 3# solution and is carried out taking turns above coating;
Scheme three: unite and use c-1) step is joined 1# solution, 2# solution and 3# solution, follows first order with usefulness 2# solution reuse 3# solution behind the 1# solution, carries out taking turns above coating.
2. but the preparation method of full-degradable biological material according to claim 1, it is characterized in that: the organic solvent of the solution of 1# step c-1) and 3# solution is a kind of in A solvent and the B solvent, wherein the A solvent is more than one in epoxychloropropane, dichloromethane or the chloroform, the B solvent be the A solvent with acetone, ethanol or n-butyl alcohol in more than one mixture that obtain after evenly mixing; Step c-1) the pure magnesium in the solution of 2# described in and the 3# solution and magnesium alloy are Powdered, graininess, lamellar, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of pure magnesium in the goods matrix or magnesium alloy.
3. but the preparation method of full-degradable biological material according to claim 1 is characterized in that: the mixture replacement of the solution of 1# step c-1) molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA; Step c-1) solution of 3# described in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, mixture with molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is the suspension replacement of liquid, and the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass.
4. but the preparation method of full-degradable biological 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 c-2); Step c-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.
5. but the preparation method of full-degradable biological 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 cured, 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 mixture, carrying out dried.
But 6. full-degradable biological 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; Described functional membrane 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 mixture 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 mixture be the degradable high polymer material based composites layer of wild phase, the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality; Degradable high polymer material in described No.1 coating and the No.2 coating is PLLA, PLGA or its mixture.
But 7. full-degradable biological material according to claim 6, 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.
8. but full-degradable biological material according to claim 6, it is characterized in that: the pure magnesium in described No.1 coating and the No.2 coating and magnesium alloy are Powdered, graininess, lamellar, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of the pure magnesium of matrix or magnesium alloy.
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