CN103276398B - Biological medical absorbable material and preparation method thereof - Google Patents

Abstract

The invention discloses a kind of Biological medical absorbable material and preparation method thereof.The preparation method of material of the present invention comprises following key step: 1) melting and shaping, 2) corrosion roughening, 3) cathodic deposition, 4) thermal treatment, and 5) coating.What material of the present invention comprised pure magnesium or magnesium alloy substrate and covered matrix surface has degraded protection and the functional membrane from degradation characteristic concurrently, and entirety has controlled degradable absorption characteristic, suits the rigors of degradable biomaterial ideal behavior.The present invention provides preferred version for solving the contradiction of absorbable biological medicinal material especially between the utilization of medical magnesium alloy biodegradation character and degradation rate control, the material related to and technology are not only applicable to general medical devices product, in advanced medical device product is as the manufacture of implantation instrument implants of especially " exempting from second operation ", have more competitive edge.

Description

Biological medical absorbable material and preparation method thereof

Technical field

The invention belongs to bio-medical novel material and medical device product manufacture thereof and applied technical field, particularly relate to a kind of Biological medical absorbable material and preparation method thereof.

Background technology

Along with socioeconomic development and growth in the living standard, the mankind just unprecedentedly pay close attention to self medical treatment & health cause.The increasing of survival pressure, the quickening of rhythm of life, the aggravation of environmental pollution, the frequent generation of the security incidents such as food, traffic and production and local war, natural disaster etc., the haze causing disease and wound to become the mankind forever can't get rid of.As the important means of modern medicine---the important foundation of medicine equipment and integral part, biomaterial is used for the Diagnosis and Treat of disease, the reparation of histoorgan, replacement or function to be promoted, and a large amount of struggle is rehabilitated in the sufferer at residual, dead painful edge.In recent years, global medical apparatus industry high speed development, average annual growth rate be the same period increasing speed of national economy more than 2 times, be described as " sunrise industry ", become the 21 century very active new source of economic growth.For China, China's Medical Device Market speedup in 2010 is up to 23%, and market scale breaks through 1 first, and 00,000,000,000 yuan of high pointes become the second-biggest-in-the-world Medical Device Market being only second to the U.S., and expecting market scale in 2015 will close to 3,40,000,000,000 yuan.Just because of the so huge society of biomaterial and economic worth, its R&D work is subject to countries in the world government, the showing great attention to of industrial 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, up to now, studied mistake exceed thousand kinds, extensively medical also have nearly hundred kinds.Wherein metallic substance is because of its intensity with the advantage such as fracture toughness property is high, easily shape, and becomes the load embedded material that current clinical medicine is especially most widely used in orthopaedics (as backbone correcting, knochenbruch joint, skull repairing etc.).But existing medical metal material such as the ubiquitous problems such as stainless steel, cochrome, nickelalloy and titanium alloy are: except expensive, mechanical compatibility, biocompatibility and biological degradability are also not fully up to expectations.To obtain the titanium alloy of widespread use at present at clinical medicine, its salient features defect comprises: (1) does not mate due to Young's modulus, cause by the dynamic changes process obstacle of implant to adjacent bone tissue, namely " stress shielding " effect is produced, make its risk as implants (as suppressed knitting, cause osteoporosis, bone resorption or osteanabrosis, even occur secondary fracture etc.) cannot evade all the time; (2) degraded of pure titanium in body can cause allergy even dead, Al and V in typical titanium alloy ti6al4v all has cytotoxicity, and wherein V can cause chronic inflammatory diseases, and Al is combined with inorganic phosphorus, also can bring out senile dementia while causing scarce phosphorus; (3) because biological degradability is poor, after damaged tissue/organ completes reconstruction, implant must take out through second operation, has therefore blocked the rehabilitation process of patient, adds additional its body and mind misery and economical load.For these reasons, under the prerequisite ensureing security, find the better novel material of over-all properties, new technology, be emphasis and the focus place of biomaterial research always.Just under this overall background, magnesium alloy leaps to the visual field of material supply section scholar, clinical medicine expert and medical equipment new high-tech enterprise with its many advantages.

Magnesium alloy uses the inherent advantage with a series of uniqueness as bio-medical material: (one) biological degradation sexual clorminance.MAGNESIUM METAL chemical property is active, at aggressiveness physiological environment (Cl ^-, organic acid, protein, enzyme and cell etc.) effect under, magnesium implant in-service can by progressively biological degradation extremely last completely dissolve, overcome the complication that metal body longer-term persistence in human body causes, make patient from second operation Kucheng for may, mean simultaneously and repeatedly can get involved intervention at same diseased region.(2) physiologically acceptable sexual clorminance.Magnesium is the non-dissident's composition of human body, is one of human body major element (Mg ²⁺be only second to Na in human body ⁺, K ⁺and Ca ²⁺occupy the 4th, in cell, be only second to K ⁺occupy the positively charged ion of the 2nd; Human body per weight magnesium average content 0.3-0.4g/kg), participate in a series of metabolic processes, closely related with the health of the maintenance of life, health, formed at biogenic apatite, ground substance of bone changes, osteocyte is formed and combine, knitting, and the normal performance aspect of the function such as nerve, muscle, heart all plays very important role.Therefore, magnesium metal is 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 close with the corresponding parameter (10-40GPa) of skeleton, is conducive to reducing even eliminating implant to potential " stress shielding " effect of body bone tissue, promotes growth and the healing of bone.(4) biological activity advantage.Animal experiment and the clinical test results of open report show, magnesium has excellent osteoinductive.(5) traditional performance advantage.Magnesium has " one is low " (density is low), " two is high " (specific tenacity, specific rigidity is high), " three is good " (casting and machinability, dimensional stability and recyclable property good) and " top four " (electromagnetic shielding capability, damping noise reduction ability and heat conduction, conductive capability is strong) feature, therefore the good reputation of " 21 century green engineering material " is enjoyed, in various fields especially in " lightweight ", " environmental protection " etc. are significant or have the field of special technical requirement, as aerospace, automobile, IT electronics, communication, the industrial sectors such as national defense and military, magnesium alloy causes in the world as the Application and Development of structured material shows great attention to.(6) resource and price advantage.On the earth, magnesium resource is very abundant, magnesium relative content 10.63% in earth's crust metallic element, and being only second to aluminium (31.51%) and the 3rd, iron (22.02%) residence, is 4.37 times of titanium content (2.43%).Wherein only just there is magnesium---the magnesium density 1.1kg/m of " inexhaustible " in seawater ³, total content is up to 2.1 × 10 ¹⁵ton.Developing rapidly of rich in natural resources and the technology such as smelting, shaping, causes the price of magnesium metal and goods thereof to seem very cheap relative to titanium etc.For starting material, latest domestic market quotes statistics shows, at present, the average price (about 17.0 yuan/kg) of 99.95% primary magnesium ingot is only (about 160.0 yuan/kg) about 10% of TA0 titanium ingot.Based on above-mentioned many advantages, magnesium alloy is expected to become desirable bio-medical metal novel material, for comprising the orthopedic fixation device tools such as (1) hone lamella, nail and skeletal framework, (2) artificial bone, (3) intravascular stent and (4) tissue engineering bracket etc. are in the manufacture of interior many high added value medical device product.

But regrettably, magnesium self thermodynamic stability difference (E ⁰=-2.37V NHE), surface autoxidation film thin (~ 10nm) and loosen (because of PBR=0.80) and without " self-healing " ability, effective protection can not be provided to matrix.It is reported, pure magnesium is through HBSS(Hank ' s balanced salt solution) erosion of 225h, mass loss is up to 99%.Therefore, the bio-medical of magnesium alloy does not only benefit from the biodegradation character of its uniqueness, on the contrary, but lock into the too fast series of problems brought of degraded always, as: a) the too early decay of material product military service performance especially mechanical integrity was even lost efficacy, b) biocompatibility is endangered, c) heavy dose has the rapid release of the alloying element of potential source biomolecule toxicity, d) host's magnesium Metabolic stress is increased, even cause hypermagnesemia, e) local ph is caused sharply to rise, and f) local organization pneumatosis, etc.For these reasons, development 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 regulate as required) while, the biocompatibility improving material even gives its biological activity, to meet the rigors of clinical medicine to material over-all properties, tool is of great significance, and becomes the important topic of bio-medical novel material and medical instruments field.

Up to now, take biomedicine as application background, the exploitation based on the Magnesium and magnesium alloys based composites technology of preparing of surface modification obtains great success.Relate to major surfaces modification technology to comprise: (1) conventional differential arc oxidation (MAO) technology (refer to nondegradation or almost without the MAO ceramic membrane of degradation capability for preparing the MAO technology of object, lower same), (2) based on the compounding technology of conventional MAO, as 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, Deng.Although above-mentioned technology and each tool advantage of obtained matrix material thereof, but also there is major defect: or the improvement of the suppression be absorbed in matrix biological degradability and biocompatibility, not only do not consider surface reforming layer " retiring from political life after winning tremendous successes " after damaged tissue/organ completes reconstruction---biological degradation problem, on the contrary, for improving modified effect, but thinking is made an effort in synthesis/applying compactness, nondegradation modified layer routinely; Although or with respect to the biological degradability of modified layer, comprehensive usage performance is unsatisfactory.With regard to the former, with utilize matrix material realizes to the MAO process of matrix be prepared as example, owing to adopting conventional electrolysis liquid (as silicate, phosphoric acid salt and fluoride-based electrolytic solution), therefore 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 magnesium alloy bio-medical maximum bright spot---the utilization of biological degradability forms serious contravention.In other words, when using as intravascular stent etc. as " exempting from second operation " implantation instrument or tubulose/cavity-like tissue/organ timbering material, even if environment lower substrate progressively can degrade, absorb according to expection under arms, nondegradation housing surface modification retes such as () MAO films or its peel off the long-term existence of fragment, also by making all effort of the permanent external source precursor reactant of release body, all that has been achieved is spoiled, even bringing on a disaster property consequence (as artery-clogging).With regard to the latter, example is prepared as in order to what be used in that matrix surface coating degradable high polymer material realizes matrix material, there is following subject matter: (1) does not consider the potential hazard of macromolecular material acid degradation products, as a. causes the acidifying of local physiological environment then to cause aseptic inflammation, b. accelerate the degraded of magnesium alloy substrate, therefore have no proposition and tackle/protection measure targetedly; (2) macromolecular material isolated use or only with nondegradation HA(hydroxyapatite) compound use, limit its modified effect and application category; (3) coating/basal body binding force is undesirable, etc.

Summary of the invention

The object of the invention is to the subject matter for existing in existing bio-medical material and utilisation technology thereof, a kind of Biological medical absorbable material and preparation method thereof is provided.

The present invention is achieved by the following technical programs:

A preparation method for Biological medical absorbable material, it comprises following key step:

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

B) roughening is corroded: immersed after surface dressing by step a) resulting product matrix in the group water solution of sodium chloride-containing 5.0-100.0g/L, hydrogenchloride 0-50.0g/L, carry out corrosion treatment, realize carrying out surface roughening object to article substrate;

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

D) thermal treatment: the article substrate through step c) process is heat-treated, obtain and have degraded protection and the functional membrane bottom from degradation characteristic concurrently, wherein said thermal treatment temp is 350-550 DEG C, and 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 mixture for solid dispersed phase, with water, acetone, ethanol, propyl carbinol or the wherein two or more mixture suspension that is liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;

3# solution: for magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture for solid dispersed phase, with the suspension that the organic solvent based sols of PLLA, PLGA or its mixture is liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture total mass;

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

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

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

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

The SODIUMNITRATE of sodium-chlor described in step b), sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, magnesium sulfate or wherein two or more mixture partly or entirely replace; The nitric acid of hydrogenchloride described in step b), sulfuric acid, acetic acid, citric acid or wherein two or more mixture partly or entirely replace; The magnesium nitrate of magnesium chloride described in step c), magnesium sulfate or its mixture partly or entirely replace.

Step e-1) described in the organic solvent of 1# solution and 3# solution be one in A solvent and B solvent, wherein A solvent is more than one in epoxy chloropropane, methylene dichloride or chloroform, and B solvent is the mixture obtained after more than one Homogeneous phase mixing in A solvent and acetone, ethanol or propyl carbinol; Step e-1) described in pure Magnesium and magnesium alloys in 2# solution and 3# solution be Powdered, particulate state, sheet, thread, banded, tubulose or crystal whisker-shaped, and its open circuit potential in any equivalent environment medium not higher than article substrate in the open circuit potential of pure magnesium or magnesium alloy.

Step e-1) described in 1# solution molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA mixture replace; Step e-1) described in 3# solution in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, replace with the suspension that the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is liquid, the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture total mass.

Step e-2) in the one 3# solution replacement of 1# solution described in scheme one and 2# solution; Step e-2) described in coating method comprise dip-coating, brushing, spin coating or spraying.

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

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

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

Pure Magnesium and magnesium alloys in described No.1 coating and No.2 coating is Powdered, particulate state, sheet, thread, banded, tubulose or crystal whisker-shaped, 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.

Melting and the shaping of material preparation method step a) of the present invention can any known or commercially available technology be carried out, as: the melting under protective atmosphere, casting, forging and stamping, extruding or cutting out shapes, etc.The effect of melting is the high-quality melt (metal or alloy liquid) that acquisition chemical composition and the level of control such as inclusion (as oxide inclusion), air content (as hydrogen) meet the demands; Shaping comprises and utilizes above-mentioned directly from melt formation (as casting) or be indirectly shaped (namely first obtain blank as ingot casting with above-mentioned melt, then process blank, as forging, extrude and cutting etc.).

In material preparation method step b) of the present invention, the object of surface dressing is the burr, dirt, oxide skin etc. of removing goods remained on surface or generation during processing, accumulating, to obtain the surface quality meeting subsequent disposal and require.Surface dressing can any known or commercially available physics and/or chemical technology carry out, as: sand paper/grinder buffing, polishing cloth polishing, organic solvent comprises dehydrated alcohol, acetone etc. directly or degreasing under the outer field actions such as ultrasonic wave, alkali cleaning, pickling, washing, etc.

The technical spirit of corroding roughening in material preparation method step b) of the present invention is the controlled corrosion of material, its object is to utilize simple, the economic surface roughening process of corrosive nature realization to body material, thus be that combining closely between coating/matrix establishes solid architecture basics.Etchant based on sodium-chlor in corrosion roughening liquid, hydrogenchloride is corrosion accelerants.Sodium chloride concentration is too low, and corrosion roughening speed is excessively slow, excessive concentration, and corrosion roughening effect does not occur obviously to improve thereupon, therefore, sodium chloride concentration should be controlled the scope at 5.0-100.0g/L.Hydrogen cloride concentration is too low, and corrosion promoter action is not obvious, excessive concentration, and roughening speed is too fast, and operation controls difficulty and strengthens, and easily causes excessive erosion.Hydrochloric acid, nitric acid, sulfuric acid, acetic acid or citric acid in corrosion roughening liquid can other any known or commercially available inorganic or organic acidity compound or its mixture replace.During corrosion roughening, electrolyte temperature should control at 5-95 DEG C.The corrosion roughening treatment time is then relevant with concentration of electrolyte and the requirement of roughening degree etc.Generally, concentration of electrolyte is larger, and the time obtaining same roughening effect needs is shorter; When electrolytic solution is identical, require to improve with roughening degree, the corrosion roughening treatment time is longer.

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

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

After corrosion roughening, cathodic deposition and thermal treatment terminate, material preferably carries out process such as cleaning, dry respectively, comprise tap water and/or distilled water, rinsed with deionized water, hot blast or pressurized air dry up or process furnace is dried, or easy volatile organic solvent is as dried after the rinsing such as ethanol, acetone.Cleaning, dry object are to remove the non-targeted product being adsorbed on workpiece surface, comprise corrosion roughening by product, corrosion roughening solution and cathodic deposition solution etc., avoid solution crossed contamination and affect subsequent disposal effect.

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

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

It should be noted that in material of the present invention may there is autoxidation film between cathodic deposition layer and matrix.Namely matrix and surrounding environment (comprise air, cleaning solution as water, dehydrated alcohol, alkaline wash or pickle solution, corrosion roughening solution and cathodic deposition solution etc.) contact time its top layer generate by natural oxidation the oxide compound primarily of matrix, oxyhydroxide (as magnesium oxide, magnesium hydroxide) or its mixture composition rete.This " autoxidation film " is most metals and the inevitable outcome of alloy under conventional manufacturing environment (what correspond is the special manufacturing environments such as vacuum) thereof, but because its thickness usual very thin (nano level), substantially negligible on the impact of material general usage performance.In addition, also may distribute between cathodic deposition layer and matrix a small amount of corrosion product, namely corrode in roughening process material deposition reaction occurring between cathodic reaction product (hydroxide ion) and reaction product of anode (being generally magnesium ion) and generates, its main component is magnesium hydroxide.

Magnesium oxide used in material of the present invention and preparation method thereof, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be the products of commercially available or homemade any shape, size and degree of crystallinity.Wherein pure Magnesium and magnesium alloys is advisable with Powdered, particulate state, sheet, thread, banded, tubulose or crystal whisker-shaped product especially.For strengthening the stability of pure Magnesium and magnesium alloys in coating, before using, surface modification treatment can be carried out by known or commercially available technology to it.The open circuit potential controlling pure magnesium or magnesium alloy in preparation method and obtained coating is not higher than the open circuit potential of magnesium pure in matrix or magnesium alloy, coating needed for object is to obtain and under guaranteeing service state coating ingredients be not accelerate the degraded of matrix as cathodic component, but preferably have precedence over matrix (as sacrificial anode) and degrade.

In material of the present invention, No.1 coating and No.2 coated designs are more than one deck, and the composition (as: consumption of magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP or CPP of different layers (" different layers " here refers to No.1 coating or No.2 coating is structure unit); The kind of macromolecular material and molecular weight thereof etc.), structure (as density, porosity, surfaceness etc.) and thickness identical or different, in addition, in No.1 coating, the composition (kind and molecular weight etc. thereof) of the polymer material layer of sandwich of layers both sides, structure and thickness are identical or different, and the characteristic that its object is all to make full use of differing materials component units is 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.In No.2 coating and No.1 coating, the concrete thickness of sandwich of layers and both sides polymer material layer thereof, can control according to actual needs flexibly.When carrying out the preparation of No.1 coating, for strengthening the bonding force of the polymer material layer of sandwich of layers and its both sides, the coating of sandwich of layers should be selected in before first floor polymer material layer solidifies completely to be carried out, or the suitable porosity controlling the polymer material layer of sandwich of layers both sides, or heat-treat with suitable specification after coating application procedures terminates.

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

It is pointed out that in the present invention, the pure magnesium of indication comprises: 1) the magnesium metal of different purity level, 2) pure magnesium goods, and 3) containing the goods of pure magnesium parts (constituent element).In the present invention, indication magnesium alloy comprises: the 1) Magnuminium of different-alloy constituent element and alloying levels, 2) magnesium base composite material, and 3) magnesium alloy product, and 4) containing the goods of magnesium alloy component (constituent element).

Compared with prior art, advantage of the present invention is many-sided, and outstanding behaviours is in following two:

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

(2) the technology synergy optimized fabrication material preparation method of the present invention that realizes material is based on to differing materials, the advantage of different technologies and fully realizing of synergistic effect thereof, by forming technique and process for modifying surface organic composite, especially combine and utilize corrosion roughening, cathodic deposition, thermal treatment and organic/inorganic paint-on technique, coating/matrix is constructed at matrix surface, coating/painting Coating combination is tight, composition, structure and thickness etc. are adjustable therefore degraded protection and controlled from degradation characteristic, there is superior bio consistency and bioactive multiple defense system simultaneously, preparation for biological medical controllable all-degradable material provides new thinking.Specifically, containing erosion carbon dioxide as the electrolytic solution of chlorion, nitrate ion or sulfate ion in carry out corrosion treatment time, due to the ununiformity of composition, microtexture etc., matrix microcell dissolution process is uneven to carry out, and corrosive nature shows selectivity, i.e. micro anode district optimum solvation, therefore, objectively, corrode, to matrix, there is certain roughening effect, can be formed micro-" anchor point " in a large number, thus be that combining closely between cathodic deposition layer/matrix creates condition.In addition, because corrosive fluid is cheap, etching operation process window is wide, therefore corrodes roughening technology and has high economy and practical value.Prepare integrated technique as coating synthesis and coating, electrochemical cathode deposition there is non-linear, low temperature operability and controllability good, the advantage such as with low cost is one of desirable technique of material surface modifying.Cathode run can realize the fabricated in situ of the prefilter layer of matrix surface magnesium hydroxide and functional membrane bottom.Heat treatment process can realize magnesium hydroxide to magnesian conversion and the sintering to existing rete, namely forms functional membrane bottom.The formation of functional membrane bottom, internally for matrix one deck of putting on has protective film from degradation characteristic, externally becomes the desirable substrate of follow-up coating (functional membrane surface layer) by means of its microtexture that is coarse, porous.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP independently use as coated material, there is the outstanding problems such as coating is difficult, bonding force is poor, and when it can be used as the disperse phase of the sandwich of layers of organic coating or macromolecular material based composites (wild phase) to use, the problems referred to above are then readily solved.Therefore, utilize technology provided by the invention, the optimized fabrication of controllable all-degradable biological material can be realized.

Accompanying drawing explanation

Fig. 1 is material preparation method process flow sheet in embodiment;

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

Fig. 3 is material function surface layer film section structure schematic diagram in embodiment;

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

Embodiment

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

As shown in Figure 1, be material preparation method process flow sheet of the present invention.The preparation method of Biological medical absorbable material of the present invention is made up of melting, the large key step of shaping → corrosion roughening → cathodic deposition → thermal treatment → coating five.The object of wherein melting, shaping is the article substrate that acquisition material (chemistry and phase composite, microtexture, grain size etc.), shape and size etc. meet the demands; The Main Function of corrosion roughening is to realize the surface roughening process to article substrate; The effect of cathodic deposition is to obtain magnesium hydroxide product layer, i.e. the prefilter layer of functional membrane bottom; Heat treated Main Function is to realize the sintering of cathodic deposition product to magnesian conversion and existing rete, obtains functional membrane bottom; The effect of coating is to carry out " reinforcement " from degradation function film bottom on the one hand, constructs functional membrane surface layer on the other hand.

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

As shown in Figure 3, be material function film section structure schematic 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, b coating belongs to the sandwich of layers of No.1 coating.Wherein d coating belongs to No.2 coating of the present invention.

Below in conjunction with the preferred embodiments of the present invention, above-mentioned feature of the present invention is described in further detail.

In embodiment, material therefor comprises high purity magnesium (purity 99.9%), magnesium alloy AZ31, AZ91, WE43 and ZK60.Carry out melting respectively according to material composition, be shaped, obtain test specimen.Wherein melting condition: temperature 750-760 DEG C, 0.3vol%SF ₆+ 50vol%CO ₂mixed gas protected with air, melt holding time 30min.Forming technique comprises permanent mold casting (high purity magnesium and above-mentioned whole magnesium alloy), die casting (magnesium alloy AZ31), forging (magnesium alloy ZK60) and hot extrusion (magnesium alloy AZ31 and AZ91), wherein permanent mold casting condition: 710-720 DEG C; Die Casting Condition: teeming temperature 660 DEG C, type temperature 220 DEG C, injection ratio pressure 50MPa, shot rate 40m/s; Forging condition: take cylindrical ingot as blank, flat-die forging, initial forging temperature 400 DEG C, final forging temperature 320 DEG C, forging ratio 1.87, the front 420 DEG C of insulation 2h of each forging; Hot extrusion condition: take cylindrical ingot as blank, extrusion temperature 350 DEG C, extrusion ratio 20, extruding rate 1.5m/min.The above-mentioned test specimen of Linear cut obtains the test sample being of a size of 20mm × 15mm × 2.5mm.By following specification, surface dressing is carried out to sample: alkali cleaning → washing → pickling → washing → silicon carbide paper polishing → washing → dehydrated alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → for subsequent use, wherein alkali cleaning condition: the combination solution of 40g/L sodium hydroxide, 10g/L sodium phosphate and 0.2g/L Sodium dodecylbenzene sulfonate, 95 DEG C, 15min; Acid washing conditions: the combination solution of 20g/L nitric acid, 50g/L magnesium nitrate and 50g/L dehydrated alcohol, 25 DEG C, 15sec; Washing conditions: tap water and distilled water rinsing successively.

Embodiment 1

With permanent mold casting state high purity magnesium sample for research object.Take distilled water as solvent, preparation 50.0g/L sodium chloride solution is as corrosion roughening liquid.Sample is immersed in the above-mentioned solution of temperature control 50 DEG C, take out after 2h, after washing, drying, find that obvious pit appears in specimen surface.To wash, dried corrosion roughening sample and stainless steel cylinder form electrode pair, sample connects DC power cathode, stainless steel cylinder connects DC positive source, immerses with in the 50.0g/L magnesium chloride solution of deionized water preparation (sample is placed in cylinder geometric centre) respectively, constant current 1.5mA/cm ²process 45min, result generates complete, the uniform field gray rete of one deck (prefilter layer of functional membrane bottom) at specimen surface.Washing, dried cathodic deposition sample are placed in retort furnace, are warming up to 450 DEG C of insulations 12 hours, cool to room temperature with the furnace afterwards, found that rete (functional membrane bottom) density is obviously improved.With the uniform mixture of epoxy chloropropane and acetone (mixed volume than for 2:1), for solvent, first prepare 25g/LPLLA solution (liquid), then add 10g/L magnesium hydroxide (solid dispersed phase), stir acquisition suspension, is labeled as S ₀₁.By following specification, washing, dried heat treatment sample are carried out to 3 and take turns dip-coating processing: sample is immersed solution S ₀₁, take out after 40sec, solidification to be coated.Result obtains the compound coating (functional membrane surface layer) be successively formed by stacking by magnesium hydroxide/PLLA composite coating uniformly at specimen surface.

Take HBSS as tested media (its composition and human plasma chemical composition contrast situation in table 1), control appearance face ratio (ratio that ie in solution volume is long-pending with specimen surface) 24ml/cm ², solution regeneration interval 24h, under probe temperature 37 DEG C of conditions, carrying out in vitro biodegradation to said sample can test.Result shows: sample matrix after about 12d just starts to occur macroscopic erosion trace, compare the result namely starting after check sample (namely only surface dressing and do not carry out corroding the sample of roughening, cathodic deposition, thermal treatment and coating processing) immerses to corrode, 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 after about 31d, shows that it has good in degradation characteristic; Sample is degradable after about 185d, shows that material monolithic has degradable characteristic.

Embodiment 2

With permanent mold casting state AZ31 magnesium alloy sample for research object.Except being changed into by solution with except the 5.0g/L sodium chloride solution of deionized water preparation, other condition of corrosion roughening controls with embodiment 1, and the pit sparse compared with embodiment 1, area is slightly little appears in result specimen surface.Change into except 0.5g/L except by density of magnesium chloride, the control of other condition of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Take chloroform as solvent, first prepare 25g/LPLLA solution totally 4 parts, then add respectively 5g/L magnesium oxide, pure magnesium (spherical, median d ₅₀=47 μm), β-TCP and CPP(solid dispersed phase) and to stir, obtain suspension, be labeled as solution S respectively ₀₁-1, S ₀₁-2, S ₀₁-3 and S ₀₁-4.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₁take out after-1,7sec, after solidification to be coated, sample is immersed solution S ₀₁take out after-2,7sec, after solidification to be coated, sample is immersed solution S ₀₁take out after-3,7sec, after solidification to be coated, sample is immersed solution S ₀₁-4, solidification to be coated.Result obtains uniform compound coating (functional membrane surface layer) at specimen surface, and this coating is successively formed by stacking by the PLLA matrix composite coating being wild phase with magnesium oxide, pure magnesium, β-TCP and CPP respectively.Carry out biodegradability test with embodiment 1 pair of said sample, result shows: sample matrix after about 24d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve after about 45d, shows that it has good in degradation characteristic; Sample is degradable after about 97d, shows that material monolithic has degradable characteristic.

Embodiment 3

With As-extruded AZ31 magnesium alloy sample for research object.Except changing into except 100.0g/L by the concentration of sodium-chlor, other condition of corrosion roughening controls with embodiment 1, and the pit higher compared with embodiment 1 density, area is larger appears in result specimen surface.Change into except 150.0g/L except by density of magnesium chloride, the control of other condition of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Take methylene dichloride as solvent, first compound concentration is respectively the PLLA solution of 75.0g/L and 0.2g/L, then adds the corresponding 75g/LPLLA solution of 0.377g/L(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 specification, washing, dried heat treatment sample are carried out to 10 and take turns dip-coating processing: sample is immersed solution S ₀₁take out after-5,7sec, after solidification to be coated, sample is immersed solution S ₀₁take out after-6,7sec, solidification to be coated.Result obtains the compound coating (functional membrane surface layer) successively superposed by magnesium hydroxide/PLLA composite coating uniformly at specimen surface.Carry out biodegradability test with embodiment 1 pair of said sample, result shows: sample matrix after about 42d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve after about 75d, shows that it has good in degradation characteristic; Sample is degradable after about 185d, shows that material monolithic has degradable characteristic.

Embodiment 4

With permanent mold casting state WE43 magnesium alloy sample for research object.Take distilled water as solvent, 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 temperature control 20 DEG C, take out after 10sec, after washing, drying, find that specimen surface presents uniform sand face effect.Except changing into except graphite flake to electrode (anode), the control of other condition of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Except changing PLLA into PLGA, 10.0g/L magnesium hydroxide being changed into outside magnesium hydroxide and each 5.0g/L of magnesium oxide, carrying out solution S with embodiment 1 ₀₁preparation.For solvent with the uniform mixture (mixed volume ratio is for 4:1) of methylene dichloride and dehydrated alcohol, prepare 30.0g/LPLLA solution, be labeled as solution S ₀₂; Take propyl carbinol as dispersion agent (liquid), add 15.0g/L magnesium oxide (solid dispersed phase), stir, obtain suspension, be labeled as solution S ₀₃.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₁, take out after 3sec, after solidification to be coated, sample immersed solution S ₀₃, take out after 12sec, after drying to be coated, sample immersed solution S ₀₂, take out after 5sec, after solidification to be coated, sample immersed solution S ₀₁, take out after 5sec, after solidification to be coated, sample immersed solution S ₀₂, take out after 45sec, solidification to be coated.Result obtains uniform by 1 at specimen surface) be sandwich of layers with magnesium oxide, both sides are respectively PLLA coating and with the coating of magnesium oxide and the magnesium hydroxide PLGA matrix composite coating that is wild phase, and 2) compound coating (functional membrane surface layer) that successively superposes with magnesium oxide and the magnesium hydroxide PLGA based composites that is wild phase the PLLA coating that is sandwich of layers.Carry out biodegradability test with embodiment 1 pair of said sample, result shows: sample matrix after about 35d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve after about 76d, shows that it has good in degradation characteristic; Sample is degradable after about 152d, shows that material monolithic has degradable characteristic.

Embodiment 5

To forge state ZK60 magnesium alloy sample for research object.Namely 37% hydrochloric acid mother liquor 114.52ml/L is added except the concentration of hydrogenchloride being changed into 50.0g/L() except, the preparation of corrosion roughening liquid is with embodiment 4.Sample is immersed in the above-mentioned solution of temperature control 20 DEG C, take out after 3sec, after washing, drying, find that roughening effect is with embodiment 4.Except changing into except forging state ZK60 magnesium alloy plate electrode (anode), the control of cathodic deposition condition and result will be with embodiment 1.Heat-treat condition control and result are with embodiment 1.Take chloroform as solvent, prepare 75.0g/L and 0.2g/LPLLA solution respectively, be labeled as solution S respectively ₀₂-1 and S ₀₂-2.With distilled water and acetone for dispersion agent (liquid), add 0.5g/L and 45.0g/L magnesium oxide (solid dispersed phase) respectively, stir acquisition suspension, is labeled as solution S respectively ₀₃-1 and S ₀₃-2.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₂take out after-1,7sec, after solidification to be coated, sample is immersed solution S ₀₃take out after-1,15sec, after drying to be coated, sample is immersed solution S ₀₂take out after-2,7sec, after solidification to be coated, sample is immersed solution S ₀₃take out after-2,15sec, after drying to be coated, sample is immersed solution S ₀₂take out after-2,7sec, solidification to be coated.Result obtains uniform compound coating (functional membrane surface layer) at specimen surface, and this coating structure unit is take magnesium oxide as the PLLA coating of sandwich of layers.Carry out biodegradability test with embodiment 1 pair of said sample, result shows: sample matrix after about 23d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve after about 44d, shows that it has good in degradation characteristic; Sample is degradable after about 125d, shows that material monolithic has degradable characteristic.

Embodiment 6

With As-extruded AZ91 magnesium alloy sample for research object.Except being changed into by sodium-chlor except SODIUMNITRATE, sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate or magnesium sulfate respectively, corrosion roughening other condition control and result are with embodiment 4.Change into except magnesium nitrate or magnesium sulfate respectively except by the magnesium chloride in electrolytic solution, the control of other condition of cathodic deposition and result are with embodiment 1.Except temperature being changed into except 350 DEG C, the time changes into outside 24h, and the control of other condition of thermal treatment and result are with embodiment 1.Solution S is carried out with embodiment 1 ₀₁preparation.Carry out spin coating, brushing and spray treatment by following specification respectively to washing, dried heat treatment sample, obtaining area density at specimen surface after solidification to be coated is 1.23mg/cm ²uniform magnesium hydroxide/PLLA composite coating.Carry out biodegradability test with embodiment 1 pair of said sample, result shows: sample matrix after about 45d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biological degradation protective capacities to matrix; Functional membrane is basic completely dissolve after about 97d, shows that it has good in degradation characteristic; Sample is degradable after about 215d, shows that material monolithic has degradable characteristic.

Embodiment 7

With die casting state AZ31 magnesium alloy sample for research object.Except being changed into by hydrogenchloride except nitric acid, sulfuric acid, acetic acid or citric acid respectively, corrosion roughening other 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 6.85.0gPLLA is heated to molten state and 210 DEG C of insulations, add 15.0g magnesium hydroxide, stir acquisition suspension, is labeled as solution S ₀₄.Dip-coating processing is carried out to through washing, dried heat treatment sample: sample is immersed solution S by following specification ₀₄, take out after 30sec, solidification to be coated.Result obtains uniform magnesium hydroxide/PLLA composite coating at specimen surface.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after 29d just starts to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve after 59d, shows that it has good in degradation characteristic; Sample is degradable after about 155d, shows that material monolithic has degradable characteristic.

Embodiment 8

To forge state WE43 magnesium alloy sample for research object.Corrosion roughening condition control and result are with embodiment 4.Solution S is carried out with embodiment 4 ₀₃preparation.The control of cathodic deposition condition and result are with embodiment 1.Except temperature being changed into except 550 DEG C, the time changes into outside 1h, and the control of other condition of thermal treatment and result are with embodiment 1.PLLA is heated to molten state and 210 DEG C of insulations, is labeled as solution S ₀₅.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₅, take out after 10sec, after solidification to be coated, sample immersed solution S ₀₃, take out after 30sec, after drying to be coated, sample immersed solution S ₀₅, take out after 5sec, solidification to be coated.Result is the PLLA coating (functional membrane surface layer) of sandwich of layers with magnesium oxide in specimen surface acquisition uniformly.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after 17d just starts to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve after 36d, shows that it has good in degradation characteristic; Sample is degradable after about 135d, shows that material monolithic has degradable characteristic.

Embodiment 9

With die casting state AZ91 magnesium alloy sample for research object.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.Take chloroform as solvent, preparation 10.0,15.0,20.0 and 25.0g/LPLLA solution, be labeled as solution S respectively ₀₆-1, S ₀₆-2, S ₀₆-3 and S ₀₆-4; Take ethanol as dispersion agent (liquid), add respectively 10.0g/L magnesium hydroxide, pure magnesium (spherical, median d ₅₀=47 μm), β-TCP and CPP(solid dispersed phase), stir acquisition suspension, is labeled as solution S respectively ₀₇-1, S ₀₇-2, S ₀₇-3 and S ₀₇-4.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₆take out after-1,7sec, after solidification to be coated, sample is immersed solution S ₀₇take out after-1,10sec, after drying to be coated, sample is immersed solution S ₀₆take out after-2,7sec, after solidification to be coated, sample is immersed solution S ₀₇take out after-2,10sec, after drying to be coated, sample is immersed solution S ₀₆take out after-3,7sec, after solidification to be coated, sample is immersed solution S ₀₇take out after-3,10sec, after drying to be coated, sample is immersed solution S ₀₆take out after-4,7sec, after solidification to be coated, sample is immersed solution S ₀₇take out after-4,10sec, after drying to be coated, sample is immersed solution S ₀₆take out after-1,7sec, solidification to be coated.The compound coating (functional membrane surface layer) that the PLLA coating that result is sandwich of layers with magnesium hydroxide, pure magnesium, β-TCP and CPP in specimen surface acquisition uniformly respectively is successively formed by stacking.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after 27d just starts to occur macroscopic erosion trace, shows that functional membrane has certain degraded protective capacities to matrix; Functional membrane is basic completely dissolve after 58d, shows that it has good in degradation characteristic; Sample is degradable after about 174d, shows that material monolithic has degradable characteristic.

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

Table 1: tested media and human plasma chemical composition contrast

Claims (9)

1. a preparation method for Biological medical absorbable material, is characterized in that comprising following key step:

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

B) roughening is corroded: immersed after surface dressing by step a) resulting product matrix in the group water solution of sodium chloride-containing 5.0-100.0g/L, hydrogenchloride 0-50.0g/L, carry out corrosion treatment, realize carrying out surface roughening object to article substrate;

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

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

E) apply: comprise following key step:

E-1) preparation of solution:

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

2# solution: for magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP(bata-tricalcium phosphate), calcium polyphosphate or wherein two or more mixture for solid dispersed phase, with water, acetone, ethanol, propyl carbinol or the wherein two or more mixture suspension that is liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;

3# solution: for magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, calcium polyphosphate or wherein two or more mixture for solid dispersed phase, with the suspension that the organic solvent based sols of PLLA, PLGA or its mixture is liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture total mass;

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

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

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

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

2. the preparation method of Biological medical absorbable material according to claim 1, is characterized in that: the SODIUMNITRATE of sodium-chlor described in step b), sodium sulfate, lithium chloride, lithium nitrate, Lithium Sulphate, Repone K, saltpetre, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, magnesium sulfate or wherein two or more mixture partly or entirely replace; The nitric acid of hydrogenchloride described in step b), sulfuric acid, acetic acid, citric acid or wherein two or more mixture partly or entirely replace; The magnesium nitrate of magnesium chloride described in step c), magnesium sulfate or its mixture partly or entirely replace.

3. the preparation method of Biological medical absorbable material according to claim 1, it is characterized in that: step e-1) described in the organic solvent of 1# solution and 3# solution be one in A solvent and B solvent, wherein A solvent is more than one in epoxy chloropropane, methylene dichloride or chloroform, and B solvent is the mixture obtained after more than one Homogeneous phase mixing in A solvent and acetone, ethanol or propyl carbinol; Step e-1) described in pure Magnesium and magnesium alloys in 2# solution and 3# solution be Powdered, particulate state, sheet, thread, banded, tubulose or crystal whisker-shaped, and its open circuit potential in any equivalent environment medium not higher than article substrate in the open circuit potential of pure magnesium or magnesium alloy.

4. the preparation method of Biological medical absorbable material according to claim 1, is characterized in that: step e-1) described in 1# solution molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA mixture replace; Step e-1) described in 3# solution in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, calcium polyphosphate or wherein two or more mixture be solid dispersed phase, replace with the suspension that the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is liquid, the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture total mass.

5. the preparation method of Biological medical absorbable material according to claim 1, is characterized in that: step e-2) in the one 3# solution replacement of 1# solution described in scheme one and 2# solution; Step e-2) described in coating method comprise dip-coating, brushing, spin coating or spraying.

6. the preparation method of Biological medical absorbable material according to claim 1, it is characterized in that: after coating is containing the coating of PLLA or PLGA, carry out spontaneous curing or artificial solidification treatment, until this coating layer portion or after solidifying completely, then carry out the coating of follow-up coating; When coating magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, calcium polyphosphate or wherein after two or more mixture, carry out drying treatment.

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

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

9. Biological medical absorbable material according to claim 7, it is characterized in that: the pure Magnesium and magnesium alloys in described No.1 coating and No.2 coating is Powdered, particulate state, sheet, thread, banded, tubulose or crystal whisker-shaped, 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.