CN104195369A - Zn-Ca series zinc alloy as well as preparation method and application of Zn-Ca series zinc alloy - Google Patents
Zn-Ca series zinc alloy as well as preparation method and application of Zn-Ca series zinc alloy Download PDFInfo
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Abstract
The invention discloses a Zn-Ca series zinc alloy as well as a preparation method and application of the Zn-Ca series zinc alloy. The zinc alloy comprises Zn and Ca, wherein the mass percent of Ca in the zinc alloy ranges from 0% to 30%, but is not equal to 0. The zinc alloy also comprises trace elements including Si, P, Li, Ag, Sn and at least one selected from rare earth elements, wherein the mass percent of the trace elements ranges from 0% to 3%, but is not equal to 0. The mechanical property of the Zn-Ca series zinc alloy disclosed by the invention meets the requirements for strength and toughness of a medical implant material, is nontoxic and favorable in tissue compatibility and blood compatibility, can be degraded by using body fluid and can be applied to preparation of medical implants; and the dissolved metal ions can be absorbed and utilized by living bodies to promote bone growth or can be discharged out of bodies through metabolism.
Description
Technical field
The present invention relates to a kind of Zn-Ca is zinc alloy and preparation method thereof and application, is specifically related to a kind of Zn-Ca and is zinc alloy and preparation method thereof and application in preparation can degraded by body fluid medical implant, belongs to medical metal material preparing technical field.
Background technology
At present for clinical bio-medical material, mainly contain biomedical metallic material, inorganic materials, macromolecular material, matrix material and biomimetic material etc.Medical metal material is compared with stupalith with macromolecular material, has higher intensity, toughness and processing characteristics, is therefore most widely used.As: 316L, 317L, 304V stainless steel, Co-Cr-Mo alloy, pure titanium, Ti-6Al-4V, TiNi alloy etc.These materials non-degradable in human body, for permanent implanted, after implant the completing the term of service in human body, must take out by second operation, thereby bring unnecessary physiology misery and economical load to patient.
Development along with medical science and Materials science, for some, need interim material of being on active service, as suture line, bone fracture fixation plate, intravascular stent, biliary tract rack etc., people wish that the material implanting just plays temporary transient alternative effect, and degraded and absorbed along with tissue or the regeneration of organ and gradually, with maximum limit reduce the long-term effect of material to body.Because Biodegradable material is easily degraded with medium interactions such as body fluid in vivo gradually, its degradation production can metabolism, and finally excrete, without second operation, take out, thereby be more and more subject to people's attention, become forward position and the study hotspot of current international bio Material Field.
Clinical conventional Biodegradable material is mainly biodegradable polymer and biodegradable ceramic at present.Though biodegradable polymer can be absorbed by the body completely, intensity is low, is difficult to provide the function of support structure; The shortcoming of biodegradable ceramic is poor toughness, cannot compatible deformation.
In recent years, degradable biological medical magnesium alloy material becomes one of study hotspot, developed a series of biological medical degradable magnesium alloy, as AZ31, WE43, Mg-Ca etc., although magnesium alloy has tempting application prospect as biomaterial, yet research finds that magnesium alloy exists corrosion speed too fast, before histoorgan does not fully heal, implant just can be lost its mechanical integrity very soon, thereby is necessary that development of new degradable alloy has met clinical demand.
Identical with magnesium and magnesium alloy, metallic zinc and alloy thereof are usually used as because chemical property is active, be easy to corrosion the anode material being sacrificed in corrosion protection.But compare with magnesium, metallic zinc and alloy thereof have higher corrosion potential, thereby compare magnesium alloy metallic zinc and alloy corrosion speed slows down, thereby more meet clinical demand, be expected to develop into new bio medical degradable embedded material and device.
Human normal zinc content is 2-3 gram.Zinc is the main component of tens of kinds of enzymes in body.During zinc is distributed in most organs and organizes, wherein liver, muscle and bone content are higher.Though zinc is trace element in human body, acts on very big.The title that has " spark of life plug ".(1) zinc is relevant with various ground substance of bone synthetic enzyme, and it can participate in bone forming and bone is rebuild.When zn deficiencie, in bone, the activity of multiple zinc enzyme declines, and the growth of bone is suppressed; (2) zinc is biomembranous key components, and it has vital role in the structure and function that maintains more than 2000 kind of transcription factor and 300 plurality of enzymes; (3) zinc can enter rapidly endotheliocyte, maintains the integrity of endotheliocyte, reduces blood vessel to atherosclerotic susceptibility; (4) zinc can be protected the Inflammatory response that myocardial cell avoids acute oxidative stress and myocardial damage to cause; (5) it is synthetic that zinc can play an active part in nucleic acid-protein, accelerated wound healing; (6) in addition, zinc also with body in various cellular metabolism effects closely related, as carbohydrate metabolism, lipid metabolism and anti-ageing waiting for a long time.Zn deficiencie can cause that arteriosclerosis, heart disorder and exhaustion, brain function deformity, hypoimmunity, diarrhea, poor appetite, growth slow down, hair loss, yctalopia, prostatomegaly, male reproductive function go down, anaemia etc.Adult often supplements 15-25mg zinc day by day.
Calcium is a kind of essential element, is also the highest metallic element of content in human body.In normal situation, become calcium contents in human body to be about 1000-1250g, wherein approximately 99% is present in bone and tooth, and mainly the form with hydroxyapatite crystal exists, and maintains bone and tooth and has hard structure and support.Approximately 1% calcium is often present in the outer liquid of soft tissue cells and blood with ionic condition that dissociate or combination in addition, is miscible calcium pool.Calcium in miscible calcium pool and bone is maintaining running balance, and the calcium in bone constantly discharges and enters miscible calcium pool from osteoclast, guarantees that plasma calcium concentration remains constant; And calcium in miscible calcium pool is constantly deposited in bone, thereby make the calcium in bone constantly be supplemented renewal, be bone and upgrade.Calcium plays an important role in the various physiology and chemistry processes of body.(1) maintain the normal physiological state of cell.Intracellular calcium ion is that cell is to stimulating aitiogenic medium.The common many important physiological functions of body that regulate such as calcium and acceptor calcium, comprise skeletal muscle and myocardium contraction, the maintaining of unstriated muscle and nonmuscle cells activity and nervous excitation.Calcium ion plays an important role to nerve, the excitement of muscle and the conduction of nerve impulse.During calcium deficiency, human body there will be the symptoms such as nerve block and dystonia.Calcium ion plays an important role to maintaining of the adhesion of cell, cell membrane function.Cytolemma is the barrier of entocyte, especially various must nutritive substance and oxygen enter the carrier of cell.The calcium ion of normal contents can guarantee cytolemma successfully nutritive substance " pump " in cell.(2) reduce the permeability of capillary vessel and cytolemma, prevent from oozing out, control inflammation and oedema; (3) participate in blood clotting process, factor V I is Ca
2+, during calcium deficiency, blood clotting generation obstacle, human body there will be the symptoms such as gingival hemorrhage, subcutaneous hemorrhage point, irregular uterine hemorrhage, menorrhagia, hematuria, spitting blood; (4) participate in the activation of many enzyme systems (as: ATP enzyme, succsinic acid desaminase, lipase and protease etc.) in body; (5) to participating in the macromole enzyme synthetic, that change of cellular metabolism, there is regulating effect; (6) calcium ion has decisive role to the secretion of human endocrine glandular hormone, most important to maintaining the function of the system organs such as circulation, breathing, digestion, uropoiesis, nerve, internal secretion, reproduction.(7) maintain the functions such as body fluid acid base equilibrium.The illnesss such as calcium deficiency can cause osteoporosis, and richets is neural lax, twitches, and clotting mechanism is poor, waist and leg ache.Adult's daily requirement supplements 600-1000mg calcium.
Also do not have at present document and patent report Zn-Ca to be associated the synthetic and performance of gold both at home and abroad, and propose Zn-Ca to be associated gold as degradable biological medical materials'use.
Summary of the invention
The object of this invention is to provide a kind of Zn-Ca is zinc alloy and preparation method thereof and application, is specifically related to a kind of Zn-Ca and is zinc alloy and preparation method thereof and application in preparation can degraded by body fluid medical implant.Zinc alloy mechanical property prepared by the present invention is excellent, and permanently effective anchorage force can be provided in vivo, has excellent cell compatibility, blood compatibility and tissue, organ consistency, can be used for the preparation that bio-medical is implanted.
Zn-Ca provided by the invention is zinc alloy, comprises Zn and Ca;
By weight percentage, in described zinc alloy, the mass percent of Ca is 0～30%, but does not comprise 0.
In above-mentioned zinc alloy, also comprise trace element, described trace element is at least one in silicon, phosphorus, lithium, silver, tin and rare earth element;
In described zinc alloy, the quality percentage composition of described trace element is 0～3%, but does not comprise 0.
The surface of above-mentioned zinc alloy also can be coated with degradable macromolecule coating, ceramic coating or medication coat;
The thickness of described degradable macromolecule coating, described ceramic coating and described medication coat all can be 0.01～5mm.
The material of preparing of described degradable macromolecule coating can be following 1) and 2) at least one:
1) in polycaprolactone (PCL), poly(lactic acid) (PLA), polyglycolic acid (PGA), PLLA (PLLA), polybutylcyanoacrylate (PACA), poly-acid anhydrides, poly phosphazene, poly-para-dioxane ketone, poly--butyric ester and poly-hydroxyl valerate any;
2) any two or more the multipolymer in poly(lactic acid) (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), PLLA (PLLA), polybutylcyanoacrylate (PACA) and poly-para-dioxane ketone;
The material of preparing of described ceramic coating can be at least one in hydroxyapatite, tricalcium phosphate or phosphoric acid oxygen four calcium;
Described medication coat can be at least one in rapamycin and derivative coating, taxol coating, everolimus coating, sirolimus coating, mitomycin coating and antimicrobial coating.
Zn-Ca provided by the invention is that zinc alloy is specially following 1)-5) in any, be weight percentage:
1) by 95～99% Zn and 1%～5% Ca, formed;
2) by 99% Zn and 1% Ca, formed;
3) by 95% Zn and 5% Ca, formed;
4) by 98.5% Zn, 1% Ca and 0.5% Li, formed;
5) by 98.5% Zn, 1% Ca and 0.5% Y, formed.
Zn-Ca prepared by the present invention is that zinc alloy is dense structure or vesicular structure, possesses good histocompatibility, is a kind of reliable biological and medicinal implant material.
The preparation method who the present invention further provides above-mentioned zinc alloy, comprises the steps:
By described Zn, described Ca and described trace element according to following 1) and 2) in any mode be mixed to get mixture;
1) Zn and Ca;
2) Zn, Ca and trace element;
According to following a) or b) step obtain described zinc alloy;
A) at CO
2and SF
6under atmosphere protection, described mixture is carried out to melting, after cooling, obtain described zinc alloy;
B) at CO
2and SF
6under atmosphere protection, described mixture is carried out to melting, after cooling, apply described degradable macromolecule coating, described ceramic coating or described medication coat and obtain described zinc alloy.
In aforesaid method, the temperature of described melting can be 700～850 ℃, specifically can be 800 ℃.
Aforesaid method also comprises the step of described zinc alloy being carried out to mechanical workout;
Described mechanical workout can be at least one in rolling, forging, rapid solidification and extruding.
Described rolling comprises carries out hot rolling and finish rolling successively, and described hot rolling can be carried out at 200～300 ℃, and described finish rolling can be carried out at 150～250 ℃, and the thickness after described zinc alloy rolling can be 1～2mm; Described hot rolling specifically can be carried out at 250 ℃, and described finish rolling specifically can be carried out at 250 ℃, and the thickness after described zinc alloy rolling specifically can be 1.5mm.
Described forging comprises the step that described zinc alloy is incubated and is forged under the condition of 200～300 ℃ under the condition of 150～200 ℃, and the time of described insulation is 3～50 hours, and the speed of described forging is not less than 350mm/s.
The temperature of described extruding can be 150～250 ℃, specifically can be 200; Extrusion ratio can be 10～70, specifically can be 20.
Described rapid solidification comprises the steps: under Ar gas protection, adopts high vacuum fast quenching system to prepare rapid coagulation band, then described strip is broken into Powdered, last under the condition of 200～350 ℃, vacuum hotpressing 1～24h.
Arranging of described high vacuum fast quenching system is as follows: feeding quantity 2～8g, induction heating power are that 3～7kW, nozzle and roller spacing are that 0.80mm, spraying pressure are that 0.05～0.2MPa, roller speed are that 500～3000r/min and nozzle slot are of a size of 1film * 8mm * 6mm.
The present invention also provides a kind of preparation method of zinc alloy, comprises the steps: described Zn, described Ca and described trace element according to following 1) and 2) in any mode be mixed to get mixture;
1) Zn and Ca;
2) Zn, Ca and trace element;
According to following a) or b) step obtain described zinc alloy;
A) at CO
2and SF
6under atmosphere protection, described mixture is carried out to sintering, after cooling, obtain described zinc alloy;
B) at CO
2and SF
6under atmosphere protection, described mixture is carried out to sintering, after cooling, apply described degradable macromolecule coating, described ceramic coating or described medication coat and obtain described zinc alloy;
Describedly be sintered to following any method: element powders mixed-sintering method, prealloy powder sintering process and self propagating high temperature synthesis method.
Described element powders mixed-sintering method is that the described vesicular structure Zn-Ca for preparing is associated to golden raw material and mixes, be pressed into base, then in vacuum sintering furnace, after being warming up at a slow speed 100～200 ℃ with 2～4 ℃/min, then with 30 ℃/min, be rapidly heated to 200～300 ℃ of sintering, then cooling, the Zn-Ca that obtains into vesicular structure is associated gold;
Described prealloy powder sintering process is that carried out to high-energy ball milling described preparation after vesicular structure Zn-Ca is associated golden raw material mixing, and then compression moulding, heat-treats 10～20 hours at 250～350 ℃, and the Zn-Ca that obtains vesicular structure is associated gold;
Described self propagating high temperature synthesis method is to be pressed into base by preparing after vesicular structure Zn-Ca is associated golden raw material mixing, and under protection of inert gas, pressure is 1 * 10
3～1 * 10
5pa, temperature is at 250～350 ℃, by Zn-Ca, is then that alloy billet lights that to carry out self propagating high temperature synthetic, the Zn-Ca that obtains vesicular structure is associated gold.
For adapting to different clinical demands, above-mentioned two kinds of methods of preparing zinc alloy also comprise the step of applying coating.
The method of described coating Biodegradable high-molecular coating is that described zinc alloy is carried out to pickling, then by its described biodegradable polymer coating prepare material be dissolved in colloid prepared by trichloroethane in dip-coating after 10～30 minutes, at the uniform velocity pull out and carry out the zinc alloy that centrifugal treating obtains being coated with Biodegradable high-molecular coating;
The method of described coated ceramic coating can be in plasma spraying, electrophoretic deposition, anodic oxidation and Hydrothermal Synthesis any;
The described plasma spraying main gas of plasma gas used is Ar, and flow is 30～100scfh, and plasma gas time gas is H
2, flow is 5～20scfh, and spraying current is 400～800A, and spray voltage is 40～80V, and spray distance is 100～500mm;
The method of described galvanic deposit degradable ceramic coating is for take zinc alloy as negative electrode is in the electrolytic solution of calcic, microcosmic salt, and current density is 2～10mA/cm
2, to process after 10～60min, cleaning-drying obtains described zinc alloy;
The method of described anodic oxidation and Hydrothermal Synthesis combination for by described zinc alloy in the electrolytic solution that contains 0.01～0.5mol/L sodium β-glycerophosphate and 0.1～2mol/L calcium acetate, under 200～500V, be oxidized 10～30min, then described zinc alloy processed to 1～4h at 200～400 ℃.
The method of described coated medicament coating is physics and chemistry method;
Described physical method coating process mainly adopts immersion, spraying method; Described chemical process mainly uses electrochemical principle to electroplate;
Described immersion process is for to be mixed with solution by active medicine and controlled release carrier (or independent active medicine), concrete concentration can be different with required drug dose because of soltion viscosity, then described medical implant is soaked in solution, then pass through necessary last handling process, as steps such as being cross-linked, being dried, solidifying, make medication coat;
Described spraying method is for to be mixed with solution by active medicine and controlled release carrier (or independent active medicine), then by sprinkling instrument or special spraying equipment, solution is evenly coated to described medical embedded surface, drying, make medication coat after the post-processing step such as solidifying;
Described chemical process is to utilize active medicine and (or) controlled release carrier that electrooxidation reduction reaction occurs on the electrode by described medical embedded making, makes described medical embedded surface form the stable medication coat being connected by chemical bond.
The present invention utilizes Zn and Zn alloy to be easy to the feature of corrosion, has selected Zn-Ca to be associated gold and has been applied to medical implant as degradation property material.Zn-Ca of the present invention is associated the requirement that golden mechanical property meets intensity and the toughness of medical implant material, simultaneously again can vivo degradation, can overcome the nondegradable weakness of conventional medical metallic substance such as the low and 316L stainless steel of medical macromolecular materials intensity, titanium or titanium alloy, can overcome again the defect that the too fast mechanical property that causes implanting of magnesium and magnesium alloy degradation rate is lost, accomplish with " can biological corrosion degradation characteristic " and " suitable erosion rate guarantees the mechanics support that provides permanently effective " dual nature.
Zn-Ca provided by the invention is that zinc alloy can be used for being prepared as follows medical implant: for treatment, implant frame, bone are repaired apparatus, gear division is repaired apparatus;
Described treatment can be intravascular stent, esophageal stents appear, enteron aisle support, trachea bracket, biliary tract rack or urethra rack with implant frame;
Described bone is repaired apparatus and be can be bone tissue restoration support, bone fracture device, static line, retaining screw, fixing rivet, locking pin, splenial bone plate, intramedullary needle or synthetism cover;
Described gear division is repaired apparatus and be can be dental pulp pin or tooth compaction material.
Tool of the present invention has the following advantages:
(1) Zn-Ca that prepared by the present invention is associated the requirement that golden mechanical property meets intensity and the toughness of medical implant material, simultaneously again can vivo degradation, there is " can biological corrosion degradation characteristic " and " suitable erosion rate guarantees the mechanics support that provides permanently effective " dual nature.
(2) when Zn-Ca of the present invention is associated gold for degradable medical implant, implanting the high strength feature that can bring into play its metallic substance in for some time, complete the function (as induction new bone tissue forms or support narrow blood vessel) of implant, can when carrying out self repairing, human lesion position by human body corrosion, be degraded gradually as " allosome " again, quantity and volume reduce gradually, the metal ion of stripping can be absorbed promotion osteogenesis by organism or metabolism eliminating is external, the finally degradable disappearance of metallic substance implant when human body finishes self to repair.
(3) medical implant that can degraded by body fluid provided by the invention is nontoxic, possesses good histocompatibility and blood compatibility.
Accompanying drawing explanation
Fig. 1 is the photo of the Zn-Ca alloy cast ingot of embodiment 1 preparation.
Fig. 2 is the photo of the Zn-Ca sheet alloy of embodiment 2 preparations.
Fig. 3 is the photo of the Zn-Ca alloy bar material of embodiment 3 preparations.
Fig. 4 is associated the photo of golden tension specimen for the Zn-Ca for preparing according to testing standard.
Fig. 5 is the stress strain curve of Zn-Ca-Li alloy.
Fig. 6 is that Zn-Ca alloy soaks SEM photo (a) low power under different amplification after 2 weeks in simulated body fluid; (b) high power.
Fig. 7 is the galvanic corrosion curve of Zn-Ca alloy in simulated body fluid.
Fig. 8 is Zn-Ca alloy platelet adhesion reaction SEM photo.
Fig. 9 is light microscopic photo (a) control group of Zn-Ca alloy to cytosis; (b) Zn-Ca alloy.
Figure 10 is the cell relative proliferation rate (* p<0.05, * * p<0.01) of Zn-Ca alloy after to cytosis different time.
Figure 11 is X-ray and the corresponding contrast figure that Zn-Ca alloy is implanted different time in Mice Body.
Figure 12 is mico-CT figure and the contrast figure that Zn-Ca alloy is implanted different time in Mice Body.
Figure 13 is that Zn-Ca alloy is implanted the histology fluorescent dye photo after 2 months in Mice Body.
Embodiment
The experimental technique using in following embodiment if no special instructions, is ordinary method.
In following embodiment, material used, reagent etc., if no special instructions, all can obtain from commercial channels.
Percentage composition used in following embodiment, if no special instructions, is quality percentage composition.
Embodiment 1, preparation as cast condition Zn-Ca are associated gold
Using pure Zn (99.99wt.%), pure Ca (99.95wt.%) (purchased from Beijing Chinese incense cedar woods non-ferrous metal technology development center) as raw material, by different mass ratio (Zn is respectively 99:1 and 95:5 with the mass ratio of Ca), mix, at CO
2+ SF
6under atmosphere protection, 800 ℃ of meltings, after raw material fully melts; after insulation 10min, recirculated water is cooling fast, makes Zn-Ca and is associated ingot (photo as shown in Figure 1); wherein, Zn-1Ca represents that the mass ratio of Zn and Ca is 99:1, and Zn-5Ca represents that the mass ratio of Zn and Ca is 95:5.
Embodiment 2, preparation are rolled state Zn-Ca and are associated gold
First the Zn-Ca for preparing as cast condition according to the step in embodiment 1 is associated ingot; Then the above-mentioned Zn-Ca of obtaining is associated to ingot and carries out hot rolling, first preheating ingot casting at 250 ℃, then adopts hot rolling mode, repeat-rolling in reciprocation type milling train, and hot-rolled temperature, at 250 ℃, finally, in finishing mill, is rolled down to 1.5mm at 250 ℃.
Fig. 2 be the present embodiment obtain roll the photo that state Zn-Ca is associated gold (Zn-1Ca).
Embodiment 3, prepare As-extruded Zn-Ca and be associated gold
According to following 1) or 2) step be prepared:
1) Zn-Ca that first prepares as cast condition according to the step in embodiment 1 is associated ingot (Zn-1Ca), adopting the mode of pushing to prepare Zn-Ca is alloy bar material (Zn-1Ca), adopt radial extrusion, extrusion temperature is 200 ℃, extrusion ratio is 20, and the Zn-Ca for preparing diameter and be 10mm is alloy bar material (Zn-1Ca).
2) Zn-Ca that first prepares as cast condition according to the step in embodiment 1 is alloy cast ingot, adopt high vacuum fast quenching system to prepare rapid solidification Zn-Ca alloy thin band, concrete grammar is: after raw material is mixed in described ratio, adopting high vacuum fast quenching system to prepare rapid solidification Zn-Ca is strip, and parameter is feeding quantity 2～8g, induction heating power 3～7kW, nozzle and roller spacing 0.80mm, spraying pressure 0.1MPa, roller speed 2000r/mln and nozzle slot size 1film * 8mm * 6mm.Then after strip being pulverized, be pressed into base, hot pressing condition is 200～350 ℃, vacuum hotpressing 1～24h.Adopting the mode of extruding to prepare Zn-Ca is alloy bar material, adopts radial extrusion, and extrusion temperature is 200 ℃, and extrusion ratio is 20, and the Zn-Ca for preparing diameter and be 10mm is alloy bar material (Zn-1Ca) (photo as shown in Figure 3).
Embodiment 4, Zn-Ca are associated golden Mechanics Performance Testing
The Zn-Ca preparing according to the method for embodiment 1-3 is associated to gold, respectively according to ASTM-E8-04 Elongation test standard system for stretching sample (as shown in Figure 4), successively through 400#, 800#, 1200# and 2000#SiC sand paper series sanding and polishing.In acetone, dehydrated alcohol and deionized water, after difference ultrasonic cleaning 15min, adopt universal material mechanical test machine at room temperature to carry out tension test, draw speed is 1mm/min.
Fig. 5 is that Zn-Ca prepared by the present invention is associated gold (as cast condition Zn-1Ca-0.5Li, it is identical that its preparation method and as cast condition Zn-Ca in embodiment 1 are associated golden preparation method, wherein the mass ratio of Zn, Ca and Li is 98.5:1:0.5) stress strain curve, as known in the figure, the tensile strength of as cast condition Zn-1Ca-0.5Li alloy is 168.37MPa, yield strength is 95.85MPa, and unit elongation is 1.372%.
Zn-Ca is associated that the room temperature tensile performance of each sample of gold is as shown in table 1, and wherein, to be associated golden preparation method identical with rolling state Zn-Ca in embodiment 2 for the preparation method of Zn-1Ca-0.5Y, and the mass ratio of Zn, Ca and Y is 98.5:1:0.5.As shown in Table 1, with the increase of Ca content, alloy becomes fragile, and intensity and unit elongation obviously decline.With respect to cast alloy, yield strength and the tensile strength of rolling state alloy and As-extruded alloy are all significantly improved, and meanwhile, unit elongation is increased considerably, and show that material mechanical property after deformation processing process is further optimized.
Table 1.Zn-Ca alloy Tensile Test Results
| Specimen coding | Tensile strength/MPa | Yield strength/MPa | Unit elongation/% |
| Zn-1Ca ingot casting | 162.42 | 122.35 | 1.835 |
| Zn-5Ca ingot casting | 60.35 | 43.26 | 0.463 |
| Zn-1Ca-0.5Y rolls plate | 172.83 | 128.47 | 1.407 |
| Zn-1Ca rolls plate | 264.13 | 210.42 | 13.727 |
| Zn-1Ca bar | 254.53 | 200.27 | 7.404 |
Embodiment 5, the test of Zn-Ca alloy corrosion performance
By in embodiment 2 through the Zn-Ca of rolling alloy, by line, cut preparation 10 * 10 * 1.5mm Zn-Ca alloy sample sheet, successively through 400#, 800#, 1200# and 2000#SiC sand paper series sanding and polishing.In acetone, dehydrated alcohol and deionized water respectively after ultrasonic cleaning 15min, dry at 25 ℃.Be immersed in afterwards Hank ' s simulated body fluid (NaCl 8.0g, CaCl
20.14g, KCl 0.4g, NaHCO
30.35g, glucose 1.0g, MgCl
26H
2o 0.1g, Na
2hPO
42H
2o 0.06g, KH
2pO
40.06g, MgSO
47H
2o 0.06g is dissolved in 1L deionized water) in, after soaking different time interval, take out, observe sample surfaces, Fig. 6 is that Zn-Ca alloy (Zn-1Ca) soaks the stereoscan photograph under different amplification after two weeks in Hank ' s simulated body fluid, (a) being low power, is (b) high power.Result shows that Zn-Ca alloy surface keeps complete and deposition great amount of hydroxy group apatite mineral, shows that Zn-Ca alloy can induce the deposition of bone mineral in degraded, thereby can promote in vivo the reparation of osseous tissue.
Fig. 7 is the galvanic corrosion polarization curve of Zn-Ca alloy (Zn-1Ca) in Hank ' s solution, from Fig. 7, can obtain, and the erosion rate of Zn-1Ca alloy is 0.16mm/.
Embodiment 6, the test of Zn-Ca alloy blood compatibility
Embodiment 2, through the Zn-Ca of rolling alloy, is cut to preparation 10 * 10 * 1.5mm Zn-Ca alloy sample sheet by line, through 400#, 800#, 1200# and 2000#SiC sand paper series sanding and polishing.In acetone, dehydrated alcohol and deionized water respectively after ultrasonic cleaning 15min, dry at 25 ℃.Gather healthy volunteer's fresh blood with it, be placed in and include 3.8wt.% Trisodium Citrate as the anticoagulant tube preservation of antithrombotics.With 0.9% physiological saline, by the dilution proportion of 4:5, make dilute blood sample.Sample is immersed in to 10mL physiological saline, and 37 ± 0.5 ℃ of insulation 30min, add 0.2mL dilute blood sample, 37 ± 0.5 ℃ of insulation 60min.Adopt 10mL physiological saline as negative control group, 10mL deionized water is as positive controls.Through 3000rpm centrifugal 5 minutes, get supernatant liquor and measure absorbancy OD value with Unic-7200 ultraviolet-visible pectrophotometer 545nm, three groups of Duplicate Samples are set to carry out statistical analysis.
With following formula, calculate hemolysis rate:
Hemolysis rate=(experimental group OD value-feminine gender group OD value)/(positive group OD value-feminine gender group OD value) * 100%.
After whole blood gathers, 1000rpm is centrifugal, and 10min prepares platelet rich plasma.Platelet rich plasma is dripped in specimen surface to 37 ± 0.5 ℃ of insulation 60min, every group of 3 Duplicate Samples.Take out sample, PBS damping fluid (pH value is 7.2) rinses and to remove, does not stick thrombocyte 3 times.Fix blood platelet method is: every hole adds the glutaraldehyde stationary liquid that 500 μ L concentration are 2.5%, under room temperature, fix 60 minutes, then by stationary liquid sucking-off, use PBS to clean 3 times, working concentration is 50%, 60%, 70%, 80%, 90%, 95%, 100% alcohol carries out gradient dehydration, each concentration gradient dehydration 10 minutes, after vacuum-drying, use scanning electronic microscope (S-4800, Hitachi, Japan) observe platelet adhesion reaction quantity and form, each sample is random selects 6 regions to carry out platelet count and statistical analysis.
Experimental result shows, the hemolysis rate of Zn-Ca alloy (Zn-1Ca) is 0.3%, is far smaller than the secure threshold 5% of clinical service requirements, shows good red corpuscle and oxyphorase consistency.
Fig. 8 is the thrombocyte pattern photo of Zn-Ca alloy (Zn-1Ca) surface adhesion, and as can be seen from the figure, the platelet counts that Zn-Ca alloy surface adheres to is rare, and be smooth spherical shape, do not have tail to flicker and stretch out with pseudopodium, be not activated, show excellent anticoagulation function.
Embodiment 7, preparation and cell compatibility experiment thereof that can the medical Zn-Ca implant of degraded by body fluid
By the method for embodiment 1-3, prepare Zn-Ca alloy, by 6 pieces of length and widths, thickness be respectively 10,10, the Zn-Ca alloy block (Zn-1Ca of the above-mentioned preparation of 1.5mm, as cast condition and roll state) through gamma-rays sterilization, be placed in sterile culture flask, by specimen surface, amassing with the ratio of MEM cell culture medium volume is 125cm
2the ratio of/mL adds MEM cell culture medium, is placed in 37 ℃, 95% relative humidity, 5%CO
272h in incubator, obtains Zn-Ca alloy vat liquor stoste, sealing, and 4 ℃ of Refrigerator stores are standby.
Vat liquor and cell inoculation culture and result are observed: after MG63 cell (Ji Niou bio tech ltd, Guangzhou) is recovered, gone down to posterity, be suspended in MEM cell culture medium, be inoculated on 96 well culture plates, negative control group adds MEM cell culture medium, Zn-Ca alloy vat liquor stoste group adds Zn-Ca alloy vat liquor stoste obtained above, and making final cell concentration is 5 * 10
4/ mL.Be placed in 37 ℃, 5%CO
2in incubator, cultivate, after 5 days, take out culture plate, under inverted phase contrast microscope, observe the form (as shown in Figure 9) of viable cell.Result shows: compare with negative control group, cell quantity is in the same order of magnitude, and pattern is rendered as the healthy fusiformis stretching and converges growth, illustrates that Zn-Ca alloy has excellent cell compatibility.
To be MG63 osteocyte be associated and in gold (Zn-1Ca) vat liquor, cultivate the relative proliferation rate experimental result of cell after different time at Zn-Ca Figure 10, as can be seen from Figure 10, add calcium constituent can effectively improve the proliferation activity of osteocyte, promote osteocyte propagation.
Embodiment 8, preparation and experimentation on animals thereof that can the medical Zn-Ca implant of degraded by body fluid
By machined into Zn-Ca alloy intramedullary needle, the intramedullary needle dimensional parameters of preparation is: length: 5mm; Diameter: 1mm.Get the Zn-Ca alloy that aforesaid method makes and implant 10 of intramedullary needles, implant respectively in 10 mouse femurs.Postoperative one week, two weeks, three weeks, surrounding, after six weeks and eight weeks, carry out X-ray observation (Figure 11), micro-CT observes (Figure 12) and tissue slice Fluirescence observation (Figure 13), result shows, latter one week of operation, two weeks, surrounding and eight weeks, 10 mouse all do not find that implant causes the foreign body reactions such as surrounding tissue inflammation, intramedullary needle keeps intact form, implant after two weeks, observe implant freshman bone tissue's (shown in arrow) around, and freshman bone tissue's thickness is greater than control group around implant, show that Zn-Ca alloy medical implant can promote the generation of osseous tissue, shorten the trauma repair times such as fracture.
Claims (10)
1. Zn-Ca is a zinc alloy, it is characterized in that: described zinc alloy comprises Zn and Ca;
By weight percentage, in described zinc alloy, the mass percent of Ca is 0～30%, but does not comprise 0.
2. zinc alloy according to claim 1, is characterized in that: in described zinc alloy, also comprise that trace element, described trace element are at least one in silicon, phosphorus, lithium, silver, tin and rare earth element;
In described zinc alloy, the quality percentage composition of described trace element is 0～3%, but does not comprise 0.
3. zinc alloy according to claim 1 and 2, is characterized in that: the surface-coated of described zinc alloy has degradable macromolecule coating, ceramic coating or medication coat;
The thickness of described degradable macromolecule coating, described ceramic coating and described medication coat is 0.01～5mm.
4. a preparation method for zinc alloy described in any one in claim 1-3, comprises the steps: described Zn, described Ca and described trace element according to following 1) and 2) in any mode be mixed to get mixture;
1) Zn and Ca;
2) Zn, Ca and trace element;
According to following a) or b) step obtain described zinc alloy;
A) at CO
2and SF
6under atmosphere protection, described mixture is carried out to melting, after cooling, obtain described zinc alloy;
B) at CO
2and SF
6under atmosphere protection, described mixture is carried out to melting, after cooling, apply described degradable macromolecule coating, described ceramic coating or described medication coat and obtain described zinc alloy;
The temperature of described melting is 700～850 ℃.
5. the preparation method of zinc alloy according to claim 4, is characterized in that: described method also comprises the step of described zinc alloy being carried out to mechanical workout;
Described mechanical workout is at least one in rolling, forging, rapid solidification and extruding.
6. the preparation method of zinc alloy according to claim 5, is characterized in that:
Described rolling comprises carries out hot rolling and finish rolling successively, and described hot rolling is carried out at 200～300 ℃, and described finish rolling is carried out at 150～250 ℃, and described zinc alloy is rolled 1～3mm;
Described forging comprises the step that described zinc alloy is incubated and is forged under the condition of 200～300 ℃ under the condition of 150～200 ℃, and the time of described insulation is 3～50 hours, and the speed of described forging is not less than 350mm/s;
The temperature of described extruding is 150～250 ℃, and extrusion ratio is 10～70;
Described rapid solidification comprises the steps: under Ar gas protection, adopts high vacuum fast quenching system to prepare rapid coagulation band, then described strip is broken into Powdered, last under the condition of 200～350 ℃, vacuum hotpressing 1～24h.
7. a preparation method for zinc alloy described in any one in claim 1-3, comprises the steps: described Zn, described Ca and described trace element according to following 1) and 2) in any mode be mixed to get mixture;
1) Zn and Ca;
2) Zn, Ca and trace element;
According to following a) or b) step obtain described zinc alloy;
A) at CO
2and SF
6under atmosphere protection, described mixture is carried out to sintering, after cooling, obtain described zinc alloy;
B) at CO
2and SF
6under atmosphere protection, described mixture is carried out to sintering, after cooling, apply described degradable macromolecule coating, described ceramic coating or described medication coat and obtain described zinc alloy;
Describedly be sintered to following any method: element powders mixed-sintering method, prealloy powder sintering process and self propagating high temperature synthesis method.
8. the application of zinc alloy in preparation can degraded by body fluid medical implant described in any one in claim 1-3.
9. application according to claim 8, is characterized in that: described application shows as following 1)-4) in any:
1) described zinc alloy promotes the reparation of osseous tissue;
2) anticoagulation function of described zinc alloy;
3) cell compatibility of described zinc alloy;
4) described zinc alloy promotes the generation of osseous tissue.
10. can a degraded by body fluid medical implant, its in claim 1-3 described in any one zinc alloy prepare.
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