AU2020104227A4 - Zinc-Calcium alloy series and preparation method and application thereof - Google Patents

Abstract

The invention discloses a Zinc-Calcium (Zn-Ca) alloy series and a preparation method and an application thereof. The zinc alloy of the invention comprises Zinc and Calcium, wherein the mass percentage of Calcium in the zinc alloy is 0-30% in percentage by weight, but 0 is not included. The zinc alloy further comprise the trace elements: wherein the trace elements are at least one of silicon, phosphorus, lithium, silver, tin and rare earth elements; wherein in the zinc alloy, the mass percentage content of the trace elements is 0-3%, but 0 is not included. The mechanical properties of the Zn-Ca series zinc alloy of the invention meet the requirements of strength and toughness of medical implant materials, and the Zn-Ca series zinc alloy has the characteristics of non-toxic, good histocompatibility and blood compatibility; meanwhile, the Zn-Ca series zinc alloy can be degraded by body fluid, and dissolved metal ions can be absorbed and utilized by organisms to promote bone growth or metabolized and discharged from the body; and the Zn-Ca series zinc alloy of the invention can be applied to the preparation of medical implants. -1/6 2n-1Ca 2n-5Ca Figure 1 Figure 2

Description

-1/6

2n-1Ca 2n-5Ca

Figure 1

Figure 2

Zinc-Calcium alloy series and preparation method and application thereof

TECHNICAL FIELD

[0001]The invention relates to a Zn-Ca series zinc alloy and a preparation method and an application thereof, in particular to a Zn-Ca series zinc alloy, a preparation method and an application thereof in preparation of body fluid degradable medical implants, and belongs to the technical field of medical metal material preparation.

BACKGROUND

[0002] At present, biomedical materials used in clinic mainly comprises biomedical metal materials, inorganic materials, polymer materials, composite materials, bionic materials and the like. Compared with high molecular materials and ceramic materials, medical metal materials have the advantages of higher strength, toughness and processability, so that the medical metal materials are most widely applied. For example, 316L, 317L, 304V stainless steel, Co-Cr-Mo alloy, pure titanium, Ti-6Al-4V, TiNi alloy and the like. These materials cannot be degraded in human body and are permanently implanted. After the service life of the implant in human body is expired, the medical metal materials must be taken out through secondary operation, thereby bringing unnecessary physiological pain and economic burden to patients.

[0003] With the development of medical science and material science, in terms of some materials which are needed for temporary service, such as suture, fracture fixation plate, vascular stent, biliary stent and the like, people hope that the materials implanted into the body only play the role of temporary replacement, and the material can be gradually degraded and absorbed along with the regeneration of tissues or organs, so that the long term impact of the materials on the body can be mitigated to the utmost extent.

[0004] At present, the common biodegradable materials used in clinic are mainly biodegradable high molecular materials and biodegradable ceramics. Although the biodegradable high molecular materials can be completely absorbed by human bodies, the biodegradable high molecular materials have low strength and are difficult to provide the function of structural support; and the biodegradable ceramics have the defects of poor toughness and are not capable of coordinating deformation.

[0005] In recent years, degradable biomedical magnesium alloy materials have become one of the research hotspots, and a series of biodegradable biomedical magnesium alloys, such as AZ31, WE43, Magnesium-Calcium and the like, have been developed. Although magnesium alloy has an attractive application prospect as a biological material, the research finds that the magnesium alloy has a fast corrosion speed, and the implant will quickly lose its mechanical integrity before tissues and organs are fully healed, so that it is necessary to develop novel degradable alloys to meet clinical requirements.

[0006] Similar to magnesium and magnesium alloys, metal zinc and alloys thereof are often used as sacrificial anode materials for corrosion protection due to their active chemical properties, but compared with magnesium, metal zinc and alloys thereof have higher corrosion potential, so that the corrosion rate of metal zinc and alloys thereof is slower than that of magnesium alloys, the metal zinc and alloys thereof are more suitable for clinical requirements, and the metal zinc and alloys thereof are expected to be developed into novel biodegradable biomedical implant materials and devices.

[0007]The normal zinc content of the human body is 2-3 g. Zinc is the main component of dozens of enzymes in the body. Zinc is distributed in most organs and tissues, especially higher in liver, muscle and bone. Although zinc is a trace element in the human body, it has a great effect. Known as the "spark plug of life": (1) Zinc is related to various bone matrix synthases, which can participate in bone formation and bone reconstruction. When zinc is deficient, the activity of a variety of zinc-containing enzymes in bone decreases, and bone growth is inhibited; (2) Zinc is a key component of biofilm, which plays an important role in maintaining the structure and function of more than 2,000 transcription factors and more than 300 enzymes; (3) Zinc can quickly enter endothelial cells, maintain the integrity of endothelial cells, and reduce the susceptibility of blood vessels to atherosclerosis; (4) Zinc can protect cardiomyocytes from acute oxidative stress and inflammatory reaction caused by myocardial damage (5) Zinc can actively participate in nucleic acid protein synthesis and accelerate wound healing; (6) In addition, zinc is also closely related to various cellular metabolism in vivo, such as sugar metabolism, lipid metabolism, anti-aging and the like. Zinc deficiency can cause arteriosclerosis, arrhythmia and failure, brain abnormalities, low immunity, diarrhea, loss of appetite, growth retardation, hair loss, night blindness, prostatauxe, male reproductive dysfunction, anemia and the like. Adults need to supplement 15-25 mg of zinc daily.

[0008] Calcium is an essential element for life, and calcium is also the highest content of metal element in the human body. Under normal circumstances, the calcium content in an adult's body is about 1,000-1,250g, of which about 99% exists in bones and teeth, mainly in the form of hydroxyapatite crystals to maintain bone and teeth with a hard structure and scaffold. In addition, about 1% of calcium usually exists in the extracellular fluid of soft tissues and blood in a free or bound ion state, and is a miscible calcium pool. The miscible calcium pool and the calcium in the bone maintain a dynamic balance, that is, the calcium in the bone is continuously released from the osteoclasts into the miscible calcium pool to ensure that the plasma calcium concentration remains constant; and the calcium in the miscible calcium pool continuously deposits in the bone, so that the calcium in the bone can be constantly replenished and renewed, i.e., the bone turnover. Calcium plays an important role in various physiological and biochemical processes of the body. (1) Maintain the normal physiological state of cells. Calcium ions in cells are the medium to respond to stimuli. Calcium and receptor calcium jointly regulate many important physiological functions of the body, including the contraction of skeletal muscle and cardiac muscle, the activity of smooth muscle and non-muscle cells, and the maintenance of nerve excitation. Calcium ions play an important role in the excitement of nerves and muscles and the conduction of nerve impulses. When calcium is lacking, the human body will have symptoms such as nerve block, abnormal muscle tension and the like. Calcium ions play an important role in cell adhesion and maintenance of cell membrane function. The cell membrane is not only a barrier to cell contents, but also a carrier to various essential nutrients and oxygen to enter the cell. The normal content of calcium ions can ensure that the cell membrane smoothly "pumps" nutrients into the cell. (2) Reduce the permeability of capillaries and cell membranes, prevent exudation, and control inflammation and edema; (3) Participate in the blood coagulation process, the coagulation factor VI is Ca2 , when calcium is lacking, coagulation disorders will occur, and the human body will appear symptoms such as gingival bleeding, subcutaneous bleeding points, irregular uterine bleeding, menorrhagia, hematuria, hematemesis and the like; (4) Participate in many enzyme systems in the body (such as ATPase, succinate deaminase, lipase, proteolytic enzymes and the like) activation; (5) Play roles on regulating the enzymes involved in the synthesis of macromolecules and transformation involved in cell metabolism; (6) Calcium ions have a decisive role on the secretion of human endocrine hormones, and are essential for maintaining the functions of system organs such as circulation, breathing, digestion, urinary, nerve, endocrine, reproductive system and the like. (7) Maintain the acid-base balance of body fluid and other functions. Calcium deficiency will lead to osteoporosis, rickets, nerve relaxation, convulsions, poor coagulation mechanism, sore and pain of waist and legs and the like. Adults need to supplement 600-1,000 mg calcium daily.

[0009] At present, there are no literature and patent reports on the synthesis and properties of Zn-Ca series alloys in China and abroad, and the proposal to use the Zn-Ca series alloy as a degradable biomedical material.

SUMMARY

[0010] The invention aims to provide a Zn-Ca series zinc alloy and a preparation method and an application thereof, in particular to a Zn-Ca series zinc alloy and a preparation method and an application thereof in the preparation of a body fluid degradable medical implant. The zinc alloy prepared by adoption of the invention has excellent mechanical property, which can provide long-term effective supporting force in vivo, has the advantages of excellent cell compatibility, blood compatibility, tissue and organ compatibility, and can be used to prepare biomedical implantation.

[0011] The Zn-Ca series zinc alloy provided by adoption of the invention comprises Zinc and Calcium;

[0012] The mass percentage of Calcium in the zinc alloy is 0-30% by weight percentage, but does not include 0.

[0013] The zinc alloy further comprises trace elements, wherein the trace elements are at least one of silicon, phosphorus, lithium, silver, tin and rare earth elements;

[0014] In the zinc alloy, the content of the trace elements is 0-3% by mass percentage, but does not include 0.

[0015] The surface of the zinc alloy can also be coated with a degradable polymer coating, a ceramic coating or a drug coating;

[0016] The thickness of the degradable polymer coating, the ceramic coating and the drug coating can be 0.01-5 mm.

[0017] The preparation material of the degradable polymer coating can be at least one of the following 1) and 2):

[0018] 1) Any one of polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), L-polylactic acid (PLLA), polycyanoacrylate (PACA), polyanhydride, polyphosphazene, polyp-dioxane ketone, poly-hydroxybutyrate and polyhydroxyvalerate;

[0019] 2) Any two or more copolymer of polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), L-polylactic acid (PLLA), polycyanoacrylate (PACA), and polyp dioxane ketone;

[0020] The preparation material of the ceramic coating can be at least one of hydroxyapatite, tricalcium phosphate or tetracalcium phosphate;

[0021] The drug coating can be at least one of a rapamycin and a derivative coating thereof, a paclitaxel coating, an everolimus coating, a sirolimus coating, a mitomycin coating, and an antibacterial coating.

[0022] The Zn-Ca series zinc alloy provided by the invention is any one of the following 1) to 5) by weight percent:

[0023] 1) The Zn-Ca series zinc alloy is composed of 95-99% of Zinc and 1-5% of Calcium;

[0024]2) The Zn-Ca series zinc alloy is composed of 99% Zinc and 1% Calcium;

[0025]3) The Zn-Ca series zinc alloy is composed of 95% Zinc and 5% Calcium;

[0026]4) The Zn-Ca series zinc alloy is composed of 98.5% Zinc, 1% Calcium and 0.5% Li;

[0027]5) The Zn-Ca series zinc alloy is composed of 98.5% Zinc, 1% Calcium and 0.5% Yttrium.

[0028] The Zn-Ca series zinc alloy prepared by adoption of the method is a compact structure or a porous structure, has good histocompatibility, and is a reliable biomedical implant material.

[0029] The invention further provides a preparation method of the aforesaid zinc alloy, which comprises the following steps:

[0030] Mixing the Zinc, the Calcium and the trace elements according to any one of the following 1) and 2) to obtain a mixture;

[0031]1) Zinc and Calcium;

[0032]2) Zinc, Calcium and trace elements;

[0033] Obtaining the zinc alloy according to the following step a) or b);

[0034] a) Smelting the mixture under the protection of C02 and SF6 atmosphere, and cooling to obtain the zinc alloy;

[0035] b) Smelting the mixture under the protection of C02 and SF6 atmosphere, and coating the degradable polymer coating, the ceramic coating or the drug coating after cooling to obtain the zinc alloy.

[0036] In the aforesaid method, the melting temperature can be 700-850 °C, specifically 800 °C.

[0037] The aforesaid method further comprises the steps of machining the zinc alloy;

[0038] The machining can be at least one of rolling, forging, rapid solidification, and extrusion.

[0039] Wherein the rolling comprises sequentially performing hot rolling and finish rolling, wherein the hot rolling can be performed at 200-300 °C, wherein the finish rolling can be performed at 150-250 °C, and the thickness of the zinc alloy after rolling can be 1-2 mm; and the hot rolling can be performed at 250 °C, wherein the finish rolling can be performed at 250 °C, and the thickness of the zinc alloy after rolling can be 1.5 mm.

[0040] Wherein the forging comprises the steps of holding the zinc alloy at 150-200 °C and forging at 200-300 °C, wherein the holding time is 3-50 hours, and the forging speed is not less than 350 mm/s.

[0041] Wherein the extrusion temperature can be 150-250 °C, specifically 200; and the extrusion ratio can be 10-70, specifically 20.

[0042] Wherein the rapid solidification comprises the following steps: preparing a rapid solidification thin strip by adoption of a high vacuum rapid quenching system under the protection of Ar gas, then crushing the thin strip into powder, and finally carrying out vacuum hot pressing for 1-24 hours under the condition of 200-350 °C.

[0043] The setting of the high vacuum rapid quenching system is as follows: the feeding amount is 2-8 g, the induction heating power is 3-7 kW, the distance between the nozzle and the roller is 0.80 mm, the injection pressure is 0.05-0.2 MPa, the rotation speed of the roller is 500-3000 r/min, and the slit size of the nozzle is 1 filmx8 mmx6 mm.

[0044] The invention also provides a preparation method for a zinc alloy, which comprises the following steps: mixing the Zinc, the Calcium, and the trace elements according to any one of the following modes 1) and 2) to obtain a mixture;

[0045] 1)Zinc and Calcium;

[0046]2) Zinc, Calcium and trace elements;

[0047] Obtaining the zinc alloy according to the following steps of a) or b);

[0048] a) Sintering the mixture under the protection of C02 and SF6 atmosphere, and cooling to obtain the zinc alloy;

[0049] b) Sintering the mixture under the protection of C02 and SF6 atmosphere, and coating the degradable polymer coating, the ceramic coating or the drug coating after cooling to obtain the zinc alloy;

[0050] The sintering is any one of the following methods: an element powder mixing sintering method, a pre-alloy powder sintering method, and a self-propagating high temperature synthesis method.

[0051] The element powder mixing sintering method comprises the following steps: uniformly mixing the raw materials for preparing the porous structure Zn-Ca alloy, pressing into a blank, slowly raising the temperature to 100-200 °C at 2-4 °C/min in a vacuum sintering furnace, then rapidly raising the temperature to 200-300 °C at 30 °C/min for sintering, and then cooling to obtain the porous structure Zn-Ca alloy;

[0052] The pre-alloy powder sintering method comprises the following steps: mixing raw materials for preparing the porous structure Zn-Ca alloy, carrying out high-energy ball milling, pressing and shaping, and carrying out heat treatment at 250-350 °C for 10-20 hours to obtain the porous structure Zn-Ca alloy;

[0053] The self-propagating high-temperature synthesis method comprises the following steps: mixing the raw materials for preparing the porous structure Zn-Ca alloy, pressing into a blank, and igniting the Zn-Ca alloy blank to carry out self-propagating high temperature synthesis with the protection of inert gas under the pressureof1x10 3 ~1x10 5 Pa and the temperature of 250-350 °C to obtain the porous structure Zn-Ca alloy.

[0054] In order to adapt to different clinical requirements, the above two methods for preparing the zinc alloy further comprise the step of coating.

[0055] Wherein the method for coating the biodegradable polymer coating comprises the following steps: pickling the zinc alloy, dipping the zinc alloy in a colloid prepared by dissolving a preparation material of the biodegradable polymer coating in trichloroethane for 10-30 minutes, and pulling out the zinc alloy at a uniform speed to perform centrifugal treatment to obtain the zinc alloy coated with the biodegradable polymer coating;

[0056] The coating method of a ceramic coating can be any one of plasma spraying, electrophoretic deposition, anodic oxidation, and hydrothermal synthesis;

[0057] Wherein the main gas of the plasma gas used for plasma spraying is Ar with flow rate of 30-100scfh, the secondary gas of the plasma gas is H2 with flow rate of 5-20 scfh, and the spraying current is 400-800 A with the spraying voltage of 40-80 V and the spraying distance of 100-500 mm;

[0058] Wherein the method for electrodepositing the degradable ceramic coating comprises the following steps: treating zinc alloy in the electrolyte containing calcium and phosphorus salts with zinc alloy serving as a cathode and a current density of 2-10 mA/cm2 for 10-60 min, and cleaning and drying to obtain the zinc alloy;

[0059] Wherein the method for combining anodic oxidation and hydrothermal synthesis comprises the following steps: oxidizing the zinc alloy in an electrolyte containing 0.01 0.5mol/L of beta-sodium glycerophosphate and 0.1-2 mol/L of calcium acetate at 200-500 V for 10-30 minutes, and then treating the zinc alloy at 200-400 °C for 1-4 hours.

[0060] The method for coating a drug coating is a physical and chemical method;

[0061] The physical method coating process mainly adopts a soaking and spraying method, and the chemical method mainly uses an electrochemical principle for electroplating;

[0062] The soaking method comprises the following steps: preparing an active drug and a controlled release carrier (or a single active medicament) into a solution, the specific concentration can be different according to the viscosity of the solution and the dosage of the required medicament; then soaking the medical implant into the solution, and then performing necessary post-treatment processes such as crosslinking, drying, curing and the like to prepare a drug coating;

[0063] Wherein the spraying method comprises the following steps: preparing an active drug and a controlled release carrier (or a single active medicament) into a solution, uniformly coating the solution on the surface of the medical implant through a spraying tool or special spraying equipment, and drying, curing and other post-treatment steps to prepare a drug coating;

[0064] By adoption of the chemical method, an active drug and/or a controlled release carrier are used to perform an electro-redox reaction on an electrode manufactured by the medical implant, so that the medical implant surface forms a stable drug coating layer connected by chemical bonds.

[0065] The characteristic that Zinc and Zinc alloy are easy to corrode is adopted in the invention, and the Zn-Ca series alloy is selected as the degradable material to apply to the medical implant. The mechanical property of the Zn-Ca series alloy of the invention accords with the requirement of the strength and toughness of the medical implant material, and can be degraded in vivo at the same time, which not only can overcome the weakness that the strength of the medical high molecular material is low and the traditional medical metal materials such as 316L stainless steel, titanium and titanium alloy are not degradable, in addition, can further overcome the defect that the mechanical properties of magnesium and magnesium alloy are lost due to the rapid degradation rate in the implanted body, thereby having the dual characteristics of "biodegradable corrosion degradation characteristics" and "suitable corrosion rate to provide long-term effective mechanical support".

[0066] The Zn-Ca series zinc alloy provided by the invention can be used for preparing the following medical implants: a therapeutic implant stent, a bone repair apparatus, and a dental repair apparatus;

[0067] Wherein the therapeutic implant stent can be a vascular stent, an esophageal stent, an intestinal stent, a tracheal stent, a biliary stent, or a urethral stent;

[0068] Wherein the bone repair apparatus can be a bone tissue repair scaffold, a connector, a fixation wire, a fixation screw, a fixation rivet, a fixation needle, a bone clamping plate, an intramedullary needle or a bone setting sleeve;

[0069] The dental prosthetic device can be a dental pulp needle or a dental filling material.

[0070] The invention has the following advantages:

[0071] (1) The mechanical properties of the Zn-Ca series alloy prepared by the invention meet the requirements of strength and toughness of medical implant materials, can be degraded in vivo at the same time, and has the dual characteristics of "biodegradable corrosion degradation characteristics" and "suitable corrosion rate to provide long-term effective mechanical support".

[0072] (2) When the Zn-Ca series alloy of the invention is used for degradable medical implants, the Zn-Ca series alloy not only can exert the high strength characteristic of metal material during implantation for a period of time to complete the functions of the implants (such as inducing the formation of new bone tissues or supporting narrow blood vessels), but also can be used as a "foreign body" to be gradually corroded and degraded by human bodies while the body lesion was repaired by itself, the quantity and volume of the Zn-Ca series alloy gradually reduce, the dissolved metal ions can be absorbed and utilized by organisms to promote bone growth or metabolism to be discharged out of the body, and finally, the metal implants will completely degrade and disappear when the human body finishes self-repairing.

[0073] (3) The body fluid degradable medical implant provided by the invention has the characteristics of non-toxic, good histocompatibility and blood compatibility.

BRIEF DESCRIPTION OF THE FIGURES

[0074] Figure 1 is a photograph of a Zn-Ca alloy ingot prepared in embodiment 1.

[0075] Figure 2 is a photograph of the Zn-Ca alloy board prepared in embodiment 2.

[0076] Figure 3 is a photograph of the Zn-Ca alloy bar prepared in embodiment 3.

Figure 4 is a photograph of a tensile sample of a Zn-Ca series alloy prepared in accordance with a test standard.

[0078] Figure 5 is a tensile curve of a Zn-Ca-Li alloy.

[0079] Figure 6 is a SEM photograph of Zn-Ca alloy at different magnification after soaked in simulated body fluid for 2 weeks(a) low magnification; (b) high magnification.

[0080] Figure 7 is an electrochemical corrosion curve of a Zn-Ca alloy in a simulated body fluid.

[0081] Figure 8 is a SEM photograph of Zn-Ca alloy platelet adhesion.

[0082] Figure 9 is a light microscope of the effect of Zn-Ca alloy on cells (a) control group;(b) Zn-Ca alloy.

[0083] Figure 10 is the relative proliferation rate of cells treated with Zn-Ca alloy after different time (*p <0.05, **p <0.01).

[0084] Figure 11 is the X-ray films and corresponding control images of Zn-Ca alloy implanted into mice at different times.

[0085] Figure 12 is the mico-CT films and control images of Zn-Ca alloy implanted into mice at different times.

[0086] Figure 13 is a histological fluorescence staining photographs of Zn-Ca alloy implanted in mice for 2 months.

DESCRIPTION OF THE INVENTION

[0087] The experimental methods used in the following embodiments are conventional methods without specific explanation.

[0088] The materials, reagents and the like used in the following embodiments are available from commercial sources unless otherwise specified.

[0089] The percentages used in the following embodiments are percentages by mass unless otherwise specified.

[0090] Embodiment 1 preparation of as cast Zn-Ca alloy

[0091] Taking pure Zinc (99.99 wt.%) and pure Calcium (99.95 wt.%)(Purchased from Trillion Metals Co.,Ltd.)

as raw material, mixing the Zinc and Calcium according in different mass ratios (the mass ratio of Zinc to Calcium is 99:1 and 95:5 respectively), smelting at 800 °C under the protection of C02+SF6 atmosphere, after fully melting the raw materials, holding for 10min, quickly cooling the circulating water to obtain a Zn-Ca alloy ingot (the photograph is as shown in Figure 1), among them, the Zn-lCa represents the mass ratio of Zinc to Calcium of 99:1, and Zn-5Ca represents the mass ratio of Zinc to Calcium of 95:5.

[0092] Embodiment 2 preparation of a rolled Zn-Ca series alloy

[0093] First, obtaining an as cast Zn-Ca series alloy ingot prepared according to the procedure in embodiment 1; then carrying out the hot rolling to the aforesaid obtained Zn Ca series alloy ingot by means of preheating the ingot at 250 °C, adopting the hot rolling mode, performing repeated rolling in a reciprocating rolling mill with the hot rolling temperature at 250 °C, and finally rolling the as cast Zn-Ca series alloy ingot to 1.5mm in a finishing mill at 250 °C.

[0094] Figure 2 is a photograph of the as rolled Zn-Ca alloy (Zn-lCa) obtained in the embodiment.

[0095] Embodiment 3 preparation of extruded Zn-Ca Alloy

[0096] The preparation is carried out according to the following steps 1) or 2):

[0097]1) obtaining the as cast Zn-Ca series alloy ingot (Zn-lCa) by means of preparation according to the steps in embodiment 1, preparing the Zn-Ca alloy bar (Zn-iCa) by means of extrusion mode, adopting radial extrusion with the extrusion temperature of 200 °C and extrusion ratio of 20 to prepare the Zn-Ca alloy rod (Zn-lCa) with diameter of 10 mm.

[0098] 2) The as cast Zn-Ca alloy ingot was first prepared according to the steps of embodiment 1 and a rapid solidification Zn-Ca alloy thin strip was prepared by adoption of a high rapid quenching system, and the specific method comprises the following steps: adopting Zn-Ca thin strip prepared by means of the high vacuum rapid quenching system after mixing the raw material according to the ratio, with the parameters including 2-8g of feed rate, 3-7 kW of induction heating power, 0.80 mm of nozzle to roller spacing, 0.1 MPa of injection pressure, 2,000 r/min of roller rotation speed and lfilmx8mmx6 mm of nozzle slit size. Then the thin strips were crushed and pressed into base, with the hot pressing conditions of 200-350 °C and vacuum hot pressing for 1-24 h. The Zn-Ca alloy bars were prepared by means of extrusion, and radial -with diameter of 10 mm (Zn-lCa) (as shown in Fig. 3).

[0099] Example 4 mechanical property test of Zn-Ca alloy

[0100] The tensile samples were prepared according to ASTM-E8-04 tensile test standard (as shown in Fig. 4) by adoption of the Zn-Ca alloy prepared according to the method of embodiment 1-3 A tensile sample and sequentially polished by 400#, 800#, 1,200# and 2,000# SiC sandpaper series. After the tensile samples were in acetone, absolute ethyl alcohol and deionized water for ultrasonic cleaning for 15 minutes, a tensile test was carried out at room temperature by means of a universal material mechanics tester at a tensile speed of 1 mm/min.

[0101] Figure 5 shows a tensile curve of the Zn-Ca series alloy prepared according to the invention (as cast Zn-1Ca-0.5Li, the preparation method of which is the same as that of the as cast Zn-Ca series alloy in embodiment 1, wherein the mass ratio of Zinc to Calcium to Lithium is 98.5:1:0.5). From this figure, it can be seen that the as cast Zn-Ca-0.5Li alloy has a tensile strength of 168.37 MPa, a yield strength of 95.85 MPa, and an elongation of 1.372%.

[0102] The tensile properties of Zn-Ca alloy samples at room temperature are shown in Table 1, among them, the preparation method of Zn-lCa-0.5Y is the same as that of the as rolled Zn-Ca alloy in embodiment 2, and the mass ratio of Zinc to Calcium to Yttrium is 98.5:1:0.5. As can be seen from Table 1, with the increase of Calcium content, the alloy becomes brittle, and the strength and elongation are obviously reduced. Compared with the as cast alloy, the yield strength and tensile strength of the rolled alloy and the extruded alloy are obviously improved, and the elongation is greatly increased at the same time, which indicates that the mechanical properties of the material are further optimized after deformation processing.

[0103] Tensile test results of Zn-Ca alloy

[0104]

Sample Number Tensile Yield strength/MPa Elongation/% strength/MPa

Zn-1Ca cast ingot 162.42 122.35 1.835

Zn-0.5Ca cast ingot 60.35 43.26 0.463

Zn-lCa-0.5Y rolled 172.83 128.47 1.407 plate

Zn-iCa rolled plate 264.13 210.42 13.727

Zn-lCa bar 254.53 200.27 7.404

[0105] Embodiment 5 corrosion performance test of Zn-Ca alloy

[0106] The rolled Zn-Ca alloy in embodiment 2 was prepared by wire cutting to prepare xlOxl.5 mm Zn-Ca alloy sample pieces, which were polished by 400#, 800#, 1,200# and 2,000# SiC sandpaper series in turn. After ultrasonic cleaning for 15 minutes in acetone, absolute ethanol and deionized water, the Zn-Ca alloy sample pieces were dried at 25 °C. Then the sample pieces were soaked in Hank's simulated body fluid (NaCI 8.0 g, CaCl2 0.14 g, KCI 0.4 g, NaHCO3 0.35 g, glucose 1.0 g, MgCl2•6H20 0.1 g, Na2HPO4•2H20 0.06 g, KH2PO4 0.06 g and MgSO4• 7H20 0.06 g dissolved in 1 L deionized water), taken out after being soaked for different time intervals, and the surface of the sample was observed. Figure 6 shows the scan SEM photos of Zn-Ca alloy (Zn iCa) in Hank's simulated body fluid for two weeks under different magnifications, (a) is low magnification, and (b) is high magnification. The results showed that the surface of the Zn Ca alloy remained intact and a large amount of hydroxyapatite minerals were deposited on the surface of Zn-Ca alloy, which indicated that the Zn-Ca alloy can induce the deposition of bone minerals while degrading, thereby promoting the repair of bone tissue in vivo.

[0107] Figure 7 is an electrochemical corrosion polarization curve of the Zn-Ca alloy (Zn ICa) in Hank's solution. As can be seen from Figure 7, the corrosion rate of the Zn-iCa alloy is 0.16 mm/year.

[0108] Embodiment 6;hemocompatibility test of Zn-Ca alloy

[0109] The rolled Zn-Ca alloy in embodiment 2 was prepared by wire cutting to prepare x10x1.5 mm Zn-Ca alloy sample pieces, which were polished by 400#, 800#, 1,200# and 2,000# SiC sandpaper series in turn. After ultrasonic cleaning for 15 minutes in acetone, absolute ethanol and deionized water, the Zn-Ca alloy sample pieces were dried at 25 °C. Fresh blood was collected from healthy volunteers and stored in an anticoagulant tube containing 3.8 wt.% sodium citrate as anticoagulant. Diluted blood sample was prepared by diluting 0.9% normal saline at the ratio of 4:5. The sample was socked in 10ml normal saline and kept at 37±0.5 °C for 30 min, 0.2 ml diluted blood sample was added, and the sample is kept at 37±0.5 °C for 60 min. 10 ml normal saline was used as negative control group and 10 ml deionized water was used as positive control group. After centrifuged at 3,000 rpm for 5 minutes, the OD value of the supernatant was measured at 545nm with a Unic-7,200 UV-Vis spectrophotometer, and three groups of parallel samples were set for statistical analysis.

[0110] The hemolysis rate was calculated by the following formula:

[0111] Hemolysis rate = (OD value of test group-OD value of negative group) / (OD value of positive group-OD value of negative group) x 100%.

[0112] After collection of whole blood, platelet-rich plasma was prepared by centrifugation at 1,000 rpm for 10 min. Platelet-rich plasma was dropped onto the surface of the sample, holding at 37±0.5 °C for 60 min, with 3 parallel samples in each group. The samples were taken out, and PBS buffer solution (pH value was 7.2) was adopted to wash three times to remove the non-adherent platelets. The platelet fixation method was as follows: 500 pL of glutaraldehyde fixation solution with concentration of 2.5% was added to each well, fixed at room temperature for 60 min, then the fixation solution was sucked out. PBS was used to wash for 3 times, gradient dehydration was performed with 50%, 60%, 70%, 80%, 90%, % and 100% alcohol, and each concentration gradient was dehydrated for 10 minutes.

After vacuum drying, scanning electron microscopy (S-4,800, Hitachi, Japan) was used to observe the number and morphology of platelet adhesion. For each sample, six regions was randomly selected for platelet count and statistical analysis.

[0113] The test results indicated that the hemolysis rate of Zn-Ca alloy (Zn-lCa) was 0.3%, which was far less than the safety threshold of 5% required by clinical use, and showed good compatibility of red blood cells and hemoglobin.

[0114] Figure 8 was a photograph of the morphology of platelets adhered to the surface of a Zn-Ca alloy (Zn-lCa), as can be seen from the figure, the number of platelets adhered to the surface of the Zn-Ca alloy was rare and had a smooth spherical shape without pseudopods stretching and was not activated, which showed an excellent anticoagulant performance.

[0115] Embodiment 7 Preparation of body fluid degradable medical Zn-Ca implant and cytocompatibility test thereof

[0116] A Zn-Ca alloy was prepared according to the method of embodiment 1-3. Six pieces of Zn-Ca alloy (Zn-lCa, as cast and rolled) with a length, a width and a thickness of , 10 and 1.5 mm respectively were sterilized with gamma rays, placed in a sterile culture flask, added with MEM cell culture medium at a ratio of sample surface area to MEM cell culture medium volume of 125 cm 2 /mL, placed in a 37 °C, 95% relative humidity, and 5% C02 incubator for 72 h to obtain the stoste of the Zn-Ca alloy leach solution, sealed, and stored in a refrigerator at 4 °C for later use.

[0117] Leach solution and cell inoculation culture and result observation: MG63 cells (Guangzhou Jennio Biotech Co., Ltd.) were resuscitated and subcultured, suspended in MEM cell culture medium and inoculated on 96-well culture plate. In negative control group, MEM cell culture medium was added. In Zn-Ca alloy extract solution group, the Zn Ca alloy extract solution obtained above was added, so that the final cell concentration was 5x10 4 / mL. MG63 cells were cultured in a 5% C02 incubator at 37 °C, and a culture plate was taken out after 5 days, and the morphology of living cells was observed under inverted phase contrast microscope (Figure 9). The results showed that compared with the negative control group, the number of cells was in the same order of magnitude, the morphology indicated a healthy and elongated fusiform growth, which indicated that Zn-Ca alloy had excellent cell compatibility.

[0118] Figure 10 indicates the experimental results of the relative proliferation rate of MG63 osteoblasts cultured in Zn-Ca alloy (Zn-lCa) leach solution for different periods of time. As can be seen from Figure 10, the addition of calcium can effectively improve the proliferation activity of bone cells and promote the proliferation of bone cells.

[0119] Embodiment 8 Preparation of body fluid degradable medical Zn-Ca implant and animal experiment thereof

[0120] A Zn-Ca alloy intramedullary nail prepared by means of lathe processing, the size parameters of the prepared intramedullary nail were as follows: length: 5 mm; diameter: 1 mm. Ten pieces of the Zn-Ca alloy intramedullary nails prepared by the above method were taken and implanted into the femurs of 10 mice respectively. After one week, two weeks, three weeks, four weeks, six weeks and eight weeks, X-ray observation (Figure 11), micro-CT observation (Figure 12) and tissue section fluorescence observation (Figure 13) were carried out. The results showed that no foreign body reaction such as inflammation of surrounding tissue was found in 10 mice one week, two weeks, four weeks and eight weeks after operation. The intramedullary nail remained intact, and new bone tissue around the implant was observed two weeks after implantation (as shown by arrow), the thickness of new bone tissue around the implant was larger than that of the control group, which indicated that the Zn-Ca alloy medical implant can promote the formation of bone tissue and shorten the repair time of fracture and other trauma.

Claims (11)

Claims

1. A Zn-Ca series zinc alloy, which is characterized in that the Zn-Ca series zinc alloy is any one of the following 1)-2) by weight percentage:

1) A Zn-Ca series zinc alloy comprises 98.5% Zinc, 1% Calcium and 0.5% Lithium;

2) A Zn-Ca series zinc alloy comprises 98.5% Zinc, 1% Calcium and 0.5% Yttrium.

2. The zinc alloy according to claim 1, which is characterized in that wherein the surface of the zinc alloy is coated with a degradable polymer coating, a ceramic coating or a drug coating;

Wherein the thickness of the degradable polymer coating, the ceramic coating and the drug coating is 0.01-5 mm.

3. A zinc alloy preparation method according to claim 1, which comprises the following steps: mixing the components to obtain a mixture according to claim 1;

Obtaining the zinc alloy according to the following steps:

a) Smelting the mixture under the protection of C02 and SF6 atmosphere, and cooling to obtain the zinc alloy, and the smelting temperature is 700-850 °C.

4. A zinc alloy preparation method according to claim 2, which comprises the steps: mixing the components to obtain a mixture according to claim 1;

Obtaining the zinc alloy according to the following steps:

b) Smelting the mixture under the protectionof C02and SF6 atmosphere, and coating the degradable polymer coating, the ceramic coating or the drug coating after cooling to obtain the zinc alloy;

And the smelting temperature is 700-850 °C.

5. A zinc alloy preparation method according to claim 3, which is characterized in that wherein the method further comprises the step of machining the zinc alloy;

And the machining is at least one of rolling, forging, rapid solidification and extrusion.

6. A zinc alloy preparation method according to claim 5, which is characterized in that:

Wherein the rolling comprises sequentially carrying out hot rolling and finish rolling, wherein the hot rolling is carried out at the temperature of 200-300 °C, wherein the finish rolling is carried out at the temperature of 150-250 °C, and the zinc alloy is rolled for 1-3 mm;

Wherein the forging comprises the steps of carrying out holding on the zinc alloy at the temperature of between 150-200 °C and carrying out forging at the temperature of 200 300 °C, wherein the heat preservation time is between 3 and 50 hours, and the forging speed is not less than 350 mm/s;

Wherein the extrusion temperature is 150-250 °C, and the extrusion ratio is 10-70;

Wherein the rapid solidification comprises the following steps: preparing a rapid solidification thin strip by adopting a high vacuum rapid quenching system under the protection of Ar gas; then crushing the thin strip into powder; and finally carrying out vacuum hot pressing for 1-24 h under the condition of 200-350 °C.

7. A zinc alloy preparation method according to claim 1, which comprises the steps: mixing the components to obtain a mixture according to claim 1;

Obtaining the zinc alloy according to the following steps:

a) Sintering the mixture under the protection of C02 and SF6 atmosphere, and cooling to obtain the zinc alloy;

The sintering is any one of the following methods: an element powder mixing sintering method, a pre-alloy powder sintering method and a self-propagating high-temperature synthesis method.

8. A zinc alloy preparation method according to claim 2, which comprises the steps: mixing the components to obtain a mixture according to claim 1;

Obtaining the zinc alloy according to the following steps:

b) Sintering the mixture under the protection of C02 and SF6 atmosphere, and coating the degradable polymer coating, the ceramic coating or the drug coating after cooling to obtain the zinc alloy;

The sintering is any one of the following methods: an element powder mixing sintering method, a pre-alloy powder sintering method and a self-propagating high-temperature synthesis method.

9. The zinc alloy according to claim 1 is applied for the preparation of a body fluid degradable medical implant.

10. The application according to claim 9, which is characterized in that wherein the application is shown in any one of the following 1)-4):

1) The zinc alloy promotes the repair of bone tissue;

2) The anticoagulant performance of the zinc alloy;

3) The cell compatibility of the zinc alloy;

4) The zinc alloy promotes the formation of bone tissue.

11. A body fluid degradable medical implant is prepared by means of the zinc alloy according to claim 1.

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Figure 1

Figure 2

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Figure 3

Figure 4

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Strain Figure 5

Figure 6

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Electric potential

Log corrosion current

Figure 7

Figure 8

Relative increment

Control

Pure zinc

Zinc-1Ca -5/6-

Figure 9

Figure 10 Culture Time (Day)

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Figure 11

Control

Figure 12

Control

Figure 13