CN107198796B

CN107198796B - Biomedical Zn-Mn-Cu zinc alloy and preparation method thereof

Info

Publication number: CN107198796B
Application number: CN201710363125.4A
Authority: CN
Inventors: 石章智; 王鲁宁; 张海军; 刘雪峰; 于静; 刘丽君
Original assignee: University of Science and Technology Beijing USTB
Current assignee: Beijing Shangning Kezhi Medical Instrument Co ltd
Priority date: 2017-05-22
Filing date: 2017-05-22
Publication date: 2020-08-25
Anticipated expiration: 2037-05-22
Also published as: CN107198796A

Abstract

The invention discloses a biomedical Zn-Mn-Cu alloy and a preparation method thereof. Belongs to the technical field of component design and preparation of medical degradable metal materials. The zinc alloy comprises 0.1-5% of Mn and 0.1-2% of Cu by mass percent, and the balance of Zn. After vacuum induction melting and plastic processing, the material has good mechanical properties and meets the requirements of strength and plasticity of medical implant materials. The dissolved metal ions can be absorbed and utilized by organisms to promote the repair of tissues and organs or be discharged out of the body through metabolism.

Description

Biomedical Zn-Mn-Cu zinc alloy and preparation method thereof

Technical Field

The invention relates to a biomedical Zn-Mn-Cu zinc alloy and a preparation method thereof, in particular to a preparation method of the Zn-Mn-Cu zinc alloy and application thereof in a degradable medical implant, belonging to the technical field of component design and preparation of medical degradable metal materials.

Technical Field

Metal materials, inorganic materials, high molecular materials, composite materials, bionic materials and the like are materials which are currently applied to clinical biomedicine, wherein the medical metal materials are most widely applied due to better mechanical property and processing property, such as: 316L stainless steel, Co-Cr-Mo alloy, WE43 magnesium rare earth alloy, Ti-6Al-4V alloy, Zn-Mg alloy, pure iron and the like. These materials can be classified into 2 types, one being degradable in the human body and the other being non-degradable in the human body. Materials which are not degradable in the human body, such as 316L stainless steel, Ti-6Al-4V alloy, Co-Cr-Mo alloy and the like, are permanently implanted, and the implant body must be taken out through a secondary operation after the service period in the human body expires, so that the physiological pain and the economic burden are added to a patient. The material degradable in human body, such as pure iron, magnesium alloy, zinc alloy, etc., is suitable for devices needing temporary service, such as blood vessel stent, urethral stent, fracture fixing plate, etc. The devices are implanted into the human body to play a role in assisting and promoting tissue repair, along with the gradual completion of tissue repair, the devices are gradually degraded by body fluid, one part of decomposition products of the devices is absorbed by the human body to promote tissue repair, the other part of the decomposition products is discharged out of the body through metabolism, and the devices are not required to be taken out through a secondary operation, so that pain and economic burden of a patient are not increased. Degradable medical biometallic material has become the research hotspot in the international biomaterial field at present.

In recent years, degradable biomedical magnesium alloy materials become one of the hot spots of research, a series of biomedical degradable magnesium alloys are developed, and magnesium alloys containing rare earth elements have the most clinical application prospect. The DREAMS 1G intravascular stent prepared by German Biotronik company with Mg-Re (rare earth) alloy has the tensile strength of 195MPa, the elongation of only 2 percent and the absorption period of 0.5 year. Therefore, the main problems of the magnesium alloy as the degradable biomedical material at present are low plasticity and too fast corrosion speed in human body.

Recently, zinc alloy has attracted attention as a degradable biomedical material, and related research is still in the beginning. In traditional engineering applications, metallic Zn is often used as a sacrificial anode material coating to protect the base metal from corrosion, such as hot-dip galvanized steel. However, in the biomedical field, compared with magnesium, metal zinc and alloy thereof have higher corrosion potential, so the metal zinc and alloy thereof have lower corrosion speed than magnesium, better meet clinical requirements and are expected to become novel biomedical degradable implant materials. A Zn-Mg series zinc alloy and a preparation method and application thereof are disclosed in Chinese invention patent CN 104212998A, a Zn-Ca series zinc alloy and a preparation method and application thereof are disclosed in Chinese invention patent CN 104195369B, and a Zn-Cu-Al-Mg series alloy for a zipper tooth belt and a preparation method thereof are disclosed in Chinese invention patent CN 102011029A.

Zinc, manganese and copper are all metal elements required by human body. Zinc has a very large effect in human body and is called a spark plug for life. The normal zinc content of human body is 2-3 g, and the adult needs 13-15 mg of zinc every day, which is the main component of various enzymes in human body. Zinc is distributed in most tissues and organs, and the content of zinc in liver, muscle and bone is high. Zinc deficiency in human body can lead to vision deterioration, slow healing speed of wound and trauma, and poor development of body and intelligence, and dwarfism in severe cases. The effect of manganese in human bodies is not small, and indexes corresponding to people in all ages are different in reference indexes of safety and proper intake of manganese formulated by the Chinese academy of nutrition, wherein the number of people in all ages above 11 years is 2-3 mg every day. The lack of manganese in human body can affect the normal growth and development of bones, influence the metabolism of sugar, cause neurasthenia syndrome, accelerate the aging of human body and other serious consequences. Copper is also an essential element of the human body, and the world health organization recommends that adults should take 0.03 mg of copper per kilogram of body weight per day, and that pregnant women and infants should be doubled. Copper is a constituent element of various proteins of a human body, and has important influence on the development and functions of a plurality of visceral organs such as a central nerve, an immune system, a brain, a liver, a heart and the like. The content of copper in human body is about 100-150 mg, and the copper is the second necessary trace metal element in the human body. Copper deficiency can cause osteoporosis, resulting in anemia, coronary heart disease, infertility, etc.

At present, no document and patent reports exist at home and abroad about the preparation method and the performance of the Zn-Mn-Cu zinc alloy invented by the patent, and the Zn-Mn-Cu zinc alloy is proposed to be used as a degradable biomedical material.

Disclosure of Invention

The invention aims to provide a Zn-Mn-Cu series zinc alloy and a preparation and application method thereof, and relates to a preparation method of a Zn-Mn-Cu series zinc alloy and application thereof in a degradable medical implant. The zinc alloy prepared by the invention has excellent comprehensive mechanical property, can provide long-term effective supporting force in a living body, has excellent cell compatibility, blood compatibility and tissue and organ compatibility, and can be used for preparing biomedical implants.

The Zn-Mn-Cu series zinc alloy provided by the invention comprises a Zn element, a Mn element and a Cu element. The alloy element composition range is 0.1-5% of Mn, 0.1-2% of Cu and the balance of Zn, the composition is calculated by mass percent, and the mass percent of Mn in the Zn-Mn-Cu alloy is 0.1-5%; the percentage of Cu is in the range of 0.1-2%.

In the Zn-Mn-Cu zinc alloy, the alloy elements are calculated by weight percent:

(1) consists of 98.5 to 99.6 percent of Zn, 0.3 to 0.8 percent of Mn and 0.1 to 0.7 percent of Cu;

(2) consists of 98.8 percent of Zn, 0.8 percent of Mn and 0.4 percent of Cu;

(3) consisting of 99.2% Zn, 0.4% Mn and 0.4% Cu.

The Zn-Mn-Cu series zinc alloy prepared by the invention has a compact structure, has good histocompatibility, and is a reliable biomedical implant material.

The preparation method of the Zn-Mn-Cu zinc alloy comprises the following specific preparation steps:

1) casting: pure Zn, pure Mn and pure Cu are used as raw materials, refined for 3-7 minutes at 750-800 ℃ in a vacuum induction smelting furnace protected by argon atmosphere, poured into a mold and cooled to room temperature;

2) plastic processing: the plastic working method includes at least one of rolling, extruding and drawing.

The rolling of the Zn-Mn-Cu based zinc alloy as described above is divided into 2 rolling process routes, and a finished plate can be produced according to any of the 2 process routes:

(1) hot rolling: the temperature is 250-380 ℃;

(2) hot rolling → cold rolling: the hot rolling temperature is 250-380 ℃, and the cold rolling temperature is room temperature; the hot rolling and cold rolling has a strain amount of 20 to 95%.

Further, the extrusion temperature is 200-350 ℃, and the extrusion ratio is 10-90.

Further, the drawing temperature is between room temperature and 250 ℃, and the drawing surface shrinkage is 5-95%.

The surface of the zinc alloy can also be coated with a degradable polymer coating, a ceramic coating or a drug coating.

The thicknesses of the degradable polymer coating, the ceramic coating and the medicine coating can be 0.01-5 mm.

The degradable high polymer coating can be prepared from at least one of the following materials: polylactic acid (PLA), L-polylactic acid (PLLA), polyglycolic acid (PGA), Polycaprolactone (PCL), Polycyanoacrylate (PACA), poly- (p-dioxanone).

The ceramic coating can be prepared from at least one of the following materials: hydroxyapatite (hydroxyapatite), tricalcium phosphate (TCP), or tetracalcium phosphate (TTCP).

The drug coating may be at least one of: rapamycin (RAPA) and its derivatives, such as the hydroxyethyl derivative everolimus (everolimus) coating.

The invention utilizes the characteristic that Zn and Zn alloy can be degraded in organisms, and selects Mn element and Cu element which are beneficial to human bodies as alloy elements to improve the mechanical property of pure Zn. The Zn-Mn-Cu alloy has mechanical performance meeting the strength and plasticity requirement of medical implant material, and may be degraded inside body to avoid the fast loss of mechanical performance caused by fast degradation of Mg and Mg alloy and to avoid the non-degradable problem of medical metal material such as Ti, Ti alloy, stainless steel, Co-Cr-Mo alloy, etc. The Zn-Mn-Cu series zinc alloy has the characteristics of biodegradability and long-term effectiveness.

The Zn-Mn-Cu series zinc alloy provided by the invention can be used for preparing the following medical implant: heart stent, urethra stent, intestinal stent, trachea stent, biliary stent, bone tissue repair stent, bone connector, fixing wire, fixing screw, fixing pin, bone clamping plate, dental needle or tooth filling material.

The invention has the following advantages:

(1) according to the Zn-Mn-Cu series zinc alloy designed by the invention, the most abundant alloy elements adopt Mn elements with low cost, the total content of the alloy elements is low, the cost of the alloy is low, and the Zn-Mn-Cu series zinc alloy is suitable for large-scale popularization and use;

(2) the mechanical property of the Zn-Mn-Cu series zinc alloy prepared by the invention meets the requirements of strength and plasticity of medical implant materials, and meanwhile, the Zn-Mn-Cu series zinc alloy can be degraded in vivo, has a proper in-vivo degradation speed and can provide a long-term effective supporting effect;

(3) when the Zn-Mn-Cu series zinc alloy designed by the invention is used for a degradable medical implant, the advantage of high strength of a metal material can be exerted within a period of time after the Zn-Mn-Cu series zinc alloy is implanted, and the function of the implant is completed. After being implanted into a diseased part of a human body, the implant is gradually corroded and degraded by body fluid of the human body along with the repair of the diseased part and is finally completely degraded. Mn ions released in the degradation process can promote the growth and the recovery of tissues and organs, and have the advantages of reducing the fat content in the liver, promoting the synthesis of cholesterol and the like. Cu ions released in the degradation process form copper-containing enzyme and copper binding protein and participate in iron metabolism and erythropoiesis. Zn, Mn and Cu which are not absorbed by human body can be discharged out of the body through metabolism of human body.

Drawings

FIG. 1 is a tensile stress-strain curve of a cast Zn-Mn-Cu system zinc alloy prepared in example 1.

Wherein FIG. 1a is a tensile stress-strain curve of a cast Zn-0.8Mn-0.4 Cu-based zinc alloy,

FIG. 1b is a tensile stress-strain curve of a cast Zn-0.4Mn-0.4 Cu-based zinc alloy;

FIG. 2 is a tensile stress-strain curve of the hot rolled Zn-Mn-Cu based zinc alloy prepared in example 2.

Wherein FIG. 2a is a tensile stress-strain curve of a hot-rolled Zn-0.8Mn-0.4 Cu-based zinc alloy,

FIG. 2b is a tensile stress-strain curve of a hot-rolled Zn-0.4Mn-0.4 Cu-based zinc alloy,

FIG. 3 is a plot of electrochemical corrosion polarization of hot rolled Zn-0.4Mn-0.4Cu alloy prepared in example 2 in simulated body fluid.

Detailed Description

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

The percentages used in the following examples are by weight unless otherwise specified.

Example 1:

preparing casting Zn-Mn-Cu alloy and measuring the mechanical property of the material.

Pure Zn (99.99%), pure Mn (99.9%) and pure Cu (99.9%) are used as raw materials, mixed according to the following 2 mass percent, and put into Al in a vacuum induction melting furnace₂O₃In the crucible: (1) 98.8% Zn, 0.8% Mn and 0.4% Cu; (2) 99.2% Zn, 0.4% Mn and 0.4% Cu. Vacuumizing, and introducing argon after the air pressure in the vacuum induction melting furnace is reduced to 30Pa to ensure that the pressure of the argon reaches 0.04 MPa. Then heating Al filled with raw materials under the protection of argon₂O₃Refining the crucible for 5 minutes at 760 ℃, then pouring the alloy melt into a cylindrical high-purity graphite mold with the diameter of 75mm, and air-cooling to room temperature to prepare Zn-0.8Mn-0.4Cu and Zn-0.4Mn-0.4Cu alloy ingots.

Preparing round bar tensile test samples according to GB/T228.1-2010 Metal Material tensile test part 1, Room temperature test method, and performing a Universal Material mechanical testTensile test was carried out at room temperature with a tensile strain rate of 10^-3And s. The tensile engineering stress-strain curve of the cast Zn-Mn-Cu series zinc alloy is shown in figure 1, and the tensile yield strength, the tensile strength and the elongation of the cast Zn-0.8Mn-0.4Cu alloy obtained from figure 1a are 113.2MPa, 120.1MPa and 0.44 percent respectively; from FIG. 1b, the cast Zn-0.4Mn-0.4Cu alloy has a tensile strength of 83.9MPa and an elongation of 0.25%, since the elongation is too low to use Rp commonly used in engineering_0.2As yield strength, Rp is therefore taken_0.1As the yield strength, the value was 76.7 MPa.

Example 2:

preparing hot-rolled Zn-Mn-Cu alloy plates and measuring the mechanical property and the corrosion property of the materials.

An ingot of a Zn-Mn-Cu alloy was prepared in accordance with the method provided in example 1, and a sheet having a thickness of 30mm was cut out from the ingot. The plate is preheated before hot rolling, and the process system is that the temperature is kept at 320 ℃ for 1 hour. Then the plate is taken out from the heating furnace and sent into a hot rolling mill, the thickness of the plate is reduced to 5mm through 5 times of hot rolling, and the hot rolling deformation reaches 83.3%.

Plate tensile test samples were prepared according to GB/T228.1-2010 part 1 of tensile test of metallic materials, Room temperature test method, and tensile tests were carried out at room temperature using a Universal Material mechanics tester with a tensile strain rate of 10^-3And s. As shown in FIG. 2, the hot-rolled Zn-Mn-Cu alloy has a tensile stress-strain curve, and the hot-rolled Zn-0.8Mn-0.4Cu alloy shown in FIG. 2a has a tensile yield strength of 195.5MPa, a tensile strength of 277.5MPa, and an elongation of 15.3%; from FIG. 2b, the hot rolled Zn-0.4Mn-0.4Cu alloy has a tensile yield strength of 198.4MPa, a tensile strength of 292.4MPa and an elongation of 29.6%.

A sample having a size of 2mm (thickness) of × 10mm × 10mm was cut from a hot-rolled Zn-0.4Mn-0.4Cu alloy, the surface of the sample was polished with 800# to 2000# SiC sandpaper, and then mechanically polished, after cleaning and drying the sample, it was immersed in a simulated body fluid having a pH of 7.40 (in 1000ml of the simulated body fluid, 8.035g of NaCl, 0.355g of NaHCO in this order₃，0.225g KCl，0.231g Na₂HPO₄·3H₂O，0.311g MgCl₂·6H₂O，39ml 1.0_M·HCl，0.292g CaCl₂，0.072g NaSO₄，6.118g Tris，0～5ml 1.0_MHCl), the electrochemical corrosion polarization curve was started after 5 minutes of immersion in a simulated body fluid maintained at 37 ℃ and the scanning speed was 1 mV/s. FIG. 3 is a measurement result from which the corrosion rate of the hot-rolled Zn-0.4Mn-0.4Cu alloy was calculated to be 0.056 mm/year.

Example 3:

and preparing the cold-rolled Zn-Mn-Cu alloy plate.

An ingot of a Zn-Mn-Cu alloy was prepared in the same manner as in example 1, and a sheet having a thickness of 30mm was cut out from the ingot. Firstly, hot rolling is carried out, the plate is preheated before hot rolling, and the process system is that the temperature is kept for 1 hour at 320 ℃. The plate was then removed from the furnace and fed to a hot rolling mill where it was hot rolled in 2 passes to reduce the thickness to 15mm with a hot rolling distortion of 50%. And when the temperature of the hot rolled plate is reduced to room temperature, the hot rolled plate is sent into a cold rolling mill, the thickness of the hot rolled plate is reduced to 3mm through 4 passes, and the cold rolling deformation is 80%.

Example 4:

preparing an extruded Zn-Mn-Cu alloy bar.

A Zn-Mn-Cu alloy ingot was prepared in the same manner as in example 1, and a bar having a diameter of 40mm was cut out from the ingot. The bar is preheated before extrusion, and the process system is that the temperature is kept at 300 ℃ for 2 hours. The rods were then removed from the furnace and placed in a forward extruder and extruded in 1 pass at an extrusion ratio of 25, to give rods of 8mm diameter.

Example 5:

and preparing the drawn Zn-Mn-Cu alloy wire.

A Zn-Mn-Cu alloy ingot was prepared in the same manner as in example 1, and a bar having a diameter of 30mm was cut out from the ingot. The bar is preheated before extrusion, and the process system is that the temperature is kept at 300 ℃ for 2 hours. The rods were then removed from the furnace and placed in an extruder and extruded in 1 pass at an extrusion ratio of 36, to give rods 5mm in diameter. A rod having a diameter of 5mm was cold-drawn at room temperature in 3 passes to form a wire having a diameter of 2mm, and the total draw face reduction was 84%.

Example 6:

the surface of the Zn-Mn-Cu alloy is coated with a therapeutic drug Rapamycin (RAPA) and a degradable polymer polylactic acid (PLA).

A sample was taken from the hot-rolled Zn-Mn-Cu system alloy sheet prepared in example 2, and the surface of the sample was sanded with 800# to 2000# SiC sandpaper, mechanically polished, then cleaned with an ultrasonic cleaner in deionized water for 15 minutes, and taken out and dried. And (3) placing the sample in an ultrasonic atomization spraying machine for spraying treatment, and placing a uniform polylactic acid-chloroform solution carrying rapamycin in a propeller, wherein chloroform is an organic solvent. The ratio of rapamycin to polylactic acid is 1:8, and the volume ratio of polylactic acid to chloroform is 1: 15. The thickness of the coating layer was 50 μm. The coated sample was placed in a vacuum oven and dried at 37 ℃ for 18 hours to remove residual chloroform.

Claims

1. A biomedical Zn-Mn-Cu series zinc alloy is characterized in that the alloy elements are calculated according to the weight percentage:

the alloy consists of 98.5-99.6% of Zn, 0.3-0.8% of Mn and 0.1-0.7% of Cu, wherein the alloy element with the largest content is Mn element.

2. The Zn-Mn-Cu-based zinc alloy according to claim 1, wherein a surface of the zinc alloy is further coated with a degradable polymer coating, a ceramic coating, or a drug coating; the thickness of each of the three coating layers is 0.01-5 mm.

3. The Zn-Mn-Cu-based zinc alloy according to claim 2, wherein the degradable polymer coating is prepared from at least one of the following materials: polylactic acid, polyglycolic acid, polycaprolactone, polycyanoacrylate, and poly-p-dioxanone.

4. The Zn-Mn-Cu-based zinc alloy according to claim 2, wherein the ceramic coating is prepared from at least one of: hydroxyapatite, tricalcium phosphate or tetracalcium phosphate.

5. The Zn-Mn-Cu-based zinc alloy of claim 2, wherein the drug coating is at least one of: rapamycin and its derivatives.

6. A method for preparing biomedical Zn-Mn-Cu-based zinc alloy according to any one of claims 1 to 5, characterized in that the method for preparing the zinc alloy comprises:

casting: pure Zn, pure Mn and pure Cu are used as raw materials, refined for 3-7 minutes at 750-800 ℃ in a vacuum induction smelting furnace protected by argon atmosphere, poured into a mold and cooled to room temperature;

plastic processing: the plastic working method includes at least one of rolling, extruding and drawing.

7. The method according to claim 6,

the rolling is divided into 2 rolling process routes, and finished plates can be prepared according to any one of the 2 process routes:

(1) hot rolling: the temperature is 250-380 ℃;

8. The method of claim 6, wherein the extrusion is carried out at a temperature of 200 to 350 ℃ and an extrusion ratio of 10 to 90.

9. The method according to claim 6, wherein the drawing temperature is from room temperature to 250 ℃ and the draw reduction is from 5 to 95%.