WO2016145955A1

WO2016145955A1 - Corrosion-resistant, high strength and ductility zn-fe-re zinc alloy degradable by human body and applications of the alloy

Info

Publication number: WO2016145955A1
Application number: PCT/CN2016/073435
Authority: WO
Inventors: 周功耀; 宫海波; 屈功奇
Original assignee: 西安爱德万思医疗科技有限公司
Priority date: 2015-03-13
Filing date: 2016-02-04
Publication date: 2016-09-22
Also published as: CN104651664A; CN104651664B

Abstract

A corrosion-resistant, high strength and ductility Zn-Fe-Re zinc alloy degradable by the human body and applications of the alloy. The zinc alloy comprises elements Zn, Fe, and RE, where the mass percentage of element Zn is: 82-99.997%, the mass percentage of element Fe is: 0.002-10%, and the mass percentage of element RE is: 0.001-8%.

Description

Title: A human body degradable corrosion resistant high strength and toughness Zn-Fe-RE zinc alloy and its application

Technical field

[0001] The present invention relates to a human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy, which belongs to the technical field of medical implant materials.

Background technique

[0002] Zinc ions are essential nutrients for the human body and participate in many metabolic activities of the human body. The American Clinical Innovation Agency (ACI) recommends that the body must consume 2.5 to 6.4 mg of zinc per day, and adults who consume about 300 mg of zinc per day may have some toxic effects. A zinc-based degradable bone nail releases about 0.3 to 0.3 mg of zinc per day. Even if all of these zinc ions are released into the blood vessels, they are far below the necessary intake. That is to say, the zinc ions released by the degradation of the zinc-based degradable orthopedic implant device do not cause systemic toxicity. Studies have also found that zinc ions are transported very quickly in human tissues, so zinc enrichment, cytotoxicity or necrosis does not occur near zinc-based degradable orthopedic implant devices.

[0003] Zinc ions have many functions in the human body and are very important to the human body. One of the most important functions is to promote bone tissue growth. The researchers found that zinc ions can activate the aminoacyl tRNA synthetase in osteoblasts and effectively inhibit the differentiation and growth of osteoclasts. Therefore, the presence of zinc ions not only promotes the increase of bone calcium content, but also facilitates bone. The increase in collagen content suggests that zinc ions have a direct osteogenesis. In addition, studies have found that zinc ions promote the binding of cartilage oligomeric matrix proteins to collagen and are catalytic elements for soft bone growth and regeneration.

[0004] Conventional vascular stents are generally made of non-degradable metal. The disadvantage is that the metal is not degradable and cannot be removed, and retention in the blood vessel tends to cause late thrombosis. A large number of clinical cases have confirmed that the thrombosis rate of patients with such stents is as high as 3%~9<3⁄4 after 1~5 years, and the mortality after thrombosis is as high as 30%. Bone nails and bone plates are commonly used medical implants for fixation of fractures and ligament injuries. Traditional bone nails and bone plates cannot be removed by non-degradable metals. Secondary surgery is required, which causes great trauma to patients. At the same time, the strength of traditional metal materials is too high, which tends to cause stress shielding, which makes it difficult for injured bone tissue to regenerate and heal.

[0005] Degradable medical materials in human body are becoming the focus of research and development, among which degradable polymer materials, Pure iron and iron-based alloys, pure magnesium and magnesium-based alloys are the most in-depth materials studied in recent years. Degradable polymer materials are too low in strength, and breakage accidents often occur during clinical use, and clinical applicability is greatly limited. The strength and toughness of pure iron and iron-based alloys are much higher than those of polymer materials, but the degradation rate of iron is too slow, and the complete degradation of the day may last for several years. More seriously, the volume of rust-like substances generated during the degradation of iron has expanded several times and has a significant migration tendency. The degradation products of pure magnesium and magnesium-based alloys are non-toxic and degradable, but their corrosion resistance is very poor, and they are quickly degraded in the human body, which cannot provide sufficient mechanical support.

[0006] Pure zinc and its alloys are also degradable materials in the human environment, but the application of medical materials still has the disadvantages of low mechanical strength and uncontrollable degradation rate. Currently, it is improved by adding other substances to it. Mechanical properties and regulation of degradation rate, such as Ce, Mg, Cu, Ca added to the zinc of application No. 201310756776.1, but the zinc alloy material prepared by the application has low plasticity, and it has not been found that low-cost iron is used as zinc. Add materials and use them as biomedical materials.

technical problem

[0007] The object of the present invention is to address the deficiencies of the existing medical implant materials, and provide a low cost, high strength, good plasticity, controllable degradation rate, no degradation or migration of degradation products, and the same can be Human body degraded Zn-Fe-RE zinc alloy and its application.

Problem solution

Technical solution

[0008] The present invention provides a human body degradable corrosion-resistant high-strength Zn-Fe-RE-based zinc alloy, wherein the zinc alloy includes Zn, Fe and RE (Rare Earth Element) elements, wherein Zn element The mass percentage is: 82~99.997<3⁄4; the mass percentage of Fe element is: 0.002~10<3⁄4; the mass percentage of RE element is: 0.001~8<3⁄4.

[0009] Based on the composition of the above alloy materials, in order to optimize the mechanical properties and the biocorrosion properties, we optimize the alloy material, the mass percentage of Zn element in the zinc alloy is: 87 to 99.993%, and the mass percentage of Fe is 0.005. ~8<3⁄4, the mass percentage of RE is 0.002~5<3⁄4.

[0010] More preferably, the elemental composition of the alloy material further includes a trace element, wherein the trace element is at least one of Mg, C a, Sr, Li, Si, and Mn, and the mass ratio of the trace element to Zn 0 to 0.054: 1.

[0011] Based on the composition of the above alloy materials, in order to optimize the mechanical properties and biocorrosion properties, we Further optimized, the mass ratio of the trace element to the Zn element in the zinc alloy is 0 to 0.025:1.

[0012] The human body degradable high-strength and tough Zn-Fe-RE zinc alloy prepared by the above invention is prepared into a degradable medical implant by a conventional method in the art.

[0013] Therefore, the present invention also provides a human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy for use in preparing a degradable medical device material.

[0014] Preferably, the degradable medical device is an implanted stent, an orthopedic implant device, a dental implant device, a surgical suture or an anastomat. The implanted stent comprises a vascular stent, a tracheal stent, a urethral stent, an esophageal stent, an intestinal stent or a biliary stent; the orthopedic implant device comprises a fixing screw, a fixed rivet, a bone plate, a bone sleeve, an intramedullary nail or a bone tissue repairing stent; The stapler includes an intestinal stapler, a vascular anastomat or a nerve stapler.

Advantageous effects of the invention

Beneficial effect

[0015] 1. The added material is low in cost, and the degradation products of the prepared alloy materials can be metabolized by the human body; [0016] 2. The corrosion resistance is much higher than that of the magnesium alloy, the degradation rate is controllable, and the degradation products are not expanded or migrated. ;

[0017] 3. The alloy material has good strength and toughness. Iron and rare earth elements have the dual functions of solid solution strengthening and precipitation strengthening at room temperature and high temperature. They can form a variety of stable intermetallic compounds with Zn, strengthen the effect, and refine grains and improve plasticity. The strength and toughness of the alloy material.

Brief description of the drawing

DRAWINGS

[0018] FIG. 1 is a schematic view showing the microstructure of an alloy of the present invention degraded in an animal.

Embodiments of the invention

[0019] The present invention will be further described below in conjunction with specific embodiments.

[0020] Due to differences in biological environment and functional requirements, different degradable implant devices have different requirements for degradation rate. The corrosion potential of zinc is -0.76V, and the corrosion potential of iron is -0.44V. Therefore, the addition of iron as an alloying element to zinc can produce two opposite effects. The first effect is that iron is dissolved in the matrix zinc. , the corrosion potential of zinc decreases, the corrosion resistance increases, and the degradation rate decreases; the second effect is iron and The zinc element forms a particulate compound, forms a microbattery with the matrix zinc, has reduced corrosion resistance, and has an increased degradation rate. By adjusting the iron content, it is possible to control the degradation rate of the zinc alloy to suit the requirements of medical implant materials.

Embodiment 1

[0022] A human body degradable corrosion-resistant high-strength Zn-Fe-RE-based zinc alloy of the present invention has an elemental composition and mass percentage of: Zn 82<3⁄4, Fe 10%, and Nd 8<3⁄4.

[0023] Example 2

[0024] A human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy of the invention has an elemental composition and mass percentage of: Zn 99.997%, Fe 0.002%, Ce 0.001%.

Embodiment 3

[0026] A human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy having a composition and mass percentage of Zn 99.975%, Fe O.01%, Y 0.015%.

Embodiment 4

[0028] A human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy of the present invention has an elemental composition and mass percentage of: Zn 97%, Fe 1%, Nd 1%, Li 1<3⁄4.

[0029] Example 5

[0030] A human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy of the invention has an elemental composition and mass percentage of: Zn 95.5<3⁄4, Fe 2%, Ce 2%, Mg 0.5<3⁄4 .

Example 6

[0032] Using the Zn-Fe-RE zinc alloy prepared by the conventional techniques in the prior art using the elemental compositions in Examples 1 to 5, a human body liquid immersion test was carried out to test the degradation rate of the Zn-Fe-RE zinc alloy. Result list

[0033] Table 1

[] Serial number

I Example 1 0.44 Example: 2 0.08

3: Example 3 0.12

4 Example 4 0.2

5 Example 5 0.21

6 pure magnesium 3.53

WE 3 magnesium alloy 3.S

[0034] This embodiment studies the in vitro degradation mechanism and degradation performance of a zinc-based Zn-Fe-RE alloy according to the ASTM-G31-72 standard test method, and simulates a human body fluid environment at 37 degrees Celsius to simulate a human body fluid environment. In the environment, the degradation rate of Zn-Fe-RE zinc alloy is slow and controllable.

[0035] Example 7

The Zn-Fe-RE-based zinc alloy prepared by the conventional techniques in the art was used for the elemental compositions in Examples 1 to 5, and the tensile strength test results are shown in Table 2.

[0037] Table 2

In this example, according to the GB/T228.1-2010 test standard, the tensile mechanical properties of the Zn-Fe-RE zinc alloy examples 1 to 5 were tested, and the results are shown in Table 2. It is found that the Zn-Fe-RE zinc alloy has the highest yield strength. Up to 340MPa, the elongation at break is as high as 29.5%. This is due to the fine distribution of fine particles of iron, rare earth and zinc, which can improve the thermal stability and creep resistance of the zinc alloy. The element further improves the mechanical properties of the material.

Example 8

The Zn-Fe-RE-based zinc alloy prepared by the conventional techniques in the art was subjected to the in vitro cytotoxicity test using the elemental compositions in Examples 1 to 5.

[0041] In this example, an in vitro cytotoxicity test was performed on a zinc alloy according to GB/T 16886.5-2003, and fibroblast L-929 was cultured in an extract of a zinc alloy degradation product, and cells of 24 hours and 72 cells were measured. The activity, and compared with the cell activity of the culture in the conventional culture solution, it was found that the cell activity in the zinc alloy degradation product extract was higher than 90%, and the cell morphology was very healthy, so the zinc alloy degradation product was considered to be a cell. The activity has no effect and the cells have no toxic reaction to the zinc alloy degradation products.

Example 9

[0043] The in vivo implantation test was carried out using the zinc alloy prepared in Example 1. The zinc alloy prepared in Example 1 was made into filaments and implanted into the abdominal aorta of New Zealand white rabbit for 12 months. As shown in Fig. 1, the bright area in the figure is the cross section of the alloy wire, and the gray area close to the alloy wire is The degradation product, the black area is a resin material for fixing the sample. It was found that the alloy wire did not show any expansion and migration after degradation, and its degradation products remained in the original shape, and no particles or fragments were found. The alloy materials prepared in the other examples were also subjected to in vivo implantation tests, and the obtained microscopic images were similar to those of the zinc alloy of Example 1.

The above is a further detailed description of the present invention in connection with the specific embodiments, and the specific embodiments of the present invention are not limited to the description. It will be apparent to those skilled in the art that the present invention may be practiced without departing from the spirit and scope of the invention.

Claims

Claim

A human body degradable corrosion-resistant high-strength Zn-Fe-RE zinc alloy, characterized in that: the zinc alloy comprises Zn, Fe and RE elements, wherein the mass percentage of Zn element is: 8 2~ 99.997<3⁄4; The mass percentage of Fe element is: 0.002~10<3⁄4; the mass percentage of RE element is: 0.001~8<3⁄4.

The human body degradable corrosion-resistant high-strength Zn-Fe-RE-based zinc alloy according to claim 1, wherein: the mass percentage of Zn element in the zinc alloy is: 87 to 99.993%, Fe element The mass percentage is: 0.005~8%, the mass percentage of RE element is: 0.002~5<3⁄4 ₀

The human body degradable corrosion-resistant high-strength Zn-Fe-RE-based zinc alloy according to claim 1 or 2, wherein: the zinc alloy further comprises trace elements, and the trace elements are Mg, Ca, At least one of Sr, Li, Si and Mn, the mass ratio of the trace element to the Zn element is 0 to 0.054:1.

The human body degradable corrosion-resistant high-strength Zn-Fe-RE-based zinc alloy according to claim 3, wherein: the mass ratio of the trace element to the Zn element in the zinc alloy is 0 to 0.025:1

[Claim 5] The human body degradable corrosion resistant high strength and toughness Zn-Fe- according to any one of claims 1 to 4

Application of RE-based zinc alloys in the preparation of biodegradable medical device materials.

[Claim 6] The use of a human body degradable corrosion-resistant high-toughness Zn-Fe-RE-based zinc alloy according to claim 5 for preparing a degradable medical device material, characterized in that: the degradable medical device is Implanted stent, orthopedic implant device, dental implant device, surgical suture or stapler, wherein the implant stent comprises a vascular stent, a tracheal stent, a urethral stent, an esophageal stent, an intestinal stent or a biliary stent; orthopedic implant device These include fixation screws, fixation rivets, bone plates, bone sleeves, intramedullary needles or bone tissue repair stents; staplers include intestinal staplers, vascular anastomoses or nerve staplers.