WO2015074354A1

WO2015074354A1 - New biodegradable magnesium-based alloy with antibacterial function

Info

Publication number: WO2015074354A1
Application number: PCT/CN2014/073600
Authority: WO
Inventors: 李扬德; 李卫荣; 林潇; 任玲; 杨柯
Original assignee: 东莞宜安科技股份有限公司; 中国科学院金属研究所
Priority date: 2013-11-21
Filing date: 2014-03-18
Publication date: 2015-05-28
Also published as: CN104645422A; CN104645422B

Abstract

A new biodegradable magnesium-based alloy with strong antibacterial function, the chemical components of the alloy as follows (in weight %): 0.05-2 of Cu and the balance of pure magnesium.

Description

Novel biodegradable magnesium alloy with antibacterial function

Technical field

The invention belongs to the field of biomaterials technology, and is particularly suitable for the field of medical metal materials, in particular to a novel biodegradable magnesium alloy with strong antibacterial function.

Background technique

In recent years, magnesium and its alloys have attracted great attention due to their good mechanical properties, biocompatibility and biodegradability, and are expected to become a new generation of biodegradable implant materials. Magnesium and its alloys have high specific strength and specific stiffness; the density of magnesium is about 1.74g/cm3, which is equivalent to the dense bone density of human bone (1.75g/cm3); the Young's modulus of magnesium is about 45GPa, closer. The elastic modulus of human bone (about 20 GPa) can significantly reduce the stress shielding effect produced by metal implants.

Magnesium and its alloys are very active in the body fluid environment, easily corroded in the body environment, thereby achieving biodegradation, which can avoid the pain and economic burden of the second surgery to remove the implant. The research and exploration of magnesium-based metals as medical implant materials can be traced back to the 1940s. Since the 1990s, with the continuous research on magnesium alloys, the technology to control the corrosion resistance and mechanical properties of alloys has been greatly improved, which makes it possible to be clinically applied as a medical implant material. A large number of experimental studies have shown the degradation and biosafety of magnesium and its alloys. Recently, biodegradable magnesium alloy implanted devices have entered clinical trials in some European countries, and the alloys have shown good clinical repair effects.

After the medical implant material is implanted in the body, bacterial infection is likely to occur around the implant, which often leads to treatment failure and causes great pain to the patient. At present, the method for enhancing the antibacterial property of implants is to perform surface treatment of the implant material, change the morphology, composition (loading antibacterial substance) or physical and chemical properties of the surface of the implant to make the surface have antibacterial adhesion. The performance of proliferation; another method is to make the implant material itself have antibacterial properties. For the degradable magnesium alloy, if the whole material has antibacterial properties, it can avoid or reduce bacterial infection during the degradation process after implantation into the body, thereby achieving better medical effects.

Copper (Cu) ions have a strong broad-spectrum antibacterial function for S. aureus and E. coli (E. Coli) and other bacteria have a strong killing effect. In 2005, F. Heidenau et al. added copper ions to the titanium dioxide coating on the surface of titanium alloy. The in vitro bacterial test showed that the copper-containing coating had obvious bactericidal effect. Yang Ke et al. of the Institute of Metal Research of the Chinese Academy of Sciences added copper to 317L stainless steel. Both in vitro and in vivo experiments have shown that copper-containing stainless steel has obvious antibacterial and antibacterial biofilm formation effects. Copper is an essential trace element in the human body, which regulates the metabolism of the human body and the functions of various enzymes. The lack of copper in the human body can lead to a series of diseases. Studies have also shown that trace copper plays an important role in promoting the health of the skeletal system, and rickets are associated with copper deficiency. In addition, copper deficiency can aggravate osteoporosis, and copper supplementation through the diet will reduce osteoporosis.

In light of the above background, the present invention adds an appropriate amount of copper to the magnesium to impart a strong antibacterial effect to the formed magnesium-copper alloy, thereby avoiding or reducing the occurrence of infection of the tissue surrounding the demagnetizable magnesium alloy implant.

Summary of the invention

The present invention provides a novel biodegradable magnesium alloy having a strong antibacterial function. The alloy of the present invention has the characteristics of being able to kill or inhibit bacteria surrounding the alloy implant on the basis of good biocompatibility and in vivo degradability, thereby avoiding or reducing the infection of tissues surrounding the implant. Further improve the medical effects of magnesium alloy implants.

The invention provides a novel biodegradable magnesium alloy with strong antibacterial function, the alloy having a biodegradable magnesium matrix, which ensures the degradation characteristics of the alloy in the body. Magnesium and its alloys have good biocompatibility and mechanical properties, which ensure the biosafety of magnesium alloy implants. The invention relates to a novel biodegradable magnesium alloy with strong antibacterial function, copper is the main antibacterial element in the alloy, and the copper content is controlled at 0.05-2 wt.% to ensure that the novel biodegradable magnesium alloy has With strong antibacterial properties, it has a controlled degradation rate and a certain mechanical properties. By adjusting the copper content, the degradation rate of the alloy can be controlled to achieve excellent antibacterial effect and good surrounding tissue reaction.

A small amount of copper element in the novel biodegradable magnesium alloy is dissolved in the magnesium matrix, and most of the copper is present in the magnesium copper precipitation phase. The novel biodegradable magnesium alloy simultaneously releases magnesium ions and appropriate amount of copper ions during the degradation process, and a certain amount of magnesium ions may contribute to human metabolism and biological reaction with surrounding tissues, and are metabolized by urine or the like. in vitro. The release of the right amount of copper ions achieves the antibacterial effect, and helps to supplement the body with copper ions and improve the adverse symptoms caused by the lack of copper ions.

The innovations and benefits of the present invention are:

1. The invention provides a novel biodegradable magnesium alloy implant material with strong antibacterial effect. The material itself has biodegradable properties, which can avoid problems such as secondary surgical removal of non-degradable implant materials and post-inflammation caused by wear in the body. At the same time, the new material has strong antibacterial properties, which effectively reduces the bacterial infection rate caused by surrounding tissue after material implantation.

2. The present invention provides an in vivo implant material that sustains the release of copper ions. The novel biodegradable magnesium alloy can continuously release an appropriate amount of copper ions to the periphery during degradation in the body. Copper ions are beneficial trace elements in the human body, especially for bone health. The release of the right amount of copper ions in the body can supplement the bone system with copper and can prevent some diseases caused by the lack of copper ions.

detailed description

The invention is further illustrated by the following examples, which are not intended to limit the invention.

The chemical compositions of the magnesium alloys of Examples 1-7 are shown in Table 1.

In all the examples, the copper-containing magnesium alloy was heated and melted in an induction furnace, the temperature was raised to 750 ° C, an appropriate amount of copper was added under nitrogen protection, and the temperature was maintained at 780 ° C for 30 minutes to finally prepare a Mg-Cu alloy. During the holding process, the molten alloy was continuously stirred under the protection of nitrogen. Cast at room temperature.

Table 1 Chemical composition design of magnesium alloy in the examples (wt.%)

Composition Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9

Cu 0.01 0.05 0.075 0.1 0.5 1 1.5 2 5

Mg balance

1. In vitro antibacterial performance test

According to "JIS Z 2801-2000 "Antibacterial processed products - Antibacterial test methods and antibacterial effects", GB/T 2591-2003 "Experimental methods and antibacterial effects of antibacterial plastic antibacterial properties" and other relevant standards stipulate that the bactericidal rate of the magnesium alloys shown in Table 1 after the action of common infectious bacteria (E. coli, Staphylococcus aureus) is quantitatively tested. The results of in vitro antibacterial performance test are shown in Table 2. The formula for calculating the sterilization rate is: Sterilization rate (%) = [(Control sample viable count - Magnesium alloy viable count) / Control sample viable count] × 100, control sample viable count is the number of viable cells after bacterial culture on the control sample (control sample is medium), The number of viable bacteria in the magnesium alloy refers to the number of viable cells after bacterial culture on the magnesium alloy.

2. Biosafety evaluation

According to the national standard GBT16886.5-2003 medical device biological evaluation, the cytotoxicity of the magnesium alloy of the example to L929 (mouse fibroblast) was evaluated. The results are shown in Table 2.

Table 2 Performance test results of the examples of magnesium alloys

Magnesium alloy antibacterial property

(sterilization rate, %) biosafety performance

Relative cell proliferation rate (%) Cytotoxicity level (≤ level 2 qualified)

Escherichia coli

Example 1 85 80 99 0

Example 2 90 87 95 0

Example 3 95 90 95 0

Example 4 98 97 90 0

Example 5 99 98 86 0

Example 6 99 99 80 0

Example 7 99 99 75 1

Example 8 99 99 75 1

Example 9 99 99 70 2

Claims

A novel biodegradable magnesium alloy having a strong antibacterial function, characterized in that the chemical composition of the magnesium alloy is as follows (% by weight), Cu: 0.05-2, and the balance is pure magnesium.

2. A novel biodegradable magnesium alloy having a strong antibacterial function according to claim 1, characterized in that the magnesium alloy has the advantage of being degradable in an in vivo environment and satisfies the premise of biosafety. Under the alloy, the antibacterial property of the alloy is significantly improved, thereby reducing the infection rate of the surrounding tissue in the clinical use of the degradable magnesium alloy implanted device, and improving the medical efficacy of the degradable magnesium alloy implanted device. The alloy can be widely used in various medical instruments for surgical implantation used in medical and clinical fields such as orthopedics, stomatology, and cardiovascular stents.