KR20180001020A - Bio materials having excellent corrosion resistance and method for manufacturing the same - Google Patents

Abstract

Provided are biomaterials with excellent corrosion resistance and a manufacturing method thereof. The biomaterials comprises: an alloy base material containing magnesium as a main component; and a corrosion resistance coating layer formed by coating a composition containing a biocompatible enzyme on at least a part of the alloy base material.

Description

TECHNICAL FIELD The present invention relates to a biomaterial having excellent corrosion resistance and a method of manufacturing the same.

TECHNICAL FIELD The present invention relates to a biomaterial excellent in biocompatibility, and more particularly, to a biomaterial excellent in corrosion resistance applied to an implant and a method of manufacturing the same.

Recently, magnesium has been used as an orthopedic implant because it is nontoxic and does not require secondary removal surgery. However, due to the low corrosion resistance of magnesium, corrosion progresses rapidly. As the corrosion of magnesium progresses, a large amount of hydrogen gas is released, and the hydrogen gas can not flow through the stagnation, so that local expansion occurs at the place where the implant is located. This leads to an inflammatory reaction in the soft tissue directly contacting the implant.

A number of studies have been conducted to make alloys using magnesium and other elements as a means to increase the corrosion resistance of magnesium. However, magnesium alloys are difficult to design because of the large variations in alloying elements such as toxicity, corrosion and mechanical properties.

It is an object of the present invention to provide a biomaterial which is resistant to inflammation in a soft tissue of a human body and which is non-toxic and which is excellent in corrosion resistance applicable to implants and a method of manufacturing the same, for solving various problems including the above- do. However, these problems are exemplary and do not limit the scope of the present invention.

According to one aspect of the present invention, a biomaterial excellent in corrosion resistance is provided. The biocompatible material having excellent corrosion resistance includes an alloy base material containing magnesium as a main component; And a corrosion-resistant coating layer formed by coating a composition containing a biocompatible enzyme on at least a part of the alloy base material.

In the biocompatible material having excellent corrosion resistance, the enzyme may include nicotinamide adenine dinucleotide (NADH) coenzyme.

In the biocompatible material excellent in corrosion resistance, the enzyme is selected from the group consisting of fumaric acid, coenzyme Q10, L-ascorbic acid, cytochrome c, pyruvate, And may include any one of oxalacetic acid, ferredoxin, glutathione, and cystine.

In the biomaterial excellent in corrosion resistance, electrons and hydrogen ions generated in the oxidation process of the alloy base material are reacted with each other using the corrosion-resistant coating layer to maintain the equilibrium state, thereby preventing corrosion of the alloy base material.

In the biomaterial excellent in corrosion resistance, the alloy base material includes pores, and the corrosion-resistant coating layer can be coated on at least a part of the surface of the alloy base material or can fill the pores.

According to another aspect of the present invention, there is provided a method for producing a biomaterial excellent in corrosion resistance. A method of manufacturing a biomaterial excellent in corrosion resistance includes the steps of: providing an alloy base material containing magnesium as a main component; And forming a corrosion-resistant coating layer by coating a composition containing a biocompatible enzyme on at least a part of the surface of the alloy base material.

In the method for producing a biomaterial excellent in corrosion resistance, the composition may be a hydrogel, a paste, a particle containing an enzyme, a film coated with the enzyme-containing particle, As shown in FIG.

In the method for producing a biomaterial excellent in corrosion resistance, the corrosion-resistant coating layer can be formed by any one of lamination, bonding, immersion, spraying, printing, spin coating, powder coating and spray coating.

According to an embodiment of the present invention, as described above, a biomaterial having excellent corrosion resistance, which can increase the corrosion resistance of a biomaterial in a chemical manner and inhibit the generation of hydrogen gas generated in a corrosion process of the biomaterial, The manufacturing method can be implemented. Of course, the scope of the present invention is not limited by these effects.

FIGS. 1 to 3 are graphs showing results of experiments on the amount of generated hydrogen of a biomaterial sample according to Comparative Examples and Examples of the present invention. FIG.
4 is a graph showing the results of current density measurement of a biomaterial sample according to Comparative Examples and Examples of the present invention.
FIG. 5 is a graph showing a result of confirming corrosion behavior of a biomaterial sample according to an embodiment of the present invention. FIG.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. It should be understood, however, that the invention is not limited to the disclosed embodiments, but may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, Is provided to fully inform the user. Also, for convenience of explanation, the components may be exaggerated or reduced in size.

The biomaterial excellent in corrosion resistance according to one embodiment of the present invention can inhibit the generation of hydrogen due to magnesium corrosion by using coenzyme which carries electrons and hydrogen in the human body. The biocompatible material having excellent corrosion resistance may include a corrosion-resistant coating layer formed by coating an alloy base material containing magnesium as a main component and a composition containing a biocompatible enzyme on at least a part of the alloy base material.

The alloy base material may contain various elements that make magnesium the main alloy element and improve the mechanical properties such as strength and hardness. The alloy base material may, for example, be fabricated in the form of a sheet, or may comprise an implant-processed structure for use in orthopedics, dentistry, and plastic surgery. The alloy base material may include pores for lighter weight in the base material itself. A corrosion resistant coating layer can be formed on at least a part of the alloy base material by coating a composition containing a biocompatible enzyme on at least a part of the surface of the alloy base material or by filling a composition containing the biocompatible enzyme into the pores of the alloy base material have. The size and distribution of the pores can be controlled in various ways depending on the characteristics required for the implant. The pores are filled with a biomaterial excellent in corrosion resistance, and thus can be used for any of orthopedics, dentistry, and plastic surgery.

Herein, the composition containing the biocompatible enzyme may be in the form of any one of hydrogel, paste, particles containing the enzyme, a film coated with the enzyme-containing particles and an emulsified particle can do. The method of forming the corrosion-resistant coating layer varies depending on the form of the composition. For example, if the composition containing the biocompatible enzyme is in the form of a hydrogel or a paste, a composition containing a biocompatible enzyme on the surface of the alloy base material is physically applied to the surface of the alloy base material As shown in Fig. On the other hand, if the composition containing the biocompatible enzyme is in the form of particles, it can be coated on the surface of the alloy base material by spraying spray coating method or the like or mixing with any solution.

In addition, although a composition containing a biocompatible enzyme can be directly coated on the surface of the alloy base material, in order to improve the adhesion of the composition, the surface of the alloy base material is surface-treated by an anodizing method or the like, The composition may also be coated.

Meanwhile, the enzyme constituting the composition may include a coenzyme of nicotinamide adenine dinucleotide (NADH). In addition, fumaric acid, coenzyme Q10, L-ascorbic acid, cytochrome c, pyruvate, oxalacetic acid, ferredoxin, ferredoxin, glutathione, and cystine.

For example, a coenzyme capable of carrying many hydrogen ions among the above enzymes can be used. Most preferably, the NADH coenzyme can be used as a coenzyme which transports a large amount of hydrogen ions. NADH coenzyme exists in the form of reduced NADH and oxidized NAD ⁺ , and is highly biocompatible because it exists in the human body.

Reduced NADH and oxidized NAD ⁺ exchange hydrogen ions and electrons and maintain chemical equilibrium as shown in Chemical Formula 1 below. The electrons generated in the magnesium corrosion and the nearby hydrogen ions chemically react with each other to maintain the chemical equilibrium expressed in Chemical Formula 1 as shown in Chemical Formula 2 and Chemical Formula 3 below. Therefore, it is judged that the concentration of electrons and hydrogen ions used for hydrogen generation gradually decreases and the rate of generation of hydrogen gas is lowered.

[Chemical Formula 1]

NADH ↔ NAD ⁺ + H ⁺ + 2e ^-

(Where H ⁺ is a hydrogen ion and e is an electron)

(2)

Mg ↔ Mg ²⁺ + 2e ^-

(Where Mh ²⁺ is magnesium ion and e is electron)

(3)

2H ⁺ + 2e ^- & lt ^{; /} RTI ^& gt ^; H ₂

(Where H ⁺ is a hydrogen ion, e is an electron, and H ₂ is a hydrogen gas)

That is, by the corrosion-resistant coating layer formed on the surface of the alloy base material, the corrosion of the alloy base material can be prevented by chemically reacting electrons and hydrogen ions generated in the oxidation process of the alloy base material and maintaining an equilibrium state.

According to another aspect of the present invention, there is provided a method of manufacturing a biomaterial excellent in corrosion resistance, comprising the steps of: providing an alloy base material containing magnesium as a main component; coating a composition containing a biocompatible enzyme on at least a part of the surface of the alloy base material; Thereby forming a corrosion-resistant coating layer.

The composition may include any one of a hydrogel, a paste, particles containing an enzyme, a film coated with the enzyme-containing particles, and an emulsified particle. A method of laminating a film according to the form of the composition, a method of physically bonding the composition to the pores or surfaces of the alloy base material by bonding the composition, a method of immersing the alloy base material in a solution, and the like. In addition, if the composition is in the form of particles, the corrosion-resistant coating layer can be formed by any one of spraying, printing, rotary coating, powder coating and spray coating. However, in addition to the above methods, a method of forming the corrosion-resistant coating layer according to the material constituting the composition or the surface condition of the alloy base material may be variously applied.

The enzyme constituting the composition may include a nicotinamide adenine dinucleotide (NADH) coenzyme. In addition, fumaric acid, coenzyme Q10, L-ascorbic acid, cytochrome c, pyruvate, oxalacetic acid, ferredoxin, ferredoxin, glutathione, and cystine. Here, the detailed description of the enzyme is the same as that described above with reference to the above Chemical Formulas 1 to 3 and thus will be omitted.

In addition, biocompatible implants can use a biomaterial excellent in corrosion resistance without any additional processing steps. For example, it can be understood that the magnesium alloy is processed into an implant form processed with an alloy base material containing magnesium as a main component, and then the composition containing the aforementioned biocompatible enzyme is coated on the surface of the processed magnesium alloy base material. In other words, the implants manufactured by processing the magnesium alloy in the implant manufacturing company can be delivered to the hospital. A corrosion resistant coating layer may be formed on the surface of the implant using a composition containing a biocompatible enzyme before the delivery of the delivered implant. Alternatively, when an implant coated with a corrosion-resistant coating layer on a surface of a magnesium alloy using a composition containing a biocompatible enzyme is directly supplied and used, a separate surface treatment process can be omitted and the time can be saved.

Meanwhile, a biocompatible metal, ceramics or polymer may be processed into a porous structure and then coated on the surface of the composition containing the biocompatible enzyme according to the present invention or filled with pores. For example, in addition to magnesium, the porous structure can use various materials such as titanium and titanium oxide. A corrosion-resistant coating layer may be formed using a composition containing a biocompatible enzyme according to a coating method suitable for the characteristics of various materials.

Hereinafter, an experimental example to which the technical idea described above is applied will be described in order to facilitate understanding of the present invention. It should be understood, however, that the following examples are for the purpose of promoting understanding of the present invention and are not intended to limit the scope of the present invention.

NADH coenzyme having different concentrations of 1 mM, 2.5 mM, 5 mM, and 10 mM were coated on the surface of pure magnesium (Mg), respectively, to prepare biomaterial samples having excellent corrosion resistance in Examples 1 to 4.

Further, the surface of pure magnesium (Mg) was coated using PEGDA hydrogel to prepare a biomaterial sample having excellent corrosion resistance in Example 5. [

On the other hand, for comparison, pure magnesium was used as a biomaterial sample of Comparative Example 1, and Comparative Examples 2 to 7 prepared by using NAD ⁺ ions having different concentrations of pure magnesium at 1 mM, 10 mM and 15 mM, respectively 4 < / RTI >

The amount of hydrogen generated in each of Examples 1 to 4 and Comparative Examples 1 to 4 was measured to compare the degree of corrosion of magnesium. The electrochemical evaluation was used to compare the influence of the current density according to the corrosion resistance of magnesium Respectively.

FIGS. 1 to 3 are graphs showing results of experiments on the amount of generated hydrogen of a biomaterial sample according to Comparative Examples and Examples of the present invention. FIG.

Referring to FIG. 1, in the immersion corrosion experiment conducted using NAD ⁺ ions for the first time, the corrosion amount of magnesium was measured through the amount of generated hydrogen. As a result, in all of Comparative Examples 1 to 4, And it was confirmed that it progressed rapidly.

2, when a NADH coenzyme other than NAD ⁺ ions was used, the biomaterial samples having excellent corrosion resistance in Examples 1 to 3, in which the coenzyme was treated as the corrosion progressed, were compared with those of Comparative Example 1 in which the coenzyme was not treated It was confirmed that the hydrogen generation amount was smaller than that of the pure biomaterial sample.

Referring to FIG. 3, it was confirmed that corrosion of the biomaterial sample excellent in corrosion resistance of Example 5 was not accelerated compared with the biomaterial sample of Comparative Example 1. FIG. It is understood that this is sufficient to capture hydrogen gas in the hydrogel, which does not lead to corrosion of the biomaterial.

FIG. 4 is a graph showing current density measurement results of a biomaterial sample according to a comparative example and an example of the present invention, and FIG. 5 is a graph showing a result of checking corrosion behavior of a biomaterial sample according to an embodiment of the present invention.

Referring to FIG. 4 and the following Table 1, the electrochemical evaluation of the biomaterial samples of Comparative Example 1 and Examples 1 to 3 confirmed that the NADH coenzyme was coated on the surface of the biomaterial, And the current density is low.

Corrosion Potential (V) Corrosion density
(μA / cm 2) Polarization
(Mm / y) Comparative Example 1 -1.7826 49.2 4.45 Example 1 -1.7684 25.4 2.29 Example 2 -1.7493 4.56 0.4 Example 3 -1.7925 30.7 2.78

Referring to FIG. 5, the corrosion resistance of the biomaterial samples of Examples 1 to 4 coated with NADH coenzyme was examined by comparing the corrosion behavior of each sample using OCP (Open Circuit Potential) It is confirmed that it is better than the material sample.

As described above, magnesium, which is widely used as an orthopedic implant, has a property of being degraded and absorbed in vivo and is known to induce bone formation at the same time. However, a large amount of hydrogen gas generated due to the progress of the corrosion of magnesium may not flow through the retentate, resulting in a local expansion, thereby causing an inflammatory reaction to the soft tissue directly contacting with the implant.

In order to solve this problem, the present invention can prevent the inflammation reaction by controlling the generation of hydrogen gas due to magnesium corrosion by using a coenzyme which carries electrons and hydrogen in the human body. The present invention can prevent local expansion of hydrogen gas generated as corrosion proceeds by suppressing initial corrosion by locally fixing a composition containing a coenzyme processed in the form of a hydrogel to a magnesium-containing implant . That is, by using a coenzyme which functions to transport electrons and hydrogen in the human body, hydrogen generation due to corrosion of the biomaterial can be suppressed.

While the present invention has been described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Accordingly, the true scope of the present invention should be determined by the technical idea of the appended claims.

Claims (8)

An alloy base material containing magnesium as a main component; And
A corrosion-resistant coating layer formed by coating a composition containing a biocompatible enzyme on at least a part of the alloy base material;
/ RTI >
Biomaterial with excellent corrosion resistance. The method according to claim 1,
Wherein the enzyme comprises a nicotinamide adenine dinucleotide (NADH) coenzyme.
Biomaterial with excellent corrosion resistance. The method according to claim 1,
The enzyme may be selected from the group consisting of fumaric acid, coenzyme Q10, L-ascorbic acid, cytochrome c, pyruvate, oxalacetic acid, ferredoxin, glutathione, and cystine.
Biomaterial with excellent corrosion resistance. The method according to claim 1,
Wherein the corrosion resistance of the alloy base material is prevented by reacting electrons and hydrogen ions generated in the oxidation process of the alloy base material with each other using the corrosion resistant coating layer to maintain an equilibrium state,
Biomaterial with excellent corrosion resistance. The method according to claim 1,
Wherein the alloy parent material comprises pores,
Wherein the corrosion-resistant coating layer is coated on at least a part of the surface of the alloy parent material,
Biomaterial with excellent corrosion resistance. Providing an alloy base material containing magnesium as a main component; And
Forming a corrosion-resistant coating layer by coating a composition containing a biocompatible enzyme on at least a part of the surface of the alloy base material;
/ RTI >
A method for producing a biomaterial excellent in corrosion resistance. The method according to claim 6,
The composition may be in the form of any one of hydrogel, paste, particles containing the enzyme, a film coated with the enzyme-containing particles, and sprayable particles.
A method for producing a biomaterial excellent in corrosion resistance. The method according to claim 6,
The corrosion-resistant coating layer may be formed by any one of the methods of lamination, bonding, immersion, spraying, printing, spin coating, powder coating and spray coating.
A method for producing a biomaterial excellent in corrosion resistance.

Images