KR101395141B1 - Manufacturing method of alloy composition for bio-material - Google Patents

Abstract

The objective of the present invention is to provide a method for manufacturing an alloy composition for a bio-material, which enables magnetic resonance imaging. In order to achieve the above-mentioned objective, the alloy composition for a bio-material, which is inserted into a human body and used as a structure, includes 20 -35 wt% of manganese and remaining amount of iron. The alloy composition for a bio-material of the present invention has iron as a basic component, thereby providing the advantages of iron, and, further, has low magnetic susceptibility by the action of manganese, thereby providing the advantages of the alloy for a biodegradable bio-material and conducting imaging through a magnetic resonance device.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method of manufacturing an alloy for a biomaterial,

The present invention relates to an alloy composition for a biomaterial and a method of manufacturing the same, and more particularly, to an alloy composition used as a structure in a human body and a method of manufacturing the same.

With the rapid development of the medical field in recent years, various metallic materials are used inside the human body to restore or replace the functions of the lost or damaged body organs.

For example, in the case of a tooth missing, there is an implant that replaces a lost tooth with titanium metal, and such an implant is one of the currently widely used techniques due to its many applications.

Also, stents disclosed in Japanese Patent No. 442330 can be mentioned. The stent is inserted into the lumen of the lumen such as blood vessels, bile track, and esophagus of the human body due to diseases, trauma, and surgery, thereby securing the passage of the lumen so that the stent can perform a smooth body function.

Such stents are known to have various structures, and most of them are made of a cylindrical structure. When the stent is bent in a predetermined shape according to its function and an external force is applied by a wire member having its own elasticity, the stent contracts or expands temporarily. The elastic stent having the function of restoring the original shape and the wire member exhibiting the constant firing are largely divided into the plastic stent which maintains the expanded or contracted state due to the self-sintering once the external force is applied, Is selected and used.

In the case of stents used for blood vessels, stent implantation is actively performed in the advanced atherosclerosis of the coronary arteries, peripheral blood vessels and cerebral blood vessels. However, the greatest disadvantage of stenting is in-stent restenosis, which results in an interaction between the stent surface and blood, resulting in neointimal hyperplasia, a response to permanent mechanical stimulation of vascular tissue. However, there is a disadvantage that the incidence of late stenosis and thrombosis increases again from the time of drug elution, although restenosis is prevented during drug elution.

In addition, improvements in the properties of material materials have been steadily attempted and have explored material materials that satisfy both strength and flexibility, biodegradability, biocompatibility, and magnetosensitivity.

For example, a cylinder made of pure iron was machined through laser cutting to produce the first corrosion-resistant iron stent with the same design as a permanent stent, and showed the possibility and safety as a biodegradable metal stent. In particular, the pure iron stent implanted in the rabbit and pig aorta maintained the patency for 6-18 months without any thrombus formation or side effects. There was no evidence of inflammation or neointimal hyperplasia or systemic toxicity. However, the decomposition rate was very low, so it was no different from a permanent stent in terms of corrosion. The medically appropriate decomposition rate is 12-24 months, which is considered to be somewhat slower than the magnesium alloy.

Iron alloys have the disadvantages of high resistance to biodegradation and magnetic susceptibility, resulting in artifacts in magnetic resonance imaging (MRI), making artifacts in magnetic resonance imaging devices and limiting the ability to image blood vessels and stents themselves.

Magnetic resonance imaging is gradually expanding clinical applications and is now an essential part of imaging diagnosis. Magnetic resonance imaging (MRI) is a method of acquiring anatomical, physiological, and biochemical information images of a body using the phenomenon of spin relaxation of hydrogen atoms in a magnetic field. It is a non-invasive and real- It is one of diagnostic equipment. If the magnetic resonance imaging of the iron-based stent, which is considered to be the most promising biodegradable stent material, is not possible, invasive catheterization instead of noninvasive magnetic resonance angiography none. Therefore, an iron alloy is inevitably required to make magnetic resonance imaging possible.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and an object of the present invention is to provide a biodegradable composition capable of magnetic resonance imaging.

It is another object of the present invention to provide a method for manufacturing a biodegradable alloy capable of magnetic resonance imaging.

In order to accomplish the above object, the present invention provides an alloy composition for a biomaterial inserted into a human body, wherein the manganese is 20 wt% to 35 wt%, and the remainder is iron.

In addition, the present invention provides a method for manufacturing an alloy for a biomaterial inserted into a human body and used as a structure, comprising: mixing a composition comprising 20 wt% to 35 wt% of manganese and the balance iron; A melting step of heating and melting the mixture of the composition mixing step; A casting step of putting the molten alloy in the melting step into a metal mold for molding; A plastic working step of processing the shaped alloy into a required shape; And a heat treatment step of heat-treating the material processed in the plastic working step.

Preferably, said melting step is carried out in a vacuum high-frequency induction furnace under argon at a pressure of 300 mbar.

Preferably, the plastic working step is performed by heating the material to 800 ° C to 1000 ° C and then processing the material into a specific shape.

Preferably, the heat treatment step is performed in such a manner that the material is treated at a temperature of 600 DEG C for 1 hour and then cooled rapidly with water.

Preferably, the heat treatment step is characterized by aging treatment at 600 ° C for 10 hours after annealing at 700 ° C for 10 minutes.

The alloy composition for a biomaterial according to the present invention is composed of iron as a basic component and has merits of iron and low magnetic susceptibility due to the action of manganese so that the advantage of biodegradable bio-material alloy and imaging through magnetic resonance apparatus are simultaneously performed There is an effect that can be done.

1 is a process diagram of a method for producing an alloy for a biomaterial according to the present invention,
2 is a photograph of the tissue after the casting process of the present invention,
FIG. 3 is a photograph of tissues of embodiments according to the present invention,
4 is an X-ray analysis graph of embodiments according to the present invention,
FIG. 5 is a graph showing signal intensity changes according to manganese content at 63.0-66.0 degrees in the 2theta period representing alpha martensite phase in FIG. 4,
6 is a graph showing signal intensity changes according to the content of manganese at 49.0-52.0 degrees in the 2 theta section representing the gamma-austenite phase in FIG. 4,
7 is a graph showing signal intensity changes according to the content of manganese in the 2theta section 46.0-48.0 degrees representing epsilon martensite phase in Fig. 4,
Figure 8 is a graph of the hardness of embodiments according to the present invention,
Figure 9 is a magnetic resonance photograph of embodiments according to the present invention.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

The alloy composition for a biomaterial according to the present invention is characterized in that manganese is added based on iron.

The alloy composition for a biomaterial according to the present invention is characterized in that 20 to 35% by weight of manganese (Mn) is added based on iron.

The manganese (Mn) is added for the change of the magnetosensitivity. When the Mn is less than 20% by weight, the magnetic susceptibility is insignificant. When it exceeds 35% by weight, the mechanical properties of iron are weakened. proper.

Hereinafter, a method for producing an alloy for a biomaterial according to the present invention will be described.

The manufacturing method according to the present invention comprises a composition mixing step (S1), a melting step (S2), a casting step (S3), a forging step (S4) and a heat treatment step (S4).

First, the composition mixing step (S1) is performed.

In the composition mixing step (S1), 20 to 35 wt% of residual iron of manganese is prepared and mixed with each other.

Most of iron and manganese used are high purity electrolytic iron and electrolytic manganese. High purity pure iron may be used, but if necessary, steel having a carbon content of 35% or less may be used. At this time, the total weight of the steel is calculated based on the content of iron present therein and mixed.

After the composition mixing step (S1) is performed, a melting step (S2) is performed.

The melting step (S2) is carried out in a high frequency induction furnace under an argon atmosphere at a pressure of 300 mbar. At this time, the temperature of the electric furnace is about 1530 ° C. to 1550 ° C. and the melting time is differently performed depending on the amount of the raw material.

In the melting step (S2), the molten metal alloy is injected into a separate metal mold and a casting step (S3) is performed to form the metal alloy into a specific shape.

In the casting step (S3), an alloy may be manufactured in various shapes depending on the shape of the mold, and a metal mold of various materials may be used, but a metal mold is preferably used.

The alloy produced in the casting step (S3) is processed into a final shape through a forging step (S4). After the casting process, homogenization heat treatment is performed to soften the casting structure and remove segregation. The homogenization heat treatment generally proceeds in the austenite region, which is a single-phase region. Therefore, heat treatment at 1000 ° C to 1200 ° C for removing the segregation is performed, and this is because the temperature at the highest point not to be re- It utilizes the characteristics that can be actively made. However, in this case, it is important to secure the optimal time for heat treatment because the tissue is not cleaned. The holding time is set to a heat treatment time of 30 to 60 minutes per 2.54 mm based on the longest thickness of the product after a temperature rising rate of 5 to 20 / min. The cooling after the homogenization heat treatment is based on air cooling, and the initial cooling and lower cooling below the process line are selected as possible conditions.

As shown in FIG. 2, it can be seen that the resinous phase and the resin are accompanied by segregation of the material in the cast state, but after the heat treatment, the casted structure such as dendritic phase is removed and the grain boundary is confirmed in the specimen.

In the plastic working step (S4), the material is heated to 1000 deg. C, and then the pressing force is applied at 300 MPa. It is preferable that the forging die is made of a durable metal unlike the casting mold, It can be applied differently depending on the shape of the material.

The annealing step (S5) is performed so that the alloy produced in the plastic working step (S4) has a proper tissue characteristic for the final product.

The heat treatment step (S5) of the present invention is divided into two types and each is performed.

First, the first heat treatment can obtain a microstructure composed of the tempered martensite structure, the remaining gamma austenite, and the precipitate in such a manner that the material is treated at a temperature of 600 ° C for 1 hour and then rapidly cooled with water.

The second heat treatment is an annealing operation in a gamma phase region at 700 ° C for 10 minutes and aging at 600 ° C for 10 hours to obtain a phase structure between metals having a large amount of gamma austenite.

Of course, the two types of heat treatment are performed in air.

When the above steps are completed, an alloy having a required heat-treated structure can be obtained.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments of the present invention.

Example  One

10% by weight of manganese and the balance of iron, dissolved in a high-frequency induction furnace with an atmospheric pressure of 300 mbar and placed in a copper mold, and then a rod-shaped specimen having a size of 35 mm × 100 mm is cast. For softening and homogenization of casting tissue After homogenization heat treatment at 1000 ℃ ~ 1200 ℃, specimens were prepared.

Example  2

Manganese alloy containing 15 wt% of residual iron, and the remainder was a test piece as in Example 1.

Example  3

Manganese alloy with 20 wt% of residual iron, and the other test pieces were prepared in the same manner as in Example 1.

Example  4

Manganese alloy containing 25 wt% of residual iron, and the other test pieces were prepared in the same manner as in Example 1.

Example  5

Manganese alloy containing 30 wt% of residual iron, and the rest were the same as in Example 1. [

Example  6

Manganese alloy containing 35 wt% of residual iron, and the rest were the same as in Example 1. [

Test Example  1 (tissue analysis)

The specimens prepared in the above examples were processed into a disk having a diameter of 10 mm and a height of 3 mm, and the surface was processed to a polished surface by diamond processing, and then the surface was observed with an optical microscope.

As a result of observation, it was confirmed that each of Examples (Example 1: Fe10Mn, Example 2: Fe15Mn, Example 3: Fe20Mn, Example 4: Fe25Mn, Example 5: Fe30Mn, Example 6: Fe35Mn As shown in FIG. 3, it can be seen that the dark portion is composed of ferromagnetic alpha 'martensite and the bright portion is composed of paramagnetic austenite and epsilon martensite.

Test Example  2 (X-ray analysis)

The above examples were analyzed by X-ray diffractometer using Cu Kα radiation and the composition and amount of various phases present in the sample. The results of the analysis are shown in Fig. 4, and the results of analysis according to each organization are shown in Fig. 5 (alpha 'martensite), Fig. 6 (gamma austenite) and Fig. 6 (epsilon martensite). As can be seen in the above figures, each embodiment is composed of ferromagnetic alpha martensite, paramagnetic gamma austenite, and epsilon martensite, and the type and distribution of each phase depend on the manganese content. I could see the reception. And the phase of ferromagnetic alpha martensite is highest in Fe10Mn and decreases with increasing manganese content. The epsilon phase showed the highest value at Fe25Mn, and the gamma phase was continuously increased with increasing manganese content. As a result, it was confirmed that the magnetic susceptibility was low overall.

Test Example  3 (hardness test)

The hardness of the above examples was tested by loading a 1 kgf load with a Vickers indenter using a micro hardness tester (Shimadzu HMV-2T) for 10 seconds and then averaging the ten measurements. The test results are shown in Fig. As shown in FIG. 8, it was found that the hardness of the stent was higher than that of the stent, and the hardness was the highest in Example 4.

Test Example  4 (magnetic resonance imaging)

A rod-like specimen with a diameter of 4 mm and a length of 15 mm was fixed in a fixture and placed in a parallel / perpendicular position to a static magnetic field. Magnetic resonance images of the axial, tubular, and occipital planes of the three-dimensional SPGR were recorded. The filming conditions were TE 3.3-8.9ms (minimum), TR 25.0ms, flip angle 20 degrees, 256X256 pixels, FOV 200mmX200mm, slice thickness 2.4mm, and Bandwidth 15.63.

The photographed image is shown in Fig. As shown in FIG. 9, a relatively large artifact was observed in Example 3 (Fe20Mn), and in Examples 4 and 6, it was confirmed that the size of artifacts gradually decreased with the content of manganese.

Therefore, it was confirmed that the content of manganese is suitable to an actual magnetic resonance method from 20 wt% to 35 wt%.

Test Example  5 (Cytotoxicity test)

MTT assay was conducted according to the Korea Food & Drug Administration 's Common Criteria for Biological Safety of Medical Devices. Fibroblasts are cultured in 37 ° C Dulbecco's medium (DMEM) containing 5% carbon dioxide. According to the ISO 10993-12 guidelines, the culture medium is prepared by culturing in a serum-free DMEM culture medium having a surface area of 1 cm ² / ml and an extraction culture ratio of 72% in a 5% carbon dioxide, 37 ° C environment. The extracted culture medium is stored at 4 ° C prior to the cytotoxicity test. For the control group, the DMEM medium containing only 10% dimethylsulfoxide is used as the positive control group. The cells are cultured for 24 hours in a 96-well cell culture dish which can contain 5 × 10 ³ cells per 100 μl culture medium per each cadmium. Then, change the culture medium to 100 μl of the extract culture medium. Cells were cultured in 96 cell culture dishes in 5% CO2, 37? Environment for 1 day, 2 days, and 4 days, and then observed with an optical microscope. MTT 10 μl was added to each cadmium and incubated at 37 ° C for 4 hours. 100 μl of formazan solution (10% sodium dodecyl sulfate and 0.01 M HCl) was added to each cadmium and cultured in an incubator for 10 hours or more. Using 630 nm as a reference wavelength, the absorbance of the sample reconstituted by the example is measured with a microplate reader (Bio-Rad 680) at a wavelength of 570 nm. The concentration of ions in the extraction solution is measured using ICP-AES (Leeman, Profile). Further, in the electrochemical measurement using the Hank's solution of PH 7.4 as the medium and the sample prepared by each example, the platinum electrode, and the saturated first mercury electrode as the functional electrode, the auxiliary electrode, and the reference electrode, Measure the speed.

The interpretation of the cytotoxicity test results of iron-manganese binary alloys was judged to be potentially cytotoxic if the survival rate was reduced to less than 70% (<70%) of the blank test solution. Therefore, when tested at 50% of the effluent of the test sample, the survival rate should be at least equal to or higher than that tested with 100% of the eluate. FIG. 9 shows the results of cytotoxicity tests conducted on 50% and 100% concentrations of an iron fermentate comprising 20% by weight of manganese, 25% by weight and 30% by weight of manganese. As shown in FIG. 9, the cell survival rate of the extract culture medium at a concentration of 50% was higher than that of the 100% extract culture medium, and the survival rate of the cells was more than 70% at 1 day, 2 days and 4 days . Therefore, it was confirmed that the iron-manganese binary alloy was not toxic to the cells.

Through the above Test Examples 1 to 5, the alloy composition for a biomaterial according to the present invention is suitable as an alloy for a biomaterial because it can be biocompatible, suitable in mechanical hardness and can be photographed by magnetic resonance imaging, It can be suitably used.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, And all of the various forms of embodiments that can be practiced without departing from the technical spirit.

S1: composition mixing step S2: melting step
S3: Casting step S4: Plastic forming step
S5: Heat treatment step

Claims (6)

delete 1. A method for manufacturing an alloy for a biomaterial which is inserted into a human body and used as a structure,
A composition mixing step of mixing 20 wt% to 35 wt% of manganese and the balance iron;
A melting step of heating and melting the mixture of the composition mixing step;
A casting step of putting the molten alloy in the melting step into a metal mold for molding;
A plastic working step of processing the shaped alloy into a required shape; And
And a heat treatment step of heat-treating the alloy processed in the plastic working step,
The melting step is carried out in a vacuum high-frequency induction furnace under an argon atmosphere at a pressure of 300 mbar,
The plastic working step may be performed by heating the material to 800 ° C to 1000 ° C,
Wherein the annealing step comprises annealing at 700 ° C for 10 minutes followed by annealing at 600 ° C for 10 hours to improve magnetic resonance characteristics.
delete delete delete delete

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