Biodegradable medical devices

Abstract

To provide a biodegradable medical appliance which can be dissolved in an organism with an appropriate dissolution rate.SOLUTION: A biodegradable medical appliance of this invention is formed of a magnesium material, wherein a layer of magnesium crystal grains of which the (0001) face in a hexagonal structure is oriented toward the surface side is formed on a predetermined cross section vertical to at least one longitudinal direction, and of which the (2-1-10) face in the hexagonal structure is oriented toward the end face side on the end face on at least one longitudinal direction.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present invention relates to biodegradable medical devices.

Background Art

[0002] Conventionally, as medical devices for attaching or fixing bones, there are those made of metal materials. At that time, in order to prevent the metal medical device from remaining in the body even after treatment, it is common to remove the medical device by reoperation after treatment or after healing. However, since reoperation places a large burden on the patient, biodegradable medical devices that dissolve in the living body have been developed. As a material for biodegradable medical devices that dissolve in the living body, a high-purity magnesium material having appropriate strength can be considered (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, a high-purity magnesium material has a problem that it dissolves quickly because its corrosion resistance in the living body is low.

Means for Solving the Problems

[0005] The inventor of the present invention studied controlling the corrosion resistance (dissolubility) of biodegradable medical devices by changing the orientation of magnesium crystal grains.

[0006] Magnesium crystal grains have a hexagonal close-packed structure, and it is known that when their (0001) plane is oriented toward the surface of a biodegradable medical device, the corrosion resistance of the magnesium crystal grains increases and they become less likely to dissolve. Therefore, the inventors of this invention studied how the corrosion resistance of a biodegradable medical device changes when the area (area ratio to the entire surface) of the portion of the magnesium crystal grains oriented toward the surface is changed relative to the surface of the biodegradable medical device.

[0007] As a result of the above research, the inventors of the present invention found that it is possible to improve the corrosion resistance of biodegradable medical devices to some extent by increasing the area of ​​the portion where the (0001) plane of magnesium crystal grains is oriented toward the surface on the surface of the biodegradable medical device. However, they found that if the proportion of the portion where the (10-10) plane, which has low corrosion resistance and is easily dissolved, is oriented toward the end face is large at the longitudinal end face of the biodegradable medical device, dissolution progresses toward the longitudinal side from that end face, thus reducing the corrosion resistance of the biodegradable medical device. Therefore, it was difficult to significantly improve the corrosion resistance of biodegradable medical devices.

[0008] Therefore, the inventors of the present invention conducted further research and found that when a layer of magnesium crystal grains is formed in a predetermined cross-section of a biodegradable medical device, with the (0001) plane in the hexagonal structure oriented toward the device surface, and when the (2-1-10) plane in the hexagonal structure is oriented toward the end face in the longitudinal direction of the biodegradable medical device, the corrosion resistance of the biodegradable medical device is greatly increased and it becomes less likely to dissolve.

[0009] In other words, the biodegradable medical device according to the present invention is made of magnesium material, and in at least one predetermined cross section perpendicular to the longitudinal direction, a layer of magnesium crystal grains is formed in which the (0001) plane in the hexagonal crystal structure is oriented toward the surface, and in at least one end face in the longitudinal direction, the proportion of magnesium crystal grains in which the (2-1-10) plane in the hexagonal crystal structure is oriented toward the end face is 47.5% or more. 52.2% or less It is characterized by being such.

[0010] In the present invention, for example, if the biodegradable medical device is a long device, in a cross section perpendicular to the longitudinal direction, "magnesium crystal grains in which the (0001) plane in the hexagonal crystal structure is oriented toward the surface" includes "magnesium crystal grains in which the (0001) plane in the hexagonal crystal structure is arranged perpendicular to the normal direction of the device surface" and "magnesium crystal grains in which the normal direction of the (0001) plane in the hexagonal crystal structure is tilted at 0 to 45 degrees with respect to the normal direction of the device surface (the direction of tilt may be any direction)." Furthermore, in the present invention, for example, if the biodegradable medical device is a long device, the "magnesium crystal grains in which the (2-1-10) planes in the hexagonal crystal structure are oriented toward the end face" at the longitudinal end face include "magnesium crystal grains in which the (2-1-10) planes in the hexagonal crystal structure are arranged perpendicular to the normal direction of the longitudinal end face of the device" and "magnesium crystal grains in which the normal direction of the (2-1-10) planes in the hexagonal crystal structure is inclined at 0 to 45 degrees with respect to the normal direction of the longitudinal end face of the device (the direction of inclination may be any direction)."

[0011] As a result, in the biodegradable medical device according to the present invention, a layer of magnesium crystal grains is formed in a predetermined cross section perpendicular to the longitudinal direction, in which the (0001) plane, which has higher corrosion resistance in the body compared to the (10-10) plane and (2-1-10) plane in the hexagonal crystal structure, is oriented toward the surface. Therefore, dissolution is less likely to progress from the surface of the biodegradable medical device toward the center of the device. Furthermore, at the end face in the longitudinal direction, the (2-1-10) plane, which has higher corrosion resistance in the body compared to the (10-10) plane in the hexagonal crystal structure, is oriented toward the end face. Therefore, dissolution is less likely to progress from the end face toward the longitudinal side of the biodegradable medical device. Thus, by slowing down the dissolution from the surface toward the center of the biodegradable medical device and slowing down the dissolution from the end face toward the longitudinal side of the biodegradable medical device, the corrosion resistance of the biodegradable medical device can be increased and it can be made less likely to dissolve.

[0014] As a result, in the biodegradable medical device according to the present invention, a layer of magnesium crystal grains that are less likely to dissolve is formed in a predetermined cross section perpendicular to the longitudinal direction, moving from the surface of the biodegradable medical device toward the center of the device. Furthermore, at the longitudinal end face, a relatively large proportion of magnesium crystal grains have a (2-1-10) plane that is less likely to dissolve moving toward the longitudinal side from the end face of the biodegradable medical device toward the end face. Therefore, the corrosion resistance of the biodegradable medical device can be further enhanced, making it less likely to dissolve.

[0015] The biodegradable medical device according to the present invention is characterized in that the magnesium material is a pure magnesium material containing 99.9% by mass or more of magnesium.

[0016] As a result, even when using a high-purity magnesium material with low corrosion resistance in the body as the magnesium material in the biodegradable medical device according to the present invention, the corrosion resistance of the biodegradable medical device can be enhanced and it can be made less likely to dissolve.

[0017] In the biodegradable medical device according to the present invention, the magnesium material is characterized by being a magnesium alloy having magnesium as its main component.

[0018] As a result, even when a magnesium alloy with magnesium as the main component is used as the magnesium material in the biodegradable medical device according to the present invention, the corrosion resistance of the biodegradable medical device can be enhanced and it can be made less likely to dissolve. [Effects of the Invention]

[0019] As described above, according to the present invention, the corrosion resistance (solubility) of biodegradable medical devices can be controlled so that they dissolve in the body at an appropriate rate. [Brief explanation of the drawing]

[0020] [Figure 1] This figure shows a sample used in an evaluation test according to an embodiment of the present invention. [Figure 2]It is a diagram showing the observation location in the cross-section of the sample (an enlarged cross-sectional view along line A-A in FIG. 1). [Figure 3] It is a diagram showing the orientation of magnesium crystal grains when observing the cross-section from the axis 3 direction. [Figure 4] It is a diagram showing the orientation of magnesium crystal grains when observing the cross-section from the axis 1 direction. [Figure 5] It is a diagram showing the orientation of magnesium crystal grains when observing the cross-section from the axis 2 direction. [Figure 6] It is a diagram showing the observation location in the longitudinal section of the sample (an enlarged cross-sectional view of the main part along line B-B in FIG. 1). [Figure 7] It is a diagram showing the orientation of magnesium crystal grains when observing the longitudinal section from the axis 3 direction. [Figure 8] It is a diagram showing the orientation of magnesium crystal grains when observing the longitudinal section from the axis 1 direction. [Figure 9] It is a diagram showing the orientation of magnesium crystal grains when observing the longitudinal section from the axis 2 direction. [Figure 10] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N1) from the axis 3 direction. [Figure 11] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N1) from the axis 1 direction. [Figure 12] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N1) from the axis 2 direction. [Figure 13] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N2) from the axis 3 direction. [Figure 14] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N2) from the axis 1 direction. [Figure 15] It is a diagram showing the orientation of magnesium crystal grains when observing the observation locations a1 to a4 in the cross-section of (sample N2) from the axis 2 direction. [Figure 16]This figure shows the orientation of magnesium crystal grains when observed from three axial directions at observation points c1 to c4 in the longitudinal section of sample N1. [Figure 17] This figure shows the orientation of magnesium crystal grains when observed at observation points c1 to c4 in the longitudinal section of sample N1 from one axis direction. [Figure 18] This figure shows the orientation of magnesium crystal grains when observation points c1 to c4 of the longitudinal section of sample N1 are observed from two axial directions. [Figure 19] This figure shows the orientation of magnesium crystal grains when observed from three axial directions at observation points c1 to c4 in the longitudinal section of sample N2. [Figure 20] This figure shows the orientation of magnesium crystal grains when observed at observation points c1 to c4 in the longitudinal section of sample N2 from one axis direction. [Figure 21] This figure shows the orientation of magnesium crystal grains when observation points c1 to c4 of the longitudinal section of sample N2 are observed from two axial directions. [Figure 22] This figure shows the distribution of magnesium crystal grain layers in a hexagonal structure, where the (0001 plane) is oriented toward the surface, when observation points a1 to a4 of the cross-section of sample N1 are observed from the direction of axis 1. [Figure 23] This figure shows the distribution of layers of magnesium crystal grains in a hexagonal structure, where the (0001 plane) is oriented toward the surface, when the cross-section of sample N1 is observed from the direction of axis 1. [Figure 24] This figure shows the distribution of layers of magnesium crystal grains in a hexagonal structure, where the (0001 plane) is oriented toward the surface, when observation points a1 to a4 of the cross-section of sample N2 are observed from the direction of axis 1. [Figure 25] This figure shows the distribution of layers of magnesium crystal grains in a hexagonal structure, where the (0001 plane) is oriented toward the surface, when observed at observation points c1 to c4 of the longitudinal section of sample N1, each from the direction of axis 1. [Figure 26]This figure shows the distribution of magnesium crystal grain layers in a hexagonal structure, where the (0001 plane) is oriented toward the surface, when observed at observation points c1 to c4 of the longitudinal section of sample N2, each from the direction of axis 1. [Figure 27] This diagram illustrates the range in which layers of magnesium crystal grains are continuous in the longitudinal direction. [Figure 28] This figure shows the data obtained from solubility evaluation tests. [Figure 29] This figure shows the longitudinal end face of the sample used in the evaluation test. [Modes for carrying out the invention]

[0021] Hereinafter, a biodegradable medical device according to an embodiment of the present invention will be described with reference to the drawings.

[0022] Examples of biodegradable medical devices according to the present invention include plates, pins, screws, etc., used in the body for purposes such as attaching or fixing bones.

[0023] Biodegradable medical devices are made from pure magnesium material containing 99.9% or more magnesium by mass. Pure magnesium material contains unavoidable impurities other than magnesium, such as Zn, Zr, and Mn, but the type of material is arbitrary.

[0024] The corrosion resistance (solubility) of biodegradable medical devices varies depending on the orientation of magnesium crystal grains relative to the surface of the biodegradable medical device. Specifically, although magnesium crystal grains have a hexagonal close-packed structure, the corrosion resistance (solubility) of the biodegradable medical device increases (solubility decreases) when its (0001) plane is oriented toward the surface of the biodegradable medical device.

[0025] Therefore, we used electron back-scatter diffraction (EBSD) to detect the orientation of magnesium crystal grains on the surface of biodegradable medical devices and conducted evaluation tests on the corrosion resistance of these biodegradable medical devices.

[0026] The equipment used in the EBSD evaluation test is as follows: (SEM observation, EDS analysis) Scanning electron microscope (SEM), JEOL Ltd. JSM-IT300HR(LA) Energy dispersive X-ray spectrometer (EDS) JEOL Ltd. JED-2300 Analysis Station Plus (EBSD data acquisition software (software for controlling the SEM stage, calculating crystal orientation, etc.)) TSL Solutions Co., Ltd. OIM Data Collection (EBSD data analysis software (software for analyzing collected data in detail and creating maps, graphs, etc.)) TSL Solutions Co., Ltd. OIM Analysis

[0027] In this embodiment, two types of samples, N1 and N2, which are cylindrical in shape with a length of 5 mm and a circular cross-section with a diameter of 2 mm, as shown in Figure 1(a), were used as samples corresponding to biodegradable medical devices.

[0028] In this embodiment, (Sample N1) and (Sample N2) are extruded materials obtained by cutting or drawing after being produced by extrusion molding. In the case of cutting, the extruded material is cut while rotating at a predetermined rotational speed to obtain the desired shape. In the case of drawing, the extruded material is heat-treated (annealed) as appropriate and then drawn using a drawing die to obtain the desired shape. The longitudinal direction of (Sample N1) and (Sample N2) coincides with the extrusion direction in extrusion molding. In this way, by applying a predetermined stress to the entire circumference of the sample while adjusting the grain size of the crystal grains of the sample by heat treatment or processing heat, such as cutting or drawing, a layer with uniform orientation can be formed inside the sample around its entire circumference. Note that the processing method for applying a predetermined stress to the entire circumference of the sample is not limited to cutting or drawing.

[0029] (Orientation of magnesium crystal grains) First, for (Sample N1) and (Sample N2), the orientation of magnesium crystal grains relative to the surface of the samples was detected by backscattered electron diffraction in the cross-section (section along line AA in Figure 1(b)) obtained by cutting with a plane perpendicular to the longitudinal direction (a plane perpendicular to the axis) as shown in Figure 1(b), and in the longitudinal section (section along line BB in Figure 1(c)) obtained by cutting through the axis and parallel to the axis as shown in Figure 1(c).

[0030] (Orientation of the cross-section) Regarding the cross-section, the orientation of magnesium crystal grains was detected when the observation point a1 shown in Figure 2 was observed from three directions. In Figure 2, the three directions are shown as axis 1 direction, axis 2 direction, and axis 3 direction when observing observation point a1. Observation from the three directions refers to observation from the outside in a direction parallel to the cross-section and perpendicular to the surface of the sample (observation from axis 1 direction), observation from a direction parallel to the cross-section and perpendicular to axis 1 (observation from axis 2 direction), and observation from a direction perpendicular to the cross-section (observation from axis 3 direction). Note that axis 3 direction is the direction perpendicular to the plane of the paper in Figure 2.

[0031] Figure 3 shows the orientation of magnesium crystal grains when observation point a1 on the cross-section is observed from the three axial directions. Therefore, the orientation of magnesium crystal grains observed from the three axial directions shown in Figure 3 represents the orientation of magnesium crystal grains that actually appear on the cross-section. In other words, it shows which faces of the magnesium crystal grains are oriented in the three axial directions when the cross-section is observed from the three axial directions.

[0032] In Figure 3, the orientation of magnesium crystal grains is shown in the lower right of the figure. Magnesium crystal grains whose (0001) plane in the hexagonal structure is tilted 0 to 45 degrees with respect to the 3 axes (the observation direction) are shown in black, magnesium crystal grains whose (10-10) plane is tilted 0 to 45 degrees with respect to the 3 axes (the observation direction) are shown in a dark gray color, and magnesium crystal grains whose (2-1-10) plane is tilted 0 to 45 degrees with respect to the 3 axes (the observation direction) are shown in a light gray color.

[0033] In the orientation of magnesium crystal grains shown in Figure 3, "the (0001) plane in the hexagonal structure is tilted 0 to 45 degrees with respect to the axial 3 direction, which is the observation direction" means "the normal direction of the (0001) plane in the hexagonal structure is tilted 0 to 45 degrees with respect to the normal direction of the surface." In this case, the direction of the tilt can be any direction. In the following diagrams showing the orientation of magnesium crystal grains, the observation direction may differ from that in Figure 3, but the method for illustrating the orientation of magnesium crystal grains is the same as in Figure 3.

[0034] As shown in Figure 3, in both (Sample N1) and (Sample N2), when observed from the three axial directions, it can be seen that the entire sample, from near the surface to near the center, consists mostly of crystal grains shown in a high-density gray color and crystal grains shown in a low-density gray color, with almost no crystal grains shown in black.

[0035] Figure 4 shows the orientation of magnesium crystal grains when the cross-sectional observation point a1 is observed from the direction of axis 1, and was obtained by calculation based on the results of observation from the direction of axis 3 shown in Figure 3.

[0036] As shown in Figure 4, in both (Sample N1) and (Sample N2), when observed from axial direction 1, it can be seen that crystal grains shown in black, crystal grains shown in a darker gray, and crystal grains shown in a lighter gray are mixed together from near the surface to near the center of the sample. In particular, in both (Sample N1) and (Sample N2), it can be seen that there are more crystal grains shown in black near the surface of the sample compared to near the center of the sample.

[0037] Figure 5 shows the orientation of magnesium crystal grains when the cross-sectional observation point a1 is observed from two axial directions, and was obtained by calculation based on the results of observation from three axial directions shown in Figure 3.

[0038] As shown in Figure 5, in both (Sample N1) and (Sample N2), when observed from two axial directions, it can be seen that crystal grains shown in black, crystal grains shown in a high-density gray, and crystal grains shown in a low-density gray are mixed throughout the entire sample, from near the surface to near the center. In particular, in both (Sample N1) and (Sample N2), it can be seen that there are many crystal grains shown in black near the center of the sample, and few crystal grains shown in black near the surface of the sample.

[0039] As described above, when the observation point a1 on the cross-section of the sample is observed from the direction of axis 1, that is, from the outer surface of the sample toward the center, many crystal grains, shown in black in Figure 4, are observed.

[0040] In this embodiment, the crystal grains shown in black in Figure 4 are "magnesium crystal grains in which the (0001) plane in the hexagonal structure is arranged perpendicular to the normal direction of the surface," or "magnesium crystal grains in which the normal direction of the (0001) plane in the hexagonal structure is tilted at 0 to 45 degrees with respect to the normal direction of the surface (the direction of tilt can be any direction)," and these magnesium crystal grains are referred to as "magnesium crystal grains in which the (0001) plane in the hexagonal structure is oriented toward the surface side of the sample."

[0041] Furthermore, when observation point a1 is observed from the direction of axis 1, as shown in Figure 4, many magnesium crystal grains are observed in which the (0001) plane in the hexagonal crystal structure is oriented toward the surface side of the sample. However, based on Figures 3 to 5, it can be seen that the (0001) plane of these magnesium crystal grains has a strong tendency to be tilted in a direction perpendicular to the longitudinal direction.

[0042] In other words, it can be seen that most of the crystal grains shown in black in Figure 4 are magnesium crystal grains in which the (0001) plane in the hexagonal structure is positioned perpendicular to the normal direction of the outer surface, or magnesium crystal grains in which the (0001) plane in the hexagonal structure is contained in one of the planes that is tilted at an angle of 0 to 45 degrees around a straight line along the longitudinal direction (the direction perpendicular to the cross-section) that is perpendicular to the normal direction of the outer surface.

[0043] (Orientation of the longitudinal section) Regarding the longitudinal section, the orientation of magnesium crystal grains was detected when the observation point c1 shown in Figure 6 was observed from three directions. In Figure 6, the three directions are shown as axis 1, axis 2, and axis 3 when observing the observation point c1. The three directions of observation are: observation from the outside in a direction parallel to the longitudinal section and perpendicular to the surface of the sample (observation from axis 1), observation from a direction parallel to the longitudinal section and perpendicular to axis 1 (observation from axis 2), and observation from a direction perpendicular to the longitudinal section (observation from axis 3). Note that axis 3 is the direction perpendicular to the plane of the paper in Figure 6.

[0044] Figure 7 shows the orientation of magnesium crystal grains when the observation point c1 in the longitudinal section is observed from the three axial directions. Therefore, the orientation of magnesium crystal grains observed from the three axial directions shown in Figure 7 represents the orientation of magnesium crystal grains that is actually present in the longitudinal section. In other words, it shows which faces of the magnesium crystal grains are oriented in the three axial directions when the longitudinal section is observed from the three axial directions.

[0045] As shown in Figure 7, in both (Sample N1) and (Sample N2), when observed from the three axial directions, it can be seen that crystal grains shown in black, crystal grains shown in a darker shade of gray, and crystal grains shown in a lighter shade of gray are mixed together from near the surface to near the center of the sample.

[0046] Figure 8 shows the orientation of magnesium crystal grains when the observation point c1 in the longitudinal section is observed from the direction of axis 1, and was obtained by calculation based on the results of observation from the direction of axis 3 shown in Figure 7.

[0047] As shown in Figure 8, in both (Sample N1) and (Sample N2), when observed from axial direction 1, it can be seen that crystal grains shown in black, crystal grains shown in a darker gray, and crystal grains shown in a lighter gray are mixed together from near the surface to near the center of the sample. In particular, near the surface of (Sample N1), there are more crystal grains shown in black compared to near the center of the sample.

[0048] Figure 9 shows the orientation of magnesium crystal grains when the observation point c1 in the longitudinal section is observed from two axial directions, and was obtained by calculation based on the results of observation from three axial directions shown in Figure 7.

[0049] As shown in Figure 9, in both (Sample N1) and (Sample N2), when observed from two axial directions, it can be seen that the entire surface and center of the sample consists mostly of crystal grains shown in a high-density gray color and crystal grains shown in a low-density gray color, with almost no crystal grains shown in black.

[0050] As described above, when the observation point c1 of the longitudinal section of the sample is observed from the direction of axis 1, that is, from the outer surface of the sample toward the center, many crystal grains, shown in black in Figure 8, are observed.

[0051] In this embodiment, the crystal grains shown in black in Figure 8 are either "magnesium crystal grains in which the (0001) plane in the hexagonal structure is arranged perpendicular to the normal direction of the surface" or "magnesium crystal grains in which the normal direction of the (0001) plane in the hexagonal structure is tilted at 0 to 45 degrees with respect to the normal direction of the surface (the direction of tilt can be any direction)".

[0052] Furthermore, when observation point c1 is observed from the direction of axis 1, as shown in Figure 8, many magnesium crystal grains are observed in which the (0001) plane in the hexagonal crystal structure is oriented toward the surface side of the sample. Based on Figures 7 to 9, it can be seen that the (0001) plane of these magnesium crystal grains has a strong tendency to tilt in a direction perpendicular to the longitudinal direction of the sample. This point is the same for the orientation in the longitudinal section as for the orientation in the transverse section.

[0053] (Orientation around the entire circumference of the sample) In this embodiment, both (Sample N1) and (Sample N2) are obtained by cutting or drawing extruded material obtained by extrusion molding, and it is considered that the orientation of magnesium crystal grains relative to the surface of the sample is substantially the same around its entire circumference in the cross-section of the sample.

[0054] Therefore, in order to confirm that the orientation of magnesium crystal grains is substantially the same around the entire circumference in the cross-section of the sample, the orientation of magnesium crystal grains was detected at observation points a2 to a4 in addition to observation point a1 as described above, in the cross-section shown in Figure 2. Observation points a1 to a4 in the cross-section are locations on the surface of the sample that are 90 degrees apart from each other in the circumferential direction.

[0055] Figures 10 to 12 show the orientation of magnesium crystal grains when observed at points a1 to a4 on the cross-section of (sample N1) from the 3-axis direction, the 1-axis direction, and the 2-axis direction, respectively. According to Figures 10 to 12, it can be seen that the orientation of magnesium crystal grains at points 90 degrees apart in the circumferential direction on the cross-section of (sample N1) is approximately the same.

[0056] Figures 13 to 15 show the orientation of magnesium crystal grains observed from three axes, one axis, and two axes at observation points a1 to a4 on the cross-section of (sample N2), respectively. As can be seen from Figures 13 to 15, similar to (sample N1), the orientation of magnesium crystal grains at points 90 degrees apart in the circumferential direction on the cross-section of (sample N2) is approximately the same.

[0057] Specifically, Figures 10 and 13 show that there are almost no crystal grains shown in black. Figures 11 and 14 show that there are more crystal grains shown in black near the surface of the sample compared to near the center of the sample. Figures 12 and 15 show that there are fewer crystal grains shown in black near the surface of the sample compared to near the center of the sample.

[0058] (Orientation in the longitudinal direction of the sample) Furthermore, both (Sample N1) and (Sample N2) were obtained by cutting or drawing extruded material obtained by extrusion molding, and it is considered that the orientation of magnesium crystal grains relative to the surface of the sample in the longitudinal section of the sample is substantially the same for most of the longitudinal direction.

[0059] Therefore, in order to confirm that the orientation of magnesium crystal grains is substantially the same for most of the longitudinal direction, the orientation of magnesium crystal grains was detected at observation points c2 to c4 in the longitudinal section shown in Figure 6, in addition to observation point c1 described above. Observation points c1 and c2 are two locations separated in the longitudinal direction on one surface along the longitudinal direction of the longitudinal section of the sample, while observation points c3 and c4 are two locations separated in the longitudinal direction on the other surface along the longitudinal direction of the longitudinal section of the sample.

[0060] Figures 16 to 18 show the orientation of magnesium crystal grains when observed at points c1 to c4 in the longitudinal section of (sample N1) from three axes, one axis, and two axes, respectively. According to Figures 16 to 18, it can be seen that in the longitudinal section of (sample N1), the orientation of magnesium crystal grains at points separated in the longitudinal direction is almost identical for most of the longitudinal direction.

[0061] Figures 19 to 21 show the orientation of magnesium crystal grains observed from axial 3, axial 1, and axial 2 directions at observation points c1 to c4 in the longitudinal section of (sample N2), respectively. As can be seen from Figures 19 to 21, similar to (sample N1), the orientation of magnesium crystal grains at two locations separated in the longitudinal direction on the surface of (sample N2) is substantially the same for most of the longitudinal direction.

[0062] Specifically, Figures 16 and 19 show that the sample contains a mixture of crystal grains, including those shown in black, those shown in a darker shade of gray, and those shown in a lighter shade of gray, from the surface to the center. Figures 17 and 20 show that there are more crystal grains shown in black near the surface of the sample compared to the center. Figures 18 and 21 show that there are almost no crystal grains shown in black.

[0063] (Distribution of crystal grains) Since the distribution of crystal grains with the (0001) plane facing the surface in a hexagonal crystal structure has a significant impact on the corrosion resistance (solubility) of the sample, the orientation of magnesium crystal grains was examined in detail for (Sample N1) and (Sample N2) when the outer peripheral surface of the samples was observed from the outside in the vertical direction (axis 1 direction).

[0064] (Distribution of crystal grains in cross-section) Regarding the cross-section of (sample N1) Figure 22 shows, in black, the distribution of crystal grains in the hexagonal structure where the (0001) plane is oriented toward the surface of the sample, when observed at points a1 to a4 on the cross-section of sample N1, each from the direction of axis 1. Note that Figure 22 is the same as Figure 11, but showing only the magnesium crystal grains shown in black.

[0065] As described above, observation points a1 to a4 are located at points 90 degrees apart from each other in the circumferential direction (direction around the axis of the sample) on the surface of the sample in the cross-section, and the left-right direction in Figure 22 corresponds to the circumferential direction of the sample. The same applies to Figure 24.

[0066] In the distribution of observation points a1 to a4, it can be seen that, for example, in the areas enclosed by dotted lines, the crystal grains shown in black are continuously distributed throughout the entire left-right direction. In this embodiment, the continuous portion of crystal grains shown in black in Figure 22 is referred to as a layer of crystal grains in which the (0001 plane) in the hexagonal structure is oriented toward the surface side of the sample. This point is also the same for Figures 24 to 26. Thus, in each of observation points a1 to a4 in Figure 22, there is at least one region in which a layer of crystal grains in which the (0001 plane) is oriented toward the surface side of the sample is distributed continuously throughout the entire circumferential direction of the sample. In this embodiment, if the biodegradable medical device is a long instrument, "the layer of magnesium crystal grains is continuous around the entire circumference" in a cross-section perpendicular to the longitudinal direction means "the layer of magnesium crystal grains surrounds the central part of the biodegradable medical device."

[0067] Figure 23 shows the distribution of observation points a1 to a4 in Figure 22 arranged to correspond to the cross-section. Layers of crystal grains in the hexagonal structure, where the (0001 plane) is oriented toward the surface of the sample, are continuously distributed along the entire circumferential direction of the sample at each of the observation points a1 to a4, which are 90 degrees apart from each other in the circumferential direction on the surface of the sample.

[0068] In the cross-section, even when observing a region of a predetermined width (length along the axis of the sample) extending from the surface to the center of the sample in a region other than the four observation points a1 to a4 in the circumferential direction (the region shown by the dotted line in Figure 23), it is considered that, similar to observation points a1 to a4, it contains at least one region in which a layer of crystal grains with (0001 plane) oriented toward the surface side of the sample is distributed continuously over the entire circumferential region of the sample. In other words, in the cross-section of the sample, it is considered that no matter which position on the surface of the sample is connected to the center of the sample by a straight line, that straight line will pass through at least one layer of crystal grains with (0001 plane) oriented toward the surface side of the sample.

[0069] Furthermore, in the cross-section of the sample, layers of crystal grains with the 0001 plane oriented toward the surface of the sample extend continuously from the surface toward the center, and layers of crystal grains adjacent to each other in the circumferential or radial direction of the sample are bonded together. As a result, especially on the side closer to the surface of the sample (the part where stress is thought to have been applied during cutting or drawing), layers of crystal grains with the 0001 plane oriented toward the surface of the sample are connected in a network-like structure.

[0070] Therefore, in the cross-section of (sample N1), a continuous layer of magnesium crystal grains, with the (0001 plane) in the hexagonal structure oriented toward the surface of the sample, extends around the entire circumference. In other words, the layer of magnesium crystal grains surrounds the central part of the biodegradable medical device.

[0071] Regarding the cross-section of sample N2 Figure 24 shows, in black, the distribution of crystal grains in the hexagonal structure where the (0001) plane is oriented toward the surface of the sample, when observed at points a1 to a4 on the cross-section of sample N2, each from the direction of axis 1. Note that Figure 24 is the same as Figure 14, but showing only the magnesium crystal grains shown in black.

[0072] In the distribution of observation points a1 to a4, it can be seen that, for example, in the region enclosed by the dotted line, the crystal grains shown in black are continuously distributed across the entire left-right direction. Thus, in each of observation points a1 to a4 in Figure 24, there is at least one region in which a layer of crystal grains with the (0001 plane) oriented toward the surface of the sample is continuously distributed across the entire circumferential direction of the sample.

[0073] Therefore, similar to the cross-section of (sample N1), the cross-section of (sample N2) shows a continuous layer of magnesium crystal grains with the (0001 plane) in the hexagonal structure oriented toward the surface of the sample, extending all the way around. In other words, the layer of magnesium crystal grains surrounds the central part of the biodegradable medical device.

[0074] (Distribution of crystal grains in the longitudinal section) Regarding the longitudinal section of (sample N1) Figure 25 shows, in black, the distribution of crystal grains in the hexagonal structure where the (0001) plane is oriented toward the surface of the sample, when observed at observation points c1 to c4 of the longitudinal section of sample N1, each from the direction of axis 1. Note that Figure 25 is the same as Figure 17, but showing only the magnesium crystal grains shown in black.

[0075] As described above, observation points c1 to c4 are located far apart in the longitudinal direction in the longitudinal section of the sample, and the left-right direction in Figure 25 corresponds to the longitudinal direction of the sample. The same applies to Figure 26.

[0076] In the distribution of observation points c1 to c4, for example, in the region enclosed by the dotted line, it can be seen that the crystal grains shown in black are continuously distributed across the entire left-right direction. Thus, in each of the observation points c1 to c4 in Figure 25, there is at least one region in which a layer of crystal grains, in which the (0001 plane) of the hexagonal structure is oriented toward the surface of the sample, is continuously distributed across the entire longitudinal direction of the sample.

[0077] In a longitudinal section, even when observing a region of a predetermined width (length along the longitudinal direction of the sample) extending from the surface to the center of the sample in a part other than the four observation points c1 to c4 in the longitudinal direction, it is considered that, similar to observation points c1 to c4, it contains at least one region in which a layer of crystal grains with (0001 plane) oriented toward the surface side of the sample is distributed continuously over the entire longitudinal direction of the sample.

[0078] Furthermore, in the longitudinal section of the sample, layers of crystal grains with the 0001 plane oriented toward the surface of the sample extend continuously from the surface toward the center, and layers of crystal grains adjacent to each other in the longitudinal or radial direction of the sample are bonded together. As a result, especially on the side closer to the surface of the sample (the part where stress is thought to have been applied during cutting or drawing), layers of crystal grains with the 0001 plane oriented toward the surface of the sample are connected in a network-like structure.

[0079] Therefore, in the longitudinal section of (sample N1), layers of crystal grains in which the (0001 plane) of the hexagonal structure is oriented toward the surface of the sample are continuously distributed in the longitudinal direction, both between the two observation points c1 and c2 and between the two observation points c3 and c4.

[0080] Regarding the longitudinal section of (sample N2): Figure 26 shows, in black, the distribution of crystal grains in the hexagonal structure where the (0001) plane is oriented toward the surface of the sample, when observed at observation points c1 to c4 of the longitudinal section of sample N2, each from the direction of axis 1. Note that Figure 26 is the same as Figure 20, but showing only the magnesium crystal grains shown in black.

[0081] In the distribution of observation points c1, c3, and c4 in Figure 26, for example, in the region enclosed by the dotted line, it can be seen that the crystal grains shown in black are continuously distributed across the entire left-right direction. Thus, each of the observation points c1 to c4 in Figure 26 contains at least one region in which a layer of crystal grains, in which the (0001 plane) of the hexagonal structure is oriented toward the surface of the sample, is continuously distributed across the entire longitudinal direction of the sample.

[0082] In contrast, the distribution at observation point c2 shows that the crystal grains, shown in black, are not continuously distributed across the entire left-right direction. Thus, at observation point c2 in Figure 26, there is no region in which the layer of crystal grains with the (0001 plane) in the hexagonal structure oriented toward the surface of the sample is continuously distributed across the entire longitudinal direction of the sample.

[0083] As described above, in the longitudinal section of (sample N1), the layer of magnesium crystal grains in which the (0001 plane) in the hexagonal structure is oriented toward the surface side of the sample is considered to be continuous in the range A1 of observation points c2 to c4, as shown in Figure 27(a).

[0084] In contrast, in the longitudinal section of (sample N2), the layer of magnesium crystal grains in which the (0001 plane) in the hexagonal structure is oriented toward the surface side of the sample is considered to be continuous in the range A2 of observation points c3 to c4, as shown in Figure 27(b).

[0085] Therefore, the range in which layers of magnesium crystal grains with the (0001 plane) oriented toward the surface side of the sample are continuous in the longitudinal direction is considered to be larger in (sample N1) than in (sample N2).

[0086] (Solubility evaluation test) Solubility evaluation tests were conducted on (Sample N1) and (Sample N2). For the solubility evaluation test, the samples were immersed in a simulated body fluid whose pH was adjusted to 7.67 by adding sodium bicarbonate [Wako Pure Chemical Industries, Ltd., product number 199-05985] to HBSS(+) [Fujifilm Wako Pure Chemical Industries, Ltd., product number 082-08961], and the weight change of the samples was measured. The containers in which the samples were immersed were placed in a multi-gas incubator [Panasonic Healthcare Co., Ltd., model MCO-170MUVH-PJ], and the internal temperature was controlled at 37 degrees Celsius and the CO2 concentration at 5%.

[0087] Figure 28 shows the data obtained from solubility evaluation tests for (Sample N1) and (Sample N2). The horizontal axis of Figure 28 represents the number of days since the start of the solubility evaluation test, and the vertical axis represents the amount of corrosion of the sample (weight reduction due to dissolution).

[0088] According to Figure 28, sample N1 showed almost no weight change until approximately 56 days after the start of immersion, and then gradually decreased in weight from approximately 56 days later. In contrast, sample N2 showed almost no weight change until approximately 10 days after the start of immersion, and then gradually decreased in weight from approximately 10 days later.

[0089] Figure 28 shows data obtained from a solubility evaluation test of the comparison material for comparison with the solubility of (Sample N1) and (Sample N2). For the solubility evaluation test of the comparison material, the comparison material was immersed in a simulated body fluid containing only HBSS(+), and the container in which the samples were immersed was controlled at an internal temperature of 37 degrees Celsius.

[0090] As a comparative material, an extruded material formed from pure magnesium containing 99.9% or more magnesium by mass and obtained by extrusion molding was used. The dimensions of samples N1 and N2 and the comparative material used in the solubility evaluation test are as follows. Samples N1 and N2: φ2 × 50 mm (volume 157 mm) 3 ) Comparison material: φ7.7×12mm (volume 558.5mm) 3 )

[0091] As described above, (Sample N1) and (Sample N2) are extruded materials obtained by extrusion molding and then machined or drawn, whereas the comparison material is an extruded material obtained by extrusion molding and has not undergone any machining or drawing. The graph of the comparison material in Figure 28 shows that all of the comparison material had dissolved and disappeared after approximately 25 days from the start of immersion.

[0092] In both (Sample N1) and (Sample N2), a layer of magnesium crystal grains with the (0001 plane) in the hexagonal structure oriented toward the surface of the sample is continuous around the entire circumference in at least one cross-section. As shown in Figure 28, the dissolution rates of (Sample N1) and (Sample N2) are significantly slower than those of the comparison material.

[0093] Although different simulated body solutions were used for the solubility evaluation tests of (Sample N1) and (Sample N2) and the comparative material, as in the comparative material solubility evaluation test, the pH is higher (more alkaline) when the simulated body solution is HBSS(+) only, as in the comparative material solubility evaluation test, compared to the solubility evaluation test of (Sample N1) and (Sample N2), as the simulated body solution is HBSS(+) with sodium bicarbonate added. Therefore, pure magnesium has the characteristic of being less soluble. In other words, despite being in a test environment that was less soluble than (Sample N1) and (Sample N2), the comparative material dissolved and disappeared more quickly. Furthermore, despite the volume of the comparative material being larger than that of (Sample N1) and (Sample N2), the comparative material dissolved and disappeared more quickly.

[0094] Furthermore, the cross-section in which the magnesium crystal grain layer described above is continuous around the entire circumference shows that the continuous layer in the longitudinal direction is wider in (Sample N1) than in (Sample N2). Therefore, it can be seen that the dissolution rate of (Sample N1) is even slower than that of (Sample N2).

[0095] Furthermore, in this embodiment, the results of detecting the orientation of magnesium crystal grains by backscatter electron diffraction show that by performing processes such as drawing, cutting, and cold forging on the extruded material obtained by extrusion molding, which apply uniform stress from the entire outer circumference toward the interior, the orientation of the crystal grains can be aligned over the entire circumference.

[0096] As described above, the biodegradable medical device of this embodiment is made of magnesium material, and in at least one cross-section, a layer of magnesium crystal grains in which the (0001 plane) in the hexagonal structure is oriented toward the surface is continuous around the entire circumference.

[0097] As a result, in the biodegradable medical device of this embodiment, in the cross-section, a layer of magnesium crystal grains oriented with the (0001) plane, which has higher corrosion resistance in vivo compared to the (10-10) plane and (2-1-10) plane in the hexagonal crystal structure, facing the surface, is continuous around the entire circumference. Therefore, dissolution is difficult to proceed from the surface of the biodegradable medical device toward the center of the device from any direction in the circumferential direction. Thus, compared to a case where magnesium crystal grains with the (10-10) plane or (2-1-10) plane, which has lower corrosion resistance in vivo, are oriented toward the surface on at least a portion of the surface of the biodegradable medical device, the corrosion resistance of the biodegradable medical device can be improved and it can be made less susceptible to dissolution by slowing down the progress of dissolution from the surface toward the center of the device.

[0098] In the biodegradable medical device of this embodiment, the layer of magnesium crystal grains is continuous in a direction perpendicular to the cross-section.

[0099] As a result, in the biodegradable medical device of this embodiment, a layer of magnesium crystal grains, which is resistant to dissolution from the surface of the biodegradable medical device toward the center of the device in any circumferential direction, is continuous in the longitudinal direction in the cross-section. Therefore, the area ratio of the portion where the magnesium crystal grain layer is located inside the entire surface of the device is relatively large. Thus, the corrosion resistance of the biodegradable medical device can be further enhanced, making it more resistant to dissolution.

[0100] As shown in Figure 29, Figure 3 shows the orientation of magnesium crystal grains when the observation point a1 of the cross-section (section along line AA in Figure 29) is observed from the 3 axes, for the cross-sections (sections along line AA) obtained by cutting the cylindrical samples (samples N1) and N2) with a plane perpendicular to the longitudinal direction. In other words, the orientation of magnesium crystal grains observed from the 3 axes shown in Figure 3 indicates which faces of the magnesium crystal grains are oriented in the 3 axes when the sample is observed along its longitudinal direction.

[0101] As described above, in Figure 3, magnesium crystal grains in which the (0001) plane in the hexagonal structure is tilted at 0 to 45 degrees with respect to the 3 axes which are the observation direction are shown in black, magnesium crystal grains in which the (10-10) plane is tilted at 0 to 45 degrees with respect to the 3 axes which are the observation direction are shown in a dark gray color, and magnesium crystal grains in which the (2-1-10) plane is tilted at 0 to 45 degrees with respect to the 3 axes which are the observation direction are shown in a light gray color.

[0102] In Figure 3, for observation point a1 on the cross-section, the percentage of magnesium crystal grains in which the (2-1-10) plane in the hexagonal structure is oriented toward the end face (percentage of low-concentration gray magnesium crystal grains) is 47.5% for (Sample N1) and 52.2% for (Sample N2).

[0103] In this embodiment, in a cross-section perpendicular to the longitudinal direction, "magnesium crystal grains in which the (2-1-10) plane in the hexagonal structure is oriented toward the end face" includes "magnesium crystal grains in which the (2-1-1) plane in the hexagonal structure is arranged perpendicular to the longitudinal direction" and "magnesium crystal grains in which the normal direction of the (2-1-1) plane in the hexagonal structure is tilted at 0 to 45 degrees with respect to the longitudinal direction (the direction of tilt may be any direction)."

[0104] Furthermore, "observing from three axial directions" means observing the sample along its longitudinal direction, as shown in Figure 29, and in the following explanation, it may be described as "observing from the longitudinal direction." In other words, "oriented toward the three axial directions" means "oriented toward the end face side."

[0105] As described above, both (Sample N1) and (Sample N2) are extruded materials obtained by extrusion molding and then machined or drawn. Assuming that the orientation of magnesium crystal grains is substantially the same in the longitudinal and circumferential directions of the samples, the orientation of magnesium crystal grains at the longitudinal end faces of (Sample N1) and (Sample N2) is considered to be substantially the same as the orientation of magnesium crystal grains in the cross-section shown in Figure 3.

[0106] In other words, at the end faces of (Sample N1) and (Sample N2), the proportion of magnesium crystal grains in which the (2-1-10) plane in the hexagonal structure is oriented toward the end face (the proportion of low-concentration gray magnesium crystal grains) is considered to be 47.5% for (Sample N1) and 52.2% for (Sample N2), similar to the observation point a1 in the cross-section of Figure 3.

[0107] The biodegradable medical device of this embodiment is made of magnesium material and has a layer of magnesium crystal grains formed in at least one predetermined cross section perpendicular to the longitudinal direction, in which the (0001) plane in the hexagonal crystal structure is oriented toward the surface side, and at least one end face in the longitudinal direction, the (2-1-10) plane in the hexagonal crystal structure is oriented toward the end face side.

[0108] As a result, in the biodegradable medical device of this embodiment, a layer of magnesium crystal grains is formed in a predetermined cross section perpendicular to the longitudinal direction, in which the (0001) plane, which has higher corrosion resistance in the body compared to the (10-10) plane and (2-1-10) plane in the hexagonal crystal structure, is oriented toward the surface. Therefore, dissolution is less likely to progress from the surface of the biodegradable medical device toward the center of the device. Furthermore, at the end face in the longitudinal direction, the (2-1-10) plane, which has higher corrosion resistance in the body compared to the (10-10) plane in the hexagonal crystal structure, is oriented toward the end face. Therefore, dissolution is less likely to progress from the end face toward the longitudinal side of the biodegradable medical device. Thus, by slowing down the dissolution from the surface toward the center of the biodegradable medical device and slowing down the dissolution from the end face toward the longitudinal side of the biodegradable medical device, the corrosion resistance of the biodegradable medical device can be increased and it can be made less likely to dissolve.

[0109] In the biodegradable medical device of this embodiment, the proportion of magnesium crystal grains in which the (2-1-10) plane in the hexagonal crystal structure is oriented toward the end face is approximately 50% at the longitudinal end face.

[0110] As a result, in the biodegradable medical device of this embodiment, a layer of magnesium crystal grains that do not easily dissolve is formed in a predetermined cross section perpendicular to the longitudinal direction, moving from the surface of the biodegradable medical device toward the center of the device. Furthermore, at the longitudinal end face, the proportion of magnesium crystal grains with a (2-1-10) plane that does not easily dissolve moving toward the longitudinal side from the end face of the biodegradable medical device is relatively large. Therefore, the corrosion resistance of the biodegradable medical device can be further enhanced, making it more resistant to dissolution.

[0111] In the biodegradable medical device of this embodiment, the magnesium material is a pure magnesium material containing 99.9% by mass or more of magnesium.

[0112] As a result, in the biodegradable medical device of this embodiment, even when a high-purity magnesium material with low corrosion resistance in the body is used as the magnesium material, the corrosion resistance of the biodegradable medical device can be enhanced and it can be made less likely to dissolve.

[0113] Although embodiments of the present invention have been described above, the configuration of this embodiment is not limited to those described above, and various modifications are possible.

[0114] For example, in the above embodiment, plates, pins, and screws used in the body, for example, to attach or fix bones, were described as biodegradable medical devices, but biodegradable medical devices are not limited to these. The shape and method of use of biodegradable medical devices are arbitrary. In the above embodiment, a cylindrical sample was described as a biodegradable medical device, but the effects of the present invention can be obtained regardless of the shape of the biodegradable medical device.

[0115] In the above embodiments, the biodegradable medical device is formed from a pure magnesium material containing 99.9% by mass or more of magnesium, but is not limited thereto. The biodegradable medical device may be formed from a magnesium alloy with magnesium as the main component. For example, the magnesium alloy of the present invention is a magnesium alloy containing, by mass%, 1.0 to 2.0% Zn, 0.05 to 0.80% Zr, 0.05 to 0.40% Mn, with the remainder being Mg and unavoidable impurities. Furthermore, the magnesium alloy of the present invention may also contain, by mass%, 0.005% or more and less than 0.20% Ca. That is, the magnesium alloy may be a magnesium alloy containing, by mass%, 1.0 to 2.0% Zn, 0.05 to 0.80% Zr, 0.05 to 0.40% Mn, 0.005% or more and less than 0.20% Ca, with the remainder being Mg and unavoidable impurities. In that case as well, the same effects as in the above embodiments can be obtained.

[0116] Other configurations can also be modified in various ways without departing from the spirit of the present invention.

Claims

1. Formed from magnesium material, In at least one predetermined cross section perpendicular to the longitudinal direction, a layer of magnesium crystal grains is formed in which the (0001) plane in the hexagonal structure is oriented toward the surface side. A biodegradable medical device characterized in that, at least one longitudinal end face, the proportion of magnesium crystal grains in which the (2-1-10) plane in the hexagonal structure is oriented toward the end face is 47.5% or more and 52.2% or less.

2. The biodegradable medical device according to claim 1, characterized in that the magnesium material is a pure magnesium material containing 99.9% by mass or more of magnesium.

3. The biodegradable medical device according to claim 1, characterized in that the magnesium material is a magnesium alloy having magnesium as its main component.

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