Medical device

Abstract

To provide an alloy which exhibits a sufficient radial force for a fixed period of time after detention and suppresses initial remodeling, but is made flexible with time after the passage of the fixed period of time, and is used for a medical instrument, and to provide a medical instrument using the same.SOLUTION: A medical instrument is formed of an alloy having an equivalent strain of a constant level or higher, wherein the alloy contains gold as a main component, and silver and / or palladium as an accessory component, or contains silver as a main component and gold and / or palladium as an accessory component, when the alloy is allowed to stand under a 37°C ambient pressure atmosphere, hardness after standing is reduced to hardness of 70% or less for 3 to 122 days.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to medical instruments.

Background Art

[0002] It has been conventionally known that metal materials are used as constituent materials for medical instruments such as stents, bone plates, and coils. Various properties are required for the metal materials constituting medical instruments in consideration of their uses and usage modes. That is, since medical instruments are instruments that directly contact the human body or are implanted into the human body, biocompatibility and chemical stability (corrosion resistance) are required. In addition, high mechanical properties (strength, elasticity) are also required for medical instruments such as stents that are applied to blood vessels that permanently pulsate and beat, etc.

[0003] For example, in the stent shown in Patent Document 1, there is a part called an interconnecting element (connecting part) that connects adjacent cylindrical elements. This connecting part secures the shape of the stent in the longitudinal direction, generates a radial force that prevents remodeling of the blood vessel after expansion, and ensures mechanical properties.

[0004] On the other hand, after the blood vessel is dilated, the implanted stent requires a radial force that prevents remodeling of the blood vessel for a certain period, but then the radial force is no longer necessary. Rather, at this time, its rigid characteristics may even cause excessive stress on the blood vessel, that is, it has been found that softening is required thereafter. It has also been found that it is necessary to consider the balance between strength and the softening period for aneurysm treatment coils and bone plates.

[0005] Here, in the basic research field of metals, it has been reported that when pure silver is subjected to severe plastic deformation at a pressure of 6 GPa and then placed at room temperature (27 °C: 300 K), it softens to the same hardness as after annealing in about 5 days each (see Non-Patent Document 1).

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Non-Patent Document

[0007]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0008] The inventor considered that the pure gold or pure silver of this Non-Patent Document 1 might be applicable as a constituent material of medical instruments.

[0009] However, when attempting to apply the pure gold or pure silver subjected to the severe plastic deformation described in Non-Patent Document 1 as a material for medical instruments, the following problems were found.

[0010] First, the strength of the severely plastically deformed pure gold or pure silver (hereinafter also referred to as tensile strength) is low. Therefore, even if these are directly applied to medical instruments, it is difficult to suppress the initial remodeling due to the high radial force. In particular, currently commercialized stents are made of stainless steel or CoCr alloy. The strength of stainless steel is 500 - 600 MPa, and the strength of CoCr alloy is as high as 1000 MPa, while the strength of the above pure gold is 300 MPa, and the strength of the above pure silver is as low as 170 MPa.

[0011] Second, for example, when the pure silver in Non-Patent Document 1 was left at 37°C after processing, the period until softening to 70% (hereinafter also referred to as the softening period) was calculated to be more than one day. Therefore, it will soften within the period when the radial force is still required.

[0012] The present invention has been made in view of such circumstances, and its object is to provide an alloy that can be used for medical devices, which exhibits sufficient radial force for a certain period after implantation to suppress initial remodeling, but softens over time after a certain period has elapsed, and furthermore, to provide a medical device using the same.

Means for Solving the Problems

[0013] In order to solve the above problems, the present inventors conducted intensive research. As a result, as an embodiment for solving at least one of the above problems, a medical device formed from an alloy having a plastic strain of a certain level or more, wherein the alloy contains gold as a main component and silver and / or palladium as sub-components, or contains silver as a main component and gold and / or palladium as sub-components, and the alloy, when left in a 37°C atmospheric pressure environment, provides a medical device whose hardness decreases to 70% or less of the hardness after leaving it within 3 days to 122 days.

Effects of the Invention

[0014] According to the above embodiment, an alloy that can be used for medical devices, which exhibits sufficient radial force for a certain period after implantation to suppress initial remodeling, but softens over time after a certain period has elapsed, can be provided, and furthermore, a medical device using the same can be provided.

Brief Description of the Drawings

[0015]

Figure 1

Figure 2

Figure 3

Figure 4(a)

Figure 4(b)

Figure 4(c)

Figure 5(a)

Figure 5(b)

Figure 5(c)

Figure 5(d)

Figure 6

Mode for Carrying Out the Invention

[0016] Hereinafter, embodiments of the present invention will be described. Note that the present invention is not limited only to the following embodiments. Also, the dimensional ratios in the drawings are exaggerated for the convenience of explanation and may be different from the actual ratios. Further, in this specification, "X to Y" indicating a range means "X or more and Y or less", and "weight" and "mass", "weight %" and "mass %", and "parts by weight" and "parts by mass" are treated as synonyms. Also, unless otherwise specified, measurements of operations and physical properties, etc. are measured under the conditions of room temperature (in the range of 25 ° C ± 5 ° C (20 to 30 ° C) / relative humidity of 40 to 50%).

[0017] <Medical device> According to one embodiment of the present invention, there is provided a medical device formed from an alloy having a equivalent strain of a certain level or more, the alloy containing gold as a main component and silver and / or palladium as sub-components, or containing silver as a main component and gold and / or palladium as sub-components, and the alloy having a hardness that decreases to 70% or less of the hardness after being left in an atmosphere of 37 ° C and atmospheric pressure within 3 days to 122 days when left to stand.

[0018] According to one embodiment of the present invention, the medical device is a stent, a bone plate, or a coil (a coil used for treating an aneurysm). According to one embodiment of the present invention, the medical device is a stent (hereinafter also referred to as a softened stent).

[0019] The thickness of the softened stent (annular body, connecting portion) according to the present embodiment has a radial force necessary for being placed in a stenotic portion and does not impede blood flow. For example, a range of 1 to 1000 μm is preferable, and a range of 50 to 300 μm is more preferable.

[0020] The softened stent according to the present embodiment is used for a balloon-expandable stent (balloon-expanded stent) in the same manner as a conventionally used stent.

[0021] The shape of the softening stent according to this embodiment preferably has a strength sufficient to be stably placed in a living body lumen such as a blood vessel. Specific shapes of the softening stent include, for example, those having an opening in a tubular body, those formed by knitting fibers into a cylindrical shape, and the like.

[0022] Hereinafter, as an aspect of the softening stent according to this embodiment, an example of a balloon-expandable stent will be given, and the stent shown in FIG. 1 will be described. As shown in FIG. 1, the stent 1 is composed of a plurality of wavy annular bodies formed in a ring shape by linear components 2 arranged in the axial direction, and adjacent wavy annular bodies are connected by a connecting portion C (both the first connecting portion and the second connecting portion: not numbered), both end portions are open, and it is a cylindrical body extending in the longitudinal direction between the two end portions. In this embodiment, being a wavy annular body has the effect of obtaining a large expansion ratio and being able to cope with overexpansion, which is often required in actual use.

[0023] Adjacent wavy annular bodies are connected by a relatively short first connecting portion or a relatively long second connecting portion. The side surface of the cylindrical body has a large number of notches communicating the outer surface and the inner surface, and by deforming these notches, the cylindrical body has a structure that can expand and contract in the radial direction. And when it is placed in a living body lumen such as a blood vessel, it maintains its shape. In the form shown in FIG. 1, the stent 1 has a substantially rhombic element A having a notch inside as a basic unit. The substantially rhombic element A is composed of a linear component 2 and a first connecting portion. Also, by continuously arranging and joining the substantially rhombic elements A in the short axis direction, an annular body B formed in a ring shape is formed. The annular bodies B are arranged in a plurality in the axial direction, and adjacent annular bodies B are further connected by a second connecting portion. As a result, adjacent annular bodies B are arranged continuously in the axial direction in a state where a part of each is joined to each other. The stent 1 has a cylindrical body with both end portions open and extending in the longitudinal direction between the two end portions with such a configuration. And the side surface of the cylindrical body has substantially rhombic notches, and by deforming these notches, the cylindrical body has a structure that can expand and contract in the radial direction.

[0024] In the stent of the present embodiment, annular bodies (wavy annular bodies) formed in a ring shape by linear components 2 are arranged in a plurality in the axial direction, and adjacent annular bodies are connected by connecting portions C (first connecting portion and second connecting portion), and the annular bodies and the connecting portions C can be formed of the alloy of an embodiment of the present invention. Thus, when each part constituting the stent is formed of the alloy of an embodiment of the present invention, sufficient radial force is exerted immediately after implantation to suppress initial remodeling, but over time, the entire stent is softened in the same way and does not prevent recovery to a normal vascular state, and a stent can be provided.

[0025] In addition, since the alloy of an embodiment of the present invention has a high specific gravity and high radiopacity, providing such a metal material has the effect of enabling good confirmation of the position of the stent under fluoroscopy. That is, in a normal stent, an radiopaque metal material may be specially installed as a marker at the stent end so that the position of the stent can be well confirmed under fluoroscopy. However, in a stent provided with an X-ray opaque marker only at the end, the entire shape of the stent cannot be grasped, and there is a problem that all or part of the branch blood vessels existing near the implantation site may be blocked by the stent body. In contrast, in the present embodiment, by using the alloy of an embodiment of the present invention having a high specific gravity and high radiopacity, the effect of excellent visibility of the position of the stent is imparted without providing a separate marker, and it can be implanted more safely into the biological lumen. That is, due to excellent radiopacity during implantation, the position of the stent is clearly understood and the operation becomes easy.

[0026] The structure of the stent in the present embodiment is not limited to the form shown in FIG. 1, and it is sufficient that annular bodies formed in a ring shape by linear components are arranged in a plurality in the axial direction and adjacent annular bodies are connected by connecting portions. Further, regarding the cross-sectional shape of the wire material (that is, the linear component) constituting the stent, examples include a rectangle, a circle, an ellipse, and other polygons, but other shapes may also be used.

[0027] Also, the size of the stent described above is not particularly limited and may be appropriately selected according to the application site. The outer diameter of the stent before expansion (when attached to the balloon) is preferably about 0.3 to 5 mm, more preferably about 0.4 to 4.5 mm, and particularly preferably about 0.5 to 1.6 mm. Also, the length of the stent is not particularly limited and can be appropriately selected according to the disease to be treated. For example, the length of the stent is preferably about 5 to 100 mm, more preferably about 6 to 50 mm. Alternatively, the length of the stent may be preferably about 1.5 to 4 mm, and more preferably about 2 to 3 mm in some cases.

[0028] <Alloy for forming a medical device> According to an embodiment of the present invention, there is provided an alloy for forming a medical device, the alloy having a certain amount or more of equivalent strain, the alloy containing gold as a main component and silver and / or palladium as sub-components, or containing silver as a main component and gold and / or palladium as sub-components, and when the alloy is left in an atmosphere of 37°C and atmospheric pressure, the hardness after the leaving decreases to 70% or less of the hardness after 3 days to 122 days.

[0029] The alloy according to this embodiment is an alloy having a certain amount or more of equivalent strain. By being such an embodiment, the alloy softens over time. An alloy having a certain amount or more of equivalent strain can be produced by severe plastic deformation. That is, it can be said that the alloy for forming the medical device according to this embodiment becomes an alloy having the certain amount or more of equivalent strain by severe plastic deformation. The alloy for forming the medical device according to this embodiment is an alloy having an equivalent strain of 1.5 or more, 3 or more, 4 or more, 12 or more, 30 or more, 48 or more, or 65 or more. The alloy for forming the medical device according to this embodiment is an alloy having an equivalent strain of 1000 or less, 500 or less, 300 or less, 100 or less, 80 or less, 60 or less, 40 or less, 20 or less, or 15 or less.

[0030] The equivalent strain of the alloy for forming the medical device according to this embodiment can be obtained by the following formula.

[0031]

Number

[0032] Note that the alloy forming the medical device according to this embodiment is not limited to the alloy processed by HPT, and may be an alloy using another severe plastic deformation process. In that case, the strain is preferably the same as the strain in the case of processing by HPT.

[0033] The alloy having a plastic strain of a certain level or more contains gold as a main component and silver and / or palladium as sub-components, or contains silver as a main component and gold and / or palladium as sub-components. By setting such an alloy composition, it is possible to adjust and control the timing of softening over time. In particular, when adding gold or palladium as a sub-component to the main component silver, by increasing the addition amount of the sub-component, the strength can be improved (solution strengthening) (the low strength, which is the first problem in Non-Patent Document 1, can be eliminated), and the softening period can be extended (the short softening period, which is the second problem in Non-Patent Document 1, can be eliminated).

[0034] The following can be considered as the mechanism of action of such an effect. First, it is considered that pure gold and pure silver exhibit room temperature softening phenomenon by severe plastic deformation described in Non-Patent Document 1 due to the following mechanism of action. That is, gold and silver have a smaller stacking fault energy than other metals such as copper, aluminum, and iron (stacking fault energy: Ag 16, Au 32, Cu 45, Al 150, Fe 950 (unit: mJ / m 2)) The stacking defect area is large. Therefore, the amount of accumulated dislocations due to severe plastic working becomes large, and the driving force for dislocation annihilation reaction and grain growth due to high strain energy is large. Therefore, reduction of dislocation density and grain coarsening occur even at room temperature. As a result, room temperature softening phenomenon is considered to occur. On the other hand, in the present embodiment, by increasing the addition amount of the sub-component, the stacking defect energy, which was small in pure silver or pure gold, becomes large, and the stacking defect area, which was large, becomes small. Therefore, the amount of accumulated dislocations due to severe plastic working, which was large in pure silver or pure gold, becomes small, and the driving force for grain growth due to strain energy, which was large, becomes small. Therefore, grain coarsening and reduction of dislocation density are less likely to occur. As a result, it is considered that the softening phenomenon is prolonged. Similarly, when adding silver or palladium as a sub-component to the main component gold, by increasing the addition amount of the sub-component, the strength is improved (solid solution strengthening), and the softening period can be extended. The action mechanism of such an effect is the same as the above-described action mechanism. Also, in order to improve the strength (solid solution strengthening), it is desirable to adjust the addition amount of the sub-component. Here, the main component refers to the case where the content rate of the main component of the alloy is 50 mol% or more. In the case of 50 mol% silver and 50 mol% gold, it is an alloy in which the main component is silver and the sub-component is gold. In one embodiment of the present invention, the main component is 60 mol% or more, 70 mol% or more, 80 mol% or more, 85 mol% or more in the alloy. In one embodiment of the present invention, the main component is 99 mol% or less, or 98 mol% or less in the alloy. In one embodiment of the present invention, the main component of the alloy is silver. In this case, the sub-component of the alloy is gold.

[0035] In one embodiment of the present invention, the gold content rate is more than 1 mol% and less than 5 mol%. By being in such a range, the softening period can be efficiently made to be within a predetermined range. Also, if the gold content rate is within the above range, an alloy having a certain amount of equivalent strain or more that can achieve both high strength and extension of the softening period can be produced at low cost without performing severe plastic working while contacting with a refrigerant. In one embodiment of the present invention, the gold content rate is more than 2 mol% and less than 5 mol%. In one embodiment of the present invention, the gold content rate is more than 3 mol% and less than 5 mol%.

[0036] In one embodiment of the present invention, the gold content is more than 5 mol% and less than 20 mol%, more than 6 mol% and less than 20 mol%, more than 7 mol% and less than 18 mol%, more than 8 mol% and less than 15 mol%, or more than 8 mol% and less than 11 mol%. By performing severe plastic deformation while bringing the alloy into contact with the refrigerant, even within such a range, the softening period can be efficiently set within a predetermined range. Furthermore, in such an embodiment, the gold content can be increased, thereby further enhancing the strength, and thereby having a technical effect of reliably preventing the remodeling phenomenon (a phenomenon in which an expanded vascular stenosis site at the initial stage of indwelling attempts restenosis).

[0037] In one embodiment of the present invention, the main component of the alloy is silver, and the sub-components are gold and palladium. By increasing the addition amount of the sub-components so as to obtain higher strength, a contradictory phenomenon that the softening period becomes too long may occur. Therefore, by combining gold having a large crystal radius and palladium having a small crystal radius with respect to the main component silver (crystal radius: Ag 1.29, Au 1.51, Pd 0.78 (unit: Å)), strength improvement (solid solution strengthening) can be achieved, and a state can be created in which although strain exists locally, the strain is canceled out as a whole. Thereby, the long-term softening period can be shortened, and the contradictory high strength and short softening period can be made compatible.

[0038] In one embodiment of the present invention, the period (softening period) from when the alloy is left in an atmosphere of 37°C and atmospheric pressure until the hardness decreases to 70% or less of the hardness after the leaving is 3 days to 122 days. In a preferred embodiment, it is more than 30 days, 40 days or more, or 60 days or more. By being within such a range (lower limit), an appropriate balance between strength and softening period can be achieved according to the application. The number of days may be calculated by rounding the first digit after the decimal point. The period from the hardness after leaving to a hardness of 70% or less is an actual measured value or a predicted value, preferably an actual measured value.

[0039] Note that the softening period may be determined by leaving the sample at 37°C. However, since the evaluation period can be shortened, for example, the number of days until the hardness decreases obtained from the accelerated tests conducted at 100°C, 75°C, and 55°C can be plotted on a graph with the horizontal axis being 1 / T (T: temperature in K) and the vertical axis being lnDe70 (De70: the period until softening from the hardness immediately after processing to 70% of that value), and an approximate straight line can be drawn through the three plotted points. Then, it may be determined based on this approximate straight line (regression line). Note that the temperatures for the above accelerated tests are not limited to the above three points, and any three or more temperatures (as long as they are higher than 37°C, but preferably temperatures of 50°C or higher where evaluation can be obtained in a shorter time) from which an approximate straight line (regression line) can be obtained are acceptable.

[0040] Here, the hardness after standing refers to the hardness of the alloy immediately after subjecting the alloy to severe plastic deformation (within 2 hours at room temperature after severe plastic deformation, particularly 2 hours). The hardness of the alloy can be determined by the Vickers hardness (Hv) measured in accordance with JIS-Z 2244:2009 "Vickers hardness test - Test method".

[0041] In one embodiment of the present invention, the strength (tensile strength TS) of the alloy within 2 hours after subjecting the alloy to severe plastic deformation is 350 MPa or more, 380 MPa or more, or 400 MPa or more. In one embodiment of the present invention, the strength (tensile strength TS) of the alloy within 2 hours after subjecting the alloy to severe plastic deformation is 620 MPa or less, or 450 MPa or less. In one embodiment of the present invention, the strength (tensile strength TS) of the alloy within 2 hours after subjecting the alloy to severe plastic deformation using a refrigerant is 400 MPa or more, 450 MPa or more, or 500 MPa or more. In one embodiment of the present invention, the strength (tensile strength TS) of the alloy within 2 hours after subjecting the alloy to severe plastic deformation using a refrigerant is 600 MPa or less, or 500 MPa or less.

[0042] <Method for manufacturing medical instruments> In one embodiment of the present invention, a step of subjecting an alloy containing gold as a main component and silver and / or palladium as sub-components, or an alloy containing silver as a main component and gold and / or palladium as sub-components, to severe plastic deformation to obtain a severely plastically deformed alloy, and a step of forming the severely plastically deformed alloy into a medical device are provided. The severe plastic deformation is such that when the alloy is subjected to a equivalent strain of a certain level or more and the alloy having the equivalent strain of a certain level or more is left in an atmosphere of 37 °C and atmospheric pressure, the hardness after leaving decreases to 70% or less of the hardness before leaving in 3 to 122 days. A method for manufacturing a medical device is provided.

[0043] The description of the alloy containing gold as a main component and silver and / or palladium as sub-components, or the alloy containing silver as a main component and gold and / or palladium as sub-components is as described above.

[0044] Note that an alloy having a desired composition component and shape (such as size and thickness) can be obtained, for example, from a professional vendor (manufacturer). It can also be manufactured by a conventionally known method. For example, pure silver as the main component and pure gold as the sub-component are melted at a predetermined blending ratio (composition ratio) and poured into a mold for casting, or an alloy obtained by cooling and solidifying the melt is struck (pressed) for molding, or rolled (formed) with a mold for forging, etc.

[0045] Severe plastic deformation is a process that applies strain while applying high pressure to a sample, and can impart extremely large strains (severe plastic strains) that are impossible with conventional processes (such as tensile processing, compression processing, rolling processing, etc.). Therefore, it is a processing technology with the potential to create materials that were impossible with conventional processing (such as tensile processing, compression processing, rolling processing, etc.) methods. Metal materials can be strengthened by increasing the number of dislocations and refining the crystal grains by applying plastic deformation (strain). However, in conventional processing (such as tensile processing, compression processing, rolling processing, wire drawing processing, etc.), the sample shape decreases with processing, so there is a limit to the amount of strain that can be introduced. In recent years, a processing method called shape-invariant processing, in which the sample shape does not change during processing, has been developed. One of them is the HPT (High-Pressure Torsion) processing method (a type of severe plastic deformation processing), and in this method, an infinite amount of strain can be introduced.

[0046] The conditions for severe plastic deformation processing vary depending on the alloy composition components and the severe plastic deformation processing method, etc. By applying a high pressure of 1 GPa or more (2 GPa or more, or 4 GPa or more. The upper limit is usually 50 GPa or less, or 20 GPa or less) to the sample and performing processing that gives a strain of 639% or more in terms of tensile strain conversion, an alloy with an equivalent strain of 2 or more can be obtained. Also, when a strain of 5360% is given in terms of tensile strain conversion, an alloy with an equivalent strain of 4 can be formed. When a strain of 298000% is given in terms of tensile strain conversion, an alloy with an equivalent strain of 8 can be formed. When a strain of 2200000% is given in terms of tensile strain conversion, an alloy with an equivalent strain of 10 can be formed.

[0047] Also, severe plastic deformation processing may be carried out at room temperature, or may be carried out while bringing the alloy into contact with a refrigerant. This is because by carrying out severe plastic deformation processing while bringing the alloy into contact with a refrigerant (for example, under liquid nitrogen), a decrease in the dislocation density during severe plastic deformation processing can be suppressed. As a result, since the accumulated dislocation amount can be increased, when compared with the same alloy composition components, a significant shortening of the softening period can be realized.

[0048] Here, in order to perform severe plastic deformation while bringing the alloy into contact with the refrigerant, (a) the alloy or a mold containing the alloy may be immersed in a liquid refrigerant (while directly contacting the refrigerant), or (b) the refrigerant (liquid refrigerant or vaporized refrigerant) may be indirectly blown (while contacting) onto a mold that sandwiches the alloy (twisted at high pressure, slid at high pressure, or repeatedly subjected to multi-pass bonding rolling), or (c) the refrigerant (liquid refrigerant or vaporized refrigerant) may be directly blown (while contacting) onto the alloy. There are no particular restrictions.

[0049] Also, as the refrigerant, conventionally known ones can be appropriately used. For example, liquid nitrogen (-196°C), liquid helium (-269°C), liquid hydrogen (-253°C), a mixed refrigerant of ethyl alcohol and dry ice (-72°C), a mixed solvent of ether and dry ice (-98°C), a mixed solvent of ethyl ether and dry ice (-77°C), a mixed solvent of acetone and dry ice (-66°C), a mixed solvent of acetonitrile and dry ice (-42°C), a mixed solvent of zinc oxide and ice (-62°C), etc. can be mentioned (the temperature in parentheses is the achievable temperature of the temperature drop by the refrigerant). However, it is not limited to these. From the perspective of the action mechanism by performing severe plastic deformation while contacting the above-mentioned refrigerant, a refrigerant with a lower temperature is preferable. However, from the perspective of equipment costs, etc. required for the production and maintenance of the liquid refrigerant, a refrigerant with a temperature not too low is preferable. Therefore, by considering both aspects, an optimal refrigerant can be appropriately selected. In one embodiment of the present invention, the achievable temperature of the temperature drop by the refrigerant (the surface temperature of the alloy to be processed) is -100°C or lower, -150°C or lower, or -170°C or lower. In one embodiment of the present invention, the achievable temperature of the temperature drop by the refrigerant (the surface temperature of the alloy to be processed) is -200°C or higher, -160°C or higher, or -120°C or higher.

[0050] As severe plastic working, when using the above HPT processing, using the HPT processing apparatus 21a or 21b shown in FIGS. 2(a) and (b), as a disk-shaped sample 23a or a ring-shaped sample 23b, for example, a disk-shaped sample 23a with a diameter (φ) of 5 to 100 mm (particularly 10 mm) and a thickness of 0.5 to 10 mm (particularly 1 mm), or an outer diameter of 5 to 150 mm (particularly 10 mm), an inner diameter of 3 to 145 mm (particularly 5 mm), and a thickness of 0.5 to 10 mm (particularly 1 mm) of the ring-shaped sample 23b is sandwiched from above and below by the upper pressing member 25a or 25b and the lower rotary pressing member 27a or 27b, and for example, a high pressure of 2 GPa or more, 4 GPa or more, particularly 6 GPa (usually 10 GPa or less, or 20 GPa or less) is applied to the sample 23a or the sample 23b while only the lower rotary pressing member 27a or 27b is rotated 0.25 to 20 rotations (particularly 1 to 5 rotations) to twist and apply strain, so that an alloy in which the equivalent strain gradually increases from the center to the outer edge of the sample 23a or the sample 23b is obtained.

[0051] In the examples described below, without separately preparing samples with different equivalent strains, an equivalent strain of approximately 1.81 to 90.69 can be obtained with one sample, so it is the one subjected to HPT processing under the above conditions. Although medical instruments may be formed using alloys with different equivalent strains for each part of the sample, severe plastic working that can form alloys with substantially the same equivalent strain for each part of the sample, for example, the HPS (High-Pressure Sliding) processing method, etc. may be used.

[0052] As described above, severe plastic deformation (also referred to as SPD: severe plastic deformation that applies severe strain) is not particularly limited, and various processing methods developed to date can be used. Specifically, examples of severe plastic deformation processing methods include those selected from the group consisting of HPT, HPS, ARB (Accumulative Roll-Bonding), ECAP (Equal-Channel Angular Pressing), MDF (Multi-Directional Forging), MF (Multiple Forging), CEC (Cyclic Extrusion and Compression), RCS (Repetitive Corrugation and Straightening), and TE (Twist Extrusion). By using these processing methods, it is possible to perform processing such that the equivalent strain becomes 2 or more. Further, these processing methods are metal processing techniques (known techniques) developed in the basic research field of metals in recent years, and are already disclosed in detail in various documents, technical books, on the Internet, etc., and patent gazettes, etc., so detailed descriptions of each processing method are omitted.

[0053] In one embodiment of the present invention, in order to reduce the hardness of the alloy to 70% or less of the hardness after standing for 3 days to 122 days, the above-described severe plastic deformation processing conditions, mainly the pressure and the strain amount (tensile strain amount), may be appropriately selected. Further, the rotation speed or the rotational speed may be adjusted. For example, when using an HPT processing apparatus, the rotation speed is, for example, 0.25 to 20 rotations, or 0.5 to 10 rotations. Further, the rotational speed is, for example, 0.25 to 10 rpm, or 0.5 to 5 rpm.

[0054] <Method for producing a medical device> In one embodiment of the present invention, medical devices such as stents, bone plates, and coils are suitable. These medical devices can be manufactured by appropriately referring to conventionally known methods, except that they are formed from an alloy having a plastic strain of a certain level or more as described above. Taking the method of manufacturing a stent as an example, the method of manufacturing a stent can directly apply the method of manufacturing a stent from existing stainless steel or CoCr alloy. However, since the softening phenomenon is promoted when the temperature rises due to processing, it is advisable to take measures to prevent the temperature from rising. For example, after subjecting a pipe to severe plastic deformation processing, the pipe is cut into the pattern of a stent by laser processing (in this case, it is preferable to use, for example, a femtosecond laser that can suppress the temperature rise of the sample), and further chemical polishing and electrolytic polishing are performed to manufacture a stent as shown in FIG. 1. Note that the raw material to which severe plastic deformation is applied is not limited to a pipe shape. After subjecting a rod shape to severe plastic deformation processing, a hole may be drilled in the center with a drill to form a pipe, or after subjecting a plate to severe plastic deformation processing, it may be rounded and welded to form a pipe shape. Further, by the following manufacturing method, the softening time and strength can be changed according to the part of the stent. That is, a member is manufactured from the alloy material that has been subjected to severe plastic deformation processing by cutting or the like, and the members are solid-phase bonded by a known solid-phase bonding method, for example, pressure welding, diffusion bonding, friction welding (friction pressure welding), or ultrasonic welding, to manufacture a bonded body (rod). When performing this bonding, it is necessary to devise a cooling method that does not affect the softening phenomenon. The rod manufactured in this way is drilled out at the center by cutting to form a pipe shape. Thereafter, alignment is performed and the pipe is cut into the pattern of a stent by laser processing, and further chemical polishing and electrolytic polishing are performed to manufacture a stent as shown in FIG. 1.

[0055] <Storage (Usage Method) of Medical Devices> In one embodiment of the present invention, a medical device (e.g., a stent) is stored at -18°C or lower, -30°C or lower, or -50°C or lower (the lower limit is, for example, -196°C or higher, or -100 or higher) until it is introduced into a living body. This is because if the softened stent is left at room temperature after being obtained until it is introduced into and used in a living body, there is a risk of softening. In particular, by storing at -18°C or lower, this storage period can eliminate the loss of being discarded as a product that cannot be used (expired) because the stent does not soften.

Example

[0056] The effects of the present invention will be described using the following experimental examples.

[0057] (Experimental Example 1) Severe plastic deformation processed alloys obtained by subjecting pure silver and an alloy having silver as the main component and gold as the sub-component to severe plastic deformation were produced, and their strength and the softening period were examined.

[0058] (Production of severely plastic deformation processed pure silver and alloy) Specifically, pure silver and various alloys having silver as the main component and sub-component gold of 0.5 mol%, 1 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 10 mol%, 20 mol%, and 50 mol% were each processed into a disk (sample) having a diameter (φ) of 10 mm and a thickness of 1 mm.

[0059] Next, a process of obtaining severely deformed pure silver and alloys was carried out. Specifically, using the HPT processing apparatus 21a shown in Fig. 2(a), which is a type of severe plastic deformation processing, a disk-shaped sample 23a with a diameter (φ) of 10 mm and a thickness of 1 mm was sandwiched from above and below by an upper pressing member 25a and a lower rotating pressing member 27a, and only the lower rotating pressing member 27a was rotated at a rotational speed of 1 rpm for 1 or 5 rotations while applying a high pressure of 6 GPa to the sample 23a to perform a process of twisting and deforming it, thereby obtaining samples of severely deformed pure silver and alloys. It was confirmed that the shape of the sample 23a' (not shown) of severely deformed pure silver and alloys obtained in this way hardly changed even after HPT processing. Also, the equivalent strains at positions 1 mm, 2 mm, 3 mm, and 4 mm away from the center to the outer edge of the obtained samples 23a' of severely deformed pure silver and alloys were determined by the following formula.

[0060] [Number]

[0061] As a result, the equivalent strains at positions 1 mm, 2 mm, 3 mm, and 4 mm away from the center of the obtained samples 23a' of severely deformed pure silver and alloys were 3.63, 7.26, 10.88, and 14.51 in the case of 1 rotation, and 18.14, 36.28, 54.41, and 72.55 in the case of 5 rotations, respectively.

[0062] (Strength, etc. of severely deformed alloy) Regarding the samples 23a' of severely deformed pure silver and alloys obtained above, within 2 hours after severe plastic deformation processing, the tensile strength (TS), yield stress (YS), and elongation at break (EL) were measured in accordance with JIS Z 2241:2011 "Test Method for Tensile Testing of Metallic Materials". Note that the tensile test specimens were prepared by cutting out using a wire electrical discharge machining machine so that the position with an equivalent strain of 36.28, which is 2 mm away from the rotation center of the sample 23a' toward the outer edge, becomes the center of the parallel part of the test specimen. The crosshead moving speed was 0.00633 mm·sec -1It is as follows. The obtained results are shown in Fig. 3. Note that the values of the tensile strength (TS), yield stress (YS), and elongation at break in Fig. 3 all represent two values for Sample 1 and Sample 2. In Fig. 3, for example, "Ag-1" represents Sample 1 of pure silver, "Ag0.5Au-1" represents Sample 1 of an alloy containing 0.5 mol% of gold as a secondary component with silver as the main component, and "Ag50Au-2" represents Sample 2 of an alloy containing 50 mol% of gold as a secondary component with silver as the main component. The same applies to other samples.

[0063] From Fig. 3, as per the high-strength action mechanism of increasing the amount (content) of the secondary component gold added to the main component silver described above, it was confirmed that the tensile strength increases as the amount of the secondary component increases.

[0064] (Softening period of severely deformed alloy: Ag-Au alloy + HPT(RT) Hardness change over time) Regarding Sample 23a' of the severely deformed pure silver obtained above and each alloy with silver as the main component and gold as the secondary component, the softening period was examined using an accelerated test as necessary depending on the alloy composition. Specifically, for Sample 23a', the hardness of the alloy was measured in accordance with JIS Z 2244:2009 "Vickers hardness test - Test method". Also, the hardness measurement interval was set to be optimal considering the alloy composition, processing conditions, and test holding temperature, as the softening rates vary. Basically, the number of hardness measurement locations for one sample was four locations with different equivalent strains as described above. That is, the equivalent strains at positions 1 mm, 2 mm, 3 mm, and 4 mm away from the center of Sample 23a' towards the outer edge were measured. For one rotation, they were 3.63, 7.26, 10.88, 14.51 in order, and for five rotations, they were 18.14, 36.28, 54.41, 72.55 in order. Also, the number of samples of pure silver and each alloy was one, and for each sample, the hardness was measured at two different locations with the same distance from the center and the same equivalent strain, and the average value of the hardness for each equivalent strain was adopted. (The average value at the same measurement locations was also used for the hardness measurement during the softening period of the alloy processed by HPT while in contact with the refrigerant).

[0065] (95Ag-5Au alloy) The number of days (softening period) until the hardness decreases to 70% or less after leaving the sample 23a' of the 95Ag-5Au alloy at 37°C under atmospheric pressure was determined by an accelerated test. Specifically, for the sample 23a', the hardness was measured in accordance with JIS Z 2244:2009 "Vickers hardness test - Test method" at a constant high temperature (specifically, the following three points: 100°C, 75°C, and 55°C) under atmospheric pressure. The obtained results are shown in FIGS. 4(a), 4(b), and 4(c) for each accelerated test temperature.

[0066]

Table 1

[0067] According to the following formula 3, the number of days De70 required for the change to the 70% equivalent value obtained from the accelerated tests at 55°C, 75°C, and 100°C was plotted for each equivalent strain on a graph with the horizontal axis being 1 / T (T: temperature of the accelerated test (absolute temperature)) and the vertical axis being lnDe70 from three plotted points, and an approximate straight line was drawn. The number of days De70 required for the change to the 70% equivalent value at 37°C was determined from this approximate straight line (regression line). The results are shown in FIGS. 5(a) to 5(d).

[0068]

Equation

[0069] Here, the method of deriving this formula will be explained. First, it is generally known that the diffusion distance of atoms can be expressed by the following formula.

[0070]

Equation

[0071] Also, the diffusion coefficient D is expressed by the following formula.

[0072]

Equation

[0073] The softening phenomenon occurs when defects such as dislocations introduced by severe plastic working decrease due to recovery and recrystallization. Since this recovery and recrystallization occur due to atomic diffusion, the above formula was derived by combining these two equations.

[0074] Therefore, in the present invention, a method for calculating the predicted value of the softening period using the above mathematical formula 3 is provided.

[0075] The specimens were left in an atmosphere of 37 °C and atmospheric pressure from the approximate straight lines in FIGS. 5(a) to 5(d), and the number of days (softening period) required for the change to the equivalent value of 70% was determined. The results are shown in Table 2 below.

[0076] [Table 2]

[0077] From the results in Table 2 above, it was found that the number of days (number of years) of softening of the 95Ag-5Au alloy varies depending on the equivalent strain, but is 4.1 to 6.7 years.

[0078] For other alloys (98Ag-2Au alloy, 97Ag-3Au alloy, 96Ag-4Au alloy), the softening period was obtained by actual measurement and / or accelerated test. In the accelerated test, an approximate straight line was created in the same manner as above, and the softening period was obtained from the approximate straight line.

[0079] The results are shown below.

[0080] [Table 3]

[0081] [Table 4]

[0082] [Table 5]

[0083] In addition, as described above, when softening is predicted to occur over a long period, the predicted value obtained by the accelerated test may be used. As a result of the above verification, it was found that the predicted value and the measured value did not deviate significantly, that is, the reliability of the predicted value was also high.

[0084] (Experimental Example 2) An alloy having silver as the main component and gold as the sub-component was subjected to severe plastic deformation while being brought into contact with a refrigerant to produce a severely plastically deformed alloy, and its strength and the softening period were examined.

[0085] (Production of Severely Plastically Deformed Alloy) Specifically, an alloy having silver as the main component and 10 mol% of gold as the sub-component (also referred to as a 90Ag-10Au alloy) and an alloy having 20 mol% (also referred to as an 80Ag-20Au alloy) were each processed into a disk-shaped sample with a diameter (φ) of 10 mm and a thickness of 1 mm (sample) and prepared.

[0086] Next, the step of obtaining a severely plastically deformed alloy was carried out. Specifically, using an HPT (high-pressure torsion) processing apparatus 21a shown in Fig. 2(a), which is a type of severe plastic deformation processing, a disk-shaped sample 23a with a diameter (φ) of 10 mm and a thickness of 1 mm was sandwiched from above and below by an upper pressing member 25a and a lower rotary pressing member 27a, and only the lower rotary pressing member 27a was rotated 5 times at a rotational speed of 1 rpm while applying a high pressure of 6 GPa to the sample 23a to perform processing for applying strain by twisting, thereby obtaining a sample 23a' of a severely plastically deformed alloy. In this Example 2, while indirectly spraying liquid nitrogen, which is a refrigerant, onto the mold (the upper pressing member 25a and the lower rotary pressing member 27a) that sandwiches the sample 23a and twists it under high pressure (while bringing them into contact), HPT processing was performed. As a result, the surface temperature of the sample 23a during HPT processing could be lowered to approximately -170°C. It was confirmed that the sample 23a' of the severely plastically deformed alloy thus obtained hardly changed in sample shape even when HPT processed at low temperature.

[0087] (Softening period of severely deformed alloy: Change in hardness over time in the accelerated test of Ag-Au alloy + HPT (LN)) For the severely deformed 90Ag-10Au alloy obtained above, an approximate straight line was created in the same manner as above. From the approximate straight line, the number of days (softening period) required for the change to the equivalent value of 70% was determined by leaving it in an atmosphere of 37°C and atmospheric pressure. The results of the 90Ag-10Au alloy are shown below.

[0088] [Table 6]

[0089] From the results in Table 6 above, it was found that the softening period of the 90Ag-10Au (LN) alloy varies depending on the equivalent strain, but is generally 11 to 81 days under an atmosphere of 37°C and atmospheric pressure.

[0090] Also, for the sample of the 80Ag-20Au alloy, the results obtained at the accelerated test temperature (100°C) are shown in Fig. 6. Fig. 6 is a graph of the hardness measurement of a sample of the 80Ag-20Au (LN) alloy processed by HPT while spraying liquid nitrogen on the mold and placed at a high temperature of 100°C and atmospheric pressure.

[0091] From Fig. 6, the softening period of the 80Ag-20Au (LN) alloy cannot be calculated. However, in Fig. 4(c) of the results obtained at the accelerated test temperature (100°C) for the sample of the 95Ag-5Au alloy, the number of days of the softening period does not require even 1 day, but the softening period of the 95Ag-5Au alloy under an atmosphere of 37°C and atmospheric pressure is 4.1 to 6.7 years. On the other hand, in Fig. 6, it can be seen that the softening period is longer than 10 days. Therefore, it can be understood that the softening period of the 80Ag-20Au alloy under an atmosphere of 37°C and atmospheric pressure is longer than 4.1 to 6.7 years of the softening period of the 95Ag-5Au alloy under an atmosphere of 37°C and atmospheric pressure.

[0092] From the above, in the Ag-Au alloy subjected to severe plastic deformation while in contact with a refrigerant, when the content of the secondary component gold is more than 5 mol% and less than 20 mol%, and it is left in an atmosphere of 37°C and atmospheric pressure, it is considered that there is a composition that decreases to 70% or less of the hardness after leaving in 3 to 122 days. And that consideration is also supported by the fact that the softening period of the 90Ag-10Au alloy is 11 to 81 days under an atmosphere of 37°C and atmospheric pressure.

Explanation of symbols

[0093] 1 stent, 2 linear component, A substantially rhombic element, B annular body C connecting part 21a, 21b HPT processing device, 23a disk-shaped sample, 23b ring-shaped sample, 25a, 25b upper pressing member, 27a, 27b lower rotating pressing member.

Claims

1. A medical device which is a stent, a bone plate, or a coil used for treating an aneurysm, formed from an alloy composed of gold and silver having a gold content of more than 1 mol% and less than 20 mol% and having a equivalent strain of a certain level or more, wherein the alloy is, (1) when the gold content of the alloy is more than 1 mol% and less than 5 mol%, the equivalent strain of a certain level or more is 1.5 or more and less than 18.14, (2) when the gold content of the alloy is more than 5 mol% and less than 20 mol%, the equivalent strain of a certain level or more is 18.14 or more and 80 or less, and is obtained by performing severe plastic deformation while contacting with a refrigerant, and when the alloy is left in an atmosphere of 37 °C and atmospheric pressure, the hardness after leaving decreases to 70% or less of the hardness after leaving in 3 days to 122 days.

2. In the above (1), the gold content of the alloy is 2 mol% or more and 4 mol% or less, In the above (2), the gold content of the alloy is more than 7 mol% and less than 15 mol%, the medical device according to Claim 1.

3. In the above (2), the gold content of the alloy is more than 8 mol% and less than 11 mol%, the medical device according to Claim 2.

4. A step of subjecting an alloy composed of gold and silver having a gold content of more than 1 mol% and less than 20 mol% to severe plastic deformation to obtain a severely plastically deformed alloy having an equivalent strain of a certain level or more, and a step of forming the severely plastically deformed alloy into a medical device, wherein the medical device is a stent, a bone plate, or a coil used for treating an aneurysm, and the severe plastic deformation is, (1) when the gold content of the alloy is more than 1 mol% and less than 5 mol%, the equivalent strain of a certain level or more is made to be 1.5 or more and less than 18.14, (2) when the gold content of the alloy is more than 5 mol% and less than 20 mol%, the equivalent strain of a certain level or more is made to be 18.14 or more and 80 or less, and is performed while contacting the alloy with a refrigerant, and in the alloy having the equivalent strain of a certain level or more, when left in an atmosphere of 37 °C and atmospheric pressure, the hardness after leaving decreases to 70% or less of the hardness after leaving in 3 days to 122 days, a method for manufacturing a medical device.

5. In the above (1), the gold content of the alloy is 2 mol% or more and 4 mol% or less, The manufacturing method according to claim 4, wherein in (2) above, the gold content of the alloy is more than 7 mol% and less than 15 mol%.

6. The manufacturing method according to claim 5, wherein in (2) above, the gold content of the alloy is more than 8 mol% and less than 11 mol%.

7. The severe plastic working is selected from the group consisting of HPT (High-Pressure Torsion), HPS (High-Pressure Sliding), ARB (Accumulative Roll-Bonding), ECAP (Equal-Channel Angular Pressing), MDF (Multi-Directional Forging), CEC (Cyclic Extrusion and Compression), RCS (Repetitive Corrugation and Straightening), and TE (Twist Extrusion). The manufacturing method according to any one of claims 4 to 6.

8. The refrigerant is selected from the group consisting of liquid nitrogen, liquid helium, liquid hydrogen, a mixed refrigerant of ethyl alcohol and dry ice, a mixed solvent of ether and dry ice, a mixed solvent of ethyl ether and dry ice, a mixed solvent of acetone and dry ice, a mixed solvent of acetonitrile and dry ice, and a mixed solvent of zinc oxide and ice. The manufacturing method according to claim 4.

9. A method of using a medical device after obtaining the medical device by the manufacturing method according to any one of claims 4 to 8 and before introducing the medical device into a living body, the method comprising refrigerating and storing at -18°C or lower. A method of using a medical device.

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