WO2018230415A1

WO2018230415A1 - Linear material for medical use

Info

Publication number: WO2018230415A1
Application number: PCT/JP2018/021738
Authority: WO
Inventors: 三宅　行一; 広夫内田; 顕成檜
Original assignee: 三井金属鉱業株式会社; 国立大学法人名古屋大学
Priority date: 2017-06-15
Filing date: 2018-06-06
Publication date: 2018-12-20

Abstract

This linear material for medical use is composed of a Zn alloy that contains from 0.05% by mass to 5% by mass (inclusive) of Cu or from 0.01% by mass to 0.4% by mass (inclusive) of Ti, and has a cross-sectional area of from 0.01 mm2 to 4.0 mm2 (inclusive). It is preferable that this linear material for medical use contains from 0.1% by mass to 5% by mass (inclusive) of Mn. It is also preferable that this linear material for medical use contains from 0.01% by mass to 0.5% by mass (inclusive) of Ca. It is also preferable that the Mg content in the Zn alloy is 50 ppm or less. It is also preferable that this linear material for medical use has the shape of a staple or the shape of a clip.

Description

Medical linear material

The present invention relates to a medical linear material.

Conventionally, various metal materials are known as implant medical materials that are implanted in a living body for treatment.
Conventionally used medical materials made of Ti alloys do not have biodegradability, so they remain permanently in the body after surgery, and there is a fear of infection and a psychological burden on patients. Since Fe alloys also have a slow biodegradation rate (hereinafter also referred to as corrosion rate), there are concerns similar to those of Ti alloys.
On the other hand, although Mg alloy is attracting attention as a biodegradable alloy, its corrosion rate is high. Therefore, as described in Patent Documents 1 and 2, as an alternative, a technique using a Zn alloy as a biodegradable implant Has also been developed in recent years.

Patent Document 3 describes that various elements are added to a Zn alloy.

Chinese publication 10986146 WO2015 / 147183 pamphlet EP0899349A1

However, Zn alloys used in conventional biodegradable implants containing magnesium as described in Patent Document 1 and aluminum described in Patent Document 2 support the structure of biological tissues such as stents. Since the composition is prescribed for the device of, the strength is high, but the bendability is poor. For this reason, it is not suitable as a medical linear material having a relatively small cross-sectional area, such as a suture or anastomosis such as a staple or a clip.

As described above, Patent Document 3 describes that various additive elements are added to the Zn alloy. However, this document does not describe any medical use such as suture or anastomosis. Furthermore, the document does not describe or suggest any linear material having a specific cross-sectional area required for this application.

An object of the present invention is to provide a medical linear material that can eliminate various drawbacks of the above-described conventional technology.

As a result of intensive studies to solve the above problems, the present inventors have found that a Zn alloy containing a specific amount of Cu or Ti is suitable as a medical linear material having a specific cross-sectional area.

The present invention is based on this finding, and includes a Zn alloy containing at least one of 0.05% by mass to 5% by mass Cu and 0.01% by mass to 0.4% by mass Ti. made, there is provided a medical linear material is cross-sectional area 0.01 mm ² or more 4.0 mm ² or less.

FIG. 1A is a schematic diagram illustrating an example of a staple shape. FIG. 1B is a schematic diagram illustrating a state in which the staple illustrated in FIG. FIG. 2A is a schematic diagram illustrating an example of a clip shape. FIG. 2B is a schematic diagram illustrating a state where the clip illustrated in FIG. It is a schematic diagram which shows the method of the bending test of the material of an Example and a comparative example.

Hereinafter, the medical linear material of the present invention will be described based on preferred embodiments thereof.
The medical linear material of this embodiment is 0.05 mass% or more and 5 mass% or less of copper (hereinafter referred to as Cu), or 0.01 mass% or more and 0.4 mass% or less of titanium (hereinafter, Ti). And zinc) (hereinafter referred to as Zn) alloy. The medical linear material of the present embodiment is suitable as a medical linear material having a specific cross-sectional area by employing a Zn alloy having this composition.

In the present embodiment, the Zn alloy preferably has a Zn ratio of 80% by mass or more, more preferably 90% by mass or more, and particularly preferably 95% by mass or more. The Zn alloy constituting the medical linear material further contains Cu or Ti.

When the Zn alloy constituting the medical linear material contains Cu, the bendability of the medical linear material is set to a certain level or more by the amount of Cu in the Zn alloy being 0.05% by mass or more. In addition, the intergranular corrosion of the linear material can be suppressed. Moreover, the ductility required for the process to a linear material can be improved, maintaining the intensity | strength of a medical linear material because the amount of Cu in Zn alloy is 0.05 mass% or more. When the amount of Cu in the Zn alloy is 5% by mass or less, it is easy to improve the bendability and ductility of the medical linear material, and it is possible to prevent the corrosion rate of the linear material from becoming too high. From these viewpoints, when the Zn alloy constituting the medical linear material contains Cu, the amount of Cu in the Zn alloy is preferably 0.1% by mass or more and 4.0% by mass or less, and 0.5% by mass or more. 3.0 mass% or less is more preferable.

In the case where the Zn alloy constituting the medical linear material contains Ti, the bendability of the medical linear material is more than a certain level when the Ti content in the Zn alloy is 0.01% by mass or more. In addition, the ductility can be increased without impairing the strength. If the amount of Ti in the Zn alloy exceeds 0.4% by mass, the bendability and ductility deteriorate and the desired function cannot be expressed, which is not preferable. From these viewpoints, when the Zn alloy constituting the medical linear material contains Ti, the amount of Ti in the Zn alloy is preferably 0.05% by mass or more and 0.4% by mass or less, and 0.1% by mass or more. 0.3 mass% or less is more preferable.

Zn alloy constituting the medical linear material may further contain Mn or Ca in addition to Cu or Ti. The Zn alloy constituting the medical linear material contains Cu and Ti, or contains Cu and Mn or Ca, so that it is easy to obtain a medical linear material having bendability, ductility, and strength. preferable. A Zn alloy containing Cu and Mn or Ca may further contain Ti. A Zn alloy containing Ti and Mn also has bendability and strength.

As a preferable composition of the Zn alloy, it is an alloy containing Zn and Cu and / or Ti and may contain at least one selected from Mn, Ca and Mg, and the balance is only an inevitable element. Preferably, the alloy contains Zn and Cu and / or Ti and may contain at least one selected from Mn and Ca, with the balance being only inevitable elements. The specific structure of such an alloy includes an alloy containing Zn and Cu and the balance being inevitable elements only; an alloy containing Zn and Ti and the balance being only inevitable elements; the balance containing Zn, Cu and Ti Is an alloy that contains only inevitable elements; an alloy that contains Zn, Cu, and Mn, and the balance that contains only inevitable elements; an alloy that contains Zn, Cu and Ca, and the balance that contains only inevitable elements; which contains Zn, Ti and Mn An alloy in which the balance is only inevitable elements; an alloy in which Zn, Cu, Mn and Ti are included, and the balance is only inevitable elements; an alloy in which the balance is Zn, Cu, Mn and Ca and the balance is only inevitable elements.

For example, it is preferable that the Zn alloy constituting the medical linear material contains 0.1% by mass or more of manganese (hereinafter referred to as Mn) from the viewpoint of increasing the strength or elongation and the bendability. Further, when the Zn alloy contains Mn, it is preferable that the amount of Mn in the Zn alloy is 5% by mass or less because the bendability and ductility are improved and a predetermined function is easily exhibited. From these points, when the Zn alloy constituting the medical linear material contains Mn, the amount of Mn in the Zn alloy is preferably 0.12% by mass or more and 3.0% by mass or less, and 0.15% by mass or more. 2.0 mass% or less is more preferable.

For example, it is preferable that the Zn alloy constituting the medical linear material contains 0.01% by mass or more of calcium (hereinafter referred to as Ca) from the viewpoint of increasing the strength and adjusting the corrosion rate. In addition, when the Zn alloy contains Ca, the amount of Ca in the Zn alloy is preferably 0.5% by mass or less because the bendability and ductility are improved and a predetermined function is easily exhibited. From these points, when the Zn alloy constituting the medical linear material contains Ca, the Ca content in the Zn alloy is preferably 0.03% by mass or more and 0.4% by mass or less, and 0.05% by mass or more. 0.3 mass% or less is more preferable. *

The Zn alloy constituting the medical linear material preferably has a low magnesium (hereinafter referred to as Mg) content in order to further improve the bendability suitable for applications such as staples and clips. It is preferably not contained. Specifically, the Mg content in the Zn alloy is preferably 50 ppm or less on a mass basis, more preferably 20 ppm or less, and particularly preferably less than 10 ppm. The smaller the Mg content in the Zn alloy, the better. However, when the content is 0.001 ppm or more, the production is easy.

The Zn alloy contains Zn and Cu and / or Ti as described above, and may contain at least one selected from Mn, Ca and Mg, and the remainder is preferably only inevitable elements. . The remainder being only inevitable elements is intended to include the case where the remainder is zero, that is, the case where no inevitable elements are contained. An inevitable element refers to an element that must be contained as an inevitable impurity due to reasons such as being present in a raw material or being mixed in a manufacturing process. Inevitable elements include, for example, Fe, Sn, and Al, and Pb and Cd are usually present in very small amounts. The Zn alloy constituting the medical linear material preferably has a total content of these inevitable elements of 0.05% by mass or less, particularly preferably 0.01% by mass or less. Further, in the Zn alloy, the content of each inevitable element is preferably 0.1% by mass or less, and more preferably 0.05% by mass or less.

The contents of Cu, Ti, Ca, Mn, and Mg and unavoidable elements in the Zn alloy can be measured by ICP emission analysis, and specifically by the method described in the examples.

Another feature of the medical linear material of the present invention is that the linear material has a specific cross-sectional area. The cross-sectional area here means a cross-sectional area of a cross section orthogonal to the extending direction of the medical linear material. When the medical linear material has a cross-sectional area of 0.01 mm ² or more, a fastening force capable of suturing or anastomosing living tissue can be obtained. In addition, when the cross-sectional area is 4.0 mm ² or less, a material having a sufficient corrosion rate for suturing or anastomosis can be obtained. From these points, it is preferable that the cross-sectional area of the medical linear material is 0.02 mm ² or more 2.0 mm ² or less, and more preferably 0.03 mm ² or more 1.0 mm ² or less. The cross-sectional area of the medical linear material indicates the maximum value Smax of the cross-sectional area when the cross-sectional area is not constant along the extending direction of the medical linear material.

The linear shape in the medical linear material includes not only a linear shape but also a curved shape. Examples of the linear material include a material having a shape in which the length X in the extending direction is very long with respect to the length Y in the width direction of the cross section perpendicular to the length in the extending direction. The medical linear material preferably has a ratio X / Y of the length X in the extending direction and the length Y in the width direction of the cross section perpendicular to the extending direction, preferably 15 or more, more preferably 20 The above is particularly preferable. The width direction length Y here means the length of the longest line segment among the line segments crossing the cross section orthogonal to the extending direction of the linear material. The length X in the extending direction here refers to the length of the road (the length along the line) when the medical linear material has a curved shape or a bent portion. Further, the width direction length Y of the medical linear material indicates a maximum value Ymax when the width direction length Y along the extending direction of the medical linear material is not constant.

The medical linear material may or may not have a constant length Y in the width direction along the extending direction. Preferably, the difference (Ymax−Ymin) between the maximum value Ymax and the minimum value Ymin of the length Y in the width direction along the extending direction in one medical linear material is 40% or less with respect to Ymax. Preferably, it is 20% or less.

The medical linear material of the present embodiment is one excluding a stent. Although there is a stent in which a linear material is formed in a mesh shape, the medical material of this embodiment does not include this.
The medical linear material of the present embodiment is preferably used for applications that are deformed during use, particularly for applications that are bent and deformed, and is particularly preferably used for applications that are bent for fastening during use. Such applications include staples and clips. The staple is formed by bending a linear medical linear material into a shape suitable for use in a stapler or the like. The clip is also formed by bending one linear medical linear material into a shape suitable for use with a clip applier or the like. Both the staple and the clip are further deformed and used for fastening in order to suture or anastomoses the living tissue. On the other hand, for example, a stent is used for maintaining the structure of a living tissue, and is not used for an application of bending deformation during use. In the present embodiment, staples and clips are examples of a suture or anastomosis body of a living tissue made of the medical linear material of the present embodiment.

The cross-sectional shape of the medical linear material may be a circular shape, a rectangular shape, a polygonal shape other than a rectangular shape, an ellipse, or the like. Further, the cross-sectional shape of the medical linear material may be constant or different along the extending direction of the medical linear material. From the viewpoint of obtaining a force for fixing a living tissue, the medical linear material is preferably not hollow, and more preferably solid. The medical linear material preferably has a bent portion, more preferably has a bent portion and a linear portion, and the linear portions have a continuous shape via the bent portion. Is particularly preferred. The bent portion preferably has R. The medical linear material may have a branch portion or may not have a branch portion. The medical linear material may form a medical device by itself, or may constitute a part of the medical device.

Further, as described above, when the cross-sectional shape perpendicular to the extending direction of the medical linear material has a long shape on one side, the aspect ratio (major axis / minor axis) of the cross section is 4 or less. It is preferable in terms of fastening force and the like, and more preferably 2 or less. The major axis refers to the length in the longitudinal direction when the cross-sectional shape is long in one direction, such as an ellipse, a rectangle, or an indefinite shape. The minor axis refers to the length in the direction orthogonal to the longitudinal direction.

The medical linear material of the present embodiment preferably has a staple shape or a clip shape. Examples of the staple shape and the clip shape include shapes formed by bending a single linear medical linear material.
Specifically, as a staple shape, for example, a staple 20 shown in FIG. 1A, a pair of

limbs

21 and 22 and end portions located on the same side of the pair of

limbs

21 and 22, respectively. What has the connection part 23 which connects 21a and 22a mutually is mentioned. In the example of FIG. 1A, the pair of

limbs

21 and 22 have substantially the same length. Moreover, the

edge parts

21b and 22b on the opposite side to the connection part 23 of the

limbs

21 and 22 have the tapering shape which becomes so thin that it goes inside toward the front. As shown in FIG. 1 (B), the staple includes one that folds a pair of

limbs

21 and 22 inward, thereby suturing or anastomosing living tissue or closing a wound. As shown in FIG. 1B, the

limb portions

21 and 22 of the staple are bent so that the

portions

21c and 22c face the connecting portion 23 and the

end portions

21b and 22b are close to each other. In the example of FIG. 1 (B), each of the

limbs

21 and 22 is bent further toward the connecting portion 23 side than the

portions

21c and 22c facing the connecting portion 23 at the

end portions

21b and 22b side. In the staple shape shown in FIG. 1 (A), the pair of

limbs

21 and 22 extend in substantially the same direction, are substantially parallel and have the same length, and the connecting portion 23 is substantially orthogonal to the

limbs

21 and 22. Since it is linear, the

limbs

21 and 22 and the connecting part 23 form a rectangular staple shape with one side missing. Examples of the rectangular shape include a rectangular shape and a square shape. In this specification, the term “rectangular shape with one side missing” includes a shape in which a corner portion of the rectangular shape has R. However, the staple shape is not limited to a rectangular shape with one side missing. For example, the staple shape may be a circular shape or an elliptical shape in which a part such as a U shape or a C shape is missing. The staple shape may be, for example, a rectangular shape with one side missing, and the connecting portion 23 may have a stepped portion or a curved portion.

From the viewpoint of obtaining good biodegradability and fixing force, when the medical linear material has a staple shape, the cross-sectional area is preferably 0.01 mm ² or more and 0.3 mm ² or less, and 0.03 mm ² or more and 0.2 mm. ² or less is more preferable.

As a clip, for example, as shown in FIG. 2A, a pair of

limbs

31 and 32 facing each other and ends 31a and 32a located on the same side of the pair of

limbs

31 and 32 are connected to each other. The connection part 33 has a convex shape toward the direction away from the pair of

limbs

31 and 32. Examples of the clip shape include a shape that is line-symmetric with respect to the center line A that is a straight line passing through the apex of the convex shape of the connecting portion 33 like the clip 30 in FIG. Therefore, the pair of

limbs

31 and 32 have substantially the same length, and are connected to the connecting part 33 in a line-symmetric state with respect to the center line A passing through the convex apex. As shown in FIG. 2B, the clip is formed by bending the connecting portion 33 so that the

inner surfaces

31b and 32b face each other, as shown in FIG. 2B. And those that sew or anastomoses living tissue or ligate vessels. In the example of FIG. 2A, the pair of

limbs

31 and 32 are provided slightly inclined with respect to the center line A so as to approach the center line A as the distance from the connecting portion 33 increases. In the shape of the clip shown in FIG. 2A, the connecting portion 33 is V-shaped. The shape of the clip is not limited to this, and various shapes such as a rectangular shape lacking one side, a V shape, and a C shape can be mentioned.

From the viewpoint of obtaining good biodegradability and fixing force, when the medical linear material has a clip shape, the cross-sectional area is preferably 0.05 mm ² or more and 4.0 mm ² or less, 0.1 mm ² or more and 2.0 mm ² or less is more preferable.

The length of the medical linear material is preferably 3 mm or more because it can be easily used for suturing or anastomosing living tissue, ligating vessels, or closing wounds. Is preferably 40 mm or less from the viewpoint of minimizing foreign matter embedded in the body. From these points, it is more preferable that the length of the medical linear material is 3 mm or more and 40 mm or less. In this specification, the length of the medical linear material refers to the length along the line of the medical linear material.

In particular, when it has a staple shape, it can be easily used for the purpose of suturing or anastomosing living tissue and the purpose of closing a wound, and from the viewpoint of minimizing foreign matter embedded in the body. The length of the linear material for use is preferably 3 mm or more and 20 mm or less, and more preferably 4 mm or more and 15 mm or less. The staple width W1 (see FIG. 1A) is preferably 1 mm or more and 10 mm or less, and more preferably 2 mm or more and 8 mm or less. The staple height H1 (see FIG. 1A) is preferably 1 mm or more and 10 mm or less, and more preferably 2 mm or more and 8 mm or less.

In particular, in the case of having a clip shape, from the point that it can be easily used for the purpose of suturing or anastomosing living tissue or ligating the blood vessels, or minimizing foreign matter embedded in the body, The length of the medical linear material is preferably 5 mm or more and 40 mm or less, and more preferably 6 mm or more and 30 mm or less. The width W2 of the clip (see FIG. 2A) is preferably 1 mm or more and 20 mm or less, and more preferably 2 mm or more and 10 mm or less. The height H2 of the clip (see FIG. 2A) is preferably 1 mm or more and 20 mm or less, and more preferably 2 mm or more and 15 mm or less.

The medical linear material of the present embodiment can satisfy the mechanical characteristics when used as a staple or a clip. For example, a medical linear material preferably has a 0.2% proof stress of 80 MPa or more because strength sufficient to hold a sutured, anastomotic or ligated portion can be obtained, more preferably 100 MPa or more, and 120 MPa or more. It is particularly preferred. The 0.2% yield strength of the medical linear material is preferably high, but it is preferably 1000 MPa or less from the viewpoint of ease of production of the medical linear material and ease of treatment, and 700 MPa or less. More preferred. The 0.2% yield strength of the medical linear material is measured according to the offset method of JIS Z 2241: 2011 so that the tensile direction is parallel to the extending direction of the medical linear material. In order to make the 0.2% proof stress of the medical linear material within the above range, the concentration of the added metal is adjusted within a predetermined range, and excessive heating at 400 ° C. or higher is avoided during processing after casting. And so on.

From the same viewpoint, the medical linear material preferably has a tensile strength of 120 MPa or more, more preferably 130 MPa or more, and particularly preferably 140 MPa or more. The tensile strength of the medical linear material is preferably high, but it is preferably 2000 MPa or less from the viewpoint of ease of production of the medical linear material and ease of treatment, and more preferably 1000 MPa or less. In order to set the tensile strength of the medical linear material within the above range, the concentration of the additive metal is adjusted within a predetermined range, or excessive heating at 400 ° C. or more is avoided during processing after casting. Good.

Further, the linear medical material preferably has an elongation at break of 30% or more from the viewpoint of obtaining sufficient extensibility, more preferably 40% or more, and particularly preferably 50% or more. In order to set the elongation at break of the medical linear material within the above range, the concentration of the additive metal may be adjusted within a predetermined range, or excessive heating at 400 ° C. or higher may be avoided during processing. The elongation at break is preferably high, but is preferably 200% or less from the viewpoint of processing.

The tensile strength and breaking elongation of the medical linear material are measured in accordance with JIS Z 2241: 2011 so that the tensile direction is parallel to the extending direction of the medical linear material.

The medical linear material is preferably used as a biodegradable implant. An implant refers to an instrument for implantation in a living body. For example, examples of a linear implant include a wire, a pin, a probe, a wire, a cable, a band, a clip, a staple, and the like. Staples or clips are preferable from the viewpoint of exhibiting the bendability, strength, elongation, and biodegradability of the linear material.

As a biodegradability of a medical linear material, in a corrosion test under the following conditions using an artificial intestinal fluid, a corrosion rate of 0.01 mm / year or more is used as a stopper for blood vessels or tissues such as staples or clips. It is preferable because suitable biodegradability can be obtained when it is used. The corrosion rate is preferably 5 mm / year or less from the viewpoint of preventing the medical linear material from being decomposed too quickly and decomposing before blood vessels, lymphatic vessels and tissues are joined together. . From this viewpoint, the corrosion rate is preferably 0.01 mm / year or more and 5 mm / year or less, and more preferably 0.05 mm / year or more and 3 mm / year or less. In order to set the corrosion rate of the medical linear material within the above range, the composition of the Zn alloy may be adjusted within the above range, and a coating for adjusting the corrosion rate may be formed on the surface.

<Corrosion test conditions>
The medical linear material is immersed in artificial intestinal fluid at the time of eating at 37 ° C., and the weight loss of corrosion is calculated from the mass change before and after the test. Further, the corrosion rate (mm / year) is calculated from the surface area of the test piece according to the following formula.

In the above formula, K: constant 10, W: mass loss (g), A: surface area (cm ² ), T: time (year), D: density (g / cm ³ ).

Examples of the artificial intestinal fluid at the time of feeding include those imitating the intestinal fluid at the time of feeding by the human body and other mammals. ˜210 mmol / L, phospholipid 0.5˜5 mmol / L, pH 5˜7. As such an artificial intestinal fluid at the time of feeding, for example, the trade name “FeSSIF” of biolevrant can be used.
The artificial intestinal fluid during feeding is preferably changed every 1 to 3 days. The test period is preferably 1 to 4 weeks, for example. The test piece is taken out after the test, washed with pure water, and dried at room temperature. After drying, it is preferable to remove the corroded test piece using a 200 g / L CrO ₃ aqueous solution, sufficiently wash with water and then dry.
The amount of the artificial intestinal fluid used is preferably 0.2 ml or more with respect to the surface area of 1 mm ² of the medical linear material.
Specifically, the corrosion test can be measured by the method described in Examples described later.

Next, the suitable manufacturing method of a medical linear material is demonstrated below.
The preferred method for producing the medical linear material of the present embodiment is as follows: (1) A metal alloy obtained by melting a raw material metal of Zn alloy at 450 ° C. or higher and 900 ° C. or lower and then casting it by a mold casting method or a continuous casting method. (2) A bar is cut out from the obtained metal lump and subjected to a wire drawing process.

In the step (1), the raw material metal of the Zn alloy may be blended with the above-described composition, such as Zn, Ti, or Cu, and, if necessary, Mn and Ca. The melting temperature of the raw material metal is preferably 450 ° C. or higher and 900 ° C. or lower, and more preferably 500 ° C. or higher and 800 ° C. or lower from the viewpoint of easy mixing of raw materials and prevention of raw material volatilization.

In the step (2), the wire drawing process may be performed either hot or cold, but in the initial stage of processing, it is performed hot to reduce the load on the processing apparatus and the soundness of the structure. To preferred. As the wire drawing treatment, extrusion molding, hole die drawing, roller die drawing, swaging, roll rolling, etc. can be appropriately combined, and in particular, extrusion molding and hole die drawing are performed in this order. Is preferred.

In the wire drawing process in (2), the reduction ratio (area reduction rate) of the obtained medical linear material relative to the cross-sectional area of the rod cut out from the metal lump is 90% or more. It is preferable from the viewpoint of miniaturization, that is, strength and elongation, and more preferably 95% or more.

The medical linear material of the present embodiment obtained by the above manufacturing method utilizes the bendability, biodegradability, strength, ductility, and the above-described staple, clip, metal wire, pin, probe, wire, cable. It can be used for various applications such as bands. Specific uses of the medical linear material of the present embodiment include in vivo application, such as small intestine, esophagus, large intestine (rectum, colon), duodenum, jejunum, ileum, cecum, uterus, etc. It can be suitably used for suturing or anastomosis of a resected part or suturing or anastomosis of a graft in a vessel such as a tissue, blood vessel, or lymphatic vessel; closing or ligating a vessel. The target of the medical linear material of the present invention is not limited to humans, but includes mammals such as mice, dogs, cats, rats, rabbits, pigs, monkeys. The present invention also provides a suture, anastomosis or ligation method using the medical linear material of the present invention for suture or anastomosis of these tissues or vessels in a living body, or ligation of vessels.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the scope of the present invention is not limited to such examples.

[Examples 1 to 9, Comparative Examples 1 to 4]
As a raw material, zinc alone or zinc and copper (64 brass plate), titanium, manganese or magnesium were used.
The raw materials were put into a graphite crucible so as to have the composition shown in Table 1 or 2 below, and dissolved at 650 ° C. in an Ar atmosphere using a vacuum melting furnace. At the same temperature, a molten metal was poured into a mold having a width of 2 cm, a length of 17 cm, and a height of 13.5 cm, and cooled and solidified to obtain a cast metal lump. “%” In the term of composition in Tables 1 and 2 means mass%.
The following evaluation was performed about the obtained material.
In Examples 1 to 8 and Comparative Examples 1 to 4, the tensile strength, 0.2% resistance, elongation at break, and bending evaluation of the material are the same regardless of the shape as long as the area reduction rate of the material is the same. Since it becomes an evaluation result, these tests were performed about the board | plate material for the convenience of implementing experiment.
Further, the amount of Zn in the “Composition” section of Tables 1 and 2 is the remainder of the additive element such as Cu, Ti, Mn, Ca, or Mg.

<Evaluation of Examples 1 to 8 and Comparative Examples 1 to 4>
A plate material having a thickness of 10 mm was cut out from the metal block cast in Examples 1 to 8 and Comparative Examples 1 to 4. The plate material heated to 200 ° C. was rolled through a pair of rolling rolls (room temperature). The rolling of one rolling pass was 1 to 2 mm, and the plate was reheated to 200 ° C. during the rolling pass. When the material is rolled to a thickness of 2 mm, the material is cooled to room temperature, the reheating is stopped, and the sheet material at room temperature is rolled so that the setting of the rolling reduction of the same rolling pass becomes 0.5 mm. Rolled repeatedly to 0.5 mm. About the obtained board | plate material, the tensile strength, the 0.2% yield strength, and elongation at break were measured with the following method, and the bending test was done with the following method. A linear test piece having a length of 10 mm, a width of 1 mm and a thickness of 0.5 mm was obtained from the obtained plate material by shearing, and this was subjected to the following corrosion test. Moreover, the composition analysis of the linear test piece was performed with the following method.

(Tensile strength, 0.2% proof stress and elongation at break)
This was performed according to JIS Z 2241: 2011. The shape of the test piece conformed to JIS Z 2241 13B. As a tester, an Instron 5582 universal tester was used, and measurement was performed at a tensile speed of 10 mm / min. In the tensile test, the tensile direction was made parallel to the rolling direction. The 0.2% proof stress was obtained by the offset method.

(Bending test)
The shape of the test piece was a plate shape 10 mm wide, 50 mm long, and 0.5 mm thick in the rolling direction.
For each of the five test pieces, a wrinkle generated in the bent portion after the test piece 13 was bent at 90 ° using a die 10 having an R of 0.5 mm, a pad 11 and a punch 12 as shown in FIG. The state of cracks was visually evaluated in 6 stages. The evaluation criteria were as follows based on FIG. 4 of the Japan Copper and Brass Association Technical Standard JCBA T307: 2007. Table 1 shows the average value of the five evaluation points. If this evaluation score is 4 or more, it can be said that the bendability is good.
No wrinkle: 5 points Small wrinkle: 4 points Large wrinkle: 3 points Small crack: 2 points Large crack: 1 point
Break: 0 points

(Corrosion test)
Artificial intestinal fluid (trade name “FeSSIF”, pH = 5.5, manufactured by biolevant) was used as a test solution. This was set to a liquid temperature of 37 ° C. 20 mL of the liquid was used, and the liquid was changed every 3 days.
Three linear test pieces were immersed in the artificial intestinal fluid. After 2 weeks, it was taken out, washed with pure water, and dried at room temperature. After drying, the corrosives were removed using a 200 g / L CrO ₃ aqueous solution, washed thoroughly with water and then dried. Corrosion weight loss was calculated from the mass change before and after the test. Further, the corrosion rate (mm / year) was calculated from the surface area of the test piece according to the following formula. Table 1 shows the average values measured at n = 4. In the following formula, K: constant 10, W: mass loss (g), A: surface area (cm ² ), T: time (year), D: density (g / cm ³ ).

(Composition analysis)
This was performed by ICP emission spectrometry using ARCOS manufactured by SPECTRO. The measurement sample was dissolved in aqua regia and adjusted to an appropriate concentration with pure water.

<Evaluation of Example 9>
(Manufacture of staples and clips)
In Example 9, a round bar with a diameter of 15 mm was cut out from the above metal lump. This round bar was swaged cold until it had a substantially circular cross section with a diameter of 10 mm. Next, in a cold, with a pair of groove rolls having a groove portion having a trapezoidal shape in which the cross section of the groove is equally divided into regular hexagons, the rod is rolled to a circle-converted diameter of 1.11 mm and drawn, A linear material was obtained. Then, after cold, the wire was drawn to a diameter of 1 mm with a cassette roller die, and then cold and drawn to a diameter of 0.4 mm with a round hole die to obtain a linear material having a circular cross section. The obtained linear material having a diameter of 0.4 mm was formed into a staple shape having the same shape as that shown in FIG. 1A using a forming machine and having a width W1 of 5 mm and a height H1 of 4 mm. . Separately, the obtained linear material having a diameter of 0.4 mm is cut to a length of 10 mm, and has the same shape as FIG. 2A, with a width W2 of 3 mm and a height H2 of 4.5 mm. To obtain a clip.
(Tensile strength, 0.2% proof stress and elongation at break)
For a linear material having a diameter of 0.4 mm, the tensile strength, 0.2% proof stress and fracture were the same as in Examples 1 to 8 and Comparative Examples 1 to 4 except that the shape of the test piece conformed to JIS Z 2241 9A. The elongation was measured. The composition analysis was performed in the same manner as in Examples 1 to 8 and Comparative Examples 1 to 4.
A corrosion test was carried out using the obtained staples. The corrosion test was performed in the same manner as in Examples 1 to 8 and Comparative Examples 1 to 4 (corrosion test) except that the amount of artificial intestinal fluid was 35 mL and 10 staples were immersed.
The average values measured at n = 4 are shown in Table 2 below.
Further, when the obtained staple was inserted into a cartridge for NT4 continuous pez suture device manufactured by Takasago Medical Industry and applied to a sponge piece, it was confirmed that it could be sutured without any problem.

From the results shown in Table 1 and Table 2, the linear material of the present invention is excellent in elongation at break, bendability and biodegradability while maintaining strength, and requires bendability such as staples or clips, and It turns out that it is suitable for a biodegradable implant which needs to be processed linearly.

The medical linear material of the present invention has excellent bendability and good ductility, strength and biodegradability, and is particularly suitable for living body staples, clips and the like.

Claims

Or containing 0.05 wt% to 5 wt% or less of Cu, or consist Zn alloy containing 0.01 mass% to 0.4 mass% of Ti, the cross-sectional area 0.01 mm 2 or more 4.0 mm 2 Medical linear material that is:
The medical treatment according to claim 1, wherein the Zn alloy contains Zn and Cu and / or Ti, and may contain at least one of Mn, Ca and Mg, and the balance is an inevitable element only. Linear material for use.
The medical linear material according to claim 1 or 2, wherein the Zn alloy further contains 0.1 mass% to 5 mass% of Mn.
The medical linear material according to any one of claims 1 to 3, wherein the Zn alloy further contains 0.01 mass% or more and 0.5 mass% or less of Ca.
The medical linear material according to any one of claims 1 to 4, wherein the Mg content of the Zn alloy is 50 ppm or less.
The linear medical material according to any one of claims 1 to 5, which is a linear material having a length of 3 mm to 20 mm and a cross-sectional area of 0.01 mm 2 to 0.3 mm 2 and having a staple shape. material.
The linear medical material according to any one of claims 1 to 5, which is a linear material having a length of 5 mm to 40 mm and a cross-sectional area of 0.05 mm 2 to 4.0 mm 2 and having a clip shape. material.
The linear medical material according to any one of claims 1 to 7, having a 0.2% proof stress of 80 MPa to 1000 MPa.
The medical linear material according to any one of claims 1 to 8, which has biodegradability and exhibits a corrosion rate of 0.01 mm / year to 5 mm / year in a corrosion test under the following conditions.
<Corrosion test conditions>
The medical linear material is immersed in artificial intestinal fluid at the time of eating at 37 ° C., and the weight loss of corrosion is calculated from the mass change before and after the test. Further, the corrosion rate (mm / year) is calculated from the surface area of the test piece according to the following formula.

In the above formula, K: constant 10, W: mass loss (g), A: surface area (cm 2 ), T: time (year), D: density (g / cm 3 ).
A suture or anastomosis body of a living tissue comprising the medical linear material according to any one of claims 1 to 9.
A biodegradable implant comprising the medical linear material according to any one of claims 1 to 9.
A biological tissue suture or anastomosis body, which is a biodegradable implant made of the medical linear material according to any one of claims 1 to 9.
A method for suturing or anastomosing living tissue, wherein the linear medical material according to any one of claims 1 to 9 is used for suturing or anastomosing living tissue.