WO2011118401A1

WO2011118401A1 - Process for production of medical instrument, and medical instrument

Info

Publication number: WO2011118401A1
Application number: PCT/JP2011/055620
Authority: WO
Inventors: 亮一早場; 村山　啓; 植村　賢介
Original assignee: テルモ株式会社; 永田精機株式会社
Priority date: 2010-03-25
Filing date: 2011-03-10
Publication date: 2011-09-29
Also published as: JPWO2011118401A1

Abstract

Disclosed are: a process for producing a medical instrument, such as a stent and a guide wire, which has an excellent fatigue life; and a medical instrument, such as a stent and a guide wire, which has an excellent fatigue life. The process for producing a medical instrument comprises: a preparation step of preparing a medical instrument comprising a NiTi-based alloy as a base material; and an ion irradiation step of irradiating the medical instrument prepared in the preparation step with Xe ions. The medical instrument is produced by irradiating a medical instrument comprising a NiTi-based alloy as a base material with Xe ions.

Description

Method for manufacturing medical device and medical device

The present invention relates to a method for manufacturing a medical device and a medical device.

Conventionally, NiTi-based alloys, which are shape-memory alloys having biocompatibility, are known as base materials for medical devices such as stents and guidewires (paragraph [0028] in Patent Document 1 and paragraph [0011] in Patent Document 2). ]reference).
Here, the NiTi alloy includes a wide range of alloys mainly composed of nickel and titanium, and a representative one is a NiTi alloy containing 43 to 57 wt% of Ni and the balance of Ti and inevitable impurities. . A small amount of other metals such as cobalt, iron, palladium, platinum, boron, aluminum, silicon, vanadium, niobium, copper, and the like may be added to such a NiTi alloy.

By the way, various performances are required for medical devices such as stents and guide wires, and various improvements are desired.
For example, Patent Document 1 discloses a technique for imparting antithrombogenicity by modifying the surface of a polymer-coated stent by ion bombardment. As these ions, “He ⁺ , C ⁺ , N ⁺ , Ne” are disclosed. ⁺ , Na ⁺ , N ₂ ⁺ , O ₂ ⁺ , Ar ⁺ , Kr ⁺ ”(see paragraph [0044]).
Patent Document 2 discloses a technique for producing a guide wire by ion-implanting a metal wire to form a guide wire in order to harden the surface of the guide wire and reduce the frictional resistance. N, F, C, B, Ti, Ca, Ni, Co, Al, O, He, Ne, P ”(see paragraph [0024]).

JP 2003-325655 A JP 9-182799 A

When the present inventor further examined the medical devices disclosed in Patent Documents 1 and 2, it was clear that the fatigue life did not reach the level required recently and improvement is necessary. became.
Therefore, an object of the present invention is to obtain a medical device such as a stent and a guide wire having excellent fatigue life.

As a result of intensive studies to solve the above problems, the present inventor has found that a medical device obtained by irradiating Xe ions in a manufacturing process has an extremely excellent fatigue life, and has completed the present invention. .
That is, the present invention provides the following (1) to (6).

(1) A medical device manufacturing method comprising: a preparation step of preparing a medical device based on a NiTi-based alloy; and an ion irradiation step of ion irradiating Xe ions to the medical device prepared by the preparation step.

(2) The method for manufacturing a medical device according to (1), further including a polishing step of polishing a surface of the medical device prepared by the preparation step.

(3) The method for producing a medical device according to (1) or (2), wherein the polishing in the polishing step is polishing by electron beam irradiation and / or electrolytic polishing.

(4) The method for manufacturing a medical device according to any one of (1) to (3), further including a heat treatment step of heat-treating the medical device prepared in the preparation step.

(5) The manufacturing of the medical device according to any one of (1) to (4), wherein the medical device prepared in the preparation step is a stent, a guide wire, an embolic coil, a venous filter, or an orthodontic wire. Method.

(6) A medical device obtained by irradiating a medical device based on a NiTi alloy with Xe ions.

According to the present invention, it is possible to obtain a medical device such as a stent or a guide wire having an excellent fatigue life.

It is a front view which shows the medical device of this invention applied to the stent. It is a graph which shows the result of fatigue life evaluation. It is a graph which shows the result of fatigue life evaluation. It is a graph which shows the result of fatigue life evaluation.

<Method for manufacturing medical device>
The method for manufacturing a medical device of the present invention includes a preparation step of preparing a medical device based on a NiTi alloy, and an ion irradiation step of ion irradiating Xe ions to the medical device prepared by the preparation step. It is a manufacturing method of a medical device.
Below, each process with which the manufacturing method of the medical device of this invention is provided is explained in full detail.

[Preparation process]
The manufacturing method of the medical device of this invention is equipped with the preparatory process which prepares the medical device which makes a NiTi type alloy a base material. The said preparatory process can be implemented according to the normal procedure at the time of manufacturing the medical device which makes a NiTi type alloy a base material.
For example, when the medical device is a stent, the non-stented portion of the pipe made of NiTi alloy is removed (removal is performed, for example, by cutting, melting, etc.) and formed into a stent shape. High temperature side shape memory processing and low temperature side shape memory processing are performed.
Other medical devices are also prepared and prepared by known manufacturing methods.
In addition, the said preparatory process is performed before the ion irradiation mentioned later. Thereby, for example, when the medical device is a stent, ion irradiation to the non-stented portion of the stent can be omitted, and when the non-stented portion of the stent is removed, the ion irradiation effect layer of the stent-constituting portion may be removed. Disappear.

The medical device prepared in the preparation step is not particularly limited, and examples thereof include a stent, a guide wire, an embolic coil, a venous filter, and an orthodontic wire.

The NiTi alloy used as the base material of the medical device prepared in the preparation step includes a wide range of alloys mainly composed of nickel and titanium. Some NiTi alloys are generally called shape memory alloys and exhibit superelasticity at least at a living body temperature (around 37 ° C.). Superelasticity here means that even if it is deformed (bending, pulling, compressing) to a region where normal metal is plastically deformed at the operating temperature, it will recover to its almost uncompressed shape without the need for heating after the deformation is released. It means to do.
As a typical NiTi alloy, there is a NiTi alloy containing 43 to 57 wt% of Ni and the balance of Ti and inevitable impurities. A small amount of other metals such as cobalt, iron, palladium, platinum, boron, aluminum, silicon, vanadium, niobium, copper, and the like may be added to such a NiTi alloy.
The NiTi alloy used as the base material of the medical device prepared in the preparation step is preferably one containing 54.5 to 57 wt% Ni and the balance being Ti and inevitable impurities. In such a NiTi alloy, in addition to Ti and Ni, C is 0.070 wt% or less, Co is 0.050 wt% or less, Cu is 0.010 wt% or less, Cr is 0.010 wt% or less, and H is 0.00. You may contain 005 wt% or less, Fe 0.050 wt% or less, Nb 0.025 wt% or less, and O 0.050 wt% or less.

[Ion irradiation process]
The manufacturing method of the medical device of this invention is equipped with the ion irradiation process which ion-irradiates Xe ion to the medical device prepared by the said preparatory process. By providing the ion irradiation step, the fatigue life of the obtained medical device is improved. This is presumably because the dislocation density of the NiTi alloy increases when Xe ions heavier than Ar or the like collide with the NiTi alloy as the base material.

The conditions for ion irradiation of Xe ions in the ion irradiation step are not particularly limited. For ion irradiation, for example, an ion implanter type II (manufactured by Nagata Seiki Co., Ltd.) can be preferably used.

At this time, the Xe gas pressure (Pressure) is preferably 0.004 to 0.008 Pa. The Penning Current is preferably 1.2 to 1.6 A. The acceleration voltage (Acc. Voltage) is preferably 10 to 30 kV. The acceleration current (Acc. Current) is preferably 35 to 50 mA. The dose is preferably 10 ¹⁶ to 10 ¹⁸ ions / cm ² .
If the Xe ion irradiation conditions are within this range, the fatigue life of the obtained medical device is more excellent.

[Acid treatment process]
The method for producing a medical device of the present invention may further include an acid treatment step of acid-treating the medical device prepared by the above preparation step.
In the NiTi-based alloy constituting the medical device, there may be inclusions generated during the manufacture of the alloy. In the preparation step, foreign matter may adhere to the surface of a medical device such as a stent or a guide wire. Therefore, in the acid treatment step, the outermost layer on the surface of the medical device in which inclusions and foreign matters may be present is removed.

The acid used for the acid treatment is not particularly limited as long as it has an action of dissolving the NiTi-based alloy. Examples thereof include nitric acid, hydrofluoric acid, hydrogen peroxide, and mixed acids thereof. A mixed acid of nitric acid and hydrofluoric acid is preferable because of its strong action of dissolving the alloy.
In addition, as the acid used for the acid treatment, a commercially available etching solution can be used, and examples thereof include Fujidiaclean FE-17 (manufactured by Fuji Acetylene Kogyo Co., Ltd.).
The method of acid treatment is not particularly limited and includes, for example, spraying, dipping, etc., but is suitable for bringing acid into contact with the surface of a medical device such as a stent having a fine and complicated shape. Is preferred.
The order of the acid treatment is not particularly limited, but is preferably after the preparation step and before the ion irradiation step.

[Polishing process]
The method for producing a medical device of the present invention includes a polishing step of polishing the surface of the medical device prepared by the above preparation step (for example, a stent after removing a non-stent component). It is preferable.
In the polishing step, the surface roughness Ra of the surface of the medical device prepared in the preparation step is preferably 1.5 μm or less, more preferably 0.32 μm or less, and 0.15 μm or less. Is more preferable.

The polishing in the polishing step is not particularly limited, but is preferably polishing by electron beam irradiation and / or electrolytic polishing.
(Polishing by electron beam irradiation)
As conditions for polishing by electron beam irradiation, for example, the following conditions are preferably satisfied.
Energy density: about 1 J / cm ² or more, preferably about 1 J / cm ² or more and 20 J / cm ² or less, more preferably about ² J / cm ² or more and 15 J / cm ² or less, more preferably about 4 J / cm ² or 12 J / cm ² or less, and most preferably from about 5 J / cm ² or more 9J / cm ² or less.
・ Pulse width: 1μs or more.
Number of irradiation (number of pulses): about 5 times or more, more preferably about 20 to 40 times.
(Electrolytic polishing)
As conditions for electropolishing, for example, the following conditions are preferably satisfied.
Electrolyte: A mixture of sulfuric acid, phosphoric acid and water.
-Voltage: 15V.

The order of the polishing steps is not particularly limited, but is preferably after the acid treatment step and before the ion irradiation step.
Moreover, when polishing by electron beam irradiation and electrolytic polishing are performed as polishing in the polishing step, polishing by electron beam irradiation and electrolytic polishing may be performed in any order.
As will be described later, the polishing by electron beam irradiation may reduce the fatigue life, but the polishing is simpler than the electrolytic polishing in which the treatment of the electrolytic solution is complicated. Therefore, after performing polishing by electron beam irradiation, if Xe ion irradiation is performed, polishing can be performed easily and uniformly, and the fatigue life can be improved.

[Heat treatment process]
The method for producing a medical device of the present invention preferably further includes a heat treatment step because a better fatigue life can be obtained. The heat treatment step is a step of heat-treating the medical device prepared in the preparation step.
As the heat treatment in the heat treatment step, an annealing treatment is preferable. The annealing treatment is performed at 300 to 1100 ° C., preferably 450 to 700 ° C., more preferably 500 to 600 ° C. for 1 minute to 10 hours, preferably 5 minutes to 5 minutes in a vacuum or a rare gas atmosphere such as argon or helium. It may be carried out for 1 hour, more preferably 5 to 30 minutes.
The order of the heat treatment step is not particularly limited, but it is preferable that the heat treatment step is after the polishing step and before the ion irradiation step.

[Other processes]
The method for producing a medical device of the present invention may further include another step as necessary. For example, a layer containing a biological physiologically active substance such as an immunosuppressive agent or an anticancer agent is provided on the surface of the medical device. A surface modification step for performing a hydrophilization treatment, a resin coating treatment, and the like. These additional steps are performed after the ion irradiation step.

<Medical tools>
The medical device of the present invention is a medical device obtained by irradiating a medical device having a NiTi-based alloy as a base material with Xe ions. Here, the “medical device based on a NiTi alloy” means a medical device prepared by the above preparation process.
The medical device of the present invention may be subjected to acid treatment in the acid treatment step, polishing in the polishing step, heat treatment in the heat treatment step, and the like.
Therefore, the medical device of the present invention substantially corresponds to the medical device obtained by the method for manufacturing the medical device of the present invention.
Below, the medical device of this invention and the medical device obtained by the manufacturing method of the medical device of this invention are collectively called "the medical device of this invention." Examples of the medical device of the present invention include a stent, a guide wire, an embolic coil, a venous filter, and an orthodontic wire.

An application example of the medical device of the present invention to a stent will be described.
FIG. 1 is a front view showing a medical device of the present invention applied to a stent. A stent 301 shown in FIG. 1 is formed in a substantially cylindrical shape. In addition, the stent 301 is a so-called self-expanding stent that is reduced in diameter when inserted into a living body and restored to a shape before reducing diameter when placed in the living body. FIG. 1 shows the external shape of the stent 301 when it is expanded.
The size of the stent 301 varies depending on the site to be placed, and is not particularly limited. However, the outer diameter at the time of expansion is preferably 2.0 to 30 mm, and more preferably 2.5 to 20 mm. The length is preferably 5 to 250 mm, more preferably 15 to 200 mm.
In particular, when the stent 301 is an intravascular placement stent, the outer diameter is preferably 2.0 to 14 mm, and more preferably 2.5 to 12 mm. Further, the length is preferably 5 to 100 mm, more preferably 10 to 80 mm.
The wall thickness is preferably 0.04 to 0.3 mm, and more preferably 0.06 to 0.22 mm.

The stent 301 formed in a substantially cylindrical shape includes a plurality of wavy annular bodies 302 in the axial direction. The number of wavy annular bodies 302 varies depending on the length of the stent 301, but is preferably 2 to 150, and more preferably 5 to 100.
The wavy line 302 is formed of an endless wavy line that is continuous in an annular shape. The wavy line forming the wavy line 302 is always curved and has very few straight portions. For this reason, the wavy body forming the annular body 302 has a sufficient length and exhibits a high expansion force during expansion. The axial length of the wavy annular member 302 is preferably 1 to 10 mm, and more preferably 1.5 to 5 mm.

The wavy annular body 302 includes a plurality of one end side bent portions having apexes 302a on one end side in the axial direction of the stent 301, and a plurality of other end side bent portions having apexes 302b on the other end side in the axial direction of the stent 301. Have.
The one end side bent portion and the other end side bent portion are alternately formed, and the number of each is the same. The number of one-end-side bent portions (other-end-side bent portions) in one wavy-line annular body 302 is preferably 4 to 20, and more preferably 6 to 12.
The vertex 302a penetrates into the space formed between the vertices 302b of the adjacent wavy annular bodies 302, and the vertex 302b penetrates into the space formed between the vertices 302a of the adjacent wavy annular bodies 302. Yes.

Moreover, the wavy annular body 302 has a shared linear portion 321.
The shared linear portion 321 has a start end 322 at or near the vertex 302b, and further has a termination 323 between the vertex 302b and the vertex 302a. Adjacent wavy-line annular bodies 302 are integrated by such a shared linear portion 321.

Furthermore, the wavy annular body 302 includes a short line portion 325 and a long line portion 324.
The short linear portion 325 connects the start end 322 of the shared linear portion 321 and the apex 302b of the other end side bent portion. The short line portions 325 are not continuous in the axial direction of the stent 301, and are formed such that a plurality of short line portions 325 are arranged in a substantially straight line.
The long linear portion 324 connects the end 323 of the shared linear portion 321 and the other apex 302b of the other end side bent portion. The long linear portion 324 is slightly longer than the combined length of the shared linear portion 321 and the short linear portion 325.
Details of the shape of the stent 301 are described in Japanese Patent Application No. 2008-238215.

The stent 301 having such a shape does not break due to large deformation even after being placed in a highly deformed blood vessel such as a lower limb. And since the Xe ion is irradiated in the manufacturing process, the stent 301 is excellent in the fatigue life.

As mentioned above, although the application example to the stent of the medical device of this invention was demonstrated, it is not limited to this.
For example, when applied to a guide wire having an elongated core member and a coil-shaped member surrounding all or part of the core member, the base material of the core member and the coil-shaped member is the above-described NiTi-based material. It is an alloy. And since Xe ion is irradiated after shaping | molding into such a core member and a coil-shaped member, the obtained guide wire is excellent in fatigue life.
In such a guide wire, the bending strength is preferably 600 N / mm ² or more, more preferably 800 to 1100 N / mm ² .

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
In the following reference examples, comparative examples, and examples, a wire (φ0.5 mm) made of a NiTi alloy (Ti: 49 atomic% (43.94 wt%), Ni: 51 atomic% (56.06 wt%)) is long. The sample was cut to a length of 20 cm (hereinafter referred to as “sample wire”) and subjected to the treatment described below. The treatments performed and their order are shown in Table 2 below.

[Acid treatment]
FUJI SECLEAN FE-17 (HNO ₃ : 53.8%, HF: 8.0%, H ₂ O: 38.2%) was diluted with water to a concentration of 25 vol%, and the sample wire was placed at room temperature for 30 seconds. Soaked.

[Polishing by electron beam irradiation]
The sample wire was irradiated with an electron beam under the following conditions.
・ Anode voltage: 20 kV
Energy density: about 7 J / cm ²
-Distance between electron gun end and sample wire: 20mm
-Number of pulses: 10 shots After irradiating three electron beams at intervals of 35 mm in the longitudinal direction of the sample wire, the sample wire was turned over and the back side was irradiated in the same manner.

[Electrolytic polishing]
Electrolytic polishing was performed at a voltage of 15 V using a mixed solution of sulfuric acid, phosphoric acid and water as the electrolytic solution.

[Heat treatment]
The heat treatment was performed by annealing at 650 ° C. for 1 hour in vacuum (pressure 8 × 10 ⁻³ Pa), and then ice quenching.

[Ion irradiation]
The sample wire was subjected to ion irradiation under the conditions shown in Table 1 below using the above-described ion implanter type II (manufactured by Nagata Seiki Co., Ltd.) (irradiated ions: Xe ions).

[Fatigue life evaluation]
A rotating bending test was performed on the sample wire after each treatment under the following conditions to evaluate the fatigue life (number of cycles). The results are shown in Table 2 below and FIGS.
・ Water bath temperature for immersing wires: 37 ° C
・ Rotation speed: 3600 rpm
In addition, in order to make the load stress in a rotation bending test into an equivalent level, the three-point bending test was implemented on the following conditions, and the center distance (center distance) at the time of a rotation bending test was adjusted about each sample.
(3-point bending test)
・ Test speed: 2 mm / min
・ Support distance: 25mm
・ Pushing amount: 0 → 2.5 → 0mm

The graph of FIG. 2 is a graph showing changes in fatigue life when electrolytic polishing or polishing by electron beam irradiation is performed.
From the graph of FIG. 2, it was found that the fatigue life of the sample wire (Comparative Example 2) that was polished by electron beam irradiation was significantly lower than that of the untreated sample wire (Reference Example 1). .

The graph of FIG. 3 is a graph comparing the fatigue lives of sample wires subjected to electropolishing.
When the graph of FIG. 3 is seen, the sample wire (Example 3) which performed the ion irradiation of Xe ion after implementing electropolishing is compared with the sample wire which did not perform the ion irradiation of Xe ion (Comparative Example 1). Thus, it was found that the fatigue life is remarkably improved.

The graph of FIG. 4 is a graph comparing the fatigue lives of sample wires that have been polished by electron beam irradiation.
As described above, the fatigue life of the sample wire (Comparative Example 2) that has been polished by electron beam irradiation is significantly reduced. However, when the graph of FIG. It was found that the fatigue life of the irradiated sample wire (Example 1) was improved over the untreated sample wire (Reference Example 1). In addition, the sample wire (Example 2) in which the electrolytic polishing was performed before polishing by electron beam irradiation and Xe ion irradiation was performed thereafter (after polishing by electron beam irradiation) (Example 2) has a fatigue life. Was found to be better.

301 Stent 302 Wave-like annular body 302a Vertex 302b Vertex 321 Shared linear portion 322 Start end 323 End 324 Long linear portion 325 Short linear portion

Claims

A preparation step of preparing a medical device based on a NiTi alloy;
An ion irradiation step of ion irradiating Xe ions to the medical device prepared by the preparation step;
A method of manufacturing a medical device comprising:
Furthermore, the manufacturing method of the medical device of Claim 1 provided with the grinding | polishing process of grind | polishing the surface of the medical device prepared by the said preparation process.
The method for producing a medical device according to claim 1 or 2, wherein the polishing in the polishing step is polishing by electron beam irradiation and / or electrolytic polishing.
The method for manufacturing a medical device according to any one of claims 1 to 3, further comprising a heat treatment step of heat-treating the medical device prepared by the preparation step.
The method for producing a medical device according to any one of claims 1 to 4, wherein the medical device prepared in the preparation step is a stent, a guide wire, an embolic coil, a venous filter, or an orthodontic wire.
A medical device obtained by irradiating a medical device based on a NiTi alloy with Xe ions.