JP2018015064A - Method for manufacturing tubular medical tool conveying device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a tubular medical appliance conveying device in which a tubular medical appliance can easily be loaded in a lumen included in the conveying device, the tubular medical appliance being diametrically reduced in order to be loaded in the lumen.SOLUTION: A method is provided for manufacturing a device for conveying a tubular medical appliance 11 into a body. The method performs the steps of the following (1) to (4) in this order. (1) A step of bringing the temperature of the tubular medical appliance of an outer diameter Dinto the temperature Tat which an austenitic phase is present. (2) A pre-loading morphogenesis step of applying an external force to the tubular medical appliance at the temperature Tlower than the temperature T, and reducing the outer diameter from the Dto D. (3) A loading morphogenesis step of weakening external force at the temperature Tlower than the austenite phase transformation completion temperature Aof the alloy constituting the tubular medical appliance, and increasing the outer diameter of the tubular medical appliance from the Dto D. (4) A step of loading the tubular medical appliance of the outer diameter Din the lumen of an inner diameter Dat the temperature T.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method for manufacturing a device for transporting a tubular medical device into a body.

  In recent years, a minimally invasive treatment technique has been developed in which a tubular medical device is transported and placed in a lesion in the body. In this technique, a transport device that transports and arranges a tubular medical device to a lesioned part through a body lumen is used. The transport device includes a tube, and the tubular medical device is transported to a lesioned part through a body lumen while the tubular medical device is held in the tube. After transporting, the tubular medical device can be placed at the lesion by releasing the tubular medical device from the lumen of the transport device.

  Examples of the tubular medical device include a stent, a stent graft, an obturator, an infusion catheter, and a prosthetic valve. Of these, stents are generally tubular medical devices that treat various diseases caused by stenosis or occlusion of blood vessels or other in vivo lumens. More specifically, the tubular medical device can expand a lumen of a lesioned part and maintain the lumen diameter at a predetermined size by arranging a stent in a lesioned part such as a stenosis site or an occlusion site. Stents are classified into balloon-expandable stents that are expanded by a balloon on which the stent is mounted, and self-expandable stents that are expanded by removing external members that suppress the expansion of the stent.

  For example, Patent Documents 1 to 4 are known as methods for loading a stent into the lumen of a delivery device.

  Among these, Patent Document 1 provides a loading device having a passage gradually narrowing from a larger first diameter to a smaller second diameter as a method of loading a stent into a catheter; Forming a sleeve encased in a sleeve by placing a flexible sleeve over the stent, such that one end of the sleeve can be grasped from the smaller diameter end of the passage. Placing a wrapped stent in the gradually narrowing portion of the passage in the loading device; and placing the catheter at or within the smaller diameter end of the passage; Pulling the sleeve through the smaller diameter end of the passage so that the stent is reduced in diameter and moved into the catheter; Method comprising is described. This method minimizes the frictional (shear) forces acting on the stent wall during the process of loading the stent into the catheter.

  In Patent Document 2, as a method of radially compressing a self-expanding stent and loading the stent into a supply sleeve, the stent has a relatively large cross-sectional area inlet and a relatively small cross-sectional area outlet, Providing a compression device configured such that the area between the inlet and the outlet gradually defines a small cross-sectional area; supporting the open end of the sleeve in alignment with the outlet; While making the relative movement between the stent, the compression device, and the sleeve, the stent moves forward through the compression device and into the sleeve, and the relative movement is performed. And detecting the force applied to the stent and ending the relative movement if the force exceeds a predetermined level. According to this method, the step of mounting the stent in the supply sheath or sleeve can be more automated, and strict quality control and process improvement can be facilitated.

  In Patent Document 3, as a method of loading a naturally expandable stent in a feeding sheath configured to hold a stent in a radially compressed state before deployment, i) the stent is compressed from a relaxed outer diameter d0. Compressing radially to the outer diameter d1, ii) providing a loading sheath having an inner diameter d2 where d0> d2> d1, and iii) translating the stent relative to the sheath, Allowing the stent to be received within the lumen of the loading sheath; iv) providing a delivery sheath having an inner diameter d3 as d0> d3> d2, and v) the loading holding the stent. Advancing a sheath into the lumen of the delivery sheath; vi) deploying the stent within the lumen of the delivery sheath; It discloses a method comprising the steps that, the. This method improves the stent delivery system, which is compatible with design simplicity and operational reliability, and which can achieve a smaller passage profile.

  Patent Document 4 describes a method of loading a stent into a delivery tube. The method includes loading a stent into an opening of a crimping device, the stent having an initial diameter, and crimping the stent through the crimping device to reduce the diameter of the stent from the initial diameter, the crimping device The stent is withdrawn from the opening of the crimping device into the delivery tube passage while vibrating the diameter of the opening of the delivery device, the passage of the delivery tube having a diameter smaller than the initial diameter of the stent. Yes. This method can reduce the force required to push or retract the compressed stent into the delivery tube.

JP-T-2002-525167 Special table 2003-530143 gazette Special table 2012-500075 gazette Special table 2014-523294 gazette

  In order to further develop the minimally invasive treatment, it is important to further reduce the diameter of the tube for holding the tubular medical device, which is provided in the tubular medical device conveying apparatus, and to improve the operability and passage. On the other hand, in order to expand the lumen of the lesion and maintain the lumen diameter, the tubular medical device is required to have a large radial expansion force (hereinafter sometimes referred to as radial force). However, when the radial force of the tubular medical device is increased, the radial force of the tubular medical device that has been reduced in diameter so as to be loaded into the lumen of the tubular medical device transport apparatus is increased. Therefore, it becomes difficult to load the tubular medical device into the lumen of the transport device, and the tubular medical device and the transport device may be damaged.

  The present invention has been made paying attention to the above-described circumstances, and its purpose is to reduce the diameter of the tubular medical device delivery device so as to be loaded into a lumen provided in the delivery device. It is an object of the present invention to provide a method for manufacturing a tubular medical device transporting apparatus that can easily load the tubular medical device thus made into the lumen of the transporting device.

Method of manufacturing a tubular medical device conveying apparatus according to the present invention that has solved the above problems is a method for manufacturing a device for conveying the tubular medical device within the body, the device comprises a tube having an inner diameter D _4, The point is that the following steps (1) to (4) are performed in this order. However, in the following (1) to (4), D ₁ > D ₄ > D ₃ > D ₂ .
(1) A step of setting the tubular medical device having an outer diameter D ₁ to a temperature T ₁ at which an austenite phase exists.
(2) A pre-loading form forming step of applying an external force to the tubular medical device at a temperature T ₂ lower than the temperature T ₁ to reduce the outer diameter from D ₁ to D ₂ .
(3) Loading for expanding the outer diameter of the tubular medical device from D ₂ to D ₃ by weakening the external force at a temperature T ₃ lower than the austenite phase transformation end temperature A _{f of} the alloy constituting the tubular medical device. Form formation process.
(4) at the temperature T _4, the tubular medical device having an outer diameter D _3, the step of loading into the lumen of the inner diameter D _4.

The difference between the outer diameter D ₂ and the outer diameter D ₃ of the tubular medical device is preferably 0.01～0.50Mm.

The temperatures T _1, it is preferable that the a temperature higher than the austenitic phase transformation start temperature A _s of the alloy. The temperature T ₂ is preferably lower than the R phase transformation start temperature R _{s of the} alloy. The temperature T ₂ is preferably lower than the R phase transformation end temperature R _{f of the} alloy. The temperature T ₃ is preferably lower than the R ′ phase transformation end temperature R _f ′ of the alloy. The temperatures T ₁ , T ₂ , T ₃ , and T ₄ preferably satisfy the relationship of T ₁ > T ₂ > T ₃ = T ₄ .

In the step (2), the radial force F _{3 at} the outer diameter D ₃ in the middle of reducing the outer diameter of the tubular medical device from D ₁ to D ₂ , and in the step (3), the diameter is expanded and the tubular It is preferable that the radial force F ₃ ′ when the outer diameter of the medical device is D ₃ satisfies the relationship of F ₃ > F ₃ ′.

  The tubular medical device is preferably a self-expanding stent.

  According to the present invention, prior to loading the tubular medical device into the lumen of the transport device, the temperature is appropriately controlled, and the outer diameter of the tubular medical device is once reduced to be smaller than the outer diameter at the time of loading. And since this is expanded to the outer diameter at the time of loading, the loading load at the time of loading a tubular medical device in the lumen | bore of a conveying apparatus can be reduced. As a result, since the tubular medical device can be easily loaded into the lumen of the transport device, the tubular medical device and the transport device can be prevented from being damaged.

FIG. 1 is a schematic diagram for explaining a method for manufacturing a tubular medical device conveying apparatus according to the present invention. FIG. 2 is a graph showing a change in calorie when the nickel-titanium alloy exhibits a one-step phase transformation. FIG. 3 is a graph showing a change in calorie when the nickel-titanium alloy exhibits a two-stage phase transformation. FIG. 4 is a perspective view showing an example of a self-expanding stent. FIG. 5 is a schematic diagram for explaining an OTW type self-expanding stent delivery catheter structure. FIG. 6 is a schematic diagram for explaining a conventional method for manufacturing a tubular medical device conveying apparatus. FIG. 7 is a development view showing the expanded state of the self-expanding stent used in the examples and comparative examples of the present invention. FIG. 8 is a partially enlarged view showing a substantially waveform component that can be expanded in the circumferential direction of FIG. 7. FIG. 9 is a partial enlarged view showing a connecting portion that connects adjacent substantially waveform components in FIG. 7.

  The inventors of the present invention have made extensive studies in order to provide a method capable of manufacturing a tubular medical device delivery device by easily loading the tubular medical device into the lumen of the delivery device. As a result, prior to loading the tubular medical device into the lumen of the transport device, the temperature is appropriately controlled and the outer diameter of the tubular medical device is once reduced to be smaller than the outer diameter at the time of loading. The present invention has been completed by discovering that the loading load when the tubular medical device is loaded into the lumen of the transport device can be reduced by expanding the diameter of the tube to the outer diameter at the time of loading.

Method of manufacturing a tubular medical device conveying apparatus according to the present invention is a manufacturing method of an apparatus for transporting a tubular medical device within the body, the apparatus includes a tube having an inner diameter D _4, the following (1) to (4 ) Is performed in this order. However, in the following (1) to (4), D ₁ > D ₄ > D ₃ > D ₂ .
(1) A step of setting the tubular medical device having an outer diameter D ₁ to a temperature T ₁ at which an austenite phase exists.
(2) A pre-loading form forming step of applying an external force to the tubular medical device at a temperature T ₂ lower than the temperature T ₁ to reduce the outer diameter from D ₁ to D ₂ .
(3) Loading for expanding the outer diameter of the tubular medical device from D ₂ to D ₃ by weakening the external force at a temperature T ₃ lower than the austenite phase transformation end temperature A _{f of} the alloy constituting the tubular medical device. Form formation process.
(4) at the temperature T _4, the tubular medical device having an outer diameter D _3, the step of loading into the lumen of the inner diameter D _4.

  Hereinafter, although the manufacturing method of the tubular medical device conveying apparatus which concerns on this invention is demonstrated using FIG. 1, this invention is not limited to this.

  FIG. 1 is a schematic view showing a manufacturing procedure of a tubular medical device conveying apparatus according to the present invention. In FIG. 1, 11 is a tubular medical device, 22 is an outer shaft, 31 is a tubular medical device contracting device, and 32 is an extrusion. Shows the rod.

[Step (1)]
In the step (1), the tubular medical device having an outer diameter D ₁ is set to a temperature T ₁ at which an austenite phase exists. The step (1) will be described with reference to FIG.

  In the step (1), the tubular medical device 11 is disposed in the tubular medical device contracting device 31 as shown in FIG. At this time, no external force is applied to the tubular medical device 11 from the tubular medical device contracting device 31.

  The tubular medical device contracting device 31 is a device capable of reducing the diameter of the tubular medical device 11 by applying an external force uniformly from the radial direction of the tubular medical device 11, and a known device can be used. When the tubular medical device contracting device 31 is used, the radial force of the tubular medical device at a certain contraction diameter (the radial force of the tubular medical device in the radial direction) can be measured.

  The tubular medical device contraction apparatus 31 is, for example, a machine solutions Inc. (Hereinafter, also referred to as MSI), Blockwise Engineering LLC (hereinafter, also referred to as Blockwise), and the like.

The outer diameter of the tubular medical device 11 is D _1, the reference outer diameter of the tubular medical device 11.

In the step (1), it is important to set the tubular medical device 11 having the outer diameter D ₁ to a temperature T ₁ (° C.) at which the austenite phase exists. By setting the temperature T _{1 at} which the austenite phase exists, it is possible to reliably obtain the effect of the phase transformation due to the temperature change in the subsequent process.

  The said tubular medical device 11 should just be comprised with the raw material containing an alloy, for example, and can use a shape memory alloy as an alloy, for example.

  The shape memory alloy has shape memory characteristics and superelastic characteristics, and is also excellent in workability. In particular, a nickel-titanium alloy can be more preferably used.

  Of the nickel-titanium alloys, a nickel-titanium alloy containing about 50 to 60% by mass of nickel and the balance being titanium can be more preferably used.

  The shape recovery by the nickel-titanium alloy is generally considered to be based on a phase transformation between the martensite phase and the austenite phase (parent phase), and this phase transformation is caused by temperature dependence or stress dependence. The martensite phase refers to a crystal phase that appears at a low temperature, whereas a crystal phase that appears at a high temperature is called an austenite phase.

  Here, the phase transformation of the nickel-titanium alloy will be described in detail with reference to FIGS.

  The nickel-titanium alloy may exhibit a one-stage phase transformation or a two-stage phase transformation. The one-step phase transformation is a reversible phase transformation between an austenite phase (B2 structure) and a martensite phase (B19 'structure). The two-stage phase transformation is a phase transformation that generates an R phase between an austenite phase (B2 structure) and a martensite phase (B19 'structure). That is, the nickel-titanium alloy depends on temperature and stress between the austenite phase (B2 structure) stable on the high temperature side and the monoclinic martensite phase (B19 ′ structure) stable on the low temperature side. A normal phase or reverse phase transformation is exhibited, but a rhombohedral crystalline phase may appear before the austenite phase transforms to the martensite phase or before the martensite phase transforms to the austenite phase. This crystal phase is called R phase (Rhombohedral phase).

  The austenite phase is a phase with relatively high strength. The martensite phase can be easily deformed by an external force, and is a phase that returns to its original state even when deformed by being strained to about 8%.

  The strain introduced into the martensite phase in the alloy to cause a change in shape is restored when the reverse phase transformation to the austenite phase is completed, thereby restoring the material to its original shape. The normal phase transformation and the reverse phase transformation are caused by loading or unloading stress (superelastic effect), changing temperature (shape memory effect), or a combination thereof. In the present specification, the term “shape memory alloy” can be used interchangeably with the term “superelastic alloy” in order to indicate a material suitable for the method of the present invention.

  Next, the change in the amount of heat when the nickel-titanium alloy undergoes one-step phase transformation will be described with reference to FIG.

  FIG. 2 shows the results of differential scanning calorimetry (DSC) of a nickel-titanium alloy showing a one-step phase transformation. The horizontal axis shows temperature, and the vertical axis shows the amount of heat. The upper graph in FIG. 2 shows the result of the change in the amount of heat when cooled, and the lower graph shows the result of the change in the amount of heat when heated. .

  First, when the nickel-titanium alloy showing the one-step phase transformation is cooled from the temperature at which it is in the austenite phase to the temperature at which it is in the martensite phase, the change in calorie becomes the upper graph in FIG.

In FIG. 2, M _s is the martensite phase transformation start temperature, and indicates the temperature at which phase transformation from the austenite phase to the martensite phase begins during cooling. M _f is the martensite phase transformation end temperature, and indicates the temperature at which the phase transformation from the austenite phase to the martensite phase ends during cooling. M _p is the martensitic phase transformation peak temperature and indicates the exothermic peak temperature of the martensitic phase transformation curve.

In the temperature range higher than the martensitic phase transformation start temperature (M _s ), only the austenite phase exists. In the temperature range below the martensitic phase transformation start temperature (M _s ) and above the martensitic phase transformation end temperature (M _f ), the austenite phase and the martensitic phase are mixed. In the temperature range lower than the martensite phase transformation end temperature (M _f ), only the martensite phase exists.

  Next, when the nickel-titanium alloy showing the one-stage phase transformation is heated from the temperature at which it is in the martensite phase to the temperature at which it is in the austenite phase, the change in calorie becomes the lower graph in FIG.

In FIG. 2, A _s is the austenite phase transformation start temperature, and indicates the temperature at which phase transformation (reverse transformation) from the martensite phase to the austenite phase starts during heating. _Af is the austenite phase transformation end temperature, and indicates the temperature at which the phase transformation (reverse transformation) from the martensite phase to the austenite phase is completed during heating. _Ap is the austenite phase transformation peak temperature and indicates the endothermic peak temperature of the austenite phase transformation curve.

In the temperature range lower than the austenite phase transformation start temperature (A _s ), only the martensite phase exists. In the temperature range from the austenite phase transformation start temperature (A _s ) to the austenite phase transformation end temperature (A _f ), the austenite phase and the martensite phase are mixed. In the temperature range higher than the austenite phase transformation end temperature (A _f ), only the austenite phase exists.

Each transformation temperature is usually M _s > M _p > M _f and A _f > A _p > A _s , but is not necessarily limited thereto.

  Next, the change in the amount of heat when the nickel-titanium alloy undergoes a two-stage phase transformation will be described with reference to FIG.

  FIG. 3 shows the results of differential scanning calorimetry (DSC) of a nickel-titanium alloy exhibiting a two-stage phase transformation. The horizontal axis indicates temperature, and the vertical axis indicates the amount of heat. The upper graph in FIG. 3 shows the result of the change in the amount of heat when cooled, and the lower graph shows the result of the change in the amount of heat when heated. .

  First, when the nickel-titanium alloy exhibiting the two-stage phase transformation is cooled from the temperature at which it is in the austenite phase to the temperature at which it is in the martensite phase, the change in calorie becomes the upper graph in FIG.

In FIG. 3, R _s is the R phase transformation start temperature, and indicates the temperature at which phase transformation from the austenite phase to the R phase begins during cooling. R _f is the R phase transformation end temperature, and indicates the temperature at which the phase transformation from the austenite phase to the R phase ends during cooling. R _p is the R phase transformation peak temperature and indicates the exothermic peak temperature of the R phase transformation curve. M _s is the martensitic phase transformation start temperature, and indicates the temperature at which phase transformation from the R phase to the martensitic phase begins during cooling. M _f is a martensite phase transformation end temperature, and indicates a temperature at which the phase transformation from the R phase to the martensite phase is completed during cooling. M _p is the martensitic phase transformation peak temperature and indicates the exothermic peak temperature of the martensitic phase transformation curve.

In the temperature range higher than the R phase transformation start temperature (R _s ), only the austenite phase exists. In the temperature range below the R phase transformation start temperature (R _s ) and above the R phase transformation end temperature (R _f ), the austenite phase and the R phase are mixed. In the temperature range lower than the R phase transformation end temperature (R _f ) and higher than the martensitic phase transformation start temperature (M _s ), only the R phase exists. In the temperature range below the martensitic phase transformation start temperature (M _s ) and above the martensitic phase transformation end temperature (M _f ), the R phase and the martensitic phase are mixed. In the temperature range lower than the martensite phase transformation end temperature (M _f ), only the martensite phase exists.

Next, when the nickel-titanium alloy exhibiting the two-stage phase transformation is heated from the temperature at which it is in the martensite phase to the temperature at which it is in the austenite phase, the change in calorie becomes the lower graph in FIG. In FIG. 3, R _s ′ is the R ′ phase transformation start temperature, and indicates the temperature at which the phase transformation from the martensite phase to the R phase starts during heating. R _f ′ is the R ′ phase transformation end temperature, and indicates the temperature at which the phase transformation from the martensite phase to the R phase ends during heating. R _p ′ is the R ′ phase transformation peak temperature and indicates the endothermic peak temperature of the R phase transformation curve. A _s is an austenite phase transformation start temperature, when heated, shows a phase transformation starts temperature to the austenite phase from R-phase. _Af is the austenite phase transformation end temperature, and indicates the temperature at which the phase transformation from the R phase to the austenite phase is completed during heating. _Ap is the austenite phase transformation peak temperature and indicates the endothermic peak temperature of the austenite phase transformation curve.

In the temperature range lower than the R ′ phase transformation start temperature (R _s ′), only the martensite phase exists. In the temperature range from the R ′ phase transformation start temperature (R _s ′) to the R ′ phase transformation end temperature (R _f ′), the martensite phase and the R phase are mixed. In the temperature range higher than the R ′ phase transformation end temperature (R _f ′) and lower than the austenite phase transformation start temperature (A _s ), only the R phase exists. In the temperature range from the austenite phase transformation start temperature (A _s ) to the austenite phase transformation end temperature (A _f ), the R phase and the austenite phase are mixed. In the temperature range higher than the austenite phase transformation end temperature (A _f ), only the austenite phase exists.

Each transformation temperature is typically R _s > R _p > R _f > M _s > M _p > M _f and A _f > A _p > A _s > R _f '> R _p '> R _s '. However, it is not necessarily limited to these.

  The differential scanning calorimetry may be performed in accordance with, for example, ASTM F2004-05 “Standard Test Method for Transformation Temperature of Nickel-Titanium Alloy by Thermal Analysis”.

  The phase transformation occurs in a state where there is no stress load on the alloy, and the phase formed by the temperature change is called “thermally induced phase”.

  On the other hand, even when the temperature does not change, a phase transformation occurs when stress is applied to the alloy. The phase formed by stress loading is called the “stress-induced phase”.

  As the nickel-titanium alloy, a commercially available product or one manufactured by a known method can be used.

  In particular, a shape memory alloy exhibiting a two-stage phase transformation is preferably produced, for example, under the following conditions.

  In order for the nickel-titanium alloy to exhibit the R phase transformation, it is effective to have a nickel-rich composition, for example, by melting about 51 atomic% nickel and about 49 atomic% titanium. It is preferable.

  Further, for example, the alloy may contain an alloy element in addition to nickel and titanium, and examples of the alloy element include an iron element. As the iron element, for example, a trivalent or tetravalent element can be used.

  It is also preferable to heat-treat the alloy at a temperature of about 400 ° C. to about 550 ° C. after cold working.

  By appropriately combining these, the martensitic phase transformation can be suppressed with respect to the R phase transformation, and the nickel-titanium alloy exhibits the R phase transformation.

  In addition, the crystal phase of nickel-titanium alloy can be identified by using an analysis method such as X-ray diffraction (XRD).

  The phase transformation of the nickel-titanium alloy has been described above.

The temperatures T ₁ is preferably be a temperature higher than the austenitic phase transformation start temperature A _s of the alloy, and more preferably to a temperature higher than the austenitic phase transformation finish temperature A _f of the alloy. In particular, by setting the temperature higher than the above _Af , an austenite phase can be obtained.

[Step (2), Step (3)]
In the step (2), an external force is applied to the tubular medical device at a temperature T ₂ lower than the temperature T ₁ to reduce the outer diameter from D ₁ to D ₂ to obtain a pre-loading configuration. The step (2) will be described with reference to (ii) of FIG.

In the step (2), as shown in FIG. 1 (ii), the tubular medical device contracting device 31 is used, and an external force is applied to the tubular medical device 11 from the radial direction to reduce the outer diameter from D ₁ to D ₂ . Let

The outer diameter D _2, in the step of which will be described later (4), a tubular medical device 11, it is important to reduce than the outer diameter D ₃ for loading the tube with an inner diameter D ₄ provided in the conveying device . That is, in the step (2), it is necessary to reduce the outer diameter of the tubular medical device 11 so that D ₁ > D ₂ and D ₁ > D ₃ > D ₂ are satisfied.

The size of the outer diameter D ₂ when the tubular medical device 11 is reduced in the step (2) is not particularly limited as long as it is smaller than the outer diameter D ₃ as described above. The medical tool 11 needs to be in a range where it does not buckle and break.

In the step (2), the difference (D ₃ -D ₂ ) from the outer diameter D ₃ when the outer diameter of the tubular medical device 11 is expanded in the step (3) is, for example, 0.01. It is preferable to reduce the diameter so as to be ˜0.50 mm. The difference is more preferably 0.03 mm or more, further preferably 0.05 mm or more, and particularly preferably 0.10 mm or more. Further, the difference is more preferably 0.40 mm or less, still more preferably 0.30 mm or less, and particularly preferably 0.20 mm or less.

The step (2) needs to be performed at a temperature T ₂ lower than the temperature T ₁ in the step (1). The temperature T ₂ is equal to or above temperatures T _1, higher than the temperatures T ₁ can not reduce the loading load when loading the tubular medical device 11 into a provided intraluminal tubular medical device conveying device . Further, by lowering the temperature T ₂ , the crystal phase of the alloy contains a large amount of thermally induced R phase and / or martensite phase, and the diameter is reduced by applying external force to the tubular medical device 11. In the process, more stress-induced martensite phases are developed, so that the reduced diameter load can be made smaller than in other temperature ranges. The temperature T ₂ is preferably lower than the R phase transformation start temperature R _{s of the} alloy, and more preferably lower than the R phase transformation end temperature R _{f of the} alloy.

In the step (3), the external force is weakened at a temperature T ₃ lower than the austenite phase transformation end temperature A _{f of} the alloy constituting the tubular medical device, and the outer diameter of the tubular medical device is changed from D ₂ to D ₃ . Increase the diameter. The step (3) will be described with reference to (iii) of FIG.

In step (3), as shown in FIG. 1 (iii), the external force applied to the tubular medical device 11 from the tubular medical device contracting device 31 is reduced, and the outer diameter of the tubular medical device 11 is changed from D ₂ to D _3. To increase the diameter.

After reducing the outer diameter of the tubular medical device 11 from D ₁ to D ₂ , the radial force F ₃ ′ of the tubular medical device 11 is increased to D ₃ larger than D _2, so that the radial force F ₃ ′ of the tubular medical device 11 is increased. It can be made smaller than the radial force F ₃ of the tubular medical device 11 when the outer diameter is directly reduced from D ₁ to D ₃ . That is, the tubular medical device outer diameter D ₁ from D ₃ to radial force and F ₃ of the tubular medical device 11 when the diameter of 11, a small D ₂ than D ₃ of outer diameter from D ₁ of the tubular medical device 11 Assuming that the radial force of the tubular medical device 11 is F ₂ , the radial force of the tubular medical device 11 increases as the outer diameter decreases, so that F ₂ > F ₃ . However, radial force of the tubular medical device 11 when the outer diameter of the tubular medical device 11 which is reduced in diameter to outer diameter D ₂ was expanded in diameter D ₃ is not the above F _3, smaller than the F ₃ F ₃ '. Therefore, even in the outer diameter of the same D ₃ tubular medical device 11, to the case of reduced diameter to the outer diameter D _3, after reducing the diameter to a smaller outer diameter D ₂ than the outer diameter D _3, the outer diameter D ₃ When the diameter is increased, a difference of F ₃ −F ₃ ′ is generated in the radial force. If the radial force can be reduced, the tubular medical device 11 can be easily manufactured because the loading load when the tubular medical device 11 is loaded onto the outer shaft 22 in the step (4) described later can be reduced.

The diameter expansion needs to be performed at a temperature T ₃ lower than the austenite phase transformation end temperature (A _f ) of the alloy constituting the tubular medical device 11. In particular, when the alloy constituting the tubular medical device 11 exhibits a two-stage phase transformation, it is preferably performed at a temperature lower than the R ′ phase transformation end temperature (R _f ′). Even _if the outer diameter is relaxed to the maximum by performing the above-mentioned diameter expansion at a temperature lower than the austenite phase transformation end temperature (A _f ) or the R ′ phase transformation end temperature (R _f ′), the crystal phase of the alloy is Since many R phases or martensite phases are included, in the process of unloading the external force applied to the tubular medical device 11 and expanding the diameter, the austenite phase becomes difficult to develop, and the reduced diameter load can be further reduced.

The temperature T ₃ is preferably lower than the temperature T ₂ . That is, the temperature is preferably T ₁ > T ₂ > T ₃ . Thus, by reducing the temperature for each process, consumption of energy necessary for cooling can be suppressed, and the tubular medical device 11 can be efficiently reduced in diameter in a state where the reduced diameter load is reduced as compared with the conventional method.

In the process (3), the difference (D ₃ -D ₂ ) between the outer diameter of the tubular medical device 11 and the outer diameter D ₂ in the process (2) described above is, for example, 0.01 to 0.50 mm. It is preferable to expand the diameter so that

[Step (4)]
(4) In the step, at a temperature T _4, the tubular medical device having an outer diameter D _3, loaded into the lumen of the inner diameter D _4. The step (4) will be described with reference to (iv) in FIG.

In the step of (4), as shown in (iv) in FIG. 1, the outer shaft 22 having a lumen with an inner diameter D ₄ on one side of the tubular medical device contraction device 31 disposed, tubular medical devices shrink device 31 Nomou The tubular medical device 11 is loaded into the lumen of the outer shaft 22 by the push rod 32 from one side.

Since the radial force of the tubular medical device 11 is F ₃ ′ smaller than the above F ₃ as described in the step (3), the frictional resistance load when the tubular medical device 11 is pushed out by the push rod 32 is reduced. It can be easily loaded into the lumen of the outer shaft 22.

(4) the temperature T ₄ to perform the step is not particularly limited, and may be the same as the temperature T ₃ of the process (3). By reducing the temperature T ₄ and the temperature T ₃ to the same temperature, the reduced diameter load reduction effect obtained in the step (3) is used as the friction load reduction effect when the tubular medical device 11 is loaded on the outer shaft 22. Applicable and smooth work is possible.

Outer diameter of the push rod 32 can be the same as the inner diameter of the tubular medical device 11 which is enlarged to the outer diameter D _3, it is preferably larger in the range 0.20mm than the inner diameter of the tubular medical device 11 of either the same as the outer diameter D _3, it is preferably smaller in 0.20mm less range than the outer diameter. By adjusting the outer diameter of the push rod 32 within this range, the entire peripheral edge of the end of the tubular medical device 11 can be pushed, so that the tubular medical device 11 is efficiently transferred from the tubular medical device contracting device 31 into the outer shaft 22. Can be pushed out.

  The material of the extrusion rod 32 is not particularly limited as long as it is a rigid material that can push the tubular medical device 11 into the outer shaft 22. Examples of such materials include metal materials such as stainless steel, aluminum, iron, nickel, titanium, and alloys thereof, and resin materials such as polyether ether ketone, polyamide, polyimide, and polycarbonate.

  The method of loading the tubular medical device 11 into the outer shaft 22 may be a known method other than pressing with the push rod 32.

The inner diameter D ₄ of the outer shaft 22 is preferably larger than the outer diameter D ₃ of the tubular medical device 11 in order to facilitate loading of the tubular medical device 11. That is, it is preferable that D ₁ > D ₄ > D ₃ > D ₂ . The outer diameter D ₃ of the tubular medical device 11, equal to the inner diameter D ₄ of the outer shaft 22, becomes greater, loading into the lumen of the outer shaft 22 it becomes difficult. However, if the diameter of the tubular medical device 11 is excessively reduced, the tubular medical device 11 may buckle and be damaged. In order to load the tubular medical device 11 into the lumen of the outer shaft 22 without buckling, the outer diameter D ₃ of the tubular medical device 11 is within a range of 0.30 mm or less from the inner diameter D ₄ of the outer shaft 22. It is preferable to make it small, more preferably in the range of 0.01 to 0.20 mm, and still more preferably in the range of 0.02 to 0.15 mm.

From the viewpoint of feeding the tubular medical device 11 into the lumen of the outer shaft 22 without buckling, the difference between the radial force F ₃ ′ and the radial force F ₃ is preferably 10N or more, more preferably 20N or more, 30N or more is more preferable.

In the steps (1) to (4), the temperatures T ₁ , T ₂ , T ₃ , and T ₄ preferably satisfy the relationship of T ₁ > T ₂ > T ₃ = T ₄ .

Conventionally, in order to reduce the loading load at the time of loading, at least the temperature at which the martensite phase develops, that is, the temperature lower than the martensite phase transformation start temperature (M _s ) has been cooled. For example, a refrigerant such as liquid nitrogen is required, and the operation is complicated. However, according to the manufacturing method of the present invention, the radial force of the tubular medical device is reduced even in a temperature range that is easy to operate by combining the reduced diameter and the expanded diameter of the tubular medical device using the tubular medical device contracting device. Therefore, the loading load at the time of loading can be reduced.

The tubular medical device 11 preferably exhibits superelastic characteristics at the body temperature of the human body, and specifically, the alloy components are designed so that the austenite phase transformation end temperature (A _f ) is 37 ° C. or lower. preferable. The austenite phase transformation end temperature (A _f ) is more preferably 35 ° C. or lower, and further preferably 33 ° C. or lower. The lower limit of the austenite transformation end temperature (A _f ) is not particularly limited, but is preferably 15 ° C. or higher, more preferably 20 ° C. or higher, and still more preferably 22 ° C. or higher.

The tubular medical device 11 is preferably designed with alloy components such that the R ′ phase transformation end temperature (R _f ′) is lower than the austenite phase transformation end temperature (A _f ). The R ′ phase transformation end temperature (R _f ′) is preferably 10 to 37 ° C., more preferably 12 to 35 ° C., and still more preferably 15 to 30 ° C.

Next, (v) in FIG. 1 will be described. FIG. 1 (v) shows a state where the tubular medical device 11 is loaded into the lumen of the outer shaft 22. When the tubular medical device 11 is loaded into the lumen of the outer shaft 22, the tubular medical device 11 expands in diameter and becomes equal to the inner diameter D ₄ of the outer shaft 22.

  As mentioned above, according to the manufacturing method of this invention, the loading load at the time of loading a tubular medical device in the lumen | bore of a conveying apparatus can be reduced. As a result, since the tubular medical device can be easily loaded into the lumen of the transport device, the tubular medical device and the transport device can be prevented from being damaged.

  Next, the tubular medical device used in the present invention will be described.

  The medical device is a tubular body, and the shape thereof is preferably a cylindrical shape.

  Although the kind of said tubular medical device is not specifically limited, For example, a stent, a stent graft, an obturator, an injection catheter, a prosthetic valve, etc. are mentioned. In particular, a stent can be preferably used.

  The form of the stent is not particularly limited. For example, (a) a coiled stent made of one linear metal or polymer material, (b) a stent obtained by cutting a metal tube with a laser, and (c) Examples include a stent assembled by welding linear members with a laser, and (d) a stent made by weaving a plurality of linear metals. A stent design is proposed, for example, in WO 2010/029928.

  The stent preferably has a mesh structure portion.

  The above-mentioned stent is generally based on an expansion mechanism. (A) A balloon expandable stent in which a stent is attached to the outer surface of the balloon and transported to the lesion, and the stent is expanded by the balloon at the lesion, and (b) the stent. It can be classified into a self-expanding stent that is loaded into a catheter having a sheath member that suppresses the expansion of the stent, transported to the lesioned part, and removed by removing the sheath member at the lesioned part.

  In the present invention, a self-expanding stent can be preferably used as the tubular medical device.

  Hereinafter, although the said self-expanding stent is demonstrated in detail, the medical device used by this invention is not limited to this.

  FIG. 4 is a perspective view of the self-expanding stent 11a. The self-expanding stent 11a shown in FIG. 4 is a tubular body having a mesh structure portion and shows an expanded state.

Nominal outer diameter of the self-expanding stent 11a is D _1, the reference length is L _1. Nominal outer diameter D ₁ is the outside diameter before being loaded into the lumen of the transfer device is deflated.

Nominal outer diameter D ₁ and reference length L ₁ of the self-expanding stent 11a is appropriately selected depending on the inside diameter and length of the lumen at the lesion varies depending on the lumen to the therapeutic purpose. For example, self-expanding stents 11a of lower limb arterial treatment, reference outer diameter _{D 1} is, for example, in 4.0～12.0Mm, reference length _{L 1} is, for example, using preferably has a 20~200mm It is done.

  As a material of the self-expanding stent 11a, a shape memory alloy can be preferably used.

The self-expanding stent 11a has a Radial Resistive Force (hereinafter sometimes referred to as RRF) that indicates an expansion force that the stent attempts to resist compression in order to effectively expand and maintain the body lumen in which the stent 11a is placed. It is preferably 0.200 to 1.500 N / mm. If the RRF is too small, it becomes difficult to expand and maintain the body lumen to be placed due to insufficient expansion force, and there is a risk of dropping from the placement position. RRF is more preferably 0.400 N / mm or more. The RRF is preferably as large as possible from the viewpoint of expanding and maintaining the body lumen. However, if the RRF is too large, the force that dilates the body lumen becomes too great and may damage the body lumen. RRF is more preferably 1.200 N / mm or less. Incidentally, RRF is under an atmosphere of 37.0 ± 1.0 ° C., the self-expanding stents 11a from the reference outer diameter _{D 1} to diameter minus 2.5 mm, at a speed of 0.1 mm / sec, the radius the contraction径荷heavy when the reduced diameter by compressing from the direction, the value obtained by dividing the reference length L ₁ of the self-expanding stent 11a.

  The RRF can be measured using, for example, a device commercially available from MSI, Blockwise, or the like.

The self-expanding stent 11a is preferably flexible so that it can follow the dynamics of the body lumen in which it is placed. Specifically, using a tensile and compression tester (for example, “EZ-Test” manufactured by Shimadzu Corporation) at a speed of 0.1 mm / second with a plane indenter in an atmosphere of 37.0 ± 1.0 ° C., from the long axis direction of the self-expanding stent 11a, the long axis compressive strength when compressed up to 7% displacement of the reference length _{L 1} is preferably a 0.030～1.500N. The long axis compressive strength is more preferably 0.050 N or more, and more preferably 1.300 N or less.

  The self-expanding stent 11a can be produced by, for example, expanding a diameter of a nickel-titanium alloy pipe that has been laser-cut, heat-treating it, forming a desired shape, and finally electrolytic polishing. .

  Next, the tubular medical device conveying apparatus manufactured by the present invention will be described. Hereinafter, although the case where a self-expanding stent is used as a tubular medical device will be described in detail, the present invention is not limited to this.

  As a delivery device for a self-expanding stent, an OTW (Over The Wire) type catheter structure and an RX (Rapid Exchange) type catheter structure are generally known. Among these, the OTW type self-expanding stent delivery catheter structure will be described with reference to FIG. 5, but the tubular medical device delivery device according to the present invention is not limited to this.

  FIG. 5 is a schematic view showing the entire self-expanding stent delivery device.

  The self-expanding stent transport device 21 transports the self-expanding stent 11a to a lesioned part (for example, a narrowed part) of a body lumen, can be inserted into the body lumen, is elongated and has flexibility. doing. FIG. 5 shows a state in which the self-expanding stent 11a is loaded inside the outer shaft 22, and the self-expanding stent 11a is in a contracted state.

  The self-expanding stent delivery device 21 shown in FIG. 5 includes a self-expanding stent 11a, an outer shaft 22, and an inner shaft 23.

(Outer shaft)
The outer shaft 22 is housed in a deflated condition a self-expanding stent 11a, the outer diameter of the self-expanding stent 11a is D _4, it is equal to the inner diameter of the outer shaft 22.

The self-expanding stents 11a and conveyed to the lesion, which is accommodated in the outer shaft 22, when released from the outer shaft 22, the outer diameter D ₄ of the self-expanding stents 11a of deflated, exceed the inner diameter of the outer shaft 22 To expand the diameter.

  The outer shaft 22 has flexibility enough to follow a lumen (for example, blood vessel) to be inserted, kink resistance, and has a tensile strength that does not extend when the self-expanding stent delivery device 21 is pulled during the procedure. It is preferable to form with a raw material.

  The inner side of the outer shaft 22 is preferably made of a material that reduces movement resistance (sliding resistance) in order to easily release the self-expanding stent 11a that is in contact with the inner peripheral surface to the lesioned part. It is preferable that the outer side is made of a material having low friction so that the moving operation in the lumen can be easily performed.

  From such a viewpoint, the outer shaft 22 is preferably formed of a tube having a three-layer structure in which, for example, an outer layer and an inner layer are formed of a resin material, and a reinforcing layer is embedded between the outer layer and the inner layer. As the reinforcing layer, for example, a metal wire layer is preferably used.

  For the outer layer of the outer shaft 22, it is preferable to use various elastic resin materials such as polyethylene, fluororesin (for example, PTFE, PFA, etc.), polyamide, polyamide-based elastomer, polyurethane, polyester, or silicone.

  For the inner layer of the outer shaft 22, it is preferable to use a low friction material such as, for example, a fluororesin (for example, PTFE, PFA, etc.) or polyethylene.

  It is preferable to use various metal materials such as stainless steel, nickel-titanium alloy, tungsten, gold, or platinum for the reinforcing layer (metal wire layer) of the outer shaft 22.

  The metal strand includes at least one of a braided structure and a coil structure, and is preferably formed from the proximal end to the distal end of the outer shaft 22.

  The proximal end (proximal end side) means the operator's hand side, and the distal end (distal end side) means the opposite side of the proximal end, that is, the side close to the lesioned part or the like.

  The portion of the outer shaft 22 that holds the self-expanding stent 11a may be formed of a tube having a single-layer structure or a structure in which two or more layers are laminated, and preferably has a single-layer structure or a two-layer structure. For such a layer, it is preferable to use the material used for the outer layer and / or the material used for the inner layer.

(Inner shaft)
The inner shaft 23 is a tubular member having a guide wire lumen, and a pusher member 24 is attached to the proximal side of the self-expanding stent 11a, a tip tip 25 is attached to the distal side, and an operation member 26 is attached to the proximal side of the proximal portion. It is preferable.

  The tubular member having the guide wire lumen of the inner shaft 23 is at least partially inserted into the lumen of the outer shaft 22. A guide wire is inserted into the lumen formed in the inner shaft 23, and the self-expanding stent delivery device 21 can be guided to the lesioned part.

  The inner shaft 23 preferably has flexibility enough to follow the lumen of the outer shaft 22, kink resistance, and tensile strength that does not extend when the catheter is pulled during the procedure.

  For the inner shaft 23, it is preferable to use various elastic resin materials such as polyethylene, fluororesin (for example, PTFE, PFA, etc.), polyamide, polyamide elastomer, polyurethane, polyester, polyimide, or silicone.

  The inner shaft 23 may be reinforced with a metal material, and examples of the metal material include stainless steel, nickel-titanium alloy, tungsten, gold, or platinum.

(Pusher member)
The pusher member 24 is preferably mounted (adhered or welded) around the inner shaft 23 and fit within the lumen of the outer shaft 22.

  The self-expanding stent 11 a can be released from the outer shaft 22 in accordance with the relative movement of the outer shaft 22 and the inner shaft 23.

The shape of the pusher member 24 is, for example, a ring shape, and the outer diameter thereof is preferably not less than the inner diameter of the contracted self-expanding stent 11a and not more than the inner diameter of the outer shaft 22 (that is, the outer diameter D ₄ ). By setting the outer diameter of the pusher member 24 within this range, the pusher member 24 covers the peripheral edge at the end portion of the self-expandable stent 11a, so that the self-expandable stent 11a can be efficiently discharged.

  For the pusher member 24, various elastic resin materials such as polyethylene, fluororesin (for example, PTFE, PFA, etc.), polyamide, polyamide-based elastomer, polyurethane, polyester, or silicone can be used.

  The pusher member 24 preferably includes an at least partially radiopaque material. By using the radiopaque material at least in part, the self-expandable stent delivery device 21 can be operated under fluoroscopy, so that the self-expandable stent 11a can be safely and efficiently placed in a body lumen. Can be transported to the affected area and released.

  Examples of the radiopaque material include a contrast material such as a contrast medium such as an X-ray contrast medium or an ultrasound contrast medium. Specifically, for example, gold, platinum, tungsten, tantalum, iridium, palladium or an alloy thereof, or a gold-palladium alloy, platinum-iridium, NiTiPd, NiTiAu, barium sulfate, a bismuth compound, or a tungsten compound. Can be mentioned.

(Tip tip)
The tip 25 is attached (for example, bonded or welded) to the tip of the inner shaft 23. The distal tip 25 makes it easier for the self-expanding stent delivery device 21 to pass through a lesion (for example, a stenosis).

  The distal tip 25 is preferably flexible enough to follow the lumen (for example, blood vessel) to be inserted and has rigidity in the long axis direction so that it can pass through the narrowed portion.

  For the tip 25, various elastic resin materials such as polyethylene, fluororesin (for example, PTFE, PFA, etc.), polyamide, polyamide-based elastomer, polyurethane, polyester, or silicone can be used.

  The tip 25 preferably includes a material that is at least partially radiopaque. By using the radiopaque material at least in part, the self-expandable stent delivery device 21 can be operated under fluoroscopy, so that the self-expandable stent 11a can be safely and efficiently placed in a body lumen. Can be transported to the affected area and released.

  Examples of the radiopaque material include a contrast material such as a contrast medium such as an X-ray contrast medium or an ultrasound contrast medium. Specifically, for example, gold, platinum, tungsten, tantalum, iridium, palladium or an alloy thereof, or a gold-palladium alloy, platinum-iridium, NiTiPd, NiTiAu, barium sulfate, a bismuth compound, or a tungsten compound. Can be mentioned.

(Operation member)
The operation member 26 is attached (for example, adhered or welded) to the proximal end of the inner shaft 23.

  The shape of the operation member 26 is not particularly limited as long as it is a shape that can be easily grasped by the operator, and for example, as shown in FIG. preferable.

  For example, a metal material such as stainless steel, aluminum, iron, nickel, or titanium, or a resin material such as polyether / etherketone, polyamide, polyimide, or polycarbonate can be used as the material of the operation member 26.

  EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited by the following examples, and may be implemented with modifications within a range that can meet the above and the gist described below. Of course, these are all possible and are included in the technical scope of the present invention.

  In manufacturing a device for transporting a tubular medical device, a loading load when the tubular medical device was loaded into a lumen provided in the transport device was measured. Specifically, a self-expanding stent was used as a tubular medical device, and the self-expanding stent was inserted into a lumen of a catheter serving as a transport device to manufacture a tubular medical device transport device.

Example 1
A self-expandable stent made of nickel-titanium alloy having a reference outer diameter D ₁ of 6.0 mm and a reference length L ₁ of 100 mm was prepared as a tubular medical device. The design of the prepared self-expanding stent is described in detail below with reference to FIGS. 7 is a development view showing an expanded state of the self-expanding stent, FIG. 8 is a partially enlarged view showing substantially waveform components in the expanded state of the self-expanding stent, and FIG. 9 is an expansion of the self-expanding stent. The partial enlarged view which shows the connection part in a state is shown, respectively.

  The self-expanding stent design has an annular section 71 of generally corrugated components 72 aligned with the longitudinal axis and having a connection 73 connecting the generally corrugated components 72 in adjacent annular sections 71. The connecting portion 73 connects the vertices 87 of the substantially waveform components. In the expanded state, a line connecting adjacent connecting portions 73 connected to each other without interposing other connecting portions 73 forms two spirals opposite to each other with respect to the longitudinal axis. The wavelengths are different from each other. More specifically, 55 annular sections 71 are aligned with respect to the longitudinal axis, the number of substantially corrugated components 72 in the annular section 71 is 16, and the number of connecting portions 73 included in the annular section 71 is. Is four.

  Further, the central axes of the inner curvature radii between the struts forming the adjacent substantially corrugated components 72 are collinear in the circumferential direction, the strut inner curvature radius center 81 of the substantially corrugated components 72 and the outer curvature radius center The distance between them is 30 μm. Further, the outer radius of curvature 84 between the struts of the substantially corrugated component 72 is 110 μm, and the inner radius of curvature 83 is 30 μm. The apex width 86 of the substantially corrugated component 71 is 110 μm, the strut width 85 is 80 μm, and the strut thickness is 200 μm.

  The nickel-titanium alloy is compliant with ASTM F2063-05.

The RRF of the self-expanding stent was calculated by the following procedure. A value obtained by subtracting 2.5 mm from the reference outer diameter D ₁ (6.0 mm) of the self-expanding stent in an atmosphere of 37.0 ± 1.0 ° C. using an RRF measuring device (“TTR2” manufactured by Blockwise). The diameter reduction load is measured when the diameter is reduced by compressing from the radial direction at a speed of 0.1 mm / second up to the diameter (that is, 3.5 mm), and the reduced diameter load is measured as the reference length of the self-expandable stent. RRF was calculated by dividing by L ₁ (100 mm). As a result of calculation, RRF was 1.001 N / mm.

The long axis compressive strength of the self-expanding stent was measured by the following procedure. The long axis of the self-expanding stent using a tensile compression tester (“EZ-Test” manufactured by Shimadzu Corporation) in an atmosphere of 37.0 ± 1.0 ° C. with a flat indenter at a speed of 0.1 mm / sec. From the direction, the load when compressed to a 7% displacement amount of the reference length L ₁ (100 mm) (that is, compressed to 7 mm) was measured as the long-axis compression strength. As a result of measurement, the long axis compressive strength was 0.081N.

  The nickel-titanium alloy is an alloy exhibiting a two-stage phase transformation, and becomes a martensite phase, an R phase, or an austenite phase depending on temperature and / or stress.

  The phase transformation temperature when the nickel-titanium alloy is cooled or heated is shown in Table 1 below.

  The phase transformation temperature of the self-expanding stent was measured according to ASTM F2004-05 and ASTM F2005-05 using a differential scanning calorimeter (“DSC7020” manufactured by Hitachi High-Tech Science). The sample mass of the self-expanding stent was 20-30 mg, the scanning temperature rate was 10 ° C./min, and the scanning temperature range was −120 ° C.-100 ° C. The measured results are shown in Table 1 below.

In Table 1 below, R _s is the transformation start temperature from the austenite phase to the R phase during cooling, R _p is the transformation peak temperature (exothermic peak temperature) from the austenite phase to the R phase, and R _f is the austenite phase to the R phase during cooling. M _s is the transformation start temperature from the R phase to the martensite phase during cooling, M _p is the transformation peak temperature from the R phase to the martensite phase (exothermic peak temperature), and M _f is the R phase during cooling. from transformation finish temperature to the martensite phase, R _s 'is transformation start temperature to the R-phase from martensite phase during heating, R _p' is the transformation peak temperature to the R-phase from martensite phase (endothermic peak temperature), R _f 'is transformation finish temperature to the R-phase from martensite phase during heating, a _s is transformation start temperature to the austenite phase from R-phase during heating, a _p is the transformation peak temperature to the austenite phase from R-phase (endothermic peak ) And A _f indicate the end temperature of transformation from the R phase to the austenite phase during heating, respectively.

  As the outer shaft 22, a tube having a braided structure using a polyamide-based elastomer for the outer layer and polytetrafluoroethylene (PTFE) for the inner layer and a stainless steel flat wire having a width of 100 μm and a thickness of 25 μm as the reinforcing layer was used. .

The inner diameter D ₄ of the lumen formed in the outer shaft 22 was 1.80 mm.

  In the procedure shown in FIG. 1, the self-expandable stent 11 was loaded into the outer shaft 22 using a tubular medical device contracting device 31 (“RFL225” manufactured by Blockwise).

  Hereinafter, the charging procedure will be described with reference to FIG.

FIG. 1 (i) shows a state in which the self-expanding stent 11 having an outer diameter D ₁ is disposed in the tubular medical device contracting device 31. In (i), the temperature T ₁ was 37.0 ± 1.0 ° C. The reference outer diameter D ₁ of the self-expanding stent 11 is 6.0 mm.

Next, (ii) of FIG. 1 shows a state in which the diameter of the self-expandable stent 11 is reduced by applying an external force using the tubular medical device contracting device 31. In (ii), the temperature T ₂ is 25.0 ± 1.0 ° C., the speed is 0.1 mm / second, and the diameter is reduced from the reference outer diameter D ₁ (6.0 mm) to 1.45 mm (outer diameter D ₂ ). I let you. When the radial force F ₂ when the diameter was reduced to the outer diameter D ₂ (1.45 mm) was measured with the tubular medical device contracting device 31, it was 151.8 N.

In addition, the radial force F ₃ when the outer diameter became 1.75 mm (outer diameter D ₃ ) in the middle of the reduction from the reference outer diameter D ₁ to the outer diameter D ₂ was 133.6N.

Next, (iii) of FIG. 1 shows a state where the external force applied from the tubular medical device contracting device 31 is weakened and the diameter of the self-expanding stent 11 is expanded. In (iii), the temperature T _{3 is set} to 25.0 ± 1.0 ° C., the speed is set to 0.1 mm / second, and the diameter is expanded from the outer diameter D ₂ (1.45 mm) to 1.75 mm (outer diameter D ₃ ). It was. The radial force F ₃ ′ when the diameter was expanded to the outer diameter D ₃ (1.75 mm) was 82.3N.

The radial force F ₃ when the outer diameter becomes D ₃ during the process of reducing the diameter from the reference outer diameter D ₁ to the outer diameter D ₂ is 133.6 N, which is expanded from the outer diameter D ₂ to the outer diameter D ₃ . Since the radial force F ₃ ′ at that time was 82.3 N, the difference between the radial force F ₃ and the radial force F ₃ ′ (F ₃ −F ₃ ′) was 51.3 N.

Next, in FIG. 1 (iv) has an inner diameter D ₄ on one side of the tubular medical device shrinkage device 31 prepares the outer shaft 22 of 1.80 mm, from the other side of the tubular medical device contraction device 31, the outer diameter D ₃ shows a state in which the self-expanding stent 11 held at (1.75 mm) is pushed into the lumen of the outer shaft 22 by being pushed by the solid push rod 32. In (iv), the temperature T ₄ was set to 25.0 ± 1.0 ° C. The solid extrusion rod 32 was made of SUS304 having an outer diameter of 1.72 mm, and the loading speed was 10 mm / second.

  A force gauge is attached to the end opposite to the end where the push rod 32 and the self-expandable stent 11 abut, and the maximum load (static friction load) when the self-expandable stent 11 starts to move by the push rod 32 is loaded. As measured. As the force gauge, “FGC-10” manufactured by Nidec Sympo Corporation was used. As a result of measurement, the loading load was 11.9N.

Next, (v) of FIG. 1 shows a state in which the self-expanding stent 11 is loaded in the lumen of the outer shaft 22. The outer diameter of the self-expanding stent 11 completely loaded in the lumen of the outer shaft 22 became equal to the inner diameter D ₄ (1.80 mm) of the outer shaft 22.

  Then, as shown in FIG. 5, the inner shaft 23 with the pusher member 24 is inserted into the lumen of the outer shaft 22 in which the self-expanding stent 11 is housed, and the distal end of the inner shaft 23 is inserted. The distal tip 25 was attached, the operation member 26 was attached to the proximal end of the inner shaft 23, and other members were appropriately attached to manufacture the tubular medical device transporting device 21.

(Example 2)
In Example 1, the temperature T ₂ in (ii) of FIG. 1 is 13.0 ± 1.0 ° C., the temperature T ₃ in (iii) of FIG. 1 is 13.0 ± 1.0 ° C., ( The self-expandable stent 11 is loaded into the lumen of the outer shaft 22 under the same conditions as in Example 1 except that the temperature T ₄ in iv) is changed to 13.0 ± 1.0 ° C. The tubular medical device conveying device 21 shown was manufactured.

The radial force F ₂ when the self-expanding stent 11 (reference outer diameter D ₁ was 6.0 mm) was reduced to the outer diameter D ₂ (1.45 mm) was 139.6 N.

In the course of reducing the diameter from the reference outer diameter D ₁ to the outer diameter D ₂ , the radial force F ₃ when the outer diameter became 1.75 mm (outer diameter D ₃ ) was 120.4 N.

When the self-expanding stent 11 was loosened from the outer diameter D ₂ (1.45 mm) to the target outer diameter D ₃ (1.75 mm) and expanded, the radial force F ₃ ′ was 67.7N.

The radial force F ₃ when the outer diameter becomes D ₃ during the process of reducing the diameter from the reference outer diameter D ₁ to the outer diameter D ₂ is 120.4 N, and the diameter increases from the outer diameter D ₂ to the outer diameter D ₃ . Since the radial force F ₃ ′ at that time was 67.7 N, the difference (F ₃ −F ₃ ′) between the radial force F ₃ and the radial force F ₃ ′ was 52.7 N.

  As a result of measuring the maximum load (static friction load) when the self-expanding stent 11 started to move by the push rod 32, the loading load was 9.4N.

(Example 3)
In Example 1, except that the temperature T ₃ in (iii) of FIG. 1 is changed to 13.0 ± 1.0 ° C., and the temperature T ₄ in (iv) of FIG. 1 is changed to 13.0 ± 1.0 ° C. The self-expandable stent 11 was loaded into the lumen of the outer shaft 22 under the same conditions as in Example 1 to manufacture the tubular medical device transport device 21 shown in FIG.

The radial force F ₂ when the self-expanding stent 11 (reference outer diameter D ₁ was 6.0 mm) was reduced to the outer diameter D ₂ (1.45 mm) was 152.3 N.

In the course of reducing the diameter from the reference outer diameter D ₁ to the outer diameter D ₂ , the radial force F ₃ when the outer diameter became 1.75 mm (outer diameter D ₃ ) was 134.2 N.

When the outer diameter of the self-expanding stent 11 was expanded from D ₂ (1.45 mm) to the target outer diameter D ₃ (1.75 mm), the radial force F ₃ ′ was 70.3N.

The radial force F ₃ is 134.2 N when the outer diameter becomes D ₃ while the diameter is reduced from the reference outer diameter D ₁ to the outer diameter D _2, and the diameter is increased from the outer diameter D ₂ to the outer diameter D ₃ . Since the radial force F ₃ ′ at that time was 70.3 N, the difference between the radial force F ₃ and the radial force F ₃ ′ (F ₃ −F ₃ ′) was 63.9 N.

  As a result of measuring the maximum load (static friction load) when the self-expanding stent 11 starts to move by the push rod 32, the loading load was 9.8N.

(Comparative Example 1)
In the first embodiment, instead of the procedure shown in FIG. 1, the tubular medical device contracting device 31 (“RFL225” manufactured by Blockwise) is used in the procedure shown in FIG. A stent 11 was loaded.

  FIG. 6 is a schematic diagram for explaining a conventional method for manufacturing a tubular medical device conveying apparatus.

  Hereinafter, the charging procedure will be described with reference to FIG.

FIG. 6 (i) shows a state in which the self-expanding stent 11 having the outer diameter D ₁ is disposed in the tubular medical device contracting device 31. In (i), the temperature T ₁ was 37.0 ± 1.0 ° C. The reference outer diameter D ₁ of the self-expanding stent 11 is 6.0 mm.

Next, (ii) of FIG. 6 shows a state in which the diameter of the self-expandable stent 11 is reduced by applying an external force using the tubular medical device contracting device 31. In (ii), the temperature T _{2 is set} to 25.0 ± 1.0 ° C., the speed is set to 0.1 mm / second, and the reference outer diameter D ₁ (6.0 mm) is reduced to 1.75 mm (target outer diameter D ₃ ). Diameter was made. When the diameter was reduced to the outer diameter D ₃ (1.75 mm), the radial force F ₃ was 132.8 N.

Next, in (iii) of FIG. 6, an outer shaft 22 having an inner diameter D ₄ of 1.80 mm is prepared on one side of the tubular medical device contracting device 31, and an outer diameter D _{3 is provided} from the other side of the tubular medical device contracting device 31. A state in which the self-expanding stent 11 held at (1.75 mm) is pushed by a solid push rod 32 and loaded into the lumen of the outer shaft 22 is shown. In (iii), the temperature T ₄ was set to 25.0 ± 1.0 ° C. The solid extrusion rod 32 was made of SUS304, had an outer diameter of 1.72 mm, and the loading speed was 10 mm / second.

  A force gauge is attached to the end opposite to the end where the push rod 32 and the self-expandable stent 11 abut, and the maximum load (static friction load) when the self-expandable stent 11 starts to move by the push rod 32 is loaded. As measured. As the force gauge, “FGC-10” manufactured by Nidec Sympo Corporation was used. As a result of measurement, the loading load was 23.4 N.

Next, (iv) of FIG. 6 shows a state in which the self-expanding stent 11 is loaded in the lumen of the outer shaft 22. The outer diameter of the self-expanding stent 11 completely loaded in the lumen of the outer shaft 22 became equal to the inner diameter D ₄ (1.80 mm) of the outer shaft 22.

  Then, as shown in FIG. 5, the inner shaft 23 with the pusher member 24 is inserted into the lumen of the outer shaft 22 in which the self-expanding stent 11 is housed, and the distal end of the inner shaft 23 is inserted. The distal tip 25 was attached, the operation member 26 was attached to the proximal end of the inner shaft 23, and other members were appropriately attached to manufacture the tubular medical device transporting device 21.

(Comparative Example 2)
In the comparative example 1, except that the temperature T ₂ in (ii) of FIG. 6 is changed to 13.0 ± 1.0 ° C. and the temperature T ₄ in (iii) of FIG. 6 is changed to 13.0 ± 1.0 ° C. The self-expanding stent 11 was loaded into the lumen of the outer shaft 22 under the same conditions as in Comparative Example 1 to manufacture the tubular medical device transporting device 21 shown in FIG.

The radial force F ₃ when the self-expanding stent 11 (reference outer diameter D ₁ was 6.0 mm) was reduced to the target outer diameter D ₃ (1.75 mm) was 119.2 N.

  As a result of measuring the maximum load (static friction load) when the self-expanding stent 11 started to move by the push rod 32, the loading load was 17.6N.

(Comparative Example 3)
In Example 1, the temperature T ₂ in (ii) of FIG. 1 is 37.0 ± 1.0 ° C., the temperature T ₃ in (iii) of FIG. 1 is 37.0 ± 1.0 ° C., ( The self-expanding stent 11 is loaded into the lumen of the outer shaft 22 under the same conditions as in Example 1 except that the temperature T ₄ in iv) is changed to 37.0 ± 1.0 ° C. The tubular medical device conveying device 21 shown was manufactured.

The radial force F ₂ when the self-expanding stent 11 (reference outer diameter D ₁ was 6.0 mm) was reduced to the outer diameter D ₂ (1.45 mm) was 168.7N.

In addition, the radial force F ₃ when the outer diameter was 1.75 mm (outer diameter D ₃ ) during the reduction from the reference outer diameter D ₁ to the outer diameter D ₂ was 149.1N.

When the outer diameter of the self-expanding stent 11 was expanded from D ₂ (1.45 mm) to the target outer diameter D ₃ (1.75 mm), the radial force F ₃ ′ was 99.0N.

The radial force F ₃ is 149.1 N when the outer diameter becomes D ₃ during the process of reducing the diameter from the reference outer diameter D ₁ to the outer diameter D _2, and is increased from the outer diameter D ₂ to the outer diameter D ₃ . Since the radial force F ₃ ′ at that time was 99.0 N, the difference (F ₃ −F ₃ ′) between the radial force F ₃ and the radial force F ₃ ′ was 50.1 N.

  As a result of measuring the maximum load (static friction load) when the self-expanding stent 11 starts to move by the push rod 32, the loading load was 15.2N.

  The above results are summarized in Table 2 below.

  It can be considered as follows from Table 2 below. Examples 1-3 are the examples which manufactured the tubular medical device conveyance apparatus on the conditions which satisfy the requirements prescribed | regulated by this invention, and Comparative Examples 1-3 are the conditions which do not satisfy one of the requirements prescribed | regulated by this invention. It is an example manufactured by.

As shown in Examples 1 to 3, after the temperature was appropriately controlled, a tubular medical device was manufactured through diameter reduction and diameter expansion under the conditions of D ₁ > D ₄ > D ₃ > D _2. As shown in Examples 1 and 2, it can be seen that the loading load can be reduced as compared with the case where the tubular medical device is manufactured without expanding the diameter as D ₁ > D ₄ > D ₃ . That is, in Examples 1 to 3, since the can greatly reduce the radial force F ₃ 'with respect to radial force F _3, the loading load is reduced.

In Comparative Example 3, since it is an example of producing a tubular medical device conveying device by the same procedure as that in Examples 1 to 3, which do not adequately control the temperature of each process, radial with respect to radial force F ₃ Force F ₃ 'has not been reduced sufficiently. As a result, the loading load became larger than the loading loads of Examples 1 to 3. That is, the temperature T _{2 at} which the step (2) is performed is lower than the R phase transformation start temperature (R _s ) as shown in Examples 1 and 3, or the R phase transformation is completed as shown in Example 2. As shown in Example 1, the temperature T _{3 at} which the temperature (R _f ) is set lower than the temperature (R _f ) or lower than the austenite phase transformation end temperature (A _f ), as shown in Example 1, or As shown, it can be seen that the loading load can be reduced by making the temperature lower than the R ′ phase transformation end temperature (R _f ′). In particular, Example 3, since the temperature is in the _{T 1> T 2> T 3} = T 4, in terms of a reduced cooling energy, sufficiently reduce the radial force F ₃ 'with respect to radial force F ₃ is made of.

  As described above, according to the manufacturing method of the present invention, even when the tubular medical device has a large radial force, it is possible to reduce the loading load when loading the tubular medical device transport apparatus. As a result, a medical device delivery system excellent in operability and passage in the body lumen can be easily manufactured.

DESCRIPTION OF SYMBOLS 11 Tubular medical device 11a Self-expandable stent 21 Tubular medical device transport device 22 Outer shaft 23 Inner shaft 24 Pusher member 25 Tip tip 26 Operation member 31 Tubular medical device contraction device 32 Extrusion rod 71 Annular section 72 Roughly corrugated component 73 Connecting portion 81 Center of inner radius of curvature 82 Center of outer radius of curvature 83 Inner radius of curvature 84 Outer radius of curvature 85 Strut width 86 Vertex width 87 Approximate waveform component apex L ₁ Reference length D ₁ Reference outer diameter D ₂ Outer diameter D ₃ Outer diameter D ₄ Inner diameter F ₂ Radial force F ₃ Radial force F ₃ 'Radial force R _s R phase transformation start temperature R _p R phase transformation peak temperature R _f R phase transformation end temperature M _s martensite phase transformation start temperature M _p martens Site phase transformation peak temperature M _f Martensite phase transformation end temperature R _s 'R' Phase transformation start temperature R _p′R ′ phase transformation peak temperature R _f′R ′ phase transformation end temperature A _s austenite phase transformation start temperature A _p austenite phase transformation peak temperature A _f austenite phase transformation end temperature T ₁ temperature T ₂ temperature T ₃ temperature T ₄ temperature

Claims (9)

A method for manufacturing a device for transporting a tubular medical device into a body,
The device includes a tube having an inner diameter D _4,
The manufacturing method of the tubular medical device conveying apparatus characterized by performing the following steps (1) to (4) in this order.
(1) A step of setting the tubular medical device having an outer diameter D ₁ to a temperature T ₁ at which an austenite phase exists.
(2) A pre-loading form forming step of applying an external force to the tubular medical device at a temperature T ₂ lower than the temperature T ₁ to reduce the outer diameter from D ₁ to D ₂ .
(3) Loading for expanding the outer diameter of the tubular medical device from D ₂ to D ₃ by weakening the external force at a temperature T ₃ lower than the austenite phase transformation end temperature A _{f of} the alloy constituting the tubular medical device. Form formation process.
(4) at the temperature T _4, the tubular medical device having an outer diameter D _3, the step of loading into the lumen of the inner diameter D _4.
However, in the above (1) to (4), a _{D 1> D 4> D 3} > D 2. The difference between the outer diameter D ₂ and the outer diameter D ₃ of the tubular medical device, The method according to claim 1 which is 0.01～0.50Mm. The temperature T ₁ is The process according to claim 1 or 2 at a temperature higher than the austenitic phase transformation start temperature A _s of the alloy. The temperature T ₂ is A process according to claim 1 wherein a temperature lower than the R-phase transformation starting temperature R _s of the alloy. The manufacturing method according to claim 1, wherein the temperature T ₂ is lower than the R phase transformation end temperature R _{f of the} alloy. The manufacturing method according to claim 1, wherein the temperature T ₃ is lower than the R ′ phase transformation end temperature R _f ′ of the alloy. Said temperature _{T 1, T 2, T 3} , T 4 The manufacturing method according to claim 1, satisfying a relation _{T 1> T 2> T 3} = T 4. In the step (2), a radial force F _{3 at} an outer diameter D ₃ in the middle of reducing the outer diameter of the tubular medical device from D ₁ to D ₂ ;
In the step (3), the radial force F ₃ ′ when the diameter is expanded and the outer diameter of the tubular medical device is set to D ₃ is:
The process according to claim 1, satisfying the relation of F _3> F ₃ '.   The manufacturing method according to claim 1, wherein the tubular medical device is a self-expanding stent.

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