Tubular medical implement delivery device and method of manufacturing a tubular medical implement delivery device

Abstract

A manufacturing method of a tubular medical tool delivery device having a tubular medical tool and a tubular tube, characterized by: a step S1 of housing at least a part of the tubular medical tool in a lumen of the tubular tube; and a step S2 of cooling the tubular medical tool to a temperature of Martensite transformation start temperature of the shape memory alloy or lower, and a tubular medical tool delivery device characterized in that a sliding load under 50°C warm water and a sliding load under 25°C warm water satisfy the following formula (1), (1) Increase rate of sliding load [%] = (Sliding load under 50°C warm water [N] - Sliding load under 25°C warm water [N]) / Sliding load under 25°C warm water [N] x 100 ≤ 30 [%].

Description

Technical Field

[0001] This invention relates to a tubular medical device delivery device for delivering tubular medical devices into the body, and a method for manufacturing the tubular medical device delivery device. Background Technology

[0002] In recent years, treatments using tubular medical device delivery systems have been employed as a method to treat various diseases caused by narrowing or blockage of the lumens of the digestive tract, such as the bile duct and pancreatic duct, and blood vessels such as the iliac artery. For example, small incisions are made in the wrist, elbow, or thigh, and the tubular medical device is inserted into an artery, reaching the lesion along the artery. At the lesion, the tubular medical device, housed within the tubular tube, expands to treat the affected area. This method is minimally invasive and less burdensome for the patient, making it an actively utilized treatment in the medical field.

[0003] However, existing tubular medical device delivery devices are prone to the phenomenon where rigid tubular medical devices become trapped inside relatively soft tubular bodies after sterilization and during storage. When the tubular medical device is deployed while trapped inside the tubular body, the frictional force between the tubular medical device and the tubular body increases during deployment. Therefore, there is a potential for damage to the tubular medical device delivery device itself, and poor deployment of the tubular medical device.

[0004] As a device that can prevent the aforementioned tubular medical device from sinking into the tubular body, a self-expanding stent delivery device with a reinforcing layer provided between the outer and inner layers of the outer sheath is known (Patent Document 1).

[0005] However, the self-expanding stent delivery device described in Patent Document 1 can suppress the self-expanding stent from sinking into the outer sheath by providing a reinforcing layer between the outer and inner layers of the outer sheath. Therefore, the diameter of the outer sheath increases accordingly with the reinforcement layer, making it difficult to achieve a smaller diameter for the self-expanding stent delivery device. For minimally invasive treatment, a smaller diameter delivery device is important; therefore, the development of a delivery device that can suppress the self-expanding stent from sinking into the outer sheath without using such a reinforcing layer and reduce the sliding load during deployment is desired.

[0006] Patent document 1: Japanese Patent Application Publication No. 11-313893. Summary of the Invention

[0007] The present invention was made in view of the above circumstances, and its object is to provide a new tubular medical device delivery device and a method for manufacturing the tubular medical device delivery device, which can suppress the insertion of tubular medical devices into tubular bodies and can suppress the sliding load when the tubular medical device is deployed to a low level.

[0008] The present invention, which solves the above-mentioned problems, is a method for manufacturing a tubular medical device delivery device having a tubular medical device and a tubular body. The tubular medical device is made of a material comprising a shape memory alloy, and the tubular body is made of a material comprising a thermoplastic resin. The method is characterized by comprising: step S1, housing at least a portion of the tubular medical device within the cavity of the tubular body; and step S2, cooling the tubular medical device to a temperature below the martensitic transformation start temperature of the shape memory alloy + 7°C. It can be considered that by cooling the tubular medical device to a temperature below the martensitic transformation start temperature of the shape memory alloy + 7°C, at least a portion of the shape memory alloy can undergo a martensitic transformation. Therefore, the tubular medical device becomes easily deformable even under low stress, thus mitigating the trapping of the tubular medical device into the tubular body and reducing the sliding load generated between the tubular medical device and the tubular body when the tubular medical device is deployed.

[0009] Preferably, in step S2 of the above-described method for manufacturing the tubular medical device delivery device, the tubular body is cooled to below the glass transition temperature of the thermoplastic resin.

[0010] Preferably, in the above-described method for manufacturing a tubular medical device delivery device, after step S1 in which at least a portion of the tubular medical device is housed within the lumen of the tubular body, and before step S2 in which the tubular medical device is cooled at a temperature below +7°C, a step S3 is performed to heat and sterilize the tubular medical device and the tubular body.

[0011] Preferably, at least a portion of the tubular medical device is housed in a state of contact with the inner wall of the tubular body.

[0012] Preferably, the shape memory alloy is a nickel-titanium alloy.

[0013] Preferably, the tubular medical device is a self-expanding stent.

[0014] The tubular medical device delivery device of the present invention, which solves the above-mentioned problems, is a tubular medical device delivery device in which a tubular medical device is housed within the lumen of a tubular tube body. The tubular medical device is made of a material containing a shape memory alloy, and the tubular tube body is made of a material containing a thermoplastic resin. The tubular medical device delivery device is characterized in that the sliding load between the tubular medical device and the tubular tube body measured at 50°C (hereinafter referred to as "sliding load at 50°C") and the sliding load between the tubular medical device and the tubular tube body measured at 25°C (hereinafter referred to as "sliding load at 25°C") satisfy the following equation (1). Therefore, even when the tubular medical device delivery device is used in a body at a temperature higher than room temperature, the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed can be suppressed to a low level.

[0015] (1) Increase rate of sliding load [%) = (Sliding load [N] at 50℃ water - Sliding load [N] at 25℃ water) / Sliding load [N] at 25℃ water × 100 ≤ 30 [%)

[0016] The increase rate of the sliding load in the aforementioned tubular medical device delivery device can be greater than 0%.

[0017] The tubular medical device delivery device of the present invention, and the tubular medical device delivery device manufactured by the manufacturing method of the tubular medical device delivery device of the present invention, can suppress the tubular medical device from sinking into the tubular body, and can suppress the sliding load generated between the tubular medical device and the tubular body when the tubular medical device is deployed to a low level. Attached Figure Description

[0018] Figure 1 This is a partial cross-sectional view showing an example of a tubular medical device delivery device according to an embodiment of the present invention.

[0019] Figure 2 This is a partial cross-sectional view showing an example of a tubular medical device delivery device according to an embodiment of the present invention.

[0020] Figure 3 This is a partial cross-sectional view showing the method for measuring the sliding load of a tubular medical device delivery device.

[0021] Figure 4 This is a bar graph showing the sliding load [N] in 37°C warm water for Comparative Examples 4-7, Comparative Examples 8-11, Comparative Examples 12-15, Examples 4-7, Examples 8-11, and Examples 12-15. Detailed Implementation

[0022] Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. The present invention is not limited to the examples shown in the drawings, and can be implemented by appropriate modifications within the scope of the above and following spirit. All such embodiments are included within the technical scope of the present invention. In the drawings, for convenience, shading, reference numerals, etc., may be omitted. In such cases, please refer to the specification and other accompanying drawings. Furthermore, the dimensions of various components in the drawings are primarily helpful in understanding the features of the present invention, and therefore may differ from the actual dimensions.

[0023] First, the manufacturing method of the tubular medical device delivery device of the present invention will be described. The manufacturing method of the tubular medical device delivery device of the present invention is a method for manufacturing a tubular medical device delivery device having a tubular medical device and a tubular body, wherein the tubular medical device is made of a material comprising a shape memory alloy, and the tubular body is made of a material comprising a thermoplastic resin. The manufacturing method of the tubular medical device delivery device is characterized by comprising: step S1, housing at least a portion of the tubular medical device within the lumen of the tubular body; and step S2, cooling the tubular medical device to a temperature below the martensitic transformation start temperature of the shape memory alloy + 7°C.

[0024] Tubular medical devices are made of materials containing shape memory alloys. Shape memory alloys are alloys that, after being deformed, will return to their original shape before deformation when heated to a temperature above a certain level (sometimes referred to as "radial force"). A tubular medical device may be composed of a portion of a shape memory alloy, or the entire tubular medical device may be composed of a shape memory alloy.

[0025] Tubular medical devices are tubular in shape, preferably cylindrical.

[0026] The size of tubular medical devices can be appropriately set according to the inner diameter and length of the blood vessels at the lesion site.

[0027] The types of tubular medical devices mentioned above are not particularly limited; for example, stents, covered stents, prosthetic valves, and balloons can be used. Stents are preferred as tubular medical devices.

[0028] The shape of the aforementioned support is not particularly limited. Examples include a spiral support made of a linear material containing shape memory alloy, a support made by laser cutting a tube made of a material containing shape memory alloy, a support made by laser welding a linear component made of a material containing shape memory alloy, and a support formed by weaving multiple linear components made of a material containing shape memory alloy.

[0029] Copper-aluminum-nickel alloys, copper-zinc-aluminum alloys, etc., can be used as the aforementioned shape memory alloys, but the shape memory alloys preferably include nickel-titanium alloys, and even more preferably nickel-titanium alloys. Using nickel-titanium alloys in shape memory alloys can improve strength, fatigue resistance, and corrosion resistance. Furthermore, when forming tubular medical devices, one type of shape memory alloy can be selected from the aforementioned shape memory alloys, or multiple types of shape memory alloys can be selected. For example, tubular medical devices can be formed by mixing materials of multiple types of shape memory alloys. Additionally, it is also possible to use one shape memory alloy to form a part of the tubular medical device and another shape memory alloy to form the remaining part of the tubular medical device.

[0030] The aforementioned tubular body is made of a material containing a thermoplastic resin. A thermoplastic resin is a resin that softens and becomes plastic when heated to a certain temperature or higher, and solidifies when cooled to a certain temperature or lower (glass transition temperature). Examples include polyethylene, polypropylene, polystyrene, vinyl chloride resin, methyl methacrylate resin, nylon, polyamide, semi-aromatic polyamide, fluoropolymer, polycarbonate, and polyester resin. To reduce the sliding load generated between the tubular medical device and the tubular body, the tubular body preferably contains an olefin resin or a fluoropolymer, and more preferably, polytetrafluoroethylene (PTFE), which has a known low coefficient of friction. Furthermore, when forming the tubular body, one type of thermoplastic resin can be selected from the aforementioned thermoplastic resins, or multiple types of thermoplastic resins can be used. For example, the tubular body can be formed by mixing a material containing multiple types of thermoplastic resins, or by forming an alloy (Japanese: アロイ) containing multiple types of thermoplastic resins. Alternatively, a tubular body can be formed using one thermoplastic resin for one portion and another thermoplastic resin for the remainder. Furthermore, a tubular body can also be formed by mixing a synthetic resin other than a thermoplastic resin with a thermoplastic resin.

[0031] The aforementioned tubular body is a tubular body, preferably cylindrical in shape. Furthermore, the tubular body can be a single layer or have multiple layers. In the case of multiple layers, each layer can be made of a different material, and each layer can have a different hardness. For example, from the viewpoint of improving the operability of the tubular medical device delivery device, the hardness of the outer layer of the tubular body can be lower than that of the inner layer. Additionally, from the viewpoint of improving the durability of the tubular medical device delivery device, the hardness of the outer layer of the tubular body can be higher than that of the inner layer. In the case of the aforementioned tubular body having multiple layers, for example, an alloy of nylon 12 and semi-aromatic polyamide is preferably used as the material constituting the outer layer, and PTFE is used as the material constituting the inner layer. With this structure, the sliding load generated between the tubular medical device and the tubular body can be reduced, thereby improving the durability of the tubular medical device delivery device.

[0032] The size of the aforementioned tubular tube can be appropriately set by taking into account the size of the aforementioned tubular medical device, the size of the lesion, and the size of the blood vessel to be passed through.

[0033] The aforementioned tubular body can be formed using known methods, such as extrusion molding.

[0034] Figure 1 and Figure 2 This is a partial cross-sectional view showing an example of a tubular medical device delivery device according to an embodiment of the present invention. Figure 1 This indicates a state in which tubular medical devices are contained within a tubular tube. Figure 2 It describes the appearance of a tubular medical device being pushed out of the lumen of a tubular body.

[0035] like Figure 1 As shown, the tubular medical device delivery device 100 according to an embodiment of the present invention includes a tubular medical device 110 and a tubular body 120. The tubular body 120 has a proximal portion serving as the anterior side of the operator and a distal portion serving as the side opposite to the anterior side of the operator, i.e., the patient side. The proximal portion is half of the anterior side of the operator, and the distal portion is half of the side opposite to the anterior side of the operator.

[0036] Preferably, the proximal end of the tubular body 120 has an operating part 130 for user operation, and preferably the shape of the operating part 130 is such that it is easy for the user to hold during operation.

[0037] Preferably, the tubular medical device delivery device 100 has an internal shaft 140 extending within the lumen of the tubular body 120, and a pushing member 141 for pushing out the tubular medical device 110 is located within the internal shaft 140. For example, the pushing member 141 can be configured to be positioned closer to the tubular medical device 110 than the tubular medical device 110. The pushing member 141 is hollow cylindrical in shape, and its outer diameter can be smaller than the inner diameter of the tubular body 120, and greater than the inner diameter of the tubular medical device 110 when it is housed within the tubular body 120. One end of the internal shaft 140 is configured to protrude from the distal end of the tubular body 120, thereby allowing the guide wire disposed within the lumen of the internal shaft 140 to advance ahead of the tubular medical device delivery device 100. In addition, for example, the other end of the internal shaft 140 can be configured to be mounted on the operating part 130, and have an insertion port for the guide wire therein.

[0038] like Figure 2 As shown, the tubular medical device delivery device 100 includes an operating section 130 and a pushing member 141, and can be configured such that the user operates the operating section 130 to push the tubular medical device 110 out of the tubular body 120. In this case, for example, the user moves the tubular body 120 proximally by operating the dial 131 mounted on the operating section 130. At this time, the tubular medical device 110 abuts against the pushing member 141, so that only the tubular body 120 moves proximally. Thus, it is possible to configure the tubular medical device 110 to unfold from the distal end of the tubular body 120 and be placed towards the lesion.

[0039] Alternatively, the aforementioned operating section 130 may be equipped with a dial 131, a button, an operating lever, etc., for adjusting the position of the internal shaft 140 and the pushing component 141 within the tubular body 120.

[0040] The above describes a tubular medical device delivery device 100 configured to place the tubular medical device 110 on the lesion by having an operating part 130 and a pushing part 141. However, the structure for delivering the tubular medical device 110 from the tubular body 120 and placing it on the lesion is not limited to the above structure, and known methods can be used.

[0041] The manufacturing method of the above-mentioned tubular medical device delivery device includes a step S1 of housing at least a portion of the tubular medical device within the lumen of the tubular body. In step S1, it is sufficient to housing at least a portion of the tubular medical device within the lumen of the tubular body, or the entire tubular medical device may be housing within the lumen of the tubular body.

[0042] Preferably, the tubular medical device is housed in the distal portion of the tubular body. The tubular medical device delivery device reaches the lesion site through the patient's blood vessel. Then, the user, by operating the proximal operating part, delivers the tubular medical device, which is located within the lumen of the tubular body, from the tubular body and positions the tubular medical device on the lesion site. This structure shortens the travel distance of the tubular medical device and reduces the time of slippage load between the tubular body and the tubular medical device. Therefore, the user of the tubular medical device delivery device can easily position the tubular medical device on the lesion site, and can prevent damage to the tubular medical device due to friction and improper deployment of the tubular medical device.

[0043] The manufacturing method of the aforementioned tubular medical device delivery device includes step S2, which involves cooling the tubular medical device to a temperature below +7°C the martensitic transformation initiation temperature of the shape memory alloy. Martensite refers to a crystalline structure that appears in a metal at low temperatures. It is a structure that is relatively easy to deform under weak external forces, but can recover its original shape if the external forces are removed. In contrast, a crystalline structure that appears at high temperatures is called austenite. Austenite has higher strength and exhibits superelasticity. The martensitic transformation initiation temperature generally refers to the temperature at which the martensitic phase begins to appear at low temperatures. It can be considered that the martensitic phase also begins to appear locally at a temperature of +7°C the martensitic transformation initiation temperature of the shape memory alloy.

[0044] Step S2, which cools the tubular medical device to a temperature below the martensitic transformation start temperature of the shape memory alloy +7°C, can be performed by immersing the tubular medical device in a chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C. In step S2, the tubular medical device is cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy +7°C. Preferably, the tubular medical device is immersed in the chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C for at least 1 minute, more preferably for at least 3 minutes, and even more preferably for at least 5 minutes. The upper limit for the time the tubular medical device is immersed in the chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C can be set to, for example, less than 24 hours, less than 12 hours, less than 8 hours, less than 4 hours, less than 3 hours, etc.

[0045] In step S2, where the tubular medical device is cooled, it is cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device plus 7°C. More preferably, the cooling temperature in step S2 is set to below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device plus 5°C, and even more preferably, it is set to below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device plus 3°C. Alternatively, the cooling temperature in step S2 may be set below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device.

[0046] In step S2, the tubular medical device is cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device +7°C. However, in this step S2, the tubular body is also preferably cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device +7°C. In this case, step S2, in which the tubular medical device and the tubular body are cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy +7°C, can be performed by placing the tubular body and the tubular medical device in a chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C. In step S2, the tubular medical device and the tubular body are cooled to a temperature below the martensitic transformation start temperature of the shape memory alloy +7°C. Preferably, the tubular medical device and tubular body are placed in a chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C for at least 1 minute, more preferably for at least 3 minutes, and even more preferably for at least 5 minutes. The upper limit for the time the tubular medical device and tubular body are placed in the chamber or liquid nitrogen at a temperature set below the martensitic transformation start temperature +7°C can be set to, for example, 24 hours or less, 12 hours or less, 8 hours or less, 4 hours or less, 3 hours or less. Regarding the cooling temperature in step S2, it is more preferably set to below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device +5°C, and even more preferably set to below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device +3°C. Alternatively, the cooling temperature in step S2 can be set below the martensitic transformation start temperature of the shape memory alloy contained in the tubular medical device.

[0047] The manufacturing method of the above-mentioned tubular medical device delivery device is less likely to cause the relatively rigid tubular medical device to sink into the relatively soft tubular body after manufacturing. Therefore, it is a manufacturing method to reduce the sliding load generated during deployment. So, it is preferable to perform steps S1 and S2 in sequence.

[0048] As described above, it can be assumed that the tubular medical device is cooled to a temperature 7°C below the martensitic transformation initiation temperature of the shape memory alloy, and at least a portion of the shape memory alloy is capable of undergoing a martensitic transformation. Consequently, the tubular medical device becomes easily deformable even under low stress, thus suppressing the manifestation of radial forces, mitigating the trapping of the tubular medical device into the tubular body, and minimizing the sliding load generated between the tubular medical device and the tubular body during deployment.

[0049] Preferably, in step S2 of the method for manufacturing the tubular medical device delivery apparatus, the tubular body is cooled to below the glass transition temperature of the thermoplastic resin. When the tubular body containing the tubular medical device is cooled to a temperature below the glass transition temperature of the thermoplastic resin contained within it, the thermoplastic resin solidifies and its elastic modulus decreases. This results in a state where the tubular body is not easily deformed even when external force is applied, thus mitigating the tendency of the tubular medical device to sink into the tubular body and reducing the sliding load generated between the tubular medical device and the tubular body when the tubular medical device is deployed.

[0050] Preferably, the manufacturing method of the above-described tubular medical device delivery device includes a sterilization step. Sterilization refers to the action or operation used to kill or remove all microorganisms capable of proliferation. As a sterilization method, any known method can be used, such as gas sterilization, electron beam sterilization, autoclave sterilization, dry heat sterilization, or radiation sterilization. Preferably, the sterilization step is performed after step S1, where at least a portion of the tubular medical device is housed within the lumen of the tubular body, and before step S2, where the tubular medical device is cooled to a temperature below the martensitic transformation initiation temperature of the shape memory alloy +7°C.

[0051] Preferably, in the above-described method for manufacturing a tubular medical device delivery device, after step S1 in which at least a portion of the tubular medical device is housed within the lumen of the tubular body, and before step S2 in which the tubular medical device is cooled at a temperature below +7°C, the tubular medical device and the tubular body are heated and sterilized.

[0052] In step S3 above, the tubular medical device and the tubular body are sterilized by heating. More specifically, the tubular medical device and the tubular body can be sterilized by methods such as EOG sterilization and electron beam sterilization, but it is preferable that the sterilization step includes a heating sterilization process. Preferably, steps S1, S3, and S2 are performed in this order. The tubular body softens by being heated to above the glass transition temperature, and the tubular medical device becomes more hyperelastic by being heated to above the austenitic phase transformation end temperature. Therefore, the trapping of the tubular medical device after heating sterilization becomes significant, and the sliding load generated between the tubular medical device and the tubular body increases. However, it can be considered that because the tubular medical device and the tubular body are cooled to a temperature below +7°C of the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device after heating sterilization, at least a portion of the shape memory alloy contained in the tubular medical device can undergo a martensitic phase transformation. Therefore, the tubular medical device becomes easily deformable even under low stress, thus suppressing the manifestation of radial forces. Consequently, it mitigates the indentation of the tubular medical device into the tubular body and reduces the sliding load generated between the tubular medical device and the tubular body during deployment. When the tubular body is cooled below its glass transition temperature, the increased hardness of the tubular body produces a synergistic effect, further mitigating the indentation of the tubular medical device into the tubular body and reducing the sliding load generated during deployment.

[0053] Regarding the temperature for heat sterilization in step S3 above, any temperature sufficient to kill the bacteria can be set appropriately. However, the lower limit of the heat sterilization temperature can be set to, for example, above 40°C, above 45°C, or above 50°C. The upper limit of the heat sterilization temperature can be set to, for example, below 130°C, below 120°C, or below 110°C.

[0054] Preferably, at least a portion of the tubular medical device is housed in a state of contact with the inner wall of the tubular body. The configuration where at least a portion of the tubular medical device contacts the inner wall of the tubular body means that this portion is configured such that no other components are disposed between the tubular medical device and the tubular body, allowing for easy reduction in the diameter of this portion.

[0055] Stents used as the aforementioned tubular medical devices can generally be classified based on their expansion mechanisms as: balloon-expandable stents, in which the stent is fitted onto the outer surface of a balloon and delivered to the lesion, where the stent is expanded by the balloon at the lesion; and self-expanding stents, in which a tubular tube is filled with a sheath component that controls the expansion of the stent and delivered to the lesion, where the sheath component is removed at the lesion to achieve self-expansion.

[0056] The manufacturing method of the tubular medical device delivery device is suitable for cases where the tubular medical device is a self-expanding stent. The self-expanding stent expands upon release from the tubular medical device delivery device. In the case of a self-expanding stent, the force attempting to expand the tubular medical device always acts on the tubular body, making it prone to sinking into the inner wall of the tubular body. However, it is considered that by implementing this manufacturing method, at least a portion of the shape memory alloy contained in the tubular medical device can initiate a martensitic phase transformation. It is considered that the force acting on the tubular body due to the martensitic phase transformation of at least a portion of the tubular medical device is suppressed. Therefore, the sinking of the tubular medical device into the tubular body can be mitigated, and the sliding load generated between the tubular medical device and the tubular body during expansion can be suppressed to a lower level.

[0057] The aforementioned self-expanding support can be manufactured, for example, by expanding the diameter of a cylindrical tube made of nickel-titanium alloy through laser cutting, heat treating it, forming the desired shape, and finally electrolytic grinding.

[0058] This concludes the description of the manufacturing method of the tubular medical device delivery device according to embodiments of the present invention. Next, the tubular medical device delivery device according to embodiments of the present invention will be described.

[0059] The tubular medical device delivery device of the present invention is a device for housing a tubular medical device within the lumen of a tubular tube body. The tubular medical device is made of a material containing a shape memory alloy, and the tubular tube body is made of a material containing a thermoplastic resin. The tubular medical device delivery device is characterized in that the sliding load between the tubular medical device and the tubular tube body measured at 50°C (hereinafter referred to as "sliding load at 50°C") and the sliding load between the tubular medical device and the tubular tube body measured at 25°C (hereinafter referred to as "sliding load at 25°C") satisfy the relationship of the following formula (1). Therefore, it is possible to mitigate the insertion of the tubular medical device into the tubular tube body and to suppress the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed.

[0060] (1) Increase rate of sliding load [%) = (Sliding load [N] at 50℃ water - Sliding load [N] at 25℃ water) / Sliding load [N] at 25℃ water × 100 ≤ 30 [%)

[0061] The following shows the results of manufacturing the tubular medical device delivery device according to the embodiments of the present invention and actually measuring the sliding load generated between the tubular medical device and the tubular body (Examples 1 to 3), and the results of measuring the sliding load generated between the tubular medical device and the tubular body of the tubular medical device manufactured by conventional methods (Comparative Examples 1 to 3).

[0062] The tubular medical device delivery devices of Examples 1 to 3 in Table 1 below were manufactured using the method described in the above-described method for manufacturing tubular medical device delivery devices. More specifically, the process includes, in sequence, step S1 (integrating the tubular medical device entirely within the lumen of the tubular body), step S3 (sterilizing the tubular medical device and the tubular body by heating), and step S2 (cooling the tubular medical device and the tubular body at a temperature 3°C above the martensitic transformation initiation temperature of the shape memory alloy), followed by storage at room temperature (25°C). Furthermore, the temperature 3°C above the martensitic transformation initiation temperature of the shape memory alloy is the glass transition temperature of the thermoplastic resin contained in the tubular body minus 67°C.

[0063] The tubular medical device delivery devices in Comparative Examples 1 to 3 in Table 1 below sequentially perform step S1, which involves the entire tubular medical device being housed within the lumen of a tubular body, and step S3, which involves the tubular medical device and the tubular body being sterilized by heating. In this comparative example, step S2, in which the tubular medical device and the tubular body are cooled, is not performed; instead, after step S3, which involves heat sterilization, the device is stored at room temperature (25°C).

[0064] Furthermore, the tubular medical device used in the manufacture of the tubular medical device delivery devices of Examples 1-3 and Comparative Examples 1-3 is a self-expanding stent formed by laser cutting of a tube made of a material containing a nickel-titanium alloy as a shape memory alloy. The diameter before being housed within the lumen of the tubular body is 10 mm, and the length of the tubular medical device is 100 mm. The tubular body has an outer layer made of nylon 12 and an inner layer made of PTFE. The inner diameter of the tubular body is 1.61 mm, and the outer diameter is 1.81 mm. The thickness of the PTFE inner layer is 15 μm. The shape of the tubular medical device, i.e., the self-expanding stent, is the same in the Examples and Comparative Examples. The martensitic phase transformation initiation temperature of the shape memory alloy contained in the tubular medical devices of Examples 1-3 and Comparative Examples 1-3 is -35°C. The glass transition temperature of the thermoplastic resin contained in the tubular bodies of Examples 1-3 and Comparative Examples 1-3 is 35°C. In step S3 of heat sterilization, EOG sterilization was performed for 30 hours at a temperature of 60°C and a humidity of 60%.

[0065] Table 1 below shows the results of the sliding load [N] generated between the tubular medical device and the tubular tube body measured at 25°C in the tubular medical device delivery devices of Examples 1-3 and Comparative Examples 1-3 (hereinafter sometimes referred to as "sliding load at 25°C"), and the results of the sliding load [N] generated between the tubular medical device and the tubular tube body measured at 50°C in the tubular medical device delivery devices of Examples 1-3 and Comparative Examples 1-3 (hereinafter sometimes referred to as "sliding load at 50°C"). Furthermore, the change in sliding load measured at 25°C and at 50°C is shown as [N] (sliding load at 50°C - sliding load at 25°C) and the increase rate of sliding load between the sliding load measured at 25°C and at 50°C is shown as [%) ((sliding load at 50°C - sliding load at 25°C) / sliding load at 25°C × 100).

[0066] Next, use Figure 3 The method for measuring sliding load is described. First, a sample 1 is prepared with the tubular medical device 10 housed within the cavity of the tubular body 20. One end of the tubular body 20 is fixed to the tensile load measuring device 40, and a support member 30 for supporting the tubular medical device 10 is placed within the cavity of the tubular body 20. The support member 30 is configured to have a hollow cylindrical pushing member 31 at one end, which pushes the tubular medical device 10 out of the cavity of the tubular body 20. The other end of the support member 30 is fixed to the tensile load measuring device 40 with the other end protruding from the tubular body 20. In this state, the SS curve is obtained by measuring the tensile load with the support member 30 fixed and the tubular body 20 being pulled at a speed of 50 mm / min. In this specification, the peak value of this SS curve is defined as the sliding load [N].

[0067] The sliding load at 25°C is the load measured when the tubular medical device and tubular tube are immersed in water that has been adjusted to 25°C.

[0068] The sliding load at 50°C is the load measured when the tubular medical device and tubular tube are immersed in water that has been adjusted to 50°C.

[0069] [Table 1]

[0070]

[0071] As shown in Table 1, the sliding load of the tubular medical device delivery devices of Examples 1-3 in 50°C warm water was 7.28-8.09 [N], while the sliding load of the tubular medical device delivery devices of Comparative Examples 1-3 in 50°C warm water was 7.97-9.75 [N]. This demonstrates that the tubular medical device delivery devices of Examples 1-3 tend to suppress the sliding load generated between the tubular medical device and the tubular body more effectively than the tubular medical device delivery devices of Comparative Examples 1-3.

[0072] Furthermore, the minimum increase rate of sliding load of the tubular medical device delivery device in Examples 1-3 was 23.0%, while the maximum increase rate of sliding load of the tubular medical device delivery device in Comparative Examples 1-3 was 55.1%. Thus, it is shown that the tubular medical device delivery devices of Examples 1-3, compared with the tubular medical device delivery devices of Comparative Examples 1-3, can suppress the increase rate of sliding load by up to 32.1%.

[0073] Furthermore, the increase rate of sliding load in the tubular medical device delivery device was 28.2% in Example 1, 27.2% in Example 2, and 23.0% in Example 3, compared to 46.2% in Comparative Example 1, 55.1% in Comparative Example 2, and 34.6% in Comparative Example 3. Thus, the tubular medical device delivery device according to the embodiments of the present invention is a tubular medical device delivery device in which a tubular medical device is housed within the lumen of a tubular tube body. The tubular medical device is made of a material containing a shape memory alloy, and the tubular tube body is made of a material containing a thermoplastic resin. The tubular medical device delivery device is characterized in that the sliding load at 50°C and the sliding load at 25°C satisfy the relationship of the following formula (1). Therefore, the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed can be suppressed to a low level.

[0074] (1) Increase rate of sliding load [%) = (Sliding load [N] at 50℃ water - Sliding load [N] at 25℃ water) / Sliding load [N] at 25℃ water × 100 ≤ 30 [%)

[0075] The increase rate of the aforementioned sliding load can be greater than 0%, or it can be 5% or more, 10% or more, etc. Furthermore, it is preferable that the increase rate of the sliding load is as small as possible.

[0076] The following shows the results of measuring the sliding load generated between the tubular medical device and the tubular body in a tubular medical device delivery device where neither the heating sterilization step S3 nor the cooling step S2 was performed, at 37°C in warm water, a condition closer to human body temperature (Comparative Examples 4-7); the results of measuring the sliding load generated between the tubular medical device and the tubular body in a tubular medical device delivery device manufactured by a conventional method, at 37°C in warm water, a condition closer to human body temperature (Comparative Examples 8-15); and the results of manufacturing a tubular medical device delivery device according to an embodiment of the present invention and measuring the sliding load generated between the tubular medical device and the tubular body in warm water at 37°C, a condition closer to human body temperature (Examples 4-15).

[0077] The tubular medical device delivery devices in Comparative Examples 4-7 of Table 2 below only perform step S1, which involves the entire tubular medical device being housed within the lumen of the tubular body. In Comparative Examples 4-7, step S2, which involves cooling the tubular medical device and the tubular body, and step S3, which involves heat sterilization, are not performed. After step S1, the devices are stored at room temperature (25°C).

[0078] The tubular medical device delivery devices in Comparative Examples 8-11 of Table 2 below sequentially perform step S1, which involves the entire tubular medical device being housed within the lumen of a tubular body, and step S3, which involves the heating and sterilization of the tubular medical device and the tubular body. In this comparative example, step S2, in which the tubular medical device and the tubular body are cooled, is not performed; instead, the device is stored at room temperature (25°C) after step S3, in which it is heated and sterilized.

[0079] The tubular medical device delivery devices in Comparative Examples 12-15 of Table 2 below sequentially perform the following steps: S1, the entire tubular medical device is housed within the lumen of the tubular body; S3, the tubular medical device and the tubular body are sterilized by heating; and S2, the tubular medical device and the tubular body are cooled at a temperature of +39°C, the martensitic transformation initiation temperature of the shape memory alloy. After the cooling step S2, they are stored at room temperature (25°C). Furthermore, the martensitic transformation initiation temperature of the shape memory alloy +39°C is the glass transition temperature of the thermoplastic resin contained in the tubular body -31°C.

[0080] The tubular medical device delivery device in Examples 4 to 7 of Table 2 below sequentially performs the following steps: S1, the entire tubular medical device is housed within the lumen of the tubular body; S3, the tubular medical device and the tubular body are sterilized by heating; and S2, the tubular medical device and the tubular body are cooled at a temperature 3°C above the martensitic transformation initiation temperature of the shape memory alloy. After the cooling step S2, the device is stored at room temperature (25°C). Furthermore, the temperature 3°C above the martensitic transformation initiation temperature of the shape memory alloy is the glass transition temperature of the thermoplastic resin contained in the tubular body minus 67°C.

[0081] The tubular medical device delivery device in Examples 8-11 of Table 2 below sequentially performs the following steps: S1, the tubular medical device is completely housed within the lumen of the tubular body; S3, the tubular medical device and the tubular body are sterilized by heating; S2, the tubular medical device and the tubular body are cooled at a temperature of -45°C, the martensitic transformation initiation temperature of the shape memory alloy; and after the cooling step S2, the device is stored at room temperature (25°C). Furthermore, the martensitic transformation initiation temperature of the shape memory alloy (-45°C) is the glass transition temperature of the thermoplastic resin contained in the tubular body (-115°C).

[0082] The tubular medical device delivery device in Examples 12-15 of Table 2 below sequentially performs the following steps: S1, the entire tubular medical device is housed within the lumen of the tubular body; S3, the tubular medical device and the tubular body are sterilized by heating; and S2, the tubular medical device and the tubular body are cooled at a temperature of -161°C, the martensitic transformation initiation temperature of the shape memory alloy. After the cooling step S2, the device is stored at room temperature (25°C). Furthermore, the martensitic transformation initiation temperature of the shape memory alloy, -161°C, is the glass transition temperature of the thermoplastic resin contained in the tubular body, -231°C.

[0083] Furthermore, the tubular medical devices used in the manufacture of the tubular medical device delivery devices in Comparative Examples 4-7, Comparative Examples 8-15, and Examples 4-15 are self-expanding stents formed by laser cutting of a tube made of a material containing a nickel-titanium alloy as a shape memory alloy. The diameter of the tubular medical device before it is housed in the lumen of the tubular body is 10 mm, and the length of the tubular medical device is 100 mm. The tubular body has an outer layer made of nylon 12 and an inner layer made of PTFE. The inner diameter of the tubular body is 1.61 mm, and the outer diameter is 1.81 mm. The thickness of the PTFE inner layer is 15 μm. The shape of the tubular medical device, i.e., the self-expanding stent, is the same in the Examples and Comparative Examples. The martensitic phase transformation initiation temperature of the shape memory alloy contained in the tubular medical device is -35°C. The glass transition temperature of the thermoplastic resin contained in the tubular body is 35°C. In step S3 of heat sterilization, EOG sterilization was performed for 30 hours at a temperature of 60°C and a humidity of 60%.

[0084] Table 2 shows the results of the sliding load [N] generated between the tubular medical device and the tubular tube body in the tubular medical device delivery devices of Comparative Examples 4-7, Comparative Examples 8-15, and Examples 4-15, measured at 37°C in warm water (hereinafter sometimes referred to as "sliding load at 37°C in warm water"), and the average values ​​of the sliding loads at 37°C in Comparative Examples 4-7, Comparative Examples 8-11, Comparative Examples 12-15, Examples 4-7, Examples 8-11, and Examples 12-15. Additionally, in Figure 4 The sliding load [N] in 37°C warm water is shown in bar graphs for Comparative Examples 4-7, Comparative Examples 8-11, Comparative Examples 12-15, Examples 4-7, Examples 8-11, and Examples 12-15.

[0085] [Table 2]

[0086]

[0087] As shown in Table 2 and Figure 4 As shown in Comparative Examples 4-7, the average sliding load of the tubular medical device delivery device under 37°C warm water was 5.91 N when heat sterilization step S3 was performed but cooling step S2 was not performed. As shown in Comparative Examples 8-11, when heat sterilization step S3 was performed but cooling step S2 was not performed, the average sliding load of the tubular medical device delivery device under 37°C warm water increased to 6.97 N. Furthermore, as shown in Comparative Examples 12-15, the average sliding load under 37°C warm water remained unchanged at 6.97 N for steps where only cooling to a temperature of +39°C (the martensitic transformation start temperature of the shape memory alloy) and -31°C (the glass transition temperature of the thermoplastic resin).

[0088] However, the average sliding load under 37°C water was 6.25 N when the step of cooling to a temperature of 3°C + 3°C and a glass transition temperature of -67°C was performed. This is close to the average value (5.91 N) of the sliding load under 37°C water in Comparative Examples 4-7, where heat sterilization was not performed. Thus, if the cooling temperature in step S2 is set to approximately 3°C + 3°C, the sliding load under 37°C water can be reduced to a value close to the average value of the sliding load under 37°C water before heat sterilization.

[0089] Furthermore, in Examples 8 to 11, where the cooling step was performed at a temperature of -45°C (martensitic transformation start temperature) and -115°C (glass transition temperature), the average sliding load under 37°C water was 5.73 N. In Examples 12 to 15, where the cooling step was performed at a temperature of -161°C (martensitic transformation start temperature) and -231°C (glass transition temperature), the average sliding load under 37°C water was 5.39 N. Thus, by setting the cooling temperature in step S2 to approximately -45°C (martensitic transformation start temperature), the sliding load under 37°C water can be suppressed to a lower level than before heat sterilization.

[0090] Furthermore, through Examples 4-7, 8-11, and 12-15, it was also demonstrated that the lower the cooling temperature during the cooling step, the greater the reduction in the sliding load generated between the tubular body and the tubular medical device. In particular, when cooled to a temperature of -161°C, the martensitic transformation initiation temperature of the shape memory alloy, which is also the glass transition temperature of the thermoplastic resin contained in the tubular body, at -231°C (Examples 12-15), most of the shape memory alloy can transform into the martensitic phase, thus making it easier to reduce the sliding load.

[0091] As described above, it is shown that by performing a cooling step below the martensitic phase transformation initiation temperature +7°C after the heat sterilization step, the sliding load between the tubular medical device and the tubular body at 37°C is reduced (Examples 4-7, Examples 8-11, Examples 12-15).

[0092] Furthermore, a temperature of 37°C is close to human body temperature. Based on the above results, it is shown that the tubular medical device delivery device according to the embodiments of the present invention, after being inserted into a blood vessel in the human body, can suppress the sliding load to a lower level than tubular medical device delivery devices manufactured by conventional methods (Comparative Examples 8-11).

[0093] Furthermore, the average sliding load of Examples 8-11, in which a cooling step was performed after heat sterilization, and the average sliding load of Examples 12-15, in which a cooling step was performed after heat sterilization, were lower than the average sliding load of Comparative Examples 4-7, in which a heat sterilization step was not performed. Based on this, it can be considered that even when a sterilization method other than heat sterilization is used, the sliding load can be reduced by performing a cooling step S2 after step 1.

[0094] As described above, the tubular medical device delivery device of the present invention can suppress the sliding load generated between the tubular medical device and the tubular body when the tubular medical device is deployed, even when used in the body at a temperature higher than room temperature.

[0095] As described above, the tubular medical device delivery device and the manufacturing method of the tubular medical device delivery device of the present invention can suppress the tubular medical device from sinking into the tubular body and can suppress the sliding load when the tubular medical device is deployed to a low level.

[0096] This application claims the benefit of priority based on Japanese Patent Application No. 2020-131676, filed on August 3, 2020. For reference, the entire contents of the description of Japanese Patent Application No. 2020-131676, filed on August 3, 2020, are incorporated herein by reference.

[0097] Explanation of reference numerals in the attached figures

[0098] 1...sample; 10...tubular medical device; 20...tubular body; 30...support component; 31...push component; 40...device for measuring tensile load; 100...tubular medical device delivery device; 110...tubular medical device; 120...tubular body; 130...operating part; 131...dial; 140...internal shaft; 141...push component.

Claims

1. A method for manufacturing a tubular medical device delivery device, comprising a tubular medical device and a tubular body, wherein the tubular medical device delivery device has a structure for ejecting the tubular medical device from the lumen of the tubular body, the tubular medical device being made of a material comprising a shape memory alloy, and the tubular body being made of a material comprising a thermoplastic resin. The method for manufacturing the tubular medical device delivery device is characterized by having: Step S1, at least a portion of the tubular medical device is housed within the lumen of the tubular body; and Step S2: Cool the tubular medical device to a temperature below the martensitic transformation start temperature of the shape memory alloy +7°C. Step S2 is performed after step S1.

2. The method for manufacturing the tubular medical device delivery device according to claim 1, characterized in that, In step S2, the tubular body is cooled to below the glass transition temperature of the thermoplastic resin.

3. The method for manufacturing the tubular medical device delivery device according to claim 1 or 2, characterized in that, After step S1, in which at least a portion of the tubular medical device is housed within the lumen of the tubular body, Furthermore, prior to step S2, when the tubular medical device is cooled at a temperature below +7°C of the martensitic phase transformation initiation temperature of the shape memory alloy, Step S3 includes heating and sterilizing the tubular medical device and the tubular tube body.

4. The method for manufacturing the tubular medical device delivery device according to claim 1 or 2, characterized in that, At least a portion of the tubular medical device is housed in contact with the inner wall of the tubular body.

5. The method for manufacturing the tubular medical device delivery device according to claim 1 or 2, characterized in that, The shape memory alloy is a nickel-titanium alloy.

6. The method for manufacturing the tubular medical device delivery device according to claim 1 or 2, characterized in that, The tubular medical device is a self-expanding stent.

7. A tubular medical device delivery device, comprising a tubular medical device housed within the lumen of a tubular body, wherein the tubular medical device is made of a material comprising a shape memory alloy, and the tubular body is made of a material comprising a thermoplastic resin, and the tubular medical device delivery device is manufactured by the manufacturing method of the tubular medical device delivery device according to any one of claims 1 to 6. The tubular medical device delivery device is characterized in that... The sliding load between the tubular medical device and the tubular body, measured at 50°C, and the sliding load between the tubular medical device and the tubular body, measured at 25°C, satisfy the following relationship (1). (1) The increase rate of sliding load [%] = (sliding load [N] at 50℃ warm water - sliding load [N] at 25℃ warm water) / sliding load [N] at 25℃ warm water × 100 ≤ 30 [%].

8. The tubular medical device delivery device according to claim 7, characterized in that, The rate of increase of the sliding load is greater than 0%.

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