Tubular medical device delivery device and method for manufacturing the same

Abstract

Provided are: a method for manufacturing a tubular medical instrument transfer device having a tubular medical instrument and a tubular tube body, the method being characterized by comprising a step S1 in which at least a part of the tubular medical instrument is accommodated in a tubular lumen of the tubular tube body, and a step S2 in which the tubular medical instrument is cooled to a temperature no higher than the martensite phase transformation start temperature + 7˚C of the shape-memory alloy; and a tubular medical instrument transfer device characterized in that a sliding load under 50˚C warm water and a sliding load under 25˚C warm water satisfy the following relational expression (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] The present invention relates to a tubular medical device delivery device for delivering a tubular medical device into the body, and to a method for manufacturing the tubular medical device delivery device. [Background technology]

[0002] Recent treatments using tubular medical device delivery devices are used as one of the treatment methods for various diseases caused by narrowing or occlusion of internal lumens such as the digestive tract, such as the bile duct and pancreatic duct, and blood vessels, such as the iliac artery. For example, a small hole is made in the wrist, elbow, thigh, etc., and the tubular medical device delivery device is inserted into the artery and guided through the artery to reach the affected area. The affected area is treated by expanding the tubular medical device housed in the tubular tube at the affected area. This method is one of the treatment methods actively used in the medical field because it is minimally invasive and places little burden on the patient.

[0003] However, conventional tubular medical device delivery devices are prone to a phenomenon in which a relatively rigid tubular medical device is embedded in a relatively flexible tubular tube body after sterilization or during storage. If the tubular medical device is deployed in a state in which the tubular medical device is embedded in the tubular tube body, the frictional force generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed increases. This can lead to problems such as damage to the tubular medical device delivery device itself and poor deployment of the tubular medical device.

[0004] As a device capable of preventing the above-mentioned tubular medical device from becoming embedded in the tubular tube body, a self-expanding stent delivery device that has a reinforcing layer provided between the outer layer and the inner layer of the outer sheath is known (Patent Document 1).

[0005] However, the self-expanding stent delivery device described in Patent Document 1 is capable of preventing the self-expanding stent from being embedded in the outer sheath by providing a reinforcing layer between the outer layer and the inner layer of the outer sheath. For this reason, the diameter of the outer sheath is increased by the amount of the reinforcing layer provided, making it difficult to reduce the diameter of the self-expanding stent delivery device. Since reducing the diameter of the delivery device is important for minimally invasive treatment, there has been a demand for the development of a delivery device that can prevent the self-expanding stent from being embedded in the outer sheath and reduce the sliding load during deployment without using such a reinforcing layer. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 11-313893 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention has been made in consideration of the above-mentioned circumstances, and its object is to provide a new tubular medical device delivery device and a method for manufacturing a tubular medical device delivery device that can prevent a tubular medical device from sinking into a tubular tube body and can keep the sliding load low when the tubular medical device is deployed. [Means for solving the problem]

[0008] The manufacturing method of the tubular medical device delivery device of the present invention, which has been able to solve the above problems, is a manufacturing method of a tubular medical device delivery device having a tubular medical device made of a material containing a shape memory alloy and a tubular tube body made of a material containing a thermoplastic resin, characterized by comprising a step S1 in which at least a part of the tubular medical device is stored in the lumen of the tubular tube body, and a step S2 in which the tubular medical device is cooled to a temperature of the martensitic phase transformation start temperature of the shape memory alloy + 7 ° C or less. It is considered that at least a part of the shape memory alloy can be transformed into a martensitic phase by cooling the tubular medical device to a temperature of the martensitic phase transformation start temperature of the shape memory alloy + 7 ° C or less. As a result, the tubular medical device is in a state where it can be easily deformed even with low stress, so that it is possible to reduce the embedding of the tubular medical device into the tubular tube body, and it is possible to reduce the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed.

[0009] In step S2 of the method for producing the tubular medical device delivery device, the tubular tube body is preferably cooled to a temperature below the glass transition temperature of the thermoplastic resin.

[0010] In the manufacturing method of the above-mentioned tubular medical device delivery device, it is preferable to have a step S3 in which the tubular medical device and the tubular tube body are heat sterilized after step S1 in which at least a portion of the tubular medical device is stored within the lumen of the tubular tube body and before step S2 in which the tubular medical device is cooled to a temperature not higher than the martensitic phase transformation start temperature of the shape memory alloy +7°C.

[0011] It is preferable that at least a portion of the tubular medical device is housed in contact with the inner wall of the tubular tube body.

[0012] The shape memory alloy is preferably 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 has been able to solve the above problems, is a tubular medical device delivery device in which a tubular medical device made of a material containing a shape memory alloy is housed in the lumen of a tubular tube body made of a material containing a thermoplastic resin, and is characterized in that the sliding load between the tubular medical device and the tubular tube body measured in hot water at 50°C (hereinafter referred to as "sliding load in hot water at 50°C") and the sliding load between the tubular medical device and the tubular tube body measured in hot water at 25°C (hereinafter referred to as "sliding load in hot water at 25°C") satisfy the relationship of the following formula (1). As a result, even when the tubular medical device delivery device is used inside the 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 kept low. (1) Sliding load increase rate [%] = (sliding load in 50°C water [N] - sliding load in 25°C water [N]) / sliding load in 25°C water [N] × 100 ≦ 30 [%]

[0015] The rate of increase in the sliding load in the tubular medical device delivery device may be greater than 0%. Effect of the Invention

[0016] The tubular medical device delivery device of the present invention, and a tubular medical device delivery device manufactured by the manufacturing method of the tubular medical device delivery device of the present invention, can prevent the tubular medical device from sinking into the tubular tube body, and can keep low the sliding load that occurs between the tubular medical device and the tubular tube body when the tubular medical device is deployed. [Brief description of the drawings]

[0017] [Figure 1] 1 is a partial cross-sectional view showing an example of a tubular medical device delivery device according to an embodiment of the present invention. [Diagram 2] 1 is a partial cross-sectional view showing an example of a tubular medical device delivery device according to an embodiment of the present invention. [Diagram 3] FIG. 11 is a partial cross-sectional view showing a method for measuring the sliding load in a tubular medical device transport device. [Figure 4] 1 is a bar graph showing the sliding load [N] in 37° C. warm water for Comparative Examples 4 to 7, Comparative Examples 8 to 11, Comparative Examples 12 to 15, Examples 4 to 7, Examples 8 to 11, and Examples 12 to 15. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The present invention will be described in detail below with reference to the drawings, but the present invention is not limited to the illustrated examples, and can be modified appropriately within the scope of the above and below, and all of these are included in the technical scope of the present invention. In each drawing, hatching and symbols may be omitted for convenience, but in such cases, the specification and other drawings should be referred to. In addition, the dimensions of various parts in the drawings may differ from the actual dimensions, since priority is given to helping understand the features of the present invention.

[0019] 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 manufacturing method of the tubular medical device delivery device having a tubular medical device made of a material containing a shape memory alloy and a tubular tube body made of a material containing a thermoplastic resin, and is characterized by comprising a step S1 in which at least a part of the tubular medical device is housed in the lumen of the tubular tube body, and a step S2 in which the tubular medical device is cooled to a temperature equal to or lower than the martensitic phase transformation start temperature of the shape memory alloy + 7°C.

[0020] The tubular medical device is made of a material that contains a shape memory alloy. A shape memory alloy is an alloy that, when it is deformed and then heated to a certain temperature or higher, exerts a force (hereinafter sometimes referred to as "radial force") that tries to return it to its original shape before the deformation. The tubular medical device may be made partially of a shape memory alloy, or the entire tubular medical device may be made of a shape memory alloy.

[0021] The tubular medical device is a tubular body, and its shape is preferably cylindrical.

[0022] The size of the tubular medical device may be appropriately determined according to the inner diameter and length of the blood vessel at the affected area.

[0023] The type of the tubular medical device is not particularly limited, and examples thereof include stents, stent grafts, prosthetic valves, balloons, etc. As the tubular medical device, a stent can be preferably used.

[0024] The shape of the above-mentioned stent is not particularly limited, and examples include a coil-shaped stent made of a single linear material containing a shape memory alloy, a stent processed by cutting out a tube made of a material containing a shape memory alloy with a laser, a stent assembled by welding linear members made of a material containing a shape memory alloy with a laser, and a stent formed by weaving multiple linear members made of a material containing a shape memory alloy.

[0025] As the shape memory alloy, a copper-aluminum-nickel alloy, a copper-zinc-aluminum alloy, etc. can be used, but the shape memory alloy preferably contains a nickel-titanium alloy, and more preferably is a nickel-titanium alloy. Among the shape memory alloys, the use of a nickel-titanium alloy can increase strength, fatigue resistance, and corrosion resistance. When forming a tubular medical device, one of the shape memory alloys may be selected and used, or multiple types of shape memory alloys may be selected and used. For example, a tubular medical device can be formed from a material in which multiple types of shape memory alloys are mixed. In addition, a configuration in which a part of the tubular medical device is formed from one shape memory alloy, and the remaining part of the tubular medical device is formed from another shape memory alloy can also be used.

[0026] The tubular tube body is made of a material containing a thermoplastic resin. A thermoplastic resin is a resin that has the property of softening and exhibiting plasticity when heated above a certain temperature, and solidifying when cooled below a certain temperature (glass transition temperature). Examples of such a resin include polyethylene, polypropylene, polystyrene, polyvinyl chloride resin, methyl methacrylate resin, nylon, polyamide, semi-aromatic polyamide, fluororesin, polycarbonate, and polyester resin. In order to reduce the sliding load generated between the tubular medical device and the tubular tube body, the tubular tube body preferably contains an olefin resin or a fluororesin, and in particular, it is preferable that the tubular tube body contains polytetrafluoroethylene (PTFE), which is known to have a low friction coefficient. When forming the tubular tube body, one type of thermoplastic resin may be selected and used from the above-mentioned thermoplastic resins, or multiple types of thermoplastic resins may be selected and used. For example, the tubular tube body can be formed from a material in which multiple types of thermoplastic resins are mixed, and the tubular tube body can also be formed from an alloy in which multiple types of thermoplastic resins are mixed. In addition, a configuration in which a part of the tubular tube body is formed from one thermoplastic resin and the remaining part of the tubular tube body is formed from another thermoplastic resin may be used. The tubular tube body may be made of a material that is a mixture of a thermoplastic resin and a synthetic resin other than the thermoplastic resin.

[0027] The tubular tube body is preferably a tubular body having a cylindrical shape. The tubular tube body may have one layer or multiple layers. When the tubular tube body has multiple layers, each layer may be made of a different material and may 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 may be lower than the hardness of the inner layer of the tubular tube body. Also, from the viewpoint of improving the durability of the tubular medical device delivery device, the hardness of the outer layer may be higher than the hardness of the inner layer of the tubular tube body. When the tubular tube body has multiple layers, for example, it is preferable to use an alloy of nylon 12 and semi-aromatic polyamide as the material constituting the outer layer, and PTFE as the material constituting the inner layer. By adopting such a configuration, it is possible to reduce the sliding load generated between the tubular medical device and the tubular tube body, and to increase the durability of the tubular medical device delivery device.

[0028] The size of the tubular tube body may be appropriately determined taking into consideration the size of the tubular medical device, the size of the lesion, the size of the blood vessel through which it passes, and the like.

[0029] The tubular tube body may be formed by a known method, for example, extrusion molding.

[0030] 1 and 2 are partial cross-sectional views showing an example of a tubular medical device delivery device according to an embodiment of the present invention. Fig. 1 shows a state in which a tubular medical device is stored in a tubular tube body. Fig. 2 shows a state in which the tubular medical device is pushed out from the lumen of the tubular tube body.

[0031] 1, a tubular medical device delivery device 100 according to an embodiment of the present invention comprises a tubular medical device 110 and a tubular tube body 120. The tubular tube body 120 has a proximal portion on the operator's side and a distal portion on the opposite side of the operator's side, i.e., the patient side. The half on the operator's side is the proximal portion, and the half on the opposite side of the operator's side is the distal portion.

[0032] The proximal end of the tubular tube body 120 preferably has an operating section 130 for operation by the user, and the shape of the operating section 130 is preferably such that it is easy for the user to grip when operating it.

[0033] The tubular medical device delivery device 100 has an inner shaft 140 extending into the lumen of the tubular tube body 120, and the inner shaft 140 preferably has a pusher member 141 for pushing out the tubular medical device 110. For example, the pusher member 141 can be configured to be disposed proximal to the tubular medical device 110. The pusher member 141 has a hollow cylindrical shape, and the outer diameter can be smaller than the inner diameter of the tubular tube body 120 and equal to or larger than the inner diameter of the tubular medical device 110 in a state where it is housed in the tubular tube body 120. By configuring one end of the inner shaft 140 to be exposed from the distal end of the tubular tube body 120, it becomes possible to advance a guide wire disposed in the lumen of the inner shaft 140 ahead of the tubular medical device delivery device 100. Also, for example, the other end of the inner shaft 140 can be attached to the operating unit 130, and configured to have a port for inserting the guide wire.

[0034] As shown in Fig. 2, the tubular medical device delivery device 100 has an operation unit 130 and a pusher member 141, and can be configured such that the operation unit 130 is operated by a user to push out the tubular medical device 110 from within the tubular tube body 120. In this case, for example, the user operates a thumb wheel 131 attached to the operation unit 130 to move the tubular tube body 120 toward the proximal side. At this time, the tubular medical device 110 hits the pusher member 141, and only the tubular tube body 120 moves toward the proximal side. As a result, the tubular medical device 110 is deployed from the distal end of the tubular tube body 120 and placed at the affected area.

[0035] The operating unit 130 may be provided with a thumb wheel 131 , a button, a lever, or the like for adjusting the position of the inner shaft 140 and the pusher member 141 within the tubular tube body 120 .

[0036] In the above, a configuration has been described in which the tubular medical device transport device 100 has an operation unit 130 and a pusher member 141, thereby placing the tubular medical device 110 at the lesion. However, the configuration for extending the tubular medical device 110 from the tubular tube body 120 and placing it at the lesion is not limited to the above configuration, and any known method can be used.

[0037] The method for manufacturing the tubular medical device delivery device includes step S1 in which at least a portion of the tubular medical device is housed within the lumen of the tubular tube body. In step S1, it is sufficient that at least a portion of the tubular medical device is housed within the lumen of the tubular tube body, and the entire tubular medical device may be housed within the lumen of the tubular tube body.

[0038] The tubular medical device is preferably stored in the distal portion of the tubular tube body. The tubular medical device delivery device passes through the patient's blood vessels and reaches the lesion. The user then operates the operation unit at hand to take out the tubular medical device present in the lumen of the tubular tube body from the tubular tube body, and the tubular medical device is placed at the lesion. With the above configuration, the travel distance of the tubular medical device can be shortened, and the time during which a sliding load occurs between the tubular tube body and the tubular medical device can be shortened, making it easier for the user of the tubular medical device delivery device to place the tubular medical device at the lesion, and preventing damage to the tubular medical device due to friction and poor deployment of the tubular medical device.

[0039] The manufacturing method of the tubular medical device delivery device includes step S2 in which the tubular medical device is cooled to a temperature equal to or lower than the martensite phase transformation start temperature of the shape memory alloy +7°C. The martensite phase refers to a crystal structure that appears in metals at low temperatures, and is relatively easily deformed by external forces, but can return to its original shape when the external forces are removed. In contrast, a crystal structure that appears at high temperatures is called an austenite phase. The austenite phase has relatively high strength and exhibits a superelastic effect. The martensite phase transformation start temperature generally refers to the temperature at which the martensite phase exhibited at low temperatures begins to appear, but it is considered that the martensite phase begins to appear partially even at a temperature equal to the martensite phase transformation start temperature of the shape memory alloy +7°C.

[0040] Step S2, in which the tubular medical device is cooled to a temperature of the martensite phase transformation start temperature of the shape memory alloy +7°C or less, can be performed by placing the tubular medical device in a chamber set to a temperature of the martensite phase transformation start temperature of the shape memory alloy +7°C or less or in liquid nitrogen. In step S2, the tubular medical device may be cooled to a temperature of the martensite phase transformation start temperature of the shape memory alloy +7°C or less. The tubular medical device is preferably placed in the chamber set to a temperature of the martensite phase transformation start temperature of the shape memory alloy +7°C or less for 1 minute or more, more preferably for 3 minutes or more, and even more preferably for 5 minutes or more. The upper limit of the time for which the tubular medical device is placed in the chamber set to a temperature of the martensite phase transformation start temperature of the shape memory alloy +7°C or less or in liquid nitrogen can be, for example, 24 hours or less, 12 hours or less, 8 hours or less, 4 hours or less, 3 hours or less, etc.

[0041] In step S2, in which the tubular medical device is cooled, the tubular medical device is cooled to a temperature of the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 7°C or less. The cooling temperature in step S2 is more preferably set to a temperature of the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 5°C or less, and further preferably set to a temperature of the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 3°C or less. The cooling temperature in step S2 may be set to a temperature of the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device or less.

[0042] In step S2, the tubular medical device may be cooled to a temperature equal to or lower than the martensite phase transformation start temperature of the shape memory alloy contained in the tubular medical device +7°C, and it is preferable that the tubular tube body is also cooled to a temperature equal to or lower than the martensite phase transformation start temperature of the shape memory alloy contained in the tubular medical device +7°C in step S2. In this case, step S2 in which the tubular medical device and the tubular tube body are cooled to a temperature equal to or lower than the martensite phase transformation start temperature of the shape memory alloy +7°C can be performed by placing the tubular tube body and the tubular medical device in a chamber set to a temperature equal to or lower than the martensite phase transformation start temperature +7°C or liquid nitrogen. In step S2, the tubular medical device and the tubular tube body may be cooled to a temperature equal to or lower than the martensite phase transformation start temperature of the shape memory alloy +7°C. It is preferable to place the tubular medical device and the tubular tube body in a chamber set to a temperature equal to or lower than the martensite phase transformation start temperature +7°C or liquid nitrogen for 1 minute or more, more preferably for 3 minutes or more, and even more preferably for 5 minutes or more. The upper limit of the time for which the tubular medical device and the tubular tube body are placed in a cabinet or liquid nitrogen set at a temperature of martensitic phase transformation start temperature + 7°C or less can be, for example, 24 hours or less, 12 hours or less, 8 hours or less, 4 hours or less, 3 hours or less, etc. The cooling temperature in this step S2 is more preferably set to the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 5°C or less, and further preferably set to the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 3°C or less. The cooling temperature in step S2 may be set to the martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical device or less.

[0043] The manufacturing method for the above-mentioned tubular medical device delivery device is intended to reduce the sliding load generated during deployment by making it less likely that a relatively rigid tubular medical device will become embedded in a relatively flexible tubular tube body after manufacturing. Therefore, it is preferable to perform steps S1 and S2 in this order.

[0044] As described above, it is believed that at least a portion of the shape memory alloy can undergo martensite phase transformation by cooling the tubular medical device to a temperature equal to or lower than the martensite phase transformation starting temperature of the shape memory alloy +7°C. This allows the tubular medical device to be in a state in which it can be easily deformed even with low stress, thereby suppressing the occurrence of radial force, mitigating the embedding of the tubular medical device into the tubular tube body, and keeping low the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed.

[0045] In step S2 of the manufacturing method of the tubular medical device delivery device, the tubular tube body is preferably cooled to a temperature below the glass transition temperature of the thermoplastic resin. When the tubular tube body containing the tubular medical device is cooled to a temperature below the glass transition temperature of the thermoplastic resin contained in the tubular tube body, the thermoplastic resin hardens and the elastic modulus decreases. This makes the tubular tube body less likely to deform even when an external force is applied to it, so that it is possible to reduce the embedding of the tubular medical device into the tubular tube body and to reduce the sliding load generated between the tubular medical device and the tubular tube body when the tubular medical device is deployed.

[0046] The manufacturing method of the tubular medical device delivery device preferably includes a sterilization step. Sterilization refers to an action or operation for achieving a state in which all proliferative microorganisms are killed or removed. A known sterilization method may be used, and may be selected from, for example, gas sterilization, electron beam sterilization, heat sterilization such as high-pressure steam sterilization (autoclave sterilization) and dry heat sterilization, radiation sterilization, etc. The sterilization step is preferably performed after step S1 in which at least a part of the tubular medical device is housed in the lumen of the tubular tube body, and before step S2 in which the tubular medical device is cooled at a temperature equal to or lower than the martensitic phase transformation start temperature of the shape memory alloy +7°C.

[0047] In the manufacturing method of the above-mentioned tubular medical device delivery device, it is preferable to have a step S3 in which the tubular medical device and the tubular tube body are heat sterilized after step S1 in which at least a portion of the tubular medical device is stored within the lumen of the tubular tube body and before step S2 in which the tubular medical device is cooled to a temperature not higher than the martensitic phase transformation start temperature of the shape memory alloy +7°C.

[0048] In the above step S3, the tubular medical device and the tubular tube body are heat sterilized. More specifically, the tubular medical device and the tubular tube body can be sterilized by a method such as EOG sterilization or electron beam sterilization, but it is preferable that the sterilization step includes a heat sterilization process. It is preferable to perform steps S1, S3, and S2 in this order. The tubular tube body is softened by being heated to a glass transition temperature or higher, and the tubular medical device is heated to an austenite phase transformation end temperature or higher, so that the superelastic effect becomes stronger. For this reason, the tubular medical device becomes more likely to sink after heat sterilization, and the sliding load generated between the tubular medical device and the tubular tube body increases. However, it is considered that at least a part of the shape memory alloy contained in the tubular medical device can be martensite phase transformed by cooling the tubular medical device and the tubular tube body at a temperature of the martensite phase transformation start temperature of the shape memory alloy contained in the tubular medical device + 7 ° C or lower after heat sterilization. As a result, the tubular medical device is in a state where it can be easily deformed even with low stress, so that the occurrence of radial force can be suppressed. This makes it possible to reduce the embedding of the tubular medical device into the tubular tube body, and to keep the sliding load generated between the tubular medical device and the tubular tube body low when the tubular medical device is deployed. When the tubular tube body is cooled to below the glass transition temperature, a synergistic effect is created by the increased hardness of the tubular tube body, which makes it possible to reduce the embedding of the tubular medical device into the tubular tube body, and to keep the sliding load generated when the tubular medical device is deployed low.

[0049] The temperature for heat sterilization in step S3 may be set appropriately as long as it is capable of killing bacteria, but the lower limit of the heat sterilization temperature may be, for example, 40° C. or higher, 45° C. or higher, 50° C. or higher, etc. The upper limit of the heat sterilization temperature may be, for example, 130° C. or lower, 120° C. or lower, 110° C. or lower, etc.

[0050] It is preferable that at least a portion of the tubular medical device is stored in a state of abutting against the inner wall of the tubular tube body. The structure in which at least a portion of the tubular medical device abuts against the inner wall of the tubular tube body means that no other member is disposed between the tubular medical device and the tubular tube body at that portion, which makes it easier to reduce the diameter of that portion.

[0051] Stents used as the above-mentioned tubular medical devices can generally be classified based on their expansion mechanism into balloon-expandable stents, in which the stent is attached to the outer surface of a balloon and transported to the lesion where it is expanded by the balloon, and self-expandable stents, in which the stent is loaded into a tubular tube having a sheath member that controls the expansion of the stent and transported to the lesion where it is expanded by removing the sheath member at the lesion.

[0052] The manufacturing method of the tubular medical device delivery device can be suitably used when the tubular medical device is a self-expanding stent. A self-expanding stent expands as soon as it is released from the tubular medical device delivery device. When the tubular medical device is a self-expanding stent, the force of the tubular medical device to expand is always acting on the tubular tube body, so the tubular medical device is likely to be embedded in the inner wall surface of the tubular tube body. However, by carrying out the manufacturing method, it is believed that at least a part of the shape memory alloy contained in the tubular medical device can start martensitic phase transformation. It is believed that the force acting on the tubular tube body is suppressed by the martensitic phase transformation of at least a part of the tubular medical device. Therefore, it is possible to reduce the embedding 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.

[0053] The self-expanding stent can be produced, for example, by laser-cutting a cylindrical pipe made of nickel-titanium alloy, expanding it, heat-treating it, forming it into the desired shape, and finally electrolytically polishing it.

[0054] The manufacturing method of the device for carrying tubular medical devices according to the embodiment of the present invention has been described above. Next, the device for carrying tubular medical devices according to the embodiment of the present invention will be described.

[0055] The tubular medical device delivery device of the present invention is a tubular medical device delivery device in which a tubular medical device made of a material containing a shape memory alloy is housed in the lumen of a tubular tube body made of a material containing a thermoplastic resin, and is characterized in that the sliding load between the tubular medical device and the tubular tube body measured in hot water at 50°C (hereinafter referred to as "sliding load in hot water at 50°C") and the sliding load between the tubular medical device and the tubular tube body measured in hot water at 25°C (hereinafter referred to as "sliding load in hot water at 25°C") satisfy the relationship of the following formula (1). This makes it possible to reduce the embedding of the tubular medical device into the tubular tube body, and to keep the sliding load generated between the tubular medical device and the tubular tube body low when the tubular medical device is deployed. (1) Sliding load increase rate [%] = (sliding load in 50°C water [N] - sliding load in 25°C water [N]) / sliding load in 25°C water [N] × 100 ≦ 30 [%]

[0056] The following describes the results of actually measuring the sliding load generated between the tubular medical device and the tubular tube body of a tubular medical device transport device according to an embodiment of the present invention (Examples 1 to 3), as well as the results of measuring the sliding load generated between the tubular medical device and the tubular tube body of a tubular medical device manufactured by a conventional method (Comparative Examples 1 to 3).

[0057] The tubular medical device delivery devices of Examples 1 to 3 in Table 1 below were manufactured by the method described in the manufacturing method for the tubular medical device delivery device. More specifically, step S1 in which the entire tubular medical device is housed in the lumen of the tubular tube body, step S3 in which the tubular medical device and the tubular tube body are heat sterilized, and step S2 in which the tubular medical device and the tubular tube body are cooled at a temperature of the martensitic phase transformation start temperature of the shape memory alloy + 3°C are performed in this order, and after the cooling step S2, the tubular medical device and the tubular tube body are stored at room temperature (25°C). The temperature of the martensitic phase transformation start temperature of the shape memory alloy + 3°C is the glass transition temperature of the thermoplastic resin contained in the tubular tube body - 67°C.

[0058] The tubular medical device delivery devices of Comparative Examples 1 to 3 in Table 1 below are those in which step S1, in which the entire tubular medical device is stored in the lumen of the tubular tube body, and step S3, in which the tubular medical device and the tubular tube body are heat sterilized, are carried out in that order. In these Comparative Examples, step S2, in which the tubular medical device and the tubular tube body are cooled, are not carried out, and the tubular medical device and the tubular tube body are stored at room temperature (25°C) after step S3, in which they are heat sterilized.

[0059] The tubular medical devices used in the manufacture of the tubular medical device delivery devices of Examples 1 to 3 and Comparative Examples 1 to 3 are self-expanding stents processed by cutting out a tube made of a material containing a nickel-titanium alloy as a shape memory alloy by a laser, and the diameter before being stored in the lumen of the tubular tube body is 10 mm, and the length of the tubular medical device is 100 mm. The tubular tube body has an outer layer made of nylon 12 and an inner layer made of PTFE. The inner diameter of this tubular tube body is 1.61 mm, and the outer diameter is 1.81 mm. The thickness of the inner layer made of PTFE is 15 μm. The shape of the self-expanding stent, which is the tubular medical device, is also the same in the Examples and Comparative Examples. The martensitic phase transformation start temperature of the shape memory alloy contained in the tubular medical devices of Examples 1 to 3 and Comparative Examples 1 to 3 is −35° C. The glass transition temperature of the thermoplastic resin contained in the tubular tube bodies of Examples 1 to 3 and Comparative Examples 1 to 3 is 35° C. In step S3, which is heat sterilization, EOG sterilization was performed at a temperature of 60° C. and a humidity of 60% for 30 hours.

[0060] Table 1 below shows the results of measuring the sliding load [N] generated between the tubular medical device and the tubular tube body in the tubular medical device delivery devices of Examples 1 to 3 and the tubular medical device delivery devices of Comparative Examples 1 to 3 under hot water at 25°C (hereinafter sometimes referred to as "sliding load under 25°C hot water"), and the results of measuring the sliding load [N] generated between the tubular medical device and the tubular tube body in the tubular medical device delivery devices of Examples 1 to 3 and the tubular medical device delivery devices of Comparative Examples 1 to 3 under hot water at 50°C (hereinafter sometimes referred to as "sliding load under 50°C hot water"). In addition, the change [N] between the sliding load measured in 25°C hot water and the sliding load measured in 50°C hot water (sliding load [N] in 50°C hot water - sliding load [N] in 25°C hot water), and the increase rate [%] of the sliding load measured in 25°C hot water and the sliding load measured in 50°C hot water ((sliding load [N] in 50°C hot water - sliding load [N] in 25°C hot water) / sliding load [N] in 25°C hot water × 100) are shown.

[0061] Next, a method for measuring the sliding load will be described with reference to FIG. 3. First, a sample 1 is prepared in a state in which a tubular medical device 10 is housed in the lumen of a tubular tube body 20. One end of the tubular tube body 20 is fixed to a device 40 for measuring a tensile load, and a support member 30 for supporting the tubular medical device 10 is placed in the lumen of the tubular tube body 20. One end of the support member 30 is provided with a hollow cylindrical pusher member 31, and the tubular medical device 10 present in the lumen of the tubular tube body 20 is pushed out by the pusher member 31 provided on the support member 30. The other end of the support member 30 is fixed to the device 40 for measuring a tensile load in a state exposed to the outside of the tubular tube body 20. In this state, an SS curve is obtained when the tubular tube body 20 is pulled at a speed of 50 mm / min with the position of the support member 30 fixed by the device 40 for measuring a tensile load. In this specification, the peak of this SS curve is defined as the sliding load [N].

[0062] The sliding load in warm water at 25°C is a load obtained by measuring the tubular medical device and the tubular tube body while they are immersed in warm water adjusted to 25°C.

[0063] The sliding load in warm water at 50°C is a load obtained by measuring the tubular medical device and the tubular tube body while they are immersed in warm water adjusted to 50°C.

[0064] [Table 1]

[0065] As shown in Table 1, the sliding loads of the tubular medical device transport devices of Examples 1 to 3 in 50°C hot water were 7.28 to 8.09 [N], whereas the sliding loads of the tubular medical device transport devices of Comparative Examples 1 to 3 in 50°C hot water were 7.97 to 9.75 [N]. This shows that the tubular medical device transport devices of Examples 1 to 3 tend to be able to reduce the sliding load generated between the tubular medical device and the tubular tube body more than the tubular medical device transport devices of Comparative Examples 1 to 3.

[0066] Furthermore, the minimum value of the increase rate of the sliding load of the tubular medical device transport device of Examples 1 to 3 is 23.0% while the maximum value of the increase rate of the sliding load of the tubular medical device transport device of Comparative Examples 1 to 3 is 55.1%. This shows that the tubular medical device transport device of Examples 1 to 3 can suppress the increase rate of the sliding load to a maximum of 32.1% lower than the tubular medical device transport device of Comparative Examples 1 to 3.

[0067] Furthermore, the increase rate of the sliding load of the tubular medical device delivery device is 28.2 [%] in Example 1, 27.2 [%] in Example 2, and 23.0 [%] in Example 3, while it is 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 embodiment of the present invention is a tubular medical device delivery device in which a tubular medical device made of a material containing a shape memory alloy is housed in the lumen of a tubular tube body made of a material containing a thermoplastic resin, and is characterized in that the sliding load under 50°C hot water and the sliding load under 25°C hot water satisfy the relationship of the following formula (1). This makes it possible to keep the sliding load generated between the tubular medical device and the tubular tube body low when the tubular medical device is deployed. (1) Sliding load increase rate [%] = (sliding load in 50°C water [N] - sliding load in 25°C water [N]) / sliding load in 25°C water [N] × 100 ≦ 30 [%]

[0068] The increase rate of the sliding load can be greater than 0% and may be 5% or more, 10% or more, etc. The smaller the increase rate of the sliding load, the more preferable it is.

[0069] The following shows the results of measuring the sliding load between the tubular medical device and the tubular tube body of a tubular medical device transport device that has not undergone either the heat sterilization step S3 or the cooling step S2 in 37°C warm water, which is closer to the temperature of the human body (Comparative Examples 4-7); the results of measuring the sliding load between the tubular medical device and the tubular tube body of a tubular medical device transport device manufactured by a conventional method in 37°C warm water, which is closer to the temperature of the human body (Comparative Examples 8-15); and the results of measuring the sliding load between the tubular medical device and the tubular tube body of a tubular medical device transport device manufactured according to an embodiment of the present invention in 37°C warm water, which is closer to the temperature of the human body (Examples 4-15).

[0070] The tubular medical device delivery devices of Comparative Examples 4 to 7 in Table 2 below are those that only carry out step S1, in which the entire tubular medical device is housed within the lumen of the tubular tube body. In Comparative Examples 4 to 7, step S2, in which the tubular medical device and the tubular tube body are cooled, and step S3, in which the tubular medical device is heat sterilized, are not carried out. After step S1, the devices were stored at room temperature (25°C).

[0071] The tubular medical device delivery devices of Comparative Examples 8 to 11 in Table 2 below are those in which step S1, in which the entire tubular medical device is stored in the lumen of the tubular tube body, and step S3, in which the tubular medical device and the tubular tube body are heat sterilized, are carried out in that order. In these Comparative Examples, step S2, in which the tubular medical device and the tubular tube body are cooled, are not carried out, and the tubular medical device delivery devices are stored at room temperature (25°C) after step S3, in which they are heat sterilized.

[0072] The tubular medical device transport devices of Comparative Examples 12 to 15 in Table 2 below are constructed in the following order: step S1 in which the entire tubular medical device is stored in the lumen of the tubular tube body, step S3 in which the tubular medical device and the tubular tube body are heat sterilized, and step S2 in which the tubular medical device and the tubular tube body are cooled at a temperature of the martensitic phase transformation start temperature of the shape memory alloy + 39°C, and the devices are stored at room temperature (25°C) after the cooling step S2. The temperature of the martensitic phase transformation start temperature of the shape memory alloy + 39°C is the glass transition temperature of the thermoplastic resin contained in the tubular tube body - 31°C.

[0073] The tubular medical device delivery devices of Examples 4 to 7 in Table 2 below are implemented in the following order: step S1 in which the entire tubular medical device is stored in the lumen of the tubular tube body, step S3 in which the tubular medical device and the tubular tube body are heat sterilized, and step S2 in which the tubular medical device and the tubular tube body are cooled at a temperature of the martensitic phase transformation start temperature of the shape memory alloy + 3°C, and after the cooling step S2, the tubular medical device and the tubular tube body are stored at room temperature (25°C). Note that the temperature of the martensitic phase transformation start temperature of the shape memory alloy + 3°C is the glass transition temperature of the thermoplastic resin contained in the tubular tube body - 67°C.

[0074] The tubular medical device delivery devices of Examples 8 to 11 in Table 2 below are implemented in the following order: step S1 in which the entire tubular medical device is stored in the lumen of the tubular tube body, step S3 in which the tubular medical device and the tubular tube body are heat sterilized, and step S2 in which the tubular medical device and the tubular tube body are cooled at a temperature of the martensitic phase transformation start temperature of the shape memory alloy minus 45°C. After the cooling step S2, the tubular medical device and the tubular tube body are stored at room temperature (25°C). Note that the temperature of the martensitic phase transformation start temperature of the shape memory alloy minus 45°C is the glass transition temperature of the thermoplastic resin contained in the tubular tube body minus 115°C.

[0075] The tubular medical device delivery devices of Examples 12 to 15 in Table 2 below are implemented in the following order: step S1 in which the entire tubular medical device is stored in the lumen of the tubular tube body, step S3 in which the tubular medical device and the tubular tube body are heat sterilized, and step S2 in which the tubular medical device and the tubular tube body are cooled at a temperature of the martensitic phase transformation start temperature of the shape memory alloy minus 161°C, and the devices are stored at room temperature (25°C) after the cooling step S2. Note that the temperature of minus 161°C, which is the martensitic phase transformation start temperature of the shape memory alloy, is the glass transition temperature of the thermoplastic resin contained in the tubular tube body minus 231°C.

[0076] The tubular medical devices used in the manufacture of the tubular medical device delivery devices of Comparative Examples 4 to 7, Comparative Examples 8 to 15, and Examples 4 to 15 are self-expanding stents processed by cutting out a tube made of a material containing a nickel-titanium alloy as a shape memory alloy by a laser, and the diameter of the tubular medical device before being housed in the lumen of the tubular tube body is 10 mm, and the length of the tubular medical device is 100 mm. The tubular tube body has an outer layer made of nylon 12 and an inner layer made of PTFE. The inner diameter of this tubular tube body is 1.61 mm, and the outer diameter is 1.81 mm. The thickness of the inner layer made of PTFE is 15 μm. The shape of the self-expanding stent, which is the tubular medical device, is also the same in the Examples and Comparative Examples. The martensitic phase transformation start 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 tube body is 35° C. In step S3, which is heat sterilization, EOG sterilization was performed at a temperature of 60° C. and a humidity of 60% for 30 hours.

[0077] Table 2 shows the results of measuring 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 to 7, Comparative Examples 8 to 15, and Examples 4 to 15 under 37°C warm water (hereinafter sometimes referred to as "sliding load under 37°C warm water"), and the average sliding load under 37°C warm water in Comparative Examples 4 to 7, Comparative Examples 8 to 11, Comparative Examples 12 to 15, Examples 4 to 7, Examples 8 to 11, and Examples 12 to 15. Fig. 4 also shows a bar graph of the sliding load [N] under 37°C warm water in Comparative Examples 4 to 7, Comparative Examples 8 to 11, Comparative Examples 12 to 15, Examples 4 to 7, Examples 8 to 11, and Examples 12 to 15.

[0078] [Table 2]

[0079] As shown in Table 2 and Comparative Examples 4 to 7 in Fig. 4, the average sliding load of the tubular medical device delivery device not subjected to the heat sterilization step S3 in 37°C warm water is 5.91 N. As shown in Comparative Examples 8 to 11, when the cooling step S2 is not performed after the heat sterilization step S3 is performed, the average sliding load of the tubular medical device delivery device in 37°C warm water increases to 6.97 N. Also, as shown in Comparative Examples 12 to 15, it is shown that the average sliding load in 37°C warm water remains 6.97 N when only the step of cooling to a temperature of +39°C, which is the martensitic phase transformation start temperature of the shape memory alloy, and -31°C, which is the glass transition temperature of the thermoplastic resin, is performed.

[0080] However, when the step of cooling to a temperature of martensite phase transformation start temperature +3°C and a temperature of glass transition temperature -67°C was performed, the average sliding load in 37°C warm water was 6.25N, which is shown to be reduced to near the average sliding load (5.91N) in 37°C warm water of Comparative Examples 4 to 7 in which the heat sterilization step was not performed. In this way, if the cooling temperature in the cooling step S2 is set to about martensite phase transformation start temperature +3°C, the sliding load in 37°C warm water can be reduced to near the average sliding load in 37°C warm water before heat sterilization.

[0081] Moreover, the average sliding load in 37°C hot water for Examples 8 to 11, in which steps of cooling to a temperature of the martensite phase transformation start temperature -45°C and a temperature of the glass transition temperature -115°C were performed, was 5.73 N. Furthermore, the average sliding load in 37°C hot water for Examples 12 to 15, in which steps of cooling to a temperature of the martensite phase transformation start temperature -161°C and a temperature of the glass transition temperature -231°C were performed, was 5.39 N. In this way, by setting the cooling temperature in the cooling step S2 to about the martensite phase transformation start temperature -45°C, the sliding load in 37°C hot water can be made lower than that before heat sterilization.

[0082] Furthermore, Examples 4 to 7, 8 to 11, and 12 to 15 show that the lower the cooling temperature in the cooling step, the lower the sliding load generated between the tubular tube body and the tubular medical device. In particular, when cooling is performed at a temperature that is the martensitic phase transformation start temperature of the shape memory alloy minus 161°C and is the glass transition temperature of the thermoplastic resin contained in the tubular tube body minus 231°C (Examples 12 to 15), most of the shape memory alloy can transform into the martensitic phase, which makes it easier to reduce the sliding load.

[0083] As described above, it has been shown that the sliding load between the tubular medical device and the tubular tube body in 37°C warm water, which increases as a result of carrying out the heat sterilization step, can be reduced by carrying out a cooling step to a temperature equal to or lower than the martensitic phase transformation starting temperature +7°C after carrying out the heat sterilization step (Examples 4 to 7, Examples 8 to 11, Examples 12 to 15).

[0084] Moreover, the temperature of 37°C is close to the body temperature of the human body. The above results show that the tubular medical device delivery device according to the embodiment of the present invention can reduce the sliding load even after being inserted into a blood vessel of the human body, compared to the tubular medical device delivery devices manufactured by conventional methods (Comparative Examples 8 to 11).

[0085] Furthermore, the average sliding load of Examples 8 to 11 in which a cooling step was performed after heat sterilization and the average sliding load of Examples 12 to 15 in which a cooling step was performed after heat sterilization were lower than the average sliding load of Comparative Examples 4 to 7 in which a heat sterilization step was not performed. From this, it is considered that even when a sterilization method other than heat sterilization is used, the sliding load can be reduced by performing step S2 of cooling after step 1.

[0086] As described above, the tubular medical device delivery device of the present invention is capable of keeping low the sliding load that occurs between the tubular medical device and the tubular tube body when the tubular medical device is deployed, even when used inside the body at temperatures higher than room temperature.

[0087] As described above, the tubular medical device delivery device and the manufacturing method for the tubular medical device delivery device of the present invention can prevent the tubular medical device from sinking into the tubular tube body, and can keep the sliding load low when the tubular medical device is deployed.

[0088] This application claims the benefit of priority based on Japanese Patent Application No. 2020-131676, filed on August 3, 2020. The entire contents of the specification of Japanese Patent Application No. 2020-131676, filed on August 3, 2020, are incorporated by reference into this application. [Explanation of symbols]

[0089] 1: Sample 10: Tubular medical devices 20: Tubular tube body 30: Support member 31: Pusher member 40: Apparatus for measuring tensile load 100: Tubular medical device delivery device 110: Tubular medical devices 120: Tubular tube body 130:Operation unit 131: Thumb wheel 140: Inner shaft 141: Pusher parts

Claims

1. A tubular medical device made of a material including a shape memory alloy; A method for manufacturing a tubular medical device delivery device having a tubular tube body made of a material including a thermoplastic resin, comprising: A step S1 in which at least a portion of the tubular medical device is housed within a lumen of the tubular tube body; and a step S2 in which the tubular medical device is cooled to a temperature equal to or lower than the martensitic phase transformation start temperature of the shape memory alloy + 7°C; A method for manufacturing a tubular medical device delivery device, characterized in that steps S1 and S2 are carried out in this order.

2. 2. The method of claim 1, wherein in step S2, the tubular tube body is cooled to a temperature below the glass transition temperature of the thermoplastic resin.

3. After step S1 in which at least a portion of the tubular medical device is housed within a lumen of the tubular tube body, Prior to step S2, in which the tubular medical device is cooled to a temperature equal to or lower than the martensitic phase transformation start temperature of the shape memory alloy +7°C, 3. The method of claim 1, further comprising a step S3 of heat sterilizing the tubular medical device and the tubular tube body.

4. 4. The method for producing a tubular medical device delivery device according to claim 1, wherein at least a portion of the tubular medical device is housed in contact with an inner wall of the tubular tube body.

5. The method for manufacturing a tubular medical device delivery device according to any one of claims 1 to 4, wherein the shape memory alloy is a nickel-titanium alloy.

6. The method of manufacturing a tubular medical device delivery device according to any one of claims 1 to 5, wherein the tubular medical device is a self-expanding stent.

7. A tubular medical device delivery device in which a tubular medical device made of a material containing a shape memory alloy is housed in a lumen of a tubular tube body made of a material containing a thermoplastic resin, A tubular medical device delivery device, characterized in that the sliding load between the tubular medical device and the tubular tube body measured in hot water at 50°C (hereinafter referred to as the "sliding load in hot water at 50°C") and the sliding load between the tubular medical device and the tubular tube body measured in hot water at 25°C (hereinafter referred to as the "sliding load in hot water at 25°C") satisfy the relationship of the following formula (1). (1) Increase rate of sliding load [%] = (sliding load in 50°C hot water [N] - sliding load in 25°C hot water [N]) / sliding load in 25°C hot water [N] x 100 ≦ 30 [%]

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

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