Catheter

Abstract

[Problem] To provide a catheter having a novel structure capable of preventing adhesion between the tip of the catheter and body tissue due to a cyanoacrylate-based embolic substance. [Solution] Provided is a catheter 10 in which a hub 42, via which a lumen 14 is open to the proximal side, is connected to the proximal side of a tubular catheter body 12 having the lumen 14, and in which a cyanoacrylate-based embolic substance-containing liquid is injected to the distal side of the catheter body 12 through the lumen 14. The catheter body 12 has an inner layer 16 defining the wall of the lumen 14, and an outer layer 18 covering the outer periphery of the inner layer 16. The outer layer 18 of the tip of the catheter body 12 is a low adhesion tip 22 that is formed of a resin elastomer containing tungsten powder 28 so as to have low adhesiveness to the cyanoacrylate-based embolic substance-containing liquid.

Description

catheter

[0001] The present invention relates to a catheter used for injecting a liquid containing a cyanoacrylate-based embolic substance into cerebral blood vessels or the like.

[0002] Conventionally, a known method for treating subdural hematomas caused by, for example, a bruise or other injury is a surgical procedure in which a drain tube is inserted into the hematoma through a hole drilled in the skull and the blood in the hematoma is drained to the outside. This treatment relieves the pressure on the brain caused by the hematoma by draining the blood, thereby alleviating or eliminating the symptoms caused by the hematoma. However, because this is a symptomatic treatment, there is a possibility that the hematoma will recur due to continued or renewed bleeding from the blood vessels. Furthermore, because trepanation, which involves drilling a hole in the skull, places a significant physical burden on the patient, less invasive medical treatment methods are being considered.

[0003] As a medical treatment method for subdural hematoma, for example, vascular embolization using a catheter has been proposed, as shown in Japanese Patent Laid-Open No. 2001-058009 (Patent Document 1). That is, this treatment method involves percutaneously inserting a catheter into a blood vessel from the leg or the like, advancing it to the bleeding site in the cerebral blood vessel that is causing the hematoma, and injecting an embolic substance into the cerebral blood vessel through the catheter lumen, thereby restricting or blocking blood flow in the cerebral blood vessel and preventing blood supply to the hematoma, thereby eliminating the cause of the hematoma.

[0004] Japanese Patent Application Laid-Open No. 2001-058009

[0005] Ethylene vinyl alcohol polymer (EVOH) has been known as an embolic material that blocks blood vessels and blocks blood flow. EVOH takes a long time to harden, making it less likely to adhere to the catheter and blood vessel, and it is easy to handle.

[0006] However, since EVOH takes several tens of minutes to harden, there is a risk that after being injected into a blood vessel, it will flow downstream with the blood flow and not harden at the intended location. Furthermore, since the solvent used to make EVOH liquid so that it can be injected into a blood vessel is dimethyl sulfoxide (DMSO), which is highly irritating to patients, general anesthesia is required when using it, which places a heavy burden on the patient's body.

[0007] Therefore, cyanoacrylate-based embolic substances have attracted attention. For example, n-butyl-2-cyanoacrylate (NBCA), a cyanoacrylate-based embolic substance, is mixed with iodized poppy oil fatty acid ethyl ester (Lipiodol (registered trademark)), which is less irritating to patients, so the procedure can be performed under local anesthesia and the physical burden on the patient is reduced. Furthermore, NBCA reacts with water in the blood and hardens quickly in a short period of time, so it is unlikely to be swept downstream by the bloodstream before hardening, making it relatively easy to embolize the blood vessel at a predetermined location.

[0008] However, when NBCA is used as an embolic material, there is a risk that the catheter may adhere to the vascular wall. Although the hardening time of NBCA can be adjusted to some extent by changing the mixing ratio with Lipiodol, the hardening time is short, and the NBCA adhering to the outer surface of the catheter tip hardens before the procedure is completed. This makes it necessary to remove the catheter from the blood vessel midway through the procedure and insert a new catheter to continue the NBCA injection. Conventionally, to prevent adhesion of the catheter to the blood vessel due to the NBCA, the catheter must be removed within a short time, for example, within one minute of the start of NBCA injection. This means that several catheters must be used to complete the embolization of the cerebral blood vessel, which increases the economic burden and lengthens the procedure time.

[0009] Furthermore, there is a significant risk that the tip of the catheter will adhere to the blood vessel, making it difficult for doctors to adopt the less invasive NBCA. In particular, it is difficult for doctors who have no experience in cerebral vascular embolization using NBCA to adopt it, and the adhesiveness of NBCA to the catheter has hindered less invasive treatment.

[0010] Patent Document 1 discloses that when the tip of a catheter is bonded to a blood vessel, the tip of the catheter can be cut by passing a high-frequency current through a metal layer, thereby making it possible to remove the catheter. However, this method has the problem that even if the tip of the catheter is successfully cut and the catheter can be removed, the tip of the catheter may remain in the blood vessel.

[0011] Furthermore, for example, Japanese Patent Application Laid-Open No. 2016-016122 proposes that, in consideration of the adhesiveness of the tip portion of the catheter to the NBCA, the catheter tube body be formed from any one of a fluorine-based resin, an olefin-based resin, or a silicone-based resin, and that the tip portion of the catheter be either an exposed tip portion without an outer surface layer (coating layer) or a coated tip portion coated with any one of a fluorine-based resin, an olefin-based resin, or a silicone-based resin. However, according to the inventor's studies and experiments, even if the tube body is formed from any one of a fluorine-based resin, an olefin-based resin, or a silicone-based resin, the low adhesiveness to the NBCA is still insufficient.

[0012] An object of the present invention is to provide a catheter having a novel structure that can prevent adhesion of the tip portion of the catheter to body tissues due to cyanoacrylate-based embolic substances.

[0013] The following describes preferred embodiments for understanding the present invention, but the embodiments described below are merely examples and may be appropriately combined with one another. Multiple components described in each embodiment may be recognized and employed independently to the greatest extent possible, and may also be appropriately combined with any of the components described in other embodiments. Accordingly, the present invention is not limited to the embodiments described below, and various other embodiments may be realized.

[0014] Initially, the inventors considered using a coating layer with low adhesion to NBCA and the like as a means of preventing adhesion between the tip of the catheter and body tissue due to cyanoacrylate-based embolic substances. However, they found that it was difficult to reliably achieve sufficiently low adhesion performance with a high degree of reliability when using a coating layer formed by application to the catheter surface, as it was difficult to stably form a uniform layer. They therefore recognized that it was necessary to achieve sufficiently low adhesion to NBCA and the like for the catheter body.

[0015] Based on this understanding, the inventors conducted extensive research and first focused on polytetrafluoroethylene (PTFE), which has low adhesiveness to NBCA and the like, but it was difficult to obtain sufficient flexibility when PTFE was used for the catheter body, and it was particularly difficult to achieve small diameters and high flexibility such as catheters used in procedures on cerebrovascular tissue, etc. Therefore, the inventors conducted further research to realize a technology that uses a resin material more flexible than PTFE and that exhibits sufficiently low adhesiveness to NBCA and the like, and as a result, they focused on a specific resin material and a specific compounding agent (filler).

[0016] When selecting the specific resin material, the inventors considered it appropriate to focus on the surface free energy of the resin solid as an indicator of low adhesion to NBCA and the like. That is, surface free energy is used as an indicator of controlling the wettability of solids and liquids and of adhesion between solids. However, since cyanoacrylate-based embolic substances such as NBCA are provided in liquid form during treatment and embolize blood vessels through a curing process, it is considered meaningful to focus on surface free energy as an indicator of low adhesion to the cyanoacrylate-based embolic substance. From this perspective, the inventors measured the surface free energy of various materials and found that polyester elastomers have a lower surface free energy than polyamide elastomers and are therefore preferable.

[0017] Regarding the latter specific compounding material, the inventors measured the change in surface free energy by compounding the resin material, using surface free energy as an index, and found that compounding tungsten powder was effective.

[0018] Further investigations by the present inventors have confirmed that, during treatment, cyanoacrylate-based embolic substances such as NBCA are mixed with iodized poppy oil fatty acid ethyl ester (lipiodol) to form a liquid containing a cyanoacrylate-based embolic substance (liquid containing NBCA, etc.), and that tungsten powder reduces the pH value of the liquid containing NBCA, etc., albeit slightly. Since a decrease in the pH value of a liquid containing NBCA, etc., leads to a delay in the polymerization reaction (curing reaction), the improvement in low adhesion performance to NBCA, etc., by incorporating tungsten powder into a resin material can be expected to be effective not only in further reducing the surface free energy as described above, but also in retarding the curing of the liquid containing NBCA, etc.

[0019] As described above, the present invention was developed based on new findings obtained through numerous experiments and studies conducted by the inventors to solve the problem of preventing adhesion of the tip of a catheter to body tissue due to cyanoacrylate-based embolic substances. Some specific aspects of the invention will be described below.

[0020] In a first aspect, the catheter has a tubular catheter body with a lumen, and a hub that opens the lumen to the proximal end is connected to the proximal end of the catheter body, and a liquid containing a cyanoacrylate-based embolic substance is injected through the lumen into the distal end of the catheter body, wherein the catheter body has an inner layer that provides the wall surface of the lumen and an outer layer that covers the outer periphery of the inner layer, and the outer layer at the distal end of the catheter body is a low-adhesion distal portion formed of a resin elastomer containing tungsten powder.

[0021] In the catheter according to this embodiment, the outer layer of the tip portion of the catheter body, where adhesion to body tissues such as blood vessels due to a liquid containing a cyanoacrylate-based embolic substance is likely to be a problem, is a low-adhesion tip portion formed of a tungsten-containing resin elastomer. It has been newly discovered that tungsten-containing resin elastomer exhibits excellent low adhesion to liquids containing a cyanoacrylate-based embolic substance, so adhesion between the low-adhesion tip portion and blood vessels is prevented during vascular embolization using a liquid containing a cyanoacrylate-based embolic substance, thereby avoiding problems such as the catheter body adhering to the blood vessel and becoming unable to be removed.

[0022] This reduces the number of times catheters need to be replaced during treatment to prevent adhesion to body tissue, thereby reducing the number of catheters required for the procedure and also shortening treatment time.

[0023] In a second aspect, in the catheter according to the first aspect, the resin elastomer forming the low-adhesion tip portion is a polyester elastomer.

[0024] According to the catheter of this embodiment, the low-adhesion tip portion is formed from a polyester elastomer containing tungsten powder, thereby achieving superior low adhesion to liquids containing cyanoacrylate-based embolic substances at the low-adhesion tip portion.

[0025] A third aspect is a catheter having a tubular catheter body with a lumen, the proximal end of which is connected to a hub that opens the lumen toward the proximal end, and for injecting a liquid containing a cyanoacrylate-based embolic substance through the lumen into the distal end of the catheter body, wherein the catheter body has an inner layer that provides the wall surface of the lumen and an outer layer that covers the outer periphery of the inner layer, and the outer layer at the distal end of the catheter body is a low-adhesion distal portion made of polyester elastomer.

[0026] In the catheter according to this embodiment, the outer layer of the tip portion of the catheter body, which is prone to adhesion to blood vessels due to the liquid containing a cyanoacrylate-based embolic substance, is made into a low-adhesion tip portion made of polyester elastomer that has low adhesion to blood vessels due to the liquid containing a cyanoacrylate-based embolic substance. Therefore, during vascular embolization using a liquid containing a cyanoacrylate-based embolic substance, for example, adhesion between the low-adhesion tip portion and the blood vessel is prevented, and problems such as the catheter body adhering to the blood vessel and becoming stuck can be avoided.

[0027] In addition, the number of times catheters need to be replaced during treatment can be reduced to prevent adhesion to blood vessels, which reduces the number of catheters required for the procedure and is expected to shorten treatment time.

[0028] In a fourth aspect, in the catheter according to any one of the first to third aspects, the low-adhesion tip section has a length from the tip of the catheter body within the range of 1 cm to 10 cm.

[0029] According to the catheter of this aspect, by providing a low-adhesion tip section extending over a range of 1 cm or more from the tip of the catheter body, adhesion of the catheter body to a blood vessel can be effectively prevented. Furthermore, by providing a low-adhesion tip section within a range of 10 cm or less from the tip of the catheter body, materials and structures that can more highly satisfy required performance characteristics other than low adhesion to the NBCA can be employed on the proximal end side of the catheter body, which is more than 10 cm from the tip. This makes it possible to effectively obtain required performance characteristics of the catheter body, such as pushability and low friction, while preventing adhesion of the catheter body to a blood vessel.

[0030] In a fifth aspect, in the catheter according to any one of the first to fourth aspects, the low-adhesion tip portion is covered with a silicone coating or a fluororesin coating.

[0031] If a conventionally known hydrophilic coating is applied to the low-adhesion tip portion in order to improve the ease of insertion of the catheter body into a blood vessel, the low adhesion to liquids containing cyanoacrylate-based embolic substances will be reduced, and the tip portion of the catheter body may become adhered to the blood vessel. Therefore, in the catheter according to this embodiment, by covering the low-adhesion tip portion with a silicone coating or a fluororesin coating, the tip portion of the catheter body maintains excellent low adhesion to liquids containing cyanoacrylate-based embolic substances, while improving ease of insertion into a blood vessel by reducing friction.

[0032] In a sixth aspect, in the catheter according to any one of the first to fifth aspects, the hub is formed from a polyester resin.

[0033] Hubs made of polycarbonate are commonly known, but polycarbonate hubs have the problem of being highly adhesive to liquids containing cyanoacrylate-based embolic substances. Therefore, in the catheter according to the present embodiment, the hub is made of a polyester-based resin, which ensures liquid resistance to contact with liquids containing cyanoacrylate-based embolic substances while also ensuring low adhesiveness of the hub to liquids containing cyanoacrylate-based embolic substances. Furthermore, the hub can be easily made transparent, making it easy to visually check for air bubbles in the liquid flowing inside.

[0034] In a seventh aspect, in the catheter according to any one of the first to sixth aspects, the inner layer of the catheter body is formed of polytetrafluoroethylene.

[0035] According to the catheter of this embodiment, the inner layer of the catheter body can also achieve sufficiently low adhesiveness to a liquid containing a cyanoacrylate-based embolic substance.

[0036] In an eighth aspect, the catheter according to any one of the first to seventh aspects is a catheter for embolizing cerebrovascular disease, for injecting a liquid containing a cyanoacrylate-based embolic substance into a cerebral blood vessel.

[0037] The catheter according to this aspect is provided with a low-adhesion tip portion that exhibits low adhesion to liquids containing cyanoacrylate-based embolic substances, making it easier to use liquids containing cyanoacrylate-based embolic substances in embolization of cerebral blood vessels, where adhesion between the catheter and blood vessel can easily lead to serious problems. Furthermore, catheters used in cerebral blood vessels, which are small in diameter and extend in a tortuous manner, require particularly excellent vascular insertion ability, and therefore require high levels of flexibility, surface slipperiness (lubricity), etc., and the configuration described in any one of the first to seventh aspects makes it possible to sufficiently obtain flexibility, surface slipperiness, etc.

[0038] In a ninth aspect, in the catheter described in any one of the first to eighth aspects, an outer layer intermediate portion formed of a resin elastomer is provided on the proximal side of the low-adhesion tip portion in the outer layer, and an outer layer proximal end portion formed of a resin having higher deformation rigidity than the extraneous intermediate portion is provided on the proximal side of the outer layer intermediate portion.

[0039] With the catheter according to this aspect, the pushability, kink resistance, flexibility, etc. required of the catheter body can be achieved on the proximal side of the low-adhesion distal end portion of the catheter body, which does not require low adhesion to liquids containing a cyanoacrylate-based embolic agent. In particular, by having the proximal portion of the outer layer comprise an outer layer intermediate portion formed of a resin elastomer and an outer layer proximal portion made of resin and provided on the proximal side with higher rigidity than the outer layer intermediate portion, the required performance of the proximal portion of the catheter body can be achieved in a balanced manner and at an even higher level.

[0040] In a tenth aspect, there is provided the catheter according to any one of the first to ninth aspects, wherein the outer layer at the distal end portion of the catheter body is formed of a polyester elastomer containing tungsten powder at a weight ratio of 30% or more to the entire material, and the thickness of the outer layer is 0.03 to 0.3 mm; the inner layer at the distal end portion of the catheter body is formed of a fluororesin, and the thickness of the inner layer is 0.005 to 0.025 mm; and the radial thickness of the distal end portion of the catheter body including the outer and inner layers is 0.035 to 0.4 mm; and the catheter is used for cerebrovascular embolization using a cyanoacrylate-based embolic substance.

[0041] The catheter according to this embodiment can stably ensure low adhesion to cyanoacrylate-based embolic substances not only on the inner circumferential surface but also on the outer circumferential surface, while maintaining flexibility and diameter dimensions particularly suitable for use in cerebrovascular embolization. That is, on the inner circumferential surface that comes into direct contact with cyanoacrylate-based embolic substances or has a long contact time, low adhesion to cyanoacrylate-based embolic substances can be ensured by the fluororesin, which has a sufficiently low surface free energy. Meanwhile, by covering the inner layer made of fluororesin with an outer layer made of polyester elastomer containing tungsten powder to form a multilayer structure, it is possible to achieve the required flexibility of the distal end of the catheter by suppressing excessive stiffness due to the fluororesin, while maintaining the thickness, strength, and durability of the outer wall of the lumen as a whole. Furthermore, the resin layer that forms the outer layer is made of polyester elastomer, which itself has a relatively low surface free energy, and by further incorporating tungsten powder, the surface free energy is further reduced.This, combined with the expectation that the tungsten powder will delay the hardening of the cyanoacrylate-based embolic substance, can reduce the risk of adhesion of the cyanoacrylate-based embolic substance to biological tissue on the outer surface of the tip of the catheter.

[0042] According to the present invention, adhesion between the tip of the catheter and body tissue can be prevented during embolization of a blood vessel using a cyanoacrylate-based embolic substance.

[0043] 1. A right side view showing a catheter according to a first embodiment of the present invention. 2. A longitudinal cross-sectional view showing an enlarged view of the distal end portion of the catheter of FIG. 1, which corresponds to the cross-section II-II in FIG. 4. 3. A cross-sectional view III-III of FIG. 1. 4-IV of FIG. 1. 5. A table showing the measured values ​​of the test results for surface free energy. 6. A table showing the test results for the measured adhesive strength.

[0044] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0045] Figure 1 shows a catheter 10 for cerebrovascular embolization as a first embodiment of a catheter constructed in accordance with the present invention. The catheter 10 is a microcatheter that is inserted into a cerebral blood vessel and used to inject a liquid containing a cyanoacrylate-based embolic agent into the cerebral blood vessel, and has a long catheter body 12. In the following description, as a general rule, the up-down direction refers to the up-down direction in Figure 1, the front-rear direction refers to the left-right direction in Figure 1, and the left-right direction refers to the left-right direction in Figure 3, which will be described later.

[0046] The catheter body 12 is tubular overall and includes a lumen 14 that is continuous along its length. The catheter body 12 includes a tapered section 15 in its intermediate section, closer to the distal end than the center. The tapered section 15 is cylindrical, tapering in diameter toward the distal end, and in this embodiment, extends over a predetermined length at a substantially constant rate of change in diameter. Both the inner and outer diameters of the catheter body 12 change along the tapered section 15, and the diameter of the lumen 14 also decreases toward the distal end. Because the tapered section 15 makes the proximal end larger than the distal end, the injection pressure when injecting liquid through the lumen 14 toward the distal end is reduced, allowing for easy and accurate control of the amount of liquid injected. The length of the tapered section 15 is preferably within a range of 1 cm to 10 cm, and more preferably within a range of 2 cm to 5 cm. The proximal end 20 may have a substantially constant diameter throughout, or the diameter may vary along the entire length or in parts of the length.

[0047] 2 to 4, the catheter main body 12 comprises an inner layer 16 that forms the inner circumferential portion and an outer layer 18 that forms the outer circumferential portion, and the outer layer 18 is integrally fixed to the outer circumferential surface of the inner layer 16. The inner layer 16 and the outer layer 18 may be integrally welded together, for example, by heat melting the boundary portion, in which case the boundary may not be clear, but for ease of understanding, the inner layer 16 and the outer layer 18 are clearly distinguished in Figures 2 to 4.

[0048] The inner layer 16 is formed continuously over the entire length of the catheter body 12, from the distal end to the proximal end, and constitutes the wall surface of the lumen 14. The inner layer 16 is in the form of a small-diameter circular tube and is made of a soft resin, such as a fluororesin, and preferably polytetrafluoroethylene (PTFE).

[0049] The outer layer 18 has a circular tubular shape overall and covers the outer periphery of the inner layer 16. The outer layer 18 has a proximal end 20 that constitutes the proximal portion of the catheter body 12, and a low-bonded distal end 22 that is provided distally of the proximal end 20. The proximal end 20 of the outer layer 18 has a portion that constitutes the tapered section 15 on the distal side, and the low-bonded distal end 22 constitutes the distal side of the tapered section 15.

[0050] The proximal end 20 of the outer layer 18 includes a first proximal end 24 as an outer layer intermediate portion constituting a proximal adjacent portion relative to the low-bonded distal end 22, and a second proximal end 26 as an outer layer proximal end portion constituting a portion more proximal than the first proximal end 24. The first proximal end 24 and the second proximal end 26 are formed from different materials, and preferably, the first proximal end 24 is made of a softer material with lower bending rigidity than the second proximal end 26. The first proximal end 24 is formed from a resin elastomer, such as a polyamide elastomer, polyurethane elastomer, or polyester elastomer having a higher hardness than the low-bonded distal end 22. The second proximal end 26 is formed from a softer resin, such as polyamide, polyurethane, or polyester elastomer having a higher hardness than the first proximal end 24. The first proximal end 24 may be made from a uniform material throughout, or the material may vary along its length. Similarly, the second proximal end 26 may be made from a uniform material throughout, or the material may vary along its length.

[0051] The low-adhesion distal end portion 22 is formed of a resin elastomer, such as a polyester elastomer, which is softer and has rubber-like elasticity than the first base end portion 24. The polyester elastomer that is the material for forming the low-adhesion distal end portion 22 is preferably, for example, Pelprene (registered trademark) manufactured by Toyobo MC Co., Ltd.

[0052] The low-bonding tip portion 22 is formed from a tungsten-containing resin elastomer in which tungsten powder 28 is mixed with polyester elastomer. The low-bonding tip portion 22 containing tungsten powder 28 has high visibility (contrast) under X-ray fluoroscopy and can be confirmed under X-ray fluoroscopy without the need for a contrast marker such as a metal ring. To ensure visibility under X-ray fluoroscopy and low adhesion to the NBCA (described below), the weight ratio of the tungsten powder 28 to the entire material forming the low-bonding tip portion 22 is preferably 30% or more, more preferably 50% or more. To achieve good moldability of the low-bonding tip portion 22, the weight ratio of the tungsten powder 28 to the entire material forming the low-bonding tip portion 22 is preferably 80% or less.

[0053] The low-adhesion tip section 22 extends to the tip of the catheter body 12, and is preferably provided so as to define a range of 1 cm to 10 cm from the tip of the catheter body 12, and more preferably so as to define a range of 2 cm to 5 cm.

[0054] The low-bonding distal end portion 22 has a diameter smaller than the maximum diameter of the proximal end portion 20. As shown in Figure 2, the distal portion of the first proximal end portion 24 forms a tapered portion 15 whose diameter decreases toward the distal end, and is connected to the small-diameter low-bonding distal end portion 22 so as to be continuous without forming a large step.

[0055] The low-adhesion tip section 22 constituting the distal end of the catheter main body 12 is designed to have low adhesion to a cyanoacrylate-based embolic substance-containing liquid. Examples of cyanoacrylate-based embolic substances include n-butyl-2-cyanoacrylate (NBCA) and isobutyl cyanoacrylate (IBCA). In this embodiment, a case in which NBCA is used as the cyanoacrylate-based embolic substance will be described. The NBCA is mixed with iodized poppy oil fatty acid ethyl ester (Lipiodol) to form a cyanoacrylate-based embolic substance-containing liquid (NBCA-containing liquid). The NBCA-containing liquid hardens when the NBCA comes into contact with the water in the blood plasma. The time required for the NBCA-containing liquid to harden can be adjusted to some extent by the blend ratio of NBCA and Lipiodol, and is adjusted to, for example, approximately several tens of seconds. The NBCA-containing liquid ensures good visibility under X-ray fluoroscopy because the solvent mixed with NBCA is lipiodol, which has contrast properties. The visibility of the NBCA-containing liquid under X-ray fluoroscopy can be improved as the blending ratio of lipiodol increases.

[0056] The low-adhesion tip portion 22, formed of a polyester elastomer containing tungsten powder 28, has low adhesion to the NBCA. The low-adhesion tip portion 22 having low adhesion to the NBCA does not necessarily mean that the low-adhesion tip portion 22 and the NBCA do not adhere to each other at all, but rather means that the low-adhesion tip portion 22 adheres to the NBCA less easily than the tip portion of a conventional catheter. Specifically, for example, the adhesive strength to the NBCA may be lower than conventionally, allowing the catheter to be easily peeled from the hardened NBCA (without damaging body tissue such as blood vessels), or the time required for the NBCA to develop an adhesive strength that makes the catheter tip unable to peel from body tissue such as blood vessels may be longer than conventionally. The low-adhesion tip portion 22 of this embodiment has low adhesion such that it does not adhere to an NBCA-containing liquid having an NBCA content (concentration) of 20% or less, even after three minutes of contact. In other words, when using an NBCA-containing liquid with an NBCA content of 20% or less, it is not necessary to replace the catheter 10 for three minutes after the start of injection of the NBCA-containing liquid.More preferably, the low-adhesion tip portion 22 is set to have low adhesiveness such that it does not adhere even when in contact with an NBCA-containing liquid with an NBCA content of 33% or less for three minutes.

[0057] The inner layer 16 made of PTFE has low adhesion to the NBCA. However, the low-adhesion tip portion 22 made of tungsten powder-containing polyester elastomer has a lower adhesion to the NBCA than the inner layer 16 made of PTFE, making it more difficult to adhere to the NBCA.

[0058] Furthermore, in the present invention, the radial thickness of the inner layer 16, the outer layer 18, and even the tip portion are not particularly limited. However, considering the use in cerebrovascular embolization, in which the tip portion is delivered to a target site in the brain for treatment, the tip portion is required to have a predetermined outer diameter, strength, durability, and flexibility to enable relatively easy insertion into a blood vessel. From such perspectives, the radial thickness of the tip portion including the outer layer and the inner layer is preferably set within the range of 0.035 to 0.4 mm, and more preferably within the range of 0.05 to 0.15 mm. Furthermore, from the viewpoint of stably ensuring sufficiently low adhesion to the NBCA while avoiding excessive rigidity, the thickness of the inner layer 16 made of PTFE is preferably set within the range of 0.005 to 0.025 mm, and more preferably within the range of 0.01 to 0.1 mm. Similarly, the thickness of the outer layer of the low-adhesion tip section 22, made of polyester elastomer containing tungsten powder 28, is preferably set within the range of 0.03 to 0.3 mm, and more preferably within the range of 0.05 to 0.1 mm. Furthermore, by setting the thickness of the outer layer of the low-adhesion tip section 22 to 0.03 mm or greater, X-ray visibility can be improved. Furthermore, reducing the thickness, i.e., reducing the diameter of the catheter, reduces the contact surface area between the catheter and the NBCA, thereby reducing adhesion.

[0059] In this embodiment, a reinforcing member 32 is fixed to the outer layer 18. The reinforcing member 32 increases the bending rigidity of the outer layer 18, thereby improving the pushability and kink resistance of the catheter body 12. For example, the reinforcing member 32 is in the form of a mesh formed from wire. The reinforcing member 32 may be made of synthetic resin, but is preferably made of metal, such as stainless steel or titanium alloy. The reinforcing member 32 is fixed to the inner periphery of the outer layer 18 and disposed at the overlapping portion of the inner layer 16 and the outer layer 18. For example, the reinforcing member 32 may be placed over the inner layer 16, the outer layer 18 may be placed over the reinforcing member 32, and the overlapping portion of the inner layer 16 and the outer layer 18 may be heated and welded together, thereby disposing the reinforcing member 32 embedded in the overlapping portion of the inner layer 16 and the outer layer 18.

[0060] In this embodiment, the reinforcing member 32 does not reach the tip of the low-bonded distal section 22, and the tip of the low-bonded distal section 22 serves as a distal tip section 34 without a reinforcing member 32. The distal tip section 34 is extremely flexible because it does not have a reinforcing member 32, and has the function of improving the insertability of the catheter body 12 by deforming to match the curvature of the blood vessel when the catheter body 12 is inserted into the blood vessel. Note that the reinforcing member 32 may be provided, for example, only on the proximal end section 20 excluding the low-bonded distal section 22, or only on the second proximal end section 26. Alternatively, the reinforcing member 32 may be provided, for example, over the entire length of the catheter body 12.

[0061] A coating layer 36 is provided on the outer peripheral surface of the outer layer 18. The coating layer 36 includes a proximal coating layer 38 that covers the proximal portion 20 and a distal coating layer 40 that covers the low-adhesion distal portion 22.

[0062] The proximal coating layer 38 is, for example, a hydrophilic coating, which reduces the coefficient of friction with the inner surface of the blood vessel or the guiding catheter when it comes into contact with blood. The hydrophilic coating of the proximal coating layer 38 reduces the frictional resistance when it comes into contact with the inner surface of the blood vessel compared to the distal coating layer 40. The proximal coating layer 38 does not necessarily have to be provided over the entire length of the proximal end 20 of the catheter body 12; for example, it does not have to be provided on the proximal end side away from the portion inserted into the body.

[0063] The tip coating layer 40 is, for example, a silicone coating or a fluororesin coating, and has a lower coefficient of friction than the outer circumferential surface of the low-adhesion tip section 22, thereby improving the insertability of the catheter body 12 into blood vessels, etc. The tip coating layer 40, made of a silicone coating or a fluororesin coating, has superior low adhesion to the NBCA compared to hydrophilic coatings. Therefore, the tip portion of the catheter body 12 has low adhesion to the NBCA even if the low-adhesion tip section 22 is covered with the tip coating layer 40. Note that the tip coating layer 40 is preferably provided over the entire length of the low-adhesion tip section 22, but may also be provided partially in the longitudinal direction, for example.

[0064] A hub 42 is attached to the proximal end of the catheter body 12. The hub 42 has an inner cavity (not shown) that communicates with the lumen 14 of the catheter body 12, and the lumen 14 of the catheter body 12 opens to the proximal end through the inner cavity of the hub 42. The proximal end of the hub 42 can be connected to, for example, a container of an NBCA-containing liquid or an external circuit for supplying a glucose solution to the lumen 14.

[0065] The hub 42 is formed of a hard resin. It is desirable that the hub 42 be formed of a material that is resistant to the NBCA-containing liquid, and particularly, that it be sufficiently resistant to the oil-based contrast agent lipiodol. The hub 42 is preferably formed of, for example, a polyester-based resin, such as a polyester or copolyester polymer, a polyamide, or a polypropylene. It is also desirable that the hub 42 be made of a material that exhibits low adhesion to the NBCA-containing liquid. However, since the hub 42 is not inserted into the patient's body and is not likely to adhere to blood vessels, it is not required to have as high a low adhesion property to the NBCA-containing liquid as the low-adhesion tip portion 22, and a material with lower adhesion property than the low-adhesion tip portion 22 can be used. The hub 42 is desirably transparent to transmit visible light so that the liquid flowing therethrough can be visually observed, and the material for forming the hub 42 is preferably selected taking transparency into consideration.

[0066] The cerebrovascular embolization catheter 10 having such a structure is used to treat, for example, chronic subdural hematoma, intracerebral hemorrhagic disease, intracerebral arteriovenous malformation, etc. The catheter body 12 is percutaneously inserted into a blood vessel from the patient's leg, arm, etc., and its distal end is delivered to a target site of treatment in the brain. The catheter body 12 is guided to a location near the target site of treatment, for example, by being inserted into the lumen of a guiding catheter that has been inserted into the patient's blood vessel in advance. The catheter 10 may be guided distally by blood flow, or, in addition to or instead of this, it may be pushed distally by applying an operating force from the proximal end toward the distal end.

[0067] The catheter body 12 has a coating layer 36 on its surface, which facilitates insertion of the catheter into the guiding catheter and blood vessel, even when the treatment target area is a narrow cerebral blood vessel. In particular, the proximal end coating layer 38 provided on the surface of the proximal end 20 of the catheter body 12 is a hydrophilic coating that reduces frictional resistance between the catheter and blood vessel, thereby achieving excellent insertability of the catheter into the guiding catheter and blood vessel.

[0068] The catheter main body 12 has a proximal end 20 of the outer layer 18, which is composed of a first proximal end 24 and a second proximal end 26 made of different materials, with the distal first proximal end 24 being made of a resin elastomer such as polyamide elastomer or polyurethane elastomer, and the proximal second proximal end 26 being made of a resin such as polyamide or polyurethane. As a result, the distal end of the proximal end 20 is made of a more flexible material with lower bending rigidity than the proximal end, and the proximal end 20, which does not require low adhesion to the NBCA, achieves a more highly balanced set of the pushability, kink resistance, flexibility, etc. required of the catheter main body 12, thereby achieving excellent insertability of the catheter main body 12 through a guiding catheter and a blood vessel.

[0069] The catheter 10, guided to the treatment site by the guiding catheter, discharges the NBCA-containing liquid supplied to the lumen 14 through the inner cavity of the hub 42 from the distal opening of the lumen 14 to the treatment site. When the NBCA-containing liquid is discharged distally from the lumen 14, the distal portion of the catheter body 12, including the low-adhesion distal end portion 22, desirably protrudes distally from the guiding catheter. More preferably, only the low-adhesion distal end portion 22 protrudes distally from the guiding catheter, while the proximal end portion 20 is housed within the guiding catheter. Note that, to prevent polymerization (hardening) of the NBCA within the lumen 14, it is desirable to fill the lumen 14 with a glucose solution before filling the lumen 14 with the NBCA-containing liquid.

[0070] The hub 42 of this embodiment is made of polyester resin, which has excellent low adhesion to NBCA compared to conventional polycarbonate hubs. Furthermore, the polyester resin hub 42 has excellent liquid resistance to Lipiodol, which is mixed with NBCA, and prevents cracks and the like caused by the penetration of Lipiodol.

[0071] Then, as the NBCA-containing liquid ejected from the lumen 14 toward the tip side solidifies, the blood vessel is blocked with an embolic substance, thereby restricting or stopping blood flow (such as preventing blood from flowing in or stopping bleeding) at the treatment site.

[0072] When the NBCA-containing liquid is discharged, for example, a glucose solution may be flowed through the lumen of the guiding catheter from the base end toward the tip end, and the glucose solution that has flowed between the guiding catheter and the catheter 10 may be discharged from the tip of the guiding catheter toward the periphery of the tip of the catheter 10. This flow of glucose solution makes it difficult for the NBCA-containing liquid discharged from the tip of the catheter 10 to come into contact with blood, thereby lengthening the setting time, and also prevents the NBCA-containing liquid from flowing proximally to the catheter 10 due to the blood flow, making it difficult for the NBCA-containing liquid to adhere to the catheter 10 and the guiding catheter.

[0073] The distal end portion of the outer layer 18 of the catheter body 12 is a low-adhesion tip portion 22 formed of a tungsten-containing resin elastomer, which makes it difficult for a cyanoacrylate-based embolic agent (NBCA) to adhere to the low-adhesion tip portion 22, even if the NBCA-containing liquid adheres to the catheter. This makes it easier to prevent the risk of adhesion between the blood vessel and the low-adhesion tip portion 22, and the practitioner does not need to pay excessive attention to adhesion between the blood vessel and the low-adhesion tip portion 22, allowing them to focus more on operating the catheter 10. In particular, adhesion between the catheter 10 and the blood vessel can easily lead to serious problems in cerebral blood vessel embolization. However, by employing the catheter 10 of this embodiment, in which the distal end portion of the outer layer 18 is a low-adhesion tip portion 22 made of a tungsten-containing resin elastomer that has low adhesion to NBCA, it becomes easier to use an NBCA-containing liquid in cerebral blood vessel embolization.

[0074] Furthermore, because adhesion between the blood vessel and the low-adhesion tip portion 22 of the catheter body 12 is unlikely to occur, the NBCA-containing liquid can be injected for a longer period of time than before using a single catheter 10. This reduces the number of times the catheter 10 needs to be replaced during treatment to prevent adhesion between the blood vessel and the catheter body 12, and reduces the number of catheters 10 required for the procedure, thereby reducing the economic burden on the patient and the burden on the environment, as well as shortening the treatment time.

[0075] Furthermore, since adhesion between the blood vessel and the low-adhesion distal end portion 22 by the NBCA is unlikely to occur, the time required for the NBCA to harden can be set to a sufficiently short time, which allows the NBCA to harden in a shorter time than ethylene butyl alcohol polymer (EVOH), which requires a longer time to harden, and prevents the hardened position of the NBCA from shifting due to being washed away by the blood flow before hardening.

[0076] The low-adhesion tip section 22 is located in a range of 1 cm or more, and more preferably 2 cm or more, from the tip of the catheter body 12, to which the NBCA discharged from the tip of the catheter body 12 is likely to adhere, and therefore the NBCA discharged from the tip of the catheter body 12 is less likely to adhere to the catheter body 12. Furthermore, because the low-adhesion tip section 22 is located in a range of 10 cm or less, and more preferably 5 cm or less, from the tip of the catheter body 12, it is possible to use a material that has excellent properties other than low adhesion to NBCA, such as insertability, kink resistance, and pushability, in the area where adhesion of NBCA is not expected.

[0077] To improve insertability through blood vessels and guiding catheters, the coating layer 36 covering the outer surface of the catheter body 12 includes a proximal coating layer 38 covering the proximal end 20, which is a hydrophilic coating that can be set to a lower coefficient of friction, thereby improving insertability through blood vessels and guiding catheters. Meanwhile, the distal coating layer 40 covering the low-adhesion distal end portion 22 is a silicone coating or a fluororesin coating, which has inferior insertability (low friction) to hydrophilic coatings. Both silicone coatings and fluororesin coatings are superior to hydrophilic coatings in terms of low adhesion to the NBCA, and thus can improve insertability of the catheter body 12 while maintaining the low adhesion of the low-adhesion distal end portion 22 to the NBCA, effectively preventing adhesion between the low-adhesion distal end portion 22 and blood vessels.

[0078] The inner layer 16 of the catheter body 12 is made of polytetrafluoroethylene. Therefore, the inner layer 16 of the catheter body 12 also achieves sufficiently low adhesiveness to NBCA. After the NBCA-containing liquid is ejected toward the distal end through the lumen 14 of the catheter body 12, the lumen 14 is flushed with a glucose solution, which makes it less likely that the NBCA-containing liquid will remain in the lumen 14. Furthermore, flushing the lumen 14 with a glucose solution can also prevent the NBCA-containing liquid ejected toward the distal end from returning to the lumen 14 due to, for example, being pushed back by the blood flow.

[0079] Lipiodol, which is mixed with NBCA, is less irritating to patients than dimethyl sulfoxide (DMSO), which is mixed with EVOH, making it possible to perform the procedure using local anesthesia. Therefore, the physical burden on the patient during the procedure is reduced, enabling minimally invasive treatment and a good prognosis can be expected. Furthermore, because Lipiodol has contrast properties, its location within the blood vessel can be easily confirmed under X-ray fluoroscopy, making it easy to confirm the location of hardening within the blood vessel and the degree of vascular embolization by contrast.

[0080] The test results for the surface free energy obtained in the present invention are shown in Figure 5. In this test, two types of probe liquid, water and diiodomethane, were used, and 1 μL of the probe liquid was dropped onto the surface of each specimen, and the actual measured values ​​were measured using a contact angle meter (DMo-502, manufactured by Kyowa Interface Science Co., Ltd.). The surface free energy of each specimen was determined by analyzing the measured values ​​according to the known Kaelble-Uy theory.

[0081] The surface free energy test results shown in Figure 5 demonstrate that adding tungsten powder to the resin material of the outer layer reduces the surface free energy. Furthermore, polyester elastomer is particularly suitable as the resin material for the outer layer, as its surface free energy is lower than that of polyamide elastomers. Furthermore, by using a specific resin material, polyester elastomer, and adding tungsten powder to the outer layer, it is possible to reduce the surface free energy to a value close to that of PTFE, although not quite.

[0082] Although the surface free energy values ​​obtained by the test contain a certain degree of error, the inventors have also separately conducted adhesion / peel tests between each resin material and NBCA, and have confirmed from the results of these adhesion / peel tests that the measured surface free energy values ​​shown in Figure 5 above are appropriate as an indication of adhesion or low adhesion with NBCA.

[0083] The inventors also conducted an adhesive strength test between the catheter body (12) and the NBCA for the examples and comparative examples of the present invention. The results are shown in Figure 6. In this test, porcine carotid arteries with approximately the same diameter, length, and other characteristics were prepared as test specimens for the examples and comparative examples. The porcine carotid arteries were filled with bovine blood, and the catheter body (12) was inserted 15 mm into the arteries. NBCA was then injected into the arteries from their tips until it overflowed. Sixty seconds after the injection of NBCA, the catheter body (12) was withdrawn from the arteries, and the force (tensile strength) required to withdraw the catheter body (12) was measured. The amount of stretch (vascular elongation) of the arteries caused by the withdrawal of the catheter body (12) was also measured. In this test, the thickness of the outer layer at the tip of the catheter was 0.08 mm, the thickness of the inner layer was 0.115 mm, and the radial thickness of the tip of the catheter body including the outer and inner layers was 0.195 mm.

[0084] In Examples 1 and 2, a catheter body (12) was used in which the low-adhesion tip section (22), including the 15 mm portion inserted into the porcine carotid artery, had an outer layer (18) formed from a material in which tungsten powder (W) was blended with Pelprene (registered trademark), a polyester elastomer, at a weight ratio of 80% to the entire material. Example 1 showed an outer layer (18) without a coating layer, while Example 2 showed an outer layer (18) with a tip coating layer (40) made of a silicon coating (Si coating) on ​​the surface of the outer layer (18). Both the catheter bodies (12) of Examples 1 and 2 had an inner layer (16) made of PTFE.

[0085] Comparative Example 1 used a catheter body (12) in which an outer layer (18) was formed from Pebax 35D (registered trademark) as a polyamide elastomer. No coating layer was provided on the surface of the outer layer (18), and the inner layer (16) was made of PTFE, as in Examples 1 and 2. Comparative Example 2 used a catheter body of a commercially available cerebrovascular embolization catheter manufactured by another company. The catheter body of Comparative Example 2, as indicated, has an outer layer made of polyamide elastomer and an inner layer made of PTFE, with a coating applied to the surface of the outer layer.

[0086] 6 shows that the catheter bodies of Examples 1 and 2, which are made of a material in which tungsten powder is blended with a polyester-based elastomer, are able to sufficiently reduce the adhesive strength of the NBCA to the blood vessel (porcine carotid artery) compared to the catheter bodies of Comparative Examples 1 and 2, which are made of a polyamide-based elastomer material. Furthermore, based on the results of numerous experiments and studies by the present inventors, the boundary (practical allowable upper limit) for adhesive strength with the NBCA is considered to be approximately 0.50 N (Newtons) in terms of tensile strength after 60 seconds.

[0087] 6, the catheter bodies (12) of Examples 1 and 2, which used the polyester elastomer Pelprene (registered trademark), were more flexible and had better passage through blood vessels than Comparative Example 1, which used the polyamide elastomer Pebax 35D (registered trademark). The influence of the presence or absence of a coating layer (36) on the surface of the outer layer (18) can be confirmed in Examples 1 and 2. However, since the main purpose of the coating layer (36) is to reduce the resistance to insertion into blood vessels and it may peel off due to friction with the blood vessels, the low adhesive strength with the NBCA, regardless of the presence or absence of the coating layer (36), is a highly commendable result.

[0088] Although the embodiments of the present invention have been described in detail above, the present invention is not limited to the specific descriptions. For example, the reinforcing member 32 is not essential to the catheter body 12. Furthermore, the reinforcing member 32 is not limited to the mesh-like member exemplified in the first embodiment, and can be formed of, for example, a spiral member, multiple ring members, a braided member, or the like.

[0089] The coating layer 36 is preferably provided to improve the insertability of the catheter body 12 through a blood vessel or a guiding catheter, but is not essential. Alternatively, for example, only the proximal coating layer 38 may be provided, and the low-adhesion distal end portion 22 may be exposed without being covered with the distal coating layer 40.

[0090] The inner layer 16, the outer layer 18, and the coating layer 36 do not need to have a constant thickness, and the thickness may vary in the longitudinal or circumferential direction. Furthermore, there are no particular limitations on the relative thicknesses or ratios between the inner layer 16, the outer layer 18, and the coating layer 36.

[0091] The catheter according to the present invention is particularly suitable for embolizing cerebral blood vessels, but is not limited to such use. It can also be used in vascular embolization of the head, chest, abdomen, lumbar region, limbs, etc. For example, it can be used to embolize abdominal blood vessels in vascular embolization of gastric varices. The catheter according to the present invention can also be applied to diseases such as vascular lesions such as aneurysms and vascular malformations, iatrogenic or traumatic breakthrough bleeding, inflammatory bleeding due to ulcers, and tumor lesions. Furthermore, the catheter according to the present invention can also be applied to venous diseases such as varicose veins. The catheter according to the present invention can also be used for embolization of body lumens other than blood vessels (including hemostasis of the lumen wall and occlusion of tears).

[0092] 10 Catheter for cerebrovascular embolization (first embodiment catheter) 12 Catheter body 14 Lumen 15 Tapered portion 16 Inner layer 18 Outer layer 20 Base end portion 22 Low-adhesion distal end portion 24 First base end portion (intermediate portion of outer layer) 26 Second base end portion (proximal end portion of outer layer) 28 Tungsten powder 32 Reinforcement body 34 Distal tip portion 36 Coating layer 38 Base end coating layer 40 Distal end coating layer 42 Hub

Claims

1. A catheter having a tubular catheter body with a lumen, the proximal end of which is connected to a hub that opens the lumen toward the proximal end, and for injecting a liquid containing a cyanoacrylate-based embolic substance into the distal end of the catheter body through the lumen, wherein the catheter body has an inner layer that provides the wall surface of the lumen and an outer layer that covers the outer periphery of the inner layer, and the outer layer at the distal end of the catheter body is formed from a resin elastomer containing tungsten powder, forming a low-adhesion distal end portion that has low adhesiveness to the liquid containing the cyanoacrylate-based embolic substance.

2. The catheter according to claim 1, wherein the resin elastomer forming the low-adhesion tip portion is a polyester elastomer.

3. A catheter having a tubular catheter body with a lumen, to the base end of which is connected a hub that opens the lumen toward the base end, for injecting a liquid containing a cyanoacrylate-based embolic substance into the distal end of the catheter body through the lumen, wherein the catheter body has an inner layer that provides the wall surface of the lumen and an outer layer that covers the outer periphery of the inner layer, and the outer layer at the distal end of the catheter body is formed from a polyester elastomer and serves as a low-adhesion distal end portion that has low adhesiveness to the liquid containing the cyanoacrylate-based embolic substance.

4. A catheter according to any one of claims 1 to 3, wherein the length of the low-adhesion tip section from the tip of the catheter body is within the range of 1 cm to 10 cm.

5. A catheter according to any one of claims 1 to 4, wherein the low-adhesion tip portion is covered with a silicone coating or a fluororesin coating.

6. A catheter according to any one of claims 1 to 5, wherein the hub is made of polyester resin.

7. A catheter according to any one of claims 1 to 6, wherein the inner layer of the catheter body is formed from polytetrafluoroethylene.

8. The catheter according to any one of claims 1 to 7, which is a catheter for embolizing cerebrovascular disease, for injecting a liquid containing a cyanoacrylate-based embolic substance into a cerebrovascular disease.

9. A catheter as described in any one of claims 1 to 8, wherein the outer layer has an outer layer intermediate portion formed of a resin elastomer on the proximal side of the low-adhesion tip portion, and an outer layer proximal end portion formed of a resin having higher deformation rigidity than the extraneous intermediate portion on the proximal side of the outer layer intermediate portion.

10. A catheter according to any one of claims 1 to 9, wherein the outer layer at the tip portion of the catheter body is formed of a polyester elastomer containing tungsten powder in a weight ratio of 30% or more to the entire material, and the thickness of the outer layer is 0.03 to 0.3 mm; the inner layer at the tip portion of the catheter body is formed of a fluororesin and the thickness of the inner layer is 0.005 to 0.025 mm; the radial thickness of the tip portion of the catheter body including the outer and inner layers is 0.035 to 0.4 mm; and the catheter according to any one of claims 1 to 9, wherein the catheter is used for cerebrovascular embolization using a cyanoacrylate-based embolic substance.

Images