Surgical method for delivering chemical liquid to cardiac muscle

Abstract

To provide a surgical method using a catheter that enables delivery of a drug to a human heart.SOLUTION: In a surgical method of delivering chemical liquid to a cardiac muscle cell, a catheter 1 having a lumen 1L, a side opening OP communicating the lumen 1L with the outside, and a radiopaque marker M indicating a position of the side opening OP is inserted to at least one of a coronary artery and a coronary vein, the catheter 1 is rotated while checking the marker M such that an orientation of the side opening becomes a predetermined orientation, a puncture needle 21 is made to project from the side opening OP in a state where the side opening OP is in the predetermined orientation, thereby, the puncture needle 21 is stuck to a cardiac muscle as a treatment target portion, and chemical liquid 50 containing a cell for treatment is injected to the cardiac muscle from the puncture needle 21.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to catheter-based surgical methods that allow drug delivery to the human heart. [Background technology]

[0002] Regenerative treatment methods are known that regenerate cardiomyocytes whose function has been impaired by myocardial infarction or other conditions. For example, Japanese Patent Publication No. 5572138 discloses a treatment method in which cardiomyocytes are produced in a sheet form outside the body and then attached to the heart to promote cardiomyocyte regeneration. Because the heart is constantly beating, it is difficult to stably attach a cell sheet to the heart for an extended period of time. Therefore, a treatment method that promotes cardiomyocyte regeneration by injecting a medicinal solution into cardiomyocytes is anticipated. This treatment method will hereinafter be referred to as "medicinal solution injection therapy." In medicinal solution injection therapy, a medicinal solution to promote cardiomyocyte regeneration is injected into the myocardium through at least one of the coronary artery and coronary vein.

[0003] For example, Japanese Patent Application Laid-Open No. 2023-048291 discloses a catheter having a lumen for projecting a puncture needle and usable for drug solution injection treatment.For example, Japanese Patent Application Laid-Open No. 2004-329487 discloses a drug solution injection device having a needle-shaped tubular body and a drug solution supply means for supplying a drug solution to the needle-shaped tubular body. Summary of the Invention

[0004] In order to insert a puncture needle into the myocardium from a catheter inserted into a coronary artery or coronary vein, it is preferable to provide the catheter with a side opening through which the puncture needle can protrude. In this regard, the devices described in JP 2023-048291 A and JP 2004-329487 A have a side opening in the catheter. In drug solution injection therapy, the surgeon rotates the catheter to align the side opening of the catheter so that it faces the myocardium, and then performs puncture with the puncture needle. The devices described in JP 2023-048291 A and JP 2004-329487 A leave room for further improvement in the alignment of such side openings with the myocardium.

[0005] The present disclosure has been made to solve at least some of the above-mentioned problems, and aims to facilitate alignment of the side opening with the myocardium and improve the efficiency of the drug injection treatment procedure.

[0006] According to one aspect of the present disclosure, there is provided a surgical method for delivering a medicinal solution to cardiomyocytes, in which a catheter having a lumen, a side opening communicating with the lumen and the outside, and a radiopaque marker indicating the position of the side opening is inserted into at least one of a coronary artery and a coronary vein, the catheter is rotated while observing the marker so that the side opening is oriented in a predetermined direction, and with the side opening oriented in the predetermined direction, a puncture needle is protruded from the side opening to pierce the myocardium as a treatment target site, and a medicinal solution containing therapeutic cells is injected from the puncture needle into the myocardium. [Brief explanation of the drawings]

[0007] [Figure 1] FIG. 1 is an explanatory diagram illustrating a configuration of a medical system. [Figure 2] FIG. 2 is an explanatory view illustrating the cross-sectional configuration of a first shaft of a first catheter. [Figure 3] FIG. 3 is a cross-sectional view taken along line A1-A1 in FIG. 2. [Figure 4]FIG. 3 is a cross-sectional view taken along line A2-A2 in FIG. 2. [Figure 5] -The shape of the marker as seen from the Z-axis direction is shown. [Figure 6] -The shape of the marker as seen from the Y-axis direction. [Figure 7] The shape of the marker as seen from the +Z axis direction is shown. [Figure 8] FIG. 2 is an enlarged view of the vicinity of the marker of the first catheter 1. [Figure 9] This is an X-ray image of the marker oriented as shown in Figure 5. [Figure 10] This is an image of the marker in the orientation shown in Figure 6 under an X-ray image. [Figure 11] This is an image of the marker in the orientation shown in Figure 7 under an X-ray image. [Figure 12] FIG. 10 is an explanatory diagram showing the shape of a marker under an X-ray image. [Figure 13] FIG. 2 is a cross-sectional view of the first shaft in section SE. [Figure 14] FIG. 2 is an explanatory diagram illustrating the configuration of a second catheter. [Figure 15] FIG. 15 is a cross-sectional view taken along line B1-B1 in FIG. [Figure 16] FIG. 15 is a cross-sectional view taken along line B2-B2 in FIG. [Figure 17] FIG. 15 is a cross-sectional view taken along line B3-B3 in FIG. [Figure 18] FIG. 10 is an enlarged view of the connector of the second catheter. [Figure 19] FIG. [Figure 20] FIG. 10 is a longitudinal cross-sectional view of a connector to which a second shaft is attached. [Figure 21] FIG. 10 is a diagram illustrating a chemical solution. [Figure 22] FIG. 1 is a diagram showing the state of a heart undergoing drug solution injection therapy. [Figure 23] FIG. 10 is a view showing the first catheter delivered to the treatment target site. [Figure 24]FIG. 10 is a diagram showing the first catheter with its side opening facing the myocardium. [Figure 25] FIG. 10 shows how a balloon catheter is delivered. [Figure 26] FIG. 10 shows a state in which a stylet wire is inserted into a second catheter. [Figure 27] FIG. 10 shows how the second catheter is delivered. [Figure 28] FIG. 10 is a diagram showing the injection of a buffer solution into the second catheter. [Figure 29] FIG. 10 is a diagram showing a state in which a medicinal liquid is injected into a second catheter. [Figure 30] FIG. 10 is a diagram showing how the myocardium is punctured. [Figure 31] FIG. 10 is a diagram showing the injection of a drug solution into the myocardium. [Figure 32] FIG. 10 is a diagram illustrating a chemical solution according to a second embodiment. [Figure 33] FIG. 11 is a diagram showing the shape of a marker as viewed from the −Y-axis direction in the first catheter of the third embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0008] First Embodiment FIG. 1 is an explanatory diagram illustrating the configuration of a medical system 1000. The medical system 1000 of this embodiment includes a first catheter 1, a second catheter 2, a stylet wire 3, and a medicinal solution 50. The medical system 1000 is a system used for medicinal solution injection therapy. Medicinal solution injection therapy refers to a treatment method that promotes the regeneration of cardiomyocytes by injecting a medicinal solution containing therapeutic cells into the myocardium through at least one of a coronary artery and a coronary vein. The target site of medicinal solution injection therapy is also referred to as the "treatment target site."

[0009] For ease of explanation, Figure 1 includes some components whose relative size ratios differ from the actual size. Figure 1 also includes exaggerated views of some of the components. Figure 1 illustrates mutually orthogonal X, Y, and Z axes. The X axis corresponds to the longitudinal direction of the first catheter 1, the second catheter 2, and the stylet wire 3. The X axis is also referred to as the axial direction. The Y axis corresponds to the height direction of the first catheter 1, the second catheter 2, and the stylet wire 3. The Z axis corresponds to the width direction of the first catheter 1, the second catheter 2, and the stylet wire 3. The left side of Figure 1 is referred to as the "distal side" of each device and component, and the right side of Figure 1 is referred to as the "proximal side" of each device and component. The left side of Figure 1 is the -X axis direction. The right side of Figure 1 is the +X axis direction. Of the two longitudinal ends of each device and component, the end located closest to the distal end is referred to as the "distal end." Of the longitudinal ends of each device and each component, the end located on the base end side is called the "base end." The tip and its vicinity are called the "tip portion." The base and its vicinity are called the "base end portion." The tip side is inserted into the living body, and the base side is operated by an operator such as a doctor. These points are also common to Figure 2 and subsequent figures. In this embodiment, "same" and "equal" mean roughly the same, and allow for variations due to manufacturing errors, etc. In this embodiment, "constant" also includes roughly constant, and allow for variations due to manufacturing errors, etc.

[0010] The first catheter 1 is a catheter for delivering the second catheter 2 to the treatment site. The first catheter 1 is also called a delivery catheter. As shown in FIG. 1, the first catheter 1 includes a distal tip 11, a first shaft 12, a marker M, and a catheter connector 19. The first catheter 1 is a single-lumen catheter having only a first lumen 1L. The first catheter 1 has a side opening OP.

[0011] The distal tip 11 is provided at the distal end of the first shaft 12 and moves through the blood vessel ahead of other components. The distal tip 11 is a cylindrical component with an outer diameter that gradually decreases from the base end to the distal end. A distal opening 1a is formed at the distal end of the distal tip 11. The distal opening 1a is an opening for inserting another device into the first catheter 1. An example of another device is a delivery guide wire known as a workhorse wire.

[0012] The first shaft 12 is a tubular body having a first lumen 1L therein and an elongated outer shape. The first shaft 12 includes a distal shaft 12D and a proximal shaft 12P. A side opening OP is provided on the side surface of the distal shaft 12D. The side opening OP is a through-hole formed on the side surface of the distal shaft 12D of the first catheter 1, and is a through-hole that connects the first lumen 1L to the outside. The side opening OP is an opening through which the distal end of the second catheter 2 protrudes from the first catheter 1. The shape of the side opening OP as viewed from the -Y axis direction is approximately rectangular. Details of the side opening OP will be described later. The shape of the side opening OP as viewed from the -Y axis direction may be a shape different from the approximately rectangular shape. Examples of different shapes include a circle, a square, and a polygon. A radiopaque marker M is provided on the distal shaft 12D near the side opening OP. The marker M is a mark that allows the surgeon to confirm the orientation of the side opening OP under an X-ray image. The X-ray image is also called an angio image. The details of the marker M will be described later. A distal tip 11 is fixed to the distal end of the distal shaft 12D. A catheter connector 19 is fixed to the proximal end of the proximal shaft 12P.

[0013] The catheter connector 19 is attached to the proximal end of the first shaft 12, making it easy for the surgeon to grasp the device. The catheter connector 19 is a substantially cylindrical member provided with a pair of wings. A proximal end opening 1b is formed at the proximal end of the catheter connector 19. The proximal end opening 1b is an opening for inserting a second catheter 2 or other device into the first catheter 1. An example of such other device is a work horse wire.

[0014] As shown by dashed lines in FIG. 1, the distal tip 11, the first shaft 12, and the catheter connector 19 are formed with a first lumen 1L that connects the interiors of the respective parts along the longitudinal direction of the first catheter 1. The first lumen 1L is a lumen into which the second catheter 2 or other devices are inserted. The inner diameter Φ1L of the first lumen 1L may be determined arbitrarily as long as it is larger than the outer diameter of the second shaft 22 of the second catheter 2. The base end of the first lumen 1L communicates with the outside through a base end opening 1b. The tip of the first lumen 1L communicates with the outside through a tip opening 1a. The tip of the first lumen 1L communicates with the outside through a side opening OP.

[0015] The distal tip 11 can be formed from a flexible resin material, such as polyurethane elastomer. The distal tip 11 may also be formed from a radiopaque resin or metal material. For example, when using a radiopaque resin material, the distal tip 11 can be formed by mixing a radiopaque material such as bismuth trioxide, tungsten, or barium sulfate with polyamide resin, polyolefin resin, polyester resin, polyurethane resin, silicone resin, or fluororesin. For example, when using a radiopaque metal material, the distal tip 11 can be formed from at least one of gold, platinum, and tungsten. The distal tip 11 may also be formed from an alloy containing at least one of gold, platinum, and tungsten. The first shaft 12 and the catheter connector 19 can be formed from known materials, such as nylon resin, polyolefin, polyester, thermoplastic resin, polyamide elastomer, polyolefin elastomer, polyurethane elastomer, silicone rubber, and latex rubber. An example of a nylon resin is polyamide. Examples of polyolefins include polyethylene, polypropylene, and ethylene-propylene copolymers. Examples of polyesters include polyethylene terephthalate. Examples of thermoplastic resins include polyvinyl chloride, ethylene-vinyl acetate copolymers, cross-linked ethylene-vinyl acetate copolymers, and polyurethanes.

[0016] The second catheter 2 is a catheter for injecting a medicinal solution into the myocardium. The second catheter 2 is also called a needle catheter. As shown in FIG. 1 , the second catheter 2 includes a puncture needle 21, a second shaft 22, a needle marker 24, and a connector 29. The second catheter 2 is a single-lumen catheter having only a second lumen 2L. The puncture needle 21 is fixed to the tip of the second catheter 2.

[0017] The puncture needle 21 is a hollow puncture needle attached to the tip of the second shaft 22. The puncture needle 21 is also simply referred to as a "needle." The puncture needle 21 has an outer diameter that gradually decreases from the base end to the tip end. The tip of the puncture needle 21 has a sharp shape to facilitate puncturing body tissue. The puncture needle 21 is curved in a specific direction. In the illustrated example, the puncture needle 21 is curved in the -Y-axis direction. The inner cavity of the puncture needle 21 forms part of the second lumen 2L. A tip opening 2a is formed at the tip of the puncture needle 21. The tip opening 2a is used to project the stylet wire 3 during delivery of the second catheter 2, and is used to eject the medicinal solution during medicinal solution injection through the second catheter 2. The puncture needle 21 may be configured integrally with the second shaft 22.

[0018] The second shaft 22 is a tubular body having a second lumen 2L therein and an elongated outer shape. The second shaft 22 includes a distal shaft 22D and a distal shaft 22P. A radiopaque needle marker 24 is provided at the tip of the distal shaft 22D. The needle marker 24 is a mark that allows the surgeon to confirm the position of the puncture needle 21 under X-ray images. The needle marker 24 is annular and surrounds the entire circumference of the distal shaft 22D. The needle marker 24 may have any shape other than annular, or may be omitted. The needle marker 24 can be formed from a radiopaque resin material or metal material. The puncture needle 21 is fixed to the tip end of the distal shaft 22D. A connector 29 is fixed to the base end of the base shaft 22P.

[0019] The connector 29 is attached to the proximal end of the second shaft 22, making it easier for the surgeon to grasp the device. The connector 29 is also used when the surgeon introduces a buffer solution or a medicinal solution into the second lumen 2L. The connector 29 is a substantially cylindrical member provided with a pair of wings. Details of the connector 29 will be described later. A proximal end opening 2b is formed at the proximal end of the connector 29. The proximal end opening 2b is an opening for inserting a stylet wire 3 or other devices into the second catheter 2. An example of such other devices is a syringe. The connector 29 can be made of a well-known resin material.

[0020] As shown by the dashed lines in FIG. 1 , the puncture needle 21, the second shaft 22, and the connector 29 have a second lumen 2L formed in them along the longitudinal direction of the second catheter 2, connecting the interiors of the respective parts. The second lumen 2L is a lumen for inserting the stylet wire 3. The second lumen 2L is a lumen for circulating a buffer solution or a medicinal solution. The inner diameter Φ2L of the second lumen 2L may be determined arbitrarily as long as it is larger than the outer diameter Φ3 of the stylet wire 3. The distal end of the second lumen 2L communicates with the outside through a distal opening 2a. The proximal end of the second lumen 2L communicates with the outside through a proximal opening 2b.

[0021] The stylet wire 3 is a wire that protects the first catheter 1 and the second catheter 2 and provides rigidity to the second catheter 2 to facilitate delivery of the second catheter 2 when the medical system 1000 is in use. The stylet wire 3 includes a core wire and a coil. For convenience of illustration, the core wire and coil are omitted from FIG. 1.

[0022] The core wire is a cylindrical member having an elongated outer shape. The core wire may have a constant outer diameter, or may have an outer diameter that decreases from the proximal end to the distal end. The coil is formed by helically winding a wire. The coil is disposed so as to surround a portion of the core wire at the distal end and is fixed to the core wire. The coil may be disposed so as to surround the entire core wire from the distal end to the proximal end. The outer diameter Φ3 of the coil is defined as the outer diameter of the stylet wire 3. In this embodiment, the outer diameter Φ3 of the stylet wire 3 is the smallest inner diameter of the puncture needle 21 of the second catheter 2 minus a predetermined clearance value. The smallest inner diameter of the puncture needle 21 is the inner diameter of the tip of the puncture needle 21. In other words, the tip of the puncture needle 21 of the second catheter 2 has an inner diameter obtained by adding a predetermined clearance value to the outer diameter Φ3 of the stylet wire 3.

[0023] The core wire can be formed using at least one of a stainless steel alloy, a superelastic alloy, a piano wire, a nickel-chromium alloy, a cobalt alloy, and tungsten. Examples of stainless steel alloys include SUS302, SUS304, and SUS316. Examples of superelastic alloys include nickel-titanium. The core wire may be formed using other known materials. The coil can be formed using at least one of a stainless steel alloy, a superelastic alloy, a radiolucent alloy, and a radiopaque alloy. Examples of stainless steel alloys include SUS304 and SUS316. Examples of superelastic alloys include nickel-titanium alloys. Examples of radiolucent alloys include piano wire, a nickel-chromium alloy, and a cobalt alloy. Examples of radiopaque alloys include gold, platinum, tungsten, and alloys containing these elements. The coil may be formed using other known materials.

[0024] FIG. 2 is an explanatory diagram illustrating the cross-sectional configuration of the first shaft 12 of the first catheter 1. FIG. 2 is a longitudinal cross-sectional view of the first shaft 12 cut on the XY plane. FIG. 3 is a transverse cross-sectional view taken along line A1-A1 in FIG. 2. FIG. 4 is a transverse cross-sectional view taken along line A2-A2 in FIG. 2. In FIGS. 2 to 4, the central axis of the first catheter 1 is shown as axis O. Axis O coincides with the axis passing through the center of the first shaft 12, and this is also the case in FIG. 5 and subsequent figures. The first shaft 12 includes an inner layer 13, an outer layer 14, a coil 15, and a reinforcing body 16. The configuration of the first catheter 1 will be described in detail below.

[0025] The inner layer 13 is a long tubular body provided inside the first catheter 1. The inner layer 13 defines a first lumen 1L. The outer layer 14 is a long tubular body provided outside the inner layer 13 and covering the outer periphery of the inner layer 13. The distal ends of the inner layer 13 and the outer layer 14 are joined to the distal tip 11. The proximal ends of the inner layer 13 and the outer layer 14 are joined to a catheter connector 19. The second catheter 2 is inserted into the first lumen 1L defined by the inner layer 13. For this reason, the inner layer 13 is preferably formed from a resin material with excellent slip properties. For example, the inner layer 13 can be formed from a fluorine-based resin, polyethylene, or the like. Examples of fluorine-based resins include PTFE, PFA, and FEP. PTFE is also known as polytetrafluoroethylene. PFA is also known as tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer. FEP is also called tetrafluoroethylene-hexafluoropropylene copolymer. The inner layer 13 may be formed of known materials other than those mentioned above.

[0026] The outer layer 14 can be formed, for example, from an elastomer resin. Examples of elastomer resins include PAE, TPU, and TPEE. PAE is also called a polyamide thermoplastic elastomer. TPU is also called a polyurethane thermoplastic elastomer. TPEE is also called a polyester elastomer. The outer layer 14 may also be formed from known materials other than those mentioned above.

[0027] In the proximal shaft 12P, the coil 15 is embedded in the outer layer 14 and covers the inner layer 13. The coil 15 is a multi-filament coil formed by winding a plurality of wires in multiple strands. The reinforcing body 16 includes wires and, like the coil 15, is embedded in the outer layer 14 and covers the coil 15. The reinforcing body 16 is a braided body in which wires are woven into a mesh. The reinforcing body 16 is a metal reinforcing body. The distal shaft 12D does not include the coil 15. In the distal shaft 12D, the reinforcing body 16 is embedded in the outer layer 14 and covers the inner layer 13. That is, the reinforcing body 16 is embedded inside both the side surfaces of the proximal shaft 12P and the distal shaft 12D.

[0028] The coil 15 can be formed from, for example, a stainless steel alloy, a superelastic alloy, a piano wire, a radiolucent alloy, a radiopaque alloy, or other known materials. Examples of stainless steel alloys include SUS304 and SUS316. Examples of superelastic alloys include a nickel-titanium alloy. Examples of radiolucent alloys include a nickel-chromium alloy and a cobalt alloy. Examples of radiopaque alloys include gold, platinum, tungsten, and alloys containing these elements. The coil 15 may be a single-strand coil formed by winding a single wire. The coil 15 may also be a single-strand stranded coil formed by winding a single strand of a twisted wire obtained by twisting multiple wires together. The coil 15 may also be a multi-strand stranded coil formed by using multiple twisted wires formed by twisting multiple wires together and winding each twisted wire multiple times.

[0029] The wires constituting the reinforcing member 16 can be made of a metal material. Examples of metal materials include stainless steel alloys, nickel-titanium alloys, and radiopaque alloys. The wires constituting the reinforcing member 16 may also be made of other known metal materials. Examples of stainless steel alloys include SUS304. Examples of radiopaque alloys include gold, platinum, tungsten, and alloys containing these elements.

[0030] 5 to 8 are enlarged views of the vicinity of the marker M of the first catheter 1. FIG. 5 shows the shape of the marker M as viewed from the -Z-axis direction. FIG. 6 shows the shape of the marker M as viewed from the -Y-axis direction. FIG. 7 shows the shape of the marker M as viewed from the +Z-axis direction. FIG. 8 shows the shape of the marker M as viewed from the +Y-axis direction. In FIGS. 5 to 8, the marker M provided on the side of the distal shaft 12D is represented by dot hatching. In FIGS. 5 to 8, a portion of the marker M that is not actually visible from each viewpoint shown in each figure is represented by a two-dot chain line.

[0031] In Figures 5 and 7, the marker M is viewed from a direction perpendicular to the axis O and the opening direction of the side opening OP. Hereinafter, the direction perpendicular to the axis O and the opening direction of the side opening OP shown in Figures 5 and 7 will also be referred to as the "first direction." Figures 5 and 7 show the shape of the marker M viewed from the side in the first direction. The "opening direction" means the direction in which the opening faces. In Figure 5, the first direction is the -Z axis direction, and the opening direction is the -Y axis direction. In Figure 7, the first direction is the +Z axis direction, and the opening direction is the -Y axis direction. The shape of the marker M viewed from the side in the first direction includes a shape in which the side opening OP faces downward, as shown in Figure 5, and a shape in which the side opening OP faces upward, as shown in Figure 7. The former is also referred to as the upward first direction, and the latter is also referred to as the downward first direction.

[0032] FIG. 6 shows the shape of the marker M when viewed from the opening direction side. The opening direction is the -Y axis direction. FIG. 8 shows the shape of the marker M when viewed from the opposite side of the opening direction side. The opposite side of the opening direction side is the +Y axis direction. In FIGS. 6 and 8, the marker M is viewed from a direction that is perpendicular to the axis O and different from the first direction. Hereinafter, the direction shown in FIGS. 6 and 8 will also be referred to as the "second direction." The second direction exemplified in FIGS. 6 and 8 is a direction perpendicular to the first direction, and is the ±Y axis direction. The second direction can be any direction as long as it is perpendicular to the axis O and different from the first direction.

[0033] As shown in Figures 5 to 8, the marker M includes a first marker portion M1 and a second marker portion M2. As shown in Figure 6, the first marker portion M1 is provided on the side surface of the distal shaft 12D so as to surround the outer edge of the side opening OP. As shown in Figure 6, the shape of the side opening OP seen from the opening direction is a substantially rectangular shape with rounded corners. In other words, the shape of the side opening OP seen from the opening direction is a shape that does not include corners.

[0034] The second marker portion M2 is provided in a remaining region R, where the first marker portion M1 is not provided, among the side surfaces of a section SE in which a side opening OP is provided in the longitudinal direction of the distal-side shaft 12D. The side surface of the section SE refers to the side surface of the distal-side shaft 12D that covers the axis O in the section SE. In this embodiment, the second marker portion M2 extends in the circumferential direction of the first shaft 12 in the remaining region R. The circumferential direction refers to the direction that rotates around the axis O. In this embodiment, the second marker portion M2 extends in the circumferential direction along the YZ plane, which is a plane perpendicular to the axis O in the remaining region R. Both ends of the second marker portion M2 extending in the circumferential direction are connected to the first marker portion M1.

[0035] As shown in Figures 5 and 7, when the marker M is viewed from the first direction, the length H2 of the second marker portion M2 along the opening direction is longer than the length H1 of the first marker portion M1 along the opening direction. Figures 5 and 7 show the viewpoint when the marker M is viewed from the first direction, and the opening direction is the -Y-axis direction. As shown in Figures 5 and 7, the length H3 of the first marker portion M1 along the longitudinal direction of the first shaft 12 is longer than the length H4 of the second marker portion M2 along the longitudinal direction of the first shaft 12.

[0036] The marker M can be formed from a radiopaque resin material or metal material. For example, when using a resin material, it can be formed by mixing a radiopaque material such as bismuth trioxide, tungsten, or barium sulfate with a polyamide resin, polyolefin resin, polyester resin, polyurethane resin, silicone resin, or fluororesin. For example, when using a metal material, it can be formed from radiopaque materials such as gold, platinum, or tungsten, or alloys containing these elements. Other well-known materials may also be used, and a bonded structure combining multiple materials may also be used.

[0037] 9 to 12 are explanatory diagrams showing the shape of the marker M under an X-ray image. FIG. 9 is an image of the marker M under an X-ray image in the orientation shown in FIG. 5. FIG. 10 is an image of the marker M under an X-ray image in the orientation shown in FIG. 6. FIG. 11 is an image of the marker M under an X-ray image in the orientation shown in FIG. 7. FIG. 12 is an image of the marker M under an X-ray image in the orientation shown in FIG. 8.

[0038] 9 and 11, when viewed from the first direction, it is clearly possible to determine whether the side opening OP faces upward or downward based on the positional relationship between the first marker portion M1 and the second marker portion M2 under the X-ray image. Specifically, the orientation of the side opening OP can be determined based on whether the first marker portion M1 is located above or below the second marker portion M2 in the image. Under the X-ray image, the shape of the marker M viewed from the downward first direction shown in FIG. 9 and the shape of the marker M viewed from the upward first direction shown in FIG. 11 can be clearly distinguished. Under the second direction, it is clear to determine whether the side opening OP faces neither upward nor downward in the image based on the positional relationship between the first marker portion M1 and the second marker portion M2 under the X-ray image. Specifically, the orientation of the side opening OP can be determined by including the second marker portion M2 inside the first marker portion M1. Under an X-ray image, the shape of the marker M viewed from the first direction facing downward as shown in Fig. 9, the shape of the marker M viewed from the first direction facing upward as shown in Fig. 11, and the shape of the marker M viewed from the second direction as shown in Figs. 10 and 12 are different. Therefore, the surgeon can easily adjust the side opening OP so that it faces the treatment target site by rotating the first catheter 1 to change the shape of the marker M under an X-ray image.

[0039] FIG. 13 is a cross-sectional view of the first shaft 12 at section SE. FIG. 13 shows a cross-section of the distal shaft 12D cut along the YZ plane. As shown in FIG. 13, the first catheter 1 further includes a coating layer 17. The coating layer 17 covers the inner surface IN of the first shaft 12, which defines the side opening OP, which is a through hole. The coating layer 17 prevents the reinforcing member 16, which is embedded in the first shaft 12 around the side opening OP, from protruding from the inner surface IN. In this embodiment, the coating layer 17 is connected to the marker M. Specifically, the coating layer 17 is connected to the first marker portion M1. The coating layer 17 may be formed of, for example, the same material as the inner layer 13 or the marker M, or may be formed of any bonding agent such as an epoxy adhesive or a cyanoacrylic adhesive. The bonding material used to form the coating layer 17 is preferably the same bonding material as the bonding material used to bond the marker M to the side surface of the first shaft 12.

[0040] FIG. 14 is an explanatory diagram illustrating the configuration of the second catheter 2. FIG. 15 is a cross-sectional view taken along line B1-B1 in FIG. 14. FIG. 16 is a cross-sectional view taken along line B2-B2 in FIG. 14. FIG. 17 is a cross-sectional view taken along line B3-B3 in FIG. 14. In FIGS. 14 to 17, the center line of the second catheter 2 is shown as axis O2. Axis O2 coincides with the axis passing through the center of the second shaft 22. The configuration of the second catheter 2 will be described in detail below.

[0041] The puncture needle 21 is the portion of the second catheter 2 located closest to the tip. As shown in FIG. 14, the center of the puncture needle 21 coincides with the axis O2 at the base end of the puncture needle 21. The tip end of the puncture needle 21 is curved in a specific direction. In the illustrated example, this specific direction is the -Y-axis direction. The curved portion of the puncture needle 21 is also referred to as the curved portion. Because the puncture needle 21 has a curved portion, the center of the puncture needle 21 is inclined with respect to the axis O2 at the tip end of the puncture needle 21. The puncture needle 21 can be made of a metal with shape memory properties. Examples of metal with shape memory properties include a nickel-titanium alloy and a CuZnAl alloy. The puncture needle 21 is provided in a section S21 from the tip of the puncture needle to the tip of the needle marker 24.

[0042] The distal shaft 22D is a portion located closer to the base end than the puncture needle 21, in other words, between the puncture needle 21 and the proximal shaft 22P. As shown in FIG. 16 , the distal shaft 22D has a coil 221 and a tube 222.

[0043] The tube 222 maintains the liquid-tightness of the second lumen 2L of the second catheter 2. The tube 222 is a tubular body having an elongated outer shape. The distal end of the tube 222 is joined to the proximal end of the puncture needle 21. The proximal end of the tube 222 is joined to the distal end of the connector 29. For joining, metal solder or an adhesive such as an epoxy adhesive or a cyanoacrylic adhesive can be used. The tube 222 can be made of a resin with excellent chemical resistance, for example, a polyimide resin.

[0044] The coil 221 provides a predetermined rigidity and flexibility to the second shaft 22 of the second catheter 2. The coil 221 is provided to improve the deliverability of the second catheter 2. The coil 221 is a multi-strand coil formed by winding a plurality of wires in multiple strands. The coil 221 is arranged to surround the outer circumferential surface of the tube 222. In the illustrated example, the inner circumferential surface of the coil 221 and the outer circumferential surface of the tube 222 are in contact with each other. The distal end of the coil 221 is bonded to the tube 222 and the puncture needle 21, respectively. The proximal end of the coil 221 is bonded to the distal end of the connector 29. For bonding, an adhesive such as a metal solder, an epoxy adhesive, or a cyanoacrylic adhesive can be used. Bonding may be performed by using two or more means in combination.

[0045] The coil 221 can be formed using at least one of a stainless steel alloy, a superelastic alloy, a radiolucent alloy, and a radiopaque alloy. Examples of stainless steel alloys include SUS304 and SUS316. Examples of superelastic alloys include a nickel-titanium alloy. Examples of radiolucent alloys include piano wire, a nickel-chromium alloy, and a cobalt alloy. Examples of radiopaque alloys include gold, platinum, tungsten, and alloys containing these elements. The coil 221 may be formed using known materials other than those mentioned above. The coil 221 may be a single-strand coil formed by winding a single wire. The coil 221 may be a single-strand stranded coil formed by winding a single strand of a twisted wire obtained by twisting multiple wires together. The coil 221 may be a multi-strand stranded coil formed by winding multiple twisted wires obtained by twisting multiple wires together. As shown in FIG. 14, the distal shaft 22D is a section S22 that extends from the base end of the needle marker 24 to the boundary between the distal shaft 22D and the base shaft 22P.

[0046] The base-side shaft 22P is a portion located closer to the base end than the tip-side shaft 22D, in other words, between the tip-side shaft 22D and the connector 29. As shown in FIG. 17, the base-side shaft 22P has a shaft 231, a coil 221, and a tube 222. The coil 221 is the same member as the coil 221 described in FIG. 16. The tube 222 is the same member as the tube 222 described in FIG. 16.

[0047] The shaft 231 imparts a predetermined rigidity and torque transmission capability to the proximal shaft 22P of the second catheter 2. The shaft 231 is provided to improve the deliverability of the second catheter 2. The shaft 231 is a tubular body having an elongated outer shape. The shaft 231 is disposed so as to surround the outer circumferential surface of the coil 221. In the illustrated example, the inner circumferential surface of the shaft 231 and the outer circumferential surface of the coil 221 are in contact with each other. The distal end of the shaft 231 is joined to a portion of the coil 221. The proximal end of the shaft 231 is joined to the connector 29. For joining, an adhesive such as a metal solder, an epoxy adhesive, or a cyanoacrylic adhesive can be used. Joining may be performed by using two or more means in combination.

[0048] The shaft 231 can be made of any known material, such as a stainless steel alloy or a superelastic alloy. Examples of stainless steel alloys include SUS302, SUS304, and SUS316. Examples of superelastic alloys include nickel-titanium alloys. As shown in FIG. 14 , the proximal shaft 22P is a section S23 extending from the boundary between the distal shaft 22D and the proximal shaft 22P to the distal end of the connector 29. In the second catheter 2 of this embodiment, the length of the distal shaft 22D in the longitudinal direction is approximately equal to the length of the proximal shaft 22P.

[0049] Figure 18 is an enlarged view of the connector 29 of the second catheter 2. Figure 19 is a longitudinal cross-sectional view of the connector 29. Figure 20 is a longitudinal cross-sectional view of the connector 29 to which the second shaft 22 is attached. The configuration of the connector 29 of the second catheter 2 will be described using Figures 18 to 20. As shown in Figure 18, the connector 29 includes a first main body portion 294, a second main body portion 295, wings 296, a first flange portion 297, and a second flange portion 298.

[0050] The first main body portion 294 is a portion having a cylindrical outer shape and disposed at the most distal end of the connector 29. As shown in FIG. 18 , a wing portion 296 is provided in the central portion of the first main body portion 294. The wing portion 296 has a wing protruding in the +Y-axis direction and a wing protruding in the −Y-axis direction. The second main body portion 295 is a portion having a cylindrical outer shape and disposed closer to the proximal end than the first main body portion 294. The first flange portion 297 is a protruding portion disposed at the distal end of the second main body portion 295. As shown in FIG. 19 , the first flange portion 297 is an annular portion that protrudes outward in the circumferential direction. The second flange portion 298 is a protruding portion disposed at the proximal end of the second main body portion 295. As shown in FIG. 19 , the second flange portion 298 is an annular portion that protrudes outward in the circumferential direction. 19, first body portion 294, second body portion 295, wing portion 296, first flange portion 297, and second flange portion 298 are integrally configured. First body portion 294, second body portion 295, wing portion 296, first flange portion 297, and second flange portion 298 may each be formed as an individual member.

[0051] 19, a first through hole TH1, a second through hole TH2, and a third through hole TH3 are formed inside the connector 29 from the base end side toward the tip end side. The first through hole TH1, the second through hole TH2, and the third through hole TH3 are connected to each other. In other words, the second through hole TH2 is connected to the first through hole TH1. The third through hole TH3 is connected to the second through hole TH2.

[0052] In the illustrated example, the first through hole TH1 is a section from the base end of the first flange 297 to the base end of the second flange 298. The portion of the connector 29 where the first through hole TH1 is formed is also referred to as the base end 293. The inner diameter of the first through hole TH1 becomes slightly smaller from the base end side to the tip end side. The inner diameter of the first through hole TH1 may be constant from the base end side to the tip end side. A first medical device is inserted into the first through hole TH1. Examples of the first medical device include a first workhorse wire 5 and a syringe 8, which will be described later.

[0053] In the illustrated example, the second through hole TH2 is a section from the base end of the first main body portion 294 to the base end of the first flange portion 297. The portion of the connector 29 where the second through hole TH2 is formed is also referred to as an intermediate portion 292. The intermediate portion 292 has a first portion P1 and a second portion P2. The first portion P1 is a portion on the inner circumferential surface of the second through hole TH2 where the inner diameter of the second through hole TH2 gradually decreases from the base end toward the tip end. The second portion P2 is a portion on the inner circumferential surface of the second through hole TH2 where the inner diameter of the second through hole TH2 gradually decreases from the base end toward the tip end. The inner diameter of the second portion P2 decreases more gradually than the first portion P1. The inner diameter of the tip end of the first portion P1 is equal to the inner diameter of the base end of the second portion P2. By including the first portion P1 and the second portion P2, the second through hole TH2 has a trumpet shape facing the base end. In the illustrated example, the length of the second portion P2 in the longitudinal direction of the connector 29 is longer than the length of the first portion P1.

[0054] In the illustrated example, the third through hole TH3 is a section from the tip of the first main body portion 294 to the base end of the first main body portion 294. The portion of the connector 29 where the third through hole TH3 is formed is also referred to as a tip portion 291. The tip portion 291 has a base end portion Pa, an intermediate portion Pb, and a tip end portion Pc. The base end portion Pa is a portion of the inner circumferential surface of the third through hole TH3 that has a substantially constant inner diameter. The inner diameter of the base end of the base end portion Pa is equal to the inner diameter of the tip of the second portion P2. The intermediate portion Pb is a portion of the inner circumferential surface of the third through hole TH3 that has a substantially constant inner diameter that is larger than that of the base end portion Pa. A step is formed between the intermediate portion Pb and the base end portion Pa. The tip end portion Pc is a portion of the inner circumferential surface of the third through hole TH3 where the inner diameter of the third through hole TH3 gradually increases from the base end side toward the tip end side. The inner diameter of the base end of the distal portion Pc is equal to the inner diameter of the intermediate portion Pb. In the illustrated example, the length of the proximal portion Pa is the shortest and the length of the distal portion Pc is the longest in the longitudinal direction of the connector 29. A second medical device is inserted into the third through-hole TH3. An example of the second medical device is the second shaft 22 described in FIG. 20.

[0055] 19 , in the longitudinal direction of the connector 29, the length L292 of the intermediate portion 292 is shorter than the length L291 of the tip portion 291 and is shorter than the length L293 of the base end portion 293. The length L293 of the base end portion 293 is shorter than the length L291 of the tip portion 291. The length L293 of the base end portion 293 may be longer than the length L291 of the tip portion 291. The length L293 of the base end portion 293 and the length L291 of the tip portion 291 may be the same.

[0056] 20, the base end of the second shaft 22 is inserted into the third through-hole TH3 of the connector 29 and fixed thereto by a bonding agent 28. As a result, the first through-hole TH1 and the second through-hole TH2 form a part of the second lumen 2L of the second catheter 2.

[0057] FIG. 21 is a diagram illustrating a drug solution 50. In the example of FIG. 21, the drug solution 50 contains a single cell 52, a cell cluster 53, an organoid 54, and a low-molecular-weight compound 54-1 in a solvent 51. In the following description, "cells" refers to any of pluripotent stem cells, pluripotent stem cell-derived cells, cardiomyocytes, and mesenchymal stem cells. Pluripotent stem cells refer to cells capable of differentiating into various cells. An example of a pluripotent stem cell is an iPS cell. Pluripotent stem cell-derived cells refer to cells differentiated from pluripotent stem cells. An example of a pluripotent stem cell-derived cell is an iPS cell-derived cardiomyocyte. Cardiomyocytes refer to cells that constitute myocardium. Mesenchymal stem cells are stem cells present in the body and are capable of differentiating into cells such as bone, cartilage, blood vessels, and myocardium. Mesenchymal stem cells are also known as MSCs. Examples of the low molecular weight compound 54-1 include ONO-1301 and a sustained release formulation of ONO-1301 (YS-1402), which have both prostaglandin I2 receptor agonism and thromboxane A2 synthase inhibitory activity.

[0058] A single cell 52 is a single cell. A cell may be of a single cell type or multiple cell types. A single cell type means a single type of cell. Multiple cell types means multiple types of cells. When a single cell 52 is of a single cell type, it means that the multiple single cells 52 contained in the drug solution 50 are each of the same type of cell among the four types mentioned above (pluripotent stem cells, cells derived from pluripotent stem cells, cardiomyocytes, and mesenchymal stem cells). When a single cell 52 is of multiple cell types, it means that the multiple single cells 52 contained in the drug solution 50 are different types of cells among the four types mentioned above.

[0059] The cell cluster 53 refers to a cluster formed by the aggregation of cells. The cell cluster is also called a sphere. The cell cluster 53 may be composed of a single cell type, or may be composed of multiple cell types. When the cell cluster 53 is of a single cell type, it means that the cell cluster 53 is formed by the aggregation of cells of the same type among the four types mentioned above. When the cell cluster 53 is of multiple cell types, it means that the cell cluster 53 is formed by the aggregation of two or more different types of cells among the four types mentioned above. An example of the cell cluster 53 is a cardiomyocyte sphere.

[0060] Organoids 54 are three-dimensional structures that mimic human organs and tissues. Organoids 54 are three-dimensional structures formed by the self-organization of multiple types of single cells or cell clusters through interaction. Organoids 54 can also be described as a group of single cells or cell clusters. Organoids 54 can be composed of, for example, cardiomyocytes and mesenchymal stem cells. For example, an operator mixes cardiomyocytes and mesenchymal stem cells in a specific ratio. An operator can form organoids 54 by culturing and organizing the mixture of cardiomyocytes and mesenchymal stem cells. A close-up of organoid 54 is shown in the speech bubble in Figure 21. The outer diameter Φ54 of organoid 54 is approximately 50 μm or greater and approximately 200 μm. Organoids 54 often have a distorted spherical shape. For this reason, the outer diameter Φ54 of the organoid 54 is determined by the outer diameter of the largest part of the organoid 54.

[0061] Low molecular weight compounds are preferred that act on fibroblasts, vascular smooth muscle cells, vascular endothelial cells, etc. to promote the expression of various protective angiogenic factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1), and the compound ONO-1301 and its sustained-release formulation YS-1402 are particularly suitable.

[0062] The solvent 51 may be, for example, physiological saline or lactated Ringer's solution. The drug solution 50 may contain at least one of a single cell 52, a cell cluster 53, and an organoid 54. That is, the drug solution 50 may be configured to contain only a single cell 52 in the solvent 51. The drug solution 50 may be configured to contain only a cell cluster 53 in the solvent 51. The drug solution 50 may be configured to contain only an organoid 54 in the solvent 51. The drug solution 50 may be configured to contain only a low molecular weight compound 54-1 in the solvent 51.

[0063] In addition to the above-described components, other substances may be added to the drug solution 50. Examples of other substances include human serum albumin and radiopaque components. Examples of radiopaque components include contrast agents. If the drug solution 50 contains human serum albumin, the single cells 52, cell clusters 53, organoids 54, and low-molecular-weight compounds 54-1 can be prevented from adhering to the inner wall of the second catheter 2, thereby reducing the loss of cells and low-molecular-weight compounds. If the drug solution 50 contains human serum albumin, the shear stress on cells caused by the movement of the drug solution 50 through the second lumen 2L can be reduced. In other words, damage to the single cells 52, cell clusters 53, and organoids 54 caused by the movement of the drug solution 50 through the second lumen 2L can be reduced. Human serum albumin is also known as HSA. If the drug solution 50 contains a radiopaque component, the surgeon can confirm the injection effect using X-ray images during the drug solution injection treatment procedure. The amount of human serum albumin added to the drug solution 50 can be determined arbitrarily. The amount of radiopaque component added to the drug solution 50 can be determined arbitrarily. The amount of contrast agent added to the drug solution 50 is preferably determined taking into consideration the effects on the single cell 52, the cell cluster 53, the organoid 54, and the low molecular weight compound 54-1.

[0064] FIG. 22 is a diagram showing a heart 90 undergoing chemical solution injection therapy. Hereinafter, a surgical method for chemical solution injection therapy will be described with reference to FIGS. 22 to 31. In the following example, a case will be illustrated in which the surgeon accesses the myocardium from a coronary artery. The surgeon may also access the myocardium from a coronary vein instead of a coronary artery. This chemical solution injection therapy may be performed simultaneously with a percutaneous coronary intervention procedure, or may be performed independently. Percutaneous coronary intervention is also known as PCI.

[0065] After administering local anesthesia to the patient, the surgeon inserts a guiding catheter 4 from an artery in the wrist or groin. As shown in FIG. 22, the surgeon inserts the tip of the guiding catheter 4 into the entrance of the left coronary artery 94. The surgeon uses the guiding catheter 4 to inject contrast medium into the left coronary artery 94 and acquires an X-ray image. The surgeon checks the acquired X-ray image to confirm that there is no problem such as blockage or stenosis in the left coronary artery 94. As shown in FIG. 22, the surgeon delivers a first workhorse wire 5 to the treatment target site. The first workhorse wire 5 is delivered to the treatment target site in the left coronary artery 94 through a lumen in the guiding catheter 4.

[0066] FIG. 23 shows the first catheter 1 delivered to the treatment site. For ease of explanation, devices inside the first catheter 1 are also shown in solid lines in FIG. 23. This also applies to FIG. 24 and subsequent figures. The surgeon inserts the proximal end of the first workhorse wire 5, which is outside the body, into the first lumen 1L from the distal opening 1a of the first catheter 1. The surgeon delivers the first catheter 1 to the treatment site along the first workhorse wire 5. At this time, as shown in FIG. 23, the side opening OP of the first catheter 1 is not aligned with the myocardium 96. Therefore, the side opening OP of the first catheter 1 can face any direction.

[0067] Figure 24 is a diagram showing the first catheter 1 with its side opening OP facing the myocardium 96. After delivering the first catheter 1, the surgeon aligns the side opening OP of the first catheter 1 with the myocardium 96. Specifically, while viewing the image of the marker M under an X-ray image, the surgeon rotates the first catheter 1 using the shape of the marker M as a guide so that the side opening OP faces the myocardium 96. As a result, the side opening OP of the first catheter 1 is aligned with the myocardium 96, as shown in Figure 24.

[0068] FIG. 25 is a diagram illustrating the delivery of the balloon catheter 7. The surgeon delivers a second workhorse wire 6, which is different from the first workhorse wire 5, to the treatment site. The surgeon delivers the balloon catheter 7 along the second workhorse wire 6 to the treatment site. The balloon catheter 7 has a balloon 71 and a marker 72. The balloon 71 is a membrane-like member that expands when fluid is supplied and contracts when fluid is discharged. The marker 72 is a radiopaque marker that allows the position of the balloon 71 to be determined under X-ray imaging. While viewing the image of the marker 72 under X-ray imaging, the surgeon positions the balloon 71 at either a first position VP1 or a second position VP2. The first position VP1 is near the side opening OP of the first catheter 1 in the extension direction of the left coronary artery 94 and is located distal to the side opening OP. The second position VP2 is near the side opening OP of the first catheter 1 in the extension direction of the left coronary artery 94, and is a position closer to the proximal end than the side opening OP. In the example of FIG. 25, the balloon 71 is positioned at the first position VP1. At this point, the surgeon has not yet inflated the balloon 71. The surgeon may omit the placement procedure of the balloon catheter 7 if he / she determines that puncture assistance by the balloon catheter 7 is not necessary or that the inner diameter of the left coronary artery 94 is not sufficient for the parallel catheter placement.

[0069] FIG. 26 is a diagram showing the insertion of the stylet wire 3 into the second catheter 2. For ease of explanation, devices inside the second catheter 2 are also shown in solid lines in FIG. 26 . This also applies to FIG. 26 and subsequent figures. The surgeon inserts the stylet wire 3 into the second lumen 2L from the proximal end opening 2b of the second catheter 2 and withdraws it from the distal end opening 1a of the second catheter 2. As a result, as shown in FIG. 26 , the distal end of the stylet wire 3 protrudes from the distal end of the second catheter 2, i.e., from the distal end of the puncture needle 21. The state shown in FIG. 26 is also referred to as the inserted state of the stylet wire 3. The length by which the stylet wire 3 protrudes from the distal end of the second catheter 2 may be determined as desired. In this way, the surgeon inserts the stylet wire 3 into the second catheter 2 before inserting the second catheter 2 into the first catheter 1.

[0070] FIG. 27 shows the delivery of the second catheter 2. The surgeon inserts the second catheter 2, with the stylet wire 3 inserted therein, into the first lumen 1L from the proximal end opening 1b of the first catheter 1. The surgeon pushes the second catheter 2 through the first lumen 1L of the first catheter 1 and delivers the second catheter 2 until the tip of the second catheter 2 is located near the side opening OP of the first catheter 1. In the illustrated example, the tip of the second catheter 2 is located just before the side opening OP. The surgeon can determine the position of the tip of the second catheter 2 from the image of the puncture needle 21 in an X-ray image. As shown in FIG. 27, when the second catheter 2 is delivered, the stylet wire 3 protruding from the tip of the second catheter 2 lifts the puncture needle 21 of the second catheter 2. In other words, a gap GP is generated between the stylet wire 3 and the inner circumferential surface 12i of the first catheter 1 due to the rigidity of the stylet wire 3. The gap GP prevents the puncture needle 21 of the second catheter 2 from coming into contact with the inner circumferential surface 12i of the first catheter 1. This prevents damage to the second catheter 2 and the first catheter 1 when the second catheter 2 is delivered. As shown in FIG. 27 , the curved shape of the puncture needle 21 of the second catheter 2 is gently corrected by the insertion of the stylet wire 3 and the inner circumferential surface 12i of the first catheter 1.

[0071] FIG. 28 shows the injection of the buffer solution 60 into the second catheter 2. The left side of FIG. 28 illustrates the first catheter 1 and a portion of the second catheter 2 inside the left coronary artery 94. The right side of FIG. 28 illustrates the connector 29 of the second catheter 2 outside the body. After delivering the second catheter 2, the surgeon removes the stylet wire 3 from the second catheter 2. Specifically, the surgeon removes the stylet wire 3 from the second catheter 2 by pulling the proximal end of the stylet wire 3 outside the body toward the operator. After removing the stylet wire 3, the surgeon prepares a syringe 8a filled with the buffer solution 60. As shown in FIG. 28, the surgeon inserts the cylindrical tip 81 of the syringe 8a into the first through-hole TH1 of the connector 29 of the second catheter 2. The surgeon pushes in the plunger of the syringe 8a. This supplies the buffer solution 60 from the syringe 8a to the second lumen 2L of the second catheter 2. The operator continues to supply the buffer solution 60 until the second lumen 2L of the second catheter 2 is filled with the buffer solution 60. Any liquid can be used as the buffer solution 60. For example, physiological saline can be used as the buffer solution 60.

[0072] FIG. 29 shows the injection of the medicinal solution 50 into the second catheter 2. The left side of FIG. 29 illustrates the first catheter 1 and a portion of the second catheter 2 inside the left coronary artery 94. The right side of FIG. 29 illustrates the connector 29 of the second catheter 2 outside the body. After filling the second catheter 2 with the buffer solution 60, the surgeon removes the syringe 8a and prepares a syringe 8b filled with the medicinal solution 50. As shown in FIG. 29, the surgeon inserts the cylindrical tip 81 of the syringe 8b into the first through-hole TH1 of the connector 29 of the second catheter 2. The surgeon then pushes in the plunger of the syringe 8b. This causes the medicinal solution 50 in the syringe 8b to be supplied to the second lumen 2L of the second catheter 2. Because the second lumen 2L of the second catheter 2 is already filled with the buffer solution 60, as the medicinal solution 50 is supplied, the buffer solution 60 pushed out by the medicinal solution 50 is discharged from the distal end opening 2a of the second catheter 2. That is, the buffer solution 60 in the second lumen 2L of the second catheter 2 is replaced with the medicinal solution 50. The surgeon continues supplying the medicinal solution 50 until the buffer solution 60 in the second lumen 2L is completely replaced with the medicinal solution 50 and the second lumen 2L is filled with the medicinal solution 50.

[0073] FIG. 30 shows the process of puncturing the myocardium 96. After filling the second catheter 2 with the medicinal solution 50, the surgeon checks the marker M under an X-ray image to confirm again that the side opening OP of the first catheter 1 is facing the myocardium 96. After confirmation, the surgeon pushes the second catheter 2 in the direction of the outline arrow while fixing the position of the first catheter 1. This allows the surgeon to protrude the puncture needle 21 of the second catheter 2 from the side opening OP of the first catheter 1 and pierce the puncture needle 21 into the myocardium 96. While checking the resistance felt by the surgeon's hand due to the puncture and the image of the puncture needle 21 under an X-ray image, the surgeon pushes the tip of the puncture needle 21 to the target position within the myocardium 96. The target position is the position within the myocardium 96 into which the surgeon intends to inject the medicinal solution 50.

[0074] If the surgeon determines that puncture assistance is necessary, he or she may inflate the balloon 71 before pushing the second catheter 2. Assisted puncture assistance may be necessary when it is expected that it will be difficult to pierce the myocardium 96 with the puncture needle 21 due to resistance from the myocardium 96, or when it is expected that the puncture depth into the myocardium 96 will be insufficient. In this case, the surgeon supplies fluid for inflating the balloon 71 to the balloon catheter 7. As shown in FIG. 30 , the balloon 71 expands radially outward as the fluid is supplied. The expanded balloon 71 presses the first catheter 1 against the inner wall of the left coronary artery 94, fixing the position of the first catheter 1. As a result, the surgeon can smoothly puncture the myocardium 96 even when there is resistance from the myocardium 96.

[0075] FIG. 31 is a diagram showing the injection of the medicinal solution 50 into the myocardium 96. The left side of FIG. 31 illustrates a portion of the first catheter 1 and the second catheter 2 inside the left coronary artery 94. The right side of FIG. 31 illustrates the connector 29 of the second catheter 2 outside the body. After inserting the puncture needle 21 to the desired position, the surgeon presses the plunger 82 of the syringe 8b to inject the medicinal solution 50 into the tissue of the myocardium 96. If the medicinal solution 50 contains a radiopaque component, the surgeon can inject the medicinal solution 50 while observing the injection of the medicinal solution 50 into the myocardium 96 under an X-ray image.

[0076] After completing the injection of the medicinal solution 50, the surgeon slowly pulls the second catheter 2 toward the operator. This causes the puncture needle 21 of the second catheter 2 to be withdrawn from the myocardium 96. The surgeon then further pulls the second catheter 2 toward the operator, thereby storing the puncture needle 21 of the second catheter 2 within the first lumen 1L of the first catheter 1. At this time, it is preferable for the surgeon to position the tip of the second catheter 2 just before the side opening OP of the first catheter 1, as shown in FIG. 28. The surgeon suctions fluid from the balloon catheter 7 to deflate the balloon 71 and release the fixation of the first catheter 1.

[0077] The surgeon moves the first catheter 1 within the left coronary artery 94 and repeats the alignment described in FIG. 24 , the delivery of the balloon catheter 7 described in FIG. 25 , the puncture of the myocardium 96 described in FIG. 30 , and the injection of the medicinal solution 50 described in FIG. 31 as many times as desired. In this manner, by moving the first catheter 1 to different positions in the left coronary artery 94 and repeating the procedure, the medicinal solution 50 can be injected into different positions in the myocardium 96. The surgeon may similarly inject the medicinal solution 50 into the myocardium 96 via the right coronary artery 95. The surgeon may inject the medicinal solution 50 only through the right coronary artery 95 instead of the left coronary artery 94, or may inject the medicinal solution 50 through both the left coronary artery 94 and the right coronary artery 95.

[0078] The surgeon confirms that the injection of the drug solution 50 into the treatment target area has been completed at the predetermined location and with the predetermined amount of drug solution 50. To obtain the desired effect of drug solution injection therapy, the number of cells contained in the predetermined amount of drug solution 50 is preferably approximately 100 million or more per patient. Furthermore, to obtain the desired effect of drug solution injection therapy, the amount of the low-molecular-weight compound contained in the predetermined amount of drug solution 50 is preferably 0.03 to 0.3 mg / kg body weight per patient. After confirmation, the surgeon removes all devices except the guiding catheter 4 from the left coronary artery 94. The surgeon uses the guiding catheter 4 to inject a contrast agent into the left coronary artery 94 and obtains an X-ray image. The surgeon checks the X-ray image to confirm whether there is any leakage of blood from the left coronary artery 94. If the drug solution 50 has been injected via the right coronary artery 95, the surgeon also checks the X-ray image of the right coronary artery 95 to confirm whether there is any leakage of blood from the right coronary artery 95. If there is no leakage of blood from the left coronary artery 94 and the right coronary artery 95, the surgeon removes the guiding catheter 4 and completes the procedure.

[0079] As described above, the first catheter 1 has a radiopaque marker M indicating the position of the side opening OP. Therefore, by checking the position of the marker M under X-ray imaging, the surgeon can easily align the side opening OP with the circumferential position of the myocardium 96. The surgeon then directly injects the medicinal solution 50 containing therapeutic cells into the myocardial tissue through the puncture needle 21 protruding from the side opening OP. This improves the therapeutic effect of the medicinal solution 50 compared to administering the medicinal solution 50 by other means. This improves the efficiency of the medicinal solution injection treatment procedure. This medicinal solution injection treatment reduces the physical burden on the patient compared to surgical treatment methods, and is expected to improve the patient's quality of life (QOL) after treatment. QOL is also known as quality of life.

[0080] Puncture needles used in drug solution injection therapy often have a curved shape. This is due to the fact that the puncture needle protrudes from the coronary artery or coronary vein into the myocardium. When a puncture needle with such a curved shape is mounted on a catheter, the central axis of the catheter shifts, resulting in poor rotation control. With this method, the surgeon delivers the first catheter 1 to the treatment site, and then delivers the second catheter 2 to the treatment site within the first lumen 1L of the first catheter 1. Because the first catheter 1 does not have a puncture needle and has excellent rotation control, the surgeon can smoothly deliver the first catheter 1 to the treatment site. Because the second catheter 2 simply needs to be pushed through the first catheter 1, where a path has already been established, the surgeon can smoothly deliver the second catheter 2 to the treatment site. As a result, the efficiency of the drug solution injection therapy procedure can be further improved. Furthermore, by using the first catheter 1 and the second catheter 2 configured as separate devices, the outer diameters of the first catheter 1 and the second catheter 2 can be reduced compared to devices equipped with multi-lumen catheters. As a result, it becomes possible to insert the catheter into narrow blood vessels such as coronary arteries or coronary veins, thereby widening the scope of application of this method.

[0081] Furthermore, before inserting the second catheter 2 into the first catheter 1, the stylet wire 3 is inserted into the second catheter 2 so that the tip of the stylet wire 3 protrudes from the tip of the second catheter 2. This allows the stylet wire 3 to function as a buffer when the second catheter 2 is delivered. Specifically, the stylet wire 3 protruding from the tip of the second catheter 2 prevents the puncture needle 21 at the tip of the second catheter 2 from contacting the inner circumferential surface 12i of the first catheter 1. As a result, damage to the puncture needle 21 and the first catheter 1 can be prevented when the second catheter 2 is delivered.

[0082] Furthermore, after the second catheter 2 is delivered, the curved shape of the puncture needle 21, which had been gently curved by the insertion of the stylet wire 3, can be restored by removing the stylet wire 3 from the second catheter 2. This makes it easier for the surgeon to protrude the puncture needle 21 to the outside through the side opening OP of the first catheter 1.

[0083] Furthermore, after removing the stylet wire 3, the surgeon fills the second catheter 2 with the buffer solution 60, thereby removing air from the second lumen 2L of the second catheter 2 using the buffer solution 60. Furthermore, by pre-wetting the inside of the second lumen 2L with the buffer solution 60 and then replacing the buffer solution 60 with the medicinal solution 50, the surgeon can suppress damage to cells in the medicinal solution 50.

[0084] Furthermore, the surgeon uses the balloon catheter 7 to press the first catheter 1 against the inner wall of the blood vessel, thereby preventing the first catheter 1 from shifting when punctured with the puncture needle 21. Shifting of the first catheter 1 when puncturing means that the first catheter 1 moves in a direction away from the myocardium 96. Furthermore, the surgeon positions the balloon 71 of the balloon catheter 7 near the side opening OP but at a position that does not overlap with the side opening OP. Therefore, when puncturing, the first catheter 1 is supported by the balloon 71, and the balloon 71 can prevent the side opening OP of the first catheter 1 from being blocked by the balloon 71.

[0085] Furthermore, the drug solution 50 contains at least one of a single cell, a cell cluster, a population of single cells or cell clusters, and a low-molecular-weight compound. Furthermore, pluripotent stem cells, pluripotent stem cell-derived cells, cardiomyocytes, and mesenchymal stem cells can be used as therapeutic cells contained in the drug solution 50. Furthermore, when the drug solution 50 contains organoids, its therapeutic effect is improved. Additionally, ONO-1301 and a sustained-release formulation of ONO-1301 (YS-1402), which possess both prostaglandin I2 receptor agonism and thromboxane A2 synthase inhibitory activity, can be used as low-molecular-weight compounds contained in the drug solution 50.

[0086] Furthermore, the medical system 1000 includes the medicinal solution 50 and the puncture needle 21 for injecting the medicinal solution 50 into the myocardium, and therefore can provide a simple medical system used for medicinal solution injection therapy.

[0087] Furthermore, according to the medical system 1000, the intermediate section 292 of the connector 29 of the second catheter 2 has a first section P1 and a second section P2 in which the diameter of the second through-hole TH2 decreases from the base end to the tip end. This reduces the capacity of the second through-hole TH2, and the amount of medicinal solution 50 remaining in the second through-hole TH2 after medicinal solution injection treatment. As a result, waste of the medicinal solution 50 is reduced. The second section P2 is located closer to the tip end than the first section P1, and the diameter of the second section P2 decreases more gradually from the base end to the tip end than the first section. This allows the pressure of the medicinal solution 50 injected from the syringe 8b as the first medical device to be dispersed during injection.

[0088] Furthermore, according to the medical system 1000, the marker M of the first catheter 1 includes a first marker portion M1 that surrounds the outer edge of the side opening OP and a second marker portion M2 that is positioned differently from the first marker portion M1. Therefore, under X-ray imaging, the surgeon can easily grasp the orientation of the side opening OP by observing the change in shape of the marker M that accompanies the change in the positional relationship between the first marker portion M1 and the second marker portion M2 when the first catheter 1 is rotated around the central axis of the first shaft 12. This improves the efficiency of the procedure. Because the second marker portion M2 is located in the remaining area where the first marker portion M1 is not provided, kinking of the first catheter 1 due to stress concentration caused by the stress difference between the side opening OP and the first marker portion M1 can be suppressed on the side of the section of the first shaft 12 where the side opening OP is provided in the longitudinal direction. This improves the safety of the procedure.

[0089] Furthermore, according to the medical system 1000, when the marker M is viewed from the side in a direction perpendicular to the central axis of the first shaft 12 and the opening direction of the side opening OP under an X-ray image, the length of the first marker portion M1 along the opening direction tends to be relatively short, and may be difficult to see. According to the first catheter 1, the length of the second marker portion M2 along the opening direction is longer than the length of the first marker portion M1 along the opening direction, so the surgeon can more easily grasp the orientation of the side opening OP. As a result, the surgeon can more easily adjust the orientation of the side opening OP to the desired orientation, further improving the efficiency of the procedure.

[0090] Furthermore, according to the medical system 1000, the shape of the side opening OP of the first catheter 1 does not include any corners, which prevents the side opening OP from getting caught on the inner wall of the blood vessel when the first catheter 1 is inserted into a coronary artery or coronary vein. As a result, damage to the inner wall of the blood vessel can be prevented, further improving the safety of the procedure.

[0091] Furthermore, according to the medical system 1000, in the first catheter 1, the length of the first marker portion M1 along the longitudinal direction of the first shaft 12 is longer than the length of the second marker portion M2. This makes it easier for the surgeon to visually distinguish between the first marker portion M1 and the second marker portion M2. Furthermore, because the second marker portion M2 extends in the circumferential direction, the surgeon can more easily grasp the orientation of the side opening OP when the first catheter 1 is rotated around the central axis of the first shaft 12 under an X-ray image. Furthermore, both ends of the second marker portion M2 extending in the circumferential direction are connected to the first marker portion M1. This further reduces the occurrence of kinking in the first catheter 1 due to stress concentration caused by the stress difference between the side opening OP and the first marker portion M1 on the side surface of the section of the first shaft 12 where the side opening OP is provided in the longitudinal direction.

[0092] Second Embodiment 32 is a diagram illustrating a medicinal solution 50A according to the second embodiment. A medical system 1000A according to the second embodiment includes a medicinal solution 50A instead of the medicinal solution 50 in the configuration described in the first embodiment. The medicinal solution 50A is configured to contain only organoids 54 in a solvent 51.

[0093] As described above, the configuration of the drug solution 50A can be modified in various ways, and it may be configured to include only the organoid 54. The configuration of the organoid 54 is as described in FIG. 21. The drug solution 50A may be configured to include only the single cell 52 described in FIG. 21 in the solvent 51. The drug solution 50A may be configured to include only the cell mass 53 described in FIG. 21 in the solvent 51. The drug solution 50A may be configured to include only the low molecular weight compound 54-1 described in FIG. 21 in the solvent 51. In the second embodiment as described above, the same effects as in the first embodiment can be achieved.

[0094] <Third embodiment> 33 is a diagram showing the shape of a marker Mb in a first catheter 1B of the third embodiment as viewed from the -Y-axis direction. A medical system 1000B of the third embodiment includes a first catheter 1B instead of the first catheter 1 in the configuration described in the first embodiment. The first catheter 1B has a side opening OPb instead of the side opening OP and a marker Mb instead of the marker M in the configuration described in the first embodiment.

[0095] As shown in FIG. 33 , the shape of the side opening OPb as viewed from the opening direction side is a shape that does not include corners. Specifically, the shape of the side opening OPb as viewed from the opening direction side is a substantially parallelogram shape with rounded corners. That is, the shape of the side opening OPb as viewed from the opening direction side is asymmetric with respect to the axis O. The marker Mb includes a first marker portion Mb1 and a second marker portion M2. The first marker portion Mb1 surrounds the outer edge of the substantially parallelogram-shaped side opening OPb on the side surface of the distal end shaft 12D. That is, the first marker portion Mb1 has an asymmetric shape with respect to the axis O when the side opening OPb is viewed from the opening direction side. The second marker portion M2 extends in the circumferential direction in the remaining region R, as in the first embodiment. Both ends of the second marker portion M2 extending in the circumferential direction are connected to the first marker portion Mb1.

[0096] As described above, the configuration of the first catheter 1B can be modified in various ways, and the first marker Mb1 may have a shape that is asymmetric with respect to the axis O when the side opening OPb is viewed from the opening direction. The medical system 1000B of the third embodiment can also achieve the same effects as the first embodiment described above. According to the medical system 1000B of the third embodiment, the shape of the marker Mb viewed from the opening direction of the first catheter 1B and the shape of the marker Mb viewed from the opposite side to the opening direction are clearly different under X-ray images, allowing the surgeon to easily grasp the orientation of the side opening OPb. As a result, the surgeon can more easily adjust the orientation of the side opening OPb to the desired orientation, further improving the efficiency of the procedure.

[0097] <Modification of this embodiment> The present disclosure is not limited to the above-described embodiments, and can be implemented in various forms without departing from the spirit thereof. For example, the following modifications are also possible.

[0098] [Variation 1] In the above first to third embodiments, one example of the configuration of the medical systems 1000, 1000A, and 1000B has been shown. The configuration of the medical systems 1000, 1000A, and 1000B can be modified in various ways. For example, the stylet wire 3 may be omitted. For example, the medicinal solution 50 may be omitted. For example, the medical system 1000 may be configured to include other devices not described above. Examples of other devices include the guiding catheter 4, the balloon catheter 7, and the syringe 8.

[0099] [Variation 2] The first to third embodiments described above show one example of the configuration of the first catheters 1, 1B. The configuration of the first catheters 1, 1B can be modified in various ways. For example, the first shaft 12 is not limited to the configuration described in FIGS. 2 to 4, and various configurations can be adopted. For example, the first shaft 12 may be configured by omitting at least some of the inner layer 13, the outer layer 14, the coil 15, the reinforcing body 16, and the coating layer 17. For example, the first shaft 12 may not have a distal shaft 12D and a proximal shaft 12P, and may have the same configuration from the distal end to the proximal end. For example, the first catheter 1 may not have a marker M. For example, the marker M may be simply annular in shape without the first marker portion M1 and the second marker portion M2.

[0100] [Variation 3] In the first to third embodiments described above, one example of the configuration of the second catheter 2 has been described. The configuration of the second catheter 2 can be modified in various ways. For example, the stylet wire 3 may be omitted. For example, the medicinal solution 50 may be omitted. For example, the second shaft 22 is not limited to the configuration described in FIGS. 15 to 17 , and various configurations can be adopted. For example, the second shaft 22 may be configured by omitting at least some of the coil 221, the tube 222, and the shaft 223. For example, the second shaft 22 may not include the distal-side shaft 22D and may have the same configuration from the distal end to the proximal end. For example, the second catheter 2 may not include the needle marker 24. For example, the connector 29 of the second catheter 2 is not limited to the configuration described in FIGS. 18 to 20 . For example, the second through-hole TH2 of the connector 29 may not include the first portion P1 and the second portion P2. For example, the connector 29 may have the same configuration as the catheter connector 19 of the first catheter 1.

[0101] [Variation 4] The first to third embodiments described above show one example of a surgical method for chemical solution injection therapy. The surgical method for chemical solution injection therapy can be modified in various ways. For example, the surgeon may omit the steps of delivering the balloon catheter 7 and the second workpiece wire 6. For example, the surgeon may omit the step of inserting the stylet wire 3 into the second catheter 2. For example, the surgeon may omit the step of injecting the buffer solution 60 into the second catheter 2. For example, the surgeon may inject the buffer solution 60 or the chemical solution 50 using a device other than the syringe 8. For example, the surgeon may further perform steps not described above in the surgical method for chemical solution injection therapy. For example, the surgeon may perform a PCI procedure before the above-mentioned steps.

[0102] [Variation 5] The configurations of the first to third embodiments and the configurations of the modifications 1 to 4 may be combined as appropriate. For example, the medical system 1000 may be configured by combining the medicinal solution 50A described in the second embodiment with the first catheter 1B described in the third embodiment.

[0103] This aspect has been described above based on embodiments and modifications. The above-described embodiments of the aspect are intended to facilitate understanding of this aspect and are not intended to limit this aspect. This aspect may be modified or improved without departing from the spirit and scope of the claims, and equivalents thereof are included in this aspect. If a technical feature is not described as essential in this specification, it may be deleted as appropriate.

Claims

1. A surgical method for delivering a drug solution to cardiomyocytes, comprising: a catheter (1, 1B) having a lumen, side openings (OP, OPb) communicating the lumen with the outside, and radiopaque markers (M, Mb) indicating the positions of the side openings (OP, OPb) is inserted into at least one of a coronary artery and a coronary vein; The catheter (1, 1B) is rotated while observing the markers (M, Mb) so that the orientation of the side openings (OP, OPb) is in a predetermined orientation; With the side openings (OP, OPb) in the predetermined direction, the puncture needle (21) is protruded from the side openings (OP, OPb) to pierce the myocardium as the treatment target site; A surgical method in which a medicinal solution (50, 50A) containing therapeutic cells is injected into the myocardium through the puncture needle (21).

2. The surgical method according to claim 1, The catheter (1, 1B) is a first catheter (1, 1B), and the lumen is a first lumen (1L), The puncture needle (21) is a second catheter (2) inserted into the first lumen of the first catheter (1, 1B) and is provided at the tip of the second catheter (2) having a second lumen (2L).

3. The surgical method according to claim 2, Before inserting the second catheter (2) into the first catheter (1, 1B), a stylet wire (3) is inserted into the second lumen of the second catheter (2) and the distal end of the stylet wire (3) protrudes from the distal end of the second catheter (2); A surgical method comprising inserting the second catheter (2) with the stylet wire (3) inserted into the first lumen of the first catheter (1, 1B), and delivering the tip of the second catheter (2) within the first lumen to the vicinity of the side opening (OP, OPb) of the first catheter (1, 1B).

4. The surgical method according to claim 3, After the second catheter (2) is delivered, the stylet wire (3) is removed from the second catheter (2).

5. The surgical method according to claim 4, After the stylet wire (3) is removed, the second lumen of the second catheter (2) is filled with a buffer solution (60).

6. The surgical method according to claim 5, After filling the buffer solution (60), the medicinal solution (50, 50A) is injected into the second lumen of the second catheter (2) to replace the buffer solution (60) in the second lumen with the medicinal solution (50, 50A).

7. The surgical method according to claim 2, The distal end of the second catheter (2) protrudes from the side opening (OP, OPb) of the first catheter (1, 1B), The surgical method includes piercing the myocardium with the puncture needle of the second catheter and injecting the medicinal solution into the myocardium.

8. The surgical method according to claim 1, The surgical method includes injecting the medicinal solution (50, 50A) into the myocardium while the catheter (1, 1B) is pressed against the inner wall of the blood vessel and fixed in position by expanding the balloon (71) of the balloon catheter (7).

9. 9. The surgical method according to claim 8, A surgical method in which the balloon (71) of the balloon catheter (7) is positioned either near the side openings (OP, OPb) of the catheter (1, 1B) and closer to the distal end than the side openings (OP, OPb) in the extension direction of the blood vessel, or near the side openings (OP, OPb) of the catheter (1, 1B) and closer to the proximal end than the side openings (OP, OPb).

10. The surgical method according to claim 1, The drug solution (50, 50A) contains at least one of a single cell (52), a cell cluster (53), a group of single cells or cell clusters (54), and a low molecular weight compound (54-1); The surgical method, wherein the cells include at least one of a single cell type and multiple cell types.

11. The surgical method according to claim 10, A surgical method, wherein the cells are any of pluripotent stem cells, cells derived from pluripotent stem cells, cardiomyocytes, and mesenchymal stem cells.

Images