Balloon catheter

Abstract

Provided is a balloon catheter by which a drug layer can be easily disposed on the surface of a balloon during expansion, and the drug layer can be efficiently brought into contact with a target tissue.　The balloon catheter comprises an expandable / contractible balloon (20). The balloon (20) comprises: a balloon body section (30) having a longitudinal direction x and a radial direction y; and a drug layer (40) disposed outward of the balloon body section (30) in the radial direction y and containing a drug. In a contracted state of the balloon (20), the drug layer (40) has a raised portion (45) that is raised in the radial direction y, and the length 45t in the radial direction y from the outer surface of the balloon body section (30) to an outermost end (45A) of the raised portion (45) is at least twice the thickness 40t of the drug layer (40).

Description

Balloon catheter

[0001] The present invention relates to a balloon catheter provided with a balloon having a drug held on its surface.

[0002] Stenosis occurs in blood vessels, which are channels for blood circulation in the body, and various diseases are caused by the stagnation of blood circulation. As one method for treating such diseases, there is angioplasty in which a balloon catheter is used to expand the stenotic portion.

[0003] Among balloon catheters, there is a drug-coated balloon catheter (DCB) in which a drug is held on the surface of the balloon and the drug can be released after the balloon is delivered into the blood vessel to administer the drug to the target tissue (for example, Patent Documents 1 to 4). For example, after the expansion of the stenotic portion, the neointima of the blood vessel may proliferate excessively and restenosis may occur, but restenosis can be prevented by administering the drug to the blood vessel wall with a drug-coated balloon.

[0004] Japanese Patent Publication No. 2012-533338, Japanese Patent Publication No. 2017-515598, International Publication No. 2019 / 059347, International Publication No. 2017 / 164281

[0005] In a conventional balloon catheter, when the balloon is expanded, the drug layer cannot follow the expansion of the balloon, and there is a problem that the drug layer cannot be sufficiently arranged at the portion where the balloon contacts the target tissue. Therefore, an object of the present invention is to provide a balloon catheter in which a drug layer can be easily arranged on the surface of the balloon during expansion and the drug layer can be efficiently brought into contact with the target tissue.

[0006] The balloon catheter according to an embodiment of the present invention that has solved the above problems is as follows. [1] A balloon catheter having an expandable balloon, the balloon having a balloon main body portion having a longitudinal direction and a radial direction, and a drug layer disposed outside the balloon main body portion in the radial direction and containing a drug, in a contracted state of the balloon, the drug layer having a raised portion that bulges in the radial direction, and the length from the outer surface of the balloon main body portion in the radial direction to the outermost end of the raised portion being at least twice the thickness of the drug layer.

[0007] The balloon of the balloon catheter described above has a drug layer located on the outside of the balloon body, and when the balloon is deflated, the drug layer has a raised portion that is more than twice the height of the drug layer in the radial direction. When the balloon is expanded, this raised portion can move radially inward and spread out over the outer surface of the balloon body. As a result, it is possible to prevent areas on the outer surface of the balloon body from being devoid of the drug layer due to the drug layer not being able to follow the expansion of the balloon body when the balloon is expanded, and the drug layer can be easily placed on the outer surface of the balloon body. By applying such a balloon to target tissue, it becomes possible to efficiently deliver the drug from the drug layer to the target tissue.

[0008] The balloon catheter described above is preferably any of the following [2] to

[15] . [2] The balloon catheter according to [1], wherein the raised portion includes a crack. [3] The balloon catheter according to [1] or [2], wherein, in a plan view from the outside in the radial direction, the area of ​​the raised portion is 5% or more of the area of ​​the drug layer other than the raised portion. [4] The balloon catheter according to [3], wherein the area of ​​the raised portion is 15% or more of the area of ​​the drug layer other than the raised portion. [5] The balloon catheter according to any of [1] to [4], wherein, in the radial direction, the length from the outer surface of the balloon body to the outermost end of the raised portion is 10 μm or more and 50 μm or less. [6] The balloon catheter according to any of [1] to [5], wherein the balloon body includes a cylindrical portion and a scoring element disposed radially outward of the cylindrical portion, and the raised portion is disposed along the long axis of the scoring element. [7] The balloon catheter according to any one of [1] to [6], wherein the balloon body includes a cylindrical portion and a scoring element located radially outward of the cylindrical portion, and the raised portion is located along the short axis of the scoring element. [8] The balloon catheter according to any one of [1] to [7], wherein the balloon body has a folded portion when deflated, and the raised portion is located in the recess of the folded portion. [9] The balloon catheter according to any one of [1] to [8], wherein the balloon body includes an expandable portion, and the expandable portion has a straight tube portion and tapered portions located distally and proximal to the straight tube portion and having a reduced diameter, wherein in the radial direction, the length from the outer surface of the balloon body in the straight tube portion to the outermost end of the raised portion is longer than the length from the outer surface of the balloon body in the tapered portion to the outermost end of the raised portion.

[10] The balloon catheter according to any one of [1] to [9], wherein the balloon has a contact area in which the outer surface of the balloon body is in contact with the drug layer and a gap in which the outer surface of the balloon body is separated from the drug layer.

[11] The balloon catheter according to any one of [1] to

[10] , wherein the drug layer comprises a plurality of elongated crystals of the drug.

[12] The balloon catheter according to

[11] , wherein the drug layer comprises a group of crystals in which each of the plurality of elongated crystals is arranged radially and each of the plurality of elongated crystals has a bonding portion to which they are bonded together.

[13] The balloon catheter according to any one of [1] to

[12] , wherein the drug is paclitaxel.

[14] The balloon catheter according to any one of [1] to

[13] , further comprising a protective layer on the radially outer side of the drug layer.

[15] The balloon catheter according to

[14] , wherein the protective layer is located on the radially outer side of the raised portion.

[0009] The above balloon catheter prevents areas on the outer surface of the balloon body from being covered by the drug layer due to the balloon's expansion not being able to follow the balloon's expansion, thus allowing the drug layer to be easily positioned on the outer surface of the balloon body. By applying such a balloon to target tissue, a balloon catheter can be provided that allows for efficient delivery of the drug from the drug layer to the target tissue.

[0010] This is a side view of a balloon catheter according to one embodiment of the present invention. This is a cross-sectional view along the line II-II in Figure 1. This is a cross-sectional view perpendicular to the longitudinal direction in the contracted state of the balloon catheter of Figure 1. This is a partially enlarged view of the longitudinal cross-section in the contracted state of the balloon according to one embodiment of the present invention. This is an SEM image of the balloon according to one embodiment of the present invention observed from the radial outside. This is a partially enlarged cross-sectional view showing a modified example of the balloon of Figure 4. This is an SEM image of the balloon according to another embodiment of the present invention observed from the radial outside. This is a perspective view of the balloon according to yet another embodiment of the present invention in the expanded state. This is a cross-sectional view along the line IX-IX in Figure 8. This is a perspective view of a scoring element according to one embodiment of the present invention. This is a partially enlarged view of the longitudinal cross-section of the flat portion of the drug layer according to one embodiment of the present invention. This is an SEM image of the balloon according to yet another embodiment of the present invention observed from the radial outside. This is a partially enlarged cross-sectional view showing the state when a water-soluble additive is applied to the outer surface of the balloon body during the manufacturing process of a balloon catheter according to one embodiment of the present invention. This is an SEM image of the balloon body observed from the radial outside when a water-soluble additive is applied to the outer surface of the balloon body during the manufacturing process of a balloon catheter according to one embodiment of the present invention. This is a partially enlarged cross-sectional view showing the state when a solution containing the drug is applied to the outer surface of the balloon body in Figure 13. This is a partially enlarged cross-sectional view showing the state when the nucleus of the water-soluble additive is removed from the state in Figure 15. This is a partially enlarged cross-sectional view showing another modified example of the balloon in Figure 4. This is a partially enlarged cross-sectional view showing yet another modified example of the balloon in Figure 4. This is a partially enlarged cross-sectional view showing a modified example of the balloon in Figure 11.

[0011] The present invention will be described below based on embodiments, but the present invention is not limited to the embodiments described below, and it is certainly possible to implement it with appropriate modifications within the scope that is consistent with the spirit of the preceding and following descriptions, and all such modifications are included within the technical scope of the present invention. In addition, hatching and component reference numerals may be omitted in the drawings for convenience, in which case please refer to the specification or other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority has been given to helping to understand the features of the present invention.

[0012] An example of the configuration of a balloon catheter according to an embodiment of the present invention will be described with reference to the drawings. Figure 1 is a side view of a balloon catheter according to one embodiment of the present invention. Figure 1 shows the balloon in an expanded state. Figure 2 is a cross-sectional view along the line II-II in Figure 1, i.e., a cross-sectional view perpendicular to the longitudinal direction. Figure 3 is a cross-sectional view perpendicular to the longitudinal direction of the balloon catheter of Figure 1 in a deflated state. Figure 4 is a partially enlarged view of the longitudinal cross-section of the balloon according to one embodiment of the present invention in a deflated state, showing the configuration of the balloon membrane. Figure 5 is an SEM image of the balloon according to one embodiment of the present invention observed from the radial outside. Figure 6 is a partially enlarged cross-sectional view showing a modified example of the balloon of Figure 4, showing a configuration in which the raised portion includes a crack. Figure 7 is an SEM image of the balloon according to another embodiment of the present invention observed from the radial outside. Figure 8 is a perspective view of the balloon in an expanded state according to yet another embodiment of the present invention, showing the expanded state of a balloon having a scoring element. Figure 9 is a cross-sectional view along the line IX-IX in Figure 8, i.e., a cross-sectional view perpendicular to the longitudinal direction. Figure 10 is a perspective view of a scoring element according to one embodiment of the present invention, showing a configuration in which the scoring elements are intermittently arranged in the longitudinal direction. Figure 11 is a partially enlarged view of a longitudinal cross-section of a flat portion of the drug layer according to one embodiment of the present invention, showing the structure of the balloon membrane at an even more microscopic level than in Figure 4. Figure 12 is an SEM photograph of a balloon according to yet another embodiment of the present invention, observed from the radial outside. In Figure 12, the observation magnification is high, and columnar crystals and crystal clusters are observed. Figure 13 is a partially enlarged cross-sectional view showing the state when a water-soluble additive is applied to the outer surface of the balloon body during the manufacturing process of a balloon catheter according to one embodiment of the present invention. Figure 14 is an SEM photograph of the balloon body observed from the radial outside when a water-soluble additive is applied to the outer surface of the balloon body during the manufacturing process of a balloon catheter according to one embodiment of the present invention. Figure 15 is a partially enlarged cross-sectional view showing the state when a solution containing a drug is further applied to the outer surface of the balloon body in Figure 13. Figure 16 is a partially enlarged cross-sectional view showing the state when the nuclei of the water-soluble additive are removed from the state in Figure 15.Figure 17 is a partially enlarged cross-sectional view showing another modification of the balloon in Figure 4, representing a configuration in which a protective layer is placed outside the drug layer. Figure 18 is a partially enlarged cross-sectional view showing yet another modification of the balloon in Figure 4, representing a configuration in which a protective layer is placed to cover the cracks in the raised portion. Figure 19 is a partially enlarged cross-sectional view showing a modification of the balloon in Figure 11, representing a configuration in which a protective layer is placed across adjacent crystal groups.

[0013] As shown in Figure 1, the balloon catheter 100 has a shaft 10 and a balloon 20 provided on the outside of the shaft 10. The balloon catheter 100 has a proximal end and a distal end, with the balloon 20 provided at the distal end of the shaft 10. The proximal end of the balloon catheter 100 refers to the direction toward the user's proximal end in the direction of extension of the balloon catheter 100 from the proximal end to the distal end, and the distal end refers to the opposite direction from the proximal end, i.e., the direction toward the treatment target. Each component or part of the balloon catheter 100 similarly has a proximal end and a distal end.

[0014] The balloon 20 has a balloon body 30. Preferably, the balloon body 30 is formed in a bag shape with openings on the proximal and distal sides. The balloon body 30 is the part that expands and contracts when fluid is supplied to or discharged from inside through the shaft 10, and is formed from a resin film to constitute the basic shape of the balloon 20. Fluid can be supplied or discharged using an indeflerator (a pressure regulator for balloons). The fluid may be a pressurized fluid pressurized by a pump or the like.

[0015] The resin film forming the balloon body 30 and the drug layer 40, which will be described later and is placed on the resin film, are sometimes collectively referred to as the balloon membrane.

[0016] The balloon body 30 has a longitudinal direction x, a radial direction y, and a circumferential direction z. The longitudinal direction x of the balloon body 30 refers to the direction extending from the proximal side to the distal side of the balloon body 30. The radial direction y of the balloon body 30 refers to the direction from the centroid of the outer edge of the balloon body 30 toward the outer edge in a plane perpendicular to the longitudinal direction x. The inner side of the radial direction y refers to the direction from the outer edge toward the centroid, and the outer side of the radial direction y refers to the direction from the outer edge toward the opposite side of the centroid. The circumferential direction z of the balloon body 30 refers to the direction along the outer edge of the balloon body 30 in a plane perpendicular to the longitudinal direction x.

[0017] The balloon catheter 100 and the other components and parts of the balloon catheter 100 besides the balloon body 30 each have a longitudinal direction, a radial direction, and a circumferential direction. The longitudinal direction, radial direction, and circumferential direction of these components and parts may coincide with the longitudinal direction x, radial direction y, and circumferential direction z of the balloon body 30, or they may be different. For the sake of clarity, in this specification, it will be explained that the longitudinal direction, radial direction, and circumferential direction of all components and parts coincide with the longitudinal direction x, radial direction y, and circumferential direction z of the balloon body 30, respectively.

[0018] When each member or part is divided into two equal parts along its longitudinal direction x, the distal portion is called the distal part of the member or part, and the proximal portion is called the proximal part of the member or part. The distal end of each member or part is the end located furthest distal to the member or part. The proximal end of each member or part is the end located furthest proximal to the member or part. The end of each member or part refers to the end of the member or part and its surrounding area. That is, the distal end of each member or part refers to the distal end of the member or part and its surrounding area, and the proximal end of each member or part refers to the proximal end of the member or part and its surrounding area.

[0019] Preferably, the balloon 20 is in a contracted state as shown in Figure 3 during transport to the lesion, and expands to an expanded state as shown in Figure 2 when it reaches the lesion. The contracted state of the balloon 20 reduces its radial y-size, thereby improving its ease of insertion into the body cavity. The balloon 20 may also have a folded portion 33 formed by folding the inner surface of the balloon body 30 inward. When the balloon 20 expands upon reaching the lesion, its radial y-size increases, allowing the drug layer 40, described later, located on the surface of the balloon 20, to come into contact with the lesion.

[0020] As shown in Figure 1, it is preferable that the balloon 20 has an expandable portion 22, a proximal sleeve portion 21 located proximal to the expandable portion 22, and a distal sleeve portion 23 located distal to the expandable portion 22 in the longitudinal direction x. It is preferable that the expandable portion 22 expands and contracts with the supply and discharge of fluid, while the proximal sleeve portion 21 and distal sleeve portion 23 do not expand or contract with the supply and discharge of fluid. This makes it easier to fix the proximal sleeve portion 21 and distal sleeve portion 23 to the shaft 10.

[0021] The size of the balloon 20 is not particularly limited. For example, the length x in the longitudinal direction can be set to 4 mm to 400 mm, and the outer diameter of the expandable portion 22 can be set to 1 mm to 30 mm as appropriate.

[0022] The thickness of the balloon body 30 can be set appropriately according to the application, required expansion pressure, flexibility, etc. For example, the thickness of the balloon body 30 can be 5 μm or more, 10 μm or more, 15 μm or more, or 100 μm or less, 50 μm or less, or 30 μm or less.

[0023] The balloon body 30 is preferably made of a resin, and more preferably a thermoplastic resin. This makes it easy to manufacture the balloon body 30 by molding. Examples of resins that make up the balloon body 30 include polyolefin resins such as polyethylene, polypropylene, and ethylene-propylene copolymer; polyester resins such as polyethylene terephthalate and polyester elastomer; polyurethane resins such as polyurethane and polyurethane elastomer; polyamide resins such as polyphenylene sulfide resin, polyamide, and polyamide elastomer; fluororesin, silicone resin, and natural rubber such as latex rubber. These may be used alone or in combination of two or more. Among these, polyamide resins, polyester resins, and polyurethane resins are preferably used. In particular, it is preferable to use elastomer resins from the viewpoint of thinning the balloon body 30 and its flexibility. For example, among polyamide resins, nylon 12 and nylon 11 are suitable materials, and nylon 12 is preferably used because it can be molded relatively easily when blow molding. Furthermore, from the viewpoint of thinning the balloon body 30 and improving its flexibility, polyamide elastomers such as polyether ester amide elastomers and polyamide ether elastomers are preferably used. Among these, polyether ester amide elastomers are preferably used because they have high yield strength and good dimensional stability of the balloon body 30.

[0024] As shown in Figures 1 to 4, the balloon 20 is positioned radially outward from the balloon body 30 and has a drug layer 40 containing the drug.

[0025] The drug layer 40 is preferably located on the outer surface of the expandable portion 22 within the balloon body 30, and more preferably on the straight tube portion. This facilitates the administration of the drug to the target tissue by expanding the balloon body 30.

[0026] The drug contained in the drug layer 40 is not particularly limited as long as it is a pharmacologically active substance, and examples include gene therapy drugs, non-gene therapy drugs, small molecules, cells, and other drugs that are accepted as pharmaceuticals. In particular, when the balloon catheter 100 is used to suppress restenosis of blood vessels after treatment in angioplasty, anti-restenotic agents such as antiproliferative agents and immunosuppressants can be preferably used as the drug, and specifically, drugs such as paclitaxel, sirolimus (rapamycin), everolimus, and zotarolimus can be used. These drugs may be used individually or in combination of two or more. Among these, paclitaxel is preferred as the drug contained in the drug layer 40. The drug layer 40 may contain, along with the pharmacologically active substance, auxiliary agents to improve the dispersibility of the drug, its transfer to the blood vessel wall, and its storage stability. Examples of auxiliary agents include stabilizers, binders, disintegrants, moisture-proofing agents, and preservatives.

[0027] As shown in Figures 4 and 5, in the deflated state of the balloon 20, the drug layer 40 has a raised portion 45 that rises in the radial direction y, and the length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45 in the radial direction y is more than twice the thickness 40t of the drug layer 40. The raised portion 45 can also be said to rise from the outer surface of the balloon body 30 in the thickness direction of the balloon body 30. In one embodiment, preferably, the radial direction y is the thickness direction of the balloon body 30.

[0028] The raised portion 45 can move inward in the radial direction y when the balloon 20 is expanded, spreading out over the outer surface of the balloon body 30. As a result, when the balloon 20 is expanded, the drug layer 40 cannot keep up with the expansion of the balloon body 30, preventing areas on the outer surface of the balloon body 30 from being covered by the drug layer 40. This makes it easy to place the drug layer 40 on the outer surface of the balloon body 30. By applying such a balloon 20 to target tissue, it becomes possible to efficiently deliver the drug in the drug layer 40 to the target tissue.

[0029] Preferably, the raised portion 45 is formed such that, when the balloon 20 is in a contracted state, the surface area of ​​the drug layer 40 is larger than the surface area of ​​the balloon body 30. When the balloon 20 moves from the contracted state shown in Figure 3 to the expanded state shown in Figure 2, fluid is supplied into the inside of the balloon body 30, which preferably causes the folded portion 33 to expand and increase the outer diameter. At this time, since the balloon body 30 is made of the resin described above, not only does the folded portion 33 expand, but the internal pressure of the balloon body 30 increases, causing the balloon body 30 to stretch and the surface area of ​​the balloon body 30 to become larger than when it is contracted. Even in such a case, since the drug layer 40 has a raised portion 45, the raised portion 45 can spread out to the outer surface of the balloon body 30 as the balloon body 30 expands, making it easy for the drug layer 40 to follow the expansion of the balloon body 30.

[0030] Furthermore, if the contracted balloon 20 has a folded portion 33, the shape change of the balloon body 30 may differ depending on the location when it changes from the contracted state to the expanded state. Even in such cases, since the drug layer 40 has a raised portion 45, the raised portion 45 can easily spread to the outer surface of the balloon body 30 as the balloon body 30 expands, making it easy for the drug layer 40 to follow the shape change of the balloon body 30.

[0031] The length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45 in the radial direction y, i.e., the height 45t of the raised portion 45, is at least twice the thickness 40t of the drug layer 40, preferably at least 2.5 times, more preferably at least 3 times, preferably at least 10 times, more preferably at least 8 times, and even more preferably at least 6 times. Having the height 45t of the raised portion 45 within this range makes it easier for the drug layer 40 to follow the expansion of the balloon body 30 when the balloon 20 expands.

[0032] The thickness 40t of the drug layer 40 and the height 45t of the raised portion 45 can be obtained, for example, by observing a cross-section of the balloon membrane along the longitudinal direction x with a microscope such as an SEM. Preferably, the thickness 40t of the drug layer 40 is the length from the outer surface of the balloon body 30 in a flat area where the raised portion 45 does not exist in the radial direction y to the outermost end of the drug layer 40. The thickness 40t of the drug layer 40 may also be determined by measuring the length from the outer surface of the balloon body 30 to the outer end of the drug layer 40 in the radial direction y at multiple locations where the raised portion 45 does not exist, and calculating the average of these measurements. The number of multiple locations may be, for example, 10.

[0033] If the balloon body 30 has a scoring element 32, which will be described later, the drug layer 40 may be placed on the outer surface of the scoring element 32. When determining the thickness 40t of the drug layer 40 placed on the outer surface of the scoring element 32, the outer surface of the balloon body 30 in the above description can be read as the outer surface of the scoring element 32, and the length from the outer surface of the scoring element 32 to the outermost edge of the drug layer 40 can be used as the thickness 40t of the drug layer 40.

[0034] The thickness 40t of the drug layer 40 can be, for example, 2 μm or more, 3 μm or more, 5 μm or more, or 30 μm or less, 20 μm or less, or 10 μm or less.

[0035] The drug layer preferably has multiple raised portions 45. When the balloon 20 is observed in a deflated state from the outside in the radial direction y with a microscope such as an SEM, the area of ​​a 100 μm square is, i.e., 10,000 μm. ２ The number of raised portions 45 per unit area is preferably one or more, more preferably two or more, even more preferably three or more, and preferably 10 or fewer, more preferably 8 or fewer, and even more preferably 6 or fewer. Observation of the balloon 20 from the outside in the radial direction y is preferably performed at the straight tube section 22S described later, for example, at 10 locations in the straight tube section 22S at a depth of 10,000 μm. ２It is preferable to count the number of raised portions 45 per unit area and ensure that the average is within the above range. When the number of raised portions 45 per predetermined area is within the above range, the drug layer 40 can easily follow the expansion of the balloon body 30 when the balloon 20 is expanded.

[0036] Alternatively, the number of raised portions 45 may be counted by observing a cross-section of the balloon membrane in the longitudinal direction x while it is in a contracted state using a microscope such as an SEM. In this case, the number of raised portions 45 per 100 μm length is preferably one or more, more preferably two or more, even more preferably three or more, and preferably 10 or less, more preferably 8 or less, and even more preferably 6 or less. The observation of the cross-section in the longitudinal direction x is preferably performed in the straight tube section 22S described later. For example, it is preferable to count the number of raised portions 45 per 100 μm length at 10 positions spaced equally apart in the circumferential direction z of the straight tube section 22S, and for the average to be within the above range. When the number of raised portions 45 per predetermined length is within the above range, the drug layer 40 can easily follow the expansion of the balloon body section 30 when the balloon 20 is expanded.

[0037] The heights 45t of each of the multiple raised sections 45 may be the same or different from one another.

[0038] In the radial direction y, the length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45, i.e., the height 45t of the raised portion 45, is preferably 10 μm or more and 50 μm or less. 45t may also be 15 μm or more, 20 μm or more, 40 μm or less, or 30 μm or less. Having the length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45, i.e., the height 45t of the raised portion 45, within the above range makes it easier for the drug layer 40 to follow the expansion of the balloon body 30 when the balloon 20 expands.

[0039] In the portion where the raised portion 45 is formed, the drug layer 40 may float away from the outer surface of the balloon body 30, thereby forming a separation portion 46 between the outer surface of the balloon body 30 and the drug layer 40. That is, the raised portion 45 may be formed by the drug layer 40 floating away from the outer surface of the balloon body 30 and forming a separation portion 46. The formation of the separation portion 46 makes it easier for the raised portion 45 to spread across the outer surface of the balloon body 30.

[0040] Preferably, the raised portion 45 moves inward in the radial direction y as the balloon body portion 30 expands, reducing the size of the separation portion 46 and allowing the drug layer 40 to spread out and be positioned on the outer surface of the balloon body portion 30. However, a swelling substance may also be placed in the separation portion 46. If the separation portion 46 contains a swelling substance that swells when it comes into contact with blood, after the balloon 20 has been delivered to the treatment site, the balloon body portion 30 expands, blood enters the separation portion 46 and comes into contact with the swelling substance, increasing the volume of the swelling substance. This causes an outward force in the radial direction y to act on the drug layer 40, making it easier for the drug layer 40 to detach from the outer surface of the balloon body portion 30. As a result, it becomes easier to obtain a balloon catheter 100 in which the drug layer 40 can effectively migrate to the target tissue.

[0041] Examples of components of the swelling substance include a hydrophilic swelling component and a hydrophobic swelling component. As the hydrophilic swelling component, a component that absorbs water but is insoluble in water is preferable, and examples thereof include hydrophilic polymers such as polyvinylpyrrolidone, sodium poly(meth)acrylate, polyvinyl alcohol, cellulose-based polymers, gelatin, and hyaluronic acid. As the hydrophobic swelling component, a component that absorbs a hydrophobic component but is insoluble in the hydrophobic component is preferable, and examples thereof include hydrophobic polymers such as octadecyl polyacrylate, low molecular weight gelling agents such as 12-hydroxystearic acid, and N-lauroyl-L-glutamic acid α,γ-bis-n-butylamide. As the low molecular weight gelling agent, a cyclic dipeptide obtained by combining a neutral amino acid such as L-leucine and an acidic amino acid derivative such as L-glutamic acid γ-ester can also be used. Since the cyclic dipeptide has no toxicity when remaining in the body, it is preferable in terms of high safety. Examples of the method for insolubilizing the hydrophilic polymer in water and the method for insolubilizing the hydrophobic polymer in the hydrophobic component include a method using a polymer with a high molecular weight and a method of crosslinking polymers with each other.

[0042] When the swelling substance is composed of a hydrophilic swelling component, by forming the surface of the balloon main body 30 to be hydrophilic, when the drug layer 40 peels off from the surface of the balloon main body 30, the swelling substance can be made to remain on the surface of the balloon main body 30. When the swelling substance is composed of a hydrophobic swelling component, by forming the surface of the balloon main body 30 to be hydrophobic, when the drug layer 40 peels off from the surface of the balloon main body 30, the swelling substance can be made to remain on the surface of the balloon main body 30. By the swelling substance remaining on the surface of the balloon main body 30, it is possible to suppress the remaining of foreign substances in the body, such as the swelling substance falling off into the blood, for example, and inhibiting blood flow.

[0043] Examples of the method for disposing the swelling substance in the separation part 46 include, for example, in the method for forming the drug layer 40 described later, a method of disposing the swelling substance on the outer surface of the balloon main body 30 before providing the drug layer 40 on the outer surface of the balloon main body 30.

[0044] It is preferable that the raised portion 45 has a proximal end 45B that starts to be thicker than the thickness 40t of the drug layer 40 inside the radial direction y from the outermost end 45A.

[0045] The maximum width of the raised portion 45 is preferably, for example, 0.1 times or more, 0.2 times or more, 0.5 times or more of the height 45t of the raised portion 45, and 5 times or less, 3 times or less, 1 time or less. The width of the raised portion 45 can be said to be the length between the proximal ends 45B.

[0046] The length of the flat portion between adjacent raised portions 45 is preferably longer than the maximum width of the raised portion 45. Thereby, since the drug layer 40 is likely to be stably held on the outer surface of the balloon main body portion 30, it is possible to prevent the drug layer 40 from falling off the balloon main body portion 30 in an unintended situation such as during the conveyance of the balloon 20.

[0047] The drug layer 40 can be provided by applying a solution containing the drug to the outer surface of the balloon main body portion 30. Since drugs suitable for embodiments of the present invention such as paclitaxel are poorly soluble in water, it is preferable to use an organic solvent as the solvent. The organic solvent is not particularly limited, and examples thereof include tetrahydrofuran, methanol, ethanol, glycerin, acetone, dichloromethane, hexane, ethyl acetate, and the like. The concentration of the drug in the solution is preferably 0.1 to 20% by mass.

[0048] The application of the solution containing the drug may be performed by a known method such as coating with a brush, dip coating, spray coating, etc., and among them, spray coating is preferable. By spraying the solution containing the drug on the outer surface of the balloon main body portion 30, it becomes easy to grow columnar crystals 41 described later.

[0049] To form the drug layer 40 having the raised portion 45 on the outer surface of the balloon body 30, for example, the internal pressure of the balloon body 30 can be increased to expand the balloon body 30, the drug layer 40 can be placed on the outside of the balloon body 30, and then the internal pressure of the balloon body 30 can be decreased to contract the balloon body 30. Although the surface area of ​​the balloon body 30 in the contracted state is reduced compared to the expanded state, the drug layer 40 does not have the same elasticity as the balloon body 30, so there will be excess drug layer 40 due to the reduction in the surface area of ​​the balloon body 30. This excess can be formed as the raised portion 45. The internal pressure of the balloon body 30 when placing the drug layer 40 may be lower than the operating pressure of the balloon catheter 100. In this case, it is preferable to prepare a mixed solvent by mixing a highly volatile organic solvent, which is a good solvent for drugs that are poorly soluble in water, and water, which is less volatile, in any ratio, and use this as a solvent to prepare the drug solution and apply the drug to the balloon body 30. After increasing the internal pressure of the balloon body 30 to expand it, a drug solution consisting of an organic solvent / water mixture is applied to the balloon body 30. Then, when the organic solvent has evaporated but the water has not completely evaporated and remains on the balloon body 30, the internal pressure of the balloon body 30 is reduced to contract it. As a result, the water remaining on the balloon body 30 causes partial peeling of the drug layer 40 from the outer surface of the balloon body 30, making it easier to form raised portions 45.

[0050] As shown in Figures 6 and 7, the raised portion 45 may contain cracks 47. The cracks 47 relieve the stress on the drug layer 40, making it easier to stably position the drug layer 40 having the raised portion 45 on the outer surface of the balloon body 30.

[0051] Furthermore, because the crack 47 is formed, when the balloon body 30 is expanded after the balloon 20 reaches the lesion, the drug layer 40 is easily peeled off from the outer surface of the balloon body 30, allowing the drug layer 40 to be easily transferred to the target tissue.

[0052] As shown in Figure 7, cracks 47 may be formed so that the drug layer 40 separates into multiple segments. In this case, it is preferable that the segments do not overlap with each other. This makes it easier to prevent the formation of areas on the outer surface of the balloon body 30 where the drug layer 40 cannot exist, as the raised portions 45 of each segment formed by the cracks 47 spread out to the outer surface of the balloon body 30 as the balloon body 30 expands.

[0053] As shown in Figures 6 and 7, due to the formation of cracks 47 in the raised portion 45, there may be areas in the radial direction y where the drug layer 40 is not present on the outside of the balloon body 30. Even if there are areas where the drug layer 40 is not present, the raised portion 45 is present in those areas, so as the balloon body 30 expands, the raised portion 45 moves inward in the radial direction y, allowing it to spread to the outer surface of the balloon body 30. This makes it possible to efficiently transfer the drug layer 40 to the target area.

[0054] To form the drug layer 40 on the outer surface of the balloon body 30 such that the raised portion 45 contains a crack 47, for example, the internal pressure of the balloon body 30 should be increased when the drug layer 40 is placed on the outer surface of the balloon body 30. A higher internal pressure increases the degree of reduction in surface area when the internal pressure of the balloon body 30 is reduced to a contracted state after the drug layer 40 has been applied. This increase increases the stress on the drug layer 40, allowing a crack 47 to form in the raised portion 45.

[0055] In a plan view from the outside in the radial direction y, the area of ​​the raised portion 45 is preferably 5% or more of the area of ​​the drug layer 40 other than the raised portion 45. By having the area of ​​the raised portion 45 within the above range, the above effect can be achieved, which is to prevent the occurrence of areas on the outer surface of the balloon body portion 30 where the drug layer 40 cannot exist.

[0056] In a plan view from the outside in the radial direction y, it is more preferable that the area of ​​the raised portion 45 is 15% or more of the area of ​​the drug layer 40 other than the raised portion 45. This makes it easier to achieve the above effect of preventing the occurrence of areas on the outer surface of the balloon body portion 30 where the drug layer 40 cannot be present.

[0057] In a plan view from the outside in the radial direction y, the area of ​​the raised portion 45 is preferably 50% or less, more preferably 40% or less, and even more preferably 30% or less, of the area of ​​the drug layer 40 other than the raised portion 45. If the area of ​​the raised portion 45 is too large, there is a risk that the drug layer 40 may detach from the balloon body 30 in unintended situations such as during the transport of the balloon 20, but by keeping the area of ​​the raised portion 45 within the above range, unintended detachment of the drug layer 40 can be prevented.

[0058] As shown in Figure 3, the balloon body 30 has a folded portion 33 when contracted, and it is preferable that the raised portion 45 is located in a recess 34 of the folded portion 33. The recess 34 is preferably a valley fold formed when the folded portion 33 is folded so that it overlaps with the outer surface of the balloon body 30 other than the folded portion 33. Since the balloon body 30 is in a contracted state during transport of the balloon 20 to the lesion, the placement of the raised portion 45 in the recess 34 of the folded portion 33 prevents the drug layer 40 from unintentionally falling off during transport.

[0059] The number of folded portions 33 formed in the contracted state of the balloon body portion 30 may be only one. Alternatively, multiple folded portions 33 may be formed in the circumferential direction z. The number of folded portions 33 can be, for example, 2 or more, 3 or more, 4 or more, 6 or more, or 12 or less, 10 or less, or 8 or less.

[0060] Figure 3 shows a configuration in which there is a gap between the folded portion 33 and the outer surface of the balloon body portion 30 where the folded portion 33 overlaps. However, the folded portion 33 and the outer surface of the balloon body portion 30 may overlap so that they are in contact with each other.

[0061] As shown in Figures 8 and 9, the balloon body portion 30 preferably includes a cylindrical portion 31 and a scoring element 32 positioned radially outward from the cylindrical portion 31, and the raised portion 45 is positioned along the long axis 32a of the scoring element 32.

[0062] As shown in Figure 9, the scoring element 32 preferably has a base portion 32A. The base portion 32A includes the boundary between the scoring element 32 and the cylindrical portion 31, that is, the portion located furthest inward on the surface of the scoring element 32 in the radial direction y. The raised portion 45 is preferably arranged along the long axis 32a on the base portion 32A of the scoring element 32. This allows the raised portion 45 to spread to the outer surface of the balloon body portion 30 even if the boundary between the scoring element 32 and the cylindrical portion 31 extends along the long axis 32a as the balloon body portion 30 expands, making it easier for the drug layer 40 to follow the expansion of the balloon body portion 30.

[0063] As shown in Figure 9, it is preferable that the cylindrical portion 31 and the scoring element 32 are integrally molded. This facilitates the manufacturing of the balloon body portion 30. The scoring element 32 can be made of, for example, resin. If the scoring element 32 is made of resin, the balloon body portion 30 having the scoring element 32 can be manufactured by resin molding. In this case, it is preferable that the cylindrical portion 31 and the scoring element 32 are made of the same resin. Alternatively, if the resin constituting the cylindrical portion 31 and the resin constituting the scoring element 32 have a certain degree of compatibility, the cylindrical portion 31 and the scoring element 32 may be made of different resins.

[0064] Alternatively, the cylindrical portion 31 and the scoring element 32 may be separate components, and the scoring element 32 may be made of metal, or a combination of metal and resin. In this case, it is preferable that the portion of the scoring element 32 including the top is made of metal. This makes it easier to crack or cut the constricted portion with the scoring element 32 when the balloon body portion 30 is expanded. Alternatively, the entire scoring element 32 may be made of metal, or the portion of the scoring element 32 including the base portion 32A may be made of resin and the portion of the scoring element 32 including the top is made of metal. Therefore, it is preferable that the scoring element 32 is made of resin, metal, or a combination thereof.

[0065] The scoring element 32 may be provided as a single unit or as a plurality in a vertical cross-section of the balloon body 30 in the longitudinal direction x. For example, in Figures 8 and 9, the balloon body 30 has three scoring elements 32, and these multiple scoring elements 32 are arranged spaced apart in the circumferential direction z.

[0066] As shown in Figure 8, the scoring element 32 may be a ridge, and it is preferable that the major axis 32a of the scoring element 32 extends substantially parallel to the longitudinal direction x. Alternatively, the major axis 32a of the scoring element 32 may extend spirally in the longitudinal direction x.

[0067] The scoring elements 32 may be arranged continuously in the longitudinal direction x or the circumferential direction z, or they may be arranged intermittently.

[0068] As shown in Figure 10, the scoring element 32 is preferably formed intermittently in the direction of the long axis 32a so as to have a plurality of segments, and each of the plurality of segments of the scoring element 32 preferably has a short axis 32b. The balloon body portion 30 includes a cylindrical portion 31 and a scoring element 32 positioned outside the radial direction y of the cylindrical portion 31, and the raised portion 45 is preferably positioned along the short axis 32b of the scoring element 32. This allows the raised portion 45 to spread out over the outer surface of the balloon body portion 30 even if each of the plurality of segments of the scoring element 32 extends in the direction of the long axis 32a so as to expand the balloon body portion 30, making it easier for the drug layer 40 to follow the expansion of the balloon body portion 30.

[0069] As shown in Figure 8, the balloon body portion 30 includes an expandable portion 22, and the expandable portion 22 has a straight tube portion 22S and tapered portions 22T that are located distally and proximal to the straight tube portion 22S and have a reduced diameter. Preferably, in the radial direction y, the length 45t from the outer surface of the balloon body portion 30 in the straight tube portion 22S to the outermost end 45A of the raised portion 45 is longer than the length 45t from the outer surface of the balloon body portion 30 in the tapered portion 22T to the outermost end 45A of the raised portion 45.

[0070] The straight tube portion 22S is formed in a substantially cylindrical shape extending in the longitudinal direction x, with the length in the radial direction y, i.e., the outer diameter, being the largest. This makes it easier for the straight tube portion 22S, which has the largest outer diameter, to come into contact with the blood vessel wall. Preferably, the tapered portions 22T located on the distal and proximal sides of the straight tube portion 22S are formed such that their outer diameter decreases as they move away from the straight tube portion 22S. Because the tapered portions 22T are reduced in diameter, when the balloon body portion 30 is deflated, the outer diameter of the proximal and distal ends of the balloon body portion 30 is reduced, thereby reducing the step difference between the shaft 10 and the balloon body portion 30, making it easier to insert the balloon 20 into a body cavity, into the forceps channel of an endoscope, or into a delivery catheter such as a guiding catheter.

[0071] With the above configuration, when the balloon body 30 expands, the elongation of the straight tube section 22S is greater than the elongation of the tapered section 22T. Therefore, the length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45 in the straight tube section 22S, i.e., the height 45t of the raised portion 45 in the straight tube section 22S, is greater than the length 45t from the outer surface of the balloon body 30 to the outermost end 45A of the raised portion 45 in the tapered section 22T, i.e., the height 45t of the raised portion 45 in the tapered section 22T. As a result, even in the straight tube section 22S, which has a large elongation, the raised portion 45 easily spreads to the outer surface of the balloon body 30. This allows the drug layer 40 in the straight tube section 22S to easily follow the expansion of the balloon body 30.

[0072] Because the tapered portion 22T has little room for elongation, even if the height 45t of the raised portion 45 is small, the raised portion 45 can spread out over the outer surface of the balloon body 30. By ensuring that the height 45t of the raised portion 45 in the tapered portion 22T is not unnecessarily large, it is possible to prevent the drug layer 40 from unintentionally detaching from the outer surface of the balloon body 30.

[0073] As shown in Figures 11 and 12, it is preferable that the drug layer 40 contains a plurality of elongated crystals 41 of the drug. Including elongated crystals 41 in the drug layer 40 makes it easier for the drug in the elongated crystals 41 to come into contact with the target tissue.

[0074] The outer diameter of the cross-section perpendicular to the longitudinal axis of the elongated crystal 41 is, for example, 0.01 μm or more, 0.1 μm or more, 0.5 μm or more, and 5 μm or less, 3 μm or less, and 1 μm or less. Here, the outer diameter corresponds to the diameter of the circle circumscribing the shape of the cross-section perpendicular to the longitudinal axis of the elongated crystal 41.

[0075] The length of the elongated crystal 41 in the longitudinal direction is, for example, 3 μm or more, 5 μm or more, 10 μm or more, 15 μm or more, or 40 μm or less, 30 μm or less, 25 μm or less, or 20 μm or less. Preferably, the length of the elongated crystal 41 in the longitudinal direction is longer than the outer diameter of the cross section perpendicular to the longitudinal axis of the elongated crystal 41. For example, the length in the longitudinal direction may be 2 times or more, 3 times or more, 5 times or more, 10 times or more, or 200 times or less, 150 times or less, 100 times or less, or 50 times or less of the outer diameter of the cross section perpendicular to the longitudinal axis.

[0076] As shown in Figure 11, it is preferable that the drug layer 40 contains a crystal group 42 in which each of the multiple elongated crystals 41 is arranged radially and each of the multiple elongated crystals 41 has a bonding portion 42J where they are bonded to each other. Because each of the multiple elongated crystals 41 is arranged radially, some of the multiple elongated crystals 41 may extend such that the component of their longitudinal axis in the radial direction y is large. Such elongated crystals 41 can come into contact with the target tissue more easily, and in some cases can even penetrate it, thus facilitating the transfer of the drug to the target tissue.

[0077] Furthermore, because the crystal group 42 has a bonding portion 42J where each of the multiple elongated crystals 41 are bonded to one another, the crystal group 42 can exist stably as a single mass. As a result, the crystal group 42 can migrate to the target tissue as a single mass from the balloon body 30 that has been expanded at the treatment site, making it easier to administer the drug effectively. Preferably, the crystal group 42 is formed by elongated crystals 41 extending radially from the bonding portion 42J.

[0078] The drug layer 40 preferably contains a plurality of crystal groups 42, and each of the plurality of crystal groups 42 may be separated from each other, in contact with each other, overlapping with each other, or fixed to each other.

[0079] In a plan view from the outside of the balloon 20 in the radial direction y, the major axis of the crystal group 42 is preferably 10 μm or more and 80 μm or less. More preferably, the major axis of the crystal group 42 is 15 μm or more and 70 μm or less, and even more preferably 20 μm or more and 60 μm or less. The body cavity walls, such as blood vessels, which are target tissues, have minute irregularities, and the size of these irregularities is often about the same as described above. Therefore, by having the major axis of the crystal group 42 within the above range, the crystal group 42 can easily fit into the irregularities of the body cavity wall, and the crystal group 42 is less likely to fall off the body cavity wall after administration, thus enabling effective delivery of the drug to the target tissue.

[0080] The maximum length in the radial direction y in each of the multiple crystal groups 42 is, for example, 3 μm or more, 5 μm or more, 7 μm or more, and 40 μm or less, 30 μm or less, and 20 μm or less.

[0081] As shown in Figure 11, it is preferable that the balloon 20 has a contact region 42a where the outer surface of the balloon body 30 and the crystal group 42 are in contact, and a gap 42b where the outer surface of the balloon body 30 and the crystal group 42 are separated. Since the crystal group 42 is formed by the radial arrangement of a plurality of elongated crystals 41, the bottom surface of the crystal group 42 is formed on the inside in the radial direction y by the elongated crystals 41 that extend in the direction along the surface of the balloon body 30. It is preferable that a gap 42b is formed between this bottom surface and the outer surface of the balloon body 30. This makes it easier for the crystal group 42 to detach from the outer surface of the balloon body 30 when the balloon 20 delivered to the treatment site is expanded, allowing the drug to be transferred to the target tissue as a crystal group 42. As a result, the drug can be administered to the target tissue more effectively.

[0082] The maximum length of the void 42b in the radial direction y is, for example, 0.1 μm or more, 0.5 μm or more, 1 μm or more, and 5 μm or less, 4 μm or less, and 3 μm or less. The maximum length of the void 42b in the radial direction y can be measured by observing the cross-section of the balloon membrane in the longitudinal direction x with a microscope such as an SEM.

[0083] Thus, it is preferable that the void 42b is smaller than the separation portion 46 which may be formed inside the raised portion 45 in the radial direction y. The presence of a smaller void 42b and a larger separation portion 46 allows the combined effect of these two factors to make it easier for the drug layer 40 to peel off from the outer surface of the balloon body 30 when the balloon 20 expands after reaching the lesion, thereby allowing the drug layer 40 to be more easily transferred to the target tissue.

[0084] It is preferable that the void 42b is maintained as a space. This makes it easier for the drug layer 40 to peel off from the outer surface of the balloon body 30 when the balloon 20 is expanded after it has been delivered to the treatment site, and as a result, it becomes possible to release the drug from the balloon body 30 more easily and transfer it to the target tissue.

[0085] Alternatively, a swelling substance may be placed in the void 42b. If the void 42b contains a swelling substance that swells when it comes into contact with a bodily fluid, such as blood, then after the balloon 20 is delivered to the treatment site, the balloon body 30 expands, and when the bodily fluid enters the void 42b and comes into contact with the swelling substance, the volume of the swelling substance increases. As a result, an outward force in the radial direction y acts on the drug layer 40, making it easier for the drug layer 40 to peel off from the outer surface of the balloon body 30. Consequently, it becomes easier to obtain a balloon catheter 100 in which the drug layer 40 can be effectively delivered to the target tissue.

[0086] One possible method for forming the void 42b is as follows. First, prior to applying the solution containing the drug to the outer surface of the balloon body 30, a water-soluble additive is applied to the outer surface of the balloon body 30 to form nuclei 42N of the water-soluble additive, as shown in Figure 13. At this time, as shown in Figures 13 and 14, it is preferable to scatter the nuclei 42N of the water-soluble additive on the outer surface of the balloon body 30 so that the outer surface of the balloon body 30 is exposed. Examples of water-soluble additives include sugars such as glucose, salts such as potassium chloride and sodium acetate, and amino acids such as glycine. As the aqueous solvent, water or a mixed solvent of water and an organic solvent such as ethanol can be used. Note that the nuclei 42N of the water-soluble additive do not need to be aligned along the cross-section in the longitudinal direction x, i.e., at the same position in the circumferential direction z, as shown in Figure 13. In Figure 13, for clarity, the nuclei 42N of the water-soluble additive are shown as being arranged at the same position in the circumferential direction z.

[0087] Next, as shown in Figure 15, a solution containing the above-described drug is applied to the outer surface of the balloon body 30 on which the water-soluble additive nuclei 42N are located to form a drug layer 40. Subsequently, the water-soluble additive nuclei 42N are removed with an aqueous solvent, so that the area where the water-soluble additive nuclei 42N were located is formed as a void 42b, as shown in Figure 16.

[0088] The water-soluble additive is preferably applied by spray coating. This makes it easy to distribute the nuclei 42N of the water-soluble additive on the outer surface of the balloon body 30.

[0089] The removal of the nuclei 42N of the water-soluble additive can be carried out, for example, by immersing the outer surface of the balloon body 30 on which the crystal group 42 is formed in water. To increase the solubility of the water-soluble additive in water and promote the removal of the nuclei 42N of the water-soluble additive, it is also preferable to heat the water to 40°C or higher when removing the nuclei 42N of the water-soluble additive.

[0090] As shown in Figure 17, it is preferable that the balloon catheter 100 further has a protective agent layer 60 outside the drug layer 40 in the radial direction y. The protective agent layer 60 prevents the drug layer 40 from unintentionally falling off or the drug from leaching out of the drug layer 40.

[0091] The protective agent layer 60 may be positioned outside the outer edge of the drug layer 40 in the radial y direction, or it may be positioned from outside to inside the outer edge of the drug layer 40 in the radial y direction, or it may be positioned from outside to inside the outer edge of the drug layer 40 in the radial y direction.

[0092] In particular, it is preferable that the protective agent layer 60 is positioned on the outside of the raised portion 45 in the radial direction y. This prevents the drug layer 40 from unintentionally falling off or the drug from leaching out from the crystal group 42, even in the area where the raised portion 45 is present.

[0093] It is preferable that the protective layer 60 does not come into contact with the outer surface of the balloon body 30. If the protective layer 60 comes into contact with the outer surface of the balloon body 30 and covers the entire surface, it may hinder the release of the drug layer 40 from the balloon body 30. However, if the protective layer 60 does not come into contact with the outer surface of the balloon body 30, the release of the drug layer 40 becomes easier.

[0094] If a separation portion 46 is formed inside the raised portion 45, or if a gap 42b is formed between the bottom surface of the crystal group 42 and the outer surface of the balloon body portion 30, it is preferable that there are portions in the separation portion 46 or gap 42b where the protective agent layer 60 is not present. This makes it easier to release the drug layer 40 from the outer surface of the balloon body portion 30.

[0095] Furthermore, when a separation portion 46 is formed inside the raised portion 45, or when a gap 42b is formed between the bottom surface of the crystal group 42 and the outer surface of the balloon body portion 30, it is also preferable that the protective agent layer 60 is positioned up to the separation portion 46 or the gap 42b. In this case, the protective agent layer 60 and the above-mentioned swelling substance may have different components, but if the protective agent layer 60 is composed of components that swell with bodily fluids, it is also preferable that the protective agent layer 60 functions as the above-mentioned swelling substance.

[0096] As shown in Figure 18, it is preferable that the protective layer 60 is positioned to cover the crack 47. This makes it easier to prevent the drug layer 40 from unintentionally falling off.

[0097] As shown in Figure 19, it is preferable that the protective layer 60 covers the drug layer 40 so as to span across adjacent crystal groups 42. This prevents the drug layer 40 from unintentionally falling off or the drug from leaching out of the drug layer 40.

[0098] The protective agent layer 60 can be composed of hydrophilic components such as water-soluble polymers. For example, when delivering the balloon 20 into a body cavity containing body fluids rich in lipid-soluble components, such as bile ducts containing bile, if a protective agent layer 60 composed of hydrophilic components is provided on the outer surface of the drug layer 40, the dissolution of the protective agent layer 60 upon contact with body fluids will be suppressed, and the protective agent layer 60 will be able to exert its protective function for the drug layer 40. Examples of hydrophilic components include hydrophilic polymers such as carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxyethylcellulose, polyvinyl alcohol, alginic acid, pectin, gum arabic, gellan gum, guar gum, xanthan gum, carrageenan, gelatin, polyethylene glycol, hyaluronic acid, and sodium polyacrylate, salts such as potassium chloride and ammonium acetate, amino acids such as glycine and glutamic acid, sugars such as glucose and fructose, and urea.

[0099] The protective layer 60 may be composed of hydrophobic components. For example, when delivering the balloon 20 into a body cavity containing body fluids with a high water content, such as blood vessels, if a protective layer 60 composed of hydrophobic components is provided on the outer surface of the drug layer 40, the dissolution of the protective layer 60 when it comes into contact with body fluids will be suppressed, and the protective layer 60 will be able to exert its protective function for the drug layer 40. Examples of hydrophobic compounds include lipid compounds such as lecithin, propylene glycol stearate, cholesterol, and terpenes; hydrocarbon compounds such as petrolatum; hydrophobic (meth)acrylic polymers such as ethyl polyacrylate and polymethyl methacrylate; hydrophobic polyester polymers such as polylactic acid and polyglycolic acid; and silicone oil.

[0100] Furthermore, even when delivering the balloon 20 to a body cavity containing body fluids with a high water content, such as blood vessels, it is also preferable that the protective layer 60 be composed of the aforementioned hydrophilic components, particularly a hydrophilic polymer with a high molecular weight. When a hydrophilic polymer with a high molecular weight is used as the protective layer 60, it is possible to prevent the dissolution of the protective layer 60 by the water in the body fluids and to maintain the protective function of the drug layer 40.

[0101] The protective layer 60 is preferably amorphous. This enhances the protective function of the protective layer 60. Examples of components of the amorphous protective layer 60 include hydrophilic polymers such as hyaluronic acid and sodium poly(meth)acrylate, hydrophobic polyester polymers such as D,L-polylactic acid and lactic acid-glycolic acid copolymers, and lipid compounds such as lecithin.

[0102] Figure 1 shows a so-called rapid exchange type balloon catheter 100, which has a guidewire port 72 located midway from the distal to the proximal end of the shaft 10, and an inner shaft 10a that functions as a guidewire insertion passage from the guidewire port 72 to the distal end of the shaft 10.

[0103] It is preferable that the shaft 10 has a fluid channel and a guide wire insertion passage inside. To configure the shaft 10 to have a fluid channel and a guide wire insertion passage inside, for example, the shaft 10 may have an inner shaft 10a and an outer shaft 10b positioned outside the inner shaft 10a, with the inner shaft 10a functioning as a guide wire insertion passage and the space between the outer shaft 10b and the inner shaft 10a functioning as a fluid channel. In such a configuration, it is preferable that the inner shaft 10a extends distally so as to penetrate the balloon 20, with the distal side of the balloon 20 connected to the inner shaft 10a and the proximal side of the balloon 20 connected to the outer shaft 10b.

[0104] The balloon catheter 100 preferably has a distal outer shaft 12 and a proximal outer shaft 11, and the distal outer shaft 12 and the proximal outer shaft 11 may be separate components, and the proximal end of the distal outer shaft 12 may be connected to the distal end of the proximal outer shaft 11 to form an outer shaft 10b that extends from the balloon 20 to the proximal end of the balloon catheter 100. Alternatively, one outer shaft 10b may extend from the balloon 20 to the proximal end of the balloon catheter 100, and the distal outer shaft 12 and the proximal outer shaft 11 may be further composed of multiple tubular members.

[0105] The shaft 10 is preferably made of resin, metal, or a combination of resin and metal. Using resin as a constituent material for the shaft 10 makes it easier to impart flexibility and elasticity to the shaft 10. Using metal as a constituent material for the shaft 10 can improve the insertion of the balloon catheter 100.

[0106] Examples of resins that make up the shaft 10 include polyamide resins, polyester resins, polyurethane resins, polyolefin resins, fluororesins, vinyl chloride resins, silicone resins, natural rubber, synthetic rubber, etc. These may be used individually or in combination of two or more. Examples of metals that make up the shaft 10 include stainless steel such as SUS304 and SUS316, platinum, nickel, cobalt, chromium, titanium, tungsten, gold, Ni-Ti alloy, Co-Cr alloy, or combinations thereof. If the shaft 10 includes a distal outer shaft 12 and a proximal outer shaft 11, for example, the distal outer shaft 12 may be formed from resin and the proximal outer shaft 11 from metal. Furthermore, the shaft 10 may have a laminated structure made of different or the same materials.

[0107] The balloon 20 and the shaft 10 can be joined by adhesive bonding, welding, or by attaching a ring-shaped member to the overlapping portion of the balloon 20 and the shaft 10 and crimping it. In particular, it is preferable that the balloon 20 and the shaft 10 are joined by welding. By welding the balloon 20 and the shaft 10, the joint between the balloon 20 and the shaft 10 is less likely to come undone even when the balloon 20 is repeatedly expanded or contracted, thus improving the joint strength.

[0108] Preferably, a tip member 80 is provided at the distal end of the balloon catheter 100. The tip member 80 may be provided at the distal end of the balloon catheter 100 by being connected to the distal end of the balloon 20 as a separate component from the inner shaft 10a, or the inner shaft 10a, which extends distal to the distal end of the balloon 20, may function as the tip member 80.

[0109] The shaft 10 may have radiopaque markers 90 positioned in the longitudinal direction x where the balloon 20 is located, in order to allow confirmation of the balloon 20's position under X-ray fluoroscopy. The radiopaque markers 90 can be positioned, for example, on the inner shaft 10a located inside the balloon 20, preferably at positions corresponding to both ends of the balloon 20's expansion portion 22, or at a position corresponding to the center of the balloon 20's expansion portion 22.

[0110] A hub 70 may be provided on the proximal side of the shaft 10, and it is preferable that the hub 70 is provided with a fluid injection section 71 that communicates with the fluid passage for the fluid supplied to the inside of the balloon 20.

[0111] The shaft 10 and the hub 70 can be joined by, for example, adhesive bonding or welding. In particular, it is preferable that the shaft 10 and the hub 70 are joined by adhesive bonding. By bonding the shaft 10 and the hub 70, the bonding strength between the shaft 10 and the hub 70 can be increased, improving the durability of the balloon catheter 100, especially when the materials constituting the shaft 10 and the hub 70 are different, for example, when the shaft 10 is made of a highly flexible material and the hub 70 is made of a highly rigid material.

[0112] Although not shown in the figures, the present invention can also be applied to so-called over-the-wire type balloon catheters, which have a guidewire insertion passage extending from the distal to the proximal end of the shaft. In the case of the over-the-wire type, it is preferable that the inflation lumen and guidewire lumen extend to a hub located on the proximal end, and that the proximal opening of each lumen is provided in a bifurcated hub.

[0113] In the case of a rapid exchange type catheter, it is preferable that the outer walls of the distal outer shaft 12 and / or the proximal outer shaft 11 are appropriately coated, and it is more preferable that both the distal outer shaft 12 and the proximal outer shaft 11 are coated. In the case of an over-the-wire type catheter, it is preferable that the outer wall of the outer shaft is appropriately coated.

[0114] The coating can be hydrophilic or hydrophobic depending on the purpose, and can be applied by immersing the shaft 10 in a hydrophilic or hydrophobic coating agent, applying a hydrophilic or hydrophobic coating agent to the outer wall of the shaft 10, or covering the outer wall of the shaft 10 with a hydrophilic or hydrophobic coating agent. The coating agent may contain chemicals or additives.

[0115] Examples of hydrophilic coating agents include hydrophilic polymers such as polyvinyl alcohol, polyethylene glycol, polyacrylamide, polyvinylpyrrolidone, and methyl vinyl ether maleic anhydride copolymer, or hydrophilic coating agents made from any combination thereof.

[0116] Examples of hydrophobic coating agents include polytetrafluoroethylene (PTFE), fluoroethylene propylene (FEP), perfluoroalkoxyalkanes (PFA), silicone oil, hydrophobic urethane resins, carbon coatings, diamond coatings, diamond-like carbon (DLC) coatings, ceramic coatings, and substances with low surface free energy terminated with alkyl groups or perfluoroalkyl groups.

[0117] This application claims the benefit of priority based on Japanese Patent Application No. 2024-232080, filed on 27 December 2024. The entire specification of Japanese Patent Application No. 2024-232080, filed on 27 December 2024, is incorporated herein by reference.

[0118] 10: Shaft 10a: Inner shaft 10b: Outer shaft 11: Proximal outer shaft 12: Distal outer shaft 20: Balloon 21: Proximal sleeve section 22: Expandable section 22S: Straight section 22T: Tapered section 23: Distal sleeve section 30: Balloon body section 31: Tube section 32: Scoring element 32A: Base of scoring element 32a: Long axis of scoring element 32b: Short axis of scoring element 33: Folding section 34: Recess 40: Drug layer 41: Long crystal 42: Crystal group 42a: Contact area 42b: Void 42J: Bonding section 42N: Nucleus 45: Raised section 45A: Outermost end 45B: Base end 46: Separation section 47: Crack 60: Protective layer 70: Hub 71: Fluid injection section 72: Guidewire port 80: Tip component 90: Radiopaque marker 100: Balloon catheter

Claims

1. A balloon catheter having an expandable and contractible balloon, wherein the balloon comprises a balloon body having a longitudinal direction and a radial direction, and a drug layer containing a drug disposed radially outward of the balloon body, and in the contracted state of the balloon, the drug layer has a raised portion that is raised radially, and the length from the outer surface of the balloon body in the radial direction to the outermost end of the raised portion is at least twice the thickness of the drug layer.

2. The balloon catheter according to claim 1, wherein the raised portion includes a crack.

3. The balloon catheter according to claim 1 or 2, wherein, in a plan view from the radially outer side, the area of ​​the raised portion is 5% or more of the area of ​​the drug layer other than the raised portion.

4. The balloon catheter according to claim 3, wherein the area of ​​the raised portion is 15% or more of the area of ​​the drug layer other than the raised portion.

5. The balloon catheter according to claim 1 or 2, wherein the length from the outer surface of the balloon body to the outermost end of the raised portion in the radial direction is 10 μm or more and 50 μm or less.

6. The balloon catheter according to claim 1 or 2, wherein the balloon body includes a cylindrical portion and a scoring element disposed radially outward from the cylindrical portion, and the raised portion is arranged along the long axis of the scoring element.

7. The balloon catheter according to claim 1 or 2, wherein the balloon body includes a cylindrical portion and a scoring element disposed radially outward from the cylindrical portion, and the raised portion is arranged along the short axis of the scoring element.

8. The balloon catheter according to claim 1 or 2, wherein the balloon body has a folded portion when contracted, and the raised portion is located in a recess of the folded portion.

9. The balloon catheter according to claim 1 or 2, wherein the balloon body includes an expandable portion, the expandable portion having a straight tube portion and tapered portions located distal to and proximal to the straight tube portion and having a reduced diameter, and in the radial direction, the length from the outer surface of the balloon body in the straight tube portion to the outermost end of the raised portion is longer than the length from the outer surface of the balloon body in the tapered portion to the outermost end of the raised portion.

10. The balloon catheter according to claim 1 or 2, wherein the drug layer comprises a plurality of elongated crystals of the drug.

11. The balloon catheter according to claim 10, wherein the drug layer comprises a group of crystals in which each of the plurality of elongated crystals is arranged radially and each of the plurality of elongated crystals has a bonding portion to which they are bonded together.

12. The balloon catheter according to claim 11, wherein the balloon has a contact region in which the outer surface of the balloon body and the crystal group are in contact, and a gap in which the outer surface of the balloon body and the crystal group are separated.

13. The balloon catheter according to claim 1 or 2, wherein the drug is paclitaxel.

14. The balloon catheter according to claim 1 or 2, further comprising a protective agent layer on the radially outer side of the drug layer.

15. The balloon catheter according to claim 14, wherein the protective layer is disposed on the radially outer side of the raised portion.

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