Balloon catheter

Abstract

To provide a balloon catheter that allows medication to be easily released from the balloon surface. [Solution] A balloon catheter comprising: a balloon body portion 20 having a longitudinal direction x and a radial direction y; a plurality of drug masses 30 containing a drug, arranged on the outer surface of the balloon body portion 20; a gap portion 50 defined by at least two adjacent drug masses 30 and the outer surface of the balloon body portion 20; and a swellable substance 40 arranged in the gap portion 50.

Description

Technical Field

[0001] The present invention relates to a balloon catheter including a balloon having a drug retained on its surface.

Background Art

[0002] When a stenosis occurs in a blood vessel, which is a flow path for blood circulation in the body, and blood circulation is stagnant, various diseases are caused. As one method for treating such diseases, there is angioplasty for expanding a stenotic portion using a balloon catheter.

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

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0005] Conventional balloon catheters had room for improvement in terms of drug release from the balloon surface. Therefore, the present invention aims to provide a balloon catheter that facilitates drug release from the balloon surface. [Means for solving the problem]

[0006] The balloon catheter according to an embodiment of the present invention that solves the above problems is as follows. [1] A balloon body having a longitudinal direction and a radial direction, The balloon body is arranged on the outer surface of a plurality of drug masses containing a drug, A gap is defined by at least two adjacent drug lumps among the plurality of drug lumps and the outer surface of the balloon body, A balloon catheter having a swelling substance disposed in the gap.

[0007] The balloon catheter described above has a gap defined by at least two adjacent drug lumps among several drug lumps and the outer surface of the balloon body, and a swellable substance placed in the gap. After the balloon body is delivered to the treatment site and expands, blood enters the gap and comes into contact with the swellable substance, causing the volume of the swellable substance to increase. This acts a radially outward force on the drug lumps, making them easier to detach from the outer surface of the balloon body. As a result, the balloon catheter can be made such that the drug lumps can be easily released from the balloon body and transferred to the target tissue.

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

[11] . [2] The balloon catheter according to [1], wherein each of the drug masses comprises a plurality of columnar crystals of the drug arranged radially. [3] The balloon catheter according to [2], wherein each of the plurality of columnar crystals has a bonding portion that connects it to one another. [4] The balloon catheter according to any one of [1] to [3], wherein the plurality of drug masses include drug masses that overlap each other radially outside the gap. [5] The balloon catheter according to any one of [1] to [4], wherein the plurality of drug masses are bonded to each other radially outside the gap. [6] In a plan view of the balloon body from the radially outer side, the major axis of the drug mass is 10 μm or more and 80 μm or less, according to any one of [1] to [5]. [7] The balloon catheter according to any one of [1] to [6], wherein the drug is paclitaxel. [8] The balloon catheter according to any one of [1] to [7], wherein the plurality of drug masses include drug masses having a gap between the drug mass and the outer surface of the balloon body. [9] The balloon catheter according to [8], wherein the swellable substance is disposed in the void.

[10] A balloon catheter according to any one of [1] to [9], wherein the swelling substance remains on the balloon body after expansion.

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

[10] , further comprising a protective layer on the radially outer side of the drug mass. [Effects of the Invention]

[0009] In the balloon catheter described above, the drug mass easily detaches from the outer surface of the balloon body, allowing the drug to be easily transferred to the target tissue. This makes it possible to provide a balloon catheter that can effectively deliver drugs to the target tissue. [Brief explanation of the drawing]

[0010] [Figure 1] This is a side view of a balloon catheter according to one embodiment of the present invention. The drug mass is omitted in this drawing. [Figure 2] This is a partially enlarged view of a longitudinal cross-section of the balloon membrane of a balloon catheter according to one embodiment of the present invention. [Figure 3]SEM photograph of the balloon membrane of the balloon catheter according to another embodiment of the present invention, observed from the radially outer side. [Figure 4] Schematic diagram of a drug mass according to an embodiment of the present invention in a plan view from the radially outer side. [Figure 5] SEM photograph of a longitudinal cross-section of the balloon membrane shown in FIG. 3. [Figure 6] Partial enlarged cross-sectional view showing a modified example of the balloon membrane of FIG. 2. [Figure 7] Perspective view of a columnar crystal according to an embodiment of the present invention. [Figure 8] Partial enlarged cross-sectional view showing still another modified example of the balloon membrane of FIG. 2. [Figure 9] Partial enlarged cross-sectional view showing still another modified example of the balloon membrane of FIG. 2. [Figure 10] Partial enlarged cross-sectional view showing still another modified example of the balloon membrane of FIG. 2. [Figure 11] Partial enlarged cross-sectional view showing still another modified example of the balloon membrane of FIG. 2. [Figure 12] Partial enlarged cross-sectional view showing the state when a water-soluble additive is applied to the outer surface of the balloon main body portion in the process of manufacturing the balloon catheter according to an embodiment of the present invention. [Figure 13] SEM photograph of the balloon main body portion observed from the radially outer side when a water-soluble additive is applied to the outer surface of the balloon main body portion in the process of manufacturing the balloon catheter according to an embodiment of the present invention. [Figure 14] Partial enlarged cross-sectional view showing the state when a solution containing a drug is further applied to the outer surface of the balloon main body portion of FIG. 12.

Embodiments for Carrying Out the Invention

[0011] The present invention will be described below based on embodiments, but the present invention is not limited by 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 refer to the specification or other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority is 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 is a diagram for understanding the overall configuration of the balloon catheter, and the drug mass is omitted. Figure 2 is a partially enlarged view of a longitudinal cross-section of the balloon membrane of a balloon catheter according to one embodiment of the present invention, showing the configuration of the balloon membrane. Figure 3 is an SEM image of the balloon membrane of a balloon catheter according to another embodiment of the present invention, observed from the radial outside. Figure 4 is a schematic diagram of a drug mass according to one embodiment of the present invention in a plan view from the radial outside. Figure 5 is an SEM image of a longitudinal cross-section of the balloon membrane shown in Figure 3. Figure 5 was obtained by SEM observation of the surface of the balloon membrane after irradiating it with a focused ion beam to expose the cross-section of the drug mass. Figure 6 is a partially enlarged cross-sectional view showing a modified example of the balloon membrane of Figure 2. Figure 7 is a perspective view of a columnar crystal according to one embodiment of the present invention. Figure 8 is a partially enlarged cross-sectional view showing yet another modified example of the balloon membrane of Figure 2. Figure 9 is a partially enlarged cross-sectional view showing yet another modified example of the balloon membrane of Figure 2. Figure 10 is a partially enlarged cross-sectional view showing yet another modification of the balloon membrane in Figure 2. Figure 11 is a partially enlarged cross-sectional view showing yet another modification of the balloon membrane in Figure 2. Figure 12 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 13 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. Figure 14 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 12.

[0013] As shown in Figure 1, the balloon catheter 100 has a balloon body 20. Preferably, the balloon body 20 is located on the outside of the shaft 10. The balloon catheter 100 has a proximal end and a distal end, with the balloon body 20 located 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 from the proximal end to the distal end of the balloon catheter 100, while 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 body 20 is preferably formed in a bag shape with openings on the proximal and distal ends. The balloon body 20 is the part that expands and contracts when fluid is supplied to or discharged from inside through the shaft 10, and is preferably formed from a resin film. Fluid supply and discharge can be performed using an indeflerator (a balloon pressure regulator). The fluid may be a pressurized fluid pressurized by a pump or the like.

[0015] The resin membrane forming the balloon body 20, along with the drug mass 30 (described later), the gap 50, and the swelling substance 40, are sometimes collectively referred to as the balloon membrane.

[0016] The balloon body 20 has a longitudinal direction x, a radial direction y, and a circumferential direction z. The longitudinal direction x of the balloon body 20 refers to the direction extending from the proximal side to the distal side of the balloon body 20. The radial direction y of the balloon body 20 refers to the direction from the centroid of the outer edge of the balloon body 20 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 20 refers to the direction along the outer edge of the balloon body 20 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 20 each have longitudinal, radial, and circumferential directions. The longitudinal, radial, and circumferential directions of these components and parts may coincide with the longitudinal x, radial y, and circumferential z of the balloon body 20, or they may be different. For the sake of clarity, in this specification, it will be explained that the longitudinal, radial, and circumferential directions of all components and parts coincide with the longitudinal x, radial y, and circumferential z of the balloon body 20, respectively.

[0018] As shown in Figure 1, it is preferable that the balloon body portion 20 has, in the longitudinal direction x, 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. 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 the 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 the distal sleeve portion 23 to the shaft 10.

[0019] Although not shown in the figures, it is preferable that the expansion portion 22 of the balloon body 20 has a straight tube portion, a proximal tapered portion located proximal to the straight tube portion, and a distal tapered portion located distal to the straight tube portion in the longitudinal direction x. The straight tube portion is formed in a substantially cylindrical shape extending in the longitudinal direction x, and the length in the radial direction y, i.e., the outer diameter, is formed to be the largest. This makes it easier for the straight tube portion, which has the largest outer diameter, to come into contact with the blood vessel wall. It is preferable that the proximal tapered portion and the distal tapered portion are formed so that the outer diameter decreases as they move away from the straight tube portion. Because the proximal tapered portion and the distal tapered portion are reduced in diameter, when the balloon body 20 is deflated, the outer diameter of the proximal and distal ends of the balloon body 20 can be reduced, thereby reducing the step between the shaft 10 and the balloon body 20, making it easier to insert the balloon body 20 into a body cavity, into the forceps channel of an endoscope, or into a delivery catheter such as a guiding catheter.

[0020] The size of the balloon body 20 is not particularly limited. For example, the length x in the longitudinal direction of the balloon body 20 can be set appropriately within the range of 4 mm to 400 mm, and the outer diameter of the expansion part 22 can be set within the range of 1 mm to 30 mm.

[0021] The balloon body 20 is preferably made of resin, and more preferably of thermoplastic resin. This makes it easy to manufacture the balloon body 20 by molding. Examples of resins that make up the balloon body 20 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 individually 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 20 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 20 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 20.

[0022] As shown in Figures 2 and 3, the balloon catheter 100 has multiple drug lumps 30 containing a drug, which are arranged on the outer surface of the balloon body 20. In Figure 2, for clarity, multiple drug lumps 30 of similar shape are shown arranged at the same position in the circumferential direction z. However, each of the multiple drug lumps 30 does not need to be arranged at the same position in the circumferential direction z, and each of the multiple drug lumps 30 may have the same shape as the others or may have different shapes. The same applies to the other cross-sectional views.

[0023] The drug mass 30 is preferably located on the outer surface of the expansion portion 22 within the balloon body 20, and more preferably located in the straight tube portion. This facilitates the administration of the drug to the target tissue by the expansion of the balloon body 20.

[0024] The drug contained in the drug mass 30 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 mass 30. The drug mass 30 may contain, along with the pharmacologically active substance, an adjuvant to improve the dispersibility of the drug, its transfer to the blood vessel wall, and its storage stability. Examples of adjuvants include stabilizers, binders, disintegrants, moisture-proofing agents, and preservatives.

[0025] As shown in Figure 3, each of the multiple drug clumps 30 is scattered on the outer surface of the balloon body 20, and it is preferable that there are portions of the outer surface of the balloon body 20 exposed between the multiple drug clumps 30. This makes it easier to form the gap 50 described later.

[0026] The shape of the outline of the drug mass 30 when viewed from the outside in the radial direction y of the balloon body 20 is not particularly limited, but may be circular, elliptical, polygonal, rounded polygonal, etc., or it may be a shape formed by a plurality of columnar crystals 31 as described later, or it may be irregular in shape. When viewed from the outside in the radial direction y of the balloon body 20, the boundaries of the plurality of drug masses 30 may be unclear, but adjacent drug masses 30 separated by a gap 50 as described later can be considered as separate drug masses 30.

[0027] In the radial direction y of the cross-section in the longitudinal direction x, the maximum thickness of the drug mass 30 can be, for example, 3 μm or more, 5 μm or more, 10 μm or more, or 40 μm or less, 30 μm or less, or 20 μm or less.

[0028] In a plan view from the outside in the radial direction y of the balloon body 20, the major axis of the drug mass 30 is preferably 10 μm or more and 80 μm or less. More preferably, the major axis of the drug mass 30 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, if the major axis of the drug mass 30 is within the above range, the drug mass 30 can easily fit into the irregularities of the body cavity wall, and the drug mass 30 is less likely to fall off the body cavity wall after administration, thus effectively delivering the drug to the target tissue.

[0029] As shown in Figure 4, in a plan view from the outside in the radial direction y, when L is the length from the centroid of the outer edge 30E of the drug mass 30 to the outer edge 30E, the area of ​​a circle with radius L / 2 centered on the centroid of the outer edge 30E is defined as the central part 30c of the drug mass 30, and the area of ​​a circle with radius L centered on the centroid of the outer edge 30E, excluding the central part 30c, is defined as the peripheral part 30p. As shown in Figure 2, it is preferable that the length of the drug mass 30 in the radial direction y at the central part 30c is longer than the length of the drug mass 30 in the radial direction y at the peripheral part 30p. This allows for the formation of irregularities on the surface of the balloon body 20 based on the size of the drug mass 30. As a result, it becomes easier to bring the drug mass 30 into contact with the body cavity wall, such as a blood vessel, which is the target tissue.

[0030] As shown in Figures 2, 5, and 6, the balloon catheter 100 has a gap 50 defined by at least two adjacent drug lumps 30 from among the multiple drug lumps 30 and the outer surface of the balloon body 20. In Figure 2, in a cross-section in the longitudinal direction x, adjacent drug lumps 30 are in contact with each other, and the gap 50 is formed as a closed space between the two adjacent drug lumps 30 and the outer surface of the balloon body 20. However, the gap 50 does not necessarily have to be a closed space; as shown in Figure 6, adjacent drug lumps 30 may be separated from each other. Also, as shown in Figure 5, the gap 50 may be defined by the columnar crystals 31 of the drug lumps 30 (described later) and the outer surface of the balloon body 20. In any case, any space defined by at least two adjacent drug lumps 30 from among the multiple drug lumps 30 and the outer surface of the balloon body 20 is a gap 50.

[0031] A single gap 50 may be defined by two adjacent drug lumps 30 and the outer surface of the balloon body 20, or by three adjacent drug lumps 30 and the outer surface of the balloon body 20, or by four adjacent drug lumps 30 and the outer surface of the balloon body 20. Alternatively, the number of drug lumps 30 defining a single gap 50 may be five or more, six or more, or ten or less, or eight or less.

[0032] In a cross-section along the longitudinal direction x, the maximum radial length y of the gap 50 can be, for example, 5% or more, 10% or more, 20% or more, or 90% or less, 70% or less, or 50% or less of the maximum radial length y of the drug mass 30. If the maximum radial length y of the gap 50 relative to the maximum radial length y of the drug mass 30 is within the above range, it becomes easy to place the swelling substance 40 described later in the gap 50, and the effects of the swelling substance 40 can be expected.

[0033] In a cross-section along the longitudinal direction x, the maximum length of the gap 50 in the radial direction y can be, for example, 0.5 μm or more, 1.5 μm or more, 3 μm or more, or 30 μm or less, 20 μm or less, or 10 μm or less.

[0034] As shown in Figure 2, the balloon catheter 100 has a swellable substance 40 placed in the gap 50. When the balloon body 20 is delivered to the treatment site and expands, blood enters the gap 50 and comes into contact with the swellable substance 40, causing the volume of the swellable substance 40 to increase. This acts on the drug mass 30 in an outward radial direction y, making it easier for the drug mass 30 to detach from the outer surface of the balloon body 20. As a result, the balloon catheter 100 can be made such that the drug mass 30 can be easily released from the balloon body 20 and easily transferred to the target tissue.

[0035] The components of the swelling substance 40 include hydrophilic swelling components and hydrophobic swelling components. Hydrophilic swelling components are preferably those insoluble in water of the absorbent material, such as hydrophilic polymers like polyvinylpyrrolidone, sodium poly(meth)acrylate, polyvinyl alcohol, cellulose polymers, gelatin, and hyaluronic acid. Hydrophobic swelling components are preferably those insoluble in the hydrophobic components of the absorbent material, such as hydrophobic polymers like octadecyl polyacrylate, and low molecular weight gelling agents like 12-hydroxystearic acid and N-lauroyl-L-glutamic acid α,γ-bis-n-butylamide. As a low molecular weight gelling agent, cyclic dipeptides combining neutral amino acids such as L-leucine and acidic amino acid derivatives such as L-glutamic acid-γ-ester can also be used. Cyclic dipeptides are preferred because they are highly safe as they do not have toxicity when they remain in the body. Methods for making hydrophilic polymers insoluble in water and hydrophobic polymers insoluble in hydrophobic components include using polymers with high molecular weight and crosslinking polymers together.

[0036] If the swelling substance 40 is composed of a hydrophilic swelling component, forming the surface of the balloon body 30 hydrophilically allows the swelling substance 40 to remain on the surface of the balloon body 20 when the drug mass 30 detaches from the surface of the balloon body 20. If the swelling substance 40 is composed of a hydrophobic swelling component, forming the surface of the balloon body 20 hydrophobic allows the swelling substance 40 to remain on the surface of the balloon body 20 when the drug mass 30 detaches from the surface of the balloon body 20. By allowing the swelling substance 40 to remain on the surface of the balloon body 20, it is possible to prevent foreign matter from remaining in the body, such as the swelling substance 40 falling into the bloodstream and obstructing blood flow.

[0037] The volume of the swellable substance 40 placed in the gap 50 is preferably 10% or more of the volume of the gap 50, more preferably 20% or more, even more preferably 30% or more, and may be 100%, but is preferably less than 95%, more preferably 90% or less, and even more preferably 80% or less. The presence of gaps 50 without the swellable substance 40 allows body fluids to enter these gaps 50, making it easier for the body fluids to come into contact with the swellable substance 40 and promoting the swelling of the swellable substance 40. As the swelling of the swellable substance 40 occurs, its volume may occupy 100% of the volume of the gap 50. As a result, when the amount of the swellable substance is within the above range, the release of the drug layer 40 is promoted by the swellable substance.

[0038] It is preferable that no non-swelling or poorly swelling substances are placed in the gap 50. If non-swelling or poorly swelling substances are placed in the gap 50, the release of the drug mass 30 may be inhibited by these substances, but the absence of such substances facilitates the release of the drug mass 30.

[0039] It is preferable that the swelling substance 40 remains on the balloon body 20 after expansion. The remaining rate of the swelling substance 40 on the balloon body 20 after expansion, that is, the ratio of the remaining swelling substance 40 to the amount of swelling substance 40 added, is preferably 50% or more, more preferably 70% or more, and even more preferably 80% or more. The remaining rate of the swelling substance 40 may also be 100% or less, 95% or less, or 90% or less. Although the drug mass 30 needs to be released from the balloon body 20 after expansion at the treatment site, if the swelling substance 40 also detaches from the balloon body 20 and falls into the bloodstream, there is a risk that the swelling substance 40 may obstruct blood flow. If the remaining rate of the swelling substance 40 is within the above range, adverse effects such as obstruction of blood flow by the swelling substance 40 can be prevented.

[0040] As shown in Figure 6, it is preferable that each drug mass 30 contains multiple columnar crystals 31 of the drug arranged radially. As shown in Figure 7, it is preferable that the columnar crystals 31 have a longitudinal axis 31L and have a first end 31a and a second end 31b in the direction of the longitudinal axis 31L. The columnar crystals 31 are preferably polygonal prisms, and the cross-sectional shape perpendicular to the longitudinal axis 31L is preferably a polygon such as a triangle, quadrilateral, pentagon, or hexagon. However, the cross-sectional shape perpendicular to the longitudinal axis 31L of the columnar crystals 31 does not necessarily have to be a polygon, and the corners of the polygon may be flattened or the sides of the polygon may be distorted. The shape and size of the cross-sectional shape on the first end 31a side and the second end 31b side of the columnar crystals 31 may be different, and the sides of the polygonal prism do not have to be straight lines. The longitudinal axis 31L of the columnar crystal 31 can be a straight line connecting the centroid 31C of the base at the first end 31a and the centroid 31C of the base at the second end 31b. The columnar crystal 31 may be solid or hollow.

[0041] The outer diameter of the cross-section perpendicular to the longitudinal axis 31L of the columnar crystal 31 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 31L of the columnar crystal 31.

[0042] The length of the columnar crystal 31 in the direction of its longitudinal axis 31L 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 columnar crystal 31 in the direction of its longitudinal axis 31L is longer than the outer diameter of the cross section perpendicular to the longitudinal axis 31L of the columnar crystal 31. For example, the length in the direction of its longitudinal axis 31L 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 31L.

[0043] As shown in Figure 7, each of the multiple columnar crystals 31 has a longitudinal axis 31L that extends in the radial direction y and a parallel component Ch that extends parallel to a plane perpendicular to the radial direction y. Preferably, the multiple columnar crystals 31 include columnar crystals 31P in which the longitudinal component Cp in the direction of extension of the longitudinal axis 31L is larger than the parallel component Ch. That is, it is preferable that the drug mass 30 placed on the outer surface of the balloon body 20 includes columnar crystals 31P in which the longitudinal axis 31L extends so as to stand in the radial direction y of the balloon body 20 rather than along the surface of the balloon body 20. Such columnar crystals 31P with a large longitudinal component Cp are more likely to come into contact with the target tissue when the balloon body 20 is expanded at the lesion site, and in some cases, they can even penetrate the tissue, thus enabling effective delivery of the drug to the target tissue.

[0044] Multiple columnar crystals 31 may be independently separated from each other, or they may be fixed to each other. For example, multiple columnar crystals 31 may be fixed to each other at the first end 31a and separated from each other at the second end 31b. Even if multiple columnar crystals 31 are fixed to each other, the longitudinal axis 31L of the columnar crystals 31 can be identified and the components in the direction of extension of the longitudinal axis 31L can be determined by observing the cross-section with a microscope such as an SEM.

[0045] As shown in Figure 6, it is preferable that the plurality of columnar crystals 31 include a plurality of columnar crystals 31P in which the vertical component Cp in the direction of extension of the longitudinal axis 31L is larger than the parallel component Ch, and it is preferable that each of the plurality of columnar crystals 31P has a portion that is not attached to each other. In particular, it is preferable that each of the plurality of columnar crystals 31P may be attached to each other at the first end 31a side, which is closer to the balloon body 20 in the radial direction y, but not attached to each other at the second end 31b side, which is further from the balloon body 20 in the radial direction y. It is more preferable that each of the plurality of columnar crystals 31P is separated from each other at the second end 31b side. This makes it easier for the columnar crystals 31P to come into contact with the target tissue when the balloon body 20 is expanded at the lesion site, and makes it possible to deliver the drug to the target tissue more effectively.

[0046] Preferably, the multiple columnar crystals 31 include columnar crystals 31 in which the component Cp perpendicular to the direction of extension of the longitudinal axis 31L is smaller than the component Ch parallel to it. This makes it easier to form a gap 50 defined by the columnar crystals 31 of adjacent drug masses 30 and the outer surface of the balloon body portion 20.

[0047] Preferably, the multiple columnar crystals 31 include both columnar crystals 31 and columnar crystals 31P, in which the component Cp perpendicular to the extension direction of the longitudinal axis 31L is smaller than the component Ch parallel to it.

[0048] The proportion of columnar crystals 31P in which the component Cp perpendicular to the direction of extension of the longitudinal axis 31L is greater than the component Ch parallel to the longitudinal axis 31L is preferably 5% or more, more preferably 10% or more, even more preferably 20% or more, and particularly preferably 30% or more, relative to the entire group of columnar crystals 31. There is no particular upper limit to the proportion of columnar crystals 31P in which the component Cp perpendicular to the direction of extension of the longitudinal axis 31L is greater than the component Ch parallel to the longitudinal axis 31L, relative to the entire group of columnar crystals 31, but for example it may be 90% or less, 80% or less, or 70% or less. The above proportion may be measured when observing a cross-section of the balloon membrane in the longitudinal direction x with a microscope such as an SEM, for example, in a range of 30 μm in length of the longitudinal direction x where 10 or more columnar crystals 31 are observed. Alternatively, it may be measured by observing a columnar crystal 31 constituting one of the drug aggregates 30.

[0049] It is preferable that the number of columnar crystals 31P with a large vertical component Cp in the central part 30c of the drug mass 30 is greater than the number of columnar crystals 31P with a large vertical component Cp in the peripheral part 30p of the drug mass 30. It is preferable that the number of columnar crystals 31 with a large parallel component Ch in the peripheral part 30p of the drug mass 30 is greater than the number of columnar crystals 31 with a large parallel component Ch in the central part 30c of the drug mass 30. It is more preferable that columnar crystals 31P with a large vertical component Cp are not present in the peripheral part 30p of the drug mass 30. It is more preferable that columnar crystals 31 with a large parallel component Ch are not present in the central part 30c of the drug mass 30. With the above configuration, it becomes easier to form irregularities on the surface of the balloon body 20 based on the size of the drug mass 30, and it becomes easier to bring the drug mass 30 into contact with the body cavity wall, such as a blood vessel, which is the target tissue. Furthermore, whether a columnar crystal 31P is located in the central part 30c or the peripheral part 30p can be determined by whether the second end 31b, which is located radially outward among the columnar crystals 31P, is located in the central part 30c or the peripheral part 30p. That is, it is preferable that the number of columnar crystals 31P whose second end 31b is located in the central part 30c is greater than the number of columnar crystals 31P whose second end 31b is located in the peripheral part 30p.

[0050] Although not shown in the diagram, in order to give the balloon catheter 100 a scoring function, the balloon body 20 may have a projection that protrudes outward in the radial direction y and extends in the longitudinal direction x. The drug mass 30 may also be placed on the surface of the projection. That is, the drug mass 30 may be placed on both the outer surface of the balloon body 20 in the portion where the projection is not formed and the outer surface of the projection. When the balloon body 20 has a projection and the drug mass 30 is also placed on the surface of the projection, it is preferable to perform microscopic observation such as SEM on the drug mass 30 placed on the outer surface of the balloon body 20 in the portion where the projection is not formed. This makes it possible to observe the direction of extension of the longitudinal axis 31L of the columnar crystal 31 contained in the drug mass 30 placed on the outer surface of the balloon body 20 in the portion where the projection is not formed, with reference to the radial direction y.

[0051] As shown in Figure 6, it is preferable that each of the multiple columnar crystals 31 has a bonding portion 31J to which they are connected. That is, it is preferable that each of the multiple drug aggregates 30 has multiple columnar crystals 31 arranged radially, and each of the multiple columnar crystals 31 has a bonding portion 31J to which they are connected. This allows the drug aggregate 30 to exist stably. As a result, the drug aggregate 30 can easily move from the balloon body 20 expanded at the treatment site to the target tissue, making effective drug administration easier.

[0052] The bonding portion 31J is preferably the starting point in a configuration in which each of the multiple columnar crystals 31 is arranged radially. The bonding portion 31J is preferably formed by the bonding of the first end 30a of the columnar crystals 31 or the vicinity of the first end 30a to each other. The bonding portion 31J is preferably located in the central part 30c of the drug mass 30.

[0053] Preferably, the binding portion 31J of each of the multiple drug aggregates 30 is located on the balloon body portion 20 side of the midpoint of the thickness of the drug aggregate 30 in the radial direction y. This makes it easier for columnar crystals 31P, in which the vertical component Cp in the direction of extension of the longitudinal axis 31L is larger than the parallel component Ch, to extend radially outward from the binding portion 31J. As a result, the columnar crystals 31P can easily come into contact with the target tissue, making it easier to efficiently transfer the drug to the target tissue.

[0054] As shown in Figure 8, it is preferable that the multiple drug chunks 30 include drug chunks 30 that overlap each other radially y-outside of the gap 50. By overlapping the drug chunks 30 radially y-outside of the gap 50, the drug chunks 30 can be stably positioned on the outer surface of the balloon body 20. As a result, it is possible to prevent the drug chunks 30 from falling off the outer surface of the balloon body 20 during delivery to the treatment site.

[0055] In a cross-section along the longitudinal direction x, it is preferable that the gap 50 is formed by being surrounded by the overlapping drug masses 30 and the outer surface of the balloon body 20. This makes it less likely for the swelling substance 40 to come into contact with blood until the balloon body 20 is delivered to the treatment site and expands, and prevents the swelling substance 40 from swelling during delivery and causing the drug mass 30 to detach from the outer surface of the balloon body 20.

[0056] The drug blocks 30 may overlap if the ends of the columnar crystals 31 in each drug block 30 have a parallel component Ch in the direction of extension of the longitudinal axis 31L that is larger than the vertical component Cp, overlap with each other. In this case, it is preferable that the columnar crystals 31P in separate drug blocks 30 have a large vertical component Cp and do not overlap with each other. As a result, the columnar crystals 31 with a large parallel component Ch overlap with each other and contribute to the stable arrangement of the drug blocks 30, while the columnar crystals 31P with a large vertical component Cp can exist separately from each other, making it easier for the columnar crystals 31P to come into contact with the target tissue. Consequently, it becomes easier to create a balloon catheter 100 in which the drug blocks 30 are less likely to fall off during delivery to the treatment site and which facilitates the transfer of the drug to the target tissue.

[0057] All of the drug lumps 30 may overlap each other outside the gap 50 in the radial direction y. Alternatively, some of the drug lumps 30 may overlap each other outside the gap 50 in the radial direction y, while the other drug lumps 30 do not overlap each other.

[0058] As shown in Figure 9, it is preferable that the multiple drug clusters 30 include drug clusters 30 that are connected to each other radially y-outside of the gap 50. Because the multiple drug clusters 30 are not only overlapping but also connected to each other, the drug clusters 30 can be more stably positioned on the outer surface of the balloon body 20. As a result, it is easier to prevent the drug clusters 30 from falling off the outer surface of the balloon body 20 during delivery to the treatment site.

[0059] In a cross-section along the longitudinal direction x, it is preferable that the gap 50 is formed by being surrounded by the drug mass 30, which are bonded together, and the outer surface of the balloon body 20. This makes it less likely for the swelling substance 40 to come into contact with blood until the balloon body 20 is delivered to the treatment site and expands, and prevents the swelling substance 40 from swelling during delivery and causing the drug mass 30 to detach from the outer surface of the balloon body 20.

[0060] The drug aggregates 30 may be bound together by the ends of the columnar crystals 31 in each drug aggregate 30, where the parallel component Ch in the direction of extension of the longitudinal axis 31L is larger than the vertical component Cp. In this case, it is preferable that the columnar crystals 31P in separate drug aggregates 30 that have a large vertical component Cp are not bound to each other. This allows the columnar crystals 31 with a large parallel component Ch to be bound to each other and contribute to the stable arrangement of the drug aggregates 30, while the columnar crystals 31P with a large vertical component Cp can exist separately from each other, making it easier for the columnar crystals 31P to come into contact with the target tissue. This makes it easier to create a balloon catheter 100 in which the drug aggregates 30 are less likely to fall off during delivery to the treatment site and which allows the drug to be easily transferred to the target tissue.

[0061] All of the drug aggregates 30 may be bonded to each other outside the gap 50 in the radial direction y. Alternatively, some of the drug aggregates 30 may be bonded to each other outside the gap 50 in the radial direction y, while the other drug aggregates 30 may not be bonded to each other but simply overlapping or separated from each other.

[0062] As shown in Figure 10, it is preferable that the multiple drug masses 30 include drug masses 30 having a gap 30a between the drug mass 30 and the outer surface of the balloon body 20. The drug mass 30 has a bottom surface facing the outer surface of the balloon body 20, and it is preferable that a gap 30a is formed between this bottom surface and the outer surface of the balloon body 20. This makes it easier for the drug mass 30 to detach from the outer surface of the balloon body 20 when the balloon body 20 is expanded after being delivered to the treatment site, and makes it easier to transfer the drug to the target tissue as a drug mass 30. As a result, the drug can be administered to the target tissue more effectively.

[0063] In the portion where the void 30a exists, it is preferable that the balloon body 20, the void 30a, and the drug mass 30 are arranged in the order from the inside to the outside in the radial direction y. This arrangement facilitates the release of the drug mass 30 from the outer surface of the balloon body 20.

[0064] Preferably, the void 30a is formed in a cross-section along the longitudinal direction x by being surrounded by the outer surface of the balloon body 20 and the drug mass 30. That is, as shown in Figure 10, the gap 50 formed between adjacent drug masses 30 is not necessarily surrounded by the outer surface of the balloon body 20 and the drug mass 30 because the adjacent drug masses 30 may be separated from each other, but it is preferable that the void 30a is formed by being surrounded by the outer surface of the balloon body 20 and the drug mass 30. This makes it possible to make the contact area between the balloon body 20 and the drug mass 30 larger than a certain area, thereby preventing the drug mass 30 from falling off while the balloon body 20 is being delivered.

[0065] The void 30a is preferably located in the central part 30c of the drug mass 30. Furthermore, it is preferable that at least a portion of the peripheral edge 30p of the bottom surface of the drug mass 30 is in contact with or fixed to the outer surface of the balloon body 20. This facilitates the retention of the drug mass 30 on the outer surface of the balloon body 20, preventing the drug mass 30 from falling off during transport of the balloon body 20, while facilitating the release of the drug mass 30 from the outer surface of the balloon body 20 when the drug mass 30 comes into contact with the target tissue.

[0066] It is preferable that the gap 30a is maintained as a space. This makes it easier for the drug mass 30 to detach from the outer surface of the balloon body 20 by expanding the balloon body 20 after it has been delivered to the treatment site, and as a result, the drug can be delivered to the target tissue more easily.

[0067] Alternatively, a swellable substance 40 may be placed in the gap 30a. By including a swellable substance 40 in the gap 30a that swells upon contact with blood, when the balloon body 20 is delivered to the treatment site and expands, bodily fluids such as blood enter the gap 30a and come into contact with the swellable substance 40, the volume of the swellable substance 40 increases. This causes an outward force in the radial direction y to act on the drug mass 30, making it easier for the drug mass 30 to detach from the outer surface of the balloon body 20. As a result, it becomes easier to obtain a balloon catheter 100 in which the drug mass 30 can be effectively delivered to the target tissue.

[0068] The volume of the swellable substance 40 placed in the void 30a is preferably 10% or more of the volume of the void 30a, more preferably 20% or more, even more preferably 30% or more, and preferably 95% or less, more preferably 90% or less, and even more preferably 80% or less. When body fluid enters the void 30a where the swellable substance 40 is not present, the body fluid can easily come into contact with the swellable substance 40, thereby promoting the swelling of the swellable substance 40. As the swellable substance 40 swells, its volume may occupy 100% of the volume of the void 30a. When the amount of the swellable substance 40 is within the above range, the release of the drug mass 30 is promoted by the swellable substance 40.

[0069] It is preferable that no non-swelling or poorly swelling substances are placed in the void 30a. That is, it is preferable that the void 30a is maintained as an empty space, or if a substance is placed in the void 30a, that substance is a swelling substance 40. The effects of the space and the swelling substance 40 on the release of the drug mass 30 are as described above. If a non-swelling or poorly swelling substance is placed in the void 30a, the release of the drug mass 30 may be inhibited by that substance, but the absence of such a substance facilitates the release of the drug mass 30.

[0070] As shown in Figure 11, the balloon catheter 100 may further have a protective layer 60 on the radial y-side of the drug mass 30. The protective layer 60 prevents the drug mass 30 from unintentionally falling off or the drug from leaching out of the drug mass 30.

[0071] The protective layer 60 may be positioned outside the outer edge of the drug mass 30 in the radial y direction, or it may be positioned from the outside to the inside of the outer edge of the drug mass 30 in the radial y direction. In particular, it is preferable that the protective layer 60 covers the drug mass 30 so as to span across adjacent drug masses 30. This prevents the drug mass 30 from unintentionally falling off or the drug from leaching out of the drug mass 30.

[0072] The protective layer 60 can be composed of hydrophilic components such as water-soluble polymers. For example, when delivering the balloon body 20 into a body cavity containing body fluids rich in lipid-soluble components, such as bile ducts containing bile, if a protective layer 60 composed of hydrophilic components is provided on the outer surface of the drug mass 30, the dissolution of the protective layer 60 upon contact with body fluids will be suppressed, and the protective layer 60 will be able to exert its protective function for the drug mass 30. 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.

[0073] The protective layer 60 may be composed of hydrophobic components. For example, when delivering the balloon body 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 mass 30, 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 mass 30. 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.

[0074] Furthermore, even when delivering the balloon body 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 mass 30.

[0075] 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 copolymer, and lipid compounds such as lecithin.

[0076] It is preferable that the protective layer 60 is positioned up to the gap 50. In this case, the protective layer 60 and the swelling substance 40 may have different components, but if the protective layer 60 is composed of components that swell with bodily fluids, it is also preferable that the protective layer 60 functions as the swelling substance 40.

[0077] Furthermore, it is also preferable that the protective agent layer 60 is not placed in the gap 50 defined by the drug mass 30 and the outer surface of the balloon body 20. In that case, it becomes easier to place a swelling substance 40, which is made of a different component from the protective agent layer 60, in the gap 50.

[0078] It is preferable that the protective agent layer 60 is not placed in the gap 30a formed between the bottom surface of the drug mass 30 and the outer surface of the balloon body 20. If the protective agent layer 60 is placed in the gap 30a, the protective agent layer 60 may hinder the release of the drug mass 30 from the balloon body 20, but if the protective agent layer 60 is not placed in the gap 30a, the release of the drug mass 30 becomes easier.

[0079] The drug mass 30 can be provided by applying a solution containing the drug to the outer surface of the balloon body 20. 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. The organic solvent is not particularly limited, but examples include tetrahydrofuran, methanol, ethanol, glycerin, acetone, dichloromethane, hexane, and ethyl acetate. The concentration of the drug in the solution is preferably 0.1 to 20% by mass.

[0080] The application of the drug-containing solution can be carried out by known methods such as brush coating, dip coating, or spray coating, with spray coating being preferred. By spraying the drug-containing solution onto the outer surface of the balloon body 20, the drug lumps 30 can be arranged on the surface of the balloon body 20 while forming gaps 50 between the drug lumps 30.

[0081] In order to arrange the drug aggregate 30 while forming gaps 50, it is preferable to pre-place nucleating agents for drug crystal formation at arbitrary intervals on the outer surface of the balloon body 20 before spray coating with a solution containing the drug. As a result, drug aggregates 30 are formed starting from the nucleating agents, and gaps 50 are formed according to the spacing between the nucleating agents and the size of the drug aggregates 30. Examples of nucleating agents include inorganic salts such as potassium chloride, amino acids such as glycine, particles made of inorganic substances such as talc, and drug particles. The size of the nucleating agent particles should be smaller than the size of the crystal aggregate 30, preferably 3 μm or less, more preferably 1 μm or less, and even more preferably 0.5 μm or less. The lower limit of the outer diameter of the particles is not limited, but may be 0.01 μm or more.

[0082] One method for placing the swellable substance 40 in the gap 50 is to pre-place the swellable substance 40 at arbitrary intervals when placing the nucleating agent on the outer surface of the balloon body 20 before coating with the drug solution. When the solution containing the drug is spray-coated with the balloon body 20 with the swellable substance 40 pre-placed on the outer surface, the swellable substance 40 can be placed in the gap 50 that is formed simultaneously with the drug mass 30.

[0083] One possible method for forming a gap 30a between the bottom surface of the drug mass 30 and the outer surface of the balloon body 20 is as follows. First, prior to applying the drug-containing solution to the outer surface of the balloon body 20, a water-soluble additive is applied to the outer surface of the balloon body 20 to form nuclei 30b of the water-soluble additive, as shown in Figure 12. At this time, as shown in Figures 12 and 13, it is preferable to scatter the nuclei 30b of the water-soluble additive on the outer surface of the balloon body 20 so that the outer surface of the balloon body 20 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 30b 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 12. In Figure 12, for clarity, the nuclei 30b of the water-soluble additive are shown as being arranged at the same position in the circumferential direction z.

[0084] Next, as shown in Figure 14, a solution containing the drug described above is applied to the outer surface of the balloon body 20 on which the water-soluble additive nuclei 30b are located to form a drug mass 30. Subsequently, the water-soluble additive nuclei 30b are removed with an aqueous solvent, thereby forming a void 30a in the area where the water-soluble additive nuclei 30b were located.

[0085] The water-soluble additive is preferably applied by spray coating. This makes it easy to distribute the nuclei 30b of the water-soluble additive on the outer surface of the balloon body 20.

[0086] The removal of the water-soluble additive nuclei 30b can be carried out, for example, by immersing the outer surface of the balloon body 20 on which the drug mass 30 is formed in water. To increase the solubility of the water-soluble additive in water and promote the removal of the water-soluble additive nuclei 30b, it is also preferable to heat the water to 40°C or higher when removing the water-soluble additive nuclei 30b.

[0087] 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.

[0088] 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 body 20, with the distal side of the balloon body 20 connected to the inner shaft 10a and the proximal side of the balloon body 20 connected to the outer shaft 10b.

[0089] Preferably, the balloon catheter 100 has a distal outer shaft 12 and a proximal outer shaft 11, and the distal outer shaft 12 and the proximal outer shaft 11 are separate components, and the proximal end of the distal outer shaft 12 is connected to the distal end of the proximal outer shaft 11, thereby forming an outer shaft 10b that extends from the balloon body 20 to the proximal end of the balloon catheter 100. Alternatively, one outer shaft 10b may extend from the balloon body 20 to the proximal end of the balloon catheter 100, and the distal outer shaft 12 and the proximal outer shaft 11 may be composed of multiple tubular members.

[0090] 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.

[0091] 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, and synthetic rubber. 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.

[0092] The balloon body 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 body 20 and the shaft 10 and crimping it. In particular, it is preferable that the balloon body 20 and the shaft 10 are joined by welding. By welding the balloon body 20 and the shaft 10, the joint between the balloon body 20 and the shaft 10 is less likely to come undone even when the balloon body 20 is repeatedly expanded or contracted, thereby improving the joint strength.

[0093] 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 body 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 body 20, may function as the tip member 80.

[0094] The shaft 10 may have radiopaque markers 90 positioned in the longitudinal direction x where the balloon body 20 is located, in order to allow confirmation of the balloon body 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 body 20, preferably at positions corresponding to both ends of the expansion portion 22 of the balloon body 20, or at a position corresponding to the center of the expansion portion 22 of the balloon body 20.

[0095] 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 flow path supplied to the inside of the balloon body 20.

[0096] 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 strength of the joint 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.

[0097] 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.

[0098] 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 walls of the outer shaft are appropriately coated.

[0099] 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.

[0100] 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.

[0101] Examples of hydrophobic coating agents include polytetrafluoroethylene (PTFE), ethylene fluoride 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. [Explanation of symbols]

[0102] 10: Shaft 10a: Inner shaft 10b: Outer shaft 11: Proximal shaft 12: Distal shaft 20: Balloon body 21: Proximal sleeve portion 22: Expansion section 23: Distal sleeve portion 30: Drug mass 30a: void 30b: The core of water-soluble additives 31: Columnar crystals 31a: 1st end 31b: 2nd end 31J:Joining part 31L: Long shaft 40: Swelling substance 50: Gap 60: Protective layer 70: Hub 71:Fluid injection part 72: Guide wire port 80: Tip component 90: X-ray opaque marker 100: Balloon catheter

Claims

1. A balloon body having a longitudinal direction and a radial direction, The balloon body is arranged on the outer surface of a plurality of drug masses containing a drug, A gap is defined by at least two adjacent drug lumps among the plurality of drug lumps and the outer surface of the balloon body, A balloon catheter having a swelling substance disposed in the gap.

2. The balloon catheter according to claim 1, wherein each of the drug masses comprises a plurality of columnar crystals of the drug arranged radially.

3. The balloon catheter according to claim 2, wherein each of the plurality of columnar crystals has a bonding portion that connects it to one another.

4. The balloon catheter according to claim 1 or 2, wherein the plurality of drug masses include drug masses that overlap each other radially outside the gap.

5. The balloon catheter according to claim 1 or 2, wherein the plurality of drug masses are bonded to each other radially outside the gap.

6. The balloon catheter according to claim 1 or 2, wherein, in a plan view of the balloon body from the radially outer side, the major axis of the drug mass is 10 μm or more and 80 μm or less.

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

8. The balloon catheter according to claim 1 or 2, wherein the plurality of drug masses include drug masses having a gap between the drug mass and the outer surface of the balloon body.

9. The balloon catheter according to claim 8, wherein the swellable substance is disposed in the void.

10. The balloon catheter according to claim 1 or 2, wherein the swelling substance remains on the balloon body after expansion.

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

Images