Balloon for balloon catheter, balloon catheter, and method for manufacturing balloon for balloon catheter

Abstract

This balloon (10) for a balloon catheter has a straight tubular potion (23), a proximal tapered potion, and a distal tapered potion. The straight tubular potion (23) has a high-elastic part (31) including a balloon membrane having a higher elastic modulus than an average elastic modulus, i.e., an average value of the elastic modulus of the whole balloon membrane along the circumferential direction (z), and a low-elastic part (32) including a balloon membrane having a lower elastic modulus than the average elastic modulus. The high-elastic part (31) is disposed at a different position from that of the low-elastic part (32) in the circumferential direction (z). The straight tubular potion (23) includes a peripheral drug layer (33) at an outer surface thereof. The average thickness of the drug layer (33) in the low-elastic part (32) is greater than the average thickness of the drug layer (33) in the high-elastic part (31), or the drug layer (33) is provided in the low-elastic part, not in the high-elastic part.

Description

Balloon for balloon catheter, balloon catheter, and method for manufacturing balloon for balloon catheter

[0001] The present invention relates to a balloon for a balloon catheter, a balloon catheter including the balloon, and a method for manufacturing the balloon.

[0002] The formation of narrowed areas due to calcification and other factors in the inner walls of blood vessels can lead to diseases such as angina pectoris and myocardial infarction. One treatment for these conditions is angioplasty, which uses a balloon catheter to dilate the narrowed area. Angioplasty is a minimally invasive treatment that does not require open chest surgery like bypass surgery, and is widely used.

[0003] A balloon catheter is inserted into a body cavity with its balloon deflated and delivered through the cavity to the treatment site. During delivery, the movement of the balloon is controlled by transmitting operation from the proximal end to the distal end where the balloon is located. In angioplasty, restenosis can occur at the dilated stenotic site. To reduce the frequency of such restenosis (restenosis rate), balloon catheters with a drug supported on the balloon surface are known. By expanding a balloon with a drug supported on its surface at the stenotic site or lesion in a body cavity such as a blood vessel, the drug can be transferred to the inner wall of the body cavity, such as the vascular wall, and this is expected to reduce the occurrence of restenosis.

[0004] For example, Patent Document 1 discloses a dilatation catheter comprising an elongated flexible shaft having at least one lumen extending from a proximal end to a distal end, an inflation balloon attached to the distal end of the shaft and fluidly communicating with the lumen, the balloon having at least three longitudinally extending portions with a wall thickness less than that of the remainder of the balloon, and an attachment portion for connecting the lumen to an inflation and deflation device. Patent Document 2 discloses a balloon catheter having a balloon joined to the distal end of the shaft, the surface of which is coated with a drug and which is inflatable with an inflation fluid supplied through the interior of the shaft, and which delivers the balloon to a lesion via a guide member, the balloon catheter comprising: a sleeve arranged to cover the outside of the balloon and having a connecting portion to which the proximal end of the guide member is connected; the connecting portion is arranged so that the guide member can be inserted therein; a retaining member facing the outer peripheral surface of the guide member and biased radially inward toward the guide member with a pressing force; the retaining member having a plurality of retaining portions with different diameters along the insertion direction of the guide member. Patent Document 3 discloses a balloon catheter having a shaft and a balloon provided on the outside of the shaft, the balloon having a base balloon and a reinforcing portion arranged in a linear or mesh pattern on the outer surface of the base balloon, the reinforcing portion protruding from the outer surface of the balloon, and a drug being retained on the outer surface of the balloon other than the reinforcing portion. Patent Document 4 discloses a balloon catheter that can be inserted into a biological lumen, the balloon catheter having a long catheter body, a radially expandable balloon provided distal to the catheter body, a drug-containing coating layer disposed on the outer surface of the balloon, and a metal layer that is not vapor-deposited on the outer surface of the balloon but is vapor-deposited on the outer surface of the coating layer.

[0005] Japanese Patent Application Laid-Open No. 03-092173 Japanese Patent Application Laid-Open No. 2014-200370 International Publication No. 2018 / 008516 International Publication No. 2018 / 169054

[0006] A balloon with a drug retained on its surface can be expanded at a stenosis or lesion in a body cavity such as a blood vessel, causing the drug to peel off from the balloon surface and migrate to the inner wall of the body cavity, such as the wall of the blood vessel. The greater the difference in strain between the balloon membrane and the drug layer during balloon expansion, the more likely the drug will peel off from the balloon surface. Therefore, in order to efficiently migrate the drug to the inner wall of the body cavity, the elastic modulus of the balloon membrane must be low. However, a low elastic modulus of the balloon membrane makes the balloon expand easily, which can easily lead to overexpansion of the inner wall of the body cavity, leaving room for improvement.

[0007] In view of the above circumstances, an object of the present invention is to provide a balloon for a balloon catheter that is prone to drug peeling from the balloon surface and that is less likely to cause over-expansion of the balloon, a balloon catheter equipped with such a balloon, and a method for manufacturing such a balloon.

[0008] The balloon for a balloon catheter and the balloon catheter including the balloon according to the embodiments of the present invention that have solved the above-mentioned problems are as follows: [1] A balloon for a balloon catheter having a longitudinal axis direction extending from a proximal side to a distal side, a radial direction perpendicular to the longitudinal axis direction, and a circumferential direction, the balloon having a straight tube section, a proximal tapered section located proximal to the straight tube section, and a distal tapered section located distal to the straight tube section, the straight tube section having a high-elasticity section in which the elastic modulus of the balloon membrane is higher than an average elasticity, which is an average value of the elastic modulus of the balloon membrane in the circumferential direction, and a low-elasticity section in which the elastic modulus of the balloon membrane is lower than the average elasticity, the high-elasticity section being located at a different position in the circumferential direction from the low-elasticity section, a drug layer being provided on the outer surface of the straight tube section, the average thickness of the drug layer in the low-elasticity section being greater than the average thickness of the drug layer in the high-elasticity section, or the drug layer being provided on the low-elasticity section and not on the high-elasticity section. [2] The balloon for balloon catheters according to [1], wherein the drug contained in the drug layer is crystalline. [3] The balloon for balloon catheters according to [1] or [2], wherein the balloon has a plurality of the high-elasticity portions and a plurality of the low-elasticity portions, and the high-elasticity portions and the low-elasticity portions are alternately arranged in the circumferential direction. [4] The balloon for balloon catheters according to any one of [1] to [3], wherein, in the deflated state of the balloon, the balloon has mountain folds where the balloon membrane forming the vertices of the wing-shaped portions is bent in a mountain-like manner, and valley folds where the boundaries between two adjacent wing-shaped portions in the circumferential direction are formed, and the average thickness of the drug layer in the valley folds is greater than the average thickness of the drug layer in the mountain folds. [5] The balloon for balloon catheters according to [4], wherein at least a portion of the mountain folds overlaps at least a portion of the high-elasticity portions, and at least a portion of the valley folds overlaps at least a portion of the low-elasticity portions.[6] The balloon for balloon catheters according to any one of [1] to [5], wherein, in a cross section perpendicular to the longitudinal axis direction, the cross-sectional shape of the balloon at the straight tube portion is a polygon having vertices and sides including vertices, the high-elasticity portions are located at the vertices, and the low-elasticity portions are located at the sides. [7] The balloon for balloon catheters according to any one of [1] to [6], wherein the balloon further has a proximal sleeve portion located proximal to the proximal tapered portion and a distal sleeve portion located distal to the distal tapered portion, and wherein, in a cross section perpendicular to the longitudinal axis direction, the cross-sectional shape of the balloon at at least one of the proximal sleeve portion and the distal sleeve portion is circular. [8] A balloon catheter comprising the balloon for balloon catheters according to any one of [1] to [7].

[0009] The method for manufacturing a balloon for a balloon catheter of the present invention is as follows: [9] A method for manufacturing a balloon for a balloon catheter according to any one of [1] to [7], comprising: a component preparation step of preparing a balloon component having a longitudinal axis direction extending from the proximal side to the distal side, and radial and circumferential directions perpendicular to the longitudinal axis direction, the balloon component having a straight tube section, a proximal tapered section located proximal to the straight tube section, and a distal tapered section located distal to the straight tube section; and an application step of applying a medicinal solution to the outer surface of the balloon component in a deflated state after expanding the balloon component.

[10] The method for manufacturing a balloon for a balloon catheter according to [9], further comprising: a parison preparation step of preparing a parison having a longitudinal axis direction extending from the proximal side to the distal side, and a radial direction and a circumferential direction perpendicular to the longitudinal axis direction, the parison having an inner cavity extending in the longitudinal axis direction; and a stretching step of stretching the parison while it is placed in the inner cavity of a mold, wherein the cross-sectional shape of the parison perpendicular to the longitudinal axis direction is circular, and the cross-sectional shape of the inner cavity of the mold perpendicular to the longitudinal axis direction is polygonal with vertices and sides including vertices.

[0010] According to the balloon for a balloon catheter, the straight tube portion has a high-elasticity portion and a low-elasticity portion, and the average thickness of the drug layer in the low-elasticity portion is greater than the average thickness of the drug layer in the high-elasticity portion, or a drug layer is provided in the low-elasticity portion and not in the high-elasticity portion, thereby preventing over-expansion of the balloon with the high-elasticity portion, while facilitating peeling of the drug layer from the balloon surface with the low-elasticity portion. As a result, a balloon for a balloon catheter in which drug peeling is likely to occur and over-expansion of the balloon is unlikely to occur, and a balloon catheter having such a balloon for a balloon catheter can be obtained. Furthermore, according to the method for manufacturing a balloon for a balloon catheter of the present invention, the balloon for a balloon catheter of the present invention can be easily manufactured.

[0011] 1 shows a side view of a balloon in an expanded state according to one embodiment of the present invention.

[0033] FIG. 1 shows a cross-sectional view II-II of the balloon shown in FIG. 1.

[0034] FIG. 1 shows a side view of the balloon in a deflated state according to one embodiment of the present invention.

[0035] FIG. 2 shows a cross-sectional view IV-IV of the balloon shown in FIG. 3.

[0036] FIG. 3 shows a cross-sectional view showing a modified version of the balloon shown in FIG. 4.

[0037] FIG. 4 shows a cross-sectional view showing a modified version of the balloon shown in FIG. 4.

[0038] FIG. 5 shows a side view of a balloon catheter having the balloon shown in FIG. 1.

[0039] FIG. 6 shows a side view of balloon components in a method for manufacturing a balloon according to one embodiment of the present invention.

[0039] FIG. 7 shows a schematic view (partial cross-sectional view) of a parison placed in the lumen of a mold in a method for manufacturing a balloon according to one embodiment of the present invention.

[0039] FIG. 8 shows a cross-sectional view XI-XI of a parison placed in the lumen of the mold shown in FIG.

[0039] FIG. 9 shows a schematic view illustrating an example of a process for non-destructively measuring the thickness of a drug layer by setting multiple measurement points at equal intervals along both the longitudinal and circumferential directions in a straight tube portion of a balloon.

[0039] FIG. 10 shows a schematic view illustrating an example of a tubular film body obtained by cutting off both ends of a straight tube portion of a balloon. 14 is a schematic diagram showing a state in which the cylindrical film body shown in FIG. 13 has been cut open along the longitudinal direction at any position in the circumferential direction and flattened. FIG. 15 is a schematic diagram showing a state in which a plurality of linear markings extending along the longitudinal direction have been provided at equal intervals in the circumferential direction on the outer surface of the flattened film body. FIG. 16 is a schematic diagram showing a state in which the film body to which the markings have been provided has been stretched in the circumferential direction. FIG. 17 is a schematic diagram showing a process in which a flat film body is cut along the longitudinal direction into regions divided based on elastic properties to obtain strip-shaped test pieces. FIG. 18 is a schematic diagram showing a state in which the strip-shaped test pieces have been stretched in the longitudinal direction.

[0012] The present invention will be described below based on the embodiments, but the present invention is not limited to the following embodiments and can be implemented with appropriate modifications within the scope of the above and below-described purposes, and all such modifications are included within the technical scope of the present invention. In addition, hatching and component symbols may be omitted in each drawing for convenience. In such cases, 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 is given to helping understand the features of the present invention.

[0013] A balloon for a balloon catheter according to an embodiment of the present invention is a balloon for a balloon catheter having a longitudinal axis direction extending from the proximal side to the distal side, and radial and circumferential directions perpendicular to the longitudinal axis direction, the balloon having a straight tube section, a proximal tapered section located proximal to the straight tube section, and a distal tapered section located distal to the straight tube section, the straight tube section having a high elasticity section in which the elastic modulus of the balloon membrane is higher than the average elasticity, which is the average value of the elasticity of the balloon membrane in the circumferential direction, and a low elasticity section in which the elastic modulus of the balloon membrane is lower than the average elasticity, the high elasticity section being located at a different position in the circumferential direction from the low elasticity section, a drug layer being provided on the outer surface of the straight tube section, the average thickness of the drug layer in the low elasticity section being greater than the average thickness of the drug layer in the high elasticity section, or a drug layer being provided on the low elasticity section and no drug layer being provided on the high elasticity section.

[0014] Hereinafter, a balloon for a balloon catheter according to an embodiment of the present invention will be described with reference to FIGS. 1 to 8 and 12 to 18. FIGS. 1 and 2 show a balloon according to an embodiment of the present invention in an expanded state. FIG. 1 is a side view of the balloon in an expanded state, and FIG. 2 is a cross-sectional view of the balloon shown in FIG. 1 taken along line II-II, perpendicular to the longitudinal axis of the straight tube portion of the balloon. FIGS. 3 and 4 show a balloon according to an embodiment of the present invention in a deflated state. FIG. 3 is a side view of the balloon in a deflated state, and FIG. 4 is a cross-sectional view of the balloon shown in FIG. 3 taken along line IV-IV, perpendicular to the longitudinal axis of the straight tube portion of the balloon. FIGS. 5 to 7 are cross-sectional views showing modified versions of the balloon shown in FIG. 4, each showing a cross-sectional view of the straight tube portion of the balloon in a deflated state, perpendicular to the longitudinal axis of the straight tube portion. FIG. 8 is a side view of a balloon catheter having the balloon shown in FIG. 1. FIG. 12 is a schematic diagram showing an example of a process for nondestructively measuring the thickness of a drug layer by setting multiple measurement points at equal intervals along both the longitudinal and circumferential directions of the straight tube portion of the balloon. Fig. 13 is a schematic diagram showing an example of a cylindrical film body obtained by cutting both ends of a straight tube portion of a balloon. Fig. 14 is a schematic diagram showing the cylindrical film body shown in Fig. 13 incised along the longitudinal direction at any circumferential position to be flattened. Fig. 15 is a schematic diagram showing a state in which a plurality of linear markings extending along the longitudinal direction are provided at equal intervals in the circumferential direction on the outer surface of the flattened film body. Fig. 16 is a schematic diagram showing a state in which the film body with the markings is stretched in the circumferential direction. Fig. 17 is a schematic diagram showing a process of obtaining strip-shaped test pieces by cutting the flat film body along the longitudinal direction into regions divided based on elastic properties. Fig. 18 is a schematic diagram showing a state in which the strip-shaped test piece is stretched in the longitudinal direction.

[0015] 1 and 3, the balloon 10 of the present invention is a balloon 10 for a balloon catheter 1 having a longitudinal axis direction x extending from the proximal side to the distal side, and a radial direction y and a circumferential direction z perpendicular to the longitudinal axis direction x. In this specification, a balloon for a balloon catheter may be simply referred to as a "balloon."

[0016] In this specification, the direction toward the user's hand in the longitudinal axis direction x is referred to as the proximal side, and the opposite side from the proximal side, i.e., the direction toward the patient, is referred to as the distal side. Furthermore, when each component or part is divided into two equal parts along the longitudinal axis direction x of the balloon 10, the distal part of each component or part is referred to as the distal portion of each component or part, and the proximal part of each component or part is referred to as the proximal portion of each component or part. The distal end of each component or part is the most distal end of each component or part. The proximal end of each component or part is the most proximal end of each component or part. The term "end" includes the peripheral portion of the end. In other words, the distal end refers to the distal end and the peripheral portion of the distal end, and the proximal end refers to the proximal end and the peripheral portion of the proximal end.

[0017] Components and parts other than the balloon 10 also have longitudinal axis directions, radial directions, and circumferential directions, which may or may not be the same as the longitudinal axis directions x, radial directions y, and circumferential directions z of the balloon 10. However, for ease of understanding, this specification will be described as assuming that all components and parts have the same longitudinal axis directions x, radial directions y, and circumferential directions z as the longitudinal axis directions x, radial directions y, and circumferential directions z of the balloon 10.

[0018] The balloon 10 is located at the distal portion of the balloon catheter 1. The balloon 10 can be expanded by introducing fluid into the lumen of the balloon 10, and can be deflated by expelling fluid from the lumen of the balloon 10.

[0019] The balloon catheter 1 dilates the stenotic site by inserting the balloon 10 provided at the distal end of the balloon catheter 1 into the lumen of the blood vessel, delivering it to the stenotic site, and then inflating the balloon 10. When inserting the balloon 10 into the stenotic site or removing it from the body, fluid is discharged from the lumen of the balloon 10 to cause it to contract, and the wing-shaped portion of the balloon 10 can be wrapped around the shaft 40 of the balloon catheter 1 to reduce the outer diameter of the balloon 10.

[0020] As shown in Figures 1 and 3, the balloon 10 has a straight tube section 23, a proximal tapered section 22 located proximal to the straight tube section 23, and a distal tapered section 24 located distal to the straight tube section 23.

[0021] The straight tube portion 23 preferably has a substantially cylindrical shape with approximately the same diameter in the longitudinal axis direction x when the balloon 10 is inflated, but may have different diameters in the longitudinal axis direction x. The proximal tapered portion 22 and the distal tapered portion 24 preferably have a substantially conical or frustum-shaped shape with a diameter decreasing with increasing distance from the straight tube portion 23 when the balloon 10 is inflated. Having the straight tube portion 23 have the largest diameter when the balloon 10 is inflated, the straight tube portion 23 can sufficiently contact the lesion when the balloon 10 is inflated at a lesion such as a stenosis, facilitating treatment such as dilation of the lesion. Furthermore, having the proximal tapered portion 22 and the distal tapered portion 24 reduced in diameter when the balloon 10 is inflated can facilitate reducing the outer diameters of the proximal and distal ends of the balloon 10 when the balloon 10 is deflated. Furthermore, the step between the shaft 40 of the balloon catheter 1 and the balloon 10 can be reduced, facilitating insertion of the balloon 10 into a body cavity.

[0022] 1 and 3, the balloon 10 preferably further includes a proximal sleeve portion 21 located proximal to the proximal tapered portion 22 and a distal sleeve portion 25 located distal to the distal tapered portion 24. The proximal tapered portion 22, the straight tube portion 23, and the distal tapered portion 24 are portions that expand when a fluid is introduced into the balloon 10, whereas the proximal sleeve portion 21 and the distal sleeve portion 25 are preferably portions that do not expand. Because the proximal sleeve portion 21 and the distal sleeve portion 25 are portions that do not expand, it is easier to firmly fix at least a portion of the proximal sleeve portion 21 and at least a portion of the distal sleeve portion 25 to a member such as the shaft 40.

[0023] Examples of materials that can be used to form the balloon 10 include polyamide resins such as nylon 11 and nylon 12, polyester resins such as polyethylene terephthalate and polybutylene terephthalate, polyurethane resins, and thermoplastic elastomers such as polyether block amide copolymers.

[0024] The balloon 10 can be obtained by biaxially stretching or blow molding a parison. The parison is a cylindrical member made of resin and has an internal cavity. The method for manufacturing the balloon 10 will be described in detail later.

[0025] As shown in Figures 2 and 4 to 7, the straight tube section 23 has a high-elasticity section 31 in which the elastic modulus of the balloon membrane is higher than the average elastic modulus, which is the average value of the elastic modulus of the balloon membrane in the circumferential direction z, and a low-elasticity section 32 in which the elastic modulus of the balloon membrane is lower than the average elastic modulus, and the high-elasticity section 31 is located at a different position in the circumferential direction z from the low-elasticity section 32.

[0026] Below, we will explain a series of steps (steps A to G) for evaluating the average thickness of drug layer 33 in high-elasticity portion 31 and low-elasticity portion 32 of balloon 10. These steps clarify the relationship between the thickness distribution of drug layer 33 and the elastic properties of balloon 10, making it possible to analyze both together.

[0027] Step A: Measuring Drug Layer Thickness As shown in FIG. 12 , multiple measurement points P are set at equal intervals along the longitudinal direction x and the circumferential direction z in the straight tube section 23 of the balloon 10, and the thickness of the drug layer 33 at each measurement point P is measured nondestructively. For example, measurement points P can be set at 10 to 50 locations along the longitudinal direction x and 10 to 30 locations along the circumferential direction z. Optical techniques such as white light interferometry, spectroscopic ellipsometry, or confocal laser microscopy can be used to measure the thickness of the drug layer 33 in the straight tube section 23 of the balloon 10. This allows the thickness of the drug layer 33 in the straight tube section 23 of the balloon 10 to be mapped as a two-dimensional distribution in the longitudinal direction x and the circumferential direction z.

[0028] Step B: Removal of Drug Layer and / or Coating The drug layer 33 formed on the balloon 10 is removed. If a coating layer is present on the surface of the balloon 10, it is preferable to remove the coating layer as well. The method for removing the drug layer 33 and the coating layer is not particularly limited, but examples include dissolution treatment using an organic solvent such as ethanol, methanol, or chloroform, or surface treatment such as plasma treatment or ultraviolet ozone treatment.

[0029] Step C: Partitioning of Regions in the Circumferential Direction z of the Balloon 10 As a preprocessing step for distinguishing between high-elasticity and low-elasticity regions of the balloon 10, the balloon 10 is partitioned into multiple regions along the circumferential direction z. Specifically, first, both ends of the straight tube portion 23 in the longitudinal direction x are cut from the balloon 10 to form a cylindrical film body as shown in FIG. 13. In FIG. 12, dashed lines L1 and L2 indicate the cutting positions of the balloon 10. The cylindrical film body is incised along the longitudinal direction x at any position in the circumferential direction z to form a flat film body F as shown in FIG. 14. In FIG. 13, dashed line L3 indicates the cutting position of the cylindrical film body. Furthermore, as shown in FIG. 15, multiple linear markings M extending at least in the longitudinal direction x are applied at equal intervals in the circumferential direction z to one main surface of the flattened film body F. Here, multiple other linear markings extending in the circumferential direction z may also be applied at equal intervals in the longitudinal direction x. This results in a grid-like marking. The number of markings M is not particularly limited, but may be, for example, 30 or more, 40 or more, 50 or more, or 360 or less, 180 or less, or 100 or less. The markings M can be formed using ink, laser engraving, indentation, or other means. As shown in FIG. 16 , a film body F bearing markings M is gripped near both ends in the circumferential direction z by chucks 91 and 92 using a tensile tester, and a tensile load is applied in the circumferential direction z under conditions of, for example, a chuck distance of 10 mm to 35 mm and a tensile speed of 100 μm / sec. The elongation rate in the circumferential direction z in the tensile test is preferably set to, for example, 3% to 15% depending on the material, as long as the difference in deformation behavior between the high elasticity portion 31 and the low elasticity portion 32 is visualized. During the tensile test, the distance S (distance) between two adjacent markings in the circumferential direction z is measured sequentially or at the end point. The distance between the chucks is preferably set so that as many markings M as possible are included in the measurement range, and may be, for example, 80% to 95% of the total length in the circumferential direction z of the film body F. During or after the tensile test, the spacing S between two adjacent markings M is compared, and a group of adjacent markings having similar spacing S is classified as one elastic property region (hereinafter simply referred to as a region).In this way, the film body is divided into multiple regions along the circumferential direction z, and each region can be treated as having substantially the same elastic properties. For example, in Figure 16, the film body is divided into regions A1 to A6. The term "spacing S" refers to a group including multiple markings whose spacings are determined to be substantially the same by sequentially evaluating the distance (spacing S) between two adjacent markings M to determine whether the difference is within ±10% of the shorter value of the comparison. Such a group of markings is determined to correspond to a region with substantially the same amount of elastic deformation and can be classified as a single elastic property region. For example, suppose the values ​​of the spacings S1 to S7 between markings arranged in order along the circumferential direction are 1.00 mm, 1.02 mm, 1.05 mm, 1.08 mm, 1.09 mm, 1.07 mm, and 1.40 mm, respectively. In this case, for each adjacent pair (S1 and S2, S2 and S3, ... S5 and S6), the difference is within ±10% of the shorter of the pairs being compared, so S1 to S6 are classified into the same elastic property range. On the other hand, when comparing S6 (1.07 mm) with S7 (1.40 mm), the ±10% tolerance range based on the shorter 1.07 mm is 0.963 mm to 1.177 mm, but S7 is far outside this range. Therefore, it is determined that there is a clear difference in elastic property between S6 and S7, and S7 and beyond are classified into different elastic property ranges.

[0030] Step D: Measurement of Elastic Modulus of Each Region As shown in Figure 17, in each region divided in step C, the film body F is cut along the longitudinal direction x to prepare strip-shaped test pieces T. In Figure 17, the broken line L4 indicates the cutting position of the film body F in step D. As shown in Figure 18, both ends of each test piece T in the longitudinal direction x are fixed with chucks 93 and 94 of a tensile tester, and a tensile test is performed with the chuck distance set to 0.9 to 0.98 times the length of the test piece T and the tensile speed set to 100 μm / sec. At this time, the relationship between the chuck distance and the load is plotted, and the tensile modulus (MPa) is calculated using the following formula. Tensile modulus (MPa) = (load change when the distance between chucks is elongated by 10-20% before the start of the test / cross-sectional area of ​​the test specimen) / (10-20% elongation / initial length of the test specimen). When the length of a certain region in the circumferential direction z is long, as shown in FIG. 17 , the tensile modulus can be measured using a strip-shaped test specimen obtained by further cutting the film body F in that region along the longitudinal direction x, and the average of the measurement results can be used as the tensile modulus of that region. In step D, when measuring the modulus of elasticity in each region, the modulus obtained by a tensile test along the longitudinal direction x of the balloon 10 is used as the modulus of elasticity in the circumferential direction z of that region. This is because the balloon membrane is thin and the material composition and manufacturing conditions are approximately the same in both the longitudinal direction x and the circumferential direction z, so it can be assumed that there is no substantial difference in the modulus of elasticity between the longitudinal direction x and the circumferential direction z. Therefore, the evaluation of the modulus of elasticity in the circumferential direction z of each region in step D is based on the results of the tensile test in the longitudinal direction z.

[0031] Step E: Measurement of Average Elastic Modulus The average value is calculated from the elastic moduli of all the regions measured in step D, and this is taken as the average elastic modulus.

[0032] Step F: Classification of high elasticity portion and low elasticity portion With regard to the elastic modulus of each region calculated in step D, a region where the elastic modulus is higher than the average elastic modulus is designated as a high elasticity portion 31, and a region where the elastic modulus is lower than the average elastic modulus is designated as a low elasticity portion 32. Note that a region where the elastic modulus is equal to the average elastic modulus may be treated as an intermediate region that does not belong to either category.

[0033] Step G: Superimposing the two-dimensional mapping results of drug layer thickness on the classification results of high elasticity and low elasticity portions. The two-dimensional mapping results of drug layer 33 thickness at each measurement point P calculated in step A are superimposed on the high elasticity portions 31 and low elasticity portions 32 classified in step F. The average value of the thicknesses of drug layer 33 at multiple measurement points P in one high elasticity portion 31 of balloon 10 is taken as the average thickness of drug layer 33 in that high elasticity portion 31. Similarly, the average value of the thicknesses of drug layer 33 at multiple measurement points in one low elasticity portion 32 of balloon 10 is taken as the average thickness of drug layer 33 in that low elasticity portion 32. This makes it possible to evaluate whether the average thickness of drug layer 33 in low elasticity portions 32 is greater than the average thickness of drug layer 33 in high elasticity portions 31 for the balloon 10 being measured, or whether drug layer 33 is provided only in low elasticity portions 32 and not in high elasticity portions 31.

[0034] In general, the elastic modulus of a balloon membrane can be calculated, for example, by taking a test specimen from the balloon membrane located at the straight tube portion 23 of the balloon 10, fixing both ends of the test specimen with chucks using a tensile tester, pulling the test specimen with a chuck distance of 1.5 mm and a pulling speed of 100 μm / sec, plotting the relationship between the chuck distance and the load, and using the following formula: Tensile elastic modulus (MPa) = (load change when the chuck distance is elongated by 10 to 20% before the start of the test / cross-sectional area of ​​the test specimen) / (10 to 20% elongation / initial length of the test specimen).

[0035] If it is difficult to obtain a test specimen from the balloon membrane of the balloon 10, for example, if the balloon 10 is a small-diameter balloon, the elastic modulus may be calculated indirectly by separately preparing balloon samples that are homogeneous all around and molded from a parison made of the same material as the parison used to mold the balloon 10, under the same stretch ratio conditions as the stretch ratios for the high elasticity portion 31 and the low elasticity portion 32 when the balloon 10 is molded, and then obtaining test specimens from these balloon samples.

[0036] Although not shown, the straight tube portion 23 may have a portion different from the high elasticity portion 31 and the low elasticity portion 32. An example of a portion different from the high elasticity portion 31 and the low elasticity portion 32 is a portion where the elastic modulus of the balloon membrane is approximately the same as the average elastic modulus.

[0037] 1 to 7, a drug layer 33 is provided on the outer surface of the straight tube portion 23. That is, the drug layer 33 containing a drug is disposed on the outer surface of the balloon membrane located at the straight tube portion 23 of the balloon 10.

[0038] 4 to 7 show cross-sectional views perpendicular to the longitudinal axis direction x of the straight tube portion 23 in a deflated state in which the balloon 10 is deflated by applying negative pressure to the balloon 10. FIGS. 4 and 5 illustrate balloons 10 having a relatively thick membrane or a relatively high rigidity, such as so-called "low-compliant balloons" or "semi-compliant balloons." FIGS. 6 and 7 illustrate balloons 10 having a relatively thin membrane or a flexible membrane that is easily deformed, such as so-called "compliant balloons." That is, when the balloon 10 is deflated, the membrane of the balloon 10 shown in FIGS. 4 and 5 does not conform closely to the outer surface of the inner tube disposed inside the balloon 10, whereas the membrane of the balloon 10 shown in FIGS. 6 and 7 tends to conform to the outer surface of the inner tube.

[0039] As shown in Figures 4 and 6, the drug layer 33 may be provided on the outer surface of the straight pipe section 23 throughout the entire circumferential direction z, or as shown in Figures 5 and 7, the drug layer 33 may be provided only on a portion of the outer surface of the straight pipe section 23 in the circumferential direction z, with no drug layer 33 being provided on the remaining portion.

[0040] As shown in Figures 4 and 6, one example of providing the drug layer 33 on the outer surface of the straight tube section 23 over the entire circumferential direction z is to apply the drug solution that forms the drug layer 33 by immersing the balloon 10 in the drug solution that forms the drug layer 33, i.e., by dipping. Also, as shown in Figures 5 and 7, one example of providing the drug layer 33 on the outer surface of the straight tube section 23 over a portion of the circumferential direction z is to apply the drug solution that forms the drug layer 33 by spraying it onto the outer surface of the balloon 10, i.e., by inkjet printing.

[0041] Furthermore, as shown in Figures 1 and 3, a drug layer 33 may be provided on the outer surface of the straight tube section 23 throughout the entire longitudinal axis direction x, or, although not shown, a drug layer 33 may be provided only on the outer surface of the straight tube section 23 in a portion of the longitudinal axis direction x, with no drug layer 33 being provided on the remaining portion.

[0042] The drug contained in the drug layer 33 is preferably a pharmacologically active substance. Examples of pharmacologically active substances include medicaments acceptable as medicines, such as gene therapy drugs, non-gene therapy drugs, small molecules, and cells. In particular, when the balloon catheter 1 is used for the purpose of suppressing restenosis of a blood vessel after angioplasty, anti-restenosis drugs such as antiproliferative agents and immunosuppressants are preferably used as the drug. Specifically, drugs such as paclitaxel, sirolimus (rapamycin), everolimus, and zotarolimus can be used. These drugs may be used alone or in combination of two or more types.

[0043] In addition to the drug, drug layer 33 may contain an auxiliary agent for improving the drug's dispersibility, solubility, migration to the vascular wall, and storage stability. Examples of the auxiliary agent that can be used include a stabilizer, a binder, a disintegrant, a moisture-proofing agent, a preservative, and a dissolution aid. Specific examples include lactose, sucrose, maltose, dextrin, xylitol, erythritol, mannitol, ethylenediamine, potassium iodide, urea, polysorbate, dibutylhydroxytoluene, polyethylene glycol, lipids, sodium pyrosulfite, ascorbic acid, tocopherol, benzoic acid, parahydroxybenzoic acid ester, polyacrylic acid, polylactic acid, polyglycolic acid, hyaluronic acid, chitosan, and gelatin.

[0044] The drug layer 33 may have a protective layer to prevent the drug from eluting into the blood or falling off during delivery to the stenosis or lesion of the balloon 10. The protective layer is preferably included as part of the drug layer 33 and constitutes the outermost layer of the drug layer 33. The protective layer may be made of, for example, a water-soluble polymer, such as carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, alginic acid, pectin, gum arabic, gellan gum, guar gum, xanthan gum, carrageenan, or gelatin.

[0045] As shown in Figures 2 and 4 to 7, the average thickness of the drug layer 33 in the low-elasticity section 32 is greater than the average thickness of the drug layer 33 in the high-elasticity section 31, or the drug layer 33 is provided in the low-elasticity section 32 and not in the high-elasticity section 31. That is, in the straight tube section 23, the drug layer 33 is provided on at least a portion of the outer surface of the balloon membrane in the low-elasticity section 32, whereas the drug layer 33 may be provided on at least a portion of the outer surface of the balloon membrane in the high-elasticity section 31, or the drug layer 33 may not be provided on the outer surface of the balloon membrane. Note that an average thickness of the drug layer 33 of 0 in the high-elasticity section 31 refers to no drug layer 33 being provided in the high-elasticity section 31. Hereinafter, an average thickness of the drug layer 33 of 0 in the high-elasticity section 31 may be expressed as (including 0).

[0046] Specifically, examples of the average thickness of the drug layer 33 in the low elasticity portion 32 being greater than the average thickness (including 0) of the drug layer 33 in the high elasticity portion 31 include a configuration in which a drug layer 33 is provided in both the high elasticity portion 31 and the low elasticity portion 32, as shown in Figures 4 and 6, and the average thickness of the drug layer 33 in the low elasticity portion 32 is greater than the average thickness of the drug layer 33 in the high elasticity portion 31, a configuration in which a drug layer 33 is provided over the entire low elasticity portion 32, and no drug layer 33 is provided in the high elasticity portion 31, as shown in Figure 5, and a configuration in which a drug layer 33 is provided only in a part of the low elasticity portion 32, and no drug layer 33 is provided in the high elasticity portion 31, as shown in Figure 7.

[0047] If the average thickness of the drug layer 33 in the low-elasticity region 32 is greater than the average thickness of the drug layer 33 in the high-elasticity region 31, or if the drug layer 33 is provided in the low-elasticity region 32 but not in the high-elasticity region 31, the balloon membrane is more likely to distort in the low-elasticity region 32, where the elastic modulus of the balloon membrane is low, resulting in a larger difference in the amount of strain between the balloon membrane and the drug layer 33. This makes it easier for the drug layer 33 to peel off from the outer surface of the balloon membrane in the low-elasticity region 32, facilitating the transfer of the drug to the inner wall of the body cavity, such as the surface of a blood vessel. Furthermore, in the high-elasticity region 31, where the elastic modulus of the balloon membrane is high, the balloon membrane is less likely to distort and stretch when the balloon 10 is inflated. As a result, over-inflation of the balloon 10 can be prevented.

[0048] At least one of the proximal tapered section 22 and the distal tapered section 24 of the balloon 10 also has a high elasticity section 31 and a low elasticity section 32, the high elasticity section 31 being located at a different circumferential position from the low elasticity section 32, a drug layer 33 being provided on the outer surface of at least one of the proximal tapered section 22 and the distal tapered section 24, and it is preferable that the average thickness of the drug layer 33 in the low elasticity section 32 is greater than the average thickness (including zero) of the drug layer 33 in the high elasticity section 31. By having the high elasticity section 31 and the low elasticity section 32 in at least one of the proximal tapered section 22 and the distal tapered section 24 and the average thickness of the drug layer 33 in the low elasticity section 32 being greater than the average thickness (including zero) of the drug layer 33 in the high elasticity section 31, it is possible to prevent over-expansion of the balloon 10 while facilitating efficient transfer of the drug to the inner wall of the body cavity.

[0049] The average thickness of drug layer 33 in low-elasticity portion 32 is preferably at least 2.0 times, more preferably at least 2.5 times, and even more preferably at least 3.0 times, the average thickness of drug layer 33 in high-elasticity portion 31. By setting the lower limit of the ratio of the average thickness of drug layer 33 in low-elasticity portion 32 to the average thickness of drug layer 33 in high-elasticity portion 31 within the above range, a sufficient amount of drug is likely to peel off due to distortion of the balloon membrane in low-elasticity portion 32 during inflation of balloon 10, allowing the drug to be efficiently transferred to the inner wall of the body cavity by balloon 10. Furthermore, the upper limit of the ratio of the average thickness of drug layer 33 in low-elasticity portion 32 to the average thickness of drug layer 33 in high-elasticity portion 31 is not particularly limited, but can be, for example, 100 times or less, 80 times or less, or 50 times or less.

[0050] The drug contained in drug layer 33 is preferably crystalline. When the drug contained in drug layer 33 is crystalline, drug layer 33 becomes brittle. Therefore, when balloon 10 is inflated and the balloon membrane is distorted, drug layer 33 is likely to peel off from the outer surface of the balloon membrane.

[0051] The average film thickness of the balloon 10 in the low-elasticity portion 32 may be smaller than the average film thickness of the balloon 10 in the high-elasticity portion 31, or may be the same as the average film thickness of the balloon 10 in the high-elasticity portion 31, but is preferably larger than the average film thickness of the balloon 10 in the high-elasticity portion 31. By making the average film thickness of the balloon 10 in the low-elasticity portion 32 larger than the average film thickness of the balloon 10 in the high-elasticity portion 31, it becomes easier to increase the strength of the balloon membrane in the low-elasticity portion 32, where the elastic modulus of the balloon membrane is low, and the pressure resistance of the balloon 10 during inflation can be improved.

[0052] The film thicknesses of the high-elasticity and low-elasticity regions 31 and 32 of the balloon 10 can be measured using the following method using the planar film or rectangular test piece obtained by the above-described steps C and D. First, measurement points are set at equal intervals in the longitudinal direction x and the circumferential direction z on the film corresponding to each region. For example, three to five locations are set along the longitudinal direction x and three to five locations along the circumferential direction z, forming a grid-like group of measurement points on the rectangular film surface. Next, the film thickness (i.e., the thickness of the balloon film) is measured at each measurement point. Measurements can be performed using techniques such as a white light interferometer, a confocal laser microscope, a laser thickness meter, a contact probe, microscopic measurement by cross-sectional observation, or X-ray imaging. These measurement techniques are appropriately selected depending on the material and structure of the film. The average film thickness in that region (high-elasticity or low-elasticity region) can be determined by averaging the film thickness measurements obtained at each measurement point.

[0053] 2 and 4 to 7, the balloon 10 has a plurality of high-elasticity portions 31 and a plurality of low-elasticity portions 32, and the plurality of high-elasticity portions 31 and the plurality of low-elasticity portions 32 are preferably arranged alternately in the circumferential direction z. By configuring the balloon 10 so that the plurality of high-elasticity portions 31 and the plurality of low-elasticity portions 32 are arranged alternately in the circumferential direction z, the high-elasticity portions 31 can prevent overexpansion of the balloon 10 throughout the entire circumferential direction z, while the low-elasticity portions 32 can facilitate peeling of the drug layer 33 from the outer surface of the balloon membrane.

[0054] In the balloon 10, it is preferable to adjust the distribution of the drug layer 33 according to the local stiffness (hardness) of the balloon membrane. Specifically, the straight tube section 23 has hard regions where the balloon membrane has a higher-than-average hardness and soft regions where the balloon membrane has a lower-than-average hardness. The hard regions are located at different positions in the circumferential direction z from the soft regions, and the average thickness of the drug layer 33 in the soft regions is greater than the average thickness of the drug layer 33 in the hard regions. Alternatively, the drug layer 33 is provided in the soft regions but not in the hard regions. With this configuration, when the balloon 10 is inflated, the membrane strain in the soft regions increases, facilitating the peeling of the drug layer 33 and improving drug delivery efficiency.

[0055] Nanoindentation testing can be used to distinguish between hard and soft regions in a balloon membrane. Specifically, a nanoindenter is pressed into multiple points on the planar film or strip-shaped test piece obtained in steps C and D, and the hardness index (e.g., nanohardness) at each point is calculated based on the obtained load-displacement curve. Two-dimensional mapping of the hardness data obtained in this manner at each point can visualize the hardness distribution on the balloon membrane surface. In the obtained hardness distribution, regions with a higher than average hardness are classified as hard regions, and regions with a lower than average hardness are classified as soft regions. By overlaying this region information with the film thickness distribution data of the drug layer 33 obtained in step A, it is possible to evaluate whether the average thickness of the drug layer 33 in the soft regions is greater than that in the hard regions, or whether the drug layer 33 is present only in the soft regions.

[0056] 2 and 4 to 7, the balloon 10 has multiple hard regions and multiple soft regions, and the multiple hard regions and multiple soft regions are preferably arranged alternately in the circumferential direction z. By configuring the balloon 10 with multiple hard regions and multiple soft regions arranged alternately in the circumferential direction z, the hard regions can prevent overexpansion of the balloon 10 throughout the entire circumferential direction z, while the soft regions can facilitate peeling of the drug layer 33 from the outer surface of the balloon membrane.

[0057] It is preferable that the hard region and the high elasticity region 31 overlap at least partially, and that the soft region and the low elasticity region 32 overlap at least partially. It is more preferable that the hard region coincides with the high elasticity region 31, and the soft region coincides with the low elasticity region 32. This allows the elastic modulus and hardness of the balloon membrane to be designed to match, enabling a well-balanced control of drug retention and release properties. Specifically, in the hard and high elasticity region, deformation of the balloon membrane is suppressed, resulting in high retention of the drug layer, while in the soft and low elasticity region, membrane deformation is large, promoting release of the drug layer.

[0058] 4 to 7, in the deflated state of the balloon 10, the balloon 10 preferably has mountain folds 12, where the balloon membrane forming the apexes P1 of the wing-shaped portions 11 is bent in a mountain-like manner, and valleys 15, which are boundaries between two adjacent wing-shaped portions 11 in the circumferential direction z. In other words, in a cross section perpendicular to the longitudinal axis direction x of the balloon 10 in the deflated state, the valleys 15 are preferably located between two mountain folds 12 aligned in the circumferential direction z.

[0059] The mountain folds 12 and valley folds 15 can function as guides when a fluid is introduced into the lumen of the balloon 10 to expand the balloon 10, and then the fluid is removed to deflate the balloon 10 and fold the balloon 10. Methods for forming the mountain folds 12 and valley folds 15 in the balloon 10 include, for example, using a folding device on the deflated balloon 10, or pressing the balloon 10 at the locations where the mountain folds 12 and valley folds 15 are to be formed and then deflating (pleating).

[0060] The average thickness of drug layer 33 in valley portions 15 is preferably greater than the average thickness of drug layer 33 in mountain fold portions 12. By making the average thickness of drug layer 33 in valley portions 15 greater than the average thickness of drug layer 33 in mountain fold portions 12, when balloon 10 is deflated and folded, valley portions 15 of wing-shaped portions 11, where drug layer 33 is thicker, are covered by wing-shaped portions 11 where drug layer 33 is thinner or where drug layer 33 is not provided at all. As a result, the drug is less likely to peel off when balloon 10 is delivered to the target site in the folded state, facilitating delivery of the drug to the target site.

[0061] When the balloon 10 is in a deflated state, it is preferable that the balloon 10 has not only multiple mountain folds 12 but also multiple valley folds 15. That is, when the balloon 10 is in a deflated state, it is preferable that the balloon 10 has multiple mountain folds 12 and multiple valley folds 15. When the balloon 10 is in a deflated state, it has multiple mountain folds 12 and multiple valley folds 15, which makes it easier to fold the balloon 10 so that its outer diameter becomes smaller when the balloon 10 is deflated, thereby enabling the balloon 10 to be minimally invasive.

[0062] The mountain folds 12 and valley folds 15 are preferably arranged at least in the straight tube portion 23 of the balloon 10. By having at least the straight tube portion 23 of the balloon 10 have the mountain folds 12 and valley folds 15, the balloon 10 can be easily folded so that the outer diameter of the balloon 10 becomes smaller when the balloon 10 is deflated and folded.

[0063] More preferably, the mountain folds 12 and valley folds 15 are disposed in the straight tube section 23 and at least a portion of the proximal tapered section 22 and distal tapered section 24 of the balloon 10. By having mountain folds 12 and valley folds 15 not only in the straight tube section 23 of the balloon 10 but also in at least a portion of the proximal tapered section 22 and distal tapered section 24, the proximal tapered section 22 and distal tapered section 24 also become easier to fold when the balloon 10 is deflated, making it easier to reduce the outer diameter of the balloon 10 in its deflated state.

[0064] 4 to 7 , it is preferable that at least a portion of the mountain fold 12 overlaps with at least a portion of the high elasticity portion 31, and at least a portion of the valley portion 15 overlaps with at least a portion of the low elasticity portion 32. In other words, it is preferable that the portion of the balloon membrane that constitutes the mountain fold 12 includes at least a portion of the high elasticity portion 31, and the portion of the balloon membrane that constitutes the valley portion 15 includes at least a portion of the low elasticity portion 32, and it is also preferable that at least a portion of the mountain fold 12 is included in the high elasticity portion 31, and at least a portion of the valley portion 15 is included in the low elasticity portion 32. In other words, it is possible that the portion of the balloon membrane that constitutes the mountain fold 12 includes a portion of the low elasticity portion 32, and it is possible that the portion of the balloon membrane that constitutes the valley portion 15 includes a portion of the high elasticity portion 31. Since at least a portion of the mountain fold portion 12 overlaps with at least a portion of the high elasticity portion 31 and at least a portion of the valley portion 15 overlaps with at least a portion of the low elasticity portion 32, the wing-shaped portion 11 is more likely to be formed when the balloon 10 is deflated, and the balloon 10 can be more easily folded so that the outer diameter of the balloon 10 in the deflated state is smaller.

[0065] As shown in Figure 2, in a cross section perpendicular to the longitudinal axis direction x, the cross-sectional shape of the balloon 10 at the straight tube section 23 is preferably a polygon having vertices 13 and sides 14, including vertices. The polygonal cross-sectional shape of the balloon 10 at the straight tube section 23 facilitates the formation of wing-shaped portions 11, with the vertices 13 of the polygonal cross-sectional shape of the balloon 10 serving as the vertices P1 of the wing-shaped portions 11. In other words, mountain folds 12 are more likely to be formed at the vertices 13 of the polygonal cross-sectional shape of the balloon 10, and valleys 15 are more likely to be formed at the sides 14. As a result, mountain folds 12 are more likely to be formed in the balloon 10 along the longitudinal axis direction x, making it easier to fold the balloon 10 so that its outer diameter is smaller when it is deflated.

[0066] In the longitudinal axis direction x, the cross-sectional shape of balloon 10 in at least one of proximal tapered portion 22 and distal tapered portion 24 is preferably a polygon having vertices 13 including vertices and sides 14. By having the cross-sectional shape of balloon 10 in at least one of proximal tapered portion 22 and distal tapered portion 24 be polygonal, at least one of proximal tapered portion 22 and distal tapered portion 24, which has a polygonal cross-sectional shape, can be easily folded when balloon 10 is deflated.

[0067] The cross-sectional shape of the balloon 10 in the longitudinal axis direction x at the proximal tapered portion 22 and the distal tapered portion 24 is preferably a polygon having vertices 13 and sides 14. That is, the cross-sectional shape of the balloon 10 in the longitudinal axis direction x is preferably a polygon at both the proximal tapered portion 22 and the distal tapered portion 24. By having the cross-sectional shape of the balloon 10 in the proximal tapered portion 22 and the distal tapered portion 24 be a polygon, both the proximal tapered portion 22 and the distal tapered portion 24 can be easily folded when the balloon 10 is in a deflated state, and the balloon 10 can be easily folded so that the outer diameter of the entire balloon 10 is small.

[0068] The polygonal cross-sectional shape of the balloon 10 includes polygons with clearly defined corners and straight sides, as well as rounded polygons with rounded corners and polygons with at least some curved sides. Examples of polygonal cross-sectional shapes of the balloon 10 include triangles, rectangles, and pentagons. Of these, a triangular cross-sectional shape of the balloon 10 is preferred. Having a triangular cross-sectional shape of the balloon 10 makes it easier to appropriately determine the number and size of the mountain folds 12 and valley folds 15 formed in the balloon 10.

[0069] When the cross-sectional shape of the balloon 10 at the straight tube portion 23 is polygonal in a cross section perpendicular to the longitudinal axis direction x, it is preferable that the high elasticity portion 31 is located at the vertex 13 and the low elasticity portion 32 is located at the side 14. The high elasticity portion 31 located at the vertex 13 indicates that at least a portion of the high elasticity portion 31 is located at at least a portion of the vertex 13 of the polygon. The low elasticity portion 32 located at the side 14 indicates that at least a portion of the low elasticity portion 32 is located at at least a portion of the side 14 of the polygon. By having the high elasticity portion 31 located at the vertex 13 and the low elasticity portion 32 located at the side 14, the vertex 13 of the polygon becomes the tip and the wing-shaped portion 11 is easily formed when the balloon 10 is deflated. Therefore, the thick drug layer 33 provided in the low elasticity portion 32 is easily covered and protected by the wing-shaped portion 11.

[0070] 1 and 3 , the balloon 10 further includes a proximal sleeve portion 21 located proximal to the proximal tapered portion 22 and a distal sleeve portion 25 located distal to the distal tapered portion 24. In a cross section perpendicular to the longitudinal axis direction x, the cross-sectional shape of the balloon 10 at at least one of the proximal sleeve portion 21 and the distal sleeve portion 25 is preferably circular. That is, the cross-sectional shape of the balloon 10 perpendicular to the longitudinal axis direction x at the straight tube portion 23 is preferably polygonal, and the cross-sectional shape of the balloon 10 perpendicular to the longitudinal axis direction x at at least one of the proximal sleeve portion 21 and the distal sleeve portion 25 is preferably circular. The circular cross-sectional shape of the balloon 10 at at least one of the proximal sleeve portion 21 and the distal sleeve portion 25 ensures that the outer surfaces of the proximal sleeve portion 21 and the distal sleeve portion 25, which are non-expandable portions of the balloon 10 and do not have the wing-shaped portions 11 formed thereon, are smooth. Therefore, when the proximal sleeve portion 21 or the distal sleeve portion 25 comes into contact with another object, it is possible to make the object less likely to be damaged, thereby making the balloon 10 highly safe.

[0071] In a cross section perpendicular to the longitudinal axis direction x, the cross-sectional shape of the balloon 10 is preferably circular at the proximal sleeve portion 21 and the distal sleeve portion 25. By having the cross-sectional shape of the balloon 10 circular at both the proximal sleeve portion 21 and the distal sleeve portion 25, the outer surfaces of both the proximal sleeve portion 21 and the distal sleeve portion 25 can be made smooth, and even if the proximal sleeve portion 21 or the distal sleeve portion 25 comes into contact with an object, it is less likely to damage the object when the balloon 10 is pushed distally or pulled back proximally.

[0072] In a cross section perpendicular to the longitudinal axis direction x, the cross-sectional shape of the balloon 10 at the proximal tapered section 22, the straight tube section 23, and the distal tapered section 24 is preferably polygonal, and the cross-sectional shape of the balloon 10 at the proximal sleeve section 21 and the distal sleeve section 25 is more preferably circular. By having the cross-sectional shapes of the balloon 10 at the proximal tapered section 22, the straight tube section 23, and the distal tapered section 24 be polygonal and the cross-sectional shapes of the balloon 10 at the proximal sleeve section 21 and the distal sleeve section 25 be circular, wing-shaped sections 11 are more likely to be formed when the balloon 10 is deflated at the proximal tapered section 22, the straight tube section 23, and the distal tapered section 24, which are the expandable portions of the balloon 10, making it easier to fold the balloon 10 to reduce its outer diameter, and by having the outer surfaces of the proximal sleeve section 21 and the distal sleeve section 25, which are the non-expandable portions of the balloon 10, be smooth, making it less likely to damage other objects.

[0073] The balloon catheter 1 according to the embodiment of the present invention includes the balloon 10 for the balloon catheter 1 described above.

[0074] As shown in FIG. 8 , a balloon catheter 1 having a balloon 10 according to an embodiment of the present invention preferably includes a shaft 40. The balloon 10 is connected to the distal end of the shaft 40. The balloon 10 can be expanded by introducing a fluid through the lumen of the shaft 40, and can be deflated by discharging the fluid. To control the expansion and contraction of the balloon 10, an indeflator (a balloon pressurizer) can be used to introduce or discharge the fluid. The fluid may be, for example, saline or a mixture of a contrast agent and saline. The fluid may also be a pressurized fluid pressurized by a pump or the like.

[0075] 8 shows a so-called rapid exchange type balloon catheter 1 having a guidewire port 50 midway from the distal side to the proximal side of the shaft 40 and an inner shaft 60 that functions as a guidewire passage from the guidewire port 50 to the distal side of the shaft 40. The balloon catheter 1 preferably has a proximal shaft 41 and a distal shaft 42. The proximal shaft 41 and the distal shaft 42 may be separate members, and the proximal end of the distal shaft 42 may be connected to the distal end of the proximal shaft 41 to form the shaft 40 that extends from the balloon 10 to the proximal end of the balloon catheter 1. Alternatively, a single shaft 40 may extend from the balloon 10 to the proximal end of the balloon catheter 1, and the proximal shaft 41 and the distal shaft 42 may each be composed of multiple tubular members.

[0076] The shaft 40 preferably has a fluid flow path and a guidewire insertion path therein. To configure the shaft 40 to have a fluid flow path and a guidewire insertion path therein, for example, an inner shaft 60 disposed inside the shaft 40 may function as a guidewire insertion path, and the space between the shaft 40 and the inner shaft 60 may function as a fluid flow path. In such a configuration, it is preferable that the inner shaft 60 extends from the distal end of the shaft 40 and passes through the balloon 10, with the distal portion of the balloon 10 connected to the inner shaft 60 and the proximal portion of the balloon 10 connected to the shaft 40.

[0077] The shaft 40 is preferably made of resin, metal, or a combination of resin and metal. Using resin as the constituent material of the shaft 40 facilitates imparting flexibility and elasticity to the shaft 40. Furthermore, using metal as the constituent material of the shaft 40 can improve the deliverability of the balloon catheter 1. Examples of resins that can be used to form the shaft 40 include polyamide resins, polyester resins, polyurethane resins, polyolefin resins, fluorine-containing resins, vinyl chloride resins, silicone resins, natural rubber, synthetic rubber, and the like. These may be used alone or in combination. Examples of metals that can be used to form the shaft 40 include stainless steels such as SUS304 and SUS316, platinum, nickel, cobalt, chromium, titanium, tungsten, gold, Ni-Ti alloys, Co-Cr alloys, and combinations thereof. When the shaft 40 is composed of a proximal shaft 41 and a distal shaft 42 that are separate members, the proximal shaft 41 may be made of resin, and the distal shaft 42 may be made of metal, for example. The shaft 40 may also have a laminated construction of different materials or the same materials.

[0078] The balloon 10 and the shaft 40 can be joined by bonding with an adhesive, welding, or by attaching a ring-shaped member to the overlapping portion of the end of the balloon 10 and the shaft 40 and crimping the end. Of these, it is preferable that the balloon 10 and the shaft 40 are joined by welding. By welding the balloon 10 and the shaft 40 together, the bond between the balloon 10 and the shaft 40 is less likely to come apart even when the balloon 10 is repeatedly expanded or contracted, thereby improving the bond strength.

[0079] A tip member 70 is preferably provided at the distal end of the balloon catheter 1. The tip member 70 may be provided at the distal end of the balloon catheter 1 as a separate member from the inner shaft 60 and connected to the distal end of the balloon 10, or the inner shaft 60 may extend distally beyond the distal end of the balloon 10 and function as the tip member 70.

[0080] Radiopaque markers 80 may be placed on the inner shaft 60 inside the balloon 10 at the location where the balloon 10 is located in the longitudinal axis direction x so that the position of the balloon 10 can be confirmed under X-ray fluoroscopy. The radiopaque markers 80 are preferably placed at positions corresponding to both ends of the straight tube portion of the balloon 10, or may be placed at a position corresponding to the center of the straight tube portion of the balloon 10 in the longitudinal axis direction x.

[0081] The number of radiopaque markers 80 is not particularly limited, and may be one or more. The shape of the radiopaque marker 80 is not particularly limited, and examples thereof include a cylindrical shape, a polygonal cylindrical shape, or another cylindrical shape, a C-shaped cross section with a notch in the cylinder, and a coil shape with a wound wire. Among these, the shape of the radiopaque marker 80 is preferably cylindrical.

[0082] Examples of materials that can be used to form the radiopaque marker 80 include radiopaque materials such as lead, barium, iodine, tungsten, gold, platinum, iridium, stainless steel, titanium, and cobalt-chromium alloys.

[0083] A hub 5 may be provided on the proximal side of the shaft 40, and the hub 5 preferably has a fluid injection section 6 that communicates with a flow path for fluid supplied inside the balloon 10.

[0084] The shaft 40 and the hub 5 can be joined by, for example, bonding with an adhesive or welding. Among these, it is preferable that the shaft 40 and the hub 5 are joined by adhesive. By bonding the shaft 40 and the hub 5, the bond strength between the shaft 40 and the hub 5 can be increased, thereby improving the durability of the balloon catheter 1, even when the shaft 40 and the hub 5 are made of different materials, for example, when the shaft 40 is made of a highly flexible material and the hub 5 is made of a highly rigid material.

[0085] Although not shown, the present invention can also be applied to so-called over-the-wire balloon catheters, which have a guidewire passage extending from the distal to the proximal side of the shaft. In the case of an over-the-wire balloon catheter, it is preferable that the inflation lumen and the guidewire lumen extend to a hub located on the proximal side, and that the proximal openings of each lumen are provided in a bifurcated hub.

[0086] In the case of a rapid exchange type catheter, it is preferable that an appropriate coating is applied to the outer wall of at least one of the proximal shaft 41 and the distal shaft 42, and it is more preferable that a coating is applied to both the proximal shaft 41 and the distal shaft 42. In the case of an over-the-wire type catheter, it is preferable that an appropriate coating is applied to the outer wall of the outer shaft.

[0087] The coating can be a hydrophilic coating or a hydrophobic coating depending on the purpose, and can be applied by immersing the shaft 40 in a hydrophilic or hydrophobic coating agent, applying a hydrophilic or hydrophobic coating agent to the outer wall of the shaft 40, or covering the outer wall of the shaft 40 with a hydrophilic or hydrophobic coating agent, etc. The coating agent may contain a drug or an additive.

[0088] Examples of hydrophilic coating agents include hydrophilic polymers such as polyvinyl alcohol, polyethylene glycol, polyacrylamide, polyvinylpyrrolidone, methyl vinyl ether maleic anhydride copolymer, and hydrophilic coating agents made from any combination thereof.

[0089] Examples of hydrophobic coating agents include polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), silicone oil, hydrophobic urethane resin, carbon coat, diamond coat, diamond-like carbon (DLC) coat, ceramic coat, and substances terminated with alkyl groups or perfluoroalkyl groups and having low surface free energy.

[0090] The manufacturing method of the balloon 10 for the balloon catheter 1 according to the embodiment of the present invention includes a component preparation step of preparing a balloon component 20 having a longitudinal axis direction x extending from the proximal side to the distal side, a radial direction y and a circumferential direction z perpendicular to the longitudinal axis direction x, and having a straight tube portion 23, a proximal tapered portion 22 located proximal to the straight tube portion 23, and a distal tapered portion 24 located distal to the straight tube portion 23; and an application step of applying a medicinal solution to the outer surface of the balloon component 20 in a state in which the balloon component 20 is expanded and then contracted.

[0091] A method for manufacturing a balloon for a balloon catheter according to an embodiment of the present invention will be described below with reference to Figures 9 to 11. Figure 9 is a side view of a balloon component, showing the balloon component in an expanded state. Figure 10 is a schematic diagram of a parison placed in the lumen of a mold, with a cross-sectional view of the mold and parison taken along the longitudinal axis of the parison. Figure 11 is a cross-sectional view taken along line XI-XI of the parison placed in the lumen of the mold shown in Figure 10, showing a cross-sectional view of the mold perpendicular to the longitudinal axis and the parison placed in the lumen of the mold.

[0092] In the member preparation step, a balloon-constituting member 20 is prepared. The balloon-constituting member 20 is a member that constitutes the balloon 10. As shown in Fig. 9 , the balloon-constituting member 20 has a longitudinal axis direction x extending from the proximal side to the distal side, a radial direction y and a circumferential direction z that are perpendicular to the longitudinal axis direction x, and has a straight pipe section 23, a proximal tapered section 22 located proximally of the straight pipe section 23, and a distal tapered section 24 located distally of the straight pipe section 23.

[0093] The balloon-forming member 20 can be obtained, for example, by biaxially stretching or blow molding the parison 100. The parison 100 is made of resin and is a cylindrical member having an internal cavity. The parison 100 can be obtained, for example, by extrusion molding the resin using a cylindrical mold.

[0094] In the application step, the balloon component 20 is expanded and then contracted, and the drug solution is applied to the outer surface of the balloon component 20. That is, the balloon component 20 is expanded, then contracted, and the drug solution is applied to the outer surface of the contracted balloon component 20, thereby forming the drug layer 33.

[0095] The chemical solution applied to the outer surface of the balloon component 20 in the application step includes the drug and auxiliary agents contained in the drug layer 33, the substances mentioned above as the protective layer, and the like.

[0096] In the application process, the drug solution is applied to the outer surface of the balloon component 20 in a contracted state after being expanded, and the surface tension on the outer surface of the balloon component 20 causes the applied drug solution to easily collect and form a pool on the outer surface of the portion that will become the low-elasticity portion 32 of the balloon 10. This allows a larger amount of drug solution to be applied to the outer surface of the balloon component 20 in the portion that will become the low-elasticity portion 32 of the balloon 10, and the thickness of the drug layer 33 on the outer surface of the low-elasticity portion 32 of the balloon 10 can be increased.

[0097] In the coating process, the drug solution may or may not be applied to the outer surface of the balloon component 20 in the portion that will become the high elasticity portion 31 of the balloon 10. In the coating process, applying the drug solution to the outer surface of the balloon component 20 in the portion that will become the high elasticity portion 31 of the balloon 10 allows the coating process to be carried out efficiently. In the coating process, not applying the drug solution to the outer surface of the balloon component 20 in the portion that will become the high elasticity portion 31 of the balloon 10 allows the amount of drug solution used in manufacturing the balloon 10 to be reduced while still forming the drug layer 33 in the low elasticity portion 32 of the balloon 10.

[0098] As shown in Figure 10, it is preferable that the method further includes a parison preparation step of preparing a parison 100 having a longitudinal axis direction x extending from the proximal side to the distal side, a radial direction y and a circumferential direction z perpendicular to the longitudinal axis direction x, and an inner cavity extending in the longitudinal axis direction x, and a stretching step of stretching the parison 100 while the parison 100 is placed in the inner cavity of the mold 110.

[0099] The parison 100 has a longitudinal axis direction x, a radial direction y, and a circumferential direction z, similar to the balloon-constituting member 20. A portion of the parison 100 in the longitudinal axis direction x is preferably placed in the inner cavity of the mold 110. The balloon-constituting member 20 can be molded by stretching the parison 100 while it is placed in the inner cavity of the mold 110. The stretching of the parison 100 in the stretching step can be performed, for example, by biaxial stretching or stretching by blow molding.

[0100] The mold 110 preferably has, in the longitudinal axis direction x, a mold straight tube section 110C that forms the straight tube section 23 of the balloon-constituting member 20, two mold tapered sections 110T that form the tapered sections of the balloon-constituting member 20, and two mold sleeve sections 110S that are arranged further from the mold straight tube section 110C than the mold tapered sections 110T and form the sleeve sections of the balloon-constituting member 20. Because the mold 110 has the mold straight tube section 110C, the two mold tapered sections 110T, and the two mold sleeve sections 110S, it becomes easy to form the straight tube section 23 of the balloon-constituting member 20 by the mold straight tube section 110C, the proximal tapered section 22 and the distal tapered section 24 by the mold tapered sections 110T, and the proximal sleeve section 21 and the distal sleeve section 25 by the mold sleeve sections 110S.

[0101] The mold 110 may be composed of a single member or multiple members. As shown in FIG. 10 , the mold may be composed of multiple mold members connected to each other in the longitudinal axis direction x. For example, the mold straight tube section 110C, the mold tapered section 110T, and the mold sleeve section 110S may each be different mold members connected to each other in the longitudinal axis direction x. The mold 110 may also be separable in the radial direction y. By allowing the mold 110 to be separable in the radial direction y, it is possible to facilitate insertion of the parison 100 into the cavity of the mold 110. As shown in FIG. 10 , the mold members may be joined by engaging adjacent mold members with each other, or, although not shown, adjacent mold members may be attached with magnets and joined by magnetic attraction.

[0102] The material constituting the mold 110 is preferably a metal, and more preferably iron, copper, aluminum, or an alloy thereof. For example, an iron alloy may be stainless steel, a copper alloy may be brass, and an aluminum alloy may be duralumin. In terms of sufficient conductivity, strength, and ease of processing, the mold 110 is preferably made of stainless steel.

[0103] 11 , the cross-sectional shape of the parison 100 perpendicular to the longitudinal axis direction x is preferably circular, and the cross-sectional shape of the cavity of the mold 110 perpendicular to the longitudinal axis direction x is preferably polygonal having vertices and sides including vertices. Since the cross-sectional shape of the parison 100 is circular and the cross-sectional shape of the cavity of the mold 110 is polygonal, the cross-sectional shape perpendicular to the longitudinal axis direction x can be made the same polygonal as the cross-sectional shape of the cavity of the mold 110 during molding of the balloon-constituting member 20. As a result, in the balloon 10 manufactured from the balloon-constituting member 20, the positions of the wing-shaped portions 11 formed during the deflation of the balloon 10 can be easily controlled.

[0104] The polygonal cross-sectional shape of the lumen of the mold 110 preferably has vertices 111 including the vertices of the polygon and sides 112 of the polygon. The polygonal cross-sectional shape of the lumen of the mold 110 includes polygons with clearly defined vertices and straight sides, as well as rounded polygons with rounded corners and polygons with at least some curved sides. Examples of polygonal cross-sectional shapes of the lumen of the mold 110 include triangles, quadrilaterals, and pentagons. Of these, the cross-sectional shape of the lumen of the mold 110 is preferably triangular. Having a triangular cross-sectional shape of the lumen of the mold 110 facilitates appropriate determination of the number and size of the wing-shaped portions 11 formed in the balloon 10 molded from the balloon-constituting member 20.

[0105] This application claims the benefit of priority based on Japanese Patent Application No. 2024-101284, filed on June 24, 2024. The entire contents of the specification of Japanese Patent Application No. 2024-101284, filed on June 24, 2024, are incorporated herein by reference.

[0106] DESCRIPTION OF SYMBOLS 1: Balloon catheter 5: Hub 6: Fluid injection section 10: Balloon 11: Wing-shaped section 12: Mountain-folded section 13: Apex section 14: Side section 15: Valley section 20: Balloon component 21: Proximal sleeve section 22: Proximal tapered section 23: Straight section 24: Distal tapered section 25: Distal sleeve section 31: High elasticity section 32: Low elasticity section 33: Drug layer 40: Shaft 41: Proximal shaft 42: Distal shaft 50: Guidewire port 60: Inner shaft 70: Distal tip member 80: X-ray opaque marker 100: Parison 110: Mold 110C: Mold straight section 110T: Mold tapered section 110S: Mold sleeve section 111: Apex section 112: Side section P1: Apex of wing-shaped section

Claims

1. A balloon for a balloon catheter having a longitudinal axis direction extending from the proximal side to the distal side and a radial direction and a circumferential direction perpendicular to the longitudinal axis direction, the balloon having 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, the straight tube portion having a high elasticity portion in which the elastic modulus of the balloon membrane is higher than an average elasticity which is the average value of the elasticity of the balloon membrane in the circumferential direction, and a low elasticity portion in which the elastic modulus of the balloon membrane is lower than the average elasticity, the high elasticity portion being located at a different position in the circumferential direction from the low elasticity portion, a drug layer being provided on the outer surface of the straight tube portion, the average thickness of the drug layer in the low elasticity portion being greater than the average thickness of the drug layer in the high elasticity portion, or the drug layer being provided on the low elasticity portion and the drug layer not being provided on the high elasticity portion.

2. The balloon for a balloon catheter according to claim 1, wherein the drug contained in the drug layer is crystalline.

3. The balloon for a balloon catheter according to claim 1, wherein the balloon has a plurality of high elasticity sections and a plurality of low elasticity sections, and the plurality of high elasticity sections and the plurality of low elasticity sections are arranged alternately in the circumferential direction.

4. A balloon for a balloon catheter as described in claim 1, wherein, in the deflated state of the balloon, the balloon has mountain folds where the balloon membrane forming the apexes of the wing-shaped portions is bent in a mountain fold, and valleys which are boundaries between two adjacent wing-shaped portions in the circumferential direction, and the average thickness of the drug layer in the valleys is greater than the average thickness of the drug layer in the mountain folds.

5. The balloon for a balloon catheter according to claim 4, wherein at least a portion of the mountain fold overlaps at least a portion of the high elasticity portion, and at least a portion of the valley portion overlaps at least a portion of the low elasticity portion.

6. A balloon for a balloon catheter according to claim 1, wherein in a cross section perpendicular to the longitudinal axis direction, the cross-sectional shape of the balloon at the straight tube section is a polygon having vertices and sides including apexes, the high elasticity sections being located at the vertices, and the low elasticity sections being located at the sides.

7. A balloon for a balloon catheter as described in claim 6, wherein the balloon further comprises a proximal sleeve portion located proximal to the proximal tapered portion and a distal sleeve portion located distal to the distal tapered portion, and in a cross section perpendicular to the longitudinal axis direction, the cross-sectional shape of the balloon in at least one of the proximal sleeve portion and the distal sleeve portion is circular.

8. A balloon catheter comprising a balloon for a balloon catheter according to any one of claims 1 to 7.

9. A method for manufacturing a balloon for a balloon catheter according to any one of claims 1 to 7, comprising: a component preparation step of preparing a balloon component having a longitudinal axis direction extending from the proximal side to the distal side, and radial and circumferential directions perpendicular to the longitudinal axis direction, the balloon component having a straight tube section, a proximal tapered section located proximal to the straight tube section, and a distal tapered section located distal to the straight tube section; and an application step of applying a medicinal solution to the outer surface of the balloon component in a state in which the balloon component is expanded and then contracted.

10. A method for manufacturing a balloon for a balloon catheter as described in claim 9, further comprising: a parison preparation step of preparing a parison having a longitudinal axis direction extending from the proximal side to the distal side, and radial and circumferential directions perpendicular to the longitudinal axis direction, and having an inner cavity extending in the longitudinal axis direction; and a stretching step of stretching the parison while it is placed in the inner cavity of a mold, wherein the cross-sectional shape of the parison perpendicular to the longitudinal axis direction is circular, and the cross-sectional shape of the inner cavity of the mold perpendicular to the longitudinal axis direction is polygonal having vertices and sides including vertices.

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