Manufacturing Method For Coated Stent

Abstract

The coated stent comprises a wire mesh and a coating film. The wire mesh is formed by weaving one or more wires, creating a spaced-out space between the wires, and consists of a mesh cylindrical body with an interior that communicates along the longitudinal direction. The coating film is formed on the surface of the wires and in the spaced-out space, forming a closed cylindrical body that communicates along the longitudinal direction, and is provided with micro-protrusions on the inner surface of the closed cylindrical body that create a lotus leaf effect.

Description

Technology Field

[0001] The present invention relates to a stent used to secure a passage by inserting it into a lumen of the human body, such as the esophagus, blood vessels, or bile ducts. More specifically, the invention relates to a coated stent having a coating film, a coating jig for forming the same, and a method for manufacturing the same. Background Technology

[0002] When a narrowing occurs in a lumen of the human body, such as the esophagus, duodenum, bile duct, urethra, or trachea due to a tumor or other causes, the organ does not function normally; therefore, a procedure is performed to expand the narrowed area by inserting an expansion device into the narrowed area. Stents are widely used for such procedures to secure or expand passages in the human body lumen.

[0003] For example, a stent can be composed of a mesh cylinder having multiple rhombus-shaped spaces by weaving wires of superelastic shape memory alloy diagonally across from above and below, and this mesh cylinder expands the stenotic area while acting elastically in a radial manner.

[0004] Restenosis can occur at the site where a stent has been implanted as tissue grows and invades the space between the stent and the implant. To prevent this, a coating is formed on the stent, resulting in the use of so-called coated stents. Since the coating separates the inner and outer layers, coated stents can block tissue from invading the stent.

[0005] In coated stents, the coating film is typically composed of a silicone material with high elongation. High elongation results in adhesive (sticky) properties on the surface. Consequently, when a coated stent is compressed and inserted into a small-diameter lumen of the human body using an insertion device, the inner surfaces of the coated stent may stick together. As a result, even after the insertion device is removed, the compressed coated stent may not expand, which can lead to a failure to achieve the procedural objective of securing a passage through the stenotic site.

[0006] To address the internal adhesion of such coated stents, starch, calcium stearate, etc. are applied to the surface of the coating film, and a pyrylene coating using polymers is additionally performed. However, with this method, stenosis failure still occurs, and furthermore, physical properties of the coating film, such as reduced elasticity of silicone, are degraded, which limits its use in the manufacture of coated stents.

[0007] [Prior Art Literature]

[0008] 1. Patent Registration No. 1657648

[0009] 2. Patent Publication No. 2013-0126776 The problem to be solved

[0010] The present invention aims to solve the problems of the prior art by providing a coated stent capable of blocking or minimizing the adhesion of the inner surface even when the inner surface is compressed and the coated stent is in close contact, a coating jig for forming the same, and a method for manufacturing the same. means of solving the problem

[0011] The coated stent of the present invention for achieving this purpose may include a wire mesh and a coating film.

[0012] The wire mesh can be composed of a net cylinder. The net cylinder is formed by weaving one or more wires, creating a spaced-out space between the wires, and the interior is connected along the longitudinal direction.

[0013] The coating film is formed in a spaced-apart space from the surface of the wire and constitutes a closed cylinder that communicates along the longitudinal direction. The coating film is provided with micro-protrusions on the inner surface of the closed cylinder that generate a lotus leaf effect.

[0014] In the coated stent of the present invention, the micro-protrusions have a dome or cone shape and are formed with a height of 5 to 20 μm, a diameter of 3 to 20 μm, and a spacing of 10 to 40 μm.

[0015] In the coated stent of the present invention, the micro-protrusions have the shape of ribs and are formed with a height of 3 to 8 μm, a width of 5 to 10 μm, a length of 30 to 60 μm, and a spacing of 10 to 40 μm.

[0016] In the coated stent of the present invention, the ribs are arranged such that their longitudinal direction follows the longitudinal direction of the coating film.

[0018] The coating jig of the present invention supports the wire mesh to be coated externally and has micro-indentations on its outer surface.

[0019] In the coating jig of the present invention, the micro-indentation has a dome or cone shape and is formed with a depth of 5.05 to 20.60 μm, a diameter of 3.03 to 20.60 μm, and a spacing of 10 to 40 μm.

[0020] In the coating jig of the present invention, the micro-indentation has a rib shape and is formed with a depth of 3.03 to 8.24 μm, a width of 5.05 to 10.30 μm, a length of 30.30 to 61.80 μm, and a spacing of 10 to 40 μm.

[0021] In the coating jig of the present invention, the ribs are arranged such that their longitudinal direction follows the length direction.

[0023] The method for manufacturing a coated stent according to the present invention comprises the steps of: combining a wire mesh of a mesh cylinder with a coating jig having micro-indentations on its outer surface; and spraying a coating liquid in a spray manner from the outside of the wire mesh toward the coating jig and drying it to form a coating film having micro-protrusions that create a lotus leaf effect on the inner surface of the coating film.

[0024] In the method for manufacturing a coated stent of the present invention, the step of forming a coating film includes a plurality of divided coating steps for forming a divided coating film with a thickness of 20 to 50% of the diameter of the micro-indentation.

[0025] In the method for manufacturing a coated stent according to the present invention, the step of joining the wire mesh uses a coating jig in which micro-indentations have a dome or cone shape and are formed with a depth of 5.05 to 20.60 μm, a diameter of 3.03 to 20.60 μm, and a spacing of 10 to 40 μm. In this case, the step of forming the coating film involves forming a divided coating film with a thickness of 0.6 to 1.5 μm and forming micro-protrusions that have a dome or cone shape with a height of 5 to 20 μm, a diameter of 3 to 20 μm, and a spacing of 10 to 40 μm.

[0026] In the method for manufacturing a coated stent according to the present invention, the step of joining the wire mesh uses a coating jig in which micro-indentations have a rib shape and are formed with a depth of 3.03 to 8.24 μm, a width of 5.05 to 10.30 μm, a length of 30.30 to 61.80 μm, and a spacing of 10 to 40 μm. In this case, the step of forming the coating film involves forming a divided coating film with a thickness of 0.6 to 1.5 μm, and forming micro-protrusions with a rib shape and a height of 3 to 8 μm, a width of 5 to 10 μm, a length of 30 to 60 μm, and a spacing of 10 to 40 μm.

[0027] In the method for manufacturing a coated stent of the present invention, the step of forming a coating film involves forming a plurality of divided coating films by stacking them to form a coating film with a thickness of 20 to 30 μm. Effects of the invention

[0028] The coating stent of the present invention having such a configuration can block or minimize the adhesion of the inner surface even when the coating stent is compressed and the inner surface is in close contact by forming embossed micro-protrusions on the inner surface of the coating film to create a lotus leaf effect.

[0029] The coating jig of the present invention can create a lotus leaf effect on the inner surface of a coating stent by forming micro-protrusions on the inner surface of the coating film when forming a coating stent by forming intaglio micro-depressions on the outer surface. Furthermore, the coating jig of the present invention can form micro-depressions larger than the size (especially the diameter) of the micro-protrusions to be formed on the inner surface of the coating film, taking into account the drying shrinkage rate (5-10%) of the silicone material of the coating film, thereby allowing the size of the micro-protrusions formed on the inner surface of the coating film of the coating stent to be formed in a shape that maximizes the lotus leaf effect.

[0030] In addition, the method for manufacturing a coated stent according to the present invention sequentially stacks a divided coating film with a thickness of 20 to 50% of the diameter of the micro-indentation of the coating jig, thereby allowing the coating liquid to be sufficiently inserted into the fine micro-indentation of the coating jig, and thereby forming micro-protrusions of an optimal size on the inner surface of the coated stent to maximize the lotus leaf effect. Brief explanation of the drawing

[0031] FIGS. 1a and 1b are a perspective view and a cross-sectional view of a coated stent according to the present invention. FIGS. 2a to 2d are perspective views and partially enlarged views illustrating a coating jig used in the manufacture of a coated stent according to the present invention and a modified example thereof. Figures 3a to 3d illustrate the process of manufacturing a coated stent using a coating jig according to the present invention. Specific details for implementing the invention

[0032] The present invention will be described in detail below with reference to the attached drawings.

[0034] FIGS. 1a and 1b are a perspective view and a cross-sectional view of a coated stent according to the present invention.

[0035] As illustrated in FIG. 1a and 1b, the coated stent (100) according to the invention comprises a wire mesh (110) and a coating film (120).

[0036] The wire mesh (110) expands elastically in the radial direction to expand and support the constricted area, and can be composed of a net-shaped cylinder formed by weaving wires. The interior of the net cylinder is connected along the longitudinal direction. The wire mesh (110) forms a spaced-out space between the wires.

[0037] The wire mesh (110) can be composed of wires made of metal, synthetic polymer, natural polymer, etc.

[0038] It is preferable to use shape memory alloys for the metal, for example, nickel-titanium shape memory alloy (Ni-Ti shape memory alloy) and martensitic nickel-titanium shape memory alloy (martensitic Ni-Ti shape memory alloy) can be used. Other metals that may be used include stainless steel, tantalum, tungsten (W), gold (Au), platinum, silver (Ag), nickel, titanium (Ti), chrome (Cr), cobalt-chrome alloy (Co-Cr), platinum-chrome alloy (Pt-Cr), platinum-iridium alloy (Pt-Ir), and magnesium alloy.

[0039] Synthetic polymers can be divided into degradable polymers and non-degradable polymers. Degradable polymers include poly(lactic acid) and its copolymers, poly(glycolic acid) and its copolymers, poly(e-caprolactone) and its copolymers, etc., and non-degradable polymers include polyamides (nylons), thermoplastic polyurethanes, low-density polyethylene, poly(tetrafluoroethylene) (PTFE), polyethylene terephthalate, polypropylene, etc.

[0040] Natural polymers such as collagen, albumin, silk protein, poly(L-lysine), poly(L-glutamic acid), poly(aspartic acid), carboxymethyl cellulose, cellulose sulfate, heparin, and glycosaminoglycan can be used.

[0041] The wire mesh (110) may be composed of two or more materials, but it is preferable to be composed of one material to maintain a uniform longitudinal expansion rate and widthwise compression rate.

[0042] The wire mesh (110) may be constructed by weaving a single wire, or by connecting two or more wires by means such as welding or hooks.

[0044] The coating film (120) can be formed in the spaced-apart space between the surface of the wire and the wire, and can be configured as a closed cylinder that separates the inside and outside of the wire mesh (110) while communicating in the longitudinal direction.

[0045] The coating film (120) can be composed of silicone, PTFE (Polytetrafluoroethylene), polyurethane, polyester, polypropylene, polyethylene, polyolefin, HDPE (High Density Polyethylene), ePTFE (expanded Polytetrafluoroethylene), etc.

[0046] The coating film (120) may have micro-protrusions (MP) on the inner surface of the closed cylinder.

[0047] Micro protrusions (MP) can be composed of raised protrusions to provide a lotus leaf effect, that is, superhydrophobic properties that prevent them from sticking to external materials as well as themselves. The raised protrusions can be composed of shapes such as domes, cones, and ribs.

[0048] The performance of micro-protrusions (MPs) can be evaluated through adhesion, stagnation, and biofilm nucleation. Adhesion refers to the adhesive force with which mucus, sludge, etc., adhere to the surface, and it is desirable to minimize this as much as possible. Stagnation refers to the accumulation of sludge by creating fine 'pockets' on the surface, and it is also desirable to minimize this as much as possible. Biofilm nucleation refers to the formation of 'seeds' to which bacteria and proteins adhere, and it is also desirable to minimize this as much as possible.

[0049] When looking at the protrusions that generate the lotus leaf effect on a lotus leaf, they have dome or cone shapes and are spaced at intervals of 10 to 40 µm, with an average interval of about 20 µm. These results provide a hint for forming the spacing of micro-protrusions (MP) at intervals of 10 to 40 µm when configuring micro-protrusions (MP) in dome or cone-shaped micro-units. In actual experiments, it was confirmed that if the spacing of micro-protrusions (MP) is less than 10 µm or exceeds 40 µm, the sludge adhesion reduction effect drops below 30%.

[0050] In addition, the dome or cone-shaped protrusions that generate the lotus leaf effect on lotus leaves are formed with a diameter of 3 to 20 µm. These results provide a clue to forming the diameter of the micro-protrusions (MP) to 3 to 20 µm when configuring them as dome or cone-shaped micro-units. In actual experiments, it was also confirmed that if the diameter of the micro-protrusions (MP) is less than 3 µm or exceeds 20 µm, the sludge adhesion reduction effect drops sharply below 20%.

[0051] In order to utilize the spacing and diameter range of the micro-protrusions of the lotus leaf in a coating stent, the effect of reducing sludge adhesion was confirmed by varying the height of the micro-protrusions (MP) based on the spacing and diameter range of the micro-protrusions of the lotus leaf.

[0052] Two worst-case scenarios were conducted for dome or cone-shaped micro-protrusions (MP): a first experiment with a spacing of 10 µm and a diameter of 20 µm, and a second experiment with a spacing of 40 µm and a diameter of 3 µm.

[0053] In both the first and second experiments, when the height of the micro-protrusions (MP) was less than 2 µm, there was almost no reduction in sludge adhesion. This result is interpreted as meaning that the lotus leaf effect was hardly induced because there was almost no reduction in the contact area. When the height of the micro-protrusions (MP) was varied from 2 µm to less than 5 µm, the contact area decreased and some lotus leaf effect was generated, but the sludge adhesion reduction effect still did not reach 50%. When the height of the micro-protrusions (MP) was increased to 5 µm or more, the sludge adhesion reduction effect exceeded 50%, reaching a level suitable for application in forming a coating film on a stent. However, when the height of the micro-protrusions (MP) exceeded 20 µm, the sludge adhesion reduction effect actually dropped below 50%. This phenomenon is interpreted as a result of 'micro-pockets' being created as the grooves between the micro-protrusions (MP) deepen, and sludge flocs entering these micro-pockets and stagnating in areas with weak flow, leading to the formation of a biofilm on top of them. Accordingly, in the present invention, when forming a micro-protrusion (MP) in a dome or cone shape with a height of 10 to 40 μm and a diameter of 3 to 20 μm, it is preferable to form the height of the micro-protrusion (MP) to be 5 to 20 μm.

[0055] Micro protrusions (MP) can also be configured in a rib shape. In this case, the rib-shaped protrusions are spaced at intervals of 10 to 40 μm, similar to dome or cone-shaped protrusions. For a width of 5 to 10 μm and a length of 5 to 10 μm (wherein the range of width and length is selected from a range that is practically easy to manufacture using lithography while considering the maximum diameter of the dome or cone-shaped protrusions), the effect of reducing sludge adhesion was measured while varying the height at the minimum / maximum values ​​of the spacing, width, and length. As a result, it was confirmed that the effect of reducing sludge adhesion was more than 50% at a height of 3 to 8 μm.

[0056] When the micro protrusions (MP) are configured in a rib shape, it was confirmed that if the longitudinal direction of the ribs is arranged to be inclined toward the longitudinal direction of the coating film (120), the effect of reducing sludge adhesion is increased compared to the direction perpendicular to the longitudinal direction, and the effect of reducing sludge adhesion is maximized when the longitudinal direction is arranged along the longitudinal direction.

[0058] FIGS. 2a to 2d are perspective views and partially enlarged views illustrating a coating jig used in the manufacture of a coated stent according to the present invention and a modified example thereof.

[0059] The coating jig (200) supports the wire mesh (110) to be coated externally and is configured in a cylindrical shape, and has micro-indentations (MR) on the outer surface of the cylindrical shape.

[0060] As illustrated in FIG. 2a, the micro-indentation (MR) can be configured to be recessed in a dome or cone shape. The dome or cone-shaped micro-indentation (MR) forms a dome or cone-shaped micro-protrusion (MP). When the dome or cone-shaped micro-protrusion (MP) is formed with a height of 5 to 20 μm, a diameter of 3 to 20 μm, and a spacing of 10 to 40 μm as described above, it can be formed with a depth of 5.05 to 20.60 μm, a diameter of 3.03 to 20.60 μm, and a spacing of 10 to 40 μm. Here, the micro-indentation (MR) is formed with a size larger than the micro-protrusion (MP), taking into account that shrinkage may occur during the drying process of the material, such as silicon, constituting the coating film (120). Silicon exhibits a shrinkage rate of 1 to 3%, and therefore, it is preferable to form the micro-indentation (MR) 1 to 3% larger than the micro-protrusion (MP).

[0061] As shown in Figure 2a, micro-depressions (MR) can be formed by methods such as micro-sandblasting and lithography, in which the micro-depressions (MR) can be arranged irregularly, that is, randomly.

[0063] As illustrated in FIG. 2b, it may be desirable to regularly arrange dome or cone-shaped indentations within a manufacturable range for the micro-indentations (MR). This regular arrangement of micro-indentations (MR) can increase the effect of reducing sludge adhesion by regularly arranging the generated dome or cone-shaped micro-protrusions (MP).

[0065] As illustrated in FIG. 2c, the micro-indentation (MR) can be formed to be indented in a rib shape. The rib-shaped micro-indentation (MR) forms a rib-shaped micro-protrusion (MP). When the rib-shaped micro-protrusion (MP) is formed with a height of 3 to 8 μm, a width of 5 to 10 μm, a length of 30 to 60 μm, and a spacing of 10 to 40 μm as described above, the micro-indentation (MR) can be formed with a depth of 3.03 to 8.24 μm, a width of 5.05 to 10.30 μm, a length of 30.30 to 61.80 μm, and a spacing of 10 to 40 μm. Here, forming the rib-shaped micro-indentation (MR) in a larger size than the rib-shaped micro-protrusion (MP) takes into account the shrinkage rate, i.e., the rate at which the material such as silicone forming the coating film (120) shrinks during the drying process, as described above.

[0066] As illustrated in FIG. 2c, when the micro-indentation (MR) is configured in a rib shape, if the longitudinal direction of the rib is arranged to be inclined in the longitudinal direction, the rib-shaped micro-protrusion (MP) can be arranged to be inclined in the longitudinal direction, and in this case, the effect of reducing sludge adhesion can be enhanced. Even when the rib is arranged at an angle, arranging them to intersect along the circumferential direction, that is, in a zigzag shape, can be effective in preventing or minimizing the occurrence of vortices.

[0068] As shown in FIG. 2d, when the micro-depression (MR) is configured in a rib shape, the longitudinal direction of the rib can be arranged along the longitudinal direction, which can further enhance the effect of reducing sludge adhesion.

[0070] The coating jig (200) of the present invention may be made of a metal with high thermal conductivity (e.g., tungsten, etc.) or a resin such as Teflon, PTFE (Polytetrafluoroethylene), polyurethane, polyester, polypropylene, polyethylene, polyolefin, HDPE (High Density Polyethylene), or ePTFE (expanded-Polytetrafluoroethylene).

[0072] Figures 3a to 3d illustrate the process of manufacturing a coated stent using a coating jig according to the present invention.

[0073] As illustrated in FIG. 3a, the method for manufacturing a coated stent according to the present invention first combines a stent, i.e., a wire mesh (110) of a mesh cylinder, with a coating jig (200), and sprays a coating liquid in the direction of the wire mesh (110) using a spray. Here, the coating jig (200) is provided with a micro-indentation (MR) having a shape such as a dome, cone, or rib on its outer surface.

[0075] As illustrated in FIG. 3b, the sprayed coating liquid can form a first divided coating film (120-1) by attaching to the surface of the outer surface of the coating jig (200), the micro-depression (MR), and the surface of the wire mesh (110) and then drying. At this time, the first divided coating film (120-1) can form at least a portion of the micro-protrusions (MP) corresponding to the micro-depression (MR) of the coating jig (200) on the inner surface in accordance with the thickness of the formed film.

[0076] In FIG. 3a and 3b, when forming the first divided coating film (120-1), if the coating liquid sprayed is too thick, the coating liquid may not be inserted into the micro-depression (MR). As a result of actual application, it was confirmed that when the first divided coating film (120-1) is formed with a thickness of 20 to 50% of the minimum diameter of the micro-depression (MR), the coating liquid is sufficiently inserted into the micro-depression (MR) and does not create micro-pockets. In the present invention, since the minimum diameter in the case of a dome or cone shape is 3㎛, the thickness of the divided coating film calculated based on this is 0.6 to 1.5㎛, and this minimum coating film thickness can also be applied to the formation of rib-shaped micro-protrusions having a larger minimum width (5㎛).

[0078] As shown in FIG. 3c, the second divided coating film (120-2) can be formed on the first divided coating film (120-1) as a divided coating film with a thickness of 0.6 to 1.5 μm in the same way as the first divided coating film (120-1).

[0079] By repeating the steps of forming such a divided coating film, the Nth divided coating film (120-N) is formed as shown in FIG. 4d, and the final thickness of the coating film (120) can be formed to, for example, 20 to 30 μm.

[0081] As such, the method for manufacturing a coated stent of the present invention sequentially forms a divided coating film with a thickness of 0.6 to 1.5 μm, thereby enabling natural drying (curing) of the coating liquid. Even when a separate drying (curing) chamber is used, additional devices or methods for drying (curing) the inner side of the divided coating film, such as inserting a heating rod, are unnecessary, which can significantly reduce manufacturing costs.

[0083] Although the present invention has been described above based on various embodiments, this is for the purpose of illustrating the invention. A person skilled in the art could change or modify these embodiments in various ways. However, since the scope of the present invention is defined by the claims below, such changes or modifications may be interpreted as being included within the scope of the present invention. Explanation of the symbols

[0084] 100: Coated Stent 110 : Wire mesh 120 : Coating film 120-1, 120-2, 120-N: Split coating film MP: Micro protrusions 200: Coating Jig 200-A, 200-B, 200-C, 200-D: Deformation coating jig MR: Micro-depression 300 : Spray

Claims

Claim 1 delete Claim 2 delete Claim 3 delete Claim 4 delete Claim 5 delete Claim 6 delete Claim 7 delete Claim 8 delete Claim 9 A method for manufacturing a coated stent, comprising: a step of combining a wire mesh of a mesh cylinder with a coating jig having micro-indentations on its outer surface; and a step of forming a coating film having micro-protrusions that create a lotus leaf effect on the inner surface of the coating film by spraying and drying a coating liquid in a spray manner from the outside of the wire mesh toward the coating jig, wherein the step of forming the coating film includes a plurality of segmented coating steps for forming a segmented coating film with a thickness of 20 to 50% of the diameter of the micro-indentations. Claim 10 delete Claim 11 A method for manufacturing a coated stent according to claim 9, wherein the step of joining the wire mesh uses a coating jig in which the micro-indentation has a dome or cone shape and is formed with a depth of 5.05 to 20.60 μm, a diameter of 3.03 to 20.60 μm, and a spacing of 10 to 40 μm, and the step of forming the coating film forms the divided coating film with a thickness of 0.6 to 1.5 μm, and the micro-protrusions have a dome or cone shape and are formed with a height of 5 to 20 μm, a diameter of 3 to 20 μm, and a spacing of 10 to 40 μm. Claim 12 A method for manufacturing a coated stent according to claim 9, wherein the step of joining the wire mesh uses a coating jig in which the micro-indentation has a rib shape and is formed with a depth of 3.03 to 8.24 μm, a width of 5.05 to 10.30 μm, a length of 30.30 to 61.80 μm, and a spacing of 10 to 40 μm, and the step of forming the coating film is to form the divided coating film with a thickness of 0.6 to 1.5 μm, and the micro-protrusion has a rib shape and is formed with a height of 3 to 8 μm, a width of 5 to 10 μm, a length of 30 to 60 μm, and a spacing of 10 to 40 μm. Claim 13 A method for manufacturing a coated stent according to claim 11 or 12, wherein the step of forming the coating film comprises forming a plurality of the divided coating films in a stacked manner to form the coating film with a thickness of 20 to 30 μm.

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