WO2022176792A1 - Stent and method for manufacturing stent - Google Patents

Stent and method for manufacturing stent Download PDF

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Publication number
WO2022176792A1
WO2022176792A1 PCT/JP2022/005551 JP2022005551W WO2022176792A1 WO 2022176792 A1 WO2022176792 A1 WO 2022176792A1 JP 2022005551 W JP2022005551 W JP 2022005551W WO 2022176792 A1 WO2022176792 A1 WO 2022176792A1
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Prior art keywords
stent
drug
coated
region
coated region
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PCT/JP2022/005551
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French (fr)
Japanese (ja)
Inventor
亮輔 上田
隆 熊澤
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テルモ株式会社
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Publication of WO2022176792A1 publication Critical patent/WO2022176792A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other

Definitions

  • the present invention relates to a stent and a method for manufacturing a stent.
  • Stents are applied, for example, to prevent restenosis in percutaneous transluminal coronary angioplasty (PTCA: Percutaneous Coronary Angioplasty, PCI: Percutaneous Coronary Intervention) used for myocardial infarction or angina pectoris.
  • PTCA percutaneous transluminal coronary angioplasty
  • PCI Percutaneous Coronary Intervention
  • Such a stent is a drug-eluting stent that prevents restenosis by coating the outer surface of the stent in contact with the vascular wall with a drug that inhibits the migration and proliferation of vascular smooth muscle cells, and eluting the drug after stent placement.
  • DES Drug Eluting Stent
  • the stent in order to place a drug-eluting stent in a lumen, the stent is first made to reach the target site in the lumen in a contracted state, and then expanded and placed. As the stent expands and contracts, the drug-coated layer, which is coated at a location where stress concentration occurs, falls off from the surface of the annular body as the stent expands and contracts.
  • Patent Document 1 discloses a stent in which a drug coat layer is formed avoiding curved portions and link portions in order to prevent peeling of the drug coat layer. According to such a stent, peeling of the drug coat layer can be prevented.
  • the present invention has been made to solve the above problems, and aims to provide a stent and a method for manufacturing a stent that can suppress the deterioration of the drug efficacy while suppressing the peeling of the drug coating layer.
  • a stent that achieves the above purpose is a cylindrical stent that can be radially expanded and contracted.
  • the stent comprises a stress concentration portion where stress concentration occurs with expansion and contraction, a non-coated area where the surface of at least a part of the stress concentration portion is not coated with a drug, and a drug-coated layer on the surface other than the non-coated area. and a convex portion provided in the coat region, made of the drug, and protruding outward in the radial direction.
  • a method for manufacturing a stent for achieving the above object is a method for manufacturing a stent having a cylindrical stent main body that can be expanded and contracted in the radial direction and a coating region containing a drug, wherein the stent is subjected to stress during expansion and contraction.
  • the agent is applied to the surface of the stent main body except for at least a part of the surface of the stress concentration portion where the stress concentration occurs, thereby forming the coating region and the protrusion projecting outward in the radial direction in the coating region.
  • the surface of at least a portion of the stress concentration portion is provided with a non-coated region that is not coated with a drug, it is possible to suppress peeling of the drug-coated layer.
  • the protruding portions made of the drug are provided in the coated region, when the stent expands and abuts against the biological tissue, the drug in the protruding portions is released from the living tissue at the position where the protruding portion is placed. It penetrates into the tissue where the uncoated regions of the stent are located. Therefore, the efficacy is improved compared to stents having no projections. As described above, it is possible to provide a stent capable of suppressing deterioration of drug efficacy while suppressing peeling of the drug coating layer.
  • FIG. 1 is a schematic diagram for explaining a stent delivery system to which a stent according to an embodiment of the invention is applied;
  • FIG. 1 is a plan view showing a stent according to this embodiment;
  • FIG. It is a partially enlarged view showing a stent according to this embodiment.
  • FIG. 4 is a plan view showing the vicinity of link portions of the stent according to the present embodiment;
  • FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 4;
  • FIG. 5 is a cross-sectional view taken along line 6-6 of FIG. 4;
  • FIG. 4 is a plan view showing the vicinity of the curved portion of the stent according to the present embodiment;
  • FIG. 8 is a cross-sectional view taken along line 8-8 of FIG.
  • FIG. 7 It is a schematic diagram for explaining the effect of the stent according to the present embodiment. It is the schematic which shows a coating device.
  • FIG. 4 is a plan view showing an application pattern in the method for manufacturing a stent according to this embodiment; It is a sectional view showing a modification of a convex part.
  • FIG. 1 is a schematic diagram for explaining a stent delivery system 100 to which a stent 10 according to an embodiment of the invention is applied.
  • a stent 10 according to an embodiment of the present invention is a drug-eluting stent (DES) having a drug-containing coating layer formed on its outer surface.
  • DES drug-eluting stent
  • the stent 10 functions as an in-vivo indwelling article that retains a lumen by being indwelled in close contact with the inner surface of the stenosis.
  • the stent 10 is applied to a stent delivery system 100, for example, as shown in FIG. 1, and used for treatment aimed at preventing restenosis.
  • the stent delivery system 100 has a hub 110, a shaft 140, a balloon 130 and a stent 10.
  • the hub 110 has a luer tapered opening 112 for connecting a device for expanding the balloon 130, as shown in FIG.
  • the shaft 140 has an outer tube shaft, an inner tube shaft, and a guidewire port 152 .
  • the stent delivery system 100 shown in FIG. 1 has a guidewire port 152 intermediate the shaft 140, and the stent delivery system 100 shown in FIG. ) type.
  • the balloon 130 has the stent 10 arranged on its outer circumference and is arranged in a folded (or contracted) state. Balloon 130 is expanded by balloon expansion fluid introduced through opening 112 of hub 110 .
  • the stent delivery system is not limited to the rapid exchange type, and can also be applied to the over-the-wire (OTW) type, in which the guidewire passes through the entire length of the stent delivery system.
  • OGW over-the-wire
  • the stent delivery system is not limited to the form applied to the stenosis caused in the coronary arteries of the heart, and can also be applied to the stenosis caused in other blood vessels, bile ducts, trachea, esophagus, urethra, and the like.
  • Placement of the stent 10 by the stent delivery system 100 according to this embodiment is performed, for example, as follows.
  • the distal end of the stent delivery system 100 is inserted into the patient's lumen, and is positioned at the stenosis, which is the target site, while leading the guide wire 150 projecting from the opening 142 of the shaft 140 .
  • a balloon expansion fluid is then introduced through the opening 112 of the hub 110 to expand the balloon 130, causing expansion and plastic deformation of the stent 10 to seal it against the stenosis.
  • the stent 10 and the balloon 130 are disengaged and the stent 10 is separated from the balloon 130 by decompressing the balloon 130 and contracting it. Thereby, the stent 10 is indwelled in the stenosis. Stent delivery system 100 with separated stent 10 is then retracted and removed from the lumen.
  • FIG. 1 the configuration of the stent 10 will be described in detail with reference to FIGS. 2 to 9.
  • FIG. 1 the configuration of the stent 10 will be described in detail with reference to FIGS. 2 to 9.
  • FIG. 2 is a plan view showing the stent 10 according to this embodiment.
  • FIG. 3 is a partially enlarged view showing the stent 10 according to this embodiment.
  • FIG. 4 is a diagram showing the vicinity of the link portion 30 of the stent 10.
  • FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 4.
  • FIG. 6 is a cross-sectional view taken along line 6--6 of FIG. 4.
  • FIG. 7 is a plan view showing the vicinity of the curved portion 24 of the stent 10 according to this embodiment.
  • 8 is a cross-sectional view taken along line 8-8 of FIG. 7.
  • FIG. 9 is a schematic diagram for explaining the effects of the stent 10 according to this embodiment.
  • the stent 10 has a plurality of annular bodies 20 provided along the axial direction D1 and link portions 30 connecting the annular bodies 20 adjacent to each other along the axial direction D1. .
  • a drug coat layer CL is formed at a predetermined position of the stent 10 .
  • the stent 10 before the drug coat layer CL is formed may be referred to as the stent main body 10A.
  • the stent main body 10A is made of a biocompatible material.
  • Biocompatible materials include, for example, iron, titanium, aluminum, tin, tantalum or tantalum alloys, platinum or platinum alloys, gold or gold alloys, titanium alloys, nickel-titanium alloys, cobalt-based alloys, cobalt-chromium alloys, Stainless steel, zinc-tungsten alloy, niobium alloy and the like.
  • the annular body 20 extends in the circumferential direction D2 while being folded in a wave shape to form an endless annular shape.
  • the annular body 20 includes linear portions 21, 22, and 23, a curved portion 24 connecting the linear portions 21 and 22, and a curved portion 25 connecting the linear portions 21 and 23. and have In this embodiment, the curved portions 24 and 25 and the link portion 30 correspond to stress concentration portions where stress concentration occurs with expansion and contraction.
  • the stent 10 has, in the vicinity of the link portion 30, a first coat region (corresponding to the coat region) 51 in which the drug coat layer CL is formed on the surface of the stent body 10A, and a stent body 10A.
  • a portion (corresponding to a convex portion) 53 is provided.
  • the first uncoated region 52 is formed on some or all of the links 30 on the stent body 10A.
  • a primer coating layer is provided between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL to reduce variations in the peelability of the drug coat layer CL. 40 are placed.
  • the primer coating layer 40 in FIG. 5 is also arranged on the surface of the stent main body 10A in the first uncoated region 52, the primer coating layer may not be arranged here.
  • the stent 10 has, in the vicinity of the link portion 30, a second coat region (corresponding to the coat region) 61 in which the drug coat layer CL is formed on the surface of the annular body 20, and an annular body A second non-coated region (corresponding to a non-coated region) 62 where the surface of 20 is not coated with a drug, and a second protrusion formed at the end of the second coated region 61 on the second non-coated region 62 side.
  • a portion (corresponding to a convex portion) 63 is provided.
  • a second uncoated region 62 is formed on some or all of the links 30 on the stent body 10A.
  • the primer coating layer 40 is arranged between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL.
  • the primer coating layer 40 in FIG. 6 is also arranged on the surface of the stent main body 10A in the second uncoated region 62, the primer coating layer may not be arranged here.
  • the stent 10 has a third coat region (corresponding to the coat region) 71 in which the drug coat layer CL is formed on the surface of the annular body 20;
  • a third uncoated region 72 is formed on part or all of the bend 24 in the stent body 10A.
  • the primer coating layer 40 is arranged between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL.
  • the primer coating layer 40 in FIG. 8 is also arranged on the surface of the stent main body 10A in the third uncoated region 72, the primer coating layer may not be arranged here.
  • the drug coated on the outer surface of the stent main body 10A is supported by a polymer to form a drug coat layer CL.
  • the drug-coated layer CL is supported by a polymer, the drug is gradually released after the stent 10 is placed in the living body, so the drug effect is sustained for a long period of time, and the risk of restenosis at the site where the stent is placed is reduced.
  • the polymer is preferably a biodegradable polymer because inflammatory reactions may occur if the polymer remains.
  • the drug coat layer CL is formed by repeatedly coating a coating liquid prepared by dissolving a drug and a polymer in a solvent.
  • Drugs (physiologically active substances) coated on the outer surface of the stent body 10A include, for example, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, and calcium.
  • Biodegradable polymers are, for example, selected from the group consisting of polyesters, aliphatic polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphates, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose. at least one polymer, a copolymer obtained by optionally copolymerizing monomers constituting the polymer, and a mixture of the polymer and/or the copolymer.
  • Aliphatic polyesters are, for example, polylactic acid (PLA), polyglycolic acid (PGA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), copolymers of lactic acid and caprolactone. Copolymers of lactic acid and caprolactone are preferred here.
  • the material of the primer coating layer is, for example, a biodegradable polymer when the drug coating layer CL is carried by the polymer.
  • the drug coat layer CL is arranged only on the outer surface side of the stent 10 . That is, the drug coat layer CL is not provided on the inner surface side of the stent 10 .
  • the stent 10 when the stent 10 is indwelled in a blood vessel, the stent 10 is quickly wrapped in the vascular tissue compared to a stent having a drug coating layer on the inner surface side as well.
  • a configuration in which the drug coat layer CL is provided on the side surface side and/or the inner surface side of the stent in addition to the outer surface side of the stent is also included in the present invention.
  • the second coated region 61 and the third coated region 71 have the same configuration as the first coated region 51, and the second non-coated region 62 and the third non-coated region 72 have the same structure as the first non-coated region 52.
  • the second convex portion 63 and the third convex portion 73 have the same configuration as the first convex portion 53, so here, the first coated region 51, the first non-coated region 52, and the first A configuration of the convex portion 53 will be described.
  • the first coat region 51 is formed by repeatedly coating a coating liquid prepared by dissolving a drug and a polymer in a solvent.
  • the drug coated layer CL has an inclined portion 51T configured so that the thickness gradually decreases toward the first uncoated region 52, as shown in FIG.
  • the inclined portion 51T is formed by overcoating so that the length of the coating on the upper layer side is shorter than the length of the coating on the lower layer side.
  • the thickness of the drug coat layer CL in the first coat region 51 is, for example, 1 to 100 ⁇ m.
  • the first convex portion 53 is composed of a drug. As shown in FIG. 5, the first convex portion 53 is configured in a droplet shape.
  • the first convex portion 53 is preferably provided at the end of the first coated region 51 on the first non-coated region 52 side. More specifically, the distance L1 from the boundary portion 54 between the first coated region 51 and the first uncoated region 52 to the center position 53P of the first convex portion 53 is preferably 1000 ⁇ m or less, more preferably 500 ⁇ m or less.
  • the first projections 53 are The drug permeates from the living tissue where the first projections 53 are placed toward the living tissue where the first uncoated region 52 of the stent 10 is placed (see the arrow in FIG. 9). Therefore, efficacy can be further improved.
  • the height H of the first projection 53 is not particularly limited, it is preferably 1 to 90 ⁇ m, more preferably 70 ⁇ m or less.
  • the height of the first convex portion is less than 1 ⁇ m, the penetration effect described above is reduced.
  • the height of the first convex portion is greater than 90 ⁇ m, the time required for endothelialization after stent placement will be prolonged and thrombus will easily adhere, increasing the risk of vascular obstruction due to the adhered thrombus.
  • the width W of the first projection 53 is preferably 0.5 to 10 times the height H of the projection 53. According to this configuration, since the slope of the first convex portion 53 is gentle, it is possible to preferably prevent the stent delivery system 100 from being caught on living tissue when delivering the stent delivery system 100 into the living body.
  • the drug on the first projections 53 is From the living tissue C where the first projections 53 are placed, it permeates toward the living tissue where the first uncoated region 52 of the stent 10 is placed. Therefore, the efficacy is improved as compared with a stent in which the first projections 53 are not provided.
  • the protrusions 53, 63, 73 have an anchoring effect, and displacement (migration) of the stent 10 can be suppressed.
  • the curved portions 24 may damage the living tissue C at both ends of the stent 10 in the axial direction D1. Even if the drug coating layer CL is not formed here, since the stent of the present invention is provided with convex portions made of a drug in the coating region, the drug can be efficiently delivered to the injured site.
  • FIG. 10 is a schematic diagram showing the coating device 90.
  • FIG. 11 is a plan view showing an application pattern in the method for manufacturing the stent 10 according to this embodiment.
  • the manufacturing method of the stent 10 according to this embodiment can be substantially the same manufacturing method as in International Publication No. 2015/046168. In the present specification, a method for manufacturing the stent 10 will be described with appropriate omission.
  • the manufacturing method of the stent 10 according to the present embodiment includes a formation step of forming the stent body 10A and an application step of applying a drug to the stent body 10A to form the drug coat layer CL.
  • a predetermined pattern is formed by removing portions other than the stent main body 10A from the tubular body (specifically, the metal pipe).
  • a predetermined pattern is formed from a metal pipe by an etching method using masking and chemicals called photofabrication, an electric discharge machining method using a mold, a cutting method (e.g., mechanical polishing, laser cutting), etc. can be formed.
  • edges of the annular body 20 are removed by chemical polishing or electropolishing, and the surface is finished to have a smooth surface.
  • annealing may be performed after molding into a predetermined pattern. Annealing improves the softness and flexibility of the stent main body 10A as a whole, improves the indwelling property in a curved blood vessel, reduces the physical irritation given to the inner wall of the blood vessel, and reduces the factors of restenosis. can be done.
  • the application device 90 shown in FIG. 10 applies the drug to a predetermined portion of the stent main body 10A to form the drug coat layer CL.
  • a dipping method such as a spray method, an inkjet method, and a nozzle injection method can be used to form the drug coat layer CL.
  • the spray method, the inkjet method, and the nozzle injection method are preferred.
  • the applicator 90 includes a holding portion 91 that holds the stent main body 10A, a moving means 92 that moves the holding portion 91, and an applicator 93 that applies a drug to a predetermined position of the stent main body 10A.
  • the holding section 91, the moving means 92, and the application section 93 are controlled by a control section (not shown). Since the holding part 91, the moving means 92, and the coating part 93 have the same configuration as that of the coating device disclosed in International Publication No. 2015/046168, detailed description thereof will be omitted.
  • the application step is the first step of applying the drug to the surface of the stent body 10A to form the coated regions 51, 61, 71 so that the non-coated regions 52, 62, 72 are not coated with the drug. and a second application step of applying a chemical to the coating regions 51 , 61 , 71 to form the protrusions 53 , 63 , 73 .
  • the drug is applied to the coated regions 51, 61, 71 so that the thickness gradually decreases toward the non-coated regions 52, 62, 72, as described above.
  • the moving means 92 or the nozzle 93A of the application unit 93 is moved along a predetermined pattern to eject the drug onto the surface of the main stent body 10A to form a thin film coating.
  • a lamination method of forming a plurality of layers is used. In the lamination method, the inclined portion 51T is formed by adjusting the coating region of each thin film coat layer and gradually reducing the number of thin film coat layers as the non-coated regions 52, 62, and 72 are approached. can be done.
  • the drug is applied to the above-described positions of the coated regions 51, 61, and 71 after the predetermined application pattern is formed on the stent main body 10A in the first application step.
  • the protrusions 53 , 63 , 73 are formed by dropping the medicine from the nozzle 93 ⁇ /b>A of the application section 93 .
  • the convex portions 53, 63, and 73 may be formed by increasing the discharge amount of the medicine for the corresponding portions in the first application step.
  • the stent 10 is a cylindrical stent that can be expanded and contracted in the radial direction. part, non-coated regions 52, 62, 72 where the surface of at least some of the stress concentration parts is not coated with the drug, and a drug coating layer CL formed on the surface other than the non-coated regions 52, 62, 72 Regions 51, 61, 71, and projections 53, 63, 73 provided in the coated regions 51, 61, 71, made of a drug, and protruding radially outward.
  • the non-coated regions 52, 62, and 72 which are not coated with the drug, are provided on the surface of the stress concentration portion, so peeling of the drug-coated layer CL can be suppressed.
  • the protruding portions 53, 63, and 73 made of a drug are provided in the coated regions 51, 61, and 71, when the stent 10 expands and comes into contact with living tissue, the protruding portions 53, The drugs 63 and 73 permeate from the body tissue where the protrusions 53, 63 and 73 are placed toward the body tissue where the non-coated regions 52, 62 and 72 of the stent 10 are placed.
  • the efficacy is improved.
  • the convex portions 53, 63, 73 are provided at the ends of the coated regions 51, 61, 71 on the non-coated regions 52, 62, 72 side.
  • the medicine on the first convex portion 53 preferably permeates into the living tissue at the position where the first uncoated region 52 is placed in a shorter period of time. Therefore, efficacy can be further improved.
  • the distance L1 from the boundary portion 54 between the first coated region 51 and the first non-coated region 52 to the center position 53P of the first convex portion 53 is 1000 ⁇ m or less. According to the stent 10 configured in this way, since the location where the first convex portion 53 is arranged can be brought close to the boundary portion 54, when the stent 10 expands and the drug comes into contact with the living tissue, The medicine on the first convex portion 53 preferably permeates into the living tissue at the position where the first uncoated region 52 is placed in a shorter period of time. Therefore, efficacy can be further improved.
  • the height H of the first projection 53 is 1 to 90 ⁇ m. According to the stent 10 configured in this manner, the risk of thrombus adhesion can be reduced by shortening the time required for endothelialization after stent placement while improving the efficacy of the non-coated region.
  • the width W of the first convex portion 53 is 0.5 to 10 times the height of the first convex portion 53 . According to the stent 10 configured in this way, since the slope of the first convex portion 53 is gentle, it is possible to preferably prevent the stent delivery system 100 from being caught on the living tissue when the stent delivery system 100 is delivered into the living body. be able to.
  • the drug coat layer CL has an inclined portion 51T configured so that the thickness gradually decreases toward the first non-coated region 52 . According to the stent 10 configured in this manner, the thickness of the drug coat layer CL located near the stress concentration portion is thinner than when there is no inclined portion, so that peeling or falling off of the drug coat layer CL is prevented. Increases the effectiveness of prevention.
  • the drug coat layer CL is formed only on the outer surface side of the coat regions 51 , 61 , 71 .
  • the method for manufacturing the stent 10 includes the cylindrical stent main body 10A that can be expanded and contracted in the radial direction, and the coated regions 51, 61, and 71 containing the drug.
  • the surface of the stent main body 10A is coated with a drug except for at least a part of the surface of a stress concentration part where stress concentration occurs with expansion and contraction such as a link part and a curved part
  • the stent 10 manufactured by this manufacturing method since the surface of the stress concentration portion is not coated with the drug, peeling of the drug coat layer CL can be suppressed. Moreover, since the protruding portions 53, 63, and 73 made of a drug are provided in the coated regions 51, 61, and 71, when the stent 10 expands and comes into contact with living tissue, the protruding portions 53, The drugs 63 and 73 permeate from the body tissue where the protrusions 53, 63 and 73 are placed toward the body tissue where the non-coated regions 52, 62 and 72 of the stent 10 are placed. Therefore, compared with the stent 10 in which the projections 53, 63, 73 are not provided, the efficacy is improved.
  • the present invention is not limited to the configurations described in the embodiments, and can be appropriately modified based on the description of the claims. be.
  • the first convex portion 53 is provided at the end of the first coated region 51 on the first non-coated region 52 side.
  • the first convex portion can be provided at any location on the first coat region 51 .
  • the drug coat layer CL has the inclined portion 51T configured so that the thickness gradually decreases toward the first non-coated region 52 .
  • the drug coat layer does not have to have an inclined portion.
  • the stent 10 has a cylindrical shape in which the ring-shaped bodies 20 that are endless ring-shaped folded back in a wavy shape are continuously connected in the axial direction by the link portions 30 .
  • the stent may be formed into a cylindrical shape by spirally winding a wavy continuous component. Further, even in this shape, the constituent elements may be connected in the axial direction by the link portion.
  • the primer coating layer 40 is arranged on the surface of the stent main body 10A, but the primer coating layer may not be arranged.
  • the shape of the first convex portion 53 is droplet-like.
  • the first convex portion 53 may have a shape in which a droplet spreads out.
  • the first protrusion may have a shape with a sharp radial outer side.

Abstract

[Problem] To provide a stent capable of suppressing a reduction in drug efficacy while preventing peeling of a drug coat layer. [Solution] A stent 10, which is a cylindrical stent expandable and contractible in the radial direction, comprises: a stress concentration part where stress concentrates with the expansion and contraction; an uncoated area 52 where at least a part of the surface of the stress concentration part is not coated with a drug; a coated area 51 where a drug coat layer CL is formed on the surface other than the uncoated area; and a convex part 53 which is formed in the coated area, comprises the drug and projects outward in the radial direction.

Description

ステントおよびステントの製造方法Stent and stent manufacturing method
　本発明は、ステントおよびステントの製造方法に関する。 The present invention relates to a stent and a method for manufacturing a stent.
　ステントは、例えば、心筋梗塞あるいは狭心症に用いられる経皮的冠状動脈血管形成術（ＰＴＣＡ：Ｐｅｒｃｕｔａｎｅｏｕｓ　Ｔｒａｎｓｌｕｍｉｎａｌ　Ｃｏｒｏｎａｒｙ　Ａｎｇｉｏｐｌａｓｔｙ、ＰＣＩ：Ｐｅｒｃｕｔａｎｅｏｕｓ　Ｃｏｒｏｎａｒｙ　Ｉｎｔｅｒｖｅｎｔｉｏｎ）において再狭窄防止のために適用される。 Stents are applied, for example, to prevent restenosis in percutaneous transluminal coronary angioplasty (PTCA: Percutaneous Coronary Angioplasty, PCI: Percutaneous Coronary Intervention) used for myocardial infarction or angina pectoris.
　このようなステントとして、血管壁に接触する外表面側に、血管平滑筋細胞の遊走および増殖を抑制する薬剤を被覆し、当該薬剤をステント留置後に溶出させて再狭窄を防止する薬剤溶出性ステント（ＤＥＳ：Ｄｒｕｇ　Ｅｌｕｔｉｎｇ　Ｓｔｅｎｔ）の開発が行われている。 Such a stent is a drug-eluting stent that prevents restenosis by coating the outer surface of the stent in contact with the vascular wall with a drug that inhibits the migration and proliferation of vascular smooth muscle cells, and eluting the drug after stent placement. (DES: Drug Eluting Stent) is being developed.
　ところが、薬剤溶出性ステントを管腔内に留置するには、一旦ステントを縮径した状態で管腔内の目的部位に到達させた後、ステントを拡張して留置するため、湾曲部やリンク部などの拡張および収縮に伴い応力集中が起きる場所にコーティングされている薬剤コート層が、ステントの拡張および収縮に伴って環状体の表面から脱落するという問題が生じる。 However, in order to place a drug-eluting stent in a lumen, the stent is first made to reach the target site in the lumen in a contracted state, and then expanded and placed. As the stent expands and contracts, the drug-coated layer, which is coated at a location where stress concentration occurs, falls off from the surface of the annular body as the stent expands and contracts.
　これに関連して、例えば下記の特許文献１には、薬剤コート層の剥がれを防止するために、湾曲部およびリンク部を避けて薬剤コート層が形成されたステントが開示されている。このようなステントによれば、薬剤コート層の剥がれを防止することができる。 In this regard, Patent Document 1 below, for example, discloses a stent in which a drug coat layer is formed avoiding curved portions and link portions in order to prevent peeling of the drug coat layer. According to such a stent, peeling of the drug coat layer can be prevented.
国際公開第２０１５／０４６１６８号WO2015/046168
　しかしながら、特許文献１に記載のステントでは、湾曲部およびリンク部等の非コート領域に薬剤が塗布されていないため、薬効が低下してしまう虞がある。 However, in the stent described in Patent Document 1, the medicine is not applied to the non-coated regions such as the curved portion and the link portion, so there is a possibility that the efficacy of the stent may be reduced.
　本発明は、上記の課題を解決するためになされたものであり、薬剤コート層の剥がれを抑制しつつ、薬効の低下を抑制できるステントおよびステントの製造方法を提供することを目的とする。 The present invention has been made to solve the above problems, and aims to provide a stent and a method for manufacturing a stent that can suppress the deterioration of the drug efficacy while suppressing the peeling of the drug coating layer.
　上記目的を達成するステントは、径方向に拡張および収縮が可能な円筒形状のステントである。ステントは、拡張および収縮に伴い応力集中が起きる応力集中部と、少なくとも一部の前記応力集中部の表面に薬剤が被覆されていない非コート領域と、前記非コート領域以外の表面に薬剤コート層が形成されたコート領域と、前記コート領域に設けられ、前記薬剤から構成され、前記径方向の外側に向かって突出する凸部と、を有する。 A stent that achieves the above purpose is a cylindrical stent that can be radially expanded and contracted. The stent comprises a stress concentration portion where stress concentration occurs with expansion and contraction, a non-coated area where the surface of at least a part of the stress concentration portion is not coated with a drug, and a drug-coated layer on the surface other than the non-coated area. and a convex portion provided in the coat region, made of the drug, and protruding outward in the radial direction.
　上記目的を達成するステントの製造方法は、径方向に拡張および収縮が可能な円筒形状のステント本体と、薬剤を含むコート領域と、を有するステントの製造方法であって、拡張および収縮に伴い応力集中が起きる応力集中部の少なくとも一部の表面を除き、前記ステント本体の表面に前記薬剤を塗布して前記コート領域および前記コート領域内で前記径方向の外側に向かって突出する凸部を形成する工程と、を有する。 A method for manufacturing a stent for achieving the above object is a method for manufacturing a stent having a cylindrical stent main body that can be expanded and contracted in the radial direction and a coating region containing a drug, wherein the stent is subjected to stress during expansion and contraction. The agent is applied to the surface of the stent main body except for at least a part of the surface of the stress concentration portion where the stress concentration occurs, thereby forming the coating region and the protrusion projecting outward in the radial direction in the coating region. and a step of
　上記のように構成したステントによれば、少なくとも一部の応力集中部の表面に薬剤が被覆されていない非コート領域を備えるため、薬剤コート層が剥がれてしまうことを抑制できる。また、コート領域に薬剤から構成される凸部が設けられるため、ステントが拡張して生体組織にステントが当接した際に、凸部の薬剤が、凸部が置かれる位置の生体組織から、ステントの非コート領域が置かれる位置の生体組織へ向けて浸透していく。このため、凸部が設けられていないステントと比較して、薬効が向上する。以上から、薬剤コート層の剥がれを抑制しつつ、薬効の低下を抑制できるステントを提供することができる。 According to the stent configured as described above, since the surface of at least a portion of the stress concentration portion is provided with a non-coated region that is not coated with a drug, it is possible to suppress peeling of the drug-coated layer. In addition, since the protruding portions made of the drug are provided in the coated region, when the stent expands and abuts against the biological tissue, the drug in the protruding portions is released from the living tissue at the position where the protruding portion is placed. It penetrates into the tissue where the uncoated regions of the stent are located. Therefore, the efficacy is improved compared to stents having no projections. As described above, it is possible to provide a stent capable of suppressing deterioration of drug efficacy while suppressing peeling of the drug coating layer.
本発明の実施形態に係るステントが適用されるステントデリバリーシステムを説明するための概略図である。1 is a schematic diagram for explaining a stent delivery system to which a stent according to an embodiment of the invention is applied; FIG. 本実施形態に係るステントを示す平面図である。1 is a plan view showing a stent according to this embodiment; FIG. 本実施形態に係るステントを示す部分拡大図である。It is a partially enlarged view showing a stent according to this embodiment. 本実施形態に係るステントのリンク部近傍を示す平面図である。FIG. 4 is a plan view showing the vicinity of link portions of the stent according to the present embodiment; 図４の５－５線に沿う断面図である。FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 4; 図４の６－６線に沿う断面図である。FIG. 5 is a cross-sectional view taken along line 6-6 of FIG. 4; 本実施形態に係るステントの湾曲部近傍を示す平面図である。FIG. 4 is a plan view showing the vicinity of the curved portion of the stent according to the present embodiment; 図７の８－８線に沿う断面図である。FIG. 8 is a cross-sectional view taken along line 8-8 of FIG. 7; 本実施形態に係るステントの効果を説明するための概略図である。It is a schematic diagram for explaining the effect of the stent according to the present embodiment. 塗布装置を示す概略図である。It is the schematic which shows a coating device. 本実施形態に係るステントの製造方法の塗布パターンを示す平面図である。FIG. 4 is a plan view showing an application pattern in the method for manufacturing a stent according to this embodiment; 凸部の変形例を示す断面図である。It is a sectional view showing a modification of a convex part.
　以下、本発明の実施の形態を、図面を参照しつつ説明する。なお、図面の寸法比率は、説明の都合上誇張されており、実際の比率とは異なる場合がある。 Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that the dimensional ratios in the drawings are exaggerated for convenience of explanation, and may differ from the actual ratios.
　図１は、本発明の実施形態に係るステント１０が適用されるステントデリバリーシステム１００を説明するための概略図である。 FIG. 1 is a schematic diagram for explaining a stent delivery system 100 to which a stent 10 according to an embodiment of the invention is applied.
　本発明の実施形態に係るステント１０は、外表面側に薬剤を含む薬剤コート層が形成された薬剤溶出性ステント（ＤＥＳ）からなる。ステント１０は、狭窄部の内面に密着させて留置されることで管腔を保持する生体内留置物として機能する。ステント１０は、例えば、図１に示すように、ステントデリバリーシステム１００に適用され、再狭窄防止を目的とした治療に利用される。 A stent 10 according to an embodiment of the present invention is a drug-eluting stent (DES) having a drug-containing coating layer formed on its outer surface. The stent 10 functions as an in-vivo indwelling article that retains a lumen by being indwelled in close contact with the inner surface of the stenosis. The stent 10 is applied to a stent delivery system 100, for example, as shown in FIG. 1, and used for treatment aimed at preventing restenosis.
　本実施形態において、ステントデリバリーシステム１００は、ハブ１１０と、シャフト１４０と、バルーン１３０と、ステント１０と、を有する。 In this embodiment, the stent delivery system 100 has a hub 110, a shaft 140, a balloon 130 and a stent 10.
　ハブ１１０は、図１に示すように、バルーン１３０を拡張させる装置を連結するためのルアーテーパーが形成された開口部１１２を有する。 The hub 110 has a luer tapered opening 112 for connecting a device for expanding the balloon 130, as shown in FIG.
　シャフト１４０は、外管シャフトと、内管シャフトと、ガイドワイヤーポート１５２と、を有する。図１に示すステントデリバリーシステム１００は、ガイドワイヤーポート１５２がシャフト１４０の中間にあり、図１に示すステントデリバリーシステム１００は、ガイドワイヤー１５０がシャフト１４０の先端から中間まで通過する、ラピッドエクスチェンジ（ＲＸ）タイプである。 The shaft 140 has an outer tube shaft, an inner tube shaft, and a guidewire port 152 . The stent delivery system 100 shown in FIG. 1 has a guidewire port 152 intermediate the shaft 140, and the stent delivery system 100 shown in FIG. ) type.
　バルーン１３０は、外周にステント１０が配置され、折り畳まれた状態（あるいは収縮された状態）で配置される。バルーン１３０は、ハブ１１０の開口部１１２から導入されるバルーン拡張流体によって拡張される。 The balloon 130 has the stent 10 arranged on its outer circumference and is arranged in a folded (or contracted) state. Balloon 130 is expanded by balloon expansion fluid introduced through opening 112 of hub 110 .
　ステントデリバリーシステムは、ラピッドエクスチェンジタイプに限定されず、ガイドワイヤーがステントデリバリーシステムの全長を通過する、オーバーザワイヤ（ＯＴＷ）タイプに適用することも可能である。また、ステントデリバリーシステムは、心臓の冠動脈に生じた狭窄部に適用する形態に限定されず、その他の血管、胆管、気管、食道、尿道等に生じた狭窄部に適用することも可能である。 The stent delivery system is not limited to the rapid exchange type, and can also be applied to the over-the-wire (OTW) type, in which the guidewire passes through the entire length of the stent delivery system. In addition, the stent delivery system is not limited to the form applied to the stenosis caused in the coronary arteries of the heart, and can also be applied to the stenosis caused in other blood vessels, bile ducts, trachea, esophagus, urethra, and the like.
　本実施形態に係るステントデリバリーシステム１００によるステント１０の留置は、例えば、以下のように実施される。 Placement of the stent 10 by the stent delivery system 100 according to this embodiment is performed, for example, as follows.
　まず、ステントデリバリーシステム１００の先端部を、患者の管腔に挿入し、シャフト１４０の開口部１４２から突出させたガイドワイヤー１５０を先行させながら、目的部位である狭窄部に位置決めする。そして、ハブ１１０の開口部１１２からバルーン拡張流体を導入して、バルーン１３０を拡張させて、ステント１０の拡張および塑性変形を引き起こし、狭窄部に密着させる。 First, the distal end of the stent delivery system 100 is inserted into the patient's lumen, and is positioned at the stenosis, which is the target site, while leading the guide wire 150 projecting from the opening 142 of the shaft 140 . A balloon expansion fluid is then introduced through the opening 112 of the hub 110 to expand the balloon 130, causing expansion and plastic deformation of the stent 10 to seal it against the stenosis.
　その後、バルーン１３０を減圧して収縮させることにより、ステント１０とバルーン１３０との係合を解除し、ステント１０をバルーン１３０から分離する。これにより、ステント１０は狭窄部に留置される。そして、ステント１０が分離されたステントデリバリーシステム１００は、後退させられ、管腔から取り除かれる。 After that, the stent 10 and the balloon 130 are disengaged and the stent 10 is separated from the balloon 130 by decompressing the balloon 130 and contracting it. Thereby, the stent 10 is indwelled in the stenosis. Stent delivery system 100 with separated stent 10 is then retracted and removed from the lumen.
　次に、図２～図９を参照して、ステント１０の構成について詳述する。 Next, the configuration of the stent 10 will be described in detail with reference to FIGS. 2 to 9. FIG.
　図２は、本実施形態に係るステント１０を示す平面図である。図３は、本実施形態に係るステント１０を示す部分拡大図である。図４は、ステント１０のリンク部３０近傍を示す図である。図５は、図４の５－５線に沿う断面図である。図６は、図４の６－６線に沿う断面図である。図７は、本実施形態に係るステント１０の湾曲部２４近傍を示す平面図である。図８は、図７の８－８線に沿う断面図である。図９は、本実施形態に係るステント１０の効果を説明するための概略図である。 FIG. 2 is a plan view showing the stent 10 according to this embodiment. FIG. 3 is a partially enlarged view showing the stent 10 according to this embodiment. FIG. 4 is a diagram showing the vicinity of the link portion 30 of the stent 10. As shown in FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 4. FIG. 6 is a cross-sectional view taken along line 6--6 of FIG. 4. FIG. FIG. 7 is a plan view showing the vicinity of the curved portion 24 of the stent 10 according to this embodiment. 8 is a cross-sectional view taken along line 8-8 of FIG. 7. FIG. FIG. 9 is a schematic diagram for explaining the effects of the stent 10 according to this embodiment.
　ステント１０は、図２、図３に示すように、軸方向Ｄ１に沿って複数設けられる環状体２０と、軸方向Ｄ１に沿って隣接する環状体２０同士を接続するリンク部３０と、を有する。ステント１０の所定の位置には、薬剤コート層ＣＬが形成されている。以下の説明において、薬剤コート層ＣＬが形成される前のステント１０をステント本体１０Ａと称する場合がある。 2 and 3, the stent 10 has a plurality of annular bodies 20 provided along the axial direction D1 and link portions 30 connecting the annular bodies 20 adjacent to each other along the axial direction D1. . A drug coat layer CL is formed at a predetermined position of the stent 10 . In the following description, the stent 10 before the drug coat layer CL is formed may be referred to as the stent main body 10A.
　ステント本体１０Ａは、生体適合性を有する材料から構成される。生体適合性を有する材料は、例えば、鉄、チタン、アルミニウム、スズ、タンタルもしくはタンタル合金、プラチナもしくはプラチナ合金、金もしくは金合金、チタン合金、ニッケル－チタン合金、コバルトベース合金、コバルト－クロム合金、ステンレス鋼、亜鉛－タングステン合金、ニオブ合金等である。 The stent main body 10A is made of a biocompatible material. Biocompatible materials include, for example, iron, titanium, aluminum, tin, tantalum or tantalum alloys, platinum or platinum alloys, gold or gold alloys, titanium alloys, nickel-titanium alloys, cobalt-based alloys, cobalt-chromium alloys, Stainless steel, zinc-tungsten alloy, niobium alloy and the like.
　環状体２０は、図２、図３に示すように、波状に折り返されつつ周方向Ｄ２に延在して、無端の環状形状を形作っている。環状体２０は、図３に示すように、線状部２１、２２、２３と、線状部２１、２２同士を接続する湾曲部２４と、線状部２１、２３同士を接続する湾曲部２５と、を有する。本実施形態において、湾曲部２４、２５、およびリンク部３０は、拡張および収縮に伴い応力集中が起きる応力集中部に相当する。 As shown in FIGS. 2 and 3, the annular body 20 extends in the circumferential direction D2 while being folded in a wave shape to form an endless annular shape. As shown in FIG. 3, the annular body 20 includes linear portions 21, 22, and 23, a curved portion 24 connecting the linear portions 21 and 22, and a curved portion 25 connecting the linear portions 21 and 23. and have In this embodiment, the curved portions 24 and 25 and the link portion 30 correspond to stress concentration portions where stress concentration occurs with expansion and contraction.
　ステント１０は、図４、図５に示すように、リンク部３０の近傍において、ステント本体１０Ａの表面に薬剤コート層ＣＬが形成された第１コート領域（コート領域に相当）５１と、ステント本体１０Ａの表面に薬剤が被覆されていない第１非コート領域（非コート領域に相当）５２と、第１コート領域５１のうち、第１非コート領域５２側の端部に形成される第１凸部（凸部に相当）５３と、を有する。第１非コート領域５２は、ステント本体１０Ａにあるリンク部３０の一部または全てに形成される。 As shown in FIGS. 4 and 5, the stent 10 has, in the vicinity of the link portion 30, a first coat region (corresponding to the coat region) 51 in which the drug coat layer CL is formed on the surface of the stent body 10A, and a stent body 10A. A first uncoated region (corresponding to a non-coated region) 52 in which the surface of 10A is not coated with a drug, and a first protrusion formed at the end of the first coated region 51 on the side of the first uncoated region 52 A portion (corresponding to a convex portion) 53 is provided. The first uncoated region 52 is formed on some or all of the links 30 on the stent body 10A.
　第１コート領域５１において、ステント本体１０Ａのうち薬剤コート層ＣＬが形成される部位および薬剤コート層ＣＬの間には、薬剤コート層ＣＬの剥離しやすさのバラつきを低減するためのプライマー被覆層４０が配置されている。なお、図５のプライマー被覆層４０は、第１非コート領域５２のステント本体１０Ａの表面上にも配置されているが、プライマー被覆層はここに配置されていなくてもよい。 In the first coat region 51, a primer coating layer is provided between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL to reduce variations in the peelability of the drug coat layer CL. 40 are placed. Although the primer coating layer 40 in FIG. 5 is also arranged on the surface of the stent main body 10A in the first uncoated region 52, the primer coating layer may not be arranged here.
　ステント１０は、図４、図６に示すように、リンク部３０の近傍において、環状体２０の表面に薬剤コート層ＣＬが形成された第２コート領域（コート領域に相当）６１と、環状体２０の表面に薬剤が被覆されていない第２非コート領域（非コート領域に相当）６２と、第２コート領域６１のうち、第２非コート領域６２側の端部に形成される第２凸部（凸部に相当）６３と、を有する。第２非コート領域６２は、ステント本体１０Ａにあるリンク部３０の一部または全てに形成される。 As shown in FIGS. 4 and 6, the stent 10 has, in the vicinity of the link portion 30, a second coat region (corresponding to the coat region) 61 in which the drug coat layer CL is formed on the surface of the annular body 20, and an annular body A second non-coated region (corresponding to a non-coated region) 62 where the surface of 20 is not coated with a drug, and a second protrusion formed at the end of the second coated region 61 on the second non-coated region 62 side. A portion (corresponding to a convex portion) 63 is provided. A second uncoated region 62 is formed on some or all of the links 30 on the stent body 10A.
　第２コート領域６１において、ステント本体１０Ａのうち薬剤コート層ＣＬが形成される部位および薬剤コート層ＣＬの間には、プライマー被覆層４０が配置されている。なお、図６のプライマー被覆層４０は、第２非コート領域６２のステント本体１０Ａの表面上にも配置されているが、プライマー被覆層はここに配置されていなくてもよい。 In the second coat region 61, the primer coating layer 40 is arranged between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL. Although the primer coating layer 40 in FIG. 6 is also arranged on the surface of the stent main body 10A in the second uncoated region 62, the primer coating layer may not be arranged here.
　ステント１０は、図７、図８に示すように、湾曲部２４の近傍において、環状体２０の表面に薬剤コート層ＣＬが形成された第３コート領域（コート領域に相当）７１と、環状体２０の表面に薬剤が被覆されていない第３非コート領域（非コート領域に相当）７２と、第３コート領域７１のうち、第３非コート領域７２側の端部に形成される第３凸部（凸部に相当）７３と、を有する。第３非コート領域７２は、ステント本体１０Ａにある湾曲部２４の一部または全てに形成される。 As shown in FIGS. 7 and 8, in the vicinity of the curved portion 24, the stent 10 has a third coat region (corresponding to the coat region) 71 in which the drug coat layer CL is formed on the surface of the annular body 20; A third non-coated region (corresponding to a non-coated region) 72 in which the surface of 20 is not coated with a drug, and a third protrusion formed at the end of the third coated region 71 on the side of the third non-coated region 72 and a portion (corresponding to a convex portion) 73 . A third uncoated region 72 is formed on part or all of the bend 24 in the stent body 10A.
　第３コート領域７１において、ステント本体１０Ａのうち薬剤コート層ＣＬが形成される部位および薬剤コート層ＣＬの間には、プライマー被覆層４０が配置されている。なお、図８のプライマー被覆層４０は、第３非コート領域７２のステント本体１０Ａの表面上にも配置されているが、プライマー被覆層はここに配置されていなくてもよい。 In the third coat region 71, the primer coating layer 40 is arranged between the portion of the stent body 10A where the drug coat layer CL is formed and the drug coat layer CL. Although the primer coating layer 40 in FIG. 8 is also arranged on the surface of the stent main body 10A in the third uncoated region 72, the primer coating layer may not be arranged here.
　ステント本体１０Ａの外側表面に被覆される薬剤は、ポリマーに担持されて薬剤コート層ＣＬを構成している。薬剤コート層ＣＬがポリマーに担持される場合、生体内にステント１０を留置した後、薬剤は徐々に放出されるため、薬効が長期にわたり持続し、ステント留置部での再狭窄のリスクが低減する。また、ポリマーが残存すると炎症反応が起きる可能性があるため、ポリマーは生分解性ポリマーであることが好ましい。 The drug coated on the outer surface of the stent main body 10A is supported by a polymer to form a drug coat layer CL. When the drug-coated layer CL is supported by a polymer, the drug is gradually released after the stent 10 is placed in the living body, so the drug effect is sustained for a long period of time, and the risk of restenosis at the site where the stent is placed is reduced. . Moreover, the polymer is preferably a biodegradable polymer because inflammatory reactions may occur if the polymer remains.
　薬剤コート層ＣＬは、薬剤およびポリマーが溶媒に溶解されて調製された塗布液を重ね塗りすることによって形成されている。 The drug coat layer CL is formed by repeatedly coating a coating liquid prepared by dissolving a drug and a polymer in a solvent.
　ステント本体１０Ａの外側表面に被覆される薬剤（生理活性物質）は、例えば、抗癌剤、免疫抑制剤、抗生物質、抗リウマチ剤、抗血栓薬、ＨＭＧ－ＣｏＡ還元酵素阻害剤、ＡＣＥ阻害剤、カルシウム拮抗剤、抗高脂血症薬、インテグリン阻害薬、抗アレルギー剤、抗酸化剤、ＧＰＩＩｂＩＩＩａ拮抗薬、レチノイド、フラボノイド、カロチノイド、脂質改善薬、ＤＮＡ合成阻害剤、チロシンキナーゼ阻害剤、抗血小板薬、抗炎症薬、生体由来材料、インターフェロン、ＮＯ産生促進物質からなる群から選択される少なくとも１つの化合物である。 Drugs (physiologically active substances) coated on the outer surface of the stent body 10A include, for example, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, and calcium. Antagonists, antihyperlipidemic agents, integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improving agents, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet agents, At least one compound selected from the group consisting of anti-inflammatory drugs, bio-derived materials, interferons, and NO production promoting substances.
　生分解性ポリマーは、例えば、ポリエステル、脂肪族ポリエステル、ポリ酸無水物、ポリオルソエステル、ポリカーボネート、ポリホスファゼン、ポリリン酸エステル、ポリビニルアルコール、ポリペプチド、多糖、タンパク質、およびセルロースからなる群から選択される少なくとも１つの重合体、前記重合体を構成する単量体が任意に共重合されてなる共重合体、並びに前記重合体および／または前記共重合体の混合物である。脂肪族ポリエステルは、例えば、ポリ乳酸（ＰＬＡ）、ポリグリコール酸（ＰＧＡ）、乳酸－グリコール酸共重合体（ＰＬＧＡ）、ポリカプロラクトン（ＰＣＬ）、乳酸とカプロラクトンの共重合体である。ここでは、乳酸とカプロラクトンの共重合体が好ましい。 Biodegradable polymers are, for example, selected from the group consisting of polyesters, aliphatic polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphates, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose. at least one polymer, a copolymer obtained by optionally copolymerizing monomers constituting the polymer, and a mixture of the polymer and/or the copolymer. Aliphatic polyesters are, for example, polylactic acid (PLA), polyglycolic acid (PGA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), copolymers of lactic acid and caprolactone. Copolymers of lactic acid and caprolactone are preferred here.
　プライマー被覆層の材料は、例えば、上記の薬剤コート層ＣＬがポリマーに担持される場合の生分解性ポリマーである。 The material of the primer coating layer is, for example, a biodegradable polymer when the drug coating layer CL is carried by the polymer.
　本実施形態では、薬剤コート層ＣＬは、ステント１０の外表面側にのみ配置されている。すなわち、薬剤コート層ＣＬは、ステント１０の内表面側には設けられていない。 In this embodiment, the drug coat layer CL is arranged only on the outer surface side of the stent 10 . That is, the drug coat layer CL is not provided on the inner surface side of the stent 10 .
　この構成によれば、ステント１０が血管内に留置された場合、内表面側にも薬剤コート層が設けられているステントと比較して、ステント１０が早期に血管組織内に包み込まれる。 According to this configuration, when the stent 10 is indwelled in a blood vessel, the stent 10 is quickly wrapped in the vascular tissue compared to a stent having a drug coating layer on the inner surface side as well.
　なお、薬剤コート層ＣＬが、ステントの外表面側に加えて側面側または／および内表面側に設けられている構成も、本発明に含まれるものとする。 A configuration in which the drug coat layer CL is provided on the side surface side and/or the inner surface side of the stent in addition to the outer surface side of the stent is also included in the present invention.
　第２コート領域６１および第３コート領域７１は、第１コート領域５１と同様の構成であって、第２非コート領域６２および第３非コート領域７２は、第１非コート領域５２と同様の構成であって、第２凸部６３および第３凸部７３は、第１凸部５３と同様の構成であるため、ここでは、第１コート領域５１、第１非コート領域５２、および第１凸部５３の構成について説明する。 The second coated region 61 and the third coated region 71 have the same configuration as the first coated region 51, and the second non-coated region 62 and the third non-coated region 72 have the same structure as the first non-coated region 52. In terms of configuration, the second convex portion 63 and the third convex portion 73 have the same configuration as the first convex portion 53, so here, the first coated region 51, the first non-coated region 52, and the first A configuration of the convex portion 53 will be described.
　第１コート領域５１は、薬剤およびポリマーが溶媒に溶解されて調製された塗布液を重ね塗りすることによって形成されている。第１コート領域５１において、薬剤コート層ＣＬは、図５に示すように、第１非コート領域５２に向かって厚さが漸減するように構成された傾斜部５１Ｔを有する。 The first coat region 51 is formed by repeatedly coating a coating liquid prepared by dissolving a drug and a polymer in a solvent. In the first coated region 51, the drug coated layer CL has an inclined portion 51T configured so that the thickness gradually decreases toward the first uncoated region 52, as shown in FIG.
　傾斜部５１Ｔは、上層側のコート長が下層側のコート長より短くなるように重ね塗りすることによって形成される。このように傾斜部５１Ｔが設けられることによって、傾斜部がない場合と比較して、リンク部３０の近傍に位置する薬剤コート層ＣＬの厚みが薄くなるため、薬剤コート層ＣＬの剥離あるいは脱落を防止する効果が高まる。 The inclined portion 51T is formed by overcoating so that the length of the coating on the upper layer side is shorter than the length of the coating on the lower layer side. By providing the inclined portion 51T in this manner, the thickness of the drug coat layer CL located near the link portion 30 becomes thinner than when there is no inclined portion. Increases the effectiveness of prevention.
　第１コート領域５１における薬剤コート層ＣＬの厚みは、例えば１～１００μｍである。 The thickness of the drug coat layer CL in the first coat region 51 is, for example, 1 to 100 μm.
　第１凸部５３は、薬剤から構成される。第１凸部５３は、図５に示すように、液滴状に構成される。 The first convex portion 53 is composed of a drug. As shown in FIG. 5, the first convex portion 53 is configured in a droplet shape.
　第１凸部５３は、図５に示すように、第１コート領域５１のうち第１非コート領域５２側の端部に設けられることが好ましい。より具体的には、第１コート領域５１および第１非コート領域５２の境界部５４から、第１凸部５３の中心位置５３Ｐまでの距離Ｌ１は、１０００μｍ以下であることが好ましく、５００μｍ以下であることがより好ましい。この構成によれば、第１凸部５３が配置される箇所を境界部５４により近づけることができるため、ステント１０が拡張して生体組織にステント１０が当接した際に、第１凸部５３の薬剤が、第１凸部５３が置かれる位置の生体組織から、ステント１０の第１非コート領域５２が置かれる位置の生体組織へ向けて浸透していく（図９の矢印参照）。したがって、薬効をより向上させることができる。 As shown in FIG. 5, the first convex portion 53 is preferably provided at the end of the first coated region 51 on the first non-coated region 52 side. More specifically, the distance L1 from the boundary portion 54 between the first coated region 51 and the first uncoated region 52 to the center position 53P of the first convex portion 53 is preferably 1000 μm or less, more preferably 500 μm or less. It is more preferable to have According to this configuration, since the location where the first projections 53 are arranged can be brought closer to the boundary portion 54, when the stent 10 is expanded and the stent 10 abuts on the biological tissue, the first projections 53 are The drug permeates from the living tissue where the first projections 53 are placed toward the living tissue where the first uncoated region 52 of the stent 10 is placed (see the arrow in FIG. 9). Therefore, efficacy can be further improved.
　第１凸部５３の高さＨは、特に限定されないが、例えば１～９０μｍであることが好ましく、７０μｍ以下であることがより好ましい。例えば、第１凸部の高さが１μｍよりも小さい場合は、上述した浸透する効果が小さくなる。一方、第１凸部の高さが９０μｍよりも大きい場合、ステント留置後の内皮化に要する時間が長期化して血栓が付着しやすくなり、付着した血栓による血管閉塞などのリスクが高まる。 Although the height H of the first projection 53 is not particularly limited, it is preferably 1 to 90 μm, more preferably 70 μm or less. For example, if the height of the first convex portion is less than 1 μm, the penetration effect described above is reduced. On the other hand, if the height of the first convex portion is greater than 90 μm, the time required for endothelialization after stent placement will be prolonged and thrombus will easily adhere, increasing the risk of vascular obstruction due to the adhered thrombus.
　第１凸部５３の幅Ｗは、凸部５３の高さＨの０．５～１０倍であることが好ましい。この構成によれば、第１凸部５３の傾斜がなだらかになるため、ステントデリバリーシステム１００を生体内にデリバリーしていくときに、生体組織に引っ掛かることを好適に抑制することができる。 The width W of the first projection 53 is preferably 0.5 to 10 times the height H of the projection 53. According to this configuration, since the slope of the first convex portion 53 is gentle, it is possible to preferably prevent the stent delivery system 100 from being caught on living tissue when delivering the stent delivery system 100 into the living body.
　以上のように第１凸部５３が設けられることによって、図９に示すように、ステント１０が拡張して生体組織Ｃにステント１０が当接した際に、第１凸部５３の薬剤が、第１凸部５３が置かれる位置の生体組織Ｃから、ステント１０の第１非コート領域５２が置かれる位置の生体組織へ向けて浸透していく。このため、第１凸部５３が設けられていないステントと比較して、薬効が向上する。 By providing the first projections 53 as described above, as shown in FIG. 9, when the stent 10 is expanded and the stent 10 abuts against the biological tissue C, the drug on the first projections 53 is From the living tissue C where the first projections 53 are placed, it permeates toward the living tissue where the first uncoated region 52 of the stent 10 is placed. Therefore, the efficacy is improved as compared with a stent in which the first projections 53 are not provided.
　また、凸部５３、６３、７３が設けられることによって、凸部５３、６３、７３がアンカー効果を備えることになり、ステント１０の位置ずれ（マイグレーション）を抑制することができる。 In addition, by providing the protrusions 53, 63, 73, the protrusions 53, 63, 73 have an anchoring effect, and displacement (migration) of the stent 10 can be suppressed.
　また、ステント１０を生体内に留置した後、ステント１０の軸方向Ｄ１の両端において、湾曲部２４が生体組織Ｃを傷つけてしまう可能性がある。ここに薬剤コート層ＣＬが形成されていなくても、本発明のステントにおいてはコート領域に薬剤から構成される凸部が設けられているため、薬剤を傷ついた部位に効率よく送ることができる。 Also, after the stent 10 is left in the living body, the curved portions 24 may damage the living tissue C at both ends of the stent 10 in the axial direction D1. Even if the drug coating layer CL is not formed here, since the stent of the present invention is provided with convex portions made of a drug in the coating region, the drug can be efficiently delivered to the injured site.
　次に、図１０、図１１を参照して、本実施形態に係るステント１０の製造方法について説明する。図１０は、塗布装置９０を示す概略図である。図１１は、本実施形態に係るステント１０の製造方法の塗布パターンを示す平面図である。 Next, a method for manufacturing the stent 10 according to this embodiment will be described with reference to FIGS. 10 and 11. FIG. FIG. 10 is a schematic diagram showing the coating device 90. As shown in FIG. FIG. 11 is a plan view showing an application pattern in the method for manufacturing the stent 10 according to this embodiment.
　本実施形態に係るステント１０の製造方法は、国際公開第２０１５／０４６１６８号と略同一の製造方法を用いることができる。本明細書では、適宜省略しつつステント１０の製造方法について説明する。 The manufacturing method of the stent 10 according to this embodiment can be substantially the same manufacturing method as in International Publication No. 2015/046168. In the present specification, a method for manufacturing the stent 10 will be described with appropriate omission.
　本実施形態に係るステント１０の製造方法は、ステント本体１０Ａを形成する形成工程と、ステント本体１０Ａに薬剤を塗布して薬剤コート層ＣＬを形成する塗布工程と、を有する。 The manufacturing method of the stent 10 according to the present embodiment includes a formation step of forming the stent body 10A and an application step of applying a drug to the stent body 10A to form the drug coat layer CL.
　形成工程では、管体（具体的には、金属パイプ）からステント本体１０Ａ以外の部分を除去して所定のパターンが形成される。形成工程では、例えば、フォトファブリケーションと呼ばれるマスキングと化学薬品を使用したエッチング方法、型による放電加工法、切削加工法（例えば、機械研磨、レーザー切削加工）などによって、金属パイプから所定のパターンを形成することができる。 In the forming step, a predetermined pattern is formed by removing portions other than the stent main body 10A from the tubular body (specifically, the metal pipe). In the formation process, for example, a predetermined pattern is formed from a metal pipe by an etching method using masking and chemicals called photofabrication, an electric discharge machining method using a mold, a cutting method (e.g., mechanical polishing, laser cutting), etc. can be formed.
　このように成形した後、化学研磨あるいは電解研磨によって環状体２０のエッジを除去し、滑らかな面となるように仕上げる。 After molding in this way, the edges of the annular body 20 are removed by chemical polishing or electropolishing, and the surface is finished to have a smooth surface.
　さらに所定のパターンに成形した後、焼きなましを行ってもよい。焼きなましによって、ステント本体１０Ａ全体の柔軟性および可撓性が向上し、屈曲した血管内での留置性が良好となり、血管内壁に与える物理的な刺激も減少し、再狭窄の要因を減少させることができる。 Further, annealing may be performed after molding into a predetermined pattern. Annealing improves the softness and flexibility of the stent main body 10A as a whole, improves the indwelling property in a curved blood vessel, reduces the physical irritation given to the inner wall of the blood vessel, and reduces the factors of restenosis. can be done.
　塗布工程では、図１０に示す塗布装置９０によって、ステント本体１０Ａの所定の箇所に薬剤が塗布されて、薬剤コート層ＣＬが形成される。 In the application step, the application device 90 shown in FIG. 10 applies the drug to a predetermined portion of the stent main body 10A to form the drug coat layer CL.
　薬剤コート層ＣＬの形成は、例えば、浸漬法、スプレー法、インクジェット法、ノズル噴射法など種々の方法を使用することができるが、本発明ではスプレー法、インクジェット法、ノズル噴射法が好ましい。 Various methods such as a dipping method, a spray method, an inkjet method, and a nozzle injection method can be used to form the drug coat layer CL. In the present invention, the spray method, the inkjet method, and the nozzle injection method are preferred.
　ここで、図１０を参照して、塗布装置９０の構成について説明する。 Here, the configuration of the coating device 90 will be described with reference to FIG.
　塗布装置９０は、図１０に示すように、ステント本体１０Ａを保持する保持部９１と、保持部９１を移動させる移動手段９２と、ステント本体１０Ａの所定の位置に薬剤を塗布する塗布部９３と、を有する。保持部９１、移動手段９２、および塗布部９３は、不図示の制御部によって制御される。保持部９１、移動手段９２、および塗布部９３は、国際公開第２０１５／０４６１６８号に開示されている塗布装置と同様の構成であるため、詳細な説明は省略する。 As shown in FIG. 10, the applicator 90 includes a holding portion 91 that holds the stent main body 10A, a moving means 92 that moves the holding portion 91, and an applicator 93 that applies a drug to a predetermined position of the stent main body 10A. , has The holding section 91, the moving means 92, and the application section 93 are controlled by a control section (not shown). Since the holding part 91, the moving means 92, and the coating part 93 have the same configuration as that of the coating device disclosed in International Publication No. 2015/046168, detailed description thereof will be omitted.
　塗布工程は、図１１に示すように、非コート領域５２、６２、７２に薬剤が塗布されないように、ステント本体１０Ａの表面に薬剤を塗布してコート領域５１、６１、７１を形成する第１塗布工程と、コート領域５１、６１、７１に、薬剤を塗布して凸部５３、６３、７３を形成する第２塗布工程と、を有する。 As shown in FIG. 11, the application step is the first step of applying the drug to the surface of the stent body 10A to form the coated regions 51, 61, 71 so that the non-coated regions 52, 62, 72 are not coated with the drug. and a second application step of applying a chemical to the coating regions 51 , 61 , 71 to form the protrusions 53 , 63 , 73 .
　第１塗布工程では、上述したように、非コート領域５２、６２、７２に向かって厚さが漸減するように、薬剤をコート領域５１、６１、７１に対して塗布する。具体的には、図１１に示すように、移動手段９２または塗布部９３のノズル９３Ａを所定のパターンに沿って移動し、ステント本体１０Ａの表面に薬剤を吐出して、薄い厚さの薄膜コート層を複数層形成する積層法が用いられる。積層法では、非コート領域５２、６２、７２に近づくにしたがって、各薄膜コート層のコーティング領域を調整し、薄膜コート層の積層数を段階的に低減することによって、傾斜部５１Ｔを形成することができる。 In the first application step, the drug is applied to the coated regions 51, 61, 71 so that the thickness gradually decreases toward the non-coated regions 52, 62, 72, as described above. Specifically, as shown in FIG. 11, the moving means 92 or the nozzle 93A of the application unit 93 is moved along a predetermined pattern to eject the drug onto the surface of the main stent body 10A to form a thin film coating. A lamination method of forming a plurality of layers is used. In the lamination method, the inclined portion 51T is formed by adjusting the coating region of each thin film coat layer and gradually reducing the number of thin film coat layers as the non-coated regions 52, 62, and 72 are approached. can be done.
　第２塗布工程では、第１塗布工程によってステント本体１０Ａに所定の塗布パターンが形成された後に、コート領域５１、６１、７１の上述した位置に、薬剤を塗布する。具体的には、塗布部９３のノズル９３Ａから薬剤を滴下することによって凸部５３、６３、７３が形成される。なお、凸部５３、６３、７３は、第１塗布工程において当該部分の薬剤の吐出量を増加させることによって形成されてもよい。 In the second application step, the drug is applied to the above-described positions of the coated regions 51, 61, and 71 after the predetermined application pattern is formed on the stent main body 10A in the first application step. Specifically, the protrusions 53 , 63 , 73 are formed by dropping the medicine from the nozzle 93</b>A of the application section 93 . Note that the convex portions 53, 63, and 73 may be formed by increasing the discharge amount of the medicine for the corresponding portions in the first application step.
　以上説明したように、本実施形態に係るステント１０は、径方向に拡張および収縮が可能な円筒形状のステントであって、湾曲部やリンク部などの拡張および収縮に伴い応力集中が起きる応力集中部と、少なくとも一部の応力集中部の表面に薬剤が被覆されていない非コート領域５２、６２、７２と、非コート領域５２、６２、７２以外の表面に薬剤コート層ＣＬが形成されたコート領域５１、６１、７１と、コート領域５１、６１、７１に設けられ、薬剤から構成され、径方向の外側に向かって突出する凸部５３、６３、７３と、を有する。このように構成されたステント１０によれば、応力集中部の表面に薬剤が被覆されていない非コート領域５２、６２、７２を備えるため、薬剤コート層ＣＬが剥がれてしまうことを抑制できる。また、コート領域５１、６１、７１に、薬剤から構成される凸部５３、６３、７３が設けられるため、ステント１０が拡張して生体組織にステント１０が当接した際に、凸部５３、６３、７３の薬剤が、凸部５３、６３、７３が置かれる位置の生体組織から、ステント１０の非コート領域５２、６２、７２が置かれる位置の生体組織へ向けて浸透していく。このため、凸部５３、６３、７３が設けられていないステント１０と比較して、薬効が向上する。以上から、薬剤コート層ＣＬの剥がれを抑制しつつ、薬効の低下を抑制できるステント１０を提供することができる。なお、ステント１０にある全ての湾曲部または／およびリンク部の表面を非コート領域とすることにより、薬剤コート層が剥がれるリスクはより低減される。 As described above, the stent 10 according to the present embodiment is a cylindrical stent that can be expanded and contracted in the radial direction. part, non-coated regions 52, 62, 72 where the surface of at least some of the stress concentration parts is not coated with the drug, and a drug coating layer CL formed on the surface other than the non-coated regions 52, 62, 72 Regions 51, 61, 71, and projections 53, 63, 73 provided in the coated regions 51, 61, 71, made of a drug, and protruding radially outward. According to the stent 10 configured in this manner, the non-coated regions 52, 62, and 72, which are not coated with the drug, are provided on the surface of the stress concentration portion, so peeling of the drug-coated layer CL can be suppressed. Moreover, since the protruding portions 53, 63, and 73 made of a drug are provided in the coated regions 51, 61, and 71, when the stent 10 expands and comes into contact with living tissue, the protruding portions 53, The drugs 63 and 73 permeate from the body tissue where the protrusions 53, 63 and 73 are placed toward the body tissue where the non-coated regions 52, 62 and 72 of the stent 10 are placed. Therefore, compared with the stent 10 in which the projections 53, 63, 73 are not provided, the efficacy is improved. As described above, it is possible to provide the stent 10 capable of suppressing deterioration of drug efficacy while suppressing peeling of the drug coat layer CL. By making the surfaces of all curved portions and/or link portions of the stent 10 non-coated regions, the risk of peeling off of the drug coating layer is further reduced.
　また、凸部５３、６３、７３は、コート領域５１、６１、７１のうち非コート領域５２、６２、７２側の端部に設けられる。このように構成されたステント１０によれば、第１凸部５３が配置される箇所を境界部５４に近づけることができるため、ステント１０が拡張して生体組織に薬剤が当接した際に、第１凸部５３の薬剤が、第１非コート領域５２が置かれる位置の生体組織に、より短時間で好適に浸透していく。したがって、薬効をより向上させることができる。 In addition, the convex portions 53, 63, 73 are provided at the ends of the coated regions 51, 61, 71 on the non-coated regions 52, 62, 72 side. According to the stent 10 configured in this way, since the location where the first convex portion 53 is arranged can be brought close to the boundary portion 54, when the stent 10 expands and the drug comes into contact with the living tissue, The medicine on the first convex portion 53 preferably permeates into the living tissue at the position where the first uncoated region 52 is placed in a shorter period of time. Therefore, efficacy can be further improved.
　また、第１コート領域５１および第１非コート領域５２の境界部５４から、第１凸部５３の中心位置５３Ｐまでの距離Ｌ１は、１０００μｍ以下である。このように構成されたステント１０によれば、第１凸部５３が配置される箇所を境界部５４に近づけることができるため、ステント１０が拡張して生体組織に薬剤が当接した際に、第１凸部５３の薬剤が、第１非コート領域５２が置かれる位置の生体組織に、より短時間で好適に浸透していく。したがって、薬効をより向上させることができる。 Also, the distance L1 from the boundary portion 54 between the first coated region 51 and the first non-coated region 52 to the center position 53P of the first convex portion 53 is 1000 μm or less. According to the stent 10 configured in this way, since the location where the first convex portion 53 is arranged can be brought close to the boundary portion 54, when the stent 10 expands and the drug comes into contact with the living tissue, The medicine on the first convex portion 53 preferably permeates into the living tissue at the position where the first uncoated region 52 is placed in a shorter period of time. Therefore, efficacy can be further improved.
　また、第１凸部５３の高さＨは１～９０μｍである。このように構成されたステント１０によれば、非コート領域への薬効を向上させつつ、ステント留置後の内皮化に要する時間が短縮されることにより、血栓付着のリスクを低減することができる。 Also, the height H of the first projection 53 is 1 to 90 μm. According to the stent 10 configured in this manner, the risk of thrombus adhesion can be reduced by shortening the time required for endothelialization after stent placement while improving the efficacy of the non-coated region.
　また、第１凸部５３の幅Ｗは、第１凸部５３の高さの０．５～１０倍である。このように構成されたステント１０によれば、第１凸部５３の傾斜がなだらかになるため、ステントデリバリーシステム１００を生体内にデリバリーしていくときに、生体組織に引っ掛かることを好適に抑制することができる。 Also, the width W of the first convex portion 53 is 0.5 to 10 times the height of the first convex portion 53 . According to the stent 10 configured in this way, since the slope of the first convex portion 53 is gentle, it is possible to preferably prevent the stent delivery system 100 from being caught on the living tissue when the stent delivery system 100 is delivered into the living body. be able to.
　また、薬剤コート層ＣＬは、第１非コート領域５２に向かって厚さが漸減するように構成された傾斜部５１Ｔを有する。このように構成されたステント１０によれば、傾斜部がない場合と比較して、応力集中部の近傍に位置する薬剤コート層ＣＬの厚みが薄くなるため、薬剤コート層ＣＬの剥離あるいは脱落を防止する効果が高まる。 In addition, the drug coat layer CL has an inclined portion 51T configured so that the thickness gradually decreases toward the first non-coated region 52 . According to the stent 10 configured in this manner, the thickness of the drug coat layer CL located near the stress concentration portion is thinner than when there is no inclined portion, so that peeling or falling off of the drug coat layer CL is prevented. Increases the effectiveness of prevention.
　また、薬剤コート層ＣＬは、コート領域５１、６１、７１の外表面側にのみ形成されている。ステント１０が血管内に留置された場合、外表面側に加えて側面側または／および内表面側にも薬剤コート層が設けられているステントと比較して、ステント留置後の内皮化に要する時間が短縮されることにより、血栓付着のリスクを低減することができる。 Also, the drug coat layer CL is formed only on the outer surface side of the coat regions 51 , 61 , 71 . When the stent 10 is placed in a blood vessel, the time required for endothelialization after stent placement compared to a stent having a drug coating layer on the side surface side and/or the inner surface side in addition to the outer surface side can reduce the risk of thrombus attachment.
　また、以上説明したように、本実施形態に係るステント１０の製造方法は、径方向に拡張および収縮が可能な円筒形状のステント本体１０Ａと、薬剤を含むコート領域５１、６１、７１と、を有するステント１０の製造方法であって、リンク部や湾曲部などの拡張および収縮に伴い応力集中が起きる応力集中部の少なくとも一部の表面を除き、ステント本体１０Ａの表面に薬剤を塗布してコート領域５１、６１、７１および前記コート領域５１、６１、７１内で径方向の外側に向かって突出する凸部５３、６３、７３を形成する工程を有する。この製造方法によって製造されたステント１０によれば、応力集中部の表面に薬剤が被覆されていないため、薬剤コート層ＣＬが剥がれてしまうことを抑制できる。また、コート領域５１、６１、７１に、薬剤から構成される凸部５３、６３、７３が設けられるため、ステント１０が拡張して生体組織にステント１０が当接した際に、凸部５３、６３、７３の薬剤が、凸部５３、６３、７３が置かれる位置の生体組織から、ステント１０の非コート領域５２、６２、７２が置かれる位置の生体組織へ向けて浸透していく。このため、凸部５３、６３、７３が設けられていないステント１０と比較して、薬効が向上する。 In addition, as described above, the method for manufacturing the stent 10 according to the present embodiment includes the cylindrical stent main body 10A that can be expanded and contracted in the radial direction, and the coated regions 51, 61, and 71 containing the drug. In a method for manufacturing a stent 10 having a drug, the surface of the stent main body 10A is coated with a drug except for at least a part of the surface of a stress concentration part where stress concentration occurs with expansion and contraction such as a link part and a curved part A step of forming protrusions 53 , 63 , 73 protruding radially outward in the regions 51 , 61 , 71 and the coat regions 51 , 61 , 71 . According to the stent 10 manufactured by this manufacturing method, since the surface of the stress concentration portion is not coated with the drug, peeling of the drug coat layer CL can be suppressed. Moreover, since the protruding portions 53, 63, and 73 made of a drug are provided in the coated regions 51, 61, and 71, when the stent 10 expands and comes into contact with living tissue, the protruding portions 53, The drugs 63 and 73 permeate from the body tissue where the protrusions 53, 63 and 73 are placed toward the body tissue where the non-coated regions 52, 62 and 72 of the stent 10 are placed. Therefore, compared with the stent 10 in which the projections 53, 63, 73 are not provided, the efficacy is improved.
　以上、実施形態を通じて本発明に係るステント１０を説明したが、本発明は実施形態において説明した構成のみに限定されることはなく、特許請求の範囲の記載に基づいて適宜変更することが可能である。 Although the stent 10 according to the present invention has been described above through the embodiments, the present invention is not limited to the configurations described in the embodiments, and can be appropriately modified based on the description of the claims. be.
　例えば、上述した実施形態では、第１凸部５３は、第１コート領域５１のうち第１非コート領域５２側の端部に設けられた。しかしながら、第１凸部は、第１コート領域５１の任意の箇所に設けられ得る。 For example, in the above-described embodiment, the first convex portion 53 is provided at the end of the first coated region 51 on the first non-coated region 52 side. However, the first convex portion can be provided at any location on the first coat region 51 .
　また、上述した実施形態では、薬剤コート層ＣＬは、第１非コート領域５２に向かって厚さが漸減するように構成された傾斜部５１Ｔを有した。しかしながら、薬剤コート層は、傾斜部を有していなくてもよい。 In addition, in the above-described embodiment, the drug coat layer CL has the inclined portion 51T configured so that the thickness gradually decreases toward the first non-coated region 52 . However, the drug coat layer does not have to have an inclined portion.
　また、上述した実施形態では、ステント１０は、波状に折り返された無端の環状形状である環状体２０が、リンク部３０により軸方向に連続して接続された円筒形状であった。しかしながら、ステントは、波線状に連続する構成要素をらせん状に巻いて円筒形状に形作られてもよい。また、当形状においてもリンク部により構成要素が軸方向に接続されていてもよい。 Further, in the above-described embodiment, the stent 10 has a cylindrical shape in which the ring-shaped bodies 20 that are endless ring-shaped folded back in a wavy shape are continuously connected in the axial direction by the link portions 30 . However, the stent may be formed into a cylindrical shape by spirally winding a wavy continuous component. Further, even in this shape, the constituent elements may be connected in the axial direction by the link portion.
　また、上述した実施形態では、ステント本体１０Ａの表面にプライマー被覆層４０が配置されたが、プライマー被覆層は配置されていなくてもよい。 Also, in the above-described embodiment, the primer coating layer 40 is arranged on the surface of the stent main body 10A, but the primer coating layer may not be arranged.
　また、上述した実施形態では、第１凸部５３の形状は、液滴状であった。しかしながら、第１凸部５３は、図１２に示すように、液滴が滲んで広がったような形状であってもよい。さらに、第１凸部は、径方向の外側が鋭い形状であってもよい。 Also, in the above-described embodiment, the shape of the first convex portion 53 is droplet-like. However, as shown in FIG. 12, the first convex portion 53 may have a shape in which a droplet spreads out. Furthermore, the first protrusion may have a shape with a sharp radial outer side.
　本出願は、２０２１年２月１９日に出願された日本国特許出願第２０２１－０２５０６６号に基づいており、その開示内容は、参照により全体として引用されている。 This application is based on Japanese Patent Application No. 2021-025066 filed on February 19, 2021, the disclosure of which is incorporated by reference in its entirety.
　　１０　　ステント、
　　１０Ａ　ステント本体、
　　２０　　環状体、
　　２１、２２、２３　　線状部、
　　２４、２５　　湾曲部、
　　３０　　リンク部、
　　５１　　第１コート領域（コート領域）、
　　５１Ｔ　傾斜部、
　　５２　　第１非コート領域（非コート領域）、
　　５３、１５３　　第１凸部（凸部）、
　　５３Ｐ　第１凸部の中心位置、
　　５４　　境界部、
　　６１　　第２コート領域（コート領域）、
　　６２　　第２非コート領域（非コート領域）、
　　６３　　第２凸部（凸部）、
　　７１　　第３コート領域（コート領域）、
　　７２　　第３非コート領域（非コート領域）、
　　７３　　第３凸部（凸部）、
　　ＣＬ　　薬剤コート層、
　　Ｈ　　　第１凸部の高さ、
　　Ｌ１　　境界部から第１凸部の中心位置までの距離、
　　Ｗ　　　第１凸部の幅。 10 stents,
10A stent body,
20 toroids,
21, 22, 23 linear portion,
24, 25 bending portion,
30 link part,
51 first coated region (coated region),
51T inclined portion,
52 first non-coated region (non-coated region),
53, 153 first convex portion (convex portion),
53P center position of the first protrusion,
54 boundaries,
61 second coat area (coat area),
62 second non-coated region (non-coated region),
63 second convex portion (convex portion),
71 third coated region (coated region),
72 third non-coated region (non-coated region),
73 third convex portion (convex portion),
CL drug coat layer,
H the height of the first convex portion;
L1 distance from the boundary to the center position of the first protrusion,
W Width of the first protrusion.

Claims (8)

  1. 　径方向に拡張および収縮が可能な円筒形状のステントであって、
    　拡張および収縮に伴い応力集中が起きる応力集中部と、
    　少なくとも一部の前記応力集中部の表面に薬剤が被覆されていない非コート領域と、
    　前記非コート領域以外の表面に薬剤コート層が形成されたコート領域と、
    　前記コート領域に設けられ、前記薬剤から構成され、前記径方向の外側に向かって突出する凸部と、を有するステント。     A radially expandable and contractible cylindrical stent comprising:
    a stress concentration portion where stress concentration occurs with expansion and contraction;
    a non-coated region in which the surface of at least a portion of the stress concentration portion is not coated with a drug;
    a coated region having a drug-coated layer formed on the surface other than the non-coated region;
    a convex portion provided in the coat region, made of the drug, and protruding outward in the radial direction.
  2. 　前記凸部は、前記コート領域のうち前記非コート領域側の端部に設けられる、請求項１に記載のステント。 The stent according to claim 1, wherein the convex portion is provided at an end of the coated region on the non-coated region side.
  3. 　前記コート領域および前記非コート領域の境界部から、前記凸部の中心位置までの距離は、１０００μｍ以下である、請求項１または請求項２に記載のステント。 The stent according to claim 1 or 2, wherein the distance from the boundary between the coated region and the non-coated region to the central position of the projection is 1000 µm or less.
  4. 　前記凸部の高さは、１～９０μｍである、請求項１～３のいずれか１項に記載のステント。 The stent according to any one of claims 1 to 3, wherein the height of the convex portion is 1 to 90 µm.
  5. 　前記凸部の幅は、前記凸部の前記高さの０．５～１０倍である、請求項１～４のいずれか１項に記載のステント。 The stent according to any one of claims 1 to 4, wherein the width of the protrusion is 0.5 to 10 times the height of the protrusion.
  6. 　前記薬剤コート層は、前記非コート領域に向かって厚さが漸減するように構成された傾斜部を有する、請求項１～５のいずれか１項に記載のステント。 The stent according to any one of claims 1 to 5, wherein the drug-coated layer has an inclined portion configured to gradually decrease in thickness toward the non-coated region.
  7. 　前記薬剤コート層は、ステント本体の外表面側にのみ形成されている、請求項１～６のいずれか１項に記載のステント。 The stent according to any one of claims 1 to 6, wherein the drug coating layer is formed only on the outer surface side of the main body of the stent.
  8. 　径方向に拡張および収縮が可能な円筒形状のステント本体と、薬剤を含むコート領域と、を有するステントの製造方法であって、
    　拡張および収縮に伴い応力集中が起きる応力集中部の少なくとも一部の表面を除き、前記ステント本体の表面に前記薬剤を塗布して前記コート領域および前記コート領域内で前記径方向の外側に向かって突出する凸部を形成する工程を有するステントの製造方法。     A method for manufacturing a stent having a cylindrical stent body that can be radially expanded and contracted and a coating region containing a drug, comprising:
    The drug is applied to the surface of the stent body except for at least a part of the surface of the stress concentration portion where stress concentration occurs with expansion and contraction, and spreads outward in the radial direction in the coated region and within the coated region. A method of manufacturing a stent, comprising a step of forming a protruding convex portion.
PCT/JP2022/005551 2021-02-19 2022-02-14 Stent and method for manufacturing stent WO2022176792A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005508671A (en) * 2001-07-26 2005-04-07 アバンテク バスキュラー コーポレーション Delivery of therapeutically effective drugs
JP2008538933A (en) * 2005-03-03 2008-11-13 アイコン メディカル コーポレーション Improved metal alloys for medical components
WO2011040218A1 (en) * 2009-09-30 2011-04-07 テルモ株式会社 Stent

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005508671A (en) * 2001-07-26 2005-04-07 アバンテク バスキュラー コーポレーション Delivery of therapeutically effective drugs
JP2008538933A (en) * 2005-03-03 2008-11-13 アイコン メディカル コーポレーション Improved metal alloys for medical components
WO2011040218A1 (en) * 2009-09-30 2011-04-07 テルモ株式会社 Stent

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