Patent Publication Number: US-2017348121-A1

Title: Stent and method of manufacturing stent

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     This application is a continuation of International Application No. PCT/JP2016/052543 filed on Jan. 28, 2016, and claims priority to Japanese Application No. 2015-039349 filed on Feb. 27, 2015, the entire content of both of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present invention generally relates to a stent and a method of manufacturing a stent. 
     BACKGROUND DISCUSSION 
     In recent years, a technique of forming a stent using metal and polymer has been proposed. For example, International Application Publication No. 2007/079363 discloses a stent in which helical outer peripheral portions are formed of metal, and a connection portion that connects the helical metal portions to each other is formed of polymer. By forming the stent using metal and polymer, it is possible for the stent to exhibit the contradictory properties of strength and flexibility. 
     SUMMARY 
     However, when a tensile force is applied to an interface between metal and polymer such that the metal and the polymer are separated from each other, fracture resistance is reduced compared to a case where the entire stent is integrally formed of only metal or only polymer. The inventor here has discovered that the fracture resistance of the stent can be improved by hindering a strong force from being applied to the interface between the metal and the polymer. 
     The stent exhibits improved fracture resistance and the manufacturing method results in a stent exhibiting such characteristics. 
     According to one aspect, a stent comprises metal portions that together form a tubular frame possessing an outer periphery, with the tubular frame including a gap extending through the tubular frame and at which two of the metal portions are positioned adjacent one another in a spaced-apart manner; and a polymer portion located in the gap and connecting the two metal portions to each other. The polymer portion includes a curved portion that is curved and possesses a concave shape that is recessed toward an outer side of the stent from an inner side of the stent in a radial direction of the outer periphery. 
     According to another aspect, a stent comprises: metal portions that together form a tubular frame possessing an outer periphery, wherein the tubular frame includes a gap extending through the tubular frame and at which two of the metal portions are positioned adjacent one another in a spaced-apart manner; and a polymer portion formed of biodegradable polymer and connecting the two metal portions to each other. The polymer portion possesses an inwardly facing side facing towards an interior of the frame, the inwardly facing side of the polymer portion being curved. 
     Another aspect involves a method of manufacturing a stent, comprising: placing polymer in contact with two metal portions of a tubular stent frame that possesses an outer periphery, with the two metal portions being spaced apart from one another so that a gap exists between the two metal portions; and heating the polymer after placing the polymer in contact with the two metal portions to connect together the two metal portions by way of the polymer portion. The heating comprising heating the polymer so that the polymer is molten and flows to the gap to form a polymer portion that connects the two metal portions and includes an inwardly facing curved portion that is curved and possesses a concave shape that is recessed toward an outer side of the stent from an inner side of the stent in a radial direction of the outer periphery. 
     The polymer portion which is relatively easily stretchable compared to the metal portions is thinned by forming the curved portion. Therefore, the polymer portion becomes more easily stretchable. For this reason, when a tensile force is applied to separate the metal portions and the polymer portion from each other, a strong force is not easily applied to an interface between the metal portions and the polymer portion by virtue of the stretch of the polymer portion. Therefore, it is possible to more improve the fracture resistance. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a stent according to an embodiment representing an example of the inventive step disclosed here. 
         FIG. 2  is a cross-sectional view taken along the section line  2 - 2  of  FIG. 1 . 
         FIGS. 3A-3C  are diagrams illustrating an overview of a method of manufacturing a stent according to an embodiment. 
         FIG. 4  is a cross-sectional view illustrating a modification of a polymer portion. 
         FIG. 5  is a cross-sectional view illustrating another modification of the polymer portion. 
         FIG. 6  is a cross-sectional view illustrating a modification in which a polymer layer is formed along with the polymer portion. 
         FIG. 7  is a cross-sectional view illustrating another modification in which a polymer layer is formed along with the polymer portion. 
         FIG. 8  is a cross-sectional view illustrating further another modification of the polymer portion. 
         FIG. 9  is an enlarged view illustrating a main portion according to a modification in which a connection portion is provided along with the polymer portion. 
         FIG. 10  is a cross-sectional view taken along the section line  10 - 10  of  FIG. 9 . 
     
    
    
     DETAILED DESCRIPTION 
     Set forth below with reference to the accompanying drawings is a detailed description of embodiments of a stent and a stent manufacturing method representing examples of the inventive stent and manufacturing method disclosed here. The dimensions or scales on the drawings may be exaggerated or different from actuality/reality for convenience of description and illustration. 
     As illustrated in  FIG. 1 , a stent  100  according to an embodiment has a plurality of struts  110  (metal portion) and a plurality of polymer portions  120 . 
     The stent  100  is used in or positionable in a lumen such as a blood vessel, a bile duct, a trachea, an esophagus, a gastrointestinal tract, and a urethra in a living body. The stent  100  treats stenosis or obstruction by forcibly widening or enlarging the lumen. The stent  100  may be a balloon-expandable stent which is expanded by inflating a balloon (i.e., the stent surrounds a balloon and inflation/expansion of the balloon expands the stent) or a self-expandable stent which expands by its own expanding function. 
     The struts  110  include linear components formed of metal as well as curved components formed of metal that interconnect the linear components as shown in the enlarged portion of  FIG. 1 . The integrated struts  110  are shaped or configured to define a tubular member or tubular frame having an outer periphery with gaps in the tubular frame. In the expanded state, the tubular frame defined by the metal portions or metal struts is a cylindrical frame. 
     For example, the struts  110  may be connected and arranged to form a wavy-shaped member, with axially oriented (axially extending) peaks and valleys as shown in  FIG. 1 , that extends helically in the axial direction D 1  of the stent  100  to form an endless annular body (endless from one axial end of the annular body/stent to the opposite axial end of the annular body/stent). In addition, some of the struts  110  are connected coaxially along the axial direction D 1  of the stent  100 , by the polymer portions  120 , so as to shape the outer periphery of the stent  100 . Alternatively, the struts  110  may be interconnected and arranged to form a plurality of wavy-shaped endless annular members that are axially arranged along the axial extent of the stent, with axially adjacent wavy-shaped endless annular members connected coaxially in the axial direction D 1  of the stent  100 , by the polymer portions  120 , so as to shape the outer periphery of the stent  100 . The shape of the struts  110  is not particularly limited. The axial direction D 1  of the stent  100  is perpendicular to a radial direction D 2  of the tubular outer periphery of the stent  100  (hereinafter, simply referred to as a radial direction D 2  of the stent  100 ). 
     The metal forming the struts  110  may include, for example, stainless steel, tantalum, tantalum alloy, titanium, titanium alloy, nickel titanium alloy, tantalum titanium alloy, nickel aluminum alloy, Inconel, gold, platinum, iridium, tungsten, tungsten alloy, cobalt-based alloy such as cobalt chromium alloy, magnesium, zirconium, niobium, zinc, or silicon, but not particularly limited thereto. The metal from which the struts  110  are fabricated may be either biodegradable metal or non-biodegradable metal. 
     Each of the polymer portions  120  is positioned in a gap between two adjacent struts  110  to connect the struts  110  to each other. In the illustrated embodiment, the polymer portions  120  connect together spaced apart (axially spaced apart) and adjacent struts (axially adjacent struts)  110 . The polymer portions  120  are located in the gaps of openings in the stent (i.e., the gaps/openings that communicate the interior of the stent with the exterior of the stent). There is no particular limitation to where the polymer portions  120  are provided or located in the gap of the outer periphery of the stent  100  as long as the polymer portions  120  connect metal members of the stent  100  to each other. 
     The polymer portions  120  are formed of, for example, biodegradable polymer. The biodegradable polymer includes, for example, a biodegradable synthetic polymer material polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polycaprolactone, lactic acid-caprolactone copolymer, glycolic acid-caprolactone copolymer, poly-γ-glutamin acid, a natural biodegradable polymer material such as cellulose or collagen, or the like. The polymer portions  120  may also be formed of non-biodegradable polymer. 
     As illustrated in  FIG. 2 , each of the polymer portions  120  has a curved portion  121  in an inner lumen side (inner side) of the stent  100 . That is, the polymer portions  120  are positioned on the inner side of the stent that faces toward the interior of the stent. The curved portion  121  is curved to be concave from the inner lumen side toward the outer side in the radial direction D 2  of the stent  100 . The curved portion  121  has a curvature different from the circumferential curvature of the stent  100 . The circumferential curvature of the stent  100  refers to the radius of curvature of the inner surface of the stent when the stent is expanded. 
     In the cross section of  FIG. 2  (a cross section taken along the separation direction of the metal portions), a peak P 1  where the curved portion (concavity)  121  is deepest is located in a center between two boundary lines L 1  and L 2  formed between the polymer portion  120  and two adjacent struts  110 . That is, the polymer portion  120  is connected to one of the two metal struts  110  at one boundary L 1  and the polymer portion is connected to the other of the two metal struts  110  at the other boundary L 2 , and the most recessed point of the concave-shaped curved portion  121  (i.e., the peak P 1  of the concave-shaped curved portion  121 ) is located at the center between the two boundaries L 1 , L 2 . In addition, the peak P 1  is deviated from a line L 3  obtained by connecting, with a straight line, two cross points P 2  and P 3  between the boundary lines L 1  and L 2  and the contour line of the curved portion  121 . That is, the peak P 1  exists in a different position that does not cross the line L 3  obtained by connecting, with a straight line, the two cross points P 2  and P 3  between the boundary lines L 1  and L 2  and the contour line of the curved portion  121 . The peak P 1  is thus spaced from the line L 3 . 
     Next, a method of manufacturing the stent  100  will be described. 
     As illustrated in  FIGS. 3A-3C , the method of manufacturing the stent  100  includes a polymer application process, a drying process, and a heating process. Before the polymer application process, the frame defined by the interconnected or integrated struts  110  and having a predetermined shape or configuration is prepared. 
     In the polymer application process, a polymer solution  122  is applied toward the gap  111  formed by the adjacent struts  110 . The polymer solution  122  is applied toward the gap  111  from the outer side of the stent (i.e., the side facing outwardly away from the stent interior). The polymer solution  122  is applied using an application device such as a micro-syringe. 
     The polymer solution  122  is obtained by dissolving polymer of the polymer portions  120  in a solvent. The solvent includes, for example, an organic solvent such as methanol, ethanol, dioxane, tetrahydrofuran, dimethylformamide, acetonitrile, dimethylsulfoxide, or acetone, and the like. 
     In the drying process after the polymer application process, the polymer solution  122  applied to the struts  110  is dried, and the solvent is evaporated. The drying of the polymer solution  122  may include, for example, natural drying. Alternatively, the drying may include heated drying by heating the polymer solution  122 . The heated drying is not limited to a particular type of heated drying. The drying reduces the volume of the polymer solution  122  and increases the viscosity of the polymer solution  122 . 
     After the drying process, the dried polymer solution  122  is heated in the heating process to further evaporate the solvent and melt the polymer contained in the solution. In the heating process, for example, the polymer solution  122 , attached to the struts  110 , is heated inside a vacuum furnace together with the struts  110 . Here, the heating temperature of the polymer solution  122  may be set to a temperature at which the polymer has sufficient fluidity. The temperature may vary depending on a type of the polymer and may be set to, for example, 35° C. to 300° C. without a particular limitation. 
     The fluidity of the polymer solution  122  heated through the heating process increases, so that the polymer solution  122  flows into the gap  111  between the adjacent struts  10  by virtue of a capillary phenomenon. As a result, the curved portion  121  is formed on a surface of the polymer solution  122  in the inner lumen side of the stent so that the inner surface of the polymer solution  122  (polymer portions  120 ) exhibits a concave shape. According to this embodiment, the polymer solution  122  is filled in the gap  111  until end portions  123  of the curved portion  121  are closer to the stent lumen-side surface  112  of the struts  110 . That is, according to one embodiment, the polymer solution  122  is filled in the gap  111  until the end portions  123  of the curved portion  121  are closer to the stent lumen-side surface  112  of the struts  110  than to the opposite surface of the struts  110 . In this manner, since the polymer solution  122  is filled in the inside of the gap  111  as much as possible, a contact area between the polymer solution  122  and the struts  110 , and further, a contact area between the polymer portions  120  and the struts  110  increases. Therefore, it is possible to improve fracture resistance on such an interface. In addition, since more polymer solution  122  is filled, a volume of the polymer portions  120  increases. Therefore, it is possible to improve a strength of the polymer portions  120  of itself. After the polymer solution  122  is filled in the gap  111 , the polymer solution  122  is solidified to form the polymer portion  120 . At the boundary lines L 1 , L 2 , the thickness of the polymer material may be at least equal to (no less than) the thickness of the struts or metal portions  110 . 
     The process or method described above for forming the polymer portion  120  positioned in the gap  111  between two adjacent struts  110  to connect the adjacent struts  110  is preferably applied to the formation of all of the polymer portions  120  in the stent  100 . The description above and below about the polymer portion  120  applies equally to all of the polymer portions  120 . 
     Next, functional effects of the above-described stent and manufacturing method will be described. 
     According to this embodiment, compared to the struts  110  formed of metal, the relatively easily stretchable polymer portions  120  are thinned by forming the curved portion  121 . Therefore, the polymer portions  120  are more easily stretchable. For this reason, for example, when a tensile force is applied tending to separate the struts  110  and the polymer portion  120  from each other at one or more of the connection regions by expanding the stent  100 , it is possible to prevent a strong force from being easily applied to the interface between the struts (adjacent struts) 110  and the polymer portion  120  by virtue of the stretching ability of the polymer portion  120 . This thus improve fracture resistance. 
     In this embodiment, the peak P 1  of the curved portion  121  (the thinnest portion of the polymer portion  120 ) is positioned in the center between two boundary lines L 1  and L 2  formed between the polymer portion  120  and the adjacent struts  110 . In this configuration, the polymer portion  120  relatively easily stretches evenly between one side and the other side of the two adjacent struts  110 , and a force is substantially uniformly applied to the two interfaces between the polymer portion  120  and both of the adjacent struts  110 . For this reason, it is possible to prevent fracture resistance from being lowered by biasedly applying a stronger force to any one of the two interfaces. 
     Unlike this embodiment, a polymer portion having a contour line, for example, as indicated by the line L 3  of  FIG. 2  is not thinned by the curved portion  121  compared to the polymer portion  120  of this embodiment. That is, if the contour of the polymer portion  120  followed the line L 3 , the polymer portion  120  would not include a thinned portion. A polymer portion having a contour that follows the line L 3  is not easily stretched relative to the struts  110 . 
     Meanwhile, according to this embodiment, the peak P 1  of the curved portion  121  is deviated (recessed) to the outer side of the stent from the line L 3 . As a result, the polymer portion  120  is thinned and becomes relatively easily stretchable. Therefore, an excessively strong force is not easily applied to the interface between the strut  110  and the polymer portion  120 . In addition, it is possible to improve fracture resistance. 
     The invention is not limited to the aforementioned embodiments, and may be modified in various forms within the scope of the claims. 
     For example, as the polymer portion  220  illustrated in  FIG. 4 , the end portions  224  of the curved portion  221  may be spaced, in the direction toward the outer side of the stent, from the stent lumen-side surface  112  of the struts  110  so that the end portions  224  of the curved portion  221  do not reach or intersect the stent lumen-side surface  112  of the struts  110 . 
     Another version of a polymer portion  320  is illustrated in  FIG. 5 . In the polymer portion  320 , the peak P 4  of the curved portion  321  (i.e., the most-thinned portion) is deviated from the center between the boundary lines L 1  and L 2 . That is, the peak P 4  is located at a position different from or spaced from the center between the boundary lines L 1  and L 2 . In this case, the stretch of the polymer portion  320  is different between one side and the other side of the two adjacent struts  110 , so that forces having different strengths are applied to the two interfaces between the polymer portion  320  and the two adjacent struts  110 . For this reason, a relatively stronger force is intentionally applied to one of the two interfaces by deviating or moving the peak P 4  away from the center. As a result, even when a fracture occurs, it is possible to control where the fracture occurs out of the two interfaces. In this embodiment, the end portions of the curved portion  321  may reach or intersect the stent lumen-side surface of the struts  110  as shown in  FIG. 5 . 
     In addition, as illustrated in  FIG. 6 , a polymer layer  130  may be formed outward of the polymer portion  120  of the stent. The polymer material may thus extend outwardly beyond the outwardly facing surfaces of the two adjacent struts  110  connected by the polymer material (i.e., the polymer layer  130  projects beyond the plane containing the outer surfaces of the two struts  110  as seen in  FIG. 6 ). The polymer layer  130  is formed to match a position of the polymer portion  120  and is interspersed on the outer periphery of the stent  100 . Since the polymer portion  120  is reinforced by the polymer layer  130 , it is possible to improve a strength of the polymer portion  120  itself. 
     In addition, as illustrated in  FIG. 7 , a polymer layer  140  may be formed to continuously extend along the surface of the struts  110 . The polymer layer  140  connects one of the polymer portions  120  and at least one of the other polymer portions  120 . Since the polymer layer  140  reinforces the struts  110  and the polymer portion  120  across a wide range, it is possible to further improve the strength of the stent  100 . The polymer layer  140  is preferably formed on or extends along the entire outer surface of the underlying struts  110 . Alternatively, without being limited thereto, the polymer layer  140  may be partially formed to extend along a part of the outer surface of the struts  110 . Furthermore, the polymer layer  140  may be formed inward of the stent  100 . That is, the polymer layer  140  may be positioned on the inner side of the struts  110  (i.e., the bottom side of the struts in  FIG. 7 ). 
     The polymer layers  130  and  140  are, for example, drug layers, but are not limited in this regard. That is, the polymer layers  130 ,  140  may contain a drug. In addition, the polymer layers  130  and  140  may be formed of the same material as that of the polymer portion  120  or a material different from that of the polymer portion  120 . The polymer layers  130  and  140  are formed, for example, by further applying the polymer solution after formation of the polymer portion  120  and heating the further applied polymer solution for drying. A primer layer may also be formed before formation of the polymer layers  130  and  140 . 
       FIG. 8  shows another variation in which a polymer portion  420  protrudes toward the stent inner lumen side with respect to the struts  110 . That is, the polymer portion  420  extends inwardly beyond the inner surface of the adjacent struts  110  (i.e., the polymer portion  420  extends inwardly beyond the plane in which the inner surfaces of each of the two struts  110  lie). As a result, a volume of the polymer portion  420  increases. Therefore, it is possible to improve the strength of the polymer portion  420  of itself. As illustrated in  FIG. 8 , the inwardly facing side of the protruding polymer portion  420  includes the curved portion  421 . Also, the polymer portion  420  may protrude to the inner side such that the polymer portion is in contact with the inwardly facing side of the metal portions or struts  110  as shown in  FIG. 8 . 
     In the polymer application process (polymer placement process) of the aforementioned embodiments, the polymer is placed in the gaps  111  by applying the polymer solution  122 . However, the invention is not limited in this regard. For example, the polymer may be placed in the gap  111  by overlaying a solid sheet formed of polymer on the gap  111 . In this case, the sheet is heated through a heating process and is molten, so that the molten polymer flows into the gap  111 . 
     Another variation is illustrated in  FIG. 9 , Here, the stent is provided with a connection portion  113  along with the polymer portion  520 . The polymer portion  520  and the connection portion  113  connect the struts  110  to each other. 
     The connection portion  113 , which may be embedded in the polymer portion, includes a first connection portion  114  and a second connection portion  115 . The first connection portion  114  is formed integrally with one of the two struts  110  connected to each other, and the second connection portion  115  is formed integrally with the other strut  110 . The first and second connection portions  114  and  115  are formed of the same metal as that of the struts  110 . The first and second connection portions  114  and  115  are configured to form a gap having a substantially S-shape therebetween. The first and second connection portions  114  and  115  may partially make contact with each other. 
     The first connection portion  114  is provided with a first through-hole  116 , and the second connection portion  115  is provided with a second through-hole  117 . The first and second through-holes  116  and  117  penetrate in a thickness direction (in a direction perpendicular to the plane of  FIG. 9 ). 
     The first and second connection portions  114  and  115  are hook-shaped as shown in  FIG. 9  and are caught with each other (axially and laterally overlap one another) when the struts  110  are separated from each other, so that connection between the struts  110  is maintained. For this reason, compared to a case where only the polymer portion  520  is provided, it is possible to more easily maintain a strength of the stent. 
     As illustrated in  FIG. 10 , the polymer portion  520  is formed in a gap between the struts  110  and the first connection portion  114 , in a gap between the first connection portion  114  and the second connection portion  115 , and in a gap between the second connection portion  115  and the struts  110 . The polymer portions  520  formed in these gaps have curved portions  521  that are concave toward the outer side from the inner side of the stent. In addition, the polymer portions  520  are also formed in the first and second through-holes  116  and  117  and also have the curved portions  521 . By virtue of the curved portions  521 , it is possible to obtain the same functional effects as those of the curved portions  121  of the aforementioned embodiment. 
     The surfaces of the first and second connection portions  114  and  115  are covered by the polymer layer  530 . The polymer layer  530  and the polymer portion  520  are formed integrally with each other. The first and second connection portions  114  and  115  are bonded to and supported by the polymer layer  530  and the polymer portion  520 . Therefore, the first and second connection portions  114  and  115  are not easily removed. 
     The detailed description above describes embodiments of a catheter and operational method representing examples of the inventive catheter and operation disclosed here. The invention is not limited, however, to the precise embodiments and variations described. Various changes, modifications and equivalents can be effected by one skilled in the art without departing from the spirit and scope of the invention as defined in the accompanying claims. It is expressly intended that all such changes, modifications and equivalents which fall within the scope of the claims are embraced by the claims.