KR101721485B1 - A stent for medical - Google Patents

Abstract

The present invention relates to a stent comprising a first stent made of a single-length metal wire and having a longitudinal axis and the metal wire being bent in a zigzag shape and cylindrically wound, a monofilament wire having a single length, And a second stent having a structure in which the monofilament wire is bent in a zigzag shape so as to be cylindrically wound, wherein the monofilament wire is connected to the metal wire so that the first stent and the second stent are in contact with each other, Thereby forming a network structure of a double structure in which the circumferential surface is rounded concentrically.

Description

A medical stent {A stent for medical}

The present invention relates to a medical stent, and more particularly, to a medical stent capable of biodegrading after a certain period of time while ensuring self-expandability and initial compression strength.

In general, blood vessels may cause stenosis of blood vessels due to thrombosis or arteriosclerosis, and aneurysms in which a part of blood vessels swell like balloons due to aging or other diseases may occur.

Among these methods for treating stenosis or aneurysm of the blood vessels, a surgical stent is used to minimize the pain given to the patient without surgery in cases where surgical or surgical operation is not possible. Esophagus, bile duct and the like, and is fixed to a stent of a reticular type in the human body to prevent stenosis and occlusion, and is used in medical treatment for securing or expanding the lumen of the human body.

For example, a vascular stent is inserted to prevent restenosis in expanding the vascular stenosis by inserting a balloon forming portion near the distal end of the catheter to expand the passage of the stenosed vessel, and expanding it. Such a stent generally forms a cylindrical structure and has an elastic force, so that it can be contracted by applying an external force, and a self inflating method is widely used when the external force is removed.

Currently, the use of metal stents for the treatment of coronary artery disease has been prominent, but the persistence of metallic stents in the body has been highlighted.

In this regard, PCT / JP2001 / 001983 (IGKI, Cage) relates to a wire stent for a blood vessel stent and a blood vessel stent using the same, wherein a bioabsorbable polymer, poly (L-lactide), is used and its crystallinity is 15 to 60% And a biodegradable stent having a diameter of 0.08 to 0.30 mm is used to solve this problem. However, a Braid stent made of PLLA (Poly-L-lactide) monofilament is used as a peripheral blood vessel stent, but it is not self-expanding, There is a problem of setting the heat with hot water.

International Publication No. WO 2001/67990 (September 20, 2001)

DISCLOSURE Technical Problem The present invention has been conceived to solve the above-mentioned problems, and it is an object of the present invention to provide a network-type dual-structure stent capable of securing self-expandability and biodegradability of a nitinol wire.

Accordingly, it is an object of the present invention to provide a medical stent that can secure initial compression strength and self-expandability, and is biodegraded after a lapse of a certain period of time, thereby reducing irritation to the inner wall of the blood vessel and minimizing damage to the blood vessel caused by the metal structure.

To this end, according to an aspect of the present invention, there is provided a stent comprising: a first stent made of a single-length metal wire and having a longitudinal axis, the metal wire being bent in a zigzag shape and cylindrically wound; And a second stent comprising a polymeric monofilament wire and having a longitudinal axis and bending the monofilament wire in a zigzag shape and cylindrically wound, and connecting the monofilament wire to the metal wire, A medical stent having a dual structure of a stent and a second stent intersecting each other to concentrically round the periphery.

In addition, the metal wire may be a nitride wire, and the monofilament wire may be a PLLA monofilament.

The connection structure of the metal wire of the first stent and the monofilament wire of the second stent may be such that the metal wire and the monofilament wire form a lattice pattern structure with each other.

In addition, in the connection structure, when the metal wire is doubly twisted by the upper and lower metal wires when the metal wire is wound in a cylindrical shape, the monofilament wire is connected between the twisted portions.

Further, in the connection structure, when the metal wire is a single wire, the monofilament wire is connected to the upper or lower side of the single-wire metal wire.

Further, in the connection structure, when the upper monofilament wire is connected to pass over the metal wire, the lower monofilament wire is connected to pass under the metal wire.

The composition ratio of the first stent and the second stent is 1: 2.

According to another aspect of the present invention, there is provided a method of manufacturing a stent, comprising the steps of: forming a first stent made of a single-length metal wire and having a longitudinal axis and bending the metal wire in a zigzag shape so as to be cylindrically wound; And a second step of forming a second stent made of a biodegradable polymeric monofilament wire having a longitudinal axis and bending the monofilament wire in a zigzag shape so as to be cylindrically wound, The monofilament wire is connected to form a network-like double structure in which the first stent and the second stent come into contact with each other to intersect and concentrically round the circumferential surface.

In addition, the metal wire may be a nitride wire, and the monofilament wire may be a PLLA monofilament.

In addition, when the upper monofilament wire is connected to pass over the metal wire, the lower monofilament wire is connected to pass under the metal wire so that the metal wire and the monofilament wire form a lattice pattern structure with each other Step < / RTI >

The method may further include connecting the monofilament wire between the twisted portions when the metal wire is doubly twisted by the upper and lower wire metal wires when the metal wire is wound cylindrically.

When the metal wire is a single wire, the monofilament wire may be connected to the upper or lower side of the single-wire metal wire.

In the first step, the metal wire is heat-treated at 400 ° C or higher, and the biodegradable polymeric monofilament is heat-treated at 100 ° C or lower in the second step.

The method may further include coating a PLGA polymer solution on the second cylindrical stent, and loading the PTX drug in the range of 25 to 35% based on the PLGA polymer solution on the PLGA surface.

The present invention comprises a nitinol wire forming a primary cylindrical stent structure and a biodegradable PLLA monofilament forming a secondary cylindrical stent structure, wherein the mixture of primary metal wire and secondary biodegradable polymer material is used for shrinkage and expansion A possible network-like double structure can be formed.

Thus, it can be more easily implemented in self-expandability and medical procedure than existing PLLA stents. That is, it is possible to self-expand by a small amount of nitinol wire even though it is a stent in which a biodegradable polymer is braided. Moreover, by reducing the amount of metal by half compared with a conventional nitinol stent and adding a biodegradable filament, It is possible to reduce side effects by reducing the amount of the drug.

In addition, due to the affinity between the polymer of the coating solution and the stent strut polymer, coating by dip coating is possible during drug coating, so that drugs such as paclitaxel can be loaded on the surface of the polymer.

FIG. 1 is a perspective view showing the structure of a stent according to a preferred embodiment of the present invention. FIG.
FIG. 2 is a side sectional view schematically showing the structure of a stent according to a preferred embodiment of the present invention,
FIGS. 3-6 schematically illustrate the structure of a stagger wire stent,
FIGS. 7A to 7C illustrate a process of connecting biodegradable PLLA monofilaments with the nitinol wire during the binding of primary and secondary cylindrical stent wires. FIGS.
FIG. 8 is a graph showing the results of G1 (general metal stent), G2 (PLLA / Nitinol stent, no drug coating), G3 (PLLA / Nitinol stent, 50% PTX / PLGA coating), G4 (PLLA / Nitinol stent, 30% PTX / PLGA Coating) of the present invention.

The "wire-shaped stent" in the present invention may mean a stent composed of a plurality of unit wires.

In the present invention, "wire" may mean a strand constituting a stent.

In the present invention, the term "cell" may refer to an empty space portion formed by a wire.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, a stent according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 is a perspective view showing the structure of a stent 100 according to a preferred embodiment of the present invention, and FIG. 2 is a side sectional view schematically showing the structure of a stent 100 according to a preferred embodiment of the present invention.

Referring to FIG. 1, a stent 100 according to a preferred embodiment of the present invention may form a cylindrical stent as a network-like double structure having a diameter of 6 mm and a cross-axis length of 30 mm. Namely, nitinol wire 10 forming a primary cylindrical stent structure and biodegradable PLLA (poly-L-lactide) monofilament 20 forming a secondary cylindrical stent structure, A mixture of the primary metal wire and the secondary biodegradable polymeric material can form a reticulated double structure that can shrink and expand.

Here, the primary cylindrical stent has a mesh-like structure composed of a single-length Naitinol wire and having a cylinder longitudinal axis (transverse axis) and the Naitinol wire being bent in a zigzag shape to be wound in a cylindrical shape. The secondary cylindrical stent also has a network-like structure composed of a biodegradable PLLA monofilament wire of a single length and having a longitudinal axis in a cylindrical shape, and the monofilament wire is bent into a zigzag shape and wound in a cylindrical shape. At this time, the biodegradable PLLA monofilament wire is connected to the nitinol wire 10 so that the first stent and the second stent come into contact with each other to be integrated into a network structure of a double structure in which the circumferential surfaces are rounded concentrically .

2, the stent 100 according to the preferred embodiment of the present invention is constructed such that a nitinol wire 10 having elasticity is subjected to primary braiding with a sparse structure having a cell size of 6 mm And a biodegradable PLLA monofilament 20 having a cell size of 3 mm and a second-order braiding in a size less than half of the cell size of the nitinol wire. At this time, the composition ratio of the stent of the primary metal wire and the secondary biodegradable polymeric monofilament stent is in the range of 30 to 35%: 65 to 70%, preferably 1: 2. This is an optimal ratio of self-expandable by a small amount of nitinol wire even though the biodegradable polymer is a braided stent. Since the amount of metal is reduced by half in the composition ratio of the integral stent, the amount of residual stent in the body is reduced, . ≪ / RTI >

Next, for binding of the two wires of the first NaCl wire and the second PLLA monofilament, the PLLA filament is braided to the already-bound NaCl wire. As a result, as shown in FIG. 1, the primary and secondary wires concentrically round the circumferential surface intersect to form an integral network structure. The structure of the stent is preferably a cylindrical shape in which the circumferential surface of the wire is rounded in a form in which the primary and secondary wires are intersected and contacted. However, the structure of the stent is not limited thereto. May be formed in various shapes so as not to be unstable, which may be advantageous in shrinking and expanding.

When forming the structure of the stent, the circumferential surfaces of the plurality of wires 100 are rounded so that the wires are connected one-to-one (1: 1) or more Of-point contact of a large number of lines or a small area of lines or faces.

Further, the stent is inserted into the blood vessel at the time of the procedure and is brought into close contact with the inner wall, thereby securing the lumen in the human body. The stent thus tightly functions to expand blood vessels to improve blood circulation, so that the stent can be made of a material having predetermined rigidity and elasticity.

At this time, nitinol wire is preferable as the primary metal wire. Nitinol is a type of Ni-Ti alloy, which is an alloy having shape memory. The most commonly used alloy is 55-nitinol, and can be composed of 54 to 56% by weight of Ni and the balance of Ti. It has no magnetism and has a relatively low density of 0.234 lb / in ³ .

Secondly, the biodegradable polymeric substance is a generic name of a polymer which is decomposed by itself in a living body or a natural environment, and PLLA monofilament is preferable. For example, copolymers or homopolymers of lactic acid, glycolic acid; Polymers containing carbohydrate-derived monomers such as glucose derivatives as constituent molecules; Biodegradable hydrogels such as alginic acid; Or natural polymers such as polypeptides, polysaccharides, or polynucleotides. Examples of the biodegradable polymers include polylactide (PLA), polylactide (PLLA), polylactide (PLLA), polyglycolide (PGA), polylactide- Polylactide-co-caprolactone (PCL), polylactide-co-caprolactone (PLL), polydioxanone (PDO) , Polydioxanone, and poly beta -hydroxybutyrate (PHB) may be used alone or in combination of two or more.

As described above, the cylindrical stent according to the present invention has a configuration in which a secondary PLLA monofilament is first applied to a nitinol wire to form a circumferential surface of a wire in a round shape, which is a stent formed only by a conventional nitinol wire The amount of metal can be reduced by half, and biodegradable filaments can be added to secure initial compression strength and self-expandability, and at the same time, biodegradation after a lapse of a certain period of time causes continuous irritation in the inner wall of the blood vessel, Vascular injury can be minimized.

FIGS. 3A to 7 are views illustrating a manufacturing process of a stent according to a preferred embodiment of the present invention.

As described above, the cylindrical stent 100 of the present invention is formed by first forming a nitinol wire cylindrical stent structure, then forming a secondary biodegradable PLLA cylindrical stent structure in the primary cylindrical stent, For binding of cylindrical stent wires, the biodegradable PLLA monofilaments 20 are connected in the form of a nickling wire when braiding the biodegradable PLLA monofilament 20.

First, in the primary cylindrical stent, a nitinol wire having a unit length has a plurality of bending points such as a first reference pin 31 or a second reference pin 32 along a circumferential surface of the jig 30, As shown in FIG. The reference turn will be described in detail with reference to FIG. 3 to FIG. 6 as follows. The reference turn 1 has a plurality of peak portions 1c and a valley portion 1b as shown in Figure 4. The peak portion 1c and the valley portions 1b have straight portions 1a ). ≪ / RTI > The reference turns 1 are arranged at an interval equal to the height h of the reference turn along the length direction of the cylinder without crossing points with each other.

As shown in FIG. 5, the first and second cylindrical stents are arranged in the left-right direction of the reference turn (arranged along the straight portion of the reference turn) And a plurality of connection turns (2) that are wound on a daily basis and connect the plurality of reference turns to each other. The connection turns 2 are arranged at the same interval as the distance d between the reference turn straight portions 1a.

By the reference turns 1 and the connection turns 2 described above, the nitinol wire forms a unit cell as shown in FIG. At this time, the nitinol wire 10 having elasticity can be formed into a unit cell through primary braiding with a sparse structure having a cell size d = 6 mm. Subsequently, the biodegradable PLLA monofilament 20 can be formed into a unit cell through secondary braiding with a cell size of d = 3 mm and a less sparse structure with a size of about half the cell size of the nitinol wire .

In the unit cell of FIG. 3, the connection turns 2 connecting the reference turns 1 arranged in a non-intersecting state to each other while being coiled in a coil form can greatly improve the flexibility of the stent, The turns 2 are wound in a coiled manner on the linear portions 1a of the reference turn overlapped with each other, and thus the expandability is excellent. It is preferable that the number of times the connection turn 2 winds the straight portion 1a of the reference turn is 2 to 10 times.

As shown in FIG. 5, the nitinol wire is rotated one turn along the first reference pin 31 and the second reference pin 32 of the stent-making jig 30 to form one reference turn 1 and the other reference turn 1 is formed in the same manner as described above at a position spaced apart by an interval H equal to the reference turn height h in the downward direction of the jig 10 from the reference turn formed as described above, To form a plurality of reference turns arranged without intersection with each other along the length of the cylinder.

Next, as shown in Figs. 5 and 6, a connecting turn 2 for connecting the rectilinear sections 1a of the reference turn in the left-right oblique direction is formed. At this time, the gap between the connection turns 2 is adjusted to be equal to the reference turn straight line section distance d, and the straight line portion 1a of the reference turn overlapped with the connection turn 2 is wound around the connection turn 2.

When the formation of the connection turn 2 is completed, the nitinol wire is positioned at the first reference pin 31 of the jig 30. At this time, the wires are knotted to complete the thinning operation of the first cylindrical stent.

7A to 7C, a method of connecting the biodegradable PLLA monofilament 20 to the nitinol wire during the braiding of the biodegradable PLLA monofilament 20 for bonding the primary and secondary cylindrical stent wires will be described.

As shown in FIG. 7A, in the connection structure through the braiding of the PLLA monofilament 20, when the nitinol wire 10 is cylindrically wound through the reference pin 33 of the jig, When the wire rope 10 is doubly twisted, the PLLA monofilament wire 20 is connected between the double twisted portions (dotted circles shown in red).

As shown in FIG. 7B, in the connection structure, when the Naitinol wire is a single wire, the PLLA monofilament wire is connected to the upper or lower side of the single-wire Naitinol wire. If the PLLA monofilament wire 20 connecting the reference pin 35 and the reference pin 36 is connected so as to pass over the nitinol wire 10 when the nitinol wire 10 is broken, The PLLA monofilament wire 20 connecting the pin 34 and the reference pin 37 is connected so as to pass underneath the nitinol wire 10 (see the dotted circle shown in red respectively).

7C, when the PLLA monofilament wire 20 on the upper side of the reference pin 39 is connected to pass over the nitinol wire 10, the PLLA monofilament wire of the lower line of the reference pin 38 To pass underneath the nitinol wire 10 (see dotted circle, red, respectively). Thus, the cells of the nitinol wire and the cell of the PLLA monofilament wire formed at the upper and lower lines form a lattice pattern structure at their cross-sections.

Here, the zigzag wire structure of the second cylindrical stent has a pattern similar to that of the first cylindrical stent, and the zigzag wire of the first cylindrical stent or the second cylindrical stent is not limited to the above-described method. That is, a first reference turn forming one end of the cylindrical structure and a second reference turn and a third reference turn successively adjacent to the first reference turn are formed. The straight portions of the first reference turn are the peaks of the second reference turn And the straight portions of the second reference turn are connected to the peaks of the neighboring third reference turns in a twisted manner so that various modifications are possible.

Next, in the heat treatment process, the braided primary Naitinol wire is subjected to a heat treatment process in which the jig 30 is heated in a heating oven at 400 DEG C or higher for 10 to 20 minutes, followed by secondary PLLA monofilament braiding, And slowly cooling the PLLA filament for 30 minutes to 4 hours while heat-treating the PLLA filament at 100 ° C or less. As such, the primary Naitinol wire requires an optimal heat treatment for self expansion, and the biodegradable filament wire needs an optimal heat treatment to prevent melting, and each of them is heat treated to form a network of rounded stent structures .

Thus, comparing the conventional PLLA stent with the PLLA / Nitinol stent according to the present invention, it is as shown in Table 1, and the radial force is improved from 0.8 N to 1.6 N twice, .

Item Conventional (PLLA stent) Invention Specification (diameter × length) 6mm × 30mm 6mm × 30mm material PLLA PLLA + Nitinol (7/3) Expansion type Balloon inflation Self-expansion Radial force
(Radial force) 0.8N 1.6N Practicality Delivery Sheath diameter of 10Frfh is difficult to perform Available in delivery with a diameter of 8 Fr sheath, Nitinol residue

In addition, dip coating can be performed due to the affinity of the coating solution polymer (PLLA, polylactide-co-glicolide) with the stent strut polymer (PLLA) during drug coating, and the surface of the polymer (PLGA) PTX), and the QCA analysis table after 4 weeks or 8 weeks is shown in Table 2 below.

G1 (n = 5) G2 (n = 5) G3 (n = 5) G4 (n = 5) p-value Pre-implantation diamete (mm) 3.68 ± 0.62 4.20 ± 0.38 3.71 + - 0.52 4.10 ± 0.38 0.26 Four weeks MLD (mm) 3.01 ± 0.52 1.97 + 0.81 2.11 + 1.66 4.06 ± 0.39 0.013 Diameter stenosis (%) 19.0 ± 12.7 39.3 ± 18.1 46.8 ± 38.0 4.8 ± 4.2 0.032 8 weeks MLD (mm) 3.03 + - 0.46 1.80 ± 1.08 1.81 + - 1.67 3.39 ± 0.45 0.108 Diameter stenosis (%) 24.6 + 4.8 47.3 ± 29.8 53.6 ± 42.5 14.6 ± 6.3 0.172

Table 2 and FIG. 8 show the results of the GLA (general metal stent), G2 (PLLA / Nitinol stent, no drug coating), G3 (PLLA / Nitinol stent, 50 PTX / PLGA coating), G4 (PLLA / Nitinol stent, / PLGA coating). ≪ / RTI >

Referring to FIG. 8, the PLLA / Nitinol stent G2 according to the present invention is advantageous in that it has an increased radial force than the general metal stent G1.

In addition, the PLLA / Nitinol stent according to the present invention can be dip-coated due to the affinity of the coating solution polymer (PLLA, polylactide-co-glicolide) and the stent strut polymer (PLLA) Drug loading such as paclitaxel (PTX) is possible on the surface. At this time, the luminal diameters of 10-60% PTX drug coating on the weight of the PLGA (polylactide-co-glicolide) material were compared. At this time, 30% PTX drug coating (G4) shows slow releasing and 50% PTX drug coating (G3) shows fast releasing. Therefore, the 30% PTX drug coating (G4) provides good performance in diamete stenosis and recoiling, so the range of PTX drug coatings is preferably in the range of 25-35% in the 5% error range.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. Accordingly, such modifications or variations are intended to fall within the scope of the appended claims.

10: nitinol wire
20: PLLA monofilament wire
30: Jig
31, 32, 33, 34, 35, 36, 37, 38, 39:

Claims (16)

A first stent made of a metal wire of a single length and having a longitudinal axis and the metal wire being bent in a zigzag shape and cylindrically wound,
And a second stent comprising a biodegradable polymer monofilament wire of a single length and having a longitudinal axis and bending the monofilament wire in a zigzag shape to be cylindrically wound,
Connecting the monofilament wire to the metal wire so that the first stent and the second stent come into contact with each other to form a network structure of a double structure in which the circumferential surfaces are rounded concentrically,
The connection structure of the metal wire of the first stent and the monofilament wire of the second stent may be such that when the metal wire is doubly twisted by the upper and lower wire metal wires when the metal wire is wound cylindrically, And the monofilament wire is passed through the upper or lower portion of the single-stranded metal wire so that the upper monofilament wire passes over the metal wire The monofilament wire of the lower line is connected so as to pass under the metal wire so that the cell of the metal wire formed at the upper line and the lower line and the cell of the monofilament wire form a lattice pattern structure at their cross- A medical stent characterized by. The method according to claim 1,
Wherein the metal wire is nitinol. The method according to claim 1,
Wherein the monofilament wire is a PLLA monofilament. The method according to claim 1,
Wherein the composition ratio of the first stent to the second stent is 1: 2. The method according to claim 1,
Wherein the metal wire is heat-treated at a temperature of 400 ° C or more, and the biodegradable polymeric monofilament is heat-treated at 100 ° C or less. The method according to claim 1,
Coating a PLGA polymer solution on the second cylindrical stent, and loading the PTX drug in the range of 25-35% of the PLGA polymer solution on the surface of the PLGA. A first step of forming a first stent of a structure made of a single-length metal wire and having a longitudinal axis and bending the metal wire in a zigzag shape so as to be cylindrically wound;
A second step of forming a second stent made of a biodegradable polymer monofilament wire of a single length and having a longitudinal axis and bending the monofilament wire in a zigzag shape so as to be cylindrically wound;
And a third step of connecting the monofilament wire to the metal wire to form a network-like double structure in which the first stent and the second stent come into contact with each other to intersect and concentrically round the circumferential surface,
In the third step, in the connection structure between the metal wire of the first stent and the monofilament wire of the second stent, when the metal wire is doubly twisted by the upper and lower wire metal wires when the wire is wound cylindrically, Wherein the monofilament wire is passed through the monofilament wire between the twisted portions, and when the metal wire is broken, the monofilament wire is connected to the upper or lower side of the disconnection metal wire, The monofilament wire of the lower line is connected to pass under the metal wire so that the cells of the metal wire formed at the upper line and the line at the lower line and the cells of the monofilament wire form a grid pattern Of the medical stent Article methods. 8. The method of claim 7,
Wherein the metal wire is nitinol. ≪ RTI ID = 0.0 > 15. < / RTI > 8. The method of claim 7,
Wherein the monofilament wire is a PLLA monofilament. 8. The method of claim 7,
Wherein the composition ratio of the first stent to the second stent is 1: 2. 8. The method of claim 7,
Wherein the metal wire is heat-treated at a temperature of 400 ° C or higher in the first step, and the biodegradable polymeric monofilament is heat-treated at a temperature of 100 ° C or lower in the second step. 8. The method of claim 7,
Coating a PLGA polymer solution on the second cylindrical stent, and loading the PTX drug in the range of 25-35% of the PLGA polymer solution on the surface of the PLGA. delete delete delete delete

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