Patent Application
20240139003
The present invention relates to a bioresorbable stent and a method for manufacturing the same.
A medical stent is a medical appliance which, when a blood vessel becomes narrower due to various diseases occurring in the human body to cause bad blood circulation, is placed inside the blood vessel to dilate the vessel.
Specifically, the stent is a medical appliance which, when a blood vessel becomes narrower due to various diseases occurring in the human body to cause bad blood circulation, is placed inside the blood vessel to dilate the vessel. There are various stent procedure methods, but the stent is mainly placed by balloon dilatation in which the stent is inserted into blood vessels such as the heart blood vessels, aorta, and cerebral blood vessels together with a balloon catheter, and expands tubular passages as the balloon inflates. Since a conventional stent expands outward along with the inflation of the balloon, it is required to have elasticity and ductility in order to expand to the original size of a vascular passage. That is, a stent is required to have ductility for insertion into a complex and curved passage during a procedure of inserting and fixing a balloon catheter to a target area and then inflating the balloon to dilate a narrowed area. In addition, after the procedure, the conditions such as elasticity for preventing deformation of a stent structure by a contraction force of a blood vessel (such as a heart blood vessel, an aorta, and a cerebral artery) tissue are required.
In addition, materials forming the stent are required to have excellent biochemical properties such as high biocompatibility and stability to the human body and chemical properties such as high corrosion resistance.
As an example, a stent including a diamond-like carbon thin film layer, a surface coating method thereof, and a surface coating device thereof are known in Korean Patent Laid-Open Publication No. 10-2010-0095942. The stent of the patent publication has a silicon-based buffer layer coated on a stent substrate and a diamond carbon thin film layer coated on the buffer layer, and has excellent physical properties of a diamond carbon such as a low friction coefficient and high corrosion resistance being applied.
However, since in the stent of the patent publication, the silicon-based buffer layer is formed between the stent substrate and the diamond carbon thin film layer, the stent has a relatively improved bonding force, but when stress is concentrated on a certain part by constantly applying a force by expansion, contraction, and the like to a stent structure, a problem that a surface coating layer is peeled off or cracks occur may not be avoided. In addition, since the silicon-based buffer layer used for improving a bonding force in the stent of the patent publication does not have better biocompatibility, a problem such as late thrombosis or induction of inflammation may arise after a stent procedure. In addition, since the silicon-based compound causes a change in a thin film layer by a rapid binding reaction with a specific material such as oxygen upon short-term exposure to air, a bonding force to a diamond-like carbon thin film layer is lowered and peeling and crack incidences are increased.
Therefore, a medical stent should have excellent biocompatibility properties as well as excellent physical properties such as friction coefficient, strength, ductility, and elasticity described above, and when stress is concentrated on a certain part by constantly applying force, a problem of surface coating layer peeling off or crack occurrence should be minimized.
An object of the present invention is to provide a bioresorbable stent which has excellent biocompatibility, high imaging resolution in radiography, and a structure showing appropriate physical properties for use in vascular insertion.
In one general aspect, a bioresorbable stent includes: a stent substrate including a bioresorbable polymer; and a contrast medium containing an iodine component, coated on the stent substrate.
In another general aspect, a method for manufacturing a bioresorbable stent includes: coating a contrast medium containing an iodine component on a stent substrate including a bioresorbable polymer.
In still another general aspect, a bioresorbable stent includes: a plurality of rings which are arranged to be spaced apart at a predetermined interval in the axial direction; and at least one bridge which is arranged between adjacent two rings of the plurality of rings and connects the adjacent two rings, wherein in each of the plurality of rings, a wave-shaped unit structure including a protrusion and a depression is arranged in a repeating manner along the circumferential direction, the unit structure includes the protrusion and the depression asymmetrically, and the bridge has a curvature.
The present invention relates to a bioresorbable stent including a stent substrate including a bioresorbable polymer and a contrast medium containing an iodine component, coated on the stent substrate. Since the stent according to the present invention is absorbed in and removed from the human body after a predetermined time, it has excellent biodegradability, since it has improved radiopacity by iodine contrast medium coating, it has a high radiography contrast and is very efficient even when a procedure is performed with real-time radiography, and since it has low foreshortening and high flexibility, radial force, and re-coil, it may be useful for insertion into a blood vessel having a small diameter, an acute occlusive lesion, an imminent occlusive lesion, and the like.
Hereinafter, the present invention will be described in detail.
Meanwhile, the exemplary embodiments of the present invention may be modified in many different forms and the scope of the invention is not be limited to the exemplary embodiments set forth herein. In addition, the exemplary embodiments of the present invention are provided in order to explain the present invention more completely to those with ordinary skill in the art. Furthermore, throughout the specification, unless explicitly described to the contrary, “comprising” any constituent elements will be understood to imply further inclusion of other constituent elements rather than exclusion of other constituent elements.
An aspect of the present invention provides a bioresorbable stent (BRS) including:
The bioresorbable polymer may be polylactic acid, polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, polypeptide, polyorthoester-based, polymaleic acid, polyphosphagen, polyanhydride, polysebacic anhydride, polyhydroxyalkanoate, polyhydroxybutylate, or polycyanoacrylate. When a stent manufactured using poly-L-lactic acid (PLLA) which is the bioresorbable polymer by an exemplary embodiment of the present invention is inserted into the human body, the stent was confirmed to be absorbed well and removed from the human body.
The contrast medium containing an iodine component may increase radiopacity, and the contrast medium containing an iodine component may be, for example, a contrast medium selected from the group consisting of Iopromide, Iopamidol, Iohexol, Iodixanol, Amidtrizoic acid, Iokisagulic acid, Ioxylan, Iotalamic acid, Isotroxylic acid meglumine, Iotrolan, Iopanoic acid, Iomeprol, sodium iofordate, Iodamide, iodochisamic acid, and combinations thereof. It is preferred that the contrast medium containing an iodine component is coated on the stent substrate by an electrospinning technique.
Another aspect of the present invention provides a method for manufacturing a bioresorbable stent including:
It is preferred that the coating is performed by a method including electrospinning a contrast medium.
Regarding the contrast medium containing a bioresorbable polymer and an iodine component, the above detailed description may be identically applied.
Hereinafter, the bioresorbable stent according to the present invention will be described in detail, referring to what is shown in the drawings.
The bioresorbable stent 1 according to an exemplary embodiment of the present invention includes:
Herein, the ring 10 is a strut.
More specifically, the ring 10 is most preferably formed of 4 to 8 cells or 6 cells, in which the cell refers to a wave-shaped unit structure including a protrusion 200 and a depression 100. When a ring positioned on one side of each of the bridges is referred to as a first ring and a ring positioned on the other side is referred to as a second ring, one side of each of the bridges is connected to the depression of the first ring and the other side is connected to the protrusion of the second ring, but the one side of each of the bridges may be connected to a position eccentric to one side from the center of the depression of the first ring in the depression of the first ring and the other side may be connected to a position eccentric to the other side from the center of the depression of the second ring in the depression of the second ring. That is, the ring 10 may have an open cell structure connected to three bridges 20. The stent according to an exemplary embodiment of the present invention has an open cell structure, thereby having significantly improved flexibility. In addition, a re-coil change after balloon inflation may be minimized by the bridge. Herein, the center refers to the most depressed portion in the depression and the most protruding portion in the protrusion. The number of rings may be 14 to 18, preferably 16, and there is no phase difference between each ring.
A spacing between the ring 10 and another ring adjacent thereto, that is, a straight distance may be 1.00 mm to 1.3 mm, and a stent substrate having a straight distance of 1.15 mm was manufactured by an exemplary embodiment.
It is preferred that the bridge 20 is manufactured to increase an amount of the bioresorbable polymer by a shape having a curvature, and a bridge having two curvatures was manufactured by an exemplary embodiment. In addition, it is preferred that the bridges intersect.
The stent substrate may have a diameter of about 2.2 mm to 2.8 mm or 2.4 mm to 2.6 mm, preferably 2.503 mm. The strut may have a thickness of about 0.09 mm to 0.13 mm or 0.10 mm to 0.12 mm, preferably 0.11 mm. The strut may have a width of about 0.10 mm to 0.20 mm or 0.13 mm to 0.17 mm, preferably 0.15 mm. The strut may have a surface area of about 30 mm2 to 50 mm2 or 35 mm2 to 40 mm2, preferably 37.325 mm2.
Since the stent provided in one aspect of the present invention is a bioresorbable stent including a bioresorbable polymer, unlike a conventional metal stent, the material physical properties and the components are different from those of the metal stent. Therefore, a stent design (structure) is very important. Therefore, the stent according to an exemplary embodiment of the present invention may include a spiral cell structure which is effective for a crimping process of the balloon catheter and the bioresorbable stent, and may have an optimized open cell structure when applied to an irregular and tortuous blood vessel. In addition, a bridge having a curvature for minimizing re-coil after balloon inflation is included. Herein, the bridge is connected to an eccentric position in the center of the protrusion and the depression, thereby more effectively minimizing the re-coil change. Therefore, since the stent according to an exemplary embodiment of the present invention has the above structure, it has low foreshortening and high flexibility and radial force, and thus, may be useful for insertion into a blood vessel having a small diameter, acute occlusive lesion, imminent occlusive lesion, and the like. In addition, since radiolucency is increased by coating the contrast medium including iodine on the stent, the stent has high radiography contrast even when a procedure is performed with real-time radiography, and thus, is very efficient.
Step 1: Manufacture of Bioresorbable Stent Substrate
For manufacturing a bioresorbable stent (BRS), a femtosecond laser was used to manufacture a stent shape including poly-L lactic acid (MatWeb— Zeus Absory PLLA bioabsorbable polymer) which is a bioresorbable polymer.
The bioresorbable stent substrate 1 according to an exemplary embodiment of the present invention basically included: a plurality of rings 10 which were arranged to be spaced apart at a predetermined interval in the axial direction; and at least one bridge 20 which was arranged between adjacent two rings of the plurality of rings and connects the adjacent two rings. Each of the plurality of rings had a wave-shaped unit structure including a protrusion 200 and a depression 100 which was arranged in a repeating manner along the circumferential direction (
Step 2: Iodine-Containing Contrast Medium Coating
In order to coat the iodine-containing contrast medium on the bioresorbable stent substrate manufactured in step 1, a vascular contrast medium used in clinical practice (Omnihexol) was filled into a hamilton syringe and coated on the stent substrate manufactured in step 1 using an electrospray system. The coating proceeded at a distance of 60 cm and an angle of 30° under the conditions of a voltage of 10 V and a rotation speed of 50 rpm while a jig moved to the x-axis at a speed of 500 mm/min and a syringe pump was sprayed at 60 μm/min.
With the finite-element analysis of the bioresorbable stent substrate manufactured in step 1 of Example 1, radial force, foreshortening, crush resistance, and flexibility were tested as follows. As a comparative example, a commonly used, commercialized stent was reversely designed and used. The stent used as the comparative example had a form in which a bridge was positioned parallel to the x-axis in a 6-cell and 16-ring structure, and had a strut width of 0.15 mm, an inner radius of 0.20 mm, an outer radius of 0.35 mm, a ring width of 0.85 mm, a spacing between rings of 0.3 mm, and a surface area of 36.8924 mm2 (
1-1. Radial Force
In order to analyze radial force of the example and the comparative example (
1-2. Foreshortening
For foreshortening analysis of the example and the comparative example, change in length when each stent was developed to the state attached to the catheter and the indicated value was measured. Specifically, the change in length when the diameter of each stent was 1.5 mm and 3 mm was measured and the results are shown in
Foreshortening (%)=[{(length before contraction)−(length after contraction)}/(length before contraction)]×100
1-3. Crush Resistance
For crush resistance analysis of the example and the comparative example (
As a result of analysis, the stent according to the example showed higher crush resistance than the commercially available comparative stent through the stent substrate structure, and thus, it was confirmed to be more appropriate for use as a stent.
1-4. Flexibility
For flexibility analysis of the example and the comparative example (
As a result, the maximum stress value of the comparative example was 0.0079628 MPa, and the maximum stress value of the example was 0.0076613 MPa. Therefore, since the stent having the structure of the stent substrate according to the example may be bent with less force, it has excellent flexibility and thus, is useful for curved blood vessels and allows a convenient procedure.
As a result of predicting the physical property values of the stent structure manufactured in the example by the finite-element analysis, the stent of the example was confirmed to be appropriate for use as a medical stent and the like. Thus, it was confirmed that the real stent of the example showed excellent physical properties by the mechanical test of the following Experimental Example 2.
With the mechanical test the bioresorbable stent substrate manufactured in step 1 of Example 1, radial force, foreshortening, flexibility, and re-coil were tested as follows.
2-1. Radial Force
It has been reported that when a stent is inserted into a blood vessel having a small diameter, a chronic total occlusion (CTO), an aorta ostial lesion, a calcified lesion, and the like, a stent having a high radial force is appropriate. The radial force may be confirmed by measuring a force applied to a blood vessel in the state in which the stent is developed during expansion and compression. The radial forces of the example and the comparative example were measured as in
As a result, as confirmed in
2-2. Foreshortening
The foreshortening may be confirmed by measuring a change in length when the stent is developed to the state of being mounted on the catheter and the indicated value. In order to use the stent as a stent for cardiovascular system, a stent having no change in foreshortening before and after expansion when the stent was developed to the state of being mounted on a balloon catheter and the indicated value is appropriate. The foreshortenings of the example and the comparative example were measured as in
As a result, as confirmed in
2-3. Flexibility
It is appropriate to use a stent having excellent flexibility in a blood vessel having a small diameter of 3 mm or less, acute occlusive and imminent occlusive lesions, proximal tortuosity, and an acute angulation lesion at 45° or more. Bending/twisting/flexibility of the stent may be confirmed by determining a minimum radius at which the developed stent is bendable without twisting or a decrease in radius of more than 50% and seeing whether its original shape is restored after the test. The flexibilities of the example and the comparative example were measured as in
As a result, as confirmed in
2-4. Re-Coil
The re-coil of the stent may be confirmed by determining the amount of re-coil after developing a balloon expansion stent in the state in which there is no internal load in order to determine a stent diameter in a developed state. A stent having no change in re-coil before and after expansion when it is developed to the state of being mounted on a balloon catheter and the indicated value is appropriate for use as a cardiovascular stent and the like. The results of confirming the re-coils of the stents of the example and the comparative example are shown in
As a result, a change in re-coil of the comparative example was smaller than that of the example, but since the stent of the example met the FDA standards (within 15%), it was confirmed to have no problem in clinical use.
Elemental analysis (EDX, Energy-Dispersive X-ray spectroscopy) and surface scanning electron microscope (SEM) analysis were performed before and after coating the contrast medium containing iodine according to step 2 of the example and the results are shown in the following Table 4 and
X-ray analysis (BV PULSERA, PHILIPS) was performed for radiolucency analysis of a bioresorbable stent before contrast medium coating (BRS) manufactured in step 1 of the example, a bioresorbable stent after contrast medium coating (with CM-BRS) manufactured in step 2, a commercialized stent (Absorb), and a metal stent (BMS). The results are shown in
As a result, since the metal BMS was formed of metal, its radiopacity was high and the metal BMS was clearly shown in the X-ray image. Since Absorb was formed of a polymer and had a metal marker made of Pt—Cr at both ends, the polymer was all radiolucent and was not shown in the X-ray and only Pt—Cr at both ends was shown. Since BRS is made of a polymer, it was radiolucent and was not shown in the X-ray image. With CM-BRS was clearly shown in the X-ray image. Thus, it was confirmed that by coating the contrast medium on the bioresorbable stent, the radiopacity was improved to improve radiography contrast.
Hereinabove, though the present invention has been described in detail by the preferred examples and experimental examples, the scope of the present invention is not limited to specific examples, and should be construed by the appended claims. In addition, it should be understood by a person skilled in the art that many modifications and variations are possible without departing from the scope of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2021-0062206 | May 2021 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2022/006929 | 5/13/2022 | WO |
