WO2004064911A1

WO2004064911A1 - Stent for percutaneous coronary intervention, coated with vascular restenosis prevention drug

Info

Publication number: WO2004064911A1
Application number: PCT/KR2004/000069
Authority: WO
Inventors: Jeong-Euy Park
Original assignee: Samsung Life Public Welfare Foundation(Samsung Medical Center)
Priority date: 2003-01-18
Filing date: 2004-01-16
Publication date: 2004-08-05
Also published as: KR20040066409A; KR100495875B1

Abstract

A stent for percutaneous coronary intervention, which is coated with a vascular restenosis prevention drug,is provided. The stent includes a plurality of struts. Here, minute wells are formed on the surface of each ofthe struts by scarring a surface of each of the struts, and the entire surface of each of the struts including thewells is coated with a vascular restenosis prevention drug. Since the stent is coated with a vascular restenosis prevention drug and a considerable amount of the vascular restenosis prevention drug is also contained in eachof the drug containing grooves and the drug containing holes, it is possible to provide a brilliant anti-restenosis effect for at least a certain period of time when restenosis is very likely to occur by slowly releasing the vascular restenosis prevention drug into blood vessel wall.

Description

STENT FOR PERCUTANEOUS CORONARY INTERVENTION, COATED WITH VASCULAR RESTENOSIS PREVENTION DRUG

Technical Field

The present invention relates to a stent for percutaneous coronary intervention (PCI), and more particularly, to a stent for PCI, which is coated with a vascular restenosis prevention drug. The stent props open arteries after a PCI procedure has been performed while preventing the arteries from renarrowing due to barotrauma. The stent is formed having minute holes or grooves on its surface and is coated with a vascular restenosis prevention drug. Therefore, once the stent is implanted into an artery, the vascular restenosis prevention drug is slowly released into the artery over several weeks or several months so that the blood vessel can be prevented from reclosing or renarrowing.

Background Art

Percutaneous coronary intervention (PCI) is a procedure that involves inserting a guidewire and a catheter with a deflated balloon into an artery of the wrist or leg of a patient with coronary artery disease, advancing the catheter into a coronary artery with a narrowed part, and inflating the balloon to dilate the narrowed part of the coronary artery.

PCI, which is considered the most effective therapy for some patients with coronary artery disease, is annually performed on more than a million patients in the U.S., a hundred thousand patients in Japan, and fifteen thousand patients in Korea.

PCI may be complete by simply implanting a balloon in the narrowed segment of an artery. However, about 70% of PCI cases involve placing a stent, which is a thin wire mesh made of stainless steel, cobalt-chrome or nitinol in a blood vessel such that the stent holds the blood vessel wide open.

A brief explanation of such a stent-based PCI procedure with reference to FIGS. 1 A through 1 D will be presented in the following paragraphs.

Before implanting a stent in a coronary artery, an affected part of the coronary artery narrowed due to coronary artery plaque, which is formed in the coronary artery protruding inward from the inner surface of the coronary artery, should be widened for easier implantation of the stent, a process which is common in an ordinary PCI procedure. More specifically, a catheter with a balloon is advanced into the narrowed portion of the coronary artery and then the balloon is inflated so that the narrowed portion of the coronary artery is dilated. For easier implantation of the stent, directional coronary atherectomy may be performed on the coronary artery plaque. A too much calcified coronary artery plaque may be removed by rotational atherectomy.

Referring to FIGS. 1 A through 1 D, a catheter 2 and a stent 1 are advanced into a narrowed portion L of a coronary artery CA. The stent 1 is customized according to the length of the narrowed portion L of the coronary artery CA and the diameter of the coronary artery CA. Thereafter, a balloon 2a of the catheter 2 is inflated, and then the stent 1 is plastically deformed by the balloon 2a so that it expands (see FIG. 1 B). Thereafter, the balloon 2a is deflated, and the catheter 2 is removed away from the coronary artery CA such that the stent 1 is left behind in the coronary artery CA holding the coronary artery wide open. Therefore, the stent 1 can prevent the coronary artery CA from renarrowing (see FIG. 1C). However, since the stent 1 is a foreign substance to the human body, tissue cells around the narrowed portion of the coronary artery CA may undesirably proliferate due to barotrauma caused by the stent 1. Then, over-proliferated tissue cells may cover part of the stent 1 in which case, vascular restenosis !_' may occur, as shown in FIG. 1 D. Vascular restenosis is more likely to be associated with a stent having a larger length and a smaller diameter. In addition, vascular restenosis is reported in about 17 - 25 % of stent-based PCI cases. In addition, most vascular restenosis cases are reported within 1 - 3 months after a PCI has been performed. However, vascular restenosis rarely occurs beyond six months after the PCI.

Once vascular restenosis occurs, the effects of PCI are considerably reduced. Thus, a variety of methods for solving vascular restenosis, such as a method of spraying a vascular restenosis prevention drug, such as a heparin-containing drug, onto an affected portion of a coronary artery where vascular restenosis has occurred by using a catheter and a method of placing a radioactive substance, for example, cobalt 60 or iridium 192, inside the balloon or onto a guidewire and then irradiating an affected portion of a coronary artery where vascular restenosis has occurred, have been developed and have been made available to patients with coronary artery disease. Recently, it has been reported that the probability of vascular restenosis occurring after a PCI has been performed can be considerably reduced by performing PCI using a stent coated with a vascular restenosis prevention drug.

In addition, recent clinical test results show that a dilated segment of an artery narrows again in about 5 - 6% of patients who have had such a stent-based PCI procedure in which a stent coated with an anti-cancer drug, such as rapamycin or paclitaxel, is used. More specifically, in about 4% of the patients who have undergone PCI, portions of a blood vessel at the proximal end (P) of a stent renarrow, and in about 2 - 3% of the patients, portions of a blood vessel at the distal end (D) of the stent renarrow. The reason that vascular restenosis seemingly occurs more often at the proximal end (P) of the coronary artery than at the distal end (D) of the stent is that a vascular restenosis prevention drug that the stent is coated with flows in a direction from the proximal end (P) to the distal end (D) of the stent along with blood in the blood vessel so that the concentration of the vascular restenosis prevention drug is slightly higher at the distal end (D) of the stent than at the proximal end (P) of the stent.

Since vascular restenosis is more likely to occur within 1 - 3 months after a PCI has been performed but rarely occurs at least six months after the PCI, patients who have had a PCI procedure are required to pay great attention to whether vascular restenosis occurs for at least five or six months after the PCI procedure. Therefore, it is expected that a stent coated with a vascular restenosis prevention drug will be used in much more PCI cases than now. However, such a drug-coated stent, which has already been adopted in many PCI cases, used to be manufactured rather than customized by simply coating a conventional stent with a polymer material and the vascular restenosis prevention drug. Therefore, it is necessary to design a new stent so that it can contain a larger amount of vascular restenosis prevention drug and keep releasing it very slowly over a long period of time.

A PCI procedure using a stent that is more effectively coated with a vascular restenosis prevention drug would be a less traumatic and result in less expensive treatment for coronary artery disease because it can considerably reduce the probability of vascular restenosis occurring after the PCI procedure has been performed.

Disclosure of the Invention

The present invention provides a stent for percutaneous coronary intervention (PCI), which stably contains a considerable amount of vascular restenosis prevention drug and can continuously release the vascular restenosis prevention drug into a blood vessel wall over a long period of time.

The present invention also provides a stent for PCI, which is designed so that it can be more effectively coated with the vascular restenosis prevention drug, can be smoothly inserted into a blood vessel, can have greater supporting power, and can considerably reduce the probability of vascular restenosis occurring after a PCI procedure has been performed.

According to an aspect of the present invention, there is provided a stent for percutaneous coronary intervention. The stent includes a plurality of struts. Here, minute wells are formed on the surface of each of the struts by scarring a surface of each of the struts, and the entire surface of each of the struts including the wells is coated with a vascular restenosis prevention drug.

According to another aspect of the present invention, there is provided a stent for PCI. The stent includes a first ring structure, a second ring structure, and a bridge. The first ring structure comprises a plurality of struts that are connected to one another in zigzag fashion along a circumference of the stent and round ends that are respectively formed at connections among the plurality of struts to have a diameter larger than a thickness of each of the plurality of struts. The second ring structure comprises a plurality of struts that are connected to one another in zigzag fashion along the circumference of the stent. The bridge connects the first ring structure and the second ring structure, the bridge being formed to have a serpentine link in the middle. Here, the first and second ring structures are alternately arranged along a longitudinal direction of the stent.

Brief Description of the Drawings

FIGS. 1 A through 1 D are schematic cross-sectional views illustrating processes of percutaneous coronary intervention (PCI) using a conventional stent, which are performed on a blood vessel where vascular narrowing occurs; FIG. 2 is a perspective view illustrating a stent for PCI when it is in closed form, according to a first embodiment of the present invention;

FIG. 3 is a diagram illustrating the stent for PCI of FIG. 2 when it is in open form and unfolded;

FIG. 4 is a diagram illustrating the stent for PCI of FIG. 3 when it is in open form and folded;

FIG. 5 is a detailed perspective view illustrating a first ring structure of the stent of FIG. 4; FIGS. 6A and 6B are exploded perspective views illustrating a strut taken along line VI - VI of FIG. 5;

FIGS. 7A and 7B are exploded perspective views illustrating a round end taken along line VII - VII of FIG. 5; FIG. 8A is a diagram illustrating a stent for PCI when it is in open form and unfolded, according to a second embodiment of the present invention; and

FIG. 8B is a diagram illustrating the stent of FIG. 8A when it is in open form and folded.

Best mode for carrying out the Invention

FIG. 2 is a diagram illustrating a closed form of a stent 1 according to a first embodiment of the present invention, which is unfolded, and FIG. 3 is a diagram illustrating an open form of the stent 1 of FIG. 2, which is folded.

Referring to FIGS. 2 and 3, the stent 1 is formed having a predetermined pattern, in which a first ring structure 10 and a second ring structure 20 are alternately arranged in a longitudinal direction of the stent 1. The first ring structure 10 is formed of a plurality of struts 11 , which are connected to one another in zigzag to form a circumference of the stent 1. A round end 12 is formed at each connection among the struts 1 1. A drug containing hole 12a is formed at the round end 12 facing a main axis of the stent 1. A drug containing groove 1 1 a is formed on the surface of each of the struts 11 extending along a longitudinal direction of each of the struts 1 1 (see FIGS. 6A and 6B).

The second ring structure 20 is formed of a plurality of struts 21 , which are connected to one another in zigzag along the circumference of the stent 1 . Accordingly, the second ring structure 20 includes peaks 22 and valleys 23.

A plurality of bridges 30 are formed to connect the first ring structure 10 to the second ring structure 20. More specifically, each of the bridges 30 connects one of the struts 11 of the first ring structure 10 to one of the peaks 22 of the second ring structure 20 so that the first ring structure 10 and the second ring structure 20 can form a single net together. Each of the bridges 30 has a serpentine link 31 , which looks like a letter N, so that it can help the stent 1 to be unfolded or expand along a winding blood vessel with a sufficient length.

FIG. 4 is a diagram illustrating the stent 1 of FIG. 2 or 3, which is yet to be unfolded before being in use. The stent 1 is formed by performing photomasking and etching processes or precise laser cutting processes on a tube so that the struts 11 and 21 can be formed. Here, the tube is formed of stainless steel, such as 316L, or cobalt-chrome. Thereafter, the stent 1 is coated with a medical polymer material in order to make the stent 1 more biocompatible with the human body and hold more restenosis prevention drug. Thereafter, the stent 1 is coated with a vascular restenosis prevention drug.

Recently, anti-cancer agents, such as rapamycin and paclitaxel, have been used to treat patients with vascular restenosis. When the anti-cancer agents are delivered into a blood vessel that is damaged due to PCI, they prevent vascular restenosis by suppressing proliferation of vascular cells around the damaged blood vessel. Anti-inflammation drugs (e.g., dexamethasone), gene treatments, drugs containing a sex hormone, such as estrogen, or drugs that inactivate mettaloproteinase, which is an enzyme closely related to generation of collagenous fiber in a cellular proliferation process, have also been used for the prevention of vascular restenosis. In the present embodiment, the stent 1 is designed so that it can contain as much vascular restenosis prevention drug as possible regardless of the type of the vascular restenosis prevention drug and can very slowly release the vascular restenosis prevention drug over time. Basically, any type of vascular restenosis prevention drug can be used for the stent 1.

FIG. 5 is a detailed perspective view illustrating some of the struts 11 and round ends 12 of the first ring structure 10 of FIG. 3. Referring to FIG. 5, each of the struts 11 is a stick-shaped with a drug containing groove 11a. The drug containing groove 11a is formed to a predetermined depth on a surface of each of the struts 11 , which is supposed to directly contact the wall of a blood vessel. Supposing that a coronary artery has a diameter of 3 mm, each of the struts 11 preferably has a thickness of 0.006 inches (0.16 mm) and a width of 0.006 inches, and the drug containing groove 11a is formed to a depth of 0.002 inches, which accounts for about two thirds of the thickness of each of the struts 11. The drug containing groove 11 a, which is a recessed portion of each of the struts 11 extending along a longitudinal direction of each of the struts 11 , is formed together with the stent 1 by precisely laser-cutting a stainless steel or cobalt-chrome tube.

The diameter of a round end 12, which is formed at each connection among the struts 11 , is larger than the thickness of each of the struts 11. A drug containing hole 12a is formed through the round end 12 at the center of the round end 12. The drug containing hole 12a, like the drug containing groove 11a, is formed together with the stent 1 through a precise laser cutting.

The second ring structure 20 is formed to maintain radial strength of the stent 1 and facilitate adaptive implantation of the stent 1 into a winding blood vessel. The second ring structure 20, unlike the first ring structure 10, is preferably formed of a plurality of struts 21 that are connected to one another in zigzag fashion along the circumference of the stent 1. Unlike the struts 11 of the first ring structure 10, the struts 21 do not have any grooves on their surfaces. However, if the stent 1 is so strong that the second ring structure 20 does not have to help the stent 1 maintain radial strength or if there is a need for the stent 1 to contain a larger amount of drug, the struts 21 of the second ring structure 20, like the struts 11 of the first ring structure 10, may be formed to have a groove on their surfaces extending along its longitudinal direction.

FIGS. 6A and 6B are cross-sectional views illustrating one of the struts 11 of the first ring structure 10 taken along line VI - VI of FIG. 5. More specifically, FIG. 6A illustrates the stent 1 coated with a medical polymer material 13, and FIG. 6B illustrates the stent 1 of FIG. 6A, which is further coated with a vascular restenosis prevention drug 14. A drug containing groove 11a formed on each of the struts 11 of the stent 1 has a very small width not larger than 0.004 inches. Therefore, even if the vascular restenosis prevention drug 14 is as thinly deposited on each of the struts 11 of the first ring structure 10 as possible, the drug containing groove 11a is very likely to be completely filled with the vascular restenosis prevention drug 14. FIGS. 7A and 7B are cross-sectional views illustrating a round end

12 of the first ring structure 10 taken along line VII - VII of FIG. 5. More specifically, FIG. 7A illustrates the stent 1 coated with the medical polymer material 13, and FIG. 7 illustrates the stent 1 of FIG. 7A, which is further coated with the vascular restenosis prevention drug 14. The drug containing hole of each of the round ends 12 of the first ring structure 10 has a very small diameter not larger than 0.01 inches. Therefore, even if the vascular restenosis prevention drug 14 is as thinly deposited on each of the struts 11 of the first ring structure 10 as possible, each of the drug containing holes 12a is very likely to be closed up with the vascular restenosis prevention drug 14.

In the present embodiment, the stent 1 is designed so that the struts 11 of the first ring structure 10 and the struts 21 of the second ring structure 20 are evenly distributed over an affected part of a coronary artery when the stent 1 is implanted into the coronary artery. Therefore, stress can be evenly distributed over the affected part of the coronary artery rather than to be concentrated on a certain part of the wall of the coronary artery.

FIGS. 8A and 8B are diagrams illustrating a stent 1 for PCI, according to a second embodiment of the present invention. More specifically, FIG. 8A illustrates the stent 1 , which is unfolded, and FIG. 8B illustrates the stent 1 , which is yet to be unfolded before being in use. In the first and second embodiments of the present invention, the same reference numerals represent the same elements.

The present embodiment is different from the previous embodiment in that a bridge 30 connects a valley 23 of a second ring structure 20 to a round end 1 1 of a first ring structure 10. In the present embodiment, like in the previous embodiment, the stent 1 is designed so that the struts 1 1 of the first ring structure 10 and the struts 21 of the second ring structure 20 are evenly distributed over an affected part of a coronary artery when the stent 1 is implanted into the coronary artery. Therefore, stress can be evenly distributed over the affected part of the coronary artery rather than to be concentrated on a certain part of the wall of the coronary artery.

In the first and second embodiments of the present invention, the stent 1 may be manufactured in consideration of the thickness and shape of a blood vessel, into which the stent 1 is to be implanted, and the size of an affected area of the blood vessel. For example, the stent 1 may be manufactured to have a diameter of 2.5 mm, 3.0 mm, 3.5 mm, or 4.0 mm and a length of 8 mm, 15 mm, 18 mm, 22 mm, 27 mm or 32 mm.

In addition, in the first and second embodiments of the present invention, the stent 1 begins and ends with an array of round ends 12 of the first ring structure 10 arranged along the outer circumference of the stent 1 in consideration of the fact that vascular restenosis may occur at either end of the stent 1 due to barotraumas. Therefore, it is possible to more effectively prevent vascular restenosis. In addition, vascular restenosis more often occurs at a proximal end P of the stent 1 than at a distal end D of the stent 1. Thus, the drug containing grooves 1 1 a and the drug containing holes 12a formed at the proximal end P of the stent 1 are preferably larger than those at the distal end D of the stent 1 so that they can contain a larger amount of vascular restenosis prevention drug. Supposing that one round end 12 and two struts 1 1 attached thereto constitute one cell C, each first ring structure 10 includes 6 cells, as illustrated in FIGS. 2, 3, and 8A. However, the density of cells of each of the first and second ring structures 10 and 20 may vary. In other words, each of the first ring structures 10 may be manufactured to have 5, 7, or 8 cells. However, given the current level of stent manufacturing technology and the diameter of coronary arteries, each ring structure of a stent with a diameter smaller than 3.0 mm preferably include 6 cells, and each ring structure of a stent with a diameter not smaller than 3.0 mm preferably includes 8 cells.

In the first or second embodiment of the present invention, the stent 1 is coated with a vascular restenosis prevention drug, and a large amount of vascular restenosis prevention drug is also contained in each of the drug containing grooves 1 1 a and the drug containing holes 12a of each of the first ring structures 1 of the stent 1.

Vascular restenosis is most likely to occur at around one month after a PCI procedure has been performed, and the probability of vascular restenosis decreases over time thereafter. Therefore, desired effects of a stent can be obtained when a considerable amount of vascular restenosis prevention drug is injected into a blood vessel for at least two weeks after the PCI procedure so that tissue cells at the walls of the blood vessel can be prevented from quickly proliferating as a repair response to the installation of the stent. Within several weeks or several months after the PCI procedure, there is still a great possibility of the blood vessel renarrowing due to intimal proliferation. Thus, it is preferable to make the stent continuously release the vascular restenosis drug into the blood vessel. The stent 1 of the present invention is coated with a vascular restenosis prevention drug so that a considerable amount of the vascular restenosis prevention drug can be directly injected into a blood vessel directly after a PCI procedure has been performed. If the vascular restenosis prevention drug on the surface of the stent 1 is used up, then a vascular restenosis prevention drug contained in each of the drug containing grooves 11 a and the drug containing holes 12a is slowly released into the blood vessel so that vascular restenosis can be prevented from occurring in the blood vessel for at least several weeks or several months.

Industrial Applicability The stent for a PCI, according to the present invention is coated with a vascular restenosis prevention drug, and thus it can help cure patients with coronary disease by providing a strong anti-restenosis effect for a long period of time. Therefore, the stent can provide a less traumatic and less expensive treatment for coronary artery disease because it considerably reduces the probability of vascular restenosis occurring and does not require additional procedures to be taken to inject the vascular restenosis prevention drug into blood vessels.

In addition, the stent is designed so that struts can be evenly distributed over an affected part of a blood vessel when the stent is implanted into the blood vessel. Therefore, stress is evenly distributed over the affected part of the blood vessel rather than to be concentrated on a certain portion of the wall of the blood vessel. Thus, it is possible to minimize the probability of vascular restenosis occurring due to barotrauma.

Claims

What is claimed is:

1 . A stent for percutaneous coronary intervention, the stent comprising: a plurality of struts, wherein minute wells are formed on the surface of each of the struts by scarring a surface of each of the struts, and the entire surface of each of the struts including the wells is coated with a vascular restenosis prevention drug.

2. The stent of claim 1 further comprising: a first ring structure, which comprises a plurality of struts that are connected to one another in zigzag fashion along a circumference of the stent and round ends that are respectively formed at connections among the plurality of struts to have a diameter larger than a thickness of each of the plurality of struts; a second ring structure, which comprises a plurality of struts that are connected to one another in zigzag fashion along the circumference of the stent; and a bridge, which connects the first ring structure and the second ring structure, the bridge being formed to have a serpentine link in the middle, wherein the first and second ring structures are alternately arranged in a longitudinal direction of the stent.

3. The stent of claim 2, wherein each of the round ends comprises a drug containing hole at its center, and the vascular restenosis prevention drug is contained in the drug containing hole.

4. The stent of claim 3, wherein each of the struts of the first ring structure comprises a drug containing groove, which is formed to a predetermined depth and width on a surface of each of the struts of the first ring structure along a longitudinal direction of each of the struts of the first ring structure, and the vascular restenosis prevention drug is contained in the drug containing groove.

5. The stent of claim 4, wherein the thickness and width of the drug containing groove account for one half to two-thirds of the thickness of each of the struts.

6. The stent of claim 2, wherein the bridge connects one of the round ends of the first ring structure to one of the struts of the second ring structure.

7. The stent of claim 2, wherein a distal end and a proximal end of the stent end with the first ring structure.

8. The stent of claim 4, wherein each of the struts of the second ring structure comprises a drug containing groove, which is formed to a predetermined depth and width on a surface of each of the struts of the second ring structure in a longitudinal direction of each of the struts of the second ring structure, and the vascular restenosis prevention drug is contained in the drug containing groove.

9. A stent for PCI, the stent comprising: a first ring structure, which comprises a plurality of struts that are connected to one another in zigzag fashion along a circumference of the stent and round ends that are respectively formed at connections among the plurality of struts to have a diameter larger than a thickness of each of the plurality of struts; a second ring structure, which comprises a plurality of struts that are connected to one another in zigzag fashion along the circumference of the stent; and a bridge, which connects the first ring structure and the second ring structure, the bridge being formed to have a serpentine link in the middle, wherein the first and second ring structures are alternately arranged along a longitudinal direction of the stent.

10. The stent of claim 9, wherein each of the round ends has a drug containing hole at its center, and the vascular restenosis prevention drug is contained in the drug containing hole.

11. The stent of claim 10, wherein the thickness and width of the drug containing groove account for one half to two thirds of the thickness of each of the struts.

12. The stent of claim 9, wherein the bridge connects one of the round ends of the first ring structure to one of the struts of the second ring structure.

13. The stent of claim 9, wherein a distal end and a proximal end of the stent end with the first ring structure.