KR101455162B1 - Dual coating stent - Google Patents

Abstract

The present invention relates to a body formed in a tubular form by a plurality of struts connected in zigzags; An outer coating layer coated on an outer surface of the body and containing a drug; And an inner coating layer coated on the inner surface of the body, wherein the body is configured to maintain the diameter of the blood flow path and to increase the fluidity of the blood flow due to movement of the blood vessel, Coated stent. ≪ RTI ID = 0.0 > A < / RTI >

Description

Dual coated stent {DUAL COATING STENT}

The present invention relates to dual coated stents.

Many blood vessels circulating the blood through the main tissues of the human body are excessively produced by factors such as fat, cholesterol, etc., resulting in narrowing of the blood vessel passage or clogging of blood vessels (Angiostenosis). Vascular stenosis may be somewhat different depending on the location of the lesion, but life may be lost if it occurs in the blood vessels connected to the main organs. In order to solve such serious problems, medication, open surgery, and stenting are suggested as methods for treating vascular stenosis. Among these, stenting is the most popular treatment method for vascular stenosis due to its high treatment efficiency and simple procedure.

Such stenting has many advantages over other methods of treatment, however, there is a problem in that vascular restenosis occurs due to an abnormal proliferation of a stent-treated vascular endothelial cell and a fatal problem of rapid thrombosis. In order to solve this problem, the drug-releasing stent which suppresses the abnormal proliferation of vascular endothelial cells by coating the drug on the surface of the stent which is in contact with the inner wall of the blood vessel has been developed to lower the vessel restenosis rate. Therefore, there is a need for a method of more effectively inhibiting abnormal proliferation of vascular endothelial cells and a method of preventing thrombogenesis due to contact with blood in order to lower the vascular restenosis rate.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a dual coated stent for coating the inside and the outside of a stent, respectively.

A dual-coated stent according to one embodiment of the present invention for realizing the above-mentioned problems includes a body formed into a tubular shape by a plurality of struts connected by a zigzag; An outer coating layer coated on an outer surface of the body and containing a drug; And an inner coating layer coated on the inner surface of the body, wherein the body is configured to maintain the diameter of the blood flow path and to increase the fluidity of the blood flow due to movement of the blood vessel, As shown in Fig.

Wherein the outer coating layer is coated on an outer surface of the body and includes a base coating layer containing an adhesive component; And a drug coating layer coated on the base coating layer and containing the drug as an immunosuppressant.

The drug coating layer may comprise a polymer that contains the immunosuppressant and is formed to modulate the release of the immunosuppressant.

The polymer may comprise an anti-inflammatory component.

The adhesive component may comprise a dimer acid.

The adhesive component may comprise paralin.

Wherein said immunosuppressive agent is selected from the group consisting of rapamycin, cyclophosphamide, nitrogene mustard, 6-mercaptopurine, azathiopurine, cytosine arabinoside, mitomycin C, actinomycin D, corticosteroid steroids, , Anti-lymphocyte serum, paclitaxel, and sirolimus.

The inner coating layer may include an undercoat layer coated on the inner surface of the body and containing a biocompatible polymer.

The inner coating layer may further include an active coating layer coated on the undercoat layer and containing a vascular endothelial active ingredient.

The biocompatible polymer may be at least one selected from the group consisting of ferialin, polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polylactide copolymer, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride , Polyamino acid, cellulose acetate butyrate, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, and polyvinylpyrrolidone, heparin, warfarin, coumadin, dextran sulfate, and decalcium At least one selected material.

The vascular endothelial active ingredient may be selected from the group consisting of VE-cadherin, N-cadherin (A-CAM), R cadherin, E cadherin (Ubomorulin), P cadherin, B cadherin Consisting of EP cadherin, caderin 5-6, caderin 8-11, M caderine, T cadherin, desmograin 1-3, desmokolin 1-3, FAT, PC42, PC43, and C-RET And at least one material selected from the group.

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According to the dual coated stent of the present invention constructed as described above, it is possible to effectively suppress the abnormal proliferation of vascular endothelial cells and prevent the formation of thrombus by dual coating the inside and the outside of the stent

1 is a conceptual diagram illustrating a main configuration of a dual-coated stent 10 according to an embodiment of the present invention.
FIG. 2 is a cross-sectional view illustrating a blood vessel into which a dual-coated stent 10 according to an embodiment of the present invention is inserted.
FIG. 3 is a cross-sectional view illustrating a structure in which a dual-coated stent 30 according to an embodiment of the present invention is inserted into a blood vessel and affects vascular endothelial cell 39 cells.

Hereinafter, a dual coated stent according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings. In the present specification, different embodiments are given the same or similar reference numerals, and the description thereof is replaced with the first explanation.

1 is a conceptual diagram illustrating a main configuration of a dual-coated stent 10 according to an embodiment of the present invention. FIG. 2 is a cross-sectional view illustrating a blood vessel into which a dual-coated stent 10 according to an embodiment of the present invention is inserted.

Referring to FIGS. 1 and 2, the stent 10 may include a body 11, an outer coating layer 13, and an inner coating layer 15.

The body 11 may be formed in a tube shape by a plurality of Struts (not shown in FIGS. 3 and 35) connected in zigzags. The tubular body 11 is supported in contact with the inner vessel wall 17 through a continuous strut to the outside and a cylindrical hollow portion is formed on the inner side so that blood can be circulated through the hollow portion.

The outer coating layer 13 is a coating layer containing a drug formed on the outer surface of the body 11 and includes a base coating layer 13a containing an adhesive component and a drug coating layer 13b containing an immunosuppressive drug The respective coating layers included in the outer coating layer 13 on the basis of the body 11 are formed in the order of the body 11, the base coating layer 13a, and the drug coating layer 13b As shown in FIG.

The base coating layer 13a is a layer for initially coating the upper surface of the outer surface of the body 11 and includes an adhesive component so as to increase the bonding force so that the outer surface of the body 11 and the drug coating layer 13b are well adhered to each other. have. The adhesive component for increasing the bonding force may be varied depending on the experiment and the process conditions, but parylene is preferred in the present invention.

Paralin is made from Dimer Acid, which is used as a surface coating agent and adhesive, and is approved by US military standard and FDA, and it is tested by biological evaluation method specified by ISO. It has insulation, corrosion resistance, chemical resistance, It is a biocompatible polymer that has been recognized for its properties such as gender, human immunity, non-toxicity, anticoagulant, and immuno-rejection.

Therefore, when parallain is included in the adhesive component of the base coat layer 13a, besides increasing the bonding force between the outer surface of the body 11 and the drug coat layer 13b, it can have a positive effect such as corrosion prevention.

The drug coating layer 13b is formed on the base coating layer 13a, and therefore, the drug coating layer 13b can be located at the top of the outer coating layer 13. As the outer coating layer 13 is on the outer surface of the body 11 and is positioned at the uppermost position in the outer coating layer 13, the drug coating layer can directly contact the inner wall 17 of the blood vessel. Accordingly, the drug coating layer 13b may include an immunosuppressant, which is a drug for preventing abnormal proliferation of vascular endothelial cells of the inner wall 17 of the blood vessel.

One of the major reasons that the stenosed blood vessel is forcibly expanded by the stent 10 is the abnormal growth of the vascular endothelial cell in the blood vessel inner wall 17 in contact with the stent 10. The abnormal proliferation of vascular endothelial cells occurs when the inner wall 17 is damaged due to contact with the stent 10 due to excessive proliferation of vascular endothelial cells to be healed, Lt; / RTI > Therefore, it is necessary to control the activation of vascular endothelial cells within a certain range in order to heal damage to the inner wall 17 of the blood vessel. For this reason, an immunosuppressant that inhibits abnormal proliferation of vascular endothelial cells may be included in the drug coating layer 13b.

An immunosuppressant is an agent having an immunosuppressive component for inhibiting the activation of vascular endothelial cells, and includes rapamycin, cyclophosphamide, nitrogene mustard, 6-mercaptopurine (6- (Cytosine Arabinoside), Mitomycin C, Actinomycin D, Adrenal Cortical Steroid, an empty alkaloid agent, an anti-lymphocyte Serum (Antilymphocyte Serum), paclitaxel (paclitaxel), and sirolimus. In the present invention, rapamycin having excellent immunosuppressive effect is preferably used.

When applied to the immunosuppressants of the present invention as an FDA-approved antifungal agent and an immunosuppressant, the rapamycin can prevent abnormal proliferation by inhibiting the immune response in contact with vascular endothelial cells. In addition, due to the nature of rapamycin, it is possible to remove the agenesis agent progenin present in the cell phase, thereby preventing aging of cells.

If such an immunosuppressant is released to the blood vessel inner wall 17 at one time, a side effect may be caused thereby, so that a component capable of controlling the immunosuppressant may be required. Thus, the drug coating layer 13b may comprise a polymer to control the release of the immunosuppressant. The polymer allows the immunosuppressant to slowly release and does not stimulate vascular endothelial cells as a biodegradable component. Furthermore, the polymer can be made to contain an anti-inflammatory component, so that it can play a direct or indirect role in preventing abnormal proliferation of vascular endothelial cells together with immunosuppressants.

The structure and the structure of the outer coating layer 13 formed on the outer surface of the body 11 have been described and the inner coating layer 15 formed on the inner surface of the body 11 will now be described .

The inner coating layer 15 is coated on the inner surface of the body 11 and further includes an undercoat layer 15a containing a biocompatible polymer and an active coating layer 15b containing a vascular endothelial active component . The inner coating layer 15 may be formed in the order of the body 11, the undercoat layer 15a, and the active coating layer 15b with reference to the inner surface of the body 11. [

The inner surface of the body 11 is formed in the direction of the central axis of the blood vessel and can be in contact with the blood circulating through the blood vessel. Therefore, a thrombus may be generated due to a clotting reaction due to contact with blood. To prevent this, an undercoat layer 15a formed on the inner surface of the body 11 may include a biocompatible polymer.

The biocompatible polymer may be selected from the group consisting of ferrolein, polyvinyl alcohol, polyethylene glycol, polylactic acid, and polylactic acid, which have anticoagulant, cell fusion, Polyglycolide (PGA), polylactide copolymer (PLGA), polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazenes, Polyanhydrides, polyamino acids, cellulose acetate butyrates, cellulose triacetates, polyacrylates, polyacrylamides, polyurethanes, polyacrylates, Polyvinylpyrrolidone, polyurethane, polysiloxane, and polyvinyl pyrrolidone, heparin, warfarin, coumadin, dextran, Sulfuric acid (Dexrean Sulfate), and decalcifying agent may be applied. In the present invention, it is preferable to apply ferulic acid having effects such as anti-clotting properties, corrosion resistance and chemical resistance.

When ferrule is applied as a biocompatible polymer, corrosion of the inner surface of the body 11 can be prevented in the same manner as the base coating layer 13a, and the formation of thrombus can be reduced or prevented by suppressing the coagulation reaction . Since the undercoat layer 15a is formed on the inner surface of the body 11, the stent 10 of the present invention can suppress the abnormal proliferation of vascular endothelial cells as well as the clotting reaction with blood.

In addition, the inner coating layer 15 may further be used to block abnormal proliferation of vascular endothelial cells. For this purpose, an active coating layer 15b containing a vascular endothelial active ingredient may be formed on the undercoat layer 15a. As described above, abnormal proliferation of vascular endothelial cells may be a cause of vascular restenosis, and abnormal proliferation can be suppressed through the drug coating layer 13b. In addition, the vascular endothelial active component may be included in the active coating layer 15b so that the vascular endothelial cell proliferation can be normally performed within a short period of time.

Proliferation of vascular endothelial cells occurs during the process of healing against certain damage of the intravascular lining 17. However, unilateral inhibition of cell proliferation in order to prevent abnormal proliferation of vascular endothelial cells may cause side effects such as inflammation because the damaged area is not healed. The best way to overcome this problem and inhibit the abnormal proliferation of vascular endothelial cells is to heal the damaged inner wall 17 in a short time through normal vascular endothelial cell proliferation.

Thus, the inner coating layer 15, that is, the active coating layer 15b, may contain a vascular endothelial active ingredient capable of promoting normal vascular endothelial cell proliferation. The vascular endothelial active component may be selected from the group consisting of VE-cadherin, N-cadherin (A-CAM), R-cadherin, E-cadherin (Ubamorulin), P cadherin, B cadherin (K CAM), L-CAM, EP caderin, caderin 5-6, caderin 8-11, M caderin, T cadherin, desmograin 1-3, 1 to 3, FAT, PC42, PC43, and C-RET. In the present invention, it is preferable to apply VE-caderin which has an effect of not only proliferating cells but also maintaining proliferated cells.

When VE-cadherin is applied as a vascular endothelial active component, the inner coating layer 15 can prevent the formation of thrombus through the undercoat layer 15a and allow normal proliferation of vascular endothelial cells through the active coating layer 15b Can help.

The effect of the vascular endothelial cell normally growing by the stent 10 having the above-described configuration and the effect of changing the thickness of the stent 10 in a certain region will be described in detail with reference to FIG.

FIG. 3 is a cross-sectional view illustrating a structure in which a dual-coated stent 30 according to an embodiment of the present invention is inserted into a blood vessel and affects vascular endothelial cell 39 cells.

Referring to the drawings, the stent 30 of the present invention, in which an outer coating layer and an inner coating layer are formed on an outer surface and an inner surface of a body, may be inserted into a blood vessel.

The stent 30 may be formed such that the thickness of a predetermined strut 35 formed at one end portion of the body, that is, one end portion and the other end portion of the body, is relatively thicker than the thickness of the strut 35 located in the central region . Accordingly, the stent 30 and the outlet side thereof are made thicker at both end regions, so that the rigidity and the supporting force of the stent 30 can be increased, and as a result, the fixing force of the entire stent 30 can be increased. In addition, since the central region maintains the existing thickness and is formed relatively thin compared to the both end regions, the central region can have flexibility corresponding to movement of the blood vessel according to the movement of the body.

2 and 13A) and a drug coating layer (shown in FIGS. 2 and 3) on the outer surface of the body 31 in the direction of the blood vessel inner wall 37, as shown in the enlarged view of the inner wall 37 and the stent 30, 13b or less) on the outer surface of the outer coating layer 31 in this order. Accordingly, the base coating layer can increase the binding force between the drug coating layer and the body 31 through ferulic acid while preventing the corrosion of the body 31. The drug coating layer can prevent the contact between the vascular endothelial cells 39 Can be suppressed.

In addition, the inner surface of the body 31 in the direction of the central axis of the blood vessel can form an inner coating layer 33 including an undercoat layer (not shown in FIGS. 2 and 15a) and an active coating layer (not shown in FIGS. 2 and 15b) . Therefore, the undercoat layer prevents corrosion of the inner surface of the body 31 through the biocompatible polymer and inhibits the coagulation reaction to prevent the formation of thrombus. In addition, it is possible to support the normal proliferation of vascular endothelial (39) cells through the vascular endothelial active component of the active coating layer.

When the vascular endothelial cell (39) cell activity is performed to damage the inner wall (37) of the blood vessel and the vascular endothelial cell (39) is not normally inhibited, the vascular endothelial cell (39) is excessively proliferated toward the blood vessel central axis to induce vascular restenosis . However, by forming a coating layer including the immunosuppressive agent and the vascular endothelial active component on the inside and the outside of the body, as in the stent 30 shown in the drawing, it is possible to control the proliferation of the vascular endothelium 39, The proliferation of the vascular endothelium 39 can be rapidly performed.

Such a dual coated stent is not limited to the construction and operation of the embodiments described above. The above embodiments may be configured so that all or some of the embodiments may be selectively combined so that various modifications can be made.

10, 30: stent
11, 31: Body
13, 32: outer coating layer
13a: base coating layer
13b: drug coating layer
15, 33: Inner coating layer
15a: undercoat layer
15b: active coating layer
17, 37: inner vessel wall

Claims (12)

A body formed into a tubular shape by a plurality of struts connected in zigzag;
An outer coating layer coated on an outer surface of the body and containing a drug; And
And an inner coating layer coated on the inner surface of the body,
Wherein the body is formed such that the thickness of the both end regions is relatively thicker than the thickness of the central region in order to maintain the diameter of the blood flow path and to maximize fluidity according to the motion of the blood vessel.
The method according to claim 1,
The outer coating layer
A base coating layer coated on an outer surface of the body and containing an adhesive component; And
And a drug coating layer coated on the base coating layer and containing the drug as an immunosuppressant.
3. The method of claim 2,
Wherein the drug coating layer comprises:
A polymer comprising said immunosuppressant and being formed to modulate release of said immunosuppressant.
The method of claim 3,
Preferably,
A dual-coated stent comprising an anti-inflammatory component.
3. The method of claim 2,
The adhesive component may comprise,
A dual coated stent, including dimer acid.
6. The method of claim 5,
The adhesive component may comprise,
Dual coated stent, including paralin.
3. The method of claim 2,
The anti-
But are not limited to, rapamycin, cyclophosphamide, nitrogene mustard, 6-mercaptopurine, azathiopurine, cytosine arabinoside, mitomycin C, actinomycin D, corticosteroid steroids, At least one substance selected from the group consisting of paclitaxel, paclitaxel, and sirolimus.
The method according to claim 1,
The inner coating layer
And an undercoat layer coated on an inner surface of the body and containing a biocompatible polymer.
9. The method of claim 8,
The inner coating layer
Further comprising an active coating layer coated on the undercoat layer and containing a vascular endothelial active component.
9. The method of claim 8,
The biocompatible polymer may be,
Polyvinyl alcohol, polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polylactide copolymer, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, polyamino acid, cellulose acetate At least one substance selected from the group consisting of butyrate, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, and polyvinylpyrrolidone, heparin, warfarin, coumadin, dextran sulfate, Includes a dual coated stent.
10. The method of claim 9,
The vascular endothelial active ingredient may be,
(CAM), L-CAM, EP cadherin, caderin 5 (cadherin), cadherin (cadmium) At least one substance selected from the group consisting of C-6, cadherin 8-11, M cadherin, T cadherin, desmoglene 1-3, desmocholine 1-3, FAT, PC42, PC43, and C- Gt; coated stent. ≪ / RTI >
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