KR101649305B1 - Medical stent and method of manufacturing irregularities are formed on the surface - Google Patents

Abstract

The present invention provides a medical stent having surface irregularities and a method of manufacturing the same, comprising: anodizing a tubular metal stent to form a metal oxide film on the surface; Removing the metal oxide film from the stent to form irregularities on the surface of the stent; Forming a porous thin film on the surface of the stent by heat treating the stent having the concavities and convexities; Changing the porous thin film to a hydrophilic state; And injecting the drug into the pores of the hydrophilic porous film. As a result, irregularities are formed on the surface of the stent, and the anodized surface is removed, so that the surface is prevented from being torn away and prevented from moving around inside the blood vessel. In addition, after forming a hydrophilic porous thin film on the uneven surface of the stent through heat treatment, an effect of inhibiting neointimal proliferation in the blood vessel can be obtained by injecting a new endogenous endothelial cell proliferation inhibitory drug.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical stent having unevenness formed on a surface thereof,

The present invention relates to a medical stent having surface irregularities and a method of manufacturing the same. More particularly, the present invention relates to a medical stent having surface irregularities formed on the surface thereof so as to form irregularities on the surface of the stent, The present invention relates to a medical stent in which unevenness is formed on a surface for preventing detachment, and a manufacturing method thereof.

A medical stent is a medical instrument that is used to expand the diameter of a blood vessel when the diameter of the blood vessel is narrowed due to various diseases occurring in the human body and the circulation of the blood does not occur smoothly.

The stent can be inserted into the human body through a variety of procedures and is mainly inserted into the blood vessels such as the cardiovascular, aortic, and cerebral blood vessels together with a balloon catheter. This is a method of inserting a balloon catheter into the blood vessel, expanding the balloon, and expanding the passage of the blood vessel as the balloon is inflated. The existing stent expands together with the inflation of the balloon and expands by the diameter of the original blood vessel . The stent is required to have elasticity and ductility so that the diameter can be expanded. That is, when the balloon catheter is inserted to fix the balloon catheter to the target site and then the balloon is expanded to expand the stenosed region, ductility is required to facilitate insertion into the passage of the complicated and curved blood vessel. Further, Elasticity is required to prevent the structure of the stent from being deformed by the contraction force of the tissue. Therefore, in order to satisfy these conditions, a stent is conventionally manufactured using stainless steel.

However, since such a stent is inserted into a blood vessel, it must be manufactured through a material suitable for a living body. In order to prevent restenosis, there is a need to provide a drug for preventing restenosis of blood vessels on the surface of the stent and supplying the drug into the blood vessel. Here, the drug uses a drug that has the function of inhibiting proliferation of neointimal intima cells by decreasing cell proliferation.

Such a conventional technique is a method of depositing a metal on the surface of a stent, such as 'a graft containing the FK506 of Korean Patent Office No. 10-0994543' and a 'medical stent and manufacturing method thereof' of the Korean Intellectual Property Office 10-2009-0074365 And then anodizing the nanostructure to form a nanostructure having a plurality of pores, and injecting the drug into the pores of the nanostructure. Drugs injected into the pores are released in the blood vessels and play a role in inhibiting the proliferation of new endometrial cells.

However, these prior art techniques allow the anodized metal oxide to move away from the stent and roam inside the vessel while the stent is inserted into the vessel and expanded by the balloon catheter. FIG. 1 is an SEM photograph showing anodic oxidation of a metal surface by a conventional method, and it is confirmed that metal oxide formed on the surface of the metal is anodically oxidized. 2 is a SEM photograph showing that the metal oxide is almost completely removed and the metal inside is exposed. It can be seen that the anodized metal oxide easily breaks off even if the shape is slightly deformed such as bending. The anodized metal oxide that has fallen away travels around the inside of the human body through the blood. However, there is a problem that if the blood rides around the human body, it seriously affects the human body.

Korea Patent Office Registration No. 10-0994543 Korean Patent Application Publication No. 10-2009-0074365

Accordingly, an object of the present invention is to provide a method of manufacturing a medical stent having an irregular surface on which anodized surface is removed by anodizing the surface of the stent, irregularities are formed on the surface, Stent and a method of manufacturing the same.

In addition, a titanium dioxide film of anatase crystal is formed through heat treatment, and a hydrophilic porous thin film is formed on the irregular surface of the stent by irradiating the titanium dioxide film with ultraviolet rays. Then, a neointimal cell proliferation inhibiting drug is injected, The present invention provides a medical stent in which unevenness is formed on a surface for inhibiting proliferation, and a method for producing the same.

The above object can be accomplished by an anodizing method comprising: forming an oxide film on a surface of a metal stent by anodic oxidation; Removing the metal oxide film from the stent to form irregularities on the surface of the stent; Forming a porous crystalline thin film on the surface of the stent by heat treating the stent having the unevenness; Changing the porous thin film to a hydrophilic state by irradiating UV light; And injecting the drug into the pores of the hydrophilic porous membrane.

Forming a polymer protective layer on the inner wall surface of the stent to prevent an inner wall surface of the stent from being anodized prior to the step of forming the metal oxide film, , And removing the polymer protective layer.

The step of removing the metal oxide film and forming the irregularities on the surface of the stent may include removing the metal oxide film using a physical method, a chemical method, and a mixing method thereof. In the physical method, And the ultrasonic wave is irradiated to the metal oxide film. It is preferable that the chemical method is a method of immersing in an acid or base solution.

The above object is achieved by a method of manufacturing a metal stent, comprising the steps of: preparing a tubular metal stent; Forming a polymeric protective layer on the inner wall surface of the stent to prevent an inner wall surface of the stent from being anodized; Anodizing the stent having the polymer protective layer formed thereon to form a metal oxide film locally on the surface; And removing the metal oxide film from the stent to form irregularities on the surface of the stent.

Herein, the step of removing the polymer protective layer before or after the step of forming the irregularities on the surface of the stent, wherein after the step of forming the irregularities on the surface of the stent, the stent having the irregularities is heat treated Forming a porous crystalline thin film on the surface of the stent; Changing the porous thin film to a hydrophilic state; And injecting the drug into the pores of the hydrophilic porous film.

The above object is also achieved by a stent comprising: a tubular stent body having an inner wall surface smooth and an outer surface uneven by anodization; A hydrophilic porous thin film stacked on the outer surface of the stent body and having a plurality of pores; And a hydrophilic polymer drug injected into the pores of the porous thin film. The present invention also provides a medical stent having surface irregularities.

According to the above-described structure of the present invention, the surface of the stent is formed with concavities and convexities, and since the anodized surface is removed, the effect of preventing the surface of the stent from being detached and moving around inside the blood vessel can be obtained.

In addition, after forming a hydrophilic porous thin film on the uneven surface of the stent through heat treatment, an effect of inhibiting neointimal proliferation in the blood vessel can be obtained by injecting a new endogenous endothelial cell proliferation inhibitory drug.

FIGS. 1 and 2 are SEM images of anodized metal oxides according to the prior art,
3 is a flowchart of a stent manufacturing method according to an embodiment of the present invention,
4 is a front view of a stent according to an embodiment of the present invention,
5 is a schematic view showing a stent manufacturing method,
6 is an SEM photograph showing the lower end portion of the titanium oxide metal oxide film after titanium anodization,
7 is a SEM photograph showing the surface of titanium from which a titanium oxide metal oxide film is removed.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a medical stent having surface irregularities according to an embodiment of the present invention and a method of manufacturing the same will be described in detail with reference to the drawings.

As shown in FIG. 3, a polymer protective layer is formed on the inner wall surface of the stent 100 (S1).

As shown in FIG. 4, a stent 100 is inserted into a blood vessel 10 to expand a blood vessel 10, and is formed into a tubular shape so that blood can move inside. In addition, the stent 100 has a lattice-like or wavy-shaped structure that is easy to contract and relax so as to increase its diameter by the balloon catheter 30. It is preferable that the inner wall surface of the stent 100 be smooth so that the blood can smoothly move through the inside of the stent 100. Therefore, in the next step, the inner wall surface of the stent 100 upon anodization forms a polymer protective layer on the inner wall surface to prevent anodic oxidation.

Here, the polymer protective layer may be formed of a material such as polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polyimide (PI), polyethylene terephthalate (PET), polyethersulfone (PES), polyethylene naphthalate ), PS (polystyrene), PU (polyurethane), PA (polyamide), FRP (fiber reinforced plastic), and mixtures thereof.

In addition, since the diameter of the stent 100 is increased in the blood vessel 10 by the balloon catheter 30, the stent 100 should be formed of a metal that is harmless to the human body and has good ductility. Such a metal is selected from the group consisting of titanium (Ti), titanium alloy, aluminum (Al), aluminum alloy, and a mixture thereof. Among them, the titanium alloy contains 30 parts by weight or more of titanium among 100 parts by weight . Also, the aluminum alloy should contain 30 parts by weight or more of aluminum in 100 parts by weight as in the case of the titanium alloy.

The stent 100 is anodized to form a metal oxide film 200 on the surface (S2).

The stent 100 having the polymer protective layer formed on the inner wall surface is anodized to form the metal oxide film 200 only on the outer surface. As shown in FIG. 5, the metal oxide film 200 is a tubular shape formed on the surface of the stent 100, and the interface between the metal oxide film 200 and the stent 100 is hemispherical like a lower portion of the tube. The size of the region recessed by the tube shape has a nano or micro size, which can be controlled by controlling the conditions of the anodic oxidation.

The polymer protective layer on the inner wall surface of the stent 100 is removed (S3).

When the anodic oxidation is completed on the outer wall surface of the stent 100, the polymer protective layer protecting the inner wall surface is removed to prevent anodic oxidation. The polymer protective layer can be simply removed using a cleaning solution such as acetone. The step of removing the polymer protective layer may be removed immediately after the anodization but may be removed after the stent 100 is finally made. That is, this step may be performed at any stage after the anodic oxidation is finished.

The metal oxide film 200 is removed to form the concavities 300 on the surface of the stent 100 (S4).

The metal oxide film 200 formed by the anodic oxidation easily falls off as shown in FIGS. 1 and 2 when external force such as a diameter of the stent 100 is increased. 1 and 2 show that the metal surface is anodized through a general anodic oxidation method as in the prior art, and even if a slight external force is applied, the metal oxide is immediately released. When the stent 100 manufactured through the conventional technique is inserted into the human body, the metal oxide film 200 is removed in the process of increasing the diameter of the stent 100. The molten metal oxide film 200 travels through the blood vessel 10 and may reach other organs in the blood to adversely affect the human body. Therefore, the metal oxide film 200 on the outer surface of the stent 100 is removed to solve this problem.

The metal oxide film 200 may be removed by various methods such as a physical method, a chemical method, or a combination thereof. The physical method is preferably a method of irradiating the metal oxide film 200 with ultrasonic waves using an ultrasonic cleaner, and the chemical method is a method of immersing the stent 100 in an acidic or basic aqueous solution so that the metal oxide film 200 is separated But the present invention is not limited to such a method.

As described above, when the metal oxide film 200 formed on the outer wall surface of the stent 100 is removed, the irregularities 300 having an almost hemispheric shape are formed on the surface of the stent 100, and semi- It is possible to obtain the stent 100 in which the nano irregularities are relatively small in size.

The porous thin film 400 is formed on the surface of the stent 100 (S5).

The porous thin film 400 is formed on the outer wall surface of the stent 100 by heat treating the stent 100 having the unevenness 300 formed on the outer wall surface. The porous thin film 400 changes the surface of the stent 100 where the protrusions and depressions 300 are present to a crystalline surface to control physicochemical properties such as hydrophilicity, hardness, strength, and oxide thickness. A plurality of pores 410 are formed in the porous thin film 400. The heat treatment temperature for forming the pores 410 is preferably 200 to 700 DEG C and at this temperature a crystalline porous thin film 400 is formed. When the temperature is lower than 200 ° C, an amorphous porous thin film is formed. Even if the UV is irradiated, the surface can not be hydrophilized.

The pores 410 formed in the porous thin film 400 may have a size of 10 to 500 nm and the size of the pores 410 may be controlled by controlling the applied voltage at the time of anodization. Also, the surface of the pore 410 itself is formed with a coarse surface having fine protrusions of several nanometers in size. By this heat treatment progress, it is possible to increase the biocompatibility by forming a thick crystalline metal oxide porous thin film 400 having a higher hardness.

For example, in the case of titanium (Ti), after the metal oxide film 200 is removed through anodization, an amorphous titanium oxide (TiO ₂ ) porous thin film 400 having a thickness of about 50 nm is formed naturally on the surface. , An anatase crystal phase is formed at a temperature of about 300 ° C or higher, and a rutile crystal metal oxide porous film 400 is formed at a temperature of 700 ° C or higher. The hardness is rutile>anatase> amorphous, and the thickness of the porous thin film 400 can be increased to 100 nm or more by heat treatment. That is, as the heat treatment is performed, the hardness of the metal surface on which the pores 410 are formed is increased and the thickness of the porous thin film 400 suitable for a living body is increased. These steps may be performed by modifying the material with various different materials besides titanium. The oxide porous thin film 400 formed by the heat treatment has pores 410 of about nano size, specifically, pores 410 having a diameter of 1 to 500 nm.

The porous thin film 400 is changed to a hydrophilic state (S6).

When a hydrophobic drug is injected in a hydrophobic state without changing the porous thin film 400 into a hydrophilic state, when the stent 100 containing the hydrophobic drug is inserted into the human body, the hydrophobic drug is released from the stent 100, which contacts the blood vessel 10, Lt; / RTI > If the drug is released in a short period of time, the concentration of the drug is increased, which has a detrimental effect on the human body. Therefore, it is preferable to use a hydrophilic drug so that the drug is slowly released and the surface of the stent 100 to be in a hydrophilic state. A method of changing the porous thin film 400 formed on the surface of the stent 100 to a hydrophilic state may be a method of applying an ultraviolet lamp having a strength of 0.1 to 10 J / cm 2 to the porous thin film 400 at a rate of 1 to 20 m / min It is preferable to treat UV having a wavelength of 300 to 400 nm. Any method that can change the porous thin film 400 to a hydrophilic state other than the UV treatment can be used without limitation.

The drug is injected into the pores 410 of the hydrophilic porous thin film 400 (S7).

In order to delay the release of the drug, the porous membrane 400 is changed to be hydrophilic, and a hydrophilic drug is injected into the pores 410 to smoothly flow the drug into the hydrophilic pores 410. Here, the hydrophilic drug is preferably a hydrophilic polymer drug that inhibits the proliferation of new endometrial cells.

Hereinafter, embodiments of the present invention will be described in more detail.

≪ Example 1 >

A stent made of titanium (Ti) metal is immersed in ethanol and acetone in an ultrasonic cleaner, followed by washing for 2 minutes. After cleaning, PDMS (Polydimethylsiloxane) is coated on the inner wall surface of the stent after drying the stent. The electrode surface is then spot-welded to titanium metal to anodize the outer surface of the stent. Then, a titanium metal stent, which is an object of anodization, and a counter electrode, platinum (Pt) metal, are immersed in the electrolytic solution. The electrolyte used here was an electrolyte having a composition of ethylene glycol (0.5 wt% NH ₄ F and 3 vol% H ₂ O), and the temperature of the electrolyte maintained at room temperature.

When a direct current voltage is applied to both ends of a stent-shaped titanium (Ti) metal as an anode and an insoluble platinum (Pt) metal as a cathode, the surface of the titanium metal is anodically oxidized with titanium oxide (TiO ₂ ). At this time, the DC voltage is applied at a constant voltage of 60 V for 30 minutes, and the anodized titanium oxide is formed as a metal oxide film, which is a nanotube structure having a thickness of several microns or more on the surface of the titanium stent.

FIG. 6 is a photograph of the lower end portion of the titanium oxide metal oxide film obtained through anodic oxidation, and it can be seen that the nanotube structure is well formed as shown in the figure.

The anodized stent is removed with acetone to remove the PDMS coated on the inner wall surface. The PDMS coated inner wall surface is not anodized and the smooth surface remains intact.

Next, the titanium oxide nanotube structure obtained through the anodic oxidation was removed from the titanium stent. In order to remove the metal oxide film as the nanotube structure, an anodized titanium stent was immersed in a 30 wt% hydrogen peroxide (H ₂ O ₂ ) solution For 10 minutes. Through such a method, the titanium oxide nanotube structure formed on the surface of the titanium stent is removed, and the surface of the titanium oxide nanotube structure is uneven as shown in FIG.

The nanotube structure is removed and the titanium stent having irregularities formed on the surface thereof is heat-treated at 200 to 700 ° C to form a porous thin film having oxide unevenness of nano-sized unevenness of about 10 to 500 nm. In this embodiment, To form a titanium stand having a porous thin film with a thickness of about 100 nm.

The porous thin film is irradiated with UV to convert it into a hydrophilic surface so that the drug is injected into the pores of the porous thin film. The UV is treated at a rate of 10 m / min using a UV lamp having a strength of 1 J / cm 2. The hydrophilic polymer drug is injected into the pores of the hydrophilic surface of the porous thin film to finally obtain the stent.

≪ Example 2 >

In order to grow a metal oxide film as a nanotube structure on a stent made of a nickel-titanium (Ni-Ti) shape memory alloy, the metal was cleaned and welded in the same manner as in Example 1, Anodic oxidation is carried out by immersing the substrate in a 1 M sulfuric acid aqueous solution containing 1% HF and applying a constant voltage of 20 V for 1 hour. Thereby obtaining a titanium-aluminum alloy stent in which a nanotube structure having a thickness of about 500 nm or more is formed.

Then, the anodized titanium-aluminum alloy stent is immersed in a 1M aqueous solution of oxalic acid and placed in a container with a stopper and left at 80 ° C for one day to remove the metal oxide film. Through this process, the irregularities can be formed on the surface of the stent. If necessary, the size of the irregularities can be controlled by adjusting the applied voltage and the anodization time.

A stent having a porous thin film having a thickness of about 100 nm can be formed by heat-treating the stent in a baking furnace at about 400 DEG C under the same conditions as in the first embodiment. The porous thin film is irradiated with UV to convert it into a hydrophilic surface so that the drug is injected into the pores of the porous thin film. The UV is treated at a rate of 10 m / min using a UV lamp having a strength of 1 J / cm 2. The hydrophilic polymer drug is injected into the pores of the hydrophilic surface of the porous thin film to finally obtain the stent.

When the medical stent 100 is manufactured through such a method, irregularities are formed on the surface of the stent 100 through anodization and the metal oxide film 200 is removed because the anodized metal oxide film 200 is removed. It is possible to obtain an effect of preventing the blood vessels from being torn away and moving around inside the blood vessel. In addition, a hydrophilic porous thin film 400 may be formed on the surface of the irregular surface of the stent 100 through heat treatment, and then the release rate of the drug may be delayed by injecting a hydrophilic neointimal cell proliferation inhibitory drug. It is possible to obtain an effect of inhibiting neointimal hyperplasia.

100: stent
200: metal oxide film
300: unevenness
400: Porous thin film
410: Porcelain

Claims (20)

A method of manufacturing a medical stent in which unevenness is formed on a surface,
Anodizing the tubular metal stent to form a metal oxide film on the surface of the nanotube structure;
Removing the metal oxide film of the nanotube structure from the stent to form irregularities on the surface of the stent;
Forming a porous crystalline thin film on the surface of the stent by heat treating the stent having the unevenness;
Changing the porous crystalline thin film to a hydrophilic state;
And injecting the drug into the pores of the hydrophilic porous crystalline thin film. The method according to claim 1,
Before the step of forming the metal oxide film of the nanotube structure,
And forming a polymer protective layer on the inner wall surface of the stent to prevent an inner wall surface of the stent from being anodized,
After the step of forming the metal oxide film of the nanotube structure,
And removing the polymer protective layer from the surface of the stent. 3. The method of claim 2,
The polymer protective layer may be,
Polymers such as PDMS (Polydimethylsiloxane), PMMA (Polymethylmethacrylate), PI (Polyimide), PET (polyethylene terephthalate), PES (Polyethersulfone), PEN (Polyethylene naphthalate), PS (Polystyrene), PU reinforced plastic, and a mixture thereof. The method for manufacturing a medical stent according to claim 1, The method according to claim 1,
The step of forming the protrusions and depressions on the surface of the stent by removing the metal oxide film of the nanotube structure comprises:
Wherein the metal oxide film of the nanotube structure is removed by a physical method, a chemical method, and a mixing method thereof. 5. The method of claim 4,
The physical method is a method of irradiating ultrasonic waves to the metal oxide film of the nanotube structure using an ultrasonic cleaner,
Wherein the chemical method is a method of immersing in an acid or a base solution. The method according to claim 1,
The step of forming the porous crystalline thin film on the surface of the stent may include:
Wherein the heat treatment is performed at 200 to 700 占 폚. The method according to claim 1,
The step of changing the porous crystalline thin film to a hydrophilic state comprises:
Wherein the porous crystalline thin film is subjected to UV treatment at a rate of 1 to 20 m / min using a UV lamp having an intensity of 0.1 to 10 J / cm 2. The method according to claim 1,
In the stent,
The method of manufacturing a medical stent according to claim 1, wherein the surface of the stent is made of a material selected from the group consisting of titanium (Ti), titanium alloy, aluminum (Al), aluminum alloy and mixtures thereof. 9. The method of claim 8,
Wherein the titanium alloy contains titanium in an amount of 30 parts by weight or more,
Wherein the aluminum alloy comprises 30 parts by weight or more of aluminum in 100 parts by weight of the whole of the aluminum alloy. The method according to claim 1,
Wherein the drug is a hydrophilic polymer drug inhibiting neointimal cell proliferation. The method according to claim 1,
Wherein the pores of the porous crystalline thin film are formed to have a diameter of 1 to 500 nm. A method of manufacturing a medical stent in which unevenness is formed on a surface,
Preparing a tubular metal stent;
Forming a polymeric protective layer on the inner wall surface of the stent to prevent an inner wall surface of the stent from being anodized;
Forming a nanotube structure metal oxide film on the surface by anodizing the stent having the polymer protective layer formed thereon;
And removing the metal oxide film of the nanotube structure from the stent to form irregularities on the surface of the stent. 13. The method of claim 12,
Before or after the step of forming irregularities on the surface of the stent,
And removing the polymer protective layer from the surface of the stent. 13. The method of claim 12,
After the step of forming the irregularities on the surface of the stent,
Forming a porous crystalline thin film on the surface of the stent by heat treating the stent having the unevenness;
Changing the porous crystalline thin film to a hydrophilic state;
And injecting the drug into the pores of the hydrophilic porous crystalline thin film. 1. A medical stent having surface irregularities,
A tubular stent body having smooth inner wall surfaces and uneven surfaces formed on the outer wall surfaces by anodic oxidation;
A hydrophilic porous crystalline thin film formed on an outer wall surface of the stent body and having a plurality of pores;
And a hydrophilic polymer drug injected into the pores of the porous crystalline thin film. 16. The method of claim 15,
Wherein the porous crystalline thin film has a thickness of 100 nm or more. 16. The method of claim 15,
Wherein the pores have a size of 1 to 500 nm. 1. A medical stent having surface irregularities,
A tubular stent body having semi-spherical concavities and convexities;
And a hydrophilic porous crystalline thin film formed on an outer wall surface of the stent body and having a plurality of pores. 19. The method of claim 18,
And a hydrophilic polymer drug injected into the pores of the porous crystalline thin film. 19. The method of claim 18,
Wherein the pores have a size of 1 to 500 nm.

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