KR20190012654A - Stent for medical use and method of manufacturing thereof - Google Patents

Abstract

A medical stent of the present invention has an effect of suppressing peeling and cracking of a surface layer which may occur when force due to warping, bending, etc. is continuously applied even though substances having different elastic properties are bonded, and has an effect of having a surface layer of high surface hardness, abrasion resistance, low friction coefficient, high chemical resistance and high corrosion resistance, and also has excellent biocompatibility and chemical stability. The present invention comprises: a metal stent substrate; a titanium oxide layer formed on the metal stent substrate; and a carbon layer formed on the titanium oxide layer.

Description

Technical Field [0001] The present invention relates to a medical stent,

The present invention relates to a medical stent and a method of manufacturing the same.

A medical stent is a medical instrument that is inserted into a blood vessel and dilates a blood vessel when a blood vessel becomes narrow due to various diseases occurring in the human body and blood circulation failure occurs.

Specifically, a stent is a medical instrument that is inserted into a blood vessel to dilate a blood vessel when a blood vessel narrows due to various diseases occurring in the human body and blood circulation failure occurs. The stent is performed by balloon dilation that extends the coronary pathway as the balloon is inflated with a balloon catheter inserted into the blood vessels such as cardiovascular, aortic, and cerebral vessels in various ways, have. Conventional stents are required to be elastic and ductile in order to expand to the original size of the vascular passage by expanding outwardly as the balloon expands. That is, the stent is required to have flexibility for insertion in a complicated and curved pathway when performing a procedure in which a balloon catheter is inserted to fix the balloon catheter to a desired site, and then the balloon is expanded to expand the stenosed region. In addition, after the procedure is completed, elasticity and other conditions are required to prevent the structure of the stent from being deformed by the force of contracting the blood vessels (cardiovascular, aorta, cerebral artery, etc.).

In addition, the material constituting the stent is required to have excellent biochemical properties such as high biocompatibility and stability to the human body, and chemical properties such as high corrosion resistance.

Accordingly, there has been known a technique for coating diamond-like-carbon (DLC) having excellent biocompatibility and stability, high friction coefficient and high corrosion resistance on the surface of a stent.

The metal stent base used in the medical stent is required to have high ductility and elasticity as described above, while the carbon layer such as diamond-like carbon coated on the metal stent base is a material having relatively brittleness and different characteristics from each other. Therefore, the interfacial bonding force between the carbon layer and the stent substrate must be improved in consideration of the different elastic properties of the carbon layer and the stent substrate, and the carbon layer coated on the stent is peeled or cracked even if the stress due to bending, .

As an example thereof, Korean Patent Laid-Open No. 10-2010-0095942 discloses " a stent having a diamond-like carbon thin film layer and its surface coating method, and its surface coating apparatus ". The stent of the patent publication is a stent to which a silicon-based buffer layer is coated on a stent substrate and a diamond carbon thin film layer is coated on the buffer layer, and the excellent physical properties of diamond carbon such as low friction coefficient and high corrosion resistance are applied.

However, the stent of the patent publication has a relatively improved bonding force as the silicon-based buffer layer is formed between the stent substrate and the diamond carbon thin film layer. However, since the stent structure is continuously applied with a force due to expansion and contraction, The problem of peeling or cracking of the surface coating layer can not be fundamentally avoided.

In addition, as a silicon-based buffer layer used for improving the bonding strength in the stent of the patent publication, biocompatibility is not comparatively excellent, and problems such as late thrombosis and inflammation after stenting may occur. Also, since the silicon-based compound undergoes a rapid bonding reaction with a specific substance such as oxygen when exposed to air for a short period of time, the adhesion of the silicon-based compound to the diamond-like carbon thin film layer is lowered and the rate of peeling and cracking increases.

Therefore, the medical stent should have excellent biocompatibility characteristics as well as good physical properties such as friction coefficient, strength, ductility and elasticity as described above. When the stress is concentrated on a specific part due to constant application of force, Or cracks that may occur during operation.

Korean Patent Publication No. 10-2010-0095942 (September 1, 2010)

It is an object of the present invention to provide a stent having a carbon layer formed on the surface of a stent capable of suppressing peeling and cracking of a surface layer which may occur when a stress is continuously increased due to warping or bending, A medical stent and a method of manufacturing the same are provided.

It is also an object of the present invention to provide a medical stent having a surface layer of high surface hardness, abrasion resistance, low coefficient of friction, high chemical resistance and high corrosion resistance, and a method of manufacturing the same.

It is another object of the present invention to provide a medical stent excellent in biocompatibility and chemical stability and a method for producing the same.

The medical stent of the present invention comprises: a metal stent base; A titanium oxide layer formed on the metal stent substrate; And a carbon layer formed on the titanium oxide layer.

In one embodiment of the present invention, the metal stent base material may include any one or two or more selected from Co, Cr, Ti, Mo, Pt, Ni, Ta and alloys thereof.

In one example of the present invention, the average thickness of the titanium oxide layer may be 8 to 25 nm.

In one example of the present invention, the carbon layer may be a diamond-like carbon thin film layer.

In one example of the present invention, the average thickness of the carbon layer may be 10 to 500 nm.

The tubular blood vessel expanding stent according to an embodiment of the present invention may be a tubular blood vessel expanding stent made of the medical stent, the outer circumferential surface portion comprising the medical stent; And a hollow portion formed inside the outer circumferential surface portion.

A method of manufacturing a medical stent according to the present invention comprises: a) coating a titanium oxide layer on the metal stent substrate; and b) coating the carbon layer on the coated titanium oxide layer.

In one embodiment of the present invention, the coating in step a) may be a plasma chemical vapor deposition method.

In one embodiment of the present invention, the coating of step b) may be one which utilizes ion beam deposition.

In one embodiment of the present invention, the reaction material used in the coating of step b) may include one or two selected from methane, benzene, and the like.

The method for manufacturing a medical stent according to an example of the present invention may further include cleaning the surface of the metal stent base material before the step a).

The medical stent of the present invention has the effect of suppressing peeling and cracking of the surface layer, which may occur when stress due to warping and bending is continuously weighted, although materials having different elastic properties are bonded.

Further, the medical stent of the present invention has an effect of having a surface layer having high surface hardness, abrasion resistance, low friction coefficient, high chemical resistance, and high corrosion resistance.

Further, the medical stent of the present invention has an excellent biocompatibility and chemical stability.

Even if the effects are not explicitly mentioned in the present invention, the effects described in the specification anticipated by the technical features of the present invention and their inherent effects are treated as described in the specification of the present invention.

FIGS. 1 to 3 are images obtained by expanding the composite stent prepared in Example 1 and observing it with a scanning electron microscope at an image size of 30, 300 and 3,000 magnifications, respectively.
FIG. 4 is an image obtained by scanning electron microscopy of the composite stent prepared in Comparative Example 1 and not expanded. FIG.
Fig. 5 (a) is an image of a cross-sectional view of a crooked composite stent, prepared in Example 1, and observed with a scanning electron microscope. Fig.
FIG. 5 (b) is an image of a cross-sectional view of a composite stent (BMS / TiO ₂ ) before the carbon layer was coated in the manufacturing process of Example 1 by scanning electron microscopy.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, a medical stent of the present invention and a method of manufacturing the same will be described in detail with reference to the accompanying drawings.

The drawings described in the present invention are provided by way of example so that a person skilled in the art can sufficiently convey the idea of the present invention. Therefore, the present invention is not limited to the illustrated drawings, but may be embodied in other forms, and the drawings may be exaggerated in order to clarify the spirit of the present invention.

In addition, unless otherwise defined, technical terms and scientific terms used in the present invention have the same meanings as those of ordinary skill in the art to which the present invention belongs. In the following description and the accompanying drawings, Description of known functions and configurations that may unnecessarily obscure the subject matter will be omitted.

Also, the singular form of the term used in the present invention can be construed as including plural forms unless otherwise indicated.

Also, units of% used unclearly in the present invention means weight percent.

The medical stent of the present invention comprises: a metal stent base; A titanium oxide layer formed on the metal stent substrate; And And a carbon layer formed on the titanium oxide layer.

The carbon layer preferably means a Diamond-Like-Carbon (DLC) thin film layer. The diamond-like carbon thin film layer is formed on the titanium oxide layer and has high surface hardness and high abrasion resistance, and is excellent in chemical resistance and corrosion resistance. In addition, the stent with a diamond-like carbon thin film layer on its surface has a low coefficient of friction so that damage to the inner wall of the vessel can be minimized even if the stent is freely moved in the vessel, and the biocompatibility is excellent. Can be minimized.

The average thickness of the carbon layer is not particularly limited, but may be 10 to 500 nm, more preferably 50 to 200 nm. If it is satisfied, peeling or cracking can be minimized even in a continuous stress and deformation environment which is weighted on a specific portion of the stent, and physical properties such as high surface strength and low friction coefficient can be further improved. However, this is a preferred example, and the present invention is not limited thereto.

The titanium oxide layer is positioned between the metal stent base and the carbon layer and tightly bonded to each other, thereby imparting a property of significantly improving the interfacial bonding strength. In particular, the titanium oxide layer is superior to the silicon-based compound in terms of the biocompatibility and the properties of improving the respective interface bonding strengths. Specifically, the silicon-based compound undergoes a rapid bonding reaction with a specific substance such as oxygen during a short-term exposure to air to cause a change in the thin film layer, so that the adhesion with the carbon layer is low, and the rate of peeling and cracking is high. On the other hand, the titanium oxide layer prevents the dislocation layer from reacting with other materials during long-term exposure, and because of its excellent adhesion, the once-coated thin film layer can be maintained for a long time without deformation of the layer and then bonded to the carbon layer, The resistance to peeling and cracking is remarkably improved.

The titanium oxide layer may have various crystal structures depending on the coating method or the reaction raw materials to be used, but the crystal structure is not limited in the present invention. For example, although the crystal structure of the titanium oxide layer has various crystal structures such as rutile, anatase, and Brookite, the above-described characteristics and effects are all realized.

The average thickness of the titanium oxide layer is not particularly limited, but may be preferably 5 to 100 nm, more preferably 10 to 50 nm. Layer structure (metal stent substrate / titanium oxide layer / metal oxide layer / metal oxide layer / metal oxide layer / metal oxide layer / metal oxide layer / metal oxide layer / Carbon layer). However, this is a preferred example, and the present invention is not limited thereto.

In one embodiment of the present invention, the titanium oxide layer may be additionally doped with a hetero-element, for example, a nitrogen-doped titanium oxide layer. Since the nitrogen-doped titanium oxide is coated on the metal stent base, antithrombogenicity can be improved together with excellent biocompatibility. Specifically, the nitrogen-doped titanium oxide layer may be a coating layer formed on the surface of the stent, for example, a compound having the form of TiO _{2 - x} N _x , where X may range from 0.001 to 1.

The metal stent base material may include any one or two or more selected from among Co, Cr, Ti, Mo, Pt, Ni, Ta and alloys thereof. Preferably, a metal stent base made of a Co-Cr alloy is used as the alloy of Co and Cr. When this is satisfied, it is preferable in terms of excellent mechanical properties such as elastic modulus and yield strength, which are characteristics of the metal stent base material itself made of a Co-Cr alloy, and is preferable in view of excellent bonding strength with the titanium oxide layer.

The average diameter and the average length of the metal stent base may be appropriately selected according to the vasculature of the coronary artery such as a blood vessel of a living body to be implanted or the size of the stent depending on the structure of the stent. For example, an average diameter of 50 to 5,000 [ .

A conventional stent for expanding a blood vessel is expanded by a balloon catheter inserted in a blood vessel and located inside the stent, thereby expanding the blood vessel and reducing the blood vessel to allow free movement in the blood vessel. As the expansion and contraction process is repeated or the stent is moved to the lesion in the blood vessel, the force such as stress and friction can be repeatedly applied to the stent, resulting in peeling and cracking of the surface layer.

However, when the medical stent of the present invention is applied to a stent for vasodilation, peeling and cracking of the surface layer can be minimized.

Specifically, the medical stent of the present invention can be used as a blood vessel expanding stent, and the blood vessel expanding stent can have a tubular structure made of the medical stent. For example, the vasodilating stent may include: an outer circumferential surface portion comprising the medical stent; And a hollow portion formed inside the outer circumferential surface portion.

The medical stent of the present invention includes a hollow portion having a passage formed inside the outer circumferential surface portion and the outer circumferential surface portion so that the medical stent of the present invention forms a plurality of bends in a predetermined unit pattern and is connected to each other, As shown in Fig. In addition, a balloon catheter capable of expanding or contracting the stent may be freely inserted into the hollow portion.

The stent for vasodilation according to the present invention uses a stent coated sequentially with a titanium oxide layer and a carbon layer to minimize peeling and cracking of the surface layer even though stress and deformation due to bending and bending are continuously increased There is an effect that can be done.

The method of manufacturing a medical stent of the present invention comprises the steps of: a) coating a titanium oxide layer on a metal stent substrate; and b) coating a carbon layer on the coated titanium oxide layer.

The coating of step a) may be performed by various methods such as a chemical vapor deposition method, a dip coating method, a physical vapor deposition method, and an aerosol deposition method. Preferably, the chemical vapor deposition method is preferable in terms of uniform deposition thickness and ease of control thereof .

Specifically, in the step a), the titanium oxide layer may be formed on the surface of the stent by Plasma Enhanced Chemical Vapor Deposition (PECVD). When the chemical vapor deposition method is used, a more uniform layer can be formed, and an extremely thin layer can be formed as needed. And then through a carbon layer coating step of step b) to finally induce a more uniform layer to be formed on the surface of the stent.

More specifically, the step a) may include forming a titanium oxide layer on the surface of the stent by reacting the titanium precursor and the oxygen gas using chemical vapor deposition. The titanium precursor may be one which reacts with oxygen to form a titanium oxide layer. Examples of the titanium precursor include titanium butoxide, tetraethylmethylaminotitanium, titanium ethoxide, titanium isopropoxide, Tetramethylheptadiene titanium, and the like. The reaction temperature in the chemical vapor deposition may be 300 to 600 ° C, the reaction time may be 1 to 10 hours, and the voltage may be 1 to 300 W, specifically 50 to 70 W. In this case, an inert gas such as argon may be used as a carrier gas, and a flow rate ratio between argon gas and oxygen gas may be 100: 5 to 30. However, it should be understood that the present invention is not limited thereto.

Various methods such as ion beam deposition, high frequency plasma method, and sputtering method can be used for the coating in the step b). However, the ion beam deposition method can be used for precisely coating the carbon layer, which is the diamond-like carbon thin film layer, on the titanium oxide layer, .

When the diamond-like carbon thin film layer is formed on the titanium oxide layer as a carbon layer by using the ion beam deposition method in the step b), the surface of the titanium oxide layer formed on the metal stent base in a vacuum state using the hydrocarbon- A diamond-like carbon thin film layer having a structure similar to that of FIG.

The hydrocarbon-based compound may include at least one selected from the group consisting of methane, benzene, pentane, hexane, cyclohexane, cis-2-pentene and hexene. Preferably, methane or benzene is used as the hydrocarbon-based compound in terms of minimizing peeling and cracking of the surface carbon layer.

The deposition rate and the deposition time can be appropriately adjusted according to the average thickness of the required carbon layer, for example, 3 to 20 [mu] m / h and 30 to 300 minutes. The deposition may proceed in vacuum or similar conditions, for example, at a pressure of 0.001 to 0.1 torr. The ion energy during deposition can be from 100 eV to 100 keV and the voltage can be from 50 to 300 volts.

The method for manufacturing a medical stent according to an embodiment of the present invention may further include a step of cleaning or stabilizing the surface of the metal stent base before the step a). Specifically, it may be a step of bringing an inert gas such as argon gas and oxygen gas into contact with the metal stent base material at a volume ratio of 100: 3 to 30 at 0.001 to 0.1 torr. At this time, the temperature may be 200 to 600 ° C. After the pretreatment, the deposition power of the titanium oxide layer on the metal stent substrate may be improved in the step a).

EXAMPLES Hereinafter, the present invention will be described in detail with reference to Examples. However, the present invention is described in more detail with reference to the following Examples. However, the scope of the present invention is not limited by the following Examples.

Preprocessing step

First, in order to improve the adhesion between the metal stent and the titanium oxide layer, the surface of the metal stent was stabilized by a pretreatment process of flowing argon into the metal stent.

Specifically, a metal stent (BMS) made of a Co-Cr alloy was placed in a chamber, argon was supplied at 100 sccm at 250 mtorr and at an RF power of 100 W for 15 minutes in the chamber to remove organic substances adhering to the surface of the metal stent The inorganic matter was removed and stabilized.

Titanium oxide layer  Coating step

A composite stent (BMS / TiO ₂ ) was prepared by depositing a titanium oxide layer on the surface of the stabilized metal stent using plasma enhanced chemical vapor deposition.

Specifically, the metal stent was fixedly rotated using a stent-specific rotary jig in a vacuum chamber in which an RF plasma generator for generating plasma and a vacuum pump were connected, and the chamber was maintained at 400 ° C. and 250 mtorr. The RF power was 60 W, the flow rate of argon gas was 100 sccm and the flow rate of oxygen gas was 16 sccm as a carrier gas. Titanium (IV) isopropoxide, 97%, Sigam-Aldrich (BMS / TiO ₂ ) was prepared by vaporizing a titanium oxide layer on a metal stent for 3.5 hours.

Carbon layer coating step

A composite stent (BMS / TiO ₂ / DLC) was prepared by coating a carbon layer on the titanium oxide layer of the composite stent (BMS / TiO ₂ ) using an ion beam deposition method.

Specifically, DLC (Diamond-Like-Carbon, DLC) coating was performed on the titanium oxide layer coated on the metal stent with methane gas as a reaction source by ion beam deposition for 100 minutes at a voltage of 0.01 torr and 150 V A composite stent (BMS / TiO ₂ / DLC) was prepared by coating a carbon layer as a diamond-like carbon thin film layer having a thickness of 100 nm.

[Comparative Example 1]

In Example 1, a composite stent (BMS / DLC) was prepared in the same manner as in Example 1 except that the carbon layer was directly coated on the metal stent without coating the titanium oxide layer on the metal stent.

Surface peeling, crack  Evaluation of stability characteristics

In order to evaluate the stability of the composite stents prepared in Example 1 and Comparative Example 1 against surface peeling and cracks, each composite stent was fixed with a clamping device using a balloon device for stent expansion, The composite stent was expanded to 20 atm using an indeflator. The surface states of the expanded and composite stents were observed with a scanning electron microscope, which is shown in FIGS. 1 and 4. FIG.

FIGS. 1 to 3 are images obtained by expanding the composite stent prepared in Example 1 and observing it with a scanning electron microscope at an image size of 30, 300 and 3,000 magnifications, respectively. From this, it can be seen that, in the case of Example 1, the layers were not peeled off and cracks did not appear even though they were extended under the condition of 20 atm.

However, FIG. 4 is an image obtained by scanning electron microscopy of the composite stent prepared in Comparative Example 1 and not expanded. In the case of Comparative Example 1, the carbon layer was peeled off before the over-expansion process, It can be seen from FIG. 4 that it is generated.

5 (a) is a cross-sectional view of the stent of the present invention, in which each layer is artificially curved and protruded so as to accurately measure each layer of the unexpanded stent prepared in Example 1, ) Was observed with a scanning electron microscope. From this, it can be seen that the titanium oxide layer and the carbon layer are properly bonded, and the thickness of the carbon layer is about 100 nm.

FIG. 5 (b) is an image of a cross-sectional view of a composite stent (BMS / TiO ₂ ) before the carbon layer is coated in a manufacturing process of Example 1 by scanning electron microscopy, It can be seen that the thickness of the oxide layer is about 20 nm.

Claims (11)

Metal stent substrates;
A titanium oxide layer formed on the metal stent substrate; And
And a carbon layer formed on the titanium oxide layer. The method according to claim 1,
Wherein the metal stent base material comprises any one or two or more selected from Co, Cr, Ti, Mo, Pt, Ni, Ta and alloys thereof. The method according to claim 1,
Wherein the titanium oxide layer has an average thickness of 8 to 25 nm. The method according to claim 1,
Wherein the carbon layer is a diamond-like carbon thin film layer. The method according to claim 1,
Wherein the carbon layer has an average thickness of 10 to 500 nm. A tubular vasodilation stent comprising a medical stent according to any one of claims 1 to 5,
An outer circumferential surface portion comprising the medical stent; And
And a hollow portion formed inside the outer peripheral surface portion. a) coating a titanium oxide layer on a metal stent substrate and
b) coating a carbon layer on the coated titanium oxide layer. 8. The method of claim 7,
Wherein the coating of step a) uses plasma enhanced chemical vapor deposition. 8. The method of claim 7,
Wherein the coating of step (b) uses ion beam deposition. 10. The method of claim 9,
Wherein the reaction material used in the coating of step b) is a hydrocarbon compound containing one or both of methane and benzene. 8. The method of claim 7,
A method of manufacturing a medical stent,
Further comprising the step of cleaning the surface of the metal stent substrate prior to step a).

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