KR101033166B1 - Silicon incorporated diamond-like carbon film having a good hemocompatibility of biomedical material and the fabrication method thereof, and biomedical material using the same - Google Patents

Abstract

The present invention relates to a silicon-containing diamond-like carbon thin film having improved blood compatibility, wherein the atoms (A) imparting hydrophilicity to the surface of the thin film are chemically bonded to the surface of the diamond-like carbon thin film containing silicon inside and on the surface thereof. The present invention provides a silicon-containing diamond-like carbon thin film having improved blood compatibility, and a method of manufacturing the same, and a medical material using the same, wherein a bond of C and A and a bond of Si and A are present on the surface of the thin film.

Silicon-containing diamond-like carbon thin film, surface modification, plasma, oxygen, hydrophilic

Description

SILICON INCORPORATED DIAMOND-LIKE CARBON FILM HAVING A GOOD HEMOCOMPATIBILITY OF BIOMEDICAL MATERIAL AND THE FABRICATION METHOD THEREOF, AND BIOMEDICAL MATERIAL USING THE SAME}

The present invention relates to a silicon-containing diamond-like carbon thin film having improved blood compatibility by modifying the surface of the Si-containing diamond-like carbon thin film having excellent corrosion resistance, thereby improving blood compatibility, and a method of manufacturing the same and a medical material using the same.

Diamond-like carbon thin films have high hardness, lubricity, high electrical resistance, wear resistance, and are widely used in various fields because of their smooth surface and synthesis at low temperatures. In addition, the surface has excellent chemical stability, excellent biocompatibility and blood compatibility, and has a feature that can be widely used as a surface treatment layer of a biological insert and a biological substitute.

As a specific example, peripheral occlusive artery disease is a relatively common disease diagnosed with noninvasive diagnostic equipment in about 3% of adults in their 40s and 50s and about 20% in those over 70s. . Interventional interventions using vascular stents for the treatment of obstructive vascular diseases are easier and safer than surgical operations, do not require general anesthesia, and have a high success rate and are widely used worldwide. Since the blood vessel stent is generally used as a bare stent (bare stent), the surface treatment of the stent wire that is in direct contact with the inner wall of the blood vessel is very important for improving biocompatibility. In addition, the vascular stent may be acute closure due to the formation of a blood clot immediately after installation, the stent itself acts as a traumatic element on the inner wall of the blood vessels to induce proliferation, thereby causing a problem of restenosis. Therefore, in order to improve the success rate of the stent procedure, there is a demand for a functional surface modification technique having a drug release function for delivering a therapeutic drug directly into a blood vessel along with a surface treatment for suppressing clotting of a blood clot.

In order to suppress the blood clot coagulation and restenosis of the blood vessel stent, a research on coating a diamond-like carbon film on the surface of the stent is being actively conducted. In particular, in order to prevent leakage of metal ions in the stent material, a coating layer having excellent corrosion resistance is required, and diamond-like carbon film is expected to satisfy these conditions.

However, it is reported that the coating effect is hardly exhibited when the existing pure diamondoid carbon thin film is used, because the corrosion resistance and blood compatibility of the pure diamondoid carbon thin film are insufficient.

The present invention has been made to solve these conventional problems, the object of the present invention is to improve the corrosion resistance of diamond-like carbon thin film (hereinafter referred to as 'DLC thin film'), and also to improve the corrosion resistance of DLC thin film It is to improve blood compatibility by modifying the surface to control surface energy.

These objects can be achieved by the following configuration of the present invention.

(1) Atoms (A) imparting hydrophilicity to the surface of the thin film are chemically bonded to the surface of the DLC thin film containing silicon on the inside and the surface thereof, and the bonding of C and A to the surface of the thin film and the A silicon-containing DLC thin film having improved blood compatibility, characterized in that a bond is present.

(2) the medical material coated with a thin film,

The thin film is a medical material, characterized in that the silicon-containing DLC thin film with improved blood compatibility according to (1).

(3) forming a DLC thin film containing silicon on the inside and on the surface of the base material;

By activating the surface of the thin film to break some of the chemical bonds of the surface of the thin film, and bonds of C and A and Si and A by bonding atoms (A) that impart hydrophilicity to the surface of the thin film to the site where the chemical bond is broken A process for producing a silicon-containing DLC thin film having improved blood compatibility, characterized in that it comprises a step of producing.

According to the present invention, a DLC thin film with remarkably improved corrosion resistance and blood compatibility can be obtained. Thin film coating technology according to the present invention can be widely used for the surface treatment of biological inserts or therapeutic material in contact with blood.

Examples of the medical material for which the effects of the present invention are expected include blood vessel stents, heart valves, heart pumps, artificial blood vessels, and the like. It can also be applied to the surface treatment of pathological laboratory substrates or blood reservoirs that should inhibit blood coagulation.

In the silicon-containing DLC thin film having improved blood compatibility according to the present invention, atoms (A) imparting hydrophilicity to the surface of the thin film are chemically bonded to the surface of the diamond-like carbon thin film containing silicon on the inside and the surface thereof, so that the thin film It is characterized in that the bond of C and A and the bond of Si and A are present on the surface of.

In the present invention, a Si-containing DLC thin film having excellent corrosion resistance is used instead of the pure DLC thin film. This Si-containing DLC thin film is distributed in the form of clusters of silicon in the size of several to several tens of nanometers inside and on the surface, thereby relieving the inherent stress of DLC and increasing durability and biocompatibility (see Experimental Example 1). . It is preferable that the ratio of silicon in the said thin film is 0.5-17 at.%. If it is less than 0.5 at.%, Sufficient corrosion resistance cannot be realized, and the hydrophilicity of the surface tends to disappear easily. If it is more than 17 at.%, The size of SiC clusters in the thin film becomes too large, resulting in deterioration of mechanical and chemical properties.

In addition, in the present invention, the Si-containing DLC thin film surface is modified in various ways to improve the blood compatibility of the surface. Specifically, some chemical bonds of the Si-containing DLC thin film surface are broken and specific atoms are bonded to modify the thin film surface to be hydrophilic. Here, the said specific atom is an atom which gives hydrophilicity to a thin film surface, For example, an oxygen atom (O), a nitrogen atom (N), etc. are mentioned. In the case where the specific atom is an oxygen atom, the Si-O bond ratio on the surface of the thin film is preferably 30 to 60%. If the specific atom is less than 30%, the hydrophilic surface is easily degraded. In general, hydrophilicity is expressed by the water contact angle (water contact angle), the contact angle of the surface of the thin film in the present invention is more than 0 ° and less than 50 °, preferably 0 ° and more than 20 ° is good in terms of blood compatibility. .

Such surface-modified Si-containing DLC thin films can be coated and used on medical materials, such as blood vessel stents, heart valves, heart pumps, artificial blood vessels, pathological laboratory substrates for inhibiting blood coagulation, or blood reservoirs.

On the other hand, the method for producing a Si-containing DLC thin film according to the present invention, (A) the step of forming a DLC thin film containing Si on the inside and the surface of the base material, (B) the surface of the thin film to activate the thin film A step of breaking some of the chemical bonds on the surface and bonding the atoms (A) imparting hydrophilicity to the surface of the thin film to the sites where the chemical bonds are broken to generate bonds of C and A and bonds of Si and A.

First, Si-containing DLC thin films can be made by various methods. For example, the Si-containing DLC thin film can be formed on the surface of the base material by using any one of the plasma CVD method, the ion beam synthesis method, the sputtering synthesis method, and the self filtration arc synthesis method alone or a combination of two or more of these methods. Specifically, a precursor gas containing carbon and silicon may be placed in a plasma CVD vessel for plasma treatment. Alternatively, silicon may be supplied by sputtering with plasma synthesis of the carbon-containing precursor. As another method, various methods may be used, such as sputtering silicon while synthesizing a DLC thin film using a carbon ion beam. In the embodiment of the present invention, the RF-PACVD (Radio frequency plasma assisted CVD) method is used, the bias voltage is preferably in the range of -100 ~ -800 V, the pressure in the device within the range of 0.5 ~ 10 Pa during thin film synthesis. However, the present invention is not limited to the above synthesis methods.

Next, the thin film surface can be activated in various ways. For example, the surface of the Si-containing DLC thin film may be activated by irradiating an RF plasma, a DC plasma, or a plasma beam on the surface of the thin film or by irradiating an ion beam. In the embodiment of the present invention, a method of irradiating the plasma was used, and the pressure in the apparatus during surface modification is preferably in the range of 0.1 to 10 Pa and a bias voltage of -100 to -800 V. However, the present invention is not limited to the above activation methods.

When the surface of the thin film is activated in this way, the reactive gas atoms (A) decomposed by the plasma or ion beam are bonded to the sites where the surface bonds are broken, thereby generating C and A bonds and Si and A bonds. In the present invention, in order to make the modified thin film surface hydrophilic, it is preferable to use oxygen or nitrogen as the reactive gas. Here, the Si-A bond further contributes to the hydrophilicity of the thin film surface among the C-A bond and the Si-A bond (see Experimental Example 2).

Hereinafter, the present invention will be described in detail with reference to examples, but these examples are only presented to more clearly understand the present invention, and are not intended to limit the scope of the present invention. It will be determined within the scope of the technical spirit of the claims.

[ Example ]

One. Si  contain DLC  Formation of a thin film

Si-containing DLC thin films were formed on the surface of the base material 17 using the RF-PACVD equipment shown in FIG.

First, the base material 17 to be deposited was washed for 20 minutes using an ultrasonic cleaner in the order of TCE (Trichloroethylene) -acetone-methyl alcohol, and then installed in an electrode 16 to be cooled with water in a vacuum reaction chamber. The vacuum pump 14 was used to maintain a vacuum up to 1.0 × 10 ⁻⁵ torr inside the reaction chamber. Argon gas was injected into the chamber through the gas inlet 15, and the substrate was dry-cleaned using a plasma generated by applying a radio wave power of -400 V to the electrode 16. Reference numeral 11 not illustrated in FIG. 1 denotes an RF matching unit, reference numeral 12 denotes an RF generator, and reference numeral 13 denotes a baratron gauge.

Next, the appropriate ratio of benzene (C ₆ H ₆ ) gas and silane (SiH ₄ ) was adjusted using a mass flow controller (MFC), and then a radio wave power was applied to adjust the ratio of Si in the DLC thin film at 1.2 at.%. Was adjusted to 2.5 at.%.

2. Surface modification

For plasma treatment of the surface of the Si-containing DLC thin film, the thin film obtained above was placed in a reactor as shown in FIG. 1 and subjected to surface treatment with oxygen, nitrogen, hydrogen, and CF ₄ plasma for 10 minutes. The result of measuring the contact angle with pure water in order to analyze the surface energy of the specimen is shown in FIG. 2. The bias voltage during the plasma treatment was -400 V and the pressure was 1.33 Pa.

As shown in FIG. 2, the surface having various characteristics could be formed from a high hydrophilic surface to a hydrophobic surface depending on the gas used in the plasma treatment. As a result of XPS analysis, it was found that the surface of the specimen treated with oxygen plasma was changed to a hydrophilic surface due to the increase of the polar component as the Si-O bond and the CO bond were formed at high concentration. On the other hand, a large amount of CF bonds were present on the surface treated with CF ₄ plasma to change to a hydrophobic surface. This change is due to the sharp decrease in polar component due to CF bonding of the surface (see Table 1).

pellicle

Chemical bonds present on the surface
(XPS analysis)
Water contact angle
(degree) Surface energy (nJ / ㎠) Dispersion
(dispersive
component) Polar component
(polar
component)
sum SiDLC C-C, Si-C 70.1 ± 3.0 28.6 ± 5.2 11.1 ± 3.7 39.7 ± 8.9 SiDLC
(H ₂ treated) C-C, Si-H 67.2 ± 1.8 29.9 ± 3.5 12.3 ± 2.5 42.1 ± 6.0 SiDLC
(CF ₄ treated) CC, Si-C,
-CF _n , C-CF 92.1 ± 2.6 29.9 ± 3.6 1.9 ± 1.1 31.8 ± 2.5 SiDLC
(N ₂ treated) CC, Si-H,
CN 42.7 ± 3.7 26.1 ± 3.2 30.3 ± 4.7 56.4 ± 1.7 SiDLC
(O ₂ treated) CC, CO, Si-H,
Si-O, OH 13.4 ± 1.3 18.0 ± 0.3 53.1 ± 0.8 71.0 ± 1.1

To measure the blood compatibility of these specimens, the specimens were immersed for 60 minutes in platelet-concentrated plasma solution (platelet concentration 3.0x10 ⁸ / ml) obtained from the blood of a healthy person, taken out and washed, and then platelet adhered to the substrate. Was measured. The result is shown in FIG. 3. The parenthesis in the horizontal axis indicates the gas used in the plasma treatment. The platelet adhesion of the surface-treated thin films was less than that of the untreated surface, and platelet adhesion was significantly reduced by nitrogen and oxygen plasma treatment.

Figure 4 shows the shape of platelets attached to the surface treated Si containing DLC thin film. It can be seen that a large amount of platelets are attached and most of the platelets are formed (pseudopodia) or platelets spread on the surface. However, as shown in FIG. 5, the adhesion area of platelets was significantly reduced on the Si-containing DLC thin film treated with oxygen plasma, and most of the adherent platelets remained inactivated. This is a result showing that the blood compatibility of the Si-containing DLC thin film was significantly increased by the oxygen plasma treatment.

[ Experimental Example  1] pure DLC  Thin film and Si  contain DLC  Comparison of Corrosion Resistance of Thin Films

In order to confirm the corrosion resistance of the Si-containing DLC thin film and the pure DLC thin film, in this Experimental Example, the Ti-6Al-4V base material which is widely used as a biomaterial is composed of Si-containing DLC thin film and pure DLC thin film with a bias voltage of -400 V. Coated polarization test was carried out by coating at. The Si composition of the Si-containing DLC thin film used at this time was 2 at.%.

According to FIG. 6, a passivation film was formed on both a Ti-6Al-4V base material, a specimen coated with a pure DLC thin film on the base material, and a specimen coated with a DLC thin film containing silicon on the base material. However, in the case of the base material, as the potential increases, the passivation film is broken at 500 mV, and a rapid increase in current density is observed. The specimens coated with the pure DLC thin film showed very unstable passivation behavior and the passivation film was destroyed at potentials above 800 mV. However, the DLC thin film coated with silicon showed the lowest corrosion current density and very stable passivation behavior. This result shows that the corrosion resistance of DLC thin films containing Si is excellent.

[ Experimental Example  2] Si Comparison of Hydrophilic Contributions of -O and C-O Bonds

The significant increase in blood compatibility by oxygen plasma treatment is due to the Si—O bonds present on the surface. FIG. 7 shows platelets in a specimen coated with pure amorphous Si thin film and then treated with oxygen plasma and a pure amorphous carbon thin film coated with oxygen plasma in order to separate and investigate the effects of Si—O and CO bonding. The degree of adsorption is compared. In each case, the surface has only Si-O bonds and C-O bonds. It was found that the adsorption of platelets was significantly reduced in the oxygen plasma treated Si thin film than in the oxygen plasma treated carbon thin film, indicating that the Si-O bond on the film surface contributed to the improvement of blood compatibility. Giving.

In the above, the present invention has been described with reference to the illustrated examples, which are merely examples, and the present invention may be embodied in various modifications and other embodiments that are obvious to those skilled in the art. Understand that you can.

1 is a schematic diagram of the RF-PACVD equipment used in the present invention.

2 is a result of measuring the contact angle with pure water in order to analyze the surface energy of each specimen when plasma treatment of the Si-containing DLC thin film surface with different reaction gases.

3 is a result of measuring the area ratio of platelets adhered to the surface of each specimen when plasma treatment of the surface of the Si-containing DLC thin film with different reaction gases.

FIG. 4 is an SEM photograph of platelets adhered to the surface of the Si-containing DLC thin film which was not subjected to plasma surface treatment.

5 is a SEM photograph of platelets adhered to the surface of a Si-containing DLC thin film surface treated with an oxygen plasma.

FIG. 6 shows the results of a coin polarization test of the base material itself, a specimen coated with a pure DLC thin film on the base material, and a specimen coated with a Si-containing DLC thin film on the base material.

7 is a result of measuring platelet adhesion behavior in pure amorphous carbon and amorphous Si surface-treated with an oxygen plasma.

Claims (12)

Part of the carbon and silicon atoms in the silicon-containing diamond-like carbon thin film composed of 0.5 to 17 at.% Of silicon and carbon chemically bonds with oxygen or nitrogen atoms existing outside of the thin film, thereby bonding CN to the surface of the thin film. And a Si-N bond, or a CO bond and a Si-O bond. delete delete The silicon-containing diamond-like carbon thin film according to claim 1, wherein a water contact angle of the surface of the thin film is greater than 0 ° and less than 50 °. The medical material characterized by coating the silicon-containing diamond-like carbon thin film according to any one of claims 1 to 4. 6. The medical material according to claim 5, wherein the medical material is a blood vessel stent, a heart valve, a heart pump, an artificial blood vessel, a pathological laboratory substrate for inhibiting blood coagulation, or a blood reservoir. Forming a silicon-containing diamond-like carbon thin film composed of 0.5 to 17 at.% Of silicon and carbon on the base material surface; By activating the surface of the thin film to break some of the CC, C-Si and Si-Si bonds in the thin film, and by chemically bonding the carbon and silicon atoms of the broken sites with oxygen or nitrogen atoms respectively, CN on the surface of the thin film Processes to generate bonds and Si-N bonds, or CO bonds and Si-O bonds Method for producing a silicon-containing diamond-like carbon thin film comprising a. The thin film forming step on the surface of the base material is any one of plasma CVD method, ion beam synthesis method, sputtering synthesis method and self filtration arc synthesis method, or a combination of two or more of these methods. A method for producing a silicon-containing diamond-like carbon thin film, characterized in that. The method for producing a silicon-containing diamond-like carbon thin film according to claim 7, wherein the surface of the thin film is activated by irradiating a plasma or an ion beam to the surface of the thin film. delete delete The method of manufacturing a silicon-containing diamond-like carbon thin film according to claim 7, wherein a water contact angle of the surface of the thin film is greater than 0 ° and less than 50 °.

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