KR100778654B1 - Alpha-Iipoic acid Coating Method of stent for blood vessel - Google Patents

Abstract

The present invention relates to a method of coating a vascular sulfate material, chioctic acid, to prevent oxidation of blood vessels on a stent used to widen narrowed blood vessels when the blood vessels are constricted. In particular, the material of the stent is a cobalt chromium alloy. In the case of the present invention, it is possible to reduce the rate of restenosis of blood vessels after a stent procedure by providing a method of coating chioctic acid using a plasma capable of coating a polymer thin film containing a functional group.

Alpha-lipoic acid, stent

Description

Alpha-Iipoic acid Coating Method of stent for blood vessel

1 is a simplified view showing a manufacturing process of the present invention

Figure 2 is a perspective view of the vessel stent of the present invention

Figure 3 is a state of blood vessel dilation procedure using a common stent

Explanation of symbols for the main parts of the drawings

11: reactor 12: sample holding plate

13: R.F power source 14: network

15: stop valve 16: stream flow control network

17: gas or liquid reservoir 18: pressure gauge

19: door valve 20: vacuum valve

21: electrode 22: stent stent

The present invention relates to a stent for expanding a blood vessel by inserting it into a corresponding area when the blood vessel is narrowed or narrowed, and in particular, when the material of the stent is a cobalt-chromium alloy, a method of coating chitosan to inhibit oxidation of the blood vessel on its surface It is about.

Vasodilation has recently been used in the art of incisions and in the traditional way of dissolving certain vascular blockers.

That is, after securing an inlet of blood vessels by a selling technique or the like, a guide catheter is inserted into the blood vessel and progressed along the vessel to approach the stenosis of the vessel, and a guide-wire in the guide catheter proximate the stenosis. When inserted into the guide wire is guided to the guide catheter is located in the constriction in the curved blood vessel (Fig. 3a). Then, the guide wire is inserted into the balloon catheter to reach the constricted part in the blood vessel, and then the balloon part of the balloon catheter is placed in the constriction part (FIG. 3b), and the air is pressurized by a separate pressurizing means coupled to the coupling part of the balloon catheter. The constriction is enlarged while inflating the portion and compressing the blood vessel blocking material (FIG. 3C).

Since the balloon part having the flexibility of nylon material has a limitation in compressing the blood vessel blocking material, the balloon part is equipped with a stent formed of a mesh of stainless steel material so that the stent is expanded when the balloon part is inflated to increase the compressive strength of the blocker. Heparin is coated on it, which reduces blood clotting on the surface of the stent, thereby solving the problem of stenosis.

However, the conventional method as described above has lowered the restenosis rate compared with the previous, but there is still a restenosis problem, and many researches and attempts have been made in the art to solve it. In particular, it is required to make the stent thinner and prevent restenosis, as well as thrombolytic action of heparin, and also anti-inflammatory action by preventing blood vessel oxidation.

The present invention has been made to solve the above problems, and compared to the case of stainless steel in the stent of the cobalt-chromium (Co-Cr) alloy material of the same strength and can be manufactured about 30% to 40% thinner Chitosan is coated on a cobalt-chromium alloy stent to prevent arteriosclerosis by inhibiting the oxidation of blood vessels by inhibiting the oxidation of blood vessels by the action of the coated chioctic acid after the stent procedure. To a method of coating.

Referring to the process configuration diagram used in the coating process of the present invention with reference to Figure 1, the tube-shaped plasma reactor 11, the electrode 21 provided on the left and right sides of the reactor 11, and the electrode 21 RF power source 13 for supplying power, a pressure gauge 18 connected to the reactor 11 to control the pressure, and a vacuum connected to the reactor 11 to control the vacuum by the door valve 19 It is composed of a pump 20, a stop valve 15 connected to the reactor 11 to supply or shut off a gas or a liquid in the gas or liquid reservoir 17, and a mass flow controller 16.

The sample support plate 12 is fixed inside the reactor, and the stent is positioned on the sample support plate 12.

The above configuration shows an arrangement of components that require a process for chioctic acid coating as an example, and other components or arrangements for the coating process of the present invention will be included in the scope of the present invention.

Figure 2 is a perspective view of the cobalt-chromium alloy stent of the present invention is formed of a mesh and has the characteristics of elasticity and elasticity, and to maintain its shape in a certain form (about 30% ~ 40 compared to conventional stainless-steel material % Thin)

Figure 3 is a state diagram showing each step of the general stent procedure

Figure 3a is a state in which a thin wire is passed through the narrowed portion of the blood vessel (step 1), Figure 3b is a state diagram in which the stent placed on the balloon is placed in the narrowed region (step 2), Figure 3c is a balloon inflated As the stent expands the vessel wall strongly and effectively expands the vessel (step 3), Figure 3d shows the state of the balloon remaining out of the body with air pressure removed (step 4). .

Hereinafter, with reference to the accompanying drawings will be described in detail an embodiment of the method for coating the chioctic acid of the stent according to the present invention.

First, the case where the stent is a cobalt-chromium alloy material and the polymer film is not coated (in this case, a plasma-diaminocyclohexane or the like in which a polymer thin film containing functional groups is coated) should be used.

(Washing process)

The stent 22 of cobalt-chromium alloy material is first cleaned before surface treatment. The cleaning method may be oxygen plasma, argon (Ar) plasma or argon + hydrogen plasma.

That is, after placing the stent 22 on the sample support 12 in the tube-shaped RF plasma reactor 11 and opening the door valve 19, the reactor 11 pressure is 0.01torr. Cleaning is performed using the rotary vacuum pump 20 until it becomes below.

After the stop valve 15 is opened, the gas reservoir 17 is opened to allow oxygen, argon or argon + hydrogen gas to flow therein, and the gas pressure is 0.05 to 5 atmospheres to perform plasma cleaning. The plasma generates a low temperature plasma with an R.F discharge power of about 150W and exposes the stent for 20 minutes or more.

This is because the cobalt-chromium alloy has a weak adhesive strength of the thin film coated later than the conventional stainless steel material, so that the discharge power (150W) and the exposure time (more than 20 minutes) are extended so that the stent surface is etched by the sputtering phenomenon. It is to improve the adhesive strength by increasing the roughness.

(Surface modification process)

When the washing process is completed, the inside of the reactor 11 is adjusted to a vacuum at 0.01 atmosphere or less, and diaminocyclohexane vapor is introduced into the liquid reservoir 17, and the gas pressure flows to be 0.01 to 0.5 torr. Adjust the speed. The R.F discharge power is 5 to 100 watts (W) to generate a low temperature plasma, and the stent 22 is exposed for 5 to 20 minutes to form a thin film.

After the surface of the stent 22 is modified as described above, the stop valve 15 is closed and cleaned at a pressure of 0.01 atm or less, and then air is introduced to allow the modified stent 22 to flow out into the air. . This coats the polymer thin film containing the functional group.

(Chioctic acid grafting process)

When the surface modification process is completed, the stent 22 is 5 ~ 80 by using a chioctic acid solution to which a small amount of chioctic acid, sodium citrate and cyanamide are added at 25 to 50 ° C. A stent made of cobalt-chromium alloy completely coated with chioctic acid is prepared by dipping for a minute and washing it in deionized water for about 1 minute to remove weakly bound chioctic acid.

So far, an embodiment of the present invention has been described.

In the above embodiment, an allyl alcohol (allyl-arcohol) plasma may be used instead of the diaminocyclohexane plasma of the surface modification process.

The diaminocyclohexane plasma treatment is for imparting an amine group, because the hydroxyl group capable of chemically bonding to a carboxyl group (COOH) in chioctic acid can be imparted to the allyl alcohol plasma treatment.

In this case, in the surface modification process of the embodiment, the R.F discharge power is preferably 20W to 30W, and the stent 22 exposure time is 5 to 10 minutes.

This is because the allyl alcohol has a thin film coating that is easier than diaminocyclohexane, and when the discharge power is too high, it is difficult to preserve the hydroxyl group.

Next, when the stent is a cobalt-chromium alloy material and the polymer film is coated, another embodiment of coating chioctic acid will be described.

In this case, there is no need to coat the polymer thin film, so the process conditions will be slightly different. First, the washing process is basically the same as the above embodiment, but the R.F discharge power is preferably 20W or less and the exposure time is 5 minutes or less. This is because the surface of the polymer may be damaged if the exposure time is too long or the discharge power is too high. In addition, water vapor (H 2 O) may be used for the type of gas.

In the surface modification process, a carboxyl group may be provided by using vapor-phase grafting. That is, after the washing process and the activation process are completed, the pressure is lowered back to 0.01 atm to the vacuum pump 20, and then, the acrylic acid vapor is introduced into the reactor 11 for 1 to 10 minutes. The acrylic acid molecules are chemically bonded to the surface of the stent 22 by being brought into contact with the treated surface to impart a carboxyl group.

So far, another embodiment of the present invention has been described.

In the above embodiments, the chioctic acid solution of the chioctic acid grafting process may be preferably configured as follows.

Add 22 g of sodium citrate to 1 liter of water to make a solution of sodium citrate and use 1N HCI to bring the acidity (pH) to 5 (pH 7-9 is possible, but pH 5 is preferred).

To 20 ml of the solution was added 0.05 g of chioctic acid and 0.04 g of cyanamide, and then activated at room temperature for 1 hour.

The sodium citrate solution may be a mixed solution using cesium carbonate or cesium hydrogen carbonate instead of sodium citrate.

In the embodiments of the present invention, it is included in the scope of the present invention to change the general elements other than the functional group applying process conditions using the low temperature plasma treatment, which is essential for coating the stent of the cobalt-chromium alloy material with chioctic acid. something to do.

As described above, the present invention is a beneficial invention for releasing the arteriosclerosis by inhibiting inflammation by coating a sulfated substance of blood vessels on the stent even after vasodilation, thereby releasing the human body from the disease.

Claims (5)

In the method of coating a blood vessel sulfate material of a blood vessel stent, A cleaning process of removing a substance attached to the surface of the stent of the cobalt-chromium alloy material by using oxygen, argon or argon + hydrogen plasma; After the washing process, the inside of the reactor is adjusted to a vacuum at 0.01 atm or less, diaminocyclohexane vapor is introduced into the liquid reservoir, the flow rate is adjusted so that the gas pressure is 0.01 to 0.5 atm, and the RF discharge power is 5 to 100 watts ( W) to generate a low-temperature plasma and to expose the stent for 5 to 20 minutes to cover the polymer thin film containing a functional group, and After the surface modification process, a small amount of chioctic acid, sodium citrate, and cyanamide-added chioctic acid solution was added at 25 ° C. to 50 ° C. for 5 minutes to 80 minutes, and then taken out to remove weakly bound chioct acid. Chioctic acid coating method of vascular stent, characterized by having a chioctic acid grafting process The method of claim 1, wherein the chioctic acid solution, Add 220 g of sodium citrate, cesium carbonate or cesium hydrogen carbonate to 1 liter of water to make a mixed solution. Use 1N (normal concentration) HCI to make acidity (pH) 5 ~ 9. After adding about 0.05g and about 0.04g of cyanamide, it is activated for about 1 hour at room temperature. The method of claim 1, Allyl alcohol plasma was used instead of the diaminocyclohexane plasma in the surface modification process, and the discharging power was 20W to 30W and the stent exposure time was 5 to 10 minutes to give hydroxyl groups capable of chemical bonding with carboxyl groups in chioctic acid. Chioctic acid coating method of blood vessel stent The method of claim 1, If the stent is coated with a polymer film, in the cleaning process, the R.F discharge power is less than 20W, exposure time is less than 5 minutes, chitosan coating method of vascular stents, characterized in that  The method of claim 4, wherein After the surface modification process, by lowering the pressure of the reactor to 0.01torr and introducing acrylic acid vapor to be in contact for 1 to 10 minutes, the acrylic acid molecules are chemically bonded to the surface of the stent to provide a carboxyl group. Chioctic acid coating method of vascular stent

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