KR101675883B1 - Methods for manufacturing stent - Google Patents

Abstract

The present invention relates to a method of manufacturing a stent, comprising the steps of: a) preparing a stent body so that a coating film can be formed evenly; b) charging the electrospinning device with a polymer solution to which silver nanoparticles have been added; And c) injecting a polymer solution containing silver nanoparticles into the stent body to form a coating film. In the step c), the polymer solution containing the silver nanoparticles loaded in the electrospinning device Injecting the stent into the stent body; And a step of placing the stent body coated with the polymer solution to which silver nanoparticles have been added in a drying oven, firstly drying at 35 ° C for 30 minutes, and secondarily drying at 180 ° C for 3 hours to form a coating film can do.
According to the present invention, the antibacterial action of the silver nanoparticles contained in the coating film prevents the bacterial growth of the lesion site, and the coating film of the stent prevents direct contact between the lesion site of the bile duct and the blood vessel and the material passing through the stent, The contact surface of the formed coating film has an effect of preventing restenosis of the biliary tract and blood vessels caused by penetration of the neointima into the stent by supporting the inner wall of the bile duct and the blood vessel.

Description

[0001] METHODS FOR MANUFACTURING STENT [0002]

The present invention relates to a method for manufacturing a stent.

Various diseases can occur when the flow of blood or body fluids such as blood vessels and bile ducts is not smooth due to the occurrence of malignant or benign diseases.

In the case of blood vessels, blood circulation disorder and muscle pain may be induced. In the case of severe symptoms, it may be necessary to sever the affected part. In the case of bile ducts, when the bile is narrowed or closed by tumor, , Itching, and sepsis may occur.

To treat these diseases, balloon catheters and other devices have been inserted into the blood vessels and bile ducts to expand the narrowed vessels and the inner wall of the bile ducts.

However, such balloon dilatation may cause restenosis due to narrowing or clogging of blood vessels and bile ducts after the procedure due to chronic shrinkage of the expanded blood vessels and bile ducts and neointimal hyperplasia.

In order to solve such a problem, in Korean Patent Laid-Open Publication No. 2012-0138974 (Announcement: 2012.12.27, hereinafter referred to as prior art), after the angioplasty, the blood vessel is inserted into the blood vessel to support the inner wall of the blood vessel, Stent to prevent vessel restenosis caused by chronic contraction of the stent.

However, in the prior art, since the stent supporting the blood vessel is composed only of a metal wire, bacteria may multiply in a lesion site due to substances such as blood, bile and protein breakage that pass through the lesion site, and substances passing through the stent The lesion can not be prevented from coming into contact with the lesion site, and the new internal membrane can propagate through the gap of the wire, resulting in restenosis.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to prevent bacterial growth of a lesion site, to protect a lesion site from a substance adhered to blood vessels and bile ducts, and to prevent restenosis of vessels and bile ducts due to proliferation of neointima The purpose of the stent is to provide.

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In order to achieve the above object, the present invention provides a stent manufacturing method comprising the steps of: a) preparing a stent body so that a coating film can be uniformly formed; b) charging the electrospinning device with a polymer solution to which silver nanoparticles have been added; And c) injecting a polymer solution containing silver nanoparticles into the stent body to form a coating film. In the step c), the polymer solution containing the silver nanoparticles loaded in the electrospinning device Injecting the stent into the stent body; And a step of placing the stent body coated with the polymer solution to which silver nanoparticles have been added in a drying oven, firstly drying at 35 ° C for 30 minutes, and secondarily drying at 180 ° C for 3 hours to form a coating film can do.
The step a) may include washing and drying the stent body to remove foreign substances; And inserting and fixing the stent body into a roller-type collector provided in the electrospinning apparatus.

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In addition, the step b) may include adding the silver nanoparticles to the polymer solution and stirring the polymer solution; And loading the polymer solution added with the silver nanoparticles into the electrospinning device.

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As described above, the present invention has the following effects.

First, through the antibacterial action of silver nanoparticles, it is possible to prevent the growth of bacteria in lesion sites.

Second, the coating layer formed on the stent can prevent the material passing through the lesion area of the bile duct and the blood vessel from contacting the lesion area through the inside of the stent.

Third, since the contact surface of the coating layer formed on the stent supports the bile duct and the inner wall of the blood vessel, it is possible to prevent restenosis of the bile duct and blood vessel caused by penetration of the new inner wall into the stent.

1 is a perspective view illustrating a section of a stent and a stent according to an embodiment of the present invention.
FIG. 2 shows the result of the antibacterial test on the coating film containing silver nanoparticles of the present invention and a common coating film of Escherichia coli ATCC 8739.
FIG. 3 shows the antibacterial test results of the coating film containing the silver nanoparticles of the present invention and the common coating film against pneumococcal bacteria (Klebsiella pneumoniae ATCC 4352).
Fig. 4 shows the result of ion detection of a coating film containing silver nanoparticles through FE-SEM and EDX scanning electron microscope.
5 is a flowchart illustrating a method of manufacturing a stent according to an embodiment of the present invention.

The preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings, in which the technical parts already known will be omitted or compressed for simplicity of explanation.

< Stent  Configuration >

1 is a perspective view illustrating a section of a stent and a stent according to an embodiment of the present invention.

The stent 100 according to an embodiment of the present invention may include a coating layer 120 formed of a stent body 110 and a polymer 122 containing silver nanoparticles 124.

The stent body 110 may include a plurality of metal wires 112 having a wavy shape along the longitudinal direction and connected in various shapes such as a lattice shape or a mesh shape, and may be provided in a cylindrical shape having a hollow in the longitudinal direction.

In addition, a tube-shaped metal can be cut and processed through a laser cutting method.

The stent body 110 may be a shape memory alloy material such as a nickel-titanium alloy, and the stent body 110 may expand or contract in the circumferential direction at a specific temperature.

In addition, the stent body 110 inserted into the lesion of the biliary tract and blood vessels may expand toward the inner wall of the bile duct and blood vessels to support the inner wall.

The coating layer 120 is formed to surround the stent body 110 to prevent direct contact of the material passing through lesions of the bile duct and the blood vessel to the lesion site and to prevent the stent body 110 from expanding toward the bile duct and the inner wall of the blood vessel When the inner wall is supported, the area of contact with the inner wall is enlarged, so that it can be brought into close contact with the lesion site.

At least one polymer 122 of medical polyurethane, silicone urethane copolymer, silicone, polyamide, polyester and fluorine resin solution may be used as the polymer 122 forming the coating layer 120, It is not limited.

In addition, bacteria can be proliferated in the lesion area due to bile and protein residue passing through the lesion site, and the addition of the silver nanoparticles 124 to the coating layer 120 can prevent the growth of bacteria through antibacterial action.

Hereinafter, the antibacterial activity of the coating film 120 including the silver nanoparticles 124 will be examined through experiments and experiments.

< Silver nano  Antibacterial experiment using polymer containing particles >

FIG. 2 shows the result of the antibacterial test for the coating film containing silver nanoparticles of the present invention and the coating film of Escherichia coli (ATCC 8739). FIG. 3 is a graph showing the results of the antibacterial test for the silver nanoparticles of the present invention and Klebsiella pneumoniae ATCC 4352).

The antimicrobial test for the coating film containing silver nanoparticles was carried out by Biotec Co., Ltd., and a comparative experiment between a coating film containing silver nanoparticles and a general coating film containing no silver nanoparticles was performed.

Here, a silicon solution was used as a coating film containing silver nanoparticles and a polymer forming a general coating film.

The coating film containing silver nanoparticles was prepared by adding silver nanoparticles to the silicon solution at a concentration of 1000 ppm or less.

Escherichia coli ATCC 8739 and Klebsiella pneumoniae ATCC 4352 were used as the strains for the antimicrobial experiments, which can breed biliary tract and blood vessels and produce toxins.

Accelerated aging tests designed to increase the rate of chemical or physical degeneration of medical devices in harsh temperature conditions and so on in order to test for a short period of time in accordance with the stability test standards of medical devices, testing.

At this time, the accelerated aging test was performed for 97 days based on the 3-year guarantee period of the product family of the stent (100), and the accelerated aging time (AAT) as a basis for 97 days was obtained through the following equation (1).

Here, the ambient temperature was about 11.3137 at the ambient temperature of 25 ° C, the accelerated aging temperature of 60 ° C, and the aging factor of 2 to obtain the accelerated aging factor (AAF) of about 11.3137. The effective life of the stent- ) Was divided by the accelerated aging factor (AAF) to obtain an accelerated aging time of about 96.7853 days.

That is, for the verification of the coating film 120 containing the silver nanoparticles 124, the same accelerated aging test for 97 days at a temperature of 60 DEG C containing the strain was conducted, Data was obtained.

[ Experimental Example 1 ]

Escherichia coli ATCC 8739) was inoculated into a chalet containing a common coating film, a coating film containing silver nanoparticles having a size of 150 nm and a coating film containing silver nanoparticles having a size of 250 nm in accordance with JIS Z 2801, The results were as shown in Table 1, by measuring the number of bacteria after the incubation for 24 hours at a temperature of 1 ° C and a relative humidity of 90 ± 5%.

An Escherichia coli ATCC 8739 strain was inoculated into a coating film containing a common coating film and 250 nm silver nanoparticles and incubated at a temperature of 60 ° C for 97 days to perform an accelerated aging test Table 2 shows the results.

In Table 1, it was difficult to confirm the relationship between the surface area and the antibacterial activity of the particles according to the size of the silver nanoparticles. However, the antibacterial activity was confirmed through the coating layer containing the silver nanoparticles having a particle size larger than 150 nm.

[ Experimental Example 2 ]

Klebsiella pneumoniae ATCC 4352 was inoculated into a chalet containing a common coating film, a coating film containing silver nanoparticles having a size of 150 nm and a coating film containing silver nanoparticles having a size of 250 nm, respectively, according to JIS Z 2801, Experiments were carried out by measuring the number of bacteria after the incubation at a temperature of ± 1 ° C and a relative humidity of 90 ± 5% for 24 hours. The results are shown in Table 3.

In addition, an accelerated aging test was conducted by inoculating pneumococcal bacteria (Klebsiella pneumoniae ATCC 4352) in a coating film containing a common coating film and 250 nm-sized silver nanoparticles, and allowing the bacteria to stand at 60 ° C for 97 days. And the results are shown in Table 4.

According to JIS (Japanese Industrial Standards), the antimicrobial activity of a product that has been subjected to antimicrobial treatment compared with the surface of a product that has not been subjected to antimicrobial treatment has an antimicrobial effect when the cell growth rate is less than 1 part or less , The results of Experimental Example 1 and Experimental Example 2 showed a value of 0.2 or less in the accelerated aging test of a general coating film containing no silver nanoparticles. However, the antibacterial activity value of the coating film containing silver nanoparticles was found to be 6.0 or more, The antibacterial activity against the Escherichia coli and the pneumococcal bacteria of the coating film containing particles can be confirmed.

In addition, KTL (Korea Institute of Industrial Technology) has performed ion detection of a coating film containing silver nanoparticles using FE-SEM and EDX scanning electron microscope, and will be described with reference to FIG.

As shown in FIG. 4, ions of Si, Ni, O, C and CO were detected in the coating film containing silver nanoparticles, and Ag ion was not detected at this time.

Here, since the polymer forming the coating film does not directly expose the silver nanoparticles to the outside, only the ions constituting the polymer are detected, and it is confirmed that the antibacterial effect is achieved even though the silver nanoparticles and the strain are not in direct contact with each other.

< Stent  Manufacturing method >

5 is a flowchart illustrating a method of manufacturing a stent according to an embodiment of the present invention.

First, the step of preparing the stent body 110 is preceded. (S100)

In step S100, a step of washing and drying the stent body 110 to remove foreign substances and inserting and fixing the stent body 110 into a roller-type collector provided in the electrospinning device may be included so that the coating film can be uniformly formed have.

Next, a step of preparing a polymer solution for forming a coating film by spraying on the stent body 100 prepared in step S100 is performed (S200)

The silver nanoparticles 124 may be added to the polymer 122 solution to stir the silver nanoparticles 124 to the electrospinning device.

At least one polymer 122 of medical polyurethane, silicone urethane copolymer, silicone, polyamide, polyester and fluorine resin solution may be used as the polymer 122 forming the coating layer 120, It is not limited.

Finally, a coating solution 120 is formed by injecting a polymer solution containing silver nanoparticles 124 into the stent body 110. In operation S300,

Here, the polymer solution to which the silver nanoparticles 124 loaded in the electrospinning device were added was injected into the stent main body 110 fixed to the collector, then dried in an oven, dried at 35 ° C for 30 minutes, C for 3 hours to prepare a stent having a coating film 120 containing silver nanoparticles 124 formed thereon.

As a result, it is possible to prevent the growth of bacteria in the lesion site due to the bile and protein residue through the antibacterial action of the silver nanoparticles, to protect the lesion site from the contact of substances passing through the inside of the stent, The present invention provides a stent for preventing a neointima of a lesion site from being generated in a stent by supporting a coating film in close contact with an inner wall of a lesion site.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. And the scope of the present invention should be understood as the following claims and their equivalents.

100: stent
110: stent body
120: Coating film
122: Polymer
124: Silver nanoparticles

Claims (6)

delete delete a) preparing a stent body so that a coating film can be formed evenly;
b) charging the electrospinning device with a polymer solution to which silver nanoparticles have been added; And
c) forming a coating layer by spraying a polymer solution containing the silver nanoparticles on the stent body,
The step c)
Injecting the polymer solution added with the silver nanoparticles loaded in the electrospinning device into the stent body; And
The stent body to which the silver nanoparticle-added polymer solution is applied is placed in a drying oven and dried at 35 ° C for 30 minutes and then dried at 180 ° C for 3 hours to form a coating film Characterized by
A method for manufacturing a stent.
The method of claim 3,
The step a)
Washing and drying the stent body to remove foreign substances; And
And inserting and fixing the stent body into a roller-type collector provided in the electrospinning apparatus
A method for manufacturing a stent.
The method of claim 3,
The step b)
Adding the silver nanoparticles to the polymer solution and stirring the mixture; And
And charging the electrospinning device with the polymer solution added with the silver nanoparticles
A method for manufacturing a stent.
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