WO2016010196A1

WO2016010196A1 - Stent

Info

Publication number: WO2016010196A1
Application number: PCT/KR2014/009962
Authority: WO
Inventors: 박도현; 한종현; 김은진; 박헌국; 장봉석; 윤호; 김선종
Original assignee: 주식회사 엠아이텍; 박도현
Priority date: 2014-07-15
Filing date: 2014-10-22
Publication date: 2016-01-21
Also published as: KR20160008758A; KR101696809B1

Abstract

The present invention relates to a stent comprising: a hollow tube-shaped stent body in which multiple metal wires having a plurality of curves are cross-linked to each other; and a coating film formed so as to cover the surface of the stent body, wherein silver (Ag) particles for inhibiting bacterial growth in a lesion region may be added in the coating film. According to the present invention, the silver particles contained in the coating film have an anti-bacterial effect which prevents the growth of bacteria in a lesion region, the coating film of the stent prevents a direct contact between a lesion region in the biliary tract and a blood vessel and substances passing through the stent, and the contact surface of the coating film formed on the stent supports the inner wall of the biliary tract and the blood vessel, thereby preventing in-stent restenosis of the biliary tract and the blood vessel, which is caused by neointima penetrating into the stent.

Description

Stent

The present invention relates to stents.

When the flow of blood or body fluids, such as blood vessels and biliary tracts, is not smooth due to the occurrence of malignant or benign diseases, various diseases may occur.

In the case of blood vessels, blood circulation disorders and muscle pain may be caused, and in severe cases, the site may need to be cut, and in the case of biliary tract, fever and jaundice may be reduced due to tumor narrowing or obstruction. Symptoms such as itching and sepsis may occur.

In order to treat such a disease, balloon dilatation is performed to expand the inner walls of narrowed blood vessels and biliary tract by inserting a balloon catheter or the like into blood vessels and biliary tract.

However, such balloon dilatation has a problem that stenosis may occur after the procedure is narrowed or blocked again due to chronic contraction of neovascularized biliary tract and endothelium proliferation.

In order to solve this problem, Korean Laid-Open Patent Publication No. 2012-0138974 (announced: 2012.12.27, hereinafter referred to as the prior art) after the angioplasty, by inserting the inside of the blood vessels by supporting the inner wall of the vessel, A stent is proposed to prevent stenosis of blood vessels caused by chronic contraction.

However, in the prior art, since the stent supporting the blood vessel is composed of only metal wires, bacteria, such as blood, bile, and protein debris, may pass through the lesion, and bacteria may grow on the lesion, and the substance may pass through the stent. There is a problem that can not prevent contact with the lesion site, the neo-intima can proliferate into the gap of the wire, the restenosis may occur.

The present invention is to solve the above-described problems, to prevent bacterial growth of the lesion site, to adhere to the blood vessels and biliary tract to protect the lesion site from the substance, preventing the restenosis of blood vessels and biliary tract due to the proliferation of neointimal The purpose is to provide a stent.

In order to achieve the above object, the stent of the present invention includes a plurality of metal wires having a plurality of bends connected to each other, and a tube-shaped stent body having a hollow therein; And a coating film formed to surround the surface of the stent body, wherein the coating film may be added with silver particles for inhibiting bacterial growth of the lesion site.

The coating film may be formed of a polymer solution in which silver (Ag) particles are added to at least one of medical polyurethane, silicone urethane copolymer, silicone, polyamide, polyester, or fluorocarbon resin.

On the other hand, the stent manufacturing method of the present invention, a) preparing a stent body so that the coating film is formed evenly; b) loading the polymer solution containing silver particles into the electrospinning apparatus; And c) spraying a polymer solution to which the silver particles are added to the stent body to form a coating film.

Here, the step a), washing and drying the stent body to remove the foreign matter; And inserting and fixing the stent body to a roller-shaped collector provided in the electrospinning apparatus.

And, step b), the step of adding and stirring the silver particles in the polymer solution; And loading the polymer solution in which the silver particles are added to the electrospinning apparatus.

In addition, the step c), the step of spraying a polymer solution containing the silver particles loaded in the electrospinning device to the stent body; And putting the stent body coated with the polymer solution to which the silver particles were added, into a drying oven, firstly dried at 35 ° C. for 30 minutes, and secondly drying at 180 ° C. for 3 hours to form a coating film. can do.

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

First, through the antimicrobial action of silver particles, it is possible to prevent bacterial growth in the lesion area.

Second, the coating layer formed on the stent can prevent the substance passing through the lesion area of the biliary tract and blood vessels to contact the lesion site through the stent.

Third, by the contact surface of the coating layer formed on the stent to support the biliary tract and the blood vessel inner wall, it is possible to prevent the restenosis of the biliary duct and blood vessels generated by the neointima penetrating into the stent.

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

Figure 2 is the antimicrobial test results of E. coli (Escherichia coli ATCC 8739) of the coating film and the general coating film containing the silver particles of the present invention.

Figure 3 is the antimicrobial test results for pneumococcal (Klebsiella pneumoniae ATCC 4352) of the coating film and the general coating film containing the silver particles of the present invention.

Figure 4 shows the results of ion detection of the coating film containing silver particles by FE-SEM and EDX scanning electron microscope.

Figure 5 is a flow chart showing a method of manufacturing a stent according to an embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings, and the well-known technical parts will be omitted or compressed for brevity of description.

<< 스텐트의 구성Composition of the stent >>

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

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

In addition, the laser cutting method may be provided by cutting the metal in the form of a tube.

The stent body 110 may be formed of a shape memory alloy material such as nickel-titanium alloy, and thus, the stent body 110 may be expanded or contracted in a circumferential direction at a specific temperature.

In addition, the stent body 110 inserted into the biliary tract and the lesion of the blood vessel may be expanded in the direction of the biliary tract and the inner wall of the blood vessel to support the inner wall.

The coating film 120 is formed surrounding the stent body 110 to prevent the substance passing through the biliary tract and the blood vessel lesion from directly contacting the lesion, and the stent body 110 expands in the direction of the biliary tract and the blood vessel inner wall. When the inner wall is supported, the area in contact with the inner wall is enlarged so that the inner wall is in close contact with the lesion.

Here, the polymer furnace 122 for forming the coating film 120 may be used at least one polymer 122 of medical polyurethane, silicone urethane copolymer, silicone, polyamide, polyester and fluororesin solution, but It is not limited.

In addition, the bile and protein residues passing through the lesion can be a bacterial growth on the lesion, by adding the silver particles 124 to the polymer 122 can prevent the growth of bacteria through antibacterial.

At this time, the size of the silver particles 124 is not limited, but the silver particles 124 according to an embodiment of the present invention is preferably provided with a size of 100nm ~ 300nm.

Hereinafter, through the results of experiments and experiments, to determine the antimicrobial power of the coating film 120 including the silver particles (124).

<< 은 입자가 함유된 고분자를 이용한 항균 실험Antimicrobial Experiments Using Polymers Containing Silver Particles >>

Figure 2 is the antimicrobial test results of the E. coli (Escherichia coli ATCC 8739) of the coating film and the general coating film containing silver particles of the present invention, Figure 3 is a pneumococcal (Klebsiella) of the coating film and the general coating film containing silver particles of the present invention pneumoniae ATCC 4352).

The antimicrobial test on the coating film containing silver particles was performed by Bioteca Co., Ltd., and the comparative experiments of the coating film containing silver particles and the general coating film containing no silver particles were performed.

Here, a silicone solution was used as a polymer for forming a coating film containing silver particles and a general coating film.

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

In addition, strains for antimicrobial experiments are capable of breeding in the biliary tract and blood vessels, and Escherichia coli (Escherichia coli ATCC 8739) and pneumococcus (Klebsiella Pneumoniae ATCC 4352) capable of producing toxins were used.

Accelerated aging tests are designed to increase the rate of chemical or physical deterioration of medical devices under harsh temperature conditions, in order to test them for a short period of time, corresponding to the actual shelf life of the product, based on the stability test criteria of the medical device. testing).

At this time, the accelerated aging test was performed for 97 days on the basis of three years, which is the warranty period of the stent 100 family, and the accelerated aging time (AAT), which is the basis of 97 days, was obtained through Equation 1 below.

[Correction under Rule 91 13.03.2015]

In this equation, the ambient temperature is 25 ° C, the accelerated aging temperature 60 ° C, and the aging coefficient 2 is obtained to obtain an accelerated aging coefficient (AAF) of about 11.3137, and 3 years (1095 days) of the shelf life of the stent-related products. ) Was divided by the accelerated aging coefficient (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 particles 124, through an accelerated aging test for 97 days at a temperature of 60 ℃ containing the strain, the same as the environment exposed to the strain for 3 years at 25 ℃ room temperature I was able to get the data.

[실험예1]Experimental Example 1

In accordance with JIS Z 2801, the E. coli (Escherichia coli ATCC 8739) microbial solution was inoculated into a chalet containing a general coating film, a coating film containing 150 nm silver particles and a coating film containing 250 nm silver particles, and then ± 35 ° C. The experiment was carried out by measuring the number of bacteria after stationary culture for 24 hours at a temperature of 1 ° C. and a relative humidity of 90 ± 5% to obtain the results shown in Table 1.

[Revisions under Rule 91 19.03.2015]

In addition, E. coli (Escherichia coli ATCC 8739) inoculum was inoculated into a separate coating film and a coating film containing 250 nm silver particles, and cultured for 97 days at a temperature of 60 ° C. to carry out an accelerated aging test. The result shown in Table 2 was obtained.

[Revisions under Rule 91 19.03.2015]

As shown in Table 1, it was difficult to confirm the correlation between the surface area of the silver particles and the antimicrobial activity according to the size of the silver particles, but the antimicrobial activity was confirmed through the coating film containing the 250 nm silver particles having a larger particle size than 150 nm.

[실험예2]Experimental Example 2

In accordance with JIS Z 2801, the bacterial solution of Klebsiella Pneumoniae ATCC 4352 was inoculated into a chalet containing a general coating film, a coating film containing 150 nm silver particles and a coating film containing 250 nm silver particles, and then inoculated at 35 ° C. The experiment was carried out by measuring the number of bacteria after stationary culture for 24 hours at a temperature of ± 1 ℃ and a relative humidity of 90 ± 5% to obtain the results shown in Table 3.

[Revisions under Rule 91 19.03.2015]

In addition, inoculated with a separate common coating film and a coating film containing silver particles of 250nm size inoculated pneumococcal bacteria (Klebsiella Pneumoniae ATCC 4352), and the accelerated aging test by measuring the number of bacteria by standing at a temperature of 60 ℃ for 97 days. The result was obtained as in Table 4.

[Revisions under Rule 91 19.03.2015]

JIS (Japanese Industrial Standard) stipulates that the cell growth rate on the surface of the antimicrobial processed product is less than 100% (antimicrobial activity value 2 or more) compared to the surface of the non-microbial processed product. In the results of Experimental Example 1 and Experimental Example 2, the accelerated aging test of the general coating film containing no silver particles recorded a value of 0.2 or less, but the antimicrobial activity of the coating film containing the silver particles was found to be 6.0 or higher. It can be confirmed that the antimicrobial activity against E. coli and pneumococcal bacteria of the coating film containing the particles has been proved.

In addition, by requesting KTL (Korea Institute of Industrial Technology), the ion detection of the coating film containing the silver particles using the FE-SEM and EDX scanning electron microscope was performed, 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 particles, respectively, and Ag ions were not detected at this time.

Here, the silver particles were not directly exposed to the outside by the polymer forming the coating film, so only ions constituting the polymer were detected, and the antimicrobial activity was confirmed even when the silver particles and the strain were not directly contacted.

<< 스텐트의 제조 방법How to Make a Stent >>

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

Here, the step S100 may include the step of removing the foreign matter by washing and drying the stent main body 110 so that the coating film is formed evenly, and inserting and fixing the stent main body 110 to the roller-type collector provided in the electrospinning apparatus. have.

Next, a step of preparing a polymer 122 solution for forming a coating film is made by spraying the stent body 100 prepared in step S100.

In this case, adding and stirring the silver particles 124 to the polymer 122 solution may include loading the polymer solution to which the silver particles 124 are added to the electrospinning apparatus.

Finally, the step of forming a coating film 120 by spraying a polymer solution containing the silver particles 124 to the stent body 110 (S300).

Here, after spraying the polymer solution to which the silver particles 124 loaded in the electrospinning apparatus is added to the stent body 110 fixed to the collector, put in a drying oven and dried first at 35 ° C. for 30 minutes, 180 ° By secondary drying at a C temperature for 3 hours, the stent on which the coating film 120 containing the silver particles 124 is formed can be manufactured.

After all, the present invention, the antimicrobial action of the silver particles to prevent the growth of bacteria in the lesion due to bile and protein residues, is installed on the lesion to protect the lesion from contact of the material passing through the stent, The coating film adheres closely to the inner wall of the lesion site, thereby providing a stent that prevents the neointima of the lesion site from being generated into the stent.

As described above, the detailed description of the present invention has been made by the embodiments with reference to the accompanying drawings. However, since the above-described embodiments have only been described with reference to preferred examples of the present invention, the present invention is limited to the above embodiments. It should not be understood that the scope of the present invention is to be understood by the claims and equivalent concepts described below.

(Explanation of the sign)

100: stent

110: stent body

120: coating film

122: polymer

124 silver particles

Claims

A plurality of metal wires having a plurality of bends cross-connected to each other and having a hollow tube-like stent body; And

It includes; coating film formed to surround the surface of the stent body,

The coating film is characterized in that the silver (Ag) particles for inhibiting the growth of bacteria in the lesion area is added

Stent.
The method of claim 1,

The coating film is formed of a polymer solution in which silver particles are added to at least one of medical polyurethane, silicone urethane copolymer, silicone, polyamide, polyester, or fluororesin.

Stent.
a) preparing a stent body so that the coating film can be formed evenly;

b) loading the polymer solution containing silver particles into the electrospinning apparatus; And

c) spraying a polymer solution to which the silver particles are added to the stent body to form a coating film.

Stent manufacturing method.
The method of claim 3,

Step a) is

Washing and drying the stent body to remove foreign substances; And

And inserting and fixing the stent body to a roller-shaped collector provided in the electrospinning apparatus.

Stent manufacturing method.
The method of claim 3,

B),

Adding the silver particles to the polymer solution and stirring the solution; And

And loading the polymer solution to which the silver particles have been added to the electrospinning apparatus.

Stent manufacturing method.
The method of claim 3,

C),

Spraying a polymer solution containing the silver particles loaded in the electrospinning device onto the stent body; And

Putting the stent body coated with the polymer solution to which the silver particles are added in a drying oven first dried at 35 ° C. for 30 minutes, and second drying at 180 ° C for 3 hours to form a coating film; Characterized by

Stent manufacturing method.