KR101807603B1

KR101807603B1 - Plate type-artificial blood stent having excellent expansiveness and flexibility

Info

Publication number: KR101807603B1
Application number: KR1020150090970A
Authority: KR
Inventors: 박주철; 안진효; 조준래
Original assignee: 주식회사서륭
Priority date: 2015-06-26
Filing date: 2015-06-26
Publication date: 2018-01-19
Also published as: KR20170001845A

Abstract

The plate-type artificial blood vessel stent according to the present invention is excellent in swelling force and flexibility, including: a plate-shaped artificial blood vessel woven with a Teflon fabric; And a plate-shaped metal stent which is shaped and stored in a cylindrical shape by etching a metal plate by a photolithography process. The artificial blood vessel and the metal stent are characterized in that a metal stent is stacked and fixed on the outer surface of the artificial blood vessel. According to a preferred embodiment of the present invention, the plate-type artificial blood vessel stent is manufactured by fixing a suture to a metal stent, inserting a synthetic blood vessel into the metal stent (lower portion), sealing the artificial blood vessel and the metal stent, In order to further increase the sealing performance and adhesion stability of the artificial vascular stent, a medical adhesive is used to adhere the stent to the artificial blood vessel, and the artificial vascular stent is designed so that it can be easily inserted into the catheter.

Description

[0001] Plate type-artificial blood stents having excellent expansiveness and flexibility [

More specifically, the present invention relates to an artificial vessel stent, which is a peripheral blood vessel treatment material manufactured by combining a plate-shaped artificial blood vessel and a cylindrical shape-processed metal stent, and has excellent flexibility, To a platelet-shaped blood vessel stent capable of being easily transported and having excellent expansion force, excellent in fitting ability, and excellent in inflation force and flexibility.

A blood vessel is a distribution network of blood that extends from the heart and connects from head to toe. In order for the blood that is pushed out from the heart to properly supply nutrients and oxygen to the organs and cells of the body, the blood vessels must be connected to the body end. It is a well-known fact to do.

In recent years, cardiovascular diseases as well as peripheral vascular diseases are increasing due to aging of blood vessels due to drinking, smoking and aging society. As the age of onset of adult diseases is gradually lowered due to westernization of eating habits, interest in health is increasing.

Vascular disease is the second most serious cause of death in Korea after cancer. According to the National Statistical Office (NSO), in 2009, Korea's vascular disease mortality rate was higher than the OECD average, and the number of patients visiting the hospital due to vascular disease increased year by year, exceeding 500,000 already (2009 Health Insurance Evaluation and Assessment Service).

Vascular disease is a disease in which blood vessels that block the blood supply to the body are clogged or burst and the brain is damaged in a part of the blood supply. If the body tissue of the blocked area continues to become unable to receive oxygen and nutrients, It happens. In particular, peripheral vascular disease is a vascular disease mainly arising in the limb artery and vein. Atherosclerosis of the heart and peripheral blood vessels is a systemic disease. When the blood vessels become narrowed or obstructed to obstruct the flow of blood flow, Necrosis occurs. Cardiovascular diseases are treated by various methods, and even if the number of products is enough, there are many products in the market both at home and abroad. If they are detected early, there is no big deal to treat. However, it is possible to diagnose peripheral blood vessels roughly, The treatment method is also technically insufficient and the number of products is not diversified and there are limitations in treatment. Relatively peripheral blood vessels are small in size and slow in blood flow velocity, requiring development of highly functional products.

These treatments include stents, balloon expendable stents, and self-expendable stents. When a self-expandable stent with excellent elasticity is applied to peripheral blood vessels with thin walls, the force to push the wall of the blood vessel is larger than the force to support the wall of the blood vessel, which may cause secondary damage to the blood vessel wall When a ballon expendable stent with low elasticity is applied, stress may be applied to the stent inserted into peripheral blood vessels according to the movement of the body, causing the blood vessels to be pushed and damaged, or the blood vessel may be dislodged from its original position.

In the stent market led by a multinational global medical device company, there are difficulties in research and development and production of patient and user-oriented products in the domestic market. The conventional stent of artificial blood vessels is bulky and hard, Is not used because of these disadvantages.

Considering these problems, it would be possible to overcome this drawback by developing a new concept of artificial vascular stent with a thin and sufficient inflatable force and showing micro-permeability with proper fiber gap.

Currently, peripheral venous stents of world-class multinational companies release about 5 to 6 products, but they are not being used with too much swelling or too little swelling power.

In order to improve the problems of existing products, it is necessary to develop a new design of artificial vascular stent which merely merits the merits of existing stents in order to develop artificial vascular stent which can be easily and safely treated. Particularly, it is very important to develop a design that matches the characteristics of each blood vessel and the characteristics of the lesion.

U.S. Patent Nos. 5,545,211 and 5,330,500 for solving these problems.

This is because the outer surface of the stent is coated with a polyurethane coating on the outer surface of the stent. When the stent is coated with a polyurethane coating layer on the outer surface of the stent, Thereby preventing infiltration of a tumor or the like generated outside the stent. At this time, placing the mesh on the stent is intended to easily form a coating with polyurethane.

However, in the case of such a stent, since a coating layer such as polyurethane is formed on the outside, it is possible to prevent the tumor and the like from penetrating into the stent. However, in the inside of the stent, So that the accumulation of various kinds of debris contained in the blood passing through the stent over time will eventually lead to the disadvantage that the desired purpose of the stent can not be achieved.

In order to solve the above-mentioned problems, recently, the artificial blood vessels have been used as biocompatible fabrics, more specifically nylon, silk, polytetrafluoroethylene (PTFE), polypropylene (PP), polyurethane (PU) (PET), polyamide (PA), polyacrylonitrile (PAN), polyethylene (PE), polyester (PES), polyvinyl chloride (PVC), polyvinylidene fluoride ), Polyvinyl alcohol (PVA), polyglycolic acid (PGA), or polylactic acid (PLA) as raw materials to be used in combination with the above stent (see Korean Patent Publication No. 2011-0107236).

However, in the above-mentioned patent, only the biocompatible fabrics are listed for the material of the artificial blood vessels, and the physical properties of the fabric are not specifically disclosed. In particular, if the density of the material selected to impart flexibility is too low, And it is difficult to use it practically, for example, when the density is too high in order to prevent the breakage, the adaptability with the body becomes poor.

Therefore, the inventor of the present invention has developed a manufacturing technique of a plate-shaped stent capable of overcoming the shortcomings of a cylindrical artificial blood vessel stent.

SUMMARY OF THE INVENTION The present invention has been made in order to solve such conventional problems, and it is an object of the present invention to provide a plate-type artificial vessel stent capable of dramatically supplementing the function of a conventional cylindrical stent by using Teflon, The purpose is to do.

To achieve these and other advantages and in accordance with the purpose of the present invention, as embodied and broadly disclosed, there is provided a plate-shaped artificial vessel stent having excellent expansion force and flexibility, comprising: a plate-shaped artificial vessel woven with a Teflon fabric; And a plate-shaped metal stent which is shaped and stored in a cylindrical shape by etching a metal plate by a photolithography process. The artificial blood vessel and the metal stent are characterized in that a metal stent is stacked and fixed on the outer surface of the artificial blood vessel.

According to a preferred embodiment of the present invention, the plate-type artificial blood vessel stent is manufactured by fixing a suture to a metal stent, inserting a synthetic blood vessel into the metal stent (lower portion), sealing the artificial blood vessel and the metal stent, In order to improve the sealing performance of the artificial vascular stent and further increase the adhesion stability, a medical adhesive is added to the stent and the artificial blood vessel to be adhered, and the artificial vascular stent is rolled like a scroll to be easily inserted into the catheter Design.

The plate-type artificial blood vessel stent constructed according to the present invention is excellent in expansion force and flexibility, and is superior in manufacturing workability to a conventional cylindrical artificial vessel stent, and can remarkably complement the delivery and mounting of the artificial blood vessel stent.

1 is a photograph showing a prototype of a plate-type artificial blood vessel stent according to the present invention.
FIG. 2 is a photograph showing a process of manufacturing a prototype of a plate-shaped blood vessel stent of FIG. 1;
3 is a SEM analysis photograph of the PTFE yarn used in the present invention before and after stretching.
FIG. 4 is a schematic view of a weaving pattern of a plate-type artificial blood vessel according to the present invention. FIG.
5 is an exemplary view showing a photolithographic process;
6 is an illustration of mask design and PR (photo resist) patterning;
7 is a photograph showing the state of being etched and heat-treated.
FIG. A stent photograph prepared for testing.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

First, the Teflon fabric according to the present invention is a Teflon fabric according to the present invention, which is disclosed in Patent Application No. 2013-0073515 (filed on June 23, 2016) and Patent Application No. 2014-0050009 (filed on Apr. 25, 2014) We use fabric. Therefore, it should be understood that the description of a teflon fabric not separately described is in accordance with the above-mentioned invention.

As shown in FIG. 1, the plate-type artificial blood vessel stent 100 to which the artificial blood vessel is applied according to the present invention comprises a synthetic blood vessel 10 composed of a Teflon fabric and a metal plate 10 which is etched by a photolithography process to form a cylindrical shape And a metal stent 20 made of a plate-shaped metal stent which is memorized and fixed on the outer surface of the artificial blood vessel.

2, the plate-type artificial blood vessel stent 100 according to the present invention is configured such that the suture 30 is fixed to the metal stent 20 (upper left portion in FIG. 2), and the artificial blood vessel 10 is inserted into the metal stent 20 2), and then the artificial blood vessel 10 and the metal stent 20 are sealed (FIG. 2, bottom left) to complete the connection (FIG. 2, bottom right).

In the case of manufacturing the artificial vessel stent using a suture, in order to prevent the artificial vessel from being distanced from the stent in the portion where the suture does not reach, and to further increase the sealing performance and adhesion stability of the artificial vessel stent, The stent and the artificial blood vessel are adhered to each other so that the artificial blood vessel and the stent can be simultaneously held by the adhesive and the suture. Also, it is desirable that the artificial vascular stent is designed to have a structure in which the artificial vascular stent is curled like two so that it can be easily inserted into the catheter.

1. Manufacture of artificial blood vessels

1) Thread processing of yarn

- Teflon yarn fineness suitable stretching temperature range setting test

: 190, 200, 210, 220, 230 < 0 > C

- Teflon Yarn Fine Size Drawing Ratio Setting Test

: DR (Draw ratio) 1.00, 1.06, 1.08, 1.10, 1.12

- Teflon yarn suitable for fineness of winding speed

: Coiling speed 100, 200, 250, 300, 350, 400, 450 m / min

- Teflon yarn has little elongation and can not be stretched at room temperature.

- The temperature (1st heater) is only 5% stretching at the general drawing draw temperature (200 ℃), and about 10% stretching at the maximum stretching machine temperature (230 ℃).

- Drawing ratio is 10% appropriate, and more work is impossible due to trimming.

- The coiling temperature is higher as the speed is higher, the workability is worse and the proper dead speed is 300 m / min.

- Optimum working temperature: 1 st Heater temperature: 230 ℃,

Draw ratio: 1.1,

Speed: 300m / min

Table 1 and Fig. 3 show the changes of the physical properties and the morphological changes as a result of the stretching operation.

Setting draw ratio (DR) The actual fineness (d) Strength (cN.d) Shinto (%) Remarks 1.0 (yarn before stretching) 88.00 5.30 7.58 1.06 87.00 6.50 4.85 1.08 82.00 5.25 4.23 1.10 80.00 5.85 4.54 Working minutes 1.12 79.00 6.25 4.58

2) Weaving density setting test

① 1st weaving test

In order to improve the touch of artificial blood vessels, 16 types were weighed while varying as shown in Table 2 based on 170T X 160T less than 220T X 160T.

division Weft density Criteria * 1.0 Criterion * 0.95 Standard * 0.90 Criterion * 0.85 160 152 144 136 slope
density Criteria * 1.0 170 330 322 314 306 Criterion * 0.95 160 320 312 304 296 Standard * 0.90 152 312 304 296 288 Criterion * 0.85 144 304 296 288 280

The results of the woven artificial blood vessels were improved satisfactorily to the touch and the tear strength was much higher than the target value (4.5 MPa) as shown in Table 3 (change in breaking strength according to the weaving density). However, When the water leakage test was started, the water leakage rate was so bad that all of the 200 ml of water leaked in about 20 to 25 seconds, which was not enough to use as the artificial blood vessel.

division
(unit : MPa ) Weft density Criteria * 1.0 Criterion * 0.95 Standard * 0.90 Criterion * 0.85 160 152 144 136 slope
density Criteria * 1.0 170 13.35 12.92 11.57 10.93 Criterion * 0.95 160 14.68 10.66 12.81 10.94 Standard * 0.90 152 12.36 10.94 11.86 9.78 Criterion * 0.85 144 12.48 9.64 8.65 7.96

② 2nd weaving test

The conclusion from the first weaving test was that when the sum of the weft and weft density was less than 50, we could not use it because the leaking rate was poor. In the second weaving test, the weft density was fixed at 160T and the warp density was 210T, 200T, 190T, and 180T.

For the woven samples, the touch was sensed, and the water leakage rate was analyzed by self-test, and the results are shown in Table 4 (change in touch and water leakage rate according to the slope density).

Inclined density 180T 190T 200T 210T 220T Remarks Weft density 160T 160T 160T 160T 160T Touch Good usually usually usually usually Leak rate
(ml / cm ² / min) - 280 260 180 120

As the slope density is less than the reference density of 220T, the touch does not change much, while the leakage rate is close to the limit value for 20T and 30T samples, and the sample with 40T touch is considered good, It was unusable. As a result, 220T X 160T was the most suitable for PTFE mono filament 80 Denier yarn considering touch, water leakage rate and burst strength.

3) Plate woven artificial blood vessel weaving

When the process of integrating the artificial blood vessel and the stent is performed, the artificial blood vessel is cylindrical and the stent is plate-shaped, so the operation is considerably inconvenient and the operation result is not good. Therefore, there is an idea that the artificial blood vessels should also be in the form of plates, so we try to integrate them with the stent by expanding the artificial blood vessels weaving in a cylindrical shape. However, artificial blood vessels that have a cylindrical shape are expected to have a problem of loosening. 3 types were woven as shown in Fig.

4) Physical property analysis table of plate type artificial blood vessel product (woven PTFE artificial blood vessel)

Evaluation items
(Key performance
Spec) unit Weight of total items
(%) World-class, owned / owned companies Domestic level before R & D Development
Target value Achievement level Assessment Methods Performance level Performance level Third year Third year Leak rate ml / cm ² / min 10 US Datascope / 300
350
280 or less
135.4 (16KPa)
164.2 (24KPa) Porosity test
(Korean Textile
Development Researcher) Burst strength MPa 10 Gore, United States
/ 1.2 1.2 4.5 or more 12.99 Punch ball test
(Korean Textile
Development Researcher)

2. Manufacture of plate stent

In order to manufacture the prototype, the conventional stent manufacturing process with a diameter of 4 mm and a length of 2 cm or less has been applied. However, a photolithography process with a larger diameter and a longer length has been developed and applied through clinical specification determination.

We confirmed the stent diameter and the length of the stent, which were clinically required, and confirmed the workable size in the photolithography process. Nitinol plates required for manufacturing test products were designed and detailed process conditions such as etching were confirmed.

The stent was determined to have a final diameter of 4 mm, 6 mm, and 8 mm, and lengths of 20 mm, 40 mm, 60 mm, and 80 mm. As the test prototype, prototype was manufactured with three kinds of 20mm, 60mm, and 80mm lengths, which are 8mm in diameter.

We also studied the surface of the stent and developed a surface polishing process to remove impurities generated by the heat treatment on the surface of the stent. The stent minimizes foreign matter reaction in the body.

This stent was developed by benchmarking a commercially available VIABAHN (Gore Medical) stent, and developed a stent with excellent properties by combining the specific features of the applicant with the processing method, design and plate shape.

Meanwhile, the fabrication process used for manufacturing the stent according to the present invention is a photolithography process in which a desired pattern is designed as a mask, and fine patterning of the mask is implemented in a plate type nitride plate by etching, And Fig.

STEP 1. PR (Photo Resist) Coating: Photo-cured PR is coated on thin plate by UV (ultraviolet ray).

STEP 2. Exposure: Using a mask that blocks the UV, we can make the desired pattern of PR.

STEP 3. Phenomenon: Only the patterned PR in the desired pattern is left in the exposure process.

STEP 4. Etching: When immersed in an etching solution, etching is carried out leaving only the patterning protected by the PR.

STEP 5. Remove PR: Removing the last remaining PR produces a nitinol pattern.

6, the PR is patterned into a mask shape as shown on the right side. As a result, a patterning design free from any shape can be achieved through a desired shape. Free patterning is an advantage of the plate-type stent, In the case of a stent, there is a limitation in patterning because photolithography can not be introduced.

The left side of FIG. 7 is a pattern in which a nitinol plate is patterned by etching, and a shape memory processing is performed by high temperature heat treatment, so that a stent as shown on the right can be manufactured. Stent design is easy because the design of various linewidths can be tested simultaneously in one process.

On the other hand, an advantage of the photolithography process is that it is easy to realize the fine line width as compared with the laser cutting. In particular, there is no burr or deterioration phenomenon occurring in laser cutting, and it is expected to have superiority in mechanical properties.

1) Photolithography process design

Design and Mask Design

In order to manufacture the stent determined according to the present invention, a mask for photolithography for a stent conforming to the initial shape was designed and the shape of the stent was designed accordingly.

Stent size setting

In the process of determining the stent spec. To be manufactured through the present invention, the final stent spec. Was determined on the basis of the dimensional limit that can be produced by the photolithography.

The Naitinol disc used for etching the Nitinol plate by photolithography process has a diameter of 100 mm, and it can be confirmed that the dimensions that can be manufactured using the Naitinol disc according to the present invention can have a diameter and a length of 8 mm x 80 mm, The stent is to be manufactured using only this size.

The design of the stent was designed to match the original mask with the mask diameter used in conventional semiconductors.

The spec. In the case of the stent made for testing, three different lengths of 8mm diameter were manufactured. Therefore, the design of the disk for Naitinol disk was set differently. Therefore, the stent was designed by applying another mask of 20mm and 60mm at the same time as 80mm length . 20 mm, 60 mm, and 80 mm, and the cell size and spacing were not changed except the length.

Stent heat treatment condition and property measurement

The results of stent heat treatment conditions and physical properties measurement according to the present invention are shown in Table 6 below.

Heat treatment
(500) sample
No, Length
(mm) Thickness (um) Swelling power flexibility
(N) Before heat treatment the year before
After polishing jig 12mm 20mm 40mm 50 minutes 16 20 150 150 1.385 2.047 Not measurable 17 60 150 150 1.299 2.034 4.004 Not measurable 18 80 150 150 1.149 1.883 3.523 Not measurable 60 minutes One 20 150 150 1.454 2.086 Not measurable 2 60 150 150 1.196 2.146 4.313 Not measurable 3 80 150 150 1.071 1.990 3.956 Not measurable 70 minutes 10 20 150 150 1.223 1.910 Not measurable 11 60 150 150 1.177 1.782 3.452 Not measurable 12 80 150 150 1.529 2.441 4.362 Not measurable 80 minutes 15 80 150 150 1.257 2.065 4.072 Not measurable 90 minutes 4 20 150 150 1.214 2.083 Not measurable 5 60 150 150 1.141 1.998 3.974 Not measurable 6 80 150 150 1.133 2.022 3.792 Not measurable

As shown in Table 6, when the stent was heat treated at 50, 60, 70, 80, and 90 for 20mm, 60mm, and 80mm stents, the expansion force was measured and found to exceed 1.1N. However, in the case of flexibility with a standard of 0.5 N or less, the stent was not flexible enough to make 3 point bending, making it impossible to measure the data because it was meaningless and impossible to measure the data. In the case of long heat treatment time, physical properties showed the standard value. However, as the heat treatment time became longer, the surface color of the stent gradually changed, and it was observed that it changed to yellow color beyond the unique index blue for stent heat treatment. It was time to decide. In other words, it was confirmed that the stent heat treatment time had a standard inflation force from 50 minutes or more, and it was determined to be 50 minutes which is the shortest time in the test. The spec. For the test product, the stent heat treatment temperature was finally determined at 500 ° C for 50 minutes.

2) Spec. for test Manufacture of prototype

Stent sample preparation

In order to manufacture plate-type stent using photolithography process, spec. test stent product was prepared as shown in Fig.

The stent was 8 mm in diameter, 20 mm in length, 60 mm, and 80 mm in length, and 9 stents were prepared for each length.

The expansion force of the stent for the specimen was measured and listed in Table 7.

Preparation of test specimens for biological test / effluent test

In the case of the test specimens for biological test and dissolution test, if the stent form was not required, a plate of a certain size was prepared by treating the existing nitinol plate with the same conditions as the stent preparation process, without preparing the stent form. The same procedure was used to cut the nitinol plate. The purpose of using Naithinol plate was to cut the stent, and when the test was performed, the biological test or the dissolution test proceeded with the weight of the stent, so the loss ratio of the raw material was too large. will be.

As described in Patent Application No. 2014-50009 of the present applicant, the stent for blood vessels to which the artificial blood vessel is applied according to the present invention is characterized in that the artificial blood vessel has high strength, that is, high density and high rupture strength, It is possible to prevent an unexpected breakage or a leak accident from occurring when the blood vessel is inserted into a blood vessel. Also, it should be noted that the Teflon raw yarn used in the present invention is stretched within a stretching ratio of 1.12, so that the strength and the like are suitable for application to artificial blood vessels, while being thinned, thereby reducing the thickness of artificial blood vessels and improving flexibility .

While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, It will be possible for any person skilled in the art to carry out various modifications.

100: Platelet-shaped blood vessel stent 10: Artificial blood vessel
20: metal stent 30: suture

Claims

The artificial vascular stent,
A plate-shaped artificial blood vessel woven from a cylindrical shape to a flat plate without cutting the Teflon fabric; And a planar metal stent which is shaped into a cylinder shape by heat treatment of a nitinol metal plate by a photolithography process and a heat treatment temperature of 500 ° C and a heat treatment time of 50 minutes,
The plate-shaped artificial blood vessel and the metal stent are formed by stacking and fixing a metal stent on the outer surface of the artificial blood vessel.
The plate-type artificial vascular stent is manufactured by fixing a suture to a metal stent, inserting a synthetic blood vessel into the metal stent (lower portion), and then sealing the artificial blood vessel and the metal stent, and further increasing the stability of the artificial blood vessel stent Wherein the stent is designed to have a structure in which a synthetic stent is attached to a catheter, and a synthetic stent is designed so that the stent can be easily inserted into the catheter.

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