JPH02241448A - Artificial blood tube and manufacture thereof - Google Patents

Abstract

PURPOSE:To provide an artificial blood tube which has excellent antithrombus property and enables the thickness of a formed false inner membrane to be controlled to a low value by a method wherein different specified fibers are used to knit or weave them to form a cylindrical body. CONSTITUTION:A fibre made of a material to which a cell is apt to adhere and a fiber made of a material to which a cell is difficult to adhere are combined together as different fibers. For example, a tetrafluoroethylene - perfluoroalkylvinyl ether copolymer filament, molten and spun and having 10% or more thermal shrinkage property in a longitudinal direction in a 200 deg.C dry oven and a polyester series fiber having thermal shrinkage property are knitted or woven to form a cylindrical body. After a core is inserted in the cylindrical body, heat treatment is effected to bring texture density of the cylindrical body into a dense state. In which case, the latter to which a cell is apt to adhere is favorable to rapid and neat formation of a false inner membrane. The former to which a cell is difficult to adhere has an effect to suppress the rapid and sudden occurrence of a thrombus, and difficult to cause the occurrence of dehiscence and kinking due to a needle hole formed during a sature.

Description

Detailed Description of the Invention <Field of Industrial Application> The present invention relates to the field of artificial blood vessels having favorable characteristics, and by providing such artificial blood vessels and a method for manufacturing the same, It is intended to be offered to

<Prior art> Artificial blood vessels currently in practical use include tubular woven and knitted fabrics of polyester fibers and porous tubes made from specially stretched polytetrafluoroethylene paste extrusions, but there are still problems that need to be solved. There are still many things left. The latter has problems in that it tends to tear due to the needle hole during suturing, has poor elasticity, and is prone to kinking.

All types of artificial blood vessels are based on the principle that they ultimately acquire antithrombotic properties through the formation of pseudointima by the living body, but all of these conventional artificial blood vessels develop antithrombotic properties due to hyperplasia of pseudointima. Narrowing of the vascular lumen may occur, which may lead to occlusion, which is a particularly serious problem in small-diameter artificial blood vessels. Therefore, the scope of application of artificial blood vessels is limited to relatively large arteries with an inner diameter of 61 mWm or more.

If there were a material that had excellent antithrombotic properties over a long period of time and did not cause the formation of pseudointima, it would be ideal as a material for artificial blood vessels, but such a material does not exist so far. do not.

<Problems to be Solved by the Invention> In order to solve the problems of the type of artificial blood vessel that acquires antithrombotic properties through the formation of pseudointima, it is necessary to develop materials with excellent antithrombotic properties and to reduce the formation of pseudointimal membranes. Needless to say, a material that can be controlled is required.

The purpose of the present invention is to combine different materials to
The object of the present invention is to provide an unprecedented new type of artificial blood vessel that simultaneously satisfies the above two required properties and also has other properties necessary for an artificial blood vessel.

Measures to solve these problems> The concept of micro-heterogeneous structure has been proposed as a design principle for antithrombotic materials (Artificial Organs, Vol. 2, p. 95, 197).
3), that is, when substances of appropriate size and different properties are distributed in a non-uniform manner, it becomes difficult for blood clots to form.The present invention is based on the concept of such a micro-heterogeneous structure. The aim is to solve the problem by expanding the method and appropriately combining different types of fibers.

That is, the present invention is characterized in that, in the artificial blood vessel,
It is formed into a cylindrical body by knitting or weaving using different types of fibers, and its unique feature is that it is made of melt-spun tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer in artificial blood vessels. It is formed into a cylindrical body from combined filaments and polyester fibers, and its unique feature is that when manufacturing an artificial blood vessel, it is melt-spun and processed in a dry oven at 200°C to form a cylindrical body with a thickness of 10% or more in the longitudinal direction. A core material is inserted into a cylindrical body knitted or woven with heat-shrinkable tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer filaments and heat-shrinkable polyester fibers, and then heat-treated. By doing so, the tissue density of the cylindrical body is made denser.

The present invention requires the use of foreign fibers, and as a result, the artificial blood vessel according to the present invention is formed of foreign fibers, but
At this time, it does not matter what state foreign fibers exist in the artificial blood vessel.

Regarding the use of such different types of fibers, a total of two or more types of fibers made of appropriate materials (for example, 2.3.4.
... Type, etc.) may be used in any state, and at least one fiber obtained by composite spinning as described later may be used.
There are no particular restrictions on the types of fibers that can be used, but for example, it is desirable to have a combination of fibers made of materials that have significantly different surface chemical properties, and preferably fibers made of materials to which cells easily adhere. An example is a combination of fibers made of a material to which cells do not easily adhere. This is because materials to which cells easily adhere are favorable for early and clean formation of pseudointima, while materials to which cells do not adhere easily have the effect of suppressing the early and rapid formation of blood clots. It's for a reason.

Examples of materials to which cells easily adhere include polyesters such as polyethylene terephthalate (hereinafter referred to as PET), polyethylene naphthalate, polyglycolic acid, and polylactic acid, as well as polyamide, polyimide, polysulfone, polyurethane, and polyvinylidene fluoride. can.

Materials to which cells do not easily adhere include, for example, polytetrafluoroethylene (hereinafter referred to as PTFE), tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (hereinafter referred to as PFA), and tetrafluoroethylene-hexafluoropropylene copolymer. , fluorine-based polymers such as tetrafluoroethylene-ethylene copolymer, tetrafluoroethylene-hexafluoropropylene-perfluoroalkyl vinyl ether copolymer, and relatively highly hydrophobic olefin-based polymers such as polyethylene and polypropylene. Alternatively, hydrophilic polymers containing units such as polyethylene glycol 5-polyacrylamide, poly(N-vinyl and lolidone), and polyvinyl alcohol can be mentioned.

As the above-mentioned material to which cells easily attach or do not easily attach, it is desirable to use fibers as thin as possible, and for this reason, the number of vine fibers currently available tends to be quite limited. There are no particular restrictions on this, and any fiber can be used. Among the fibers to which cells easily attach, PE, which belongs to polyester fibers, is currently selected because it has a low biological reaction, is durable, and has been used as an artificial blood vessel.
A preferable example is fibers made of T. Examples of fibers to which cells do not adhere are those made of PTFE, PFA, and polypropylene;
FA fibers can be exemplified as preferred. PTF
E and PFA are both fluorine-based polymers that are characterized by non-adhesive properties, but PFA is thermoplastic and therefore can be melt-extruded, has better surface properties than PTFE, and has antithrombotic properties. But it is advantageous. Furthermore, the world of fibrous tissue formed around PFA is
It has been revealed that there are fewer cases compared to artificial organs (artificial organs,
17, p. 553, 1988), it is also advantageous in that it forms a thin pseudointima and suppresses its hyperplasia.

PFA fibers, preferably filaments, which are exemplified as preferred fibers in the present invention, can be exemplified by those melt-spun using a common extruder for fluororesins. This filament has low oriented crystallinity, so it has excellent flexibility and bending fatigue resistance. Such PFA filaments, and polyester fibers exemplified as preferred fibers in the present invention,
For example, the thread diameter of PET fiber, preferably filament, is
The thinner the material, the better, and such thin material tends to have excellent flexibility, bending fatigue resistance, and needle passability when molded into an artificial blood vessel.

There is no particular restriction on the diameter of the single yarn, but preferably PFA
Examples of filaments include those with a diameter of 50 μφ or less, and PET filaments with a diameter of 30 μφ or less.

As an artificial blood vessel, having porosity is closely related to the flexibility of the blood vessel, ease of handling, ease of suturing, ease of fitting with host blood vessels, speed of organization, etc. Control of porosity is an important issue. As mentioned above, for example, PFA,
When PET filaments are used, if necessary, the tissue density can be reduced by utilizing the heat shrinkability of the filaments to control the perforated state of the cylindrical body.

Of course, such heat shrinkability may be imparted as necessary, and in the present invention, a wide range of materials can be used, from those with little heat shrinkage to those with high heat shrinkability, and those without heat shrinkability, depending on the situation.

Next, an example of a method for manufacturing PFA filament will be described. PFA filaments are preferably melt-spun using a rapid compression type that is commonly used for melt extrusion of fluororesins, but this is not particularly limited. Further, the spinning conditions are not particularly limited and may be arbitrary.

When making a filament with heat shrinkability, it is sufficient to control the L/D value of the nozzle during spinning, the cooling temperature, etc., that is, the cooling rate, etc., but there are no particular restrictions on this. It is not something that can be received. Regarding stretching after spinning,
You can freely set the conditions, including the presence or absence of such stretching, but specific examples include hot stretching, cold stretching, etc., and the stretching ratio, stretching temperature, etc. may be set as appropriate.Afterwards, if necessary, annealing etc. may be performed. good. In order to obtain filaments with high heat shrinkability, it is preferable to omit annealing.

At this time, regarding the heat shrinkage rate of heat-shrinkable PFA filaments, a suitable example is one that exhibits a value of 10% or more, preferably 15% or more in the longitudinal direction in a 200°C dry oven. However, there is no particular restriction, and in order to impart such heat shrinkability, the above-described spinning, stretching conditions, etc. may be appropriately manipulated.

Preferred conditions for producing a PFA filament having such suitable heat shrinkability will be described below. Regarding melt spinning conditions, the nozzle L/D value is 3 to 3.
The cooling temperature at the time of take-up during spinning is preferably 200 to 350 °C at 5 cm below the nozzle, 50 to 200 °C at 20 cm, and more preferably 260 °C at 5 cm below the nozzle. ~320℃, 20c
It is desirable to set the temperature to 100 to 150°C in m.Of course, the above values are not particularly limited and are only preferred examples.Stretching has the greatest relationship with heat shrinkability, and the above-mentioned preferred In order to produce a PFA filament with good heat shrinkability, either cold stretching or hot stretching can be used (
2. The stretching ratio, stretching temperature, etc. may be determined as appropriate, but preferably the stretching ratio is 2 times or more, more preferably 2.5 to 4.
5 times, and the stretching temperature is preferably hot stretching at 200 to 300°C, more preferably cold stretching at 20 to 50°C. At this time, in order to obtain a PFA filament having heat shrinkability, it is not preferable to perform annealing after stretching, but it may be performed as appropriate if necessary. Further, spinning and stretching may be carried out in a continuous process or in separate processes, but generally they are often carried out in a continuous process.

The above is an example of filament production conditions for PFA filament having suitable heat shrinkability, but of course the artificial blood vessel of the present invention either does not have heat shrinkage or reaches 10%, which is set as the above-mentioned preferable value. PF with no heat shrinkage
A filament may be used, or a PFA filament having a heat shrinkage of less than 10% may be used, and heat treatment may be performed, for example, by a method similar to the method described in claim (5). It is clear from the previous explanation that this is not the case. Furthermore, it is of course possible to use a PFA filament having a heat shrinkage of 10% or more, which is determined as the above-mentioned preferable value, and to make an artificial blood vessel without performing a heat treatment process.

Next, let's talk about PET filament. P
ET filaments can be used in a wide variety of ways, from commercially available filaments to those that are subjected to heat shrinkage, for example, those that are only melt-spun and drawn but not double-ringed, and are not particularly limited. There is no particular restriction on the heat shrinkage rate of PET filament having heat shrinkability, but it is preferably 20
10% or more, more preferably 15% or more can be added to the longitudinal direction in a dry oven at 0°C.

As a specific example of producing an artificial blood vessel, for example, an appropriate PF
A cylindrical body may be formed by knitting or weaving the A filament and a suitable PET filament as appropriate, and knitting may be performed using, for example, a circular knitting machine, flat knitting machine, warp knitting machine, etc. However, the weaving can be carried out using an appropriate loom, etc., and there is no particular restriction on this. PFA filament and PFA filament
The ratio of ET filaments can be set freely, and the number of filaments is not particularly limited, but preferably PF
It is desirable to keep the number of A fillers to 36 or less and the number of PET fillers to 72 or less. If this number is too large, the flexibility and sutability of the artificial blood vessel may not be desirable. PFA filler and PET filler can be used in any desired ratio, such as by aligning them in the desired ratio, twisting them, or otherwise using them. Also, when knitting, the yarns can be alternately fed every appropriate number of stitches, or they can be woven. In this case, warp threads and weft threads may be woven alternately in appropriate numbers, and there are no particular restrictions on these, and knitting, weaving, etc. may be performed as appropriate. At this time, PF
The blending ratio in terms of volume of filament A is preferably 2 to 98% by volume, more preferably 10% by volume of the total volume of the cylindrical body.
~60% by volume, but this value is not particularly limited.

When making an artificial blood vessel as described above using a heat-shrinkable PFA filament and a heat-shrinkable PET filament, for example, they are knitted or woven into a cylindrical body, and then heat-treated if necessary to form a cylindrical body. It is also possible to make the tissue of the body denser. When performing heat treatment, it is necessary to insert an appropriate core material into the cylindrical body before heat treatment, and examples of the core material include a rod-shaped body, a pipe-shaped body, and the like. The heat treatment temperature is not particularly limited, but preferably 160~
An example of heat treatment is 240°C, more preferably about 180 to 220°C, and the tissue density can be increased by such heat treatment. At this time, if the diameter of the core material is made smaller than the inner diameter of the cylindrical body, the la density in the circumferential direction of the cylindrical body (number of wales in the case of woven fabric) is determined by the degree of diameter, and the la density in the axial direction of the cylindrical body is determined by the degree of diameter of the core material. The tissue density (number of courses in the case of knitted fabrics) is usually determined by the heat shrinkability of the filaments, the degree of density in the circumferential direction, and other factors. Of course, in place of the heat-shrinkable PFA filament and heat-shrinkable PET filament, it is also possible to appropriately use other heat-shrinkable fibers and increase the tissue density by the same method. It is.

The explanation so far has been made using filaments as an example, but the filaments described above may be replaced with fibers as necessary. Examples of such fibers include short fibers,
Any fibrous material such as spun yarn can be used, and this applies to all of the present invention.

Generally speaking, the cylindrical body in the present invention is formed by, for example, knitting or blending different types of fibers, and is not particularly limited. As a specific example, the cylindrical body is formed by using different types of fibers, using an appropriate knitting machine, etc. Examples include those made into a tubular shape by knitting or weaving with an appropriate m machine, etc. In this case, the shape when formed into a cylindrical body includes a straight pipe, a pipe with a branch pipe, and a pipe with a taper. etc., but there is no particular restriction.

In order to prevent IF from kinking of the artificial blood vessel according to the present invention,
For example, it is possible to provide an external support by winding the outer surface of a knitted, woven and, if necessary, heat-treated tubular product in a spiral with thread, such as polypropylene or PFA monofilament. It can also be easily processed. If necessary, it is also possible to reduce the porosity of the outer surface to a blunt end while maintaining the porosity of the inner surface.

As exemplified above, the heterogeneous fibers according to the present invention can be obtained not only by appropriately combining individual fibers made of various polymers, but also by blending different polymers and performing composite spinning. A blend of the above-mentioned dissimilar polymers, including fibers, etc., and is not particularly limited (for example, a blend of a polymer of a material to which cells easily adhere and a polymer of a material to which cells do not easily adhere, a blend of multiple appropriate polymers) Fibers obtained by composite spinning (such as, but not limited to) have a non-uniform structure when viewed microscopically even in the form of fibers, for example, and from this perspective, such fibers, etc. Naturally, it is included within the scope of the present invention.

The above is an illustrative explanation of preferred embodiments of the present invention, and the present invention is not limited to these descriptions, but includes all embodiments within the scope of the claims.

<Example 1> PFA resin (desirably Ml value is 7 to 18) is melt-spun using a Hastelloy extruder. At that time, the nozzle L/D
The extruded resin was spun in heated air in order to slowly cool the extruded resin. The temperature at that time was 310°C below 5c+a from the nozzle, and 120°C 20cm below the nozzle.The filament was then naturally cooled to near room temperature (approximately 25°C).
The film was stretched 3 times at 30°C (°C) and directly wound onto a wine sieve.

Annealing, which is usually done after stretching, was excluded. The filament thus obtained had a heat shrinkage of 15% in a dry oven at 200°C.

The PFA filament thus obtained (21μφ×24
Filler) and PET filament (loμΦX60 filler) having a heat shrinkage rate of 19% in a dry oven at 200°C were knitted into a cylindrical shape using a round liA machine with a pot diameter of 12 mmΦ and 24 needles. Ta. At this time, these two types of filaments were simultaneously drawn and fed, and the tension applied to the fabric was approximately 30 g. The diameter of the thus obtained cylindrical body in the longitudinal direction is 30 to 33 stitches/1 nch.
, the inner diameter was 4.8 mmΦ. Furthermore, this cylindrical body has 4
．． Insert a stainless steel rod-shaped jig of 2v+eΦ,
The fabric was heat-shrinked in a 0°C dry oven to reduce the knitting density. The stitches in the warp direction at that time were 50 to 55 stitches/1 nch, and the knitting density was quite dense.

The artificial blood vessel made of a cylindrical body thus obtained had sufficient flexibility and elasticity, and there was no problem of tearing in the longitudinal direction.

<Example 2> PFA filament similar to that used in Example 1 (21μ
Φ×24 filler multi) and PET filament (1
It was woven into a cylindrical shape using a mulch of 0μΦ×60 fillers. At this time, the total number of warp threads was 300 (240 PFA multifila, 60 PET multifila, the former 4
PET multifila was used for the weft, and the weft density was 76.81, 86.
Three types of wire/1nch, each with an inner diameter of 4-
It was ugly. Note that the cylindrical body thus obtained was not subjected to a heat shrinking process by heat treatment.

Water leakage test of these three types of cylindrical bodies was conducted at 120■■Hg.
The results are shown in Table 1.

By changing the weaving density in this manner, the amount of water leakage can be adjusted as desired, and this indicates that a desired porosity can be selected when used as an artificial blood vessel.

Table 1 When the thus obtained cylindrical body was used as an artificial blood vessel, it had sufficient flexibility and elasticity as in Example 1, and there was no problem of tearing in the longitudinal direction. (Effects of the Invention) The present invention As described above, the artificial blood vessel formed using the foreign fiber according to the present invention has characteristics such as being able to avoid various problems such as tearing and kinking caused by needle holes during suturing, and For example, by using fibers to which cells easily adhere and fibers to which cells do not adhere as different fibers,
Compared to conventional products, it is advantageous in that it has antithrombotic properties and prevents lumen occlusion due to pseudointimal hyperplasia. This tendency is particularly noticeable when using different types of fibers, such as PFA filaments and PET fibers.

Furthermore, the artificial blood vessel of the present invention is a desirable product that is expected to be used in a wide variety of fields, including a hybrid type artificial blood vessel that combines biologically derived materials and cells.

Furthermore, the composition and pore state of the artificial blood vessel obtained by the specific manufacturing method according to the present invention can be easily controlled as desired, and can be used in a wider range of applications, including the above-mentioned hybrid type artificial blood vessel. It is expected.

Claims (1)

[Scope of Claims] (1) An artificial blood vessel characterized by being knitted or woven using foreign fibers and formed into a cylindrical body. (2) The artificial blood vessel according to claim (1), wherein the foreign fibers are fibers to which cells easily adhere and fibers to which cells do not adhere easily. (3) An artificial blood vessel characterized by being formed into a cylindrical body from melt-spun tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer filaments and polyester fibers. (4) The artificial blood vessel according to claim (3), wherein the mixing ratio of the tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer filaments is 2 to 98% by volume. (5) A tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer filament that is melt spun and has a heat shrinkability of 10% or more in the longitudinal direction in a dry oven at 200°C, and a polyester fiber that has heat shrinkability. A method for manufacturing an artificial blood vessel, in which the tissue density of the cylindrical body is made dense by inserting a core material into a cylindrical body that is knitted or woven by a method, and then heat-treating the cylindrical body. (6) The method for producing an artificial blood vessel according to claim (5), wherein the mixing ratio of the tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer filaments is 2 to 98% by volume.