JP2814415B2 - Artificial blood vessel and its manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a polytetrafluoroethylene artificial blood vessel having excellent biocompatibility and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, as artificial blood vessels, knitted or woven fabrics of polyester fiber, polytetrafluoroethylene (hereinafter referred to as P
Tubes (abbreviated as TFE) have been used. Among them, expanded PTFE tubes, PTFE material itself is excellent in antithrombotic property and fiber obtained by drawing - for porous structure due to nodule is excellent in living body tissue compatibility, as compared to polyester fibers, a smaller It has been put to practical use as an artificial blood vessel in the area of caliber. However, an expanded PTFE tube does not always have sufficient antithrombotic properties, and in particular, a sufficient patency rate has not been obtained with an artificial blood vessel having an inner diameter of 6 mm or less.

[0003] As a method for improving the antithrombotic property of an artificial blood vessel, (1) a method for improving the antithrombotic property of the material itself,
(2) A method of inducing a living tissue after transplanting an artificial blood vessel to form an intima to impart antithrombotic properties, and the like are being studied. However, in the method (1), although development of an antithrombotic polymer material having a phase-separated structure or the like and a material for immobilizing an antithrombotic agent has been studied, a material exhibiting good antithrombotic properties for a long time after transplantation has been studied. Has not been obtained.
In the method (2), a method of promoting invasion of a living tissue or a capillary from the outside of a blood vessel in order to promote intimal formation after transplantation has been studied at present.

[0004] The artificial blood vessel made of expanded PTFE, which has been conventionally used, has poor tissue penetration, and it is impossible to form an intima after transplantation. This is because the pore size in the porous structure of expanded PTFE is not large enough for the penetration of living tissue or capillaries, and the tissue cannot physically penetrate sufficiently. Therefore, in order to solve this problem, it is necessary to make the pore diameter of the porous structure sufficiently large for penetration of living tissue. Since the expanded PTFE tube has a fine fiber structure composed of very fine fibers and knots connected to each other by the fibers, in order to increase the pore diameter, it is necessary to increase the drawing ratio and lengthen the fibers. good.

However, in the drawn PTFE tube, since the fine fibers generated by drawing are strongly oriented in the drawing direction, the tensile strength in the tube axis direction of the tube is high, but the strength in the tube circumferential direction is low, and the tube axis direction is low. It has the drawback of easily tearing. For this reason, if the stretching ratio is increased and the fiber is lengthened, the mechanical properties of the tube are significantly reduced.In particular, when a living body is sutured, a suture needle or a suture tears the tube, and when the fiber is further elongated, the tube becomes longer. Cannot maintain the luminal structure, and cannot withstand use as an artificial blood vessel.

[0006] As means for solving the decrease in mechanical properties when the expanded PTFE tube is made into a long fiber, a method of increasing the wall thickness of the tube or reinforcing the outside of the tube with a reinforcing material such as a mesh is considered. However, the former method causes a problem that the invasiveness of the living tissue is reduced, and the latter method causes a problem such as peeling of the reinforcing material.

[0007] For this reason, in the prior art, there is a limit in elongation of the fiber in the fiber-knot structure of the expanded PTFE tube used for the artificial blood vessel, and it has excellent tissue penetration and sufficient mechanical properties for practical use. It was not possible to produce an artificial blood vessel having

[0008]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an artificial blood vessel made of expanded PTFE having a long-fiber structure excellent in penetration of living tissues and capillaries and having an excellent mechanical property. Is to provide.

The inventor of the present invention has made intensive studies to overcome the problems of the prior art, and as a result, it has been found that both the inner surface and the outer surface of the expanded PTFE porous tube have a sintering temperature of 327.
Heat at a temperature of at least 5 ° C, with the outer surface being 5
By heating at a high temperature ranging from 0 ° C to 300 ° C,
Continuous temperature gradient between the inner and outer surfaces of the porous tube
Thus, the fiber-knot structure is substantially composed of two parts, a long part of the fiber and a short part of the fiber, from the inner surface to the outer surface of the tube, and the short part of the fiber is formed of the tube. It has been found that a porous PTFE tube can be obtained which is distributed in the circumferential direction and in a mesh form from the inner surface to the outer surface of the tube.

[0010] The PTFE porous tubes, fibers - long fiber portion in nodular structure body tissue component or capillaries has sufficient fiber length in order to either et intrusion artificial blood vessels outside,
The short fiber portion plays a role of maintaining the strength by having a structure distributed in a mesh shape in the circumferential direction of the tube and the thickness direction of the tube tube wall. Therefore, an artificial blood vessel made of expanded PTFE having an integral structure and having excellent penetration into living tissues and capillaries and excellent mechanical properties can be obtained. The present invention has been completed based on these findings.

[0011]

Thus, according to the present invention, there is provided a fiber-knot structure comprising a polytetrafluoroethylene porous tube having a fine fibrous structure composed of fibers and knots connected to each other by the fibers. Is substantially composed of two parts, a long part of the fiber and a short part of the fiber, from the inner surface to the outer surface of the tube, and the short part of the fiber is out of the circumferential direction of the tube and from the inner surface of the tube. There is provided an artificial blood vessel characterized in that the artificial blood vessel is distributed in a mesh form up to the surface.

Further, according to the present invention, both the inner surface and the outer surface of a porous tube obtained by extruding a green polytetrafluoroethylene mixture containing a liquid lubricant and stretching it in at least one direction after extrusion molding. Is heated at a sintering temperature of 327 ° C. or higher, and at this time, the outer surface is 50 ° C. higher than the inner surface.
To a high temperature in the range of
A method for producing an artificial blood vessel is provided, wherein a temperature gradient is continuously provided between an inner surface and an outer surface of a tube .

Hereinafter, the present invention will be described in detail. The expanded PTFE artificial blood vessel targeted by the present invention is basically manufactured by the method described in JP-B-42-13560. In the production method of the present invention, first, a liquid lubricant is mixed with the unsintered PTFE powder and extruded into a tube by a ram extruder. When the tube is stretched at least in the tube axis direction with or without removing the liquid lubricant from the tube, a PTFE porous tube having a fine fibrous structure composed of fibers and knots connected to each other by the fibers is obtained. Is obtained. When this PTFE porous tube is heated to 327 ° C. or more in a state where it is fixed so as not to shrink and sintered in a stretched state, a porous tube with improved strength can be obtained. In the present invention, the following operation is performed. It has a feature in performing it.

[0014] That is, the porous tube ends fixed to so as not to shrink, but heating the both sides of the inner and outer surfaces of the tube at 327 ° C. or higher sintering temperature, time, the outer surface
50 ° C to 300 ° C from inner surface, preferably 100 to 2
Heat at a high temperature up to 50 ° C to
A temperature gradient is continuously provided between the inner surface and the outer surface of the valve. As a result, rearrangement of the fiber-knot structure occurs from the inner surface to the outer surface of the porous tube, and a portion that is further stretched to be longer than before treatment and a portion that is shorter than before treatment are obtained. Can be

The inner and outer surfaces of the porous PTFE tube are 32
As a method of heating to 7 ° C. or more and providing a temperature difference on both sides, for example, a stainless steel rod is inserted into the tube lumen, the inner surface is heated by the stainless steel rod, and hot air is blown on the outer surface. This can heat both surfaces and provide a temperature difference between the inner and outer surfaces. It is desirable to control the inner surface temperature to 500 ° C. or lower so that PTFE does not decompose.

The heating time depends on the heating temperature, but is usually
It is about 10 to 200 seconds. In addition, when both surfaces of the PTFE porous tube are not heated at a temperature of 327 ° C. or more, or when the temperature difference is not controlled within a range of 50 to 300 ° C., the specific fiber-knot consisting of long fibers and short fibers is used. The structure cannot be formed.

FIG. 1 is a schematic view of the microstructure on the inner surface of an artificial blood vessel comprising a PTFE porous tube of the present invention. FIG. 2 is a schematic diagram of a microstructure of a cross section in a stretching direction of an artificial blood vessel made of a PTFE porous tube of the present invention. Each of these schematic diagrams was created based on the observation result of a micrograph of the PTFE porous tube.
1 indicates a long fiber portion, 2 indicates a short fiber portion, 3 indicates a nodule, and the longitudinal direction of the fiber indicates a stretching direction.

By the way, in Japanese Patent Publication No. 58-1656,
A method for producing a PTFE porous body having excellent strength properties in the direction perpendicular to the stretching direction is disclosed. In the invention described in the publication, a part of the PTFE porous body, for example, P
By heating the outside of the TFE porous tube, the fibers connecting between the nodules are cut, and some nodules are gathered more and the heating surface finally becomes a net-like having a pore size of several tens μm to several mm. An uneven structure is formed, and as a result, a PTFE porous tube having a portion in which the orientation of the fine fibrous structure is strong in one direction and a portion in which the orientation is strong in a direction perpendicular to the direction is obtained.

However, in the method described in the publication,
One surface of the expanded porous PTFE body is heated to 327 ° C. or higher to heat a part of the expanded PTFE porous body, but the other surface is lower than 327 ° C., so that the PTFE porous body as in the present invention is used. There is no rearrangement of the fiber-knot structure from the inner surface to the outer surface of the tube, and it is divided into long fiber portions and short fiber portions, and the short fiber portions are stitched in the circumferential direction and thickness direction of the tube. structure distribution is not obtained.

In the artificial blood vessel according to the present invention, since the long fiber portion has a large pore diameter and a high porosity, it is easy for physical tissue components such as cells and capillaries to physically pass therethrough. Can invade from outside the blood vessel wall. Thus, a tissue that has invaded quickly and in a large amount can form a stable intima over a long period of time, so that the artificial blood vessel according to the present invention can obtain good patency over a long period after transplantation. The average fiber length of the long fiber portion is required to be 60 μm or more, but is preferably 100 μm or more, more preferably 150 μm or more, in order to allow the living tissue to penetrate quickly.

The portion composed of short fibers has excellent strength characteristics due to the high knot density, but the short fiber portion is continuous in a mesh shape from the inner surface to the outer surface of the tube in the circumferential direction and the tube wall. By adopting the structure, even if it has the long fiber structure as described above, it is possible to maintain the structure as a tube and to impart necessary tear strength or tensile strength at the time of suturing. The fiber length of the short fiber part is 20μ
m or less.

The expanded PTFE porous tube having the above-mentioned long fiber / short fiber structure is more flexible than the conventional expanded PTFE porous tube, and the compliance is one order of magnitude higher than that of a commercially available expanded PTFE tube. high,
It has compliance closer to that of living blood vessels. For this reason, the intimal thickening at the anastomotic portion, which is pointed out in the conventional expanded PTFE artificial blood vessel, is unlikely to occur, and a stable intima can be maintained for a long period of time.

As described above, the mechanical properties are imparted by the short fiber portions which are continuous in a network, so that the fibers have a long fiber structure excellent in penetration into living tissues and capillaries, and are flexible and good for a long time. It is possible to provide an artificial blood vessel which exhibits excellent patency and has mechanical characteristics required for practical use.

[0024]

EXAMPLES The present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to these examples.

The method for measuring physical properties is as follows. <Average fiber length> The average value of the internodal distance measured with a scanning electron microscope. <Bubble point> After the expanded PTFE tube is impregnated with isopropyl alcohol, the inside of the tube wall is filled with isopropyl alcohol, and when air pressure is gradually applied from the inside of the tube, the pressure at which bubbles come out for the first time is reduced. Measure. <Water leak pressure> When the water pressure is gradually applied from the inside of the expanded PTFE tube, the water pressure when water first comes out of the tube wall is measured. <Porosity> Permeation amount of water under a pressure load of 120 mmHg (ml / min.cm ² ) <Circumferential tensile strength> The cross-sectional area indicates the strength at which the tube breaks when it is cut open in the circumferential direction and pulled at a tensile speed of 100 mm / min. Divided by <Tear strength> 0.2m at 3mm from tube end
The load at which tearing occurs when pulled through a wire of mφ. <Possibility of mechanical practicality> Judgment was made from circumferential tensile strength and tear strength. <Circumferential compliance> The tube is cut open in the circumferential direction, and the reciprocal of the tensile modulus (initial gradient) at a tensile speed of 100 mm / min.

Example 1 PTFE powder (manufactured by Daikin Industries, trade name: Polyflon F-
104) To 100 parts by weight, 27 parts of a liquid lubricant was added and mixed.
It was extruded into a tube having a diameter of 5 mm and an outer diameter of 2.5 mm. After drying and removing the liquid lubricant from this tube, 1000%
, And the tube was heated to 390 ° C. and sintered in the stretched state. A stainless steel rod having an outer diameter of 1.5 mm was inserted into the drawn tube, and the outer surface side was heated at 650 ° C. and the inner surface side at 450 ° C. for 35 seconds.

Table 1 shows the measurement results of the physical properties of the obtained tubes.
Shown in This porous PTFE tube was transplanted into an abdominal aorta of a 10-week-old rat as an artificial blood vessel, and the coverage of endothelial cells and the state of formation of capillaries were examined two weeks later. As a result, the endothelial cell coverage was 55%, and the inside of the tube wall was filled with living tissue components such as fibroblasts.

Example 2 To 100 parts by weight of PTFE powder (Polyflon F-104), 27 parts of a liquid lubricant was added and mixed. After preforming under pressure, the inner diameter was 3 mm and the outer diameter was ram extruder. Extruded into a 4 mm tube. After drying and removing the liquid lubricant from the tube, the tube was stretched at a stretching ratio of 1000%, and the tube was heated to 390 ° C. while being stretched and sintered. A stainless steel rod having an outer diameter of 3 mm was inserted into the drawn tube, and the outer surface side was heated at 680 ° C. and the inner surface side at 460 ° C. for 70 seconds. Table 1 shows the measurement results of the physical properties of the obtained tube.

Comparative Example 1 PTFE powder (Polyflon F
-104) 27 parts of a liquid lubricant was added to and mixed with 100 parts by weight, and after preforming under pressure, the mixture was extruded with a ram extruder into a tube having an inner diameter of 1.5 mm and an outer diameter of 2.5 mm.
After drying and removing the liquid lubricant from this tube, 100
The film was stretched at a stretch ratio of 0%. The entire tube was sintered by heating it to about 390 ° C. in a stretched state. Table 1 shows the measurement results of the physical properties of the obtained tube.
This tube was low in strength, could not maintain the luminal structure, and had low tear strength, so that it was impossible to implant it into a rat as an artificial blood vessel.

Comparative Example 2 PTFE powder (Polyflon F
-104) 27 parts of a liquid lubricant was added to and mixed with 100 parts by weight, and after preforming under pressure, the mixture was extruded with a ram extruder into a tube having an inner diameter of 1.5 mm and an outer diameter of 2.5 mm.
After drying and removing the liquid lubricant from this tube, 500
%. The entire tube was sintered by heating it to about 390 ° C. in a stretched state.
Table 1 shows the measurement results of the physical properties of the obtained tube.

This porous PTFE tube was transplanted as an artificial blood vessel into the abdominal aorta of a 10-week-old rat, and the coverage of endothelial cells and the state of formation of capillaries were examined two weeks later. As a result, the endothelial cell coverage was as low as 8%, and almost no invasion of living tissue components into the tube wall was observed.

Comparative Example 3 To 100 parts by weight of PTFE powder (Polyflon F-104), 27 parts of a liquid lubricant was added and mixed. After preforming under pressure, the inside diameter was 3 mm and the outside diameter was ram extruder. Extruded into a 4 mm tube. After drying and removing the liquid lubricant from the tube, the tube was stretched at a stretching ratio of 1000%, and then heated to 390 ° C. in a stretched state and sintered. A stainless steel rod having an outer diameter of 3 mm was inserted into the drawn tube, and the outer surface side was set to 600 mm.
° C, the inner surface side was heated at 285 ° C for 65 seconds. Table 1 shows the measurement results of the physical properties of the obtained tube. This tube was low in strength, could not maintain the luminal structure, and had low tear strength, so that it was impossible to implant it into a rat as an artificial blood vessel.

[0033]

[Table 1]

[0034]

The artificial blood vessel made of the porous PTFE tube of the present invention has a fiber-knot structure composed of a long fiber portion and a short fiber portion, and the long fiber portion has excellent penetration of living tissue and capillaries. It is possible to form a stable inner membrane over a long period of time, and the short fiber portion has excellent strength characteristics due to the high density of the nodule portion. By providing a structure in which the short fiber portion is distributed in a mesh shape from the inner surface to the outer surface of the tube in the circumferential direction of the tube and the outer surface thereof, it imparts tear strength and tensile strength, which are the mechanical properties required for the tube. . Therefore, even if the artificial blood vessel has a long fiber structure, the structure as a tube can be maintained, and trouble such as tearing does not occur at the time of suturing. As described above, the artificial blood vessel according to the present invention is an artificial blood vessel that is superior in both invasiveness to living tissue and, in addition, both long-term stability and mechanical properties of the intima, which cannot be achieved by the conventional technology. Even when the artificial vascular device has an inner diameter of 3 mm or less, excellent performance cannot be obtained.

[Brief description of the drawings]

FIG. 1 is a schematic diagram created based on a scanning electron micrograph of the inner surface of a tubular porous PTFE body of the present invention.

FIG. 2 is a schematic diagram created based on a scanning electron micrograph of a cross section in the stretching direction of the tubular PTFE porous body of the present invention.

[Explanation of symbols]

 1 long part of fiber 2 short part of fiber 3 nodule

Continued on the front page (51) Int.Cl. ⁶ Identification code FI C08J 9/00 CEW C08J 9/00 CEWA // B29K 27:18 C08L 27:18

Claims (3)

(57) [Claims] 1. A polytetrafluoroethylene porous tube having a fine fibrous structure composed of fibers and nodes connected to each other by the fibers, wherein a fiber-node structure extends from the inner surface to the outer surface of the tube. The fiber is substantially composed of two parts, a long part of the fiber and a short part of the fiber, and the short part of the fiber is distributed in the circumferential direction of the tube and in a mesh form from the inner surface to the outer surface of the tube. And artificial blood vessels. 2. The artificial blood vessel according to claim 1, wherein the average length of the fibers in the long part of the fiber in the fiber-knot structure is 60 μm or more, and the average length of the fibers in the short part of the fiber is 20 μm or less. 3. An inner surface of a porous tube obtained by extruding an unsintered polytetrafluoroethylene mixture containing a liquid lubricant, stretching in at least one direction after extrusion molding, and heating at a temperature of 327 ° C. or higher. both sides of the outer surface was heated again at 327 ° C. or more temperatures sintering temperature, whereby the outer table
The surface has a higher temperature in the range of 50 ° C to 300 ° C than the inner surface.
Heat between the inner and outer surfaces of the porous tube
A method for producing an artificial blood vessel, wherein a temperature gradient is applied to the artificial blood vessel.