JPH06343688A - Artificial blood vessel - Google Patents

Abstract

PURPOSE:To generate an artificial blood vessel excellent in the blocking performance of a pierced hole at the time of piercing with a needle by furnishing a multilayer structure in which a pipe wall consists of two or more porous layers made of ethylene tetrafluoride resin (PTFE), and forming a non-adhesion part at the interface between at least two of the porous substance layers. CONSTITUTION:An artificial blood vessel 1 to be favorably used in blood dialysis shunt is of a multilayer structure consisting of an inner layer tube 2 and outer layer tube 3 both made of a PTFE porous substance, and the interface between the two tubes 2, 3 is made non-adhesive. At least one of the layers 2, 3 is made from a PTFE porous substance which has a fine fibrous structure consisting of fibers and node coupling them and whose intersecting angle between the fiber orientation direction and the tube long axis direction is no less than 10deg. Thereby a needle is put piercing in the condition that a dislocation is generated between the two layers by a shearing force in the direction toward the plane at the time of piercing with a needle, and after draw-off of the needle, the pierced hole is blocked by a force generated by the layers willing to return each other due to strain.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an artificial blood vessel used for medical use, and more particularly to an artificial blood vessel made of a tetrafluoroethylene resin (hereinafter abbreviated as PTFE) porous material.

[0002]

2. Description of the Related Art A porous material made of PTFE is PT
FE itself has heat resistance, chemical resistance, weather resistance, nonflammability, and other characteristics, as well as low friction coefficient, water / oil repellency, non-adhesive surface characteristics, etc. Flexibility, fluid permeability, collection / filtration of fine particles, low dielectric constant / dielectric loss tangent, etc. are added, and these unique properties expand applications to general industrial fields as well as medical fields. is doing. For example, the PTFE porous body is used as a medical material such as an artificial blood vessel as well as a filtration membrane, a diaphragm, and a sealing material.

An artificial blood vessel is used as a bypass for filling a lesion site of a living blood vessel and excised defect, bypassing the lesion site and maintaining blood circulation, or as a blood conduit used for extracorporeal circulation of blood in hemodialysis. Is used as a shunt tube. Among the applications as an artificial blood vessel, the artificial blood vessel for dialysis shunt is a large field of application. The internal shunt is widely used as a blood access for hemodialysis for long-term dialysis patients, but this is for the case where the anastomoses or punctures due to frequent reoperations of the shunt have disappeared. Hemodialysis shunts are usually anastomosed in a bypass shape that connects the arteries and veins of the forearm and brachia. For this purpose, a PTFE porous tube with excellent flexibility and biocompatibility is often used. There is.

Although this PTFE porous tube is excellent in biocompatibility and flexibility, it is inferior in elasticity as compared with a living blood vessel. Therefore, when the PTFE porous tube is used as a shunt for hemodialysis, if the thick needle of the dialysis machine is repeatedly punctured, the hole of the puncture needle remains unobstructed after the puncture needle is removed, and blood / plasma leakage occurs from there. As a result, there has been a problem that a hematoma or a seroma occurs, blood leaks due to this puncture, and the intima abnormally thickens during repeated blood coagulation, eventually leading to an aneurysm / vascular occlusion.

On the other hand, an artificial blood vessel using a resin having a high elasticity, such as a silicone rubber resin or a urethane resin, can easily close its hole after puncture and withdrawal and has good hemostasis, but has tear strength and buckling resistance. There is a problem with sex. That is, these elastic resin tubes are unsuitable as an artificial blood vessel because they have low tear strength against surgical threads and the like and cannot be anastomosed during anastomosis with a living blood vessel, and particularly as an inner shunt application, such as forearm and upper arm. There is a problem that it does not have the flexibility required for transplantation into a narrow area and is easily buckled. Further, although the elastic resin tube has better local hemostatic property than the PTFE porous tube, the strength of the entire tube is severely deteriorated due to repeated puncture, so that the risk of tube rupture is high, and the PTFE tube Since it is not fibrous like a porous tube, there is also a risk of releasing agglomerates into the blood.

[0006]

The object of the present invention is to provide a PT
An object of the present invention is to provide an artificial blood vessel having excellent puncture hole occlusion properties during needle puncture, without impairing the surface characteristics, biocompatibility, and flexibility of the FE porous tube. As a result of intensive studies, the present inventors have found that the multilayer structure of the PTFE porous tube can provide the puncture of the puncture hole. That is, the tube wall of the artificial blood vessel is composed of a plurality of PTFE porous body layers, and at the interface between the respective layers or at the interface between at least two layers, simply adhered or partially fused or adhered, By providing the non-adhesive portion, the needle is punctured in a state in which the shear force at the time of puncturing the needle causes a gap between the layers of the non-adhesive portion, and as a result,
It has been found that the effective puncture area becomes small without forming a continuous through hole after the needle is removed. Also, PTFE
It has been found that the occluding property of the puncture hole is improved by shifting the fiber orientation direction of the porous tube from the normal tube axis direction to the circumferential direction. Furthermore, it has been found that by combining these two methods, the occlusive property of the puncture hole can be improved more effectively. The present invention has been completed based on these findings.

[0007]

Thus, according to the present invention, the tube wall has a multi-layer structure composed of two or more porous layers of tetrafluoroethylene resin, and the porous layer is An artificial blood vessel is provided, which has a non-adhesive portion at an interface between at least two layers of the above. Further, according to the present invention, in an artificial blood vessel composed of a tetrafluoroethylene resin porous body having a fine fibrous structure in which the tube wall has fibers and a nodule connecting the fibers, the orientation direction of the fibers is There is provided an artificial blood vessel characterized by having a crossing angle of 10 degrees or more with the long axis direction of the tube.

Further, according to the present invention, the tube wall has a multi-layered structure composed of two or more layers of the tetrafluoroethylene resin porous body layer, and the interface between at least two layers of the porous body layer. In the artificial blood vessel having a non-contacting portion, at least one layer of the porous body layer has a fine fibrous structure composed of fibers and a nodule connecting the fibers, and the tetrafluoroethylene resin porous body is An artificial blood vessel is provided, which is characterized in that the crossing angle between the fiber orientation direction and the long axis direction of the tube is 10 degrees or more.

The present invention will be described in detail below. PTFE
The porous tube has a problem that it is difficult to close the puncture hole. The present invention addresses this problem from a structural point of view. In the present invention, PTFE
As the porous body, a tube-molded product or a sheet-molded product further molded into a tubular shape can be used.

The PTFE porous tube used in the present invention can be manufactured, for example, by the method described in Japanese Patent Publication No. 42-13560. Specifically, first, P
A liquid lubricant is mixed with TFE unsintered powder and molded into a tube by extrusion or the like. The liquid lubricant is removed from the molded product by heating evaporation or the like, or the liquid lubricant is not removed, and the molded product is stretched in at least one axial direction. When the structure stretched by heating to a sintering temperature of 327 ° C. or higher in a state of preventing heat shrinkage is fixed by sintering, a PTFE porous tube having improved strength can be obtained.

This PTFE porous tube has a fine fibrous structure composed of very thin fibers and nodules connected to each other by the fibers, and this fine fibrous structure forms a porous space. . The fiber diameter and length, the size of knots and the number thereof can be changed depending on the conditions of stretching and sintering, and the pore size and porosity of the obtained PTFE porous tube can be freely determined. The PTFE porous sheet can be obtained by the same method. The long axis direction of the fiber connecting the respective nodes is called the fiber orientation direction. These PTFs
As described above, the pores of the E porous body are not blocked by the puncture.

The first feature of the present invention is that the PTFE porous body has a multi-layer structure, so that the puncture holes in each layer are
Even if it is left as it is, it is used that the area of the hole penetrating from the outer surface to the inner surface is reduced when the displacement between the layers occurs. Multiple PTFs that make up a multilayer structure
E When at least two layers of the porous body layers have a degree of freedom that causes a displacement in the plane direction, the needle is punctured in a state in which the shear force in the plane direction at the time of needle puncture causes the displacement between the two layers. Is punctured. When the needle is removed, the strain applied to each layer during straining tends to return to each other, and as a result, the puncture hole in each layer is no longer a continuous through hole, and the effective puncture area is reduced.

Generally, a puncture needle used for dialysis has an outer diameter of 1 mm or more. Therefore, in order to effectively reduce the effective puncture hole area, at least 0.1
It is preferable to have a degree of freedom that causes a displacement between layers of not less than mm.

In order to have such a "degree of freedom of displacement" in the multilayer structure, (1) simply expanded PT
A method in which the FE tube is covered on the PTFE tube which is the inner layer, contracted at a temperature lower than the melting point, and each layer is adhered and fixed only by frictional force, (2) Each laminated layer is partially heated to the melting point or higher. And (3) a resin having a lower melting point than PTFE, for example, FEP, silicone resin, urethane resin,
It is possible to employ a method in which each layer is partially adhered by using a fluororubber, a thermoplastic elastomer, or the like, but a non-adhered portion is present, or a method in which these methods are combined.

The second feature of the invention is that the puncture hole cross section changes to an elongated shape by making the orientation direction of the fibers of the PTFE porous tube asymptotic to the circumferential direction. It utilizes the fact that the area of the holes is small. Generally, when puncturing a needle, the long axis of the needle is made to coincide with the long axis of the artificial blood vessel, so the cutting edge at the tip of the needle has an approach angle of about 90 degrees with respect to the long axis of the artificial blood vessel. It will be. At this time, if the fibers of the artificial blood vessel are oriented in the circumferential direction, the approach angle of the cutting edge and the orientation direction of the fibers match, and the puncture hole opens so as to tear in the direction of the fiber. The hole has a narrow and long cross section, and as a result, the area of the puncture hole can be kept small.

As described above, in order to effectively reduce the size of the puncture hole, it is necessary to set the entering angle of the cutting edge of the puncture needle with respect to the fiber orientation direction to be at least 80 degrees or less. It is necessary that the orientation direction has an angle of 10 degrees or more with the major axis direction. Generally, when a PTFE porous tube is manufactured, the orientation ratio of the fibers coincides with the long axis direction of the tube because the stretching ratio in the long axis direction of the tube is large. In order to make the orientation direction of the fiber have an angle of 10 degrees or more with respect to the long axis direction of the tube, for example, an expanded PTFE tube molded product is fixed in a state in which it is twisted and deformed, and the temperature is kept at a temperature higher than the melting point. A method of heating for a time and cooling can be adopted. By this method, a PTFE porous tube having a structure in which the fibers are spirally oriented on the circumference centering on the long axis direction of the tube can be obtained.

Further, the PTFE porous tube in which the fiber orientation direction has an angle of 10 degrees or more with respect to the long axis direction of the tube is a PTFE sheet molded product, so that the fiber orientation is in the circumferential direction. It can be obtained by wrapping around a cylinder, fixing, heating to a temperature above the melting point for a certain period of time, cooling, and then removing the cylinder. When the fiber orientation direction coincides with the circumferential direction, the crossing angle between the fiber orientation direction and the long axis direction of the tube is 90 degrees.

In this way, a PTFE porous tube having an intersection angle between the fiber orientation direction and the long axis direction of the tube of 10 degrees or more can be prepared. Here, the intersection angle is 1
0 degree or more means that the smaller one of the two intersection angles formed by the fiber orientation direction and the long axis direction of the tube is 10 degrees or more. Further, by combining the first and second characteristics of the present invention, it becomes possible to obtain a larger puncture hole blocking property. If the area of at least one puncture hole is small, the effective puncture hole area will be extremely small even if the displacement between the layers is small.

As described above, when the needle is punctured and withdrawn from the artificial blood vessel having the multilayer structure, the puncture hole is displaced in the axial direction, and the effective area of the hole continuous from the inner surface to the outer surface is reduced. Therefore, bleeding from the hole is minimized and
The holes are quickly clogged with thrombus, and the time for hemostasis can be shortened. Further, in the artificial blood vessel in which the orientation direction of the fibers is asymptotic to the circumferential direction, the puncture hole is opened literally in parallel with the orientation direction of the fiber, and the area of the hole is reduced. Therefore, bleeding from the hole can be suppressed to a minimum, and the hole can be quickly blocked by a thrombus to shorten the hemostasis time. Furthermore, the area of the perforated puncture hole is extremely reduced by using a multilayer structure and combining layers in which the orientation direction of the fibers is asymptotic to the circumferential direction. Therefore, the amount of bleeding from the hole is extremely small, the occlusion by the thrombus is extremely fast, and the hemostasis time can be extremely shortened.

[0020]

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.

Example 1 To 100 parts by weight of PTFE fine powder (F104 manufactured by Daikin Industries, Ltd.), naphtha (manufactured by Esso Co., Ltd., drysol) was added.
After mixing 3 parts by weight as an auxiliary agent and molding into a tube by a ram extruder, DRYSOL was dried at 50 ° C. for 48 hours. This extruded tube is placed in an electric furnace for 400
500% while heating at 80 ℃ for 80 seconds in the furnace
Stretched, porosity 77%, fiber length 33 μm, inner diameter 4 mm,
PTFE porous tube with 300 μm wall thickness (Sample N
o. 1) was obtained.

Further, at room temperature, a stainless steel column having an inner diameter of 5 mm or 6 mm was inserted into the inner cavity of the tube and expanded to obtain a tube having an inner diameter of 5 mm and a tube having an inner diameter of 300 μm and a diameter of 6 mm. The inner diameter of the tube with an inner diameter of 4 mm and a cylinder made of stainless steel with an outer diameter of 4 mm were inserted into the inner lumen of the tube with an inner diameter of 5 mm, which was the outer layer, and the tube with an inner diameter of 5 mm was placed in a furnace at 300 ° C. By contracting in the direction, the inner layer was brought into close contact with a tube having an inner diameter of 4 mm to obtain a tube (sample No. 2) having a two-layer structure of an inner layer and an outer layer having an inner diameter of 4 mm.

Similarly, a stainless steel cylinder having an outer diameter of 4 mm is inserted into the inner lumen of a tube having an inner diameter of 4 mm, and the tube is inserted into the inner lumen of a tube having an inner diameter of 5 mm, which serves as an intermediate layer. Insert into a 6 mm tube
Tubes with inner diameters of 5 mm and 6 mm are contracted in the furnace at 0 ° C. in the radial direction so as to be closely adhered to the inner layer tubes with inner diameter of 4 mm. . 3) was obtained.

18G of the original tube having an inner diameter of 4 mm (Sample No. 1), the two-layer structure tube (Sample No. 2) and the three-layer structure tube (Sample No. 3) according to the present invention, which are not multilayered The amount of water leakage from the puncture hole with the needle at an internal pressure of 120 mmHg was measured.
The results are shown in Table 1. As is clear from Table 1, it was found that the effect of reducing the amount of water leakage was obtained by increasing the number of layers. Further, when observing the puncture holes in each layer, as shown in FIG. 1, the effective area of the puncture holes was reduced due to the displacement between the layers.

[Embodiment 2] The inner diameter used in Embodiment 1 is 4 mm.
Insert a stainless steel cylinder with an outer diameter of 4 mm into the inner lumen of the tube, and twist the tube so that the fibers of the tube are oriented at an angle of 60 degrees with respect to the long axis direction The tube was fixed and heated in a furnace at 350 ° C. for 5 minutes to orient the fibers at an angle of 60 degrees with respect to the long axis direction of the tube.
o. 4) was obtained. In this case, the fibers are helically oriented on the circumference at an angle of 60 degrees with respect to the long axis direction of the tube.

The obtained spiral orientation tube (Sample N
o. Regarding 4), the amount of water leakage was measured in the same manner as in Example 1. As a result, as shown in Table 1, with respect to the original tube having an inner diameter of 4 mm (Sample No. 1) in which the fibers were oriented in the long axis direction of the tube, a water leakage reduction effect of 20% or more was recognized. Further, when the puncture hole was observed, as shown in FIG. 2, the shape of the puncture hole was different from that of the long-axis oriented product, and the area of the hole was reduced.

[Example 3] A ram extruder was prepared by mixing 23 parts by weight of naphtha (Drysol, trade name, manufactured by Esso Co.) with 100 parts by weight of PTFE fine powder (CD123, manufactured by Asahi Glass Co., Ltd.) as an auxiliary agent. After being molded into a tube shape by, the drysol was dried at 50 ° C. for 48 hours. This extruded tube was stretched by 450% while being heated in an electric furnace at a temperature of 550 ° C. for 30 seconds in the furnace, and a porous PTFE tube having a porosity of 82%, a fiber length of 40 μm, an inner diameter of 6 mm, and a wall thickness of 800 μm was formed. (Sample No. 5) was obtained.

On the other hand, the tube having an inner diameter of 4 mm used in Example 1 was expanded at room temperature while being inserted into a stainless steel column having an outer diameter of 6 mm, and the fiber was formed at an angle of 60 degrees with respect to the longitudinal direction of the tube. Add twist deformation to orient,
By heating in a furnace at 350 ° C for 5 minutes, the inner diameter is 6m
m, and a wall thickness of 300 μm or less was obtained. A stainless steel cylinder with an inner diameter of 6 mm is inserted into the inner wall of a thick-walled tube, and a spirally oriented thin-walled tube is covered on the tube while expanding, and fibers are oriented in the inner layer of the PTFE porous body. A tube (Sample No. 6) having a two-layer structure of a PTFE porous body layer in which fibers were spirally oriented was obtained as the layer and the outer layer.

The resulting two-layer tube (Sample N
o. 6) and the thick-walled tube (Sample No. 5) used for manufacturing this tube, the amount of water leakage was measured in the same manner as in Example 1. As a result, as shown in Table 1,
By changing the thickness of a single-layer tube from a single-layer tube to a two-layer tube covered with a spiral orientation thin tube,
A 0% reduction in water leakage was obtained. When the inner surface and the outer surface of the tube were observed, the area of the puncture hole in the inner layer was large, but the puncture hole in the outer layer was almost closed.

[Example 4] Uniaxially stretched PTFE sheet F
P030 (wall thickness 80 μm, pore diameter 30 μm, manufactured by Sumitomo Electric Industries, Ltd.) was used. As shown in FIG.
After the sheet was wrapped around a stainless steel cylinder having an outer diameter of 6 mm for 10 turns so that the fibers were oriented in the circumferential direction of the cylinder, and both ends of the sheet were fused using a trowel heated to a temperature equal to or higher than the melting point. By pulling out the cylinder, a 10-layer tube (Sample No. 7) in which the fibers were oriented in the circumferential direction (the angle of intersection with the long axis direction of the tube was 90 degrees) was produced.

The resulting 10-layer tube (Sample N
o. Using 7), the amount of water leakage was measured in the same manner as in Example 1. As a result, as shown in Table 1, a reduction in water leakage of about 75% was obtained with respect to the single-layer long-axis oriented product (Sample No. 1 or 5). Further, when the inner surface and the outer surface were observed, the puncture holes in the inner layer and the outer layer were almost closed.

[0032]

[Table 1] (Footnote) (Mean ± SD) Each n = 4, internal pressure = 120 mmHg (0.16 kg / cm
² ) 18G (φ1.20mm) needle puncture

[Embodiment 5] Sample No. 3 of the third embodiment. 6
An artificial blood vessel having a length of about 40 mm (Sample No. 8) manufactured by the same method as described above and a commercially available artificial blood vessel having a length of about 40 mm (Sumitomo Electric Industrial Co., Ltd., technograft having an inner diameter of 6 mm) were respectively placed in rabbits ( A comparative study was conducted on the time required for hemostasis after removal of the 18G needle puncture by substituting the abdominal aorta of a mature New Zealand White rabbit (2 males, body weight: about 3 kg).

After pentobarbital (manufactured by Dynabot Co., Ltd., trade name pentocillin) was intravenously injected through the ear vein of a rabbit, and when deep anesthesia was reached, the abdomen was incised and the abdominal aorta was exposed and peeled from the surrounding tissue. The renal artery and the inferior mesenteric artery were ligated with No. 4-0 silk suture. Next, blood flow was stopped upstream and downstream of the abdominal aorta using a vascular clip. Then, in order to anastomose the artificial blood vessel of φ6 mm, the artificial blood vessel was anastomosed to the abdominal aorta through a special connector, the clip was removed, and the blood flow was restarted.

[0035] for its portability artificial blood vessels, 18G needle in
After puncturing with in situ and observing bleeding immediately after removal, immediately press the puncture site with a specially made compression device with a pressure of 120 mmHg, and confirm the hemostasis every minute. Was performed 4 times. As a result, technograft has a relatively large amount of bleeding and requires a time of 15 minutes or more, whereas sample No. At 8 with almost no bleeding, 0
Hemostasis was completed within ~ 3 minutes.

[0036]

According to the present invention, there is provided an excellent artificial blood vessel having both the biocompatibility of the PTFE porous tube and the puncture hole blocking property due to a special structure. Therefore, the artificial blood vessel according to the present invention is very effective especially as an artificial blood vessel for a hemodialysis shunt.

[Brief description of drawings]

FIG. 1 is a multilayer artificial blood vessel of Example 1 (Sample N).
o. It is the figure which expanded the cross section of the puncture hole after 18G needle puncture extraction of 2).

FIG. 2 is an enlarged view of the puncture hole of the spirally oriented artificial blood vessel (Sample No. 4) of Example 2 after the 18G needle puncture and withdrawal, as seen from the outer surface.

3 is a schematic diagram showing the structure of a 10-layer artificial blood vessel (Sample No. 7) of Example 4. FIG.

[Explanation of symbols]

1: Two-layer PT used in Example 1 but not bonded to each other
It is an artificial blood vessel of FE porous body. 2: Inner layer tube of PTFE porous body. 3: PTFE outer layer tube. 4: Layer deviation caused by the operation of puncturing / withdrawing the 18G needle. 5: A portion (effective hole) where the holes of each layer overlap due to the deviation of the layers. 6: An artificial blood vessel using the spirally oriented PTFE porous body used in Example 2. 7: An arrow indicating the direction of fiber orientation. 8: A hole showing an elongated shape that remains after the 18G needle is punctured and removed. 9: 10-layer artificial blood vessel used in Example 4. 10: A portion where each layer is not adhered and the effect of blocking the puncture hole of a 10-layer structure is obtained. 11: A part where each layer is bonded at a temperature equal to or higher than the melting point. 12: An arrow indicating the orientation direction of the fibers.

Claims (3)

[Claims] 1. A pipe wall has a multi-layer structure composed of two or more layers of a tetrafluoroethylene resin porous body layer, and a non-adhesive portion at an interface between at least two layers of the porous body layer. An artificial blood vessel having: 2. An artificial blood vessel whose tube wall is made of a tetrafluoroethylene resin porous body having a fine fibrous structure composed of fibers and nodules connecting the fibers, in an orientation direction of the fibers and a tube length. An artificial blood vessel having a crossing angle with the axial direction of 10 degrees or more. 3. The tube wall has a multi-layer structure composed of two or more layers of a tetrafluoroethylene resin porous body layer, and has a non-contact portion at the interface between at least two layers of the porous body layer. An artificial blood vessel, wherein at least one layer of the porous body layer is made of a tetrafluoroethylene resin porous body having a fine fibrous structure composed of fibers and a nodule connecting the fibers, and An artificial blood vessel, wherein the crossing angle between the fiber orientation direction and the long axis direction of the tube is 10 degrees or more.