JPH05237141A - Artificial blood vessel and its production - Google Patents

Abstract

PURPOSE:To stably maintain the initially formed thrombomembranes while maintaining the antithrombotic property of PTFE by providing rugged structures formed of the parts where fine fibrous tissues are cut and/or decomposed and removed on the inside cavity surface of the artificial blood vessel. CONSTITUTION:Many recessed parts 3 and projecting parts 4 are formed on the inside cavity surface of the artificial blood vessel made of the stretched PTFE. Such rugged structures can be imparted to the artificial blood vessel by forming the recessed parts 3 which are formed by treating the inside cavity surface made of a porous tubular tetrafluoroethylene resin body having the fine fibrous tissues consisting of fibers 1 and knods 2 connected by the fibers 1 to each other thereby cutting or decomposing away the fine fibrous tissues and the projecting parts 4 where the nodal parts remain and shrink. The rugged structures of the inside cavity surface to be imparted to the artificial blood vessel are 10 to 50mum in the average width of the recessed parts in the blood flow direction and 5 to 20mum in the average depth of the recessed parts. As a result, the artificial blood vessel has the property to stably maintain the thrombomembranes formed by the rugged structures in addition to the property to form the thin thrombomembranes the PTFE material.

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 excellent in biocompatibility and a method for producing the same.

[0002]

2. Description of the Related Art Artificial blood vessels are replacement transplants for filling a defect in a lesion site of a living blood vessel, bypass transplants for bypassing the lesion site to maintain blood circulation, or blood conduits such as short circuits between arteries and veins. Is used as. Conventionally, as a material for an artificial blood vessel, a polyester fiber knitted fabric or a woven fabric having a braided structure, or an expanded polytetrafluoroethylene (hereinafter abbreviated as PTFE) tube having a fine porous structure has been used.

Among these, the expanded PTFE tube (tubular tetrafluoride ethylene resin porous body) is a product obtained by expanding PTFE and then firing it, and although it is not braided, it is made of fibers (fibrils) and the fibers. A fine porous structure is formed by the connected nodes, and this porous structure has excellent biocompatibility and P
Since the TFE material itself has excellent antithrombotic properties, it has been put to practical use mainly as an artificial blood vessel in the areas of small-diameter arteries and large-diameter veins.

An artificial blood vessel is required to have a high initial patency rate and a long-term patency rate. Various factors are involved in the patency rate, and among them, the antithrombogenicity of the material has a very important influence. However, it cannot be said that the expanded PTFE tube also has sufficient antithrombotic properties, and in particular, a sufficient long-term patency rate has not been obtained with a small-diameter artificial blood vessel having an inner diameter of 6 mm or less.

As a method for improving the antithrombotic property of the artificial blood vessel, (1) a method for improving the antithrombotic property of the material itself,
(2) A method of inducing an intima by inducing a living tissue after transplanting an artificial blood vessel to impart antithrombotic properties, and the like have been studied. However, in the method (1), although development of an antithrombotic polymer material such as a phase-separated structure or an antithrombotic agent-immobilized material is being studied, a material that exhibits good antithrombotic properties for a long period after transplantation. Has not been obtained.
In the method (2), in order to promote intimal formation after transplantation, a method for promoting invasion of living tissue or capillaries from outside the blood vessel is currently being studied.

The initial patency of a vascular prosthesis depends on what initial interactions the material's antithrombotic properties exhibit. When an artificial blood vessel is transplanted into a living body, as a result of the initial interaction, an initial thrombus membrane is formed on the surface of the lumen due to adhesion of platelets and the like. This initial thrombus membrane undergoes tissue healing by fibroblasts, and a neointima due to proliferation of neoendothelial cells or a pseudointimal membrane in which collagen and fibrin are mixed is formed. This intima provides long-term antithrombotic properties and long-term patency. However, for that purpose, it is necessary to stably form the thinnest initial thrombus membrane on the luminal surface of the artificial blood vessel and thin the intimal membrane formed during the tissue healing process, that is, to prevent intimal thickening. is necessary.

By the way, conventionally used expanded PTF
As described above, the artificial blood vessel made of E has an excellent antithrombotic property to some extent, but the improvement of the antithrombotic property by the method (1) is limited, and is non-adhesive. There are also disadvantages in. The inner membrane described above is formed in the following order, for example. First, the adhesion of platelets and the thrombus membrane due to fibrin are formed on the inner surface of the artificial blood vessel. After that, the blood reaction after transplantation settles down, and the formed thrombus membrane becomes stable. Smooth muscle cells and endothelial cells extend as an intima mainly from the anastomosis part with the living blood vessel, and an intima is formed on the inner surface of the artificial blood vessel.

However, in the expanded PTFE artificial blood vessel, the thrombus membrane to be formed first is not stably formed on the inner surface of the artificial blood vessel due to the non-adhesiveness of PTFE, and the intima may be extended. Also, peeling occurs at the interface between the artificial blood vessel and the thrombus membrane. As a result, thrombus is again induced by the separated thrombus membrane and intima, and the artificial blood vessel undergoes stenosis / occlusion. On the other hand, an artificial blood vessel made of polyester fiber knitted fabric or woven fabric is made of polyester, which has better adhesiveness than PTFE, so that the stability of the thrombus membrane is excellent, but the thickness of the thrombus membrane formed in the initial stage is thick, and therefore the intimal thickening However, there is a problem that the stenosis is likely to occur.

[0009]

SUMMARY OF THE INVENTION An object of the present invention is to artificially form an intimal membrane similar to a living blood vessel on the inner surface of an artificial blood vessel thinly and stably, and particularly well in a small diameter region with an inner diameter of 6 mm or less. To provide blood vessels. As described above, in order to form a thin and stable intima on the inner surface of the artificial blood vessel, it is first necessary to form a thin and stable thrombus in the process of forming the thrombus, which is the preceding step.

The present inventor has conducted extensive studies in order to overcome the above-mentioned problems of the prior art, and as a result, made of expanded PTFE porous tube having a fine fibrous structure composed of fibers and nodules connected to each other by the fibers. Cutting, contraction and / or decomposition of fine fibrous tissue on the inner surface of the artificial blood vessel
It was found that by forming an uneven structure formed by the removed portion, it is possible to stably hold the thrombus membrane initially formed while maintaining the antithrombotic property of PTFE.

Particularly, regarding the concavo-convex structure on the surface of the lumen of the expanded PTFE tube-made artificial blood vessel, the average depth of the concavities is 5
It was found that a thin initial thrombotic membrane can be stably formed and retained by setting the average initial width of the concave portion of the tubular structure in the long axis direction (blood flow direction) to be in the range of 10 to 50 μm. .. Furthermore, as a method of forming such a concavo-convex structure, cutting of fine fibrous tissue on the surface of the lumen is performed.
It has been found that there are various methods of shrinking and / or disassembling / removing. The present invention has been completed based on these findings.

[0012]

Thus, according to the present invention, there is provided an artificial blood vessel made of a tubular tetrafluoroethylene resin porous body having a fine fibrous structure comprising fibers and nodules connected to each other by the fibers. An artificial blood vessel is provided, which has an uneven structure formed at least on the surface of its lumen by a cut / contracted and / or decomposed / removed portion of a fine fibrous tissue.

Further, according to the present invention, at least the inner surface of the tubular tetrafluoroethylene resin porous body having a fine fibrous structure composed of fibers and nodules connected to each other by the fibers is treated with an alkali metal compound organic compound. Treated with a solvent solution,
There is provided a method for producing an artificial blood vessel, which comprises decomposing a fine fibrous tissue and then removing the decomposed product to form an uneven structure at least on the surface of the lumen.

The present invention will be described in detail below. Many factors are involved in thrombus formation, but in the case of artificial blood vessels, materials such as PTFE and polyester, as described above,
The two major factors are the shape of the inner surface of the artificial blood vessel. Blood flows through an artificial blood vessel with a smooth inner surface (similar to a living blood vessel) with the flow direction aligned in one direction, but if there is a change in the inner surface shape of the artificial blood vessel, such as a step or diameter change, the flow is disturbed. And generate a local eddy current. This turbulence in the flow induces thrombus formation, the degree of which depends on the degree of shape change of the inner surface of the blood vessel.

Conventionally, thrombus formation by changing the shape of the inner surface of the artificial blood vessel has been used, for example, in the case of an artificial blood vessel of a polyester fabric having a large diameter, by raising the inner surface of the artificial blood vessel to enhance the healing property. Since the thickness of the thrombus film formed is increased as compared with a smooth inner surface, it has been exclusively limited to application with a larger diameter, and it has been said that the smaller the diameter, the smoother the inner surface needs to be. That is, it can be said that such an artificial blood vessel has been applied for the purpose of forming a relatively thick thrombus membrane or intima.

The present inventors rather give the physical property of stability of the thrombotic membrane due to the change in shape of the inner surface to the chemical property of PTFE which is non-adhesive and low thrombotic, so that Stretched PTFE that does not peel off and adhere stably
We came to think that we could overcome the drawbacks of artificial blood vessels.
As a result of earnest research, the present inventors have found that expanded PTFE
It was found that the thickness of the thrombus membrane formed on the inner surface of the artificial blood vessel can be controlled by imparting an uneven structure to the inner surface of the artificial blood vessel, and changing the degree of the unevenness.

Further, as a result of earnest research, the present inventors have found that
The concavo-convex structure provided on this inner surface stably holds the initial thrombus membrane on the inner surface of the artificial blood vessel, and the stability of this thrombus membrane is determined by the inner membrane that replaces this thrombus membrane during the subsequent healing process of the artificial blood vessel. It was found that the healing rate is promoted and that the uneven structure has an effect of stably retaining the intima of the healed inner surface of the artificial blood vessel.

The effect of forming such an uneven structure is as follows.
It can be said that it is a kind of anchoring effect by expanding the adhesion area due to the uneven structure, thereby improving the non-adhesiveness that is a characteristic feature of PTFE and realizing the purpose of preventing peeling of the thrombus membrane and intima. It becomes possible to do.

The expanded PTFE artificial blood vessel of the present invention is shown in FIG.
As shown in the schematic diagram, a large number of concave portions (3) and convex portions (4) are formed on the surface of the lumen. As shown in FIG. 2, such a concavo-convex structure is made of a tubular tetrafluoroethylene resin porous body having a fine fibrous structure composed of fibers (1) and nodules (2) connected to each other by the fibers. Recesses (3) in which the surface of the lumen is treated to cut or decompose and remove fine fibrous tissue, and protrusions (4) in which nodules remain or contract
Can be imparted by forming.

In the concavo-convex structure on the surface of the lumen given to the artificial blood vessel of the present invention, the average width of the concave portions in the blood flow direction (long axis direction of the tubular structure) is preferably 10 to 100 µm, more preferably 10 to 50 µm. is there. If the average width of the concave portions in the blood flow direction is too small, the effect of improving the formation and stabilization of the thrombus membrane is small, and conversely, if the width is larger than 100 μm, the blood flow is greatly disturbed and a thick thrombus is formed. The film grows rapidly.

The average depth of the concave portions of the concavo-convex structure is preferably 3 to 30 μm, more preferably 5 to 20 μm. If the average depth of the recesses is too small, formation of a thrombus film and
If the stabilization effect is small, on the contrary, if it is too large,
The initial thrombotic membrane becomes too thick and premature obstruction occurs more frequently. For example, when the average width of the recesses in the blood flow direction exceeds 20 μm, the formed thrombus membrane becomes too thick at an average depth of the recesses of 30 μm or more, and the frequency of early occlusion slightly increases. However, when the average width of the recesses in the blood flow direction is 20 μm or less, there is no problem even if the average depth of the recesses is 30 μm or more.
However, even if the depth exceeds 30 μm, there is no difference in the stabilizing effect on the thrombus membrane, and it is difficult to form a deep uneven structure with a short width in terms of manufacturing. The thickness is 30 μm, preferably 5 to 20 μm.

From the above, the concavo-convex structure formed on the inner surface of the lumen can be controlled so as to have recesses having an average depth of 5 to 20 μm and an average width of 10 to 50 μm in the longitudinal direction of the tubular structure. desirable.

The artificial blood vessel of the present invention is, for example, Japanese Patent Publication No.
It can be manufactured by producing an expanded PTFE tube (PTFE porous tube) by the method described in No. -13560, and then performing a treatment of forming a concavo-convex structure on the surface portion to be the lumen surface.

First, a liquid lubricant is mixed with PTFE unsintered powder, and preformed into a tubular shape by extrusion, rolling or the like. The liquid lubricant is removed from the molded body or is stretched in at least uniaxial direction without being removed. Next, in a state where the molded body is fixed so as not to shrink, it is heated to 327 ° C. or higher, which is the melting point of the resin, and the stretched structure is sintered and fixed to obtain a PTFE porous tube having improved strength. This PTFE porous tube is a porous tube having a fine fibrous structure composed of fibers and nodules connected to each other by the fibers.

The product of the present invention can be obtained by imparting an uneven structure to the inner surface of the expanded PTFE artificial blood vessel.
In order to impart an uneven structure without changing the properties of E, the cut / shrinked and / or decomposed / removed portion of the fine fiber structure is provided. Examples of the method for forming such a concavo-convex structure include (1) the method described in JP-B-58-1656, that is, whether a part of the PTFE porous body is heated to a higher temperature than the other part in the heating and sintering step. Or, after uniformly heating and sintering the whole, a part of the PTFE porous body is further heated to cause cutting or fusion bonding of fine fibers, and fusion bonding of knots due to shrinkage between the knots,
(2) The method described in JP-B-63-23215, that is, the method in which the surface of the PTFE porous body is heated to a temperature higher than the thermal decomposition temperature of PTFE by hot air, flame, carbon dioxide laser or the like to decompose and remove a part of the surface. , Can be used.

When a part of the PTFE porous body is heated by these methods, the PTFE fibers are cut by heat to spread the internodal spaces into recesses, the other internodal spaces shrink, and the nodules gather to form convex parts. However, PTFE is decomposed when the fiber is cut, and is gasified and removed. 70
When heat treatment is performed in a heating furnace at 0 to 1000 ° C., decomposition and removal of fibers do not occur so much, and particularly when performed at a low temperature, they hardly occur. On the other hand, when directly treating with the flame of the gas burner, the decomposition and removal of the fiber is superior to the cutting and shrinking. Normally, both cutting and shrinking of fine fibrous tissue and decomposition and removal occur.

In the surface processing by these heat treatments,
Rapid heating at a higher temperature produces a fine relief structure, and slower heating at a lower temperature produces a rough relief structure. In other words, by controlling the processing temperature and speed, it is possible to provide a concavo-convex structure having a desired shape.

However, in these methods, it is difficult to apply the energy such as heat to a part of the PTFE porous body, so that it is difficult to apply the energy to the inner surface of the thin PTFE porous tube. Requires devising. PTFE
As a method for imparting an uneven structure to the inner surface of the porous tube, for example, there is a method in which the outer surface of the PTFE porous tube is heat-treated to provide the uneven structure and then the inner and outer surfaces are inverted. In this method, distortion may occur due to the difference in length between the inner circumference and the outer circumference, and the tube may collapse,
In this case, it is advisable to insert a stainless rod or the like into the lumen and heat it to such an extent that the fine fibrous tissue structure is not affected.

Further, in addition to the cutting / shrinking and the decomposition / removal of the fine fibrous tissue by the heat, the PT is produced by a chemical treatment.
There is a method to decompose and remove the FE fiber. Specifically, an alkali metal compound such as methyllithium or a complex of an alkali metal such as sodium or potassium with an anion radical such as naphthalene or anthracene is a PTF.
E can be decomposed. The inventors of the present invention properly control the type of alkali metal compound, the concentration of the organic solvent solution, the treatment time, the temperature, etc., without destroying the nodules of the fine fibrous structure of the PTFE porous tube, and only the fibers Found that you can disconnect.

Specific conditions of the chemical treatment include, for example,
A solution of an alkali metal compound such as methyllithium, sodium-naphthalene complex or sodium-anthracene complex in an organic solvent such as tetrahydrofuran (concentration of 0.1 to 1).
The PTFE porous tube is immersed in 0 mol / liter) and kept at a liquid temperature of 20 to 68 ° C. for about 5 to 60 minutes.

Further, sodium fluoride generated on the surface of the PTFE porous tube by these chemical treatments, a decomposition product of PTFE such as a carbon-carbon double bond, these and naphthalene,
Decomposition products such as a polymer with anthracene can be removed by oxidative decomposition with hydrogen peroxide or sodium hypochlorite.

This chemical treatment method does not require labor such as inversion of the inner and outer surfaces and correction of the distortion of the tubular structure due to it, as compared with the method of utilizing heat, and particularly the inner diameter of 3 m which is the object of the present invention.
This is a useful method for artificial blood vessels having a small diameter of m or less.

The artificial blood vessel of the present invention is required to have a concavo-convex structure on at least the surface of its inner cavity, and the concavo-convex structure may be formed on both inner and outer surfaces. Even if the concavo-convex structure is formed on both the inner and outer surfaces, a large decrease in strength does not occur with the thickness of an ordinary artificial blood vessel (about 300 to 1000 mm). In addition, if a concavo-convex structure is formed also on the outer surface, organizing and healing (invasion of tissues such as fibroblasts) will proceed from the outer surface of the artificial blood vessel.

To treat only the inner surface of the artificial blood vessel by the chemical treatment, for example, one end of the PTFE porous tube may be sealed and the treatment liquid may be injected from the other end by a pump or a syringe. By immersing the PTFE porous tube in the treatment liquid, an uneven structure is formed on both inner and outer surfaces.

PTF by heat or chemical treatment as described above
The provision of the concavo-convex structure on the inner surface of the E lumen is a method of processing the fine fibrous tissue itself on the inner surface of the PTFE porous tube. In other words, in the porous structure of the inner surface of the PTFE porous tube, the knotted portion is formed into a convex portion and the fiber portion is formed into a concave portion. Therefore, the concavo-convex structure that can be applied is limited by the tissue structure such as the distance between the nodules on the surface of the PTFE porous tube before the concavo-convex structure is applied. For example, PT with internodal distance longer than 30 μm
With a FE porous tube, it is virtually impossible to form a recess having a width of 30 μm or less. Therefore, in order to form a concavo-convex structure having a desired average depth and width of the recesses, it is necessary to prepare a fine fibrous tissue on the surface of the lumen, particularly a PTFE porous tube with a different internodal distance, For example, according to the method described in Japanese Examined Patent Publication No. 42-13560, it is possible to prepare PTFE porous tubes having various porous structures by changing the stretching ratio in the stretching step.

The product of the present invention obtained by the above manufacturing method has the following features. (1) PT Since it is obtained by a method of processing the inner surface of the tube itself, rather than adding or adding a substance other than PTFE to the porous tube, PT
It does not hinder the characteristics of FE itself as an artificial blood vessel. (2) Since the concavo-convex structure is integrally provided on the inner surface of the porous tube, there is no problem such as peeling or separation of the concavo-convex structure portion.

Due to these characteristics, the product of the present invention has a stretched P
The advantage of the TFE artificial blood vessel, while maintaining the property of forming a thin thrombus film based on non-adhesiveness, it is possible to stably hold the formed thrombus film by its inner surface concavo-convex structure. Stable intimal formation of the artificial blood vessel lumen can be realized.

[0038]

EXAMPLES The present invention will be specifically described below with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.

The methods for measuring the physical properties are as follows. <Average fiber length> The internodal distance was measured with a scanning electron microscope, and the average value was calculated.

<Bubble point> When the artificial blood vessel is dipped in isopropyl alcohol and the hole in the tube wall is filled with isopropyl alcohol, and air pressure is gradually applied from the inside of the tube, the first time air bubbles come out. Was measured.

<Water Leakage Pressure> When water pressure was gradually applied from the inside of the artificial blood vessel, the water pressure when water came out from the outer wall of the artificial blood vessel for the first time was measured.

<Patency> The artificial blood vessel was transplanted and kept alive for a certain period of time, and the ratio of the number of artificial blood vessels in which blood flow was observed at that time to the total number of transplanted artificial blood vessels was shown.

<Thrombus Thickness> An artificial blood vessel was transplanted, and after being kept alive for a certain period of time, the artificial blood vessel was fixed with formalin, dried at a critical point, and then, on a scanning electron microscope, the inner surface of the cross section cut in the longitudinal direction was examined. The thickness of the attached thrombus membrane was measured, and the average value was displayed.

<Endothelial Cell Coverage> Same as above The ratio of the area of the inner surface of the sample coated with vascular endothelial cells to the total area of the inner surface is shown.

[Example 1] PTFE fine powder (manufactured by Daikin Industries, Ltd., PTFE fine powder F10)
4) 20 parts by weight of dryzole was mixed with 100 parts by weight as an auxiliary agent and molded into a tube by a ram extruder, and then dryzol was dried at 50 ° C. for 48 hours. This extruded tube was stretched 250% while being heated in an electric furnace under conditions of a furnace temperature of 350 ° C. and a residence time in the furnace of 120 seconds, a porosity of 65%, an average fiber length of 10 μm, and an inner diameter of 2 mm.
A PTFE porous tube with φ and an outer diameter of 3 mmφ was obtained.

Next, with a propane gas flow rate of 15 to 18 liters / minute and a supply air flow rate of 12 liters / minute, a six-port burner (six burners on the same circumference so that the burner port faces the central point through which the tube passes). The flame was concentrated in the center of (the ones evenly arranged in) and passed through the PTFE porous tube at a linear velocity of 15 m / min to give an uneven structure to the outer surface. After that, the inner and outer surfaces of the tube are turned over, a stainless rod with an outer diameter of 2 mmφ is inserted into the tube, and the inner and outer surfaces are distorted by heating in an electric furnace at a furnace temperature of 800 ° C. and a residence time in the furnace of 15 seconds. Was canceled and it was restored to a tubular shape. As a result, an artificial blood vessel made of a PTFE porous tube having an inner diameter of 2 mmφ, an outer diameter of 3 mmφ, a concave-convex tubular structure having an average width of 10 μm in the long axis direction and an average depth of 5 μm on the inner surface of the lumen was obtained.

[Example 2] Using the same PTFE porous tube as in Example 1 which had not been provided with the concavo-convex structure, it was immersed in a tetrahydrofuran solution of a sodium-naphthalene complex at a liquid temperature of 60 ° C for 30 minutes, and then thoroughly washed with water. , 60 ℃ 30
% Aqueous solution of hydrogen peroxide for 24 hours to obtain an artificial blood vessel made of a PTFE porous tube having an inner diameter of 2 mmφ, an outer diameter of 3 mmφ and a concave-convex structure with an average width of recesses of 10 μm and an average depth of 20 μm on the inner surface of the lumen.

[Example 3] PTFE fine powder (manufactured by Daikin Industries, Ltd., PTFE fine powder F10)
4) With respect to 100 parts by weight, 23 parts by weight of DRYSOL was mixed as an auxiliary agent, and the mixture was molded into a tube by a ram extruder, and then DRYSOL was dried at 50 ° C. for 48 hours. This extruded tube was stretched by 500% while being heated in an electric furnace under the conditions of a furnace temperature of 350 ° C. and a residence time in the furnace of 120 seconds, a porosity of 75%, an average fiber length of 30 μm, and an inner diameter of 2 mm.
A PTFE porous tube with φ and an outer diameter of 3 mmφ was obtained.

Then, the same process as in Example 1 was performed by using the propane gas burner except that the linear velocity was set to 12 m / min.
Distortion of the inner and outer surfaces due to heating is removed, and the inner diameter is 2 mmφ,
An artificial blood vessel made of a PTFE porous tube having an outer diameter of 3 mmφ, a concave-convex structure having a concave-convex structure on the surface of the inner cavity with an average width of 30 μm in the long axis direction and an average depth of 20 μm was obtained.

[Example 4] PTFE fine powder (manufactured by Daikin Industries, Ltd., PTFE fine powder F10)
4) With respect to 100 parts by weight, 23 parts by weight of DRYSOL was mixed as an auxiliary agent, and the mixture was molded into a tube by a ram extruder, and then DRYSOL was dried at 50 ° C. for 48 hours. This extruded tube was stretched 700% while being heated in an electric furnace under the conditions of a furnace temperature of 350 ° C. and a residence time in the furnace of 120 seconds, a porosity of 77%, an average fiber length of 50 μm, and an inner diameter of 2 mm.
A PTFE porous tube with φ and an outer diameter of 3 mmφ was obtained.

Then, in the same manner as in Example 2 except that the immersion time in the sodium-naphthalene complex solution was set to 20 minutes, the inner diameter was 2 mmφ, the outer diameter was 3 mmφ, and the inner surface of the tubular structure having a recessed portion in the longitudinal direction was formed. An artificial blood vessel made of a PTFE porous tube having an uneven structure with an average width of 50 μm and an average depth of 20 μm was obtained.

[Comparative Example 1] The porosity of 65%, the average fiber length of 10 μm, and the inner diameter of 2 used in Example 1 before the concavo-convex structure was provided.
Comparative Example 1 was a PTFE porous tube having a mmφ and an outer diameter of 3 mmφ.

[Comparative Example 2] The porosity of 75%, the average fiber length of 30 μm and the inner diameter of 2 used in Example 3 before the concavo-convex structure was provided.
Comparative Example 2 was a PTFE porous tube having a diameter of 3 mm and an outer diameter of 3 mm.

[Comparative Example 3] The porosity of 77%, the average fiber length of 50 μm, and the inner diameter of 2 used in Example 4 before the concavo-convex structure was provided.
Comparative Example 3 was a PTFE porous tube having a mmφ and an outer diameter of 3 mmφ.

[Comparative Example 4] Using the PTFE porous tube used in Example 3, the concavo-convex structure was imparted by the same propane gas burner as in Example 1 except that the linear velocity was set to 10 m / min. Similar to the first embodiment, the inner and outer surfaces are reversed,
Internal diameter is 2 mm after removing the distortion of the inner and outer surfaces by heating.
An artificial blood vessel made of a PTFE porous tube having a concavo-convex structure of φ, an outer diameter of 3 mmφ, and an inner cavity surface having a concave-convex tubular structure with an average width of 30 μm in the long axis direction and an average depth of 30 μm was obtained. This was designated as Comparative Example 4.

Comparative Example 5 Example 1 was repeated except that the PTFE porous tube used in Example 3 was used and the linear velocity was 7 m / min at a propane gas flow rate of 12 to 15 liters / min.
The same propane gas burner is used to apply the concavo-convex structure, the inner and outer surfaces are reversed and the inner and outer surface strains are removed by heating in the same manner as in Example 1, and the inner diameter is 2 mmφ and the outer diameter is 3 m.
mφ, the average width in the major axis direction of the tubular structure of the concave portion on the surface of the lumen 9
PTFE having an uneven structure of 0 μm and average depth of 30 μm
An artificial blood vessel made of a porous tube was obtained. This was designated as Comparative Example 5.

(Transplantation Experiment) The artificial blood vessels obtained in the above Examples and Comparative Examples were transplanted into a carotid artery of a rabbit having a body weight of 13 to 15 kg at a transplantation length of 2 cm. 5 after transplant
After 1 minute, 24 hours, 6 weeks of growth, the artificial blood vessel was taken out, the patency rate was investigated, and after fixing with formalin, critical point drying was performed, and a thrombus membrane formed on the inner surface of the artificial blood vessel was observed with a scanning electron microscope. Was observed and measured. Further, the endothelial cell coverage was observed and measured in the sample 6 weeks after transplantation. Similarly, a pathological tissue specimen was prepared and the state of organizing was observed.

As a result, as compared with the comparative example, the artificial blood vessel of each example had a good patency rate and a thin thrombus film thickness, which was thin and uniform. From 5 minutes to 1 hour after the transplantation, an increase in thrombus membrane and an active state were observed, but one day later, the thrombus membrane was already covered with a fibrin-like substance with few platelets. In addition, the endothelial cell coverage after 6 weeks was significantly higher in Examples than in Comparative Examples. In the artificial blood vessels of the respective examples, the portion coated with endothelial cells was continuously connected from the anastomosis, and the engrafted endothelial cells showed a stable morphology oriented in the blood flow direction. From the observation of the histopathological specimen, the inner surface of the artificial blood vessel of the example was all organized, and the portion covered with endothelial cells became the intimal-like pseudointimal membrane of the living blood vessel containing smooth muscle cells. The part that was not covered by the slab was also an organized and stable thrombus membrane. There was no part where the fresh thrombus and the inner surface of the artificial blood vessel were exposed.

On the other hand, in the artificial blood vessels of Comparative Examples 1 to 3, the formed thrombus membrane had an uneven thickness 5 minutes to 1 day after the transplantation, and the unstable thrombus containing platelets was partially present even 1 day after the transplantation. Was observed. In addition, 6 weeks after the transplantation, an obstructed case was also seen, and even in the patency case, there was a part where the fresh blood clot and the inner surface of the artificial blood vessel were exposed on the inner surface of the artificial blood vessel. Although there was a portion covered with endothelial cells, a relatively new thrombus membrane was found just below it, and it is considered that several thrombus membranes were re-formed on the thrombus membrane that was initially formed. In the artificial blood vessels of Comparative Examples 1 to 3, the continuity from the anastomotic part observed in the artificial blood vessels of Examples is not observed, and there is a portion not covered with the endothelial cells in the covered portion, The part where the orientation was disturbed occupied half of the coated area.

In the artificial blood vessels of Comparative Examples 4 to 5, remarkable thrombotic properties were observed immediately after transplantation, and the patency rate gradually decreased.
In particular, the artificial blood vessel of Comparative Example 5 was completely blocked one hour after transplantation. The artificial blood vessel of Comparative Example 4 was also completely blocked 6 weeks after transplantation. Table 1 shows the structures and characteristics of the artificial blood vessels of the above Examples and Comparative Examples, and the evaluation results.

[0061]

[Table 1]

[0062]

The artificial blood vessel of the present invention has not only the property of forming a thin thrombus membrane made of PTFE material, but also the property of stably holding the formed thrombus membrane due to the minute concavo-convex structure provided on the surface of the lumen. .. The thin and stable thrombus membrane formed by these two properties promotes the formation of a thin and stable pseudointimal membrane on the inner surface of the artificial blood vessel, particularly the formation of the endothelial cell membrane necessary to acquire the antithrombotic property equivalent to that of the living blood vessel. However, it is possible to complete organizing like a living blood vessel within a very short period of time after transplantation and to achieve a good patency rate for a long period of time by the formed stable intimal membrane.

An artificial blood vessel with an inner diameter of 6 mm or less, especially an inner diameter of 3 m
In an artificial blood vessel with a small diameter region of m or less, the thrombus membrane having the same thickness as the large diameter or the pseudointimal membrane has a higher reduction rate of the diameter of the lumen through which blood flows. Blood flow is slow, and because it has a high thrombotic property and is easy to occlude,
The early and stable completion of this thin pseudointimal membrane is very effective in achieving long-term patency. Therefore,
The artificial blood vessel of the present invention exhibits excellent properties in vascular replacement in obstructive vascular disease in large and medium diameter areas and aneurysms, but artificial blood vessels with an inner diameter of 6 mm or less, particularly peripheral blood vessels and coronary arteries with an inner diameter of 3 mm or less. It is particularly effective for artificial blood vessels used for the treatment of vascular diseases in the small diameter region.

[Brief description of drawings]

FIG. 1 is a schematic diagram showing an example of an artificial blood vessel of the present invention.

FIG. 2 is an enlarged schematic view of a section (A) surrounded by a dotted line in FIG.

[Explanation of symbols]

 1 PTFE fiber (fibril) 2 Nodule (node) 3 Recessed portion of uneven structure on artificial lumen inner surface 4 Convex portion of uneven structure on artificial blood vessel lumen surface 5 Tubular tetrafluoroethylene resin porous body (artificial blood vessel)

Claims (4)

[Claims] 1. An artificial blood vessel made of a tubular tetrafluoroethylene resin porous body having a fine fibrous tissue composed of fibers and nodules connected to each other by the fine fibrous tissue at least on the inner surface of the lumen. An artificial blood vessel characterized by having a concavo-convex structure formed by cut / contracted and / or decomposed / removed portions. 2. The artificial blood vessel according to claim 1, wherein the concavo-convex structure formed on the surface of the lumen has a recess having an average depth of 5 to 20 μm and an average width of the tubular structure in the longitudinal direction of 10 to 50 μm. 3. A tubular tetrafluoroethylene resin porous body having a fine fibrous structure composed of fibers and nodules connected to each other is treated at least on the inner surface with an organic solvent solution of an alkali metal compound, A method for producing an artificial blood vessel, which comprises decomposing a fine fibrous tissue and then removing the decomposed product to form an uneven structure at least on the surface of the lumen. 4. A tubular tetrafluoroethylene resin porous body is treated with a solution of methyllithium, sodium-naphthalene complex or sodium-anthracene complex in an organic solvent at least on the inner surface thereof, and then hydrogen peroxide water or hypochlorous acid is added. The method for producing an artificial blood vessel according to claim 3, which is treated with soda.