JPS63270048A - Artificial blood vessel - Google Patents

Abstract

PURPOSE:To obtain an artificial blood vessel improved in the piercing property of a suturing needle, having durability against repeated puncture and excellent in blood impermeability, by bringing the outermost layer having an open cell structure, the innermost layer composed of macro-pore groups and the intermediate layer positioned therebetween to a porous structure composed of closed cells independent each other. CONSTITUTION:An artificial blood vessel has the outermost layer 1 participated in the adhesion to connective tissue and the innermost tissue composed of macro- pore groups. An intermediate layer 2 is composed of a large number of independent closed cells having a size of 0.01mum or more but these closed cells having function of enhancing the needle piercing property of the artificial blood vessel and adjusting the physical properties thereof and the diameter thereof is pref. 0.1-100mum, more pref., 1-3mum and the thickness of the intermediate layer is pref. 5-500mum, especially pref., 50-300mum. As the constituent material of the artificial blood vessel whose intermediate layer has this structure, polyether type polyurethane or polyurethane urea is pref.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides an artificial material that has good penetrability with suture needles, etc., has durability against repeated punctures, and prevents blood from penetrating through the tube wall. Concerning blood vessels.

[Prior Art] Artificial blood vessels are required to have good penetrability of suture needles during anastomosis with biological blood vessels from the viewpoint of their use and surgical operation. In addition, blood access for hemodialysis, which is used to connect arteries and veins, requires frequent punctures, so it is difficult to withstand repeated punctures, and hematomas and heptomas (plasmomas) occur due to bleeding after puncture. It is required that the tube wall be impermeable to blood to avoid blood loss.

Here, blood impermeability means 450% per artificial blood vessel.
am) It means that blood cells and plasma do not pass through even if the internal pressure of Ig is applied.

As an artificial blood vessel that satisfies such requirements, Japanese Patent Application Laid-Open No. 57-15
There is one disclosed in the No. 0954 publication. but,
This artificial blood vessel has a homogeneous, dense layer containing no vacuoles of at least 0.1+ul+, which is obtained by applying a solution of a polymer compound to a rod-shaped mold, drying it, and then removing the solvent. For this reason, even if the thickness of this layer is approximately 5 mm, for example, the passage of a suture needle is significantly obstructed when connecting to a biological blood vessel, making surgical operations difficult. As a result, repeated punctures may make it difficult to stop bleeding, which may cause the formation of seroma, or the stump surface of the living blood vessel may be exposed on the lumen side of the anastomosis with the living blood vessel, causing panus growth into the lumen. It becomes. In addition, turbulence on the inner surface causes blood turbulence and partial stagnation, leading to thrombus formation.Therefore, the tube wall is coated with antithrombotic material to suppress occlusion by the initial thrombus that forms on the inner surface after implantation. In addition to this, it is important not to have such a dense layer.

Moreover, the presence of such a dense layer is also undesirable for suppressing occlusion of the lumen, that is, kinking, caused by bending of the artificial blood vessel.

[Problems to be Solved by the Invention] As mentioned above, conventional artificial blood vessels have good suture needle penetration, are durable against repeated punctures, and have excellent blood impermeability, and are not suitable for practical use. There were no supplies available.

The present invention was made against this background, and aims to provide an artificial blood vessel that solves the above problems and can be used for a long period of time.

[Means and effects for solving the problems] In order to achieve the above object, the present invention has studied the structure of the wall of an artificial blood vessel. the result.

An artificial blood vessel that has an outermost layer that participates in fusion with connective tissue and an innermost layer consisting of a group of giant pores, as well as an intermediate layer with a specific structure, solves the problems of conventional artificial blood vessels mentioned above. The present invention was completed based on this discovery.

That is, the present invention provides an artificial blood vessel in which the vessel wall is composed of an outermost layer having an open pore structure, an innermost layer consisting of a group of large pores, and one or more intermediate layers located between these layers. The middle layer is a porous structure consisting of mutually independent closed pores, and.

The present invention relates to an artificial blood vessel characterized by being impermeable to blood.

This at least 1 intermediate layer consists of a large number of independent obturator pores of 0.01μ or more, and these obturator pores are intended to improve the penetrability of the needle of the artificial blood vessel and to adjust its physical properties, and the diameter thereof is preferably is in the range of 0.1 to tou,
The most preferred range is 1 to 3-.

If the diameter of the obturator foramen is greater than the above-mentioned value (100- or more), the pressure resistance of the canal wall will decrease, causing the inner diameter to increase over time or due to leaping after transplantation, and the formation of minute pinholes. This is because. On the other hand, if the diameter of the obturator pore is less than the above value (0.01 μm or less), this layer becomes dense and the tube wall becomes rigid.

Further, the thickness of the layer is preferably in the range of 5 to soog, particularly preferably in the range of 50 to 300 mm. If the thickness is less than 5 p1, the pressure resistance decreases, and the above-mentioned leakage over time reduces the present invention. The desired blood impermeability cannot be maintained.

The material for constructing the artificial blood vessel of the present invention having such a structure in which at least l of the intermediate layer is a material that has excellent compatibility with blood and tissues, that is, has no acute or chronic toxicity, pyrogenicity, or hemolysis, and is long-term Polymers that do not cause inflammation in surrounding tissues even when implanted over a long period of time are preferred. Examples of such polymers include polyvinyl halides, polystyrene and its derivatives, polyolefin polymers, polyester condensates, and cellulose polymers. molecules, polyurethane polymers,
Examples include polysulfone resins and polyamide polymers. Of course, copolymers or mixtures containing these materials may also be used; polyurethane-based materials are preferred from the viewpoint of mechanical properties, in-vivo stability, and antithrombotic properties. . Specific examples include polyurethane,
Mention may be made of polyurethane ureas, blends of these with silicone polymers, or those having an interpenetrating network structure. These also include segmented polyurethanes or polyurethane ureas, those containing polydimethylsiloxane in the main chain, and those containing fluorine in the hard and soft segments. Polyether-type polyurethane or polyurethane urea is preferable to polyester-type because it is less susceptible to biodegradation.

The polyether constituting the polyether segment such as polyurethane is most preferably polytetramethylene oxide, but other polyalkylene oxides (however, alkylene has 2 and/or 3 carbon atoms) are also preferred.
Specific examples of such polyalkylene oxides include polyethylene oxide, polypropylene oxide, ethylene oxide-propylene oxide copolymers, and block copolymers. Furthermore, a polyurethane having both hydrophilicity and mechanical properties, which contains a polytetramethylene oxide segment and a polyalkylene oxide (alkylene has 2 and/or 3 carbon atoms) in the same main chain, may also be used. Polyurethane is more preferable as a constituent material of the artificial blood vessel of the present invention because it has outstanding antithrombotic properties and biocompatibility.

The molecular weight of the polyether forming these soft segments is usually in the range of 400 to 3,000, preferably 450 to 2.500, more preferably 500 to 2.5
00, and the best polyether segments have a molecular weight of 800 to 2.500, especially a molecular weight of 1.3.
00 to 2.000 polytetramethylene oxide chains. The molecular weight of this polyether soft segment is 3.
If it exceeds 000, the mechanical properties of the polyurethane artificial blood vessel will be poor, and if it is less than 400, it will be too hard to be used even if it is molded as an artificial blood vessel.

Synthesis of polyurethane involves reacting the polyether described above with hydroxyl groups at both ends with diisocyanates used in known polyurethane synthesis, such as 4,4'-diphenylmethane diisocyanate, toluidine diisocyanate, 4,4'-dicyclohexylmethane diisocyanate, and hexamethylene diisocyanate. A prepolymer with a terminal incyanate is prepared, and this is mixed with diamines such as ethylene diamine, propylene diamine, tetramethylene diamine, etc.
It may be synthesized using a conventional method of chain extension with a diol such as ethylene glycol, propylene glycol, or butanediol.

[Examples] Hereinafter, the present invention will be described in more detail by presenting examples and using the accompanying drawings. In addition, "1%" used below regarding the components of the constituent materials all represent "% by weight", and the attached drawing is a sketch of a micrograph taken at a magnification of 50 times in a cross section of a tube wall.

Example 1 Polytetramethylene glycol having a molecular weight of 1500 and having hydroxyl groups at both ends was reacted with 4,4'-diphenylmethane diisocyanate to obtain a prepolymer having incyanate groups at both ends.Next, the prepolymer was reacted with butanediol. Polyurethane (average molecular ff11.2X1
04) was obtained. The obtained polyurethane was reprecipitated three times in total in a tetrahydrofuran-ethanol mixed solvent and purified.Next, the purified polyurethane was dissolved in a mixed solvent of 60% dimethylamide and 40% tetrahydrofuran to obtain polyurethane. A solution with a concentration of 17% was prepared. A chrome-plated stainless steel plate with an outer diameter of 4 mm and an average surface roughness of 0.3- was placed in the solution obtained in this manner so as to be placed concentrically with the orifice with a diameter of 6 mm. A rod is pushed out at a constant speed. By this operation, a uniform amount of polyurethane solution was deposited on the entire circumferential surface of the cup through the uniformly spaced gap between the orifice and the stainless steel rod. The extruded rod was immediately introduced into water at 35° C. and rapidly solidified from the outside. Thereafter, the rod was kept in water to remove the solvent, then pulled out of the water, the rod was taken out, washed, and dried at about 40° C. to obtain a polyurethane tube.

This is the artificial blood vessel of the present invention, with an inner diameter of 4 am and an outer diameter of 511 mm.
No. 111, the thickness of the tube wall was 0.6 ma+, and the entire tube wall was porous as shown in the drawing.

The outermost layer 1 located on the outside of this artificial blood vessel has a thickness of 80 mm.
-, the porosity due to pores was 97%.

Furthermore, the minute pores in layer 1 have an average diameter of 15 mm on the outer surface of the tube wall.
It was opened at ~70° and partitioned with fibrous or thin plate polyurethane. Then, by observing the cross section, we found that these empties “
It was confirmed that the pores communicated with each other through holes having a diameter of 5J1j or more, and that the outermost layer 1 had an open pore structure.

Moreover, within this layer, all positions had the same structure.

Inside said layer 1, there was an intermediate layer 2 with a thickness of 5 to 10 mm, containing a large number of mutually independent spherical obturator pores with a diameter of about 1 micron.

Furthermore, the inner side of this intermediate layer 2 has an average diameter of 200 to 300.
There was an innermost layer 3 consisting of a huge group of holes.

Here, the innermost layer 3 is a portion that imparts flexibility to the tube wall, prevents kinking, and contributes to long-term patency.

It is preferable that the pore group has a diameter of at least 4 or more than the thickness of the tube wall, and that each pore extends over the entire radial direction of the layer, with the wall membrane of the pores remaining intact on the blood contacting surface side. It is preferable that it is formed continuously and thinly.

In this way, due to the presence of huge pore groups, the inner anastomosis is smoothly connected due to the flexibility of the blood contacting surface, causing partial blood stagnation that causes the formation of a large amount of thrombus. Therefore, the generation of panus from the biological blood vessel at the cut end surface of the material of the artificial blood vessel is suppressed, and patency is significantly improved.

Furthermore, since the contact area with the biological blood vessel at the cut end of the material of the artificial blood vessel is reduced, foreign body reaction stimulation is reduced, and healing of the biological blood vessel is promoted.

The lumen of this blood vessel was filled with fresh blood and an internal pressure of 450 am) Ig was applied for 48 hours, but no plasma passed through and the vessel wall was impermeable. The blood used in this experiment was washed with physiological saline and fixed with geltaraldehyde' as a specimen, and its cross section was observed with a metallurgical microscope.

As a result, it was confirmed that blood infiltrated into the giant pores of the innermost layer 3, but not into the obturator pores existing in the middle layer outside of it.

This artificial blood vessel, 5c+s, was transplanted into the iliac artery of an adult mongrel dog. The N operation was extremely easy and there was no bleeding from the needle hole.

This blood vessel remained patent even after 8 months and was extremely excellent as a small-diameter artificial blood vessel.

When the blood vessel was extracted after one month, the outer surface was covered with connective tissue approximately 1.5 m thick, and the fusion with the artificial blood vessel was complete and it could not be peeled off. The inner surface of the anastomosis part is smoothly connected to the living blood vessel, and the inner surface of the anastomosis part is 0.1 to 0.
A thin intima with a thickness of 2-■ completely covered the inner surface, and no panus or thrombus was observed.

Therefore, since it has excellent patency, unlike conventional artificial blood vessels, it can be used for blood vessels of 61 cm or less.

Example 2 A polyurethane porous tube having an inner diameter of 5 layers and 1 layer was prepared in the same manner as in Example 1.

The obtained artificial blood vessel had an inner diameter of 5111 mm and an entire wall thickness of 0.0 mm.
It was 8 mrs and porous.

The outermost layer located on the outside of this artificial blood vessel has a thickness of 80~
120μ, the porosity due to pores was 96-98%. Further, the pores have an average diameter of 3ON100- to the outer surface of the wall surface.
It was open. Observation of the cross section revealed that within this layer, fibrous polyurethane having a thickness of 2 to 10 were intertwined, forming an open pore structure in which adjacent pores communicated with each other.

Inside this layer, there is an intermediate layer having a thickness of about 80μ and containing a large number of 1-3-independent obturator pores, and further inside this layer, having an average diameter of 300-500- There was an innermost layer with huge holes.

8CI of this blood vessel was bypass-grafted between the carotid artery and vein of an adult mongrel dog and implanted subcutaneously.

After 3 weeks, an 18G needle was punctured from the outside, and it smoothly penetrated the wall of the artificial blood vessel. The needle was left in place for 4 hours and then removed, but bleeding stopped completely after 10 seconds, demonstrating excellent hemostasis.

After this, continue to puncture this blood vessel 5 times daily.
The treatment continued for several months, but no hematoma or plasmama occurred.

It showed excellent performance as a blood access for hemodialysis.

Three months later, this blood vessel was extracted and its condition was observed. As a result, the external connective tissue was firmly fused to the artificial blood vessel. There was also no panus or thrombus present on the inner surface.

[Effects of the Invention] The artificial blood vessel of the present invention has a porous structure in which at least one intermediate layer has closed pores, and is impermeable to blood, so that it is effective as a barrier against blood and cells. Furthermore, due to its porous structure, it has good penetrability with a suture needle and has excellent durability against repeated punctures. As a result, the cut end surface is not exposed at the anastomotic site with the biological blood vessel, so thrombus formation due to panus growth, blood turbulence, etc. is suppressed, and this artificial blood vessel has excellent long-term patency and durability.

[Brief explanation of the drawing]

The accompanying drawing is a sketch of a micrograph of a cross section of a tube wall.

Claims (5)

[Claims] 1. In an artificial blood vessel in which the tube wall is composed of an outermost layer with an open-pore structure, an innermost layer with a group of large pores, and one or more intermediate layers located between these layers, at least one of the intermediate layers is mutually connected. Porous structure consisting of independent obturator pores,
An artificial blood vessel characterized by being impermeable to blood. 2. The artificial blood vessel according to claim 1, wherein the tube wall is made of polyurethane. 3. The artificial blood vessel according to claim 1, wherein the tube wall is made of polyurethane urea. 4. The at least one intermediate layer has a thickness of 5 to 500 mm.
The artificial blood vessel according to any one of claims 1 to 3, which is in the μm range. 5. 5. The artificial blood vessel according to claim 4, wherein the obturator foramen has a diameter within a range of 0.01 to 100 μm.