JPH01250249A - Artificial blood vessel for accessing blood - Google Patents

Abstract

PURPOSE:To provide excellent kinking resistance or pressure resistance, by allowing a monofilament to be present spirally in spite of a U-shape. CONSTITUTION:A monofilament, whose diameter is 0.01-1mm, having a circular or oval cross-sectional shape is allowed to be spirally present inside the tubular structure, which is constituted of a fiber, being the blood noncontact surface of an artificial blood vessel. The monofilament is allowed to be spirally present, for example, in the vicinity of the central and anastomotic parts of a U-shape requiring kinking resistance and pressure resistance and the curvature diameter of the U-shape is set to 10-200mm. In this case, as the material quality of the monofilament, polytetrafluoroethylene rigid and withstanding external pressure at the time of spriral molding or subcutaneous pressure, neglected in the deterioration in a living body and withstanding sterilizing operation is used. Form a test result, the U-shape part having the monofilament of the artificial blood vessel is not kinked and has sufficient rigidity as compared with a non-present and part and cavity is not easily collapsed even under pressure.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an artificial blood vessel for blood access. More specifically, the present invention relates to an artificial blood vessel for blood access used as an internal shunt for artificial dialysis.

[Prior Art] Artificial dialysis is used as a life-saving measure for patients with renal failure, and is an important medical procedure that currently sustains the lives of about 70,000 patients with renal failure in Japan. Artificial dialysis requires a blood access, which is a blood inlet/outlet for guiding a sufficient amount of the patient's blood to the dialyzer and returning purified blood to the patient. In the early stages of dialysis patients, blood access is created using autologous blood vessels.

Dialysis is usually performed three times a week for about 5 hours each time, and a dialysis needle (outer diameter of 1 ms+) is inserted into the blood access each time, so the blood access may become dilapidated within a few years. It becomes unbearable to use. When a blood access using an autologous blood vessel becomes unusable, a blood access using an artificial blood vessel (hereinafter referred to as an artificial blood vessel for blood access) is formed. As an artificial blood vessel for blood access, an artificial blood vessel (for example, trade name: Boretex (registered trademark), manufactured by Boa Corporation) is used, most of which is made of stretched polytetrafluoroethylene (hereinafter referred to as EPTPE). .

However, with blood access using this EPTFE artificial blood vessel, the puncture hole remains even after the dialysis needle is removed, so bleeding does not stop. It is necessary to wait for the puncture to close, and infection at the puncture site, hematoma, and pseudoaneurysm have been pointed out as problems, and the disadvantage is that the yearly patency rate is poor at 60 to 80%.

In order to solve these problems, Japanese Patent Application Laid-Open No. H-5354
The publication discloses an artificial blood vessel in which polyurethane is arranged at least on the blood-contacting surface of a normal artificial blood vessel made by crimping a tubular structure made of knitted or plain-woven polyester polymer fibers. Since it is not formed into a specific shape, if it is implanted in a 0-shape as a blood access, there is a problem of kinking at the curved portion and anastomotic portion. Furthermore, since the compliance is lower than that of a living artery, there is a drawback that a thrombus is likely to form due to compliance mismatching near the arterial side anastomosis, resulting in poor patency results. In addition, Yoshihiko Nakayo et al.
Artificial Organs, 1B(3), pp. 1428-1481 (198
7) discloses a υ-shaped polyether-type polyurethane artificial blood vessel, but this has the disadvantage of being inferior in strength because it is made only of polyurethane, and furthermore, it does not have communicating holes in the tube wall. It has the disadvantage of slow organization and poor patency. JP-A No. 82-47383 discloses a structure consisting of a porous tubular structure having communicating holes from the inside to the outside of a tube wall made of an elastomer and a tubular structure made of fibers, which has a compliance similar to that of a living blood vessel. An artificial blood vessel is disclosed.

It has communicating holes in the tube wall and has compliance similar to that of biological blood vessels, so it has excellent patency results, and it also has sufficient strength because it is a composite tubular structure made of fibers. However, if it is implanted in a 0-shape as a blood access, kinking may occur.

[Problem to be solved by the invention 1] As mentioned above, the conventional techniques have the following problems: ■ Poor hemostasis at the puncture site, ■ Poor patency results, ■ Poor anti-kinking properties, ■
There are problems such as poor strength and slow organization. In view of these circumstances, the present inventors have conducted various studies to comprehensively solve the above problems, and as a result, have completed the present invention.

[Means for Solving the Problems] The present invention provides an artificial blood vessel consisting of a porous tubular structure having pores communicating from the inside to the outside of the tube wall made of an elastomer, and a tubular structure made of fibers. o
, ot- is present in a spiral shape other than the blood contacting surface of the artificial blood vessel, and the curvature diameter is 0-shaped with a diameter of 10 to 200. .

[Example] In the present invention, the porous tubular structure is made of an elastomer, and has pores that communicate throughout the entire thickness from the inner surface to the outer surface of the tube wall. At least a portion of the pores communicate with each other, and at least a portion of the pores are open toward the outside on the inner surface and the outer surface, so that the pores have porosity. The partition walls forming the holes are made of elastomer and are continuously connected. Furthermore, it is preferable that the partition wall itself contains a large number of minute pores or holes with a diameter of 1 μm or less inside, in order to obtain an artificial blood vessel with a sparse wall structure and a compliance similar to that of a living blood vessel.

It is particularly preferred that the pores present throughout the thickness of the tube wall from the inner surface to the outer surface are of substantially uniform size. The areas near the inner surface and the area near the outer surface of the tube wall are slightly denser than the area between them, which accounts for most of the porous body, and the pores may not be completely uniform throughout the thickness. . However, unless the pores are extreme enough to impair porosity, the pores may be considered substantially uniform. The maximum diameter of the cross section of the hole is not particularly limited, but it is preferably 1 to 100 μl, and 3 to 7 μl.
More preferably, the thickness is 5 μm. Maximum diameter is 100μ
If it is larger than m, the strength tends to be poor or the porosity becomes too large, and if it is smaller than 1 μm, the porosity tends to be poor or the compliance becomes too small.

Although there is no particular limitation on the shape of the pores present on the inner surface and outer surface of the porous tubular structure, the shape of the pores present on the inner surface is preferably circular or elliptical. The maximum diameter of this circular or oval shape is preferably 1 to 100 μm, more preferably 3 to 50 μm, and particularly preferably 5 to 20 μm. When the maximum diameter is larger than 100 μm,
Blood flow tends to be squeezed out and the antithrombotic properties tend to decrease, and when the intestine is smaller than 1 μm, the organization of the artificial blood vessel tends to be delayed.

The porous tubular structure preferably has a porosity of 95 to 70%. Furthermore, it is preferably 90 to 75%. In particular, the porosity in the part of the tube wall with a thickness of at least 50 μl from the inner surface is 90 to 83%, and the porosity of the part outside said part is at least 50 μl. The porosity of the entire porous tubular structure is preferably 90 to 80%.

The porosity referred to in this specification is the formula (1): % formula % (1) (where ■ is the volume of the porous tubular structure, D is the specific gravity of the material constituting the porous tubular structure, and W is the weight of the porous tubular structure). The porosity is determined by the amount of pores existing in the tube wall and the amount of minute pores or holes with a pore diameter of 1 μm or less existing in the partition wall forming the chain pores.

In the porous tubular structure, the porosity greatly affects the mechanical strength, compliance, and organization of the blood contact surface. When the porosity exceeds 95%, the strength becomes weak and cannot withstand repeated punctures with a dialysis needle. Porosity is 7
When it is less than 0%, the compliance tends to be too small compared to that of a living blood vessel, and the organization tends to be slow and the patency tends to be poor. Therefore, in order to adjust the mechanical strength, compliance, organization of the blood contact surface, and the associated patency, the porosity of the tube wall at least 50 μm thick from the inner surface is increased. By increasing the number of pores existing on the blood contact surface, good organization is induced, and by reducing the porosity of the outer part of the above-mentioned part, the porosity of the tube wall as a whole is reduced. It is advantageous to adjust the porosity so as to reduce the porosity and improve mechanical strength and compliance.

The elastomer used in the present invention is an elastomer that does not contain low-molecular eluates that cause acute toxicity, inflammation, hemolysis, exothermic reactions, etc., does not cause significant damage to blood physiological functions, and has excellent antithrombotic properties. It is. Examples of such elastomers include polystyrene elastomers, polyurethane elastomers, polyolefin elastomers, and polyester elastomers, and these may be used alone or in combination of two or more.

Among the elastomers, thermoplastic polyether-type segmented polyurethane (including segmented polyurethane urea, hereinafter the same) is more preferable because it has excellent strength, elongation, durability, antithrombotic properties, processability, etc. Further preferred are segmented polyurethanes containing fluorine in the hard or soft segments, and segmented polyurethanes containing polydimethylsiloxane in the main chain as disclosed in JP-A-57-211358.

In the present invention, the tubular structure composed of fibers has been developed to eliminate concerns about the rupture or damage of the artificial blood vessel in the event of abnormally high blood pressure during surgery, as well as concerns about maintaining durability over a long period of time. Used to reinforce the strength of the material. The tubular structure refers to fibers and at least IF! It consists of woven fabrics, knitted fabrics, braided fabrics, nonwoven fabrics, and combinations of these, using yarns spun from the above, multifilaments of at least one type of fiber, yarns that are combinations of these, and the like.

Preferably, the tubular structure is an artificial blood vessel that is a combination of the tubular structure and the porous tubular structure made of an elastomer, and has a compliance similar to that of a biological blood vessel.

In particular, it is preferable that the stress-strain curve of the artificial blood vessel has a property similar to that of a biological blood vessel.

Such properties of the tubular structure can be achieved, for example, by the following two methods alone or in combination. The first method is to adjust the frequency of fiber combinations and loosely adjust the combination points, and the second method is to use stretchable fibers.

In addition, from the viewpoint of obtaining compliance and stress-strain curves similar to biological blood vessels, the tubular structure is preferably a tubular structure made of knitted fibers, and preferably a tubular structure made of knitted stretchable fibers. It is even more preferable that there be.

The fibers constituting the tubular structure are thin, long, flexible objects whose length is 100 times or more the diameter and are used to make threads, nets, woven fabrics, knitted fabrics, braided fabrics, nonwoven fabrics, and the like. The fibers may be used without particular limitations as long as they are safe for living organisms, have negligible deterioration in vivo, can withstand sterilization, and can be processed into desired tubular structures. processability,
In terms of availability, flexibility, uniformity, etc., recycled artificial fibers, semi-synthetic fibers, and synthetic fibers are preferred. Specific examples of these include cellulose-based, protein-based,
Examples include polyamide-based, polyester-based, polyurethane-based, polyethylene-based, polystyrene-based, polyvinyl chloride-based, polyvinylidene chloride-based, polyfluoroethylene-based, polyacrylic-based, and polyvinyl alcohol-based fibers. Among these, fibers that are stretchable are more preferable, and specific examples include fibers that themselves are stretchable, such as rubber-based, polyurethane elastic, and polyester elastic fibers; Examples include those that have elasticity depending on the processing method, such as bulky yarns, covered yarns, fancy yarns, bulky yarns, A to Z yarns, and conjugate fibers.

In order for the artificial blood vessel to have compliance and stress-strain curves similar to those of biological blood vessels, among the stretchable fibers,
Particularly preferred are stretchable bulky yarns such as woolly nylon and woolly polyester, and covered yarns, which are yarns made by stretching rubber or spandex filaments and wrapping them around other spun yarns or filaments.

The tubular structure may be present at least partially in contact with and/or bonded to the porous tubular structure made of an elastomer.

In order to prevent the fibers constituting the tubular structure from fraying and to maintain antithrombotic properties on the blood contact surface, it is preferable that the tubular structure is incorporated into the outer portion of the porous tubular structure. .

Note that contact and/or bonding as used in the present invention means that the porous tubular structure made of an elastomer and the tubular structure made of fibers are in contact with each other to the extent that they both undergo almost the same strain in response to blood pressure or stress applied from the outside. This means that there is a mechanical interaction of

In the present invention, a monofilament is used to improve the anti-kinking properties of the artificial blood vessel.

The monofilament referred to in the present invention is rigid, has strength to withstand external pressure and subcutaneous pressure when formed into a spiral shape, has negligible deterioration in the living body, can withstand sterilization operations, and has the desired spiral shape. Any material can be used without particular limitation as long as it can be processed into a shape.

From the viewpoint of processability, ease of availability, uniformity, etc., synthetic resins are preferred. Specific examples of these include polyfluoroethylene, polyester, polyethylene, polypropylene, and polyamide. Among these, polytetrafluoroethylene and saturated polyester, which have a proven track record as materials for artificial blood vessels, are more preferred from the standpoint of safety for living organisms.

By allowing the monofilament to exist in a spiral shape in a region other than the blood-contacting surface within the wall of the artificial blood vessel, the anti-kinking property and pressure resistance of the lumen of the spirally formed monofilament can be imparted to the artificial blood vessel. Incidentally, in the present invention, the term "helical shape" refers to the shape obtained when a single thread is wound in the circumferential direction on the surface of a cylinder without intersecting it.

Although there is no particular limitation on the cross-sectional shape of the monofilament,
A circle or an ellipse is preferred. The diameter of the cross-sectional shape is 0.01~
l sum. Furthermore, 0.05 to 0.5 is preferable, and 0.1 to 0.3! I11 is particularly preferred. Note that the term "diameter" refers to the diameter of a circle, the length of the major axis of an ellipse, and the maximum diameter of a shape other than a circle or an ellipse. If the diameter is larger than 1 am, the wall thickness of the artificial blood vessel will become too large, making it difficult to anastomose with a biological blood vessel or puncture with a dialysis needle. Sexuality becomes worse.

The monofilament may be present anywhere other than the blood-contacting surface of the artificial blood vessel, but it is preferably present in a spiral shape on the outside or inside of the tubular structure made of fibers. Considering the resistance of the monofilament to coming off and the development of anti-kinking properties, it is more preferable that the monofilament be present in a spiral shape inside a tubular structure composed of fibers.

The monofilament can be used in areas where anti-kinking properties and pressure resistance are required, such as the central part of the U-shape (see Figure 1), or the vicinity of the anastomosis and the central part of the U-shape (see Figure 2). Preferably, it exists in a spiral shape. Among these, artificial blood vessels for blood access are repeatedly punctured by a dialysis needle, so if a monofilament is present at the puncture site, it is thought that it will prevent the dialysis needle from entering.Moreover, monofilament is used because it is necessary to have a long puncture area. It is more preferable that the oxide exists in a spiral shape only in the central part of the U-shape where anti-kinking properties are strongly required. FIGS. 1 and 2 are schematic diagrams showing, with diagonal lines, the location of the monofilament spiral structure incorporated into the blood access artificial blood vessel of the present invention.

Here, the U-shaped shape is defined as an arc with a length of 0.5πR, and two arcs extending in the tangential direction from both ends, as shown in Figure 1, where the curvature diameter of the U-shaped shape is R. By using an artificial blood vessel formed into a U-shape in advance, the puncture site can be longer than if it is used straight for blood access. This has the advantage that when a straight artificial blood vessel is transplanted in a U-shape, no excessive force is applied to the whole body, so it has excellent anti-kinking properties, smooth blood flow, and excellent patency. be.

In addition, the central part of the U-shape in which the monofilament preferably exists in a spiral shape has a length of 0.2π in the U-shape.
It is preferable that it is an arc of R to πR to a U0-shaped shape, and more preferably a circular arc of length 0.4πR to 0.8πR to a U0-shaped shape of the 0-shaped shape. When the length exceeds πR, the number of punctureable sites tends to be too small, and when the length is less than 0.2πR, the anti-oxidation properties tend to be poor.

The interval in the longitudinal direction of the spiral artificial blood vessel is 0.01 to 10
mm is preferable, O, 1-8 mm is more preferable, 1-8 mm is more preferable,
5 am is particularly preferred. If the distance between the spirals exceeds to am, the anti-kinking property and compression resistance tend to be poor.
If it is smaller than 0,01+u, the contact and/or bonding between the monofilament and the porous tubular structure, the tubular structure made of fibers, etc. tends to be poor.

The curvature diameter of the U-shaped shape according to the present invention may be determined depending on the part of the living body where it will be used, but it may range from lo to 200 tars.
It is. Furthermore, 20 to 100 +u is preferable, and 3
A range of 0 to 70 is particularly preferred. If the curvature diameter of the U-shape is larger than 200 mm, there is no application site to the living body, and if it is smaller than %101111, the turbulence of blood flow at the curved portion becomes large, and thrombus is likely to occur, resulting in poor patency results.

The compliance referred to in this specification is expressed by the formula (z: ΔV c-xtoo (2) VoΦΔP (where C is compliance and Vo is the internal pressure of 50 Hg
The internal volume of the measured blood vessel when ΔP is the internal pressure 50m5+t1
g to 150mmHg, 100mm11g,
ΔV is defined as the internal volume of the I#J constant blood vessel that increases between the internal pressure of 50 mm and 1 g to 150 mm and 11 g.

For specific measurements, a measurement blood vessel is inserted into a closed circuit, a liquid is injected into this circuit using a micrometer metering pump, the amount of injected liquid and the change in pressure in the circuit are measured, and the compliance is calculated from equation (2). seek. Compliance measurement of a porous artificial blood vessel may be performed after closing the communicating holes in the vessel wall by pre-clotting or the like.

The compliance of living blood vessels varies depending on the diameter of the artery, vein, blood vessel, etc. Therefore, the preferable compliance for an artificial blood vessel varies depending on the caliber of the artificial blood vessel, the site of use, etc., and cannot be generally determined. By the way, the artificial blood vessel of the present invention is for blood access, and a particular problem with the artificial blood vessel for blood access is anastomotic occlusion caused by thrombus thickening due to compliance mismatching near the arterial side anastomosis. The arterial anastomosis preferably has a compliance of 0.1 to 0.8, particularly preferably 0.3 to 0.6. Note that the compliance of living arteries is 0.1 to 0.8.

In addition, the stress-strain curve of a living blood vessel cannot be determined unconditionally because it differs depending on the diameter of the artery, vein, blood vessel, etc., but essentially the stress-strain curve like (1) in Figure 3 or (IID) In Fig. 3, (1) is the stress-strain curve of the carotid artery, and (2) is the stress-strain curve of the thoracic aorta.

In other words, it has a stress-strain curve in which the modulus of elasticity is small in the normal blood pressure range, and the modulus of elasticity suddenly becomes large when stress exceeding the normal blood pressure range is applied.

FIG. 3 (I) is a stress-strain curve at the end where no monofilament is present in an embodiment of the artificial blood vessel for blood access of the present invention, and is a stress-strain curve that approximates that of a biological blood vessel. The stress-strain curve can be measured using a tensile testing machine commonly used in the field of polymer materials (for example, Autograph AC-200OA manufactured by Shimadzu Corporation).

It is preferable to use an artificial blood vessel as it is as a sample for stress-strain curve measurement. Cut the artificial blood vessel in the axial direction,
For example, when measured in a similar manner, the strength of tubular structures constructed from fibers varies and tends to exhibit different stress-strain curves. Although there is no particular limitation on the stress-strain curve in the circumferential direction of the artificial blood vessel, it is preferable to approximate that in the axial direction.

Note that stress in the present invention is the value obtained by dividing the load during the tensile test by the cross-sectional area of the test piece before loading (pipe wall cross-sectional area), and strain is the value obtained by dividing the elongation during the tensile test by the length of the test piece before loading. This is the divided value.

The region of low stress in the stress-strain curve roughly corresponds to the normal blood pressure range over which compliance is measured.
If the compliance is similar to that of biological blood vessels, the stress -
This region of the strain curve also approximates a biological blood vessel. On the other hand, the main role of areas of high stress is to prevent rupture and damage in the event of abnormally high blood pressure such as during surgery, and to maintain long-term durability. The approximation can be made within a range that satisfies the role.

Next, the method for manufacturing the artificial blood vessel of the present invention will be explained.

The artificial blood vessel of the present invention coats the mandrel with a pore-forming agent and/or an elastomer solution having a cloud point, and then
When manufacturing an artificial blood vessel by repeating the operation of immersing the mandrel in a coagulation solution once or twice, at any stage of the operation a tubular structure composed of fibers and a monofilament are placed on the mandrel. It can be manufactured by the presence of a spiral structure.

The elastomer solution used in the present invention can be classified into (1) a solution having a pore-forming agent, (2) a solution having a cloud point, and (2) a solution having a pore-forming agent and a cloud point.

The elastomer solution containing the pore-forming agent (2) contains the pore-forming agent, the elastomer, and a solvent that dissolves the elastomer (hereinafter referred to as a good solvent) as essential components, and the pore-forming agent is uniformly dispersed therein. When this solution is immersed in a coagulating liquid, the elastomer is precipitated by replacing the good solvent with the coagulating liquid. By dissolving and removing the pore-forming agent from the obtained material, it is possible to form a porous tubular structure which is a component of the artificial blood vessel of the present invention. If necessary, a solvent that is miscible with the good solvent but does not dissolve the elastomer (hereinafter referred to as a poor solvent) may be added for the purpose of adjusting the coagulation rate, porous structure, etc. of the elastomer solution. ■Eras with cloud point! - The essential components of the mer solution are the elastomer, a good solvent, and the amount of poor solvent necessary to form a cloud point.

The cloud point is the temperature at which a polymer precipitates from a dissolved state into a colloid, that is, undergoes a phase change. If this solution is handled below its cloud point temperature, it will be difficult to achieve a uniform coating.
Since the porous tubular structure tends to be difficult to remove, the solution is maintained at a temperature above the cloud point and coated on the mandrel, and then the solution is coated on the mandrel immediately or after a phase change occurs. Preferably, the mandrel is immersed. By this operation, the phase change of the elastomer solution in the coating layer and the precipitation of the elastomer in the coagulation liquid can occur simultaneously or sequentially, and the porous tubular structure can be moved.

The elastomer solution having a pore-forming agent and a cloud point (2) contains, as essential components, a pore-forming agent, an elastomer, a good solvent, and a poor solvent in an amount necessary to form a cloud point. This solution can be applied to the porous tubular structure by precipitating the elastomer in the same manner as the solution (2) and then dissolving and removing the pore-forming agent.

The elastomer concentration in the elastomer solution cannot be unconditionally limited because it varies depending on the type of elastomer and the composition of the solution, but it is usually 5 to 35% (wt%).
The same applies below), more preferably 8 to 30%, particularly preferably 10 to 25%.

If the elastomer concentration is lower than 5%, uniform molding tends to be difficult. Furthermore, when the elastomer concentration exceeds 35%, the viscosity of the solution is high, and uniform coating tends to become difficult.

The pore-forming agent used in the present invention is insoluble in a good solvent and can be removed from the manufactured artificial blood vessel. For example, salt
Specific examples include inorganic salts such as calcium carbonate, water-soluble saccharides such as glucose and starch, and proteins such as casein, collagen, gelatin, and albumin.

The particle size of the pore-forming agent is preferably 74 μm or less, more preferably 50 μm or less, and particularly preferably 30 JA or less. The particle size here refers to the length of one side of the mesh of the sieve, and refers to the particles classified by these sieves. When the particle size is larger than 74 mm, the pores of the porous structure tend to become too large.

The amount of the pore-forming agent used in the present invention cannot be determined in general because it varies depending on the required porosity, the particle size of the pore-forming agent, and the composition of the elastomer solution (especially the presence or absence of a cloud point). However, preferably 1 to 500% (pore forming agent/
% by volume of the elastomer (the same applies hereinafter), more preferably 20 to 350%, particularly preferably 50 to 200%.

If the amount of the pore-forming agent exceeds 500%, the porosity tends to become too large and the viscosity of the elastomer solution tends to become too high. On the other hand, when the amount of the pore-forming agent is less than 1%, the porosity tends to become poor.

When the elastomer solutions (■ and ■) containing the pore-forming agent are used in the present invention, the pore-forming agent is dissolved and removed after the elastomer is deposited. The method for dissolving and removing the material depends on the properties of the pore-forming agent used, but it is generally carried out by immersion in water, an acidic or alkaline aqueous solution, a proteolytic enzyme aqueous solution, or the like.

The good solvent used in the present invention varies depending on the type of elastomer, so it cannot be determined unconditionally, but for example, N, N
Examples include solvents such as -dimethylacetamide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, dioxane, and tetrahydrofuran, and these may be used alone or in combination of two or more.

The poor solvent used in the present invention may be any solvent that is miscible with the good solvent but does not dissolve the elastomer, such as water, lower alcohols, ethylene glycol, propylene glycol, 1,4-butanediol, and glycerin. These may be used alone or in combination of two or more.

The coagulating liquid used in the present invention may be substantially a poor solvent. Examples include water, lower alcohols, ethylene glycol, propylene glycol, 1,4-butanediol, glycerin, etc., and these may be used alone or in combination of two or more.

Among these, preferred are ethylene glycol, propylene glycol, or poor solvents containing these as main components, and more preferred are 99 to 50 volume % of the poor solvent and 1 to 50 volume % of a good solvent. This is the mixed solvent added. This is because, by including a good solvent in the coagulation liquid, the coagulation rate of the elastomer solution in the coagulation liquid is slowed down, so that porosity can be easily obtained.

The mandrel used in the present invention is not particularly limited as long as it is not dissolved in the elastomer solution, and for example, a glass rod, a Teflon rod, or a stainless steel rod with a smooth surface is preferably used.

Methods of placing a tubular structure made of fibers on the mandrel include a method of covering the mandrel with a tubular structure made of fibers, and a method of placing fibers or a band-like object made of fibers on the mandrel so as to form a tubular structure. The most typical method is to wrap it around.

The tubular structure composed of fibers may be placed directly on the mandrel or on the mandrel on which the elastomer has been precipitated, but after being placed on the mandrel on which the elastomer has been deposited, the elastomer solution is removed. A method in which coating and elastomer precipitation are performed one or more times is preferred.

Methods for making the monofilament spiral structure exist on the mandrel include a method of covering the monofilament spiral structure over the mandrel on which the elastomer is deposited or on the mandrel where the tubular structure composed of fibers is present; There is a method of spirally winding monofilament. The procedure is to place a monofilament helical structure on the mandrel on which the elastomer has been deposited, and then coat it directly or with an elastomer solution and deposit the elastomer one or more times, and then remove it from the fiber. A method is preferred in which the structured tubular structure is placed thereon, and then the coating of the elastomer solution and the precipitation of the elastomer are carried out one or more times.

Methods for forming the 0-shaped shape include using a mandrel that has been previously formed into a 0-shaped shape, or after covering the outer surface of a straight artificial blood vessel with a hollow body such as a non-kinking silicone tube, or by There is a method of inserting a hollow body such as a non-kinking rod or silicone tube into the cavity, forming it into a 0-shape, and heat setting it at a temperature that does not cause denaturation of elastomers, fibers, and monofilaments. A method of heat setting the blood vessel into a 0-shape is preferred because it can be easily formed into any 0-shape.

The artificial blood vessel of the present invention obtained as described above has porosity suitable for organization due to the porous tubular structure made of elastomer, the blood contact surface has excellent blood compatibility, and the compliance is excellent in living organisms. Because it resembles an artery, it has excellent patency, and because the puncture hole of the dialysis needle self-occludes, it has excellent hemostasis. Furthermore, since the porous tubular structure is reinforced with a tubular structure made of fibers, it has excellent strength and durability, and has sufficient strength even after repeated punctures with a dialysis needle. In addition, monofilaments with a diameter of 0.01 = 1 mm are arranged in a spiral shape, and prior to use, they are shaped into a 0-shape to suit the area of the living body, so they have excellent anti-kinking properties and pressure resistance. There is. In addition, suturing work with biological blood vessels is also easy.

The artificial blood vessel of the present invention has such characteristics and effectively compensates for the deficiencies of conventional artificial blood vessels in a complex manner, and is particularly excellent as an artificial blood vessel for blood access.

Next, the present invention will be explained in more detail using Examples, but the present invention is not limited to these.

Example 1 4.4'-diphenylmethane diisocyanate 27.3
After synthesizing a prepolymer using 5 parts by weight (the same applies hereinafter) and 54.7 parts of polyoxytetramethylene glycol (molecular weight 2000), 4.7 parts of ethylene glycol
5 parts and polyethylene glycol at both ends polydimethylsiloxane (average molecular weight of polyethylene glycol at both ends 6811, average molecular weight of polydimethylsiloxane 1040)
) Chain extension was performed using 13.2 parts to synthesize a segmented polyurethane containing polydimethylsiloxane in the main chain.

The obtained polyurethane had a tensile strength of 350 kg/cj, an elongation of 670%, and a critical surface tension determined from a Zisman plot of 28 dyn/cm.

50 ml of dioxane and 5 ml of N,N-dimethylacetamide
casein 2 with a particle size of 30μ or less in a mixed solvent with 0ml
0 g and the polyurethane 14r were added and stirred to obtain a dispersion solution. Glass rods of four diameters were immersed in this dispersion solution and then taken out to uniformly coat the glass rods with the dispersion solution. This glass rod was immersed in ethylene glycol to precipitate the elastomer. This operation was repeated one more time.

Next, a spiral structure made of polyester monofilament with a diameter of 0.2 mm and an inner diameter of 5 B and a spiral spacing of 2 IIll was placed over a length of 8 ca+ over the central portion of the glass rod on which the elastomer was deposited on the surface. Further, over the entire length of the glass rod, a tubular structure made of fibers having a diameter of about 5 mm knitted using a 30-needle ribbon knitting machine using 50 denier woolly processed polyester fibers was placed.

The glass rod was immersed in a doubly diluted dispersion solution and then taken out, and then immersed in ethylene glycol to precipitate the elastomer.

After the elastomer was sufficiently deposited, the glass rod was washed with water and the glass rod was taken out to obtain a tubular structure. This tubular structure was immersed in a sodium hydroxide aqueous solution having a pH of 13.5 to dissolve and remove the casein, and then thoroughly washed with water.

- Next, insert a silicone tube as a support into the inner cavity of the obtained tubular structure, and shape the part where the monofilament spiral structure exists into a 0-shaped shape with a curvature diameter of 50 + u. After high-pressure steam treatment with C for 20 minutes, the silicone tube was removed to obtain the artificial blood vessel of the present invention.

The obtained artificial blood vessel has an inner diameter of 4 fins and an outer diameter of approximately 5.5 fins.
The curvature diameter of the 0-shaped portion was 50 am. When the inner surface of this artificial blood vessel was observed with the naked eye, it was found to be smooth over the entire length. When this artificial blood vessel was observed with a scanning electron microscope, there were many circular to oval pores with a maximum diameter of 5 to 20 mm on the inner surface, and on the outer surface, the maximum diameter was about 1 to 10 mm. m circular or irregularly shaped pores were present.

The porosity was determined from equation (1) and was 77%.

A tubular structure made of fibers is incorporated into the outer part of the tube wall cross section of the 0-shaped portion where the monofilament is present, and a spiral structure of monofilament is incorporated inside the tubular structure. Furthermore, the partition walls in the inner part had a mesh structure made of elastomer. A tubular structure composed of fibers was incorporated in the outer part of the tube wall cross section at the end where no monofilament was present, and the inner part had a network structure with partition walls made of elastomer. Moreover, the pores were almost uniform from the inner surface to the outer surface of the tube wall.

The 0-shaped portion of this artificial blood vessel where the monofilament was present did not kink even when the curvature diameter was lh. It also had sufficient rigidity compared to the end without monofilament, and the lumen did not collapse easily even when pressed. This shows that the artificial blood vessel of the present invention has excellent anti-kinking properties and pressure resistance due to the monofilament spiral structure.

When a water pressure of 12 hmHg was applied to this artificial blood vessel, approximately 30 ml of water penetrated into the outer surface of the artificial blood vessel per minute per IC on the inner surface of the artificial blood vessel, indicating that the artificial blood vessel had porosity.

The compliance of the end of this artificial blood vessel where no monofilament is present was calculated from equation (2) and was found to be 0.40.
Met. Further, the results of measuring the stress-strain relationship are shown in FIG. 3 as the stress-strain curve (1). From this, it can be seen that the artificial blood vessel of the present invention has a compliance and response strain relationship that is similar to that of a biological blood vessel.

゛Next, the end of this artificial blood vessel where no monofilament was present was punctured with a 17-gauge needle, and after the needle was removed, the puncture site was observed using a scanning electron microscope, and the puncture hole was found to be occluded on both the outer and inner surfaces. .

Furthermore, even after repeating puncture and removal of the 17-gauge needle 250 times with a length of 1.5 cm and a circumferential width of 0.5 CI+, the artificial blood vessel did not rupture even when an internal pressure of 300 mm and 11 g was applied. . This shows that the artificial blood vessel of the present invention has excellent strength even after repeated punctures with a dialysis needle.

When this artificial blood vessel (1) was A-V (arterial-venous) shunted with a length of approximately 20 J from the right carotid artery of a mongrel adult to the human jugular vein, it showed a patency of more than 3 months. This shows that the artificial blood vessel of the present invention has excellent patency.

[Effects of the Invention] Although the artificial blood vessel of the present invention has a U-shape, since the monofilaments exist in a spiral shape, it has excellent anti-kinking properties and pressure resistance. Furthermore, it has excellent hemostasis at the puncture site and strength after repeated punctures.
In addition, because it has a blood contact surface with excellent porosity and blood compatibility, and a compliance similar to that of a living body's arteries, it has excellent patency and is extremely effective as an artificial blood vessel for blood access.

[Brief explanation of the drawing]

FIGS. 1 and 2 are schematic diagrams showing, with diagonal lines, the location of the monofilament spiral structure incorporated in the blood access artificial blood vessel of the present invention, and FIG. 3 shows the carotid artery (1), In fact, it is a graph showing stress-strain curves of the end portion (1) of the artificial blood vessel and the thoracic aorta (8) obtained in Absolute 1. (Main symbols in the drawing) (1) Two artificial blood vessels (2): Location of monofilament

Claims (1)

[Claims] 1. In an artificial blood vessel consisting of a porous tubular structure having pores communicating from the inner surface to the outer surface of the tube wall made of an elastomer and a tubular structure made of fibers, a monofilament with a diameter of 0.01 to 1 mm Exists in a spiral shape other than the blood contact surface of blood vessels, and has a curvature diameter of 10 to 20
An artificial blood vessel for blood access characterized by a U-shaped shape of 0 mm.