JPH0436020B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an artificial blood vessel whose end portions of the tube wall can be sutured and which has a compliance similar to that of a living blood vessel, and whose central portion has excellent antithrombotic properties.

[Background Art] In recent years, along with advances in vascular surgery, research on artificial blood vessels has progressed, and a large number of artificial blood vessels have been developed. Currently, artificial blood vessels for medium or large diameter arteries with an inner diameter of approximately 6 mm or more are available in the United States, for example.
Dobesky artificial blood vessels made of Dacron knitted fabric manufactured by USCI and Gore-Tex made of expanded polytetrafluoroethylene (hereinafter referred to as EPTFE) manufactured by Gore, Inc. in the United States are used clinically.

These artificial blood vessels have a hole that communicates from the inside to the outside of the blood vessel, and after being implanted in a living body, they are immediately covered with a pseudoendothelium, and tissue enters from the living tissue side through this hole. It has been stably organized and is fulfilling its mission as an artificial blood vessel. Having communicating pores that are useful for organizing the artificial blood vessel in this way is hereinafter referred to as having porosity.

However, these artificial blood vessels have the disadvantage of poor patency and cannot be used clinically as small-caliber arterial or venous artificial blood vessels with an inner diameter of about 6 mm or less. Therefore, autologous veins are currently used for revascularization surgeries for arteries below the knee, coronary arteries, and the like.

The reason for this poor patency is that current artificial blood vessels achieve patency through organization through the formation of pseudointima and neointima; It is possible that the thickness of the membrane cannot be adjusted and it becomes occluded. In addition, artificial blood vessels with an inner diameter of 6 mm or more currently used clinically have mechanical properties (especially compliance) that are similar to biological blood vessels.
Because of the large difference between the two, anastomotic occlusion has become a problem, and when it comes to small-caliber artificial blood vessels with an inner diameter of 6 mm or less, this compliance mismatch is also considered to be a major cause of occlusion.

[Problems to be Solved by the Invention] From the above points of view, the purpose of the present invention is to provide an artificial blood vessel with excellent patency, particularly in a revascularization surgery for small-caliber arteries, by solving the following two problems. The aim is to obtain an artificial blood vessel that can be applied to

It improves the antithrombotic properties of the central blood contact surface of the artificial blood vessel and prevents occlusion due to thickening of pseudointima and neointima.

The compliance of the end of the artificial blood vessel is approximated to that of a living blood vessel, thereby preventing compliance mismatch at the anastomosis.

[Means for Solving the Problems] The end portion of the artificial blood vessel of the present invention has a porous structure made of elastomer, which provides compliance similar to that of a living blood vessel and allows suturing. In addition, the central part is made of a material with excellent antithrombotic properties.
The present invention was completed by improving antithrombotic properties by making the blood contact surface a smooth surface to prevent blood flow from flowing out or blood stagnation. That is, in the present invention, the end of the tube wall is made of an elastomer, the porous body has communication holes extending from the outer surface to the inner surface, and has a compliance within the range of 0.1 to 0.8, which approximates that of a biological blood vessel. is at least 10 μm in diameter and has a smooth surface with substantially no pores or holes on the inner surface when observed with a scanning electron microscope at 1000x magnification.
This invention relates to an artificial blood vessel consisting of a porous body with a homogeneous layer of thickness and an outer layer made of elastomer.

[Example] Next, the artificial blood vessel of the present invention will be explained using the drawings. FIG. 1 shows a schematic diagram of a vertical cross section of the artificial blood vessel of the present invention, in which the end portion 1 of the artificial blood vessel is made of a porous body 3 made of an elastomer, and the central portion 2 of the artificial blood vessel is located on the inner side. That is, the blood contact surface side is a homogeneous layer 4 having a smooth inner surface, and the outer side is a porous body 3 made of an elastomer. Further, the artificial blood vessel of the present invention is preferably reinforced with a tubular member 5 made of fibers as shown in FIG.

In the present invention, the ends of the tube wall mean both end portions of the artificial blood vessel as shown in FIGS. 1 and 2, and the central portion refers to the central portion sandwiched between the ends. means.

The tube wall at the end of the artificial blood vessel of the present invention is made of a porous body made of elastomer. The porous body has pores throughout its thickness from the inner surface to the outer surface of the tube wall. It is further preferred that at least a portion of the pores communicate with each other, and that at least a portion of the pores are open toward the outside and have porosity on the inner and outer surfaces. The partition walls forming the holes are made of elastomer and are continuous. Furthermore, the partition wall itself contains a large number of minute pores and holes with a pore diameter of 1 μm or less inside, which results in a loose structure of the vessel wall, and the end of the artificial blood vessel has a compliance similar to that of a biological blood vessel. preferred for obtaining

Particularly preferred porous bodies are network structures in which pores are substantially uniform throughout the thickness of the tube wall from the inner surface to the outer surface.

Preferably, the pores present throughout the thickness of the tube wall from the inner surface to the outer surface are of substantially uniform size. The area near the inner surface and the area near the outer surface of the tube wall are slightly denser than the area between the two, which accounts for most of the porous body, and the pores are not completely uniform throughout the thickness. There is. However, unless the pores are extreme enough to impair porosity, the pores may be considered substantially uniform. Although there is no particular limitation on the maximum diameter of the cross section of the hole, it is preferably 1 to 100 μm, and more preferably 3 to 75 μm. If the maximum diameter is larger than 100μm, the strength will be poor,
The porosity tends to become too large, and if it becomes 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 body, it is preferable that the shape of the pores present on the inner surface is circular or elliptical. The maximum diameter of this circle or oval is 1
-100 micrometers are preferable, 5-50 micrometers are more preferable, and 10-30 micrometers are especially preferable. The maximum diameter
When it is larger than 100 μm, blood flow tends to be squeezed out and antithrombotic properties tend to decrease, and when it is smaller than 1 μm, the organization of the artificial blood vessel tends to be delayed.

The porosity of the end portion of the artificial blood vessel of the present invention is preferably 95 to 75%. In addition, the porosity of the part with a thickness of at least 30 μm from the inner surface of the tube is 95 ~
80% and the porosity of the outer part of said part is preferably less than the porosity of the part with a thickness of at least up to 30 μm. In particular, the porosity of the part up to a thickness of at least 50 μm from the inner surface of the tube is 95 to 83%, and the porosity of the part outside said part is greater than the porosity of the part of the thickness up to at least 50 μm. The porosity of the entire artificial blood vessel is preferably 90 to 80%.

The porosity referred to in this specification is expressed by the formula (1): Porosity = (Volume of the wall of the artificial blood vessel - Weight of the artificial blood vessel / Specific gravity of the material constituting the artificial blood vessel / Volume of the wall of the artificial blood vessel )×100(1). The porosity is determined by the amount of pores present in the tube wall and the amount of minute pores or pores with a diameter of 1 μm or less existing in the partition wall forming the pores.

In the artificial blood vessel of the present invention, the porosity greatly affects the mechanical properties, particularly the compliance and organization of the blood contact surface. There is a positive correlation between porosity and compliance, and as the porosity increases, the compliance also increases. When the porosity exceeds 95%, the compliance of the artificial blood vessel becomes too large than that of the biological blood vessel, which is not preferable.

At least from the inner surface of the end of the graft
There is a nearly proportional relationship between the porosity of the portion up to 30 μm in thickness and the number of pores present on the inner surface of the end of the artificial blood vessel, that is, the blood contact surface, and the greater the number of pores on the blood contact surface, the better the result. In general, favorable organization occurs, blood compatibility is excellent, and the patency of the artificial blood vessel tends to improve. If the porosity of the portion having a thickness of at least 30 μm from the inner surface of the end of the artificial blood vessel is less than 75%, organization tends to be poor. Therefore, in order to adjust the mechanical properties, especially the compliance and the number of pores present on the blood contact surface, by adjusting the porosity, it is necessary to at least
By increasing the porosity of the part with a thickness of up to 30 μm, the number of pores existing on the blood contact surface is increased,
It is advantageous to adjust the mechanical properties, in particular the compliance, by reducing the porosity in the outer part of said part.

The elastomer used in the present invention has acute toxicity,
It is an elastomer that does not contain low-molecular eluates that can cause inflammation, hemolysis, or exothermic reactions, does not cause significant damage to blood physiological functions, and has excellent antithrombotic properties. 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. Furthermore, the elastomer used in the present invention is
As long as it has the properties of an elastomer when molded into an artificial blood vessel, even if it is a composition of the above-mentioned elastomer and a polymer that does not have properties as an elastomer, the final molded product will be an elastomer. If it has the following properties, it can be used as the elastomer used in the present invention.

Among the above elastomers, thermoplastic polyether-type segmented polyurethane (including segmented polyurethane urea, hereinafter the same) is more preferred because it has excellent strength, elongation, durability, antithrombotic properties, processability, etc. Preferably, segmented polyurethane containing fluorine in the hard segment or soft segment or JP-A-57-
Segmented polyurethane containing polydimethylsiloxane in the main chain as disclosed in Japanese Patent No. 211358 is preferred. Particularly preferred is polydimethylsiloxane as part of the soft segment. (In the formula, R ₁ to _{R 6} are alkylene groups having 1 or more carbon atoms, preferably alkylene groups having 2 to 6 carbon atoms such as ethylene, propylene, butylene, hexamethylene, etc., a and g are integers of 0 to 30, b , c, e, f are 0 or 1, and d is an integer of 2 or more, preferably 5 to 135).

The compliance referred to in this specification is expressed by the formula (2): C=ΔV/Vo.ΔP×100 (2) (where C is compliance and Vo is the internal pressure 50
The internal volume of the measured blood vessel when mmHg, ΔP is the internal pressure 50mm
100mmHg from Hg to 150mmHg, ΔV is internal pressure 50mm
It is defined as the internal volume of the measured blood vessel that increases between Hg and 150 mmHg. In actual measurement, a measurement blood vessel is inserted into a closed circuit, 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 compliance is calculated from equation (2). . Compliance measurement of a porous artificial blood vessel may be performed after the communicating holes in the vessel wall are closed by pre-clotting or the like.

Compliance of biological blood vessels is determined by arteries, veins,
It varies depending on the caliber of the blood vessel. 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 determined unconditionally, but the end portion of the artificial blood vessel of the present invention has a compliance that approximates each biological blood vessel, For example, it is preferable to have a compliance of 0.1 to 0.8. As an artificial blood vessel for small-caliber arteries, it is particularly preferable to have a compliance of 0.1 to 0.5.

The purpose of making the end of the artificial blood vessel of the present invention a porous body made of elastomer is to enable suturing, approximate compliance to that of a living blood vessel, prevent compliance mismatch, and promote organization of the sutured portion. The purpose is to prevent the occurrence of pannus. The length of the end portion varies depending on the transplant site and is not particularly limited, but for the above purpose, the length of the end portion at the time of transplantation is 3 to 70 mm,
Preferably 5 to 50 mm, more preferably 10 to 40 mm
It is.

The central part of the artificial blood vessel of the present invention is a homogeneous layer with a thickness of at least 10 μm having a smooth inner surface,
The outside is made of a porous body made of elastomer. The homogeneous layer has a structure consisting only of the material and does not substantially contain voids such as pores or holes therein. The smooth inner surface means a blood-contacting surface that does not contain holes or holes where blood can flow or accumulate, and is actually
This can be confirmed by the fact that no pores or holes are observed on the inner surface when observed at 1000x magnification. Of course, this does not include holes, holes, scratches, etc. that occurred accidentally during manufacturing.

The material constituting the homogeneous layer is not particularly limited as long as it has excellent antithrombotic properties, but the above-mentioned elastomers are preferred. This central part occupies most of the part that comes into contact with blood as an artificial blood vessel,
The blood contact surface is made of a material with excellent antithrombotic properties and has a smooth surface that is difficult to form a thrombus, thereby ensuring patency as an artificial blood vessel.

The thickness of the homogeneous layer must be at least 10 μm or more, preferably 50 to 600 μm, more preferably 100 to 400 μm, in view of strength and long-term maintenance of a smooth surface.

The porous body made of elastomer that exists outside the homogeneous layer in the center of the artificial blood vessel of the present invention is the same in material and shape as the porous body made of elastomer that constitutes the end portion of the artificial blood vessel. It is preferable that The homogeneous layer and the porous body made of the elastomer must be in strong physical or chemical contact in order to maintain the shape of the artificial blood vessel over a long period of time. Furthermore, it is preferable that the material forming the homogeneous layer and the material forming the porous body are the same, and that the interface between the two is homogeneously bonded.

The artificial blood vessel of the present invention has sutureable and porous ends, a compliance similar to that of a biological blood vessel, and a blood contact surface suitable for organization, and the center portion is made of a material with excellent antithrombotic properties. It is said to have excellent patency because it has a smooth surface that prevents thrombus formation. However, there may be concerns about rupture or damage if the suture thread comes off from the suture site, abnormally high blood pressure occurs during surgery, or concerns about maintaining durability over a long period of time. In such cases, it is preferable to reinforce the artificial blood vessel with a tubular material made of fibers, if necessary.

Furthermore, although artificial blood vessels reinforced with tubular materials made of fibers can be sterilized using gamma rays or ethylene oxide gas, they have the disadvantage that they contract when sterilized by boiling or high-pressure steam. In order to obtain an artificial blood vessel that does not shrink even when subjected to boiling sterilization or high-pressure steam sterilization, it is particularly preferable to reinforce it with a tubular material made of heat-set fibers.

Heat setting as referred to in the present invention refers to boiling sterilization or high-pressure steam sterilization (for example, high-pressure steam sterilization at 121°C for 20 minutes).
This means applying heat to a tubular material made of fibers until the tubular material does not shrink. Specific operations include, for example, boiling, exposing to steam, maintaining in a high-temperature atmosphere, and performing the same treatment as high-pressure steam sterilization. Among these, a method that performs the same treatment as high-pressure steam sterilization is preferable because it is easy to operate and heat setting can be performed reliably.

The tubular object made of heat-set fibers used in the present invention may be one that is formed into a tubular object after heat-setting the fibers. Furthermore, it may be heat-set, or it may be a tubular product itself made of fibers that has been heat-set. Among these methods, from the viewpoint of ease of operation, it is preferable to heat set the tubular material itself made of fibers.

The artificial blood vessel reinforced with a tubular material made of fibers as used herein refers to an artificial blood vessel in which at least a portion of the tubular material is in contact with and/or bonded to a porous body made of an elastomer. This means that there is a mechanical interaction between the porous body made of elastomer and the tubular body to the extent that they cause approximately the same strain in response to blood pressure or stress applied from the outside.

The above-mentioned fibers are used only to make threads, nets, ropes, woven fabrics, knitted fabrics, braided fabrics, non-woven fabrics, etc.
It is a thin and long object over 100 times larger. The fiber is
Any material can be used without particular limitation as long as it is safe for living organisms, has negligible deterioration in the living body, can withstand sterilization operations, and can be processed into the desired tubular product. From the viewpoint of processability, ease of handling, flexibility, uniformity, etc., recycled artificial fibers, semi-synthetic fibers, and synthetic fibers are preferred. Specific examples of these include cellulose-based, protein-based, polyamide-based, polyester-based, polyurethane-based, polyethylene-based, polystyrene-based, polyvinyl chloride-based, polyvinylidene chloride-based, polyfluoroethylene-based,
Examples include polyacrylic fibers and polyvinyl alcohol 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; Such as high-bulk processing type, covered yarn, fancy yarn, bulky yarn, AtoZ type, conjugate fiber, etc.
Examples include those that have elasticity depending on the processing method.

The tubular material made of fibers used in the present invention is
Woven fabrics, knitted fabrics, braided fabrics, nonwoven fabrics using the above fibers, yarns spun with at least one type of the above fibers, multifilaments of at least one type of the above fibers, yarns that are combinations of these, and combinations of these. It is a tubular object made of foam or a sponge-like material such as polyurethane foam.

The tubular object is preferably used so that the end of the artificial blood vessel, which is a combination of the tubular object and a porous body made of an elastomer, has a compliance similar to that of a biological blood vessel.

In order to impart such properties to an artificial blood vessel using the tubular article, it can be achieved, for example, by the following two methods alone or in combination. The first method is to adjust the frequency of combinations of fibers, etc., or to loosen the combination points. The second method is to use stretchable fibers.

The tubular material may be formed into a tubular shape by itself as a fiber or a material made from fibers, or may be formed into a tubular shape when combined with a porous material made of an elastomer to form an artificial blood vessel.
From the viewpoint of processability, workability, and obtaining compliance similar to that of living blood vessels, a tubular article made of knitted fibers is preferable, and a tubular article made of knitted stretchable fibers is particularly preferable.

In order for the end of the artificial blood vessel to have a compliance similar to that of a biological blood vessel, it is necessary to use stretchable fibers such as woolly nylon and woolitetron, which are particularly stretchable and bulky, as well as rubber or spandex filaments. Covered yarn, which is a yarn in which other spun yarn or filament is wound, is preferable.

Next, one embodiment of the method for manufacturing an artificial blood vessel of the present invention will be described.

First, create a homogeneous layer that will form the inside of the central part of the artificial blood vessel. This homogeneous layer may be produced by extrusion molding, or a homogeneous layer with a desired thickness may be produced by repeatedly coating a material solution on the mandrel and then removing the solvent with hot air or the like.

Next, the cylindrical molded body forming the homogeneous layer thus obtained is inserted into the center of the mandrel. In the artificial blood vessel of the present invention, the mandrel in which this homogeneous layer exists in the center is coated with a pore-forming agent and/or an elastomer solution having a cloud point, and then the mandrel is immersed in a coagulation solution once or once. It can be manufactured by repeating the process two or more times. The porosity can be adjusted by adjusting the particle size and amount of the pore-forming agent, the solvent composition of the elastomer solution, the type of coagulation liquid, etc. In order to increase the porosity of the inner part of the tube wall, these conditions may be adjusted during the operation of forming the inner part.

In the case of reinforcing with a tubular material made of fibers, by placing the tubular material made of fibers on the mandrel in any step of the above operation,
can be manufactured.

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

The elastomer solution containing the pore-forming agent has the pore-forming agent, the elastomer, and a solvent (hereinafter referred to as a good solvent) that dissolves the elastomer as essential components, and the pore-forming agent is uniformly dispersed therein. The pore-forming agent is 1 to 250
% (pore-forming agent/elastomer volume %, hereinafter the same) is preferable, more preferably 20 to 200%, especially
50-150% is preferred. 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, the porous body portion of the artificial blood vessel of the present invention can be obtained. 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.

An elastomer solution having a cloud point of 100 ml contains an elastomer, a good solvent, and an amount of a poor solvent necessary to form a cloud point as essential components. The cloud point is the temperature at which a polymer precipitates from a dissolved state into a colloid, that is, undergoes a phase change. It is difficult to coat this solution uniformly if it is handled below the cloud point temperature.
Since the porous structure tends to be difficult to form, the solution is maintained at a temperature above the cloud point and coated on the mandrel, and then the mandrel is immersed in a coagulating liquid at a temperature below the cloud point, either immediately or after a phase change occurs. Immersion is preferred. 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 a porous structural part can be obtained.

An elastomer solution having a pore-forming agent and a cloud point has 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. The porous structural part of the present invention can be obtained by using this solution to precipitate the elastomer in the same manner as in the above solution, and then dissolving and removing the pore-forming agent.

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. The particle size of the pore-forming agent is preferably 1 to 100 μm, more preferably 10 to 74 μm, and particularly preferably 20 to 50 μm. Examples of such pore-forming agents include calcium carbonate, glucose, starch, casein, collagen, gelatin, albumin, and the like.

A good solvent to be used in the present invention varies depending on the type of elastomer, so it cannot be determined unconditionally.
For example, when the elastomer is a polyurethane elastomer, N,N-dimethylacetamide, N,N dimethylformamide, N-methyl-
Examples include solvents such as 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. For example, water, lower alcohols, ethylene glycol, propylene glycol, 1,4
Examples include butanediol and glycerin, and these may be used alone or in combination of two or more.

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 for placing a tubular object made of fibers on the mandrel include a method of covering the mandrel with a tubular object made of fibers, and a method of wrapping fibers or a band-like object made of fibers on the mandrel to form a tubular structure. The most typical method is to attach it. The tubular article composed of fibers may be present directly on the mandrel or on the mandrel on which the elastomer has been deposited, but after being present on the mandrel on which the elastomer has been deposited, it may be coated with an elastomer solution. A method in which precipitation of the elastomer and the elastomer are carried out once or twice or more is preferred.

The artificial blood vessel of the present invention thus obtained is
It has the following excellent properties.

The central blood contact surface has excellent antithrombotic properties.

The compliance of the end portion is similar to that of a biological blood vessel.

Further, since the tube wall at the end of the artificial blood vessel of the present invention is made of an elastomer and is made of a porous material, it has good penetrability with a suture needle and can be easily sutured.

The suture needle's through hole self-closes.

Furthermore, if it is reinforced with a tubular material made of fibers, it has excellent strength and durability.

The artificial blood vessel of the present invention having such properties is
It has excellent patency and is also excellent in workability during revascularization surgery.

Therefore, the artificial blood vessel of the present invention can be used as an artificial blood vessel, a bypass artificial blood vessel, and a patch material in revascularization surgery for arteries and veins, and can also be used for blood access, etc. can. Furthermore, it is preferable to use it as an arterial artificial blood vessel having a compliance of 0.1 to 0.8. In particular, it is preferable to use it as a small-caliber arterial artificial blood vessel having a compliance of 0.1 to 0.5 and an inner diameter of about 1 to 6 mm, which is not the case for artificial blood vessels currently used in clinical practice. Therefore, it can be suitably used for revascularization of arteries below the knee or as an artificial blood vessel for aorta-coronary artery bypass. Furthermore, the artificial blood vessel of the present invention can also be used as a substitute for a soft tubular body such as a ureter.

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
After synthesizing a prepolymer using 27.35 parts (by weight, same hereinafter) and 54.7 parts of polyoxytetramethylene glycol (molecular weight 2000), 4.75 parts of ethylene glycol and polyethylene glycol polydimethylsiloxane at both ends (polyethylene glycol at both ends) Chain extension was performed using 13.2 parts of glycol (average molecular weight: 681) and polydimethylsiloxane (average molecular weight: 1940) to synthesize a segmented polyurethane containing polydimethylsoloxane in the main chain.

The tensile strength of the obtained polyurethane is 350Kg/cm ² ,
The elongation was 670%, and the critical surface tension determined from the Zisman plot was 28 dyn/cm.

Add 50g of the polyurethane to 140ml of dioxane and N.
After dissolving in a mixed solvent of 60 ml of N-dimethylacetamide, the mixture was defoamed under reduced pressure. A glass rod with a diameter of 3 mm was immersed in this polyurethane solution and then taken out, and the polyurethane solution was uniformly coated onto the glass rod. This glass rod was dried with hot air at 80°C to remove the solvent. This operation was repeated to uniformly form a 250 μm thick urethane layer on the glass rod. After drying this glass rod under reduced pressure at 50℃ for 24 hours to completely remove the solvent, the glass rod was removed while soaked in warm water at 60℃, and both ends were trimmed.
A urethane tube with a diameter of 250 μm, an inner diameter of 3 mm, and a length of 5 cm was obtained.

Add 68.2 g of casein with a particle size of 30 to 40 μm and 54.6 g of the above polyurethane to a mixed solvent of 200 ml of dioxane and 200 ml of N,N-dimethylacetamide, stir and dissolve overnight to form a dispersion in which casein is uniformly dispersed in the urethane solution. (hereinafter referred to as dispersion A).

The urethane tube (thickness: 250 μm, inner diameter: 3 mm, length: 5 cm) was inserted into the center of a glass rod with a diameter of 3 mm and a length of 40 cm. The glass rod was vertically immersed in the A dispersion, then taken out, and the A dispersion was uniformly coated onto the glass rod. The glass rod was then immersed in water to precipitate the elastomer.

The porosity of a portion approximately 100 μm thick from the inner surface of the end of the artificial blood vessel, which will be described later, is the porosity measured at this stage.

The amount of casein is 54.6g, and the other composition is A.
The above operation was repeated two more times using the same dispersion (hereinafter referred to as dispersion B). After the elastomer was sufficiently precipitated, it was washed with water and the glass rod was taken out to obtain a tubular structure. This tubular structure was immersed in an aqueous sodium hydroxide solution of pH 13.5 to extract and remove casein, and finally thoroughly washed with water to obtain an artificial blood vessel according to the present invention.

The end of the obtained artificial blood vessel has an inner diameter of 3 mm and an outer diameter of approx.
It was 4.5mm. When this artificial blood vessel was observed using a scanning electron microscope, it was found that approximately
There were many circular to oval pores of 20 μm in diameter, circular to irregularly shaped pores of about 1 to 10 μm in diameter on the outer surface, and the tube wall cross section at the end had a network structure.
Furthermore, when the inner surface of the central portion was observed using a scanning electron microscope at a magnification of 1000 times, no pores or holes were found.

The porosity of the end of this artificial blood vessel calculated from equation (1) is approximately 88% from the inner surface of the artificial blood vessel to a thickness of approximately 100 μm, and the porosity of the entire end of the artificial blood vessel is approximately 88%. The porosity was 81%.

Next, when we measured the water permeability at the end of this artificial blood vessel using water pressure of 120 mmHg, we found that the inner surface of the artificial blood vessel 1
Approximately 30 ml of water per cm ² per minute penetrated the outer surface of the artificial blood vessel, which was found to be porous.

Next, the end of this artificial blood vessel was pre-clotted with bovine blood, cut into 8cm lengths, inserted into a closed circuit, and fed with bovine ACD blood into the closed circuit using a metering pump that pumps 0.05ml per stroke. Send the liquid,
Changes in internal pressure were measured. Compliance was measured from equation (2) based on the stroke number of the metering pump and changes in internal pressure, and was found to be 0.20.

Next, the end was cut to a length of 1.5 cm and an 8 cm total length of the artificial blood vessel was transplanted into the carotid artery of an adult mongrel dog, and it showed patency for more than 2 months. Furthermore, even if this artificial blood vessel was cut at any point on the end thereof, the cut portion did not fray, and the sutureability was excellent, and the through hole of the suture needle self-occluded when the needle was removed.

From the above, it can be seen that this artificial blood vessel is excellent, especially as an artificial blood vessel for small diameter arteries.

Example 2 When manufacturing an artificial blood vessel in the same manner as in Example 1, before the second operation of immersing a glass rod in the B dispersion, a cover made of 50 denier Tetron fibers wrapped around 10 denier spandex was prepared. A tubular article with a diameter of approximately 4 mm, knitted using yarn using a 24-needle ribbon knitting machine, was placed over a glass rod on which elastomer was deposited. Next, this glass rod was immersed in a dispersion solution prepared by diluting the A dispersion liquid twice, and then taken out and the dispersion liquid was uniformly coated on the glass rod, after which the elastomer was precipitated by dipping this glass rod in water. . After sufficiently depositing the elastomer, wash with water and remove the glass rod.
Obtained a tubular structure. The following operations were performed in the same manner as in Example 1 to obtain the artificial blood vessel of the present invention.

The end of the obtained artificial blood vessel has an inner diameter of 3 mm and an outer diameter of approx.
It was 4.8mm. The porosity of this artificial blood vessel, calculated from equation (1), is approximately from the inner surface of the end of the artificial blood vessel to
The porosity of the part up to 100μm thickness is 88%,
The porosity of the entire end of the artificial blood vessel was 83%.

The compliance measured by the same method as in Example 1 was 0.35, and the water permeation amount was about 50 ml.

Next, an animal experiment was conducted in the same manner as in Example 1, and the result showed patency of more than 2 months.

Example 3 Instead of a tube with a diameter of about 4 mm knitted with a 24-needle ribbon knitting machine using covered yarn made of 10-denier spandex wrapped with 50-denier Tetron fiber, 24 needles of 50-denier polyester woolly yarn were knitted. A tube knitted using a ribbon knitting machine was heated at 121℃ for 20 minutes.
An artificial blood vessel of the present invention was obtained in the same manner as in Example 2, except that a tubular material with a diameter of about 4 mm, which had been dried after high-pressure steam sterilization for a minute, was used.

The end of the obtained artificial blood vessel has an inner diameter of 3 mm and an outer diameter of approx.
It was 4.8mm. When this artificial blood vessel was observed with a scanning electron microscope, the inner surface of the end portion, the outer surface, and the inner surface of the center portion were the same as in Example 1. In the cross section of the central part, there was a homogeneous layer with a thickness of 250 μm on the inside, a porous body made of elastomer on the outside, and a tubular object made of fibers existed inside the porous body. Furthermore, at the interface between the homogeneous male and the porous structure, both were uniformly bonded. A sketch of a scanning electron micrograph of a cross section of this central portion is shown in FIG.

The compliance measured by the same method as in Example 1 was 0.4, and the water permeation amount was about 50 ml.

Even when this artificial blood vessel was subjected to high-pressure steam sterilization at 121°C for 20 minutes, no change in shape or dimensions occurred. Using this sterilized artificial blood vessel, an experiment was conducted in the same manner as in Example 1, and the result showed that it remained patent for more than two months.

[Effects of the Invention] Since the artificial blood vessel of the present invention is made of a porous body whose end portion is made of an elastomer, it has a compliance similar to that of a living blood vessel, has a shape suitable for organization, and can be easily sutured.

The central part is made of a material with excellent antithrombotic properties and has a smooth surface that is less likely to generate thrombi, so it has excellent patency.

In addition, when reinforced with a tubular material made of fibers, it has excellent strength and durability, and when reinforced with a tubular material made of heat-set fibers, boiling sterilization and high-pressure steam sterilization are possible. . Therefore, the artificial blood vessel of the present invention can be used not only as an artificial blood vessel for currently performed revascularization surgery, but also as an artificial blood vessel for small-caliber arteries that are not currently used clinically.

[Brief explanation of drawings]

FIGS. 1 and 2 are schematic diagrams showing longitudinal cross sections of the artificial blood vessel of the present invention. Figure 3 shows
3 is a sketch of a scanning electron micrograph of a cross section of the central part of the artificial blood vessel of the present invention obtained in Example 3. FIG. Reference numbers in the drawings: 1...end, 2...center, 3...
... Porous body, 4 ... Homogeneous layer, 5 ... Tubular object.

Claims (1)

[Scope of Claims] 1. The end of the tube wall is made of an elastomer, and is made of a porous body with communication holes extending from the outer surface to the inner surface and has a compliance within the range of 0.1 to 0.8, which approximates that of a biological blood vessel, The inner surface is a homogeneous layer with a thickness of at least 10 μm having a smooth surface with substantially no pores or holes on the inner surface when observed with a scanning electron microscope at 1000x magnification, and the outer surface is composed of an elastomer. An artificial blood vessel made of a porous material. 2. The artificial blood vessel according to claim 1, which is reinforced with a tubular material made of fibers. 3. The artificial blood vessel according to claim 1, which is reinforced with a tubular material made of heat-set fibers.