JPH0547219B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to an artificial blood vessel that has a stress-strain curve and compliance similar to that of a biological blood vessel, and that has pores throughout its wall from the inside to the outside, and a method for manufacturing the same. . [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 invades 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, the compliance of these artificial blood vessels is significantly different from that of biological blood vessels, and therefore, after a long period of time after implantation in a living body, various problems related to incompatibility such as hyperplasia of pannus occur at the anastomotic site. Furthermore, when used as a small-caliber arterial artificial blood vessel with an inner diameter of about 6 mm or less, the difference in compliance is noticeable and the patency is poor, making it impossible to use clinically.
Therefore, autologous veins are used in revascularization surgeries for arteries below the knee, coronary arteries, and the like. Based on the above, when developing artificial blood vessels, especially artificial blood vessels for small-caliber arteries, it is important to ensure that the artificial blood vessels have porosity and to improve the blood compatibility of the artificial blood vessel material. It is said that it is important to approximate the compliance of blood vessels to that of living blood vessels. However, the compliance of currently developed artificial blood vessels is limited by the reports of Sasashima et al. (Artificial Organs 12(1),
179-182, 1983), as shown in Table 1.

[Table] As described above, the compliance of existing artificial blood vessels is extremely small compared to that of living arteries, and compared to arteries, they are considered rigid vessels. In order to solve this mismatch in compliance between biological blood vessels and artificial blood vessels, U.S. Patent No.
No. 4,173,689 discloses a method for manufacturing an artificial blood vessel that uses an elastomer as a material constituting the artificial blood vessel, has a porous tube wall, and has a compliance similar to that of a biological blood vessel. However, this artificial blood vessel has no porosity. Moreover, the manufactured artificial blood vessel has only very small pores in its wall cross section, and has a relatively dense structure.
Although the compliance of artificial blood vessels manufactured in this way is greater than that of conventional artificial blood vessels, it still tends to be lower than that of biological blood vessels. We have developed an artificial blood vessel with a porous structure made of elastomer that solves this problem and has the optimal porosity for organization, and have applied for a patent (patent application).
No. 59-39972, patent application No. 1983-44396, patent application No. 1983-
No. 44397, Patent Application No. 59-44398, Patent Application No. 59-51738
(Japanese Patent Application No. 59-52674). [Problems to be solved by the invention] Stress in the artificial blood vessel developed by the present inventor
As shown in () in Fig. 4, the strain curve becomes different from that of a biological blood vessel (() and () in Fig. 4) when a high stress exceeding the normal blood pressure range is applied. Therefore, when abnormally high blood pressure occurs, such as during surgery, there are concerns about rupture and damage, as well as concerns about maintaining long-term durability. The present invention has been made in order to eliminate the above-mentioned concerns. [Means for Solving the Problems] The present invention provides an artificial blood vessel that has porosity and compliance similar to that of a living blood vessel, and also has a stress-strain curve similar to that of a living blood vessel. It is made of an elastomer and is composed of a porous structure having continuously connected partition walls, and fibers that are present in contact with and/or bonded to at least a part of the porous structure. An artificial blood vessel with porosity consisting of a tubular part and a compliance of 0.1
~0.8, and in the stress-strain curve, the stress
A point corresponding to 0.01Kg/ ^mm2 exists between strain 0.2 and 0.6, the elastic modulus at that point is 0.1Kg/ ^mm2 or less, and a point corresponding to stress 0.05Kg/ ^mm2 has strain 0.5 to 1.0. and is greater than the strain corresponding to a stress of 0.01Kg/ ^mm2 , the elastic modulus at that point is 0.12Kg/ ^mm2 or more, and the strain at a point corresponding to a stress of 0.12Kg/ ^mm2 is 0.55 to 1.2. ^An artificial material ^{that exists} between When producing an artificial blood vessel by coating a mandrel with a blood vessel, a pore-forming agent, and (or) an elastomer solution having a cloud point, and then repeating the operation of immersing the mandrel in a coagulation solution once or twice, The present invention relates to a method for manufacturing the artificial blood vessel, characterized in that a tubular object made of fiber is placed on the mandrel at any stage of the operation. [Example] The elastomer used in the present invention is a thermoplastic elastomer with excellent blood compatibility, that is, it does not contain low-molecular eluates that cause acute toxicity, inflammation, hemolysis, exothermic reactions, etc., and is compatible with the physiological functions of blood. It is a thermoplastic elastomer that does not cause serious damage to the body and has excellent antithrombotic properties. Examples of such elastomers include polystyrene elastomers, polyurethane elastomers, polyolefin elastomers, polyester elastomers, etc.
These elastomers may be blended with polymers other than elastomers within a range that maintains the properties of elastomers. These may be used alone or in combination of two or more. Among these, hydrophobic elastomers with a critical surface tension of less than 35 dyn/cm are more preferred, and hydrophobic elastomers with a critical surface tension of less than 30 dyn/cm are particularly preferred. The more hydrophobic the elastomer is, the more favorable phenomena will appear, such as a decrease in affinity with the biological soft tissue surrounding the outer periphery of the transplanted artificial blood vessel, a decrease in interaction with blood components, and an improvement in water resistance. If the affinity is strong, the biological soft tissue surrounding the transplanted artificial blood vessel tends to be thick and adhere strongly to the artificial blood vessel, which may cause the artificial blood vessel to contract or deform. There is. Among hydrophobic elastomers, strength, elongation,
Polyether-type segmented polyurethane (including segmented polyurethane urea, hereinafter the same) is more preferable from the viewpoint of excellent durability, antithrombotic properties, and the like. Furthermore, segmented polyurethane containing fluorine in the hard segment or soft segmenter and JP-A-57-211358
Segmented polyurethanes containing polydimethylsiloxane in the main chain as disclosed in the above publication are preferred. Particularly preferred is polydimethylsiloxane as part of the soft segment: (In the formula, R ₁ to _{R 6} are alkyl groups having 1 or more carbon atoms,
Preferably an alkylene group 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 represent an integer of 2 or more). The tube wall of the artificial blood vessel of the present invention is composed of a porous structure part made of the elastomer and a tubular part made of fibers. The porous structure portion made of the elastomer has pores throughout its thickness from the inside to the outside. 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 are porous. The partition walls forming the holes are made of elastomer and are continuous. Furthermore, it is preferable for the partition wall itself to have a sparse structure and to have a large number of minute pores or holes therein, in order to obtain an artificial blood vessel having compliance and a stress-strain curve similar to that of a living blood vessel. Although it is difficult to produce partition walls having such a sparse structure by drying a solution coating or from a molten state, it can be easily produced by the production method of the present invention. A particularly preferred porous body structure is a network structure in which pores are substantially uniform throughout the thickness of the tube wall from the inside to the outside. The area near the inner surface and the area near the outer surface of the tube wall are slightly denser than the area between them, which occupies most of the porous structure, and the pores are completely formed throughout the thickness. It may not be uniform. However, unless the pores are so extreme as to impair porosity, the pores may be considered to be substantially uniform. There is no particular limitation on the maximum diameter of the cross section of the pores, but it is preferably 1 to 100 μm, and 3 to 75 μm.
More preferably, it is m. 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 body structure, it is preferable that the shape of the pores present on the inner surface is circular or elliptical. The maximum diameter of this circular or elliptical shape is preferably 1 to 100 μm, more preferably 5 to 50 μm, and particularly preferably 10 to 30 μm. 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 compliance of the porous structure portion may be close to that of a biological blood vessel or exhibit a value larger than that of a living blood vessel. If the compliance value is larger than that of a living blood vessel, it is possible to adjust the compliance to approximate that of a living blood vessel by combining it with a tubular material made of fibers. The compliance of such a porous structure can be adjusted by adjusting the proportion of pores in the porous structure, the strength of the partition wall forming the pores, the strength of the elastomer used, and the like. The fibers used in the present invention include threads, nets, ropes, woven fabrics,
It is a long, thin object with a flow rate of more than 100 times its diameter, which is used to make knitted fabrics, plaited fabrics, non-woven fabrics, etc. The fibers are particularly limited, regardless of whether they are organic or inorganic, as long as they are safe for living organisms, have negligible deterioration in vivo, can withstand sterilization, and can be processed into desired tubular products. It can be used without any problems. In terms of processability, ease of availability, flexibility, uniformity, etc., recycled artificial fibers, semi-synthetic fibers, and synthetic fibers are preferred. Specific examples of these include cellulose, proteinaceous, polyamide, polyester, polyurethane, polyethylene, polystyrene, polyvinyl chloride, polyvinylidene chloride, polyfluoroethylene, polyacrylic, and polyvinyl alcohol. Examples include fibers such as fibers. Among these, stretchable fibers are more preferable, and specific examples thereof include:
Fibers that have elasticity themselves, such as rubber-based, polyurethane elastic-based, and polyester elastic-based fibers, elastic bulky processed systems such as woolly nylon and wooly tetron, and rubber or spandex filaments. Examples include covered yarn, which is a yarn made by stretching yarn and wrapping it around other spun yarn or filament. The tubular material made of fibers used in the present invention is
Woven fabrics, knitted fabrics, plaited fabrics, non-woven fabrics, and combinations of these fibers, yarns spun with at least one of the above fibers, multifilaments of at least one of the above fibers, yarns that are combinations of these, etc. , or a tubular material made of a sponge-like material such as polyurethane foam. The tubular material may be formed into a tubular structure by itself as a fiber or a material made from fibers, and when combined with a porous structure part made of an elastomer to form an artificial blood vessel, it forms a tubular structure. You can leave it there. From the viewpoint of processability, workability, and obtaining a stress-strain curve similar to that of biological blood vessels, a tubular material made of knitted fibers is preferable, and a tubular material made of stockinette knitted stretchable fibers is more preferable. preferable. The tubular material is not particularly limited as long as it has compliance and stress-strain curves similar to those of living blood vessels when combined with the porous structure made of elastomer. Such properties of the tubular material include, for example, the following two
This can be achieved by using two methods alone or in combination. The first is to adjust the frequency of fiber combinations,
This is a method of loosely adjusting the points to be combined. The second method is to use stretchable fibers. It is sufficient that the tubular object is present at least partially in contact with and/or bonded to the porous structure made of an elastomer. For example, as shown in FIG. 2, the tubular object 2 is made of an elastomer. It may be located outside the porous body structure part 1, with a part of the tubular body exposed on the outer surface of the porous body structure part 1, and as shown in FIG. It may be located in the inner part of the body structure part 1, and a part of the tubular object 2 may be exposed on the inner surface of the porous body structure part 1. Furthermore, as shown in FIG. 1, the tubular material 2 may be completely incorporated into the porous structure portion 1, in which case the fibers constituting the tubular material 2 are prevented from fraying. , or because the antithrombotic properties of the blood contact surface are maintained. Note that contact and/or bonding as used herein means that the porous structure made of elastomer and the tubular part made of fibers are bonded to such an extent that they both experience almost the same strain in response to blood pressure or stress applied from the outside. This means that there is a mechanical interaction of 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 artificial blood vessel of the present invention is designed to have a compliance similar to each biological blood vessel. Can be manufactured. Since the compliance of living blood vessels in which normal revascularization surgery is performed is about 0.1 to 0.8, it is considered preferable to set the compliance within this range. The compliance of the artificial blood vessel of the present invention can be adjusted as described above, and any compliance within the range of 0.1 to 0.8 can be manufactured. Artificial blood vessels with a compliance of 0.1 to 0.8 are suitable for applications such as arterial blood vessels, depending on their thickness, and those with an inner diameter of 1 to 6 mm and a compliance of 0.1 to 0.5 are suitable as artificial blood vessels for small arteries. It can be used for The compliance referred to in this specification is expressed by the formula (1) C=△V/V ₀・△P×100 (1) (where C is compliance and V ₀ is the internal pressure of 50 mm
The internal volume of the measured blood vessel when Hg is measured, △P is the internal pressure 50 mm
100 mmHg from Hg to internal pressure 150 mmHg, ΔV is the internal volume of the measurement blood vessel that increases between internal pressure 50 mmHg and internal pressure 150 mmHg). The actual measurement involves inserting the measurement blood vessel into a closed circuit.
Inject liquid into this circuit using a micrometer metering pump, measure the amount of injected liquid and the change in pressure in the circuit,
Compliance can be calculated from equation (1). The stress-strain curve of the artificial blood vessel of the present invention will be explained based on FIG. In FIG. 4, () indicates a porous structure made of an elastomer, () indicates an artificial blood vessel of the present invention,
() is an example of the stress-strain curve of each of the thoracic aorta, which is a biological blood vessel, and the carotid artery, which is a biological blood vessel. Stress-strain curves of biological blood vessels include arteries, veins,
It is difficult to quantify because it varies depending on the caliber of blood vessels, age, individual differences, etc., but the common thing is that blood pressure is within the normal range, as shown in () and () in Figure 4. It has a stress-strain curve in which the modulus of elasticity is small, but when stress exceeding the normal blood pressure range is applied, the modulus of elasticity suddenly becomes large. As can be seen from FIG. 4, the artificial blood vessel ( ) of the present invention has a stress-strain curve that approximates such a biological blood vessel. In this specification, the stress-strain curve is similar to a biological blood vessel if it is similar to the curves () and () shown in FIG. In other words, stress -
In the strain curve, a point corresponding to a stress of 0.01 Kg/ ^mm2 exists between strain 0.2 and 0.6, and the elastic modulus at that point is 0.1.
Kg/ ^mm2 or less, and a point corresponding to stress 0.05Kg/ ^mm2 exists between strain 0.5 and 1.0 and is greater than strain corresponding to stress 0.01Kg/ ^mm2 , and the elastic modulus at that point is 0.12.
Kg/ ^mm2 or more, the strain at the point corresponding to the stress of 0.12Kg/ ^mm2 exists between 0.55 and 1.2, and the stress is 0.05Kg/mm2.
greater than the strain corresponding to mm ² , and the elastic modulus at that point is
It is 0.2Kg/mm ² or more, and the elastic modulus at a stress of 0.05Kg/mm ² or more. Furthermore, stress
A point corresponding to 0.01Kg/ ^mm2 exists between strain 0.2 and 0.6, and the elastic modulus at that point is 0.07 to 0.007Kg/ ^mm2 ,
The strain at a point corresponding to a stress of 0.05 Kg/ ^mm2 exists between 0.5 and 1.0 and is greater than the strain corresponding to a stress of 0.01 Kg/ ^mm2 , and the elastic modulus at that point is 0.2 to 10 Kg/ ^mm2 . ,
The strain at a point corresponding to a stress of 0.12 Kg/ ^mm2 exists between 0.55 and 1.2, and is greater than the strain corresponding to a stress of 0.05 Kg/ ^mm2 , and the elastic modulus at that point is 0.3 Kg/ ^mm2 or more. ,
The elastic modulus at a stress of 0.05 Kg/mm ² or higher. The stress-strain curve was measured in the axial direction of the artificial blood vessel using a tensile testing machine commonly used in the field of polymer materials (for example, Autograph IS2000 manufactured by Shimadzu Corporation). It is preferable to use an artificial blood vessel as it is as a sample for stress-strain curve measurement. When an artificial blood vessel is cut in the axial direction, for example into a strip, and measured, the strength of the tubular material made of fibers changes 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 a 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 ivy value. Further, the elastic modulus used in the present invention is the slope of a tangent line at an arbitrary position on a stress-strain curve, so-called tangential elastic modulus. The region of small stress in the stress-strain curve approximately coincides with the normal blood pressure range in which compliance is measured, so if the compliance approximates that of a biological blood vessel, this region of the stress-strain curve also approximates that of a biological blood vessel. On the other hand, areas of high stress can be caused by rupture or rupture when abnormally high blood pressure occurs, such as during surgery.
Since its main role is to prevent damage and maintain long-term durability, it may be approximated within a range that satisfies these roles. In the artificial blood vessel of the present invention, the compliance and small stress values measured in the normal blood pressure range are determined mainly by the strength of the porous structure made of elastomer, and the large area where stress exceeding the normal blood pressure range is applied is determined mainly by the strength of the porous structure made of elastomer. The value of stress is determined primarily by the strength of the tubular material made of fibers. By combining the two, it becomes possible to approximate stress-strain curves of biological blood vessels at various locations. Since the artificial blood vessel of the present invention has a stress-strain curve similar to that of a biological blood vessel, it is possible to prevent rupture or damage even if an abnormal increase in blood pressure occurs during surgery. It also has excellent durability over a long period of time after transplantation. Since the artificial blood vessel of the present invention is composed of an elastomer with excellent blood compatibility, its inner side, that is, the blood contact surface, has good blood compatibility, but the antithrombotic property at the initial stage of implantation into a living body can be further improved. For this purpose, the surface may be coated with albumin, gelatin, chondroitin sulfate, heparinized material, etc. As explained above, the artificial blood vessel of the present invention includes a porous structure portion made of an elastomer in which pores are present throughout the thickness from the inside to the outside of the vessel wall;
Since it is manufactured by comprising a tubular part made of fibers that is in contact with and/or bonded to at least a part of the porous structure part, the compliance and stress-strain curves approximate those of biological blood vessels. You can get an artificial blood vessel that is Next, the method for manufacturing the artificial blood vessel of the present invention will be explained. The artificial blood vessel of the present invention is manufactured by coating a mandrel with a pore-forming agent and/or an elastomer solution having a cloud point, and then repeating the operation of immersing the mandrel in a coagulation solution once or twice or more. In some cases, it can be produced by having a tube made of fibers present on the mandrel at any stage of the operation. 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. 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 structural 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 contains an elastomer, a good solvent, and a poor solvent in an amount 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. If this solution is handled below the cloud point temperature, it is difficult to achieve a uniform coating and the porous structure tends to be difficult to form. After the change has occurred, it is preferable to immerse the mandrel in a coagulating liquid at a temperature below the cloud point. 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 elastomer concentration in the elastomer solution can be adjusted in the same way as the solvent in this solution.After the elastomer is precipitated, the porous structural part of the present invention can be obtained by dissolving and removing the pore-forming agent. Although it cannot be absolutely limited as it varies depending on the type of elastomer and the composition of the solution, it is usually preferably 5 to 35% (wt%, the same applies hereinafter), and more preferably 10 to 30%. It is preferably 12.5% to 25%, particularly preferably 12.5% to 25%. If the elasmer concentration is lower than 5%, uniform molding tends to be difficult. Also, the elastomer concentration is 35%
If it exceeds , the viscosity of the solution is so high that 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. When considering use in artificial blood vessels to be implanted in a living body, it is preferable to use a pore-forming agent that is safe for the living body. Therefore, as pore-forming agents, inorganic salts such as common salt and calcium carbonate,
Water-soluble sugars such as glycose and starch, or proteins are preferred. However, inorganic salts such as table salt and soluble sugars are inherently hygroscopic, so if they are made into fine particles, their surface area increases and they tend to cause secondary aggregation due to moisture in the air, making them difficult to handle. You need to be very careful. On the other hand, even if the particles are made of protein, they can be uniformly and stably dispersed without causing secondary aggregation due to moisture in the air. Therefore, proteins are particularly preferred as pore-forming agents. Furthermore, when a protein is used, the pore-forming agent can be easily dissolved and removed from the molded artificial blood vessel using an alkaline solution, an acid solution, a solution containing an enzyme, or the like. Specific examples of such preferred proteins include casein, collagen, gelatin, and albumin, and among these, casein is particularly preferred. The particle size of the pore-forming agent is preferably 74 μm or less,
It is more preferably 50 μm or less, and particularly preferably 30 μm 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 μm, the pores of the porous structure tend to become too large. The amount of the pore-forming agent used in the present invention 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), so it cannot be determined in general. not possible, but preferably
It is 20 to 500% (volume % of pore-forming agent/elastomer, hereinafter the same), more preferably 50 to 350%, particularly preferably 100 to 300%. The amount of pore forming agent is 500%
If it exceeds this, 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 pore-forming agent is less than 20%, porosity tends to become poor. 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, N,N-dimethylacetamide, N,N
-formamide, N-methyl-2-pyrrolidone,
Examples include solvents such as 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-butadienol, 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
-Butanediol, glycerin, etc.
These may be used alone or in combination of two or more. Among these, the preferred ones are:
Examples include ethylene glycol, propylene glycol, or poor solvents containing these as main components, and more preferred is a mixed solvent in which 1 to 50 volume % of a good solvent is added to 99 to 50 volume % of the poor solvent. 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. It goes without saying that by using a mold of any shape in place of the mandrel, various medical molded articles other than tubular molded articles can be manufactured by the method of the present invention. For example, if a flat plate is used as a mold, a film-like molded product can be obtained, which can be used for artificial skin, etc. Methods for placing a tubular object made of fibers on a mandrel include a method of covering the mandrel with a tubular material made of fibers, or a method of wrapping fibers or a band-like object made of fibers on the mandrel to form a tubular structure. method is the most representative. 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. It has porosity that helps organize the artificial blood vessel. Compliance approximates that of biological blood vessels. The stress-strain curve approximates that of a biological blood vessel. Furthermore, since the tube wall of the artificial blood vessel of the present invention is a structure in which at least a portion of a tubular material made of fibers is in contact with and/or bonded to a substantially continuous porous structure of an elastomer, It also has useful properties such as: The suture needle has good penetrability and suturing is easy. The suture needle's through hole self-closes. Nodules are unlikely to form under actual conditions of use where blood pressure is high. The artificial blood vessel of the present invention having such properties is
It has excellent patency when transplanted into a living body, and problems such as hyperplasia of pinneuf at the anastomotic site rarely occur. In addition, there is little fear of rupture or damage in the event of abnormally high blood pressure during surgery, etc., and it has excellent long-term durability. Furthermore, it has excellent 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, veins, etc., and can also be used for blood access, etc. . In particular, it is preferable to use it as an arterial artificial blood vessel having a compliance of 0.1 to 0.8.
In particular, the compliance and stress-strain curves are similar to those of biological blood vessels, so it has a compliance of 0.1 to 0.5, which is currently not available in clinically used artificial blood vessels, and can also be used as a small-caliber artificial blood vessel with an inner diameter of about 1 to 6 mm. Can be used. 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 artificial blood vessel of the present invention and its manufacturing method will be explained based on Examples. 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 poldimethylsiloxane at both ends (polyethylene glycol at both ends) were synthesized. A segmented polyurethane containing polydimethylsiloxane in the main chain was synthesized by carrying out chain extension using 13.2 parts of polydimethylsiloxane with an average molecular weight of 681 and an average molecular weight of 1040. 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. In a mixed solvent of 50 ml of dioxane and 30 ml of N,N-dimethylacetamide, 22.5 g of casein having a particle size of 30 μm or less was stirred and dispersed using a homogenizer, and then 15 g of the polyurethane was added and dissolved with stirring. A glass rod with a diameter of 3 mm was immersed in this dispersion solution and then taken out, and the glass rod was uniformly coated with the dispersion solution. This mandrel was immersed in ethylene glycol to precipitate the elastomer. Next, a glass rod with the elastomer precipitated on the surface is made into a tube with a diameter of about 3 mm, which is knitted by a ribbon knitting machine with a 12-needle head using covered yarn made of 20-denier spandex wrapped with 70-denier nylon fiber. I covered it. The glass rod was immersed in the dispersion solution and then taken out, the surface of the glass rod was coated with the dispersion solution, and then immersed in the coagulation solution. After the elastomer was sufficiently deposited, the mandrel was taken out and the coagulated liquid on the surface was removed.
Further, the dispersion solution was applied onto the mandrel in the same manner as described above, and then the elastomer was precipitated in the coagulation solution. Thereafter, the glass rod was thoroughly washed with water, and the glass rod was removed to obtain a composite tube product. This composite tubular object has a PH
The artificial blood vessel according to the present invention was obtained by immersing it in a 13.5 aqueous sodium hydroxide solution to extract and remove casein, and finally washing thoroughly with water. The resulting artificial blood vessel has an inner diameter of approximately 3 mm and an outer diameter of approximately 4.5 mm.
It was hot. When this artificial blood vessel was observed using a scanning electron microscope, it was found that circular to elliptical pores of about 20 to 30 μm were present on the inner surface, and about 1 to 10 μm on the outer surface.
m round to irregularly shaped pores were present. The cross-section of the tube wall contained a tubular material made of fibers in the center, and the remaining elastomer part had a network structure of connected elastomers that formed the partition walls of the pores. Next, when water was passed through this artificial blood vessel at a water pressure of 120 mmHg, approximately 50 ml of water per minute per 1 cm ² of the inner surface of the artificial blood vessel penetrated to the outer surface of the artificial blood vessel.
It was found that it has porosity. Next, this artificial blood vessel was pre-clotted with bovine blood, cut into 8 cm lengths, inserted into a closed circuit, and bovine ACD blood was pumped into the closed circuit using a metering pump that pumped 0.05 ml per stroke. The changes in internal pressure were measured. Compliance was measured from equation (1) based on the stroke number of the metering pump and changes in internal pressure, and was found to be 0.30. When the stress-strain curve of this artificial blood vessel was measured using a Shimadzu Autograph IS2000, the graph shown in parentheses in FIG. 4, which approximates that of a biological blood vessel, was obtained. Next, when this artificial blood vessel was transplanted to a length of about 7 cm into the femoral artery of an adult mongrel dog, it showed patency for more than 2 months. In addition, even if this artificial blood vessel is cut at any point, the cut part will not fray, and it has excellent suturing properties.
The suture needle penetration hole self-occluded when the needle was removed. In addition, the artificial blood vessel tends not to form knots when the internal pressure is 50 to 150 mmHg. 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 22.5 g of casein with a particle size of 30 μm or less was mixed with 45 ml of propylene glycol, 57.8 ml of dioxane, and N,N-
The mixture was stirred and dispersed in a mixed solvent of 24.8 ml of dimethylacetamide using a homogenizer. This dispersion was added to 22.5 g of the polyurethane used in Example 1, and the polyurethane was dissolved at 80°C. The cloud point of the resulting solution was approximately 45°C. A glass rod with a diameter of 3 mm was immersed in this solution kept at 80°C and then taken out, and the solution was uniformly coated onto the glass rod. Next, immerse this glass rod in 18℃ water,
The elastomer was deposited. Next, a tube with a diameter of about 3 mm was knitted into a very loose structure using a ribbon knitting machine with a 12-needle head using a yarn made of about 48 2-denier Woolly Tetron yarns, and the elastomer was deposited on the surface. I covered it with a glass rod. The glass rod was immersed in the dispersion solution and then taken out, the surface of the glass rod was coated with the dispersion solution, and then immersed in the coagulation solution. Thereafter, the glass rod was thoroughly washed with water and the glass rod was removed to obtain a composite tubular article. This composite tubular material is immersed in an aqueous sodium hydroxide solution with a pH of 13.5 to dissolve and remove the casein.
Finally, it was thoroughly washed with water to obtain the artificial blood vessel of the present invention. The resulting artificial blood vessel has an inner diameter of approximately 3 mm and an outer diameter of approximately 4.5 mm.
It was warm in mm. When the inner surface, outer surface, and cross section of the tube wall of this artificial blood vessel were observed using a scanning electron microscope, it was found that oval pores of about 15 to 20 μm were present on the inner surface, and irregularly shaped pores of about 5 μm were present on the outer surface. . In the pipe wall cross section,
There was a tube made of fibers in the center, and the remaining elastomer part had a uniform network structure. When the water permeation amount, compliance and stress-strain curve were measured in the same manner as in Example 1, the water permeation amount was about 110 ml and the compliance was 0.25.
In the stress-strain curve of this artificial blood vessel, the strain corresponding to a stress of 0.01Kg/ ^mm2 is 0.35, and the elastic modulus at that point is 0.06.
Kg/mm ² , and the strain corresponding to stress 0.05Kg/mm ² is
0.65, and the elastic modulus at that point is 0.3Kg/ ^mm2 ,
The strain corresponding to the stress of 0.12 Kg/mm ² was 0.75, and the elastic modulus at that point was 1.0 Kg/mm ² . Example 3 15 g of the polyurethane described in Example 1 was mixed with 55 ml of N,N-dimethylacedeamide and propylene glycol.
It was stirred and dissolved in a mixed solvent of 30 ml at 70°C. The cloud point of this solution was approximately 40°C. A glass rod covered with a tubular material having a diameter of about 3 mm woven by the method of Example 1 using covered yarn made of 20 denier spandex and 30 denier Dacron fibers was immersed in the solution kept at 70°C. The glass rod was taken out and the solution was evenly coated on the glass rod. After the coating layer was left in the air until it became cloudy, the glass rod was immersed in water at 15°C, and the mixed solvent was sufficiently replaced with water. Thereafter, this operation was repeated once more, and after thorough washing with water, the glass rod was removed and an artificial blood vessel was obtained. The resulting artificial blood vessel has an inner diameter of approximately 3 mm and an outer diameter of approximately 4.5 mm.
It was hot. When the inner surface, outer surface, and cross section of the tube wall of this artificial blood vessel were observed using a scanning electron microscope, oval pores with a maximum size of about 10 μm were almost uniformly present on the inner surface.
Tubular fibers were observed in some parts. There were pores with a smaller maximum diameter on the outer surface than on the inner surface. In the cross section of the tube wall, there existed a tubular part made of fibers and a porous structure part in which partition walls forming pores were continuously connected. When the water permeation amount, compliance and stress-strain curve were measured in the same manner as in Example 1, the water permeation amount was about 20 ml and the compliance was 0.35. In the stress-strain curve of this artificial blood vessel, the strain corresponding to a stress of 0.01Kg/ ^mm2 is 0.45, and the elastic modulus at that point is 0.045.
It was Kg/ ^mm2 . Also, the strain corresponding to a stress of 0.05Kg/mm ² is 0.8, the elastic modulus at that point is 0.21Kg/mm ² , and the strain corresponding to a stress of 0.12Kg/mm ² is 1.0.
The elastic modulus at that point was 0.5 Kg/mm ² .

[Brief explanation of the drawing]

Figures 1 to 3 are explanatory diagrams of different embodiments of the artificial blood vessel of the present invention for explaining the position of the tubular material made of fibers on the wall of the artificial blood vessel, and Figure 4 is a porous body structure. A graph showing the stress-strain curves of the artificial blood vessel obtained in Example 1 (graph ()), the thoracic aorta (graph ()), and the carotid artery (graph ()). be. (Symbols in drawings), 1: Porous structure portion, 2: Tubular object.

Claims (1)

[Claims] 1. A porous body structure made of an elastomer and having continuously connected partition walls, and fibers existing in contact with and/or bonded to at least a portion of the porous body structure. A perforated artificial blood vessel consisting of a tubular part,
Compliance is 0.1 to 0.8 and stress -
In the strain curve, a point corresponding to a stress of 0.01 Kg/ ^mm2 exists between strain 0.2 and 0.6, and the elastic modulus at that point is 0.1.
Kg/mm ² or less, a point corresponding to stress 0.05Kg/mm ² exists between strain 0.5 and 1.0, and stress 0.01Kg/mm ²
is greater than the strain corresponding to , and the elastic modulus at that point is 0.12
Kg/ ^mm2 or more, the strain at the point corresponding to the stress of 0.12Kg/ ^mm2 exists between 0.55 and 1.2, and the stress is 0.05Kg/mm2.
greater than the strain corresponding to mm ² , and the elastic modulus at that point is
An artificial blood vessel having an elastic modulus of 0.2 Kg/mm ² or more and a stress of 0.05 Kg/mm ² or more. 2 After coating the mandrel with a pore-forming agent and/or an elastomer solution having a cloud point, the mandrel is immersed in a coagulation solution once or twice or more to produce an artificial blood vessel (artificial blood vessel is manufactured using a wet method). A porous body structure part made of an elastomer and having continuously connected partition walls, characterized in that a tubular body made of fibers is placed on the mandrel in any of the above steps when manufacturing a blood vessel. and a tubular part made of fibers existing in contact with and/or bonded to at least a part of the porous structure part, the artificial blood vessel having porosity and having a compliance of 0.1 to 0.8. , and in the stress-strain curve, the stress is 0.01Kg/mm ²
A point corresponding to the strain exists between 0.2 and 0.6, the elastic modulus at that point is 0.1Kg/mm2 or less, and the stress is 0.05Kg/ ^mm2 .
The point corresponding to mm ² exists between strain 0.5 and 1.0 and is greater than the strain corresponding to stress 0.01Kg/mm ² , the elastic modulus at that point is 0.12Kg/mm ² or more, and stress 0.12Kg/mm 2 .
The strain at the point corresponding to mm ² exists between 0.55 and 1.2,
A method for manufacturing an artificial blood vessel, which is greater than the strain corresponding to a stress of 0.05 Kg/mm ² and has an elastic modulus at that point of 0.2 Kg/mm ² or more, and which is greater than or equal to the elastic modulus at a stress of 0.05 Kg/mm ² .