Artificial blood vessel and artificial blood vessel manufacturing method

Abstract

To provide a flexible artificial blood vessel and an artificial blood vessel manufacturing method.SOLUTION: An artificial blood vessel VE is composed of stretched polytetrafluoroethylene having nodes and fibrils formed between the nodes. In an axial direction D1 of the artificial blood vessel VE, high-density areas R1 in which the nodes and the fibrils are compressed and dense in the axial direction D1 and low-density areas R2 in which the nodes and the fibrils are in a lower-density state compared with the high-density areas R1 are provided alternately.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to an artificial blood vessel and a method for producing the artificial blood vessel. [Background technology]

[0002] Artificial blood vessels made of expanded polytetrafluoroethylene (hereinafter referred to as ePTFE) are used as a material for artificial blood vessels. Artificial blood vessels made of ePTFE are made by forming polytetrafluoroethylene (PTFE) into a cylindrical shape and rapidly stretching it, resulting in a structure with nodes and fibrils formed between the nodes, as shown in Patent Document 1. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2005-530549 Summary of the Invention [Problem to be solved by the invention]

[0004] Although artificial blood vessels made of ePTFE are biocompatible and flexible, there is a demand for artificial blood vessels made of ePTFE that are even more flexible.

[0005] Therefore, an object of the present invention is to provide a highly flexible artificial blood vessel and a method for producing the artificial blood vessel. [Means for solving the problem]

[0006] The artificial blood vessel of the present invention is an artificial blood vessel made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes, and is provided with alternating high-density regions in the axial direction of the artificial blood vessel, in which the nodes and fibrils are axially compressed and densely packed, and low-density regions in which the nodes and fibrils are in a lower density state than the high-density regions.

[0007] The method for producing an artificial blood vessel of the present invention comprises the steps of: a) providing a tubular artificial blood vessel substrate made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes; b) compressing the artificial blood vessel substrate in the axial direction of the artificial blood vessel substrate with a core material inserted inside the artificial blood vessel substrate; c) releasing the compressive force on the artificial blood vessel substrate and stretching the artificial blood vessel substrate; d) re-compressing the stretched artificial blood vessel substrate one or more times; and e) re-stretching the artificial blood vessel substrate compressed in step d). [Effects of the Invention]

[0008] According to the artificial blood vessel and the method for producing the artificial blood vessel of the present invention, it is possible to provide an artificial blood vessel with high flexibility. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a schematic diagram of an artificial blood vessel according to one embodiment of the present invention. [Figure 2] FIG. 2 is an enlarged schematic view of an area A1 in FIG. [Figure 3] This is a 25x SEM photograph of the surface of a sample piece cut from a part of an artificial blood vessel, taken in the thickness direction. [Figure 4] This is a 100x SEM photograph of the position of region A2 in FIG. 3. [Figure 5] 1A and 1B are diagrams showing an artificial blood vessel substrate preparation step in a method for producing an artificial blood vessel. [Figure 6] FIG. 2 is a diagram showing a first firing step in the method for producing an artificial blood vessel. [Figure 7] 10A and 10B are diagrams showing a marker application step in a method for manufacturing an artificial blood vessel. [Figure 8] FIG. 2 is a diagram showing a first compression step in a method for producing an artificial blood vessel. [Figure 9] 10A and 10B are diagrams showing a band-shaped portion forming step in a method for manufacturing an artificial blood vessel. [Figure 10] FIG. 2 is a diagram showing a first elongation step in a method for producing an artificial blood vessel. [Figure 11] 10A and 10B are diagrams showing an additional compression step in the manufacturing method of an artificial blood vessel. [Figure 12] 10A and 10B are diagrams showing an additional elongation step in the method for manufacturing an artificial blood vessel. [Figure 13] This is a 33x SEM photograph of a sample piece cut from an artificial blood vessel taken obliquely. [Figure 14] This is an SEM photograph at 130x magnification, showing the cross section of a sample piece obtained by cutting a part of an artificial blood vessel, taken in the axial direction of the sample piece. [Figure 15] 1 is a photograph showing a band of an artificial blood vessel. [Figure 16] FIG. 1 is a schematic diagram showing a method for evaluating the flexibility of an artificial blood vessel. [Figure 17] This is a microscope image of a sample piece cut from a part of an artificial blood vessel, photographed in the thickness direction using a microscope. DETAILED DESCRIPTION OF THE INVENTION

[0010] An artificial blood vessel and a method for manufacturing an artificial blood vessel according to one embodiment of the present invention will be described below with reference to the drawings. Note that the embodiment shown below is merely an example, and the artificial blood vessel and the method for manufacturing an artificial blood vessel of the present invention are not limited to the following embodiment.

[0011] In this specification, the expressions "perpendicular to A" and similar expressions do not refer only to a direction that is completely perpendicular to A, but also refer to a direction that is approximately perpendicular to A. In this specification, the expressions "parallel to B" and similar expressions do not refer only to a direction that is completely parallel to B, but also refer to a direction that is approximately parallel to B. In this specification, the expressions "C-shape" and similar expressions do not refer only to a perfect C-shape, but also refer to a shape that visually resembles a C-shape (approximately a C-shape).

[0012] The artificial blood vessel VE (see FIG. 1) of one embodiment of the present invention is used, for example, to replace a diseased biological blood vessel and to bypass the biological blood vessel. The artificial blood vessel VE is composed of a tubular body having a predetermined length.

[0013] The diameter of the artificial blood vessel VE can be varied depending on the site of use and is not particularly limited. For example, the artificial blood vessel VE may be a large-diameter artificial blood vessel with an inner diameter of 10 mm or more (for the thoracic and abdominal aorta), a medium-diameter artificial blood vessel with an inner diameter of 6 mm or more but less than 10 mm, such as 6 mm or 8 mm (for arteries in the lower limbs, neck, and axillary regions), or a small-diameter artificial blood vessel with an inner diameter of less than 6 mm, such as 4 mm or 5 mm. The thickness of the artificial blood vessel VE can be varied appropriately depending on the inner diameter and length of the artificial blood vessel used and is not particularly limited. For example, the thickness of the artificial blood vessel VE can be 0.1 to 2 mm. For example, when the inner diameter of the artificial blood vessel VE is 5 to 6 mm, the wall thickness can be 0.3 to 0.7 mm, preferably 0.4 to 0.6 mm.

[0014] The length of the artificial blood vessel VE in the axial direction D1 is not particularly limited and can be changed depending on the site where it is used, etc. For example, the length of the artificial blood vessel VE in the axial direction D1 can be 50 to 1000 mm.

[0015] The artificial blood vessel VE of this embodiment is made of expanded polytetrafluoroethylene (ePTFE). Specifically, as shown in FIG. 4, the artificial blood vessel VE is made of expanded polytetrafluoroethylene having nodes 1 and fibrils 2 formed between the nodes 1. FIG. 3 is a 25x SEM photograph taken in the thickness direction from the outer peripheral surface of the artificial blood vessel VE, which was obtained by cutting a tubular artificial blood vessel VE manufactured by the manufacturing method described below with a cutter knife to obtain a sample piece, flattening the sample piece, and then vapor-depositing Au. FIG. 4 is an enlarged photograph of region A2 in FIG. 3.

[0016] As described in, for example, Japanese Patent Publication No. 13560 / 1967, artificial blood vessels made of expanded polytetrafluoroethylene are first prepared by mixing a lubricant with unsintered PTFE powder to prepare a mixture. This mixture is then extruded into a tube using a ram extrusion molding machine, and the tube is then stretched axially at a desired stretch ratio. The resulting tube is heated to or above the sintering temperature while being held in place to prevent shrinkage, sintering and fixing the stretched structure. This results in a cylindrical expanded polytetrafluoroethylene artificial blood vessel substrate, which is then subjected to the prescribed processing described below to obtain an artificial blood vessel VE. Note that the method for producing an expanded polytetrafluoroethylene artificial blood vessel (artificial blood vessel substrate) is not limited to the above method, as long as it can produce a structure with nodes and fibrils.

[0017] The porosity and fibril length of the artificial blood vessel substrate can be set as desired by adjusting the stretching ratio and stretching strain rate. The tube that forms the base material for the artificial blood vessel substrate is stretched uniaxially. The stretching ratio is not particularly limited, but is selected, for example, from within the range of 1.2 to 15 times, preferably 2 to 10 times, and more preferably 2 to 5 times. The sintering temperature for sintering the artificial blood vessel substrate is not particularly limited, but can be, for example, 350 to 800°C.

[0018] The artificial blood vessel base material is produced in the extrusion molding process at an extrusion molding speed calculated by the product of the extrusion reduction ratio (hereinafter sometimes referred to as "extrusion RR") and the ram speed (mm / min), which is used in the production of known artificial blood vessel base materials.

[0019] To improve high-speed extrusion moldability, it is considered preferable to mix a relatively high proportion of liquid lubricant with respect to the unsintered PTFE powder. However, mixing an excessive amount of liquid lubricant can result in a decrease in the strength of the artificial blood vessel substrate. Therefore, the proportion of liquid lubricant is preferably 30 parts by mass or less, more preferably 26 parts by mass or less, per 100 parts by mass of unsintered PTFE powder. The lower limit of the proportion of liquid lubricant is preferably 15 parts by mass, more preferably 18 parts by mass, and particularly preferably 20 parts by mass, per 100 parts by mass of unsintered PTFE powder. The amount of liquid lubricant mixed per 1 kg of unsintered PTFE powder is preferably 380 ml or less, more preferably 330 ml or less.

[0020] The nodes 1 are connected three-dimensionally in the artificial blood vessel VE (see FIGS. 3, 4, 13, and 14). Specifically, the nodes 1 are connected in the axial direction D1, the circumferential direction D2, and the radial direction D3 (see FIG. 1) of the artificial blood vessel VE. As shown in FIG. 4, the fibrils 2 extend in the axial direction D1 to connect between parts of the nodes 1 that are spaced apart in the axial direction D1.

[0021] In this embodiment, as shown in Figures 2 and 3, high-density regions R1 in which nodes 1 and fibrils 2 are compressed and densely packed in the axial direction D1 of the artificial blood vessel VE are alternately arranged, and low-density regions R2 in which nodes 1 and fibrils 2 are in a lower density state compared to the high-density regions R1.

[0022] The high-density region R1 is a region where the nodes 1 and fibrils 2 (particularly node 1) are densely packed together in a compressed state in the axial direction D1 of the artificial blood vessel VE. As shown in FIGS. 2 and 3, the high-density region R1 is annularly arranged in the circumferential direction D2 of the artificial blood vessel VE. The structure and method of forming the high-density region R1 are not particularly limited, as long as the high-density region R1 is configured such that the nodes 1 and fibrils 2 are densely packed together in a compressed state compared to other regions (low-density regions R2). In this embodiment, the high-density region R1 is configured by a compression stripe portion (a bent portion centered on the bottom of a valley of the artificial blood vessel base material VEB that has been compressed into a bellows-like shape by compressing the tubular artificial blood vessel base material VEB in the axial direction D1) that is generated when the tubular artificial blood vessel base material VEB is compressed in the axial direction D1 (see FIG. 8). In this embodiment, the high-density region R1, which is provided as a compressed stripe, is compressed in the axial direction D1 when a core material C (see FIG. 8, etc.) is inserted into the artificial blood vessel substrate VEB, as described below. In this case, some portions of the artificial blood vessel substrate VEB are displaced outward in the radial direction D3, while others are displaced inward in the radial direction D3. The portions displaced inward in the radial direction D3 tend to come into contact with the core material C and become highly dense. The widths of the high-density region R1 and the low-density region R2 in the axial direction D1 and their relative width ratios can be appropriately changed depending on the method of compressing the artificial blood vessel substrate and the artificial blood vessel substrate used, and are not particularly limited. The boundary between the high-density region R1 and the low-density region R2 is not clearly defined as shown in FIG. 3. However, when the surface of the artificial blood vessel VE is enlarged, such as in an SEM photograph, it is sufficient to confirm that the high-density region R1 (visually dark-colored region), which indicates a high density, and the low-density region R2 (visually light-colored region), which indicates a lower density relative to the high-density region R1, alternate. Alternatively, the boundary between the high-density region R1 and the low-density region R2 may be determined using brightness contrast or the like in an image of the high-density region R1 and the low-density region R2. Note that the density of nodes 1 and fibrils 2 in the high-density region R1 is not limited to a specific value as long as it is relatively high compared to the density of nodes 1 and fibrils 2 in the low-density region R2.

[0023] The low-density region R2 is a region where the density of nodes 1 and fibrils 2 (particularly node 1) is relatively lower than that of the high-density region R1. The low-density region R2 is a non-compressed region sandwiched in the axial direction D1 between the high-density regions R1, where the nodes 1 and fibrils 2 are densely packed when compressed in the axial direction D1 of the artificial blood vessel VE. As shown in Figures 2 and 3, the low-density region R2 is provided annularly in the circumferential direction D2 of the artificial blood vessel VE. The structure and method of forming the low-density region R2 are not particularly limited as long as the low-density region R2 is configured so that the density of nodes 1 and fibrils 2 is lower than that of other regions (high-density region R1). In this embodiment, the low-density region R2 is provided in the axial direction D1 between the compression stripes (high-density region R1) that are generated when the artificial blood vessel base material VEB is compressed in the axial direction D1 (see Figure 8). The density of the nodes 1 and fibrils 2 in the low-density region R2 is not limited to a specific value as long as it is relatively low compared to the density of the nodes 1 and fibrils 2 in the high-density region R1.

[0024] 2 and 3, the artificial blood vessel VE of this embodiment has high-density regions R1 and low-density regions R2 alternately arranged in the axial direction D1. This improves the flexibility of the artificial blood vessel VE. Specifically, the high-density regions R1, in which the density of nodes 1 and fibrils 2 is high (particularly, the density of relatively hard nodes 1 is high), and the low-density regions R2, in which the density of nodes 1 and fibrils 2 is low (particularly, the density of relatively hard nodes 1 is low), are alternately formed in the axial direction D1 of the artificial blood vessel VE, causing the artificial blood vessel VE to function like a bellows, improving the flexibility of the artificial blood vessel VE.

[0025] In this embodiment, as shown in Figures 1 and 15, the artificial blood vessel VE further includes a band-like portion B that extends continuously in a band-like manner along the axial direction D1 of the artificial blood vessel VE so as to provide resistance to the artificial blood vessel VE (artificial blood vessel base material VEB) from being extended beyond a predetermined length in the axial direction D1 after the artificial blood vessel VE (artificial blood vessel base material VEB) is compressed in the axial direction D1.

[0026] As will be described in detail later, the band-shaped portion B is a portion that resists elongation of the artificial blood vessel base material VEB, preventing the artificial blood vessel base material VEB from stretching beyond a predetermined length when the artificial blood vessel base material VEB is compressed in the axial direction D1 and then expanded after the compressive force is removed. Here, the "predetermined length" refers to a length shorter than the length of the artificial blood vessel base material VEB in its natural state before compression. Specifically, the "predetermined length" refers to a length shorter than the length of the artificial blood vessel base material VEB when it is expanded after a sufficient amount of time has passed since an artificial blood vessel base material VEB with a similar structure but without the band-shaped portion B is compressed and the compressive force is removed. More specifically, the "predetermined length" is preferably 60 to 80%, and more preferably 65 to 75%, of the length of the artificial blood vessel base material VEB in its natural state before compression.

[0027] The structure and method of forming the band-shaped portions B are not particularly limited as long as they are configured to resist elongation of the compressed artificial blood vessel VE (artificial blood vessel substrate VEB). For example, the band-shaped portions B are made harder than the remaining areas where the band-shaped portions B are not formed (areas where high-density regions R1 and low-density regions R2 are alternately formed). This allows the remaining areas, which are softer and relatively more stretchable than the band-shaped portions B, to resist elongation in the axial direction D1. The band-shaped portions B may be formed, for example, by hardening the artificial blood vessel substrate VEB at predetermined positions by localized heat treatment or the like (e.g., laser baking, heating with a heater, etc.). Alternatively, tape may be applied to the artificial blood vessel substrate VEB in a predetermined pattern, or pressure may be applied locally in a predetermined pattern.

[0028] The band-shaped portion B extends continuously in a band-like shape along the axial direction D1 of the artificial blood vessel VE. Here, "extending continuously along the axial direction D1" means that the band-shaped portion B is connected from one side to the other in the axial direction D1 so as to provide resistance to the artificial blood vessel base material VEB from extending beyond a predetermined length. In this embodiment, the band-shaped portion B extends continuously in the axial direction D1 while being inclined with respect to the axial direction D1, but a portion of the band-shaped portion B may have a portion parallel to the axial direction D1.

[0029] As described above, the shape of the band-shaped portion B is not particularly limited as long as it extends continuously along the axial direction D1 so as to provide resistance to the elongation of the compressed artificial blood vessel VE (artificial blood vessel base material VEB). In this embodiment, as shown in Figures 1 and 2, the band-shaped portion B is provided so that a region in which high-density regions R1 and low-density regions R2 are alternately formed is disposed between a portion P1 (see Figure 1) of the band-shaped portion B at one point in the axial direction D1 of the artificial blood vessel VE and another portion P2 (see Figure 1) spaced apart from the portion P1 in the axial direction D1.

[0030] In this embodiment, as shown in FIG. 1, the band-shaped portion B extends in a spiral shape around the axis of the artificial blood vessel VE. In this case, the resistance of the artificial blood vessel VE to outward forces in the radial direction D3 is increased. Furthermore, because the band-shaped portion B extends in a spiral shape, the band-shaped portion B functions like a coil spring, improving the shape retention of the artificial blood vessel VE and making it easier to prevent the artificial blood vessel VE from stretching beyond a predetermined length. In addition to the spiral shape described above, the band-shaped portion may also have, for example, multiple ring-shaped portions spaced apart in the axial direction D1 and an axial portion connecting the ring-shaped portions to each other in the axial direction D1.

[0031] In this embodiment, the band-shaped portion B described above prevents the alternating high-density and low-density regions R1 and R2 adjacent to the band-shaped portion B from elongating. This prevents the bellows-like portion formed by the alternating high-density and low-density regions R1 and R2 in the axial direction D1 from overstretching, thereby reducing flexibility. Furthermore, in an unloaded state where no force is applied to the artificial blood vessel VE (in other words, a state of free length with no residual stress), the band-shaped portion B resists elongation of the high-density and low-density regions R1 and R2, restricting the elongation of the artificial blood vessel VE. However, the resistance of the band-shaped portion B is designed to allow the high-density and low-density regions R1 and R2 to elongate when an external force is applied to the artificial blood vessel VE. Therefore, the high-density and low-density regions R1 and R2 are prevented from overstretching in the axial direction D1 by the band-shaped portion B, allowing them to easily expand and contract in the axial direction D1. As shown by the two-dot chain line in Figure 1, when a bending force is applied to the artificial blood vessel VE, the high-density region R1 and the low-density region R2 easily contract at the inner portion P3 of the curved portion of the artificial blood vessel VE, and the high-density region R1 and the low-density region R2 easily expand at the outer portion P4 of the curved portion of the artificial blood vessel VE. Therefore, the artificial blood vessel VE bends easily. Therefore, the high-density region R1 and the low-density region R2 are prevented from fully expanding in the axial direction D1 by the band-shaped portion B, and are maintained in a state where they can easily expand and contract in the axial direction D1. This makes it possible to suppress changes in the length of the artificial blood vessel VE over time (i.e., the length of the artificial blood vessel VE shrinking or expanding relative to its designed length when the artificial blood vessel VE is left for a predetermined period of time).

[0032] The angle θ (see FIG. 1 ) of the spiral band-shaped portion B relative to the axis X of the artificial blood vessel VE is not particularly limited, but is preferably greater than 45°, more preferably 50 to 80°, and even more preferably 60 to 70° in the completed state of the artificial blood vessel VE. When the angle θ of the spiral band-shaped portion B relative to the axis X is within the above range, the artificial blood vessel VE can be easily compressed and expanded, thereby improving its flexibility. As will be described later, the band-shaped portion B can be formed by heat-treating the artificial blood vessel base material VEB in a compressed state. The angle θ is the angle when the artificial blood vessel base material VEB is in a released state. When the band-shaped portion B is formed during compression of the artificial blood vessel base material VEB, the angle of the heat treatment used to form the band-shaped portion B can be determined taking into account the compression rate of the artificial blood vessel base material VEB and the elongation rate of the artificial blood vessel base material VEB when it expands from the compressed state.

[0033] The width of the band-shaped portions B (the length in the axial direction D1) is not particularly limited as long as the band-shaped portions B are configured to resist the elongation of the compressed artificial blood vessel VE (artificial blood vessel substrate VEB). The width of the band-shaped portions B can be changed appropriately depending on the performance, such as flexibility, required of the artificial blood vessel VE. The width of the band-shaped portions B is not limited, but can be, for example, 1 / 6 to 1 / 4 of the width of the portion of the artificial blood vessel VE other than the band-shaped portions B (the portion where the high-density regions R1 and the low-density regions R2 are alternately arranged) (the width of the portion sandwiched between the band-shaped portions B in the axial direction D1 is 4 to 6 times the width of the band-shaped portions B).

[0034] Next, an example of a method for manufacturing an artificial blood vessel VE will be described with reference to the schematic diagrams of Figures 5 to 12. Note that the manufacturing method described below is merely an example, and the artificial blood vessel VE of the present invention is not limited to the manufacturing method described below, and may be manufactured by other manufacturing methods as long as it has the characteristics described in the claims.

[0035] First, as shown in Figure 5, a cylindrical artificial blood vessel base material VEB is prepared, which is made of expanded polytetrafluoroethylene having nodes 1 and fibrils 2 formed between the nodes 1 (artificial blood vessel base material preparation step). This artificial blood vessel base material VEB is an ePTFE tube stretched at a predetermined stretch ratio. The artificial blood vessel base material VEB can be obtained, for example, by mixing unsintered PTFE powder with a lubricant to prepare a mixture, extruding the mixture into a tube using a ram extrusion molding machine, and then stretching the tube in the axial direction D1 at the desired stretch ratio.

[0036] Next, the entire surface of the artificial blood vessel substrate VEB is baked (first baking step; see Figure 6). Specifically, the entire surface of the artificial blood vessel substrate VEB is heated and baked. This baking roughens the entire surface of the artificial blood vessel substrate VEB. This makes it easier for the marker M, described below, to be attached to the surface of the artificial blood vessel substrate VEB when it is applied.

[0037] After the entire surface of the artificial blood vessel substrate VEB has been baked, linear markers M extending in the axial direction D1 are applied to the surface of the artificial blood vessel substrate VEB (the marker application step; see FIG. 7). The markers M are provided to check the linearity of the artificial blood vessel VE. In this embodiment, the markers M are made of cobalt and are applied as a single linear coating layer extending in the axial direction D1 of the artificial blood vessel substrate VEB. After the markers M have been applied, the entire artificial blood vessel substrate VEB is further baked (the second baking step; not shown). Specifically, the artificial blood vessel substrate VEB is baked by heating the entire outer periphery of the artificial blood vessel substrate VEB. This completes the artificial blood vessel substrate VEB. Note that it has been confirmed that, by heating and baking the outer periphery of the artificial blood vessel substrate VEB using a heating means in the first baking step and the second baking step, the nodes 1 and fibrils 2 on the surface of the artificial blood vessel substrate VEB partially melt and become closer to each other, forming a repeated uneven portion along the axial direction D1 (see FIGS. 13 and 14). As a result, the recesses between the nodes 1 become deeper compared to before the artificial blood vessel base material VEB was baked, and the unevenness of the artificial blood vessel base material VEB is clearly formed. Therefore, compared to a surface with a flat surface or with only small differences in unevenness, the flexibility of the artificial blood vessel VE is improved, and the artificial blood vessel VE is more easily fixed to the surrounding tissue when placed in a living body.

[0038] Next, as shown in Fig. 8, with a core material C inserted inside the artificial blood vessel base material VEB, the artificial blood vessel base material VEB is compressed in the axial direction D1 of the artificial blood vessel base material VEB (first compression step). This step is performed, for example, by applying a force to the artificial blood vessel base material VEB in the axial direction D1 with a core material inserted inside the artificial blood vessel base material VEB. The compression ratio of the artificial blood vessel base material VEB (the percentage of the length of the artificial blood vessel base material VEB after compression (indicated by the solid line in Fig. 8) relative to the original state of the artificial blood vessel base material VEB (indicated by the two-dot chain line in Fig. 8)) is not particularly limited, but can be, for example, 40 to 70%, preferably 50 to 60%.

[0039] Next, a band-like portion B is provided on the artificial blood vessel substrate VEB compressed in the first compression step, extending continuously in a band shape along the axial direction D1 of the artificial blood vessel substrate VEB so as to provide resistance to the artificial blood vessel VE from extending beyond a predetermined length in the axial direction D1 (band-like portion forming step; see FIG. 9 ). The method for forming the band-like portion B is not particularly limited. For example, the band-like portion B is formed by baking the surface of the compressed artificial blood vessel substrate VEB in a predetermined pattern using a heating means that partially heats the surface. In this embodiment, the band-like portion B is formed in a spiral shape around the axis of the compressed artificial blood vessel substrate VEB. More specifically, the spiral band-like portion B is formed by heating the artificial blood vessel substrate VEB while rotating it around the axis and moving the heating means in the axial direction D1 (or by heating the artificial blood vessel substrate VEB while moving the heating means in a spiral shape).

[0040] Next, the compressive force on the artificial blood vessel base material VEB is released, and the artificial blood vessel base material VEB is stretched to a predetermined length (first stretching step; see FIG. 10). In this first stretching step, the artificial blood vessel base material VEB is stretched to a length that is, for example, 75 to 85% of the length of the artificial blood vessel base material VEB in the above-mentioned artificial blood vessel base material preparation step.

[0041] After the artificial blood vessel base material VEB is stretched in the first stretching step, this embodiment includes, in addition to the first compression step and the first stretching step, a step of compressing the stretched artificial blood vessel base material VEB again one or more times (additional compression step), and a step of stretching again the artificial blood vessel base material VEB compressed in the additional compression step (additional stretching step) (see Figures 11 and 12). The artificial blood vessel base material VEB is removed from the core material C and stretched to the desired length required for the artificial blood vessel VE.

[0042] In the additional compression and extension steps, the artificial blood vessel base material VEB is compressed and extended in multiple sets. This allows for more clearly defined compression stripes, where high-density regions R1 and low-density regions R2 are alternately formed, compared to when the artificial blood vessel base material VEB is compressed and extended only once. Furthermore, in the additional compression and extension steps, the artificial blood vessel base material VEB is repeatedly compressed and extended in the axial direction D1, causing the stiff nodes 1 to repeatedly bend and form bends (creases). (A single compression step does not create a bend, or the bends disappear when the artificial blood vessel base material VEB is extended.) This gradually softens the stiff nodes 1, improving the flexibility of the artificial blood vessel VE. In this embodiment, the additional compression and extension steps described above sharpen the compression stripes, where high-density regions R1 and low-density regions R2 are alternately formed, and form bends (creases) in the stiff nodes 1, resulting in a synergistic effect.

[0043] Furthermore, in this embodiment, the formation of the band-shaped portion B prevents the artificial blood vessel VE from stretching beyond a predetermined length. This makes it easier to retain the compression stripes and the bending tendency of the node 1, thereby facilitating the maintenance of the artificial blood vessel VE in a flexible state. Even if the high-density region R1 and the low-density region R2 alternate, if the artificial blood vessel base material VEB is left for a sufficient period of time, the density of the high-density region R1 will gradually decrease due to the elongation of the artificial blood vessel base material VEB. However, the band-shaped portion B prevents the elongation of the artificial blood vessel base material VEB, thereby preventing the high-density region R1 from being fully stretched in the axial direction D1. Furthermore, the bending tendency (folding tendency) of the node 1 is also maintained by the band-shaped portion B. Therefore, the alternating formation of the high-density region R1 and the low-density region R2 and the bending tendency of the node 1 are maintained, thereby improving the flexibility of the artificial blood vessel VE. Furthermore, the artificial blood vessel VE is maintained in a state where it can easily stretch and contract in the axial direction D1. Therefore, the stretching of the artificial blood vessel VE during anastomosis thread pulling makes it possible to determine the tensile limit by the stretching of the artificial blood vessel VE, facilitating the procedure.

[0044] SEM photographs of the surface and cross section of an artificial blood vessel VE manufactured by the above-described manufacturing method are shown in Figures 4, 13, and 14. In this embodiment, as shown in Figure 4, on the surface of the artificial blood vessel VE, the portion of node 1 extending in a direction perpendicular to the extension direction of fibrils 2 (the portion extending in the vertical direction in Figure 4) is curved in a wave-like manner. As described above, when the additional compression step and the additional elongation step are included, node 1 is displaced in a wave-like manner in the axial direction D1 as it progresses in the circumferential direction D2. Furthermore, as shown in Figures 13 and 14, it was observed that the depth and width in the axial direction D1 of the irregularities formed between a pair of nodes 1, 1 increase on the surface of the artificial blood vessel VE. Furthermore, in the photograph shown in Figure 17, node 1 of the artificial blood vessel VE has a pair of node portions N1, N2 adjacent to each other in the axial direction D1. The pair of node portions N1, N2 are connected by a pair of contact points E1, E2 on both sides of the artificial blood vessel VE in the circumferential direction D2. In this embodiment, the pair of contact points E1, E2 have creases (folds) configured to change the angle θE formed by the pair of node portions N1, N2. Specifically, the above-described manufacturing method (additional compression process and additional elongation process) creates creases (folds) at the contact points E1, E2, making them more flexible. Therefore, when the artificial blood vessel VE expands or contracts in the axial direction D1, the angle θE formed between the node portions N1 and N2 is more likely to change. The change in the angle θE makes it easier for the node portions N1 and N2, connected by the contact points E1 and E2, to move closer to or farther away from each other, facilitating the expansion or contraction of the artificial blood vessel VE.

[0045] The number of additional compression steps and additional extension steps is not particularly limited, but can be, for example, 1 to 20 times, preferably 5 to 15 times. The total length in the axial direction D1 of the artificial blood vessel VE after the final additional extension step is not limited, but is preferably 60 to 80%, and more preferably 65 to 75%, of the length of the artificial blood vessel base material VEB (as shown in Figures 5 to 7) in the artificial blood vessel base material preparation step. The total length in the axial direction D1 of the artificial blood vessel VE after the final additional extension step is shorter than the total length of the artificial blood vessel base material VEB (as shown in Figure 10) after the first extension step.

[0046] Next, we will explain the effect of the additional compression and extension steps on improving flexibility. As shown in Figure 16, the flexibility of the artificial blood vessel VE was evaluated by attaching it so that a 150 mm portion from the tip of the artificial blood vessel VE protruded from the fixing base F, and measuring the vertical length L from the reference plane FR of the fixing base F to the tip T of the curved artificial blood vessel VE. The samples used were artificial blood vessel base materials with the same conditions, both without the additional compression and extension steps (Comparative Example) and with the additional compression and extension steps (Example). Specifically, artificial blood vessel base materials were made of ePTFE with a thickness of 0.6 mm, an outer diameter of 7.2 mm, a length of 207 mm, and a stretch ratio of 2.9. Regarding the manufacturing method, the additional compression and extension steps were performed 10 times in the Example, while the additional compression and extension steps were not performed in the Comparative Example, and the compression and extension steps were performed only once. As a result, in the Comparative Example, the vertical length L from the reference plane FR of the fixing base F to the tip T of the curved artificial blood vessel VE was 17.3 mm. In contrast, in the example, the vertical length L from the reference plane FR of the fixing base F to the tip T of the curved artificial blood vessel VE was 80 mm. This shows that the flexibility of the artificial blood vessel VE is greatly improved by performing the additional compression process and the additional extension process.

[0047] Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments. Note that the above-described embodiments mainly describe the invention having the following configurations.

[0048] (1) An artificial blood vessel made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes, In the axial direction of the artificial blood vessel, high-density regions in which the nodes and fibrils are compressed in the axial direction and densely packed, and low-density regions in which the nodes and fibrils are in a lower density state compared to the high-density regions are alternately provided. Artificial blood vessel.

[0049] (2) The artificial blood vessel further comprises: a band-like portion extending continuously in a band-like manner along the axial direction of the artificial blood vessel so as to provide resistance to the artificial blood vessel being extended beyond a predetermined length in the axial direction after the artificial blood vessel is compressed in the axial direction; (1) The artificial blood vessel described in (1).

[0050] (3) The artificial blood vessel described in (1) or (2), wherein the node has a pair of node portions adjacent in the axial direction, the pair of node portions being connected by a pair of contact points on both sides in the circumferential direction of the artificial blood vessel, and the pair of contact points have creases (fold portions) configured to change the angle formed by the pair of node portions at the pair of contact points.

[0051] (4) A method for producing an artificial blood vessel, the method comprising: a) providing a cylindrical artificial blood vessel substrate made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes; b) compressing the artificial blood vessel substrate in the axial direction of the artificial blood vessel substrate while a core material is inserted inside the artificial blood vessel substrate; c) releasing the compressive force on the artificial blood vessel substrate to elongate the artificial blood vessel substrate; d) recompressing the stretched artificial vascular substrate one or more times; e) a step of re-stretching the artificial blood vessel base material compressed in the step d); A method for manufacturing an artificial blood vessel, comprising:

[0052] (5) The method for producing an artificial blood vessel according to (4), further comprising the step of providing a band-like portion on the artificial blood vessel base material compressed in step b) that extends continuously in a band-like manner along the axial direction of the artificial blood vessel base material so as to provide resistance to the artificial blood vessel being stretched beyond a predetermined length in the axial direction.

[0053] (6) A method for producing an artificial blood vessel according to (4) or (5), wherein the band-shaped portion extends spirally around the axis of the artificial blood vessel. [Explanation of symbols]

[0054] 1 node 2 Fibrils B. Band C Core material D1 Axial direction D2 Circumferential direction D3 radial direction E1, E2 contacts F Fixed stand FR Fixed base reference surface L: Vertical length from the reference plane of the fixing table to the tip of the artificial blood vessel M marker N1, N2 node part P1 Part of the fascia P2 Other part of the fascia P3 The inner part of the curved part of the artificial blood vessel P4 Outer part of curved part of artificial blood vessel R1 high density area R2 low density region T Tip of artificial blood vessel VE Artificial Blood Vessel VEB artificial blood vessel base material X Axis of artificial blood vessel θ Angle of the band with respect to the axis of the vascular prosthesis θE Angle between node parts

Claims

1. An artificial blood vessel made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes, In the axial direction of the artificial blood vessel, high-density regions in which the nodes and fibrils are compressed in the axial direction and densely packed, and low-density regions in which the nodes and fibrils are in a lower density state compared to the high-density regions are alternately provided. Artificial blood vessels.

2. The artificial blood vessel further comprises: a band-like portion extending continuously in a band-like manner along the axial direction of the artificial blood vessel so as to provide resistance to the artificial blood vessel being extended beyond a predetermined length in the axial direction after the artificial blood vessel is compressed in the axial direction; The artificial blood vessel according to claim 1.

3. 2. The artificial blood vessel according to claim 1, wherein the node has a pair of node portions adjacent to each other in the axial direction, the pair of node portions being connected by a pair of contact points on both sides in the circumferential direction of the artificial blood vessel, and the pair of contact points have creases configured such that an angle formed by the pair of node portions changes at the pair of contact points.

4. A method for manufacturing an artificial blood vessel, the method comprising: a) providing a cylindrical artificial blood vessel substrate made of expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes; b) compressing the artificial blood vessel substrate in the axial direction of the artificial blood vessel substrate while a core material is inserted inside the artificial blood vessel substrate; c) releasing the compressive force on the artificial blood vessel substrate to expand the artificial blood vessel substrate; d) recompressing the stretched artificial vascular substrate one or more times; e) a step of re-stretching the artificial blood vessel base material compressed in the step d); A method for manufacturing an artificial blood vessel, comprising:

5. 5. The method for producing an artificial blood vessel according to claim 4, further comprising the step of providing, on the artificial blood vessel substrate compressed in step b), a band-like portion that extends continuously in a band-like shape along the axial direction of the artificial blood vessel substrate so as to provide resistance to the artificial blood vessel being stretched beyond a predetermined length in the axial direction.

6. 6. The method for producing an artificial blood vessel according to claim 5, wherein the band-shaped portion extends spirally around the axis of the artificial blood vessel.

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