JP7602895B2 - Mock blood vessel - Google Patents

Description

The technology disclosed in this specification relates to simulated blood vessels.

To restore blood flow in narrowed or blocked areas (hereinafter referred to as "lesions") in blood vessels, percutaneous transluminal angioplasty (hereinafter referred to as "PTA") and percutaneous transluminal coronary angioplasty (hereinafter referred to as "PTCA") are widely performed. In PTA and PTCA (hereinafter referred to as "PTA, etc."), various techniques such as balloon dilation are used.

The procedure using the balloon dilation method is performed, for example, by the following procedure. That is, a guidewire is inserted into a blood vessel and advanced until it passes through the lesion in the blood vessel. Next, a balloon catheter is advanced to the lesion, using the guidewire as a rail. The balloon of the balloon catheter is then expanded to push open the blood vessel wall at the lesion from the inside. These procedures ensure a blood passage and restore blood flow.

PTA and other procedures require delicate manipulation by the operator, and the location and condition of the lesion in the blood vessels vary from patient to patient, making it difficult to master such procedures. For this reason, various simulated blood vessels that mimic blood vessels have been proposed for training purposes to improve PTA and other procedures.

Here, actual blood vessels generally have a relatively elastic, tubular tunica intima, a tunica media surrounding the outside of the tunica intima, and a tunica adventitia surrounding the outside of the tunica media. In addition, in actual blood vessels, there is also an internal elastic lamina between the tunica intima and the tunica media, and an external elastic lamina between the tunica media and the tunica adventitia.

On the other hand, a simulated blood vessel that simulates the intima, media, and adventitia of an actual blood vessel has been proposed for training purposes to improve techniques such as incision of a blood vessel, anastomosis of an incision, and anastomosis between blood vessels in surgical operations (see, for example, Patent Document 1). Specifically, the simulated blood vessel has an intima layer, a media layer disposed outside the intima layer, and an adventitia layer disposed outside the media layer. The simulated blood vessel further has mesh layers between the intima layer and the media layer, and between the media layer and the adventitia layer. The intima layer, the media layer, and the adventitia layer are formed of silicone rubber or the like. The mesh layer is a flexible sheet-like member with multiple through holes formed therein, and is composed of a sheet-like member formed of a synthetic resin such as polyethylene terephthalate, polyurethane, or polypropylene.

In addition, a technique has been proposed that uses polyvinyl alcohol as a material for forming simulated blood vessels (see, for example, Patent Document 2).

JP 2017-53897 A JP 2011-8213 A

As mentioned above, the condition of the actual lesion is diverse. For example, there may be cases where a lesion such as a chronic total occlusion exists in an actual blood vessel. In such cases, it is difficult to adopt a procedure in which a guidewire is pushed toward the lesion. For this reason, a procedure may be performed in which a guidewire that advances through the blood vessel penetrates the blood vessel wall (intima), and then the guidewire is advanced between the intima and media to pass the position of the lesion, and the gap between the intima and media is pushed apart by a balloon catheter. This is because the guidewire can be advanced between the intima and media with less load than the thickened parts of the intima and media. This procedure ensures a blood passage between the intima and media, and blood flow is restored.

In order to practice such procedures, it is desirable to provide a simulated blood vessel with a layered structure similar to that of a real blood vessel. More specifically, it is desirable to provide a simulated blood vessel similar to a real blood vessel that allows the user to feel the sensation of penetrating the guidewire into the intima while also feeling the sensation of advancing the guidewire between the intima and media.

The above-mentioned issues are not limited to simulated blood vessels used in training to improve procedures such as PTA, but are also common to vascular lesion models that include simulated blood vessels and simulated lesions, and biological models in general, such as organ models with layered structures.

This specification discloses a technology that can solve the above-mentioned problems.

The technology disclosed in this specification can be realized, for example, in the following forms:

(1) The simulated blood vessel disclosed in this specification is a tubular simulated blood vessel formed of polyvinyl alcohol gel and having a hollow portion, and the simulated blood vessel has a specific structure having a first portion having a penetration force value exceeding a first value, a second portion located on the outer wall side of the first portion and having a penetration force value exceeding a second value, and a third portion located between the first portion and the second portion and having a penetration force value equal to or less than a third value that is smaller than both of the first value and the second value, on a virtual straight line in a cross section of the simulated blood vessel, the virtual straight line passing through a specific point on the inner wall of the simulated blood vessel and having the shortest distance between the specific point and the outer wall of the simulated blood vessel.

This simulated blood vessel is made of PVA gel. Therefore, this simulated blood vessel can have good elasticity and flexibility similar to that of an actual blood vessel. In addition, this simulated blood vessel has a first part and a second part with a relatively high value of the penetration force, and a third part that is disposed between the first part and the second part and has a value of the penetration force smaller than that of either the first part or the second part. Therefore, for example, the first part located inside the simulated blood vessel and the second part located on the outer wall side of the first part can respectively simulate the relatively elastic intima and media of an actual blood vessel, and the third part can simulate the space between the intima and media of an actual blood vessel. In this way, according to this simulated blood vessel, it is possible to provide a simulated blood vessel that simulates the sensation of penetrating a guidewire into the intima while simulating the sensation of advancing a guidewire between the intima and media.

(2) In the above simulated blood vessel, the first part, the second part, and the third part may each be formed from a polyvinyl alcohol gel. That is, the first part, the second part, and the third part are formed from a single material. This improves the affinity between adjacent parts, making it possible to form them as a whole in an integrated manner. Therefore, this simulated blood vessel can provide a simulated blood vessel that more effectively simulates an actual blood vessel.

(3) In the above simulated blood vessel, the maximum value of the penetration force in the third portion may be 40% or less of the maximum value of the penetration force in the first portion. With this simulated blood vessel, it is easier to advance the guidewire in the third portion compared to the first portion, so that a simulated blood vessel can be provided that more effectively simulates the sensation of advancing the guidewire between the intima and media.

(4) In the above-mentioned simulated blood vessel, the penetration force value in the first portion and the second portion may be more than 50 g, and the penetration force value in the third portion may be 50 g or less. According to this simulated blood vessel, it is possible to provide a simulated blood vessel that more effectively simulates the sensation of advancing a guidewire between the intima and media while approximating the penetration force values in the first portion and the second portion to the penetration force values in the intima and media of an actual blood vessel.

(5) In the above simulated blood vessel, the ratio of the length of the third portion to the total length of the first portion, the second portion, and the third portion on the virtual straight line may be 30% or less. According to this simulated blood vessel, since the length (thickness) of the third portion is smaller than the length (thickness) of the first portion and the length (thickness) of the second portion, it is possible to provide a simulated blood vessel that more effectively simulates the intima and media of an actual blood vessel, and the space between the intima and media.

(6) In the above simulated blood vessel, the first portion and the second portion may each be configured to be composed of a chemically cross-linked portion. According to this simulated blood vessel, since the first portion and the second portion are each composed of a chemically cross-linked portion, it is possible to provide a simulated blood vessel that more effectively simulates the flexibility and penetrating force of an actual blood vessel.

(7) The above simulated blood vessel may have a fourth portion located on the outer wall side of the second portion, the fourth portion being composed only of chemically cross-linked portions, and the value of the penetration force in the fourth portion may be smaller than the maximum value in the second portion and larger than the third value in the third portion. According to this simulated blood vessel, for example, it is possible to provide a simulated blood vessel that more effectively simulates the layer structure of an actual blood vessel having an adventitia.

The technology disclosed in this specification can be realized in various forms, such as a biological model, a training kit including a biological model, a simulator including a biological model, a manufacturing method thereof, etc.

FIG. 1 is an explanatory diagram illustrating a schematic external configuration of a simulated blood vessel 100 according to a first embodiment. FIG. 1 is an explanatory diagram showing an enlarged cross-sectional configuration of the simulated blood vessel 100 according to the first embodiment. A flowchart showing a method for manufacturing the simulated blood vessel 100 according to the first embodiment. FIG. 1 is an explanatory diagram conceptually illustrating a method for manufacturing the simulated blood vessel 100 according to the first embodiment. FIG. 11 is an explanatory diagram showing an enlarged cross-sectional configuration of the simulated blood vessel 100a in the second embodiment. FIG. 13 is an explanatory diagram showing an enlarged cross-sectional configuration of the simulated blood vessel 100b in the third embodiment. FIG. 13 is an explanatory diagram showing an enlarged cross-sectional configuration of the simulated blood vessel 100c according to the fourth embodiment.

A. First embodiment:
A-1. Configuration of simulated blood vessel 100:
FIG. 1 is an explanatory diagram showing the outline of the external configuration of the simulated blood vessel 100 in the first embodiment, and FIG. 2 is an explanatory diagram showing an enlarged cross-sectional configuration of the simulated blood vessel 100 in the first embodiment. FIG. 2 shows the YZ cross-sectional configuration of the simulated blood vessel 100 at the position II-II in FIG. 1. Each figure shows mutually orthogonal XYZ axes for specifying a direction. In this specification, for convenience, the positive direction of the Z axis is referred to as the upward direction, and the negative direction of the Z axis is referred to as the downward direction, but the simulated blood vessel 100 may actually be installed or used in a direction different from these directions. The same applies to FIG. 3 and subsequent figures.

The simulated blood vessel 100 is a device that mimics an actual blood vessel. The simulated blood vessel 100 can be used alone, in combination with other simulated blood vessels or simulated lesions, or as part of a training kit or simulator, for example, in training to improve procedures such as PTA, or to evaluate the performance of medical devices such as guidewires used in PTA, etc.

As shown in FIG. 1, the simulated blood vessel 100 is a cylindrical member extending in the X-axis direction and has a hollow portion H. The simulated blood vessel 100 has an inner wall S1 and an outer wall S2 that define the hollow portion H. The outer diameter ED of the simulated blood vessel 100 is, for example, 10 to 50 mm (preferably 20 to 40 mm), and the inner diameter ID (diameter of the hollow portion H) is, for example, 5 to 45 mm (preferably 15 to 35 mm). The simulated blood vessel 100 is formed of a PVA gel obtained by gelling polyvinyl alcohol (hereinafter also referred to as "PVA"). For this reason, the simulated blood vessel 100 has good flexibility, similar to that of an actual blood vessel. More specifically, the simulated blood vessel 100 includes a chemically crosslinked gel obtained by gelling PVA by chemical crosslinking. Here, in this specification, "gel" means that the simulated blood vessel 100 is in a gel state at room temperature or at the temperature at which the simulated blood vessel 100 is used (for example, 20°C to 50°C). Examples of PVA, which is a material for forming the simulated blood vessel 100, include PVA homopolymers obtained by saponification of polyvinyl acetate, PVA copolymers obtained by saponification of a copolymer of vinyl acetate and another monomer copolymerizable therewith, and modified PVAs in which some hydroxyl groups contained in PVA are replaced with other substituents. The other monomers used in the PVA copolymers are not particularly limited, and examples thereof include conventionally known monomers such as vinyl formate, vinyl propionate, vinyl benzoate, and vinyl t-butyl benzoate. The other substituents used in the modified PVAs are not particularly limited, and examples thereof include carboxyl groups, sulfonic acid groups, acetoacetyl groups, and amine groups. The PVA is preferably a polymer in which the total of polymerization units based on vinyl acetate and polymerization units based on vinyl alcohol is 90 mol % or more, more preferably a polymer in which the total of polymerization units based on vinyl acetate and polymerization units based on vinyl alcohol is 95 mol % or more, and even more preferably a PVA homopolymer. This is because the PVA exhibits physical properties closer to those of actual blood vessels in terms of shape stability, flexibility, and the like, and is safe to the living body, and therefore is easy to handle as a living body model. The above PVAs can be used alone or in combination of two or more types.

In this embodiment, the average degree of polymerization of PVA is, for example, about 500 or more and 3000 or less. If the average degree of polymerization is less than 500, the resulting gel tends to be soft and difficult to maintain an independent shape as a simulated blood vessel. In contrast, if the average degree of polymerization exceeds 3000, the solubility of PVA in a solvent (e.g., water) decreases, making it difficult to mold into a uniform gel shape, and therefore it tends to be difficult to mold into a desired shape. The average degree of polymerization is more preferably about 1000 or more and 2000 or less, and even more preferably about 1500 or more and 1800 or less. The saponification degree of PVA is, for example, about 80 mol% or more. If the saponification degree is less than 80 mol%, it tends to be difficult to mold the PVA gel. The saponification degree is more preferably 90 mol% or more, and even more preferably 98 mol% or more.

PVA gels are classified into "physically cross-linked gels" and "chemically cross-linked gels." "Physically cross-linked gels" are gels that are cross-linked by non-covalent bonds such as hydrogen bonds and ionic bonds, and refer to gels in which cross-linking points are reversibly generated and eliminated by external forces such as temperature changes. On the other hand, "chemically cross-linked gels" are gels that are cross-linked by covalent bonds, and refer to gels in which cross-linking points do not disappear due to external forces such as temperature changes. The degree of chemical cross-linking in a PVA gel affects the hardness of the PVA gel. More specifically, the higher the proportion of chemical cross-linking formed in the PVA gel, the higher the hardness of the PVA gel, and the higher the degree of chemical cross-linking in the PVA gel, the higher the hardness of the PVA gel. In other words, the more the chemical cross-linking in the PVA gel progresses, the higher the hardness of the PVA gel.

Here, the "degree of chemical cross-linking" in the PVA gel can be expressed by a conventionally known method, such as the intensity of the spectrum of the substituents formed by chemical cross-linking in the PVA gel. The intensity of the spectrum of the substituents formed by chemical cross-linking in the PVA gel can be evaluated by a conventionally known method, for example, by the following method. For example, when PVA is chemically cross-linked by using glutaraldehyde as a chemical cross-linking agent, ester groups are formed in the PVA gel. A spectrum (chemical shift or peak) specific to this ester group is identified using nuclear magnetic resonance spectroscopy (NMR spectroscopy) or infrared spectroscopy (IR spectroscopy), and the intensity of the identified spectrum is calculated.

As shown in FIG. 2, the simulated blood vessel 100 of this embodiment has a four-layer structure. More specifically, from the inner wall S1 side, it has an inner hard layer 10, a soft layer 30, an outer hard layer 20, and an outer lubricating layer 40. Each layer is formed of PVA gel. The compositions of the PVA gels forming each layer may be the same or different. The inner hard layer 10 is an example of the first part in the claims, and the outer hard layer 20 is an example of the second part in the claims. The soft layer 30 is an example of the third part in the claims, and the outer lubricating layer 40 is an example of the fourth part in the claims.

The inner hard layer 10 is a relatively hard PVA gel layer and is composed of a chemically cross-linked gel. The thickness T1 of the inner hard layer 10 may be, for example, 0.5 mm or more and 20 mm or less, or 3 mm or more and 15 mm or less. The value of the penetration force of the inner hard layer 10 is, for example, more than 30 g, more than 40 g, or even more than 50 g. Thus, since the inner hard layer 10 contains a chemically cross-linked gel, it has a relatively high value of penetration force. Therefore, the inner hard layer 10 can exhibit properties (relatively high elasticity and flexibility) similar to the intima of an actual blood vessel. The values of the penetration force of the inner hard layer 10, 30 g, 40 g, and 50 g, are each an example of the first value in the claims.

The outer hard layer 20 is located on the outer wall S2 side with respect to the inner hard layer 10. The outer hard layer 20 is a relatively hard PVA gel layer, similar to the inner hard layer 10, and is composed of a chemically cross-linked gel. The layer thickness T2 of the outer hard layer 20 may be, for example, 0.5 mm or more and 20 mm or less, or 3 mm or more and 15 mm or less. The value of the penetration force of the outer hard layer 20 is, for example, more than 30 g, more than 40 g, or even more than 50 g. In this embodiment, the layer thickness T2 and the value of the penetration force of the outer hard layer 20 are equal to the layer thickness T1 and the value of the penetration force of the inner hard layer 10, respectively. Thus, the outer hard layer 20 contains a chemically cross-linked gel, similar to the inner hard layer 10, and therefore has a relatively high value of the penetration force. For this reason, the outer hard layer 20 can exhibit properties (relatively high elasticity and flexibility) similar to the tunica media in an actual blood vessel. The penetration force values of 30g, 40g, and 50g in the outer hard layer 20 are each an example of the second value in the claims.

The soft layer 30 is located between the inner hard layer 10 and the outer hard layer 20. The soft layer 30 is a relatively weak PVA gel layer containing a small amount of chemically cross-linked gel. The degree of chemical cross-linking in the soft layer 30 is lower than the degree of chemical cross-linking in the inner hard layer 10, the outer hard layer 20, and the outer lubricating layer 40. The layer thickness T3 of the soft layer 30 may be, for example, about 0.01 mm or more and 3 mm or less, or about 0.05 mm or more and 1 mm or less. In this embodiment, the layer thickness T3 of the soft layer 30 is smaller than the layer thickness T1 of the inner hard layer 10 and the layer thickness T2 of the outer hard layer 20, and furthermore, the ratio of the layer thickness T3 to the total thickness of the layer thicknesses T1, T2, and T3 (layer thickness T3/(layer thickness T1+layer thickness T2+layer thickness T3)×100) is 30% or less, and furthermore, 15% or less. Furthermore, the value of the penetration force of the soft layer 30 is smaller than both the value of the penetration force of the inner hard layer 10 and the value of the penetration force of the outer hard layer 20. In this embodiment, the maximum value of the penetration force of the soft layer 30 is smaller than the maximum value of the penetration force of the inner hard layer 10, and furthermore, the maximum value of the penetration force of the soft layer 30 is 40% or less, and furthermore, 20% or less, of the maximum value of the penetration force of the inner hard layer 10. In this embodiment, the value of the penetration force in the soft layer 30 is, for example, 50 g or less, 40 g or less, or even 30 g or less. In this way, the soft layer 30 has a relatively low value of penetration force because the degree of chemical cross-linking is low. Therefore, the soft layer 30 can exhibit properties (relatively low elasticity and flexibility) that are similar to the gap between the intima and media in an actual blood vessel. The values of the penetration force in the soft layer 30 of 30 g, 40 g, and 50 g are each an example of the third value in the scope of the claims.

The outer lubricating layer 40 is located on the outer wall S2 side relative to the outer hard layer 20. The outer lubricating layer 40 is a relatively soft PVA gel layer, and is composed only of chemically cross-linked gel. The layer thickness T4 of the outer lubricating layer 40 may be, for example, about 0.5 mm or more and 20 mm or less, and may be about 3 mm or more and 15 mm or less. In this embodiment, the layer thickness T4 of the outer lubricating layer 40 is equal to the layer thickness T1 of the inner hard layer 10 and the layer thickness T2 of the outer hard layer 20. In this embodiment, the value of the penetration force in the outer lubricating layer 40 is smaller than the maximum value of the penetration force in the outer hard layer 20 and is larger than the value of the penetration force in the soft layer 30. In this way, the outer lubricating layer 40 has a relatively high value of penetration force because it contains chemically cross-linked gel, like the inner hard layer 10 and the outer hard layer 20. For this reason, the outer lubricating layer 40 can exhibit properties (relatively high elasticity and flexibility) similar to the adventitia in an actual blood vessel. In this embodiment, the degree of chemical cross-linking in the outer lubricating layer 40 is lower than the degree of chemical cross-linking in the inner hard layer 10 and the outer hard layer 20.

One example of the simulated blood vessel 100 is a layer structure in which the penetration force is greater than 30 g in the inner hard layer 10 and the outer hard layer 20, with a maximum value of 80 g or more (or 100 g or more, or even 120 g or more), less than 30 g in the soft layer 30, and greater than 35 g and less than 120 g (or less than 100 g, or even less than 80 g, and less than 70 g) in the outer lubricating layer 40. Another example of the simulated blood vessel 100 is a layer structure in which the penetration force is greater than 50 g in the inner hard layer 10 and the outer hard layer 20, with a maximum value of 80 g or more (or 100 g or more, or even 120 g or more), less than 50 g in the soft layer 30, and greater than 35 g and less than 120 g (or less than 100 g, or even less than 80 g, and less than 70 g) in the outer lubricating layer 40.

The above-mentioned "value of the penetration force in the inner hard layer 10" can be, for example, the average value when the penetration force of the inner hard layer 10 is measured at five equally spaced points in the circumferential direction around the center point PO in the cross section of the simulated blood vessel 100 shown in FIG. 2 (for example, two points on each side of the circumferential direction from the center point, which is the point on the virtual line VL in FIG. 2). The above-mentioned "maximum value of the penetration force in the inner hard layer 10" can be, for example, the maximum value when the penetration force (average value) of the inner hard layer 10 is measured in order from P1 in the radial direction toward the soft layer 30 on the virtual line VL in FIG. 2. The above is also true for the "value of the penetration force" or "maximum value of the penetration force" in other layers.

In this specification, the value of the penetration force can be measured, for example, by the following method. A Texture Analyzer manufactured by Stable Micro Systems and a needle-shaped measurement probe are used. The measurement probe is lowered at a speed of 2 mm/sec to the point on the cross section of the simulated blood vessel 100 where the penetration force is to be measured, and the maximum load when the measurement probe enters the simulated blood vessel 100 is taken as the penetration force.

In this specification, the above layers can be identified, for example, by the following method. As shown in FIG. 2, the penetration force is measured at a plurality of points on a virtual straight line VL in the cross section of the simulated blood vessel 100 from the inner wall S1 side to the outer wall S2 side. For example, when the value of the penetration force of the inner hard layer 10 and the outer hard layer 20 exceeds 50 g, a specific point P1 on the inner wall S1 is set as the starting point, and among the measurement points where the measured values of the penetration force are continuously greater than 50 g, the measurement point farthest from the starting point is set as the end point, and the section from the starting point to the end point can be identified as the inner hard layer 10. Among the measurement points where the measured values of the penetration force are greater than 50 g, the measurement point closest to the end point of the inner hard layer 10 toward the outer wall S2 side is set as the starting point, and the measurement point from the starting point to the end point where the highest penetration force is measured on the outer wall S2 side is set as the end point, and the section from the starting point to the end point can be identified as the outer hard layer 20. The soft layer 30 can be specified as the portion from the end point of the inner hard layer 10 to the start point of the outer hard layer 20. The outer lubricating layer 40 can be specified as the portion from the end point of the outer hard layer 20 to a specific point P2 of the outer wall S2. In the above, the virtual straight line VL is a straight line passing through a specific point P1 of the inner wall S1 of the simulated blood vessel 100 and a specific point P2 of the outer wall S2. The specific point P2 is a point where the distance between the specific point P1 and the outer wall S2 of the simulated blood vessel 100 is the shortest. In this embodiment, the virtual straight line VL passes through the center point PO of the simulated blood vessel 100.
Although the above describes the case where the penetration force of the inner hard layer 10 and the outer hard layer 20 exceeds 50 g, each layer can be specified in the same manner even if the penetration force exceeds 40 g or exceeds 30 g. The same applies to the embodiments described later.

A-2. Manufacturing method of the simulated blood vessel 100:
Next, a method for manufacturing the simulated blood vessel 100 in the first embodiment will be described. Fig. 3 is a flow chart showing the method for manufacturing the simulated blood vessel 100 in this embodiment. Fig. 4 is an explanatory diagram conceptually showing the method for manufacturing the simulated blood vessel 100 in this embodiment. The right column of Fig. 4 shows a partially enlarged view of the X1 portion shown in the left column.

First, a first cylindrical body CB1 formed of a physically cross-linked gel PG impregnated with an acid catalyst AC is prepared (S110, see FIG. 4(A)). More specifically, a first cylindrical body CB1 having a diameter approximately equal to the diameter of the hollow portion H of the simulated blood vessel 100 is prepared. More specifically, the physically cross-linked gel PG can be prepared by known methods such as a cast-dry method or a freeze-thaw method. The cast-dry method is a method in which a PVA aqueous solution of a predetermined concentration is prepared by adding PVA to water and performing a heat treatment, and the PVA aqueous solution is dried to obtain a physically cross-linked gel. The freeze-thaw method is a method in which a physically cross-linked gel is obtained by repeating a freezing process and a thawing process a predetermined number of times for the same PVA aqueous solution as above. When preparing the physically cross-linked gel PG, the concentration of PVA constituting the physically cross-linked gel PG is increased to increase the degree of physical cross-linking, thereby increasing the hardness and elasticity of the simulated blood vessel 100. Thereafter, the physically crosslinked gel PG obtained by the above-mentioned known method is molded into a tubular shape, and the molded tubular body is immersed in an acid catalyst AC to produce a first tubular body CB1. The acid catalyst AC is not particularly limited, and examples thereof include citric acid and hydrochloric acid. The concentration of the acid catalyst AC is, for example, about 0.01 mol/L or more and 1.0 mol/L or less, and more preferably, about 0.1 mol/L or more and 0.3 mol/L or less. The first tubular body CB1 can be obtained, for example, by immersing the above-mentioned tubular body in a 0.5 N citric acid aqueous solution at 1 atm and 25° C. for 10 minutes.

Next, a PVA solution PS containing a crosslinking agent CL (hereinafter referred to as "PVA solution PS") and an aqueous solution AS containing a crosslinking agent CL (hereinafter referred to as "aqueous solution AS") are prepared (S120, S130). The crosslinking agent CL is not particularly limited, and examples thereof include dialdehydes such as glutaraldehyde, glyoxal, formalin, and terephthalaldehyde. Here, a dialdehyde is an aldehyde having two aldehyde groups (formyl groups). The concentration of the dialdehyde is, for example, about 0.01 mol/L or more and 1.0 mol/L or less, and more preferably about 0.1 mol/L or more and 0.3 mol/L or less.

Next, the hollow portion H of the first cylindrical body CB1 is filled with the aqueous solution AS, and the first cylindrical body CB1 is immersed in the PVA solution PS (S140, see FIG. 4B). The process of step S140 can be performed, for example, by immersing the first cylindrical body CB1, whose hollow portion H is filled with the 25% aqueous solution of glutaraldehyde, in the 25% PVA solution of glutaraldehyde at 1 atm and 25° C. for 10 minutes. By performing step S140, a coexistence system of the physically cross-linked gel PG and the chemically cross-linked gel CG is formed around the inner wall S1 and the outer wall S2p of the first cylindrical body CB1.

The right column of FIG. 4(B) will be used to explain the catalytic exchange reaction. In FIG. 4(B), citric acid as the acid catalyst AC is shown by a "△" and dialdehyde as the cross-linking agent CL is shown by a "○". On the inner wall S1 side of the first cylindrical body CB1, the acid catalyst AC contained in the first cylindrical body CB1 reacts with the cross-linking agent CL contained in the aqueous solution AS, forming a coexistence system of the physical cross-linking gel PG and the chemical cross-linking gel CG (formation of the inner hard layer 10P before treatment). On the outer wall S2p side of the first cylindrical body CB1, a catalytic exchange reaction proceeds between the first cylindrical body CB1 containing the acid catalyst AC and the PVA solution PS containing the cross-linking agent CL. As a result, new chemical cross-links are formed around the outer wall S2p of the first cylindrical body CB1 and on the outside of the outer wall S2p. As a result, a coexistence system of the physically cross-linked gel PG and the chemically cross-linked gel CG is formed around the outer wall S2p of the first cylindrical body CB1 (formation of the pre-treatment outer hard layer 20P), and outside the outer wall S2p, the chemically cross-linked gel CG is formed from the PVA in the PVA solution PS (formation of the outer lubricating layer 40). In addition, the part between the inner wall S1 and the outer wall S2p that contains the physically cross-linked gel PG and has an extremely low degree of chemical cross-linking is formed as the pre-treatment soft layer 30P. In this way, the second cylindrical body CB2 is produced, which includes the pre-treatment inner hard layer 10P, the pre-treatment soft layer 30P, the pre-treatment outer hard layer 20P, and the outer lubricating layer 40 (see FIG. 4C).

The above-mentioned chemical cross-linking reaction proceeds stepwise from the inner wall S1 of the first cylindrical body CB1 toward the outer wall S2p side, or from the outer wall S2p toward the inner wall S1 side, or toward the outside of the first cylindrical body CB1. Therefore, in the second cylindrical body CB2, the chemical cross-linking density is high in the inner hard layer 10 and the outer hard layer 20 close to the inner wall S1 and the outer wall S2p, and the chemical cross-linking density is low in the soft layer 30 away from the inner wall S1 and the outer wall S2p. As described above, the penetration force of the PVA gel increases with the degree of chemical cross-linking. Therefore, in the second cylindrical body CB2, the penetration force of the inner hard layer 10 and the outer hard layer 20 is high, and the penetration force of the soft layer 30 is low. The degree of formation of the chemical cross-linked gel CG can be changed by adjusting the amount of cross-linking agent CL and acid catalyst AC added, the pH of the acid catalyst AC, the reaction pressure, the reaction temperature, the reaction time, etc. The chemical cross-linking reaction may also be stopped by immersing the second cylindrical body CB2 in an alkaline solution such as sodium carbonate.

The outer lubricating layer 40 forms chemical crosslinks using the acid catalyst AC contained in the physically crosslinked gel PG that was not consumed in the chemical crosslinking in the inner hard layer 10 and the outer hard layer 20. Therefore, the chemical crosslink density in the outer lubricating layer 40 is lower than that in the inner hard layer 10 and the outer hard layer 20. Furthermore, the inner hard layer 10 and the outer hard layer 20 form a coexistence system of the physically crosslinked gel PG and the chemical crosslinks, while the outer lubricating layer 40 forms chemical crosslinks from the PVA in the PVA solution PS. In other words, in the part where the physically crosslinked gel PG exists, the PVA molecular chains are already bonded to each other by physical crosslinks, so a chemical crosslinked gel CG in which the PVA molecules are more densely packed is formed. On the other hand, in the PVA in the PVA solution PS, the PVA molecular chains are not bonded to each other, so a chemical crosslinked gel CG in which the PVA molecules are relatively sparsely packed is formed. Therefore, in the manufacturing method of this embodiment, the penetration force value of the outer lubricating layer 40 is lower than the penetration force values of the inner hard layer 10 and the outer hard layer 20.

Next, the second cylindrical body CB2 is treated with hot water HW to prepare the simulated blood vessel 100 (S150, see FIG. 4(D)). The hot water HW is, for example, hot water at 80°C to 100°C. The process of step S150 can be performed, for example, by boiling the second cylindrical body CB2 in hot water at 80°C under 1 atm for 10 minutes. By performing step S150, the physical crosslinks of the physically crosslinked gel PG in the pre-treatment inner hard layer 10P, pre-treatment soft layer 30P, and pre-treatment outer hard layer 20P disappear, and the soft layer 30 is formed. The degree to which the physical crosslinks of the simulated blood vessel 100 disappear can be changed by adjusting the temperature, time, etc. of the hot water HW. This allows the simulated blood vessel 100 to be prepared, which includes the inner hard layer 10, the soft layer 30, the outer hard layer 20, and the outer lubricating layer 40 (see FIG. 4(E)).

A-3. Advantages of the first embodiment:
As described above, the simulated blood vessel 100 of this embodiment has a layered structure including the inner hard layer 10, the outer hard layer 20, and the soft layer 30. The penetration force value of the soft layer 30 is smaller than the penetration force values of the inner hard layer 10 and the outer hard layer 20.

The simulated blood vessel 100 of this embodiment is formed of PVA gel. Therefore, the simulated blood vessel 100 of this embodiment can have good elasticity and flexibility similar to that of an actual blood vessel. In addition, the simulated blood vessel 100 of this embodiment has an inner hard layer 10 and an outer hard layer 20 having a relatively high value of penetration force, and a soft layer 30 arranged between the inner hard layer 10 and the outer hard layer 20 and having a value of penetration force smaller than that of either the inner hard layer 10 or the outer hard layer 20. Therefore, for example, the inner hard layer 10 located on the inside of the simulated blood vessel 100 and the outer hard layer 20 located on the outer wall S2 side with respect to the inner hard layer 10 can respectively simulate the intima and media of an actual blood vessel, which are relatively elastic, and the soft layer 30 can simulate the space between the intima and media of an actual blood vessel. In this way, the simulated blood vessel 100 of this embodiment can provide a simulated blood vessel 100 that simulates the sensation of penetrating the guidewire into the intima while also simulating the sensation of advancing the guidewire between the intima and media.

In addition, in the simulated blood vessel 100 of this embodiment, the inner hard layer 10, the outer hard layer 20, and the soft layer 30 are each formed of polyvinyl alcohol gel. That is, the inner hard layer 10, the outer hard layer 20, and the soft layer 30 are formed of a single forming material. This results in good affinity between adjacent layers, making it possible to form the entire structure as a single unit. Therefore, according to the simulated blood vessel 100 of this embodiment, it is possible to provide a simulated blood vessel 100 that more effectively simulates an actual blood vessel.

In the simulated blood vessel 100 of this embodiment, the maximum value of the penetration force in the soft layer 30 is 40% or less of the maximum value of the penetration force in the inner hard layer 10. According to the simulated blood vessel 100 of this embodiment, the soft layer 30 makes it easier to advance the guidewire compared to the inner hard layer 10, so that it is possible to provide a simulated blood vessel 100 that more effectively simulates the sensation of advancing the guidewire between the intima and the media. Although the simulated blood vessel 100 of this embodiment has been described above, in the simulated blood vessel of the present invention, the maximum value of the penetration force in the soft layer may be 30% or less of the maximum value of the penetration force in the inner hard layer, or may be 20% or less.

In addition, in the simulated blood vessel 100 of this embodiment, the penetration force value in the inner hard layer 10 and the outer hard layer 20 is more than 50 g, and the penetration force value in the soft layer 30 is 50 g or less. According to the simulated blood vessel 100 of this embodiment, the penetration force value of the inner hard layer 10 and the outer hard layer 20 is approximated to the penetration force value of the intima and media of an actual blood vessel, and a simulated blood vessel 100 can be provided that more effectively simulates the sensation when the guide wire advances between the intima and media. Although the simulated blood vessel 100 of this embodiment has been described above, in the simulated blood vessel of the present invention, the penetration force value in the inner hard layer and the outer hard layer may be more than 40 g or more than 30 g. Furthermore, the penetration force value in the soft layer 30 may be 40 g or less or 30 g or less.

In addition, in the simulated blood vessel 100 of this embodiment, the ratio of the thickness T3 of the soft layer 30 to the total length of the thickness T1 of the inner hard layer 10, the thickness T2 of the outer hard layer 20, and the thickness T3 of the soft layer 30 is 30% or less. According to the simulated blood vessel 100 of this embodiment, since the thickness T3 of the soft layer 30 is smaller than the thickness T1 of the inner hard layer 10 and the thickness T2 of the outer hard layer 20, it is possible to provide a simulated blood vessel 100 that more effectively simulates the intima and media of an actual blood vessel, and the space between the intima and media. The simulated blood vessel 100 of this embodiment has been described above, but in the simulated blood vessel of the present invention, the ratio of the thickness T3 of the soft layer 30 to the total length of the thickness T1 of the inner hard layer 10, the thickness T2 of the outer hard layer 20, and the thickness T3 of the soft layer 30 may be 15% or less, or 10% or less, or may even be 5% or less.

In addition, in the simulated blood vessel 100 of this embodiment, the inner hard layer 10 and the outer hard layer 20 are each composed of a chemically cross-linked gel CG. According to the simulated blood vessel 100 of this embodiment, since the inner hard layer 10 and the outer hard layer 20 are each composed of a chemically cross-linked gel CG, it is possible to provide a simulated blood vessel 100 that more effectively simulates the flexibility and high penetrating force of an actual blood vessel. In addition, in the simulated blood vessel 100 of this embodiment, the soft layer 30 is composed of a chemically cross-linked gel that has a lower degree of chemical cross-linking compared to the inner hard layer 10 and the outer hard layer 20.

The simulated blood vessel 100 of this embodiment has an outer lubricating layer 40 composed only of the chemically cross-linked gel CG, and the value of the penetration force of the outer lubricating layer 40 is smaller than the maximum value of the penetration force of the outer hard layer 20 and is larger than the value of the penetration force of the soft layer 30. According to the simulated blood vessel 100 of this embodiment, for example, it is possible to provide a simulated blood vessel 100 that more effectively simulates the layer structure of an actual blood vessel having an adventitia.

B. Second embodiment:
Fig. 5 is an explanatory diagram that shows a schematic configuration of the simulated blood vessel 100a in the second embodiment. Fig. 5 shows a YZ cross-sectional configuration of the simulated blood vessel 100a in the second embodiment at the same position as Fig. 2 (position II-II in Fig. 1). In the following, the description of the configuration of the simulated blood vessel 100a in the second embodiment that is the same as that of the simulated blood vessel 100 in the first embodiment described above will be omitted as appropriate.

The simulated blood vessel 100a of the second embodiment has a four-layer structure, similar to the simulated blood vessel 100 of the first embodiment. The simulated blood vessel 100a differs from the simulated blood vessel 100 of the first embodiment in that it does not have an outer lubricating layer 40, but has an inner lubricating layer 50.

As described above, the simulated blood vessel 100a has a four-layer structure. More specifically, from the inner wall S1 side, it has an inner lubricating layer 50, an inner hard layer 10, a soft layer 30, and an outer hard layer 20. The materials, thicknesses, and penetration strengths of each layer are the same as those of the simulated blood vessel 100. Similarly to the simulated blood vessel 100, the outer diameter EDa of the simulated blood vessel 100a is, for example, 10 to 50 mm (preferably 20 to 40 mm), and the inner diameter IDa (diameter of the hollow portion H) is, for example, 5 to 45 mm (preferably 15 to 35 mm).

The inner lubricating layer 50 is located on the inner wall S1 side relative to the inner hard layer 10. The inner lubricating layer 50 is a relatively soft PVA gel layer, and is composed only of a chemically cross-linked gel. The layer thickness T5 of the inner lubricating layer 50 may be, for example, about 0.5 mm or more and about 20 mm or less, and may be about 3 mm or more and about 15 mm or less. In this embodiment, the layer thickness T5 of the inner lubricating layer 50 is equivalent to the layer thickness T1 of the inner hard layer 10 and the layer thickness T2 of the outer hard layer 20. In addition, in this embodiment, the value of the penetration force in the inner lubricating layer 50 is equivalent to the value of the penetration force in the outer lubricating layer 40 of the first embodiment. That is, the value of the penetration force in the inner lubricating layer 50 is smaller than the maximum value of the penetration force in the inner hard layer 10 and the outer hard layer 20, and is larger than the value of the penetration force in the soft layer 30. In this way, the inner lubricating layer 50, like the inner hard layer 10 and the outer hard layer 20, contains a chemically crosslinked gel and therefore has a relatively high penetration force value. Therefore, the inner lubricating layer 50, together with the outer hard layer 20, can exhibit properties (relatively high elasticity and flexibility) similar to the intima of an actual blood vessel.

As an example of the simulated blood vessel 100a, a layer structure can be mentioned in which the penetration force value is more than 30 g in the inner hard layer 10 and the outer hard layer 20, respectively, and the maximum value is 80 g or more (or 100 g or more, or even 120 g or more), 30 g or less in the soft layer 30, and 35 g or more and less than 120 g (or less than 100 g, or even less than 80 g, and 70 g or less) in the inner lubricating layer 50. As another example of the simulated blood vessel 100a, a layer structure can be mentioned in which the penetration force value is more than 50 g in the inner hard layer 10 and the outer hard layer 20, respectively, and the maximum value is 80 g or more (or 100 g or more, or even 120 g or more), 50 g or less in the soft layer 30, and 35 g or more and less than 120 g (or less than 100 g, or even less than 80 g, and 70 g or less) in the inner lubricating layer 50.

In this embodiment, the above layers can be identified, for example, by the following method. As shown in FIG. 5, the penetration force is measured at multiple points on a virtual straight line VL in the cross section of the simulated blood vessel 100a from the inner wall S1 side to the outer wall S2 side. For example, when the value of the penetration force of the inner hard layer 10 and the outer hard layer 20 exceeds 50 g, a specific point P2 on the outer wall S2 is set as the starting point, and among the measurement points where the measured penetration force value is continuously greater than 50 g, the measurement point farthest from the starting point is set as the end point, and the portion from the starting point to the end point can be identified as the outer hard layer 20. Among the measurement points where the measured penetration force value exceeds 50 g, the measurement point closest to the end point of the outer hard layer 20 toward the inner wall S1 side is set as the starting point, and the measurement point with the highest penetration force from the starting point on the inner wall S1 side is set as the end point, and the portion from the starting point to the end point can be identified as the inner hard layer 10. The soft layer 30 can be determined from the end point of the outer hard layer 20 to the start point of the inner hard layer 10. The inner lubricating layer 50 can be determined from the end point of the inner hard layer 10 to a specific point P1 on the inner wall S1. In the above, the virtual straight line VL is a straight line passing through a specific point P1 on the inner wall S1 of the simulated blood vessel 100 and a specific point P2 on the outer wall S2. The specific point P2 is the point where the distance between the specific point P1 and the outer wall S2 of the simulated blood vessel 100 is the shortest. In this embodiment, the virtual straight line VL passes through the center point PO of the simulated blood vessel 100.

The simulated blood vessel 100a in this embodiment can be manufactured by modifying some of the steps of the manufacturing method for the simulated blood vessel 100 in the first embodiment. Specifically, the simulated blood vessel 100a can be manufactured, for example, by replacing step S140 in the first embodiment with the following steps:

That is, in the manufacturing method of the simulated blood vessel 100a, the hollow part of the first cylindrical body is filled with the PVA solution PS, and the first cylindrical body is immersed in the aqueous solution AS. By performing this step, a chemical cross-linked gel CG is formed from the physical cross-linked gel PG around the inner wall and the outer wall of the first cylindrical body. More specifically, on the inner wall side of the first cylindrical body, a catalyst exchange reaction proceeds between the first cylindrical body containing the acid catalyst AC and the PVA solution PS containing the cross-linking agent CL. As a result, a new chemical cross-link is formed around the inner wall of the first cylindrical body and on the inside of the inner wall. As a result, a coexistence system of the physical cross-linked gel PG and the chemical cross-linked gel CG is formed around the inner wall of the first cylindrical body (formation of the inner hard layer 10P before treatment), and a chemical cross-linked gel CG is formed from the PVA in the PVA solution PS on the inside of the inner wall (formation of the inner lubricating layer 50). In addition, on the outer wall side of the first cylindrical body, the acid catalyst AC contained in the first cylindrical body reacts with the cross-linking agent CL contained in the aqueous solution AS, forming a coexistence system of the physically cross-linked gel PG and the chemically cross-linked gel CG (formation of the pre-treatment outer hard layer 20P). In addition, the part between the inner wall and the outer wall that contains the physically cross-linked gel PG and has an extremely low degree of chemical cross-linking is formed as the pre-treatment soft layer 30P. In this way, a second cylindrical body is produced that includes the inner lubricating layer 50, the pre-treatment inner hard layer 10P, the pre-treatment soft layer 30P, and the pre-treatment outer hard layer 20P.

The second cylindrical body produced in the above step is treated with hot water HW in the same manner as step S150 in the first embodiment to produce a simulated blood vessel 100a. This allows the production of a simulated blood vessel 100a that includes an inner lubricating layer 50, an inner hard layer 10, a soft layer 30, and an outer hard layer 20.

The simulated blood vessel 100a of this embodiment, which has the above configuration, has the same effects as the simulated blood vessel 100 of the first embodiment, except for the effects of having the outer lubricating layer 40.

C. Third embodiment:
Fig. 6 is an explanatory diagram that shows a schematic configuration of a simulated blood vessel 100b in the third embodiment. Fig. 6 shows a YZ cross-sectional configuration of the simulated blood vessel 100b in the third embodiment at the same position as Fig. 2 (position II-II in Fig. 1). In the following, the description of the configuration of the simulated blood vessel 100b in the third embodiment that is the same as that of the simulated blood vessels 100 and 100a in the first and second embodiments described above will be omitted as appropriate.

The simulated blood vessel 100b of the third embodiment differs from the simulated blood vessel 100 of the first embodiment in that it further comprises an inner lubricating layer 50. In other words, the simulated blood vessel 100b has a five-layer structure.

As described above, the simulated blood vessel 100b has a five-layer structure. More specifically, from the inner wall S1 side, it has an inner lubricating layer 50, an inner hard layer 10, a soft layer 30, an outer hard layer 20, and an outer lubricating layer 40. The materials, thicknesses, and penetration strengths of each layer are the same as those of the simulated blood vessels 100 and 100a. The outer and inner diameters of the simulated blood vessel 100b are the same as those of the simulated blood vessels 100 and 100a.

An example of the simulated blood vessel 100b is a layer structure in which the penetration force value is greater than 30 g and has a maximum value of 80 g or more (or 100 g or more, or even 120 g or more) for the inner hard layer 10 and the outer hard layer 20, respectively, is 30 g or less for the soft layer 30, and is 35 g or more and less than 120 g (or less than 100 g, or even less than 80 g, and 70 g or less) for the outer lubricating layer 40 and the inner lubricating layer 50, respectively. Another example of the simulated blood vessel 100b is a layer structure in which the penetration force is greater than 50 g for the inner hard layer 10 and the outer hard layer 20, with the maximum value being 80 g or more (or 100 g or more, or even 120 g or more), less than 50 g for the soft layer 30, and greater than 35 g and less than 120 g for the outer lubricating layer 40 and the inner lubricating layer 50 (or less than 100 g, or even less than 80 g, and less than 70 g).

The simulated blood vessel 100b in this embodiment can be manufactured by changing some of the steps of the manufacturing method of the simulated blood vessel 100 in the first embodiment. Specifically, the simulated blood vessel 100b can be manufactured, for example, by replacing step S140 with the following steps without requiring step S130 (preparation of the aqueous solution AS) in the first embodiment. That is, the first cylindrical body is immersed in the PVA solution PS. As a result, a coexistence system of the physically cross-linked gel PG and the chemically cross-linked gel CG is formed around both the inner and outer walls of the first cylindrical body (formation of the pre-treatment inner hard layer 10P and the pre-treatment outer hard layer 20P). In addition, the chemically cross-linked gel CG is formed from the PVA in the PVA solution PS on both the outside of the outer wall of the first cylindrical body and the inside of the inner wall of the first cylindrical body (formation of the outer lubricating layer 40 and the inner lubricating layer 50). In this way, a second cylindrical body is produced that includes an inner lubricating layer 50, an untreated inner hard layer 10P, an untreated soft layer 30P, an untreated outer hard layer 20P, and an outer lubricating layer 40.

The second cylindrical body produced in the above step is treated with hot water HW in the same manner as step S150 in the first embodiment to produce the simulated blood vessel 100b. This produces the simulated blood vessel 100b that includes an inner lubricating layer 50, an inner hard layer 10, a soft layer 30, an outer hard layer 20, and an outer lubricating layer 40.

The simulated blood vessel 100b of this embodiment, which has the above configuration, has the same effects as the simulated blood vessel 100 of the first embodiment.

D. Fourth embodiment:
Fig. 7 is an explanatory diagram that shows a schematic configuration of a simulated blood vessel 100c in the fourth embodiment. Fig. 7 shows a YZ cross-sectional configuration of the simulated blood vessel 100c in the fourth embodiment at the same position as Fig. 2 (position II-II in Fig. 1). In the following, the description of the configuration of the simulated blood vessel 100c in the fourth embodiment that is the same as that of the simulated blood vessel 100 in the first embodiment described above will be omitted as appropriate.

The simulated blood vessel 100c of the fourth embodiment differs from the simulated blood vessel 100 of the first embodiment in that it does not have an outer lubricating layer 40. In other words, the simulated blood vessel 100c has a three-layer structure.

As described above, the simulated blood vessel 100c has a three-layer structure. More specifically, from the inner wall S1 side, it has an inner hard layer 10, a soft layer 30, and an outer hard layer 20. The materials, thickness, and penetration force of each layer are the same as those of the simulated blood vessel 100. The outer and inner diameters of the simulated blood vessel 100c are also the same as those of the simulated blood vessel 100.

One example of the simulated blood vessel 100c is a layer structure in which the penetration force is greater than 30 g in the inner hard layer 10 and the outer hard layer 20, with a maximum value of 80 g or more (or 100 g or more, or even 120 g or more), and is less than 30 g in the soft layer 30. Another example of the simulated blood vessel 100c is a layer structure in which the penetration force is greater than 50 g in the inner hard layer 10 and the outer hard layer 20, with a maximum value of 80 g or more (or 100 g or more, or even 120 g or more), and is less than 50 g in the soft layer 30.

The simulated blood vessel 100c in this embodiment can be manufactured by changing a part of the steps of the manufacturing method of the simulated blood vessel 100 in the first embodiment. Specifically, the simulated blood vessel 100c can be manufactured, for example, by replacing step S140 with the following steps without requiring step S120 (preparation of the PVA solution PS) in the first embodiment. That is, the first cylindrical body is immersed in the aqueous solution AS. As a result, a coexistence system of the physically cross-linked gel PG and the chemically cross-linked gel CG is formed around both the inner wall and the outer wall of the first cylindrical body (formation of the pre-processing inner hard layer 10P and the pre-processing outer hard layer 20P). In this way, a second cylindrical body having the pre-processing inner hard layer 10P, the pre-processing soft layer 30P, and the pre-processing outer hard layer 20P is manufactured.

The second cylindrical body produced in the above step is treated with hot water HW in the same manner as step S150 in the first embodiment to produce the simulated blood vessel 100c. This allows the production of the simulated blood vessel 100c having an inner hard layer 10, a soft layer 30, and an outer hard layer 20.

The simulated blood vessel 100c of this embodiment, which has the above configuration, has the same effects as the simulated blood vessel 100 of the first embodiment, except for the effects of having the outer lubricating layer 40.

E. Variations:
The technology disclosed in this specification is not limited to the above-described embodiments, and can be modified in various forms without departing from the spirit of the invention. For example, the following modifications are also possible.

In the above embodiment, the simulated blood vessel 100 is described as having a circular tube shape, but this is not limited thereto. For example, the simulated blood vessel 100 may have a cylindrical shape with a polygonal cross section.

In the above embodiment, the simulated blood vessel 100 has a layered structure, but is not limited to this. For example, the simulated blood vessel 100 may have the above structure in a portion of its cross section. That is, one cross section of the simulated blood vessel 100 may have a first portion, a second portion, a third portion, and a fourth portion, which correspond to the inner hard layer 10, the outer hard layer 20, the soft layer 30, and the outer lubricating layer 40, respectively.

In the above embodiment, the inner hard layer 10 and the outer hard layer 20 are made of chemically cross-linked gel, but this is not limited thereto. For example, at least one of the inner hard layer 10 and the outer hard layer 20 may have a physically cross-linked gel. Also, in the above embodiment, the soft layer 30 is configured to include a small amount of chemically cross-linked gel, but this is not limited thereto. For example, the soft layer 30 may not include a chemically cross-linked gel.

In the above embodiment, the degree of chemical cross-linking in the inner hard layer 10, the outer hard layer 20, the soft layer 30, and the outer lubricating layer 40 is approximately uniform, but is not limited to this. For example, the degree of chemical cross-linking may be partially different in at least one of the above layers.

In the above embodiment, the thickness of each layer can be changed as appropriate. In the above embodiment, the thickness T1 of the inner hard layer 10 and the thickness T2 of the outer hard layer 20 may be different from each other. In the above embodiment, the ratio of the thickness T3 to the total thickness of the thickness T1, the thickness T2, and the thickness T3 (thickness T3/(thickness T1+thickness T2+thickness T3)×100) may be more than 30% or more than 15%. The lower limit of the ratio of the thickness T3 to the total thickness of the thickness T1, the thickness T2, and the thickness T3 is not particularly limited and may be set as appropriate, and may be, for example, 1% or more, or 2% or more.
In the above embodiment, the ratio of the thickness of the soft layer 30 (layer thickness T3) to the thickness of the simulated blood vessel ((outer diameter-inner diameter)/2) may be 30% or less, 15% or less, or 10% or less, or even 5% or less. The ratio of the thickness of the soft layer 30 (layer thickness T3) to the thickness of the simulated blood vessel ((outer diameter-inner diameter)/2) may be 1% or more, or 2% or more.

In the above embodiment, the value of the penetration force of each layer can be changed as appropriate. In the above embodiment, the value of the penetration force of the inner hard layer 10 and the value of the penetration force of the outer hard layer 20 may be different from each other. In the above embodiment, the values of the penetration force of the inner hard layer 10 and the outer hard layer 20 may be 30 g or less, 40 g or less, or 50 g or less. In the above embodiment, the value of the penetration force of the soft layer 30 may be more than 50 g, more than 40 g, or more than 30 g. In the above embodiment, the maximum value of the penetration force of the soft layer 30 may be more than 40%, more than 30%, or more than 20% of the maximum value of the penetration force of the inner hard layer 10.

In the above embodiment, the thickness T4 of the outer lubricating layer 40 may be different from the thickness T1 of the inner hard layer 10 and the thickness T2 of the outer hard layer 20. In addition, in the above embodiment, the value of the penetration force of the outer lubricating layer 40 may be equal to or greater than the maximum value of the penetration force of the outer hard layer 20, or may be less than the value of the penetration force of the soft layer 30.

In the above embodiment, the thickness T5 of the inner lubricating layer 50 may be different from the thickness T1 of the inner hard layer 10 and the thickness T2 of the outer hard layer 20. In addition, in the above embodiment, the value of the penetration force of the inner lubricating layer 50 may be equal to or greater than the maximum value of the penetration force of the outer hard layer 20, or may be less than the value of the penetration force of the soft layer 30.

In the above embodiment, the inner hard layer 10 may have a penetrating force that varies within the layer, for example, the penetrating force may increase stepwise from the soft layer 30 side toward the hollow portion H side of the simulated blood vessel 100. Moreover, since the inner hard layer 10 can exhibit properties (relatively high elasticity and flexibility) more similar to the tunica media of an actual blood vessel, the maximum penetrating force is preferably 80 g or more, more preferably 90 g or more, and even more preferably 100 g or more.
The outer hard layer 20 may have a penetrating force that changes within the layer, similar to the inner hard layer 10, and for example, the penetrating force may increase stepwise from the soft layer 30 side toward the outer wall S2 side.

In the above embodiment, the degree of chemical cross-linking in the inner hard layer 10 and the outer hard layer 20 may be approximately uniform, or may vary within the layer. For example, the degree of chemical cross-linking in the inner hard layer 10 may increase stepwise from the soft layer 30 side toward the hollow portion H side of the simulated blood vessel 100. The degree of chemical cross-linking in the outer hard layer 20 may also be approximately uniform, or the value of the penetration force may change within the layer, for example, the degree of chemical cross-linking may increase stepwise from the soft layer 30 side toward the outer wall S2 side.

The manufacturing method of the simulated blood vessel 100 in the above embodiment is merely an example and is not limited thereto. Any manufacturing method that can realize the layered structure of the simulated blood vessel 100 may be used.

10: Inner hard layer 20: Outer hard layer 30: Soft layer 30P: Soft layer before treatment 40: Outer lubricant layer 50: Inner lubricant layer 100: Simulated blood vessel 100a: Simulated blood vessel 100b: Simulated blood vessel 100c: Simulated blood vessel ED: Outer diameter EDa: Outer diameter H: Hollow part ID: Inner diameter IDa: Inner diameter P1: Specific point P2: Specific point PO: Center point S1: Inner wall S2: Outer wall T1: Layer thickness T2: Layer thickness T3: Layer thickness T4: Layer thickness T5: Layer thickness VL: Virtual straight line

Claims (6)

A tubular simulated blood vessel formed of polyvinyl alcohol gel and having a hollow portion,
The simulated blood vessel is a virtual line in a cross section of the simulated blood vessel, which passes through a specific point on the inner wall of the simulated blood vessel and has a shortest distance between the specific point and the outer wall of the simulated blood vessel.
a first portion having a penetration force value greater than a first value;
a second portion located on the outer wall side relative to the first portion and having a penetration force value greater than a second value;
a third portion located between the first portion and the second portion and having a penetration force value equal to or less than a third value that is smaller than both the first value and the second value;
Equipped with a specific structure ,
a penetration force value of the first portion and the second portion is greater than 50 g;
The penetration force value in the third portion is 50 g or less .
Simulated blood vessel. The simulated blood vessel according to claim 1,
the first portion, the second portion, and the third portion are each formed of a polyvinyl alcohol gel;
Simulated blood vessel. The simulated blood vessel according to claim 1 or 2,
The maximum value of the penetration force in the third portion is 40% or less of the maximum value of the penetration force in the first portion.
Simulated blood vessel. The simulated blood vessel according to any one of claims 1 to 3 ,
a ratio of the length of the third portion to a total length of the first portion, the second portion, and the third portion on the virtual straight line is 30% or less;
Simulated blood vessel. The simulated blood vessel according to any one of claims 1 to 4 ,
The first portion and the second portion are each composed of a chemically crosslinked chemical crosslinking site.
Simulated blood vessel. A tubular simulated blood vessel formed of polyvinyl alcohol gel and having a hollow portion,
The simulated blood vessel is a virtual line in a cross section of the simulated blood vessel, which passes through a specific point on the inner wall of the simulated blood vessel and has a shortest distance between the specific point and the outer wall of the simulated blood vessel.
a first portion having a penetration force value greater than a first value;
a second portion located on the outer wall side relative to the first portion and having a penetration force value greater than a second value;
a third portion located between the first portion and the second portion and having a penetration force value equal to or less than a third value that is smaller than both the first value and the second value;
Equipped with a specific structure,
a fourth portion located on the outer wall side relative to the second portion,
the fourth portion is composed only of chemically crosslinked sites that are chemically crosslinked,
a value of the penetration force in the fourth portion is smaller than a maximum value of the second portion and is larger than the third value of the third portion;
Simulated blood vessel.

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