Simulated blood vessels

Abstract

To improve lubricity of a simulated blood vessel simply and stably.SOLUTION: A simulated blood vessel is formed by a gel of polyvinyl alcohol containing a specific group which is a carboxyl group or a salt thereof.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The technology disclosed herein relates to simulated blood vessels. [Background technology]

[0002] Percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA) are widely performed to restore blood flow at narrowed or blocked areas of blood vessels (hereinafter referred to as "lesions"). PTA and PTCA (hereinafter referred to as "PTA, etc.") employ various procedures, such as balloon dilatation.

[0003] A procedure using the balloon dilation method is performed, for example, by the following procedure: A guidewire is inserted into a blood vessel and advanced until it passes through the lesion within 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 inflated, expanding the blood vessel wall at the lesion from the inside. This procedure secures a blood passage and restores blood flow.

[0004] PTA and other procedures require delicate manipulation by the operator, and the position and condition of the lesion in the blood vessel vary from patient to patient, making it difficult to master such procedures. Therefore, various simulated blood vessels that mimic blood vessels have been proposed for use in training to improve PTA and other procedures. For example, a simulated blood vessel made of polyvinyl alcohol (hereinafter referred to as "PVA") gel (hereinafter referred to as "PVA gel") has been proposed (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-8213 Summary of the Invention [Problem to be solved by the invention]

[0006] Conventional simulated blood vessels formed from PVA gel lack lubricity compared to real blood vessels, and there is room for improvement in terms of their approximation to real blood vessels.

[0007] In order to improve the lubricity of simulated blood vessels formed from PVA gel, methods such as treating the PVA gel with hot water or homogenizing the microcrystals of the PVA gel are conceivable. However, the hot water treatment method has a short duration of the lubricity improvement effect and is uneven in the lubricity improvement effect, making it impossible to obtain simulated blood vessels with consistently high lubricity. Furthermore, the method of homogenizing the microcrystals requires a complex process of hybridizing PVA gel prepared by the cast dry gel method with a general PVA gel, making it difficult to easily obtain simulated blood vessels with high lubricity.

[0008] As described above, conventionally, there is a problem that it is not possible to easily and stably obtain a simulated blood vessel having high lubricity similar to that of a real blood vessel. Note that this problem is not limited to simulated blood vessels used in training to improve techniques such as PTA, but is a problem common to simulated blood vessels in general.

[0009] This specification discloses a technique that can solve the above-mentioned problems. [Means for solving the problem]

[0010] The technology disclosed in this specification can be realized, for example, in the following forms.

[0011] (1) The simulated blood vessel disclosed in this specification is formed from a polyvinyl alcohol gel containing a specific group, which is a carboxyl group or a salt thereof. This simulated blood vessel can easily and stably improve the lubricity of the simulated blood vessel, thereby realizing a simulated blood vessel with high lubricity similar to that of a real blood vessel.

[0012] (2) In the simulated blood vessel, the ratio of the total number of the specific groups to the total number of hydroxyl groups, acetate groups, and the specific groups in the polyvinyl alcohol gel may be 0.2 mol % or more. This simulated blood vessel can effectively improve the lubricity of the simulated blood vessel, and can realize a simulated blood vessel with lubricity very close to that of a real blood vessel.

[0013] The technology disclosed in this specification can be realized in various forms, such as a simulated blood vessel, a biological model including a simulated blood vessel, a training kit including a biological model, a simulator including a biological model, and methods for manufacturing these. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is an explanatory diagram showing a schematic external configuration of a simulated blood vessel 10 according to the present embodiment. [Figure 2] Explanatory diagram showing performance evaluation results DETAILED DESCRIPTION OF THE INVENTION

[0015] A. Implementation: A-1. Configuration of simulated blood vessel 10: 1 is an explanatory diagram showing a schematic external configuration of a simulated blood vessel 10 according to this embodiment. The simulated blood vessel 10 is a device that simulates an actual blood vessel. The simulated blood vessel 10 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 for evaluating the performance of medical devices such as guidewires used in PTA.

[0016] 1, the simulated blood vessel 10 is a substantially cylindrical member having a hollow portion 12. The outer diameter of the simulated blood vessel 10 is, for example, about 10 to 50 mm, and the inner diameter of the simulated blood vessel 10 is, for example, about 5 to 45 mm.

[0017] The simulated blood vessel 10 is formed from a polyvinyl alcohol gel (PVA gel) obtained by gelling polyvinyl alcohol (PVA). More specifically, the simulated blood vessel 10 is formed from a physically crosslinked gel obtained by gelling PVA through physical crosslinking. Here, in this specification, "gel" means a substance that is in a gel state at room temperature or the temperature at which the simulated blood vessel 10 is used (e.g., 20°C to 50°C). Furthermore, a physically crosslinked gel is a gel crosslinked by non-covalent bonds such as hydrogen bonds or ionic bonds, and is distinguished from a chemically crosslinked gel crosslinked by covalent bonds. The simulated blood vessel 10 of this embodiment is formed from PVA gel and therefore has good flexibility similar to that of a real blood vessel.

[0018] PVA can be obtained by, for example, saponifying polyvinyl acetate obtained by polymerizing vinyl acetate monomer. In this embodiment, the saponification degree of the PVA used to form the simulated blood vessel 10 is preferably 90 mol % or more, and more preferably 98 mol % or more.

[0019] In this embodiment, the PVA gel used to form the simulated blood vessel 10 contains a carboxyl group or a salt group thereof. Hereinafter, the carboxyl group or a salt group thereof will also be referred to as a "specific group." The PVA gel containing a specific group means that some of the hydroxyl groups contained in the PVA used to form the PVA gel have been substituted with the specific group. Because the specific group is highly hydrophilic, the simulated blood vessel 10 of this embodiment, formed from the PVA gel containing the specific group, has high lubricity similar to that of an actual blood vessel. An example of the salt group of the carboxyl group contained in the PVA is a sodium carboxylate group. PVA containing a sodium carboxylate group is represented by the following structural formula (1): [ka]

[0020] The content of the specific group in the PVA gel used to form the simulated blood vessel 10 is preferably 0.2 mol% or more, more preferably 0.3 mol% or more, and even more preferably 0.4 mol% or more, from the viewpoint of improving the lubricity of the simulated blood vessel 10 and making the simulated blood vessel 10 more similar to a real blood vessel. On the other hand, if the content of the specific group in the PVA gel is excessive, the specific group inhibits the hydrogen bonds between the hydroxyl groups that constitute the physical crosslinks, thereby reducing the strength (elasticity) of the PVA gel. Therefore, from the viewpoint of ensuring the strength of the PVA gel and maintaining the shape of the simulated blood vessel 10 independently, the content of the specific group in the PVA gel used to form the simulated blood vessel 10 is preferably 0.7 mol% or less, more preferably 0.6 mol% or less. Note that, in this specification, the content of the specific group in the PVA gel refers to the ratio (mol%) of the total number of specific groups to the total number of hydroxyl groups, acetate groups, and specific groups.

[0021] The content of specific groups in the PVA gel forming the simulated blood vessel 10 can be determined by an appropriate combination of NMR (nuclear magnetic resonance), FT-IR (Fourier transform infrared spectroscopy), elemental analysis, X-ray fluorescence analysis, and neutralization titration. For example, in the case of PVA containing sodium carboxylate groups as specific groups, the amounts of hydroxyl groups, acetate groups, and carboxylate groups can be quantified by FT-IR. If necessary, the amount of sodium atoms can be identified by elemental analysis such as EDX (energy dispersive X-ray analysis). For example, the sodium content can be detected using EDX elemental analysis and compared with the elemental amount of the forming unit, thereby indirectly calculating the content of sodium carboxylate groups in the PVA gel.

[0022] A-2. Method for manufacturing simulated blood vessel 10: The simulated blood vessel 10 of this embodiment can be produced, for example, by the following method.

[0023] The PVA gel used to form the simulated blood vessel 10 can be obtained as a physically crosslinked gel by gelling PVA using a known method, such as the freeze-thaw method. The freeze-thaw method involves adding PVA to water and heat-treating it to prepare a PVA aqueous solution of a predetermined concentration, and then repeatedly freezing and thawing the PVA aqueous solution a predetermined number of times to obtain a physically crosslinked gel. In this case, a PVA containing a specific group at a predetermined content is used as the PVA used to form the gel. Alternatively, a mixture of PVA with and without the specific group may be used as the PVA used to form the gel.

[0024] When producing the PVA gel described above, the PVA resin dissolved in hot water or the like is poured into a hollow mold made of acrylic resin or the like to form the simulated blood vessel 10. The model mold can be produced, for example, by outputting information on the actual blood vessel structure using a 3D printer or the like, and the shape of the PVA simulated blood vessel can be freely produced to fit the mold.

[0025] A-3. Advantages of this embodiment: As described above, the simulated blood vessel 10 of this embodiment is formed from a polyvinyl alcohol gel having a specific group, which is a carboxyl group or a salt group of the carboxyl group or a salt group of the carboxyl group. Therefore, according to the simulated blood vessel 10 of this embodiment, the lubricity of the simulated blood vessel 10 can be easily and stably improved, and a simulated blood vessel 10 having high lubricity close to that of a real blood vessel can be realized.

[0026] Furthermore, in the polyvinyl alcohol gel that is the material for forming the simulated blood vessel 10 of this embodiment, the ratio of the total number of specific groups to the total number of hydroxyl groups, acetate groups, and specific groups is preferably 0.2 mol % or more. With this configuration, the lubricity of the simulated blood vessel 10 can be effectively improved, and a simulated blood vessel 10 having lubricity very close to that of a real blood vessel can be realized.

[0027] A-4. Performance evaluation: The simulated blood vessel 10 formed from PVA gel was evaluated for strength and lubricity. Figure 2 is an explanatory diagram showing the results of the performance evaluation.

[0028] As shown in Figure 2, in this performance evaluation, six samples (samples S1 to S6) of simulated blood vessel 10 formed from PVA gel were prepared, and for each sample, the storage modulus (G') as an index value of strength (elasticity) and the static friction coefficient as an index value of lubricity were measured, and evaluation was performed based on each measured value.

[0029] The samples differed in the content of specific groups (sodium carboxylate groups in this performance evaluation) in the PVA gel, which was the material for forming the simulated blood vessel 10. That is, the PVA gel in sample S1 did not contain the specific group, while the PVA gels in samples S2 to S6 contained the specific group. Among samples S2 to S6, the larger the sample number, the greater the content of specific groups in the PVA gel. Note that, in this performance evaluation, samples S2 to S6 were prepared by mixing PVA (molecular weight: 1700, degree of saponification: 98 mol % or more) that did not contain specific groups with PVA (molecular weight: 1800, degree of saponification: 99 mol %) that contained a predetermined proportion (4 mol %) of specific groups (sodium carboxylate groups), in such a ratio that the content of specific groups determined for each sample was achieved, thereby adjusting the content of specific groups in each sample.

[0030] The storage modulus, which is an index value of strength (elasticity), was measured as follows. First, PVA gel sheets with varying contents of carboxylic acid-containing PVA were prepared using a glass petri dish of φ150 × 25 mm. The prepared gel sheets were molded into shapes of 10 mm (height) × 10 mm (width) × 5 mm (thickness), and measurements were carried out using a dynamic viscoelasticity measuring device DMA7100 (manufactured by Hitachi High-Tech Corporation). For the measurements, a shear measuring jig was used, and measurements were repeated five times at a temperature of 30°C and an amplitude width of 10 μm, and the average value was used as the measured value. When the storage modulus was 1.0 × 10 4 If the storage modulus is 5.0 × 10 Pa or more, the strength is evaluated as "extremely high (A)" and the storage modulus is 5.0 × 10 3 Pa or more, 1.0×104 When the storage modulus is less than 1.0 × 10 Pa, the strength is evaluated as "sufficiently high (B)". 3 Pa or more, 5.0×10 3 When the storage modulus is less than 1.0 × 10 Pa, the strength is evaluated as "high (C)" 3 If the strength was less than 100 Pa, the strength was rated as "low (D)".

[0031] The static friction coefficient, an index of lubricity, was measured as follows. PVA gel sheets containing various amounts of carboxylic acid-containing PVA were prepared in a φ150 × 25 mm glass Petri dish. The smooth glass contact surface was placed facing up, and a portable tribometer Type: 94i-II (Shinto Scientific Co., Ltd.) was placed on top of the sheets to measure the static friction coefficient. The contact surface of the portable tribometer was stainless steel, and all subsequent static friction coefficients were measured relative to the stainless steel. To prevent the PVA gel sheet from drying out, it was immersed in distilled water until immediately before measurement. Within 5 minutes of removal, the static friction coefficient was measured 10 times in succession, and the average value was used as the measured value. Note that the value "0.000" in Figure 2 indicates that the static friction coefficient could not be measured. If the static friction coefficient was 0.005 or less, the lubricity was rated as "extremely high (A)." If the static friction coefficient was greater than 0.005 and less than or equal to 0.007, the lubricity was rated as "sufficiently high (B)." If the static friction coefficient was greater than 0.007 and less than or equal to 0.009, the lubricity was rated as "high (C)." If the static friction coefficient was greater than 0.009, the lubricity was rated as "low (D)."

[0032] For the overall evaluation, if one of strength or lubricity was rated as "extremely high (A)" and the other was rated as "sufficiently high (B)" or higher, the overall performance was rated as "extremely high (A)." If both strength and lubricity were rated as "sufficiently high (B)" or higher, excluding cases where the overall performance was rated as A, the overall performance was rated as "sufficiently high (B)." If both strength and lubricity were rated as "high (C)" or higher, excluding cases where the overall performance was rated as A or B, the overall performance was rated as "high (C)." If either strength or lubricity was rated as "low (D)," the overall performance was rated as "low (D)."

[0033] For sample S1, the lubricity was evaluated as "low (D)", and therefore the overall performance was evaluated as "low (D)". In sample S1, the PVA gel does not contain a specific group, which is thought to be why the lubricity of the PVA gel is very low and the lubricity was evaluated as "low (D)".

[0034] On the other hand, samples S2 to S6 were rated as "high (C)" or higher in both strength and lubricity, and therefore their overall performance was rated as "high (C)" or higher. It is believed that the PVA gel in samples S2 to S6 contains specific groups, which increases the lubricity of the PVA gel, leading to the lubricity evaluation of "high (C)" or higher. Therefore, this performance evaluation confirms that if the PVA gel, which is the material forming the simulated blood vessel 10, contains specific groups, the lubricity of the simulated blood vessel 10 can be improved, and a simulated blood vessel 10 with high lubricity close to that of a real blood vessel can be realized.

[0035] According to this performance evaluation, from the viewpoint of further improving the lubricity of the simulated blood vessel 10 to obtain a simulated blood vessel 10 that is closer to a real blood vessel, it is preferable that the content of the specific group in the PVA gel that is the material for forming the simulated blood vessel 10 is 0.2 mol% or more. Furthermore, from the viewpoint of improving the strength and lubricity of the simulated blood vessel 10 in a well-balanced manner, it is more preferable that the content of the specific group in the PVA gel that is the material for forming the simulated blood vessel 10 is 0.3 mol% or more and 0.7 mol% or less, and even more preferably 0.4 mol% or more and 0.6 mol% or less.

[0036] B. Variations: The technology disclosed in this specification is not limited to the above-described embodiments, and can be modified into various forms without departing from the spirit thereof, for example, the following modifications are also possible.

[0037] The configuration of the simulated blood vessel 10 in the above embodiment is merely an example and can be modified in various ways. For example, although the simulated blood vessel 10 is substantially cylindrical in the above embodiment, the simulated blood vessel 10 may have other shapes, such as a cylindrical shape with a polygonal or elliptical cross section. Furthermore, although the simulated blood vessel 10 has a single layer configuration in the above embodiment, the simulated blood vessel 10 may have a multi-layer configuration. In this case, the compositions of the PVA gels forming the layers of the simulated blood vessel 10 may be different from each other.

[0038] In the above embodiment, the simulated blood vessel 10 is formed from a physically cross-linked gel in which PVA is gelled by physical cross-linking, but the simulated blood vessel 10 may also include a chemically cross-linked gel in which PVA is gelled by chemical cross-linking.

[0039] The manufacturing method of the simulated blood vessel 10 in the above embodiment is an example, and the simulated blood vessel 10 may be manufactured by other methods. [Explanation of symbols]

[0040] 10: Simulated blood vessel 12:Hollow part

Claims

[Claim 1] A simulated blood vessel, It is formed by a gel of polyvinyl alcohol containing a specific group which is a sodium salt group of a carboxyl group, a ratio of the total number of the specific groups to the total number of hydroxyl groups, acetate groups, and the specific groups in the polyvinyl alcohol gel is 0.4 mol% or more and 0.6 mol% or less; Simulated blood vessels.

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