JP2018178069A - Hydrogel structure, method for producing the same, active energy ray-curable liquid composition, and use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hydrogel structure having a hollow tube structure having excellent transparency, useful as a blood vessel model, etc., and having a good usability of a surgical device such as an electric knife. SOLUTION: This is a hydrogel structure having a hollow tube structure having an inner diameter of 1.0 mm or less and having a transmittance of 80% or more in a visible light region. An embodiment in which the inner diameter is 0.3 mm or less, an embodiment in which the transmittance in the visible light region is 90% or more, and an embodiment in which a solid material whose phase changes to liquid by heat exists in the hollow of the hollow tube structure. Etc. are preferable. [Selection diagram] None

Description

  The present invention relates to a hydrogel structure, a method for producing the same, an active energy ray-curable liquid composition, and a use.

Vascular treatments mainly include treatment of aneurysms (aneurysms), bypassing of blood vessels, cutting, anastomosis and the like.
These blood vessel treatments are often performed by intubation of a catheter in the form of a wire in the blood vessel. With regard to the catheter intubation, it is necessary to carry out technique training, but the technique training is carried out using a non-human animal when not using a human body or using a blood vessel model.

However, in the case of using a non-human animal, since blood vessels exist in the body, catheter intubation is performed by irradiating the affected area with X-rays to visualize the blood vessels. Therefore, there is a problem that the amount of X-ray exposure to the operator increases when the technique training is repeatedly performed.
Therefore, a catheter treatment simulator formed of a transparent material has been proposed (see, for example, Patent Document 1).

  In addition, a blood vessel model (see, for example, Patent Document 2) imitating a patient's blood vessel, a blood vessel lesion model (for example, see Patent Document 3) formed of a plurality of small lesion parts having different hardnesses A method for producing a blood vessel model (see, for example, Patent Document 4) has been proposed.

  Furthermore, organ models made of silicone, urethane elastomer, styrene elastomer or the like are used for practice practice such as surgery. Surgeons and auxiliary staffs are also required to improve the level of procedure above a certain level in order to improve the post-operative recovery of patients and improve the quality of life (QOL). Therefore, it is required to provide an organ model that is more similar to human organs in terms of feel, internal structure, and usability of surgical devices such as ultrasonic scalpels and electric scalpels.

Also, in recent years, in organ models made of hydrogel, even when blood vessels are arranged, there is no exudation of simulated blood imitating blood when the blood vessels are incised, and there is a problem that the realistic sense of surgical training is lacking. In order to give a sense of reality in the surgical training model, it is required that simulated blood is released when the blood vessel in the organ model is cut.
Then, the molding material for organ models which mainly has polyvinyl alcohol is proposed as an organ model aiming at reproducing the texture of a human organ (for example, refer patent document 5).
Furthermore, there has been proposed an organ model using a material which is liquefied by the heat of the heat generating device to elute simulated blood when cut by a heat generating device such as an electric scalpel (see, for example, Patent Document 6).

  An object of the present invention is to provide a hydrogel structure having a hollow tubular structure which has excellent transparency, is useful as a blood vessel model and the like, and has a good feeling of use of a surgical device such as an electric scalpel.

  The hydrogel structure of the present invention as means for solving the above problems has a hollow tube structure with an inner diameter of 1.0 mm or less, and the transmittance in the visible light region is 80% or more.

  According to the present invention, it is possible to provide a hydrogel structure having a hollow tubular structure which is excellent in transparency, is useful as a blood vessel model and the like, and has a good feeling of use of a surgical device such as an electric scalpel.

FIG. 1 is a schematic view showing an example of a blood vessel model (hydrogel structure) of the present invention. FIG. 2A is a schematic view showing an example of a blood vessel model (hydrogel structure) of the present invention. FIG. 2B is a schematic view showing another example of the blood vessel model (hydrogel structure) of the present invention. FIG. 3A is a schematic top view showing an example of a hydrogel structure attached with a transparent hard body. FIG. 3B is a schematic side view showing an example of a hydrogel structure attached with a transparent hard body. FIG. 4 is a schematic view showing an example of a process for producing a shaped body using a three-dimensional shaping apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 5 is a schematic view showing an example (laminate modeling method) of a three-dimensional modeling apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet discharge method. FIG. 7 is a schematic view showing an organ model whose outer shape is a shape simulating the shape of an organ (liver) as one embodiment of the hydrogel structure of the present invention.

(Hydrogel structure, blood vessel model, and organ model)
The hydrogel structure of the present invention has a hollow tube structure having an inner diameter of 1.0 mm or less, and has a transmittance of 80% or more in the visible light region. It is preferable that the hydrogel structure further includes a mineral and a polymer, and the hydrogel includes water in a three-dimensional network structure formed by complexing the polymer and the mineral. . In addition, the said hydrogel means the gel which contains water as a main component.
The hydrogel structure of the present invention has a problem that the conventional catheter treatment simulator is limited in the manufacturing method from the materials used, and can not be applied to 3D printing that can reproduce the complicated shape and the shape along the patient's personal data. However, the blood vessel model to be produced can be arranged only on a two-dimensional plane, and has the disadvantage that the actual three-dimensional three-dimensional structure can not be reproduced, and can not be applied to preoperative simulation for treating affected areas of three-dimensional structure. It is based on the finding that there is a problem of
In addition, the hydrogel structure of the present invention is produced by three-dimensionally shaping a flexible material such as silicone rubber in a conventional blood vessel model, but is an opaque model, and the texture is also an actual blood vessel and Are based on the finding that they have the problem of being different.
Furthermore, the hydrogel structure of the present invention has a problem that, in the conventional vascular lesion model, a plurality of materials are required to form a plurality of small lesion parts having different hardnesses. In addition, it is based on the finding that it is difficult to perform modeling based on patient personal data because of modeling using a mold, and it is difficult to reproduce a detailed structure.
Furthermore, although the hydrogel structure of the present invention can form a somewhat complicated shape by the conventional method of producing a blood vessel model, the permeability of the blood vessel model is not high, and the texture is also an actual blood vessel and Are based on the finding that they have the problem of being different.
Moreover, the hydrogel structure of the present invention is based on the finding that the conventional organ model has a problem that the feel, the internal structure, and the feeling of use are different from those of a real human organ.

The blood vessel model of the present invention comprises the hydrogel structure of the present invention.
The organ model of the present invention comprises the hydrogel structure of the present invention, and its outer shape is a shape that simulates the shape of an organ.

  The hydrogel structure, blood vessel model, and organ model of the present invention can be suitably used for catheter intubation procedure training or preoperative simulation.

  The hydrogel structure may be a hollow tube having an inner diameter of 1.0 mm or less, and the hydrogel structure itself is a hollow tube having a hollow diameter of 1.0 mm or less. It is preferred to have a tubular structure. For example, in the case of a blood vessel model, a blood vessel having an inner diameter of 1.0 mm or less and a blood vessel having an inner diameter of 1.0 mm or more continuously and bifurcatedly connect to a blood vessel closer to an actual human body. It is possible to reproduce the net.

The hydrogel structure of the present invention has a hollow tube structure having an inner diameter of 1.0 mm or less, preferably 0.5 mm or less, and more preferably 0.3 mm or less. The inner diameter can be measured by a method of mechanically measuring like a caliper, a method of measuring using a microscope or the like, or a method of measuring by a one-shot 3D shape measuring instrument (for example, manufactured by Keyence Corporation) is there.
It is also possible to insert the inside of the hollow tube structure and measure the inside diameter by using a catheter having a known outside diameter and the like.
In the hydrogel structure of the present invention, the tip of the hollow tube may be thin, the middle portion may be thin, and one end opening may be thinner than the other end opening. Moreover, it may be branched or dendritic, and a vascular shape as shown in FIG. 1 is preferable.
The structure may be in communication, there may be an occlusion at a portion of the tube, or an occlusion at the end. Also, the hollow tube may be a double tube or may be stacked.

  Examples of the hollow tube structure include blood vessels, lymphatic vessels, esophagus, nasal cavities, external auditory canal, pharynx, larynx, oral cavity, trachea, bronchi, bronchioles, stomach, small intestine (eg, duodenum, jejunum, ileum, etc.), large intestine (eg, For example, it can be used for various kinds of preoperative simulation, technique practice, etc. by forming into a shape such as a cecum, colon, rectum, anal canal, etc., pancreatic duct, gallbladder duct, urethra, bile duct and the like.

The hydrogel structure having the blood vessel structure can be suitably used as a blood vessel model.
There is no restriction | limiting in particular as said blood-vessel model, According to the objective, it can select suitably, For example, what reproduced the artery, the vein, the capillary, etc. is mentioned.
FIG. 1 is a schematic view showing an example of a blood vessel model (hydrogel structure) of the present invention. As shown in FIG. 1, the blood vessel wall 51 and the blood vessel cavity 50 are provided. By adjusting the thickness of the blood vessel wall, it is possible to change the texture when inserting the catheter. For example, by increasing the thickness of the vascular membrane, it is possible to reproduce, for example, the texture of a blood vessel or the like that has hardened due to a disease or the like.
As the hydrogel structure, in order to allow a fluid imitating blood to flow in the blood vessel model, a fluid inlet / outlet can be provided and a fluid circulation device can be attached.

  FIG. 2A is a schematic view showing an example of the hydrogel structure of the present invention. As shown in FIG. 2A, handling and storage properties are improved by covering the periphery of a blood vessel model 52 having a blood vessel cavity 50 and a blood vessel wall 51 made of hydrogel with another structure 53. Can. Note that the other structure 53 may be a hydrogel, in which case the other structure 53 may also serve as the blood vessel wall 51 (the other structure 53 being a hydrogel). Hydrogel structure in which the cavity 50 is contained.

FIG. 2B is a schematic view showing another example of the hydrogel structure of the present invention. As shown in FIG. 2B, in a blood vessel model having a blood vessel cavity 50 and a blood vessel wall 51 consisting of a first hydrogel body, a site such as a lump 55 having a low elastic modulus as compared with a normal blood vessel. The vascular lesion model can also be reproduced by reproducing the second hydrogel with a second hydrogel body having a modulus of elasticity different from that of the first hydrogel.
In addition, a blood vessel model having a blood vessel wall composed of at least a first hydrogel body and a second hydrogel body can also be produced, whereby the texture of a hardened blood vessel due to a disease or the like can be reproduced.

  Further, the other structural body 53 may have an outer shape imitating an organ, and can be suitably used as an organ model.

  The organ model is not particularly limited and can be appropriately selected according to the purpose. It is possible to reproduce any visceral site in the human body, for example, as shown in FIG. 7, brain, heart, bladder. Liver, kidney, pancreas, spleen, gallbladder, uterus, etc.

The transmittance of the hydrogel structure in the visible light region is 80% or more, preferably 85% or more, more preferably 90% or more, and particularly preferably 95% or more. The inside of a hydrogel structure can be visualized as the said transmittance | permeability is 80% or more. The transmittance can be measured, for example, using a spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, using an integration unit) or the like. The visible light range means a wavelength range of 400 nm or more and 700 nm or less.
As a method of measuring the transmittance, the hydrogel structure is cut in the longitudinal direction to form a flat sample. Under the present circumstances, in order to prevent the irregular reflection under the influence of the unevenness | corrugation of the sample surface, it measures in the state which used the integrating sphere unit. Moreover, when measuring details, it is also possible to measure using an optical fiber etc. The flat shape is sufficient as long as the irradiation light can be applied to the flat portion of the sample, and the shape of the sample may have a curve or may be planar.

The arithmetic mean surface roughness of the inner wall of at least a part of the hollow tube structure of the hydrogel structure is not particularly limited, but is 50 μm or less from the viewpoint of the visibility from the outside and the inner wall reproducibility of blood vessels and the like. Is preferred. In addition, the slipperiness of the catheter when the catheter is inserted into the blood vessel can be reproduced. Besides, the inner wall of an organ such as the large intestine can also be reproduced, and the arithmetic mean surface roughness can be adjusted so that the endoscope does not get caught on the inner wall when the endoscope is inserted. 40 micrometers or less are preferable, as for the said arithmetic mean surface roughness, 30 micrometers or less are more preferable, and 20 micrometers or less are especially preferable. The lower limit of the arithmetic mean surface roughness is not particularly limited, but is preferably 0.1 μm or more from the viewpoint of the reproducibility of the inner wall texture of blood vessels and organs.
The arithmetic mean surface roughness is a surface roughness in an area of 500 μm square. The arithmetic mean surface roughness can be measured, for example, using a laser microscope (device name: VK-X100, manufactured by Keyence Corporation). The arithmetic mean surface roughness is preferably uniform throughout the hollow tube inner wall.

The static friction coefficient of the inner wall of at least a part of the hollow tube structure of the hydrogel structure is preferably 0.1 or less, more preferably 0.05 or less. When the static friction coefficient is 0.1 or less, a hydrogel structure closer to the texture of a living body and closer to an actual blood vessel or the like when a medical device such as a catheter is inserted can be produced. The lower limit value of the static friction coefficient is not particularly limited, but is preferably 0.01 or more, and more preferably 0.02 or more.
The coefficient of static friction is measured from the cut surface by cutting the hydrogel structure in the longitudinal direction at the center of the hollow tube. For example, using a ball-on-plate method with a surface property measuring instrument (device name: TYPE: 38, manufactured by Shinto Scientific Co., Ltd.), the probe may be dropped onto the blood vessel equivalent part and the static friction coefficient may be measured by point contact. it can. The coefficient of static friction is preferably uniform throughout the inner wall of the hollow tube.

  The static friction coefficient of the inner wall of at least a part of the hollow tubular shape of the hydrogel structure is, for example, a solvent, an oil, a surfactant that can be used for a wet wire drawing lubricant, etc. in the hydrogel structure. It can be adjusted by applying These may be applied to the inner wall of the hydrogel structure or may flow into the tube in the form of a liquid.

  There is no restriction | limiting in particular as said solvent, According to the objective, it can select suitably, For example, water, an organic solvent, etc. are mentioned. These may be used alone or in combination of two or more. Among these, an organic solvent is preferable from the viewpoint of preventing absorption into the hydrogel structure, and a high boiling point solvent is preferable from the viewpoint of preventing drying.

  There is no restriction | limiting in particular as said oil, According to the objective, it can select suitably, For example, synthetic oils, such as mineral oil and silicone, vegetable oil, wax, animal oil etc. are mentioned.

  There is no restriction | limiting in particular as said surfactant, According to the objective, it can select suitably, For example, nonionic surfactant, anionic surfactant, cationic surfactant, amphoteric surfactant, etc. It can be mentioned. These may be used alone or in combination of two or more. Among these, non-ionic surfactants are preferable because they are less susceptible to the influence of the electrolyte in the hydrogel structure.

  There is no restriction | limiting in particular as said nonionic surfactant, According to the objective, it can select suitably, For example, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene alkyl phosphoric acid ester, poly Examples thereof include oxyethylene fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, fatty acid monoglyceride, sucrose fatty acid ester, higher fatty acid alkanolamide and the like.

  There is no restriction | limiting in particular as said anionic surfactant, According to the objective, it can select suitably, For example, sulfuric acid alkyl, sulfuric acid alkyl ether, sulfuric acid alkylamide ether, sulfuric acid alkylaryl polyether, sulfuric acid monoglyceride, alkyl sulfone Acid, alkylamidosulfonic acid, alkylaryl sulfonic acid, olefin sulfonic acid, paraffin sulfonic acid, alkyl sulfosuccinic acid, alkyl ether sulfosuccinic acid, alkylamido sulfosuccinic acid, alkyl succinamic acid, alkyl sulfoacetic acid, alkyl phosphate, alkyl phosphate alkyl ether, And metal salts such as acyl sarcosine, acyl isethionate, and acyl-N-acyl taurine, ammonium salts, amine salts, amino alcohol salts, magnesium salts, basic amino acid salts and the like. .

  There is no restriction | limiting in particular as said cationic surfactant, According to the objective, it can select suitably, For example, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, stearyl trimethyl ammonium chloride, behenyl trimethyl ammonium chloride, chloride And cetyl trimethyl ammonium, myristyl dimethyl benzyl ammonium chloride, ethyl lanolin ethyl acetate, fatty acid amino propyl ethyl ammonium, dicocoyl dimethyl ammonium chloride, lauryl trimethyl ammonium chloride, ethyl sulfate branched fatty acid amino propyl ethyl dimethyl ammonium and the like.

  There is no restriction | limiting in particular as said amphoteric surfactant, According to the objective, it can select suitably, For example, the amide amino acid type amphoteric surfactant which has a C8 or more and 24 or less alkyl group, an alkenyl group, or an acyl group , Secondary amide type or tertiary amide type imidazoline type amphoteric surfactant, carbobetaine type having an alkyl group having 8 to 24 carbon atoms, alkenyl group or acyl group, amide betaine type, sulfobetaine type, hydroxysulfobetaine And amidosulfobetaine amphoteric surfactants and the like. Specifically, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, stearyldihydroxyethylbetaine, laurylhydroxysulfobetaine, bis (stearyl-N-hydroxyethylimidazoline) chloroacetate complex, lauryl dimethylamino Betaine acetate, cocoylamidopropyl betaine, cocoyl alkyl betaine and the like can be mentioned.

The hydrogel structure preferably satisfies at least one of the following (1) to (2).
(1) At least a part of the hollow tubular shape is in contact with a hydrogel (second hydrogel body) having a modulus of elasticity different from that of the hydrogel (first hydrogel body) constituting the hollow tube (a second hydrogel body) 2) The hollow tube shape is formed of at least two types of hydrogels having different elastic moduli

  The elastic modulus of the hydrogel structure (first hydrogel body) at 20% compression is preferably 0.1 MPa or more and 1 MPa or less, and more preferably 0.2 MPa or more and 0.8 MPa or less. The elastic modulus is measured by using a universal testing machine (AG-I, manufactured by Shimadzu Corporation), a load cell 1 kN, a compression jig for 1 kN, and a hydroderivative containing a cylindrical metal with a diameter of 1 mm as a main component The stress to compression on the load cell can be recorded on a computer by pressing into the gel structure, the stress against displacement can be plotted, and the modulus of elasticity can be measured. The elastic modulus can be controlled by adjusting the water content of the hydrogel structure.

  A hydrogel having the hollow tubular structure (first hydrogel body) 52 and hydrogel bodies (second hydrogel body) having different elastic moduli as shown in FIGS. 2A and 2B. In the case of a gel structure, the elastic modulus at 20% compression of the second hydrogel body 53 in FIG. 2A and the bump portion (second hydrogel body) 55 in FIG. 2B is 0.005 MPa or more and 0.1 MPa or less Is preferable, and 0.01 MPa or more and 0.05 MPa or less is more preferable. Moreover, as compressive strength at the time of 70% compression, 0.3 MPa or more and 1 MPa or less are preferable, and 0.4 MPa or more and 0.7 MPa or less are more preferable.

  Assuming that the elastic modulus of one portion in the hydrogel structure is X (MPa), and the elastic modulus of another portion adjacent to the one portion is Y (MPa), the absolute value of the elastic modulus change (| X As -Y |), it is 0.1 MPa or more, and 0.11 MPa or more is preferable. When the absolute value (| X-Y |) of the elastic modulus change is 0.1 MPa or more, the elastic modulus is different in the same hydrogel structure, so that it is more than a normal blood vessel such as an aneurysm in a blood vessel. The texture of the vascular lesion model as shown in FIG. 2B, which has a region with low elastic modulus, can be realized.

As the water content of the hydrogel structure having the hollow tubular structure, the water content of the hydrogel (second hydrogel) having an elastic modulus different from that of the hydrogel structure (first hydrogel) By being lower than that, the elastic modulus of the hydrogel structure can be made higher than the elastic modulus of the hydrogel having an elastic modulus different from that of the hydrogel structure, and the reproducibility of the actual texture of blood vessels is more excellent.
There is no restriction | limiting in particular as a moisture content of the hydrogel structure (1st hydrogel body) which has the said hollow tubular shape, Although it can select suitably according to the objective, 30 to 75 mass% Is preferred.
The water content (second hydrogel body) of the hydrogel having an elastic modulus different from that of the hydrogel structure is not particularly limited and may be appropriately selected depending on the purpose, but is 50% by mass or more and 90 or more. % Or less is preferred.
The water content can be measured, for example, using a heat-drying moisture meter (device name: MS-70, manufactured by A & D Co., Ltd.) or the like.

  The hydrogel structure is further optionally mixed with water, polymer, mineral, organic solvent, and other components by an appropriate method, inked as a hydrogel precursor, and the ink is cured by an appropriate method. You can get it.

<Polymer>
There is no restriction | limiting in particular as said polymer, Although it can select suitably according to the objective, Since a hydrogel has water as a main component, a water-soluble polymer is preferable. By containing the water-soluble polymer, the strength of the water-based hydrogel can be maintained.
The water solubility of the water-soluble polymer means, for example, one in which 90% by mass or more is dissolved when 1 g of the water-soluble polymer is mixed with 100 g of water at 30 ° C. and stirred.

  As said polymer, the polymer etc. which have an amido group, an amino group, a hydroxyl group, a tetramethyl ammonium group, a silanol group, an epoxy group etc. are mentioned, for example.

  The polymer may be a homopolymer (homopolymer), may be a heteropolymer (copolymer), may be unmodified, or may have a known functional group introduced. It may be well or in the form of a salt. Among these, homopolymers are preferred.

  The polymer can be obtained by polymerizing a polymerizable monomer. The polymerizable monomer will be described in the method for producing a hydrogel structure described later.

  The water-soluble polymer is obtained by polymerizing a polymerizable monomer, and as the polymerizable monomer, for example, acrylamide, N-substituted acrylamide derivative, N, N-di-substituted acrylamide derivative, N-substituted methacrylamide derivative, N, N-disubstituted methacrylamide derivatives and the like can be mentioned. These may be used alone or in combination of two or more.

  By polymerizing the polymerizable monomer, a water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethyl ammonium group, a silanol group, an epoxy group and the like can be obtained. The water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethyl ammonium group, a silanol group, an epoxy group or the like is an advantageous component for maintaining the strength of the aqueous gel.

  There is no restriction | limiting in particular as content of the said polymer, Although it can select suitably according to the objective, 0.5 mass% or more and 20 mass% or less are preferable with respect to hydrogel structure whole quantity.

Minerals
The mineral is not particularly limited and may be appropriately selected according to the purpose. However, since the hydrogel contains water as a main component, a layered clay mineral which can be dispersed uniformly in primary crystals in water is suitable. Preferably, water-swellable layered clay minerals are more preferred.

  The water-swellable layered clay mineral exhibits a state in which two-dimensional disc-like crystals having unit cells in the crystal are stacked, and when the water-swellable layered clay mineral is dispersed in water, each single layer state To separate into disc-shaped crystals.

The water-swellable clay mineral is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include water-swellable smectite and water-swellable mica. These may be used alone or in combination of two or more. Among these, water-swellable hectorite containing sodium as an interlayer ion, water-swellable montmorillonite, water-swellable saponite, and water-swellable synthetic mica are preferable, and a water-swellable hectorite is a highly elastic bolus. More preferable. The water swellability means that water molecules are inserted between the layers of the layered clay mineral and dispersed in water.
As said mineral, it may be synthesize | combined suitably, and a commercial item may be sufficient.

  There is no restriction | limiting in particular as said commercial item, According to the objective, it can select suitably, For example, synthetic hectorite (Laponite XLG, product made by RockWood), SWN (made by Coop Chemical Ltd. company), fluorinated hectorite SWF (made by Coop Chemical Ltd.) etc. are mentioned. These may be used alone or in combination of two or more.

  There is no restriction | limiting in particular as content of the said mineral, Although it can select suitably according to the objective, It is 1 mass% with respect to the hydrogel structure whole quantity from the point of the elasticity modulus and hardness of a hydrogel structure. The content is preferably 40% by mass or less, and more preferably 1% by mass to 25% by mass.

<Organic solvent>
In the present invention, an organic solvent can be added to enhance the moisture retention of the hydrogel structure.
Examples of the organic solvent include water-soluble organic solvents. The water solubility of the water soluble organic solvent means that the organic solvent can be dissolved in water in an amount of 30% by mass or more.

  There is no restriction | limiting in particular as said water-soluble organic solvent, According to the objective, it can select suitably, For example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol, alkyl alcohols having 1 to 4 carbon atoms such as tert-butyl alcohol; amides such as dimethylformamide, dimethylacetamide; ketones such as acetone, methyl ethyl ketone and diacetone alcohol or ketone alcohols; ethers such as tetrahydrofuran and dioxane; Ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1 Polyhydric alcohols such as 2,6-hexanetriol, thioglycol, hexylene glycol and glycerin; polyalkylene glycols such as polyethylene glycol and polypropylene glycol; ethylene glycol monomethyl (or ethyl) ether, diethylene glycol methyl (or ethyl) ether, Lower alcohol ethers of polyhydric alcohols such as triethylene glycol monomethyl (or ethyl) ether; alkanolamines such as monoethanolamine, diethanolamine and triethanolamine; N-methyl-2-pyrrolidone, 2-pyrrolidone, 1,3 -Dimethyl-2- imidazolidinone etc. are mentioned. These may be used alone or in combination of two or more. Among these, polyhydric alcohols, glycerin and propylene glycol are preferable, and glycerin and propylene glycol are more preferable from the viewpoint of moisture retention.

  As content of the said organic solvent, 10 mass% or more and 50 mass% or less are preferable with respect to hydrogel structure whole quantity. When the content is 10% by mass or more, the effect of preventing drying is sufficiently obtained. Moreover, a mineral is disperse | distributed uniformly as it is 50 mass% or less.

<Water>
As the water, for example, deionized water, ultrafiltered water, reverse osmosis water, pure water such as distilled water, ultrapure water, etc. can be used.
In the water, other components such as an organic solvent may be dissolved or dispersed depending on the purpose of imparting moisture retention property, imparting of antibacterial property, imparting conductivity, adjusting hardness, and the like.

  The content of water is preferably 10% by mass to 99% by mass, more preferably 50% by mass to 98% by mass, and particularly preferably 60% by mass to 97% by mass, based on the total amount of the hydrogel structure. preferable.

<Other ingredients>
There is no restriction | limiting in particular as said other component, According to the objective, it can select suitably, For example, a stabilizer, a surface treatment agent, a polymerization initiator, a coloring agent, a viscosity modifier, an adhesiveness imparting agent, oxidation Examples include inhibitors, antiaging agents, crosslinking accelerators, ultraviolet light absorbers, plasticizers, preservatives, dispersants, surfactants and the like.

In the hydrogel structure of the present invention, the surface is preferably covered with a transparent hard body.
FIG. 3A is a schematic top view showing an example of the hydrogel structure 60 to which the transparent hard body 61 is attached. FIG. 3B is a schematic side view showing an example of the hydrogel structure 60 to which the transparent hard body 61 is attached. As shown in FIGS. 3A and 3B, by covering the surface with a transparent hard body 61, the shape of the blood vessel model is further maintained to improve the handling property at the time of treatment and the preservation property of the blood vessel model ( The drying resistance and the antiseptic property can be improved, that is, the water vapor permeability and the oxygen permeability of the hard body can be reduced, and the appearance of the blood vessel model can be improved.

There is no restriction | limiting in particular as a forming material of the said hard body, According to the objective, it can select suitably, For example, highly transparent plastic materials, such as an acrylic resin and polycarbonate resin, highly transparent inorganic materials, such as glass Etc.
There is no restriction | limiting in particular as a shape of the said hard body, and average thickness, According to the objective, it can select suitably.
The water vapor permeability is preferably 500 g / m ² · d or less. The water vapor transmission rate can be measured, for example, by a water vapor transmission rate meter (device name: Lyssy L80, manufactured by SYSYTECH Co., Ltd.) or the like based on JIS K7129.
The oxygen permeability is preferably 100,000 cc / m ² / hr / atm or less. The oxygen permeability can be measured, for example, by a differential pressure type gas permeability meter (device name: Lyssy L100, manufactured by SYSYTECH) or the like based on JIS Z1702.

(Procedure trainer)
The technique exerciser of the present invention has at least one selected from a hydrogel structure, a blood vessel model, a structure, and an organ model, and at least one of a catheter and an endoscope, and further, as required. It has other members.

  There is no restriction | limiting in particular as said catheter, According to the objective, it can select suitably, For example, an angiographic catheter, a balloon catheter, cerebrovascular catheter, cancer catheter treatment, vascular indwelling catheter, suction indwelling catheter, urethra catheter Etc.

  There is no restriction | limiting in particular as said endoscope, According to the objective, it can select suitably, For example, a laryngoscope, a bronchoscope, an upper digestive tract endoscope, a duodenum endoscope, a small intestine endoscope, a large intestine Endoscope, thoracoscope, cystoscope, cholangioscope, angioscope, etc. are mentioned.

The hydrogel structure, blood vessel model and organ model of the present invention can be used for catheter intubation training and simulation before surgery.
The catheter intubation technique training referred to here is to intubate a catheter in a blood vessel model and train a procedure until reaching a target location. At this time, training is also included such as changing the thickness of the catheter according to the purpose, providing a stent, a wire, a balloon or the like at the tip and treating or installing the same at an assumed affected part.
It is also part of the training to select an optimal catheter according to the blood vessel shape, and it is useful to handle one or more catheters and the hydrogel structure of the present invention as a set.

In such training, it is preferable to resemble the actual intravascular condition. The blood vessel model or structure of the present invention is composed of a hydrogel, and its texture is very similar to that of a living body, which makes it a useful material. It is also useful to provide a mechanism for flowing the liquid through the hydrogel structure and to train in a state where blood flow is generated.
It is also a useful point of the present invention that, since there were few transparent blood vessel models in the past, training conducted by X-ray irradiation visualization could also be performed without risk of X-ray exposure. .

(Method of producing hydrogel structure)
Although the first embodiment of the method for producing a hydrogel structure of the present invention is not particularly limited, for example, a columnar core (a support-forming material, an active energy ray-curable liquid composition) is used. It can manufacture by forming a tubular part so that the above-mentioned pillared core part may be covered with a hydrogel formation material while forming a support body, and then removing the pillared core part. Under the present circumstances, it is preferable to produce using lamination | stacking modeling methods (The method of modeling a three-dimensional object by lamination | stacking by repetition of a layer formation process and a layer hardening process), such as the conventionally well-known material jet method. In addition, the said coating | coated core part should just be at least one part covered by the said hydrogel formation material, and it is preferable that all is covered. Moreover, it is preferable that both the said core part formation material (support body formation material) and the said hydrogel formation material are active energy ray hardening-type compositions. The number of repetitions differs depending on the size, shape, structure, etc. of the hydrogel structure to be produced, and can not be generally defined, but if the average thickness per layer is in the range of 10 μm to 50 μm, It is possible to form accurately and without peeling.

The second aspect of the method for producing a hydrogel structure of the present invention is a method for producing a hydrogel structure having a hollow tubular structure, wherein a columnar core portion is formed using a core portion forming material, and Covering the columnar core portion with a hydrogel forming material to form a tubular portion, wherein the core portion forming material is an active energy ray curable composition, and the active energy ray curable composition The cured product is a material that is liquefied by heat, and further includes other steps as necessary.
The second aspect of the method for producing a hydrogel structure does not include the step of removing the columnar core (removal step) in the first aspect of the method for producing a hydrogel structure.

  Hereinafter, an example of a method for producing a hydrogel structure by the material jet method will be described in detail.

<< layer formation process and layer formation means >>
The layer formation step is a step of discharging a hydrogel-forming material containing water and a polymerizable monomer and a support-forming material to be removed later to form a layer composed of these materials.
The support-forming material is applied to a position different from that of the hydrogel-forming material, and after curing, becomes a support for supporting the hydrogel component. In the present invention, in order to form a hollow tube structure, at the time of lamination, the hollow upper portion is supported by the support. The "position different from the hydrogel-forming material" means that the application position of the support-forming material and the application position of the hydrogel-forming material do not overlap, and the application position of the support-forming material And the application position of the hydrogel forming material may be adjacent to each other.

  The method for applying the forming material as the layer forming step is not particularly limited as long as the droplet can be applied to the target place with appropriate accuracy, and can be appropriately selected according to the purpose, for example , A dispenser system, a spray system, an inkjet system, etc. are mentioned. In addition, in order to implement these systems, a well-known apparatus can be used suitably.

  Among these, although the dispenser method is excellent in quantitative property of droplets, the application area becomes narrow, and the spray method can easily form a fine discharge, and the application area is wide and the application property is excellent. The quantitablity of the droplets is poor and scattering by the spray flow occurs. Therefore, in the present invention, the inkjet method is particularly preferable. The inkjet method has the advantage of better quantitative property of droplets compared to the spray method, and the advantage that the application area can be wider than the dispenser method, and it is preferable in that complex three-dimensional shapes can be formed accurately and efficiently. .

  When it is based on the said inkjet method, it has a nozzle which can discharge the said formation material. In addition, the nozzle in a well-known inkjet printer can be used suitably as this nozzle.

-Hydrogel-forming material (hydrogel precursor)-
The hydrogel-forming material contains water and a polymerizable monomer, preferably contains a mineral and an organic solvent, and further contains a polymerization initiator and other components as required.
As the water, the mineral, the organic solvent, and the other components, those similar to the hydrogel structure can be used.

--Polymerizable monomer--
The polymerizable monomer is a compound having one or more unsaturated carbon-carbon bonds, and is preferably a polymerizable monomer which is polymerized by active energy rays such as ultraviolet rays and electron beams.
Examples of the polymerizable monomer include monofunctional monomers and polyfunctional monomers. These may be used alone or in combination of two or more.
Examples of the polyfunctional monomer include bifunctional monomers, trifunctional monomers, and monomers having four or more functional groups.

  The monofunctional monomer is a compound having one unsaturated carbon-carbon bond, and examples thereof include acrylamide, N-substituted acrylamide derivative, N, N-disubstituted acrylamide derivative, N-substituted methacrylamide derivative, N, N -Disubstituted methacrylamide derivatives, other monofunctional monomers, etc. may be mentioned. These may be used alone or in combination of two or more.

  Examples of the N-substituted acrylamide derivative, the N, N-disubstituted acrylamide derivative, the N-substituted methacrylamide derivative, or the N, N-disubstituted methacrylamide derivative include, for example, N, N-dimethyl acrylamide (DMAA), N- An isopropyl acrylamide etc. are mentioned.

  Examples of the other monofunctional monomers include 2-ethylhexyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, acryloyl morpholine (ACMO), caprolactone-modified tetrahydrofurfuryl (meth ) Acrylate, isobornyl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, lauryl (meth) acrylate, 2-phenoxyethyl (meth) acrylate, isodecyl (meth) acrylate, isooctyl (meth) ) Acrylates, Tridecyl (meth) acrylates, caprolactone (meth) acrylates, ethoxylated nonylphenol (meth) acrylates, urethane (meth) aclays And the like. These may be used alone or in combination of two or more.

  By polymerizing the monofunctional monomer, a water-soluble polymer having an amido group, an amino group, a hydroxyl group, a tetramethyl ammonium group, a silanol group, an epoxy group and the like can be obtained.

  The water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethyl ammonium group, a silanol group, an epoxy group or the like is an advantageous component to maintain the strength of the blood vessel model.

  Examples of the bifunctional monomer include tripropylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, neopentyl glycol hydroxypivalic acid Ester di (meth) acrylate, hydroxypivalate neopentyl glycol ester di (meth) acrylate, 1,3-butanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (Meth) acrylate, 1,9-nonanediol di (meth) acrylate, diethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, tripropylene glycol Cole di (meth) acrylate, caprolactone modified hydroxypivalic acid neopentyl glycol ester di (meth) acrylate, propoxylated neopentyl glycol di (meth) acrylate, ethoxy modified bisphenol A di (meth) acrylate, polyethylene glycol 200 di (meth) acrylate And polyethylene glycol 400 di (meth) acrylate, methylene bis acrylamide and the like. These may be used alone or in combination of two or more.

  Examples of the trifunctional monomer include trimethylolpropane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, triallyl isocyanate, tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate, and ethoxylated trimethylolpropane. Tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, propoxylated glyceryl tri (meth) acrylate and the like can be mentioned. These may be used alone or in combination of two or more.

  Examples of the tetrafunctional or higher functional monomer include pentaerythritol tetra (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, penta ( Examples thereof include meta) acrylate esters and dipentaerythritol hexa (meth) acrylate. These may be used alone or in combination of two or more.

  There is no restriction | limiting in particular as content of the said monofunctional monomer, Although it can select suitably according to the objective, 1 mass% or more and 10 mass% or less are preferable with respect to the hydrogel formation material whole quantity, 1 mass% More than 5 mass% is more preferred. When the content is 1% by mass or more and 10% by mass or less, the dispersion stability of the mineral in the hydrogel-forming material is maintained, and the stretchability of the hydrogel structure is improved. The stretchability refers to the property of stretching when the hydrogel structure is pulled and not breaking.

  As content of the said polyfunctional monomer, 0.001 mass% or more and 1 mass% or less are preferable with respect to the hydrogel forming material whole quantity, and 0.01 mass% or more and 0.5 mass% or less are more preferable. The elastic modulus and hardness of the hydrogel structure obtained as the said content is 0.001 mass% or more and 1 mass% or less can be adjusted in an appropriate range.

  As content of the said polymerizable monomer, 0.5 mass% or more and 20 mass% or less are preferable with respect to hydrogel forming material whole quantity. The strength of the hydrogel structure can be made closer to that of human organs when the content is 0.5% by mass or more and 20% by mass or less.

--Polymerization initiator--
There is no restriction | limiting in particular as said polymerization initiator, According to the objective, it can select suitably, For example, a photoinitiator, a thermal-polymerization initiator, etc. are mentioned.
As said photoinitiator, the arbitrary substance which produces | generates a radical by irradiation of a light (especially ultraviolet-ray of wavelength 220 nm-400 nm) can be used.

  There is no restriction | limiting in particular as said photoinitiator, According to the objective, it can select suitably, For example, acetophenone, 2, 2- diethoxy acetophenone, p- dimethylamino acetophenone, benzophenone, 2-chloro benzophenone, p , P'-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, Michler's ketone, benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin n-propyl ether, benzoin isobutyl ether, benzoin n-butyl ether, Benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2-methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) -2-hydride Carboxymethyl-2-methylpropan-1-one, methyl benzoyl formate, 1-hydroxycyclohexyl phenyl ketone, azobisisobutyronitrile, benzoyl peroxide, and di -tert- butyl peroxide. These may be used alone or in combination of two or more.

  There is no restriction | limiting in particular as said thermal polymerization initiator, According to the objective, it can select suitably, For example, an azo initiator, a peroxide initiator, a persulfate initiator, a redox (oxidation-reduction) initiator Etc. These may be used alone or in combination of two or more. Among these, peroxide initiators are preferred.

  There is no restriction | limiting in particular as said peroxide initiator, According to the objective, it can select suitably, For example, potassium persulfate, sodium persulfate, ammonium persulfate, sodium peroxodisulfate, potassium peroxodisulfate etc. are mentioned. Be These may be used alone or in combination of two or more. Among these, potassium peroxodisulfate is preferred.

<< hardening process and hardening means >>
The curing step is a step of irradiating and curing active energy rays on predetermined regions of the hydrogel-forming material layer and the support-forming material layer formed in the curing means.

Examples of means for curing the layer include an ultraviolet (UV) irradiation lamp and an electron beam. Preferably, a mechanism for removing ozone is provided.
As a kind of said ultraviolet (UV) irradiation lamp, a high pressure mercury lamp, an ultra-high pressure mercury lamp, a metal halide, an ultraviolet-ray light emitting diode (UV-LED) etc. are mentioned, for example.
Although the said ultra-high pressure mercury lamp is a point light source, DeepUV type which made the light utilization efficiency high in combination with an optical system can irradiate light in a short wavelength region.
The metal halide is effective for coloring materials because the wavelength range is wide, and halides of metals such as Pb, Sn, and Fe are used, and can be selected according to the absorption spectrum of the polymerization initiator. There is no restriction | limiting in particular as a lamp used for hardening, According to the objective, it can select suitably, For example, commercially available things, such as H lamp made from Fusion System, D lamp, or V lamp, etc. It can be used.
There is no restriction | limiting in particular as an emission wavelength of the said ultraviolet-ray light emitting diode, According to the objective, it can select suitably, Although there exists a thing of 365 nm, 375 nm, 385 nm, 395 nm, 405 nm generally, Considering the influence of color, short wavelength emission is advantageous so that the absorption of the polymerization initiator is large. Among them, an ultraviolet light emitting diode (UV-LED) which generates less heat is used as an ultraviolet (UV) irradiation lamp in that it is used also for a three-dimensional object of the present invention which is a hydrogel susceptible to thermal energy. Is preferred.

  The hydrogel material layer after curing is preferably a hydrogel in which water and a component that dissolves in water are included in a three-dimensional network structure formed by complexing a polymer and a mineral. . The hydrogel is improved in extensibility, can be peeled off integrally without breaking, and processing after shaping is greatly simplified.

-Support (core) forming material-
The support-forming material (active energy ray-curable liquid composition) is not particularly limited as long as it can be a support capable of supporting the hydrogel structure of the present invention. From the viewpoint of removing the support present, it is preferable to use one which exhibits solubility in a solvent, and one which exhibits phase transition upon heating and the like to be liquid. Since the hydrogel structure of the present invention is a hydrogel, immersion in water may promote swelling of the shaped article upon removal of the support-forming material, which is not desirable. For this reason, those showing solubility in a solvent that does not attack the hydrogel are preferable, and those showing a solid at 25 ° C. but a phase change that becomes a liquid at 50 ° C. are preferable. When the support-forming material is a phase-changeable material, removal becomes easy after formation of the hydrogel structure.
In the hydrogel structure of the present invention, the support-forming material (core-forming material) for supporting the inside of the hollow shape and the support-forming material for supporting the outside of the structure may be the same or different. Further, the hollow interior does not have to be filled with the support, and it is sufficient if it has a support that can be supported to a minimum support shape, in which case removal can be performed more efficiently than in the case of filling with the support.

The support-forming material contains a polymerizable monomer, and further contains, if necessary, a polymerization initiator, a colorant and the like, and these can be the same as the above-mentioned hydrogel-forming material.
The material that undergoes the phase change is, for example, a liquid before curing, and, as in the case of the hydrogel, the environment temperature at room temperature (25 ° C.) by solidification by irradiation with active energy rays such as ultraviolet rays. Under the solid state, those having the property of being liquid at 60 ° C. may be mentioned.

  In one embodiment, a monofunctional ethylenically unsaturated monomer (A) (hereinafter sometimes referred to as "monomer (A)") having a linear C14 or more linear chain, a polymerization initiator (B) and It is preferable to include a solvent (C) capable of dissolving the monomer (A), and it is more preferable to further include a solvent (D) that is difficult to dissolve the monomer (A).

<Monofunctional Ethylenically Unsaturated Monomer (A) Having a Straight Chain of 14 or More Carbons>
The monofunctional ethylenically unsaturated monomer (A) having a linear chain having 14 or more carbon atoms is not particularly limited and may be appropriately selected depending on the purpose. For example, acrylates such as stearyl acrylate and docosyl acrylate Methacrylates such as stearyl methacrylate and docosyl methacrylate; acrylamides such as palmityl acrylamide and stearyl acrylamide; and vinyls such as vinyl stearate and vinyl docosylate. These may be used alone or in combination of two or more. Among these, acrylates and acrylamide derivatives are preferable from the viewpoint of photoreactivity, and stearyl acrylate is more preferable from the viewpoint of solubility in a solvent.

  Examples of the polymerization reaction of the monomer (A) include radical polymerization, ionic polymerization, coordination polymerization, ring opening polymerization and the like. Among these, radical polymerization is preferable from the viewpoint of control of the polymerization reaction. Therefore, the monomer (A) having a hydrogen bonding ability is preferably an ethylenically unsaturated monomer. Among these, monofunctional ethylenically unsaturated monomers are preferable from the viewpoint of meltability.

<Polymerization initiator (B)>
There is no restriction | limiting in particular as said polymerization initiator (B), According to the objective, it can select suitably, For example, a thermal-polymerization initiator, a photoinitiator, etc. are mentioned. Among these, when modeling a three-dimensional object, a photoinitiator is preferable.

As the photopolymerization initiator, any substance that generates a radical upon irradiation with light (in particular, ultraviolet light with a wavelength of 220 nm or more and 400 nm or less) can be used.
Examples of the photopolymerization initiator include acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p, p'-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, Michler's ketone , Benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin n-propyl ether, benzoin isobutyl ether, benzoin n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) 2-hydroxy-2-methylpropan-1-one, methyl benzoyl phenyl Formates, 1-hydroxycyclohexyl phenyl ketone, azobisisobutyronitrile, benzoyl peroxide, di-tert-butyl peroxide and the like. These may be used alone or in combination of two or more. Further, it is preferable to select a photopolymerization initiator in accordance with the ultraviolet wavelength of the ultraviolet irradiation device.

<Solvent (C) capable of dissolving monomer (A)>
The solvent (C) is not particularly limited as long as it can dissolve the monomer (A), and can be appropriately selected according to the purpose. However, the crystallinity of the polymer side chain is significantly reduced From the viewpoint of prevention, it is preferable to have a straight chain having 6 or more carbon atoms.

  Examples of the straight chain solvent (C) having 6 or more carbon atoms include esters such as hexyl acetate and octyl acetate; alcohols such as hexanol, decanol and dodecanol. Among these, straight-chain alcohols are preferable in order to increase the support of the cured product to the model material. A hydrogen bond can be constructed by a hydroxyl group while maintaining the crystallinity of the polymer side chain. Furthermore, a linear alcohol having at least one hydroxyl group bonded to a primary carbon is preferable because the inhibition of crystallinity is suppressed, and 1-dodecanol is more preferable.

<Solvent (D) which hardly dissolves monomer (A)>
The said solvent (D) is added in order to reduce the curvature of the support to be shaped. It is thought that the internal stress generated at the time of curing can be dispersed by adding a hardly soluble or insoluble solvent to the monomer.

  The solvent (D) is not particularly limited as long as it is a solvent that does not easily dissolve the monomer (A), and can be appropriately selected according to the purpose, but the monomer (A), the solvent (C) and the solvent (D) It is preferable to compatibilize and exist as a liquid in a 60 ° C. environment when Furthermore, a polyol which can be retained in the cured product without inhibiting the crystallinity of the polymer side chain and which can reduce the viscosity as a support material ink is more preferable.

Examples of the polyol include polyethylene glycol (PEG), polypropylene glycol (PPG), polybutylene glycol, ethylene oxide / propylene oxide copolymer, ethylene oxide / butylene oxide copolymer, polytetramethylene ether glycol (PTMEG), etc. Polyethers represented by the following, polycaprolactone diol (PCL), polycarbonate diol, polyester represented by the polyester polyol consisting of polyol / polybasic acid, castor oil, acrylic polyol and the like. These may be used alone or in combination of two or more. Among these, polypropylene glycol is preferable.
In addition, as said copolymer, block, random, or these can be used together.

  There is no restriction | limiting in particular as polymerization degree of the said polyol, Although it can select suitably according to the objective, 10 or more and 10,000 or less are preferable, 100 or more and 5,000 or less are more preferable, 1,000 or more 3, Particularly, 000 or less is preferable. When the degree of polymerization is 10 or more, it does not volatilize even when heated, and can remain in the cured product. Moreover, it can exist in a liquid, without raising a viscosity excessively at 60 degreeC as the said polymerization degree is 10,000 or less.

It is judged whether the monomer (A) can be dissolved or dissolved based on whether 1% by mass of the monomer can be dissolved. That is, the solvent (C) can dissolve 1% by mass or more of the monomer (A) of its own weight, and the solvent (D) can not dissolve 1% by mass or more of the monomer (A) of its own weight.
The method of the said judgment can be performed by adding 1 mass% monomer (A) to a solvent (C) or a solvent (D), stirring for 12 hours, and whether undissolved monomer remains or not.

The support-forming material (active energy ray-curable liquid composition) contains 20% by mass or more and 70% by mass or less of the monofunctional ethylenically unsaturated monomer (A) having a linear chain having 14 or more carbon atoms. It is more preferable to contain 30 mass% or more and 60 mass% or less.
The active energy ray-curable liquid composition of the present invention preferably contains 0.5% by mass or more and 10% by mass or less of the polymerization initiator (B), and more preferably 3% by mass or more and 6% by mass or less preferable.
The active energy ray-curable liquid composition of the present invention preferably contains 20% by mass or more and 70% by mass or less of the solvent (C) capable of dissolving the monomer (A), and contains 30% by mass or more and 60% by mass or less Is more preferred.

  The active energy ray-curable liquid composition of the present invention preferably contains 0% by mass or more and 40% by mass or less of the solvent (D) for dissolving the monomer (A), and contains 10% by mass or more and 30% by mass or less Is more preferred. The curvature can be reduced, hold | maintaining a shape as the said content is 0 mass% or more and 40 mass% or less. If the above range is exceeded, the support-forming material tends to be deformed by the weight of the hydrogel structure or an external force applied during formation.

  In addition, when the mass of the monomer (A) is Wa, the mass of the solvent (C) is Wc, and the mass of the solvent (D) is Wd, a relationship of 60 <[(Wc + Wd) / (Wa + Wc + Wd)] <75 is satisfied. As a result, warpage can be suppressed while securing sufficient compressive stress.

In order to obtain a cured product from the liquid support-forming material, for example, it is preferable to cure by curing by irradiating a UV exposure dose of 200 mJ / cm ² or more using a UV irradiation device. As the said ultraviolet irradiation device, the same thing as what hardens a hydrogel structure can also be used.

  It is preferable that temperature and humidity are controlled in the modeling space from the start to the end of modeling. It is for suppressing that a shaped article causes moisture absorption or drying, or solidification of a precursor. Specifically, the temperature is preferably 25 ° C. or less, the humidity is preferably within ± 5% RH of the target, and more preferably 95% ± 5% RH.

  In addition, it is necessary to shield the surroundings so that the ultraviolet light emitted from the ultraviolet irradiation device is not emitted to the outside during modeling. The shielding may be a structure that shields all light, or ultraviolet light may be selectively shielded.

When the monomer (A) contains the polymerization initiator (B) and is irradiated with ultraviolet light to become a polymer, the solvent (C) is held by the polymer. The polymer (A) becomes solid by arranging carbon chains in a 25 ° C. environment. When the solvent (C) is held by the polymer (A), it has an effect of suppressing shrinkage and warpage due to crystallization. In addition, a solvent (C) having a straight chain having 6 or more carbon atoms is preferable from the viewpoint of curability.
Moreover, it is preferable that the solvent (C) which can melt | dissolve the said monomer (A) is a non-reactive compound which does not react with the said polymerization initiator (B).
In the present invention, the solvent (C) capable of dissolving the monomer (A) refers to a solvent in which the monomer (A) dissolves in the solvent (C) to be a uniform liquid.
In the present invention, the non-reactive compound refers to a compound which does not react chemically even when irradiated with ultraviolet light.
It is preferable that the solvent (C) is nonreactive because it does not chemically react with the photopolymerization initiator and does not inhibit the polymerization reaction of the monomer or the crystallization of the polymer side chain.

-Surface tension-
There is no restriction | limiting in particular as surface tension of the support body formation material in this invention, Although it can select suitably according to the objective, 20 mN / m or more and 45 mN / m or less are preferable in 25 degreeC, 25 mN / m or more 34 mN / M or less is more preferable. When the surface tension is 20 mN / m or more, the discharge is stable during shaping, and the discharge direction is not curved or not discharged, and when it is 45 mN / m or less, the discharge nozzle for shaping or the like is used. When filling the liquid, it can be completely filled. The surface tension can be measured, for example, using a surface tension meter (automatic contact angle meter DM-701, manufactured by Kyowa Interface Science Co., Ltd.) or the like.

-Viscosity-
The viscosity of the support-forming material in the present invention is preferably 1,000 mPa · s or less, more preferably 300 mPa · s or less, further preferably 100 mPa · s or less, and 3 mPa · s or more and 20 mPa · s or less at 25 ° C. Particularly preferred is 6 mPa · s or more and 12 mPa · s or less. If the viscosity exceeds 1,000 mPa · s, discharge may not occur even if the temperature of the head is raised. The viscosity can be measured under an environment of 25 ° C. using, for example, a rotational viscometer (VISCOMATE VM-150III, manufactured by Toki Sangyo Co., Ltd.) or the like.

<<< Removal process and removal means >>>
The removing step is a step of removing the support including the columnar core portion.
Examples of the removal of the columnar core include liquefying with heat, using a solvent insoluble in the tubular portion, and the like. In addition, when the said tubular part is mixed and stirred in 100 g of water of 30 degreeC, for example, the said insoluble means that 90 mass% or more do not melt | dissolve.

<< Other process and other means >>
There is no restriction | limiting in particular as said other process, According to the objective, it can select suitably, For example, the layer smoothing process, the peeling process, the discharge stabilization process, the cleaning process of a shaped body, the grinding process of a shaped body, etc. Can be mentioned.

(Method for producing three-dimensional object and apparatus for producing three-dimensional object)
The method for producing a three-dimensional object of the present invention produces a three-dimensional object using the active energy ray-curable liquid composition of the present invention, and further includes other steps as necessary.
The method for producing a three-dimensional object according to the present invention is a method for producing a three-dimensional object by laminating layers of an active energy ray-curable liquid composition, which comprises the active energy ray-curable liquid composition according to the present invention The layered product is formed such that the cured product becomes a support part, and the layered part is heated to remove the support part after the layered formation, and may further include other steps as necessary.
Furthermore, according to the manufacturing apparatus of the three-dimensional object of the present invention, a container in which an active energy ray-curable liquid composition is contained, a discharge means for discharging the active energy ray-curable liquid composition, and the discharge means And curing means for curing the discharged active energy ray-curable liquid composition, and, if necessary, other means.

  The active energy ray-curable liquid composition may be the same as the active energy ray-curable liquid composition of the present invention (a support-forming material used in the layer forming step in the method for producing a hydrogel structure). it can.

  Moreover, as a manufacturing method of the said three-dimensional model, it is preferable to carry out lamination modeling so that the hardened | cured material of an active energy ray hardening-type liquid composition may become a support part, and the hydrogel structure of this invention may turn into a model part.

  The container containing the active energy ray-curable composition can be used as an ink cartridge or an ink bottle, which eliminates the need to directly touch the ink in operations such as ink conveyance and ink replacement It can prevent the dirt of clothes and clothes. In addition, it is possible to prevent mixing of foreign matter such as dust into the ink. Further, the shape, size, material, etc. of the container itself may be any suitable one for use and usage, and is not particularly limited. However, the material is a light shielding material which does not transmit light, or the container It is preferable that the sheet is covered with an elastic sheet or the like.

FIG. 4 is a schematic view showing an example of a process for producing a shaped body using a three-dimensional shaping apparatus used in the method for producing a hydrogel structure of the present invention.
The three-dimensional model forming apparatus 10 uses a head unit in which ink jet heads (forming material discharge means, discharge means) movable in any direction of arrows A and B are arrayed from the head unit 12 on the object support substrate 14 The hydrogel-forming material is sprayed from the head unit 11 with the support-forming material, and is laminated while curing the hydrogel-forming material by the adjacent UV irradiator (curing means) 13.
That is, a support forming material (support material) is jetted from the head unit 12 and solidified to form a first support layer having a reservoir, and the reservoir forming portion of the first support layer is formed of hydrogel. The hydrogel is sprayed from the head unit 11, the hydrogel forming material is irradiated with UV light to be cured, and smoothing is performed using the smoothing member 16 to form a first formed object layer.

Then, a support forming material is jetted and solidified on the first support layer, and a second support layer having a reservoir is laminated, and hydrogel is formed in the reservoir of the second support layer. The material is jetted, UV light is irradiated, and the second shaped object layer is laminated on the first shaped object layer, and the surface is further smoothed to produce the shaped object 17.
When a roller-shaped smoothing member is used, the effect of smoothing is more effectively exhibited when the roller is rotated in the reverse direction with respect to the operation direction.

  Furthermore, in order to keep the gap between the head unit 11, the head unit 12, the UV irradiator 13 and the shaped body 17 and the support 18 constant, stacking is performed while lowering the stage 15 in accordance with the number of times of stacking.

  Moreover, as the three-dimensional model forming apparatus 10, it is also possible to add a collection | recovery of a formation material, a recycling mechanism, etc. You may comprise the detection mechanism of the braid | blade which removes the formation material adhering to the nozzle surface, and a non-discharge nozzle. Furthermore, it is also preferable to control the in-apparatus environmental temperature at the time of modeling.

  By using the above-mentioned apparatus, composition distribution and shape control can be performed according to the condition of the treatment site of the individual patient, and a blood vessel model or organ model having distribution of patient specific shape and physical properties is formed. Can.

  For example, it is possible to provide the hardness distribution (composition distribution) of the blood vessel as needed, as well as having the shape of the blood vessel of the affected area to be treated with the catheter using personal data of the treated person (patient). Also in this case, it is created based on the patient's individual data.

  As a method of providing compositional distribution, adjusting the amount of the solvent contained in the hydrogel can be mentioned. This can be realized by using an apparatus of a mechanism which ejects a plurality of compositions from the respective inkjet heads in a method using the inkjet.

As a first liquid, a hydrogel-forming material (hereinafter sometimes referred to as "solution A") is used and discharged from a first head. In addition, as a second liquid, a liquid comprising a solvent capable of diluting the hydrogel-forming material, mainly water and a solvent soluble in water (hereinafter sometimes referred to as “liquid B”), the second head Discharge from. Furthermore, the support-forming material used when forming a hollow tube of a blood vessel model is used as the third liquid and discharged from the third head.
The liquid A and the liquid B are printed by predetermined amounts from each ink jet head, and it is possible to precisely control the volume ratio of the liquid to be dropped to the same position.

Hereinafter, specific embodiments of the method for producing a hydrogel structure of the present invention will be described.
The method of obtaining hydrogel structures having different hardness, compressive stress and elastic modulus will be described in more detail.
First, surface data or solid data of a three-dimensional shape designed by three-dimensional CAD or a three-dimensional shape taken in by a three-dimensional scanner or digitizer is converted into an STL format and input to the layered manufacturing apparatus.

  Next, measurement of the three-dimensional compressive stress distribution is performed. The method is not particularly limited, but, for example, by using MR Elastography (hereinafter, MRE), compressive stress distribution data of a three-dimensional shape is obtained, and this data is input to the layered manufacturing apparatus. Based on the input compression stress data, the mixing ratio of A liquid and B liquid discharged to the position corresponding to three-dimensional shape data is determined.

Based on the input data, the forming direction of the three-dimensional shape to be formed is determined. There is no particular limitation on the forming direction, but usually, the direction in which the Z direction (height direction) is the lowest is selected.
Once the modeling direction is determined, the projected area of the three-dimensional shape on the XY plane, the XZ plane, and the YZ plane is determined. The obtained block shape is sliced at a single layer thickness in the Z direction. The thickness of the single layer depends on the material used, but is usually 20 μm or more and 60 μm or less. In the case of one object to be formed, this block shape is arranged to be in the middle of the Z stage (a table on which the object which descends one layer for each formation) is placed. Moreover, although block shape is arrange | positioned at Z stage when modeling in two or more simultaneously, it is also possible to stack block shape. It is also possible to automatically create the block shape, the rounding data (slice data: contour data) and the arrangement on the Z stage by designating the material to be used.

  Next, the shaping process is performed. FIG. 5 is a schematic view showing an example of a three-dimensional shaping apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet discharge method. By moving different heads α and β (FIG. 5) in both directions, A liquid and B liquid are discharged to a predetermined area at a predetermined ratio to form dots. At that time, as shown in FIG. 6, it is possible to mix the A solution and the B solution in the dots to obtain a predetermined mixing ratio. Furthermore, by forming continuous dots, it is possible to produce a mixed liquid film of the A liquid and the B liquid in which a predetermined mixing ratio is in a predetermined area. Then, the mixed liquid film of the liquid A and the liquid B is cured by irradiation with ultraviolet (UV) light to form a hydrogel film (layer) having a predetermined mixing ratio in a predetermined area as shown in FIG. Can.

  After forming the hydrogel film (layer), the stage (FIG. 5) is lowered by the height of one layer. Again, by forming continuous dots on the hydrogel film, a mixed liquid film of solution A and solution B with a predetermined mixing ratio in a predetermined region is produced. The mixture film of solution A and solution B is cured by irradiation with ultraviolet (UV) light to form a hydrogel film. Three-dimensional modeling becomes possible by repeating these laminations.

  Thus, the three-dimensionally shaped hydrogel structure has different mixing ratios of A solution and B solution in the hydrogel obtained by stericizing the liquid film of FIG. 5, and the elastic modulus can be changed continuously. By adjusting the mixing ratio pattern for each fault, it is possible to obtain a hydrogel structure having partially arbitrary physical properties.

  Moreover, by making an ultraviolet (UV) light irradiator adjoin the inkjet head which injects hydrogel formation material, the time which smoothing processing requires can be saved and high-speed modeling is possible.

  In the hydrogel structure used in the present invention, the hardness can be arbitrarily varied by changing the composition ratio while using the same material by combining the hydrogel-forming material and the diluent. For this reason, it is possible to easily provide the hardness distribution of the blood vessel along personal data by using a plurality of inkjet heads and changing the ratio of the two when forming by inkjet method.

  The hydrogel is a composition containing a large amount of water, very close to the composition of the human body, and very similar in texture. Combining this with 3D printing is very useful in forming a blood vessel model.

The hydrogel structure, blood vessel model, and organ model of the present invention can be produced by 3D printing technology, so it is possible to form a model that reproduces the shape and physical properties based on the patient's affected area data. . Therefore, it can be usefully used for simulation before difficult surgery.
For example, in the conventional operation (stent insertion to the aneurysm), the shape of the aneurysm is read from the X-ray image, and a stent which seems to be an appropriate shape is selected during the operation and used. However, this is performed by the experience of a doctor (operator), and there are many cases where it takes time to make a decision or it is not possible to select an optimal one.
The success rate of surgery can be increased by examining the problem of what shape member (such as a stent) should be selected depending on the shape and physical properties of the aneurysm, before the surgery. I can expect it.

In the present invention, another form of blood vessel model and organ model to which the technology of the present invention is applied are also disclosed.
The hydrogel structure of the present invention is to have a hollow tube structure having an inner diameter of 1.0 mm or less. In order to make this structure formable, as described above, a support-forming material is used to form a hollow tubular structure. As the support-forming material, it is effective to use a solid material which changes its phase to a liquid state by heat, but this technique can be applied.

When modeling the blood vessel model having the hollow structure and the organ model, the shaping is completed without removing the support material filling the inside of the hollow structure. This completes the blood vessel model and organ model in which the phase change support material remains while the hollow structure is maintained. The support material used here is preferably colored in red imitating blood by containing a coloring material or the like.
The blood vessel model and the organ model can be obtained according to the second embodiment of the method for producing a hydrogel structure of the present invention.

  The blood vessel model and the organ model can be used for procedure training of surgical devices such as ultrasonic scalpels and electric scalpels. Specifically, in training for performing an incision in the vicinity of a blood vessel placed in an organ model, it can be used as a bleeding model and is very useful when blood vessels are accidentally damaged.

Examples of the present invention will be described below, but the present invention is not limited to these examples.
The inner diameter of the structure was measured as follows.

(Inside diameter of structure)
The inner diameter of the structure was measured with a one-shot 3D shape measuring instrument (manufactured by Keyence Corporation).
In order to determine the certainty of measurement, several samples were measured in advance, sections of these samples were cut out, and measurement with a caliper was also performed to confirm that they were equivalent values.
In the following examples, measurement was performed nondestructively using a one-shot 3D shape measuring instrument.

(Preparation Example 1 of Hydrogel Forming Material)
<Preparation of Hydrogel Forming Material A>
[Mg _5.34 Li _0.66 Si ₈ O] as a layered clay mineral while stirring 120.0 parts by mass of ion exchanged water (hereinafter sometimes referred to as "pure water") subjected to vacuum degassing for 30 minutes 12.0 parts by mass of synthetic hectorite (Laponite XLG, manufactured by RockWood) having a composition of ₂₀ (OH) ₄ ] Na ⁻ _0.66 was added little by little and stirred. Further, 0.6 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and stirred to prepare a dispersion.
Acryloyl morpholine (manufactured by KJ Chemicals, Inc.) 44.0 parts by mass, methylene bis acrylamide (manufactured by Tokyo Kasei Kogyo Co., Ltd.), obtained by passing through a column of activated alumina as a polymerizable monomer and removing the polymerization inhibitor in the obtained dispersion liquid ) 0.4 parts by mass were added.
Furthermore, 20.0 mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.), 0.8 parts by mass of N, N, N ', N'-tetramethylethylenediamine (manufactured by Tokyo Kasei Kogyo Co., Ltd.), Surfron S-243 (AGC Seimi A hydrogel forming material A (ink A) was prepared by adding 0.6 parts by mass of Chemical Co., Ltd. and 1.2 parts by mass of Irgacure 184 (manufactured by BASF, 4% by mass methanol solution).

(Preparation Examples 2 to 4 of Hydrogel-Forming Material)
<Preparation of Hydrogel Forming Materials B to D>
Hydrogel-forming materials B to D were prepared in the same manner as in Preparation Example 1 of the hydrogel-forming material, except that in Preparation Example 1 of the hydrogel-forming material, the composition was changed to that shown in Table 1 below.

(Preparation Example 5 of Hydrogel-Forming Material)
<Preparation of Gel Forming Material E>
Polyvinyl alcohol having an average degree of polymerization of about 2,000 and a degree of saponification of 89 mol% was dissolved in water containing 0.9 mass% NaCl. Under the present circumstances, in order to promote melt | dissolution of polyvinyl alcohol, it heated and melt | dissolved in 60 degreeC. After dissolution, it was cooled to room temperature to prepare gel-forming material E.

In addition, in said Table 1, it is as follows about the brand name of a component, and a manufacturing company name.
Acryloyl morpholine: manufactured by KJ Chemicals Ltd. Methylene bis acrylamide: manufactured by Tokyo Chemical Industry Co., Ltd. Synthetic hectorite: manufactured by RockWood, trade name: Laponite XLG
Glycerin: manufactured by Sakamoto Yakuhin Kogyo Co., Ltd. Ethidolonic acid: manufactured by Tokyo Chemical Industry Co., Ltd. N, N, N ', N'-Tetramethylethylenediamine: manufactured by Tokyo Chemical Industry Co., Ltd. Emulgen LS106: manufactured by Kao Corp. Surfron S-243: AGC Seimi Chemical Co., Ltd. Irgacure 184: BASF company 4% by mass methanol solution

(Preparation Example 1 of Support (Core) Forming Material)
<Preparation of Support-Forming Material A>
18.0 parts by mass of 1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (C)), 48.0 parts by mass of stearyl acrylate (manufactured by Tokyo Chemical Industry Co., Ltd., polymer (A)), Irgacure 819 (manufactured by BASF, polymerization) 4.0 parts by mass of the initiator (B) was stirred, mixed and dissolved to prepare a support-forming material A. The composition is shown in Table 2 below.

(Preparation Example 2 of Support (Core) Forming Material)
<Preparation of Support-Forming Material C>
1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (C)) 58.0 parts by mass, 15.0 parts by mass of polypropylene glycol 2000 (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (D)), stearyl acrylate (Tokyo Chemical Industry Co., Ltd.) A support-forming material C was prepared by stirring, mixing and dissolving 48.0 parts by mass of a polymer (A), and 4.0 parts by mass of Irgacure 819 (polymerization initiator (B), manufactured by BASF Corp.). . The composition is shown in Table 2 below.

(Preparation Example 3 of Support (Core) Forming Material)
<Preparation of support forming material D>
1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (C)) 58.0 parts by mass, polypropylene glycol 2000 (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (D)) 30.0 parts by mass, stearyl acrylate (Tokyo Chemical Industry Co., Ltd.) A support-forming material D was prepared by stirring, mixing and dissolving 48.0 parts by mass of a polymer (A), and 4.0 parts by mass of Irgacure 819 (polymerization initiator (B), manufactured by BASF Corp.). . The composition is shown in Table 2 below.

(Preparation Example 4 of Support (Core) Forming Material)
<Preparation of support forming material E>
1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (C)) 58.0 parts by mass, 20.0 parts by mass of polypropylene glycol 2000 (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (D)), stearyl acrylate (Tokyo Chemical Industry Co., Ltd.) A support-forming material E was prepared by stirring, mixing and dissolving 28.0 parts by mass of a polymer (A), and 4.0 parts by mass of Irgacure 819 (polymerization initiator (B), manufactured by BASF Corp.). . The composition is shown in Table 2 below.
Show.

In addition, in the said Table 2, it is as follows about the brand name of a component, and a manufacturing company name.
Stearyl acrylate: manufactured by Tokyo Chemical Industry Co., Ltd. 1-dodecanol: manufactured by Tokyo Chemical Industry Co., Ltd. Propylene glycol 2000: manufactured by Tokyo Chemical Industry Co., Ltd. Irgacure 819: manufactured by BASF

(Preparation Example 5 of Support (Core) Forming Material)
Preparation of Support-Forming Material B
A support forming material B was prepared by mixing and dispersing 3 parts by mass of a magenta pigment dispersion prepared as described below in 100 parts by mass of the support forming material A.

Preparation of Magenta Pigment Dispersion
After thoroughly replacing the inside of a 1 L flask equipped with a mechanical stirrer, thermometer, nitrogen gas inlet tube, reflux tube, and dropping funnel with nitrogen gas, 11.2 g of styrene, 2.8 g of acrylic acid, 12 lauryl methacrylate .0 g, 4.0 g of polyethylene glycol methacrylate, 4.0 g of styrene macromer, and 0.4 g of mercaptoethanol were mixed, and the temperature was raised to 65 ° C. Next, 100.8 g of styrene, 25.2 g of acrylic acid, 108.0 g of lauryl methacrylate, 36.0 g of polyethylene glycol methacrylate, 60.0 g of hydroxylethyl methacrylate, 36.0 g of styrene macromer, 3.6 g of mercaptoethanol, azobismethyl valero A mixed solution of 2.4 g of nitrile and 18 g of methyl ethyl ketone is dropped into the flask over 2.5 hours, and then a mixed solution of 0.8 g of azobis methyl valeronitrile and 18 g of methyl ethyl ketone is taken for 0.5 hour The mixture was dropped into it and aged at 65 ° C. for 1 hour. Further, 0.8 g of azobismethylvaleronitrile was added, and after aging for 1 hour, 364 g of methyl ethyl ketone was added to the flask to obtain 800 g of a 50% by mass polymer solution.

  After sufficiently stirring 28 g of polymer solution, 42 g of magenta pigment (CI pigment red 122), 13.6 g of 1 mol / L aqueous potassium hydroxide solution, 20 g of methyl ethyl ketone and 13.6 g of ion exchanged water, using a roll mill It knead | mixed and obtained the paste. Next, the paste was poured into 200 g of pure water and sufficiently stirred, and then methyl ethyl ketone and water were distilled off using an evaporator. Furthermore, pressure filtration was performed using a polyvinylidene fluoride membrane filter having an average pore diameter of 5.0 μm, to obtain a magenta pigment dispersion having a pigment content of 15% by mass and a solid content of 20% by mass.

Example 1
The hydrogel-forming material A and the support-forming material A (both active energy ray-curable compositions) were discharged using the shaping apparatus shown in FIG. 4, and curing was repeated with ultraviolet light to produce a laminate-molded article. Next, the layered product is allowed to stand in a thermostat at 50 ° C. for 30 minutes, and the columnar core portion which is a cured product of the support-forming material A is liquefied to remove it, and it is further heated at 50 ° C. By washing away the remaining columnar core, a hydrogel structure (blood vessel model) having a hollow tubular structure as shown in FIG. 2 was obtained.
The internal diameter (hollow) of the blood vessel cavity in the obtained hydrogel structure was 5 mm in the thick portion and 0.4 mm in the narrowest portion. The doctor was able to evaluate the catheter insertion from the outside of the blood vessel after the catheter insertion evaluation by the doctor. In addition, it was confirmed that the microcatheter reached the tip of the blood vessel cavity in the hydrogel structure, and the hollow tube structure could be reproduced.
After the test, the hydrogel structure is cut at the hollow tube portion in the longitudinal direction and made into a flat plate, and the transmittance in the wavelength range of 400 nm to 700 nm is a commercially available spectrophotometer (device name: UV-3100, Ltd. It measured by Shimadzu Corporation make, integral unit use). As a result, a transmittance of 91% or more was exhibited in the wavelength range of 400 nm to 700 nm.

(Example 2)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel-forming material A was changed to a hydrogel-forming material B in Example 1.
The result of the texture at the time of catheter insertion was equivalent to Example 1. Moreover, the transmittance | permeability showed 87% or more of the transmittance | permeability in the wavelength range of 400 nm-700 nm. In addition, the inside diameter (hollow) of the blood vessel cavity in the hydrogel structure in the obtained structure was 5 mm in the thick portion and 0.3 mm in the thinnest portion.

(Example 3)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel-forming material A was changed to a hydrogel-forming material C in Example 1.
The transmittance was measured in the same manner as in Example 1. As a result, the transmittance was 81% or more in the wavelength range of 400 nm to 700 nm. In addition, the inside diameter (hollow) of the blood vessel cavity in the hydrogel structure in the obtained structure was 4 mm in the thick portion and 0.2 mm in the thinnest portion.

(Example 4)
The hydrogel structure obtained in Example 1 was incorporated in a glass container as shown in FIGS. 3A and 3B. As a result of the catheter insertion evaluation by the doctor, the feel of the insertion of the catheter and the visual confirmation condition of the catheter operation did not change, and the handleability was improved.

(Example 5)
The hydrogel structure obtained in Example 1 was incorporated in a container made of polycarbonate resin. As a result of the catheter insertion evaluation by the doctor, the feel of the insertion of the catheter and the visual confirmation condition of the catheter operation did not change, and the handleability was improved.

(Example 6)
In Example 1, a hydrogel structure was obtained in the same manner as in Example 1 except that the modeling data used for modeling was changed to data generated from a blood vessel CT image of an actual patient. Next, a CT image of the obtained hydrogel structure was taken and compared with a patient's vascular CT image.
As a result, it became clear that the hollow shape of the detail can be almost reproduced, and the data is reproduced with an accuracy of ± 2%.

(Example 7)
An organ model (liver model) is prepared in the same manner as in Example 1 except that the external shape of the hydrogel that forms the periphery of the hollow structure in Example 1 is a shape that simulates a liver as shown in FIG. 7. Obtained.
The texture during catheter insertion, visual recognition from the outside, and the transmittance data were the same as in Example 1. It turned out that it is excellent in reality because the appearance resembles an organ.

(Comparative example 1)
Using the gel-forming material E, cast it into a mold that encloses a cylindrical hollow cylinder with a diameter of 8 mm and a height of 50 mm, and subject it to nine freeze / thaw cycles to further promote gelation. The cylinder was pulled out of the alcohol gel to obtain a gel structure having a hollow tubular structure.
When the transmittance was measured in the same manner as in Example 1, the transmittance was a low value below 80% in the wavelength range of 400 nm to 700 nm.
Although the gel structure was subjected to a catheter insertion test, due to the opacity of the gel structure, it was not possible to confirm the fine movement of the catheter by visual observation from the outside. In addition, the hollow tube in the obtained gel structure had an inner diameter of 8 mm.

(Comparative example 2)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel-forming material B was changed to the hydrogel-forming material D in Example 1.
When the transmittance was measured in the same manner as in Example 1, the transmittance was a low value below 80% in the wavelength range of 400 nm to 700 nm.
The obtained hydrogel structure was subjected to a catheter insertion test, but due to the opacity (the permeability is less than 80%) of the structure, the fine movement of the catheter can not be confirmed from the outside, and the catheter slips It was a bad result. Further, the obtained hydrogel structure had an inner diameter (hollow) of 5 mm at the thick portion and 1.0 mm at the thinnest portion.

(Comparative example 3)
A shaped article was obtained in the same manner as Example 1, except that the blood vessel part was made of SUP 706 (made by Stratasys), and the blood vessel wall part and the main body part were made of TangoBlack (made by Stratasys). The resulting shaped article was immersed in water for 12 hours to remove the support-forming material to obtain a structure.
When the catheter was inserted into the obtained structure and the texture was confirmed, the blood vessel was very hard and stuck, and the texture was far from the real thing. In addition, the hollow tube in the obtained hydrogel structure had an inner diameter (hollow) of 5 mm in the thick portion and 1 mm in the thinnest portion. Furthermore, the transmittance of the structure was less than 80%.

  Next, "visibility", "texture", and "preservability" were evaluated as follows. The results are shown in Table 3 below.

(Visibility)
Using a spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, using an integration unit), measure the transmittance in the visible light range (wavelength 400 nm or more and 700 nm or less), and based on the following evaluation criteria: "Visibility" was evaluated. When the transmittance is high, the hydrogel structure is excellent in transparency.
-Evaluation criteria-
○: The lowest transmittance in the wavelength range of 400 nm to 700 nm is 90% or more Δ: The lowest transmittance in the wavelength range of 400 nm to 700 nm is 80% to 90% ×: Most in the wavelength range of 400 nm to 700 nm Low transmittance less than 80%

(Texture)
The obtained structure was used for catheter insertion evaluation by a doctor, and the texture of insertion of a catheter (trade name: ESHLON 10, manufactured by COVIDIEN Co., Ltd.) was evaluated for "texture" based on the following evaluation criteria.
-Evaluation criteria-
○: A texture very close to an actual blood vessel ×: A texture far from an actual blood vessel

(Preservability)
Using the hydrogel structure prepared in Example 1, Example 4, and Example 5, it is stored for 3 days in the atmosphere (25 ° C., 55% RH) as it is, based on the following evaluation criteria The “preservability” was evaluated.
-Evaluation criteria-
○: The initial state is maintained ×: The surface is slightly dried to increase the hardness

(Example 8)
In Example 1, a support-forming material B was used instead of the support-forming material A to prepare a hydrogel structure (blood vessel model). In order to prevent the support-forming material B contained in the hollow structure from flowing out, the produced laminate-molded product was wiped clean with cotton impregnated with ethanol at room temperature (25 ° C.), and the formation was completed. .
The produced laminate-molded article was tested with an electric knife (general electrosurgical unit, Program DS3-M, manufactured by Morita Tokyo Seisakusho Co., Ltd.). When the blood vessel site was incised, the support-forming material B melted and flowed out as simulated blood.

(Example 9)
A hydrogel structure (blood vessel model) having a hollow tubular structure was obtained in the same manner as in Example 5 except that the support forming material A was changed to a support forming material C in Example 5.
About the obtained hydrogel structure, it carried out similarly to Example 1, and evaluated the internal diameter of a structure, the catheter insertion result, and the permeability. The inner diameter of the structure, the result of catheter insertion, and the result of permeability were the same as in Example 5.

(Example 10)
A hydrogel structure (blood vessel model) having a hollow tubular structure was obtained in the same manner as in Example 5 except that the support forming material A was changed to a support forming material D in Example 5.
About the obtained hydrogel structure, it carried out similarly to Example 1, and evaluated the internal diameter of a structure, the catheter insertion result, and the permeability. The inner diameter of the structure, the result of catheter insertion, and the result of permeability were the same as in Example 5.

(Example 11) A hydrogel structure (blood vessel model) having a hollow tubular structure is obtained in the same manner as in Example 5 except that the support forming material A is changed to a support forming material E in Example 5. Obtained.
About the obtained hydrogel structure, it carried out similarly to Example 1, and evaluated the internal diameter of a structure, the catheter insertion result, and the permeability. The inner diameter of the structure, the result of catheter insertion, and the result of permeability were the same as in Example 5.

  Next, "warping of the support" was evaluated as follows. The results are shown in Table 4 below.

(Warping of the support)
During molding of the hydrogel structure, stop the molding machine when half of the whole is shaped, observe the condition of the hydrogel and the support, and based on the following evaluation criteria, "warp of the support" evaluated. In addition, also in Example 5, it carried out similarly to Examples 9-11, and evaluated the curvature of the support body. In the state of ×, modeling can not be continued-Evaluation criteria-
○: The hydrogel and the support are integrated. Δ: The periphery of the support is slightly warped ×: The support is largely warped and interferes with the inkjet head

  In Example 5, when a shaped object formed and completed in the state of Δ was confirmed, disorder of formation was confirmed at the end portion or the upper portion of the hollow tube.

  In Examples 9 to 11, by adding the solvent (D) which does not easily dissolve the monomer (A) in the support-forming material, the warpage of the shaped support is reduced and a shaped article with high accuracy is obtained. be able to.

Preparation Example 6 of Hydrogel-Forming Material
Preparation of First Liquid A1
[Mg _5.34 Li _0.66 Si ₈ O] as a layered clay mineral while stirring 51.0 parts by mass of ion-exchanged water (hereinafter sometimes referred to as "pure water") subjected to vacuum degassing for 30 minutes 5.5 parts by mass of synthetic hectorite (Laponite XLG, manufactured by RockWood) having a composition of ₂₀ (OH) ₄ ] Na ^- _0.66 was added little by little and stirred. Furthermore, 0.3 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added, and the mixture was stirred at 40 ° C. for 2 hours to prepare a dispersion.
Acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) 16.8 parts by mass, methylene bis acrylamide (manufactured by Tokyo Kasei Kogyo Co., Ltd.), obtained by passing through a column of activated alumina as a polymerizable monomer and removing the polymerization inhibitor into the obtained dispersion. 0.2 parts by mass and 3.0 parts by mass of N, N-dimethyl acrylamide (manufactured by KJ Chemicals, Inc.) were added.
Furthermore, 22.0 mass of glycerin (made by Sakamoto Yakuhin Kogyo Co., Ltd.) and 0.3 mass part of Emargen LS106 (made by Kao Corporation) were added. Next, after shielding the container from light, 0.5 parts by mass of Irgacure 1173 (manufactured by BYK) and 0.4 parts by mass of N, N, N ', N'-tetramethylethylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) are added. The mixture was stirred and mixed for 30 minutes. Next, after performing vacuum degassing for 10 minutes, filtration was performed using a syringe filter (manufactured by ADVANTEC) having an average pore diameter of 0.8 μm to obtain a homogeneous first liquid A1.

(Preparation Example 1 of Dilution Material)
<Preparation of Second Liquid B1>
A second liquid B1 was prepared in the same manner as in Preparation Example 6 of the hydrogel-forming material, except that the composition was changed to the composition shown in Table 5 below in Preparation Example 6 of the hydrogel-forming material.

In addition, in said Table 5, it is as follows about the brand name of a component, and a manufacturing company name.
Acryloyl morpholine: manufactured by KJ Chemicals, Inc. Methylene bis acrylamide: manufactured by Tokyo Chemical Industry Co., Ltd. N, N-dimethyl acrylamide: manufactured by KJ Chemicals, monofunctional monomer Synthetic hectorite: manufactured by RockWood, trade name: Laponite XLG
Glycerin: manufactured by Sakamoto Yakuhin Kogyo Co., Ltd. Ethidolonic acid: manufactured by Tokyo Chemical Industry Co., Ltd. N, N, N ', N'-Tetramethylethylenediamine: manufactured by Tokyo Chemical Industry Co., Ltd. Emulgen LS106: manufactured by Kao Corp. Irgacure 1173 : BYK company

(Preparation Example 6 of Support (Core) Forming Material)
Preparation of Support Forming Material 1
55.0 parts by mass of 1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd.), 42.0 parts by mass of stearyl acrylate (manufactured by Tokyo Chemical Industry Co., Ltd.), and 3.0% by mass of Irgacure 819 (manufactured by BASF Corporation) at 40 ° C. The mixture was temperature-controlled and stirred for 30 minutes, mixed and dissolved to prepare a support-forming material 1. The composition is shown in Table 6 below.

In addition, in said Table 6, it is as follows about the brand name of a component, and a manufacturing company name.
Stearyl acrylate: made by Tokyo Chemical Industry Co., Ltd. 1-dodecanol: made by Tokyo Chemical Industry Co., Ltd. Irgacure 819: made by BASF

(Reference Examples 1 and 2)
The first liquid A1 and the second liquid B1 are mixed at a volume ratio of Table 7 below, poured into a 30 mm × 30 mm × 8 mm mold, and an ultraviolet irradiator (apparatus name: SPOT CURE SP 5-250 DB, Ushio Inc. stock After hardening using the product made in the company, the hydrogel sample for the compression test of the reference example 1-2 was obtained by leaving still at 27 degreeC for 12 hours. The moisture content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 7 below.

(Water content)
The water content was measured using a heat-drying moisture meter (device name: MS-70, manufactured by A & D Co., Ltd.).

(Elastic modulus)
The elastic modulus was provided with a universal testing machine (device name: AG-I, manufactured by Shimadzu Corporation), a load cell 1 kN, a compression jig for 1 kN, and a sample shaped in a shape of 30 mm × 30 mm × 8 mm was installed. The stress for compression applied to the load cell was recorded in a computer, and the stress was plotted against the amount of displacement. In addition, an elastic modulus shows the inclination of the compressive stress at the time of 20% compression.

(Examples 12 to 13)
Using the shaping apparatus shown in FIG. 4, the first liquid A1, the second liquid B1 and the support-forming material 1 (both active energy ray curable compositions) were discharged at volume ratios shown in Table 8 below. Curing was repeated with ultraviolet light to produce a laminate-molded article. Next, the layered product is allowed to stand in a constant temperature bath at 50 ° C. for 30 minutes, and the support (columnar core) which is a cured product of the support-forming material 1 is removed by liquefaction, and 50 By washing away the remaining support (columnar core) with warm water of ° C., a hydrogel structure having a hollow tubular shape as shown in FIG. 1 was obtained. The hydrogel structures obtained each had a harder composition in the blood vessel wall than in the surrounding other hydrogels. As a result of inserting a catheter into this and confirming a texture, it was a texture very similar to an actual blood vessel. The moisture content and the elastic modulus are the same as in Reference Example 1.

(Comparative Examples 4 to 5)
A hydrogel structure was obtained in the same manner as in Example 12 except that the volume ratio was changed as shown in Table 8 below. When the catheter was inserted into the obtained hydrogel structure and the texture was confirmed, it was a texture different from the real thing. The elastic modulus was measured in the same manner as in Reference Example 1. As a result, Comparative Example 4 was 0.21 MPa as a blood vessel wall, 0.21 MPa as another hydrogel, 0.02 MPa as a blood vessel wall in Comparative Example 5, and 0.02 MPa as another hydrogel.

(Comparative example 6)
A shaped article was obtained in the same manner as Example 12, except that the support (columnar core) was made of SUP 706 (made by Stratasys), and the blood vessel wall and the main body were made of TangoBlack (made by Stratasys). . The resulting shaped article was immersed in water for 12 hours to remove the support-forming material to obtain a structure.
When the catheter was inserted into the obtained structure and the texture was confirmed, the blood vessel was very hard and stuck, and the texture was far from the real thing. The elastic modulus was measured in the same manner as in Reference Example 1. The result was 2.0 MPa for both the blood vessel wall and the other hydrogels.

  Next, "texture" was evaluated as follows. The results are shown in Table 8 below.

(Texture)
The obtained hydrogel structure was used for catheter insertion evaluation by a doctor, and the texture of insertion of a catheter (trade name: ESHLON 10, manufactured by COVIDIEN) was evaluated for “texture” based on the following evaluation criteria.
-Evaluation criteria-
○: A texture very similar to an actual blood vessel, which is a level that can be preferably used for catheter insertion practice Δ: A texture that is different from an actual blood vessel, but is a level that can be used for catheter insertion practice Is a far-off texture, a level that can not be used for catheter insertion practice

(Example 14)
The hydrogel structure obtained in the same manner as in Example 12 was incorporated into a glass container. The texture during catheter insertion did not change, and the handling was improved.

(Example 15)
The hydrogel structure obtained in the same manner as in Example 12 was incorporated into a container made of polycarbonate resin. The texture during catheter insertion did not change, and the handling was improved.

  Next, "preservability" was evaluated as follows.

(Preservability)
Using the hydrogel structures prepared in Example 12, Example 14, and Example 15, it was stored for 3 days under the atmosphere (25 ° C., 55% RH) in the same state.
As a result, the surface of the hydrogel structure of Example 12 dried slightly and its hardness increased, but no change was observed in the structures of Examples 14 and 15.

Preparation Example 7 of Hydrogel-Forming Material
Preparation of First Liquid A2
Hereinafter, the ion-exchange water which implemented pressure reduction degassing for 30 minutes is made into a pure water.
First, synthetic hectorite having a composition of [Mg _5.34 Li _0.66 Si ₈ O ₂₀ (OH) ₄ ] Na ⁻ _0.66 as a layered clay mineral while stirring 60.0 parts by mass of pure water Name: Laponite XLG (manufactured by RockWood) was added little by little to a total of 6.0 parts by mass, and the mixture was stirred to prepare a dispersion. Next, 0.3 parts by mass of etidronic acid was added as a dispersant for synthetic hectorite.
Next, 22.0 parts by mass of acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) from which a column of activated alumina was passed as a polymerizable monomer to remove the polymerization inhibitor in the obtained dispersion, and 22.0 parts by mass of methylene bis acrylamide (organic crosslinker 0.2 parts by mass of Tokyo Chemical Industry Co., Ltd., 10.2 parts by mass of glycerin as an anti-drying agent, and 0.3 parts by mass of EMALGEN LS106 (manufactured by Kao Corporation) were added and mixed.
Next, 0.4 parts by mass of N, N, N ', N'-tetramethylethylenediamine is added as a polymerization accelerator, and then 0.6 parts by mass of Irgacure 184 (manufactured by BASF Corporation) is added as a polymerization initiator, followed by stirring and mixing. did.
After stirring and mixing, vacuum degassing was performed for 10 minutes. Subsequently, the resultant was subjected to filtration to remove impurities and the like to obtain a homogeneous first liquid A2. The composition is shown in Table 9 below.

(Preparation Example 2 of Dilution Material)
Preparation of Second Liquid B2
A second liquid B2 was obtained in the same manner as in Preparation Example 7 of the hydrogel-forming material, except that in Preparation Example 7 of the hydrogel-forming material, the composition was changed to that shown in Table 9 below.

In addition, in said Table 9, it is as follows about the brand name of a component, and a manufacturing company name.
Acryloyl morpholine: manufactured by KJ Chemicals Ltd. Methylene bis acrylamide: manufactured by Tokyo Chemical Industry Co., Ltd. Synthetic hectorite: manufactured by RockWood, trade name: Laponite XLG
Glycerin: manufactured by Sakamoto Yakuhin Kogyo Co., Ltd. Ethidolonic acid: manufactured by Tokyo Chemical Industry Co., Ltd. N, N, N ', N'-Tetramethylethylenediamine: manufactured by Tokyo Chemical Industry Co., Ltd. Emulgen LS106: manufactured by Kao Corp. Irgacure 184 : Made by BASF

(Reference Examples 3 to 5)
As a hydrogel forming material, a first liquid A2 and a second liquid B2 are mixed at a volume ratio of Table 10 below, poured into a 30 mm × 30 mm × 8 mm mold, and an ultraviolet irradiator (Device name: SPOT CURE SP5 After curing using −250 DB (manufactured by USHIO INC.), The hydrogel sample for the compression test of Reference Examples 3 to 5 was obtained by leaving it to stand at 27 ° C. for 12 hours. The moisture content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 10 below.

  From the results of Table 10, it was found that in the reference examples 3 to 5, it is possible to set predetermined strength (compression stress, elastic modulus) and moisture content by adjusting the volume ratio of the first liquid and the second liquid .

(Preparation Example 7 of Support (Core) Forming Material)
Preparation of Support Forming Material 2
1-Dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd.) 50.0 parts by mass, acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) 46.0 parts by mass, and Irgacure 819 (manufactured by BASF Corporation) 4.0 parts by mass are stirred and mixed and dissolved. Thus, a support-forming material 2 was prepared. The composition is shown in Table 11 below.

(Example 16)
Using the shaping apparatus shown in FIG. 4, the first liquid A2, the second liquid B2 and the support-forming material 2 (both active energy ray curable compositions) were discharged at volume ratios shown in Table 12 below. Curing was repeated with ultraviolet light to produce a laminate-molded article. Next, the layered product is allowed to stand in a constant temperature bath at 50 ° C. for 30 minutes, and the support (columnar core) which is a cured product of the support-forming material 2 is removed by liquefaction, and 50 By washing away the remaining support (columnar core) with warm water of ° C., a hydrogel structure having a hollow tubular shape as shown in FIG. 2B was obtained. As in Example 1, the modulus of elasticity, the maximum inside diameter of the narrowest part, and the permeability were measured. The results are shown in Tables 12 and 13 below.

(Example 17)
A structure having a bump portion as shown in FIG. 2B was obtained in the same manner as in Example 16 except that the volume ratio shown in Table 12 below was changed in Example 16. As in Example 1, the modulus of elasticity, the maximum inside diameter of the narrowest part, and the permeability were measured. The results are shown in Tables 12 and 13 below.

(Comparative Examples 7 to 8)
A hydrogel structure was obtained in the same manner as in Example 16 except that the volume ratios shown in Table 12 below were changed in Example 16. As in Example 1, the modulus of elasticity, the maximum inside diameter of the narrowest part, and the permeability were measured. The results are shown in Tables 12 and 13 below.

(Comparative example 9)
The same procedure as in Example 16 is performed except that the support (columnar core) is made of SUP 706 (made by Stratasys) and the other hydrogel, the blood vessel wall and the aneurism part are made by TangoBlack (made by Stratasys). , I got a shaped object. The resulting shaped article was immersed in water for 12 hours to remove the support-forming material to obtain a structure. The elastic modulus was measured in the same manner as in Reference Example 1. The results were each 2.0 MPa.

  Moreover, it carried out similarly to Example 1, and evaluated "the texture." The results are shown in Table 13 below.

In Example 16, the aneurysm could reproduce the texture close to the actual aneurysm and could reproduce the texture very close to the actual blood vessel.
In Example 17, the blood vessel wall had the same degree of hardness as the peripheral part, but it was possible to reproduce the texture of the same hardness as that of the mouse having a low blood vessel wall hardness.
In Comparative Examples 7 to 9, the blood vessels were very hard, stuck, and had a texture far from the real thing.

  From the above results, as in the example, the blood vessel model composed of the hydrogel structure and partially adjusted in hardness and water content has pre-simulation and an insertion of an angiocatheter that the texture is very close to the real thing It became clear that it was suitable for practice.

As an aspect of this invention, it is as follows, for example.
<1> A hydrogel structure having a hollow tube structure having an inner diameter of 1.0 mm or less and having a transmittance of 80% or more in a visible light region.
<2> The hydrogel structure according to <1>, wherein the inner diameter is 0.3 mm or less.
<3> The hydrogel structure according to any one of <1> to <2>, wherein the transmittance in the visible light region is 90% or more.
<4> The hydrogel structure according to any one of <1> to <3>, wherein a solid material that changes to a liquid state by heat is present in the hollow of the hollow tube structure.
<5> The hydrogel structure according to <4>, wherein a coloring material is contained in the hollow of the hollow tube structure.
<6> (1) At least a part of the hollow tubular structure is in contact with a second hydrogel body having a modulus of elasticity different from that of the first hydrogel body constituting the hollow tube structure, or (2) the above It is a hydrogel structure in any one of said <1> to <5> in which the hollow tube structure is formed of at least 2 types of hydrogel bodies from which an elastic modulus differs.
<7> The water content of the first hydrogel body having the hollow tubular structure is lower than the water content of the second hydrogel body having a modulus of elasticity different from that of the first hydrogel body. It is a hydrogel structure as described in <>.
<8> The elastic modulus of the first hydrogel body having the hollow tube structure is 0.1 MPa or more and 0.5 MPa or less,
The hydrogel according to any one of <6> to <7>, wherein a modulus of elasticity of a second hydrogel body having a modulus of elasticity different from that of the first hydrogel body is 0.005 MPa or more and 0.1 MPa or less It is a gel structure.
<9> Assuming that the elastic modulus of one portion in the hollow tubular structure is X (MPa) and the elastic modulus of another portion adjacent to the one portion is Y (MPa), the absolute value of the elastic modulus change It is a hydrogel structure in any one of said <1> to <8> whose (| X-Y |) is 0.1 Mpa or more.
<10> The arithmetic mean surface roughness of the inner wall of at least a portion of the hollow tube structure is 50 μm or less, or the static friction coefficient of the inner wall of at least a portion of the hollow tube structure is 0.1 or less It is a hydrogel structure in any one of <1> to <9>.
<11> A blood vessel model comprising the hydrogel structure according to any one of <1> to <10>.
<12> An organ model comprising the hydrogel structure according to any one of <1> to <11>, wherein the outer shape is a shape that simulates an organ shape.
<13> At least one of the blood vessel model according to <11> and the organ model according to <12>.
It is a procedure exerciser characterized by having at least one of a catheter and an endoscope.
<14> A method for producing a hydrogel structure having a hollow tube structure, comprising:
A columnar core portion is formed using a core portion forming material, and the columnar core portion is covered with a hydrogel forming material to form a tubular portion, and the columnar core portion is removed. It is a manufacturing method of a gel structure.
<15> The method for producing a hydrogel structure according to <14>, wherein the columnar core portion and the tubular portion are formed by a lamination molding method.
<16> The method for producing a hydrogel structure according to any one of <14> to <15>, wherein the core-forming material and the hydrogel-forming material are both active energy ray-curable compositions.
<17> The method for producing a hydrogel structure according to any one of <14> to <16>, wherein the columnar core portion is removed by liquefaction with heat.
<18> A method for producing a hydrogel structure having a hollow tube structure, comprising:
Forming a columnar core using a core forming material, and covering the columnar core with a hydrogel forming material to form a tubular part,
In the method for producing a hydrogel structure, the core-forming material is an active energy ray-curable composition, and a cured product of the active energy ray-curable composition is liquefied by heat. is there.
<19> A solvent (C) capable of dissolving a monofunctional ethylenically unsaturated monomer (A) having a linear chain of 14 or more carbon atoms, a polymerization initiator (B), and the monofunctional ethylenically unsaturated monomer (A) And, and
It is an active energy ray-curable liquid composition characterized in that the cured product is solid at 25 ° C. environment and liquid at 60 ° C. environment.
<20> The active energy ray-curable liquid composition according to <19>, further including a solvent (D) in which the monofunctional ethylenically unsaturated monomer (A) is difficult to dissolve.
<21> A method for producing a three-dimensional object, comprising producing a three-dimensional object using the active energy ray-curable liquid composition according to any one of <19> to <20>.
<22> A method for producing a three-dimensional object by laminating layers of an active energy ray-curable liquid composition,
Layering is performed such that the cured product of the active energy ray-curable liquid composition according to any one of <19> to <20> is a support part, and the layer part is removed by heating after the layer formation. It is a manufacturing method of the three-dimensional molded object characterized by these.
<23> The cured product of the active energy ray-curable liquid composition according to any one of <19> to <20> is a support portion,
It is a manufacturing method of the three-dimensional molded article according to any one of <21> to <22>, in which the hydrogel structure according to any one of <1> to <10> forms a model part by lamination. .
<24> A container containing the active energy ray-curable liquid composition according to any one of <19> to <20>.
A discharge means for discharging the active energy ray-curable liquid composition;
And a curing means for curing the active energy ray-curable liquid composition discharged by the discharging means.

  The hydrogel structure according to any one of <1> to <10>, the blood vessel model according to <11>, the organ model according to <12>, and the procedure exercise device according to <13>, The method for producing a hydrogel structure according to any one of <14> to <18>, the active energy ray-curable composition according to any one of <19> to <20>, and the above <21> According to the method of producing a three-dimensional object according to any one of <24>, the problems of the prior art can be solved, and the object of the present invention can be achieved.

DESCRIPTION OF SYMBOLS 10 Three-dimensional model formation apparatus 11, 12 Head units 13 UV irradiation machine 14 Modeled object support substrate 15 Stage 16 Smoothing member 17 Modeled object 18 Support body (support material)

JP, 2015-69054, A JP, 2015-219371, A JP, 2012-189909, A JP, 2009-273508, A Patent No. 4993519 gazette Patent No. 5745155 gazette

Claims (21)

A hydrogel structure having a hollow tube structure having an inner diameter of 1.0 mm or less and having a transmittance of 80% or more in a visible light region.   The hydrogel structure according to claim 1, wherein the inner diameter is 0.3 mm or less.   The hydrogel structure according to any one of claims 1 to 2, wherein the transmittance in the visible light region is 90% or more.   The hydrogel structure according to any one of claims 1 to 3, wherein a solid material which changes its phase to a liquid state by heat is present in the hollow of the hollow tubular structure.   The hydrogel structure according to claim 4, wherein a coloring material is contained in the hollow of the hollow tube structure. (1) At least a part of the hollow tube structure is in contact with a second hydrogel body having a modulus of elasticity different from that of the first hydrogel body constituting the hollow tube structure, or (2) the hollow tube The hydrogel structure according to any one of claims 1 to 5, wherein the structure is formed of at least two types of hydrogel bodies having different elastic moduli.   The arithmetic mean surface roughness of the inner wall of at least a portion of the hollow tube structure is 50 μm or less, or the static friction coefficient of the inner wall of at least a portion of the hollow tube structure is 0.1 or less. The hydrogel structure according to any one of 6.   A blood vessel model comprising the hydrogel structure according to any one of claims 1 to 7.   An organ model comprising the hydrogel structure according to any one of claims 1 to 7, wherein the outer shape is a shape simulating an organ shape. A blood vessel model according to claim 8, and at least one of an organ model according to claim 9.
A procedure exerciser comprising a catheter and / or an endoscope. A method for producing a hydrogel structure having a hollow tubular structure, comprising:
A columnar core portion is formed using a core portion forming material, and the columnar core portion is covered with a hydrogel forming material to form a tubular portion, and the columnar core portion is removed. Method for producing a gel structure.   The method for producing a hydrogel structure according to claim 11, wherein the columnar core portion and the tubular portion are formed by a lamination molding method.   The method for producing a hydrogel structure according to any one of claims 11 to 12, wherein both the core-forming material and the hydrogel-forming material are active energy ray-curable compositions.   The method for producing a hydrogel structure according to any one of claims 11 to 13, wherein the columnar core portion is removed by liquefying with heat. A method for producing a hydrogel structure having a hollow tubular structure, comprising:
Forming a columnar core using a core forming material, and covering the columnar core with a hydrogel forming material to form a tubular part,
The method for producing a hydrogel structure, wherein the core-forming material is an active energy ray-curable composition, and a cured product of the active energy ray-curable composition is liquefied by heat. A monofunctional ethylenically unsaturated monomer (A) having a linear C14 or more chain, a polymerization initiator (B), and a solvent (C) capable of dissolving the monofunctional ethylenically unsaturated monomer (A) Including
An active energy ray-curable liquid composition characterized in that the cured product is solid at 25 ° C. environment and liquid at 60 ° C. environment.   The active energy ray-curable liquid composition according to claim 16, further comprising a solvent (D) in which the monofunctional ethylenically unsaturated monomer (A) is difficult to dissolve.   A method for producing a three-dimensional object, comprising producing a three-dimensional object using the active energy ray-curable liquid composition according to any one of claims 16 to 17. A method of producing a three-dimensional object by laminating layers of an active energy ray-curable liquid composition, comprising:
18. The laminate molding is carried out so that the cured product of the active energy ray curable liquid composition according to any one of claims 16 to 17 becomes a support part, and after lamination molding the support part is removed by heating. Method of producing a three-dimensional object. The cured product of the active energy ray-curable liquid composition according to any one of claims 16 to 17 is a support portion,
The method for producing a three-dimensional object according to any one of claims 18 to 19, wherein the hydrogel structure according to any one of claims 1 to 7 is laminated and formed so as to be a model part. A container containing the active energy ray-curable liquid composition according to any one of claims 16 to 17;
A discharge means for discharging the active energy ray-curable liquid composition;
And a curing means for curing the active energy ray-curable liquid composition discharged by the discharging means.