WO2019044848A1

WO2019044848A1 - Composition for three-dimensional surgical procedure training model and method for producing said composition

Info

Publication number: WO2019044848A1
Application number: PCT/JP2018/031807
Authority: WO
Inventors: 高橋　宏明; 細川　真幸; 肇小野; 高橋　和也; 瑛規白川
Original assignee: ユシロ化学工業株式会社
Priority date: 2017-08-29
Filing date: 2018-08-28
Publication date: 2019-03-07
Also published as: JPWO2019044848A1

Abstract

The present invention addresses the problem of providing a composition for a three-dimensional surgical procedure training model that can be repeatedly used despite being cut. The composition for a three-dimensional surgical procedure training model contains a self-healing polymer gel.

Description

Composition for three-dimensional surgical treatment training model and method for producing the same

The present application relates to a three-dimensional surgical treatment training model composition and a method of manufacturing the same.

Surgical treatment training models used to practice treatments for skin, blood vessels, heart, liver, etc. have been developed. The surgical treatment training model is a model that simulates the shape and texture of human body organs, and in recent years, development of a three-dimensionally sophisticated surgical treatment training model has been promoted by the development of modeling technology using a 3D printer.

Currently, various products are developed and marketed as three-dimensional surgical treatment training models. The three-dimensional surgical treatment training model is used especially by medical personnel such as medical department students, nursing department students, trainees and doctors at medical sites. For example, skin models for practicing sutures and incisions, blood collection, etc. There are models of blood vessels that practice injection, and models of organs such as heart and liver that practice surgery.
Thus, the three-dimensional surgical treatment training model greatly contributes to the improvement of the skills of medical workers.

Heretofore, polyvinyl alcohol, silicone, urethane, polylactic acid, ABS resin and the like have been known as materials used for a three-dimensional surgical treatment training model.
For example, Patent Documents 1 and 2 disclose organ models using polyvinyl alcohol. By using polyvinyl alcohol, it is possible to create a hydrogel containing water, so it is possible to create a model having a feel similar to that of a real organ. In other words, it is possible to create a model having reality in performing technique training. Moreover, patent documents 3 and 4 are mentioned as an example of a three-dimensional surgical treatment training model using materials other than polyvinyl alcohol.

Unexamined-Japanese-Patent No. 2015-41020 JP, 2010-277003, A JP, 2015-138192, A Unexamined-Japanese-Patent No. 2017-21137

The conventional three-dimensional surgical treatment training model can not be used repeatedly if it is subjected to surgical training with cutting as training for surgical treatment, and is currently discarded at one use. The conventional model that can not be used repeatedly includes, for example, the following problems.

(I) At the actual treatment site, the time taken for preoperative simulation may be limited depending on the condition of the patient, and in the conventional model which can not be used repeatedly, it is multi-directional in a short time (various operating images) Simulation is difficult. In addition, in the blood collection training model, since the simulated blood in which pressure is applied is placed inside the simulated blood vessel, there is a possibility that the simulated blood may spill out from the needle hole generated in the blood collection training. As a result, not only the working environment becomes poor at the time of training, but there is a significant problem of the consumption of simulated blood and blood collection models.
(Ii) The 3D surgical treatment training model is relatively expensive, so the conventional model discarded in one use may not have the necessary number for practice, and the medical worker practices enough. There is a risk of failure.
(Iii) Since individual differences appear in the shape, texture, etc., the reproducibility of practice is poor, and there is a possibility that it will hinder the improvement of the treatment skill.
(Iv) The amount of waste also increases because it is disposed of once.

Thus, the present application solves the above-mentioned problems by providing a composition for a three-dimensional surgical treatment training model that can be used repeatedly even when cut or when a needle hole is generated.

As a result of intensive studies to solve the above problems, the present inventors have found that by using a polymer gel having self-repairing property, it is possible to prepare a composition for a three-dimensional surgical treatment training model that can be repeatedly used. Completed the invention.

That is, the present application is one means for solving the above problems.
Disclosed is a three-dimensional surgical treatment training model composition comprising a polymer gel having self-repairing properties.

Here, the “three-dimensional surgical treatment training model” is a structure three-dimensionally imitating human organs such as skin, blood vessels, and organs, and is provided with not only a single organ but a plurality of organs. Also included. The term "organ" refers to a group of several tissues that form a unique form and exert a certain physiological action.

In the composition, it is preferable that the polymer gel comprises a polymer that is self-repairing using the principle of host-guest interaction.

Further, the polymer contains 1 mol% to 8 mol% of structural units derived from a host group-containing acrylamide monomer, 1 mol% to 8 mol% of structural units derived from a guest group-containing acrylamide monomer, and an acrylamide monomer The polymer gel contains an aqueous solvent in the gaps of the network structure of the polymer, and the hardness of the composition is 931 mN to 4264 mN or less in conversion value Is preferred.

Here, the “converted value” is a converted value calculated from the measured value of a device that measures the hardness of the composition, and for example, the converted value can be calculated from the measured value of the spring load of a rubber hardness tester.

Furthermore, the structural unit derived from the host group-containing acrylamide monomer is the following general formula (1), the structural unit derived from the guest group-containing acrylamide monomer is the following general formula (2), and the acrylamide monomer is derived It is preferable that a structural unit is following General formula (3).

Here, R ¹ to R ⁷ each represent hydrogen or a methyl group. R ^H represents a host group and is either α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin. R ^G represents a guest group, which is any of n-butyl, n-dodecyl, t-butyl, isobornyl and adamantyl groups.

Preferably, the aqueous solvent comprises water, or water and a hydrophilic solvent having a boiling point higher than that of water. The hydrophilic solvent is not particularly limited, and includes, for example, at least one selected from the group consisting of ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, glycerin and diethylene glycol monoethyl ether. preferable.

The content of the aqueous solvent in the composition is 49.45 wt% or more and 85.45 wt% or less based on the polymer gel, and the content of water in the aqueous solvent is 15 based on the polymer gel. It is preferable that it is 40 weight% or more.

In the composition, it is preferable that the polymer gel contains a filler. Moreover, it is preferable that the said filler is an organic type filler. Furthermore, when the polymer gel contains a filler, the content of the aqueous solvent is 45.85% by weight or more and 69.21% by weight or less based on the polymer gel, and the content of water in the aqueous solvent is the above Preferably, the content is 14.50% by weight or more based on the polymer gel, and the content of the filler is 15.00% by weight or more and 26.00% by weight or less based on the polymer gel.

Furthermore, the present application is one means for solving the above problems.
A method of producing the above composition, which comprises the steps of mixing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, and the aqueous solvent, and a solution obtained by the mixing step. And a step of polymerizing the polymerization initiator, and a step of polymerizing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, and the acrylamide monomer, and the host in the solution in the polymerization step. Composition for three-dimensional surgical treatment training model which adjusts the hardness of the composition by adjusting the content of a group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, and the aqueous solvent Disclosed is a method of manufacturing a product.

When the above composition contains a filler, the present invention is one means for solving the above problems.
A method for producing the composition containing a filler, which comprises mixing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, the aqueous solvent, and the filler; Including the steps of adding a polymerization initiator to the solution obtained by the step of adding, the step of polymerizing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, and the acrylamide monomer; The hardness of the composition is adjusted by adjusting the content of the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, the aqueous solvent, and the filler in the solution in , 3D Surgical Research Institute It discloses a process for the production of a model composition.

In these production methods, a polymerization accelerator is added in at least one of the mixing step and the adding step, and the content of the polymerization accelerator in the solution in the polymerization step is adjusted to adjust the content of the composition. The hardness can be adjusted.

The method further comprises the step of immersing the gel obtained by the polymerization step in a solvent for immersion, wherein the solvent for immersion comprises the hydrophilic solvent, or contains the hydrophilic solvent and water, and the immersion time of the gel and The hardness of the composition can be adjusted by adjusting at least one of the concentration of the hydrophilic solvent in the immersion solvent.

Since the composition for three-dimensional surgical treatment training model of the present disclosure has self-repairing property, the cut interface can be self-repaired even if it is cut, and can be used repeatedly. Thus, the compositions of the present disclosure can provide healthcare professionals with the opportunity to practice treatment well. In addition, since it can be used repeatedly, the reproducibility of treatment practice is high. In addition, model waste can be reduced.

It is a figure explaining one aspect (manufacturing method 10) of a manufacturing method of a composition.

Hereinafter, embodiments of the composition for a three-dimensional surgical treatment training model of the present disclosure and a method of manufacturing the same will be described.

<Composition for 3D surgical treatment training model>
The composition for a three-dimensional surgical treatment training model of the present disclosure includes a polymer gel having self-repairing properties.

(Polymer gel)
A preferred form of the above-mentioned polymer gel is one comprising a polymer that is self-repairing utilizing the host-guest interaction principle.
The host-guest interaction is a non-covalent interaction that occurs when a guest group is included in a host group to form an inclusion complex.

(Polymer)
Polymers utilizing the principle of host-guest interaction form a complex in which a host group and a guest group form an inclusion complex, thereby forming a cross-linked site in the molecule. Have. And the aqueous solvent mentioned later is contained in the gap of this network structure. In addition, noncovalent bond means bond form other than covalent bond, and is a concept including hydrophobic interaction, hydrogen bond, intermolecular force, electrostatic interaction, coordination bond, π electron interaction, etc. .
By constructing a polymer using the principle of host-guest interaction, it is possible to impart a self-repairing function to a polymer gel, and additionally, in conventional materials (eg, silicon, urethane, etc.) It is possible to impart high stretchability, shape memory and toughness that could not be achieved. In particular, when toughness is imparted, for example, when a skin model is produced, cracking does not easily occur in the model even when sutured with a needle or thread.

It is preferable that the said polymer is comprised by the structural unit derived from an acrylamide type monomer. Specifically, a structural unit derived from a host group-containing acrylamide monomer (hereinafter sometimes referred to as "host group-containing AA monomer"), a guest group-containing acrylamide monomer (hereinafter, "guest group-containing AA monomer" A polymer gel comprising a polymer comprising a structural unit derived from “monomer” and a structural unit derived from an acrylamide monomer (hereinafter sometimes referred to as “AA monomer”).
The compositions can also be rendered antiseptic by synthesizing polymers using these AA monomers. In addition, in the hydrogel using the polyvinyl alcohol used conventionally, there exists a subject which does not have antiseptic property and is easy to deteriorate.

Here, the preferable content of the structural unit derived from these AA monomers constituting the polymer is as follows.
In the polymer, it is preferable that structural units derived from the host group-containing AA monomer be 0.5 mol% or more and 10 mol% or less, and structural units derived from the guest group-containing AA be 0.5 mol% or more and 10 mol% or less. As a result, interaction between the host group and the guest group easily occurs, a crosslinked structure is formed in the polymer, a stable structure is easily obtained, and a polymer excellent in self-repairing property is obtained. More preferably, the structural unit derived from the host group-containing AA monomer in the polymer is 1 mol% to 8 mol%, and the structural unit derived from the guest group-containing AA monomer is 1 mol% to 8 mol%. This improves self-healing properties. Particularly preferably, the structural unit derived from the host group-containing AA monomer in the polymer is 2 mol% or more and 4 mol% or less, and the structural unit derived from the guest group-containing AA monomer is 2 mol% or more and 4 mol% or less. Thereby, the self-repairing property is further improved, and the stretchability is also improved.
The structural unit derived from the AA monomer in the polymer is preferably contained at 80 to 99 mol%, more preferably 84 to 98 mol%, and 92 to 96 mol%. Is particularly preferred.

The polymerization form of the polymer is not particularly limited as long as it has self-healing properties, and may be random copolymerization, block copolymerization, or graft copolymerization.

Specific examples of structural units derived from host group-containing AA monomers include structures of the following formula (1). The structural unit derived from the host group-containing AA monomer represented by the following formula (1) may be only one type or two or more types in the polymer.

Here, R ¹ and R ² each represent hydrogen or a methyl group. R ^H represents a host group.

As a structural unit derived from a guest group containing AA monomer, the structure of following formula (2) is mentioned. The structural unit derived from the guest group-containing AA monomer represented by the following formula (2) may be only one type or two or more types in the polymer.

Here, R ³ and R ⁴ each represent hydrogen or a methyl group. R ^G represents a guest group.

Specific examples of structural units derived from AA monomers include structures of the following formula (3). The structural unit derived from the AA monomer represented by the following formula (3) may be only one type or two or more types in the polymer.

Here, R ⁵ , R ⁶ and R ⁷ each represent hydrogen or a methyl group.

As a preferable combination of a host group and a guest group forming an inclusion complex, for example, when α-cyclodextrin (cavity size: 4.7 to 5.2 Å) is used as the host group, the guest group has 4 carbon atoms. Examples thereof include alkyl groups of to 18 and alcohol derivatives thereof, carboxylic acid derivatives, amino derivatives, azobenzene derivatives having a cyclic alkyl group or a phenyl group, cinnamic acid derivatives and the like. Examples of the alkyl group having 4 to 18 carbon atoms include n-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, Hexadecyl group, heptadecyl group and octadecyl group can be mentioned.

When β-cyclodextrin (cavity size: 6.0 to 6.5 Å) is used as a host group, a t-butyl group, an adamantyl group, an isobornyl group, an aromatic compound and an alcohol derivative thereof, a carboxylic acid derivative as a guest group And amino derivatives, ferrocene derivatives, azobenzenes, naphthalene derivatives, dansyl groups and the like.

When γ-cyclodextrin (cavity size: 7.5 to 8.5 Å) is used as a host group, as a guest group, an alkyl group having up to 18 carbon atoms and its alcohol derivative, carboxylic acid derivative, amino derivative, adamantyl group, Examples thereof include clusters composed of carbon atoms such as fullerene, and aromatic dansyl groups, ferrocene derivatives, anthracene derivatives and the like.

Besides the above, as host groups, calix [6] arenesulfonic acid, calix [8] arenesulfonic acid, 12-crown-4 ether, 18-crown-6 ether, [6] paracyclophane, [2,2 ] May be mentioned paracyclophane, cucurbit [6] uril and cucurbit [8] uril. As a guest group to be combined with this, any of the guest groups exemplified above can be used.

From the viewpoint of facilitating host-guest interaction and further improving the self-repairing property, it is preferable that the host group is either α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin. For the same reason, it is preferable that the guest group is any of n-butyl group, n-dodecyl group, t-butyl group, isobornyl group or adamantyl group. As a combination of host group and guest group, α-cyclodextrin and n-dodecyl group, or β-cyclodextrin and adamantyl group are particularly preferable.

(Water-based solvent)
The polymer gel preferably contains an aqueous solvent in the interstices of the polymer network structure. The aqueous solvent is not particularly limited as long as it is a solvent containing water, but it is preferable to use water or a hydrophilic solvent having a boiling point higher than water and water.
By including water, the composition can be given a texture and feel close to the actual organ. Further, by including a hydrophilic solvent having a boiling point higher than that of water, the composition becomes difficult to be dried, and deterioration due to drying, for example, deterioration of self-repairing property and deterioration such as texture and feel are suppressed. That is, it becomes a form suitable for long-term use as a training model.

As water, pure water, ion exchange water, tap water or the like can be used.

Hydrophilic solvents having a boiling point higher than that of water are those having a boiling point of over 100 ° C. at normal pressure. The upper limit of the boiling point is not particularly limited, but if the pressure is 300 ° C. or less at normal pressure, the swelling property of the polymer gel is excellent, and the deterioration of physical properties is hardly caused. In addition, a solvent having a hydroxyl group with high affinity to the polymer gel is preferable.
Specifically, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, glycerin and diethylene glycol monoethyl ether can be mentioned, and these may be one kind or may be mixed. More preferably, it is a solvent containing glycerin.

The content of the aqueous solvent in the polymer gel is preferably 49.45% by weight or more and 85.45% by weight or less based on the entire polymer gel. If the content of the aqueous solvent in the polymer gel exceeds 85.45% by weight, the shape of the polymer gel may not be maintained. On the other hand, when the content of the aqueous solvent in the polymer gel is less than 49.45% by weight, the hardness of the composition tends to be hard, and it becomes difficult to adjust the hardness of the composition.
The water-based solvent preferably contains 14.50% by weight or more, more preferably 15.40% by weight or more, based on the total weight of the polymer gel. This can give the composition a texture and feel close to the actual organ. In addition, the aqueous solvent can contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 56.00% by weight or less based on the entire polymer gel. The reason that “0% by weight or more” is used is that it is not essential that the aqueous solvent contains a hydrophilic solvent. However, in order to enhance the drying resistance, the content of the hydrophilic solvent is preferably 10.00% by weight or more.

(Other additives)
The polymer gel can contain other additives as long as the self-repairing property is not impaired. For example, colorants, antioxidants, ultraviolet light absorbers, light stabilizers, organic fillers, fillers such as inorganic compound fillers, metal fillers, electrolytes, ionic liquids, preservatives, antibacterial agents, etc. may be mentioned.

(Filler)
As mentioned above, the polymer gel can comprise a filler. By containing the filler in the polymer gel, the hardness of the composition can be adjusted to a desired hardness. In addition, the tackiness of the composition can be reduced. Furthermore, the processability of the composition can be improved. Thus, the inclusion of the filler in the polymer gel facilitates handling of the composition.

Here, the tackiness refers to the tackiness of the composition. The tackiness of the composition is preferably such that the composition does not stick to the finger when touching the surface. This makes it possible to obtain a feeling close to the actual organ. In a polymer gel not containing a filler, the tackiness appears strongly, and when the surface of the composition is touched, the composition may stick to the finger.
Further, the processability refers to the easiness of processing the shape of the composition, and examples include cutability and cuttability. The improvement of the processability of the composition facilitates the production of an organ model that requires processing. For example, in the case of a skin model, a plurality of layers with different hardness may be laminated to be brought close to the actual skin texture. In that case, it is preferable that the processability of the composition be better, since the sheet-like compositions having different hardnesses are cut and laminated after being adjusted in size. In addition, since the shape of the composition depends on the type (container) for producing the polymer gel, by improving the processability, the shape of the composition is processed after producing the polymer gel without using a precise organ shape type It becomes easy to do. In addition, by improving the processability of the composition, the feel at the time of cutting the composition also approaches real organs.

The type of filler that can be contained in the polymer gel is not particularly limited, and fillers such as organic fillers, inorganic compound fillers, and metal fillers can be used. Preferably, it is an organic filler. Organic fillers have less influence on the human body and are suitable for organ models. As the organic filler, it is preferable to use at least one selected from the group consisting of acrylic acid amide polymer, gelatin and agar. From the viewpoint of enhancing the transparency of the composition, an acrylic acid amide polymer close to the refractive index of the composition is more preferable.

The content of the filler in the polymer gel is preferably 15.00% by weight or more and 26.00% by weight or less based on the entire polymer gel. This makes it possible to obtain a composition having appropriate tackiness as the organ model (tackiness that does not stick to the finger when the surface of the composition is touched). More preferably, it is 21.00 wt% or more and 26.00 wt% or less. Thereby, a composition more suitable for processing can be obtained.
When the polymer gel contains a filler, the content of the aqueous solvent is preferably 45.85% by weight or more and 69.21% by weight or less based on the whole polymer gel. At this time, the content of water in the aqueous solvent is preferably 14.50% by weight or more based on the polymer gel. In addition, the aqueous solvent can contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% by weight or less based on the entire polymer gel.

(Hardness of composition)
The hardness of the composition is a very important factor to reproduce the texture, feel, etc. of the actual organ. In the present invention, the hardness of the composition is preferably 931 mN or more and 4264 mN or less in terms of a conversion value. Thereby, the texture and feel close to the desired organ can be imparted to the composition.

Here, the “converted value” is a converted value calculated from the measured value of a device that measures the hardness of the composition, and for example, the converted value can be calculated from the measured value of the spring load of a rubber hardness tester. The measuring method can be performed in accordance with JIS K6253-3. Examples of the rubber hardness tester include Asker rubber hardness tester CSC2 (manufactured by Kobunshi Keiki Co., Ltd.).

(Shape of composition)
The compositions of the present disclosure can be shaped to mimic a model organ. For example, a desired shape can be formed by performing the manufacturing method described later in a mold imitating an organ. The above mold can be produced by, for example, a 3D printer. In addition, the composition can be colored or the like in order to resemble the model organ.

(Composition suitable for each model)
The composition of the composition suitable for each model is described below.

When producing a liver model as a three-dimensional surgical treatment training model, in the polymer constituting the polymer gel, the structural unit derived from the host group-containing AA monomer is 1 mol% or more and 8 mol% or less, derived from the guest group-containing AA monomer It is preferable that a structural unit is 1 mol% or more and 8 mol% or less, and a structural unit derived from an AA monomer is 84 mol% or more and 98 mol% or less.
The content of the aqueous solvent in the polymer gel is preferably 55.60% by weight or more and 85.45% by weight or less based on the entire polymer gel. At this time, the aqueous solvent preferably contains water at 15.4 wt% or more based on the entire polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 56.00% by weight or less based on the entire polymer gel.
On the other hand, when a filler is included in the polymer gel, the content of the filler in the polymer gel is preferably 15.00% by weight or more and 21.00% by weight or less based on the entire polymer gel. The content of the aqueous solvent in the polymer gel is preferably 64.41% by weight or more and 69.21% by weight or less based on the entire polymer gel. At this time, the aqueous solvent preferably contains 17.30% by weight or more of water based on the entire polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% by weight or less based on the entire polymer gel.
The hardness of the composition is preferably 931 mN or more and 1911 mN or less.
By satisfying the above-mentioned range, it is possible to reproduce the texture and feel very close to the actual healthy liver. However, since the hardness of the liver varies depending on the sex and age of the patient to be reproduced, it may be changed appropriately without staying in the above range. The same applies to the case of reproducing a diseased liver (cirrhosis, liver cancer, etc.).

When producing a cardiac model as a three-dimensional surgical treatment training model, in the polymer constituting the polymer gel, the structural unit derived from the host group-containing AA monomer is 1 mol% or more and 8 mol% or less, the guest group containing AA monomer derived It is preferable that a structural unit is 1 mol% or more and 8 mol% or less, and a structural unit derived from an AA monomer is 84 mol% or more and 98 mol% or less.
The content of the aqueous solvent in the polymer gel is preferably 55.60% by weight or more and 71.40% by weight or less based on the entire polymer gel. At this time, it is preferable that the aqueous solvent contains 25.15% by weight or more of water based on the entire polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water, in an amount of 0% by weight or more and 37.00% by weight or less based on the entire polymer gel.
On the other hand, when the filler is contained in the polymer gel, the content of the filler in the polymer gel is preferably 23.00% by weight or more and 26.00% by weight or less based on the whole polymer gel. The content of the aqueous solvent in the polymer gel is preferably 55.00% by weight or more and 62.00% by weight or less based on the whole polymer gel, and is 58.00% by weight or more and 61.00% by weight or less Is preferred. At this time, the aqueous solvent more preferably contains water at 16.20% by weight or more based on the entire polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water, in an amount of 0% to 44.11% by weight based on the entire polymer gel.
The hardness of the composition is preferably 2068 mN to 2696 mN.
By satisfying the above-mentioned range, it is possible to reproduce the texture and feel very close to the actual healthy heart. However, since the hardness of the heart varies depending on the sex and age of the patient to be reproduced, it may be appropriately changed without being limited to the above range. The same applies to the case of reproducing a diseased heart (myocardial infarction, cardiac hypertrophy, etc.).

When preparing a skin model as a three-dimensional surgical treatment training model, in the polymer constituting the polymer gel, the structural unit derived from the host group-containing AA monomer is 1 mol% or more and 8 mol% or less, derived from the guest group-containing AA monomer It is preferable that a structural unit is 1 mol% or more and 8 mol% or less, and a structural unit derived from an AA monomer is 84 mol% or more and 98 mol% or less.
The content of the aqueous solvent in the polymer gel is preferably 49.45% by weight or more and 71.89% by weight or less based on the entire polymer gel. At this time, the aqueous solvent preferably contains water at 19.55% by weight or more based on the whole polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 52.00% by weight or less based on the entire polymer gel.
On the other hand, when the filler is contained in the polymer gel, the content of the filler in the polymer gel is preferably 15.00% by weight or more and 26.00% by weight or less based on the whole polymer gel. The content of the aqueous solvent in the polymer gel is preferably 45.85% by weight or more and 69.21% by weight or less based on the entire polymer gel. At this time, the aqueous solvent preferably contains water at 14.50% by weight or more based on the entire polymer gel. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% or less based on the entire polymer gel.
The hardness of the composition is preferably 1166 mN to 4264 mN.
By satisfying the above-mentioned range, it is possible to reproduce the texture and feel very close to the actual skin. However, since the hardness of the skin varies depending on the sex and age of the patient to be reproduced, it may be changed appropriately without being limited to the above range. The same is true for reproducing the skin that has been affected (burn, skin cancer, keloid, etc.).
In addition, since the skin is a multi-layered organ such as the epidermis and the dermis, by laminating a plurality of polymer gels adjusted to various hardness and using it, it is possible to obtain a more realistic texture. Under these circumstances, the hardness of the skin model composition is set to a wider range than that of the liver model composition and the heart model composition.

(Self-healing using the principle of host-guest interaction)
Here, the mechanism by which the polymer gel self-repairs by host-guest interaction is briefly described.
The above-mentioned composition is usually constituted in a state where at least a part of the host group and the guest group form an inclusion complex. When the composition is subjected to therapeutic training and cleaved, the host and guest groups become dissociated at the cleavage interface. Then, after training or the like is completed, when the cleavage interface is recontacted to restore the composition, the dissociated host group and guest group are again included, and the cleavage interfaces adhere and fuse.

The composition of the present disclosure is self-repairing utilizing the host-guest interaction principle as described above, so that the cutting interface can be simplified easily at normal temperature and pressure without the use of special tools and complicated configuration requirements. Self-healing is possible.
On the other hand, in the case of a polymer gel having self-healing properties based on another principle, heating or irradiation with ultraviolet light / visible light is performed, or microcapsules encapsulated in the polymer gel are broken, and contents (monomers etc. Release self-healing, etc., to enable self-healing. Thus, a polymer gel having self-repairing properties using other principles needs to be equipped with the use of a special tool and complicated configuration requirements.

<Method of Producing Composition for 3D Surgical Treatment Training Model>
Next, a method of producing the composition for training a model for three-dimensional surgical treatment described above will be described.

One aspect of the method for producing the composition (hereinafter sometimes referred to as “production method 10”) will be described.
Production method 10 is obtained by the step of mixing a host group-containing acrylamide monomer, a guest group-containing acrylamide monomer, an acrylamide monomer, and an aqueous solvent (hereinafter sometimes referred to as "S11"), and S11. Adding a polymerization initiator to the solution (hereinafter sometimes referred to as "S12"), and a step of polymerizing a host group-containing acrylamide monomer, a guest group-containing acrylamide monomer, and an acrylamide monomer ((S12)) In the following, it may be written as "S13".
The hardness of the composition is adjusted by adjusting the contents of the host group-containing acrylamide monomer, guest group-containing acrylamide monomer, acrylamide monomer, and aqueous solvent in the solution in S13 in the above S11 and S12. be able to.
A flow chart of manufacturing method 10 is shown in FIG.

(S11: step of mixing)
In S11, a host group-containing AA monomer, a guest group-containing AA monomer, an AA monomer, and an aqueous solvent are mixed. If necessary, a polymerization accelerator is added in S11. Also, fillers may be added and mixed. The addition of the filler makes it possible to reduce the tackiness and to improve the processability of the produced composition.
In addition, after mixing in S11, heating, standing, ultrasonic dispersion treatment, or the like is preferably performed to clathrate the host group and the guest group to form an inclusion complex.

As a polymerization accelerator, N, N, N ', N'-tetramethylethylenediamine (TEMED), sodium ascorbate, etc. can be mentioned.

(S12: step to be added)
In S12, a polymerization initiator is added to the solution obtained by S11. Moreover, the said polymerization accelerator can be added also in S12 as needed.

As a polymerization initiator, ammonium persulfate (APS), azobisisobutyronitrile (AIBN), 2,2′-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride (VA-044), 1,1'-azobis (cyclohexanecarbonitrile), di-tert-butylperoxide, tert-butyl hydroperoxide, benzoyl peroxide, hydrogen peroxide, photopolymerization initiators (IRGACURE (registered trademark) series etc.), etc. . Preferably, it is APS, VA-044.

(S13: step of polymerizing)
In S13, the host group-containing AA monomer, the guest group-containing AA monomer, and the AA monomer are polymerized.
At this time, the hardness of the composition to be produced is determined according to the contents of the host group-containing AA monomer, guest group-containing AA monomer, AA monomer, and aqueous solvent in the solution in S13. Therefore, in order to adjust the hardness of a composition to the target hardness, it is preferable to adjust content of the component in the solution in S13 in a front process (S11, S12). When a filler is added, the hardness of the composition to be produced is determined according to the content of host group-containing AA monomer, guest group-containing AA monomer, AA monomer, aqueous solvent, and filler in the solution in S13. . In addition, when the polymerization accelerator is added, the hardness of the composition also changes depending on the content of the polymerization accelerator in the solution in S13. Therefore, it is preferable to adjust the content of the filler and / or the content of the polymerization accelerator in S11 and S12.

Specifically, the content of the host group-containing AA monomer in the solution at S13 is 2.00% by weight or more and 26.00% by weight or less based on the entire solution, and the content of the guest group-containing AA monomer is the entire solution 0.35% by weight or more and 3.90% by weight or less, the content of the AA monomer is 9.00% by weight or more and 29.60% by weight or less based on the entire solution, and the content of the aqueous solvent is It is preferable that it is 49.45 weight% or more and 85.45 weight% or less based on the whole solution.
The aqueous solvent preferably contains water at 14.50% by weight or more based on the whole solution, and more preferably at least 15.40% by weight. In addition, the aqueous solvent can contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 56.00% by weight or less based on the entire solution. The reason that “0% by weight or more” is used is that it is not essential that the aqueous solvent contains a hydrophilic solvent. In order to enhance the drying resistance, the content of the hydrophilic solvent is preferably 10.00% by weight or more.
Thereby, the composition can be adjusted to a desired hardness.

When the filler is added, the content of the host group-containing AA monomer in the solution in S13 is 4.80% by weight or more and 10.00% by weight or less based on the entire solution, and the content of the guest group-containing AA monomer is 0.70% by weight or more and 1.50% by weight or less based on the whole solution, the content of AA monomer is 8.00% by weight or more and 16.30% by weight or less based on the whole solution, and containing an aqueous solvent The amount is adjusted to 45.85% by weight or more and 69.21% by weight or less based on the whole solution, and the content of the filler is 15.00% by weight or more and 26.00% by weight or less based on the whole solution preferable.
The aqueous solvent preferably contains water at 14.50% by weight or more based on the entire solution. In addition, the aqueous solvent can include a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% by weight or less based on the entire solution.
Thereby, the composition can be adjusted to a desired hardness. In addition, a composition having appropriate tackiness as an organ model can also be obtained. Moreover, when the content of the filler is 21.00% by weight or more and 26.00% by weight or less based on the entire solution, a composition more suitable for processing can be obtained.

When a polymerization accelerator is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.01% by weight or more and 3.00% by weight or less based on the entire solution. When a filler is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.01% by weight or more and 1.00% by weight or less based on the entire solution, and 0.05% by weight or more. The content is more preferably 50% by weight or less, still more preferably 0.09% by weight or more and 0.25% by weight or less.
If the content of the polymerization accelerator is less than 0.01% by weight, the polymerization reaction may not proceed rapidly. On the other hand, when the content of the polymerization accelerator exceeds 3.00% by weight, the polymerization reaction proceeds excessively, the resulting polymer gel tends to be too soft, and the shape becomes difficult to maintain.

When the aqueous solvent is composed of two or more components, the hardness of the composition can be adjusted also by the ratio of these components.
In addition, when the content of water in the aqueous solvent is less than 14.50% by weight based on the entire solution, the solubility of the monomer tends to be deteriorated.

Furthermore, the preferred content for producing a composition suitable for each model is described.
When producing a composition for a liver model, the content of the host group-containing AA monomer in the solution in S13 is 2.00% by weight or more and 11.00% by weight or less based on the whole solution, and a guest group The content of the contained AA monomer is 0.35% to 1.80% by weight based on the whole solution, and the content of the AA monomer is 9.00% to 18.50% by weight on the whole solution The content of the aqueous solvent is preferably 55.60% by weight or more and 85.45% by weight or less based on the entire solution.
The aqueous solvent preferably contains water at 15.40% by weight or more based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 56.00% by weight or less based on the entire solution.
When adding a polymerization accelerator, it is preferable that content of the polymerization accelerator in the solution in S13 is 0.50 weight% or more and 3.00 weight% or less based on the whole solution.

When the filler is added, the content of the host group-containing AA monomer in the solution in S13 is 5.10% by weight or more and 5.50% by weight or less based on the entire solution, and the content of the guest group-containing AA monomer is 0.80% by weight or more and 0.90% by weight or less based on the whole solution, the content of the AA monomer is 8.50% by weight or more and 9.20% by weight or less based on the whole solution, and containing an aqueous solvent It is preferable that the amount is 64.41% by weight or more and 69.21% by weight or less based on the whole solution, and the content of the filler is 15.00% by weight or more and 21.00% by weight or less based on the whole solution.
The aqueous solvent preferably contains 17.30% by weight or more of water based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% by weight or less based on the entire solution.
When a polymerization accelerator is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.01% by weight or more and 1.00% by weight or less based on the whole solution, 0.05% by weight The content is more preferably 0.50% by weight or less, still more preferably 0.09% by weight or more and 0.25% by weight or less.

When producing the composition for the heart model, the content of the host group-containing AA monomer in the solution in S13 is 10.00 wt% or more and 15.50 wt% or less based on the entire solution, and the guest group is The content of the contained AA monomer is 1.50% by weight or more and 2.50% by weight or less based on the whole solution, and the content of the AA monomer is 16.50% by weight or more and 26.00% by weight or less based on the whole solution It is preferable that the content of the aqueous solvent is 55.60% by weight or more and 71.40% by weight or less based on the entire solution.
The aqueous solvent preferably contains 25.15% by weight or more of water based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 37% by weight or less based on the entire solution.
When a polymerization accelerator is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.40 wt% or more and 0.60 wt% or less based on the entire solution, and 0.45 wt% or more The content is more preferably 0.55% by weight or less, particularly preferably 0.50% by weight.

When the filler is added, the content of the host group-containing AA monomer in the solution in S13 is 4.80% by weight or more and 5.00% by weight or less based on the entire solution, and the content of the guest group-containing AA monomer is 0.70% by weight or more and 0.75% by weight or less based on the whole solution, the content of the AA monomer is 8.00% by weight or more and 8.30% by weight or less based on the whole solution, and containing the aqueous solvent The amount is 55.00% by weight to 62.00% by weight based on the whole solution (more preferably 58.00% by weight to 61.00% by weight), and the content of the filler is the whole solution It is preferable that it is 23.00 weight% or more and 26.00 weight% or less based on.
The aqueous solvent preferably contains water at 16.20% by weight or more based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 44.11% by weight or less based on the entire solution.
When a polymerization accelerator is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.01% by weight or more and 1.00% by weight or less based on the whole solution, 0.05% by weight The content is more preferably 0.50% by weight or less, still more preferably 0.09% by weight or more and 0.25% by weight or less.

When producing the composition for the skin model, the content of the host group-containing AA monomer in the solution in S13 is 10% by weight or more and 26% by weight or less based on the entire solution, and the guest group-containing AA monomer The content is 1.50 wt% or more and 3.90 wt% or less based on the whole solution, the content of AA monomer is 13.90 wt% or more and 29.60 wt% or less based on the whole solution, water system The content of the solvent is preferably 49.45% by weight or more and 71.89% by weight or less based on the entire solution.
The aqueous solvent preferably contains 19.95% by weight or more of water based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 52.00% by weight or less based on the entire solution.
When adding a polymerization accelerator, it is preferable that content of the polymerization accelerator in the solution in S13 is 0.01 weight% or more and 1.50 weight% or less based on the whole solution.

When the filler is added, the content of the host group-containing AA monomer in the solution in S13 is 4.80% by weight or more and 10.00% by weight or less based on the entire solution, and the content of the guest group-containing AA monomer is 0.70% by weight or more and 1.50% by weight or less based on the whole solution, the content of AA monomer is 8.00% by weight or more and 16.30% by weight or less based on the whole solution, and containing an aqueous solvent Preferably, the amount is 45.85% by weight to 69.21% by weight based on the whole solution, and the content of the filler is 15.00% by weight to 26.00% by weight based on the whole solution.
The aqueous solvent preferably contains water at 14.50% by weight or more based on the entire solution. The aqueous solvent can also contain a hydrophilic solvent having a boiling point higher than that of water in an amount of 0% by weight or more and 50.61% by weight or less based on the entire solution.
When a polymerization accelerator is added, the content of the polymerization accelerator in the solution in S13 is preferably 0.01% by weight or more and 1.00% by weight or less based on the whole solution, 0.05% by weight The content is more preferably 0.50% by weight or less, still more preferably 0.09% by weight or more and 0.25% by weight or less.

Further, the concentration of the polymerization initiator in the solution at S13 is not particularly limited as long as the above monomers can be appropriately polymerized, but it is 0.03 wt% or more and 0.10 wt% or less based on the whole solution. preferable.
The conditions of the polymerization reaction can be set as appropriate, for example, by stirring the solution at 0 to 80 ° C., preferably 5 to 25 ° C. The reaction time of the polymerization reaction can be 30 seconds to 24 hours, preferably 30 seconds to 1 hour. When a photopolymerization initiator is used as the polymerization initiator, for example, the polymerization reaction can be performed by irradiating the solution with UV light having a wavelength of 200 to 405 nm.

In addition, the gel obtained by S13 can perform refinement | purification, drying, and curing as needed.

Although the composition of the present disclosure can be produced by the above-described steps S11 to S13, the following immersion step (which may be hereinafter referred to as "S14") may be further performed.

(S14: step of immersing)
In S14, the gel obtained by S13 is immersed in the immersion solvent.
The immersion solvent preferably comprises the above-mentioned hydrophilic solvent, or preferably comprises the above-mentioned hydrophilic solvent and water.
Immersion conditions can be performed at room temperature. In addition, when immersing, it is preferable to completely immerse the gel in the immersion solvent.

The immersion time of the gel in S14 can be suitably adjusted in order to make the composition to be manufactured into a desired hardness. For example, the immersion time can be 0.1 hours or more and 48 hours or less. As a result, at least a portion of the water in the polymer gel is replaced by the hydrophilic solvent, and the polymer gel contains water and the hydrophilic solvent.
The immersion time is 12 hours or more and 48 hours or less when producing the composition for the liver model, and the immersion time is 6 hours or more and 24 hours or less when the composition for the heart model is produced, When manufacturing the composition for skin model, it is preferable to make immersion time into 1 to 6 hours. However, these preferable immersion times are one example, and are suitably changed according to the size and surface area of a shaped article.

The hardness of the composition is also adjusted by the concentration of the hydrophilic solvent in the immersion solvent. For example, as a preferable density | concentration of the hydrophilic solvent in the solvent for immersion, the range of 20 weight% or more and 100 weight% or less can be mentioned.

As mentioned above, the composition of this indication is obtained by the manufacturing method 10. In addition, by performing the manufacturing method 10 in a mold imitating a model organ, it is possible to easily form a three-dimensionally sophisticated model even if it has a complicated shape.

Examples will be described below, but the composition of the present disclosure and the method for producing the same are not limited thereto.

The monomers used in the examples are as follows.
Host group-containing acrylamide monomer (host group-containing AA monomer): mono-6-deoxy-6- (acrylamide) -β-cyclodextrin (prepared according to WO 2012/036069, purity 88%) . When this is polymerized, it becomes a structural unit in which R ¹ and R ² are hydrogen and R ^H is β-cyclodextrin (bonded at the 6-position hydroxy group) in the above-mentioned formula (1).
Guest group-containing acrylamide-based monomer (guest group-containing AA monomer): N- (1-adamantyl) acrylamide (prepared according to WO 2012/036069, purity of 99% or more) was used. When this is polymerized, it becomes a structural unit in which R ³ and R ⁴ are hydrogen and R ^G is an adamantyl group (bonded at the 1-position) in the above formula (2).
Acrylamide-based monomer (AA monomer): Acrylamide (manufactured by Wako Pure Chemical Industries, Ltd., purity 98% or more) was used. When this is polymerized, structural units in which R ⁵ , R ⁶ and R ⁷ are hydrogen in the above formula (3) become.

(Examples 1 to 4 and 8 to 13; Comparative Examples 1 and 2 and 5 to 8)
In a sample tube (3 ml), host group-containing AA monomer, guest group-containing AA monomer, AA monomer, and water were placed and mixed. Then, the mixture was stirred for 5 minutes while being irradiated with ultrasonic waves to completely dissolve the monomer. Subsequently, APS (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization initiator and TEMED (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization accelerator are added to a solution, and the obtained solution is subjected to polymerization reaction conditions (room temperature) Left for 1 hour). In this state, it was allowed to stand for 12 hours in a wet state (Rh 80 ± 5%) at room temperature (25 ° C.). As a result, compositions (polymer gels) according to Examples 1 to 4 and 8 to 13 and Comparative Examples 1 and 2 to 5 were obtained.
The components of the solution at the start of polymerization are as shown in Tables 1 and 3 to 5.

(Example 5)
In a sample tube (3 ml), host group-containing AA monomer, guest group-containing AA monomer, AA monomer, and water were placed and mixed. Then, the mixture was stirred for 5 minutes while being irradiated with ultrasonic waves to completely dissolve the monomer. Subsequently, APS (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization initiator and TEMED (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization accelerator are added to a solution, and the obtained solution is subjected to polymerization reaction conditions (room temperature) Left for 1 hour). The resulting gel was then transferred to a 100 ml beaker and glycerin was poured until the gel was completely immersed. In this state, it was allowed to stand at room temperature (25 ° C.) for 12 hours. Thus, a composition (polymer gel) according to Example 5 was obtained.
The components of the solution at the start of polymerization are as shown in Table 2.

(Examples 6, 7, 14 to 19, Comparative Examples 3, 4, 9)
In a sample tube (3 ml), a host group-containing AA monomer, a guest group-containing AA monomer, an AA monomer, water, and glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) were placed and mixed. Then, the mixture was stirred for 5 minutes while being irradiated with ultrasonic waves to completely dissolve the monomer. Subsequently, APS (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization initiator and TEMED (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization accelerator are added to a solution, and the obtained solution is subjected to polymerization reaction conditions (room temperature) Left for 1 hour). As a result, compositions (polymer gels) according to Examples 6, 7 and 14 to 19 and Comparative Examples 3 and 4 and 9 were obtained.
The components of the solution at the start of polymerization are as shown in Tables 2, 3, 5, and 6.

(Examples 20 to 25, Comparative Examples 10 to 13)
First, 200 mg of acrylamide (manufactured by Wako Pure Chemical Industries, Ltd.), 3000 mg of water, 17 mg of TEMED (manufactured by Wako Pure Chemical Industries, Ltd.), 34 mg of APS (manufactured by Wako Pure Chemical Industries, Ltd.) are mixed, and left at room temperature for 1 hour. The polymer was obtained. Next, the obtained polymer was ground with a mortar to prepare a filler (polymer of acrylic acid amide).
Next, host group-containing AA monomer, guest group-containing AA monomer, AA monomer, water, glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.), and the above-mentioned filler were placed in a sample tube (3 ml) and mixed. Then, the mixture was stirred for 5 minutes while being irradiated with ultrasonic waves to completely dissolve the monomer. Subsequently, APS (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization initiator and TEMED (made by Wako Pure Chemical Industries, Ltd.) which is a polymerization accelerator are added to a solution, and the obtained solution is subjected to polymerization reaction conditions (room temperature) Left for 1 hour). Thus, compositions (polymer gels) according to Examples 20 to 25 and Comparative Examples 10 to 13 were obtained.
The components of the solution at the start of polymerization are as shown in Table 6.

(Status evaluation)
The state of the composition prepared as described above was evaluated visually and with a finger. The composition which maintains the shape of the composition and has the appearance and texture suitable as a composition for three-dimensional surgical treatment training model is "○", and the other compositions are "×" evaluated. In addition, since Comparative Examples 6, 11 and 12 did not gel, no finger touch evaluation was performed, and it was set as "x". Moreover, the color of the composition was described in parenthesis about the composition of evaluation "(circle)". The composition states were described in parenthesis with respect to the compositions evaluated as "x". The results are shown in Tables 1 to 6.

(Self-healing evaluation)
The self repairability of the composition prepared above was evaluated. The composition having self-repairing property was evaluated as "o", and the composition having no self-repairing property was evaluated as "x". The results are shown in Tables 1 to 6.
The evaluation method is as follows.
The composition was cut, and then the cut interfaces were brought into contact with each other and allowed to stand for 10 minutes under an environment of temperature 23 ° C. and humidity 50%, and then it was confirmed whether or not the cut interfaces adhered. When it adhered, it judged that it had self-repairing property.

(Evaluation of hardness)
The hardness (converted value) of the composition prepared above was measured according to Japanese Industrial Standard (JIS K6253-3) using an Asker rubber hardness meter CSC2 (manufactured by Kobunshi Keiki Co., Ltd.) according to Japanese Industrial Standard (JIS K6253-3). The converted value was calculated from the spring load of the rubber hardness tester. The results are shown in Tables 1 to 6.

(Tackiness)
The tackiness of the composition prepared above was evaluated by finger touch. The case where the composition did not adhere to the finger was evaluated as "o", and the case where it adhered was evaluated as "x".

(Processability)
With respect to the processability of the composition prepared as described above, the composition was cut using a cutter (PAPER CUTTER DN-1 manufactured by KOKUYO CO., LTD.), And the fractured surface was visually evaluated. The evaluation method is as follows.
When a composition (polymer gel) formed into a sheet shape having a thickness of 3 mm and an area of 50 mm × 50 mm is cut with a constant load, it can be cut without resistance and the broken surface of the composition is smooth. The case where the composition was caught by the blade at the time of cutting and the blade did not move or the resistance at the time of cutting was strong and the broken surface of the composition was rough was evaluated as “X”.

Here, each of Tables 1 to 6 will be briefly described.
Table 1: Relationship between the blending amount of monomers and the hardness of the composition.
Table 2: Relationship between the presence or absence of the immersion step and the hardness of the composition.
Table 3: Relationship between water content and hardness of the composition.
Table 4: Relationship between TEMED content and hardness of the composition.
Table 5: Relationship between water and glycerin content and hardness of the composition.
Table 6: Relationship between the presence or absence of the filler and the hardness, tackiness and processability of the composition.

In Tables 1 to 6, "the concentration of monomers in the solution" represents the molar concentration of each monomer based on the entire monomers in the solution at the start of the polymerization, and "the concentration of the monomers (mol / kg)" Represents the total number of moles of all monomers per weight of the whole solution, and the “content of each component in the solution (% by weight)” means the content of each component based on the whole solution at the start of the polymerization It represents the content.
Further, in Tables 1 to 6, the blanks indicate that the component relating to the blanks is not included, and that the method and evaluation relating to the blanks can not be performed.

(result)
All the compositions produced by the manufacturing method according to the examples have realized the texture and hardness of any organ of the human body, particularly the liver, heart, skin. Table 7 below summarizes the hardness of the composition and examples suitable for models of each organ. The numerical values in the table represent example numbers.

From Table 7, the compositions suitable for the liver model are Examples 1, 6-8, 12-16, 22-24, and the composition of Example 13 added the filler particularly when the filler is not added. In this case, the composition of Example 24 had a texture very close to that of the liver, in consideration of tackiness and processability. The hardness is in a range similar to that of a real liver. Similarly, compositions suitable for cardiac models are Examples 2, 3, 17, 18, 25 and the composition of Example 17 is tacky, particularly when no filler is added, and when filler is added. In particular, the composition of Example 25 had a texture very close to the heart in consideration of moldability and processability. The hardness is in the same range as the real heart. The compositions suitable for the skin model are Examples 2 to 6, 9 to 12, and 15 to 25. By combining one or more of them, the texture and hardness very similar to those of the skin can be reproduced. In particular, the composition of Examples 16, 18 and 19 had texture and hardness very close to the skin.

On the other hand, the manufacturing method according to the comparative example is not suitable as a method for manufacturing a three-dimensional surgical treatment training model composition for the following reason.
In Comparative Example 1, the produced composition was slime-like, and the shape of the composition could not be maintained. In Comparative Example 2, the produced composition was brittle. In addition, he was also poor in self-healing ability. In Comparative Examples 3 and 4, the monomer did not dissolve in the solution, and the composition could not be prepared. In Comparative Example 5, the produced composition was slime-like, and the shape of the composition could not be maintained. In Comparative Example 6, the polymerization reaction did not proceed and gelation occurred. In Comparative Example 7, the produced composition was softer than a predetermined hardness and could not maintain the shape of the polymer gel. In Comparative Example 8, the produced composition became slime-like, and the shape of the composition could not be maintained. In Comparative Example 9, the monomer concentration (mol / kg) was high, and the solution bumped due to the heat of reaction during the polymerization reaction, resulting in numerous bubbles in the composition. Therefore, it was unsuitable as a composition for a three-dimensional surgical treatment training model. In Comparative Examples 10 and 13, the self-repairing property of the produced composition was poor. In Comparative Examples 11 and 12, the composition produced did not gel.

Claims

A composition for a three-dimensional surgical treatment training model, comprising a polymer gel having self-repairing properties.
The composition according to claim 1, characterized in that the polymer gel comprises a polymer that self-heals using the principle of host-guest interaction.
The polymer comprises 1 mol% to 8 mol% of structural units derived from a host group-containing acrylamide monomer, 1 mol% to 8 mol% of structural units derived from a guest group-containing acrylamide monomer, a structure derived from an acrylamide monomer Contains 84 mol% or more and 98 mol% or less of the unit,
The polymer gel comprises an aqueous solvent in the interstices of the polymer network,
The composition according to claim 2, wherein the hardness of the composition is 931 mN or more and 4264 mN or less in a converted value.
The structural unit derived from the host group-containing acrylamide monomer is the following general formula (1), the structural unit derived from the guest group-containing acrylamide monomer is the following general formula (2), and the structural unit derived from the acrylamide monomer The composition according to claim 3, wherein is a group represented by the following general formula (3).

(R 1 to R 7 each represents hydrogen or a methyl group. R H represents a host group, which may be α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin. R G is Represents a guest group, which may be n-butyl, n-dodecyl, t-butyl, isobornyl or adamantyl).
The composition according to claim 3 or 4, wherein the aqueous solvent comprises water, or water and a hydrophilic solvent having a boiling point higher than that of water.
The composition according to claim 5, wherein the hydrophilic solvent comprises at least one selected from the group consisting of ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, glycerin and diethylene glycol monoethyl ether.
The content of the aqueous solvent is 49.45 wt% or more and 85.45 wt% or less based on the polymer gel, and the content of water in the aqueous solvent is 15.40 wt% or more based on the polymer gel The composition according to any one of claims 3 to 6, which is
The composition according to any one of claims 3 to 6, wherein the polymer gel comprises a filler.
The composition according to claim 8, wherein the filler is an organic filler.
The content of the aqueous solvent is 45.85 wt% or more and 69.21 wt% or less based on the polymer gel, and the content of water in the aqueous solvent is 14.50 wt% or more based on the polymer gel And
The composition according to claim 8 or 9, wherein the content of the filler is 15.00% by weight or more and 26.00% by weight or less based on the polymer gel.
A method of producing the composition according to any one of claims 3 to 7, comprising
Mixing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, and the aqueous solvent;
Adding a polymerization initiator to the solution obtained by the mixing step;
And D. polymerizing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, and the acrylamide monomer.
The hardness of the composition is adjusted by adjusting the content of the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, and the aqueous solvent in the solution in the polymerization step. Do,
Method for producing a composition for a three-dimensional surgical treatment training model.
A method of producing the composition according to any one of claims 8 to 10, wherein
Mixing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, the aqueous solvent, and the filler;
Adding a polymerization initiator to the solution obtained by the mixing step;
And D. polymerizing the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, and the acrylamide monomer.
Hardening the composition by adjusting the content of the host group-containing acrylamide monomer, the guest group-containing acrylamide monomer, the acrylamide monomer, the aqueous solvent, and the filler in the solution in the polymerization step. Adjust the
Method for producing a composition for a three-dimensional surgical treatment training model.
The hardness of the composition is adjusted by adding a polymerization accelerator in at least one of the mixing step and the adding step, and adjusting the content of the polymerization accelerator in the solution in the polymerization step. A manufacturing method according to claim 11 or 12.
The method further includes a step of immersing the gel obtained by the step of polymerizing in a solvent for immersion, the solvent for immersion comprising the hydrophilic solvent, or containing the hydrophilic solvent and water, the immersion time of the gel and the immersion The method according to any one of claims 11 to 13, wherein the hardness of the composition is adjusted by adjusting at least one of the concentration of the hydrophilic solvent in the solvent.