WO2016047329A1 - Aqueous-gel composition for model of living-body organ and model of living-body organ - Google Patents
Aqueous-gel composition for model of living-body organ and model of living-body organ Download PDFInfo
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- WO2016047329A1 WO2016047329A1 PCT/JP2015/073543 JP2015073543W WO2016047329A1 WO 2016047329 A1 WO2016047329 A1 WO 2016047329A1 JP 2015073543 W JP2015073543 W JP 2015073543W WO 2016047329 A1 WO2016047329 A1 WO 2016047329A1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
- C08L29/02—Homopolymers or copolymers of unsaturated alcohols
- C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
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- G—PHYSICS
- G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
- G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
- G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
- G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
Abstract
Provided are: an aqueous-gel composition for models of living-body organs which gives a model of an organ of the living body, the model making it possible to obtain a sensation of cutting similar to that with the real organ; and a model of an organ of the living body, the model comprising the aqueous-gel composition. The aqueous-gel composition for models of living-body organs contains a polyvinyl alcohol and gelatin and has an electrical conductivity at frequency 1 MHz of 0.15-5.00 S/m.
Description
本発明は、生体臓器模型用水性ゲル組成物および生体臓器模型に関する。
The present invention relates to an aqueous gel composition for a biological organ model and a biological organ model.
従来、外科医の手術トレーニングには、実物の生体臓器に似せた生体臓器模型が使用されている。例えば、特許文献１の［請求項１］には、「平均重合度が３００～３５００であり、ケン化度が９０モル％以上であるポリビニルアルコールからなる水性ゲルおよびシリカ粒子を含有することを特徴とする臓器モデル用成形材料」が開示されている。
Conventionally, a living organ model resembling a real living organ has been used for a surgeon's surgical training. For example, [Claim 1] of Patent Document 1 includes “an aqueous gel composed of polyvinyl alcohol having an average polymerization degree of 300 to 3500 and a saponification degree of 90 mol% or more, and silica particles. "A molding material for organ model" is disclosed.
生体臓器（とりわけ、肝臓）の切開には、主に、ペアン鉗子および高周波電気メス（単に「電気メス」とも呼ばれる）が手術器具として使用される。ペアン鉗子は、先端部に鉤のない鉗子であり、組織を押しつぶして切離する。高周波電気メスは、高周波電流を用いて組織を切開したり、切開した部分を凝固（止血）したりする。
For incision of living organs (particularly the liver), Pean forceps and a high-frequency electric scalpel (also simply called “electric scalpel”) are mainly used as surgical instruments. A pair of forceps is a forceps without a heel at the tip, and crushes and separates tissue. The high-frequency electric knife uses a high-frequency current to incise the tissue and coagulate (hemostaze) the incised portion.
本発明者が、特許文献１に記載された臓器モデルについて詳細に検討を行なったところ、ペアン鉗子を用いて組織を押しつぶす感触、および、高周波電気メスを用いて組織を凝固させながら切離する感触（以下、これらをまとめて「切開感触」ともいう）が、実物の生体臓器である肝臓の切開感触と異なることを明らかにした。
The inventor has examined the organ model described in Patent Document 1 in detail, and feels that the tissue is crushed using Pean forceps, and that the tissue is separated while coagulating the tissue using a high-frequency electric knife. (Hereinafter, these are collectively referred to as “incision feel”) and the incision feel of the liver, which is a real living organ, was clarified.
本発明は、以上の点を鑑みてなされたものであり、生体臓器模型にしたときに実物の生体臓器と類似した切開感触が得られる生体臓器模型用水性ゲル組成物および上記生体臓器模型用水性ゲル組成物を用いた生体臓器模型を提供することを目的とする。
The present invention has been made in view of the above points, and an aqueous gel composition for a biological organ model that can provide an incision feel similar to that of a real biological organ when the biological organ model is obtained, and the aqueous biological organ model An object is to provide a living organ model using a gel composition.
本発明者は、上記目的を達成するために鋭意検討した結果、特定の水性ゲル組成物を用いることで、切開感触が実物の生体臓器に類似することを見出し、本発明を完成させた。
As a result of intensive studies to achieve the above object, the present inventor found that the incision feel is similar to a real living organ by using a specific aqueous gel composition, and completed the present invention.
すなわち、本発明は、以下の（１）～（８）を提供する。
（１）ポリビニルアルコールとゼラチンとを含有し、周波数１ＭＨｚにおける電気伝導率が０．１５～５．００Ｓ／ｍである、生体臓器模型用水性ゲル組成物。
（２）さらに電解質を含有する、上記（１）に記載の生体臓器模型用水性ゲル組成物。
（３）上記電解質の濃度が、０．１５～１．５０質量％である、上記（２）に記載の生体臓器模型用水性ゲル組成物。
（４）上記ポリビニルアルコールと上記ゼラチンとの質量比が、９０／１０～６０／４０である、上記（１）～（３）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（５）肝臓模型に用いられる、上記（１）～（４）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（６）手術の手技練習用の生体臓器模型に用いられる、上記（１）～（４）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（７）上記（１）～（６）のいずれかに記載の生体臓器模型用水性ゲル組成物を用いた、生体臓器模型。
（８）手術の手技練習用である、上記（７）に記載の生体臓器模型。 That is, the present invention provides the following (1) to (8).
(1) An aqueous gel composition for a living organ model containing polyvinyl alcohol and gelatin and having an electric conductivity at a frequency of 1 MHz of 0.15 to 5.00 S / m.
(2) The aqueous gel composition for living organ models according to (1), further comprising an electrolyte.
(3) The aqueous gel composition for a biological organ model according to (2), wherein the concentration of the electrolyte is 0.15 to 1.50% by mass.
(4) The aqueous gel composition for living organ models according to any one of (1) to (3), wherein the mass ratio of the polyvinyl alcohol to the gelatin is 90/10 to 60/40.
(5) The aqueous gel composition for living organ models according to any one of (1) to (4), which is used for a liver model.
(6) The aqueous gel composition for a biological organ model according to any one of (1) to (4), which is used for a biological organ model for practicing a surgical technique.
(7) A living organ model using the aqueous gel composition for living organ models according to any one of (1) to (6) above.
(8) The living organ model according to (7), which is used for surgical technique practice.
（１）ポリビニルアルコールとゼラチンとを含有し、周波数１ＭＨｚにおける電気伝導率が０．１５～５．００Ｓ／ｍである、生体臓器模型用水性ゲル組成物。
（２）さらに電解質を含有する、上記（１）に記載の生体臓器模型用水性ゲル組成物。
（３）上記電解質の濃度が、０．１５～１．５０質量％である、上記（２）に記載の生体臓器模型用水性ゲル組成物。
（４）上記ポリビニルアルコールと上記ゼラチンとの質量比が、９０／１０～６０／４０である、上記（１）～（３）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（５）肝臓模型に用いられる、上記（１）～（４）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（６）手術の手技練習用の生体臓器模型に用いられる、上記（１）～（４）のいずれかに記載の生体臓器模型用水性ゲル組成物。
（７）上記（１）～（６）のいずれかに記載の生体臓器模型用水性ゲル組成物を用いた、生体臓器模型。
（８）手術の手技練習用である、上記（７）に記載の生体臓器模型。 That is, the present invention provides the following (1) to (8).
(1) An aqueous gel composition for a living organ model containing polyvinyl alcohol and gelatin and having an electric conductivity at a frequency of 1 MHz of 0.15 to 5.00 S / m.
(2) The aqueous gel composition for living organ models according to (1), further comprising an electrolyte.
(3) The aqueous gel composition for a biological organ model according to (2), wherein the concentration of the electrolyte is 0.15 to 1.50% by mass.
(4) The aqueous gel composition for living organ models according to any one of (1) to (3), wherein the mass ratio of the polyvinyl alcohol to the gelatin is 90/10 to 60/40.
(5) The aqueous gel composition for living organ models according to any one of (1) to (4), which is used for a liver model.
(6) The aqueous gel composition for a biological organ model according to any one of (1) to (4), which is used for a biological organ model for practicing a surgical technique.
(7) A living organ model using the aqueous gel composition for living organ models according to any one of (1) to (6) above.
(8) The living organ model according to (7), which is used for surgical technique practice.
本発明によれば、生体臓器模型にしたときに実物の生体臓器と類似した切開感触が得られる生体臓器模型用水性ゲル組成物および上記生体臓器模型用水性ゲル組成物を用いた生体臓器模型を提供できる。
According to the present invention, an aqueous gel composition for a biological organ model that can provide an incision feel similar to that of a real biological organ when the biological organ model is obtained, and a biological organ model using the aqueous gel composition for a biological organ model are provided. Can be provided.
以下では、まず、本発明の生体臓器模型用水性ゲル組成物の好適態様について説明した後、本発明の生体臓器模型の好適態様について説明する。
なお、本明細書において「～」を用いて表される数値範囲は、「～」前後に記載される数値を下限値および上限値として含む範囲を意味する。 Below, after describing the suitable aspect of the aqueous gel composition for biological organ models of this invention first, the suitable aspect of the biological organ model of this invention is demonstrated.
In the present specification, a numerical range expressed using “to” means a range including numerical values described before and after “to” as a lower limit value and an upper limit value.
なお、本明細書において「～」を用いて表される数値範囲は、「～」前後に記載される数値を下限値および上限値として含む範囲を意味する。 Below, after describing the suitable aspect of the aqueous gel composition for biological organ models of this invention first, the suitable aspect of the biological organ model of this invention is demonstrated.
In the present specification, a numerical range expressed using “to” means a range including numerical values described before and after “to” as a lower limit value and an upper limit value.
［生体臓器模型用水性ゲル組成物］
本発明の生体臓器模型用水性ゲル組成物は、ポリビニルアルコールとゼラチンとを含有し、周波数１ＭＨｚにおける電気伝導率が０．１５～５．００Ｓ／ｍである、生体臓器模型用水性ゲル組成物である。
以下では、生体臓器模型用水性ゲル組成物を、単に「水性ゲル組成物」ともいう。
本発明の水性ゲル組成物を、生体臓器模型（特に、ヒトの肝臓模型）に用いたときに、実物の生体臓器（特に、ヒトの肝臓）と類似した切開感触が得られる。この理由は、以下のように推測される。 [Aqueous gel composition for biological organ model]
The aqueous gel model for living organ models of the present invention is an aqueous gel composition for living organ models containing polyvinyl alcohol and gelatin and having an electric conductivity of 0.15 to 5.00 S / m at a frequency of 1 MHz. is there.
Hereinafter, the aqueous gel composition for a living organ model is also simply referred to as “aqueous gel composition”.
When the aqueous gel composition of the present invention is used for a living organ model (particularly, a human liver model), an incision feel similar to that of a real living organ (particularly, a human liver) can be obtained. The reason is presumed as follows.
本発明の生体臓器模型用水性ゲル組成物は、ポリビニルアルコールとゼラチンとを含有し、周波数１ＭＨｚにおける電気伝導率が０．１５～５．００Ｓ／ｍである、生体臓器模型用水性ゲル組成物である。
以下では、生体臓器模型用水性ゲル組成物を、単に「水性ゲル組成物」ともいう。
本発明の水性ゲル組成物を、生体臓器模型（特に、ヒトの肝臓模型）に用いたときに、実物の生体臓器（特に、ヒトの肝臓）と類似した切開感触が得られる。この理由は、以下のように推測される。 [Aqueous gel composition for biological organ model]
The aqueous gel model for living organ models of the present invention is an aqueous gel composition for living organ models containing polyvinyl alcohol and gelatin and having an electric conductivity of 0.15 to 5.00 S / m at a frequency of 1 MHz. is there.
Hereinafter, the aqueous gel composition for a living organ model is also simply referred to as “aqueous gel composition”.
When the aqueous gel composition of the present invention is used for a living organ model (particularly, a human liver model), an incision feel similar to that of a real living organ (particularly, a human liver) can be obtained. The reason is presumed as follows.
まず、肝臓の組織は、径：約１ｍｍおよび高さ：約１ｍｍの角柱または円柱形状の肝小葉という構造単位が集まって構成されている。このため、肝臓には、特有の脆さがあり、この脆さにもとづく独特の切開感触が存在する。
一方で、本発明の水性ゲル組成物は、ポリビニルアルコールとゼラチンとを含有することにより、２種以上のゲルが互いに相分離した構造（相分離構造）が形成され、これにより、実物の生体臓器（特に肝臓）が有する特有の脆さが再現されるため、特に、ペアン鉗子を用いて組織を押しつぶす感触に関して、実物との類似性が高くなると考えられる。 First, the liver tissue is composed of structural units such as prismatic or cylindrical liver lobes having a diameter of about 1 mm and a height of about 1 mm. For this reason, the liver has a unique fragility, and there is a unique incision feel based on this fragility.
On the other hand, the aqueous gel composition of the present invention contains polyvinyl alcohol and gelatin to form a structure in which two or more kinds of gels are phase-separated from each other (phase-separated structure). Since the peculiar fragility of (especially the liver) is reproduced, it is considered that the similarity to the real thing becomes high particularly with respect to the feeling of crushing the tissue using the Pean forceps.
一方で、本発明の水性ゲル組成物は、ポリビニルアルコールとゼラチンとを含有することにより、２種以上のゲルが互いに相分離した構造（相分離構造）が形成され、これにより、実物の生体臓器（特に肝臓）が有する特有の脆さが再現されるため、特に、ペアン鉗子を用いて組織を押しつぶす感触に関して、実物との類似性が高くなると考えられる。 First, the liver tissue is composed of structural units such as prismatic or cylindrical liver lobes having a diameter of about 1 mm and a height of about 1 mm. For this reason, the liver has a unique fragility, and there is a unique incision feel based on this fragility.
On the other hand, the aqueous gel composition of the present invention contains polyvinyl alcohol and gelatin to form a structure in which two or more kinds of gels are phase-separated from each other (phase-separated structure). Since the peculiar fragility of (especially the liver) is reproduced, it is considered that the similarity to the real thing becomes high particularly with respect to the feeling of crushing the tissue using the Pean forceps.
また、本発明の水性ゲル組成物は、生体臓器の組織と同様に、タンパク質（より詳細には、タンパク質を主成分とするゼラチン）を含有し、かつ、一定の電気伝導率を有するため、特に、高周波電気メスを用いて組織のタンパク質を凝固させながら切離する感触に関して、実物との類似性が高くなると考えられる。
In addition, the aqueous gel composition of the present invention contains a protein (more specifically, gelatin containing protein as a main component) and has a certain electric conductivity, as in the case of a living organ tissue. It is considered that the similarity to the real thing becomes higher with respect to the feeling of separating while coagulating tissue proteins using a high-frequency electric knife.
＜電気伝導率および電解質＞
本発明の水性ゲル組成物は、周波数１ＭＨｚにおける電気伝導率（以下、単に「電気伝導率」ともいう）が、０．１５～５．００Ｓ／ｍ（Ａ・Ｖ-1・ｍ-1）である。
電気メスは、ＪＩＳ規格によると３００ｋＨｚ～５ＭＨｚの主要搬送周波数帯にある高周波電流を生体組織に流して切開および凝固を行う電気手術器であり、特に、１ＭＨｚの周波数を使用したものが多いこと、および、電気伝導率は周波数依存性があることから、本発明においては、電気伝導率の測定周波数を１ＭＨｚとした。 <Electric conductivity and electrolyte>
The aqueous gel composition of the present invention has an electrical conductivity at a frequency of 1 MHz (hereinafter also simply referred to as “electrical conductivity”) of 0.15 to 5.00 S / m (A · V −1 · m −1 ). is there.
The electrosurgical unit is an electrosurgical device that performs incision and coagulation by flowing a high-frequency current in a main carrier frequency band of 300 kHz to 5 MHz to a living tissue according to JIS standards, and in particular, there are many that use a frequency of 1 MHz. And since electrical conductivity has frequency dependence, in this invention, the measurement frequency of electrical conductivity was 1 MHz.
本発明の水性ゲル組成物は、周波数１ＭＨｚにおける電気伝導率（以下、単に「電気伝導率」ともいう）が、０．１５～５．００Ｓ／ｍ（Ａ・Ｖ-1・ｍ-1）である。
電気メスは、ＪＩＳ規格によると３００ｋＨｚ～５ＭＨｚの主要搬送周波数帯にある高周波電流を生体組織に流して切開および凝固を行う電気手術器であり、特に、１ＭＨｚの周波数を使用したものが多いこと、および、電気伝導率は周波数依存性があることから、本発明においては、電気伝導率の測定周波数を１ＭＨｚとした。 <Electric conductivity and electrolyte>
The aqueous gel composition of the present invention has an electrical conductivity at a frequency of 1 MHz (hereinafter also simply referred to as “electrical conductivity”) of 0.15 to 5.00 S / m (A · V −1 · m −1 ). is there.
The electrosurgical unit is an electrosurgical device that performs incision and coagulation by flowing a high-frequency current in a main carrier frequency band of 300 kHz to 5 MHz to a living tissue according to JIS standards, and in particular, there are many that use a frequency of 1 MHz. And since electrical conductivity has frequency dependence, in this invention, the measurement frequency of electrical conductivity was 1 MHz.
本発明の水性ゲル組成物の電気伝導率は、生体の電気伝導率（およそ０．３Ｓ／ｍ）に近づけるという観点からは、０．１５～３．００Ｓ／ｍが好ましく、０．１５～１．００Ｓ／ｍがより好ましい。
The electric conductivity of the aqueous gel composition of the present invention is preferably from 0.15 to 3.00 S / m, preferably from 0.15 to 1 from the viewpoint of approaching the electric conductivity of a living body (approximately 0.3 S / m). 0.000 S / m is more preferable.
本発明の水性ゲル組成物は、電解質を含有していてもよい。電解質は、本発明の水性ゲル組成物の電気伝導率を上昇させ、生体の電気伝導率により近づけることができる。
The aqueous gel composition of the present invention may contain an electrolyte. The electrolyte increases the electrical conductivity of the aqueous gel composition of the present invention, and can be made closer to the electrical conductivity of a living body.
本発明に用いる電解質としては、特に限定されないが、例えば、水溶性の塩が挙げられ、その具体例としては、塩化ナトリウム（食塩）、塩化カリウム、塩化リチウム、塩化カルシウム、塩化マグネシウムなどの塩化物；硫酸ナトリウムなどの硫酸塩；硝酸ナトリウムなどの硝酸塩；有機酸塩；等が挙げられる。
これらのうち、入手の容易さおよび安全性の観点から、塩化ナトリウムが好ましい。 The electrolyte used in the present invention is not particularly limited, and examples thereof include water-soluble salts. Specific examples thereof include chlorides such as sodium chloride (salt), potassium chloride, lithium chloride, calcium chloride, and magnesium chloride. A sulfate such as sodium sulfate; a nitrate such as sodium nitrate; an organic acid salt;
Of these, sodium chloride is preferred from the viewpoint of availability and safety.
これらのうち、入手の容易さおよび安全性の観点から、塩化ナトリウムが好ましい。 The electrolyte used in the present invention is not particularly limited, and examples thereof include water-soluble salts. Specific examples thereof include chlorides such as sodium chloride (salt), potassium chloride, lithium chloride, calcium chloride, and magnesium chloride. A sulfate such as sodium sulfate; a nitrate such as sodium nitrate; an organic acid salt;
Of these, sodium chloride is preferred from the viewpoint of availability and safety.
電解質の濃度は、本発明の水性ゲル組成物の全体の質量に対して、０．１５～２．００質量％が好ましく、０．１５～１．９０質量％がより好ましく、０．１５～１．５０質量％がさらに好ましく、０．２０～１．５０質量％が特に好ましい。
電解質の濃度が低すぎると、水性ゲル組成物の電気伝導率が不足する場合があるが、電解質の濃度が０．１５質量％以上であれば、十分な電気伝導率が得られ、高周波電気メスでの切開感触がより優れる。
その一方で、電解質の濃度が高すぎると、水性ゲル組成物を製造する際に調製する溶液（後述する「ＰＶＡ／ゼラチン水溶液」に相当）の粘度が高くなりすぎて均一な溶液を得ることが難しくなる場合があり、かつ、この溶液をゲル化して得られる水性ゲル組成物の柔軟性が不足する場合がある。この場合、水性ゲル組成物の電気伝導率は、必ずしも電解質の濃度に比例して高くなるとは限らず、また、ペアン鉗子での切開感触について、実物との類似性が十分でないことがある。
したがって、ペアン鉗子での切開感触がより優れる等の理由から、電解質の濃度は、２．００質量％以下が好ましく、１．９０質量％以下がより好ましく、１．５０質量％以下がさらに好ましい。 The concentration of the electrolyte is preferably 0.15 to 2.00% by mass, more preferably 0.15 to 1.90% by mass, and more preferably 0.15 to 1% with respect to the total mass of the aqueous gel composition of the present invention. Is more preferably 50% by mass, particularly preferably 0.20 to 1.50% by mass.
If the concentration of the electrolyte is too low, the electric conductivity of the aqueous gel composition may be insufficient. However, if the concentration of the electrolyte is 0.15% by mass or more, sufficient electric conductivity can be obtained and the high-frequency electric knife is used. The incision feel at is better.
On the other hand, if the concentration of the electrolyte is too high, the viscosity of the solution prepared when producing the aqueous gel composition (corresponding to “PVA / gelatin aqueous solution” described later) becomes too high, and a uniform solution can be obtained. It may be difficult, and the flexibility of the aqueous gel composition obtained by gelling this solution may be insufficient. In this case, the electrical conductivity of the aqueous gel composition is not necessarily increased in proportion to the concentration of the electrolyte, and the incision feeling with the Pean forceps may not be sufficiently similar to the real thing.
Accordingly, the concentration of the electrolyte is preferably 2.00% by mass or less, more preferably 1.90% by mass or less, and even more preferably 1.50% by mass or less for reasons such as better incision feeling with Pean forceps.
電解質の濃度が低すぎると、水性ゲル組成物の電気伝導率が不足する場合があるが、電解質の濃度が０．１５質量％以上であれば、十分な電気伝導率が得られ、高周波電気メスでの切開感触がより優れる。
その一方で、電解質の濃度が高すぎると、水性ゲル組成物を製造する際に調製する溶液（後述する「ＰＶＡ／ゼラチン水溶液」に相当）の粘度が高くなりすぎて均一な溶液を得ることが難しくなる場合があり、かつ、この溶液をゲル化して得られる水性ゲル組成物の柔軟性が不足する場合がある。この場合、水性ゲル組成物の電気伝導率は、必ずしも電解質の濃度に比例して高くなるとは限らず、また、ペアン鉗子での切開感触について、実物との類似性が十分でないことがある。
したがって、ペアン鉗子での切開感触がより優れる等の理由から、電解質の濃度は、２．００質量％以下が好ましく、１．９０質量％以下がより好ましく、１．５０質量％以下がさらに好ましい。 The concentration of the electrolyte is preferably 0.15 to 2.00% by mass, more preferably 0.15 to 1.90% by mass, and more preferably 0.15 to 1% with respect to the total mass of the aqueous gel composition of the present invention. Is more preferably 50% by mass, particularly preferably 0.20 to 1.50% by mass.
If the concentration of the electrolyte is too low, the electric conductivity of the aqueous gel composition may be insufficient. However, if the concentration of the electrolyte is 0.15% by mass or more, sufficient electric conductivity can be obtained and the high-frequency electric knife is used. The incision feel at is better.
On the other hand, if the concentration of the electrolyte is too high, the viscosity of the solution prepared when producing the aqueous gel composition (corresponding to “PVA / gelatin aqueous solution” described later) becomes too high, and a uniform solution can be obtained. It may be difficult, and the flexibility of the aqueous gel composition obtained by gelling this solution may be insufficient. In this case, the electrical conductivity of the aqueous gel composition is not necessarily increased in proportion to the concentration of the electrolyte, and the incision feeling with the Pean forceps may not be sufficiently similar to the real thing.
Accordingly, the concentration of the electrolyte is preferably 2.00% by mass or less, more preferably 1.90% by mass or less, and even more preferably 1.50% by mass or less for reasons such as better incision feeling with Pean forceps.
＜ポリビニルアルコール＞
ポリビニルアルコール（以下、便宜的に「ＰＶＡ」と表記することがある）は、一般的には、酢酸ビニルモノマーが重合したポリ酢酸ビニルをケン化して得られる。
本発明に用いるポリビニルアルコールとしては、特に限定されず、従来公知のポリビニルアルコールを適宜使用できる。
例えば、ポリビニルアルコールの粘度法により求められる平均重合度（粘度平均重合度）は、特に限定されないが、得られる生体臓器模型における機械的強度およびヒトの臓器に類似した適度な弾性という観点から、３００～３５００が好ましく、５００～３０００がより好ましく、１０００～２５００がさらに好ましい。
また、ポリビニルアルコールのケン化度は、特に限定されないが、得られる生体臓器模型の機械的強度および弾性率の観点から、９０モル％以上が好ましく、９５モル％以上がより好ましく、９８モル％以上がさらに好ましい。なお、ポリビニルアルコールのケン化度の上限値には限定がなく、高ければ高いほど好ましく、完全ケン化のポリビニルアルコールが特に好ましい。
ポリビニルアルコールは、１種単独で用いてもよく、２種以上を併用してもよい。 <Polyvinyl alcohol>
Polyvinyl alcohol (hereinafter sometimes referred to as “PVA” for convenience) is generally obtained by saponifying polyvinyl acetate obtained by polymerizing a vinyl acetate monomer.
It does not specifically limit as polyvinyl alcohol used for this invention, A conventionally well-known polyvinyl alcohol can be used suitably.
For example, the average degree of polymerization (viscosity average degree of polymerization) determined by the viscosity method of polyvinyl alcohol is not particularly limited, but from the viewpoint of mechanical strength in the obtained biological organ model and appropriate elasticity similar to a human organ, 300 To 3500 is preferable, 500 to 3000 is more preferable, and 1000 to 2500 is more preferable.
The degree of saponification of polyvinyl alcohol is not particularly limited, but is preferably 90 mol% or more, more preferably 95 mol% or more, and 98 mol% or more from the viewpoint of mechanical strength and elastic modulus of the obtained living organ model. Is more preferable. The upper limit of the degree of saponification of polyvinyl alcohol is not limited, and the higher the value, the more preferable, and the completely saponified polyvinyl alcohol is particularly preferable.
Polyvinyl alcohol may be used alone or in combination of two or more.
ポリビニルアルコール（以下、便宜的に「ＰＶＡ」と表記することがある）は、一般的には、酢酸ビニルモノマーが重合したポリ酢酸ビニルをケン化して得られる。
本発明に用いるポリビニルアルコールとしては、特に限定されず、従来公知のポリビニルアルコールを適宜使用できる。
例えば、ポリビニルアルコールの粘度法により求められる平均重合度（粘度平均重合度）は、特に限定されないが、得られる生体臓器模型における機械的強度およびヒトの臓器に類似した適度な弾性という観点から、３００～３５００が好ましく、５００～３０００がより好ましく、１０００～２５００がさらに好ましい。
また、ポリビニルアルコールのケン化度は、特に限定されないが、得られる生体臓器模型の機械的強度および弾性率の観点から、９０モル％以上が好ましく、９５モル％以上がより好ましく、９８モル％以上がさらに好ましい。なお、ポリビニルアルコールのケン化度の上限値には限定がなく、高ければ高いほど好ましく、完全ケン化のポリビニルアルコールが特に好ましい。
ポリビニルアルコールは、１種単独で用いてもよく、２種以上を併用してもよい。 <Polyvinyl alcohol>
Polyvinyl alcohol (hereinafter sometimes referred to as “PVA” for convenience) is generally obtained by saponifying polyvinyl acetate obtained by polymerizing a vinyl acetate monomer.
It does not specifically limit as polyvinyl alcohol used for this invention, A conventionally well-known polyvinyl alcohol can be used suitably.
For example, the average degree of polymerization (viscosity average degree of polymerization) determined by the viscosity method of polyvinyl alcohol is not particularly limited, but from the viewpoint of mechanical strength in the obtained biological organ model and appropriate elasticity similar to a human organ, 300 To 3500 is preferable, 500 to 3000 is more preferable, and 1000 to 2500 is more preferable.
The degree of saponification of polyvinyl alcohol is not particularly limited, but is preferably 90 mol% or more, more preferably 95 mol% or more, and 98 mol% or more from the viewpoint of mechanical strength and elastic modulus of the obtained living organ model. Is more preferable. The upper limit of the degree of saponification of polyvinyl alcohol is not limited, and the higher the value, the more preferable, and the completely saponified polyvinyl alcohol is particularly preferable.
Polyvinyl alcohol may be used alone or in combination of two or more.
ポリビニルアルコールの濃度は、本発明の水性ゲル組成物の全体の質量に対して、例えば、４～２０質量％が挙げられ、５～２０質量％が好ましく、５～１５質量％がより好ましい。
The concentration of polyvinyl alcohol is, for example, 4 to 20% by mass with respect to the total mass of the aqueous gel composition of the present invention, preferably 5 to 20% by mass, and more preferably 5 to 15% by mass.
＜ゼラチン＞
ゼラチンは、一般的には、コラーゲンに熱を加えて、抽出して得られる。なお、コラーゲンの由来は特に限定されず、魚、牛、豚、山羊、遺伝子組み換え等、いかなる由来であってもよい。
本発明に用いるゼラチンとしては、特に限定されず、従来公知のゼラチンを適宜使用でき、具体的には、例えば、コラーゲンからの誘導過程で石灰などによる処理を伴うアルカリ処理ゼラチン；塩酸などによる処理を伴う酸処理ゼラチン；加水分解酵素などの処理を伴う酸素処理ゼラチン；ゼラチン分子中に含まれる官能基（例えば、アミノ基、イミノ基、ヒドロキシ基、カルボキシ基）と反応しうる基を有する試薬で処理した変性ゼラチン（例えば、フタル化ゼラチン、コハク化ゼラチン、トリメトリト化ゼラチン）；等が挙げられ、これらを１種単独で用いてもよく、２種以上を併用してもよい。 <Gelatin>
Gelatin is generally obtained by applying heat to collagen and extracting it. The origin of collagen is not particularly limited, and any origin such as fish, cow, pig, goat, genetic recombination may be used.
The gelatin used in the present invention is not particularly limited, and a conventionally known gelatin can be used as appropriate. Specifically, for example, alkali-treated gelatin accompanied by treatment with lime or the like in the process of induction from collagen; treatment with hydrochloric acid or the like Acid-treated gelatin accompanying; oxygen-treated gelatin accompanied by treatment with hydrolase, etc .; treated with a reagent having a group capable of reacting with a functional group (eg, amino group, imino group, hydroxy group, carboxy group) contained in the gelatin molecule Modified gelatins (for example, phthalated gelatin, succinated gelatin, trimethylated gelatin), and the like. These may be used alone or in combination of two or more.
ゼラチンは、一般的には、コラーゲンに熱を加えて、抽出して得られる。なお、コラーゲンの由来は特に限定されず、魚、牛、豚、山羊、遺伝子組み換え等、いかなる由来であってもよい。
本発明に用いるゼラチンとしては、特に限定されず、従来公知のゼラチンを適宜使用でき、具体的には、例えば、コラーゲンからの誘導過程で石灰などによる処理を伴うアルカリ処理ゼラチン；塩酸などによる処理を伴う酸処理ゼラチン；加水分解酵素などの処理を伴う酸素処理ゼラチン；ゼラチン分子中に含まれる官能基（例えば、アミノ基、イミノ基、ヒドロキシ基、カルボキシ基）と反応しうる基を有する試薬で処理した変性ゼラチン（例えば、フタル化ゼラチン、コハク化ゼラチン、トリメトリト化ゼラチン）；等が挙げられ、これらを１種単独で用いてもよく、２種以上を併用してもよい。 <Gelatin>
Gelatin is generally obtained by applying heat to collagen and extracting it. The origin of collagen is not particularly limited, and any origin such as fish, cow, pig, goat, genetic recombination may be used.
The gelatin used in the present invention is not particularly limited, and a conventionally known gelatin can be used as appropriate. Specifically, for example, alkali-treated gelatin accompanied by treatment with lime or the like in the process of induction from collagen; treatment with hydrochloric acid or the like Acid-treated gelatin accompanying; oxygen-treated gelatin accompanied by treatment with hydrolase, etc .; treated with a reagent having a group capable of reacting with a functional group (eg, amino group, imino group, hydroxy group, carboxy group) contained in the gelatin molecule Modified gelatins (for example, phthalated gelatin, succinated gelatin, trimethylated gelatin), and the like. These may be used alone or in combination of two or more.
ゼラチンの濃度は、本発明の水性ゲル組成物の全体の質量に対して、０．１～８．０質量％が好ましく、０．３～５．０質量％がより好ましい。
The concentration of gelatin is preferably 0.1 to 8.0% by mass and more preferably 0.3 to 5.0% by mass with respect to the total mass of the aqueous gel composition of the present invention.
＜ポリビニルアルコールおよびゼラチンの合計濃度＞
ポリビニルアルコールとゼラチンとの合計濃度は、本発明の水性ゲル組成物の全体の質量に対して、例えば、５．１～２８．０質量％が挙げられ、５．１～２１．０質量％が好ましく、５．１～１５．０質量％がより好ましく、５．１～９．０質量％がより好ましい。 <Total concentration of polyvinyl alcohol and gelatin>
The total concentration of polyvinyl alcohol and gelatin is, for example, 5.1 to 28.0% by mass with respect to the total mass of the aqueous gel composition of the present invention, and 5.1 to 21.0% by mass. Preferably, 5.1 to 15.0 mass% is more preferable, and 5.1 to 9.0 mass% is more preferable.
ポリビニルアルコールとゼラチンとの合計濃度は、本発明の水性ゲル組成物の全体の質量に対して、例えば、５．１～２８．０質量％が挙げられ、５．１～２１．０質量％が好ましく、５．１～１５．０質量％がより好ましく、５．１～９．０質量％がより好ましい。 <Total concentration of polyvinyl alcohol and gelatin>
The total concentration of polyvinyl alcohol and gelatin is, for example, 5.1 to 28.0% by mass with respect to the total mass of the aqueous gel composition of the present invention, and 5.1 to 21.0% by mass. Preferably, 5.1 to 15.0 mass% is more preferable, and 5.1 to 9.0 mass% is more preferable.
＜ポリビニルアルコールとゼラチンとの質量比＞
本発明の水性ゲル組成物におけるポリビニルアルコールとゼラチンとの質量比（ポリビニルアルコール／ゼラチン）としては、例えば９５／５～６０／４０が挙げられ、９０／１０～６０／４０が好ましく、８５／１５～６５／３５がより好ましく、８０／２０～７０／３０がより好ましい。
上記質量比がこの範囲内であれば、本発明の水性ゲル組成物の切開感触は、実物との類似性により優れる。 <Mass ratio of polyvinyl alcohol and gelatin>
The mass ratio of polyvinyl alcohol and gelatin (polyvinyl alcohol / gelatin) in the aqueous gel composition of the present invention is, for example, 95/5 to 60/40, preferably 90/10 to 60/40, and 85/15. ~ 65/35 is more preferable, and 80/20 to 70/30 is more preferable.
If the said mass ratio is in this range, the incision feeling of the aqueous gel composition of the present invention will be more excellent due to the similarity to the real thing.
本発明の水性ゲル組成物におけるポリビニルアルコールとゼラチンとの質量比（ポリビニルアルコール／ゼラチン）としては、例えば９５／５～６０／４０が挙げられ、９０／１０～６０／４０が好ましく、８５／１５～６５／３５がより好ましく、８０／２０～７０／３０がより好ましい。
上記質量比がこの範囲内であれば、本発明の水性ゲル組成物の切開感触は、実物との類似性により優れる。 <Mass ratio of polyvinyl alcohol and gelatin>
The mass ratio of polyvinyl alcohol and gelatin (polyvinyl alcohol / gelatin) in the aqueous gel composition of the present invention is, for example, 95/5 to 60/40, preferably 90/10 to 60/40, and 85/15. ~ 65/35 is more preferable, and 80/20 to 70/30 is more preferable.
If the said mass ratio is in this range, the incision feeling of the aqueous gel composition of the present invention will be more excellent due to the similarity to the real thing.
＜相分離構造＞
上述したように、実物の生体臓器、とりわけ肝臓の組織は、約１ｍｍ程度の肝小葉という構成単位の集合体である。
このため、実物に類似した感触を模倣する観点から、本発明の水性ゲル組成物は、２種以上のゲルが互いに相分離した構造（相分離構造）を有するのが好ましく、ゲルが海島構造を形成して相分離しているのがより好ましく、直径０．１～１０ｍｍのゲル（島）が、他のゲル（海）に分散して相分離しているのがさらに好ましい。
なお、相分離構造の確認は、目視および光学顕微鏡観察により行なう。 <Phase separation structure>
As described above, a real living organ, particularly a liver tissue, is an assembly of structural units of about 1 mm of liver lobule.
For this reason, from the viewpoint of imitating the feeling similar to the real thing, the aqueous gel composition of the present invention preferably has a structure in which two or more kinds of gels are phase-separated from each other (phase-separated structure), and the gel has a sea-island structure. More preferably, it is formed and phase-separated, more preferably a gel (island) having a diameter of 0.1 to 10 mm is dispersed in another gel (sea) and phase-separated.
The phase separation structure is confirmed by visual observation and observation with an optical microscope.
上述したように、実物の生体臓器、とりわけ肝臓の組織は、約１ｍｍ程度の肝小葉という構成単位の集合体である。
このため、実物に類似した感触を模倣する観点から、本発明の水性ゲル組成物は、２種以上のゲルが互いに相分離した構造（相分離構造）を有するのが好ましく、ゲルが海島構造を形成して相分離しているのがより好ましく、直径０．１～１０ｍｍのゲル（島）が、他のゲル（海）に分散して相分離しているのがさらに好ましい。
なお、相分離構造の確認は、目視および光学顕微鏡観察により行なう。 <Phase separation structure>
As described above, a real living organ, particularly a liver tissue, is an assembly of structural units of about 1 mm of liver lobule.
For this reason, from the viewpoint of imitating the feeling similar to the real thing, the aqueous gel composition of the present invention preferably has a structure in which two or more kinds of gels are phase-separated from each other (phase-separated structure), and the gel has a sea-island structure. More preferably, it is formed and phase-separated, more preferably a gel (island) having a diameter of 0.1 to 10 mm is dispersed in another gel (sea) and phase-separated.
The phase separation structure is confirmed by visual observation and observation with an optical microscope.
＜水性ゲル組成物の製造方法など＞
本発明の水性ゲル組成物は、例えば、上述したポリビニルアルコール、ゼラチンおよび電解質を含有する水溶液（以下、便宜的に、「ＰＶＡ／ゼラチン水溶液」ともいう）を、－１０℃以下の温度で冷却し、その後、解凍することによって製造できる。ＰＶＡ／ゼラチン水溶液は、上記冷却によって凍結するが、このとき、ゲル化する。
冷却温度は、－１５～－３５℃が好ましく、－２０～－３０℃がより好ましい。冷却時間は、１～１０時間が好ましく、３～８時間がより好ましい。
解凍は、室温中での放置により自然解凍させてもよく、加熱により解凍させてもよい。解凍温度は、特に限定されず、通常、室温～４０℃程度である。
解凍した水性ゲル組成物は、組織を均一化する観点から、必要に応じて、例えば乾燥室内で加熱してもよい。加熱温度は、例えば８０℃以下であり、３５～７５℃が好ましく、４０～７０℃がより好ましい。なお、加熱後は、室温まで放冷すればよい。 <Method for producing aqueous gel composition>
The aqueous gel composition of the present invention, for example, cools an aqueous solution containing the above-mentioned polyvinyl alcohol, gelatin, and electrolyte (hereinafter, also referred to as “PVA / gelatin aqueous solution” for convenience) at a temperature of −10 ° C. or lower. Then, it can manufacture by defrosting. The PVA / gelatin aqueous solution is frozen by the cooling, but at this time, it gels.
The cooling temperature is preferably −15 to −35 ° C., more preferably −20 to −30 ° C. The cooling time is preferably 1 to 10 hours, and more preferably 3 to 8 hours.
Thawing may be performed by natural thawing by standing at room temperature or by heating. The thawing temperature is not particularly limited, and is usually about room temperature to 40 ° C.
The thawed aqueous gel composition may be heated, for example, in a drying chamber, if necessary, from the viewpoint of homogenizing the tissue. The heating temperature is, for example, 80 ° C. or less, preferably 35 to 75 ° C., more preferably 40 to 70 ° C. In addition, what is necessary is just to cool to room temperature after a heating.
本発明の水性ゲル組成物は、例えば、上述したポリビニルアルコール、ゼラチンおよび電解質を含有する水溶液（以下、便宜的に、「ＰＶＡ／ゼラチン水溶液」ともいう）を、－１０℃以下の温度で冷却し、その後、解凍することによって製造できる。ＰＶＡ／ゼラチン水溶液は、上記冷却によって凍結するが、このとき、ゲル化する。
冷却温度は、－１５～－３５℃が好ましく、－２０～－３０℃がより好ましい。冷却時間は、１～１０時間が好ましく、３～８時間がより好ましい。
解凍は、室温中での放置により自然解凍させてもよく、加熱により解凍させてもよい。解凍温度は、特に限定されず、通常、室温～４０℃程度である。
解凍した水性ゲル組成物は、組織を均一化する観点から、必要に応じて、例えば乾燥室内で加熱してもよい。加熱温度は、例えば８０℃以下であり、３５～７５℃が好ましく、４０～７０℃がより好ましい。なお、加熱後は、室温まで放冷すればよい。 <Method for producing aqueous gel composition>
The aqueous gel composition of the present invention, for example, cools an aqueous solution containing the above-mentioned polyvinyl alcohol, gelatin, and electrolyte (hereinafter, also referred to as “PVA / gelatin aqueous solution” for convenience) at a temperature of −10 ° C. or lower. Then, it can manufacture by defrosting. The PVA / gelatin aqueous solution is frozen by the cooling, but at this time, it gels.
The cooling temperature is preferably −15 to −35 ° C., more preferably −20 to −30 ° C. The cooling time is preferably 1 to 10 hours, and more preferably 3 to 8 hours.
Thawing may be performed by natural thawing by standing at room temperature or by heating. The thawing temperature is not particularly limited, and is usually about room temperature to 40 ° C.
The thawed aqueous gel composition may be heated, for example, in a drying chamber, if necessary, from the viewpoint of homogenizing the tissue. The heating temperature is, for example, 80 ° C. or less, preferably 35 to 75 ° C., more preferably 40 to 70 ° C. In addition, what is necessary is just to cool to room temperature after a heating.
本発明の水性ゲル組成物となるＰＶＡ／ゼラチン水溶液には、表面層の乾燥を防止する観点から、多糖類を添加でき、多糖類としては、例えば、キトサンおよびその誘導体が好適に挙げられる。
さらに、本発明の目的の範囲内で、例えば、顔料、染料などの着色剤；香料、酸化防止剤、防黴剤、抗菌剤などの添加剤；等を適量で添加してもよい。 From the viewpoint of preventing the surface layer from being dried, polysaccharides can be added to the PVA / gelatin aqueous solution that is the aqueous gel composition of the present invention. Examples of suitable polysaccharides include chitosan and derivatives thereof.
Further, within the scope of the object of the present invention, for example, colorants such as pigments and dyes; additives such as fragrances, antioxidants, antifungal agents and antibacterial agents;
さらに、本発明の目的の範囲内で、例えば、顔料、染料などの着色剤；香料、酸化防止剤、防黴剤、抗菌剤などの添加剤；等を適量で添加してもよい。 From the viewpoint of preventing the surface layer from being dried, polysaccharides can be added to the PVA / gelatin aqueous solution that is the aqueous gel composition of the present invention. Examples of suitable polysaccharides include chitosan and derivatives thereof.
Further, within the scope of the object of the present invention, for example, colorants such as pigments and dyes; additives such as fragrances, antioxidants, antifungal agents and antibacterial agents;
本発明の水性ゲル組成物およびＰＶＡ／ゼラチン水溶液における含水率は、特に限定されないが、例えば、７０～９５質量％が挙げられ、７５～９４質量％が好ましく、８７～９４質量％がより好ましく、９２～９４質量％がさらに好ましい。
The water content in the aqueous gel composition and the PVA / gelatin aqueous solution of the present invention is not particularly limited, and examples thereof include 70 to 95% by mass, preferably 75 to 94% by mass, more preferably 87 to 94% by mass, More preferably, it is 92 to 94% by mass.
［生体臓器模型］
本発明の生体臓器模型は、上述した本発明の水性ゲル組成物を用いて得られるものであり、例えば、その一部または全部が、本発明の水性ゲル組成物からなる。
例えば、本発明の水性ゲル組成物を製造するのと同時に、本発明の生体臓器模型を製造できる。この場合、臓器の形態に対応した内面形状を有する成形型内に、上述したＰＶＡ／ゼラチン水溶液を注入し、この成形型内のＰＶＡ／ゼラチン水溶液を冷却および解凍することで、本発明の生体臓器模型を製造できる。なお、冷却および解凍などの条件については、水性ゲル組成物の製造方法における条件として記載したものを採用できる。 [Body organ model]
The living organ model of the present invention is obtained using the above-described aqueous gel composition of the present invention. For example, a part or all of the living organ model is composed of the aqueous gel composition of the present invention.
For example, the living organ model of the present invention can be produced simultaneously with the production of the aqueous gel composition of the present invention. In this case, the above-described PVA / gelatin aqueous solution is injected into a mold having an inner shape corresponding to the form of the organ, and the PVA / gelatin aqueous solution in the mold is cooled and thawed, whereby the living organ of the present invention. A model can be manufactured. In addition, about conditions, such as cooling and thawing | decompression, what was described as conditions in the manufacturing method of an aqueous gel composition is employable.
本発明の生体臓器模型は、上述した本発明の水性ゲル組成物を用いて得られるものであり、例えば、その一部または全部が、本発明の水性ゲル組成物からなる。
例えば、本発明の水性ゲル組成物を製造するのと同時に、本発明の生体臓器模型を製造できる。この場合、臓器の形態に対応した内面形状を有する成形型内に、上述したＰＶＡ／ゼラチン水溶液を注入し、この成形型内のＰＶＡ／ゼラチン水溶液を冷却および解凍することで、本発明の生体臓器模型を製造できる。なお、冷却および解凍などの条件については、水性ゲル組成物の製造方法における条件として記載したものを採用できる。 [Body organ model]
The living organ model of the present invention is obtained using the above-described aqueous gel composition of the present invention. For example, a part or all of the living organ model is composed of the aqueous gel composition of the present invention.
For example, the living organ model of the present invention can be produced simultaneously with the production of the aqueous gel composition of the present invention. In this case, the above-described PVA / gelatin aqueous solution is injected into a mold having an inner shape corresponding to the form of the organ, and the PVA / gelatin aqueous solution in the mold is cooled and thawed, whereby the living organ of the present invention. A model can be manufactured. In addition, about conditions, such as cooling and thawing | decompression, what was described as conditions in the manufacturing method of an aqueous gel composition is employable.
また、本発明の生体臓器模型としては、本発明の水性ゲル組成物からなる表面層を有する態様も好適に挙げられ、軽量化を図るとともに実際の臓器に近似させる観点から、内部が空洞であることが好ましい。
この場合、本発明の生体臓器模型の製造方法としては、例えば、内部が空洞であるバルーンの表面に、本発明の水性ゲル組成物からなる表面層を形成させることによって製造する方法；シート状の本発明の水性ゲル組成物を湾曲させて筒状にし、このシートの端部同士を接着することによって製造する方法；等が挙げられる。
なお、内部を空洞にする場合、必要に応じて、液体またはゲルを充填してもよい。
さらに、本発明の生体臓器模型は、より一層、実物の生体臓器に近似させる観点から、内部に臓器に対応した形状を有する基体上に、本発明の水性ゲル組成物からなる表面層を形成したものであってもよい。 In addition, the biological organ model of the present invention preferably includes an embodiment having a surface layer made of the aqueous gel composition of the present invention, and from the viewpoint of reducing the weight and approximating an actual organ, the interior is hollow. It is preferable.
In this case, as a method for producing the living organ model of the present invention, for example, a method of producing a surface layer made of the aqueous gel composition of the present invention on the surface of a balloon having a hollow interior; And the like. The method of manufacturing by curving the aqueous gel composition of the present invention into a cylindrical shape and bonding the ends of the sheet to each other.
In addition, when making an inside into a cavity, you may fill with a liquid or a gel as needed.
Furthermore, in the living organ model of the present invention, a surface layer made of the aqueous gel composition of the present invention is formed on a substrate having a shape corresponding to the internal organ from the viewpoint of further approximating an actual living organ. It may be a thing.
この場合、本発明の生体臓器模型の製造方法としては、例えば、内部が空洞であるバルーンの表面に、本発明の水性ゲル組成物からなる表面層を形成させることによって製造する方法；シート状の本発明の水性ゲル組成物を湾曲させて筒状にし、このシートの端部同士を接着することによって製造する方法；等が挙げられる。
なお、内部を空洞にする場合、必要に応じて、液体またはゲルを充填してもよい。
さらに、本発明の生体臓器模型は、より一層、実物の生体臓器に近似させる観点から、内部に臓器に対応した形状を有する基体上に、本発明の水性ゲル組成物からなる表面層を形成したものであってもよい。 In addition, the biological organ model of the present invention preferably includes an embodiment having a surface layer made of the aqueous gel composition of the present invention, and from the viewpoint of reducing the weight and approximating an actual organ, the interior is hollow. It is preferable.
In this case, as a method for producing the living organ model of the present invention, for example, a method of producing a surface layer made of the aqueous gel composition of the present invention on the surface of a balloon having a hollow interior; And the like. The method of manufacturing by curving the aqueous gel composition of the present invention into a cylindrical shape and bonding the ends of the sheet to each other.
In addition, when making an inside into a cavity, you may fill with a liquid or a gel as needed.
Furthermore, in the living organ model of the present invention, a surface layer made of the aqueous gel composition of the present invention is formed on a substrate having a shape corresponding to the internal organ from the viewpoint of further approximating an actual living organ. It may be a thing.
本発明の生体臓器模型の表面、内部および内面には、より実物の生体臓器に近似させるため、必要に応じて、本発明の水性ゲル組成物を用いて、襞、皺、血管などに見立てた管および表面薄膜などを形成してもよい。
The surface, inside and inner surface of the living organ model of the present invention are more closely approximated to real living organs, and if necessary, the aqueous gel composition of the present invention is used to make it look like sputum, sputum, blood vessel, etc. Tubes and surface thin films may be formed.
なお、以上の記載では、主として、ヒトの肝臓に似せた肝臓模型を例に説明したが、本発明はこれに限定されるものではなく、その他の生体臓器としては、例えば、脳、心臓、食道、胃、膀胱、小腸、大腸、腎臓、膵臓、脾臓、子宮などが挙げられる。
In the above description, a liver model resembling a human liver has been mainly described as an example. However, the present invention is not limited to this, and other biological organs include, for example, the brain, heart, and esophagus. , Stomach, bladder, small intestine, large intestine, kidney, pancreas, spleen, uterus and the like.
本発明の水性ゲル組成物を用いて得られる本発明の生体臓器模型は、実物の生体臓器と類似した切開感触が得られることから、手術の手技練習用の生体臓器模型として好適に用いられる。
The living organ model of the present invention obtained by using the aqueous gel composition of the present invention can be suitably used as a living organ model for practicing surgical techniques because it provides an incision feel similar to that of a real living organ.
以下に、実施例を挙げて本発明を具体的に説明する。ただし、本発明はこれらに限定されるものではない。
Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not limited to these.
＜実施例１＞
（肝臓模型の製造）
まず、粘度平均重合度が１７００であり、ケン化度が約９９．３モル％以上であるポリビニルアルコール（クラレ社製、商品名：クラレポバールＰＶＡ－１１７Ｈ）を濃度が７質量％、ゼラチン（和光純薬工業社製）を濃度が３質量％、および、電解質としての塩化ナトリウム（和光純薬工業社製）を濃度が０．５質量％となるように、水に添加して、ＰＶＡ／ゼラチン水溶液５００ｍＬを調製した。
調製したＰＶＡ／ゼラチン水溶液を、８５℃に加温しながら３時間攪拌した後、約６０℃まで放冷した。次いで、ヒトの肝臓の色に近づける目的で、食用色素 赤（共立食品社製）０．１５ｇおよび食用色素 緑（共立食品社製）０．０１５ｇを添加し、均一な組成となるように攪拌して着色した。着色したＰＶＡ／ゼラチン水溶液５００ｍＬを、１Ｌ容のビーカーに入れた。
ヒトの肝臓の形態に対応した内面形状を有する石膏製の成形型（上下割の成形型）を作製し、その内面に離型剤を塗布した後、型合わせをし、接合面を密閉し、成形型をあらかじめ冷凍室（室温：－２０℃）で冷却し、成形型の上面に設けられた注入孔から、上記着色したＰＶＡ／ゼラチン水溶液（液温：６０℃）を注入した。
次に、ＰＶＡ／ゼラチン水溶液を注入した成形型を、冷凍室（室温：－２０℃）内に入れ、５時間冷却した後、冷凍室から取り出し、室温となるまで室温中で放置した。
次に、室温中で放置した成形型を、乾燥器内に入れ、６０℃となるまで加熱し、同温度で１時間保持した後、乾燥器から取り出し、放冷した。その後、成形型を型開きし、肝臓模型（生体臓器模型）を取り出し、肝臓模型を得た。 <Example 1>
(Manufacture of liver model)
First, polyvinyl alcohol having a viscosity average polymerization degree of 1700 and a saponification degree of about 99.3 mol% or more (made by Kuraray Co., Ltd., trade name: Kuraray Poval PVA-117H) with a concentration of 7% by weight, gelatin (Japanese PVA / gelatin is added to water so that the concentration is 3% by mass and the sodium chloride (Wako Pure Chemical Industries) as the electrolyte is 0.5% by mass. 500 mL of an aqueous solution was prepared.
The prepared PVA / gelatin aqueous solution was stirred for 3 hours while heating to 85 ° C., and then allowed to cool to about 60 ° C. Next, 0.15 g of food dye red (manufactured by Kyoritsu Foods Co., Ltd.) and 0.015 g of food dye green (manufactured by Kyoritsu Foods Co., Ltd.) are added and stirred to obtain a uniform composition for the purpose of bringing the color of human liver closer. And colored. 500 mL of colored PVA / gelatin aqueous solution was placed in a 1 L beaker.
After creating a gypsum mold that has an inner shape corresponding to the shape of the human liver (upper and lower molds), applying a release agent to the inner surface, matching the mold, and sealing the joint surface, The mold was cooled in advance in a freezer (room temperature: −20 ° C.), and the colored PVA / gelatin aqueous solution (liquid temperature: 60 ° C.) was injected from an injection hole provided on the upper surface of the mold.
Next, the mold into which the PVA / gelatin aqueous solution was injected was placed in a freezer (room temperature: −20 ° C.), cooled for 5 hours, taken out of the freezer, and left at room temperature until it reached room temperature.
Next, the mold that was allowed to stand at room temperature was placed in a dryer, heated to 60 ° C., held at that temperature for 1 hour, then removed from the dryer and allowed to cool. Thereafter, the mold was opened and the liver model (biological organ model) was taken out to obtain a liver model.
（肝臓模型の製造）
まず、粘度平均重合度が１７００であり、ケン化度が約９９．３モル％以上であるポリビニルアルコール（クラレ社製、商品名：クラレポバールＰＶＡ－１１７Ｈ）を濃度が７質量％、ゼラチン（和光純薬工業社製）を濃度が３質量％、および、電解質としての塩化ナトリウム（和光純薬工業社製）を濃度が０．５質量％となるように、水に添加して、ＰＶＡ／ゼラチン水溶液５００ｍＬを調製した。
調製したＰＶＡ／ゼラチン水溶液を、８５℃に加温しながら３時間攪拌した後、約６０℃まで放冷した。次いで、ヒトの肝臓の色に近づける目的で、食用色素 赤（共立食品社製）０．１５ｇおよび食用色素 緑（共立食品社製）０．０１５ｇを添加し、均一な組成となるように攪拌して着色した。着色したＰＶＡ／ゼラチン水溶液５００ｍＬを、１Ｌ容のビーカーに入れた。
ヒトの肝臓の形態に対応した内面形状を有する石膏製の成形型（上下割の成形型）を作製し、その内面に離型剤を塗布した後、型合わせをし、接合面を密閉し、成形型をあらかじめ冷凍室（室温：－２０℃）で冷却し、成形型の上面に設けられた注入孔から、上記着色したＰＶＡ／ゼラチン水溶液（液温：６０℃）を注入した。
次に、ＰＶＡ／ゼラチン水溶液を注入した成形型を、冷凍室（室温：－２０℃）内に入れ、５時間冷却した後、冷凍室から取り出し、室温となるまで室温中で放置した。
次に、室温中で放置した成形型を、乾燥器内に入れ、６０℃となるまで加熱し、同温度で１時間保持した後、乾燥器から取り出し、放冷した。その後、成形型を型開きし、肝臓模型（生体臓器模型）を取り出し、肝臓模型を得た。 <Example 1>
(Manufacture of liver model)
First, polyvinyl alcohol having a viscosity average polymerization degree of 1700 and a saponification degree of about 99.3 mol% or more (made by Kuraray Co., Ltd., trade name: Kuraray Poval PVA-117H) with a concentration of 7% by weight, gelatin (Japanese PVA / gelatin is added to water so that the concentration is 3% by mass and the sodium chloride (Wako Pure Chemical Industries) as the electrolyte is 0.5% by mass. 500 mL of an aqueous solution was prepared.
The prepared PVA / gelatin aqueous solution was stirred for 3 hours while heating to 85 ° C., and then allowed to cool to about 60 ° C. Next, 0.15 g of food dye red (manufactured by Kyoritsu Foods Co., Ltd.) and 0.015 g of food dye green (manufactured by Kyoritsu Foods Co., Ltd.) are added and stirred to obtain a uniform composition for the purpose of bringing the color of human liver closer. And colored. 500 mL of colored PVA / gelatin aqueous solution was placed in a 1 L beaker.
After creating a gypsum mold that has an inner shape corresponding to the shape of the human liver (upper and lower molds), applying a release agent to the inner surface, matching the mold, and sealing the joint surface, The mold was cooled in advance in a freezer (room temperature: −20 ° C.), and the colored PVA / gelatin aqueous solution (liquid temperature: 60 ° C.) was injected from an injection hole provided on the upper surface of the mold.
Next, the mold into which the PVA / gelatin aqueous solution was injected was placed in a freezer (room temperature: −20 ° C.), cooled for 5 hours, taken out of the freezer, and left at room temperature until it reached room temperature.
Next, the mold that was allowed to stand at room temperature was placed in a dryer, heated to 60 ° C., held at that temperature for 1 hour, then removed from the dryer and allowed to cool. Thereafter, the mold was opened and the liver model (biological organ model) was taken out to obtain a liver model.
（電気伝導率の測定）
得られた肝臓模型から、円形の切片（直径２０ｍｍ、厚さ０．５ｍｍ）を切り取り、直径２０ｍｍの円形ステンレス板で挟み込んで、測定用セルを作製した。作製した測定用セルについて、ソーラトロン（Ｓｏｌａｒｔｒｏｎ）社製の１４７０Ｅ型マルチスタットを用いて、温度２５℃、測定周波数１ＭＨｚ、印加電圧５ｍＶの条件で、交流インピーダンス測定を行った。測定データの実数のインピーダンス値から電気伝導率を計算したところ、電気伝導率は、０．５１Ｓ／ｍであった。 (Measurement of electrical conductivity)
A circular slice (diameter 20 mm, thickness 0.5 mm) was cut out from the obtained liver model and sandwiched between circular stainless steel plates with a diameter of 20 mm to produce a measurement cell. The produced measurement cell was subjected to AC impedance measurement using a 1470E type multistat manufactured by Solartron under the conditions of a temperature of 25 ° C., a measurement frequency of 1 MHz, and an applied voltage of 5 mV. When the electrical conductivity was calculated from the real impedance value of the measurement data, the electrical conductivity was 0.51 S / m.
得られた肝臓模型から、円形の切片（直径２０ｍｍ、厚さ０．５ｍｍ）を切り取り、直径２０ｍｍの円形ステンレス板で挟み込んで、測定用セルを作製した。作製した測定用セルについて、ソーラトロン（Ｓｏｌａｒｔｒｏｎ）社製の１４７０Ｅ型マルチスタットを用いて、温度２５℃、測定周波数１ＭＨｚ、印加電圧５ｍＶの条件で、交流インピーダンス測定を行った。測定データの実数のインピーダンス値から電気伝導率を計算したところ、電気伝導率は、０．５１Ｓ／ｍであった。 (Measurement of electrical conductivity)
A circular slice (diameter 20 mm, thickness 0.5 mm) was cut out from the obtained liver model and sandwiched between circular stainless steel plates with a diameter of 20 mm to produce a measurement cell. The produced measurement cell was subjected to AC impedance measurement using a 1470E type multistat manufactured by Solartron under the conditions of a temperature of 25 ° C., a measurement frequency of 1 MHz, and an applied voltage of 5 mV. When the electrical conductivity was calculated from the real impedance value of the measurement data, the electrical conductivity was 0.51 S / m.
（相分離構造）
得られた肝臓模型について、目視および光学顕微鏡を用いた観察により、相分離構造を確認した。直径０．１～１０ｍｍのゼラチンがＰＶＡに分散して相分離しているのが確認された場合には「Ａ」を、直径１０ｍｍ超のゼラチンがＰＶＡに分散して相分離しているのが確認された場合には「Ｂ」を、相分離構造が確認されなかった場合には「Ｃ」を、下記第１表に記載した。 (Phase separation structure)
About the obtained liver model, the phase-separation structure was confirmed by visual observation and observation using an optical microscope. When it is confirmed that gelatin having a diameter of 0.1 to 10 mm is dispersed in PVA and phase-separated, “A” is indicated, and gelatin having a diameter of more than 10 mm is dispersed in PVA and phase-separated. Table 1 below shows “B” when confirmed, and “C” when no phase separation structure was confirmed.
得られた肝臓模型について、目視および光学顕微鏡を用いた観察により、相分離構造を確認した。直径０．１～１０ｍｍのゼラチンがＰＶＡに分散して相分離しているのが確認された場合には「Ａ」を、直径１０ｍｍ超のゼラチンがＰＶＡに分散して相分離しているのが確認された場合には「Ｂ」を、相分離構造が確認されなかった場合には「Ｃ」を、下記第１表に記載した。 (Phase separation structure)
About the obtained liver model, the phase-separation structure was confirmed by visual observation and observation using an optical microscope. When it is confirmed that gelatin having a diameter of 0.1 to 10 mm is dispersed in PVA and phase-separated, “A” is indicated, and gelatin having a diameter of more than 10 mm is dispersed in PVA and phase-separated. Table 1 below shows “B” when confirmed, and “C” when no phase separation structure was confirmed.
（切開感触の評価）
得られた肝臓模型の切開感触を１人の外科医に評価してもらった。
具体的には、ペアン鉗子（日本フリッツメディコ社製の１４．５ｃｍペアン止血鉗子）を用いて組織を押しつぶす感触、および、１ＭＨｚの高周波電気メス（藤栄電気社製のベストサージＴＭＥ－７０１型）を用いて組織を凝固させながら切離する感触を、それぞれ、実物の生体臓器（ヒトの肝臓）との類似性の観点から、下記Ａ～Ｄの４段階で評価してもらった。なお、高周波電気メスの設定は、ＣＵＴモード、出力メモリ３、チップ＃２とした。
ＡまたはＢであれば、切開感触が実物の生体臓器（肝臓）に類似しており、手術における手技練習に適しているものとして評価できる。
Ａ：非常によく似ている
Ｂ：似ている
Ｃ：やや異なる
Ｄ：異なる (Evaluation of incision feel)
One surgeon evaluated the incision feel of the obtained liver model.
Specifically, a tissue crushing feeling using a Pean forceps (14.5 cm Pean hemostatic forceps manufactured by Fritz Medical Japan) and a 1 MHz high frequency electric knife (Best Surge TME-701 type manufactured by Fujiei Electric Co., Ltd.) The feeling of using the tissue while coagulating the tissue was evaluated in the following four grades A to D from the viewpoint of similarity to the actual living organ (human liver). The high frequency electric knife was set to CUT mode, output memory 3, and chip # 2.
If it is A or B, the incision feel is similar to that of a real living organ (liver), and it can be evaluated as being suitable for practicing a surgical procedure.
A: Very similar B: Similar C: Slightly different D: Different
得られた肝臓模型の切開感触を１人の外科医に評価してもらった。
具体的には、ペアン鉗子（日本フリッツメディコ社製の１４．５ｃｍペアン止血鉗子）を用いて組織を押しつぶす感触、および、１ＭＨｚの高周波電気メス（藤栄電気社製のベストサージＴＭＥ－７０１型）を用いて組織を凝固させながら切離する感触を、それぞれ、実物の生体臓器（ヒトの肝臓）との類似性の観点から、下記Ａ～Ｄの４段階で評価してもらった。なお、高周波電気メスの設定は、ＣＵＴモード、出力メモリ３、チップ＃２とした。
ＡまたはＢであれば、切開感触が実物の生体臓器（肝臓）に類似しており、手術における手技練習に適しているものとして評価できる。
Ａ：非常によく似ている
Ｂ：似ている
Ｃ：やや異なる
Ｄ：異なる (Evaluation of incision feel)
One surgeon evaluated the incision feel of the obtained liver model.
Specifically, a tissue crushing feeling using a Pean forceps (14.5 cm Pean hemostatic forceps manufactured by Fritz Medical Japan) and a 1 MHz high frequency electric knife (Best Surge TME-701 type manufactured by Fujiei Electric Co., Ltd.) The feeling of using the tissue while coagulating the tissue was evaluated in the following four grades A to D from the viewpoint of similarity to the actual living organ (human liver). The high frequency electric knife was set to CUT mode, output memory 3, and chip # 2.
If it is A or B, the incision feel is similar to that of a real living organ (liver), and it can be evaluated as being suitable for practicing a surgical procedure.
A: Very similar B: Similar C: Slightly different D: Different
＜実施例２＞
ポリビニルアルコールの濃度を９．５質量％、ゼラチンの濃度を０．５質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 2>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of polyvinyl alcohol was 9.5 mass% and the concentration of gelatin was 0.5 mass%. The results are shown in Table 1 below.
ポリビニルアルコールの濃度を９．５質量％、ゼラチンの濃度を０．５質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 2>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of polyvinyl alcohol was 9.5 mass% and the concentration of gelatin was 0.5 mass%. The results are shown in Table 1 below.
＜実施例３＞
塩化ナトリウムの濃度を０．２質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 3>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 0.2% by mass. The results are shown in Table 1 below.
塩化ナトリウムの濃度を０．２質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 3>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 0.2% by mass. The results are shown in Table 1 below.
＜実施例４＞
塩化ナトリウムの濃度を１．９質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 4>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 1.9% by mass. The results are shown in Table 1 below.
塩化ナトリウムの濃度を１．９質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 4>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 1.9% by mass. The results are shown in Table 1 below.
＜実施例５＞
ポリビニルアルコールの濃度を５．２５質量％、ゼラチンの濃度を２．２５質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 5>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of polyvinyl alcohol was 5.25% by mass and the concentration of gelatin was 2.25% by mass. The results are shown in Table 1 below.
ポリビニルアルコールの濃度を５．２５質量％、ゼラチンの濃度を２．２５質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Example 5>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of polyvinyl alcohol was 5.25% by mass and the concentration of gelatin was 2.25% by mass. The results are shown in Table 1 below.
＜比較例１＞
ゼラチンおよび塩化ナトリウムを添加しなかった以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。
なお、電解質である塩化ナトリウムを添加しなかったことから、下記第１表の「電解質濃度」の欄には「－」を記載した（以下、同様）。 <Comparative Example 1>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that gelatin and sodium chloride were not added. The results are shown in Table 1 below.
Since sodium chloride as an electrolyte was not added, “-” was described in the “electrolyte concentration” column of Table 1 below (the same applies hereinafter).
ゼラチンおよび塩化ナトリウムを添加しなかった以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。
なお、電解質である塩化ナトリウムを添加しなかったことから、下記第１表の「電解質濃度」の欄には「－」を記載した（以下、同様）。 <Comparative Example 1>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that gelatin and sodium chloride were not added. The results are shown in Table 1 below.
Since sodium chloride as an electrolyte was not added, “-” was described in the “electrolyte concentration” column of Table 1 below (the same applies hereinafter).
＜比較例２＞
塩化ナトリウムを添加しなかった以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative example 2>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that sodium chloride was not added. The results are shown in Table 1 below.
塩化ナトリウムを添加しなかった以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative example 2>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that sodium chloride was not added. The results are shown in Table 1 below.
＜比較例３＞
まず、粘度平均重合度が１７００であり、ケン化度が約９８～９９モル％以上であるポリビニルアルコール（クラレ社製、商品名：クラレポバールＰＶＡ－１１７）を、濃度が１０質量％となるように水に添加して、ＰＶＡ水溶液を調製した。調製したＰＶＡ水溶液を、８５℃に加温しながら３時間攪拌した後、常温まで放冷した。放冷したＰＶＡ水溶液５００ｍＬを、１Ｌ容のビーカーに入れた。
次に、コロイダルシリカ（日産化学工業社製、商品名：スノーテックスＸＰ、シリカの粒子径：約５ｎｍ、シリカの含有量：５質量％）１５ｍＬを、上記ビーカー内に添加し、ビーカー内の内容物を、均一な組成となるように攪拌した。その後、ヒトの肝臓の色に近い赤茶色で半透明のアクリル系ポスターカラー（デルタ社製、商品名：デルタ セラムコート）０．５ｍＬを添加し、均一な組成となるように攪拌して、着色した。
ヒトの肝臓の形態に対応した内面形状を有する石膏製の成形型（上下割の成形型）を作製し、その内面に離型剤を塗布した後、型合わせをし、接合面を密閉し、成形型の上面に設けられた注入孔から、上記着色したＰＶＡ水溶液（液温：２０℃）を注入した。
次に、ＰＶＡ水溶液を注入した成形型を、冷凍室（室温：－２０℃）内に入れ、５時間冷却した後、冷凍室から取り出し、室温となるまで室温中で放置した。
次に、室温中で放置した成形型を、乾燥器内に入れ、６０℃となるまで加熱し、同温度で１０分間保持した後、乾燥器から取り出し、放冷した。その後、成形型を型開きし、肝臓模型（生体臓器模型）を取り出し、肝臓模型を得た。
得られた肝臓模型について、実施例１と同様にして、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。なお、比較例３の肝臓模型の態様は、特許文献１に記載の態様に相当する。 <Comparative Example 3>
First, polyvinyl alcohol having a viscosity average polymerization degree of 1700 and a saponification degree of about 98 to 99 mol% or more (made by Kuraray Co., Ltd., trade name: Kuraray Poval PVA-117) is set so that the concentration becomes 10% by mass. Was added to water to prepare an aqueous PVA solution. The prepared PVA aqueous solution was stirred for 3 hours while being heated to 85 ° C., and then allowed to cool to room temperature. 500 mL of the cooled PVA aqueous solution was placed in a 1 L beaker.
Next, 15 mL of colloidal silica (manufactured by Nissan Chemical Industries, Ltd., trade name: Snowtex XP, silica particle size: about 5 nm, silica content: 5 mass%) is added to the above beaker, and the contents in the beaker The product was stirred to a uniform composition. After that, add 0.5 mL of red-brown and translucent acrylic poster color (product name: Delta Serum Coat), which is close to the color of human liver, and stir to give a uniform composition. did.
After creating a gypsum mold that has an inner shape corresponding to the shape of the human liver (upper and lower molds), applying a release agent to the inner surface, matching the mold, and sealing the joint surface, The colored PVA aqueous solution (liquid temperature: 20 ° C.) was injected from an injection hole provided on the upper surface of the mold.
Next, the mold into which the PVA aqueous solution was poured was placed in a freezer (room temperature: −20 ° C.), cooled for 5 hours, then taken out of the freezer and allowed to stand at room temperature until it reached room temperature.
Next, the mold that was allowed to stand at room temperature was placed in a dryer, heated to 60 ° C., held at that temperature for 10 minutes, then removed from the dryer and allowed to cool. Thereafter, the mold was opened and the liver model (biological organ model) was taken out to obtain a liver model.
About the obtained liver model, it carried out similarly to Example 1, and measured and evaluated electrical conductivity. The results are shown in Table 1 below. In addition, the aspect of the liver model of Comparative Example 3 corresponds to the aspect described in Patent Document 1.
まず、粘度平均重合度が１７００であり、ケン化度が約９８～９９モル％以上であるポリビニルアルコール（クラレ社製、商品名：クラレポバールＰＶＡ－１１７）を、濃度が１０質量％となるように水に添加して、ＰＶＡ水溶液を調製した。調製したＰＶＡ水溶液を、８５℃に加温しながら３時間攪拌した後、常温まで放冷した。放冷したＰＶＡ水溶液５００ｍＬを、１Ｌ容のビーカーに入れた。
次に、コロイダルシリカ（日産化学工業社製、商品名：スノーテックスＸＰ、シリカの粒子径：約５ｎｍ、シリカの含有量：５質量％）１５ｍＬを、上記ビーカー内に添加し、ビーカー内の内容物を、均一な組成となるように攪拌した。その後、ヒトの肝臓の色に近い赤茶色で半透明のアクリル系ポスターカラー（デルタ社製、商品名：デルタ セラムコート）０．５ｍＬを添加し、均一な組成となるように攪拌して、着色した。
ヒトの肝臓の形態に対応した内面形状を有する石膏製の成形型（上下割の成形型）を作製し、その内面に離型剤を塗布した後、型合わせをし、接合面を密閉し、成形型の上面に設けられた注入孔から、上記着色したＰＶＡ水溶液（液温：２０℃）を注入した。
次に、ＰＶＡ水溶液を注入した成形型を、冷凍室（室温：－２０℃）内に入れ、５時間冷却した後、冷凍室から取り出し、室温となるまで室温中で放置した。
次に、室温中で放置した成形型を、乾燥器内に入れ、６０℃となるまで加熱し、同温度で１０分間保持した後、乾燥器から取り出し、放冷した。その後、成形型を型開きし、肝臓模型（生体臓器模型）を取り出し、肝臓模型を得た。
得られた肝臓模型について、実施例１と同様にして、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。なお、比較例３の肝臓模型の態様は、特許文献１に記載の態様に相当する。 <Comparative Example 3>
First, polyvinyl alcohol having a viscosity average polymerization degree of 1700 and a saponification degree of about 98 to 99 mol% or more (made by Kuraray Co., Ltd., trade name: Kuraray Poval PVA-117) is set so that the concentration becomes 10% by mass. Was added to water to prepare an aqueous PVA solution. The prepared PVA aqueous solution was stirred for 3 hours while being heated to 85 ° C., and then allowed to cool to room temperature. 500 mL of the cooled PVA aqueous solution was placed in a 1 L beaker.
Next, 15 mL of colloidal silica (manufactured by Nissan Chemical Industries, Ltd., trade name: Snowtex XP, silica particle size: about 5 nm, silica content: 5 mass%) is added to the above beaker, and the contents in the beaker The product was stirred to a uniform composition. After that, add 0.5 mL of red-brown and translucent acrylic poster color (product name: Delta Serum Coat), which is close to the color of human liver, and stir to give a uniform composition. did.
After creating a gypsum mold that has an inner shape corresponding to the shape of the human liver (upper and lower molds), applying a release agent to the inner surface, matching the mold, and sealing the joint surface, The colored PVA aqueous solution (liquid temperature: 20 ° C.) was injected from an injection hole provided on the upper surface of the mold.
Next, the mold into which the PVA aqueous solution was poured was placed in a freezer (room temperature: −20 ° C.), cooled for 5 hours, then taken out of the freezer and allowed to stand at room temperature until it reached room temperature.
Next, the mold that was allowed to stand at room temperature was placed in a dryer, heated to 60 ° C., held at that temperature for 10 minutes, then removed from the dryer and allowed to cool. Thereafter, the mold was opened and the liver model (biological organ model) was taken out to obtain a liver model.
About the obtained liver model, it carried out similarly to Example 1, and measured and evaluated electrical conductivity. The results are shown in Table 1 below. In addition, the aspect of the liver model of Comparative Example 3 corresponds to the aspect described in Patent Document 1.
＜比較例４＞
塩化ナトリウムの濃度を０．１質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative example 4>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 0.1% by mass. The results are shown in Table 1 below.
塩化ナトリウムの濃度を０．１質量％とした以外は、実施例１と同様にして、肝臓模型の製造、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative example 4>
A liver model was produced, and electrical conductivity was measured and evaluated in the same manner as in Example 1 except that the concentration of sodium chloride was 0.1% by mass. The results are shown in Table 1 below.
＜比較例５＞
まず、６５ｇのゼラチンと蒸留水１７５ｃｃとをビーカーに入れ、８０±５℃までゆっくり加熱した。８０±５℃に達したら、この温度を２０分またはそれ以上維持して、ゼラチンが完全に溶解したゼラチン溶液を得た。
次に、２５０ｇの市販の蜂蜜（純粋な蜂蜜１２５ｇ、オリゴ糖７５ｇ、ならびに、果糖およびぶどう糖５０ｇを含む）を、ゼラチン溶液にゆっくり加えた。
蜂蜜が溶けた後、溶液を十分混合しながら、さらに１０ｇの食塩を加えた。この間、水の温度は８０±５℃に保った。
加熱された溶液を、実施例１と同じ成形型に注入し、実施例１と同様にして、肝臓模型を得た。
得られた肝臓模型について、実施例１と同様にして、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative Example 5>
First, 65 g of gelatin and 175 cc of distilled water were placed in a beaker and slowly heated to 80 ± 5 ° C. When the temperature reached 80 ± 5 ° C., this temperature was maintained for 20 minutes or longer to obtain a gelatin solution in which gelatin was completely dissolved.
Next, 250 g of commercially available honey (containing 125 g of pure honey, 75 g of oligosaccharides, and 50 g of fructose and glucose) was slowly added to the gelatin solution.
After the honey melted, an additional 10 g of salt was added while thoroughly mixing the solution. During this time, the water temperature was kept at 80 ± 5 ° C.
The heated solution was poured into the same mold as in Example 1, and a liver model was obtained in the same manner as in Example 1.
About the obtained liver model, it carried out similarly to Example 1, and measured and evaluated electrical conductivity. The results are shown in Table 1 below.
まず、６５ｇのゼラチンと蒸留水１７５ｃｃとをビーカーに入れ、８０±５℃までゆっくり加熱した。８０±５℃に達したら、この温度を２０分またはそれ以上維持して、ゼラチンが完全に溶解したゼラチン溶液を得た。
次に、２５０ｇの市販の蜂蜜（純粋な蜂蜜１２５ｇ、オリゴ糖７５ｇ、ならびに、果糖およびぶどう糖５０ｇを含む）を、ゼラチン溶液にゆっくり加えた。
蜂蜜が溶けた後、溶液を十分混合しながら、さらに１０ｇの食塩を加えた。この間、水の温度は８０±５℃に保った。
加熱された溶液を、実施例１と同じ成形型に注入し、実施例１と同様にして、肝臓模型を得た。
得られた肝臓模型について、実施例１と同様にして、電気伝導率の測定および評価を行なった。結果を下記第１表に示す。 <Comparative Example 5>
First, 65 g of gelatin and 175 cc of distilled water were placed in a beaker and slowly heated to 80 ± 5 ° C. When the temperature reached 80 ± 5 ° C., this temperature was maintained for 20 minutes or longer to obtain a gelatin solution in which gelatin was completely dissolved.
Next, 250 g of commercially available honey (containing 125 g of pure honey, 75 g of oligosaccharides, and 50 g of fructose and glucose) was slowly added to the gelatin solution.
After the honey melted, an additional 10 g of salt was added while thoroughly mixing the solution. During this time, the water temperature was kept at 80 ± 5 ° C.
The heated solution was poured into the same mold as in Example 1, and a liver model was obtained in the same manner as in Example 1.
About the obtained liver model, it carried out similarly to Example 1, and measured and evaluated electrical conductivity. The results are shown in Table 1 below.
上記第１表に示す結果から明らかなように、ＰＶＡとゼラチンとを併用し、かつ、電気伝導率が０．１５～５．００Ｓ／ｍである実施例１～５の肝臓模型については、切開感触が実物の肝臓に類似しており、手術における手技練習に適していることが分かった。
As is clear from the results shown in Table 1 above, for the liver models of Examples 1 to 5 in which PVA and gelatin are used in combination and the electrical conductivity is 0.15 to 5.00 S / m, incision is performed. It was found that the feel is similar to the real liver and is suitable for practicing surgical procedures.
このとき、電解質の濃度が同じであり、かつ、ＰＶＡおよびゼラチンの合計濃度が同じである実施例１と実施例２とを対比すると、質量比（ＰＶＡ／ゼラチン）が９０／１０～６０／４０の範囲内である実施例１の方が、上記質量比がこの範囲外である実施例２よりも、ペアン鉗子での切開感触がより優れていた。
なお、実施例１と実施例２とは、電解質の濃度は同じ（０．５質量％）であるが、電気伝導率は異なる値であった。これは、質量比（ＰＶＡ／ゼラチン）の違いによって組成が異なるためと考えられる。 At this time, when Example 1 and Example 2 having the same electrolyte concentration and the same total concentration of PVA and gelatin are compared, the mass ratio (PVA / gelatin) is 90/10 to 60/40. In Example 1, which is within the range, the incision feeling with the Pean forceps was more excellent than Example 2 in which the mass ratio was outside this range.
Note that Example 1 and Example 2 had the same electrolyte concentration (0.5% by mass), but different electrical conductivity values. This is presumably because the composition differs depending on the difference in mass ratio (PVA / gelatin).
なお、実施例１と実施例２とは、電解質の濃度は同じ（０．５質量％）であるが、電気伝導率は異なる値であった。これは、質量比（ＰＶＡ／ゼラチン）の違いによって組成が異なるためと考えられる。 At this time, when Example 1 and Example 2 having the same electrolyte concentration and the same total concentration of PVA and gelatin are compared, the mass ratio (PVA / gelatin) is 90/10 to 60/40. In Example 1, which is within the range, the incision feeling with the Pean forceps was more excellent than Example 2 in which the mass ratio was outside this range.
Note that Example 1 and Example 2 had the same electrolyte concentration (0.5% by mass), but different electrical conductivity values. This is presumably because the composition differs depending on the difference in mass ratio (PVA / gelatin).
また、質量比（ＰＶＡ／ゼラチン）が同じであり、かつ、ＰＶＡおよびゼラチンの合計濃度が同じである実施例１と実施例３と実施例４とを対比すると、電解質の濃度が１．９０質量％である実施例４よりも、電解質の濃度が１．５０質量％以下である実施例１および実施例３の方が、ペアン鉗子での切開感触がより優れていた。
なお、実施例１と実施例３との対比では、電解質の濃度が高い実施例１の方が電気伝導率も高い値となっていたが、実施例１よりも電解質の濃度が高い実施例４は、電気伝導率が実施例３よりも低い値となっていた。 Further, when Example 1, Example 3, and Example 4 having the same mass ratio (PVA / gelatin) and the same total concentration of PVA and gelatin are compared, the concentration of the electrolyte is 1.90 mass. In Example 1 and Example 3 in which the concentration of the electrolyte was 1.50% by mass or less, the incision feeling with the Pean forceps was superior to Example 4 that is%.
In contrast to Example 1 and Example 3, Example 1 with a higher electrolyte concentration had a higher electrical conductivity, but Example 4 with a higher electrolyte concentration than Example 1 was used. The electric conductivity was a value lower than that of Example 3.
なお、実施例１と実施例３との対比では、電解質の濃度が高い実施例１の方が電気伝導率も高い値となっていたが、実施例１よりも電解質の濃度が高い実施例４は、電気伝導率が実施例３よりも低い値となっていた。 Further, when Example 1, Example 3, and Example 4 having the same mass ratio (PVA / gelatin) and the same total concentration of PVA and gelatin are compared, the concentration of the electrolyte is 1.90 mass. In Example 1 and Example 3 in which the concentration of the electrolyte was 1.50% by mass or less, the incision feeling with the Pean forceps was superior to Example 4 that is%.
In contrast to Example 1 and Example 3, Example 1 with a higher electrolyte concentration had a higher electrical conductivity, but Example 4 with a higher electrolyte concentration than Example 1 was used. The electric conductivity was a value lower than that of Example 3.
また、電解質濃度および質量比（ＰＶＡ／ゼラチン）が同じである実施例１と実施例５とを対比すると、ＰＶＡおよびゼラチンの合計濃度が異なっていても、切開感触は同等に優れることが分かった。
Further, when Example 1 and Example 5 having the same electrolyte concentration and mass ratio (PVA / gelatin) were compared, it was found that the incision feel was equally excellent even when the total concentrations of PVA and gelatin were different. .
一方、電解質である塩化ナトリウムを添加せず、電気伝導率が０．１５Ｓ／ｍ未満である比較例１～３では、高周波電気メスでの切開感触が劣っていた。なお、ゼラチンを含有しない比較例１および３は、ペアン鉗子での切開感触も劣っていた。
また、塩化ナトリウムを添加したが、電気伝導率が０．１５Ｓ／ｍ未満である比較例４も、やはり、高周波電気メスでの切開感触が劣っていた。
そして、比較例５は、ペアン鉗子での切開感触が劣っていた。これは、ＰＶＡを含有しないため相分離構造が形成されず、また、電解質の濃度が高いため柔軟性が不足したためと考えられる。 On the other hand, in Comparative Examples 1 to 3 in which sodium chloride as an electrolyte was not added and the electric conductivity was less than 0.15 S / m, the incision feeling with a high frequency electric knife was inferior. In addition, Comparative Examples 1 and 3 containing no gelatin were inferior in incision feeling with Pean forceps.
Moreover, although sodium chloride was added, the comparative example 4 whose electrical conductivity is less than 0.15 S / m was also inferior in the incision feeling with a high frequency electric knife.
And the comparative example 5 was inferior in the incision feeling with a pair of forceps. This is probably because the phase separation structure was not formed because PVA was not contained, and the flexibility was insufficient due to the high concentration of the electrolyte.
また、塩化ナトリウムを添加したが、電気伝導率が０．１５Ｓ／ｍ未満である比較例４も、やはり、高周波電気メスでの切開感触が劣っていた。
そして、比較例５は、ペアン鉗子での切開感触が劣っていた。これは、ＰＶＡを含有しないため相分離構造が形成されず、また、電解質の濃度が高いため柔軟性が不足したためと考えられる。 On the other hand, in Comparative Examples 1 to 3 in which sodium chloride as an electrolyte was not added and the electric conductivity was less than 0.15 S / m, the incision feeling with a high frequency electric knife was inferior. In addition, Comparative Examples 1 and 3 containing no gelatin were inferior in incision feeling with Pean forceps.
Moreover, although sodium chloride was added, the comparative example 4 whose electrical conductivity is less than 0.15 S / m was also inferior in the incision feeling with a high frequency electric knife.
And the comparative example 5 was inferior in the incision feeling with a pair of forceps. This is probably because the phase separation structure was not formed because PVA was not contained, and the flexibility was insufficient due to the high concentration of the electrolyte.
なお、実施例１～５の肝臓模型を、外科医に見てもらったところ、「この肝臓模型の形態は、ヒトの肝臓の形態に近似している」との評価が得られた。
また、実施例１～５の肝臓模型については、ペアン鉗子および高周波電気メス以外の手術器具、具体的には、コッヘル鉗子、メス、ハーモニックスカルペル、レーザーメスを用いた取り扱いも可能であった。 In addition, when the surgeon looked at the liver models of Examples 1 to 5, the evaluation that “the form of this liver model approximates the form of a human liver” was obtained.
In addition, the liver models of Examples 1 to 5 could be handled using surgical instruments other than Pean forceps and high-frequency electric scalpels, specifically Koch forceps, scalpels, harmonic scalpels, and laser scalpels.
また、実施例１～５の肝臓模型については、ペアン鉗子および高周波電気メス以外の手術器具、具体的には、コッヘル鉗子、メス、ハーモニックスカルペル、レーザーメスを用いた取り扱いも可能であった。 In addition, when the surgeon looked at the liver models of Examples 1 to 5, the evaluation that “the form of this liver model approximates the form of a human liver” was obtained.
In addition, the liver models of Examples 1 to 5 could be handled using surgical instruments other than Pean forceps and high-frequency electric scalpels, specifically Koch forceps, scalpels, harmonic scalpels, and laser scalpels.
Claims (8)
- ポリビニルアルコールとゼラチンとを含有し、
周波数１ＭＨｚにおける電気伝導率が０．１５～５．００Ｓ／ｍである、生体臓器模型用水性ゲル組成物。 Contains polyvinyl alcohol and gelatin,
An aqueous gel composition for a biological organ model having an electric conductivity of 0.15 to 5.00 S / m at a frequency of 1 MHz. - さらに電解質を含有する、請求項１に記載の生体臓器模型用水性ゲル組成物。 The aqueous gel composition for living organ models according to claim 1, further comprising an electrolyte.
- 前記電解質の濃度が、０．１５～１．５０質量％である、請求項２に記載の生体臓器模型用水性ゲル組成物。 3. The aqueous gel composition for a biological organ model according to claim 2, wherein the concentration of the electrolyte is 0.15 to 1.50 mass%.
- 前記ポリビニルアルコールと前記ゼラチンとの質量比が、９０／１０～６０／４０である、請求項１～３のいずれか１項に記載の生体臓器模型用水性ゲル組成物。 The aqueous gel composition for living organ models according to any one of claims 1 to 3, wherein a mass ratio of the polyvinyl alcohol to the gelatin is 90/10 to 60/40.
- 肝臓模型に用いられる、請求項１～４のいずれか１項に記載の生体臓器模型用水性ゲル組成物。 The aqueous gel composition for a biological organ model according to any one of claims 1 to 4, which is used for a liver model.
- 手術の手技練習用の生体臓器模型に用いられる、請求項１～４のいずれか１項に記載の生体臓器模型用水性ゲル組成物。 The aqueous gel composition for a biological organ model according to any one of claims 1 to 4, which is used for a biological organ model for practicing surgical techniques.
- 請求項１～６のいずれか１項に記載の生体臓器模型用水性ゲル組成物を用いた、生体臓器模型。 A biological organ model using the aqueous gel composition for a biological organ model according to any one of claims 1 to 6.
- 手術の手技練習用である、請求項７に記載の生体臓器模型。 The living organ model according to claim 7, which is used for practicing surgical techniques.
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| JP2017186474A (en) * | 2016-04-07 | 2017-10-12 | 日本ライフライン株式会社 | Pseudo cardiac muscle and manufacturing method therefor, analyte for evaluating cauterization performance and evaluation device of cauterization performance |
| RU2647373C1 (en) * | 2017-03-21 | 2018-03-15 | Эрнест Арамович Базикян | Artificial gum to simulate the effect of laser radiation on biological tissue |
| JP2020095245A (en) * | 2018-11-29 | 2020-06-18 | 多木化学株式会社 | Therapeutic testing composition for surgical energy device |
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| JPH0226567A (en) * | 1988-07-15 | 1990-01-29 | Nippon Oil Co Ltd | Phantom for hyperthermia |
| JP2007316434A (en) * | 2006-05-26 | 2007-12-06 | Tohoku Techno Arch Co Ltd | Mucous membrane material for living body model |
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| JPH0226567A (en) * | 1988-07-15 | 1990-01-29 | Nippon Oil Co Ltd | Phantom for hyperthermia |
| JP2007316434A (en) * | 2006-05-26 | 2007-12-06 | Tohoku Techno Arch Co Ltd | Mucous membrane material for living body model |
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| JP2017186474A (en) * | 2016-04-07 | 2017-10-12 | 日本ライフライン株式会社 | Pseudo cardiac muscle and manufacturing method therefor, analyte for evaluating cauterization performance and evaluation device of cauterization performance |
| RU2647373C1 (en) * | 2017-03-21 | 2018-03-15 | Эрнест Арамович Базикян | Artificial gum to simulate the effect of laser radiation on biological tissue |
| JP2020095245A (en) * | 2018-11-29 | 2020-06-18 | 多木化学株式会社 | Therapeutic testing composition for surgical energy device |
| JP7221163B2 (en) | 2018-11-29 | 2023-02-13 | 多木化学株式会社 | Treatment test composition for surgical energy device |
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