JP2005304907A - Method of evaluating medicament deglutition disorder in animal experiment - Google Patents
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- 239000003814 drug Substances 0.000 title claims abstract description 63
- 241001465754 Metazoa Species 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 45
- 208000019505 Deglutition disease Diseases 0.000 title claims abstract description 40
- 238000002474 experimental method Methods 0.000 title claims abstract description 16
- 238000012360 testing method Methods 0.000 claims abstract description 32
- 210000003238 esophagus Anatomy 0.000 claims abstract description 22
- 210000003800 pharynx Anatomy 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 238000001454 recorded image Methods 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims description 57
- 239000002872 contrast media Substances 0.000 claims description 39
- 230000009747 swallowing Effects 0.000 claims description 15
- 238000010191 image analysis Methods 0.000 claims description 5
- 230000001678 irradiating effect Effects 0.000 claims description 4
- 230000014759 maintenance of location Effects 0.000 claims description 4
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims 1
- 238000011156 evaluation Methods 0.000 abstract description 3
- 230000002618 waking effect Effects 0.000 abstract 2
- 230000009748 deglutition Effects 0.000 abstract 1
- 241000282472 Canis lupus familiaris Species 0.000 description 12
- 238000010171 animal model Methods 0.000 description 7
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
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- 230000003444 anaesthetic effect Effects 0.000 description 2
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- 210000003437 trachea Anatomy 0.000 description 2
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000020992 canned meat Nutrition 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000005195 poor health Effects 0.000 description 1
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- 239000007787 solid Substances 0.000 description 1
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- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
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Abstract
Description
本発明は、動物実験における薬物嚥下障害を評価する方法に関する。 The present invention relates to a method for evaluating drug dysphagia in animal experiments.
嚥下反応を実験動物において検討している報告は極めてわずかである（非特許文献１参照）。近年、現場の臨床においては薬物による嚥下障害は問題視されている。 There are very few reports examining swallowing reactions in experimental animals (see Non-Patent Document 1). In recent years, dysphagia caused by drugs has been regarded as a problem in clinical practice.
実験動物における薬物嚥下障害評価は、前記の臨床での課題を解決するための有益な予見として大いに期待される。よって、動物実験における薬物嚥下障害を簡単にかつ精度よく評価することができる方法の開発が望ましい。 Evaluation of drug dysphagia in laboratory animals is highly expected as a useful predictor for solving the above clinical problems. Therefore, it is desirable to develop a method that can easily and accurately evaluate drug dysphagia in animal experiments.
本発明者等は、かかる状況下において鋭意検討した結果、本発明に至った。
即ち、本発明は、
１．動物実験における薬物嚥下障害を評価する方法であって、
（１）予め被験薬物が投与された覚醒下動物を側臥位にて頚部側面より、咽頭及び上部食道の両部位にエックス線透視装置を用いてエックス線を連続照射しながら、当該動物に造影剤を咽頭内投与することにより嚥下反応を誘発させた状態でエックス線透視画像を動画として記録する第一工程、及び
（２）収録された画像を解析することにより前記造影剤の嚥下障害を評価する第ニ工程、を有することを特徴とする方法（以下、本発明方法と記すこともある。）；
２．第二工程における嚥下障害が、造影剤の食道内滞留又は造影剤の食道内滞留であることを特徴とする前項１記載の方法；
３．第二工程における画像解析が、デジタル画像に基づいた画像解析であることを特徴とする前項１又は２記載の方法；
４．対照として、予め被験薬物が投与された覚醒下動物の代わりに、当該薬物が投与されていない動物を用いて第一工程を為し、対照との比較に基づき第二工程を為すことを特徴とする前項１、２又は３記載の方法；
等を提供するものである。
As a result of intensive studies under such circumstances, the present inventors have arrived at the present invention.
That is, the present invention
1. A method for evaluating dysphagia in animal experiments,
(1) Awakening animals that have been pre-administered with the test drug are placed in the lateral position from the side of the neck to the pharynx and the upper esophagus while continuously irradiating X-rays using an X-ray fluoroscopy device. A first step of recording an X-ray fluoroscopic image as a moving image in a state in which a swallowing reaction is induced by internal administration, and (2) a second step of evaluating the dysphagia of the contrast agent by analyzing the recorded image A method characterized by comprising (hereinafter, also referred to as the method of the present invention);
2. The method according to
3. The method according to
4). As a control, instead of an awake animal to which a test drug has been administered in advance, a first step is performed using an animal to which the drug has not been administered, and a second step is performed based on comparison with the control. The method according to the preceding
Etc. are provided.
本発明により、動物実験における薬物嚥下障害を簡単にかつ精度よく評価することができる方法が提供可能となる。 According to the present invention, it is possible to provide a method capable of easily and accurately evaluating a drug dysphagia in an animal experiment.
以下に本発明を詳細に説明する。
本発明方法は、動物実験における薬物嚥下障害を評価する方法として極めて有効である。また、本発明方法は、嚥下障害改善薬等の薬物を探索するための試験としても有用であり、医薬品開発へも応用可能である。
The present invention is described in detail below.
The method of the present invention is extremely effective as a method for evaluating drug dysphagia in animal experiments. In addition, the method of the present invention is useful as a test for searching for a drug such as a dysphagia improving drug, and can be applied to drug development.
本発明方法において対象となる動物としては、上記のような特徴的な工程を与えることができる動物であれば如何なるものであってもよいが、その操作性等の面から、例えば、イヌを好ましい。より好ましくはビーグル種のイヌが挙げられる。尚、これら動物、例えば、ビーグル種のイヌは、エルエスジー株式会社等から商業的に入手することができる。 The target animal in the method of the present invention may be any animal as long as it can provide the characteristic steps as described above. From the viewpoint of its operability, for example, a dog is preferable. . More preferred is a beagle dog. These animals, for example, beagle dogs, can be obtained commercially from LSG Corporation.
本発明方法における覚醒下動物とは、麻酔薬の投与により動物が意識を喪失することなく、中枢・末梢神経が正常に機能しているような状態である被験動物である。麻酔薬の投与は通常の方法により行えばよい。
当該実験方法を行うに際し、予め当該実験方法を数週間経験させてトレーニングを施すことにより、被験動物が実験環境及び実験操作等に十分馴化し、苦痛やストレスを最大限感じないように措置しておくことが好ましい。
The awake animal in the method of the present invention is a test animal in which the central and peripheral nerves are functioning normally without the animal losing consciousness by administration of an anesthetic. An anesthetic may be administered by a normal method.
When conducting the experimental method, let the test animal become fully accustomed to the experimental environment and experimental operation, etc. by training the experimental method for several weeks in advance, and take measures to prevent pain and stress to the maximum extent. It is preferable to keep.
本発明方法において用いられるエックス線透視装置としては、生体を透過させるだけに十分な線量を連続的に発生するエックス線発生装置であって、エックス線透視画像を動画として記録できる機能を有し、かつ、動物を側臥位の姿勢で保定できる土台を据え付けた装置であればよい。具体的には、小動物専用エックス線システム（型式：VPX-20、東芝医療用品（株））等の市販品をあげることができる。 The X-ray fluoroscopic apparatus used in the method of the present invention is an X-ray generating apparatus that continuously generates a dose sufficient to transmit a living body, has a function of recording an X-ray fluoroscopic image as a moving image, and an animal Any device may be used as long as it is installed with a base that can be held in a lateral position. Specifically, commercially available products such as X-ray systems for small animals (model: VPX-20, Toshiba Medical Products Co., Ltd.) can be mentioned.
エックス線透視装置を用いてエックス線を連続照射するには、例えば、62 kW、5.0 mAs、0.03 sというエックス線発生電力下での連続エックス線を照射すればよい。尚、動物種、動物個体差等により、上記エックス線発生電力は、鮮明なエックス線透視画像を収録可能となるように適宜調節すればよい。 In order to continuously irradiate X-rays using the X-ray fluoroscope, for example, continuous X-rays under X-ray generation power of 62 kW, 5.0 mAs, and 0.03 s may be irradiated. The X-ray generated power may be adjusted as appropriate so that a clear X-ray fluoroscopic image can be recorded depending on animal species, individual animal differences, and the like.
このようにエックス線を連続照射下しながら、覚醒下動物に、カテーテルをエックス線透視画像下で確認しながらその先端が咽頭内へと到達するように挿管し、カテーテルを介して硫酸バリウム等の造影剤をゆっくりと咽頭内投与すればよい。これにより嚥下反応を当該動物に誘発させる。 In this way, while continuously irradiating X-rays, the awakened animal is intubated so that the tip reaches the pharynx while confirming the catheter under an X-ray fluoroscopic image, and a contrast medium such as barium sulfate is passed through the catheter. May be administered slowly in the pharynx. This induces a swallowing response in the animal.
尚、造影剤として用いられる硫酸バリウムは、例えば、バリトップ150（堺化学工業）等があげられ、これを60%濃度に精製水で希釈したものを使用すればよいが、勿論これに相当する他の一般市販品を使用してもよい The barium sulfate used as a contrast agent is, for example, Varitop 150 (Sakai Chemical Industry), etc., which may be diluted with purified water to a concentration of 60%, and of course corresponds to this. Other general commercial products may be used
本発明方法では、頚部側面より咽頭及び食道の両部位にエックス線を連続照射することが重要である。これにより、頚部側面より撮影することが可能となり、咽頭内投与された造影剤の咽頭及び食道の両部位での造影剤の移行の様子を詳細にかつ明確に把握することができる。 In the method of the present invention, it is important to continuously irradiate X-rays on both the pharynx and esophagus from the side of the neck. As a result, it is possible to take an image from the side of the cervix, and it is possible to grasp in detail and clearly the state of the contrast agent transferred in both the pharynx and esophagus of the contrast agent administered intrapharyngeally.
本発明方法においてエックス線透視画像を動画として記録するには、ビデオ装置を用いて記録すればよい。収録される画像は、アナログ画像であっても、アナログ画像から変換されたデジタル画像であっても、デジタル画像であってもよい。
アナログ画像をデジタル画像に変換するハードウェア／ソフトウェアとしては、例えば、TVキャプチャBOX（型式：PC-MV5/U2、メルコ）等があげられるが、これに相当するハードウェア／ソフトウェアであれば代替可能である。
In order to record an X-ray fluoroscopic image as a moving image in the method of the present invention, it may be recorded using a video device. The recorded image may be an analog image, a digital image converted from the analog image, or a digital image.
For example, TV capture BOX (model: PC-MV5 / U2, Melco) can be used as hardware / software to convert analog images into digital images, but any hardware / software equivalent to this can be substituted. It is.
本発明方法において造影剤の嚥下障害を評価するには、収録された画像を解析すればよい。咽頭内投与された造影剤の咽頭及び食道の両部位での造影剤の動態が確認される限り如何なるビデオ画像であってもよい。
デジタル画像に基づいた画像解析を行う場合には、例えば、デジタル画像（デジタル連続画像）をフレーム解析（コマ送り解析）することにより、咽頭内投与された造影剤の咽頭及び食道の両部位での造影剤の動態がより詳細かつ簡便に追跡することが可能となる。その結果として、例えば、（１）造影剤が咽頭から上部食道へ、次いで下部食道へと順次下行性に移行するが、薬物の作用により造影剤が上部食道から咽頭へ逆流したり、上部食道に溜まる画像が確認される場合には、造影剤の食道内滞留とみなすことにより、嚥下障害が存在するとして評価すればよい。また（２）造影剤が食道ではなく、気管内へ混入する画像が確認される場合には、造影剤の気管内誤嚥とみなすことにより、嚥下障害が存在するとして評価すればよい。
In order to evaluate the dysphagia of the contrast medium in the method of the present invention, the recorded image may be analyzed. Any video image may be used as long as the dynamics of the contrast medium at both the pharynx and esophagus are confirmed.
When performing image analysis based on a digital image, for example, by performing frame analysis (frame advance analysis) on a digital image (digital continuous image), the contrast agent administered intrapharyngeally at both the pharynx and esophagus sites The dynamics of the contrast agent can be traced in more detail and simply. As a result, for example, (1) Contrast agent gradually moves downward from the pharynx to the upper esophagus, then to the lower esophagus, but due to the action of the drug, the contrast agent flows back from the upper esophagus to the pharynx, or into the upper esophagus When the accumulated image is confirmed, it may be evaluated that the dysphagia is present by considering the contrast agent to stay in the esophagus. In addition, (2) when an image in which the contrast medium is not in the esophagus but mixed into the trachea is confirmed, it may be evaluated that the dysphagia is present by regarding the contrast medium as an intratracheal aspiration.
本発明方法では、対照として、予め被験薬物が投与された覚醒下動物の代わりに、当該薬物が投与されていない動物を用いて第一工程を為し、対照との比較に基づき第二工程を為すことにより、第二工程における造影剤の嚥下障害をより正確に評価することが可能となる。具体的には例えば、同一個体である動物を用いて、被験薬物の投与前後において、本発明方法に基づく造影剤の嚥下障害を評価すればよい。この場合には、造影剤の嚥下障害として、対照との比較において、造影剤の食道内滞留回数や造影剤の気管内誤嚥有無等の変化・差異等に基づき評価することにより被験薬物の嚥下障害作用を検出することが可能となる。 In the method of the present invention, as a control, instead of an awake animal pre-administered with the test drug, the first step was performed using an animal not administered with the drug, and the second step was performed based on comparison with the control. By doing so, it becomes possible to more accurately evaluate the dysphagia of the contrast medium in the second step. Specifically, for example, the contrast agent swallowing disorder based on the method of the present invention may be evaluated before and after the administration of the test drug using an animal which is the same individual. In this case, as a dysphagia of the contrast agent, swallowing the test drug by evaluating the contrast agent based on changes or differences in the number of stays in the esophagus or the presence or absence of intratracheal aspiration in contrast to the control It becomes possible to detect the obstacle action.
さらに、本発明方法では、動物の薬物レスポンスに基づき被験薬物の嚥下障害作用を検出することも可能である。具体的には例えば、本発明方法において、覚醒下動物に対して嚥下障害作用を有する薬物が有効量投与された場合には、本発明方法に基づく造影剤の嚥下反応を与えても、嚥下反応を誘発させることなく、造影剤の食道内滞留又は気管内誤嚥等の造影剤の嚥下障害を生じるような薬物レスポンスを生じる。一方、覚醒下動物に対して嚥下障害作用を有する薬物が非有効量投与された場合や、覚醒下動物に対して嚥下障害作用を有さない薬物が投与された場合には、本発明方法に基づく造影剤の嚥下反応を与えると、嚥下反応を生じる薬物レスポンスを生じる。 Furthermore, in the method of the present invention, it is also possible to detect the dysphagia action of the test drug based on the drug response of the animal. Specifically, for example, in the method of the present invention, when an effective amount of a drug having a dysphagia action is administered to an awake animal, the swallowing reaction is performed even if a contrast agent swallowing reaction based on the method of the present invention is given. Without causing a drug response, causing a contrast agent dysphagia such as retention in the esophagus or intratracheal aspiration. On the other hand, when an ineffective amount of a drug having a dysphagia action is administered to an awake animal, or when a drug having no dysphagia action is administered to an awake animal, the method of the present invention is used. Giving a contrast agent-based swallowing response produces a drug response that produces a swallowing response.
本発明方法において造影剤の嚥下障害が評価される被験薬物とは、如何なる薬物であってもよいが、好ましくは本発明方法により誘発される嚥下反応に対して動物の薬物レスポンスを与えるような薬物であって、例えば、当該嚥下反応を抑制するような薬物等をあげることができる。 The test drug for which the dysphagia of the contrast medium is evaluated in the method of the present invention may be any drug, but preferably a drug that gives an animal drug response to the swallowing reaction induced by the method of the present invention. Thus, for example, a drug or the like that suppresses the swallowing reaction can be given.
予め被験薬物が投与された覚醒下動物を調製・準備するには、上記の被験薬物を覚醒下実験動物に通常の薬物投与方法を用いて投与することにより調製・準備すればよい。当該被験薬物の覚醒下動物への投与量は、薬物の種類に応じて適宜選択すればよいが、例えば、１〜１００ｍｇ／ｋｇ体重の投与量をあげることができる。そして、このような投与量となるように、当該被験薬物を精製水又は生理食塩液にて適当な濃度に希釈し、これを覚醒下実験動物に経口投与又は皮下投与すればよい。 In order to prepare / prepare an awake animal to which a test drug has been administered in advance, the above test drug may be prepared / prepared by administering the test drug to an awake experimental animal using a normal drug administration method. The dose of the test drug to the awake animal may be appropriately selected according to the type of drug, and examples include a dose of 1 to 100 mg / kg body weight. Then, the test drug may be diluted to an appropriate concentration with purified water or physiological saline so as to obtain such a dose, and this can be administered orally or subcutaneously to an awake experimental animal.
本発明方法を利用すれば、薬物による嚥下障害を動物実験の早期段階で発見することが可能となり、臨床上で誘発され得る薬物による嚥下障害（例えば、気管内誤嚥）、ひいてはそれにより発症され得る肺炎障害を事前に予見し、より安全な新薬開発、既存医薬品の副作用発現の警告が期待される。また、嚥下改善薬を見込む薬物のスクリーニングにも利用可能であり、嚥下改善治療薬の発見にも貢献が期待される。 By using the method of the present invention, it becomes possible to detect drug-induced dysphagia at an early stage of animal experiments, and clinically-induced drug-induced dysphagia (for example, endotracheal aspiration), which is caused thereby Predicting the pneumonia disorder to be obtained in advance, the development of safer new drugs and the warning of side effects of existing drugs are expected. It can also be used to screen for drugs that anticipate anti-swallowing drugs, and is expected to contribute to the discovery of anti-swallowing drugs.
以下、本発明をより詳細に説明するため、実施例を挙げて説明するが本発明はこれらの例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
実施例１
本発明方法の実施態様の一つを図のとおり例示する。
実験動物としてイヌ（ビーグル種、１０ｋｇ程度）を用いた場合における具体例である。
雌雄ビーグル犬（日本エルエスジー）を検疫、馴化した後に実験に供給した。当該動物は室温２３±２℃、湿度４０〜８０％、換気回数１０回以上/時間、人工照明１２時間（８時〜２０時）に設定された飼育室で、ステンレス・アルミケージ（７００W×９００L×８００H mm）に１頭ずつ飼育した。飼育期間中に用いた飼料は、イヌ用固形飼料（TC−１、マルハペットフード）であり、これを１頭につき１日３００gずつを給餌した。健康状態が不良となった個体には補助食として動物用缶詰肉（健犬テシオ、マルハペットフード）を１頭あたり１日１００gずつ給餌する。また飼育期間中に用いた飲料水は水道水であり、これを自由摂取させた。
造影剤の嚥下障害を引き起こす被験薬物は、精製水に５、１５、４５mg/mLの濃度に溶解させたものを用いた。尚、当該実験では、対照として被験薬物が投与されていない覚醒下動物を用いた試験を実施した後に、同一個体である覚醒下動物に予め被験薬物が経口投与された覚醒下動物を用いた試験を実施した。
前記被験薬物による薬物レスポンスを観察するために、当該被験薬物の投与前及び投与開始から一定時間後に本発明方法に基づく被験薬物の嚥下障害作用を検出した。その結果、当該被験薬物の投与前と投与後との造影剤の嚥下障害が増大するような薬物レスポンスが観察された。さらに、十分な休息を与えることにより、前記覚醒下動物の造影剤の嚥下障害は、当該被験薬物の投与前における造影剤の嚥下障害と同等までに回復する現象が確認された。これに対して、対照（被験薬物が投与されていない覚醒下動物を用いた試験：前記被験薬物の代わりに精製水を用いること以外は同様な方法を用いた試験）では、造影剤の嚥下障害を増大させるような薬物レスポンスは観察されなかった。
Example 1
One embodiment of the method of the present invention is illustrated as shown in the figure.
This is a specific example when a dog (beagle type, about 10 kg) is used as an experimental animal.
Male and female beagle dogs (Japan LSG) were quarantined and acclimated before being supplied to the experiment. The animal is a stainless steel / aluminum cage (700 W × 900 L) in a breeding room set at room temperature 23 ± 2 ° C., humidity 40-80%, ventilation rate 10 times / hour, artificial lighting 12 hours (8-20 hours). X800H mm) were raised one by one. The feed used during the breeding period was a dog solid feed (TC-1, Maruhappet food), which was fed at a rate of 300 g per animal per day. Individuals who are in poor health are fed 100 g of canned meat for animals (healthy dog Tesio, Marupet food) as a supplement. The drinking water used during the breeding period was tap water, which was freely ingested.
The test drug causing the dysphagia of the contrast agent was dissolved in purified water to a concentration of 5, 15, 45 mg / mL. In this experiment, after conducting a test using an awake animal to which the test drug was not administered as a control, a test using an awake animal in which the test drug was orally administered in advance to the awake animal that is the same individual. Carried out.
In order to observe the drug response due to the test drug, the swallowing disorder action of the test drug based on the method of the present invention was detected before administration of the test drug and after a certain time from the start of administration. As a result, a drug response was observed that increased the dysphagia of the contrast medium before and after administration of the test drug. Furthermore, it was confirmed that by giving sufficient rest, the contrast agent dysphagia of the awake animal was recovered to the same level as the contrast agent dysphagia before administration of the test drug. On the other hand, in the control (test using awake animals to which no test drug was administered: test using the same method except that purified water was used instead of the test drug), dysphagia of contrast medium No drug response was observed to increase.
本発明により、動物実験における薬物嚥下障害を簡単にかつ精度よく評価することができる方法が提供可能となる。 According to the present invention, it is possible to provide a method capable of easily and accurately evaluating a drug dysphagia in an animal experiment.
Claims (4)
（１）予め被験薬物が投与された覚醒下動物を側臥位にて頚部側面より、咽頭及び上部食道の両部位にエックス線装置を用いてエックス線を連続照射しながら、当該動物に造影剤を咽頭内投与することにより嚥下反応を誘発させた状態でエックス線透視画像を動画として記録する第一工程、及び
（２）収録された画像を解析することにより前記造影剤の嚥下障害を評価する第二工程、
を有することを特徴とする方法。 A method for evaluating dysphagia in animal experiments,
(1) Awakening animals that have been pre-administered with the test drug are placed in the pharynx while continuously irradiating X-rays using X-ray devices to the pharynx and upper esophagus from both sides of the neck in the lateral position from the side of the neck. A first step of recording an X-ray fluoroscopic image as a moving image in a state in which a swallowing reaction is induced by administration, and (2) a second step of evaluating dysphagia of the contrast agent by analyzing the recorded image,
A method characterized by comprising:
As a control, instead of an awake animal to which a test drug has been administered in advance, a first step is performed using an animal to which the drug has not been administered, and a second step is performed based on comparison with the control. The method according to claim 1, 2, or 3.
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