JP6401028B2 - Medium / long-term memory disorder prevention / improvement agent consisting of whale muscle extract - Google Patents
Medium / long-term memory disorder prevention / improvement agent consisting of whale muscle extract Download PDFInfo
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- JP6401028B2 JP6401028B2 JP2014239739A JP2014239739A JP6401028B2 JP 6401028 B2 JP6401028 B2 JP 6401028B2 JP 2014239739 A JP2014239739 A JP 2014239739A JP 2014239739 A JP2014239739 A JP 2014239739A JP 6401028 B2 JP6401028 B2 JP 6401028B2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
本発明は、鯨の筋肉から抽出した鯨筋肉抽出物からなる中長期記憶障害予防改善剤に関する。 The present invention relates to an agent for preventing and improving medium to long-term memory impairment comprising a whale muscle extract extracted from whale muscle.
動物の筋肉組織中に含まれるイミダゾールジペプチド(ヒスチジン及びアラニンが結合したジペプチド)として、カルノシン、アンセリン、バレニン、π−メチルヒスチジン、τ−メチルヒスチジン等が知られている。 Known examples of imidazole dipeptides (dipeptides combined with histidine and alanine) contained in animal muscle tissue include carnosine, anserine, valenin, π-methylhistidine, and τ-methylhistidine.
特許文献1には、カルノシンを有効成分とし、虚血後に過剰放出される亜鉛に基づく神経細胞死を抑制することを特徴とする脳血管性認知症の予防又は治療薬について開示されている。 Patent Document 1 discloses a preventive or therapeutic agent for cerebrovascular dementia characterized in that it contains carnosine as an active ingredient and suppresses neuronal cell death based on zinc that is excessively released after ischemia.
また、特許文献2には、アンセリン、カルノシン、バレニン、π−メチルヒスチジン及びτ−メチルヒスチジンの群から選ばれた1種以上のイミダゾール化合物を含有してなる学習能力向上組成物について開示されている。
しかし、特許文献2の実施例は、健常人にアンセリン及びカルノシンを含有する組成物を摂取させ、該組成物摂取による短期記憶力試験(9桁の数列を5秒間呈示し、直後に制限時間5秒で該数列を記述させる試験)の実施に止まり、10秒より長い期間や中期又は長期記憶力試験は行われておらず、しかも健康体を対象にした試験であり、老化等で中長期記憶障害を受けている個体を対象にしたものでもなかった。更に、特許文献2の実施例では、バレニンを含有した組成物での記憶の検証試験も行われていない。
Patent Document 2 discloses a composition for improving learning ability comprising one or more imidazole compounds selected from the group of anserine, carnosine, valenin, π-methylhistidine and τ-methylhistidine. .
However, in the example of Patent Document 2, a healthy person is ingested with a composition containing anserine and carnosine, and a short-term memory test by ingesting the composition (presenting a 9-digit number sequence for 5 seconds and immediately after a time limit of 5 seconds) This is a test that is not conducted for a period longer than 10 seconds or a medium-term or long-term memory ability test, and is intended for a healthy body. Nor was it intended for the individual receiving it. Furthermore, in the Example of patent document 2, the verification test of memory | storage with the composition containing a barenine is not performed.
バレニンは、鯨の筋肉に特異的に多く含まれる成分である。鯨は、半年間絶食状態で出産・子育てをし、その後数千kmを不眠不休で泳ぎ続けることができ、その理由は、抗疲労効果を有するバレニンを鯨肉中に多く含むためと考えられている(非特許文献1)。しかしながら、非特許文献1においても、バレニンと記憶の関係については報告されていない。 Valenin is a component that is abundantly contained in whale muscles. Whales can give birth and raise their children in a fasted state for half a year, and then continue to swim thousands of kilometers without sleeplessness, because the whale meat contains a lot of anti-fatigue anti-fatigue effects. (Non-Patent Document 1). However, even in Non-Patent Document 1, there is no report on the relationship between valenin and memory.
本発明は上記背景技術に鑑みてなされたものであり、その課題は、学習記憶障害を効果的に予防及び/又は改善可能な、新規な記憶障害予防改善剤を提供することにある。 The present invention has been made in view of the above-described background art, and a problem thereof is to provide a novel memory disorder prevention / improving agent capable of effectively preventing and / or improving learning memory disorder.
本発明者は、上記の課題を解決すべく、「鯨の筋肉から抽出した鯨筋肉抽出物」の未知なる作用を探索し、特に学習記憶障害に対する種々の効果を確認し、鯨の筋肉から抽出した鯨筋肉抽出物が、中期及び長期の記憶障害を改善することを見出して、本発明を完成するに至った。
本発明は、「鯨の筋肉から抽出した鯨筋肉抽出物」に、医療分野等において極めて顕著で有効な効果が初めて見出され、該効果が規定された剤、すなわち「中長期記憶障害予防剤」として新たになされたものである。
In order to solve the above problems, the present inventor searches for an unknown action of “whale muscle extract extracted from whale muscle”, particularly confirms various effects on learning memory impairment, and extracts from whale muscle. The found whale muscle extract ameliorates medium and long-term memory impairments, leading to the completion of the present invention.
The present invention is the first to find an extremely significant and effective effect in the medical field etc. in the “whale muscle extract extracted from whale muscle”. ”Was newly made.
すなわち、本発明は、鯨の筋肉から抽出した鯨筋肉抽出物からなるものであることを特徴とする中長期記憶障害予防改善剤を提供するものである。 That is, the present invention provides an agent for preventing and improving medium- to long-term memory impairment characterized by comprising a whale muscle extract extracted from whale muscle.
また、本発明は、上記の中長期記憶障害予防改善剤を含有するものであることを特徴とする認知症予防改善剤を提供するものである。 The present invention also provides a dementia prevention / amelioration agent characterized by containing the above-mentioned medium / long-term memory disorder prevention / improvement agent.
本発明によれば、前記問題点や上記課題を解決し、中期記憶障害又は長期記憶障害の予防又は改善効果を奏する中長期記憶障害予防改善剤を提供できる。 ADVANTAGE OF THE INVENTION According to this invention, the said problem and the said subject can be solved, and the intermediate-long-term memory disorder prevention improving agent which has the prevention or improvement effect of a medium-term memory disorder or a long-term memory disorder can be provided.
また、本発明の中長期記憶障害改善剤は、老化が進み記憶障害を呈している哺乳類の中期記憶又は長期記憶を改善する効果を有する。
すなわち、本発明の中長期記憶障害予防改善剤は、特に、老化若しくはアルツハイマー型による学習記憶障害を持ったヒト等に対し、それを改善する効果を奏し、また、認知症を予防したいヒト等に対し、それを予防する効果を奏する。
The agent for improving medium- to long-term memory impairment of the present invention has an effect of improving the medium-term memory or long-term memory of a mammal that is aging and exhibits memory impairment.
That is, the agent for improving the prevention of middle- and long-term memory impairment of the present invention has an effect of improving it particularly on humans having learning memory impairment due to aging or Alzheimer type, and also for humans who want to prevent dementia. It has the effect of preventing it.
本発明の中長期記憶障害予防改善剤は、「鯨の筋肉から抽出した鯨筋肉抽出物」からなるものであり、ヒト等に対して安全である。すなわち、本発明の中長期記憶障害予防改善剤は、対象者にとって負担や副作用が少ないという効果を奏する。
従って、本発明の中長期記憶障害予防改善剤は、医薬品としてはもちろん、疾患を有さないヒト向けの予防薬、食品等に用いることができ、また、健常者の更なる学習記憶の改善等にも有効に用いることができる。
The medium / long-term memory disorder preventive / ameliorating agent of the present invention is composed of “whale muscle extract extracted from whale muscle” and is safe for humans and the like. That is, the medium / long-term memory disorder preventive / ameliorating agent of the present invention has the effect of reducing the burden and side effects on the subject.
Therefore, the agent for preventing and improving medium- to long-term memory impairment of the present invention can be used not only as a pharmaceutical product but also as a prophylactic agent for humans having no disease, foods, etc., and further improvement of learning memory of healthy subjects, etc. Can also be used effectively.
また、本発明の認知症予防改善剤は、対象者にとって負担や副作用が少ない中長期記憶障害改善剤を含有するので安全である。そして、本発明の中長期記憶障害予防改善剤を含有する認知症予防改善剤は、中期記憶障害又は長期記憶障害の予防改善効果を奏する。 In addition, the dementia prevention / amelioration agent of the present invention is safe because it contains a medium- to long-term memory disorder-improving agent with less burden and side effects for the subject. And the dementia prevention improving agent containing the middle-long-term memory disorder prevention improving agent of this invention has the prevention improvement effect of a medium-term memory disorder or a long-term memory disorder.
以下、本発明について説明するが、本発明は、以下の具体的形態に限定されるものではなく、技術的思想の範囲内で任意に変形することができる。 Hereinafter, the present invention will be described, but the present invention is not limited to the following specific embodiments, and can be arbitrarily modified within the scope of the technical idea.
[中長期記憶障害予防改善剤]
本発明の中長期記憶障害予防改善剤は、鯨の筋肉から抽出した鯨筋肉抽出物からなるものであることを特徴とする。
[Medium and long-term memory disorder prevention / improvement agent]
The agent for improving medium- to long-term memory impairment prevention of the present invention is characterized by comprising a whale muscle extract extracted from whale muscle.
本発明の中長期記憶障害予防改善剤は、中期記憶障害及び/又は長期記憶障害を、予防及び/又は改善することができる。 The medium / long-term memory disorder prevention / amelioration agent of the present invention can prevent and / or improve medium-term memory disorder and / or long-term memory disorder.
本発明において、「短期記憶」とは、数秒〜10分未満保持される記憶のことをいい、「中期記憶」とは、10分間〜24時間保持される記憶のことをいい、「長期記憶」とは、24時間を超える期間保持される記憶のことをいう。 In the present invention, “short-term memory” refers to memory retained for several seconds to less than 10 minutes, “medium-term memory” refers to memory retained for 10 minutes to 24 hours, and “long-term memory”. The term “memory” refers to memory that is retained for a period exceeding 24 hours.
本発明の中長期記憶障害予防改善剤は、鯨の筋肉から抽出した鯨筋肉抽出物からなるが、鯨の筋肉から抽出した鯨筋肉抽出物の全てからなるものである必要はなく、1種以上の成分を全鯨筋肉抽出物から除外した成分からなっていてもよい。また、鯨の筋肉から抽出した1種の成分からなっていても、2種以上の成分からなっていてもよい。 The medium / long-term memory disorder preventive / ameliorating agent of the present invention comprises a whale muscle extract extracted from whale muscle, but need not be composed of all whale muscle extracts extracted from whale muscle. May be composed of components excluded from the whole whale muscle extract. Moreover, even if it consists of 1 type of component extracted from the muscle of a whale, it may consist of 2 or more types of components.
本実施例で使用したクジラエキス(まるげい社製)には、クジラエキス100質量部に対して、8.3質量部のバレニン、91.2質量部のタンパク質、0.1質量部未満の粗脂質、5.1質量部の灰分、15.0質量部の全窒素、2.7質量部の水分が含まれる。
本実施例の結果より、該クジラエキスは、中期記憶障害及び/又は長期記憶障害を改善することがわかった。該改善効果は、該クジラエキス(本発明の中長期記憶障害予防改善剤)に含まれるバレニンによるものであることは明らかである。
The whale extract (manufactured by Marugei Co., Ltd.) used in this example has 8.3 parts by weight of valenin, 91.2 parts by weight of protein and less than 0.1 parts by weight of 100 parts by weight of whale extract. The crude lipid contains 5.1 parts by weight of ash, 15.0 parts by weight of total nitrogen, and 2.7 parts by weight of water.
From the results of this example, it was found that the whale extract improves medium-term memory impairment and / or long-term memory impairment. It is clear that the improvement effect is due to the valenin contained in the whale extract (medium / long-term memory disorder prevention / improving agent of the present invention).
従って、本発明の中長期記憶障害予防改善剤は、有効成分としてバレニン(balenin)を含有していることが好ましい。バレニンはイミダゾールペプチドであり、正式名称はβ−アラニル−3−メチル−L−ヒスチジンである。 Therefore, it is preferable that the agent for preventing and improving medium- and long-term memory impairment of the present invention contains valenin as an active ingredient. Valenin is an imidazole peptide and the official name is β-alanyl-3-methyl-L-histidine.
特許文献2により、バレニンと同じイミダゾールペプチドであるアンセリン及びカルノシンを含有する組成物が、短期記憶力試験(9桁の数列を5秒間呈示し、直後に制限時間5秒で該数列を記述させる試験、トータル10秒間のテスト)により、約10秒間の短期記憶の改善効果を有することが開示されている。
前記した通り、本発明においては、「短期記憶」とは数秒〜10分未満保持される記憶のことをいい、「中期記憶」とは10分間〜24時間保持される記憶のことを言うが、特許文献2では、短期記憶の中でも更に短い約10秒間の記憶についてしか試験されていない。
According to Patent Document 2, a composition containing anserine and carnosine, which are the same imidazole peptides as barenin, is a short-term memory test (a test that presents a 9-digit sequence for 5 seconds and immediately describes the sequence with a time limit of 5 seconds, It has been disclosed that it has an effect of improving short-term memory of about 10 seconds.
As described above, in the present invention, “short-term memory” refers to memory retained for several seconds to less than 10 minutes, and “medium-term memory” refers to memory retained for 10 minutes to 24 hours. In Patent Document 2, only a short-term memory of about 10 seconds is tested even in a short-term memory.
「短期記憶」、「中期記憶」及び「長期記憶」は、それぞれの記憶のメカニズム機序が異なるため(例えば、長期記憶は新しいタンパク質の形成と成長が必要となるが、短期記憶では必要がない等)、たとえ「短期記憶」が改善するとしても、「中期記憶」又は「長期記憶」が改善されると言うことはできない。 “Short-term memory”, “medium-term memory”, and “long-term memory” have different memory mechanisms (for example, long-term memory requires formation and growth of new proteins, but short-term memory is not necessary Etc.) Even if “short-term memory” is improved, it cannot be said that “medium-term memory” or “long-term memory” is improved.
特許文献2では、上記した通り、中期記憶力試験も長期記憶力試験も実施されていないことに加えて、バレニンについては試験すら行われていない(バレニンについて記憶力試験を行った実施例がない)。
バレニンは、そもそもアンセリン(β−アラニル−1−メチル−L−ヒスチジン)及びカルノシン(β−アラニル−L−ヒスチジン)とは異なる化学構造であり、記憶障害予防改善や認知症予防改善については、化学構造が異なれば薬効が異なることは周知の事実である。
In Patent Document 2, as described above, in addition to neither a medium-term memory test nor a long-term memory test being conducted, even a test for barenin has not been performed (there is no example of performing a memory test for barenin).
Valenin has a chemical structure different from anserine (β-alanyl-1-methyl-L-histidine) and carnosine (β-alanyl-L-histidine) in the first place. It is a well-known fact that different structures have different medicinal effects.
以上のことから、特許文献2には、「バレニンが中期記憶又は長期記憶を改善する」ということは、記載も示唆もされていないので、本発明の中長期記憶障害予防改善剤は、新規性及び進歩性の何れをも有する。 From the above, in Patent Document 2, it is neither described nor suggested that “valenin improves medium-term memory or long-term memory”. And inventive step.
本発明の中長期記憶障害予防改善剤で使用する、「鯨の筋肉から抽出した鯨筋肉抽出物」(以下、単に「鯨筋肉抽出物」と略記する場合がある)は、何れの種類の鯨の筋肉から抽出した抽出物であってもよい。
バレニンを多く含有する点等から、ヒゲクジラ亜目に属する鯨の筋肉から抽出した鯨筋肉抽出物が好ましく、ナガスクジラ属に属する鯨の筋肉から抽出した鯨筋肉抽出物がより好ましく、ナガスクジラ、ミンククジラ、イワシクジラの筋肉から抽出した鯨筋肉抽出物が特に好ましい。
The “whale muscle extract extracted from whale muscle” (hereinafter sometimes simply abbreviated as “whale muscle extract”) used in the present invention for preventing and improving medium to long-term memory impairment is any type of whale. It may be an extract extracted from the muscle.
The whale muscle extract extracted from the whale muscle belonging to the baleen whale subclass is preferable, the whale muscle extract extracted from the whale muscle belonging to the fin whale genus is more preferable, the fin whale, minke whale, Particularly preferred is a whale muscle extract extracted from sardine whale muscle.
鯨筋肉抽出物の抽出方法は、特に限定されないが、公知の抽出方法に従って抽出することができる。バレニンを抽出できる条件であることが好ましく、例えば、鯨の筋肉を細かく裁断処理後、水性溶媒、有機溶媒等の抽出溶媒を用いて抽出することができる。 Although the extraction method of a whale muscle extract is not specifically limited, It can extract according to a well-known extraction method. It is preferable that the conditions allow the extraction of valenin. For example, the whale muscle can be finely cut and extracted using an extraction solvent such as an aqueous solvent or an organic solvent.
鯨の筋肉から抽出した鯨筋肉抽出物をそのまま中長期記憶障害予防改善剤として使用してもよく、又は、該鯨筋肉抽出物に何らかの処理を施した鯨筋肉抽出物処理物を中長期記憶障害予防改善剤として使用してもよい。
鯨筋肉抽出物の処理物としては、具体的には、鯨筋肉抽出物の濃縮物;ペースト化物;噴霧乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物;液状化物;希釈物;破砕物;殺菌加工物等が挙げられる。
Whale muscle extract extracted from whale muscle may be used as it is as an agent for preventing or improving medium- to long-term memory impairment, or processed whale muscle extract that has been subjected to some treatment to the whale muscle extract may be used for medium- to long-term memory impairment. It may be used as a preventive / ameliorating agent.
Specifically, the processed products of whale muscle extract include concentrates of whale muscle extract; pasted products; dried products such as spray dried products, vacuum dried products and drum dried products; liquefied products; diluted products; A sterilized processed product and the like.
本発明の中長期記憶障害予防改善剤は、老人性若しくはアルツハイマー型認知症による学習記憶障害の予防及び/又は改善に用いられることが好ましい。
老人性認知症とは、加齢により引き起こされる血管性認知症のことである。アルツハイマー型認知症とは、神経細胞が変性することにより引き起こされる変性性認知症のことである。
The medium / long-term memory disorder prevention / amelioration agent of the present invention is preferably used for the prevention and / or improvement of learning memory disorder due to senile or Alzheimer type dementia.
Senile dementia is vascular dementia caused by aging. Alzheimer-type dementia is degenerative dementia caused by degeneration of nerve cells.
また、本発明の中長期記憶障害予防改善剤は、医薬品及び/又は飲食品にも添加することが可能であり、医薬品及び/又は飲食品の形態等によらず様々な医薬品及び/又は飲食品に応用できる。
本発明の中長期記憶障害予防改善剤の投与量としては、特に制限はなく、投与対象である個体の年齢、体重、所望の効果の程度、投与方法等に応じて適宜選択することができるが、例えば、経口投与の場合、成人への1日の投与量は、1mg〜30gが好ましく、10mg〜10gがより好ましく、100mg〜3gが特に好ましい。
In addition, the medium-to-long-term memory disorder prevention / improving agent of the present invention can be added to pharmaceuticals and / or foods and beverages, and various pharmaceuticals and / or foods and beverages regardless of the form of the pharmaceuticals and / or foods and beverages. It can be applied to.
The dosage of the agent for improving the prevention of middle to long-term memory impairment of the present invention is not particularly limited, and can be appropriately selected depending on the age, weight, desired degree of effect, administration method, etc. of the individual to be administered. For example, in the case of oral administration, the daily dose to an adult is preferably 1 mg to 30 g, more preferably 10 mg to 10 g, and particularly preferably 100 mg to 3 g.
[認知症予防改善剤]
本発明の中長期記憶障害予防改善剤は、認知症予防改善剤の構成成分として特に有用である。すなわち、本発明の認知症予防改善剤は、前記中長期記憶障害予防改善剤を含有する。
[Dementia prevention and improvement agent]
The medium / long-term memory disorder preventive / ameliorating agent of the present invention is particularly useful as a component of the dementia prevention / ameliorating agent. That is, the dementia prevention-improving agent of the present invention contains the above-mentioned medium- to long-term memory disorder prevention-improving agent.
本発明の認知症予防改善剤に対する中長期記憶障害予防改善剤の含有量は、特に制限がなく、目的に応じて適宜選択することができるが、認知症予防改善剤全体を100質量部としたときに、中長期記憶障害予防改善剤は、0.1〜100質量部の含量で配合することが好ましく、より好ましくは1〜98質量部、更に好ましくは10〜95質量部、特に好ましくは20〜90質量部の含量で配合することができる。 The content of the medium / long-term memory disorder prevention / amelioration agent relative to the dementia prevention / amelioration agent of the present invention is not particularly limited and can be appropriately selected according to the purpose, but the entire dementia prevention / amelioration agent is 100 parts by mass. Sometimes, the medium / long-term memory impairment prevention / amelioration agent is preferably blended in a content of 0.1 to 100 parts by weight, more preferably 1 to 98 parts by weight, still more preferably 10 to 95 parts by weight, and particularly preferably 20 parts. It can mix | blend by the content of -90 mass parts.
本発明の認知症予防改善剤は、前記中長期記憶障害予防改善剤に加えて、「その他の成分」を含有することができる。 The agent for improving and preventing dementia of the present invention can contain “other components” in addition to the agent for preventing and improving medium- to long-term memory impairment.
前記認知症予防改善剤における、上記「その他の成分」としては、特に制限はなく、本発明の効果を損なわない範囲内で、目的に応じて適宜選択することができ、例えば、薬学的に許容され得る担体等が挙げられる。
かかる担体としては、特に制限はなく、例えば、後述する剤型等に応じて適宜選択することができる。また、前記認知症予防改善剤中の前記「その他の成分」の含有量としても、特に制限はなく、目的に応じて適宜選択することができる。
The “other component” in the dementia prevention / amelioration agent is not particularly limited and may be appropriately selected depending on the purpose within a range not impairing the effects of the present invention. For example, pharmaceutically acceptable And a carrier that can be used.
There is no restriction | limiting in particular as this support | carrier, For example, according to the dosage form etc. which are mentioned later, it can select suitably. In addition, the content of the “other components” in the dementia prevention / amelioration agent is not particularly limited and may be appropriately selected depending on the intended purpose.
本発明の認知症予防改善剤の剤型としては、特に制限はなく、例えば、後述するような所望の投与方法に応じて適宜選択することができる。
具体的には、例えば、経口固形剤(錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等)、経口液剤(内服液剤、シロップ剤、エリキシル剤等)、注射剤(溶剤、懸濁剤等)、軟膏剤、貼付剤、ゲル剤、クリーム剤、外用散剤、スプレー剤、吸入散布剤等が挙げられる。
There is no restriction | limiting in particular as a dosage form of the dementia prevention improving agent of this invention, For example, it can select suitably according to the desired administration method which is mentioned later.
Specifically, for example, oral solids (tablets, coated tablets, granules, powders, capsules, etc.), oral liquids (internal solutions, syrups, elixirs, etc.), injections (solvents, suspensions, etc.) , Ointments, patches, gels, creams, powders for external use, sprays, inhalation sprays and the like.
前記経口固形剤としては、例えば、前記有効成分に、賦形剤、更には必要に応じて結合剤、崩壊剤、滑沢剤、着色剤、矯味・矯臭剤等の添加剤を加え、常法により製造することができる。
前記賦形剤としては、例えば、乳糖、白糖、塩化ナトリウム、ブドウ糖、デンプン、炭酸カルシウム、カオリン、微結晶セルロース、珪酸等が挙げられる。
前記結合剤としては、例えば、水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン液、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルスターチ、メチルセルロース、エチルセルロース、シェラック、リン酸カルシウム、ポリビニルピロリドン等が挙げられる。
前記崩壊剤としては、例えば、乾燥デンプン、アルギン酸ナトリウム、カンテン末、炭酸水素ナトリウム、炭酸カルシウム、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、乳糖等が挙げられる。
前記滑沢剤としては、例えば、精製タルク、ステアリン酸塩、ホウ砂、ポリエチレングリコール等が挙げられる。
前記着色剤としては、例えば、酸化チタン、酸化鉄等が挙げられる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。
Examples of the oral solid preparation include, for example, excipients and further additives such as binders, disintegrants, lubricants, colorants, flavoring and flavoring agents as necessary, in addition to the active ingredients. Can be manufactured.
Examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid and the like.
Examples of the binder include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphate, polyvinylpyrrolidone and the like. It is done.
Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose.
Examples of the lubricant include purified talc, stearate, borax, and polyethylene glycol.
Examples of the colorant include titanium oxide and iron oxide.
Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
前記経口液剤としては、例えば、前記有効成分に、矯味・矯臭剤、緩衝剤、安定化剤等の添加剤を加え、常法により製造することができる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。前記緩衝剤としては、例えば、クエン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、トラガント、アラビアゴム、ゼラチン等が挙げられる。
The oral solution can be produced by a conventional method, for example, by adding additives such as a flavoring / flavoring agent, a buffering agent, and a stabilizer to the active ingredient.
Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like. Examples of the buffer include sodium citrate. Examples of the stabilizer include tragacanth, gum arabic, and gelatin.
前記注射剤としては、例えば、前記有効成分に、pH調節剤、緩衝剤、安定化剤、等張化剤、局所麻酔剤等を添加し、常法により皮下用、筋肉内用、静脈内用等の注射剤を製造することができる。
前記pH調節剤及び前記緩衝剤としては、例えば、クエン酸ナトリウム、酢酸ナトリウム、リン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、ピロ亜硫酸ナトリウム、EDTA、チオグリコール酸、チオ乳酸等が挙げられる。前記等張化剤としては、例えば、塩化ナトリウム、ブドウ糖等が挙げられる。前記局所麻酔剤としては、例えば、塩酸プロカイン、塩酸リドカイン等が挙げられる。
As the injection, for example, a pH adjuster, a buffer, a stabilizer, a tonicity agent, a local anesthetic, etc. are added to the active ingredient, and subcutaneous, intramuscular, intravenous use are performed by a conventional method. Etc. can be manufactured.
Examples of the pH adjusting agent and the buffering agent include sodium citrate, sodium acetate, sodium phosphate and the like. Examples of the stabilizer include sodium pyrosulfite, EDTA, thioglycolic acid, thiolactic acid, and the like. Examples of the isotonic agent include sodium chloride and glucose. Examples of the local anesthetic include procaine hydrochloride and lidocaine hydrochloride.
前記軟膏剤としては、例えば、前記有効成分に、公知の基剤、安定剤、湿潤剤、保存剤等を配合し、常法により混合し、製造することができる。
前記基剤としては、例えば、流動パラフィン、白色ワセリン、サラシミツロウ、オクチルドデシルアルコール、パラフィン等が挙げられる。前記保存剤としては、例えば、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル等が挙げられる。
As the ointment, for example, a known base, stabilizer, wetting agent, preservative and the like may be blended with the active ingredient and mixed by a conventional method.
Examples of the base include liquid paraffin, white petrolatum, white beeswax, octyldodecyl alcohol, and paraffin. Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and the like.
本発明の認知症予防改善剤は、例えば、中期記憶及び/又は長期記憶の改善を必要とする個体(例えば、健康維持を必要とする個体;老人性又はアルツハイマー型認知症の予防や治療を必要とする個体;等)に投与することにより使用することができる。 The agent for improving and preventing dementia of the present invention is, for example, an individual who needs to improve medium-term memory and / or long-term memory (for example, an individual who needs to maintain health; senile or Alzheimer-type dementia needs to be prevented or treated. It is possible to use it by administering to an individual.
本発明の認知症予防改善剤の投与対象動物としては、特に制限はないが、例えば、ヒト;マウス;サル;ウマ;ウシ、ブタ、ヤギ、ニワトリ等の家畜;ネコ、イヌ等のペット;等が挙げられる。 The animal to be administered with the agent for improving and preventing dementia of the present invention is not particularly limited. For example, humans; mice; monkeys; horses; livestock such as cows, pigs, goats and chickens; pets such as cats and dogs; Is mentioned.
また、前記認知症予防改善剤の投与方法としては、特に制限はなく、例えば、前記中長期記憶障害予防改善剤の剤型等に応じ、適宜選択することができ、経口投与、腹腔内投与、血液中への注射、腸内への注入等が挙げられる。
また、前記認知症予防改善剤の投与量としては、特に制限はなく、投与対象である個体の年齢、体重、所望の効果の程度、投与方法等に応じて適宜選択することができるが、例えば、成人への1日の経口投与量は、有効成分の量として、1mg〜30gが好ましく、10mg〜10gがより好ましく、100mg〜3gが特に好ましい。
また、前記認知症予防改善剤の投与時期としても、特に制限はなく、目的に応じて適宜選択することができ、例えば、予防的に投与されてもよいし、治療(改善)的に投与されてもよい。
Further, the method for administering the dementia prevention improving agent is not particularly limited, and can be appropriately selected according to, for example, the dosage form of the medium to long-term memory disorder prevention improving agent, such as oral administration, intraperitoneal administration, Examples thereof include injection into blood and infusion into the intestine.
The dosage of the dementia prevention / amelioration agent is not particularly limited and may be appropriately selected depending on the age, weight, desired degree of effect, administration method, etc. of the individual to be administered. The daily oral dose to an adult is preferably 1 mg to 30 g, more preferably 10 mg to 10 g, and particularly preferably 100 mg to 3 g as the amount of the active ingredient.
Moreover, there is no restriction | limiting in particular also as an administration time of the said dementia prevention improving agent, According to the objective, it can select suitably, For example, you may administer prophylactically or administer therapeutically (improvement). May be.
[作用]
本発明において、鯨筋肉抽出物を摂取することにより、中期記憶及び/又は長期記憶が改善される作用・原理は明らかではなく、また、本発明は、かかる作用・原理の範囲に限定されるわけではないが、以下のことが考えられる。
中長期記憶において、脳の神経細胞でタンパク質が合成される必要がある。鯨筋肉抽出物を摂取することにより、鯨筋肉抽出物に含まれるバレニンが該タンパク質合成経路を活性化させることにより、中長期記憶障害が改善された。
[Action]
In the present invention, the action / principle of improving medium-term memory and / or long-term memory by ingesting a whale muscle extract is not clear, and the present invention is not limited to the scope of such action / principle. However, the following can be considered.
In medium- and long-term memory, proteins need to be synthesized in brain neurons. By ingesting the whale muscle extract, valenin contained in the whale muscle extract activates the protein synthesis pathway, thereby improving medium- to long-term memory impairment.
以下に、実施例及び比較例を挙げて本発明を更に具体的に説明するが、本発明は、その要旨を超えない限りこれらの実施例に限定されるものではない。 EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to these examples unless it exceeds the gist.
<オープンフィールドテスト(自発運動量の測定)>
オープンフィールドテスト(自発運動量の測定)は、既に知られている常法に従って行った。すなわち、オープンフィールドにマウスを投入し、5分間の総移動距離を自発運動量として測定した。
総移動距離が長い程、マウスの自発運動量は多いと判断する。
<Open field test (measurement of spontaneous momentum)>
The open field test (measurement of spontaneous exercise amount) was performed according to a known method. That is, a mouse was introduced into the open field, and the total movement distance for 5 minutes was measured as the amount of spontaneous movement.
It is determined that the spontaneous movement amount of the mouse is larger as the total moving distance is longer.
<新規物体認識テスト(中期記憶テスト)>
新規物体認識テスト(中期記憶テスト)は、既に知られている常法に従って行った。
1日目に、2つの同じ大きさ及び同じ色の物体が設置されたオープンフィールドにマウスを10分間入れ、各物体に接触する回数をカウントした。そして、2日目に、2つの物体のうち、一方を違う色の物体に交換した。物体を交換後、マウスを5分間入れ、各物体に接触する回数をカウントした。
以下、1日目と2日目が同じ色の物体を「物体1」、1日目と2日目が異なる色の物体を「物体2」とする。
総接触回数に対する「物体2」への接触回数の割合(2日目)が、総接触回数に対する「物体2」への接触回数の割合(1日目)と比べて大きいときに、マウスの中期記憶力は高いと判断する。一方、総接触回数に対する「物体2」への接触回数の割合(2日目)が、総接触回数に対する「物体2」への接触回数の割合(1日目)とほとんど変わらない場合は、マウスの中期記憶力は低いと判断する。
<New object recognition test (medium term memory test)>
The new object recognition test (medium term memory test) was performed according to a known method.
On the first day, the mouse was placed in an open field where two objects of the same size and color were placed for 10 minutes, and the number of contact with each object was counted. On the second day, one of the two objects was replaced with an object of a different color. After changing the object, the mouse was placed for 5 minutes, and the number of contact with each object was counted.
Hereinafter, an object having the same color on the first day and the second day is referred to as “object 1”, and an object having a different color on the first day and the second day is referred to as “object 2”.
When the ratio of the number of contacts to “object 2” with respect to the total number of contacts (day 2) is larger than the ratio of the number of contacts with “object 2” to the total number of contacts (day 1), Judgment is high in memory. On the other hand, if the ratio of the number of contacts to “object 2” with respect to the total number of contacts (second day) is almost the same as the ratio of the number of contacts with “object 2” to the total number of contacts (first day), the mouse It is judged that the medium term memory is low.
<マルチプルT字水迷路テスト(長期記憶テスト)>
図6に示した水迷路を作製した。1日目は、遊泳訓練用コースでマウスを遊泳訓練させた。2日目以降に、スタート(図6B中、「S」位置)からゴール(図6B中、「G」位置)に到達するまでの到達時間(上限時間:360秒)を測定した。また、エラー領域(図6B中、太枠(合計6ヶ所))に進入した回数をエラー回数として測定した。これを1日3試行、連続3日間行った。
到達時間が短い及び/又はエラー回数が少ない程、マウスの長期記憶力は高いと判断する。
<Multiple T-shaped water maze test (long-term memory test)>
The water maze shown in FIG. 6 was produced. On the first day, mice were trained to swim on a course for swimming training. After the second day, the arrival time (upper limit time: 360 seconds) from the start (“S” position in FIG. 6B) to the goal (“G” position in FIG. 6B) was measured. Further, the number of times of entering the error area (thick frame (total of 6 places in FIG. 6B)) was measured as the number of errors. This was performed for 3 consecutive days for 3 consecutive days.
The shorter the arrival time and / or the smaller the number of errors, the higher the long-term memory of the mouse.
<モリス水迷路テスト(長期記憶テスト)>
モリス水迷路テスト(長期記憶テスト)は、既に知られている常法に従って行った。マウスを水が入った円形プールに放してからゴールとなるプラットホーム(水面直下に設置)までの到達時間を測定した。1日1試行、連続6日間行った。
到達時間が短い程、マウスの長期記憶力は高いと判断する。
<Morris water maze test (long-term memory test)>
The Morris water maze test (long-term memory test) was performed according to a known method. The arrival time from the release of the mouse into a circular pool with water to the goal platform (installed directly below the water surface) was measured. 1 trial per day for 6 consecutive days.
The shorter the arrival time, the higher the long-term memory of the mouse.
<Y字迷路テスト(短期記憶テスト)>
Y字迷路テスト(短期記憶テスト)は、既に知られている常法に従って行った。
3本のアームから構成される、Y字型に配置された迷路にマウスを投入し、8分間自由に行動させた。マウスが各アームに進入した回数の合計を総進入回数とし、連続して異なる3つのアームを選択した回数を自発的交替行動数とした。例えば、3本のアームをそれぞれA、B、Cとしたときに、進入したアームの順番が「ACBACBCBACB」の場合は、重複も含めて7回とカウントした。そして、以下のように計算し、交替行動率として求めた。
交替行動率(%)={自発的交替行動数/(総進入回数−2)}×100
交替行動率の値が大きい程、マウスの短期記憶力は高いと判断する。
<Y-maze test (short-term memory test)>
The Y-shaped maze test (short-term memory test) was performed according to a known method.
A mouse was put into a maze arranged in a Y-shape composed of three arms and allowed to move freely for 8 minutes. The total number of times that the mouse entered each arm was defined as the total number of times of entry, and the number of times that three different arms were selected in succession was defined as the number of spontaneous alternation actions. For example, when the three arms are A, B, and C, and the order of the arms that have entered is “ACBACBCBACB”, it is counted as 7 times including the overlap. And it calculated as follows and calculated | required as an alternation action rate.
Replacement action rate (%) = {number of voluntary replacement actions / (total number of entrances−2)} × 100
It is judged that the short-term memory of the mouse is higher as the value of the alternation behavior rate is larger.
検討例1
<対象マウス及び摂食期間の検討>
Study example 1
<Examination of target mice and feeding period>
本実施例では、学習記憶障害老化モデルマウスであるSAMP8/TaSlcマウス(以下、「SAMP8」と略記する場合がある)、及び、正常老化モデルマウスであるSAMR1/TaSlcマウス(以下、「SAMR1」と略記する場合がある)を用いた。 In this example, a learning memory disorder aging model mouse, SAMP8 / TaSlc mouse (hereinafter sometimes abbreviated as “SAMP8”), and a normal aging model mouse, SAMR1 / TaSlc mouse (hereinafter, “SAMR1”). (May be abbreviated).
図1は、一般に老化モデルマウスとして実験で用いられるマウス(SAMP6、SAMP8、SAMP10、SAMR1)の週齢と生存率の関係を示したグラフである。縦軸は生存率(%)、横軸は週齢を示す。
図1より、SAMP8は、生後35週齢前後から生存率が低下したことがわかった。
また、SAMP8は、生後24週前後から老化度が増加していることがわかった(図示せず)。
FIG. 1 is a graph showing the relationship between the age and survival rate of mice (SAMP6, SAMP8, SAMP10, SAMR1) generally used in experiments as aging model mice. The vertical axis represents the survival rate (%), and the horizontal axis represents the age of the week.
From FIG. 1, it was found that the survival rate of SAMP8 decreased from around 35 weeks of age.
In addition, SAMP8 was found to increase in aging degree from around 24 weeks after birth (not shown).
以上の結果から、一般に老化モデルマウスとして使用されているマウスの中から、SAMP8及びSAMR1を用いることとした。
生後8〜24週の16週間は予備飼育を行い、生後26週目から、コントロール餌(以下、「LSO食」と略記する場合がある)を食用させるSAMP8群、鯨筋肉抽出物を含有させた餌(以下、「JP食」と略記する場合がある)を食用させるSAMP8群、及び、LSO食を食用させるSAMR1群の3群を設定し、生後32週目及び生後50週目において、行動解析を行うこととした。実験のスキームを図2に示す。
以下、LSO食を食用させるSAMP8群を「SAMP8 LSO群」、JP食を食用させるSAMP8群を「SAMP8 JP群」、LSO食を食用させるSAMR1群を「SAMR1 LSO群」と略記する場合がある。
From the above results, SAMP8 and SAMR1 were used from the mice generally used as aging model mice.
16 weeks from 8 to 24 weeks of age were preliminarily reared, and from the 26th week of age, 8 groups of SAMPs for feeding control food (hereinafter sometimes abbreviated as “LSO food”) and whale muscle extract were included. Three groups were set: SAMP8 group for feeding food (hereinafter sometimes abbreviated as “JP meal”) and SAMR1 group for eating LSO food. Behavior analysis at 32 weeks and 50 weeks after birth It was decided to do. The experimental scheme is shown in FIG.
Hereinafter, the SAMP8 group that consumes the LSO food may be abbreviated as “SAMP8 LSO group”, the SAMP8 group that consumes the JP food may be abbreviated as “SAMP8 JP group”, and the SAMR1 group that consumes the LSO food may be abbreviated as “SAMR1 LSO group”.
LSO食及びJP食の組成を表1に示す。各数字の単位は、質量(%)である。 Table 1 shows the composition of the LSO meal and JP meal. The unit of each number is mass (%).
鯨筋肉抽出物として、「クジラエキス(まるげい社製)」を使用した。SAMP8マウスにおいて、抗疲労効果が認められた投与量と同じになるように、クジラエキスをJP食に含有させた。表1に示した組成により、JP食は2.4質量%の鯨筋肉抽出物を含有する。鯨筋肉抽出物100質量%に対して、バレニンは8.3質量%含まれることにより、JP食には0.2質量%のバレニンが含まれる。 As a whale muscle extract, “whale extract (manufactured by Marugei)” was used. In the SAMP8 mice, the whale extract was added to the JP diet so that the dose was the same as the dose at which the anti-fatigue effect was observed. According to the composition shown in Table 1, the JP diet contains 2.4% by weight of whale muscle extract. The JP diet contains 0.2% by weight of barenine by containing 8.3% by weight of barenine with respect to 100% by weight of the whale muscle extract.
実施例1
<32週齢マウスの行動解析>
32週齢マウスに対し、オープンフィールドテスト(自発運動量の測定)、新規物体認識テスト(中期記憶テスト)、及び、モリス水迷路テスト(長期記憶テスト)を行った。
図3Aはオープンフィールドテスト(自発運動量の測定)、図3Bはモリス水迷路テスト(長期記憶テスト)、図3Cは新規物体認識テスト(中期記憶テスト)の結果を示す。
Example 1
<Behavioral analysis of 32-week-old mice>
An open field test (measurement of spontaneous exercise amount), a new object recognition test (medium term memory test), and a Morris water maze test (long term memory test) were performed on 32-week-old mice.
3A shows the results of an open field test (measurement of spontaneous exercise amount), FIG. 3B shows the results of a Morris water maze test (long-term memory test), and FIG. 3C shows the results of a new object recognition test (medium-term memory test).
図3A及びB中の丸数字について、「1」は「SAMP8 LSO群」、「2」は「SAMP8 JP群」、「3」は、「SAMR1 LSO群」を示す。縦軸は5分間の総移動距離(cm)を示す。
図3Bの縦軸は、マウスを水が入った円形プールに放してからゴールとなるプラットホームまでの到達時間(秒)を示す。
図3Cの横軸中、「a」は1日目の物体1、「b」は1日目の物体2、「c」は2日目の物体1、「d」は2日目の物体2を示す。縦軸は、各試験日の総接触回数に対する物体1又は物体2への接触回数の割合を表す(%)。
3A and B, “1” indicates “SAMP8 LSO group”, “2” indicates “SAMP8 JP group”, and “3” indicates “SAMR1 LSO group”. The vertical axis represents the total travel distance (cm) for 5 minutes.
The vertical axis in FIG. 3B shows the arrival time (seconds) from the release of the mouse into a circular pool containing water to the goal platform.
In the horizontal axis of FIG. 3C, “a” is the first day object 1, “b” is the first day object 2, “c” is the second day object 1, and “d” is the second day object 2. Indicates. The vertical axis represents the ratio of the number of times of contact with the object 1 or the object 2 to the total number of times of contact on each test day (%).
図3A及びBの結果より、生後32週齢(8ヶ月齢)であるSAMP8においては、鯨筋肉抽出物を含有させた餌を食用させることにより、自発運動量及び長期記憶の改善は見られなかった。
ただ、図3Cの結果より、新規物体認識テスト(中期記憶テスト)において、鯨筋肉抽出物を含有させた餌を食用させることにより、中期記憶が改善傾向にあった。
From the results of FIGS. 3A and B, in SAMP8, which is 32 weeks old (8 months old), no improvement in locomotor activity and long-term memory was observed by feeding food containing whale muscle extract. .
However, from the results shown in FIG. 3C, in the new object recognition test (medium term memory test), the medium term memory tended to be improved by feeding food containing the whale muscle extract.
実施例2
<50週マウスの行動解析>
50週齢マウスに対し、オープンフィールドテスト(自発運動量の測定)、新規物体認識テスト(中期記憶テスト)、及び、マルチプルT字水迷路テスト(長期記憶テスト)を行った。
Example 2
<Behavioral analysis of 50-week mouse>
50-week-old mice were subjected to an open field test (measurement of spontaneous momentum), a novel object recognition test (medium term memory test), and a multiple T-shaped water maze test (long term memory test).
<<自発運動量>>
オープンフィールドテスト(自発運動量の測定)の結果を図4に示す。
図4の横軸中の丸数字について、「1」は「SAMP8 LSO群」、「2」は「SAMP8 JP群」、「3」は、「SAMR1 LSO群」を示す。縦軸は5分間の総移動距離(cm)を示す。
<< voluntary momentum >>
The result of the open field test (measurement of spontaneous exercise amount) is shown in FIG.
As for the circled numbers in the horizontal axis of FIG. 4, “1” indicates “SAMP8 LSO group”, “2” indicates “SAMP8 JP group”, and “3” indicates “SAMR1 LSO group”. The vertical axis represents the total travel distance (cm) for 5 minutes.
図4の結果より、SAMP8 JP群(「2」)の自発運動量は、SAMP8 LSO群(「1」)の自発運動量とほとんど変わらなかった。
この結果から、鯨筋肉抽出物は、学習記憶障害を有する老化促進マウスには、直接、自発運動量に影響を与えないことが示唆された。
From the results of FIG. 4, the spontaneous exercise amount of the SAMP8 JP group (“2”) was almost the same as the spontaneous exercise amount of the SAMP8 LSO group (“1”).
This result suggests that the whale muscle extract does not directly affect the locomotor activity in aging-promoted mice with learning and memory impairment.
<<中期記憶テスト>>
新規物体認識テスト(中期記憶テスト)の結果を図5に示す。
図5中、「a」は1日目の結果、「b」は2日目の結果を示す。縦軸は、各試験日の総接触回数に対する物体1(A)又は物体2(B)への接触回数の割合を表す(%)。
<< Medium term memory test >>
The result of the new object recognition test (medium term memory test) is shown in FIG.
In FIG. 5, “a” indicates the result of the first day, and “b” indicates the result of the second day. The vertical axis represents the ratio of the number of contacts to the object 1 (A) or the object 2 (B) to the total number of contacts on each test day (%).
図5Aの結果より、SAMP8 JP群、SAMP8 LSO群、及びSAMR1 LSO群について、1日目と2日目共に同じ色である物体1への接触回数の割合は、1日目と2日目でほとんど変わらなかった。
図5Bの結果より、SAMP8 JP群は、1日目と2日目で色が異なる物体2への接触回数の割合が、1日目より2日目の方が多かった。一方、SAMP8 LSO群では、1日目と2日目で接触回数の割合にほとんど変化がなかった。
以上の結果から、鯨筋肉抽出物を食用することにより、学習記憶障害を有する老化促進マウスの中期記憶が改善傾向になることが示唆された。なお、正常老化モデルマウスであるSAMR1 LSO群も同様に、物体2への接触回数の割合が、2日目の方が多かった。
From the result of FIG. 5A, the ratio of the number of times of contact with the object 1 that is the same color on the first day and the second day for the SAMP8 JP group, the SAMP8 LSO group, and the SAMR1 LSO group is the first day and the second day. Almost unchanged.
From the result of FIG. 5B, in the SAMP8 JP group, the ratio of the number of times of contact with the object 2 having different colors on the first day and the second day was higher on the second day than on the first day. On the other hand, in the SAMP8 LSO group, there was almost no change in the ratio of the number of contact between the first day and the second day.
These results suggest that the use of whale muscle extract tends to improve the medium-term memory of aging-promoted mice with impaired learning memory. Similarly, the ratio of the number of times of contact with the object 2 was higher on the second day in the SAMR1 LSO group which is a normal aging model mouse.
<<長期記憶テスト>>
マルチプルT字水迷路テスト(長期記憶テスト)の結果を図7に示す。
図7中の丸数字について、「1」は「SAMP8 LSO群」、「2」は「SAMP8 JP群」、「3」は、「SAMR1 LSO群」を示す。縦軸は5分間の総移動距離(cm)を示す。
図7Aの縦軸は、マルチプルT字水迷路をスタートしてからゴールするまでの平均時間(秒)を示す。図7Bの縦軸は、マルチプルT字水迷路をスタートしてからゴールするまでの間にエラー領域に進入した平均回数を示す。
<< Long-term memory test >>
The result of the multiple T-shaped water maze test (long-term memory test) is shown in FIG.
Regarding the circled numbers in FIG. 7, “1” indicates “SAMP8 LSO group”, “2” indicates “SAMP8 JP group”, and “3” indicates “SAMR1 LSO group”. The vertical axis represents the total travel distance (cm) for 5 minutes.
The vertical axis in FIG. 7A represents the average time (seconds) from the start of the multiple T-shaped water maze to the goal. The vertical axis in FIG. 7B indicates the average number of times that the error area has been entered between the start of the multiple T-shaped water maze and the goal.
図7の結果より、SAMP8 JP群は、SAMP LSO群と比べて、2日目及び3日目の到達時間が短縮した。SAMP8 JP群の1日目〜3日目の到達時間は、それぞれ、SAMR1 LSO群とほぼ同じであった。
これらの結果から、鯨筋肉抽出物は、学習記憶障害を有する老化促進マウスの長期記憶の改善に関与していることが示唆された。
From the result of FIG. 7, the arrival time of the 2nd day and the 3rd day was shortened in the SAMP8 JP group compared with the SAMP LSO group. The arrival times on the first to third days of the SAMP8 JP group were almost the same as those of the SAMR1 LSO group, respectively.
These results suggest that whale muscle extract is involved in improving long-term memory in senescence-accelerated mice with learning memory impairment.
以上の結果より、学習記憶障害を有する老化促進マウス(50週齢マウス)において、本発明の中長期記憶障害予防改善剤を食用することにより、中期記憶及び長期記憶が改善することがわかった。 From the above results, it was found that, in the aging-promoting mice (50-week-old mice) having learning memory impairment, the medium-term memory and long-term memory are improved by eating the medium- and long-term memory impairment preventing / ameliorating agent of the present invention.
参考例1
<<短期記憶テスト>>
実施例1で用いた32週齢マウス、及び実施例2で使用した50週齢マウスに対し、Y字迷路テスト(短期記憶テスト)を行った。結果を図8に示す。
Reference example 1
<< Short-term memory test >>
A Y-maze test (short-term memory test) was performed on the 32-week-old mice used in Example 1 and the 50-week-old mice used in Example 2. The results are shown in FIG.
図8の横軸中の丸数字について、「1」は「SAMP8 LSO群」、「2」は「SAMP8 JP群」、「3」は、「SAMR1 LSO群」を示す。縦軸は5分間の総移動距離(cm)を示す。縦軸は交替行動率(%)を示す。 Regarding the circled numbers in the horizontal axis of FIG. 8, “1” indicates “SAMP8 LSO group”, “2” indicates “SAMP8 JP group”, and “3” indicates “SAMR1 LSO group”. The vertical axis represents the total travel distance (cm) for 5 minutes. The vertical axis shows the alternation action rate (%).
図8Aの結果より、32週齢であるSAMP8において、鯨筋肉抽出物を含有させた餌を食用させることにより、数秒〜10分未満記憶が保持されると言う本発明の「短期記憶」の改善は見られなかった。
また、図8Bの結果より、SAMP8 JP群は、SAMP8 LSO群と比べて、交替行動率が上昇した。この結果から、鯨筋肉抽出物は、学習記憶障害を有する老化促進マウスの、数秒〜10分未満の記憶が保持されると言う本発明の「短期記憶」が改善傾向にあることが示唆された。
From the result of FIG. 8A, the improvement of the “short-term memory” of the present invention that memory is maintained for less than a few seconds to 10 minutes by feeding food containing a whale muscle extract in SAMP8 which is 32 weeks old. Was not seen.
Moreover, from the result of FIG. 8B, the alternation action rate increased in the SAMP8 JP group compared to the SAMP8 LSO group. From this result, it was suggested that the “short-term memory” of the present invention that the whale muscle extract retains the memory of less than a few seconds to 10 minutes of the aging-promoted mice having learning memory impairment is suggested to be improved. .
本発明の中長期記憶障害予防改善剤は、鯨筋肉抽出物からなるものであるから安全であり、製剤化、飲食品への添加等に適しており、医薬品や食品等の分野において広く利用されるものである。 The medium / long-term memory disorder preventive / ameliorating agent of the present invention is safe because it consists of a whale muscle extract, is suitable for formulation, addition to foods and drinks, etc., and is widely used in the fields of pharmaceuticals and foods. Is.
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