JP6401028B2 - Medium / long-term memory disorder prevention / improvement agent consisting of whale muscle extract - Google Patents

Description

  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.

  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.

  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.

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.

  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.

JP 2007-314467 A Japanese Patent Laid-Open No. 9-020661

Nakajima Takuma, “Anti-fatigue effect by ingesting whale meat extract (containing valenine)”, Food and Development, 41 (11): 62-64, 2006

  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.

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.

  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.

  The present invention also provides a dementia prevention / amelioration agent characterized by containing the above-mentioned medium / long-term memory disorder prevention / improvement agent.

  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.

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.

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.

  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.

It is a graph showing the relationship between the age of each aging model mouse (SAMP6, SAMP8, SAMP10, SAMR1) and survival rate. It is a figure which shows the protocol for confirming the effect of a whale muscle extract. Graph showing results of open field test (measurement of spontaneous exercise amount) (A), Morris water maze test (long-term memory test) (B), and new object recognition test (medium-term memory test) (C) in 32-week-old mice It is. It is a graph which shows the result of the open field test (measurement of spontaneous exercise amount) in a 50-week-old mouse. It is a graph which shows the result of the novel object recognition test (medium term memory test) in a 50-week-old mouse. (A) is a change in the ratio of the number of times of contact with the object 1 (the same color for the first day and the second day) with respect to the total number of times of contact, and (B) is an object 2 with respect to the total number of times of contact with the first and second days. It is a graph which shows the result of the change of the ratio of the frequency | count of contact to (a color differs). It is the photograph (A) and schematic diagram (B) of a multiple T-shaped water maze used in the multiple T-shaped water maze test (long-term memory test). It is a graph which shows the result of the multiple T-shaped water maze test (long-term memory test) in a 50-week-old mouse. (A) is a graph showing a change in arrival time, and (B) is a graph showing a result of a change in the number of errors. It is a graph which shows the result of a Y-maze test (short-term memory test) in a 32 week-old mouse (A) and a 50-week-old mouse (B).

  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.

[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.

  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.

  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.

  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.

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).

  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.

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.

  “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.

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.

  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.

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.

  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.

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.

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.

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.

[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.

  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.

  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.

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.

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.

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.

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.

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.

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.

  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.

  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.

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.

[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.

  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.

<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.

<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.

<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.

<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-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.

Study example 1
<Examination of target mice and feeding period>

  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).

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).

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”.

  Table 1 shows the composition of the LSO meal and JP meal. The unit of each number is mass (%).

  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.

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).

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 (%).

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.

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).

<< 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.

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.

<< 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 (%).

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.

<< 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.

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.

  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.

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.

  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 (%).

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. .

  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.

Claims (4)

  An agent for preventing and improving medium- to long-term memory impairment, characterized by comprising a whale muscle extract extracted from whale muscle.   The medium / long-term memory disorder preventive / ameliorating agent according to claim 1, which contains balenin as an active ingredient.   The medium / long-term memory disorder prevention / improvement agent according to claim 1 or 2, which is used for the prevention and / or improvement of learning memory impairment due to senile or Alzheimer's dementia.   A dementia prevention / amelioration agent comprising the medium / long-term memory disorder prevention / improvement agent according to any one of claims 1 to 3.