JPH0358926A - Cerebral function-improving composition, learning ability-improving agent, mneme-improving agent, dementia-preventing agent, dementia remedy and functional food having cerebral function-improving activity - Google Patents

Abstract

PURPOSE:To provide a cerebral function-improving composition, learning ability- improving agent, mneme-improving agent, dementia-preventing agent, dementia remedy or functional food having a cerebral function-improving effect by compounding an eicosapentaenoic acid as an active ingredient. CONSTITUTION:Eicosapentaenoic acid (EPA) or a derivative thereof, e.g. at least one kind of fatty acids, phospholipids, triglycerides or the salt, amide or alcoholyzed ester of the EPA is compounded as an active ingredient to pro vide the above-mentioned drug or functional food having a cerebral function- improving activity, thereby improving a learning ability and a mneme, previously preventing a dementia caused by a cerebral disoder and exhibiting an activity for treating various dementias.

Description

Detailed Description of the Invention "Industrial Application Field" The present invention relates to a substance having the effect of improving brain function, that is, a brain function improving composition, and a drug embodied using the brain function improving composition. The present invention relates to a learning ability enhancer, a memory enhancer, a dementia preventive agent, a dementia therapeutic agent, and a functional food having a brain function improving effect.

``Conventional technology'' In recent years, many studies and studies have been conducted in various fields regarding substances and methods that improve brain functions such as learning ability, memory, and dementia, and the results are being announced little by little.

According to the research, the methods to improve brain function that have been studied in the past include improving brain energy metabolism, which allows brain cells to efficiently absorb nutrients and activate their functions, and improving cerebral blood circulation. It is broadly divided into cerebral circulation improvement methods that aim to supply sufficient nutrition and oxygen to brain cells, and research is progressing on drugs and treatments that have pathological effects for each. Dementia) is recognized as being divided into two types: Alzheimer's dementia, which is caused by nervous system disorders, and cerebrovascular dementia, which is caused by cerebrovascular disorders, and there are drugs and treatments for each type. It appears that research is underway.

However, research in this field is still far from being fully researched and elucidated, both in terms of theory and practical application. There are fewer substances and drugs.

Examples of memory enhancers and senile dementia therapeutics that have been announced in recent years include: ■2-(7-inzonyloxymethyl)
A memory enhancer containing morpholine or its acid addition salt as an active ingredient (JP-A-56-123915); ■ A therapeutic agent for Alzheimer's disease characterized by consisting of a salt of deferoxamine to which pharmaceutically acceptable tucolic acid has been added ( Japanese Unexamined Patent Publication No. 1983-
12123), ■Memory improving agent containing a dipeptide compound represented by H-X-Y-OH (in the formula, X and Y are different and mean Tyr or Arg)
70719), ■3.7-Sihydro-3-methyl-1
-(5-oxohexyl)-7-broby-IH-purine-2,6-dione is a therapeutic agent for memory disorders containing as an active ingredient (Japanese Unexamined Patent Publication No. 61-229823), and other treatments for geriatric memory disorders. To some extent, the PCT international application (Patent Application Publication No. 1988-501564) has been filed as a law.

As society has become more sophisticated in recent years, the development of such substances and drugs has been desired not only medically but also socially.

"Problems to be Solved by the Invention" The present invention addresses the above-mentioned needs by improving brain function,
Through this, we aim to realize a functional food that enhances learning ability, enhances memory, prevents and treats senile dementia, and has the effect of improving brain function.

The present inventors have been researching the physiological and drug activities of eicosabencitric acid, which is abundantly contained in oils obtained from herrings and sardines. , has surprisingly strong effects on improving learning ability, improving memory, and preventing and treating dementia. These substances exist as part of the composition of foods in nature, and their safety has been empirically confirmed. The present invention has been completed based on the discovery that it is extremely useful as a drug or food that has the effect of improving brain function.

"Means for Solving the Problems" In the present invention, eicosaben citric acid (hereinafter referred to as r
It is called EPAJ. ) is C20I(3o02, molecule f
It is a linear bencitric acid with i302.49 and a carbon number of 20 having a cis-double bond at the 5.8°, 11, 14, and 17th positions.

It is contained in large amounts in fish oils such as herrings and sardines, and has also been detected as a phospholipid in various organs such as the liver of mammals. In recent years, it has been discovered that EPA has physiological effects such as preventing hypercholesterolemia by lowering plasma cholesterol and suppressing platelet aggregation ability. It is attracting attention as being effective in the prevention and treatment of thrombotic diseases such as cerebral infarction and color.

However, the pathological effects of this EPA, such as improving learning ability, improving memory, and preventing and treating dementia, have not yet been reported.

The present inventor has found through experimental results that the EPA has pharmacological effects that are effective in improving learning ability, improving memory, and preventing and treating senile dementia.
The aim is to utilize these pharmacological effects to create products such as drugs and foods.

Hereinafter, the above pharmacological effects will be explained in detail based on experiments. Specifically, rats fed a diet containing at least one kind of eicosapentaenoic acid derivative as an active ingredient were used together with control rats to test the effect of improving learning ability and memory using a delayed discrimination reaction device. It is for conducting experiments.

In other words, in order to examine whether EPA has an effect on improving learning ability, we prepared Wistar rats, feed containing EPA ethyl ester as an active ingredient, and a delayed discrimination reaction device, and placed the rats in the delayed discrimination reaction device. In addition, we conducted the following experiment.

First, the Wistar rat is a male Wistar rat 4
A total of 60 adult rats were prepared and divided into 4 groups of 15 rats each, with 3 test groups and 1 control group depending on the type of feed fed for a predetermined period.

Next, in the experiment, the test feed that was divided into three test groups and one control group was a feed containing the following ingredients. In other words, the compound feed used in the experiment is composed of raw materials with the mixing ratio shown in Table 1, and the fatty acid composition of the fat that is its constituent component is different between the three types of tests as shown in Table 2. Try to use feed.

Table 1: Comparison of each ingredient in the feed Experimental Example 1. 〉 ” Experiment on the learning ability improvement and memory ability improvement effect of EP A ester group PA.

Fifteen male twin star rats, 4 weeks old, are preliminarily fed for one week and then fed with a test feed mixed with ethyl ester containing DMA (test feed group E in Table 2) for 18 weeks. Then, for 2 weeks, Shapp was used to reduce the rat's body weight to 85%.
ing, provide initial training and get used to the experimental equipment.

After 6 weeks of initial training, the correct response rate of the control group was 50%.
%, so I entered the main exam. Below, like this, E
The group of rats fed with the test sample is referred to as the "EPA ester group."

The experiment was conducted with 15 animals in the EPA ester group, one trial per day (24 times) for 30 days, and the results were measured.

In the experimental method, an animal is first placed in a delayed discrimination reaction experimental apparatus (FIG. 1). There are two lever switches on the left and right on the front panel of the experiment box, and there are red lamps (Ll, L2) above each lever.
) An orange lamp (L3) is installed in the center of the panel, and a concave tray connected to an automatic feeder is installed on the center floor. Ll
Alternatively, L2 is turned on for 5 seconds, L1 or L2 is turned off for 5 seconds, and L3 is turned on after a certain period of time.

The delay time at that time is 4.16.32 seconds are repeated at random at the same ratio, and if you press the switch on the lighting lamp side within 15 seconds, it will be a positive response and food will be fed from the automatic feeder on the center floor. give. If you press the switch on the opposite side, it will be a false response and no food will be fed.

The control group used rats that were fed and raised with a control feed containing a mixture of safflower oil and olive oil instead of EPA (control feed group in Table 2).

The results of the test for 30 days are shown in FIG.

<Experimental Example 2> Similar to Experimental Example 1, the results of an experiment using the EPA-triglyceride group are shown in FIG.

<Experimental Example 3> Similar to Experimental Example 1, the results of an experiment using the EPA phospholipid group are shown in FIG.

As mentioned above, the present invention provides that a composition containing at least one type of eicosabencitric acid or its derivatives as an active ingredient can improve brain function whether it is used as a drug or as a functional food. It has been found that this effect not only enhances learning ability and memory, but also improves brain function, such as preventing and treating dementia.

Therefore, the scope of the invention for which the inventor wishes to obtain a patent for the present invention is as follows.

The first invention to be patented is a brain function improving composition containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. This is the basic invention, and the following will be applied inventions.

The second invention for which a patent is sought is a learning ability enhancer containing at least one kind of eicosabencitric acid or its derivatives as an active ingredient.

The third invention for which a patent is sought is a memory enhancer containing at least one kind of eicosabencitric acid or its derivatives as an active ingredient.

The fourth invention for which a patent is sought is a dementia preventive agent containing at least one kind of eicosabencitric acid or its derivatives as an active ingredient.

The fifth invention for which a patent is sought is a dementia therapeutic agent containing at least one kind of eicosabencitric acid or its derivatives as an active ingredient.

The sixth invention for which a patent is sought is a brain function improving effect characterized by mixing a brain function improving composition containing at least one or more of eicosabencitric acid or its derivatives as an active ingredient into a food. It is a functional food with

The seventh invention for which a patent is sought is the first invention to the sixth invention.
A composition for improving brain function, a learning ability enhancer, a memory enhancer, a dementia preventive agent, a dementia therapeutic agent, or a brain function improving agent, wherein the eicosapentaenoic acid derivative described in the invention is a fatty acid, phospholipid, or triglyceride extracted from natural oils and fats. It is a functional food that has ameliorating effects.

The eighth invention for which a patent is sought is the first invention to the sixth invention.
The derivative of eicosapentaenoic acid described in the invention is a salt,
A brain function improving composition, a learning ability enhancer, a memory ability enhancer, which is an amide or an ester obtained by alcoholysis;
It is a dementia preventive agent, a dementia treatment agent, or a functional food that has the effect of improving brain function.

Supplement [1] Drug The eicosapentaenoic acid used in the present invention can be used as the acid itself, or can be used as a pharmacologically acceptable salt, ester, or amide derivative.

Preferred salts for this purpose include sodium or potassium salts, and also salts with organic bases such as amines.

Furthermore, preferred esters include esters with polyhydric alcohols such as aliphatic triglycerides, and esters with lower alkyl alcohols such as methanol and ethanol.

Eicosapentaenoic acid and its pharmacologically acceptable salts and derivatives according to the present invention can be used as a learning ability enhancer, a memory enhancer, a dementia treatment agent, and a preventive agent as they are, and can also be used as a pharmaceutically acceptable agent. Accordingly, it can be formulated in admixture with pharmaceutically acceptable diluents and/or other pharmacologically active substances, or in dosage unit form. Possible forms of such medicines include powders, granules, tablets,
Sugar-coated tablets, capsules, tablets, liquids, ampoules, injections, etc. are included.

Further, the formulation means includes an embodiment in which the compound is contained in the form of a mixture with a pharmaceutically acceptable diluent. Here,
Examples of diluents include excipients, plate fillers, binders, wetting agents, surfactants, activators, dispersants, buffers, flavoring agents, fragrances, preservatives, solubilizing agents, solvents, and coatings. However, it is not limited to these, and it can also be used as a mixture of one or more of these.
Such pharmaceutically acceptable diluents may also be used in mixtures with other pharmacologically active substances.

Formulation may be carried out in any known manner, eg by mixing the active ingredient with a diluent, eg into granules, and then shaping the composition into tablets.

Some examples of formulations according to the invention are described.

·tablet It was prepared by a tablet formulation containing the following ingredients:

Eicosapentaenoic acid 300mg (Assuming EPA concentration of 95%) starch lactose Polyvinylpyrrolidone Magnesium stearate Butylated hydroxytoluene 3mg 250n+8 3.5mg 3.5mg ppm The tablets were coated with sugar. However, other coatings may also be used.

- Hard capsules Hard capsules were filled with 600 mg of the above untabletted powder formulation to obtain hard capsules.

- Soft capsules 300 mg of ethyl eicosapentaenoate was suspended in fatty acid triglyceride, an antioxidant was added and soft capsules were filled according to a conventional method to obtain soft capsules.

*The purity of EPA used in the drug should be 50% or more, but preferably 90% or more.

Supplement [2] Functional food The functional food containing eicosaben citric acid according to the present invention may be any oil or fat containing 10% or more of eicosapentaenoic acid, but in order to enhance eicosaben citric acid, Oils and fats containing 18% or more are desirable.

Next, examples of functional foods will be shown.

・Eicosaben Citric acid-containing margarine formulation example Liquid oil 25% Eicosapentaenoic acid Oil Hardened oil Monoglyceride Lecithin Flavor added Water Skim milk powder Salt Vitamin E 32.3% 1O80% 42.3% 0.25% 0.1% 0.044% 12.566% 1.0% 1.4% 0.04% 00% - Example of formulation of mayonnaise containing eicosapentaenoic acid Egg yolk 8 Salad oil 70 25% eicosapentaenoic acid oil 10 Vinegar 11 Salt 0.8
Seasoning 0.2 Note that the form of the functional food is not limited to these foods.

"Effects of the present invention" As mentioned above, the present invention provides eicosapentaenoic acid (EP).
A brain function-improving composition containing at least one of A or its derivatives as an active ingredient enhances brain function or recovers from brain damage, and uses its pharmacological effects to produce drugs and functional foods. or by mixing it with appropriate pharmacologically acceptable carriers, excipients, and diluents to produce solutions, powders, granules, tablets, injections, capsules, spreaders, etc. It may be processed into a desired form and commercialized. It goes without saying that the solution may be administered orally or parenterally in the form described above. It goes without saying that when administering medication, the dose m may be increased or decreased depending on age, body weight, symptoms, etc.

Thus, according to the present invention, in the form of a drug or a food product,
When at least one of eicosabencitric acid or its derivatives, which is a substance that has the effect of improving brain function, is ingested into the human body, its active ingredients enhance learning ability and memory. It turns out.

In addition, as in the present invention, the brain function improving composition is used as a drug,
Or, by ingesting it as food, it is effective in preventing dementia caused by brain damage or in treating various types of dementia.

- Figure % Let's learn from the export test of export countries (EPA
Work now - Nisko Shin figure % 4? ! +l tik et al. After the 19th line, add the following.

[Brief explanation of drawings]

Figure 1 is an explanatory diagram showing the scheme of the delayed discrimination reaction of the animals in Experimental Example 1.2.3, Figure 2 is a graph showing the results of the delayed discrimination reaction test in Experimental Example 1, and Figure 3 is the experimental FIG. 4 is a graph showing the results of the delayed discrimination reaction test of Example 2. FIG. 4 is a graph showing the results of the delayed discrimination reaction test of Experimental Example 3. November 28, 1999 (Shipping) As shown in the attached sheet.

Claims (8)

[Claims] (1) A brain function improving composition containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. (2) A learning ability enhancer containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. (3) A memory enhancer containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. (4) A dementia preventive agent containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. (5) A dementia therapeutic agent containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient. (6) A functional food having a brain function improving effect, which is characterized in that a brain function improving composition containing at least one kind of eicosapentaenoic acid or its derivatives as an active ingredient is mixed into the food. (7) A brain function improving composition, a learning ability enhancer, wherein the eicosapentaenoic acid derivative according to claim 1, 2, 3, 4, 5, or 6 is a fatty acid, a phospholipid, or a triglyceride extracted from natural fats and oils; A functional food that is a memory enhancer, a dementia preventive agent, a dementia treatment agent, or has a brain function improving effect. (8) A brain function improving composition, a learning ability enhancer, wherein the eicosapentaenoic acid derivative according to claim 1, 2, 3, 4, 5, or 6 is a salt, an amide, or an ester obtained by alcoholysis. , a memory enhancer, a dementia preventive agent, a dementia treatment agent, or a functional food that has a brain function improving effect.