JPH0656671A - Functional food - Google Patents

Abstract

PURPOSE:To provide the novel non-toxic functional food containing sn-glycerol-3- phosphocholine as an active ingredient and having a learning ability-improving effect. CONSTITUTION:sn-Glycerol-3-phosphocholine is added as an active ingredient to one of various foods to provide the objective food, where the ingredient is to be added so as to reach a daily dose of 50mg to 10g/60kg of the body weight of a person. The sn-glycerol-3-phosphocholine is a pale yellow, granular and strongly hygroscopic water-soluble substance which is a phosphatidyl choline deacylated product comprising glycerol, phosphoric acid and choline, the glycerol and the phosphoryl choline being to each other through a phosphate ester bond.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to functional foods. More specifically, it relates to a functional food for improving learning ability.

[0002]

2. Description of the Related Art In recent years, the search for substances that enhance brain functions such as learning ability and memory ability has been studied in various fields.
As a result, substances that enhance brain function are classified into cerebral circulation improving agents that improve blood circulation in the brain and increase the supply of oxygen and nutrients to brain cells, and cerebral metabolism improving agents that activate the function of brain cells. Substances have been chemically synthesized aiming at pharmaceuticals. On the other hand, α-linolenic acid and docosahexaenoic acid are known as natural food ingredients that improve learning ability. [Alpha] -linolenic acid described in Biochemistry, Vol. 59, p. 1235, 1987 was used in a rat lightness discrimination learning experiment.
Docosahexaenoic acid described in Japanese Patent No. 9827 is known to improve the positive reaction rate (%) in a rat Y-shaped maze light / dark discrimination food feeding experiment.

Furthermore, sn-glycerol-3-phosphocholine (hereinafter abbreviated as GPC), which is a natural food ingredient, is L-
Also referred to as α-glycerylphosphorylcholine or glycerophosphocholine, the description in JP-A No. 119926/1987 describes peripherally acetylcholine-like arterial relaxing action, and the description in Japanese Patent Publication No. 28580/1990 discloses centrality. Was found to be effective in treating vascular or neurotraumatic diseases, and increasing NREM sleep. In recent years, from the idea of actively incorporating the function of natural food ingredients, there is a social demand for the development of a food product designed and processed so that the function can be sufficiently expressed in the living body.

[0004]

However, although the expression of the function of substances that enhance the function of the brain generally requires long-term intake, many of these chemically synthesized substances have side effects. Extremely strong and difficult to administer for long periods of time. An object of the present invention is to provide a novel non-toxic functional food that is easily obtained from natural foods and has an effect of improving learning ability.

[0005]

Means for Solving the Problems As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that phosphatidylcholine (hereinafter abbreviated as PC), which is a main component of phospholipids of soybeans and egg yolks, has physiological activity and drug activity. As a result of an animal test, it was found that this substance or this degradation product had a surprisingly powerful effect of improving learning ability. In particular, GPC, which is a decomposed product, is present as a constituent of PC, which is a constituent of foods in the natural world, can be easily obtained by hydrolysis, and is physiologically safe. Therefore, it has an effect of improving brain function. The present invention has been completed by finding that it is extremely useful as a food. The present invention is a functional food containing GPC as an active ingredient.

[0006] GPC is a deacylated product of PC, which is a main constituent phospholipid that constitutes a biological membrane in a living body. Glycerol and phosphorylcholine are bound by a phosphoric acid ester to form a pale yellow, granular and strong mixture of glycerol, phosphoric acid and choline. It is a water-soluble substance that exhibits hygroscopicity. The three-dimensional structure of GPC metabolized from PC in the living body and GPC existing as a constituent of PC which is a natural food ingredient is the same.

Naturally-structured GPC is readily available by hydrolysis of natural PC. For example, GPC with a natural structure
Japanese Unexamined Patent Publication No. 119926/1987 and Japanese Unexamined Patent Publication No. 1988/6
It can be obtained by the chemical hydrolysis method of natural soybean PC described in Japanese Patent No. 1490. In order to process GPC into a food that can be easily consumed, it is preferable to uniformly disperse GPC in the food material. Specific forms include an aqueous solution and a powder. GPC can be made into a colorless and transparent aqueous solution by a homomixer, a juice mixer, an ultrasonic emulsifier, or the like. A 10% by weight solution of GPC can also be obtained by such a dispersion method.

Various sweeteners, edible organic acids (eg acetic acid, lactic acid, succinic acid, citric acid, malic acid, etc.) dairy products (eg condensed milk, evaporated milk, lactose, fermented milk, etc.), concentrated juice, soup, liquor are added to this aqueous solution. , Sauce, fruit juice, essence, fragrance, etc. can be added as appropriate and used for processing various foods or as a beverage. Further, a powder can be obtained by a method of adding 25 to 70% by weight of carbohydrate (eg, starch, dextrin, lactose, etc.) and protein (eg, casein, albumin, etc.) to GPC in the above aqueous solution and then spray-drying. .

Since the powder thus obtained has good fluidity and is water dispersible, it can be processed into pizza, bread, cookie, pie, etc. as a raw material for confectionery bread in addition to being used as the above-mentioned aqueous solution. Also, it can be mixed with skim milk or the like to be processed into an instant food. G in food
Along with increasing the PC content, amino acids, vitamins, and minerals can be supplemented to provide a comprehensive nutrition-enhancing food.

GPC is safe from the viewpoint of toxicity, and LD ₅₀ for oral administration to mice is 13,000 mg / kg.
Thus, the LD ₅₀ for intravenous administration is 650 mg / kg or more. The administration of the functional food having the learning ability improving effect of the present invention is carried out in an amount of 50 mg as GPC as an active ingredient.
10 g / body weight 60 kg / day can be orally administered.

[0011]

[Effect] Orally administered GPC is absorbed in the intestine with the same structure, or is absorbed into the intestine and then hydrolyzed to choline and glycerol-3-phosphate by GPC phosphoesterase in the intestine, and is then passed through the portal vein. Carried to the liver. As described above, GPC is promptly metabolized and excreted, so that there is no problem that long-term administration adversely affects or causes dependence.

[0012]

The present invention will be described in more detail with reference to the following examples. In the text, percentages represent% by weight. Example of GPC production Soy PC 10 in a 2 liter flask equipped with a calcium chloride tube
0 g was weighed and dissolved by adding 500 ml of distilled methanol, then 0.5 g of sodium methylate was added, and the mixture was allowed to stand at room temperature for 12 hours with stirring. The solvent in the reaction solution was evaporated under reduced pressure, 500 ml of chloroform was added to dissolve the residue, and the mixture was left at -20 ° C for 2 hours. The solvent was decanted, the residue was dissolved in 100 ml of methanol and then acidified with hydrochloric acid.

1 ml of this containing 500 ml of chloroform
The mixture was dropped into a 1-flask with stirring and left at -20 ° C for 2 hours. The precipitate was separated with a glass filter and washed with acetone. The washed product was dried under reduced pressure, and dried in a desiccator under vacuum with phosphorus pentoxide for 12 hours to give GPC2 as pale yellow granules.
7 g was obtained. The obtained GPC has a hygroscopic property, and is proton NMR (dissolved in CDCl ₃ and N (CH ₃ ) at 3.1 ppm).
Signal from ₃ ) and FAB / MS
The structure was identified from ([M ⁺ ]: 258), and the purity was 9 based on the choline content (Reinecke salt precipitation method: 41.0%).
It was 9.3%.

Toxicity of GPC A 36% GPC distilled aqueous solution was prepared, and this was used as a test solution and was orally administered once to each of 10 mice of 5 weeks old, 20 to 24 gdd Y-N mouse, by a gastric sonde. LD ₅₀ value is 13,365 mg / kg for males and 13,688 mg / kg for females
Met. A 2% GPC physiological saline solution was prepared and used as a test solution for 22 to 24 g of a ddY-N mouse 5-week-old male,
Ten females each were injected once into the tail vein at a rate of 10 to 15 seconds using a tuberculin syringe and a 1/4 needle. LD ₅₀ values are 655 mg / kg for males and 706 mg / k for females
It was g.

Pharmacological test As experimental animals, male F344 rats (body weight 250 to 300 g) aged 10 to 14 weeks were used. We confirmed the formation process of so-called operant learning, which is discontinuous active avoidance learning that avoids electric shock given after conditioning stimulus by pushing the lever,
The effect of GPC on the process was examined. The outline of the experimental apparatus is shown in FIG. A transparent acrylic resin box (200 × 100 × 100 mm) was prepared as an experiment box.
In the box, stainless steel round bars (outer diameter: 5 mm) were arranged on the floor surface at intervals of 1.5 cm to serve as electric shock electrodes. A lever connected to the microswitch was inserted and fixed in the box at a position of 2 cm on the floor of the box. A light emitting diode was attached to the inner wall of the experimental box so that it could be confirmed that the lever was operated reliably, and the diode was turned on when the lever was pressed firmly. Buzzer sound generation, light emitting diode
The personal computer was used to control the power supply to the floor and the detection of lever pressing.

In the learning experiment schedule, the following 1-3
The above steps were set as one trial, and 100 trials were continuously performed for each animal to make one session. Presentation of buzzer sound for 1.5 seconds 2. If the lever is pressed even once before the end of the buzzer sound, the light emitting diode is turned on and the power supply circuit to the floor is cut off. If there is no lever operation, DC70V to the floor, 0.1
The mA was energized for 4 seconds and rested for 4.25 seconds. The experiment was conducted only once a day, and the training was conducted every two days. The result is that the average electric shock avoidance rate is 90%.
It shows up to the 5th session beyond.

Test Example 5 experimental animals were each administered with 1 ml of physiological saline in which 0.3 to 0.5 mg of GPC was dissolved. That is, GPC
The dose was 1-2 mg / kg. By the end of the experiment, all the experimental animals showed no weight loss or behavioral abnormality. One session was divided into 5 blocks every 20 trials, and GPC was intraperitoneally administered immediately before the learning experiment of the 1st block and the 2nd block, and the average value of the electric shock avoidance rate for each block in 1 session is shown in FIG. Indicated. The learning establishment process appears in one session. The total number of lever pushes and the electric shock avoidance rate were averaged for each session and shown in FIG. 3 together with the standard deviation.

Comparative Example 1 1 ml of physiological saline was administered to each of 11 experimental animals. By the end of the experiment, all the experimental animals showed no weight loss or behavioral abnormality. One session was divided into 5 blocks every 20 trials, and physiological saline was intraperitoneally administered immediately before the learning experiment of the 1st block and the 2nd block, and the average value of the electric shock avoidance rate for each block in the 1st session was 4th.
As shown in the figure. The learning establishment process appears in one session. The total number of lever pushes and the electric shock avoidance rate were averaged for each session and shown in FIG. 5 together with the standard deviation. The number of lever pushes tended to decrease as the number of sessions increased, and a mirror image showed the learning success process in this experimental system.

Results From the results of FIGS. 2 to 5, it was proved that the GPC-administered group promoted the establishment of learning more than the physiological saline-administered group, and that GPC had the effect of improving the learning efficiency. The difference in the avoidance rate between the last block of each session and the first block of the next session means memory between sessions, and G
The PC-administered group maintains better memory between sessions than the saline-administered group. GPC regarding the number of lever pushes
Although there was no significant difference between the administration group and the physiological saline administration group, the avoidance rate was greatly improved in the GPC administration group, so this effect simply increased the motility of the experimental animals. Not due to.

[0020]

EFFECT OF THE INVENTION GPC, which is the active ingredient of the present invention, is as safe as oral toxicity as PC, and is easily water-soluble and easily powdered. Since it can be added to, it can be a functional food having a learning ability improving effect. Moreover, since orally administered PC is hydrolyzed after intestinal absorption and is metabolized to GPC, this effect is expected by ingesting PC.

[Brief description of drawings]

[Figure 1] Schematic diagram of the learning experiment device

[Fig. 2] Electric shock avoidance rate for each block when each session was divided into 5 blocks in the GPC administration group. GP
C was intraperitoneally administered immediately before the start of the block indicated by the arrow.

[Fig. 3] Mean value and standard deviation of the number of lever pushes (upper row) and the electric shock avoidance rate (lower row) per session in the GPC administration group. GPC was intraperitoneally administered just before the start of the block indicated by the arrow.

[Fig. 4] Electric shock avoidance rate for each block when each session was divided into 5 blocks in a physiological saline administration group.
Saline was administered intraperitoneally just before the start of the block indicated by the arrow.

[FIG. 5] Mean value and standard deviation of the number of times of lever pressing (upper row) and the electric shock avoidance rate (lower row) in each session in the physiological saline administration group. Saline was administered intraperitoneally just before the start of the block indicated by the arrow.

Claims (1)

[Claims] 1. A functional food containing sn-glycerol-3-phosphocholine as an active ingredient.