JPH07173059A - Agent for promoting synthesis of nerve growth factor - Google Patents

Abstract

PURPOSE:To obtain an agent promoting the synthesis of nerve growth factor, containing theanine as an active component and useful for the prevention and treatment of Alzheimer's disease and diseases caused by the damage on peripheral neurocytes. CONSTITUTION:This agent for promoting the synthesis of nerve growth factor contains theanine which is a kind of amino acid rich in tea as an active component. It is effective for promoting the synthesis of nerve growth factor having actions on the differentiation, survival and keeping of the function of peripheral sympathetic neurocyte, sensory neurocyte, procephalic basal ganglia cholinergic neurocyte of central nervaus system, striatal intrinsic cholinergic neurocyte, etc. It can be administered by oral or parenteral administration, however, it is preferable to take the agent by adding to daily foods and drinks. The amount of theanine in the nerve growth factor synthesis promoting agent is so as to reach 0.1-40% in various foods and drinks, and the foods and drinks incorporated with theanine are administered in an amount to take 50-5,000mg of theanine per day.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nerve growth factor synthesis promoter, and more specifically to peripheral sympathetic nerve cells, sensory nerve cells and forebrain basal ganglia cholinergic nerve cells of central nerve cell system containing theanine as an active ingredient. TECHNICAL FIELD The present invention relates to a nerve growth factor (Nerve growth factor) synthesis promoter having an action of maintaining differentiation and survival / function of endogenous cholinergic neurons and striatum and a method of using the same.

[0002]

2. Description of the Related Art Nerve growth factor is used for differentiation and survival of peripheral sympathetic nerve cells, sensory nerve cells, basal forebrain cholinergic neurons of the central nervous system, and striatal endogenous cholinergic neurons. It is a basic protein having a dimer structure in which the same polypeptide chain of 118 amino acids having a function maintaining action is non-covalently bound. Recently, it has been confirmed that this nerve growth factor is mainly present in the brain, particularly in the hippocampus and cerebral cortex of the central nervous system, and it acts on cholinergic neurons in the basal forebrain and regenerates or regenerates disconnected neurons. It has been shown to significantly promote germination. Degeneration of cholinergic neurons in the brain is one of the major lesions in Alzheimer's disease, and nerve growth factor is considered to be an essential factor for survival and function maintenance of these neurons. Expectations are rising that the factor may be applied to the treatment of Alzheimer's disease. In addition, since nerve growth factor is also involved in the repairing action against damage to peripheral nerve cells, it can be expected to have a therapeutic or preventive effect on diseases caused by nerve cell damage.

Under these circumstances, research on nerve growth factor itself and substances that promote the synthesis of nerve growth factor has been actively conducted, and a method for secretory production of human nerve growth factor by yeast (Bioscience and Industry, vol.49). , 1991)
And catecholamines (epinephrine, norepinephrine, dopamine) have been found as nerve growth factor synthesis promoters (Y. Furukawa et al., FEBS Lett., Vol.208).
(1986), 258).

However, in consideration of practical application such as prevention or treatment of Alzheimer's disease and diseases caused by damage to peripheral nerve cells, nerve growth factor is a polymer substance, and thus there is a problem in administration method. Further, since catecholamines are endogenous active substances and are hormones originally, their administration in the body for the purpose of promoting the synthesis of nerve growth factor may impair the quantitative balance in the body and may be dangerous.

[0005]

Therefore, the present invention does not affect other cells or organs, selectively has nerve growth factor synthesis promoting activity, and can be taken daily from the diet. It is to provide a nerve growth factor synthesis promoter.

[0006]

[Means for Solving the Problems] The present inventors have investigated the nerve growth factor synthesis promoting activity of theanine, which is one of the amino acids abundantly contained in tea, and as a result, found that this compound has a strong nerve growth factor synthesis promoting activity. It has been found that it has an action, and has completed the present invention. That is, the present invention relates to a nerve growth factor synthesis promoter containing theanine as an active ingredient and a method for promoting nerve growth factor synthesis, which comprises providing a human with a food or drink containing theanine.

The theanine used in the present invention is contained in a large amount in tea leaves, especially in gyokuro, sencha and matcha, and the content thereof is 1 to 1.
It is 2.5 g / 100 g, and accounts for about 50% of tea leaf amino acids. In this way, theanine is a highly safe substance that can be taken from the green tea you drink on a daily basis. It is also known that theanine is absorbed by ingestion and taken up in the brain (R. Kimura and T. Murata, Chem. P.
harm. Bull., 19, 1971, p1257), suggesting that it not only promotes nerve growth factor synthesis in peripheral sympathetic nerve cells,
It is a substance that can also promote nerve growth factor synthesis in nerve cells in the brain.

As a method for producing theanine, a method of extracting from tea leaves and a method of synthesizing glutamic acid or glutamine and ethylamine are known. For example, glutamic acid is benzylated to protect the carboxyl group, and then the amino group is protected with trityl chloride. Then, this compound is reacted with an ethylamine aqueous solution, and then a protective group is eliminated to obtain theanine (Chemical synthesis, Sugiyama, Bioscience, Biotechnology and Biochemistry, Vol. 56, 1992, p. 689), glutaminase A method for enzymatically producing theanine by reacting glutamine and ethylamine in the presence of (Baljan et al., Bioscience, Biotechnology and Biochemistry, 57, 1993, p. 481) and tea tissue culture cells were used. Method for producing theanine (JP-A-3-
187388).

The nerve growth factor synthesis promoter of the present invention can be used either orally or parenterally, but it is preferable to use it by incorporating it into food or drink since it can be taken from daily diet. The foods and drinks referred to here include not only beverages and foods, but also liquor, favorite foods such as cigarettes, feeds, foods, mouthwashes, cosmetics such as toothpaste, etc.
It means all the products that can take theanine, including pharmaceuticals such as oral sachets, troches, and oral solutions, and quasi-drugs. Specific examples of these foods and drinks include tea drinks, coffee drinks, soft drinks, seasonings, confectionery,
In addition to normal food and drink such as syrups, processed fruits, processed vegetables, pickles, meat products, fish products, delicacies, canned and bottled products, alcoholic beverages, instant foods, livestock and cultured fish, etc. There are animal feed, foodstuffs, troches, capsules, tablets, oral liquids, liver oil drops, mouthwash, mouthwash, mouthwash, etc. These forms are arbitrary, solid, paste, liquid etc. Either is fine.

Further, when the nerve growth factor synthesis promoter of the present invention is ingested parenterally, it should be used as a suppository so that it can be absorbed through the mucous membrane in the form of injection, drip and solid or suspension viscous liquid. In addition to local tissue administration, intradermal, subcutaneous, intramuscular or intravenous injection, topical application,
Topical administration methods such as nebulization and intravesical injection can also be used.

The blending amount of theanine in the nerve growth factor synthesis promoter of the present invention may be appropriately determined in consideration of the purpose of use and the like, but usually 0.1 to 4 for various foods and drinks.
It is 0%, preferably 1 to 10%. Furthermore, according to the present invention, by supplying humans with the theanine-added food and drink so that the daily intake of theanine is 50 to 5000 mg, nerve growth factor synthesis is promoted in the body, and Alzheimer's disease and peripheral nerves are stimulated. Methods for treating or preventing diseases caused by cell damage are provided.

[0012]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples. Example The brain of a rat just after birth was excised, the meninges were removed, and then the pieces were shredded. The brain was trypsinized and cultured with a culture medium containing fetal bovine serum for 2-3 days at 37 ° C. in the presence of 5% carbon dioxide. Subsequently, the medium was changed to a serum-free medium and the cells were cultured under the same conditions for 3 days. Furthermore, the serum-free medium was replaced once every 3 days and cultured for 6 days to prepare static astrocytes. Theanine is added to the resting astrocytes at 1.4, 4.
1, 12.3, 37.0, 111 and 333 μg / ml were added, and the cells were cultured for 24 hours.

The concentration of nerve growth factor in this culture was measured by the enzyme immunoassay developed by Furukawa et al. (Furukawa et al., Journal of
Neurochemistry, 40, 1983, p. 734)
Was measured using. The above-mentioned concentrations of epinephrine were used for comparison. The results are shown in Fig. 1. As is clear from the figure, theanine showed a nerve growth factor synthesis promoting activity equivalent to that of epinephrine.

[0014]

INDUSTRIAL APPLICABILITY The nerve growth factor synthesis promoter of the present invention is highly safe because it contains theanine, which is abundantly contained in tea, as an active ingredient, and is easily taken into the body by oral ingestion. It can be used by adding it to food and drink. This nerve growth factor synthesis promoter can be very effectively utilized for treatment and prevention of Alzheimer's disease and diseases caused by damage to peripheral nerve cells.

[Brief description of drawings]

FIG. 1 is a graph showing the activity of promoting the synthesis of nerve growth factor by theanine or epinephrine.

Front page continued (72) Inventor Masahiko Hara 2-1-17 Fujieda, Fujieda City, Shizuoka Mitsui Norin Co., Ltd. Food Research Institute

Claims (2)

[Claims] 1. A nerve growth factor synthesis promoter containing theanine as an active ingredient. 2. A method for promoting the synthesis of nerve growth factor, which comprises providing a human with a food or drink containing theanine.