JP7588892B2 - Oral Compositions - Google Patents

Description

Patent Act Article 30, paragraph 2 applies. Publication start date: March 7, 2016. Publication address: http://www.caa.go.jp/foods/docs/ichiran.xls https://www.fld.caa.go.jp/caaks/cssc02/pdf/A244-ippan.pdf https://www.fld.caa.go.jp/caaks/cssc02/pdf/A244-kihon.pdf https://www.fld.caa.go.jp/caaks/cssc02/pdf/A244-kihon.pdf jp/caaks/cssc02/pdf/A244-kinou. pdf https://www. fld. caa. go. jp/caaks/cssc02/pdf/A244-anzen. pdf

The present invention relates to a composition used for sound sleep, and more specifically, to an oral composition containing theanine and certain other ingredients.

In modern society, many people suffer from insomnia due to autonomic nervous system disorders caused by various factors such as changes in lifestyle and increased stress. Insomnia has various effects such as reduced concentration and work efficiency, fatigue and lethargy, physical discomfort, and depression, so good quality, restful sleep is desired from the perspective of social life and health.

Such compositions for restful sleep have been proposed as steam-distilled water of lavender (see Patent Document 1), compositions containing hastatoside (see Patent Document 2), and compositions containing verbenaline (see Patent Document 3).

JP 2006-104073 A JP 2005-154311 A JP 2005-154310 A

The objective of the present invention is to provide a composition that has a high sleep-inducing effect.

As a result of extensive research and studies into further improving the functionality of theanine, which has a sleep-inducing effect, the inventors discovered that an even better sleep-inducing effect can be achieved by combining theanine with specific ingredients, leading to the completion of the present invention.

That is, the present invention relates to an oral composition comprising theanine and at least one other ingredient selected from the group consisting of the following (a) and (b):
(a) at least one plant material selected from barley, sweet potato, oat, rice, rooibos, pu-erh, jasmine, and terminalia; (b) at least one functional material selected from lactic acid bacteria and fructooligosaccharides.

The present invention also relates to a functional food composition for sound sleep, which contains theanine as an active ingredient and is formulated with at least one other ingredient selected from the group consisting of (a) and (b) above.

The present invention relates to a functional food composition for promoting sound sleep, which contains theanine as an active ingredient and is formulated with at least one other ingredient selected from the group consisting of (a) and (b) above.

The present invention relates to a functional food composition for sleep that contains theanine and at least one other ingredient selected from the group consisting of (a) and (b) above, and that inhibits the influx of Ca ions into nerve cells.

The present invention relates to a functional food composition for sound sleep that contains theanine and at least one other ingredient selected from the group consisting of (a) and (b) above, which promotes the inhibition of calcium ion influx into nerve cells.

The present invention relates to a functional food composition for sleep that contains theanine and at least one other ingredient selected from the group consisting of (a) and (b) above, and binds to glutamate receptors in nerve cells.

The present invention further relates to a functional food composition for sound sleep that contains at least one other ingredient selected from the group consisting of (a) and (b) above, which promotes the binding of theanine to glutamate receptors in nerve cells.

The present invention relates to a method for producing a functional food composition for sleep, which is characterized by blending at least one other ingredient selected from the group consisting of (a) and (b) above in an oral composition containing theanine.

The oral composition of the present invention can provide a high level of restful sleep by suppressing nervous excitation.

FIG. 1 is a graph showing the results of the intracellular Ca fluorescence intensity change ratio when the oral composition of the present invention (theanine + other ingredients) was applied to primary rat cerebral cortex-derived nerve cells.

The composition of the present invention is characterized by containing theanine and at least one component selected from the group consisting of the following (a) and (b) (hereinafter sometimes referred to as other component). The components (a) and (b) used together with theanine may be used alone (for example, only component (a)), or two or more may be used in combination. When two or more other components are used in combination, it is preferable to combine other components that have a high synergistic effect with theanine.

The oral composition of the present invention, by combining theanine with other ingredients, increases inhibitory neurotransmitters while suppressing the action of excitatory neurotransmitters, effectively suppressing nerve excitation, suppressing excessive excitement, and providing a restful sleep and relaxation effect.

[Theanine]
The theanine in the oral composition of the present invention is preferably L-theanine, regardless of the method of production, such as those obtained by extraction from plants, those obtained by chemical synthesis, those obtained by fermentation, etc. Theanine is commercially available as a reagent, food additive, etc., and commercially available products can be used.

[Other ingredients]
(a) Plant Material In the oral composition of the present invention, it is preferable to use at least one plant material selected from barley, sweet potato, oat, rice, rooibos, pu-erh, jasmine, and terminalia together with theanine.

These plant materials may be any part of the plant, such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant itself, processed plant products such as dried products, crushed products, juice, extracts, etc. can be used. Examples of crushed products include powders and granules. The juice and extracts may be in liquid form, but can also be used in paste form or as dry powder. Extracts can be obtained by extraction using a suitable solvent, and examples of the solvent that can be used include water (warm water, hot water), ethanol, and aqueous ethanol. Commercially available plant materials may be used.

(barley)
Barley is a plant of the genus Hordeum, family Poaceae, native to Central Asia, and two-rowed barley, six-rowed barley, etc. can be used. As the plant material of the present invention, stems and leaves are preferred, and young leaves are more preferred. Young leaf powder obtained by drying and finely pulverizing young leaves, and extracts from young leaves are particularly preferred.

(Sweet potato)
Sweet potato refers to a plant belonging to the Convolvulaceae family, and is generally called Satsuma Imo (sweet potato). There are no particular limitations on the variety of sweet potato, and examples thereof include Suio, Joy White, Koganesengan, Shiroyutaka, Satsuma Sachi, and Ayamurasaki. As the plant material of the present invention, stems and leaves are preferred, and young leaves are more preferred. Young leaf powder obtained by drying and finely pulverizing young leaves, and extracts from young leaves are particularly preferred.

(Oats)
Oats are plants of the genus Avena, family Poaceae, native to Patagonia, Chile, and their scientific name is Avena sativa. As plant materials for the present invention, ears, stems, and leaves are preferred, and dried powders obtained by drying and finely pulverizing ears, stems, and leaves, and extracts from ears, stems, and leaves are more preferred.

(Rice)
Rice is a plant of the genus Oryza in the family Poaceae. As the plant material of the present invention, rice (brown rice) is preferable, and rice milk produced from rice is particularly preferable. The type of rice is not particularly limited, and examples thereof include japonica and indica.

(Terminaria)
Examples of Terminalia include Terminalia bellirica (belerica), Terminalia catappa, Terminalia tomentosa, Terminalia citrina, Terminalia phellocarpa, Terminalia copelandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, Terminalia chebula, etc., and among these, Terminalia bellirica (belerica) is preferred. The part of the plant used as the plant material of the present invention is preferably the fruit. A dried powder obtained by drying and finely grinding the fruit, or an extract from the fruit is particularly preferred.

(Rooibos)
Rooibos is a plant belonging to the genus Aspalathus of the family Fabaceae, and the plant material in the present invention is preferably leaves and branches that are usually used for tea. Dry powder obtained by drying and finely grinding the leaves and branches, and extracts from the leaves and branches are particularly preferred.

(Pu'er)
Pu-erh is a type of Chinese tea (black tea) originating from Yunnan Province, People's Republic of China, and is available in both raw and aged varieties. In the present invention, the plant material is preferably leaves that are normally used as tea. Dry powder obtained by drying and finely pulverizing the leaves, or an extract from the leaves is particularly preferred.

(jasmine)
Jasmine is a plant belonging to the Oleaceae family, and the plant material in the present invention is preferably flowers that are usually used for tea. Dry powder obtained by drying and finely grinding the flowers, or an extract from the flowers is particularly preferred.
(b) Functional Ingredients In the oral composition of the present invention, it is preferable to use at least one functional ingredient selected from lactic acid bacteria and fructooligosaccharides together with theanine.

(Lactic acid bacteria)
Lactic acid bacteria include Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium adolescentis, Bifidobacterium mongoliense, Lactbacillus brevis, Lactbacillus gasseri, Lactobacillus acidophilus, Lactobacillus buchneri, Lactobacillus bulgaricus, Lactobacillus delburvecki, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus curvatus, Lactobacillus halivaticus, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, Lactobacillus sakei, Lactobacillus fructivorans, Lactobacillus hilgardii, Lactobacillus reuteri, Lactobacillus fermentum, Enterococcus faecalis (sometimes called Streptococcus faecalis), Enterococcus faesium (sometimes called Streptococcus faesium), Streptococcus thermophilus, Lactococcus lactis (sometimes called Streptococcus lactis), Leuconostoc mesenteroides, Leuconostoc oenos, Pediococcus acidilactici, Pediococcus pentosaceus, Staphylococcus carnosus, Staphylococcus xylosus, Tetragenococcus halophilus, Bacillus Examples of the lactic acid bacteria include Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus gasseri, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus paracasei, Enterococcus faecalis (Streptococcus faecalis), Enterococcus faesium (Streptococcus faesium), Streptococcus thermophilus, Lactococcus lactis (Streptococcus lactis), Bacillus coagulans, and Bacillus mesentericus. These lactic acid bacteria can be used alone or in combination of two or more. Depending on the dosage form and quality of the composition of the present invention, for example, lactic acid bacteria having properties such as heat resistance, acid resistance, sugar tolerance, salt tolerance, spore formation, etc. The method for obtaining the lactic acid bacteria is not particularly limited, and for example, lactic acid bacteria isolated from foods such as yogurt and vegetables, or commercially available products can be used.

These other ingredients act as promoters of theanine's sleep-inducing effects.

Examples of the oral composition of the present invention include so-called health foods, such as pharmaceuticals (including quasi-drugs), functional foods such as foods for specified health uses, foods with nutrient function claims, and foods with functional claims whose efficacy has been approved by a designated organization, as well as general foods, food additives, and feed. The oral composition of the present invention can be taken by anyone who is concerned about the above effects, regardless of gender or age. It is also preferable to take the composition 30 minutes to 2 hours before going to bed.

The oral composition of the present invention can be used as a composition for restful sleep, and there is no particular limitation on the composition for restful sleep, so long as it contains theanine and other specified ingredients and can be distinguished from other products in terms of its use for restful sleep. For example, the scope of the present invention includes products that indicate that the product has the ability to promote restful sleep on the product itself, packaging, instructions, or advertising materials. The composition for restful sleep of the present invention is not limited to products that indicate on the product packaging, etc., the combination of ingredients in the present invention (theanine and other specified ingredients) as the active ingredients for restful sleep. For example, the active ingredient may not be specified, theanine and other specified ingredients may be indicated as active ingredients, or only theanine may be indicated as the active ingredient.

Specific examples of the sleep-promoting composition of the present invention include medicines (including quasi-drugs) and so-called health foods. Examples of so-called health foods include those that claim to "improve sleep quality," "reduce fatigue and sleepiness upon waking," "reduce fatigue (feeling of tiredness and lethargy) upon waking the next morning," "provide healthy sleep," "refreshing awakening," "help reduce sleepiness upon waking and recover from fatigue," "support quality sleep at night," "support healthy sleep," and "support healthy sleep at night."

Examples of the form of the oral composition of the present invention include tablets, capsules, powders, granules, liquids, grains, rods, plates, blocks, solids, rounds, pastes, creams, caplets, gels, chewable tablets, and sticks. Among these, tablet, capsule, powder, granule, and liquid forms are particularly preferred. Specific examples include supplements, packaged beverages filled in PET bottles, cans, bottles, etc., instant beverages that are dissolved in water (hot water), milk, fruit juice, green juice, etc., and food additives. These are preferred because they are easy to drink during meals and can increase palatability.

The amount of theanine and other components (components of the present invention) contained in the oral composition of the present invention may be appropriately determined within the range in which the effects are achieved.

In general, when the oral composition of the present invention is a pharmaceutical or supplement, the components of the present invention are preferably contained in an amount of 0.1 to 100% by mass, more preferably 1 to 85% by mass, and even more preferably 5 to 70% by mass, of the total mass calculated on a dry weight basis.

When the oral composition of the present invention is a packaged beverage, the components of the present invention are preferably contained in an amount of 0.0001 to 30% by mass, more preferably 0.001 to 25% by mass, and even more preferably 0.01 to 20% by mass, calculated as the dry mass of the entire composition.

When the oral composition of the present invention is an instant beverage, the components of the present invention are preferably contained in an amount of 0.001 to 80% by mass, more preferably 0.005 to 70% by mass, and even more preferably 0.1 to 60% by mass, calculated on a dry weight basis.

In order to more effectively exert the effects of the present invention, the components of the present invention are preferably contained in an amount of 80% or more, more preferably 90% or more, even more preferably 95% or more, and particularly preferably 100% of the total oral composition of the present invention, calculated on a dry mass basis.

There is no particular limit to the amount of intake of the oral composition of the present invention, but from the viewpoint of more significantly exerting the effects of the present invention, it is preferable that the daily intake of the components of the present invention for adults is 50 mg/day or more, more preferably 100 mg/day or more, and even more preferably 150 mg/day or more. The upper limit is not particularly limited, but is, for example, 10,000 mg/day, and preferably 5,000 mg/day.

The oral composition of the present invention can be stored as a daily dose in a single container or divided into, for example, two or three containers so that the daily intake is the above-mentioned amount.

The blending ratio of theanine to other ingredients is preferably in the range of 1:0.001 to 1:50, more preferably 1:0.01 to 1:40, even more preferably 1:0.1 to 1:30, and particularly preferably 1:1 to 1:20, in terms of dry mass. By having the blending ratio of theanine to other ingredients in the above range, the effects of the present invention can be more effectively exhibited.

The oral composition of the present invention can be produced by known methods by adding, as necessary, ingredients other than the ingredients of the present invention that are acceptable for oral use.

The pH of the oral composition of the present invention when dissolved in water is not particularly limited, but is preferably in the range of pH 2.0 to 7.0, more preferably pH 3.0 to 6.5, and most preferably pH 4.5 to 6.5.

The present invention will now be described with reference to examples.
[Example 1]
1. Cell culture
(1) Primary rat cerebral cortex-derived nerve cells (manufactured by Thermo) were seeded at a cell density of 1.0×10 ⁴ cells/well into each well of a 96-well black plate coated with Poly-L-Lysine at ^a density of 2 μg/cm 2 .
(2) The cells were pre-cultured for one week in a _CO2 incubator at 37°C. The medium was changed every 1-2 days.
(3) After removing the medium from each well, 100 μL of medium containing the test substance adjusted to a predetermined concentration with normal medium was added to each well, and the cells were cultured in a CO ₂ incubator for 24 hours.
The normal medium used was 48.875 ml of Neurobasal medium (manufactured by Thermo) to which 125 μl of 200 mM Glutamax ^™ (manufactured by Thermo) and 1 ml of B27 Serum Free Supplement (50×) (manufactured by Thermo) were added.

Commercially available L-theanine was used for theanine. The other ingredients used together with L-theanine were the substances shown in Table 1.

2. Evaluation of intracellular Ca

It is generally believed that when NMDA receptors (glutamate receptors, an excitatory amino acid) on the surface of nerve cells are activated by an excitatory amino acid (glutamate), a large amount of Ca ions flow into the nerve cells, which then activates various Ca ion-dependent enzymes, causing nerve hyperexcitation. In this study, we investigated the effect of the test substance in suppressing the influx of Ca ions into nerve cells.

Specifically, the following tests were carried out.
Intracellular Ca was measured using Calcium Kit Fura2 (Dojindo Laboratories).
(1) After the above-mentioned 24-hour culture, the medium was removed from each well, which was then washed once with PBS(-), and 100 μL of Loading Buffer was added thereto, followed by culturing for 1 hour.
(2) The Loading Buffer was removed, the plate was washed once with PBS(-), 90 μL of Recording Buffer was added, and the plate was allowed to acclimate in an incubator for 10 minutes.

(3) 10 μL of 250 μM Glutamate was added to the sample to give a final concentration of 25 μM, and the fluorescence intensities Ftest(340) (excitation wavelength 340 nm, fluorescence wavelength 510 nm) and Ftest(380) (excitation wavelength 380 nm, fluorescence wavelength 510 nm) of the sample (2) were measured 1 minute after the addition. The fluorescence intensities Fpre(340) and Fpre(380) immediately before the addition of Glutamate were also measured in the same manner. Furthermore, after the test was completed, _MnCl2 was added to give a final concentration of 0.33 M, and the fluorescence intensities Fblank(340) and Fblank(380) were also measured in the same manner, and the autofluorescence was calculated.
(4) Based on the measured values, the change in the fluorescence intensity ratio was calculated using the following formula.

ΔChange in fluorescence intensity ratio=Rtest-Rpre
・Rtest = (Ftest(340) - Fblank(340)) / (Ftest(380) - Fblank(380))
・Rpre = (Fpre(340) - Fblank(340)) / (Fpre(380) - Fblank(380))

The results are shown in Table 1 and Figure 1. In Figure 1, the numbers following the component names indicate the final concentrations (μg/mL) of the other components. For example, "Barley_200" in Figure 1 indicates 200 (μg/mL). The vertical axis indicates the "intracellular Ca fluorescence intensity change ratio."

For barley, dried and ground powder of young leaves was used.
For sweet potatoes, dried and crushed young leaves were used.
For oats, Oats Green (manufactured by Toyo Shinyaku Co., Ltd.), which is an extract from the entire above-ground part of the plant including ears and stems and leaves, was used.
For rice (rice milk), commercially available rice milk was used.
For rooibos, ground powder of commercially available rooibos tea was used.
For pu-erh, ground powder of commercially available pu-erh tea was used.
For jasmine, ground powder of commercially available jasmine tea was used.
For Terminalia, a hot water extract (dried powder) of Terminalia bellirica fruit was used.
Bacillus coagulans was used as the lactic acid bacterium.
As for the fructooligosaccharides, commercially available fructooligosaccharides were used.
For mugwort, dried and crushed powder of the leaves was used.
For lavender, ground powder of commercially available lavender tea was used.

As shown in Table 1 and Figure 1, a reduction in the intracellular Ca fluorescence intensity ratio was confirmed by combining L-theanine with certain other ingredients. In other words, it is believed that the combination ingredients of the present invention antagonize the stimulation of glutamate to the NMDA receptor and inhibit the influx of Ca ions into nerve cells. Therefore, the composition of the present invention can suppress neural hyperexcitation and provide a high level of restful sleep.

[Example 2] (Preparation of tablets)
Five tablets were prepared consisting of the following ingredients:

Oat dry extract powder 400mg
Fructooligosaccharides 250mg
L-theanine 200mg
Hydroxypropyl cellulose 350mg
Calcium stearate 250mg
Silicon dioxide 50mg

Take the above tablets once or two or three times a day with water.

[Example 3] (Production of capsules)
The following mixture was encapsulated in a soft capsule to produce a capsule formulation.

L-theanine 200mg
Terminalia bellirica powder 100mg
Lactic acid bacteria 400mg
Maltose 50mg
Silicon dioxide 10mg

Take 4 capsules of the above once a day or 2 to 4 divided doses with water.

[Example 4] (Preparation of granules)
The following ingredients were mixed and prepared into granules (3,000 mg) in a conventional manner.

Dried barley leaf extract powder 1200mg
Theanine 200mg
Sucralose 150mg
Thiamine hydrochloride 10mg
Riboflavin 10mg
Vitamin B6 5mg
Cyanocobalamin 6.5mg
Fragrance 5mg
Reduced Palatinose 200mg
Calcium stearate 100mg
Hydroxypropyl cellulose Remainder

[Example 5] (Production of instant powder)
The following ingredients were mixed together to prepare an instant powder (2 g) in a conventional manner:

Rooibos tea processed food 800mg
Theanine 200mg
Aspartame 150mg
Sucralose 50mg
Malic acid 10mg
Pigment preparation 10mg
Fragrance 5mg
Polydextrose Remainder

[Example 6] (Production of liquid formulation)
A solution (200 mL) consisting of the following components was prepared.

Theanine 200mg
Pu-erh tea processed food 250mg
Jasmine tea processed food 300mg
Fructooligosaccharides 150mg
Vitamin C 500mg
Water remaining

The composition of the present invention has a high sleep-inducing effect and can be used as an oral preparation, so the present invention is highly useful industrially.

Claims (2)

An oral composition for aiding sleep, comprising theanine and fructooligosaccharides (excluding liquid dairy products and foods containing gamma-aminobutyric acid, taurine, 5-hydroxytryptophan, mineral substances and vitamins). 2. The oral composition for aiding sleep according to claim 1, which is in the form of a tablet, capsule, powder, granule, or liquid.