TW201322990A - Agent for increasing serotonin in brain - Google Patents

Abstract

A composition that exerts an effect that increases serotonin in the brain through ingestion is provided. This agent for increasing serotonin in the brain contains epicatechin, which is obtained by steaming and drying camellia leaves to obtain dried camellia leaves, pouring an extract obtained by subjecting the dried camellia leaves thus obtained to distilled water or ethanol extraction on an ion exchange resin column, and then concentrating a 20% ethanol eluate to dryness.

Description

Serotonin increase agent in the brain

The present invention relates to an agent which affects the increase of serotonin in the brain and a food or drink containing the substance.

Serotonin (5-hydroxytryptamine; 5-HT) is a physiologically active amine belonging to guanamines. About 10 mg in the human body, of which 2% is present in the central nervous system, is known as an important neurotransmitter. The suture nucleus (Raphe nucleus) and so on from the brain stem to the brain. The central serotonin-operating pathway is widely distributed in the spine, and it participates in the regulation of emotion and mood, sleep and wakefulness, appetite, exercise, body temperature, and cognition through various receptor subtypes (Non-Patent Documents 1 and 2).

The intracerebral neurotransmitter serotonin, which is a substance related to mental stability, has an effect of reducing the 5-HT for stress. In particular, 5-HT, γ-butyric acid (GABA), dopamine (DA), and norepinephrine (NA) are associated with stress (Non-Patent Document 3). When 5-HT is insufficient, mood will not change. Stable, sleepy or getting up, etc., mentally unstable state. As a result of the waking up, the 5-HT is increased. As a result, it is known that the brain is activated by the 5-HT, and it becomes a clear state, and it is mentally positive and the mood becomes calm (Non-Patent Document 4).

For example, in the onset of depression, the lack of NA or 5-HT in the emotional or sleep-related central monoamine nerve cells in the brain results in The conduction of learning becomes insufficient, and it is considered that the symptoms of depression occur both physically and psychologically (Non-Patent Document 5). In particular, the main factor for depression is considered to be 5-HT (Non-Patent Document 6), and it is reported that the 5-HT concentration in the brain of a suicide person is decreased (Non-Patent Document 7). Therefore, if 5-HT is increased, it is considered to be related to improvement of morning, daytime waking feeling, emotional stability, stress relief, and improvement of depression.

So far, serotonin-promoting release, serotonin reuptake inhibition, etc., and the increase in serotonin in the brain have been reported in the materials used, including kale, propolis or its extract (Patent Document 11), N-Anise Sulfhydryl-γ-butyric acid, p-anisic acid (Patent Document 12), glycine (Non-Patent Document 9), St. John's Wort (Non-Patent Document 10), etc., as a drug, selective serotonin Resorbing inhibitors (SSRIs) may also have side effects such as loss of appetite or weight gain or loss, and abnormal libido. It is necessary as a material for the addition of serotonin, and is stable and safe.

Epicatechin, also known as 3,3',4',5,7-pentahydroxyflavan, which is one of the flavonoids contained in catechins, is contained in the skin or trunk of the resin, especially Gambier and betel nut are particularly high in content. Further, the carbons at the 2nd and 3rd positions become asymmetric carbon, and four structures are obtained in the same chemical structure. These are distinguished by (-)-catechin, (+)-catechin, (-)-epicatechin, and (+)-epicatechin. The epicatechin here is (-)-epicatechin, and it is reported that there are various physiological effects. For example, a pancreatic β-cell protective agent has been disclosed so far (Patent Document 1), a method and composition for improving cognitive function (Patent Document 2), and hyaluronic acid activity inhibition Preparation (Patent Document 3), an antioxidant, a method for producing the same, a food or drink containing the antioxidant (Patent Document 4), a skin external preparation for whitening (Patent Document 5), and a Bifidobacterium growth promoter (Patent Document 6) A heat-treated cocoa product which is useful for improving the health of a blood vessel system (Patent Document 7), a food and beverage product containing the adiponectin secretion-promoting composition and the composition (Patent Document 8), a deodorant composition (Patent Document 9), Neutral protease activity inhibitor and its use (Patent Document 10) and the like.

Regarding brain or 5-HT, the intracerebral perfusion test was carried out by microdialysis, and it was found that catechins have an increase in 5-HT release from rat hippocampus, especially epicatechin and epicatechin. Acidate or (+)-catechin, etc., has an effect of increasing by more than 100 times compared with other catechins. Further, regarding catechins, release of 5-HT can be seen even by oral administration (Non-Patent Document 8). Further, it has been reported that in the test system in which the synaptosome is cultured, the catechin has a serotonin absorption-suppressing effect which promotes serotonin regulation (Non-Patent Document 11). However, in these studies, there was no evaluation of the oral intake of epicatechin, and even if the epicatechin was ingested, it was caused by the absorption of the intestinal tract and the conjugate of glucuronate and glucuronic acid, because of the epicatechin. The substance does not migrate in the brain. As a result of Non-Patent Document 11, it is not certain whether the effect on serotonin is a conjugation.

However, as a raw material for epicatechin, there are green tea leaves, cocoa beans, grape seeds, apple peel, soybeans, broad beans, and camellia leaves.

[Previous Technical Literature] [Patent Document]

[Patent Document 1] JP-A-2008-7452

[Patent Document 2] Japanese Patent Publication No. 2009-539991

[Patent Document 3] Japanese Patent Publication No. 06-9391

[Patent Document 4] JP-A-2007-254508

[Patent Document 5] Japanese Patent Laid-Open No. Hei 10-120546

[Patent Document 6] JP-A-2006-298821

[Patent Document 7] Japanese Patent Publication No. 2009-501161

[Patent Document 8] JP-A-2006-131512

[Patent Document 9] Japanese Patent Publication No. 09-38183

[Patent Document 10] JP-A-2007-186457

[Patent Document 11] JP-A-2003-300892

[Patent Document 12] JP-A-2002-154956

[Non-patent literature]

[Non-Patent Document 1] Annuals New York Academy of Science, 600, 9-35, 1990

[Non-Patent Document 2] Pharmacology Biochemistry and Behavior, 54, 129-141, 1996

[Non-Patent Document 3] "New Life Science Series Stress Exploration - Seen by Molecular Level", Science Fellow, Kyoto, 81-91, 1994

[Non-Patent Document 4] Serotonin is deficient in brain-angry brain. Retraining Brain for Depression - Japan Broadcasting and Publishing Association, Tokyo, 49-56, 2003

[Non-Patent Document 5] "Science and Health of Depression - For General Medicine -", Morning Warehouse, Tokyo, 15-20, 1987

[Non-Patent Document 6] Journal of Pharmacy and Pharmacology, 57, 651-656, 2005

[Non-Patent Document 7] The British Journal of Psychiatry, 113 (505), 1407-1411, 1967

[Non-Patent Document 8] The Essentials of the Japan Nutrition and Food Research Society, 2D-13p, 2008

[Non-Patent Document 9] Psychiatry and Clinical Neurosciences, 65, 142-149, 2011

[Non-Patent Document 10] British Journal of Pharmacology, 142, 414-418, 2004

[Non-Patent Document 11] Phytomcdicine, 14, 396-402, 2007

A composition is provided which exerts an increasing effect on serotonin in the brain via oral ingestion.

As mentioned above, in the prior art, there was no review of the oral intake of epiphylla. Therefore, the present invention provides a detailed review of whether epicatechin can increase serotonin in the brain by oral ingestion. As a result, only a single oral ingestion of epicatechin via intragastric administration was observed in mice, and it was confirmed that serotonin in the brain was increased. In addition, the camellia leaf which is a raw material of epicatechin was found, and it was confirmed that the high concentration composition of epicatechin in the extract increased the serotonin in the brain. That is to say, the solution of the present invention is a catechin-containing substance, in particular, the tea flower leaf extract is taken orally to exert the brain. Serotonin increases the effect.

That is, the object of the present invention is to increase the amount of serotonin in the brain, and as a result of the study, it was found that only a single oral ingestion was administered via intragastric administration, and it was confirmed that serotonin in the brain was increased. Further, it does not contain other catechins derived from camellia leaves, and a method of preparing a composition containing only epicatechin as a high content is established, and an effect of increasing serotonin in the brain is found.

The oral intake of epicatechin effectively increases the serotonin in the brain, and further, does not contain other catechins derived from camellia leaves, and establishes a preparation method in which only epicatechin is a highly contained component.

[Embodiment of the Invention]

The present invention relates to an intracerebral serotonin increasing agent containing epicatechin.

Further, the present invention is characterized in that epicatechin is derived from a camellia leaf, and is related to an intracerebral serotonin increasing agent containing a high content of epicatechin.

Furthermore, the present invention is a method for preparing epicatechin from camellia leaves, which is obtained by drying dried tea leaves obtained by drying the dried tea leaves, and extracting the dried tea leaves with distilled water or ethanol. The extract is injected into the column of the ion exchange resin, and is obtained by a method in which the 20% ethanol eluate is concentrated and dried to obtain a high content of epicatechin.

In addition, the present invention is associated with an increase in serotonin in the brain containing epicatechin. Related to food and drink.

The present invention relates to a composition which exerts an effect of improving the serotonin level in the brain by means of oral ingestion. Serotonin is a neurotransmitter in the brain that is emotionally or in connection with arousal. In general, it can make the emotion clear and improve concentration. Therefore, in the composition which raises the level of serotonin, it may be possible to give emotional conversion and improve the efficiency of concentration, and it is expected to be applied as a functional material of fruit or health food.

Further, the present invention provides a food or drink containing an epicatechin-containing serotonin-increasing agent. For food and beverage, it includes animal foods such as fresh food, meat, and fish; vegetable foods such as cereals and wild vegetables; processed foods such as dairy products, breads, and instant foods; foods such as fruits; sweeteners and seasonings. Materials for conditioning and other seasonings; health foods, special-purpose foods; beverages for water, refreshing beverages, alcoholic beverages, tea, food processing materials, food additives, etc.

[Examples] [Example 1] Test on the effect of serotonin in the brain of epicatechin (test animals)

In this test, Wistar male rats (270-310 g, 8-10 weeks old) were used. The rats were housed in a 12-hour light-dark cycle at room temperature of about 24 ° C and humidity of 45-50%. The feed and water in the breeding are free to ingest.

(test drug class)

The reagent used in this test is (-)-epicatechin [EC (Wako, Osaka), purity 98% or more] and catechin mixture [Mix (Wako, Osaka), catechins is 85%) Above; containing (-)-epigallocatechin gallate (hereinafter, EGCG) about 36.2%, (-)-catechin gallate (hereinafter, EGC) about 23.2%, (-) - epicatechin gallate (hereinafter, ECG) about 10.6%, EC about 7.4%, (+)-catechin (below, CA) about 2.4%, (-)-gallocatechin About 5.7%, (-)-epigallocatechin gallate, about 1.6%, etc.] were each prepared to be 1 mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg, and each test was made. It was dissolved in 0.5 ml or 1 ml of physiological saline (0.9% NaCl), and each solution was directly administered into the stomach of the rat by oral detection. However, the same amount of physiological saline was used as a control. In each treatment group, 4 to 5 rats were used in each group.

(test method)

The mice were anesthetized with sodium pentobarbital, and the guide cannula was embedded with reference to the Paxinos and Watson brain maps. After confirming that the guide cannula is completely fixed, insert a dummy cannula. After recovery, the rats were anesthetized with sodium pentobarbital, and a dialyzed probe was inserted into a guide cannula, and dialysate (standard Ringer's solution) was perfused (infusion rate of 1 μl/min). The amount of 5-HT of the dialysate was measured by high speed liquid chromatography every 20 minutes. After 60 minutes, the EC will be Or Mix was administered into the stomach of the rat, and the measurement was continued until the maximum outflow of 5-HT was observed. All data were expressed as mean ± standard deviation (SD), and statistical analysis was performed using the Mann-Whitney test (non-paired and non-parametric) and single factor analysis using statistical analysis software SPSS 17.0J. (One-way analysis of variance), the risk is significantly different than the 5%.

(result)

The results obtained by the above-mentioned brain 5-HT promoting release effect test are shown in Figs.

It is judged from Fig. 1 that when the drug is administered in the case of EC, the outflow of 5-HT is 110±16% in the administration of EC 1 mg/kg, 133±10% in the administration of 10 mg/kg, and 513±535% in the administration of 50 mg/kg. The dose of 100 mg/kg was 987±643%, and the amount of 5-HT efflux increased in response to EC concentration (Fig. 1). There was no significant difference in 5-HT outflow between EC administration at 1 mg/kg and 10 mg/kg. Further, the 5-HT outflow amount at the highest concentration of EC 100 mg/kg was significantly increased as compared with the case of EC 1 mg/kg and 10 mg/kg.

On the other hand, as shown in Fig. 2, when the catechin mixture is administered, the 5-HT outflow amount, the Mix administration 1 mg/kg is 113 ± 12%, and the administration 10 mg/kg is 135 ± 17 %, the dose of 50 mg / kg was 148 ± 39%, and the dose of 100 mg / kg was 227 ± 112%. The case of Mix administration also showed a concentration-dependent tendency to increase the amount of 5-HT.

Comparison of the 5-HT outflow of Mix 1mg/kg and 10mg/kg With the increase of the same degree, it was found that any of EC and Mix at a level of 10 mg/kg is not a concentration that greatly increases the amount of 5-HT efflux from the brain.

Further, when the EC administration of 1 mg/kg was compared with the EC administration of 100 mg/kg, the 5-HT outflow amount was approximately 9 times different. In contrast, Mix 1 mg/kg and Mix 100 mg/kg and catechins have a 100-fold difference, and the difference in 5-HT efflux is about 2 times.

Further, EC administration of 50 mg/kg and 100 mg/kg showed an increase in 5-HT outflow of about 4 to 5 times higher than that of Mix 50 mg/kg and 100 mg/kg.

From the above, it can be seen that the administration of epicatechin significantly increases the serotonin in the brain compared to the oral intake of the catechin mixture.

[Embodiment 2] The catechin from the camellia leaves contains a composition of the composition-1

5.477 kg of Camellia Japonica leaves were cooked on a boiling water bath for 5 minutes and then dried in hot air to obtain 1.89 kg of dried camellia leaves. 18.9 L of distilled water was added to the dried camellia leaves, and the mixture was allowed to stand at room temperature for 4 hours for extraction. The insoluble matter was removed by filtration, and the filtrate was poured into a column packed with 3 L of formaldehyde resin HP-20 (manufactured by Mitsubishi Chemical Corporation), and washed out in the order of 6 L of distilled water, 6 L of 10% ethanol, and 6 L of 20% ethanol. The 20% ethanol eluate was concentrated under reduced pressure and freeze-dried to obtain 23.52 g of a high content of epicatechin (the epicatechin content of 24.7%).

[Example 3] The catechin from the camellia leaves contains a composition of the composition-2

151.64 g of camellia leaves were cooked on a boiling water bath for 5 minutes and then dried in hot air to obtain 58.48 g of dried camellia leaves. 1.175 L of distilled water was added to the dried camellia leaves, and the mixture was allowed to stand overnight at room temperature for extraction. The insoluble matter was removed by filtration, and the filtrate was freeze-dried to obtain 12.18 g of a tea leaf water extract. The epicatechin content of camellia leaf water extract was 3.12%. 10 g of the obtained camellia leaf water extract was dissolved in 1 L of distilled water, and poured into a column packed with 250 ml of formaldehyde resin HP-20 (manufactured by Mitsubishi Chemical Corporation), 1 L of distilled water, 1 L of 10% ethanol, and 1 L of 20 The order of % ethanol is washed out. The 20% ethanol eluate was concentrated under reduced pressure, and freeze-dried to obtain 0.932 g of a high content of epicatechin (the epicatechin content of 32.94%).

[Example 4] The catechin from the camellia leaves contains a composition of the composition-3

90.12g of camellia leaves were cooked on a boiling water bath for 5 minutes and then dried in hot air to obtain 34.50 g of dried camellia leaves. 690 ml of 70% ethanol was added to the dried camellia leaves, and the mixture was allowed to stand overnight at room temperature for extraction. The insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure, and then freeze-dried to obtain 6.58 g of a tea leaf extract of 70% ethanol. The epicatechin content of the 70% ethanol extract of Camellia sinensis was 6.75%. 1 g of the 70% ethanol extract of the obtained camellia leaf was dissolved in 1 L of distilled water, and poured into the filling. 250 ml of a formaldehyde resin HP-20 (manufactured by Mitsubishi Chemical Corporation) was washed out in the order of 1 L of distilled water, 1 L of 10% ethanol, and 1 L of 20% ethanol. The 20% ethanol eluate was concentrated under reduced pressure, and freeze-dried to obtain 0.12 g of a high content of epicatechin (the epicatechin content of 44.09%).

[Example 5] 5-HT promoted release test in the brain with high content of epicatechin

The epicatechin high content fraction obtained in Example 2 was used as a sample, and the effect of 5-HT level in the brain was verified in the same manner as in Example 1, and it was confirmed that the content of the catechin was high. Oral administration can increase the level of 5-HT in the brain.

[Embodiment 6]

The chocolate, throat lozenge, chewing gum, candy, elastic jelly, and beverage containing the intracerebral serotonin increasing agent containing a high content fraction of epicatechin are produced by a conventional method. These are as follows. However, the scope of the invention is not limited by the terms.

Chocolate place

Chocolate place

Throat ingot

Throat ingot

Chewing gum place

Chewing gum place

Candy place

Candy place

Elastic jelly place

Gelatin 60.0% by weight

Elastic jelly place

Drink place

Drink place

[Industrial use possibility]

A serotonin-inducing agent containing a tea leaf extract, which can be applied to a wide variety of products.

Fig. 1 is a graph showing the amount of 5-HT outflow administered via epicatechin.

Fig. 2 is a graph showing the amount of 5-HT outflow administered via a catechin mixture.

Claims (4)

A brain serotonin increasing agent containing epicatechin. The intracerebral serotonin increasing agent according to the first aspect of the invention, wherein the epicatechin is a fraction of the high epicatechin content extracted from the camellia leaf. A method for preparing a high epicatechin content fraction from a camellia leaf, characterized in that the tea leaves are steamed, dried to obtain dried tea leaves, and the obtained dried tea leaves are extracted with distilled water or ethanol and the extract is injected into the ions. In the exchange resin column, a method of dividing the high epicatechin content by a 20% ethanol eluate after concentration and drying is obtained. A food containing an intracerebral serotonin increasing agent containing epicatechin.