JP6964974B2 - Composition for autonomic nerve regulation containing black tea extract as an active ingredient - Google Patents

Description

The present invention relates to a composition for autonomic nerve regulation containing black tea extract as an active ingredient.

In order to keep the homeostasis of the living body constant against various external changes, the autonomic nervous system, the endocrine system, the immune system, etc. interact with each other to achieve a balance. Among these, it can be said that the most important system in the living body is the autonomic nervous system.

The autonomic nervous system unknowingly regulates the activity of organs in response to the external and internal environments, regardless of conscious control. This autonomic nervous system is composed of a sympathetic nervous system whose activity increases in a tense state and a parasympathetic nervous system whose activity increases in a relaxed state such as during relaxation. These two types of autonomic nervous system respond to changes in the external environment such as temperature and mental stress and changes in the internal environment such as nutritional status, and each works antagonistically, and the body responds to those changes. It plays an important role in maintaining the homeostasis of the living body.

In recent years, attempts have been made to maintain health and cure various diseases by actively controlling autonomic nerves, and promote tear secretion (Patent Document 1) and prevent eye strain (Patent Document 2). , A pharmaceutical composition for preventing asthenopia (Patent Document 3) has been reported.

When the autonomic nerves are out of balance, various symptoms caused by it appear. For example, when the sympathetic nerve is increased, the blood flow in the skin is reduced and the skin becomes rough. It is expected to invent a daily and simple solution for adjusting the autonomic nerves by acting on the autonomic nerves for the physical disorder caused by the disorder of homeostasis.

To date, odor stimulation with lavender essential oil suppresses the sympathetic nerves that control white adipose tissue, brown adipose tissue, adrenal glands and kidneys, and promotes the parasympathetic nerves that control the stomach, resulting in lipolysis and energy consumption (heat production). , Body temperature), lowers blood pressure, and enhances appetite (Non-Patent Documents 1 and 2). It has also been reported that the application of a cream containing urea, which suppresses the activity of cutaneous arterial sympathetic nerves, increases the blood flow of the skin and restores the barrier function of the skin (Non-Patent Document 3).

However, the actions of these components are local, and there are restrictions on the daily and convenient regulation of autonomic nerves.

Japanese Unexamined Patent Publication No. 2005-272445 Japanese Unexamined Patent Publication No. 2007-302577 Japanese Unexamined Patent Publication No. 2011-37785

Shen J, et al. Neurosci. Lett. 383188-193, 2005 Tanida M, et al. Neurosci. Lett. 398: 155-160, 2006 Horii Y, et al., Skin Research and Technology 17: 75-81, 2011

An object of the present invention is to provide a novel composition for autonomic nerve regulation that can effectively regulate autonomic nerves and can be easily ingested on a daily basis.

The present inventors have found that oral ingestion of a black tea extract containing a high amount of black tea polyphenols suppresses cutaneous arterial sympathetic nerve activity. The present invention is based on this finding.

Therefore, according to the present invention, there is provided a composition for regulating autonomic nerves, which comprises black tea extract as an active ingredient.

That is, the present invention includes the following inventions.
(1) A composition for autonomic nerve regulation, which comprises black tea extract as an active ingredient.
(2) The composition for autonomic nerve regulation according to (1), which is used for suppressing cutaneous arterial sympathetic nerve activity.
(3) The composition for autonomic nerve regulation according to (1) or (2), for obtaining an effect selected from the group consisting of increased blood flow in the skin, promotion of cosmetology, promotion of hair growth and promotion of wound healing.

According to the present invention, there is provided a novel composition for autonomic nerve regulation that can be easily ingested on a daily basis to suitably regulate autonomic nerve activity. In particular, the composition for autonomic nerve regulation according to the present invention can suppress the activity of the cutaneous arterial sympathetic nerve. Among the autonomic nerves, it is known that when the cutaneous arterial sympathetic nerve is excited, the blood flow in the skin is reduced. By suppressing the excitement of the cutaneous arterial sympathetic nerve, it becomes possible to promote increased blood flow in the skin, cosmetology, hair growth, and wound healing.

FIG. 1 shows cutaneous arterial sympathy when 1 ml / 300 g body weight or 1 ml / 300 g body weight of a water suspension containing 0.3 mg / ml, 3 mg / ml or 30 ml / ml of BTP was orally administered to rats. The measured data of the change of the nerve activity (cutaneous arterial sympathetic nerve activity (CASNA)) is shown. FIG. 2 shows a water suspension containing 0.3 mg / ml, 3 mg / ml, or 30 ml / ml of BTP at a percentage of 100% of CASNA neural activity before oral gastric administration (0 minutes) in rats. It shows the change in CASNA when 1 ml / 300 g body weight or 1 ml / 300 g body weight of water is orally administered intragastrically. The vertical axis shows the percentage when the neural activity of CASNA before sample administration (0 minutes) is 100%. The horizontal axis shows the elapsed time (minutes) after administration of the sample. The black circle is a graph when BTP is administered at 0.3 mg / L, the black triangle is a graph when BTP is administered at 3 mg / L, and the black rhombus is a graph when BTP is administered at 30 mg / L. Yes, the black square is a graph when water is used as a control. FIG. 3 shows the transition of the blood flow change rate (%) with respect to the elapsed time (minutes) after ingestion of each test food in the human test. The vertical axis shows the rate of change when the blood flow before ingestion of the test food (0 minutes) is 100% as a percentage. The horizontal axis shows the elapsed time (minutes) after ingesting the test food. The black triangle is a graph when a BTP-containing test food is ingested, and the black rhombus is a graph when a placebo test food is ingested.

Specific description of the invention

The composition for autonomic nerve regulation according to the present invention contains black tea extract as an active ingredient.

Black tea extract Black tea extract has already been used as a black tea polyphenol-enhancing component in black tea beverages, and its safety to the living body has been established. Therefore, the composition for autonomic nervous regulation of the present invention is highly safe for the living body, can be ingested on a daily basis and continuously, and is a food or drink (beverage and food), food or drink additive, feed, feed additive, etc. It is suitable for use as an ingredient in pharmaceutical products and the like.

In the present invention, the "black tea extract" means a black tea extract containing a high content of black tea polyphenols, and the total polyphenol content of the black tea extract is preferably 20 to 30% by weight, more preferably 22 to 28% by weight. In such a case, the caffeine content of the black tea extract is preferably 1% by weight or less, more preferably 0.5% by weight or less. The lower limit of the caffeine content of the black tea extract is not particularly limited and may be 0.00% by weight (for example, the black tea extract does not contain caffeine), but is preferably 0.01% by weight. More preferably, it is 0.05% by weight. The theaflavin content of the black tea extract is preferably 0.05 to 1.3% by weight, more preferably 0.1 to 1.0% by weight, and most preferably 0.25 to 0.75% by weight.

The total amount of polyphenols referred to here is referred to in "Explanation of the 5th Edition Japanese Food Standard Ingredients Analysis Manual" edited by Japan Food Research Laboratories, Central Regulations, July 2001, p. It refers to a value obtained according to the official method (iron tartrate reagent method) described in 252.

Theaflavin is a dimer obtained by oxidative polymerization of catechin, and specifically, theaflavin, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3', 3'-O-digalate and isothea flavin. Say. These are a group of substances that are the main origins of the light blue color of the black tea extract, and are a group of substances that can be an index of the appearance of the black tea extract.

The amount of theaflavin referred to in the present invention represents the total amount of theaflavin, theaflavin 3-O-gallate, theaflavin 3'-O-gallate and theaflavin 3', 3'-O-jigallate, and is measured by using, for example, the following method. can do. In order to adjust the amount of theaflavin, it is conceivable to extract using a plurality of black tea leaves, mix a plurality of extracts, or use a separate extract.

Measurement method of theaflavin After filtering the sample solution with a 0.45 μm hydrophilic PTFE filter (DISMIC-13HP, manufactured by Advantech Co., Ltd.), it can be quantified by HPLC under the following conditions.

(HPLC analysis conditions):
Equipment: Alliance HPLC / PDA system (manufactured by Japan Waters Corp.)
Column: CAPCELL PAK UG120 (4.6 mm ID × 100 mm, SHISEIDO).
Mobile phase A solution: 0.05% phosphoric acid water.
Mobile phase B liquid: acetonitrile: ethyl acetate = 985: 15.
Gradient: A linear gradient that reaches 81% to 77% of Liquid A from 13.3 minutes to 26.6 minutes after injection.
Flow velocity: 1.5 mL / min.
Detection: UV 280 nm.
Column temperature: 25 ° C.
Sample amount: 20 μL.
Suitable measurement concentration range: 0.25 mg / 100 mL-10 mg / 100 mL.

Caffeine measurement method After filtering the sample solution with a 0.45 μm hydrophilic PTFE filter (DISMIC-13HP, manufactured by Advantech Co., Ltd.), caffeine is quantified using HPLC under the following conditions. be able to.

(HPLC analysis conditions):
Equipment: Alliance HPLC / PDA system (manufactured by Japan Waters Corp.).
Column: Mightysil RP-18 GP, 4.6 mm I. D. × 150 mm (manufactured by Kanto Chemical Co., Inc.).
Mobile phase A solution: Acetonitrile: 0.05% phosphate water = 10: 400 solution.
Mobile phase B solution: Methanol: acetonitrile: 0.05% phosphate water = 200.10: 400 solution.
Gradient: A linear gradient that reaches 100% of solution A to 100% of solution B 3 to 25 minutes after injection.
Flow rate: 1 mL / min.
Detection: UV275 nm (caffeine).
Column temperature: 40 ° C.
Sample amount: 10 μL.

Method for Producing Black Tea Extract The black tea extract used as a raw material for the black tea extract of the present invention can be produced, for example, as follows. First, the black tea beverage of the present invention can be produced by selecting tea leaves and adjusting extraction conditions. Many types of black tea leaves are known, including Darjeeling, Dimbula, Assam, Uva, Kenya, and Nuwara Eliya, depending on the place of origin, and the ingredients differ depending on the type of tea plant used as the raw material and the fermentation method. .. Furthermore, strictly speaking, the ingredients differ depending on the harvest each year.
By analyzing the components of these tea leaves, one or more kinds of tea leaves can be used as raw materials.

When using a plurality of black tea leaves, they may be blended and extracted with hot water by a usual method, or a plurality of black tea extracts obtained by extracting different black tea leaves may be appropriately mixed and adjusted. You may. In particular, it may be difficult to adjust the amount of caffeine only by selecting tea leaves. In that case, a method of decaffeination treatment by a known method can be mentioned. The decaffeination treatment may be performed on the tea leaves before extraction, or may be performed on the tea leaves and a part of the extract to adjust the amount of caffeine.

Further, a method for producing a black tea extract of the present invention by producing a black tea extract obtained by sterilizing a black tea extract prepared in advance and then blending an appropriate amount with a black tea extract prepared separately based on the component analysis values. Can be disclosed. At this time, the black tea extract may be decaffeinated if necessary. At that time, the caffeine content of the black tea extract is preferably 1% by weight or less, more preferably 0.5% by weight or less. Specific methods for decaffeination include activated carbon treatment, supercritical gas extraction treatment, and synthetic adsorption resin treatment. The lower limit of the caffeine content of the black tea extract is not particularly limited and may be 0.00% by weight (for example, the black tea extract does not contain caffeine), but is preferably 0.01% by weight. More preferably, it is 0.05% by weight. The amount of theaflavin in the black tea extract is preferably 0.05 to 1.3% by weight. The total polyphenol content of the black tea extract is preferably 20 to 30% by weight, more preferably 22 to 28% by weight. The black tea extract may be concentrated or dried. The method using such a black tea extract is most suitable for producing the extract of the present invention in that the amount of components can be easily adjusted.

As used herein, black tea extract has been demonstrated to suppress cutaneous arterial sympathetic nerve activity. Therefore, the composition for autonomic nerve regulation according to the present invention is preferably used for suppressing cutaneous arterial sympathetic nerve activity. More specifically, the composition for autonomic nerve regulation according to the present invention is used to obtain an effect selected from the group consisting of, for example, increased blood flow in the skin, promotion of cosmetology, promotion of hair growth, and promotion of wound healing.

Application of the composition for autonomic nerve regulation according to the present invention as a pharmaceutical product When the composition for autonomic nerve regulation according to the present invention is provided as a pharmaceutical product, such a pharmaceutical product is a pharmaceutically acceptable carrier for the tea extract according to the present invention. Can be manufactured by mixing with.

The composition for autonomic nervous regulation according to the present invention can be orally or parenterally administered as an active ingredient, and is preferably orally administered. Examples of oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. Parenteral preparations include injections (eg, subcutaneous injections, intravenous injections, intramuscular injections, intraperitoneal injections), infusions, external preparations (eg, nasal preparations, transdermal preparations, ointments). ), Suppositories (eg, rectal suppositories, vaginal suppositories). These formulations can be formulated using a pharmaceutically acceptable carrier by a method usually used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. For example, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragant, methyl cellulose, sodium carboxymethyl cellulose, low melting point wax, and cacao butter can be used as carriers.

The pharmaceutical product can be produced, for example, as follows.

Oral preparations include, for example, excipients (eg, lactose, sucrose, starch, mannitol), disintegrants (eg, calcium carbonate, carboxymethyl cellulose calcium), binders (eg, pregelatinized starch, arabic gum, carboxy) as active ingredients. Methyl cellulose, polyvinylpyrrolidone, hydroxypropyl cellulose) or lubricants (eg, starch, magnesium stearate, polyethylene glycol 6000) are added and compression molded, then if necessary for taste masking, enteric or persistent purposes. Therefore, it can be produced by coating by a method known per se. As the coating agent, for example, ethyl cellulose, hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, Eudragit (manufactured by Rohm Co., Ltd., Germany, methacrylic acid / acrylic acid copolymer) and the like can be used.

Injectables contain active ingredients as dispersants (eg, Tween 80 (Atlas Powder, USA), HCO60 (Nikko Chemicals), polyethylene glycol, carboxymethyl cellulose, sodium alginate, etc.), preservatives (eg, methylparaben). , Propylene paraben, benzyl alcohol, chlorobutanol, phenol), isotonic agents (eg, sodium chloride, glycerin, sorbitol, glucose, converted sugar), etc., and aqueous solvents (eg, distilled water, physiological saline, Ringer's solution, etc.) Alternatively, it can be produced by dissolving, suspending or emulsifying in an oil-based solvent (for example, olive oil, sesame oil, cotton seed oil, vegetable oil such as corn oil, propylene glycol) or the like. At this time, if desired, additives such as a solubilizing agent (for example, sodium salicylate and sodium acetate), a stabilizer (for example, human serum albumin), and a soothing agent (for example, benzalkonium chloride and prokine hydrochloride) are added. May be good.

The external preparation can be produced by making the active ingredient into a solid, semi-solid or liquid composition. For example, the above-mentioned solid composition may contain the active ingredient as it is, or an excipient (for example, lactose, mannitol, starch, microcrystalline cellulose, sucrose), a thickener (for example, natural gums, cellulose derivative, acrylic acid). It can be produced by adding (polymer) or the like and mixing them into a powder. The liquid composition can be produced in much the same manner as in the case of an injection. The semi-solid composition is preferably an aqueous or oily gel agent or an ointment. In addition, all of these compositions include pH regulators (eg, carbonic acid, phosphoric acid, citric acid, hydrochloric acid, sodium hydroxide) and preservatives (eg, paraoxybenzoic acid esters, chlorobutanol, benzalkonium chloride). Etc. may be included. Suppositories can be produced by making the active ingredient an oily or aqueous solid, semi-solid or liquid composition. Examples of the oily base used in the composition include glycerides of higher fatty acids [for example, cocoa butter, witepsols (manufactured by Dynamite Nobel)], intermediate fatty acids [for example, migliols (manufactured by Dynamite Nobel)], or vegetable oils (for example, manufactured by Dynamite Nobel). , Sesame oil, soybean oil, cottonseed oil). Examples of the aqueous base include polyethylene glycols and propylene glycol. Examples of the aqueous gel base include natural gums, cellulose derivatives, vinyl polymers, and acrylic acid polymers.

Application of the composition for autonomic nerve regulation according to the present invention as a food The composition for autonomic nerve regulation according to the present invention can also be used as a food additive. Therefore, according to another aspect of the present invention, there is provided a food additive comprising the same ingredients as the composition for autonomic nerve regulation according to the present invention. According to still another aspect of the present invention, there is provided the composition for autonomic nerve regulation according to the present invention, or a food containing the same ingredients as the composition for autonomic nerve regulation according to the present invention.

As described above, black tea extract exerts a physiological action of regulating autonomic nerves, particularly suppressing cutaneous arterial sympathetic nerve activity. Therefore, the food additives according to the present invention include those intended to be added to foods expected to have this physiological effect. The addition target and addition mode can follow the description regarding foods according to the present invention.

The food according to the present invention is a food or drink containing an effective amount of the same component as the composition for autonomic nerve regulation according to the present invention or the composition for autonomic nerve regulation according to the present invention. Here, "containing an effective amount" means a content in which black tea extract is ingested within a range as described later when an amount normally eaten in each food or drink is ingested.

When the composition for autonomic nerve regulation according to the present invention is provided as a food, the same ingredients as the composition for autonomic nerve regulation according to the present invention or the composition for autonomic nerve regulation according to the present invention can be blended into the food as it is. .. More specifically, the food according to the present invention is prepared by preparing the composition for autonomic nerve regulation according to the present invention as it is as a food or drink, further containing various proteins, sugars, fats, trace elements, vitamins, etc., or liquid. , Semi-liquid or solid, aqueous solution of potassium salt, sodium salt, etc., or added to general foods and drinks.

In the present invention, the term "food" is used to include health foods, functional foods, foods for specified health uses, foods with functional claims, and foods for the sick.

The form of the "food" is not particularly limited, but is preferably a food (excluding beverages) or a non-alcoholic beverage. As used herein, the term "non-alcoholic beverage" may mean a beverage having an ethanol concentration of less than 1% by weight, but preferably less than 0.5% by weight, more preferably 0.05% by weight. Less than, more preferably less than 0.005% by weight. Beverages that do not contain ethanol (0% by weight) may be used.

As described above, black tea extract has a physiological effect of regulating autonomic nerves, particularly suppressing cutaneous arterial sympathetic nerve activity. Therefore, by blending the same components as the composition for autonomic nerve regulation according to the present invention or the composition for autonomic nerve regulation according to the present invention into foods to be ingested daily, health foods to be ingested as supplements, functional foods, etc., health is achieved. It can be provided as a food that is useful for the maintenance and promotion of foods, specifically, a food that also has functions such as regulation of autonomic nerves, particularly suppression of cutaneous arterial sympathetic nerve activity. More specifically, the food according to the present invention can be provided as a food having functions such as increasing blood flow in the skin, promoting beauty, promoting hair growth, and promoting wound healing. That is, the food according to the present invention is a food suitable for consumers who have an imbalance of autonomic nerves and an increase in sympathetic nerves, resulting in a decrease in skin blood flow and a continuous or rough skin condition, particularly a food for specified health use. , Can be provided as.

Examples of the beverage include water, soft drinks, fruit juice beverages, milk beverages, sports drinks, nutritional drinks and the like. Examples of foods include breads, noodles, rice, tofu, dairy products, soy sauce, miso, and confectionery.

The food product according to the present invention may further contain additives usually used in the art as long as the effects of the present invention are not affected. Such additives include, for example, sweeteners, acidulants, fragrances, antioxidants, bitterness agents, apple fiber, soybean fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils; gluten and the like. Proteins; amino acids; peptides; monosaccharides such as glucose and fructose; disaccharides such as sucrose; polysaccharides such as dextrose, starch and crystalline cellulose; sugar alcohols such as erythritol, xylitol, sorbitol and mannitol; vitamins such as vitamin C Minerals such as zinc, copper and magnesium; functional materials such as CoQ10, α-lipoic acid, carnitine, capsaicin and polyphenols; fruit juice; milk, milk components and the like. Each of these additives can be used alone or in combination of two or more.

Dose and Usage of Autonomic Nervous System Regulatory Composition According to the Present Invention The autonomic nervous system regulatory composition, pharmaceuticals and foods according to the present invention have low toxicity because they utilize the tea components that human beings have ingested as foods and drinks for many years. It is safely used for mammals in need (eg, humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs, monkeys, etc.). The dose or intake of the composition for autonomic nervous regulation according to the present invention can be determined depending on the recipient, the age and weight of the recipient, symptoms, administration time, dosage form, administration method, combination of agents, and the like. For example, when the composition for autonomic nervous regulation according to the present invention is orally administered or ingested, the dose thereof is in the range of 250 to 3000 mg, preferably 250 to 1500 mg in terms of black tea extract for administration or ingestion in an adult having a body weight of 60 kg. It can be administered or ingested once or multiple times per day as needed.

When ingested as a food, the composition for autonomic nerve regulation according to the present invention can be added to the food so that such a dose can be ingested. Therefore, it can be blended in the range of 50 to 900 mg, preferably 50 to 450 mg. According to a preferred embodiment of the present invention, the composition for autonomic nerve regulation according to the present invention is blended in foods so as to be 50 mg or more in terms of black tea polyphenols.

According to another aspect of the present invention, the composition for autonomic nerve regulation according to the present invention, or the same components as the composition for autonomic nerve regulation according to the present invention, comprises administering to a mammal including a human. A method of regulating nerves, a method of suppressing cutaneous arterial sympathetic nerve activity, and a method of obtaining an effect selected from the group consisting of increased blood flow in the skin, promotion of beauty, promotion of hair growth, and promotion of wound healing are provided.

According to yet another aspect of the present invention, the use of black tea extract for the production of compositions for autonomic nerve regulation is provided.

The present invention will be specifically described with reference to the following examples, but the present invention is not limited to these examples.

Example 1: Effect of intragastric administration of black tea polyphenols on cutaneous arterial exchange nerves
(1) Preparation of black tea extract 90 g of commercially available black tea leaves were put into 810 mL of hot water, and then extracted for 45 minutes with occasional stirring. This extract was filtered through a filter paper to obtain the first extract filtrate. The tea leaves remaining in the above extraction step were collected, put into 720 mL of hot water again, and extracted for 45 minutes with occasional stirring. This extract was filtered through a filter paper to obtain a second extract filter. The first and second extraction filtrates were mixed to obtain 1,250 g of black tea extract. 400 g of this black tea extract was separated, 5 g of activated carbon was added thereto, the mixture was stirred for 1 hour, and then filtered through a filter plate. This filtrate was concentrated and then freeze-dried to obtain 6 g of black tea extract suitable for use in the present invention (total polyphenol amount = 23.5% by weight, theaflavin amount = 0.31% by weight). The obtained black tea extract is referred to as BTP in the present specification.

(2) Test method In the experiment, a Wistar male rat (about 9 weeks) weighing about 300 g was bred in a warm-blooded animal room at 24 ° C for 1 week or more under a light-dark cycle (lights up from 8:00 to 20:00) every 12 hours. Age) was used. On the day of the experiment, after fasting for 3 hours, urethane anesthesia was performed, and a catheter for oral intragastric administration was inserted. Then, the distal branch of the cutaneous arterial sympathetic nerve in the left thigh was lifted with a silver electrode, and the method described above (Shen J, et al. Neurosci. Lett. 383188-193, 2005, and Tanida M, et al., Neurosci). The electrical activity of these nerves was measured in Lett. 389: 109-114, 2005). At a time when the measured values of neural activity settled down (around 13:00), a 1 ml / 300 g body weight of a water suspension containing 0.3 mg / ml, 3 mg / ml or 30 ml / ml of BTP, respectively, was applied using a catheter. It was administered orally and intragastrically, and the change in electrical activity of the sympathetic efferent branch of the cutaneous artery that occurred at that time was electrophysiologically measured for 90 minutes. From the start of surgery to the end of measurement, a tube was inserted into the trachea to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C with a heat insulating device.

As a control experiment, changes in the electrical activity of the distal branches of the cutaneous arterial sympathetic nerve were electrophysiologically measured for 90 minutes when 1 ml / 300 g of water as a solvent was orally administered intragastrically.

These neural activity data are analyzed by the average value of the firing frequency (pulse / 5 s) per 5 seconds every 5 minutes, and the average value (0 minute value) for 5 minutes before the start of stimulation is taken as 100% as a percentage. expressed. In addition to calculating the mean ± standard error from the data, the statistically significant difference as a group was tested by analysis of variance (ANOVA) with repeated measures, and the neural activity before the start of oral intragastric administration (0 minutes). The statistically significant difference between the absolute values of was tested by the Mann-Whitney U-test. In addition, this test has been approved by ANBAS Animal Experiment Ethics Review Board.

(3) Changes in activity of cutaneous arterial sympathetic efferent branches when 1 ml / 300 g body weight of a water suspension containing 0.3 mg / ml, 3 mg / ml or 30 ml / ml of BTP was orally administered intragastrically. Examination results Fig. 1 shows the skin when 1 ml / 300 g of water suspension containing 0.3 mg / ml, 3 mg / ml or 30 ml / ml of BTP or 1 ml / 300 g of water was orally administered intragastrically. The measured data of the change of arterial sympathetic nerve activity (CASNA) is shown.

FIG. 2 shows 1 ml of an aqueous suspension containing 0.3 mg / ml, 3 mg / ml or 30 ml / ml of BTP at a percentage of 100% of CASNA neural activity before oral gastric administration (0 minutes), respectively. It shows the change in CASNA when / 300 g body weight or 1 ml / 300 g body weight of water is orally administered intragastrically.

When 1 ml / 300 g of water body weight was subcutaneously administered as a control experiment, CASNA hardly changed, and the CASNA value reached a maximum value of 104.17 ± 4.34% 10 minutes after administration and a minimum value of 97.12 ± 3.91% 20 minutes after administration. During the rest of the measurement period, the values remained between those values (Fig. 2).

On the other hand, when 1 ml / 300 g body weight of a solution containing 0.3 mg / ml of BTP was orally administered intragastrically, CASNA hardly changed, and the CASNA value was the highest value of 105.76 ± 7.07% 40 minutes after administration and the lowest value 70 minutes after administration. It took a value of 97.93 ± 1.47% and remained between those values during the rest of the measurement period (Fig. 2). Even when 1 ml / 300 g body weight of a solution containing 3 mg / ml of BTP was orally administered intragastrically, CASNA hardly changed, and the CASNA value reached a maximum of 103.81 ± 6.72% 75 minutes after administration and a minimum of 94.05 5 minutes after administration. It took ± 2.67% and remained between those values during the rest of the measurement period (Fig. 2).

On the other hand, when 1 ml / 300 g body weight of a solution containing 30 mg / ml of BTP was orally administered intragastrically, CASNA slowly and gradually decreased, and 90 minutes after administration, the CASNA value was the lowest value of 82.93 ± 8.81%. (Fig. 2).

From 5 minutes after the start of administration of cutaneous arterial sympathetic nerve activity (CASNA) when 1 ml / 300 g body weight of a water suspension containing 0.3 mg / ml, 3 mg / ml or 30 mg / ml of BTP was orally administered intragastrically. Statistically examining the significant difference between the value up to 90 minutes and the value between 5 minutes and 90 minutes after the start of CASNA administration when 1 ml / 300 g body weight of water was orally administered to the stomach, control water It was revealed that the CASNA value of the aqueous suspension administration group containing 30 mg / ml of BTP was significantly lower than the CASNA value of the administration group (P <0.0005, F = 60.9 by ANOVA with repeated measures). However, there was a significant difference in the CASNA value between the 0.3 mg / ml administration group (NS, F = 1.4) and the 3 mg / ml administration group (NS, F = 0.132) of BTP compared with the CASNA value of the control water administration group. Was not recognized.

Table 1 shows the absolute value of CASNA before the start of oral intragastric administration (0 minutes) in these 4 groups, and Mann-Whitney U-test between each of the previous values (0 minutes) in these 4 groups. No significant difference was observed.

(4) Discussion From the above experiments, in urethane-anesthetized rats, 1) oral intragastric administration of 1 ml / 300 g body weight of a water suspension containing 30 mg / ml of BTP significantly reduces cutaneous arterial sympathetic nerve activity (CASNA). 2) However, it was revealed that oral gastric administration of 0.3 mg / ml suspension and 3 mg / ml suspension of BTP in a body weight of 1 ml / 300 g did not affect CASNA.

Those that lower CASNA relax and dilate the blood vessels of the cutaneous arteries that supply oxygen and nutrients to the skin and increase blood flow, thus increasing the moisture retention of the skin, promoting hair growth, enhancing the wound healing effect, etc. The above facts indicate that BTP may have a cosmetic effect and a wound healing promoting effect. It seems necessary to examine this possibility in detail in the future.

(5) Conclusion The results of this study suggest that BTP may have the effect of increasing blood flow in the skin and promoting cosmetology, hair growth, wound healing, etc. in urethane-anesthetized rats.

Example 2: Effect of black tea polyphenol intake on human skin blood flow
(1) Preparation of test food In this test, BTP produced by the method described in Example 1 (1) was used. As a BTP-containing test food, capsules filled with 1000 mg of BTP per 5 capsules were prepared. As a placebo test food, capsules filled with crystalline cellulose were prepared.

(2) Test method The following test was conducted on healthy men and women aged between 20 and 60 years old. Using the BTP-containing test food and placebo test food prepared in (1), the test was conducted by a double-blind crossover method. The subjects were allowed to rest in a room where the temperature and humidity were maintained, and both feet were barefoot, and a blood flow meter probe was attached to the left big toe to maintain the sitting posture. Subjects were allowed to ingest 5 capsules of each test food with 200 ml of water.

The blood flow of the subjects was measured using a laser Doppler blood flow meter, and the test was conducted on a different day for each subject.

The blood flow data was analyzed by the average value every 5 minutes, expressed as a percentage with the average value (0 minute value) for 5 minutes before ingestion as 100%, and the blood flow change rate at each elapsed time was obtained. The average value ± standard error was calculated from the data.

(3) Results of Examination of Effect of Oral Ingestion of BTP on Skin Blood Flow Figure 3 shows the transition of the blood flow change rate (%) with respect to the elapsed time (minutes) after ingestion of each test food. When the control placebo test food was ingested, the blood flow change rate gradually decreased from 45 minutes after ingestion to 42.8 ± 4.5% after 90 minutes from ingestion as compared with before ingestion. On the other hand, when a BTP-containing test food containing 1000 mg of BTP was ingested, the rate of change in blood flow 90 minutes after ingestion was 82.8 ± 15.8% as compared with that before ingestion.

(4) Discussion From the above studies, it was clarified that oral ingestion of BTP in adult men and women has the effect of suppressing the decrease in blood flow. This result indicates that the decrease in CASNA may relax and dilate the blood vessels of the cutaneous arteries to increase blood flow.

(5) Conclusion The results of this study suggest that BTP may have the effect of increasing blood flow in the skin and promoting cosmetology, hair growth and wound healing in adult men and women.

Claims (2)

A composition for autonomic nerve regulation (blood vessel) for ingesting the tea extract orally at a dose of 250 to 1500 mg / 60 kg body weight per day for suppressing cutaneous arterial sympathetic nerve activity containing the tea extract as an active ingredient. (Excluding compositions for improving endothelial function, compositions for improving brachial artery dilatation, and compositions for improving microvascular circulation).
Autonomic nerves having a total polyphenol content of 22 to 28% by weight, a theaflavin content of 0.05 to 1.3% by weight, and caffeine content of 0.5% by weight or less in the black tea extract. Adjustment composition. A method of regulating autonomic nerves for suppression of cutaneous arterial sympathetic nerve activity, comprising feeding tea extract orally to mammals, including humans, at a dose of 250-1500 mg / 60 kg body weight per day (humans). Except for medical practice, methods for improving vascular endothelial function, methods for improving brachial artery dilatation, and methods for improving microvascular circulation).
A method in which the total polyphenol content in the black tea extract is 22 to 28% by weight, the theaflavin content is 0.05 to 1.3% by weight, and the caffeine content is 0.5% by weight or less.

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