NZ623816B2 - Non-alcoholic beverage containing eudesmol - Google Patents

Abstract

Provided is a non-alcoholic beverage, which has an autonomic nerve modulating effect, shows an excellent cool taste and has an alcohol content of less than 1%, characterized by comprising, as the active component, one or more kinds of eudesmols selected from among ?-eudesmol, ?-eudesmol and ?-eudesmol and the content of the active component being 5-100 ppb. Also provided is an autonomic nerve modulating agent characterized by comprising, as the active component, the eudesmol(s) contained in the aforesaid beverage and the content of the active component, in terms of the total content of the eudesmol(s) therein, being 5-100 ppb. ol and the content of the active component being 5-100 ppb. Also provided is an autonomic nerve modulating agent characterized by comprising, as the active component, the eudesmol(s) contained in the aforesaid beverage and the content of the active component, in terms of the total content of the eudesmol(s) therein, being 5-100 ppb.

Description

DESCRIPTION TITLE OF THE INVENTION NON-ALCOHOLIC BEVERAGE CONTAINING EUDESMOL Technical Field The present invention relates to a non-alcoholic beverage having an autonomic nerve-modulating effect, excellent in cool feeling, and having an alcohol content of less than 1%, which comprises one or more eudesmols selected from the group consisting of α-eudesmol, β- eudesmol, and γ-eudesmol as an active ingredient, and to an autonomic nerve-modulating agent comprising the eudesmol as an active ingredient.

Background Art In the field of beverages, beverages to which various health functions are imparted using various additives or beverages to which various flavors or tastes are imparted have recently been provided because of diversified preferences or from the viewpoint of health consciousness. For the addition of the flavor of "cool feeling" to a beverage, it is disclosed, for example, that a refreshing fruit juice-containing beverage to which "refresh feeling" or "cold feeling" is imparted is produced by adding a refresh-feeling substance such as menthol, menthone, camphor, mint oil and peppermint oil, or a cold-feeling substance such as 3-l-menthoxypropane- 1,2-diol and N-ethyl-p-menthanecarboxamide, in producing a fruit juice-containing beverage (Japanese unexamined Patent Application Publication No. 2005-143461).

Thus, for soft drinks, a means has conventionally been carried out to intentionally impart the impression of coolness as described by the expression of "refreshed" to the periphery of the base of the throat during drinking by using synthetic perfumes such as menthol as additives.

For fermentative alcoholic beverages such as beer, a method is disclosed for producing fermentative alcoholic beverages excellent in cool feeling by devising a fermentation method and the component ratio and incorporating specified amounts of β-eudesmol, limonene, and α-terpineol (Japanese unexamined Patent Application Publication No. 2010-63431).

However, for fermentative alcoholic beverages as described above, it has not previously been studied what flavor or function such as health can be imparted when various adjusted components are incorporated as components of each non-alcoholic beverage, not affected by the influence of the formation, metabolism, and the like of various substances due to fermentation by the device of a fermentation method and the component ratio.

Prior Art Documents Patent Documents Patent Document 1: Japanese unexamined Patent Application Publication No. 2005-143461 Patent Document 2: Japanese unexamined Patent Application Publication No. 2010-63431 Summary of the Invention Object to be Solved by the Invention An object of the present invention is to provide a non-alcoholic beverage of refreshing taste excellent in cool feeling by a simple means excellent in terms of cost and to provide a functional beverage having a health function under mild conditions as a health beverage from the viewpoint of health consciousness, and/or to provide an agent for health function comprising a component of the functional beverage as an active ingredient, and/or to provide the public with a useful choice.

Means to Solve the Object In intensive studies on the provision of a non- alcoholic beverage of refreshing taste excellent in cool feeling and the addition of a health function to the beverage for solving the above problems, it has been found that the present invention can provide a non-alcoholic beverage of refreshing taste excellent in cool feeling by incorporating a specified amount of a eudesmol, such as α- eudesmol, β-eudesmol, and γ-eudesmol, in a non-alcoholic beverage having an alcohol content of as low as less than 1% and also can provide a healthy functional beverage having an autonomic nerve-modulating function due to an autonomic nerve-modulating effect, thereby accomplishing the present invention.

Specifically, the present invention is composed of a non-alcoholic beverage having an alcohol content of less than 1%, comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ- eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb. According to the present invention, preferable combinations of eudesmols can include a combination of α-eudesmol and β-eudesmol.

A eudesmol as an active ingredient of the present invention can be properly obtained as an extracted component from a plant body containing the ingredient or the like; however, preferred examples of the plant body can include hop or Eucalyptus globulus.

According to the present invention, examples of the non-alcoholic beverage having an alcohol content of less than 1% can include a tea beverage, a carbonated beverage, or a non-alcoholic beer beverage. The non-alcoholic beverage may be prepared in the form of a container-packed beverage. The container-packed beverage may be prepared as a product in which the total amount of the eudesmol as an active ingredient is adjusted so that the daily ingestion amount is 50 µg to 2.5 µg.

The present invention also provides a use of one or more eudesmols selected from the group consisting of α- eudesmol, β-eudesmol, and γ-eudesmol as active ingredient, in the manufacture of a medicament in the form of a non- alcoholic beverage, having an alcohol content of less than 1%, wherein the content of the active ingredient is 5- 100ppb, for reducing stress in a subject in need thereof.

Also described is an autonomic nerve-modulating agent comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ-eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb in terms of a total amount of the eudesmol contained.

The eudesmol contained in a non-alcoholic beverage of the present invention imparts cool feeling to the beverage and imparts an autonomic nerve-modulating effect to the beverage. The autonomic nerve system responsible for the autonomic nerve-modulating effect is a system modulating the activity of organs under unconsciousness so as to adjust itself to the external environment or the internal environment independently of intentional control.

The autonomic nerve system consists of the sympathetic division, whose activity is increased in a tense state, and the parasympathetic division, whose activity is increased in a relaxed state. The two autonomic nervous divisions act in an opposing manner by responding to changes in external environments, such as air temperature and mental stress, or changes in internal environments, such as nutritional state, to adjust the body to these changes. It is considered that continuation of exposure to excessive stress results in the imbalance of autonomic nerve, the excessively increased activity of sympathetic nerve, and the predominance of sympathetic nerve activity over parasympathetic nerve activity to allow the tense state to continue, and causes autonomic imbalance typified by a poor physical condition such as insomnia. Thus, in modern society where stress is often felt, a beverage having an autonomic nerve-modulating function can effectively work in terms of health function as a safe and simple means capable of keeping the autonomic nerve balance normal, suppressing the excessive excitation of sympathetic nerve, and increasing the parasympathetic nerve activity.

Specifically, the present invention is composed of (1) a non-alcoholic beverage having an alcohol content of less than 1%, comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ-eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb, (2) the non- alcoholic beverage having an alcohol content of less than 1% according to (1) above, wherein the active ingredient comprises α-eudesmol and β-eudesmol, or (3) the non- alcoholic beverage having an alcohol content of less than 1% according to (1) or (2) above, wherein the eudesmol is a component extracted from hop or Eucalyptus globulus.

The present invention is also composed of (4) the non-alcoholic beverage having an alcohol content of less than 1% according to any one of (1) to (3) above, wherein the non-alcoholic beverage having an alcohol content of less than 1% is a tea beverage, a carbonated beverage, or a non-alcoholic beer beverage, (5) the non-alcoholic beverage having an alcohol content of less than 1% according to any one of (1) to (3) above, wherein the non- alcoholic beverage having an alcohol content of less than 1% is a container-packed beverage, (6) the non-alcoholic beverage having an alcohol content of less than 1% according to (5) above, wherein the container-packed beverage consisting of the non-alcoholic beverage having an alcohol content of less than 1% is prepared so that the daily ingestion amount of eudesmol is 50 µg to 2.5 µg in terms of total amount of eudesmol as an active ingredient, or (7) a use or more eudesmols selected from the group consisting of of one α-eudesmol, β-eudesmol, and γ- eudesmol as active ingredient, in the manufacture of a medicament in the form of a non-alcoholic beverage, having an alcohol content of less than 1%, wherein the content of the active ingredient is 5-100ppb, for reducing stress in a subject in need thereof.

Also described is an autonomic nerve-modulating agent comprising the eudesmol described in (1) above as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb in terms of a total amount of the eudesmol contained.

Effect of the Invention Described herein is a non-alcoholic beverage of refreshing taste excellent in cool feeling, has an autonomic nerve-modulating effect, and provides a functional beverage having a health function under mild conditions as a health beverage.

Brief Description of Drawings [Figure 1] Figure 1 is a graph showing GVNA activity when a 0.5% aqueous CMC solution containing 5, 50, or 500 ppb of β-eudesmol or 0.5% aqueous CMC was intragastrically administered to 1 ml/300 g body weight. Experiment was performed in n = 3 per group. Values are indicated by setting the nervous activity of GVNA before sample administration (0 minute) to 100%. *** indicates that a significant difference was observed. (P < 0.0005, ANOVA with repeated measures) [Figure 2] Figure 2 is a graph showing ASNA activity when a 0.5% aqueous CMC solution containing 5, 50, or 500 ppb of β-eudesmol or 0.5% aqueous CMC was intragastrically administered to 1 ml/300 g body weight. Experiment was performed in n = 3 per group. Values are indicated by setting the nervous activity of ASNA before sample administration (0 minute) to 100%. *** indicates that a significant difference was observed. (P < 0.0005, ANOVA with repeated measures) Mode of Carrying Out the Invention The present invention comprises a non-alcoholic beverage having an alcohol content of less than 1%, comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ-eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb as the total amount of the eudesmol contained, and an autonomic nerve-modulating agent comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ-eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb as the total amount of the eudesmol contained. α-Eudesmol, β-eudesmol, or γ-eudesmol as an active ingredient of a non-alcoholic beverage described herein may be a commercially available one, or one purified from a natural product or a synthetic perfume containing any of these eudesmols. The natural product or synthetic perfume containing any of these eudesmols, or an extract from the natural product or synthetic perfume may also be used as a material containing α-eudesmol, β-eudesmol, or γ-eudesmol.

Examples of the natural product used for the extraction include hop as a plant belonging to Moraceae perennial plants (Humulus Lupulus), and Eucalyptus globulus as an evergreen tall tree belonging to Myrtaceae.

These plants may be used directly in the form of their bodies, or may be used as treated products obtained by physicochemically and biologically treating the plant bodies. Bodies of these plants include leaves or cones for hop; however, cones are preferably used. A lupulin part of the cone may be used. Species of hop include German Hersbrucker species, German spalt select species, and Czech Zatsu species, and German Hersbrucker species is preferably used because it highly contains β-eudesmol.

For Eucalyptus globulus (eucalyptus), its bodies include leaves, twigs, flowers, or fruits, and leaves are preferably used.

Examples of the physicochemical treatment of plant bodies include drying treatments such as solar drying, draught drying, and freeze drying, and crushing treatments using a blender, a homogenizer, a ball mill, and the like, and examples of the physicochemically treated product include a drying-treated product and a crushing-treated product. Examples of the biological treatment include fermentation treatments using bacteria, yeasts, and the like, and examples of the biologically treated product include fermentation treated products. Examples of the treated product of a plant body include a hop pellet as a compressed product of hop cones. Extracts of a plant body described herein include extracts capable of being obtained by methods for extracting a substance, such as solvent extraction, supercritical fluid extraction, and steam distillation, from the plant body, and solvent extraction is preferable.

The solvent used for the solvent extraction may be any of, for example, aqueous media such as water, purified water, deionized water, and distilled water and organic solvents such as alcohols, alkyl acetates, aliphatic ketones, aliphatic ethers, aliphatic hydrocarbons, and alicyclic hydrocarbons, provided that it is a solvent capable of extracting α-eudesmol, β-eudesmol, or γ- eudesmol from plant bodies used herein or treated products thereof; preferred are aqueous media or alcohols, and more preferably used is ethanol. These solvents may be used alone, or as a mixed solvent in which a plurality thereof is combined.

Apparatus used in conventional solvent extraction, such as a stirrer, an ultrasonic generator, a reflux extractor, or a Soxhlet extractor is used in the solvent extraction. The amount of the solvent used for the solvent extraction is not particularly limited; however, the extraction is performed using the solvent in an amount of 0.1 to 10,000 parts by weight, preferably 1 to 1,000 parts by weight, more preferably 5 to 100 parts by weight, based on 1 part by weight of a plant body. The extraction temperature is not particularly limited provided that it is a temperature of not less than the melting point of the solvent and not more than the boiling point thereof; however, it is preferably 0 to 100°C, more preferably 20 to 80°C for aqueous media and preferably 0 to 1,000°C, more preferably 20 to 80°C for organic solvents.

The extraction time is not particularly limited; however, it is preferably 1 minute to 1 year, more preferably 30 minutes to 1 week. After the end of solvent extraction, the resultant extract liquid may be subjected to a solid-liquid separation method such as sedimentation separation, cake filtration, clarification filtration, centrifugal filtration, centrifugal sedimentation, compression, separation, or filter press, preferably filtration, to provide an extract liquid, which is used as an extract. The extraction residue obtained by the solid- liquid separation method may be further extracted using an extraction solvent to use the resultant as an extract.

The extract obtained from a plant body by an extraction method such as solvent extraction or supercritical fluid separation may be further treated using a solid-liquid separation method, a concentrating or drying method, a purification method, or the like.

Means for obtaining extracts from plant bodies which may be used include the use of commercially available hop essential oil, hop extract, eucalyptus essential oil, eucalyptus extract, and the like, provided that they contain α-eudesmol, β-eudesmol, or γ-eudesmol. After, if necessary, dissolving the extract in a solvent, a purification method may be used, such as a membrane separation process, a liquid membrane separation process, a solvent partition method, and a fractionation technique, to increase the concentration of α-eudesmol, β-eudesmol, or γ-eudesmol in the extract or remove undesired substances.

In preparing a plant body extract described herein, to avoid the inactivation of α-eudesmol, β-eudesmol, or γ- eudesmol, for example, the addition of an antioxidant, a preservative, or the like and the adjustment of heating temperature may be performed. A beverage described herein can be produced by a conventional method for producing a non-alcoholic beverage (a beverage having an alcohol content of less than 1%) except for adding α-eudesmol, β- eudesmol, or γ-eudesmol, or a material containing the same so that the content thereof in the beverage totals 5 to 100 ppb, during production or after production.

The content of α-eudesmol, β-eudesmol, and γ- eudesmol in a beverage described herein can be quantified by an ordinary method, such as using a commercial GC/MS apparatus.

Examples of the non-alcoholic beverage described herein include, but not limited to, mineral water, near water, sports drink, tea beverage, milk beverage, coffee beverage, fruit juice beverage, vegetable juice beverage, fruit/vegetable juice beverage, and carbonated beverage.

The non-alcoholic beverage may be a beer beverage having an alcohol content of less than 1%, such as a non- alcoholic beer. The mineral water encompasses both effervescent and non-effervescent mineral waters.

The tea beverage refers to a beverage for drinking by decocting leaves (tea leaves) of a tea plant as a theaceous evergreen tree or leaves of a plant other than the tea plant, or a cereal or the like, and encompasses all of fermented tea, semi-fermented tea, and unfermented tea. Specific examples of the tea beverage include Japanese teas (for example, green tea and barley tea), black tea, tisanes (for example, jasmine tea), Chinese teas (for example, Chinese green tea and oolong tea), and roasted tea.

The milk beverage refers to a beverage using raw milk, cow milk, or the like, or a food produced made therefrom as the main raw material, and encompasses, for example, a beverage using processed milk as a raw material, such as nutrient-reinforced milk, flavor-added milk, or sweetened hydrolyzed milk, in addition to one using cow milk or the like per se as a material.

Examples of the fruit used in the fruit juice beverage and the fruit/vegetable juice beverage include apple, orange, grape, banana, pear, peach, and mango.

Examples of the vegetable used in the vegetable juice beverage and the fruit/vegetable juice beverage include tomato, carrot, celery, pumpkin, celery, and cucumber.

Also described is a non-alcoholic beverage excellent in cool feeling and having a health function containing an autonomic nerve-modulating function, and also provides an autonomic nerve-modulating agent having an autonomic nerve-modulating function. When the beverage described herein is ingested as an autonomic nerve-modulating agent, it is preferably ingested so that the total amount of eudesmol, β-eudesmol, and γ-eudesmol per day per adult is 50 µg to 5 µg, preferably 50 µg to 3 µg, more preferably 50 µg to 2.5 µg.

The present invention will be more specifically described below with reference to Examples. However, the present invention is not intended to be limited to these Examples.

The term “comprising” as used in this specification and claims means “consisting at least in part of”. When interpreting statements in this specification, and claims which include the term “comprising”, it is to be understood that other features that are additional to the features prefaced by this term in each statement or claim may also be present. Related terms such as “comprise” and “comprised” are to be interpreted in similar manner.

Examples Example 1 Aqueous solutions were prepared each containing 2.5 ppb, 5 ppb, 10 ppb, and 50 ppb of β-eudesmol. Using an aqueous solution not containing β-eudesmol as a control, it was evaluated in blind by 8 panelists whether cool feeling was felt or not compared to for the control.

As a result, 4 panelists for the aqueous solution containing 2.5 ppb of β-eudesmol, 6 for the aqueous solution containing 5 ppb of β-eudesmol, 7 for the aqueous solution containing 10 ppb of β-eudesmol, and all of 8 for the aqueous solution containing 50 ppb of β-eudesmol answered that cool feeling was felt for the β-eudesmol- containing aqueous solutions compared to for the water.

Example 2 Male Wistar rats about 300 g in body weight (about 9-week old) were housed for 1 week or more in a constant temperature animal room at 24°C under 12-hour light and 12-hour dark cycles (with lights on from 8 to 20 o'clock) and then fasted for 3 hours. After fasting, urethane anesthetization was performed; a cannula for intragastric administration was inserted; and the efferent branch of gastric vagal nerve as a parasympathetic nerve or adrenal sympathetic nerve was lifted using a silver electrode to measure the electrical activity of these nerves (Shen J, et al. Neurosci. Lett. 383188-193, 2005; Tanida M, et al., Neurosci. Lett. 389: 109-114, 2005). 0.5% carboxymethylcellulose (CMC) aqueous solutions each containing 5, 50, or 500 ppb of β-eudesmol (hereinafter referred to as a β-eudesmol CMC aqueous solution) were prepared. At the time the measured values thereof stabilized, 1.0 ml/300 g body weight of each β- eudesmol CMC aqueous solution was intragastrically administered to electrophysiologically measure a change in the electrical activity of the efferent branch of gastric vagal nerve or adrenal sympathetic nerve produced here for 90 minutes. In this respect, a tube was inserted into the trachea from the start of surgery until the end of measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5°C using a thermostat. The same operation was performed except for using a CMC aqueous solution not containing β- eudesmol as a control, which was defined as a control administration group.

These nerve activity data were analyzed using the average firing rate for 5 seconds (pulses/5 seconds) every minutes, and expressed in percentages by setting the average value for 5 minutes before the start of stimulation (the value at 0 minute) to 100%. The average value + standard error was calculated from the data; the statistically significant difference between groups was tested by using analysis of variance (ANOVA) with repeated measures; and the statistically significant difference between absolute values of nerve activities before the start of intragastric administration (at 0 minute) was tested by using Mann-Whitney U-test.

The results for the gastric vagal nerve activity (GVNA) are shown in Figure 1, and the results for the adrenal sympathetic nerve activity (ASNA) are shown in Figure 2.

As shown in Figure 1, any concentration of β- eudesmol kept GVNA at a high level in the groups of intragastric administration of the β-eudesmol CMC aqueous solutions compared to that in the control administration group. Particularly, administration at 5 ppb kept the GVNA activity in the highest state.

When GVNA values from 5 minutes after the start of intragastric administration until 90 minutes thereafter were statistically compared between the groups of administration of the β-eudesmol CMC aqueous solutions and the control administration group, all the GVNA values of the groups of administration of the β-eudesmol CMC aqueous solutions were significantly higher than the GVNA value of the control administration group. There was no statistically significant difference between the absolute values of nerve activities before the start of intragastric administration (at 0 minute).

As shown in Figure 2, any concentration of β- eudesmol decreased the level of ASNA at 90 minutes after administration in the groups of administration of the β- eudesmol CMC aqueous solutions compared to that in the control administration group. Particularly, the values always remained low from 5 minutes after administration until 90 minutes thereafter in the group of administration of the CMC aqueous solution of 5 ppb of β-eudesmol compared to in the control administration group. When ASNA values from 5 minutes after the start of intragastric administration until 90 minutes thereafter were statistically compared between the groups of administration of the β-eudesmol CMC aqueous solutions and the control administration group, all the ASNA values of the group of administration of the CMC aqueous solution of ppb or 50 ppb of β-eudesmol were significantly lower than the ASNA value of the control administration group.

There was no statistically significant difference between the absolute values of nerve activities before the start of intragastric administration (at 0 minute); thus, it was considered that there was probably no influence of individual difference among the animals used for the test.

The effects shown above, that is, the effect of increasing GVNA as a parasympathetic nerve activity and the effect of decreasing ASNA as a sympathetic nerve activity, suggest that β-eudesmol has an autonomic nerve- modulating effect.

Example 3 A beverage (1 L) is produced by an ordinary method using the following combination. The eudesmol perfume is prepared by converting an extract from a plant body containing eudesmol to a perfume.

Fructose glucose liquid sugar (fructose content: 55%) 40 g Citric acid (anhydrous) 1.1 g Trisodium citrate (crystal) 0.4 g Eudesmol perfume (containing a final concentration of 5 ppb of β-eudesmol) 0.05 g Water appropriate amount Total 1,000 g Industrial Applicability The present invention provides a non-alcoholic beverage of refreshing taste excellent in cool feeling by a simple means excellent in terms of cost and the non- alcoholic beverage of the present invention has an autonomic nerve-modulating effect, and the present invention provides a functional beverage having a health function under mild conditions as a health beverage.

In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.

In the description in this specification reference may be made to subject matter that is not within the scope of the claims of the current application. That subject matter should be readily identifiable by a person skilled in the art and may assist in putting into practice the invention as defined in the claims of this application.

Claims (6)

1. A non-alcoholic beverage having an alcohol content of less than 1%, comprising one or more eudesmols selected from the group consisting of α-eudesmol, β-eudesmol, and γ-eudesmol as an active ingredient, wherein the content of the active ingredient is 5 to 100 ppb.

2. The non-alcoholic beverage having an alcohol content of less than 1% according to claim 1, wherein the active ingredient comprises α-eudesmol and β-eudesmol.

3. The non-alcoholic beverage having an alcohol content of less than 1% according to claim 1 or 2, wherein the eudesmol is a component extracted from hop or Eucalyptus globulus.

4. The non-alcoholic beverage having an alcohol content of less than 1% according to any one of claims 1 to 3, wherein the non-alcoholic beverage having an alcohol content of less than 1% is a tea beverage, a carbonated beverage, or a non-alcoholic beer beverage.

5. The non-alcoholic beverage having an alcohol content of less than 1% according to any one of claims 1 to 3, wherein the non-alcoholic beverage having an alcohol content of less than 1% is a container-packed beverage.

6. The non-alcoholic beverage having an alcohol content of less than 1% according to claim 5, wherein the container-