JP7677784B2 - Relaxation inducer - Google Patents

Description

The present invention relates to a herbal medicine that exhibits a relaxation-inducing effect.

In modern society, there are many opportunities to be exposed to stress in daily life, and it is important to know how to relieve mental tension and deal with stress effectively.

The idea of self-medication, which involves managing and appropriately controlling one's own mental and physical ailments, is becoming more widespread these days. As part of this, opportunities to use herbal medicines are increasing.

Many herbal medicines contain extracts of a mixture of multiple herbal medicines as their active ingredient. Some herbal medicines not only regulate various organs, but also improve mental disorders such as anxiety and tension. Herbal medicines used for mental disorders include Hange-Kouboku-to extract, Keishi-Ka-Ryukotsu-Boreito extract, and Kamikihi-to.

Specifically, the efficacy of Hange-Kouboku-to extract is said to be "for the following symptoms in people with a weak constitution who easily get tired and excited: anxiety neurosis, nervous gastritis, morning sickness, cough, hoarse voice" (Non-Patent Document 1), the efficacy of Keishi-Karyukotsu-Boreito extract is said to be "for the following symptoms in people with a weak constitution who easily get tired and excited: nervousness, insomnia, crying at night, bedwetting, eyestrain" (Non-Patent Document 2), and the efficacy of Kamikihi-to extract is said to be "for the following symptoms in people with a weak constitution and pale complexion: anemia, insomnia, mental anxiety, neurosis" (Non-Patent Document 3).

Pharmaceutical interview form, Kampo formulation Teikoku Hange-Kobokuto extract granules, July 2014 (revised 6th edition) Pharmaceutical interview form, Kampo formulation Teikoku Keishikaryuukotsuboreito extract granules, August 2017 (revised 6th edition) Pharmaceutical interview form, Kampo preparation Osugi Kamikihito Extract G, revised February 2018 (3rd edition)

As mentioned above, some herbal medicines are used to treat mental disorders such as neurosis, but in the stressful daily lives of modern people, it would be desirable to have a way to use herbal medicines that would provide a more direct relaxation effect when one feels a state of mental tension.

Therefore, the present invention aims to provide a new use of herbal medicine that has a relaxing effect.

After extensive research, the inventors discovered that a relaxing effect can be induced by selecting a herbal extract containing a specific aroma component, dissolving the extract in water, and taking it with the scent. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A relaxation effect inducer which contains a herbal extract containing an aroma component selected from the group consisting of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione and furfural, and which is dissolved in water and taken.
Item 2. The relaxant effect inducer according to Item 1, wherein the content of the aroma component is 1.5 μg or more per 1 g of the dried extract of the herbal extract.
Item 3. The relaxant effect inducer according to Item 1 or 2, wherein the herbal extract has not been subjected to a heat history of 110° C. or higher.
Item 4. The relaxant effect inducer according to any one of Items 1 to 3, which contains a concentrated solution of the herbal extract.
Item 5. The relaxant effect inducer according to any one of Items 1 to 3, comprising a freeze-dried product of the herbal extract.

The present invention provides a new way to use herbal medicine that provides a relaxing effect.

The content of the aroma component (1-cyclopentene-3,5-dione) in the herbal extract used in the examples is shown. In the figure, FD stands for freeze-dried product, and SD stands for spray-dried product. The same applies to Figures 2 and 3. The content of the aroma component (cyclopentane-1,2-dione) in the herbal extract used in the examples is shown below. The content of the aroma component (furfural) in the herbal extract used in the examples is shown below.

The relaxing effect inducer of the present invention is characterized by containing a herbal extract containing a specific aromatic component, and being dissolved in water and consumed. The relaxing effect inducer of the present invention is described in detail below.

The herbal extract used in the present invention contains an aroma component selected from the group consisting of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural. From the viewpoint of further enhancing the relaxation-inducing effect, the herbal extract used in the present invention preferably contains at least two aroma components selected from 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural, and more preferably contains all of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural.

The content (total amount) of the above-mentioned aroma components contained in the Kampo extract is not particularly limited and can be appropriately determined depending on the relaxation-inducing effect to be imparted, but from the viewpoint of further improving the relaxation-inducing effect, it is preferably 1.5 μg or more, more preferably 10 μg or more, and even more preferably 12 μg or more per 1 g of the dried extract of the Kampo extract. The upper limit of the content (total amount) range of the above-mentioned aroma components contained in the Kampo extract is not particularly limited, but it can be, for example, 20 μg or less or 15 μg or less per 1 g of the dried extract of the Kampo extract.

The content of 1-cyclopentene-3,5-dione contained in the Kampo extract is not particularly limited and can be determined appropriately depending on the inducing effect of the relaxing effect to be imparted, but from the viewpoint of further improving the inducing effect of the relaxing effect, it is preferably 0.4 μg or more, more preferably 2 μg or more, even more preferably 3 μg or more, and even more preferably 4 μg or more per 1 g of the dried extract equivalent of the Kampo extract. The content of cyclopentane-1,2-dione contained in the Kampo extract is not particularly limited and can be determined appropriately depending on the inducing effect of the relaxing effect to be imparted, but from the viewpoint of further improving the inducing effect of the relaxing effect, it is preferably 0.4 μg or more, more preferably 2 μg or more, even more preferably 3 μg or more, and even more preferably 3.5 μg or more per 1 g of the dried extract equivalent of the Kampo extract. The content of furfural contained in the Kampo extract is not particularly limited and can be determined appropriately depending on the relaxation-inducing effect to be imparted, but from the viewpoint of further improving the relaxation-inducing effect, the content is preferably 0.5 μg or more, more preferably 2 μg or more, even more preferably 4 μg or more, and even more preferably 5 μg or more per 1 g of the dried extract equivalent of the Kampo extract.

The type of herbal extract is not particularly limited as long as it contains the above-mentioned aromatic components. From the viewpoint of further enhancing the relaxation-inducing effect, an example of the herbal extract is yokukansan extract.

Yokukansan is a mixed herbal medicine consisting of Angelica acutiloba, Chotoukou, Cnidium Root, Byakujutsu, Poria Coccineum, Bupleurum Root, and Licorice. There are no particular limitations on the mixing ratio of the herbal medicines that make up the herbal medicine preparation used to manufacture Yokukansan extract, but examples include 1.5-3 parts by weight of Angelica acutiloba, 1.5-3 parts by weight of Chotoukou, 1.5-3 parts by weight of Cnidium Root, 2-4 parts by weight of Byakujutsu, 2-4 parts by weight of Poria Coccineum, 1-5 parts by weight of Bupleurum Root, and 0.75-1.5 parts by weight of Licorice.

A concentrated solution of a Kampo extract can be obtained by extracting a herbal preparation according to a Kampo prescription and concentrating the resulting extract. The extraction solvent used in the extraction is not particularly limited, and may be water or aqueous ethanol, preferably water. The extraction method may be a method in which about 10 to 20 times the amount of the extraction solvent is added to the herbal preparation, and the mixture is stirred at about 40 to 100°C, 50 to 100°C, 60 to 100°C, 80 to 100°C, or 90 to 100°C for about 1 to 3 hours to extract the mixture. The concentration method is not particularly limited, and may be, for example, a vacuum concentration method, a membrane concentration method, or a heat concentration method. A dried product of a Kampo extract can be obtained by drying a concentrated solution of a Kampo extract. The drying method is not particularly limited, and may be, for example, a freeze-drying method, a method in which a suitable adsorbent (e.g., silicic anhydride, starch, etc.) is added to a soft extract with a high extract concentration to obtain an adsorbed powder, a vacuum distillation method, or a spray-drying method.

In the herbal extract preparation of the present invention, the herbal extract may be in the form of a concentrated solution of the herbal extract, or in the form of a dried herbal extract. A concentrated herbal extract is one that contains a herbal extract and a solvent (e.g., an extraction solvent used to extract the herbal extract), and the concentration of the herbal extract (equivalent to the amount of dried extract) contained in the concentrated extract is higher than the concentration of the herbal extract (equivalent to the amount of dried extract) contained in the decoction of the herbal medicine, or is increased to such an extent that dilution is required when taking the herbal extract. The dried herbal extract may be one from which the solvent used to extract the herbal extract has been removed. In the herbal extract preparation of the present invention, the herbal extract is more preferably in the form of a concentrated solution of the herbal extract, from the viewpoint of further enhancing the relaxation effect induction effect, among these forms.

In the Kampo extract preparation of the present invention, it is preferable that the Kampo extract has not been subjected to a heat history of at least 110°C or more, from the viewpoint of suppressing the loss of the above-mentioned aroma components during the preparation process and further enhancing the relaxation-inducing effect. For example, it is preferable that the Kampo extract is obtained by extracting the extract at the above-mentioned temperature, and then concentrating or drying it at a temperature condition of less than 90°C, preferably less than 80°C, more preferably less than 60°C, even more preferably less than 50°C, and even more preferably less than 40°C. From this viewpoint, when the Kampo extract is contained in the form of a concentrated liquid, the concentrated liquid is preferably a product concentrated under reduced pressure, and when the Kampo extract is contained in the form of a dried product, the dried product is preferably a freeze-dried product.

In addition, in the Kampo extract preparation of the present invention, from the viewpoint of suppressing the loss of the above-mentioned aroma components during the preparation process and further enhancing the relaxation-inducing effect, it is also preferable that the Kampo extract has not been subjected to a process of microparticulating the Kampo extract liquid and rapidly evaporating the solvent. From this viewpoint as well, when the Kampo extract is contained in the form of a concentrated liquid, the concentrated liquid is preferably a product concentrated under reduced pressure, and when the Kampo extract is contained in the form of a dried product, the dried product is preferably a freeze-dried product.

The herbal extract preparation of the present invention does not exclude cases in which the herbal extract has been subjected to a thermal history of 110°C or higher, and/or the herbal extract has been prepared via a process of microparticulating the herbal extract liquid and rapidly evaporating the solvent. In these cases, the aroma components described above can be added as additives to the herbal extract prepared via a thermal history of 110°C or higher and/or the herbal extract prepared via a process of microparticulating the herbal extract liquid and rapidly evaporating the solvent.

The content of the herbal extract in the herbal extract preparation of the present invention (as calculated as a dry extract) is not particularly limited and may vary depending on the dosage form of the herbal extract preparation, but may be, for example, 20 to 100% by weight, preferably 25 to 100% by weight.

Other components The herbal extract preparation of the present invention may be composed of only the herbal extract, or may contain additives and bases according to the preparation form. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and may include, for example, excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavorings, fragrances (such as the above-mentioned hydroxyketone-based aroma components), powders, thickeners, dyes, chelating agents, etc. These additives may be used alone or in combination of two or more. In addition, the content of these additives and bases is appropriately set according to the type of additives and bases used, the preparation form of the herbal extract preparation, etc.

In addition to the above-mentioned herbal extract, the herbal extract preparation of the present invention may contain other nutritional components and pharmacological components as necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, but examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, menthols, etc. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of components to be used.

Formulation The formulation of the herbal extract formulation of the present invention is not particularly limited as long as it can be dissolved in water and taken.Specific formulation forms include, for example, solid formulations such as powder, fine granules, and granules (including dry syrup); semi-solid formulations such as jelly; and liquid formulations such as liquid, suspension, and syrup.To prepare the herbal extract formulation of the present invention into these formulation forms, it is sufficient to use the above-mentioned herbal extract as an active ingredient, and additives, bases, and pharmacological ingredients that are added as necessary, and prepare the formulation according to a normal formulation method.

Method of administration The herbal extract preparation of the present invention is dissolved in water and drunk. The dosage per administration is, for example, 0.5 to 5 g, preferably 0.75 to 2 g, more preferably 1 to 1.5 g, in terms of the amount of dried herbal extract, and can be administered 1 to 3 times a day. The temperature of the water is not particularly limited, but is preferably 20 to 75°C, more preferably 30 to 65°C, more preferably 35 to 40°C, from the viewpoint of making it easier for the aroma components to be released and further enhancing the relaxation effect induction effect. Dissolving in water does not require complete dissolution in water, and also includes dispersing in water. The amount of water used is, for example, about 80 to 150 ml, preferably 90 to 120 ml, of the total amount of the herbal extract preparation dissolved in water.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

(1) Preparation of herbal extract formulations As raw herbs, 1.5g of Angelica sinensis, 1.5g of Chotoukou, 1.5g of Cnidium officinalis, 2.0g of Atractylodes orbiculatus, 2.0g of Poria cocos Rhizome, 1.0g of Bupleurum Root, and 0.75g of Licorice were used, which were then chopped and extracted with 15 times the weight of water at about 100°C for 1 hour, followed by centrifugation to obtain an extract. The extract was concentrated under reduced pressure to obtain a concentrated solution of Yokukansan extract. The concentrated solution was also dried at -30°C or lower to obtain a freeze-dried product of Yokukansan extract. Furthermore, the concentrated solution was dropped into an atomizer rotating at 10,000 rpm, and dried by supplying hot air at 150°C to obtain a spray-dried product of Yokukansan extract. The single dose of the concentrated liquid is 5 g, the single dose of the spray-dried product is 1.25 g, and the single dose of the freeze-dried product is 1.25 g (each equivalent to 1.25 g of dried herbal extract).

(2) Measurement of aroma components The content of aroma components contained in the herbal extract was measured using GC/MS. DB-WAX (film thickness 0.25 μm, length 30 m, inner diameter 0.25 mm) was used for the column. The column temperature was increased at a rate of 10°C/min from 60°C to 150°C, 10°C/min from 45°C to 160°C, 15°C/min from 100°C to 160°C, and 20°C/min from 160°C to 240°C. During the analysis, the temperature of the detector was kept at 300°C. Quantitative analysis was performed using a calibration curve calculated from each standard. For the concentrated solution, the original solution was used, and 0.5 μL was injected. For the spray-dried product, purified water was added to 5 g of the spray-dried product to adjust the weight to 20 g, and 0.5 μL was injected. For the freeze-dried product, purified water was added to 5 g of the freeze-dried product to adjust the total weight to 20 g, and 0.5 μL of the mixture was injected.
The results are shown in Figures 1 to 3.

(3) Evaluation of the relaxation effect induction effect The obtained Kampo extract (concentrate 5g, spray-dried product 1.25g, and freeze-dried product 1.25g; each is equivalent to 1.25g of dried Kampo extract) was mixed with water at 37°C to make the total volume 100ml, and 10 men and women in their 20s to 50s were asked to drink it as subjects, and the degree of realization of the relaxation effect was evaluated on a 5-point scale of "realized", "somewhat felt", "cannot say either way", "somewhat did not feel" and "did not feel". The ratio of the number of people who evaluated "realized" and "somewhat felt" among all the subjects was regarded as the effectiveness rate. The results are shown in Table 1.
The results are shown in Table 1.

As shown in Figure 1, the herbal extracts of Examples 1 and 2 contained 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural. Also, as shown in Table 1, the herbal extract preparations of Examples 1 and 2, which contain 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural, showed a significantly improved relaxation effect induction effect compared to the herbal extract preparation of Comparative Example 1. Also, when comparing the herbal extract preparations of Examples 1 and 2, not only was the effectiveness rate higher in Example 1, but the proportion of subjects who evaluated that they "felt" the effect was also higher in Example 1, at 70% in Example 1 and 50% in Example 2.

Claims (5)

A relaxation effect inducer which contains a yokukansan extract containing 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione and furfural and is dissolved in water and taken. 2. The relaxing effect inducer according to claim 1, wherein the total content of said 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione and furfural is 1.5 μg or more per 1 g of the dry extract of said yokukansan extract. The relaxation effect inducer according to claim 1 or 2, wherein the yokukansan extract has not been subjected to a heat history of 110°C or higher. The relaxation effect inducer according to any one of claims 1 to 3, comprising a concentrated solution of the yokukansan extract. The relaxant effect inducer according to any one of claims 1 to 3, comprising a freeze-dried product of the yokukansan extract.