JP7677783B2 - 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 for exposure 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 mental and physical disorders, 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 is desirable to have new herbal medicines that can have a more direct relaxing effect when one feels a state of mental tension.

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

After extensive research, the inventors discovered that Shimotsuto extract and Dokkatsu-Kakkonto extract have the ability to induce a relaxing effect. 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 comprising a Shimotsuto extract and/or an Dokkatsu-Kakkonto extract.
Item 2. The relaxant according to item 1, which is dissolved in water and taken.
Item 3. The relaxant effect inducer according to Item 1 or 2, wherein the total content of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione and furfural is 0.4 μg or more per 1 g of the dried extract of the Shimotsuto extract and the Dokukatsu-Kakkonto extract.
Item 4. The relaxant effect inducer according to any one of Items 1 to 3, wherein the Shimotsuto extract and the Dokukatsu-Kakkonto extract have not been subjected to a heat history of 110° C. or higher.
Item 5. The relaxant effect inducer according to any one of Items 1 to 4, comprising a concentrated solution of the Shimotsuto extract and/or the Dokkatsu-Kakkonto extract.
Item 6. The relaxant effect inducer according to any one of Items 1 to 4, comprising a freeze-dried product of the Shimotsuto extract and/or the Dokkatsu-Kakkonto extract.

The present invention provides a new herbal medicine that has a relaxing effect.

The relaxing effect inducer of the present invention is characterized by containing a specific herbal extract. The relaxing effect inducer of the present invention is described in detail below.

Specific Kampo Extract The specific Kampo extract used in the present invention is Shimotsuto extract and/or Dokukatsu-Kakkonto extract.

Shimotsuto is a mixture of herbal medicines consisting of Peony Root, Rehmannia Root, Cnidium Root, and Angelica Root. There are no particular limitations on the ratio of the herbal medicines that make up the herbal medicine preparation used to manufacture Shimotsuto extract, but examples include 1.5 to 5 parts by weight of Peony Root, 1.5 to 5 parts by weight of Rehmannia Root, 1.5 to 5 parts by weight of Cnidium Root, and 1.5 to 5 parts by weight of Angelica Root. Udo-kakkonto is a mixture of herbal medicines consisting of Pueraria root, Cinnamon bark, Peony Root, Ephedra Root, Dokkatsu Root, Ginger, Rehmannia Root, Chinese Scutellaria Root, and Licorice Root. The mixing ratio of the herbs that make up the herbal preparation used to manufacture Udo Kakkonto extract is not particularly limited, but examples include 2.5 to 5 parts by weight of Pueraria lobata, 1.5 to 3 parts by weight of Cinnamon Bark, 1.5 to 3 parts by weight of Peony Root, 1 to 2 parts by weight of Ephedra Root, 1 to 2 parts by weight of Dokkatsu Root, 0.25 to 1 part by weight of Ginger Root, 2 to 4 parts by weight of Rehmannia Root, 0.5 to 2 parts by weight of Taiso Root, and 0.5 to 2 parts by weight of Licorice Root.

A concentrated solution of a specific herbal extract can be obtained by subjecting a herbal preparation according to a herbal prescription to an extraction process and concentrating the resulting extract. The extraction solvent used in the extraction process is not particularly limited, and may be water or aqueous ethanol, preferably water. The extraction process may be performed by adding about 10 to 20 times the amount of the extraction solvent to the herbal preparation and stirring for about 1 to 3 hours at 40 to 100°C, 50 to 100°C, 60 to 100°C, 80 to 100°C, or 90 to 100°C. The concentration process is not particularly limited, and may be, for example, a vacuum concentration process, a membrane concentration process, or a heat concentration process. A dried product of a specific herbal extract can be obtained by drying the concentrated solution of the herbal extract. The drying process is not particularly limited, and may be, for example, a freeze-drying process, a process 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 process, or a spray-drying process.

In the present invention, the above-mentioned specified Kampo extract may include either Shimotsuto extract or Dokkatsu-Kakkonto extract, or may include both. From the viewpoint of further enhancing the relaxation-inducing effect, Shimotsuto extract is more preferably used as the above-mentioned specified Kampo extract.

From the viewpoint of further enhancing the effect of inducing a relaxing effect, the above-mentioned specified herbal extract preferably contains an aroma component selected from the group consisting of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione, and furfural. The content of the aroma component contained in the above-mentioned specified herbal extract is not particularly limited, but from the viewpoint of further enhancing the effect of inducing a relaxing effect, the total amount is, for example, 0.4 μg or more, preferably 5 μg or more, more preferably 8 μg or more, even more preferably 10 μg or more, and even more preferably 13 μg or more per 1 g of the dried extract equivalent of the herbal extract. The upper limit of the content (total amount) range of the above-mentioned aroma components contained in the above-mentioned specified herbal extract is not particularly limited, but examples include 20 μg or less or 16 μg or less per 1 g of the dried extract equivalent of the herbal extract.

The content of 1-cyclopentene-3,5-dione in the above-mentioned specified 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 0.1 μg or more, more preferably 1 μg or more, even more preferably 2 μg or more, and even more preferably 3 μg or more per 1 g of the dried extract equivalent of the Kampo extract. The content of cyclopentane-1,2-dione in the above-mentioned specified 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 0.1 μg or more, preferably 1 μg or more, even 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 in the specified 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 0.2 μg or more per 1 g of the dried extract equivalent of the Kampo extract, more preferably 2 μg or more, even more preferably 4 μg or more, even more preferably 6 μg or more, and even more preferably 7 μg or more.

In the herbal extract preparation of the present invention, the above-mentioned specified herbal extract may be contained in the form of a concentrated solution of the herbal extract, or in the form of a dried product of the herbal extract. A concentrated solution of a herbal extract 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 a decoction of the herbal medicine, or is high enough to require dilution when taken. A dried product of a 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 above-mentioned specified herbal extract is preferably one that 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, the above-mentioned specified herbal extract is preferably one obtained by extracting the extract at the above-mentioned temperature, and then concentrating or drying the extract 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 above-mentioned specified herbal extract is contained in the form of a concentrated liquid, the concentrated liquid is preferably a product concentrated under reduced pressure, and when the above-mentioned specified herbal extract is contained in the form of a dried product, the dried product is preferably a freeze-dried product.

In addition, in the herbal extract preparation of the present invention, from the viewpoint of suppressing the loss of the aroma components in the preparation process and further enhancing the relaxation-inducing effect, it is also preferable that the above-mentioned specified herbal extract is one that has not been subjected to a process of microparticulating the herbal extract liquid and rapidly evaporating the solvent. From this viewpoint as well, when the above-mentioned specified herbal extract is contained in the form of a concentrated liquid, the concentrated liquid is preferably a product concentrated under reduced pressure, and when the above-mentioned specified herbal 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 where the above-mentioned specified herbal extract includes one that has been subjected to a thermal history of 110°C or more, and/or where the above-mentioned specified herbal extract includes one that has been prepared via a process of microparticulating the herbal extract liquid and rapidly evaporating the solvent. In these cases, the above-mentioned aroma component can be added as an additive to the above-mentioned specified herbal extract prepared via a thermal history of 110°C or more and/or the above-mentioned specified herbal extract prepared via a process of microparticulating the herbal extract liquid and rapidly evaporating the solvent.

The content of the specified 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 above-mentioned specific 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 fragrance components), powders, thickeners, pigments, chelating agents, etc.These additives may be used alone or in combination of two or more. The contents of these additives and bases are appropriately set depending on the types of additives and bases used, the formulation form of the herbal extract preparation, etc.

In addition, the herbal extract preparation of the present invention may contain other nutritional components and pharmacological components as necessary, in addition to the above-mentioned specified herbal extract. 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.

Formulations The formulations of the herbal extract formulations of the present invention are not particularly limited, but specific formulations include, for example, solid formulations such as powders, fine granules, and granules (including dry syrups); semi-solid formulations such as jellies; and liquid formulations such as liquids, suspensions, and syrups. To prepare the herbal extract formulations of the present invention into these formulations, the above-mentioned specific herbal extracts as active ingredients, and additives, bases, and pharmacological ingredients added as necessary, may be formulated according to conventional formulation methods.

Method of administration The herbal extract preparation of the present invention may be administered orally. The dosage per administration may be, 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 may be administered 1 to 3 times a day. In order to further enhance the effect of inducing a relaxing effect, the herbal extract preparation of the present invention is preferably dissolved in water and then drunk. 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, in order to easily release the aroma of the above-mentioned aroma components and to further enhance the effect of inducing a relaxing effect. Dissolving in water does not require complete dissolution in water, and also includes dispersing in water. The amount of water used may be, for example, about 80 to 150 ml, preferably about 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 Kampo Extract Preparation (1-1) Preparation of Dokkatsu-Kakkonto Extract Concentrate As raw herbs, 1.5g of Kakkon, 1.5g of Cinnamon, 1.5g of Peony, 1.0g of Ephedra, 1.0g of Dokukatsu, 0.167g of Zingiber, 1.0g of Rehmannia, 0.5g of Taiso, and 0.5g of Licorice were used, chopped, and extracted with 15 times the weight of water at about 100°C for 1 hour, and centrifuged to obtain an extract. The extract was concentrated under reduced pressure to obtain a Dokkatsu-Kakkonto extract concentrate. The single dose of the concentrate was 5g (equivalent to 1.25g of dried extract of Kampo extract).

(1-2) Preparation of Shimotsuto Extract Concentrate The raw herbs used were 1.5g of Peony Root, 1.5g of Rehmannia Root, 1.5g of Cnidium Root, and 1.5g of Angelica Root. After chopping, they were extracted with 15 times the weight of water at about 100°C for 1 hour and centrifuged to obtain an extract. The extract was concentrated under reduced pressure to obtain a concentrated Shimotsuto extract. The single dose of the concentrate was 5g (equivalent to 1.25g of dried extract of Kampo 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 the calibration curve calculated from each standard. The concentrate was the original solution, and 0.5 μL was injected. The results are shown in Table 1.

(3) Evaluation of the relaxation effect induction effect 5 g of the obtained Kampo extract (1.25 g of dried Kampo extract equivalent) was mixed with water at 37°C to make the total volume 100 ml, and 10 men and women in their 20s to 50s were asked to drink it as subjects, and the degree of the relaxation effect they felt was evaluated on a 5-point scale: "felt", "felt somewhat", "can't say", "somewhat did not feel", and "did not feel". The ratio of the number of people who rated "felt" 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 Table 1, the herbal extract preparations of Examples 1 and 2 were found to have an excellent effect of inducing a relaxing effect. In addition, the relaxing effect of the Shimotsuto extract concentrate (Example 1) was significantly higher than that of the Udo-Kakkonto extract concentrate (Example 2), and this result corresponds to the fact that the content of the above-mentioned aroma components is higher in the Shimotsuto extract concentrate than in the Udo-Kakkonto extract concentrate.

Claims (6)

A relaxation effect inducer containing Shimotsuto extract and/or Dokkatsu Kakkonto extract (excluding those containing Ryokeijutsukanto) . The relaxant according to claim 1, which is dissolved in water and consumed. The relaxant according to claim 1 or 2, wherein the total content of 1-cyclopentene-3,5-dione, cyclopentane-1,2-dione and furfural is 0.4 μg or more per 1 g of the dried extract equivalent of the Shimotsuto extract and Dokkatsu-Kakkonto extract. The relaxation effect inducer according to any one of claims 1 to 3, wherein the Shimotsuto extract and Dokkatsu Kakkonto extract have not been subjected to a heat history of 110°C or higher. The relaxation effect inducer according to any one of claims 1 to 4, which contains a concentrated solution of the Shimotsuto extract and/or Dokkatsu-Kakkonto extract. A relaxation effect inducer according to any one of claims 1 to 4, comprising a freeze-dried product of the Shimotsuto extract and/or the Udo-Kakkonto extract.