WO2025053239A1 - Agent for improving quality of sleep - Google Patents

Abstract

Disclosed is the use of a plant belonging to the genus Trapa or a processed product thereof in the production of an agent for improving the quality of sleep.

Description

Sleep quality improver

The present invention relates to a sleep quality improving agent, etc.

Humans spend about one-third of their lives sleeping, and sleep is considered to be the most important human activity. However, the quality and quantity of sleep that modern people get is declining due to various external environmental factors, and many people complain of symptoms of sleep deprivation and insomnia. A decline in sleep quality not only leads to serious illnesses such as myocardial infarction and cerebral infarction, but also affects concentration and work performance, so there is a demand for products that have a more effective effect on improving sleep.

On the other hand, it has been reported that extracts from plants belonging to the Trachyspermum genus have excellent Maillard reaction inhibitory effects (Patent Document 1).

It has also been reported that compounds isolated from hot water extracts of either or both of the pericarp and fruit of plants belonging to the family Trachycarpa, and having molecular weights in the ranges of 70 to 130 and 290 to 380 as measured by gel filtration chromatography, have a high ability to inhibit the formation of advanced glycation end products (Patent Document 2).

Furthermore, it has been reported that one or more compounds contained in either or both of the pericarp and fruit of plants belonging to the family Trachycarpa have the activity of improving infertility (Patent Document 3).

It has also been reported that one or more compounds contained in either or both of the pericarp and fruit of plants belonging to the family Trachycarpa have high adiponectin secretion promoting activity and adipose precursor cell differentiation promoting activity (Patent Document 4).

It has been reported that one or more compounds contained in either or both of the pericarp and fruit of plants belonging to the family Trachycarpa have high amyloid-β aggregation inhibitory activity and BACE1 inhibitory activity, and can be used as a component of an anti-Alzheimer's composition (Patent Document 5).

Japanese Patent Application Publication No. 2014-94964 Japanese Patent Application Publication No. 2015-209420 Japanese Patent Application Publication No. 2016-145182 Japanese Patent Application Publication No. 2019-52122 Japanese Patent Application Publication No. 2020-83815

As such, it is known that extracts of plants belonging to the Trachyspermum genus have various effects, but it is not known that extracts of plants belonging to the Trachyspermum genus have the effect of improving sleep quality, etc.

The present invention aims to provide an agent that improves sleep quality.

The inventors conducted extensive research to achieve the above-mentioned objective, and discovered that a hot water extract of water chestnut peel exhibits a significantly excellent effect in improving sleep quality.

The present invention was completed based on these findings and through further investigation, and provides the following sleep quality improving agents, etc.

Item 1. Use of a plant belonging to the genus Trapa or a processed product thereof in the manufacture of a sleep quality improving agent.
Item 2. The use according to Item 1, wherein the plant belonging to the genus Trapa is Trapa.
Item 3. The use according to Item 1 or 2, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of a plant belonging to the genus Trapa.
Item 4. The use according to Item 1 or 2, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trapa.
Item 5. The use according to Item 1 or 2, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of Trapa bisporus pericarp.
Item 6. A sleep quality improving agent (or a composition for improving sleep quality) containing a plant belonging to the genus Trapa or a processed product thereof.
Item 7. The sleep quality improving agent according to Item 6, wherein the plant belonging to the genus Trapa is Trapa.
Item 8. The sleep quality improving agent according to Item 6 or 7, wherein the plant belonging to the genus Trachyspermum or a processed product thereof is an extract of a plant belonging to the genus Trachyspermum.
Item 9. The sleep quality improving agent according to Item 6 or 7, wherein the plant belonging to the Trachys genus or a processed product thereof is an extract of the pericarp of a plant belonging to the Trachys genus.
Item 10. The sleep quality improving agent according to Item 6 or 7, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of Trapa bisporus pericarp.
Item 11. A method for improving quality of sleep, comprising the step of administering a plant belonging to the genus Trapa or a processed product thereof to a mammal in need thereof.
Item 12. The method according to Item 11, wherein the plant belonging to the genus Trapa is Trapa.
Item 13. The method according to Item 11 or 12, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of a plant belonging to the genus Trapa.
Item 14. The method according to Item 11 or 12, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trapa.
Item 15. The method according to Item 11 or 12, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of Trapa bispinosa pericarp.

Plants belonging to the genus Trapa or processed products thereof have a remarkably excellent effect of improving sleep quality, and are therefore useful as active ingredients in sleep quality improvers.

In addition, plants belonging to the Trachyspermum genus or processed products thereof are highly safe because they are naturally derived ingredients.

Graph showing the results of the daytime wakefulness score of the Pittsburgh Sleep Quality Index in an embodiment. Left: Daytime wakefulness score (EMM (Estimated Marginal Mean)), p value based on ANCOVA, Right: Daytime wakefulness score change (Mean)

The following is a detailed explanation of an embodiment of the present invention.

The sleep quality improving agent of the present invention is characterized by containing a plant belonging to the genus Trapa or a processed product thereof.

Plants belonging to the genus Trapa or processed products thereof Plants belonging to the genus Trapa are not particularly limited, and examples thereof include Trapa japonica, Trapa natans L. ver. Japonica, Trapa incisa, Trapa bispinosa Roxb., Trapa acornis, Trapa natans, etc. Among them, Trapa bispinosa is preferred.

As the plant belonging to the genus Trachysperm, a part or the whole of a plant belonging to the genus Trachysperm may be used. Examples of parts of a plant include flowers, inflorescences, fruit skin, fruit, flesh, stems, leaves, branches, foliage, trunks, bark, rhizomes, root bark, roots, seeds, galls, heartwood, above-ground parts, and underground parts, and these parts may be used alone or in combination.

In the present invention, the term "processed product" is not particularly limited, but may be, for example, a product that has been subjected to some kind of processing on a plant belonging to the genus Trachysus. Examples of processed products include extracts, ground products, dried powders, crushed products, squeezed juice, crushed products, heat-treated products, chemically treated products, enzyme-treated products, and combinations thereof. A dried powder of a plant belonging to the genus Trachysus can be produced by drying and further crushing a plant belonging to the genus Trachysus. A plant belonging to the genus Trachysus can be dried by, for example, sun drying, hot air drying, freeze drying, spray drying, etc. Crushing and crushing can be performed, for example, using a crusher, a crusher, etc., respectively. A processed product of a plant belonging to the genus Trachysus is preferably an extract of a plant belonging to the genus Trachysus.

To produce an extract of a plant belonging to the genus Trachysperm, a part or the whole of the plant belonging to the genus Trachysperm can be used. Examples of parts of a plant include flowers, inflorescences, pericarp, fruit, flesh, stems, leaves, branches, foliage, trunks, bark, rhizomes, root bark, roots, seeds, galls, heartwood, above-ground parts, and underground parts, and these can be used alone or in combination of multiple parts. The parts of the plant used to produce the extract are preferably fruits and pericarp, and particularly preferably pericarp. In addition, to produce the extract, any state of the plant, such as raw, dried, cut, or crushed, can be used. The extract of a plant belonging to the genus Trachysperm is preferably an extract of the pericarp of a plant belonging to the genus Trachysperm, and particularly preferably a pericarp extract.

The method for producing an extract of a plant belonging to the genus Trapa is not particularly limited, and can be a commonly used method. For example, each part of the plant belonging to the genus Trapa is cut into pieces of appropriate size or whole, and then squeezed or extracted with a solvent. Hot water extraction is particularly preferred as an extraction method. As such an extraction solvent, water, an organic solvent, or a water-containing organic solvent can be used. Examples of the organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 2-methyl-2-propanol, 1-pentanol, 2-pentanol, and 3-pentanol, ethers such as diethyl ether, esters such as methyl acetate and ethyl acetate, ketones such as acetone, and organic acids such as acetic acid, glacial acetic acid, and propionic acid. The extraction solvent is preferably water, methanol, ethanol, or an aqueous solvent obtained by mixing any two or more of these in any ratio, and the particularly preferred extraction solvent is water, or an aqueous solvent obtained by mixing ethanol, an organic solvent approved as a food additive, and water in any ratio.

The temperature of the extraction solvent can be any temperature above room temperature and below the boiling point of the extraction solvent, and is desirably determined taking into consideration the extraction efficiency, heat resistance, volatility, etc. of the substance to be extracted. If necessary, a heated extraction solvent can be used to improve the extraction efficiency. The extraction time can be within the range of 1 hour to 15 days. When water or an aqueous solvent is used as the extraction solvent, an acid, a base, a salt, etc. can be appropriately contained as necessary to improve the extraction efficiency. There are no particular limitations on the pH of the water used for extraction, and it is preferably near neutral in consideration of use on living organisms, more preferably pH 4 to 9, and even more preferably pH 6 to 8.

Hot water extraction can be carried out by any known method, for example, a method in which a plant belonging to the genus Trapa is mixed in an extraction solvent for a predetermined time and then separated from the solid matter by filtration, centrifugation, decantation, etc., or a continuous extraction method such as the Soxhlet extraction method can be used.

When removing insoluble matter by filtration, adsorbents and filter aids such as activated carbon, bentonite, celite, etc. can be added to remove impurities as necessary. In particular, when using the extract in the form of a liquid, it is preferable to also perform sterilization filtration using a membrane filter, etc.

　Solvent extracts of plants belonging to the genus Trapa can be used as is, or, if necessary, can be purified by ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, affinity chromatography, high performance liquid chromatography (HPLC), dialysis, or a combination of these.

Solvent extracts of plants belonging to the genus Trapa include the recovered extract (including those further purified as necessary), concentrates obtained by concentrating the extract, and solids obtained by removing the solvent from the extract by freeze-drying, spray-drying, etc. Here, the concentration, freeze-drying, and spray-drying of the extract can be carried out according to conventional methods.

Sleep quality improving agent The proportion of a plant belonging to the genus Trachysus or a processed product thereof contained in the sleep quality improving agent of the present invention is not particularly limited and may be, for example, 0.001 to 100% by mass of the total amount of the sleep quality improving agent. The upper or lower limit of the range is, for example, 0.01% by mass, 0.1% by mass, 1% by mass, 5% by mass, 10% by mass, 20% by mass, 30% by mass, 40% by mass, 50% by mass, 60% by mass, 70% by mass, 80% by mass, 90% by mass, 95% by mass, 99% by mass, or 99.9% by mass.

In the present invention, "improving sleep quality" means improving the quality of sleep. "Improvement" means improving or maintaining symptoms or conditions, preventing or delaying the worsening of symptoms or conditions, etc.

One method for assessing sleep quality is, for example, the Pittsburgh Sleep Quality Index (PSQI).

　The sleep quality improving agent of the present invention may contain, as appropriate, known ingredients other than plants belonging to the genus Trapa or processed products thereof, as long as the effects of the present invention are not impaired.

The sleep quality improving agent of the present invention can be used as food and beverages (particularly (non-therapeutic) food and beverages intended for health, maintenance, or promotion (e.g., health foods, functional foods, nutritional supplements, supplements, foods for specified health uses, foods with nutrient functions, or foods with functional claims)), medicines (including quasi-drugs), etc. Furthermore, the sleep quality improving agent of the present invention also encompasses the meaning of additives that impart an effect of improving sleep quality.

　In the above-mentioned foods and beverages, extracts of plants belonging to the genus Trapa can be used as is, but if necessary, vitamins, flavonoids, minerals, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, colorants, flavorings, stabilizers, preservatives, disintegrants, lubricants, sustained-release regulators, surfactants, solubilizers, wetting agents, etc. can also be added.

Food and drink includes all foods and drink that can be consumed by animals (including humans). There are no particular limitations on the types of food and drink, and examples include dairy products; fermented foods (yogurt, cheese, etc.); beverages (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, drinks containing lactic acid bacteria, yogurt drinks, carbonated drinks, sake, Western liquor, and alcohol such as fruit wine); spreads (custard cream, etc.); pastes (fruit paste, etc.); Western sweets (chocolate, donuts, pies, cream puffs, gum, candy, jelly, cookies, cakes, puddings, etc.); Japanese sweets (daifuku, mochi, manju, castella, anmitsu, yokan, etc.); frozen desserts (ice cream, popsicles, sorbet, etc.); foods (curry, beef bowl, porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); and seasonings (dressing, furikake, umami seasonings, soup bases, etc.).

The method for producing the food and beverages is not particularly limited, and any known method can be used as appropriate.

When using foods and beverages as supplements, the dosage unit form is not particularly limited and can be selected appropriately, and examples include tablets, capsules, granules, liquids, powders, etc.

The amount of food and drink to be consumed can be set appropriately depending on various conditions such as the consumer's weight, age, sex, symptoms, etc.

The above medicines can use only plants belonging to the genus Trapa or processed products thereof, or they can be mixed with other medicinal ingredients listed in the Japanese Pharmacopoeia, such as vitamins and herbal medicines.

When prepared as a medicine, plants belonging to the genus Trapa or processed products thereof can be used as is, or can be prepared together with pharmaceutical acceptable ingredients into pharmaceutical preparations in the form of tablets (including plain tablets, sugar-coated tablets, film-coated tablets, effervescent tablets, chewable tablets, troches, etc.), capsules, pills, powders (dispersed medicines), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, injections (including cases where they are mixed with distilled water or infusions such as amino acid infusions or electrolyte infusions at the time of use to prepare them as liquids), etc.

In addition to plants belonging to the genus Trapa or processed products thereof, pharmaceuticals may contain pharma- ceutical acceptable ingredients such as excipients, binders, disintegrants, lubricants, suspending agents, thickeners, antioxidants, absorption promoters, pH regulators, colorants, preservatives, surfactants, stabilizers, sweeteners, flavorings, and fragrances, as necessary.

The method of administration of the pharmaceutical is not particularly limited, and can be, for example, oral administration, intra-arterial administration, intravenous administration, buccal administration, rectal administration, enteral administration, transdermal administration, etc.

The dosage of a pharmaceutical product can be determined appropriately depending on various conditions such as the patient's weight, age, sex, symptoms, administration method, and type of dosage form.

The dosage and intake of foods, beverages, and medicines for humans is generally the amount of active ingredient contained in the formulation, and is preferably 0.1 to 2000 mg/day per adult. Of course, the dosage and intake will vary depending on various conditions, so there are cases where a smaller dosage and intake than the above is sufficient, and cases where a greater amount than the above range is required.

The sleep quality improving agent of the present invention described above is applicable to mammals, including humans.

The sleep quality improving agent of the present invention is effective for people who wake up during sleep, feel sleepy during the day, and have light sleep.

When the sleep quality improving agent of the present invention is used as a food or beverage, it may be labeled as "It has been reported to have the function of improving sleep quality" or a similar labeling may be used.

As shown in the examples below, the inventors have found that plants belonging to the genus Trapa or processed products thereof have an excellent effect of improving sleep quality. Therefore, since plants belonging to the genus Trapa or processed products thereof have an excellent effect of improving sleep quality, they can be suitably used as an active ingredient in sleep quality improvers.

In addition, plants belonging to the Trachyspermum genus or processed products thereof are highly safe because they are naturally derived ingredients.

In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present invention includes any combination of the constituent elements described in this specification.

Furthermore, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present invention above may be combined in any way to identify the subject matter encompassed by the present invention. In other words, the present invention encompasses all subject matter consisting of any combination of the combinable characteristics described in this specification.

The following examples are provided to further explain the present invention. However, the present invention is not limited to these examples.

I. Preparation of water chestnut extract After harvest, the fruits of Trapa bispinosa were dried and dried skin was collected. The dried skin was crushed and extracted with hot water (6 parts by mass of 90°C hot water was used per 1 part by mass of dried skin). 33% by mass of dextrin was added to 67% by mass of the extract, and the mixture was spray-dried with a spray dryer to obtain water chestnut skin extract powder.

The test food was prepared as a capsule (total mass 234 mg) containing 100 mg of water chestnut peel extract powder, 83.62 mg of corn starch as excipients, and 1.38 mg of calcium stearate encapsulated in 49 mg of hard capsules.

II. Placebo-controlled, double-blind, randomized, parallel-group study II-1. Study method [Subjects]
The subjects of this study were healthy Japanese men and women aged 40 to 64 years.

[intervention]
The intervention period was 8 weeks, and participants were instructed to take one tablet of the test food or placebo food per day before breakfast with water or lukewarm water. The placebo food used an excipient that did not contain water chestnut extract, and was indistinguishable in appearance, shape, color, odor, and taste.

[Evaluation items]
Measurements using the Pittsburgh Sleep Quality Index (Japanese version) were conducted before intake, 4 weeks after intake, and 8 weeks after intake.

The Pittsburgh Sleep Quality Index (PSQI) allows for self-reporting, scoring and evaluation of overall sleep quality, and is the sleep scale with the most accumulated evidence among existing sleep scales. The Pittsburgh Sleep Quality Index is composed of seven subscales, including sleep quality, time to fall asleep, sleep duration, sleep efficiency, difficulty sleeping, use of sleeping pills and daytime activity disorders, and is evaluated based on the total score of these subscales. Therefore, it is considered appropriate as an index for observing "sleep quality in a broad sense (overall evaluation of sleep)" (Reference: Ministry of Health, Labor and Welfare, Systematic review examining the relationship between "sleep quality" and health outcomes using the Pittsburgh Sleep Quality Index as an index, https://mhlw-grants.niph.go.jp/system/files/report_pdf/202009018A-buntan2.pdf)

II-2. Study results [Subjects for analysis of intergroup comparison]
Of the 56 subjects enrolled in the study (28 in the test food group and 28 in the placebo group), one subject (test food group) did not visit the hospital for the measurement at week 4 only, one subject (test food group) did not visit the hospital for the measurement at week 8 only, and one subject (placebo group) did not visit the hospital for either the measurement at week 4 or week 8. Therefore, in the test food group, 28 subjects were included in the total number of subjects for analysis, including subjects with missing data at either week 4 or week 8, and 27 subjects each were included in the data for analysis, excluding one subject each who did not visit the hospital at week 4 or week 8. In the placebo group, 27 subjects were included in the analysis, excluding one subject for whom measurement data could not be obtained at weeks 4 and 8, and an intergroup comparison analysis was performed.

[Evaluation results: comparison between groups]
The Pittsburgh Sleep Quality Index scores and statistical analysis results are shown in Table 1 and Figure 1. The score of [C7: Difficulty waking during the day] after 4 weeks of intake was significantly lower in the test food group (TBE (Trapa bispinosa Roxb. Pericarp Extract) group) compared to the placebo group, confirming an improvement in sleep quality.

[Subjects for before-and-after comparison analysis]
Of the 56 cases enrolled in the study (28 in the test food group, 28 in the placebo group), one case (test food group) did not visit the hospital for the measurement at week 4, one case (test food group) did not visit the hospital for the measurement at week 8, and one case (placebo group) did not visit the hospital for either the measurements at weeks 4 or 8. Therefore, 26 cases (excluding 2 cases) from the test food group were analyzed, and 27 cases (excluding 1 case) from the placebo group were analyzed, and a before-and-after comparison analysis was performed.

[Evaluation results before and after comparison]
As shown in Table 1, in the test food group, the Pittsburgh Sleep Quality Index total score, C1: sleep quality, and C7: daytime difficulty waking were significantly lower after 4 and 8 weeks of intake, and C2: time to fall asleep was significantly lower after 4 weeks of intake, compared to before intake.

[Discussion]
The Pittsburgh Sleep Quality Index is a widely accepted method for evaluating sleep quality. A significant decrease in the Pittsburgh Sleep Quality Index was confirmed in the test food group compared to the placebo group. Since the only ingredient in the test food with health benefits was water chestnut extract, it was shown that taking water chestnut extract may have an effect of improving sleep quality.

Claims (5)

　The use of a plant belonging to the genus Trapa or a processed product thereof in the manufacture of a sleep quality improvement agent. The use according to claim 1, wherein the plant belonging to the genus Trapa is Trapa. The use according to claim 1 or 2, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of a plant belonging to the genus Trapa. The use according to claim 1 or 2, wherein the plant belonging to the genus Trachysperm or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trachysperm. The use according to claim 1 or 2, wherein the plant belonging to the genus Trapa or a processed product thereof is an extract of Trapa bisporus pericarp.

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