Agent for improving quality of sleep

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

[0001] The present invention relates to an agent for improving sleep quality, etc.

[0002] Humans spend approximately one-third of their lives sleeping, making sleep one of the most important activities for humans. However, due to various external environmental factors, the quality and quantity of sleep that modern people get is declining, and many people complain of symptoms of sleep deprivation and insomnia. Poor 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 superior sleep-improving effects.

[0003] On the other hand, it has been reported that extracts of plants belonging to the genus Trapa have excellent Maillard reaction inhibitory effects (Patent Document 1).

[0004] In addition, it has been reported that compounds isolated from a hot water extract of either or both of the pericarp and fruit of plants belonging to the family Trachycarpae, 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).

[0005] 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 activity in improving infertility (Patent Document 3).

[0006] In addition, 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 Trachycarpus have high adiponectin secretion-promoting activity and adipose precursor cell differentiation-promoting activity (Patent Document 4).

[0007] 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 Trachycarpae have high amyloid beta aggregation inhibitory activity and BACE1 inhibitory activity, and are used as components of anti-Alzheimer's compositions (Patent Document 5).

[0008] Japanese Patent Publication No. 2014-94964 Japanese Patent Publication No. 2015-209420 Japanese Patent Publication No. 2016-145182 Japanese Patent Publication No. 2019-52122 Japanese Patent Publication No. 2020-83815

[0009] As described above, it is known that extracts of plants belonging to the Trachycarpus genus have various effects, but it is not known that extracts of plants belonging to the Trachycarpus genus have an effect of improving sleep quality, etc.

[0010] An object of the present invention is to provide an agent for improving sleep quality.

[0011] As a result of extensive research to achieve the above object, the present inventors have discovered that a hot water extract of water chestnut peel exhibits a significantly excellent effect of improving sleep quality.

[0012] The present invention was completed based on these findings and through further investigation, and provides the following sleep quality improving agents, etc.

[0013] Item 1. Use of a plant belonging to the genus Trachyspermum or a processed product thereof in the manufacture of a sleep quality improver. Item 2. The use according to Item 1, wherein the plant belonging to the genus Trachyspermum is Trachyspermum. Item 3. The use according to Item 1 or 2, 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 4. The use according to Item 1 or 2, wherein the plant belonging to the genus Trachyspermum or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trachyspermum. Item 5. The use according to Item 1 or 2, wherein the plant belonging to the genus Trachyspermum or a processed product thereof is a Trachysperm pericarp extract. Item 6. A sleep quality improver (or a composition for improving sleep quality) containing a plant belonging to the genus Trachyspermum or a processed product thereof. Item 7. The sleep quality improver according to Item 6, wherein the plant belonging to the genus Trachyspermum is Trachyspermum. Item 8. The sleep quality improver 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. Item 10. The sleep quality improver according to Item 6 or 7, wherein the plant belonging to the genus Trachycarpus or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trachycarpus. Item 11. A method for improving sleep quality, comprising administering a plant belonging to the genus Trachycarpus 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 Trachycarpus is Trachycarpus. Item 13. The method according to Item 11 or 12, wherein the plant belonging to the genus Trachycarpus or a processed product thereof is an extract of a plant belonging to the genus Trachycarpus. Item 14. The method according to Item 11 or 12, wherein the plant belonging to the genus Trachycarpus or a processed product thereof is an extract of the pericarp of a plant belonging to the genus Trachycarpus. Item 15. The method according to Item 11 or 12, wherein the plant belonging to the genus Trachycarpus or a processed product thereof is a Trachycarpus pericarp extract.

[0014] Plants belonging to the genus Trapa or processed products thereof have a significantly excellent effect of improving the quality of sleep, and are therefore useful as active ingredients in agents for improving the quality of sleep.

[0015] Furthermore, plants belonging to the genus Trapa or processed products thereof are naturally occurring ingredients and therefore highly safe.

[0016] 1 is a graph showing the results of the daytime wakefulness score of the Pittsburgh Sleep Quality Index in an example. Left: Daytime wakefulness score (EMM (estimated marginal mean)), p-value based on ANCOVA, right: Daytime wakefulness score change (Mean (average value)).

[0017] Hereinafter, embodiments of the present invention will be described in detail.

[0018] 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.

[0019] Plants belonging to the genus Trapa or processed products thereof Plants belonging to the genus Trapa include, but are not limited to, Trapa japonica, Trapa natans L. ver. Japonica, Trapa incisa, Trapa bispinosa Roxb., Trapa acornis, Trapa natans, etc. Of these, Trapa bispinosa is preferred.

[0020] As the plant of the genus Trachycarpus, a part or the whole of the plant of the genus Trachycarpus can be used. Examples of the part of the 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 parts can be used alone or in combination.

[0021] In the present invention, the term "processed product" is not particularly limited, and may be, for example, a product obtained by subjecting a plant belonging to the genus Trachycarpus to some kind of processing. Examples of processed products include extracts, ground products, dried powders, pulverized products, squeezed juices, crushed products, heat-treated products, chemically treated products, enzyme-treated products, and combinations thereof. Dried powders of plants belonging to the genus Trachycarpus can be prepared by drying and further pulverizing plants. Drying of plants belonging to the genus Trachycarpus can be carried out by, for example, sun drying, hot air drying, freeze drying, spray drying, etc. Pulverization and crushing can be carried out using, for example, a crusher, a grinder, etc., respectively. The processed product of a plant belonging to the genus Trachycarpus is preferably an extract of a plant belonging to the genus Trachycarpus.

[0022] To produce an extract of a plant belonging to the genus Trachycarpus, part or the whole of the plant can be used. Examples of plant parts 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. The plant parts used to produce the extract are preferably fruits and pericarp, and particularly preferably pericarp. Furthermore, any state of the plant, such as fresh, dried, cut, or crushed, can be used to produce the extract. The extract of a plant belonging to the genus Trachycarpus is preferably an extract of the pericarp of a plant belonging to the genus Trachycarpus, and particularly preferably a pericarp extract.

[0023] The method for producing an extract of a plant belonging to the genus Trachycarpus is not particularly limited and can be carried out by a commonly used method. For example, various parts of a plant belonging to the genus Trachycarpus may be extracted with juice or a solvent, either as is or after cutting into appropriate sizes. Hot water extraction is particularly preferred as an extraction method. Examples of such an extraction solvent include water, an organic solvent, or a water-containing organic solvent. 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 particularly preferred extraction solvents are water and an aqueous solvent obtained by mixing water and ethanol, an organic solvent approved as a food additive, in any ratio.

[0024] The temperature of the extraction solvent can be any temperature above room temperature but 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 added as necessary to improve the extraction efficiency. The pH of the water used for extraction is not particularly limited, but is preferably near neutral in consideration of use in living organisms, more preferably pH 4 to 9, and even more preferably pH 6 to 8.

[0025] 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 content by filtration, centrifugation, decantation, or the like, or a continuous extraction method such as Soxhlet extraction can be used.

[0026] When removing insoluble matters by filtration, adsorbents and filter aids such as activated carbon, bentonite, celite, etc. can be added to remove impurities, if necessary. In particular, when using the extract in the form of a liquid extract, it is preferable to also perform sterilization filtration using a membrane filter, etc.

[0027] The solvent extract of a plant belonging to the genus Trapa can be used as it 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, a combination of these, or the like.

[0028] Solvent extracts of plants belonging to the genus Trapa include recovered extracts (including those further purified as necessary), concentrates obtained by concentrating the extracts, and solids obtained by removing the solvent from the extracts by freeze-drying, spray-drying, etc. Concentration, freeze-drying, and spray-drying of the extracts can be carried out according to conventional methods.

[0029] The proportion of the plant belonging to the genus Trapa or a processed product thereof contained in the sleep quality improver 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 improver. The upper and lower limits of this range are, 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, and 99.9% by mass.

[0030] 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.

[0031] As a method for evaluating the quality of sleep, for example, the Pittsburgh Sleep Quality Index (PSQI) can be used.

[0032] The sleep quality improving agent of the present invention may contain known ingredients other than plants belonging to the genus Trapa or processed products thereof as appropriate, provided that the effects of the present invention are not impaired.

[0033] The sleep quality improving agent of the present invention can be used as a food or drink (particularly, a food or drink (for non-therapeutic purposes) intended for health, maintenance, or improvement of health (e.g., health food, functional food, nutritional supplement, dietary supplement, food for specified health use, food with nutrient function claims, or food with functional claims)), a pharmaceutical product (including quasi-drugs), etc. Furthermore, the sleep quality improving agent of the present invention also encompasses the meaning of an additive that imparts an effect of improving sleep quality.

[0034] In the above-mentioned foods and beverages, extracts of plants belonging to the genus Trapa can be used as they are, 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, humectants, etc. can also be blended.

[0035] Food and drink products include all foods and drink products that can be ingested by animals (including humans). The types of foods and drink products are not particularly limited, and examples thereof include dairy products, fermented foods (yogurt, cheese, etc.), beverages (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, lactic acid bacteria-containing drinks, yogurt drinks, carbonated drinks, sake, Western liquor, and alcoholic beverages such as fruit wine), spreads (custard cream, etc.), pastes (fruit paste, etc.), Western confectionery products (chocolate, donuts, pies, cream puffs, gum, candy, jelly, cookies, cakes, puddings, etc.), Japanese confectionery products (daifuku, mochi, manju, castella cakes, anmitsu, yokan, etc.), frozen desserts (ice cream, popsicles, sorbet, etc.), foods (curry, beef bowls, rice porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.), and seasonings (dressings, sprinkles, umami seasonings, soup bases, etc.).

[0036] The method for producing the food or drink is not particularly limited, and any known method can be used as appropriate.

[0037] When using foods and drinks as supplements, the dosage unit form is not particularly limited and can be selected appropriately, and examples include tablets, capsules, granules, liquids, powders, etc.

[0038] The intake amount of food and drink can be appropriately determined depending on various conditions such as the weight, age, sex, and symptoms of the person consuming the food and drink.

[0039] The above-mentioned pharmaceuticals may contain only plants belonging to the genus Trapa or processed products thereof, or may be used in combination with other medicinal ingredients listed in the Japanese Pharmacopoeia, such as vitamins and herbal medicines.

[0040] When prepared as a pharmaceutical, a plant belonging to the genus Trapa or a processed product thereof can be used as is, or can be prepared together with pharmaceutical acceptable ingredients into pharmaceutical formulations 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 the plant is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare a liquid), etc.

[0041] In addition to the plant belonging to the genus Trapa or a processed product thereof, pharmaceuticals may contain, as necessary, appropriate pharmaceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, suspending agents, thickeners, antioxidants, absorption enhancers, pH adjusters, colorants, preservatives, antiseptics, surfactants, stabilizers, sweeteners, flavoring agents, and fragrances.

[0042] The method of administering 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, or the like.

[0043] The dosage of a pharmaceutical can be determined appropriately depending on various conditions such as the patient's weight, age, sex, symptoms, administration method, and type of dosage form.

[0044] The dosage and intake of foods, beverages, and pharmaceuticals for humans is generally the amount of active ingredient contained in the preparation, preferably 0.1 to 2000 mg / day per adult. Of course, the dosage and intake vary depending on various conditions, so in some cases a dosage or intake amount less than the above range is sufficient, or in other cases a dosage or intake amount exceeding the above range is required.

[0045] The sleep quality improving agent of the present invention described above is applicable to mammals including humans.

[0046] The sleep quality improving agent of the present invention is effective for people who wake up during sleep, people who feel sleepy during the day, people who have light sleep, and the like.

[0047] When the sleep quality improving agent of the present invention is used as a food or drink, it may be labeled as "It has been reported to have the function of improving sleep quality" or a similar label may be used.

[0048] As will be shown in the Examples below, the present inventors have found that plants belonging to the genus Trapa or processed products thereof exhibit excellent effects of improving sleep quality. Therefore, because plants belonging to the genus Trapa or processed products thereof have excellent effects of improving sleep quality, they can be suitably used as active ingredients in sleep quality improvers.

[0049] Furthermore, plants belonging to the genus Trapa or processed products thereof are naturally occurring ingredients and therefore highly safe.

[0050] In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." Furthermore, the present invention encompasses all arbitrary combinations of the constituent elements described in this specification.

[0051] Furthermore, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present invention may be combined in any way to specify the subject matter encompassed by the present invention, i.e., the present invention encompasses all subject matter consisting of any combination of the combinable characteristics described herein.

[0052] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0053] I. Preparation of Water chestnut Extract: Harvested water chestnut (Trapa bispinosa) fruits were dried, and dried pericarp was collected. The dried pericarp 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 pericarp). 33% by mass of dextrin was added to 67% by mass of the extract, and the mixture was spray-dried using a spray dryer to obtain water chestnut pericarp extract powder.

[0054] As the test food, capsules (total mass 234 mg) were prepared by encapsulating 100 mg of water chestnut peel extract powder, 83.62 mg of corn starch as an excipient, and 1.38 mg of calcium stearate in 49 mg of hard capsules.

[0055] 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.

[0056] [Intervention] The intervention period was 8 weeks, and participants were instructed to take one tablet of the test food or placebo food per day with water or lukewarm water before breakfast. The placebo food used an excipient that did not contain water chestnut extract and was indistinguishable in appearance, shape, color, odor, and taste.

[0057] [Evaluation Items] Measurements were performed using the Pittsburgh Sleep Quality Index (Japanese version) before intake, and after 4 and 8 weeks of intake.

[0058] The Pittsburgh Sleep Quality Index (PSQI) allows for self-reporting, scoring, and evaluation of overall sleep quality, and has accumulated the most evidence among existing sleep scales. The PSQI is composed of seven subscales: sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep difficulties, use of sleeping pills, and daytime activity disorders, and is evaluated using the total score. Therefore, it is considered appropriate as an index for assessing "sleep quality in a broad sense (overall assessment 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, https: / / mhlw-grants.niph.go.jp / system / files / report_pdf / 202009018A-buntan2.pdf)

[0059] II-2. Study Results [Subjects for Analysis of Intergroup Comparisons] Of the 56 subjects enrolled in the study (28 in the test food group, 28 in the placebo group), one subject (test food group) did not visit the clinic for the 4-week measurement only, one subject (test food group) did not visit the clinic for the 8-week measurement only, and one subject (placebo group) did not visit the clinic for either the 4-week or 8-week measurements. 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 4 or 8 weeks, and 27 subjects each were included in the analysis data, excluding one subject each who did not visit the clinic at 4 or 8 weeks. In the placebo group, 27 subjects were included in the analysis, excluding one subject for whom measurement data at 4 and 8 weeks could not be obtained, and an intergroup comparison analysis was performed.

[0060] [Evaluation Results Intergroup Comparison] The Pittsburgh Sleep Quality Index scores and statistical analysis results are shown in Table 1 and Figure 1. The score for [C7: Difficulty waking up 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.

[0061]

[0062] [Subjects for before-and-after comparison analysis] Of the 56 subjects enrolled in the study (28 in the test food group, 28 in the placebo group), one subject (test food group) did not visit the clinic for the measurement at week 4, one subject (test food group) did not visit the clinic for the measurement at week 8, and one subject (placebo group) did not visit the clinic for either the measurements at week 4 or week 8. Therefore, 26 subjects (excluding 2 subjects) from the test food group were analyzed, and 27 subjects (excluding 1 subject) from the placebo group were analyzed, and a before-and-after comparison analysis was performed.

[0063] [Evaluation Results - Comparison Before and After] As shown in Table 1, in the test food group, compared to before intake, the Pittsburgh Sleep Quality Index total score, C1: sleep quality, and C7: daytime awakening difficulty were significantly lower after 4 and 8 weeks of intake, and C2: time to fall asleep was significantly lower after 4 weeks of intake.

[0064] [Discussion] The Pittsburgh Sleep Quality Index is a widely accepted method for assessing sleep quality. A significant decrease in Pittsburgh Sleep Quality Index scores 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 suggested that intake of water chestnut extract may have an effect on improving sleep quality.

Claims

1. Use of a plant belonging to the genus Trapa or a processed product thereof in the manufacture of an agent for improving sleep quality.

2. The use according to claim 1, wherein the plant belonging to the genus Trapa is Trapa.

3. 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.

4. 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.

5. 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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