JP2023070130A - sleep quality improver - Google Patents

Abstract

To provide a new agent that can improve the quality of sleep more safely and effectively.SOLUTION: To solve the foregoing problem, the inventors have paid attention to arctigenin and arctiin included in burdocks and Forsythia fruit, providing an agent, a food composition and a pharmaceutical composition for improving the quality of sleep, each including arctigenin and/or arctiin as an active ingredient. Taking or administering the inventive agent or composition can improve the quality of sleep more safely and effectively.SELECTED DRAWING: Figure 1

Description

The present invention relates to agents and compositions for improving sleep quality.

BACKGROUND ART In recent years, many people have sleep-related problems such as poor sleep quality, light sleep and waking up quickly, not feeling asleep, residual fatigue when waking up, and insomnia. Poor quality of sleep inhibits recovery from fatigue, and may lead to a decline in physical and mental activity ability due to fatigue and a decline in work efficiency. Therefore, improving sleep quality is important for maintaining mental and physical health.

Pharmaceutical sleeping pills are often used to reduce the quality of sleep. However, conventional sleeping pills have been reported to have dependence and side effects, and cannot be taken casually. Therefore, development of a safer sleep quality improving agent is desired.

On the other hand, theanine (Patent Document 1), glycine (Patent Document 2), and the like have been reported as food-derived ingredients having an effect of improving sleep quality. However, it cannot be said that sleep-improving foods containing these ingredients are necessarily sufficiently effective in improving the quality of sleep. Therefore, there is a demand for the development of a technique that is more effective in improving sleep quality.

By the way, forsythia is a deciduous broadleaf shrub belonging to the Oleaceae family, and is known as a plant rich in lignans having various physiological and biological activities including antioxidant and estrogenic effects (Non-Patent Document 1 ). It has been reported that forsythia leaves contain more arctigenin, which is a lignan, than fruits, flowers and stems (Non-Patent Document 2).

Patent No. 4961087 Japanese Patent Application Laid-Open No. 2006-333872

Naoki Hata, Akio Kobayashi, Toshiya Muranaka, Atsushi Okazawa., “Multifunctionality of arctin and arctigenin and utilization of plants with high content”, Agriculture and Horticulture, 2011, Vol.86, No.1, p.10- 20 Seibu Sansho, Tomoko Kawamura, Toshihiro Tanaka, Herman A., "Lignan content of forsythia and forsythia leaves", Natural Medicines, 2001, Vol.55, No.6, p.300-3 Yuka Yamamoto, Hideki Tanaka, Miki Takase, Katsuo Yamazaki, Kazuo Azumi, Shuichiro Shirakawa, “Development and standardization of OSA sleep questionnaire (MA version) for middle-aged and elderly people”, Brain and Psychiatric Medicine, 1999 10, pp.401-409 Ellis B W, Johns M W, Lancaster R, Raptopoulos P, Angelopoulos N, Priest R G., “The St. Mary's Hospital sleep questionnaire: a study of reliability.” Sleep, 1981, Vol. 4, No. 1, p. .93-7 “The Japan Society for Fatigue, “Anti-fatigue clinical evaluation guidelines (clinical evaluation guidelines for the effects of anti-fatigue products on fatigue that is a problem in daily life)” 5th edition”, 2011 Fukuda S, Takashima S, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y., “Development and validation of a new fatigue scale for fatigued subjects with and without chronic fatigue syndrome.”, Fatigue science for human health., Springer, 2008 pp.89-102

An object of the present invention is to provide a new drug capable of improving sleep quality more safely and effectively.

In order to solve the above problems, the present inventors focused on arctigenin and arctiin contained in burdock and forsythia. A forsythia leaf extract containing arctigenin and arctiin was prepared and administered to subjects in a randomized, double-blind, placebo-controlled, parallel-group study. A survey using the MA version of the OSA Sleep Questionnaire showed that intake of the forsythia leaf extract-containing food tended to improve drowsiness upon awakening, sleep onset and sleep maintenance, dreaming, recovery from fatigue, and sleep time.

In addition, when a survey was conducted using a sleep questionnaire at St. Mary's Hospital, ingestion of food containing forsythia leaf extract revealed that the depth of sleep, degree of awakening during sleep, feeling of deep sleep, feeling of refreshment upon awakening, satisfaction of sleep, and presence or absence of awakening in the early morning, respectively. tended to improve. These results confirmed that the forsythia leaf extract has the effect of improving the quality of sleep.

Furthermore, the present inventors prepared a burdock sprout extract containing arctigenin and arctiin, ingested it to subjects, and conducted a randomized, double-blind, placebo-controlled, parallel group comparison study. A survey using the MA version of the OSA Sleep Questionnaire revealed that intake of food containing burdock sprout extract tended to improve sleepiness upon awakening, sleep onset and sleep maintenance, dreaminess, recovery from fatigue, and sleep time.

In addition, when a survey was conducted using a sleep questionnaire at St. Mary's Hospital, intake of food containing burdock sprout extract revealed that the depth of sleep, the degree of wakefulness during sleep, the feeling of deep sleep, the feeling of refreshment upon waking up, the satisfaction of sleep, and the presence or absence of early-morning awakening, respectively. tended to improve. These results confirmed that the burdock sprout extract has the effect of improving the quality of sleep.

These results strongly suggest that arctigenin and arctiin, which are commonly contained in the forsythia leaf extract and the burdock sprout extract, have the effect of improving the quality of sleep. The present invention was made based on these findings.

The present invention provides a sleep quality improving agent containing arctigenin and/or arctiin as an active ingredient.

The present invention also provides an agent for improving sleep quality, wherein the arctigenin and/or arctiin is contained in burdock, burdock, burdock sprout, or forsythia, or an extract thereof.

The present invention also provides that the improvement of the quality of sleep is sleepiness upon waking, sleep onset and sleep maintenance, dreaminess, fatigue recovery, sleep time, sleep depth, degree of awakening in the middle of the night, feeling of deep sleep, refreshment upon waking, and satisfaction of sleep. and the presence or absence of early-morning awakening, improving at least one item selected from the group.

The present invention also provides a food composition for improving sleep quality, containing arctigenin and/or arctiin as active ingredients.

The present invention also provides a food composition for improving the quality of sleep, wherein the arctigenin and/or arctiin is contained as burdock, burdock, burdock sprout or forsythia or an extract thereof.

The present invention also provides that the improvement of the quality of sleep is sleepiness upon waking, sleep onset and sleep maintenance, dreaminess, fatigue recovery, sleep time, sleep depth, degree of awakening in the middle of the night, feeling of deep sleep, refreshment upon waking, and satisfaction of sleep. and the presence or absence of waking up early in the morning.

Sleep quality can be improved more safely and effectively by ingesting or administering the agent or composition of the present invention. By ingestion or administration of the agent or composition of the present invention, suppression of drowsiness upon waking, improvement of sleep onset and sleep maintenance, improvement of dreaminess, promotion of fatigue recovery, increase of sleep time, improvement of sleep depth, suppression of awakening in the middle of the night, It is possible to obtain effects such as an improvement in deep sleep, an improvement in refreshment upon awakening, an improvement in sleep satisfaction, and suppression of early-morning awakening.

Graph showing measured scores for factor I (wake-up sleepiness) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract, which is an example of the present invention, and the placebo group. FIG. 2 is a graph showing the amount of change in the scores for factor I (wake-up sleepiness) of the MA version of the OSA Sleep Questionnaire in the test food group containing the forsythia leaf extract, which is an example of the present invention, and the placebo group. Graph showing measured values of scores for factor II (sleep onset and sleep maintenance) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract, which is an example of the present invention, and the placebo group. FIG. 10 is a graph showing the amount of change in score regarding factor II (sleep onset and sleep maintenance) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. FIG. Graph showing measured values of scores for factor III (dreaming) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract, which is an example of the present invention, and the placebo group. 4 is a graph showing the amount of change in the scores for factor III (dreaming) of the MA version of the OSA Sleep Questionnaire in the test food group containing the forsythia leaf extract, which is an example of the present invention, and the placebo group. Graph showing measured values of scores for factor IV (recovery from fatigue) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract, which is one example of the present invention, and the placebo group. 4 is a graph showing the amount of change in score regarding factor IV (recovery from fatigue) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. Graph showing the measured score of factor V (sleep time) of OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. 4 is a graph showing the amount of change in the score of factor V (sleep time) of the OSA Sleep Questionnaire MA version in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. Graph showing the measured values of the sleep depth score of the St. Marie's Hospital Sleep Questionnaire in the test food group and the placebo group containing the forsythia leaf extract that is one example of the present invention. 4 is a graph showing the amount of change in the sleep depth score of the St. Marie's Hospital Sleep Questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. Graph showing measured values of scores related to sleep awakening degree in St. Marie's Hospital Sleep Questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. Graph showing the amount of change in the score regarding the degree of wakefulness in the St. Marie's Hospital sleep questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. Graph showing the actual measurement values of the score regarding deep sleep in the sleep questionnaire at St. Marie's Hospital in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. FIG. 10 is a graph showing the amount of change in scores relating to feeling of deep sleep in the St. Marie's Hospital Sleep Questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. FIG. A graph showing the measured scores of refreshment on waking in the St. Marie's Hospital Sleep Questionnaire in the test food group and the placebo group containing the forsythia leaf extract that is one example of the present invention. FIG. 10 is a graph showing the amount of change in score regarding refreshment upon waking in St. Marie's Hospital Sleep Questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. FIG. 4 is a graph showing changes in VAS (feeling of fatigue) in the test food group containing the forsythia leaf extract that is one example of the present invention and in the placebo group. 4 is a graph showing the amount of change in each score of the Chalder Fatigue Questionnaire in the test food group containing the forsythia leaf extract that is one example of the present invention and the placebo group. A graph showing the measured values and the amount of change in scores for factor I (wake-up sleepiness) of the MA version of the OSA Sleep Questionnaire in the test food group containing the burdock sprout extract, which is an example of the present invention, and the placebo group. A graph showing the measured values and the amount of change in the OSA Sleep Questionnaire MA version score for factor II (sleep onset and sleep maintenance) in the test food group containing the burdock sprout extract that is one example of the present invention and the placebo group. Graph showing measured values and changes in scores for factor III (dreaming) of the OSA Sleep Questionnaire MA version in the test food group and the placebo group containing the burdock sprout extract, which is an example of the present invention. A graph showing the measured values and the amount of change in the score of factor IV (recovery from fatigue) of the OSA Sleep Questionnaire MA version in the test food group and the placebo group containing the burdock sprout extract, which is an example of the present invention. Graph showing measured values and changes in scores for factor V (sleep time) of the OSA Sleep Questionnaire MA version in the test food group containing the burdock sprout extract, which is an example of the present invention, and the placebo group. A graph showing the measured values and the amount of change in the sleep depth score of the St. Marie's Hospital sleep questionnaire in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention. A graph showing the measured values and the amount of change in the score regarding the degree of awakening in the St. Marie's Hospital Sleep Questionnaire in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention. A graph showing the measured values and the amount of change in the scores regarding deep sleep in the sleep questionnaire at St. Marie's Hospital in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention. A graph showing the measured values and the amount of change in the refreshed feeling upon awakening of the St. Marie's Hospital Sleep Questionnaire in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention. A graph showing the measured values and the amount of change in the sleep satisfaction score of the St. Marie's Hospital sleep questionnaire in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention. A graph showing the measured values and the amount of change in the sleep difficulty score of the St. Marie's Hospital Sleep Questionnaire in the test food group and the placebo group containing the burdock sprout extract that is one example of the present invention.

The present invention provides a sleep quality improving agent containing arctigenin and/or arctiin as an active ingredient.

"Sleep quality" in the present invention can be generally evaluated by subjective or objective indices. The quality of sleep includes, for example, sleepiness upon awakening, time until sleep onset, whether sleep is maintained, dreaming (for example, presence or absence of nightmares and number of dreams), fatigue recovery, sleep time, sleep depth, presence or absence of awakening in the middle of the night, and It can be evaluated by indicators such as the number of times, feeling of deep sleep, refreshing feeling upon awakening, satisfaction of sleep, and presence or absence of early morning awakening.

As used herein, "improving sleep quality" refers to sleepiness upon waking, sleep onset and sleep maintenance, dreaminess, recovery from fatigue, sleep time, depth of sleep, degree of awakening in the middle of the night, feeling of deep sleep, refreshment upon waking, and satisfaction of sleep. and at least one item selected from the group consisting of the presence or absence of early morning awakening.
That is, the ``improvement of sleep quality'' in the present invention includes, for example, suppression of drowsiness upon awakening, improvement of sleep onset and sleep maintenance, improvement of dreaminess, promotion of recovery from fatigue, increase of sleep time, improvement of depth of sleep, and awakening in the middle of the night. This includes suppression of irritability, improvement of feeling of deep sleep, improvement of refreshment upon awakening, improvement of sleep satisfaction, suppression of early morning awakening, and the like.

Each item of "wake-up sleepiness", "sleep onset and sleep maintenance", "dreaming", "fatigue recovery" and "sleep time" can be evaluated by OSA Sleep Questionnaire MA version (Non-Patent Document 3). . The MA version of the OSA Sleep Questionnaire has been standardized and is a questionnaire with sufficiently high reliability and reproducibility. The MA version of the OSA Sleep Questionnaire asks you to answer 16 sleep-related questions on a 4-point scale to evaluate your feeling of sleep upon awakening. It consists of five factors: III (dreaming), Factor IV (fatigue recovery), and Factor V (sleep time). In the present invention, improvement in the items "drowsiness upon waking", "sleep onset and sleep maintenance", "dreaming", "recovery from fatigue" and/or "sleep time" was found in a survey using, for example, the OSA Sleep Questionnaire MA version. , may be assessed by improving scores on these items.

Each item of "depth of sleep", "degree of awakening during the middle of the night", "feeling of deep sleep", "refreshing feeling upon awakening", "satisfaction of sleep", and "presence or absence of early morning awakening" was evaluated using a sleep questionnaire at St. Mary's Hospital. (Non-Patent Document 4). The St. Marie's Hospital Sleep Questionnaire is also a sufficiently reliable and reproducible questionnaire. The St. Marie's Hospital Sleep Questionnaire is a self-administered questionnaire that assesses sleep over the previous 24 hours to assess sleep quality. The sleep questionnaire at St. Marie's Hospital consists of seven items: depth of sleep, degree of awakening during sleep, feeling of deep sleep, refreshed feeling upon waking, satisfaction of sleep, presence or absence of early awakening, and degree of difficulty falling asleep. In the present invention, the improvement of the items "depth of sleep", "degree of awakening in the middle of the night", "feeling of deep sleep", "refreshing feeling upon waking up", "satisfaction of sleep" and/or "presence or absence of early morning awakening" can be achieved by, for example, Improvements in the scores of these items in a study using the St. Marie's Hospital Sleep Questionnaire may be assessed.

"Improvement in sleep quality" may also be evaluated by the subject's subjective feeling that at least one of the above items has improved. "Improvement in sleep quality" can be evaluated, for example, by improving at least one of the above items after ingestion of the test food compared to before ingestion. "Improvement in sleep quality" can also be evaluated by improving at least one of the above items in the test food intake group compared to the placebo group.

Arctigenin and arctiin are one of the diphenylpropanoids (lignans) contained in plants such as burdock. Arctiin is a precursor of arctigenin and is known to be metabolized in vivo to arctigenin. As arctigenin and/or arctiin, chemically synthesized arctigenin and/or arctiin may be used, or arctigenin and/or arctiin isolated from plants may be used. As arctigenin and/or arctiin, a plant itself containing arctigenin and/or arctiin or an extract of this plant may be used.

Plants containing arctigenin and/or arctiin include, for example, burdock (sprout, leaf, rhizome, burdock root), Ainoko forsythia (flower, leaf, fruit, rhizome), Forsythia japonicum (flower, leaf, fruit, rhizome), Forsythia (flower, leaf, fruit, rhizome).・Leaf/fruit/rhizome), forsythia (flower/leaf/fruit/rhizome), safflower, cornflower, thistle thistle, Santorisou (thistle thistle), cardoon, thistle thistle, Aniuroko thistle, sesame, maple bindweed, sagebrush, Included are: knotweed, knotweed, thaliana, knotweed, licorice, edible tress, trefoil, leopard, wild cherry, wild cherry, Arabidopsis, amaranth, walnut, oat, spelt wheat, soft wheat, Mexican cypress, and kaya. Burdock (especially burdock and burdock sprouts) and forsythia (especially leaves) are particularly preferred because of their high arctigenin and/or arctiin content. When the plant itself is used, it can be used fresh or dried and chopped, or dried and powdered.

Plants containing arctigenin and/or arctiin may be used singly or in combination of two or more. The agent and composition of the present invention may contain the above-described plants alone or in combination of two or more as arctigenin and/or arctiin. For example, the agent and composition of the present invention may contain, as arctigenin and/or arctiin, burdock, burdock, burdock sprout or forsythia or extracts thereof alone, or may contain two or more in combination. good too.

When a plant extract is used as arctigenin and/or arctiin, the extract may be prepared from the plant, for example, by the following method. The extract used in the present invention may be extracted, for example, from a plant containing arctigenin and/or arctiin by two steps, an enzymatic conversion step and an extraction step with an organic solvent.

The enzymatic conversion step is a step of enzymatically converting arctiin contained in the plant into arctigenin by β-glucosidase, which is an enzyme endogenous to the plant. Specifically, by keeping the dried and cut plants at an appropriate temperature, the endogenous β-glucosidase is activated and the reaction from arctiin to arctigenin proceeds. For example, the plant can be maintained at an arbitrary temperature by adding an arbitrary solution such as water to the cut plant and stirring the mixture at a temperature of around 30°C (20 to 50°C).

The organic solvent extraction step is the extraction of arctigenin and arctiin from the plant using any suitable organic solvent. That is, it is a step of extracting an extract from a plant by adding an appropriate solvent in a state where the content of arctigenin is high by the above enzymatic conversion step. For example, an appropriate solvent is added to the plant, and the extract is extracted by heating and stirring for an appropriate time. In addition to heating and stirring, any extraction method known to those skilled in the art, such as heat reflux, drip extraction, immersion extraction, or pressure extraction, can be used to extract the extract.

Since arctigenin is sparingly soluble in water, the yield of arctigenin can be improved by adding an organic solvent. Any organic solvent can be used as the organic solvent. For example, alcohols such as methanol, ethanol and propanol, as well as acetone can be used. Considering safety, it is preferable to use 30% ethanol as the organic solvent. A paste-like concentrate is obtained by distilling off the solvent from the extract, and a dry product can be obtained by further drying this concentrate.

The agent for improving sleep quality of the present invention comprises arctigenin and/or arctiin, the above-mentioned plant itself or an extract of this plant, the above-mentioned dried and chopped plant, or the above-mentioned plant dried and powdered. may contain By containing these, it is possible to obtain better effects than containing arctigenin and/or arctiin alone.

The agent of the present invention can be any form of formulation. The agent of the present invention can be used as an oral preparation, for example, tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets; lozenges; pills; powders; capsules including hard capsules and soft capsules; They can be suspensions, emulsions, liquid formulations such as syrups and elixirs, and the like.

In addition, the agent of the present invention can be used for parenteral administration such as intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection, transdermal administration, nasal administration, pulmonary administration, enteral administration, buccal administration and transmucosal administration. It can be a formulation. The agents of the present invention can be, for example, injections, transdermal absorption tapes, aerosols, suppositories, and the like.

In addition, the agent of the present invention can be provided as an external preparation. The external preparation of the present invention can be pharmaceuticals, cosmetics, and the like. The topical preparation of the present invention can be a topical preparation for application to the skin, scalp, hair, mucous membranes, nails, and the like. External preparations include, for example, creams, ointments, liquids, gels, lotions, emulsions, aerosols, sticks, sheet masks, solids, foams, oils and coatings such as ticks; patches such as agents, plasters, tapes and patches; and sprays.

The present invention also provides a composition for improving sleep quality, containing arctigenin and/or arctiin as active ingredients. The compositions of the present invention can be configured similarly to the agents described above. The composition of the present invention can be in any edible form, such as solid, liquid, granular, granular, powdery, capsule-like, cream-like and paste-like.

The composition of the present invention can be a composition for use in pharmaceuticals, cosmetics, foods, and the like. The compositions of the present invention can further comprise any ingredient commonly used in pharmaceuticals, cosmetics and foods. For example, the compositions of the present invention may further comprise pharmaceutically acceptable carriers, carriers, excipients, binders, disintegrants, lubricants, colorants and the like.

Examples of carriers and excipients for use in the compositions of the present invention include lactose, glucose, sucrose, mannitol, dextrin, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate, microcrystalline cellulose, and the like.

Examples of binders include starch, gelatin, syrup, gum tragacanth, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, hydroxypropylcellulose, methylcellulose, ethylcellulose, carboxymethylcellulose, and the like.

Examples of disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, sodium alginate, sodium carboxymethylcellulose and calcium carboxymethylcellulose.

Examples of lubricants include magnesium stearate, hydrogenated vegetable oils, talc, macrogol, and the like. Any coloring agent that is allowed to be added to pharmaceuticals, quasi-drugs and foods can be used as the coloring agent.

In addition, the composition of the present invention may optionally contain sucrose, gelatin, purified shellac, gelatin, glycerin, sorbitol, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, It may be coated in one or more layers, such as with methyl methacrylate and methacrylic acid polymers.

In addition, the composition of the present invention may optionally contain pH adjusters, buffers, stabilizers, preservatives, preservatives, diluents, coating agents, sweeteners, flavoring agents, solubilizers, and the like. good too.

The present invention also provides a food composition for improving sleep quality, containing arctigenin and/or arctiin as active ingredients. The food composition of the present invention can be composed similarly to the agents and compositions described above.

As used herein, the term "food composition" includes not only general food and drink, but also foods for sick people, health foods, foods with function claims, foods for specified health uses, nutritional supplements, supplements, and the like. Common foods and drinks include, for example, various beverages, various foods, processed foods, liquid foods (such as soups), seasonings, nutritional drinks, confectionery, and the like. As used herein, the term "processed food" refers to processed and/or cooked natural ingredients (animals, plants, etc.), such as processed meat products, processed vegetable products, processed fruit products, frozen foods, Retort food, canned food, bottled food and instant food are included. The food composition of the present invention improves the quality of sleep, suppresses drowsiness upon awakening, improves sleep onset and sleep maintenance, improves dreaminess, promotes recovery from fatigue, increases sleep time, improves sleep depth, and suppresses awakening in the middle of the night. , an improvement in deep sleep, an improvement in refreshment upon awakening, an improvement in sleep satisfaction, and/or a suppression of early-morning awakening. Moreover, the food composition of the present invention may be provided in a form enclosed in a bag, container, or the like. The bags and containers used in the present invention can be any bags and containers normally used for food.

The content of arctigenin and/or arctiin in the agent and composition of the present invention may be an amount that can exhibit the effect of improving the quality of sleep, and is appropriately selected according to the subject to be applied, purpose and intake method (administration method). Can be set. For example, when orally ingested by humans, it preferably contains arctigenin and/or arctiin such that the daily intake (dosage) in terms of arctigenin equivalent is 10 mg or more, preferably 20 mg or more, and more preferably 40 mg or more. can be done. The upper limit of the daily intake (dosage) of arctigenin and/or arctiin is not particularly limited, but can be, for example, 2000 mg or less in terms of arctigenin equivalent. In addition, considering that arctiin is metabolized into arctigenin in vivo, the "arctigenin equivalent amount" is the amount of arctigenin when all arctiin contained in the agent and composition is metabolized to arctigenin, and the amount of arctigenin contained in the composition.

The agents and compositions of the present invention can be ingested (administered) continuously, for example, continuously ingested (administered) for 2 days, 3 days, 5 days, 1 week, 2 weeks, or 3 weeks or more. good. In addition, the timing of ingestion (administration) of the agent and composition of the present invention is not particularly limited, but preferably on an empty stomach, more preferably before meals or 2 to 3 hours after meals, more preferably before breakfast or 2 to 2 hours after breakfast. Can be after 3 hours.

The agent and composition of the present invention are not particularly limited and can be applied to any subject. Subjects to which the agents and compositions of the present invention are applied include mammals such as humans, mice, rats, rabbits, cats, dogs, cows, horses and monkeys. The agent and composition of the present invention are also not particularly limited, but subjects for whom improvement of sleep quality is desired, such as light sleep, poor sleep, feeling asleep, waking up in the middle of the night, and unrefreshed awakening , and/or subjects experiencing sleep disturbances, such as feeling sleepy during the day.

[Example 1]
(forsythia leaf extract)
As an example of the present invention, a forsythia leaf extract was prepared. Forsythia forsythia was used as a raw material, 2000 kg of hydrous ethanol was added to 95 kg of leaves, heated to 50±5° C., stirred for 2 hours, and filtered through an 80-mesh filter to obtain a forsythia leaf extract. After addition of 11.2% each of gum arabic and dextrin to the solid content of the extract of this solution, the mixture was concentrated under reduced pressure and spray-dried. 32.6 kg of forsythia leaf extract powder with an arctigenin equivalent of 8.60% was obtained.

(subject)
Subjects were men and women aged 20 to 65 who had a Body Mass Index (BMI) of 25.0 kg/m ² or more and less than 30.0 kg/m ² and who were aware of fatigue on a daily basis.

(test food)
As a test food, a forsythia leaf extract-containing food (test food; 10 mg of arctigenin equivalent per tablet) was used. As a placebo, a food (placebo) containing no forsythia leaf extract was used. During the study period, the subjects took the test food or placebo once every morning, 8 capsules (80 mg of arctigenin equivalent per day) with water or lukewarm water. The timing of ingestion was on an empty stomach, 30 minutes before breakfast, or 2-3 hours after breakfast.

(Test method)
The effect on sleep quality was examined in a randomized, double-blind, placebo-controlled, parallel-group trial.

Sleep quality was evaluated using a sleep questionnaire upon awakening once a week from 1 week before the start of intake to 3 weeks after intake. The OSA Sleep Questionnaire MA Version (Non-Patent Document 3) and the St. Marie Hospital Sleep Questionnaire (Non-Patent Document 4) were used as questionnaires on sleep.

We also investigated the effect of reducing fatigue as a secondary effect of improving sleep quality. Fatigue was assessed using the VAS (feeling of fatigue) and the Chalder Fatigue Questionnaire upon awakening once a week from 1 week before the start of intake to 3 weeks after intake.

VAS was performed according to the method recommended by the Japanese Society for Fatigue, with the item being fatigue (Non-Patent Document 5). In the VAS evaluation, the right end of the line was defined as the best feeling (100) and the left end was the worst feeling (0). The length from the left end was measured and used as a score.

The Chalder Fatigue Questionnaire is one of the questionnaires used internationally. It consists of 14 fatigue-related questions, and it is possible to evaluate the medium-term state of fatigue over a period of several weeks (Non-Patent Document 6). The subjects were asked to answer 14 questions on a 4-point scale, and evaluated using a physical fatigue score (8 items), a mental fatigue score (6 items), and a total score that was the sum of these scores.

[1. Evaluation by OSA sleep questionnaire MA version]
In the test food group and the placebo group, the effect on the feeling of sleep was evaluated using the OSA Sleep Questionnaire MA version. Table 1 shows the measured values for the scores of Factors I to V of the MA version of the OSA Sleep Questionnaire, and Table 2 shows the changes from 1 week before the start of intake. Fig. 1 shows measured values of factor I (sleepiness upon waking) in the test food group and placebo group, Fig. 2 shows changes in factor I (sleepiness upon waking), and Fig. 3 shows measured values of factor II (sleep onset and sleep maintenance) Fig. 4 is the amount of change in factor II (sleep onset and sleep maintenance), Fig. 5 is the measured value of factor III (dreaming), Fig. 6 is the amount of change in factor III (dreaming), Fig. 7 is factor IV (recovery from fatigue) FIG. 8 is a graph showing changes in factor IV (recovery from fatigue), FIG. 9 shows actual measurements of factor V (sleep hours), and FIG. 10 shows changes in factor V (sleep hours).

As shown in the table and figure, factor I (wake-up sleepiness), factor II (sleep onset and sleep maintenance), factor III (dreaming), factor IV (fatigue recovery) and factor V (sleep duration) , tended to be higher after ingestion than before ingestion. In particular, factor I (sleepiness upon waking), factor II (sleep onset and sleep maintenance), factor IV (fatigue recovery), and factor V (sleep duration) were shown to increase significantly after ingestion compared to before ingestion. was done.

In addition, changes in factors I to V tended to be higher in the test food group than in the placebo group. In particular, the amount of change in factor IV (recovery from fatigue) was significantly higher in the test food group than in the placebo group after two weeks of intake.

The MA version of the OSA Sleep Questionnaire can evaluate the psychological aspect of sleep (feeling of sleep), and the higher the score, the better the feeling of sleep (Non-Patent Document 3). From these results, it was confirmed that the ingestion of the forsythia leaf extract-containing food improved the feeling of sleep (in particular, drowsiness upon waking, sleep onset and sleep maintenance, sleep time, and recovery from fatigue).

[2. Evaluation by St. Marie Hospital Sleep Questionnaire]
The St. Marie's Hospital Sleep Questionnaire was used to assess effects on sleep quality in the test food and placebo groups. Table 3 shows the measured scores of depth of sleep, degree of awakening during sleep, feeling of deep sleep, refreshed feeling upon awakening, satisfaction of sleep, and degree of difficulty falling asleep in the St. Marie Hospital sleep questionnaire, and the presence or absence of early morning awakening. Table 4 shows the amount of change in each score from 1 week before the start of intake. Figure 11 is the measured value of depth of sleep in the test food group and the placebo group, Figure 12 is the amount of change in depth of sleep, Figure 13 is the measured value of the degree of awakening in the middle, Figure 14 is the amount of change in the degree of awakening in the middle, and Figure 15 is the feeling of deep sleep. FIG. 16 is a graph showing the amount of change in feeling of deep sleep, FIG. 17 is the measured value of refreshing feeling upon waking up, and FIG. 18 is a graph showing the amount of change in refreshing feeling upon waking up.

As shown in the table and figure, the scores for depth of sleep, degree of wakefulness during sleep, feeling of deep sleep, refreshed feeling upon awakening, and satisfaction with sleep tended to improve after ingestion compared to before ingestion in the test food group. was done. In particular, the depth of sleep was significantly higher in the 2nd and 3rd weeks of ingestion, the feeling of deep sleep and satisfaction with sleep was significantly higher in the 3rd week of ingestion, and the refreshing feeling upon awakening was significantly higher in the 1st to 3rd weeks of ingestion. Furthermore, the presence or absence of early morning awakening was significantly improved in the 1st and 3rd weeks of intake compared to the placebo group.

In addition, changes in depth of sleep, feeling of deep sleep, and feeling of refreshment upon waking were generally higher in the test food group than in the placebo group, showing a trend of improvement. In particular, the depth of sleep was significantly higher in the 2nd week of intake, and the feeling of deep sleep was significantly higher in the 3rd week of intake. In addition, the amount of change in midway alertness was generally lower in the test food group than in the placebo group, indicating a trend toward improvement.

The St. Marie's Hospital Sleep Questionnaire can subjectively evaluate the quality of sleep. A lower value indicates a higher quality of sleep (Non-Patent Document 4). From these results, it was confirmed that ingestion of the forsythia leaf extract-containing food improved the quality of sleep, such as depth of sleep, feeling of deep sleep, feeling of refreshment upon awakening, and awakening early in the morning.

[3. Evaluation by VAS (feeling of fatigue)]
Table 5 shows the amount of change in VAS (feeling of fatigue) from one week before the start of intake in the test food group and the placebo group. FIG. 19 is a graph showing changes in VAS (feeling of fatigue) in the test food group and the placebo group.

In terms of change in VAS (feeling of fatigue), the test food group showed a significant decrease in score in the 1st and 3rd weeks of intake compared to the placebo group.

[4. Evaluation by Chalder Fatigue Questionnaire]
Table 6 shows the amount of change in each score of the Chalder Fatigue Questionnaire from one week before the start of intake in the test food group and the placebo group. FIG. 20 is a graph showing the amount of change in each score of the Chalder Fatigue Questionnaire in the test food group and the placebo group.

The amount of change in each score of the Chalder Fatigue Questionnaire was compared between the test food group and the placebo group at weeks 1 and 3 for the total score, and at weeks 2 and 3 for the physical fatigue score. However, the mental fatigue score showed a significantly lower value at the 3rd week.

From the results of the VAS (Fatigue) and Chalder Fatigue Questionnaire, it was considered that the Forsythia Leaf Extract had the effect of reducing physiological fatigue in terms of both physical and mental fatigue. It was suggested that this fatigue-reducing effect may be related to the fact that the intake of the forsythia leaf extract-containing food improved the quality of sleep.

[Example 2]
(burdock sprout extract)
As an example of the present invention, burdock sprout extract powder was prepared. 1680 kg of water was added to 125 kg of dried burdock sprouts, heated to 35±5° C. and stirred for 60 minutes. Next, 720 kg of ethanol was added, the temperature was raised, the mixture was further stirred for 2 hours, and filtered through an 80-mesh filter to obtain a burdock sprout extract. This was sterilized at 70° C. for 1 hour, dextrin was added in an amount of about 30% relative to the solid content of the extract, concentrated under reduced pressure, and spray-dried. The arctigenin and arctiin contents were 13.7% and 0.4%, respectively, and a burdock sprout extract powder with an arctigenin equivalent content of 13.9% was obtained.

(subject)
Subjects were men and women aged 20 to 65 who had a BMI of 23.0 kg/m ² or more and less than 30.0 kg/m ² and who felt fatigued on a daily basis.

(test food)
As a test food, a burdock sprout extract-containing food (test food; containing 10 mg of arctigenin equivalent per grain) was used. As a placebo, a food (placebo) containing no burdock sprout extract was used. During the study period, the subjects took 4 tablets of the test food or placebo once every morning (40 mg of arctigenin equivalent per day) with water or lukewarm water. The timing of ingestion was on an empty stomach, 30 minutes before breakfast, or 2-3 hours after breakfast.

(Test method)
The effect on sleep quality was examined in a randomized, double-blind, placebo-controlled, parallel-group trial.

Sleep quality was evaluated using a sleep questionnaire upon awakening once a week from 1 week before the start of intake to 3 weeks after intake. The OSA Sleep Questionnaire MA Version (Non-Patent Document 3) and the St. Marie Hospital Sleep Questionnaire (Non-Patent Document 4) were used as questionnaires on sleep.

[1. Evaluation by OSA sleep questionnaire MA version]
In the test food group and the placebo group, the effect on the feeling of sleep was evaluated using the OSA Sleep Questionnaire MA version. Table 7 shows the measured values of factors I to V scores of the MA version of the OSA Sleep Questionnaire, and Table 8 shows the changes from 1 week before the start of intake. Figure 21 shows measured values and changes in factor I (sleepiness upon waking) in the test food group and placebo group, Figure 22 shows measured values and changes in factor II (sleep onset and sleep maintenance), and Figure 23 shows factor III ( FIG. 24 is a graph showing measured values and changes in factor IV (recovery from fatigue), and FIG. 25 shows measured values and changes in factor V (sleep time).

As shown in the table and figure, factor I (wake-up sleepiness), factor II (sleep onset and sleep maintenance), factor III (dreaming), factor IV (fatigue recovery) and factor V (sleep duration) , tended to be higher after ingestion than before ingestion. In particular, factor I (sleepiness upon waking), factor II (sleep onset and sleep maintenance), factor IV (fatigue recovery), and factor V (sleep duration) were shown to increase significantly after ingestion compared to before ingestion. was done.

In addition, changes in factors I to V tended to be higher in the test food group than in the placebo group. In particular, changes in factor I (sleepiness upon waking) and factor II (sleep onset and sleep maintenance) were significantly higher in the test food group than in the placebo group after 3 weeks of ingestion.

The MA version of the OSA Sleep Questionnaire can evaluate the psychological aspect of sleep (feeling of sleep), and the higher the score, the better the feeling of sleep (Non-Patent Document 3). From these results, it was confirmed that ingestion of the burdock sprout extract-containing food improved the feeling of sleep (in particular, sleepiness upon waking, sleep onset and sleep maintenance, sleep time, and recovery from fatigue).

[2. Evaluation by St. Marie Hospital Sleep Questionnaire]
The St. Marie's Hospital Sleep Questionnaire was used to assess effects on sleep quality in the test food and placebo groups. Table 9 shows the measured values of depth of sleep, degree of awakening during sleep, feeling of deep sleep, refreshing feeling upon awakening, satisfaction of sleep, and degree of sleep difficulty in the St. Marie Hospital sleep questionnaire, and the presence or absence of early morning awakening. Table 10 shows the amount of change in each score from 1 week before the start of intake. Figure 26 shows measured values and changes in depth of sleep in the test food group and placebo group, Figure 27 shows measured values and changes in sleep depth, Figure 28 shows measured values and changes in feeling of deep sleep, and Figure 29 shows values upon awakening FIG. 30 is a graph showing measured values and changes in exhilaration, actual measured values and changes in sleep satisfaction, and FIG. 31 showing measured values and changes in sleep difficulty.

As shown in the table and figure, depth of sleep, degree of wakefulness during sleep, feeling of deep sleep, refreshing feeling upon waking up, feeling of satisfaction with sleep, and degree of difficulty falling asleep were compared with those before and after 3 weeks of ingestion only in the test food group. scores improved significantly.

In addition, changes in depth of sleep, feeling of deep sleep, refreshing feeling upon awakening, and satisfaction of sleep were generally higher in the test food group than in the placebo group, showing a trend of improvement. In particular, the feeling of deep sleep was significantly higher at 3 weeks of ingestion. In addition, changes in the degree of awakening during sleep and difficulty falling asleep were generally lower in the test food group than in the placebo group, indicating a trend toward improvement. In particular, difficulty falling asleep was significantly lower after 3 weeks of ingestion.

The St. Mary's Hospital Sleep Questionnaire is a subjective assessment of sleep quality, with higher scores for depth of sleep, feeling of deep sleep, refreshedness upon awakening, and satisfaction with sleep; A lower score indicates a higher quality of sleep (Non-Patent Document 4). From these results, it was confirmed that the intake of food containing burdock sprout extract improved sleep quality such as depth of sleep, degree of wakefulness during sleep, feeling of deep sleep, feeling of refreshment upon awakening, feeling of satisfaction of sleep, and degree of difficulty falling asleep. .

These results strongly suggest that arctigenin and arctiin, which are commonly contained in the forsythia leaf extract of Example 1 and the burdock sprout extract of Example 2, have the effect of improving the quality of sleep.

INDUSTRIAL APPLICABILITY The present invention can be used for foods and medicines useful for improving sleep quality.

Claims (6)

A sleep quality improving agent containing arctigenin and/or arctiin as an active ingredient. 2. The agent for improving sleep quality according to claim 1, wherein said arctigenin and/or arctiin is contained as burdock, burdock, burdock sprout or forsythia or an extract thereof. The improvement of sleep quality includes sleepiness upon awakening, sleep onset and sleep maintenance, dreaminess, recovery from fatigue, sleep time, sleep depth, degree of awakening during sleep, feeling of deep sleep, refreshment upon awakening, satisfaction of sleep, and presence or absence of early morning awakening. 3. The agent for improving sleep quality according to claim 1, wherein at least one item selected from the group consisting of is improved. A food composition for improving the quality of sleep, containing arctigenin and/or arctiin as active ingredients. 5. The food composition according to claim 4, wherein said arctigenin and/or arctiin is contained as burdock, burdock root, burdock sprout or forsythia or an extract thereof. The improvement of sleep quality includes sleepiness upon awakening, sleep onset and sleep maintenance, dreaminess, recovery from fatigue, sleep time, sleep depth, degree of awakening during sleep, feeling of deep sleep, refreshment upon awakening, satisfaction of sleep, and presence or absence of early morning awakening. 6. The food composition according to claim 4 or 5, which is an improvement in at least one item selected from the group consisting of:

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