JP2015218119A - Sleep-improving agent and foods and drinks using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sleep-improving agent which can effectively improve quality of sleep, is excellent in safety, and can be ingested for a long period of time, and to provide foods and drinks using the same.SOLUTION: Disclosed are a sleep-improving agent containing D-ribose as an active ingredient, and foods and drinks containing the sleep-improving agent, which is used, for example, so that D-ribose is administered to a human at a dose of 350-3000 mg/kg body weight one or more times a day, and can facilitate decreasing core temperature after sleeping.

Description

  The present invention relates to a sleep-improving agent that improves the quality of sleep, and a food or drink using the sleep-improving agent.

  Sleep is the most basic physiological function. Although the physiological significance of sleep is still elucidated, it is known to be involved in higher-order functions such as memory consolidation and reconstruction, as well as recovery from mental and physical fatigue. It is a big problem that the movement that exceeds the time difference due to the modern 24-hour society and the globalization, the aging, and the stress loaded from various social environments disturb the sleep essential for physiological functions.

  By measuring the electroencephalogram, sleep is divided into non-REM sleep and REM sleep. NREM sleep is deep sleep in a state of resting brain activity. In addition, REM sleep is sleep corresponding to a state in which the body is weak and rests while the brain is actively active and memory is fixed and a dream is seen (Non-Patent Document 1). Sleep disorders are characterized by various occurrences in various time zones such as sleep deprivation, awakening in the middle, awakening in the early morning, a decrease in deep sleep, and daytime sleepiness. In the case of stress sleep disorder, there are many complaints such as sleep deprivation and arousal during sleep. In addition, in the case of age-related sleep disorder, there are many complaints such as mid-wake awakening, early morning awakening, or a decrease in the degree of deep sleep (Non-patent Document 2).

  For such sleep disorders, treatment using a sleeping pill is generally performed. However, the present situation is that it is not a sufficient solution for sleep disorders due to side effects, anxiety about taking or dependency problems. In addition, there are overwhelming cases in which sleep disorder is recognized but not a serious disorder, or in a non-disease state that does not progress to diagnosis and medication in medical institutions. Specifically, although it is in a sleep state, it may be ill even if it is diagnosed by an expert such as a doctor, such as a state of sleep that is lightly sleepy (half-sleep state), or does not feel like sleeping even after sleeping Is often not diagnosed and there is often no effective treatment. For this reason, development of a sleep improving agent containing a functional ingredient derived from food as an active ingredient is desired.

  Examples of the composition for improving sleep quality include a sleep promoting composition containing theanine (Patent Document 1), a deep sleep disorder improving agent containing glycine (Patent Document 2), and ornithine. Sleeping and waking improvement agent (patent document 3), sleep disorder improving agent containing sesamin (patent document 4), sleep improving agent containing cruciferous extract (patent document 5), and sleep containing γ-aminobutyric acid A quality improving composition (Patent Document 6) has been reported.

  In addition, it has been reported that D-ribose has an effect of improving depression-like symptoms (Patent Document 7). D-ribose is a kind of sugar and is a constituent of adenosine triphosphate (ATP), which is an energy source in the body. They are also recognized as additives and sweeteners, and are also used in supplements and energy supplement drinks. Furthermore, it has been known that it has an action of promoting ATP biosynthesis in myocardium and skeletal muscle, and is effective in the recovery phase of patients with cardiac ischemia (Non-patent Document 3).

JP 2005-289948 A International Publication No. 2005/067738 JP 2006-342148 A JP 2010-285427 A JP 2007-031371 A JP 2007-063236 A JP 2007-529494 A

Shiba Chiba, Circadian Rhythm Sleep Clinic, Emerging Medical Publishers, 2003, “Epidemiology of Sleep Disorders” Siegel JM, Science, 2001, 294: 1058-1063 Shecterle LM, Terry KR, St Cyr JA. Recent Pat. Cardiovasc. Drug Discov., 2010, 5 (2): 138-42

  Even if it is not a disease, if the sleeping state is not necessarily in a good state, a vibrant life cannot be desired, which may lead to a reduction in various productivity. For this reason, it is a potential social problem that many people are not in a good sleep state. Accordingly, there is a strong social demand for improving the quality of sleep by relieving symptoms that cannot be said to be ill, and providing an agent for that purpose. However, even when the compositions and the like reported in Patent Documents 1 to 6 are used, there are individual differences in the effects, and it cannot be said that they are necessarily sufficient. In Patent Document 7, the effect of D-ribose on sleep has not been reported.

  The present invention has been made in view of such problems of the prior art, and the problem is that it can effectively improve the quality of sleep and is excellent in safety. And it is providing the sleep improving agent which can be ingested for a long term, and the food-drinks using the same.

  As a result of intensive studies to solve the above problems, the present inventors have found that the above problems can be solved by using D-ribose as an active ingredient, and have completed the present invention.

That is, according to this invention, the sleep improving agent shown below is provided.
[1] A sleep improving agent containing D-ribose as an active ingredient.
[2] The sleep improving agent according to [1], which is used so that 350 to 3000 mg / kg body weight of the D-ribose per day is administered to a human.
[3] The sleep improving agent according to [1] or [2], which promotes a decrease in deep body temperature after going to bed.

Moreover, according to this invention, the food / beverage products shown below are provided.
[4] A food or drink containing the sleep improving agent according to any one of [1] to [3].

  The sleep-improving agent and food / beverage products of the present invention can effectively improve the quality of sleep, are excellent in safety, and can be taken for a long time.

It is a graph which shows the daily change of the awakening time of a normal mouse | mouth, non-REM sleep time, and REM sleep time. It is a graph which shows the daily change of the awakening time of a sleep disorder | damage | failure mouse | mouth, non-REM sleep time, and REM sleep time. It is a graph which shows transition of the non-REM sleep accumulation time in the rest period of a sleep disorder mouse. It is a graph which shows the influence of D-ribose with respect to the deep body temperature change of a sleep disorder mouse | mouth. It is a graph which shows the influence of D-ribose with respect to the deep body temperature change of a sleep disorder mouse | mouth.

  Embodiments of the present invention will be described below, but the present invention is not limited to the following embodiments.

  Conventionally, screening for sleep-improving agents has been performed using experimental animals such as mice and rats. For this reason, it was evaluated based on the effect of improving sleep when the sleep state is normal or the effect of inducing sleep by giving it to the awakened time zone. As a result, there has been a problem that even if there is an effect of improving the quality of sleep, it is difficult to detect, or only a substance that exhibits a hypnotic effect can be found in a time zone that requires awakening. Therefore, the present inventors have established a method of raising a model mouse on a rotating wheel set in a cage filled with water, and causing a sleep disorder in the model mouse by applying chronic stress. Then, various food-derived ingredients were given to the model mice in which sleep disturbance was intentionally caused to evaluate the effects, and screening for ingredients that improve sleep quality was performed.

  As a result, surprisingly, D-ribose, which was considered to be effective in improving energy supply, promotes an increase in non-REM sleep in model mice in which sleep disorders are caused by stress load, and decreases REM sleep. It was found that the effect of suppressing the above is shown. On the other hand, it was found that D-ribose shows little of the above effects on healthy mice that are not stressed.

  Moreover, the increase of non-REM sleep and REM sleep was recognized only in the rest period, and even if it took D-ribose, sleep was not induced in the active period, and it turned out that the circadian rhythm is kept healthy. Furthermore, it was also found that taking D-ribose promotes a decrease in deep body temperature after going to bed. From the above, the present inventors have found that D-ribose is an effective component capable of improving the quality of sleep at the time of sleep disorder due to stress load, and have completed the present invention. Hereinafter, the details of the sleep improving agent of the present invention will be described.

<Sleep improver>
The sleep improving agent of the present invention contains D-ribose as an active ingredient. The “D-ribose” in the present invention includes not only D-ribose but also derivatives of D-ribose and derivatives that can be converted into D-ribose in vivo.

  The sleep improving agent of the present invention can effectively improve the quality of sleep. Here, “improving the quality of sleep” in the present invention means improving the quality of sleep in general, such as promoting the introduction of natural sleep (promoting sleep) and improving the feeling of deep sleep. More specifically, it means increasing sleep satisfaction of people who have sleep dissatisfaction, such as being sleepless, not awake, or not sleeping well, but not enough to take sleeping pills or sleep-inducing drugs. .

  The amount of D-ribose contained as an active ingredient in the sleep-improving agent of the present invention is usually 5 to 100% by mass, preferably 10 to 80% by mass, and more preferably 15 to 70% by mass. This is because if the content of D-ribose is less than 5% by mass, it is necessary to ingest a large amount in order to exert the effect.

  The sleep improving agent of the present invention is usually preferably used as a drink. The drink preparation includes so-called sports drinks (sports drinks), energy drinks, jelly drinks and the like. It can also be used as oral liquid preparations such as syrups; intravenous administration preparations such as injections and infusions; oral solid preparations such as lozenges, lozenges, chewables, jelly preparations and supplements. These preparations can be produced according to conventionally known methods. Furthermore, you may ingest by adding the sleep improving agent of this invention to food-drinks, such as a drink and a foodstuff. For example, the quality of sleep of an inpatient can also be improved by giving the inpatient a hospital meal to which a sleep improving agent is added.

  The sleep-improving agent of the present invention is preferably used so that 350 to 3000 mg / kg body weight of D-ribose is administered per day, so that 500 to 2500 mg / kg body weight of D-ribose is administered per day. More preferably, it is used such that 750-2000 mg / kg body weight of D-ribose is administered per day. By using D-ribose so that the dose (intake) falls within the above numerical range, sleep quality can be improved more effectively and can be taken in the long term without difficulty. . In addition, it is preferable not only to administer (ingest) once a day but also to divide it into multiple times because it can be ingested over a long period of time.

  Subjects to which the sleep improving agent of the present invention is administered are mainly humans. However, it can be administered to sleeping animals to improve the quality of sleep. Examples of animals to which sleep-improving agents can be administered include mammals such as dogs, cats, horses, cows, pigs, sheep, mice, rats, guinea pigs, and hamsters; and birds such as juvenile pine, parakeets and parrots Can do.

  As a method for evaluating whether or not the quality of sleep is improved, in addition to a method for observing the state by administering a sleep improving agent to a human, for example, a sleep disorder model mouse creation device (Merquest, model number “SW- 15-SD ") or the like, and a method of screening using a model mouse prepared (bred) by continuously applying a gentle stress.

<Food and drink for sleep improvement>
The food / beverage products of this invention contain the above-mentioned sleep improving agent. By eating the food or drink of the present invention, D-ribose contained as an active ingredient in the sleep improving agent can be easily ingested, so that the quality of sleep can be improved effectively without difficulty.

  Since D-ribose is a component that can generally be used as a sweetener, the food and drink of the present invention can be processed food and drink using the sweetness of D-ribose. Specific examples of processed foods and drinks include pie, crackers, chips, pudding, chocolate, castella, waffles, donuts, cookies, biscuits, cakes, creams, rice crackers, okonomiyaki, manju, sea bream, bean paste, mutton, water sheep jelly, jelly Sweets such as candy, candy, etc .; staple foods such as breads, potatoes, noodles, macaroni, cooked rice, premixed flour, etc .; fish products such as artificial meat, rice cakes, chikuwa, tempura; Various delicacies; processed meat products such as ham, sausage and bacon; seasonings such as soy sauce and miso; various beverages such as sports drinks and jelly beverages; processed paste, potato salad, meat potato, boiled beans, boiled beans, boiled simmered, kelp Examples include prepared foods such as rolls.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to these Examples.

(Example 1: Effects of D-ribose on normal sleep EEG)
Twelve mice (C3H) were subjected to an indwelling operation of a transmitter for measuring EEG (DSI, TA10M2-F20-EET) under anesthesia. Specifically, an electroencephalogram measurement electrode was placed at two locations on the skull of the mouse and a myoelectric potential measurement electrode was placed at two locations on the cervical muscle, and a transmitter was stored subcutaneously on the back. Post-operative recovery was performed in a normal cage for 1 to 2 days after surgery, and in a cage with a rotating wheel for 12 to 13 days thereafter. The cage containing the mouse containing the transmitter was placed on the receiving board (DSI, RPC-1) and measurement was started. The detection data was acquired on a PC using data analysis software (DSI, Dataquest ART). After measuring the electroencephalogram before administration of D-ribose for 3 days, an aqueous D-ribose solution (3.5 mg / mL) was administered in drinking water. The daily intake was 6 mL on average, and converted to the intake of 1000 mg / kg body weight of D-ribose per day. One day after the administration, the electroencephalogram was measured for 3 days to obtain sleep EEG measurement data of D-ribose administration at normal time. Data obtained every 3 days obtained by the data analysis software was analyzed by a sleep analysis software (Kissei Comtech, Sleep Sign), and stage determination of wakefulness, non-REM (NREM) sleep, and REM (REM) sleep was performed. Moreover, about NREM sleep, the electroencephalogram frequency analysis was performed and the grade of the delta wave sleep was evaluated. The results are shown in FIG.

  As shown in FIG. 1, the effects of administration of D-ribose were hardly observed for the awakening time and the NREM sleep time under normal rearing. In addition, it is estimated that there is almost no effect on daily fluctuations. Moreover, about REM sleep time, the tendency for becoming short by administering D-ribose was recognized.

(Example 2: Effect of D-ribose on sleep EEG during sleep disorder)
In Example 1 described above, after obtaining sleep electroencephalogram measurement data of D-ribose administration at normal time, drinking water of all mice was used as tap water, and was kept as it was for 3 days until D-ribose remaining in the body was metabolized. did. The mice were divided into two groups of 6 mice, and for one group (D-ribose group), the cage floor was changed to a D-ribose aqueous solution, and the D-ribose aqueous solution (3 .5 mg / mL) was taken in free drinking water. Moreover, about the mouse | mouth of the other group (control group), while changing the flooring of a cage into a tap water, the tap water put into the drinking bottle was ingested by free drinking water. The daily intake was 6 mL on average, and for the mice in the D-ribose group, the conversion was equivalent to ingesting 1000 mg / kg body weight of D-ribose per day. All groups of mice were reared on a rotating wheel, and chronic stress was applied to induce sleep disturbance. Then, the electroencephalogram was measured for 3 days after 1 day from the start of stress loading. The results are shown in FIGS.

  As shown in FIG. 2, about the mouse | mouth which induced sleep disorder, the decrease in awakening time and the increase in sleep time are recognized by ingesting D-ribose in a rest period (8: 00-20: 00). It was. In particular, in the second half of the rest period (12:00 to 20:00), the decrease in wakefulness and the increase in sleep time are significant, and thus it is considered that the influence of D-ribose intake is more strongly affected. . Furthermore, the effect of administering D-ribose was observed for both NREM sleep and REM sleep. Moreover, as shown in FIG. 3, it was recognized that the accumulation time of the NREM sleep in the resting period tends to increase in the D-ribose group.

(Example 3: Effect of D-ribose on circadian variation of deep body temperature)
Eight mice (C3H-HeN) were housed one by one in a cage with a rotating wheel for 4 weeks and acclimated to the behavior. A data logger (KN Laboratories, Thermoclone SL) for body temperature measurement was placed in the abdominal cavity under anesthesia using an anesthetic (Mylan Pharmaceutical, Sevoflurane). And it used for the following experiment, after passing through the postoperative recovery for 3 days. The mice were divided into 2 groups (4 mice each), a D-ribose group administered with an aqueous D-ribose solution (3.5 mg / mL) and a control group administered with tap water (4 mice each). The body temperature data were continuously measured while rearing in this order. The daily intake was 6 mL on average, and for the D-ribose group of mice, the daily intake of 1000 mg / kg body weight of D-ribose was converted. The results are shown in FIG. Moreover, the 24-hour fluctuation | variation of the body temperature average value was analyzed from the body temperature data on the 6th-7th day of the 2nd week of stress breeding. The results are shown in FIG.
(1) 6 days prior to administration (2) 7 days during administration (3) Week 1 of stress breeding (7 days)
(4) 2nd week of stress breeding (7 days)

  It is known that the circadian variation is recognized in the deep body temperature, and that the circadian variation in the deep body temperature is deeply linked to sleep induction and arousal. As shown in FIG. 4, it can be seen that D-ribose has little influence on the circadian variation of the deep body temperature in the stage before stress is applied. Specifically, there was no difference in the average values of the maximum body temperature and the minimum body temperature between the D-ribose group and the control group. On the other hand, when D-ribose was administered to mice loaded with stress to induce sleep disorder, the deep body temperature transitioned lower from the first week when stress was applied, and the deep body temperature also decreased at the second week. It can be seen that the price has remained low. Further, as shown in FIG. 5, even when the transition of the daily deep body temperature is observed, the influence of D-ribose is recognized after the second day after the stress is applied, and the deep body temperature is observed during the stress period. It can be seen that is decreasing. This suggests that ingestion of D-ribose during sleep disorders may induce a decrease in deep body temperature and induce sleep during the rest period.

  If the sleep improving agent and food / beverage products of this invention are used, although it is not so much as taking a sleeping pill or a sleep introduction | transduction drug, the sleep satisfaction of those who have dissatisfaction about sleep, such as a shallow sleep, can be raised.

Claims (4)

  A sleep improving agent comprising D-ribose as an active ingredient.   The sleep improving agent according to claim 1, which is used so that 350 to 3000 mg / kg body weight of the D-ribose per day is administered to a human.   The sleep improving agent according to claim 1 or 2, which promotes a decrease in deep body temperature after going to bed.   Food-drinks containing the sleep improving agent as described in any one of Claims 1-3.

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