JPWO2020004182A1 - Sleep improver - Google Patents

Abstract

It is possible to further subdivide the evaluation of the sleep improving effect of the scent and provide a sleep improving agent containing a fragrance component having a sleep improving effect as an active ingredient. That is, the present invention relates to a sleep improving agent containing one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives as active ingredients. The present invention also relates to a sleep-improving fragrance composition containing the sleep-improving agent, and a method for improving the sleep of the subject, which comprises presenting the subject with the scent of the sleep-improving agent during sleep.

Description

The present invention relates to a sleep improving agent. Specifically, the present invention relates to a sleep improving agent containing at least one compound selected from a macrocyclic musk compound and a 2,2,6-trimethylcyclohexane derivative as an active ingredient. Furthermore, the present invention relates to a sleep-improving fragrance composition containing the sleep-improving agent, and a method for improving the sleep of a subject.

In recent years, with changes in social life, an increasing number of people are suffering from insomnia, which presents with symptoms such as sleep onset disorder, mid-career awakening, deep sleep disorder, and early morning awakening. Possible factors for insomnia include environmental factors, physiological factors, psychological factors, organic disease factors, mental illness factors, and the like. Insomnia caused by psychological factors such as worries, anxiety, and stress is increasing, reflecting the modern society called stress society.
Aromatherapy may be used as one of the coping methods caused by stress. Essential oils effective for insomnia include ylang ylang oil, orange oil, chamomile roman oil, cumin oil, coriander oil, petitgrain oil, bergamot oil, majorum oil, mandarin oil, lavender oil, lemon verbena oil, lemon balm oil, etc. Are known.
The essential oils used in aromatherapy may cause discomfort due to the palatability of the scent and the intensity of the fragrance. As a technology to solve such a problem, by using a layered fragrance sheet or the like, the initial fragrance is not too strong, it lasts moderately, the desired effect is exhibited, and the fragrance does not remain after use. Has been studied (see, for example, Patent Document 1).
In addition, as an essential oil composition for sleep supplementation and / or introduction without causing the side effects of conventional sleeping pills, one or more essential oils obtained from Labiatae plants, one or more essential oils obtained from Rutaceae plants, and Aoi Techniques for using one or more essential oils obtained from Labiatae plants, Myrtaceae plants, Rutaceae plants, Labiatae plants and Labiatae plants in combination have been studied. Among these technologies, the usefulness of aromatic products using lavender essential oil and the effectiveness of combining lavender oil, neroli oil, orange oil, and hop oil to form an aroma tape have been investigated (for example, Patent Document 2). reference).
Further, as an aroma component having a sleep improving effect, a combination of cypress oil and lavender oil (see Patent Document 3), a fragrance component having a benzene skeleton and an aldehyde group (see Patent Document 4), camphorenyl type sandals (Patent Document 5). (See), jasmine lactone (see Patent Document 6), cineole and / or methyl epijasmonate (see Patent Document 7), essential oil components obtained from 荊 芥, fine spicy, crispy sand, Masuchi or Kabushi (Patent Document 8). (See), a mixture of mandarin oil, lavender oil, chamomile oil, and in some cases sweet almond oil (see Patent Document 9), and sesquiterpene alcohols having a boiling point of 250 ° C. or higher under atmospheric pressure (see Patent Document 10). Has been proposed.
However, even lavender essential oils, which are listed as essential oils that are effective for insomnia, may appear differently depending on the application method, may not be effective depending on the combined essential oils, or may not improve sleep, but may be used. Depending on the combination of plant essential oils, the effect of the active ingredient may not be obtained.
In addition, not only perfumes and skin care cosmetics, but also fragrance products may cause discomfort due to the intensity of the scent. In particular, the quality of the scent causes discomfort, which adversely affects sleep improvement. Will have an effect.

On the other hand, recent cutting-edge research has revealed that psychology, neuroscience, endocrine science, and immunology form a close network. Traditionally, the immune system was thought to operate independently of the autonomic nervous system and be unaffected by other systems. However, the result that the immune system responds sensitively to stress was reported by the NASA (National Aeronautics and Space Administration) medical team as a relationship between astronaut stress and changes in white blood cell count. Taking this opportunity, research on the connection between psychology (mental) and the immune system was reviewed by stress experiments, and now the field of psychoneuroimmunology has been established. It is thought that the defense and repair mechanism of body cells and secretory gland function are linked to brain activity by the action of a related network of neuropeptides and their receptors due to psychological stress.

However, when measuring and evaluating the physiological and psychological effects of humans, most of them evaluated the effects on some indicators. For example, a psychological evaluation (see Patent Document 11) that measures a subjective questionnaire, and a neurological evaluation (patent) that measures the measurement of the consciousness level by a contingent negative variation (CNV), which is an index of the nervous system. Reference 10, Non-Patent Document 1), Physiological evaluation of cortisol, which is an index of the endocrine system (see Patent Document 12, Patent Document 13, Non-Patent Documents 2 to 4), Perfume component that induces a reward effect, Accord Alternatively, a method of evaluating the blended fragrance using the fMRI imaging method (see Patent Document 14) and the like can be mentioned. In addition, although there was an evaluation that measured these multiple indexes (see Patent Document 15), each mechanism was regarded as an independent system, and there was almost no mention of a complicated examination that evaluated the relationship between them.
The present inventor evaluates the sleep improving effect of fragrance by combining at least three kinds of indexes selected from an index belonging to a psychological index, an index belonging to a neurological index, an index belonging to an endocrine index, and an index belonging to an immune index. I went there (see Patent Document 16). However, the evaluation of the sleep improving effect of the scent at the time of awakening is limited, and the evaluation of the sleep improving effect of the scent has not been reached.
That is, although the sleep-improving effect of scents on humans is extremely complex, most of the conventional research methods for scent sleep are the results of focusing on one of the specific indicators for a specific scent. Yes, I was only looking at some of the effects in fragments. This must be considered insufficient to evaluate the sleep-improving effect of scents.

Japanese Unexamined Patent Publication No. 2008-56594 Japanese Unexamined Patent Publication No. 2000-355545 Japanese Unexamined Patent Publication No. 2011-5970 JP-A-2007-197334 Japanese Unexamined Patent Publication No. 2007-31421 Japanese Unexamined Patent Publication No. 6-40911 Japanese Unexamined Patent Publication No. 6-40906 Japanese Unexamined Patent Publication No. 5-178754 Japanese Patent Application Laid-Open No. 2012-510513 International Publication No. 2001/58435 Japanese Unexamined Patent Publication No. 2007-106719 JP-A-11-19076 International Publication No. 2017/004281 Japanese Unexamined Patent Publication No. 2012-177112 International Publication No. 2005/05/97773 Japanese Patent Application No. 2017-75720

Journal of the Anthropological Society of Japan, Vol. 8, No. 2: 25-29, May 2003 Biomedical Engineering, 52 (6): pp. 282-287, 2014 Journal of the Japanese Association for the Study of Taste and Smell, Vol. 21, No. 1: 69-75 pages, 2014 IEEJ Transactions on Electronics, Information and Systems, 133 (6), pp. 1277-78, 2013

In view of the above circumstances, it is desired to further subdivide the evaluation of the sleep improving effect of the scent and to provide a sleep improving agent containing a fragrance component having an appropriate sleep improving effect as an active ingredient.

The present inventors evaluated the sleep improving effect of fragrance by combining an index belonging to a psychological index, an index belonging to a neurological index, an index belonging to an endocrine index, and an index belonging to an immune index. To provide a sleep-improving fragrance component based on the basis of the interaction of psychological, neuroendocrine, endocrine and immune homeostatic mechanisms in vivo by simultaneous measurement of multiple indicators over time based on neuroendocrine immunology. Can be done.

That is, the present invention relates to the following [1] to [10].
[1] A sleep improving agent containing one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives as active ingredients.
[2] The macrocyclic musk compounds are 3-methylcyclopentadecane-1-one (muscone), 3-methyl-4-cyclopentadecene-1-one (dehydromuscone), and 9-cycloheptadecene-1-one (muscone). Civetone), cyclopentadecaneone, 5-cyclohexadecan-1-one, cyclohexadecanone, cyclopentadecanolide, 11 (12) -cyclopentadecenolide, 9-cyclopentadecenolide, cyclohexadecanone. One or more compounds selected from the group consisting of de, ethylene brushate, ethylene dodecandioate, 12-oxahexadecanonelide, 11-oxahexadecanonelide, and 10-oxahexadecanonelide. The sleep improving agent according to [1].
[3] The sleep improving agent according to [1] or [2], wherein the macrocyclic musk compound is an ethylene brassylate.
[4] The 2,2,6-trimethylcyclohexane derivative is
Ethyl 2,2,6-trimethylcyclohexanecarboxylic acid, allyl 2,2,6-trimethylcyclohexanecarboxylic acid, ethyl 2,2,6-trimethyl-4,6-cyclohexadienecarboxylic acid, 2,2,6-trimethyl- Methyl 4-cyclohexenecarboxylic acid, methyl α-cyclogerate, methyl β-cyclogerate, methyl γ-cyclogerate, ethyl α-cyclogerate, ethyl β-cyclogerate, ethyl γ-cyclogerate, and 2,2-dimethyl- A 2,2,6-trimethylcyclohexanecarboxylic acid ester derivative selected from the group consisting of ethyl 6-ethyl-5-cyclohexenecarboxylic acid;
α-Damasenone, β-Damasenone, γ-Damasenone, α-Damascon, β-Damascon, γ-Damascon, δ-Damascon, α-Yonone, β-Ionone, γ-Yonone, δ-Yonone, α-Methylyonone, β- Methyl Ionone, γ-Methyl Ionone, δ-Methyl Ionone, α-Isomethyl Ionone, β-Isomethyl Ionone, γ-Isomethyl Ionone, δ-Isomethyl Ionone, α-Iron, β-Iron, γ-Iron, δ-Iron, α-Allyl Ionone, β-Allyl Ionone, A (2,2,6-trimethylcyclohexane-1-yl) butane-2 (3) -one derivative selected from the group consisting of γ-allyl ionone and δ-allyl ionone; and α-damasenor, β-damasenor, γ-damasenor , Α-Damasconol, β-damasconol, γ-damasconol, δ-damasconol, α-yonone, β-yonone, γ-yonone, δ-yonone, α-methylyonone, β-methylyonone, γ-methylyonone, δ -Methylyonone, α-isomethylyonone, β-isomethylyonone, γ-isomethylyonone, δ-isomethylyonone, α-ironol, β-ironol, γ-ironol, δ-ironol, α-allylyonone , Β-allyl ionone, γ-allylyonone, δ-allylyonone, 2,2,6-trimethylcyclohexyl-3-hexanol, and 2,2,3,6-tetramethylcyclohexyl-3-hexanol (2) , 2,6-trimethylcyclohexane-1-yl) Butan-2 (3) -one or more compounds selected from the group consisting of all derivatives, any one of [1] to [3]. The sleep improver described in.
[5] The sleep improving agent according to any one of [1] to [4], wherein the 2,2,6-trimethylcyclohexane derivative is ethyl 2,2,6-trimethylcyclohexanecarboxylic acid.
[6] Sleep improving effect promotes smooth wake-up, lowers tension at wake-up, enhances sympathetic nerve before wake-up, enhances parasympathetic nerve after wake-up, and endocrine after wake-up. The sleep improving agent according to any one of [1] to [5], which is one or more sleep improving effects selected from the group consisting of effects that promote the increase of substances.
[7] A method for improving the sleep of a subject, which comprises presenting the subject with the scent of the sleep improving agent according to any one of [1] to [6] during sleep.
[8] A sleep-improving fragrance composition containing the sleep-improving agent according to any one of [1] to [6].
[9] Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care containing the sleep improving agent according to any one of [1] to [6]. Products selected from the group consisting of products, skin care products, body care products, laundry detergents, soft finishing agents for clothing, tobacco products, quasi-drugs and pharmaceuticals.
[10] Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care products, skin care products, body care containing the sleep-improving fragrance composition according to [8]. Products selected from the group consisting of products, clothing detergents, clothing softeners, tobacco products, quasi-drugs and pharmaceuticals.

The present invention also relates to the following [1] to [15].
[1] A sleep improving agent characterized in that a sleep improving effect was evaluated by combining an index belonging to a psychological index, an index belonging to a neurological index, an index belonging to an endocrine index, and an index belonging to an immune index.
[2] As indexes belonging to the psychological index, POMS (Profil of Mode States), OSA (Oguri-Shirakawa-Azumi) sleep questionnaire MA version, SSS (Standor Sleep Sleepiness Scale), KSS_J (Japane sleeves) The sleep improving agent according to [1], wherein the sleep improving effect was evaluated using any one of (Visual Analogue Scale).
[3] The sleep improving agent according to [1] or [2], wherein any one of brain wave, heart rate, heart rate variability and skin temperature is used as an index belonging to the nerve index.
[4] Any of [1] to [3], wherein any one of cortisol, cortisone, chromogranin A, dopamine, amylase, serotonin and adrenocorticotropic hormone is used as an index belonging to the endocrine index. The sleep improver described.
[5] The sleep improving agent according to any one of [1] to [4], which comprises using any one of immunoglobulin (IgA), natural killer cell activity and interleukin as an index belonging to the immune index. ..
[6] A sleep improving agent containing one or more compounds selected from macrocyclic musk compounds and / or 2,2,6-trimethylcyclohexane derivatives as active ingredients.
[7] The macrocyclic musk compounds are 3-methylcyclopentadecane-1-one (muscone), 3-methyl-4-cyclopentadecene-1-one (dehydromuscone), and 9-cycloheptadecene-1-one (muscone). Civetone), cyclopentadecaneone, 5-cyclohexadecan-1-one, cyclohexadecanone, cyclopentadecanolide, 11 (12) -cyclopentadecenolide, 9-cyclopentadecenolide, cyclohexadecanone. The compound according to [6], which is one or more compounds selected from de, ethylene brush rate, ethylene dodecandioate, 12-oxahexadecanonelide, 11-oxahexadecanonelide, and 10-oxahexadecanonelide. Sleep improver.
[8] The sleep improving agent according to [6] or [7], wherein the macrocyclic musk compound is an ethylene brassylate.
[9] The 2,2,6-trimethylcyclohexane derivative is a 2,2,6-trimethylcyclohexanecarboxylic acid ester derivative [ethyl 2,2,6-trimethylcyclohexanecarboxylate, allyl 2,2,6-trimethylcyclohexanecarboxylate] , 2,2,6-trimethyl-4,6-cyclohexadienecarboxylate, methyl 2,2,6-trimethyl-4-cyclohexenecarboxylate, methyl α-cyclogerate, methyl β-cyclogerate, methyl γ-cyclogerate , Α-Ethyl cyclogerate, ethyl β-cyclogerate, ethyl γ-cyclogerate, and ethyl 2,2-dimethyl-6-ethyl-5-cyclohexene carboxylate]; (2,2,6-trimethylcyclohexane-1- Il) Butan-2 (3) -one derivative [α-damasenone, β-damasenone, γ-damasenone, α-damascon, β-damascon, γ-damascon, δ-damascon, α-yonone, β-yonone, γ- Ionone, δ-yonone, α-methylyonone, β-methylyonone, γ-methylyonone, δ-methylyonone, α-isomethylyonone, β-isomethylyonone, γ-isomethylyonone, δ-isomethylyonone, α-iron, β-iron, γ-iron, δ-Iron, α-allyl ionone, β-allyl ionone, γ-allyl ionone, δ-allyl ionone]; (2,2,6-trimethylcyclohexane-1-yl) butane-2 (3) -ol derivative [α-damasenol, β -Damasenol, γ-Damasenol, α-Damasconol, β-Damasconol, γ-Damasconol, δ-Damasconol, α-yonone, β-yonone, γ-yonone, δ-yonone, α-methylyonone, β-methylyonone , Gamma-methylionol, δ-methylyonone, α-isomethylyonone, β-isomethylyonone, γ-isomethylyonone, δ-isomethylyonone, α-ironol, β-ironol, γ-ironol, δ -Ironone, α-allylyonone, β-allylyonone, γ-allylyonone, δ-allylyonone, 2,2,6-trimethylcyclohexyl-3-hexanol, 2,2,3,6-tetramethylcyclohexyl-3-hexanol] The sleep improving agent according to [6] to [8], which is one or more compounds.
[10] The sleep improving agent according to [6] to [9], wherein the 2,2,6-trimethylcyclohexane derivative is ethyl 2,2,6-trimethylcyclohexanecarboxylic acid.
[11] The sleep improvement has an effect of promoting smooth waking up, an effect of reducing tension at the time of waking up, an effect of enhancing sympathetic nerves before waking up, an effect of enhancing parasympathetic nerves after waking up, and an endocrine substance after waking up. The sleep-improving agent according to any one of [6] to [10], which is any sleep-improving effect selected from the effects of promoting the increase in.
[12] By presenting the scent during sleep, each index of the subject before sleep, during sleep, and after waking up is measured, and the psychology of the subject is measured from the obtained psychological index, neurological index, endocrine index, and immune index. The method for using a sleep-improving agent according to any one of [6] to [11], which comprises inferring a state and a physiological response and estimating the effect of a scent based on them.
[13] A sleep-improving fragrance composition containing the sleep-improving agent according to any one of [6] to [11].
[14] Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care products, skin care containing the sleep improving agent according to any one of [6] to [11]. Products, body care products, laundry detergents, soft finishing agents for clothing, tobacco products, quasi-drugs or pharmaceuticals.
[15] Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care products, skin care, which contain the sleep-improving fragrance composition according to [13]. Products, body care products, laundry detergents, soft finishing agents for clothing, tobacco products, non-pharmaceutical products or pharmaceuticals.

The present invention is a sleep improving agent containing one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives as active ingredients, and sleep improving fragrance compositions containing the same. And provide a way to improve the subject's sleep. According to a preferred embodiment of the present invention, a fragrance component having a sleep improving effect, which is characterized by an index belonging to the psychological index of the present invention, an index belonging to a neurological index, an index belonging to an endocrine index, and an index belonging to an immune index, is evaluated. Therefore, it is possible to provide a fragrance sample having a sleep improving effect.

Hereinafter, the present invention will be described in detail.
Examples of the psychological index adopted in the method for evaluating the sleep improvement effect according to the present invention include POMS (Profile of Mode States), OSA, SSS, KSS_J (Japanese version of Karolinska Sleepiness Scale), and VAS. Either or a combination thereof is used. In the present invention, any one of the above indexes, POMS, OSA, VAS, SSS, and KSS_J, or a combination thereof is preferable.

POMS (and POMS shortened version) has 65 questions (30 items in the shortened version), "tension-anxiety", "depression-depression", "anger-hostility", "liveliness", "fatigue", "confusion" The mood and emotional state of the six items can be evaluated. It is widely used for verification of relaxation effect, quality of life (QOL), verification of medical / medical intervention effect, and the like.
VAS checks the subject's condition with respect to the question item, with the left end of the straight line as "nothing;0" and the right end as "no more strong; 100". It was developed for the assessment of pain and has also been used to assess subjective health and mood. In the present invention, the question items of VAS are set to 6 items of "tension", "effort", "concentration", "fatigue", "irritability", "boring", and "sickness". In addition, the evaluation of the scent used at the end of the evaluation was carried out by VAS. The question items were "comfort,""strength,""preference," and "alertness."
OSA is a psychological scale that evaluates sleep introspection when waking up, targeting clinical sites where it is not possible to take sufficient time to fill in, and middle-aged and elderly people who cannot respond appropriately with items that have many options. .. OSA consists of 16 items of 5 factors: 1st factor: drowsiness when waking up, 2nd factor: sleep onset and sleep maintenance, 3rd factor: dream, 4th factor: recovery from fatigue, 5th factor: sleep time. Is also a four-limb selection type. The sleep sensation obtained from this questionnaire is a statistical scale of the sleep sensation that fluctuates daily, and does not capture the constant sleep sensation peculiar to the subject, but serves as a scale for evaluating the sleep state peculiar to the subject. A sleep health questionnaire is provided.
SSS is a self-assessment scale for drowsiness created by Stanford University. Wakefulness is determined by the circadian rhythm of the body clock and the periodic activity of the sleep center. Considering both, the state of consciousness such as attention becomes high around 9 am and 9 pm, and the lowest at around 3 pm. Become. Therefore, it is also important to change the time zone for measuring this scale. If it is 1 or 2 points, the wakefulness is good, and if it is higher than that, it is possible that the person has sleep debt (sleep deprivation). Even if you live a regular life, if there are chronic times of 3 points or more during the daytime, there is a possibility of hypersomnia.
KSS_J is a 9-case rating scale. Words indicating the degree of drowsiness are attached to odd-numbered stages. KSS_J has been developed as a Japanese version of KSS, and its validity and reliability have been confirmed by Kaida et al.
Of course, in the present invention, the psychological index is not limited to those described above, and various known methods may be adopted for evaluation.

As the nerve index adopted in the method for evaluating the sleep improving effect according to the present invention, measurement of the ratio of α wave, β wave, θ wave, etc. of brain wave (Ratio of α, β and θwave), frequency fluctuation measurement of α wave (α). Fluctuation), measurement of consciousness level by CNV, measurement of brain wave P300 (P300), measurement of sleep polygraph (Polysomnography), measurement of cerebral blood flow (fMRI), measurement of intracerebral blood flow (near-infrared spectrum) : NIRS), pupil diameter (Pupil diamond), electrocardiogram measurement (Electrocardiogram: ECG), blood pressure measurement (Blood pressure), sweating measurement (Perspiration), breath measurement (Respiration), surface blood flow measurement (Surface) Flow), fingertip volume pulse measurement (Finger Plethysmogram), heartbeat (Heart rate), heart rate variability (HRV), skin temperature (Skin temperature), skin electrical response (Galvanic skin) (Adrenaline), measurement of the amount of acetylcholine (Aceticcholine), and the like, and any one of the above or a combination thereof is used. In the present invention, among the above indicators, any one of heart rate, heart rate variability, and skin temperature, or a combination thereof is preferable. In the experimental results, the combination of the three indicators of heart rate, heart rate variability, and skin temperature is a preferable combination.

Nervous index is roughly divided into central nervous system index and autonomic nervous system index.
As an index of the central nervous system, measurement of the ratio of α wave, β wave, θ wave of brain wave, measurement of frequency fluctuation of α wave of brain wave, measurement of fragrance consciousness level by CNV, measurement of P300 of brain wave, sleep polygraph Measurements can be mentioned.

The method of measuring the consciousness level by CNV is a known method as one method of evaluating the function of the scent, and the brain wave of the frontal lobe after smelling the scent is measured for the arousal / sedative effect of the scent to evaluate the scent function. The method.
The polysomnography measurement is to determine the sleep stage in 6 stages of awakening, sleep stages 1 to 4, and REM sleep by simultaneously recording various biological indicators such as brain waves.
(Reference: Sleep Psychology, edited by Tadao Hori, Kitaooji Shobo, 2008)

Examples of the autonomic nervous system index include electrocardiogram, measurement of blood pressure and respiration, measurement of surface blood flow, measurement of fingertip vein wave, measurement of pupillary response, and the like. The autonomic nerves are roughly divided into sympathetic nerves and parasympathetic nerves, and are responsible for the regulation of internal organs. In measuring the action of the scent on the autonomic nervous system, the measuring method is not particularly limited as long as it is an appropriate method. Heart rate variability and skin temperature are exemplified as typical indexes belonging to the autonomic nervous system index.

Heart rate variability includes the evaluation of total heart rate variability and the operation of power spectrum analysis of the frequency components of heart rate variability. The power spectrum analysis of heart rate variability is divided by frequency domain. The Low Frequency (LF) component is a power integration in the frequency band of 0.04 to 0.15 Hz, and is used as a sympathetic nerve activity index. The High Frequency (HF) component is a power integration in the frequency band of 0.15 to 0.40 Hz, and is used as a parasympathetic nerve activity index.

The skin temperature is used as an index of sympathetic nerve activity by continuously measuring the skin temperature of a human fingertip or nose. When the outside air temperature is constant, it changes depending on the blood flow circulating in the skin tissue, and the blood flow circulating in the skin tissue is regulated by the contraction / expansion of vascular smooth muscle. When vascular smooth muscle dilates, local blood flow increases and skin temperature rises. It is known that this vascular smooth muscle is mainly controlled by sympathetic vasoconstrictor fibers, and when sympathetic nerve activity is enhanced, the vascular smooth muscle contracts and peripheral circulation is suppressed, resulting in a decrease in blood flow. And the skin temperature drops.

Adrenocorticotropic hormone (ACTH) (Adrenocorticotropic Hormone), cortisol, cortisol, chromogranin A, dopamine D, as endocrine indices adopted in the method for evaluating the sleep improving effect according to the present invention. ), Amylase, Hormonin, Catecholamine, or a combination thereof. In measuring the action of the scent on the endocrine system, the measuring method is not particularly limited as long as it is an appropriate method. In the experimental results, it was found that it is preferable to use cortisol as an index. Cortisol is exemplified as a typical index belonging to the endocrine system index.

Cortisol is a hormone secreted from the adrenal cortex during stress loading and is responsible for physiological actions such as anti-stress and anti-inflammatory. Cortisol is known to be secreted not only by the physical intensity of stress, but also by various psychosocial factors.

As an immune index adopted in the method for evaluating the sleep improving effect according to the present invention, any one of immunoglobulin (IgA: Immunoglobulin A), natural killer cell (Natural Killer Cell), interleukin (Interleukin), or a combination thereof can be used. Used. In measuring the action of the scent on the immune system, the measuring method is not particularly limited as long as it is an appropriate method. In the experimental results, it was found that it is preferable to use IgA as an index. IgA is exemplified as a typical index belonging to the endocrine system index.

IgA is a type of antibody produced by B cells and has a physiological action of suppressing the growth of pathogens on mucous membranes such as the oral cavity, respiratory tract, and intestinal tract. Increased concentrations of IgA have been reported for acute stress such as mental arithmetic tasks and oral presentations.

The subjects were healthy adults with no olfactory dysfunction by subject screening. Subjects were banned from alcohol, drug, and excessive caffeine intake on the day of the experiment. In addition, on the day of the experiment, he was warned to wake up at the same time as usual, not to take a nap (nap / doze), to refrain from excessive exercise, perfume, colon and other scented substances.
The subject wore a heart rate monitor 60 minutes before falling asleep and started the measurement. Before going to bed, a questionnaire and saliva were collected, and a designated fragrance was installed before going to bed. After waking up, a questionnaire and saliva were collected, and saliva was collected 15 minutes, 30 minutes, and 45 minutes after waking up. The heart rate monitor was stopped after all saliva was collected. In the polysomnography measurement performed in the laboratory, electrodes for electroencephalogram, eye movement, and mentalis electromyogram measurement were attached 30 minutes before the start of the experiment, and the patient was allowed to fall asleep at the start of the experiment. After recording the data in the off state for 70 minutes, the subject was awakened and the experiment was completed.
In the present invention, these experimental methods can be appropriately used, and the evaluation method is not particularly limited. The experiment was planned within the subject, and there was an interval of one week or more between the experiments. The order in which the scents were presented was random, and the scents to be presented were not notified to the subjects.

As a result of applying the above-mentioned method for evaluating the sleep improving effect of fragrance to a fragrance component, it was found that the following fragrance component is effective as a sleep improving agent.
That is, a macrocyclic musk compound and / or a 2,2,6-trimethylcyclohexane derivative.

In the present invention, the macrocyclic musk compound is a cyclic compound containing 15 to 17 carbon atoms, and may further have one or more oxygen atoms. The oxygen atom may form a ring together with 15 to 17 carbon atoms, or may have an oxygen atom as a substituent of the ring. Preferred macrocyclic musk compounds are 3-methylcyclopentadecanol-1-one (muscone), 3-methyl-4-cyclopentadecene-1-one (dehydromuscone), 9-cycloheptadecene-1-one (cibeton). , Cyclopentadecanol (Exalton: Firmenich), 5-Cyclohexadecene-1-one (Umbleton: Takasago Perfume Industry Co., Ltd.), Cyclohexadecanone, Cyclopentadecanolide, 11 (12) -Cyclopentadecanolide (Habanoride: Firmenich), 9-Cyclopentadecenolide (Amblet Ride: Zivodan), Cyclohexadecanolide (Hexadecanolide: IFF), Ethylene Brush Rate (Musk T: Takasago Fragrance Industry Co., Ltd.) ), Ethethylenedodecandioate (Muscone C-14: Takasago Fragrance Industry Co., Ltd.), 12-Oxahexadecanolide (Muscone 781: IFF), 11-Oxahexadecanolide (Muscone R-1: Quest) , And 10-oxahexadecanolide (Oxalide T: Takasago Perfume Industry Co., Ltd.) and the like can be exemplified. As these compounds, those prepared by a known production method may be used, or commercially available products may be purchased and used.
The macrocyclic musk compound is already known as a fragrance component, but it is not known that the fragrance component is effective as a sleep improving agent by being presented at the time of sleep, let alone those fragrance components. , The effect of promoting smooth wake-up, the effect of reducing tension at the time of waking up, the effect of enhancing sympathetic nerve before waking up, the effect of enhancing parasympathetic nerve after waking up, and the effect of promoting the increase of endocrine substances after waking up. Was never known to have.

The 2,2,6-trimethylcyclohexane derivative has, for example, a 2,2,6-trimethylcyclohexane skeleton and has an alkoxycarbonyl group, an alkylcarbonyl group, an alkenyloxycarbonyl group, an alkenylcarbonyl group, and a hydroxyl group on the cyclohexane ring. A compound having a substituent such as an alkyl group or an alkenyl group having a hydroxyl group is preferably mentioned.
Examples of the 2,2,6-trimethylcyclohexane derivative include ethyl 2,2,6-trimethylcyclohexanecarboxylic acid (Tesalon: Takasago Fragrance Industry Co., Ltd.) and allyl 2,2,6-trimethylcyclohexanecarboxylic acid (kajitsu ester: Takasago fragrance). Kogyo Co., Ltd.), Ethyl 2,2,6-trimethyl-4,6-cyclohexadienecarboxylate (ethyl safranate: Dibodan), Methyl 2,2,6-trimethyl-4-cyclohexene carboxylate (methyl safranate:) Dibodan), Methyl α-cyclogerate, Methyl β-cyclogerate, Methyl γ-cyclogerate, Ethyl α-cyclogerate, Ethyl β-cyclogerate, Ethyl γ-cyclogerate, and 2,2-dimethyl-6-ethyl 2,2,6-trimethylcyclohexanecarboxylic acid ester derivatives such as ethyl-5-cyclohexenecarboxylate (Divescon: Dibodan);
α-Damascone, β-Damascone, γ-Damascone, α-Damascone, β-Damascone, γ-Damascone, δ-Damascone, α-Yonone, β-Ionone, γ-Yonone, δ-Yonone, α-Methylyonone, β- Methyl Ionone, γ-Methyl Ionone, δ-Methyl Ionone, α-Isomethyl Ionone, β-Isomethyl Ionone, γ-Isomethyl Ionone, δ-Isomethyl Ionone, α-Iron, β-Iron, γ-Iron, δ-Iron, α-Allyl Ionone, β-Allyl Ionone, (2,2,6-trimethylcyclohexane-1-yl) butane-2 (3) -one derivatives such as γ-allyl ionone and δ-allyl ionone;
α-Damasenol, β-Damasenol, γ-Damasenol, α-Damasconol, β-Damasconol, γ-Damasconol, δ-Damasconol, α-Yonol, β-Yonol, γ-Yonol, δ-Yonol, α- Methylyonol, β-methylyonol, γ-methylyonol, δ-methylyonol, α-isomethylyonol, β-isomethylyonol, γ-isomethylyonol, δ-isomethylyonol, α-ironol, β-ironol, γ-Ironol, δ-Ironol, α-allylyonol, β-allylyonol, γ-allylyonol, δ-allylyonol, 2,2,6-trimethylcyclohexyl-3-hexanol, 2,2,3,6-tetramethylcyclohexyl-3 A (2,2,6-trimethylcyclohexane-1-yl) butane-2 (3) -ol derivative such as -hexanol;
Etc. can be exemplified. As these compounds, those prepared by a known production method may be used, or commercially available products may be purchased and used.
The above 2,2,6-trimethylcyclohexane derivative is already known as a fragrance component, but it is not known that the fragrance component is effective as a sleep improving agent by presenting a scent during sleep. Not to mention, these fragrance components have the effect of promoting smooth wake-up, the effect of reducing tension at the time of wake-up, the effect of enhancing sympathetic nerve before wake-up, the effect of enhancing parasympathetic nerve after wake-up, and the endocrine substance after wake-up. It was not known at all to have the effect of promoting the increase of.
In the sleep improving agent of the present invention, the above-mentioned fragrance component may be used alone or in combination of two or more.

The sleep improving agent of the present invention contains one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives as active ingredients. According to one embodiment of the present invention, the active ingredient of the sleep improving agent of the present invention is only one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives. It is preferably composed of.

The above-mentioned fragrance component has a sleep-improving effect as a sleep-improving agent, and a sleep-improving fragrance composition can be obtained by blending the component with the fragrance composition. Alternatively, it may be a sleep-improving fragrance composition composed of the above fragrance components.
The sleep-improving fragrance composition of the present invention comprises known sleep-improving fragrance components (eg, lavender oil, neroli oil, orange oil, hop oil, cypress oil, mandarin oil, chamomile oil, sweet almond oil, cedarwood oil, etc. Essential oil components obtained from 荊芥, spicy, crispy sand, Masuchi or Kabushi, piperonal (3,4-methylenedioxybenzoaldehyde), anisaldehyde, benzaldehyde, fanylacetaldehyde, phenylpropylaldehyde, synamic aldehyde, α- Amilcinnamic aldehyde, cumin aldehyde, helional, cyclamen aldehyde, vanillin, methyl vanillin, lilial, jasmine lactone, cineole, methyl epijasmonate, sedrol, sedrenol, sedrenol, farnesol, pacholi alcohol, eugenol, α-santalol, α -Visabolol, β-cariophyllene alcohol, vetiverol, sclareiol, geranyllinalol, isofitol, nerolidol, globrol, guaiol, sandalol (dibodan), evanol (dibodan), polysantor (filmenich), etc. (eg , Patent Documents 2 to 10))) can be mixed and used. These fragrance components may be used alone or in combination of two or more.

Further, the sleep-improving fragrance composition of the present invention is a known method for evaluating a sleep-improving effect (for example, an index belonging to a psychological index, an index belonging to a neurological index, an index belonging to an endocrine index, and an index belonging to an immune index (for example, a patent). It can be used in combination with other fragrance components for which findings as a sleep improving effect have been obtained by using Documents 10 to 16 and Non-Patent Documents 1 to 4)).

In addition, the sleep-improving fragrance composition of the present invention may contain commonly used fragrance components as long as it does not interfere with palatability or the effects of the present invention.
Examples of the "usually used fragrance component" here include various synthetic fragrances, natural essential oils, synthetic essential oils, citrus oils, and animal fragrances. For example, "Perfume and Flavor Chemicals (Aroma Chemicals) 1,2" (Steffen Arctander (1969)), "Synthetic Fragrance Chemistry and Product Knowledge <Augmented Revised Edition>" by Motokazu Indo, The Chemical Daily, March 2005. Uses a wide variety of fragrance ingredients as described in "Public and Conventional Techniques (Fragrance) Part I" (issued by the Patent Office on January 29, 1999). be able to. Among them, typical ones are, for example, α-pinene, limonene, cis-3-hexenol, phenylethyl alcohol, styralyl acetate, ammonium isovalerate, eugenol, rose oxide, linalool, benzaldehyde, menthol and menthol skeleton. Examples thereof include fragrances having a cooling sensation effect such as derivatives having.

In the sleep improving fragrance composition of the present invention, the content of the sleep improving agent of the present invention may be appropriately determined according to the intended use and purpose, but from the viewpoint of the sleep improving effect, 0.00000001 to 100% by mass is preferable. It is more preferably 0.000000001 to 100% by mass, and even more preferably 0.000001 to 100% by mass. The rest of the sleep-improving fragrance composition of the present invention is other fragrance components that have been found to have a sleep-improving effect and commonly used fragrance components.

The sleep-improving agent and sleep-improving fragrance composition of the present invention can be used in various fields. For example, beverages; foods; fragrance products, basic cosmetics, finishing cosmetics, hair cosmetics, tanning cosmetics, cosmeceuticals and other cosmetics; cleaning agents, kitchen detergents, bleaching agents and other toiletry products; deodorants and fragrances, etc. Air care products; Daily and quasi-drugs; Oral compositions; Hair care products; Skin care products such as soap; Body care products such as body cleansers; Bath products; Clothes cleaners; Clothes soft finishes; Aerosols; Tobacco It can be contained in, that is, blended or aromatized in products such as quasi-drugs or pharmaceuticals.

The beverages include fruit juice beverages, fruit liquors, dairy beverages, carbonated beverages, soft beverages, drinks, alcoholic beverages (beer, beer-flavored beverages, high balls, chu-hi, etc.); green tea, oolong tea, etc. Tea, persimmon leaf tea, chamomile tea, kumazasa tea, mulberry tea, dokudami tea, puard tea, mate tea, louis boss tea, gymnema tea, guaba tea, coffee, cocoa and other tea beverages or favorite beverages; Japanese-style soup, Western-style Soups, soups such as Chinese soup; various instant beverages, etc.;
The foods include frozen desserts such as ice cream, sherbets, and ice candies; desserts such as jelly and pudding; Western confectionery such as cakes, cookies, chocolate, and chewing gum; Japanese confectionery such as buns, sheep candies, and willows; Jam; Candy; Bread; Flavor seasoning; Various instant foods; Various snack foods;
The fragrance products include perfumes, eau de parfum, eau de toilette, cologne, etc .;
The basic cosmetics include facial cleansing cream, vanishing cream, cleansing cream, cold cream, massage cream, milky lotion, lotion, beauty essence, facial mask, makeup remover, etc.
Examples of the finishing cosmetics include foundation powder, powder powder, solid powder, talcum powder, lipstick, lip balm, blusher, eyeliner, mascara, eye shadow, eyebrow, eye pack, nail enamel, enamel rim bar, etc.;
The hair cosmetics include pomade, brilantin, set lotion, hair stick, hair solid, hair oil, hair treatment, hair cream, hair tonic, hair liquid, hair spray, bandolim, hair nourishing agent, hair dye, etc .;
Examples of the tanning cosmetics include suntan products and sunscreen products;
Examples of the medicated cosmetics include antiperspirants, after-shaving lotions and gels, permanent wave agents, medicated soaps, medicated shampoos, medicated skin cosmetics, etc.
Examples of the cleaning agent include cleansers, house cleaners, toilet cleaning agents, bathroom cleaning agents, glass cleaners, mold removers, drain pipe cleaning agents, and the like;
Examples of the kitchen detergent include kitchen soap, synthetic kitchen soap, and dishwashing detergent;
Examples of the bleaching agent include oxidation-type bleaching agents (chlorine-based bleaching agents, oxygen-based bleaching agents, etc.) and reducing-type bleaching agents (sulfuric acid-based miscellaneous goods such as tissue paper and toilet paper;
Examples of the deodorant / fragrance include solid type, gel type, liquid type (water-based, oil-based), etc.
Examples of the oral composition include toothpaste, oral cleansers, mouthwashes, troches, chewing gums, and the like;
The hair care products include shampoo, conditioner, rinse-in shampoo, conditioner, treat men, hair pack, etc.
Examples of the soap include cosmetic soap, bath soap, perfume soap, transparent soap, synthetic soap and the like;
Examples of the body cleanser include body soap, body shampoo, hand soap, face cream and the like;
Examples of the bath salt include bath salts (bath salts, bath tablets, bath liquids, etc.), foam baths (bubble baths, etc.), bath oils (bath perfume, bath capsules, etc.), milk baths, bath jelly, bath tubs, etc.
Examples of the detergent include heavy laundry detergent, light detergent for clothing, liquid detergent, laundry soap, compact detergent, powder soap and the like;
Examples of the soft finishing agent include softener, furnicia care, etc .;
Yellow bleach, etc.), optical bleach, etc .;
Examples of the aerosol agent include spray type and powder spray;
The tobacco includes cigarettes, cigars, pipes, xel, water tobacco, smokeless tobacco, heat-not-burn tobacco, electronic cigarettes, etc.;
Quasi-drugs include liquid bath salts, mouthwashes, repellents, etc., and repellents include mist spray type, aqueous liquid type, etc.;
Pharmaceuticals include medicated cosmetics and medicated lotions;
Various forms of Needless to say, the products or products in which the sleep-improving agent and the sleep-improving fragrance composition of the present invention are used are not limited thereto.
The amount of the sleep improving agent of the present invention to be blended or aromatized in these products is appropriately determined according to the type of the product and the purpose of use, and is not particularly limited, but is, for example, relative to the total mass of the product. The sleep improving agent of the present invention is preferably in the range of 0.00001 to 10000 ppm, more preferably 0.0001 to 1000 ppm, still more preferably 0.001 to 100 ppm, and the sleep improving effect is likely to be obtained. ..

The sleep-improving agent and sleep-improving fragrance composition of the present invention present the scent of the sleep-improving agent of the present invention to a subject during sleep, either as it is or by blending or perfume it in various products. By doing so, the sleep of the subject can be improved. The present invention also includes methods for improving a subject's sleep, including presenting the subject with the scent of the sleep improver of the present invention during sleep.
Further, for example, the sleep improving agent of the present invention is
Steps to measure the subject's psychological, neurological, endocrine and immune indicators before, during sleep and after waking up,
Steps to infer the psychological state and physiological response of the subject from the obtained psychological index, neurological index, endocrine index and immune index, and
It may be used by a method including a step of estimating the effect of the scent by presenting the scent to the subject during sleep.

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto, and various changes and modifications are made without departing from the scope of the present invention. Is also good.

[Example 1]
During sleep, Musk T (Musk T: manufactured by Takasago International Corporation: ethylene brassylate) was presented to the subjects, and the method for evaluating the physiological and psychological effects of scent using the above psychological, neuroendocrine and immune indicators was applied. Figure 1-3 shows the measurement results. FIG. 1 shows the measurement results when Musk T is applied to the tension caused by VAS, which is a psychological index of the present invention. FIG. 2 shows the measurement results when Musk T is applied to the heartbeat interval (RR Interval, hereinafter “RRI”) measured by electrocardiogram, which is a neural index of the present invention. FIG. 3 shows the measurement results when Musk T is applied to the heart rate (Heart Rate, hereinafter “HR”) measured by electrocardiogram, which is a neural index of the present invention. From the results of the experiment, the presentation of musk T showed suppression of tension after waking up, a decrease in RRI 30 to 90 minutes before waking up, and an increase in HR. This indicates that the psychological tension at the time of waking up was alleviated by the physiological action of gradually predominantly sympathetic nervous system activity, which is the autonomic nervous system, and promoting smooth waking up from before waking up.

[Example 2]
During sleep, the subject was presented with a mixed fragrance containing musk T (Musk T Key), and the method for evaluating the physiological and psychological effects of fragrance using the above psychological, neuroendocrine and immune indicators was applied. The formulation of the blended fragrance (Musk T Key) is shown below.

The measurement results are shown in FIG. 4-7. FIG. 4 shows the measurement results when Musk T Key is applied to anger by POMS, which is a psychological index of the present invention. FIG. 5 shows the measurement results when Musk T Key is applied to irritation by VAS, which is a psychological index of the present invention. FIG. 6 shows the measurement results when Musk T Key was applied to the skin temperature, which is a neural index of the present invention. FIG. 7 shows the measurement results when Musk T Key was applied to cortisol, which is an endocrine index of the present invention. From the results of the experiment, the presentation of the mixed fragrance (Musk T Key) suppressed anger and irritation after waking up, decreased the skin temperature 30 to 60 minutes before waking up, and increased cortisol after waking up. This is because the sympathetic nervous system activity, which is the autonomic nervous system, gradually becomes dominant before waking up, and after waking up, the increase in cortisol promotes physiological arousal, which alleviates psychological anger and irritation when waking up. Indicates that it was done.

[Example 3]
During sleep, the subject was presented with Thesaron (Tesalon: manufactured by Takasago International Corporation: ethyl 2,2,6-trimethylcyclohexanecarboxylic acid), and the psychological and psychological effects of the scent using the above psychological, neuroendocrine and immune indicators. The evaluation method was applied. The measurement results are shown in FIG. 8-11. FIG. 8 shows the measurement results when Thesaron is applied to boredom by VAS, which is a psychological index of the present invention. FIG. 9 shows the measurement results when Thesaron was applied to the skin temperature, which is a neural index of the present invention. FIG. 10 shows the measurement results when Thesaron is applied to HF by electrocardiogram measurement, which is a neural index of the present invention. FIG. 11 shows the measurement results when Thesaron was applied to cortisol, which is an endocrine index of the present invention. From the results of the experiment, the presentation of Thesaron showed suppression of boredom after waking up, a decrease in skin temperature 30 to 60 minutes before waking up, an increase in HF after waking up, and an increase in cortisol. This is because the sympathetic nervous system activity, which is the autonomic nervous system, gradually becomes dominant before waking up, and after waking up, the increase in cortisol promotes physiological arousal, and then the parasympathetic nerve is enhanced. Indicates that the general boredom has been alleviated.

[Example 4]
During sleep, the subject was presented with a blended fragrance (Thesaron Key) containing Thesaron (Tesalon: manufactured by Takasago Fragrance Industry Co., Ltd .: ethyl 2,2,6-trimethylcyclohexanecarboxylic acid), and the above psychological, neuroendocrine and immune indicators were used. A method for evaluating the physiological and psychological effects of the scent was applied. The formulation of the blended fragrance (Thesaron Key) is shown below.

FIG. 12 shows the measurement results. FIG. 12 shows the measurement results when Thesaron Key was applied to LF / (LF + HF) by electrocardiogram measurement, which is a neural index of the present invention. From the results of the experiment, the presentation of the blended fragrance (Thesaron Key) increased LF / (LF + HF) 60 to 90 minutes before waking up. This indicates that the sympathetic nervous system, which is the autonomic nervous system, gradually became dominant before waking up and promoted smooth waking up.

[Example 5]
During sleep, subjects were presented with Musk T or Thesaron and polysomnography was measured for 70 minutes. Electrodes for electroencephalogram measurement were attached to C3 and O1, and the sleep latency and the time indicating each sleep stage (wakefulness, sleep stage 1, sleep stage 2) were measured. Sleep electroencephalograms were measured with a polygraph EEG-1100 (manufactured by Nihon Kohden) and recorded in real time on a sleep stage automatic determination system (manufactured by AIC Co., Ltd.) at 256 Hz sampling. FIG. 13 shows the measurement results of sleep latency. FIG. 13 shows the sleep latency when Musk T or Thesaron is presented in the polysomnography measurement, which is a neural index of the present invention, as a difference from the blank condition, that is, when the scent is not presented. Since the sleep latency was shortened in both Musk T and Thesaron as compared with the non-scented condition, it was shown that the presentation of Musk T or Thesaron promoted smooth sleep onset. 14 and 15 show the time during which each sleep stage (wakefulness, sleep stage 1, sleep stage 2) was shown when Musk T or Thesaron was presented in the polysomnography measurement, which is a neural index of the present invention, respectively. In both Musk T and Thearon, the time showing the arousal stage was shortened and the time showing the sleep stage 2 was extended compared to the unscented condition. Therefore, the presentation of Musk T or Thearon increased the sleep efficiency. Shown. Since this experiment was carried out for 70 minutes during the day, almost no sleep stage 3 or later and REM sleep were observed.

FIG. 1 shows the measurement results when Musk T is applied to the tension caused by VAS, which is a psychological index of the present invention. FIG. 2 shows the measurement results when Musk T is applied to RRI by electrocardiogram measurement, which is a neural index of the present invention. FIG. 3 shows the measurement results when Musk T is applied to HR by electrocardiogram measurement, which is a neural index of the present invention. FIG. 4 shows the measurement results when Musk T Key is applied to anger by POMS, which is a psychological index of the present invention. FIG. 5 shows the measurement results when Musk T Key is applied to irritation by VAS, which is a psychological index of the present invention. FIG. 6 shows the measurement results when Musk T Key was applied to the skin temperature, which is a neural index of the present invention. FIG. 7 shows the measurement results when Musk T Key was applied to cortisol, which is an endocrine index of the present invention. FIG. 8 shows the measurement results when Thesaron is applied to boredom by VAS, which is a psychological index of the present invention. FIG. 9 shows the measurement results when Thesaron was applied to the skin temperature, which is a neural index of the present invention. FIG. 10 shows the measurement results when Thesaron is applied to HF by electrocardiogram measurement, which is a neural index of the present invention. FIG. 11 shows the measurement results when Thesaron was applied to cortisol, which is an endocrine index of the present invention. FIG. 12 shows the measurement results when Thesaron Key was applied to LF / (LF + HF) by electrocardiogram measurement, which is a neural index of the present invention. FIG. 13 shows the sleep latency when Musk T or Thesaron is presented in the polysomnography measurement, which is a neural index of the present invention, as a difference from the blank condition, that is, when no scent is presented. FIG. 14 shows the time indicating each sleep stage when Musk T was presented in the polysomnography measurement, which is a neural index of the present invention. FIG. 15 shows the time indicating each sleep stage when Thesaron was presented in the polysomnography measurement, which is a neural index of the present invention.

Claims (10)

A sleep improving agent containing one or more compounds selected from the group consisting of macrocyclic musk compounds and 2,2,6-trimethylcyclohexane derivatives as active ingredients. The macrocyclic musk compounds are 3-methylcyclopentadecane-1-one (muscone), 3-methyl-4-cyclopentadecene-1-one (dehydromuscone), 9-cycloheptadecane-1-one (cibetone), Cyclopentadecaneone, 5-cyclohexadecan-1-one, cyclohexadecanone, cyclopentadecanolide, 11 (12) -cyclopentadecenolide, 9-cyclopentadecenolide, cyclohexadecanonelide, ethylene Claimed to be one or more compounds selected from the group consisting of brushlate, ethylenedodecandioate, 12-oxahexadecanonelide, 11-oxahexadecanonelide, and 10-oxahexadecanonelide. Item 1. The sleep improving agent according to Item 1. The sleep improving agent according to claim 1 or 2, wherein the macrocyclic musk compound is an ethylene brassylate. 2,2,6-trimethylcyclohexane derivative
Ethyl 2,2,6-trimethylcyclohexanecarboxylic acid, allyl 2,2,6-trimethylcyclohexanecarboxylic acid, ethyl 2,2,6-trimethyl-4,6-cyclohexadienecarboxylic acid, 2,2,6-trimethyl- Methyl 4-cyclohexenecarboxylic acid, methyl α-cyclogerate, methyl β-cyclogerate, methyl γ-cyclogerate, ethyl α-cyclogerate, ethyl β-cyclogerate, ethyl γ-cyclogerate, and 2,2-dimethyl- A 2,2,6-trimethylcyclohexanecarboxylic acid ester derivative selected from the group consisting of ethyl 6-ethyl-5-cyclohexenecarboxylic acid;
α-Damasenone, β-Damasenone, γ-Damasenone, α-Damascon, β-Damascon, γ-Damascon, δ-Damascon, α-Yonone, β-Ionone, γ-Yonone, δ-Yonone, α-Methylyonone, β- Methyl Ionone, γ-Methyl Ionone, δ-Methyl Ionone, α-Isomethyl Ionone, β-Isomethyl Ionone, γ-Isomethyl Ionone, δ-Isomethyl Ionone, α-Iron, β-Iron, γ-Iron, δ-Iron, α-Allyl Ionone, β-Allyl Ionone, A (2,2,6-trimethylcyclohexane-1-yl) butane-2 (3) -one derivative selected from the group consisting of γ-allyl ionone and δ-allyl ionone; and α-damasenor, β-damasenor, γ-damasenor , Α-Damasconol, β-damasconol, γ-damasconol, δ-damasconol, α-yonone, β-yonone, γ-yonone, δ-yonone, α-methylyonone, β-methylyonone, γ-methylyonone, δ -Methylyonone, α-isomethylyonone, β-isomethylyonone, γ-isomethylyonone, δ-isomethylyonone, α-ironol, β-ironol, γ-ironol, δ-ironol, α-allylyonone , Β-allyl ionone, γ-allylyonone, δ-allylyonone, 2,2,6-trimethylcyclohexyl-3-hexanol, and 2,2,3,6-tetramethylcyclohexyl-3-hexanol (2) , 2,6-trimethylcyclohexane-1-yl) Butan-2 (3) -All The compound according to any one of claims 1 to 3, which is one or more compounds selected from the group consisting of all derivatives. Sleep improver. The sleep improving agent according to any one of claims 1 to 4, wherein the 2,2,6-trimethylcyclohexane derivative is ethyl 2,2,6-trimethylcyclohexanecarboxylic acid. Sleep improving effects promote smooth wake-up, reduce tension when waking up, enhance sympathetic nerves before waking up, enhance parasympathetic nerves after waking up, and increase endocrine substances after waking up. The sleep improving agent according to any one of claims 1 to 5, which is one or more sleep improving effects selected from the group consisting of the effects of promoting. A method for improving a subject's sleep, which comprises presenting the subject with the scent of the sleep improving agent according to any one of claims 1 to 6 during sleep. A sleep-improving fragrance composition containing the sleep-improving agent according to any one of claims 1 to 6. Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care products, skin care products, which contain the sleep improving agent according to any one of claims 1 to 6. Products selected from the group consisting of body care products, laundry detergents, soft finishing agents for clothing, tobacco products, quasi-drugs and pharmaceuticals. Beverages, foods, cosmetics, toiletry products, air care products, daily / miscellaneous goods, oral compositions, hair care products, skin care products, body care products, clothing containing the sleep-improving fragrance composition according to claim 8. Products selected from the group consisting of detergents for clothing, soft finishes for clothing, tobacco products, quasi-drugs and pharmaceuticals.

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