WO2018123163A1

WO2018123163A1 - Fragrance composition having activity to improve concentration and to decrease impulsivity corresponding to each menstrual phase in female menstrual cycle

Info

Publication number: WO2018123163A1
Application number: PCT/JP2017/034205
Authority: WO
Inventors: 一之篠原; 雄一郎菊野; 裕和土居
Original assignee: 株式会社マザー＆チャイルド
Priority date: 2016-12-27
Filing date: 2017-09-22
Publication date: 2018-07-05
Also published as: JP2018104378A

Abstract

[Problem] To provide a fragrance composition which can increase concentration and control impulsivity without relying on the ingestion of caffeine or a highly stimulant food or beverage and corresponds to each menstrual phase in a female menstrual cycle. [Solution] A fragrance composition having an activity to improve concentration and to decrease impulsivity corresponding to each menstrual phase (e.g., follicular phase, luteal phase) in a female menstrual cycle, which contains, as an active ingredient, a substance selected from β-caryophyllene, methyl epijasmonate, 1,8-cineol, methyl cinnamate, linalool and limonene each of which is synthesized and β-caryophyllene, methyl epijasmonate, 1,8-cineol, methyl cinnamate, linalool and limonene each of which is isolated or purified from a naturally occurring substance, and which is administered as a fragrance or a flavoring agent in a food additive to act on the olfactory nerve through the nasal cavity or the oral cavity, respectively, so as to be delivered to the brain.

Description

[Replenishment based on Rule 26 12.10.2017] Fragrance composition with the effect of improving concentration and reducing impulsiveness corresponding to each menstrual stage in the female menstrual cycle

The present invention is administered so as to be transmitted to the brain via the olfactory nerve to improve concentration, such as continuous attention ability and selective attention ability corresponding to each menstrual stage in the female menstrual cycle, and to reduce impulsiveness. The present invention relates to a fragrance composition having an action.

In general, pay attention to important information (concentration) and take unnecessary actions / feelings in order to take action according to the purpose of the occasion, such as driving a car, studying for an examination, work (work, negotiation, etc.) It is necessary to suppress distracting ideas (impulsiveness control).
Concerning the brain mechanisms of concentration and impulsivity control, it is known that concentration and impulsivity control are mainly borne by the prefrontal cortex.
Many people drink many cups of energy drink, coffee or caffeinated soft drinks to increase their concentration. However, recently, the first domestic poisoning caused by poisoning occurred in Japan (2015/12/22 Kyodo News). In the United States, more than 30 deaths suspected of being caused by energy drinks have been reported so far, and after taking energy drinks, some patients were brought into the emergency room of a medical facility due to symptoms such as a heart attack or arrhythmia. In 2011 alone, there are about 20,700 people.
Thus, in order to increase concentration, caffeine has been ingested in the past, but in recent years, the danger of excessive intake of caffeine has been reported.

For controlling concentration and impulsivity by methods other than caffeine intake, by orally ingesting a composition containing one or both of the pepper extract and ginger extract of Patent Document 1 and theanine, It is disclosed that drowsiness is suppressed, concentration is enhanced, and that these actions can last for a long time.
Further, Patent Document 2 discloses a composition that is a food and drink material but has a novel combination and has a concentration-improving effect and a relaxation-inducing action.

JP 2013-180960 A JP 2013-159573 A

Since the above-mentioned Patent Document 1 uses a pepper extract and a ginger extract, there is a concern about the adverse effect on the digestive system, and Patent Document 2 has the same problem.
In order to avoid excessive intake of caffeine, the present invention is not limited to caffeine intake and is not food or drink with strong irritation, in particular, continuous attention ability and selective attention ability corresponding to each menstrual stage in the female menstrual cycle. Aroma composition that controls the impulsivity by administering it so that the concentration can be improved by reducing the impulsiveness and improving the concentrating power, etc., and transmitted from the nasal cavity or oral cavity to the brain via the olfactory nerve The purpose is to provide.

As a result of intensive studies to solve the above problems, the present inventor has found that the invention of claim 1 is synthesized β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene Or a composition containing a substance selected from β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene isolated from natural products as an active ingredient In particular, it has been found that, for each menstrual stage in the female menstrual cycle, when administered so as to act on the olfactory nerve and be transmitted to the brain, it has the effect of improving concentration and reducing impulsiveness.
The invention of claim 2 is a fragrance composition having an effect of improving concentration and reducing impulsivity corresponding to each menstrual stage in the menstrual cycle according to claim 1, wherein the methyl epijasmonate is Cis jasmon, jasmine It is characterized by using at least one of lactone, jasmine aldehyde, methyl jasmonate and derivatives thereof.
According to a third aspect of the present invention, there is provided an aromatic composition having an effect of improving concentration and reducing impulsiveness corresponding to the follicular stage in the menstrual stage according to the first aspect, wherein the synthesized β-caryophyllene, epijasmon It is characterized by being methyl acid, linalool, or β-caryophyllene isolated from natural products, methyl epijasmonate, and linalool.
The invention of claim 4 is characterized in that the fragrance composition having the effect of improving concentration and reducing impulsiveness corresponding to the luteal phase in the menstrual stage according to claim 1, the synthesized 1,8-cineole, It is characterized by being methyl cinnamate, limonene, or 1,8-cineole, methyl cinnamate, and limonene isolated and purified from natural products.

The synthesized β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene or natural products isolated and purified β-caryophyllene, methyl epijasmonate, 1,8 -A composition containing, as an active ingredient, a substance selected from cineole, methyl cinnamate, linalool, limonene is applied to the olfactory nerve through the nasal cavity as an incense or through the oral cavity as a food additive to women. When administered so that it acts and is transmitted to the brain, it has the effect of improving the concentration of continuous attention ability, selective attention ability and impulsiveness, so it occurs with the reduction of concentration and impulsiveness control, especially, Reduction of follicular and late luteal phase traffic accidents in women's menstrual stage, improvement of concentration during work and study, caffeine overdose and smoking for those purposes The effect of relieving the addiction of can be expected.
In particular, synthesized β-caryophyllene, methyl epijasmonate, linalool, or β-caryophyllene, methyl epijasmonate, linalool isolated and purified from natural products are effective in the follicular phase of the female menstrual stage. Demonstrate.
Synthetic 1,8-cineole, methyl cinnamate, limonene, or 1,8-cineole, methyl cinnamate, and limonene isolated and purified from natural products are also in the luteal phase of women's menstrual stages. Demonstrate the effect.

Attention is made by scenting only a solution of β-caryophyllene (β-Caryophyllene) in a solvent (dipropylene glycol) and a solvent in female subjects in the follicular phase, female subjects in the luteal phase, and male subjects. Figure of graph of experiment result that verified "concentration ability (sustainable attention ability)" by Network Test (hereinafter, ANT), For female subjects in the follicular phase, female subjects in the luteal phase, and male subjects, stop Signal Task (hereinafter referred to as `` Smell '') with the solution of methyl epijasmonate (Methyl Epi-Jasmonate) in the solvent and the solvent alone. , SST) is a graph of the experimental results verifying the “impulsiveness”, For female subjects in the follicular phase and female subjects in the luteal phase, we verified the concentration (selective attention ability) by ANT by sniffing the solution of linalool (Linalool) of the example in the solvent and only the solvent. Graph of the experimental results For female subjects in the follicular phase, female subjects in the luteal phase, and male subjects, sniff the solution of 1,8-cineole (1,8-Cineole) in Example and the solvent alone, Fig. 4 (b) is a graph of similar experimental results for 10 adult males. Fig. 4 (b) is a graph of similar experimental results for 10 adult men. For female subjects in the follicular phase, female subjects in the luteal phase, and male subjects, the “impulsiveness” by SST was verified by sniffing the solution of the methyl cinnamate solution of the example and the solvent alone. Graph of the experimental results For female subjects in the follicular phase, female subjects in the luteal phase, and male subjects, the solution of methyl cinnamate (Methyl だけ Cinnamate) in the example and only the solvent were sniffed, and ANT concentration by the ANT Figure of graph of experiment result that verified "attention ability)" For female subjects in the follicular phase, female subjects in the luteal phase, and male subjects, the selective abilities (Conflicting Score) were obtained by smelling the solution of the methyl cinnamate solution of the example in the solvent and only the solvent. ) For female subjects in the follicular phase and female subjects in the luteal phase, we verified the “concentration (selective attention)” by ANT by sniffing the solution of Limonene in the example and the solvent alone. It is a figure of the graph of the experimental result which was done.

The present invention will be described in detail below, but will be described according to examples.
First, women were synthesized for non-smoking women in their twenties who are healthy mentally and physically that return to the normal menstrual cycle (26th to 34th) (adult subjects are also experimental subjects as controls). β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene, or β-caryophyllene, methyl epijasmonate, 1,8 cineole, cinnamic acid isolated and purified from natural products Changes in concentration and impulsivity that occurred when smelling methyl, linalool, or limonene were examined.

1. Experimental method 1-1. Briefing session The subjects explained the contents of the experiment in advance and obtained consent, and on the day of the experiment, they gave food and stimulants (such as garlic, onion, spices, and herbs) in the morning. I tried not to eat anything from 30 minutes before the start of the experiment. In addition, female subjects were asked to describe their basal body temperature, and the ovulation day (LH surge) was confirmed using an ovulation test.
1-2. On the day of the experiment Female subjects were divided into two groups according to the menstrual cycle: follicular phase (5-10 days after menstruation started) and late corpus luteum (9-12 days after LH surge). A group of names was established. Each group of subjects included 3.0% β-caryophyllene, 100% methyl epijasmonate, 1.5% 1,8 cineole, 3.0% methyl cinnamate, 30.0% linalool, Alternatively, a behavioral task for evaluating “concentration” and “impulsiveness” was conducted by sniffing only a solvent (propylene glycol) containing 3.0% limonene or a solvent. In the experiment, air was sent at a flow rate of 2 L / min to a glass bottle containing one of the above-mentioned fragrance-containing solvents (propylene glycol: PG), and the air that came out of the funnel was 10 cm away from the subject's nose. This was done by letting go, and this was continued for 20 minutes. During the experiment, subjects took a behavioral task by sitting on a chair and breathing as usual in a relaxed state. At this time, if any abnormality was observed, the experiment was stopped on the spot and appropriate measures were taken.
The ovulation period of the menstrual stage of the female menstrual cycle was as short as 1 to 2 days, and it was difficult to acquire data, so it was excluded from this experiment because the reliability of the data was low.

[1. Verification direction: Concentration]
In order to verify “concentration”, ANT (Attention Network Test), which is a cognitive task by PC operation, was used to compare the change in concentration before and after smelling a fragrance compared with the case of PG alone (control).
The above-mentioned ANT is a verification means developed to efficiently evaluate human concentration (continuous attention ability, selective attention ability) in a short time. In the ANT, when an experimental trial is started, a gaze point is displayed for 1000 ms in the center of the background. Next, “*” is displayed as a cue stimulus. 500 ms after the cue stimulus is presented, images of five arrows are presented above or below the gazing point.
The subject's task is to answer the direction of the center arrow among the five arrows as quickly and accurately as possible using the numeric keypad buttons. Let RT (reaction time) be the time from when the arrow is displayed until the button is pressed. The central arrow is called a target stimulus, and the other four arrows are called distractor stimuli. In the experiment, a total of four types of cue stimulation conditions are presented.
First, in the No Cue condition, the cue stimulus is not displayed. Next, under the Central Cue condition, a cue stimulus is presented at the position of the gazing point, that is, at the center of the screen. In the Congruent Cue condition, the cue stimulus is presented at the position where the target stimulus is presented. That is, when the arrow is presented above the gazing point, the cue stimulus is also presented above the gazing point. Finally, in the Incongruent Cue condition, a cue stimulus is presented at a position symmetrical to the target stimulus with respect to a horizontal line crossing the center of the screen. That is, when the target stimulus is presented above the gazing point, the cue stimulus is presented at a position opposite to the target stimulus across the gazing point.
Here, the relation between the above-mentioned conditions will be described with respect to [Alerting Score] and [Selective Attention Ability (Conflicting Score)].
[Alerting Score]
The difference between RT of No Cue condition and RT of Central Cue condition was calculated. This is considered to be an indicator of sustained attention ability, and the higher the persistent attention ability, the greater the Alerting Score.
[Conflicting Score]
The difference between RT of Incongruent Cue condition and RT of Congruent Cue condition was calculated. This is considered as an index of selective attention ability, and it is considered that Conflicting Score decreases as the selective attention ability increases.

[2. Verification direction: Impulsiveness]
For verification of “impulsiveness”, the change in concentration before and after smelling a fragrance was compared with that of PG (control) using SST (Stop Signal Task) which is a cognitive task by PC operation.
The SST described above is a verification means devised for evaluating human impulsivity. In SST, when an experimental trial is started, a gaze point is displayed for 1000 ms in the center of the background. Next, a right or left arrow is displayed at the center. The experiment consists of two types of stimulation conditions, Go trial and Stop trial. In the Go trial, the challenge is to answer the direction of the arrow as quickly and accurately as possible using the numeric keypad buttons. In the Stop trial, after presenting an arrow, a stop signal is generated with a beep sound after a certain delay time. If a stop signal is presented, the subject is asked not to press any key. The delay time is initially set to 200 ms. If the reaction suppression is successful, the delay time of the next trial is increased by 50 ms. On the other hand, when the suppression fails, the delay time of the next trial is reduced by 50 ms. In this way, the delay time is changed for each trial and finally converges to the delay time accordingly. In this experiment, the value obtained by subtracting the average delay time of Stop Signal from the average reaction time of Go trial was used as an index of impulsiveness as Stop Signal Reaction Time (SSRT).
Therefore, if SSRT is shortened, the impulsiveness is considered to be lowered.

1. Experimental results 1-1 [β-Caryophyllen]
According to the ANT experimental method, 3.0% solvent (propylene glycol) or only the solvent of β-Caryophyllen is synthesized in female subjects in the follicular phase, female subjects in the luteal phase, and men. Then, the persistent attention ability (Alerting Score) is examined, and the result is shown in FIG.
The results of these experiments are the graph of FIG. FIG. 1 (a) shows an alerting score of p <0.05 (P = significant difference%) compared to control (PG) before and after sniffing β-caryophyllene of Examples in 13 follicular stage female subjects. It is considered that the ability to sustain attention has increased because of the significant difference between the two, and the results can be applied to improve concentration.
In addition, there was no significant difference in 11 female subjects in the luteal phase in FIG. 1B (ns), and there was no significant difference in 10 male subjects in FIG. 1C (ns).

1-2 [Methyl Epi-Jasmonate]
According to the SSRT experimental method, the impulsivity (SSRT) when sniffing only methyl epijasmonate and a solvent was investigated in female subjects in the follicular phase, female subjects in the luteal phase, and men, and the results are shown in FIG. I will explain. The methyl epijasmonate uses at least one of Cis jasmon, jasmine lactone, jasmine aldehyde, methyl jasmonate and derivatives thereof. In this example, a 100% solution of synthesized methyl jasmonate was used. .
[Impulse (SSRT)]
A value obtained by subtracting the average delay time of Stop Signal from the average reaction time of Go trial in SST was used as an index of impulsiveness as Stop Signal Reaction Time (SSRT). A longer SSRT means more impulsive.
The results of these experiments are the graph of FIG. Compared to the control (PG) before and after sniffing the methyl jasmonate of the example epijasmonate, Fig. 2 (a) shows the impulsiveness of 17 female subjects in the follicular phase using SSRT. However, there was a significant tendency at p <0.08, and it was considered that the impulsiveness was lowered because SSRT was shortened, and these results can be applied to improve the impulsiveness.
In addition, there was no significant difference in 14 female subjects in the luteal phase in FIG. 2B (ns), and there was no significant difference in 16 male subjects in FIG. 2C (ns).

1-3 [Linalool]
According to the ANT experiment method, linalool isolated and purified from natural products was diluted to 30.0% with a solvent for 6 female subjects in the follicular phase and 6 female subjects in the luteal phase, and only the solvent. The selective attention score (Conflicting Score) at the time of sniffing is investigated, and the result is shown in FIG.
The results of these experiments are the graphs in FIG. FIG. 3 (a) shows a significant difference of p <0.04 in 6 female subjects in the follicular stage before and after sniffing the lineol of the example of the present invention. It is thought that the selective attention ability has increased because of the decrease, and these results can be applied to improve concentration.
In addition, there was no significant difference in 6 female subjects in the luteal phase in FIG. 3B (ns).

1-4 [1,8-Cineole]
According to the ANT experiment method, selective selection of a solvent in which 1.5% of synthesized 1,8 cineol was dissolved and only the solvent was selected for female subjects in the follicular phase, female subjects in the late corpus luteum, and men. The attention ability (Conflicting Score) is examined, and the result is shown in FIG.
The results of these experiments are the graphs in FIG. Compared to the control (PG) before and after sniffing 1,8-cineole of the Example of the present invention, a significant difference in Conflicting Score was observed in 6 female subjects in the follicular stage of FIG. 4 (a). (Ns), Fig. 4 (b) In female subject 6 in the late luteal phase, p <0.07, there was a significant tendency, and the Conflicting Score decreased. It can be applied to improve concentration.
In addition, as shown in the graph of FIG.4 (c), there was no significant difference (ns) when ten male adults were objected.

1-5 [Methyl Cinnamate]
(A) (SSRT) A solvent in which 3.0% of methyl cinnamate isolated and purified from natural products is dissolved in follicular stage female subjects, luteal phase female subjects, and men according to the SSRT experimental method. And the impulsiveness when smelling only the solvent is examined, and the result is shown in FIG.
The results of these experiments are the graph of FIG. Before and after smelling the methyl cinnamate of the example of the present invention, it was verified as compared with the control (PG).
For female subject 6 in the late luteal phase in FIG. 5 (b), it was considered that the impulsiveness was reduced because SSRT was shortened with a significant difference of p <0.05. From these results, the impulsiveness was improved. It is applicable to.
However, there was no significant difference (ns) when 6 female subjects in the follicular stage of FIG. 5 (a) were targeted, and there was no significant difference when 7 male subjects of FIG. 5 (c) were targeted ( ns).

(B) (ANT) According to the above ANT experimental method, when a female subject in the follicular phase, a female subject in the luteal phase, and a male were similarly sniffed with a solvent in which methyl cinnamate was dissolved and only the solvent, The attention ability (Alerting Score) is examined, and the result is shown in FIG.
The results of these experiments are the graphs in FIG. Before and after smelling the methyl cinnamate of the example of the present invention, it was verified as compared with the control (PG).
For female subject 6 in the late corpus luteum in FIG. 6 (b), the sustained attention ability (Alerting Score) improved with a significant difference of p <0.03. From these results, the sustained attention ability (Alerting Score) was improved. Applicable to improvement.
However, there was no significant difference when 6 female subjects in the follicular stage of FIG. 6A were targeted (ns), and there was no significant difference when 7 male subjects of FIG. 6C were also targeted. (ns).

(C) For female subjects in the follicular stage, female subjects in the late corpus luteum, and men, the selective attention ability (Conflicting Score) when smelling only the solvent in which methyl cinnamate was dissolved and the solvent alone was investigated, The results will be described with reference to FIG.
The results of these experiments are shown in the graph of FIG. 7, which is compared to the control (PG) before and after sniffing the methyl cinnamate of the Example, and the follicle of FIG. 7 (a). No significant difference in Conflicting Score was observed in 6 female subjects in the period (ns), no significant difference was observed in 6 female subjects in the luteal phase (ns), and p <0.09 in 7 men. There was no significant difference.

As a result of the experiments when sniffing methyl cinnamate according to (A), (B) and (C) above, for female subjects in the late luteal phase, (A) improved impulsiveness, (B) sustained attention ability It has been found that there is a possibility of application to improvement.

1-6 [Limonene]
Selection by smelling only a solvent in which 3.0% of limonene isolated and purified from a natural product for female subjects in the follicular phase and female subjects in the late corpus luteum was dissolved by the ANT experimental method. The attention ability (Conflicting Score) is examined, and the result is shown in FIG.
The results of these experiments are the graph of FIG. Before and after sniffing the limonene of the example, compared with the control (PG), in FIG. 8A, no significant difference in Conflicting Score was observed for 6 female subjects in the follicular stage (ns). However, for female subject 6 in the luteal phase in Fig. 8 (b), it was thought that the selective attention ability increased because Conflicting Score decreased with a significant difference of p <0.02, and these results were concentrated. It can be applied to improve power.

As explained above, according to the embodiments of the present invention, in particular, synthesized β-caryophyllene, methyl epijasmonate, 1, corresponding to each menstrual stage in the menstrual cycle such as female follicular phase and late corpus luteum, Effective substances selected from 8-cineole, methyl cinnamate, linalool, limonene or β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene isolated from natural products Since the composition contained as an ingredient acts on the olfactory nerve via the nasal cavity and oral cavity, and is administered to be transmitted to the brain, it is a fragrance composition that has the effect of improving concentration and reducing impulsiveness, Women's menstrual steps that occur due to reduced concentration and impulsiveness control due to continuous attention ability and selective attention ability corresponding to each menstrual stage in the menstrual cycle Caffeine overdose and smoking preferences to reduce traffic accidents, improve concentration during work and study, reduce traffic accidents, and improve concentration during work and study Can be expected to alleviate

In particular, synthesized β-caryophyllene, methyl epijasmonate, linalool, or β-caryophyllene, methyl epijasmonate, linalool isolated and purified from natural products are effective in the follicular phase of the female menstrual stage. Demonstrate.
Synthetic 1,8-cineole, methyl cinnamate, limonene, or 1,8-cineole, methyl cinnamate, and limonene isolated and purified from natural products are also in the luteal phase of women's menstrual stages. Demonstrate the effect.

It should be noted that the present invention is not limited to the above examples as long as the characteristics of the present invention are not impaired. For example, in the examples, the fragrance composition of the present invention dissolves the target fragrance composition. However, in addition to sniffing through the nasal cavity, it can be applied to the olfactory nerve via the oral cavity as a food additive. Of course, it may be transmitted.

Claims

Synthesized β-caryophyllene, methyl epijasmonate, 1,8-cineole, methyl cinnamate, linalool, limonene, or β-caryophyllene, methyl epijasmonate, 1,8- Corresponding to each menstrual stage in the female menstrual cycle, which contains a substance selected from cineol, methyl cinnamate, linalool, limonene as an active ingredient and is administered so as to be transmitted to the brain via the olfactory nerve A fragrance composition having an effect of improving concentration and reducing impulsiveness.
2. The concentration corresponding to each menstrual stage in the female menstrual cycle according to claim 1, wherein the methyl epijasmonate uses at least one of Cis jasmon, jasmine lactone, jasmine aldehyde, methyl jasmonate and derivatives thereof. A fragrance composition for women having the effect of improving strength and reducing impulsiveness.
2. The synthesized β-caryophyllene, methyl epijasmonate, linalool, or β-caryophyllene, methyl epijasmonate, linalool isolated and purified from a natural product is a follicle of the menstrual stage according to claim 1. A fragrance composition having an effect of improving concentration and reducing impulsiveness corresponding to the season.
2. The female menstrual stage according to claim 1, wherein the synthesized 1,8-cineole, methyl cinnamate, limonene, or 1,8-cineole, methyl cinnamate, limonene isolated and purified from a natural product is Among these, the composition for fragrance which has the effect | action of the concentration improvement corresponding to the luteal phase, and the impulsiveness fall.