JP7811272B2 - Motivation-increasing composition - Google Patents

Description

The present invention relates to a composition for increasing motivation, etc.

People may experience days in a row of feeling unmotivated due to factors such as aging, sleep status, and mental state. Lack of motivation can lead to a decline in concentration and negative thinking. Research and development aimed at improving this situation is described in Patent Document 1. Furthermore, apart from or in conjunction with a lack of motivation, people may also experience difficulty waking up.

Japanese Patent Application Laid-Open No. 2022-097984 Japanese Patent Application Laid-Open No. 2006-096715

Tanaka H, Shirakawa S: Sleep health, lifestyle and mental health in the Japanese eilderly sleep ensuring to promote a healthy brain and mind. JPsychosomatic Research. 2004;56:465-477 Maxwell C. Sensitivity and accuracy of the visual analogue scale: apsycho-physical classroom experiment. Br J Clin Pharmacol. 1978;6:15－24.

The composition described in Patent Document 1 contains an extract and/or a pulverized product of a plant of the genus Salacia. As a composition for increasing motivation, it is preferable to be able to provide more of these, so there is still room for research.
The present invention has been made in view of the above problems, and an object of the present invention is to provide a novel composition for increasing motivation and/or a novel composition for improving wakefulness upon waking up.

The present inventors have found that a composition containing a specific guar gum decomposition product has a motivation-increasing effect, and have basically completed the present invention.
Thus, the composition for increasing motivation after sleep according to the present invention is a guar gum hydrolysate having an average molecular weight of 1.0 x ¹⁰ to 2.0 x ¹⁰ , with 70% by mass or more of the components falling within this average molecular weight range, and the viscosity of a 1% by mass aqueous solution measured at 25°C and 60 rpm using a B-type viscometer is 50 mPa·s or less, and the guar gum hydrolysate is obtained by hydrolyzing and lowering the molecular weight of a galactomannan polysaccharide contained in guar-derived endosperm and having a galactose to mannose content ratio (galactose:mannose) of 1:1.3 to 1:2.1 using microbial β-mannanase, and the composition is characterized by containing at least 70% by mass of dietary fiber as determined by enzymatic HPLC.

Another invention provides a composition for improving alertness upon waking, which is a guar gum hydrolysate having an average molecular weight of 1.0 x ¹⁰ to 2.0 x ¹⁰ , with 70% by mass or more of the hydrolysate falling within this average molecular weight range, and which has a viscosity of 50 mPa·s or less in a 1% by mass aqueous solution when measured at 25°C and 60 rpm using a B-type viscometer. The guar gum hydrolysate is obtained by hydrolyzing a galactomannan polysaccharide contained in guar-derived endosperm, which has a galactose to mannose ratio (galactose:mannose) of 1:1.3 to 1:2.1, using a microbial β-mannanase to reduce the molecular weight of the polysaccharide. The composition contains at least 70% by mass of dietary fiber as determined by enzymatic HPLC.
In the above invention, the composition for increasing motivation or the composition for improving wakefulness is preferably intended for healthy individuals without sleep disorders.
The present invention provides a food, drink, or pharmaceutical product containing the motivation-increasing composition or wakefulness-improving composition of the present invention. Food and drink products include foods and beverages, such as nutritional supplements, health foods, foods for specified health uses, foods with functional claims, dietary foods, comprehensive health foods, supplements, tea drinks, coffee drinks, juices, soft drinks, energy drinks, cooked rice, bread, noodles, dairy products, processed egg products, processed seafood and livestock foods, confectioneries, oils and fats and processed foods, seasonings, and prepared dishes. Pharmaceutical products include pharmaceuticals and quasi-drugs, and are preferably oral or enteral preparations, and can be in the form of liquids, tablets, granules, pills, syrups, and the like.

The present invention provides a novel composition for increasing motivation and/or improving wakefulness upon waking.

1 is a bar graph showing the results of the PHGG sleep health risk total score. This is a bar graph showing the results of an investigation into PHGG's feeling of refreshment upon waking up. 1 is a bar graph showing the results of an investigation into PHGG's sense of fatigue upon waking. This is a bar graph showing the results of PHGG's survey on motivation for work and study. This is a bar graph showing the results of examining PHGG's vigor-vitality (VA) upon waking. 1 is a bar graph showing the results of examining PHGG's sleepiness upon waking.

Next, embodiments of the present invention will be described with reference to the drawings. However, the technical scope of the present invention is not limited to these embodiments, and can be embodied in various forms without changing the gist of the invention.
Guar gum refers to a water-soluble natural polysaccharide obtained from the endosperm (specifically, the cotyledons) of guar beans. It is a polysaccharide having two linearly linked mannose molecules and one galactose side chain, with an average molecular weight of approximately 2.0 × 10 ⁵ to 3.0 × 10 ⁵ . Guar gum is known to have physiological effects such as suppressing blood sugar elevation, lowering cholesterol, and improving bowel movements. In the present invention, guar gum hydrolyzate refers to a water-soluble dietary fiber obtained by hydrolyzing and lowering the molecular weight of the galactomannan polysaccharide contained in the endosperm of guar (scientific name: Cyanopsis tetragoloba), an annual legume plant consumed in India, Pakistan, and other countries. Methods for hydrolyzing guar gum include, but are not limited to, enzymatic hydrolysis and acid hydrolysis. However, enzymatic hydrolysis is preferred because it facilitates the adjustment of the molecular weight of the hydrolyzed product.

The enzyme used in the enzymatic hydrolysis method is not particularly limited as long as it is an enzyme that hydrolyzes linear mannose chains, but it is preferable to use β-mannanase derived from fungi such as Aspergillus or Rhizops. The upper limit of the average molecular weight distribution of the guar gum hydrolyzate is 2.0 x 10 ⁵ or less, preferably 1.0 x 10 ⁵ or less, and more preferably 2.5 x 10 ⁴ or less. The lower limit of the average molecular weight distribution of the guar gum hydrolyzate is 1.0 x 10 ² or more, preferably 2.0 x 10 ³ or more. If the average molecular weight distribution is less than 1.0 x 10 ² , it becomes difficult to fully exert the motivation-increasing activity, and if the average molecular weight exceeds 2.0 x 10 ⁵ , the viscosity becomes too high, making it difficult to incorporate it into foods and beverages. The method for measuring the molecular weight distribution is not particularly limited, but examples thereof include a method using polyethylene glycol (average molecular weights: 2×10 ² , 2×10 ³ , 2×10 ⁴ and 1×10 ⁵ ) as a molecular weight marker and gel filtration chromatography.
The guar gum decomposition product of the present invention contains 70% by mass or more, preferably 80% by mass or more, of the guar gum decomposition product within the above average molecular weight range.

Galactose is a type of monosaccharide classified as an aldohexose, with the molecular formula C ₆ H ₁₂ O ₆ and a molecular weight of 180 (both the same as glucose). The configuration is the same at the 2-position (second from the top in the Fischer projection) and 5-position -OH, with the 3- and 4-positions pointing in opposite directions; the configuration at the 5-position of D-galactose is the same as that of D-glyceraldehyde.
Mannose is a type of monosaccharide classified as an aldohexose, with the molecular formula C ₆ H ₁₂ O ₆ and a molecular weight of 180 (both the same as glucose). The configuration is such that the -OH at positions 2 and 3 face the same direction, while the -OH at positions 4 and 5 face the opposite direction, and the configuration at position 5 of D-mannose is the same as that of D-glyceraldehyde. Mannose is not metabolized much in humans, and when ingested orally, it hardly enters the glycolytic pathway.

"Motivation" is an expression that refers to the positive feelings and desire to do or accomplish things on one's own. Motivation is recognized to be brought about by dopamine secreted by the brain. It is known that motivation can be lost due to irregular lifestyle habits, accumulated fatigue, lack of sleep, etc.
The motivation-increasing composition of the present invention can be orally ingested as is or mixed with food, beverages, etc. The dosage of the motivation-increasing composition when orally ingested is not particularly limited, but is 0.5 g to 70 g (preferably 3 g to 30 g, more preferably 6 g to 18 g) per adult per day.

<Preparation of Guar Gum Degradation Product (PHGG)>
Example 1
900 g of water was adjusted to pH 4.5 with 0.1 N hydrochloric acid, and then 0.2 g of commercially available β-mannanase derived from Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 40 to 45°C for 24 hours. After the reaction, the enzyme was inactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the insoluble matter was removed. The resulting clear solution was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained. This was dried using a spray dryer (Okawahara Kakoki Co., Ltd.) to obtain 65 g of guar gum decomposition product as a powder.
The guar gum hydrolyzate was dissolved in water to obtain a 0.5% (w/v) aqueous solution. The average molecular weight was determined to be approximately 20,000 using gel filtration chromatography (column: YMC-Pack Diol-120, detector: differential refractometer) and polyethylene glycol (average molecular weights: 2 x 10 ² , 2 x 10 ³ , 2 x 10 ⁴ , and 1 x 10 ⁵ ) as a molecular weight marker. At least 80% by mass of the solution contained molecules with molecular weights of 1.0 x 10 ³ to 2.0 x 10 ⁵ .
The viscosity of a 1% by mass aqueous solution was measured at 25° C. and 60 rpm using a Brookfield viscometer and was found to be 8 mPa·s.
The ratio of galactose to mannose (galactose:mannose) was measured and found to be 1:1.7.
The dietary fiber content was measured by enzymatic HPLC and was found to be 90% by mass.

Example 2
900 g of water was adjusted to pH 3 with 0.1 N hydrochloric acid, and then 0.15 g of commercially available β-mannanase derived from Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 40 to 45°C for 24 hours. After the reaction, the enzyme was inactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the insoluble matter was removed. The resulting clear solution was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained. This was dried using a spray dryer (Okawahara Kakoki Co., Ltd.) to obtain 68 g of guar gum decomposition product as a powder.
The average molecular weight of the guar gum decomposition product was determined in the same manner as in Example 1 and was found to be approximately 2.5 x 10 ^4. The results of the HPLC chart showed that 80% by mass or more of the product had a molecular weight of 1.0 x 10 ³ to 2.0 x 10 ⁴ .
The viscosity of a 1% by mass aqueous solution was measured at 25° C. and 60 rpm using a Brookfield viscometer and was found to be 10 mPa·s.
The content ratio of galactose to mannose (galactose:mannose) was measured and found to be 1:1.8.
The dietary fiber content was measured by enzymatic HPLC and was found to be 89% by mass.

Example 3
900 g of water was adjusted to pH 4 with 0.1 N hydrochloric acid, and then 0.25 g of commercially available β-mannanase derived from Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 50 to 55°C for 12 hours. After the reaction, the enzyme was inactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the insoluble matter was removed. The resulting clear solution was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained. This was dried using a spray dryer (Okawahara Kakoki Co., Ltd.) to obtain 70 g of guar gum decomposition product as a powder.
The average molecular weight of the guar gum decomposition product was determined in the same manner as in Example 1 and was found to be approximately 1.5 x 10 ^4. The results of the HPLC chart showed that 80% by mass or more of the product had a molecular weight of 1.0 x 10 ³ to 2.0 x 10 ⁵ .
The viscosity of a 1% by mass aqueous solution was measured at 25° C. and 60 rpm using a Brookfield viscometer and was found to be 9 mPa·s.
The ratio of galactose to mannose (galactose:mannose) was measured and found to be 1:2.0.
The dietary fiber content was measured by enzymatic HPLC and was found to be 88% by mass.

Example 4
A guar gum decomposition product was prepared according to the description in the Examples of JP-A-5-117156 (page 4, line 3 to page 4, line 10 ⁾ . The average molecular weight was determined in accordance with Example 1 and was found to be 5.5 x 10.

<Test Method 1>
A placebo-controlled, double-blind, randomized, parallel-group comparative study was conducted to verify the effects of PHGG on morning sensation and motivation. Sixty healthy subjects aged 30 to under 50 were divided into three groups of 20 subjects each, and were given a placebo powdered food, 3 g/day of PHGG from Example 1, or 5 g/day of PHGG daily for eight weeks.
A questionnaire survey on sleep and motivation was conducted at weeks 0, 4, and 8, and scores for the total sleep health risk score, feeling refreshed upon waking, feeling tired upon waking, and motivation for work or study were calculated.
The "total sleep health risk score (SHRI total score)" was calculated from the sum of the scores for each evaluation item of the Sleep Health Risk Index (SHRI) (Non-Patent Document 1), including Factor 1 (sleep maintenance disorders), Factor 2 (sleep-associated symptoms), Factor 3 (sleep apnea), Factor 4 (difficulty waking up), and Factor 5 (difficulty falling asleep). A higher score indicates a higher overall risk to sleep health.
Scores for feeling and motivation upon waking were calculated using a visual analog scale (VAS) (Non-Patent Document 2) ranging from 0 (worst) to 10 (best). A higher score indicates better performance.

<Test result 1>
Table 1 and Figure 1 show the total score for sleep health risk, and Table 2 and Figures 2 to 4 show the results of the VAS questionnaire regarding the feeling of refreshment upon waking, the feeling of fatigue upon waking, and motivation for work or study. Note that because there were cases of dropout in each group, data analysis was performed on 19 cases in the placebo group, 14 cases in the PHGG (3g intake group), and 17 cases in the PHGG (5g intake group).

Patent Document 2 discloses that dietary fiber has the effect of improving sleep health. According to a test in this document, cookies containing dietary fiber (gum arabic) showed an improvement in the total sleep health risk score (paragraph 0021). Based on this disclosure, the present inventors conducted tests on dietary fiber containing a specific low-molecular-weight guar gum, hoping that it would have a sleep-improving effect. However, surprisingly, no significant difference in the total sleep health risk score was observed between the placebo group and the PHGG group (both 3g and 5g) for the composition of the present invention (Table 1 and Figure 1). This forced us to abandon the use of the PHGG of the present invention for comprehensive sleep improvement.
However, when the effects of the PHGG of the present invention were examined from a different perspective, significant effects were observed. That is, significant differences were observed between the placebo group and the PHGG group in terms of the feeling of refreshment upon waking, the feeling of fatigue upon waking, and motivation for work or study (Table 2 and Figures 2 to 4). The PHGGs of Examples 2 to 4 were also examined, and similar effects were observed. Thus, it was found that specific PHGGs have not only an overall effect of improving sleep health, but also an effect of increasing motivation and/or improving alertness upon waking. What is particularly novel is that they have an effect of increasing motivation after sleep and/or improving alertness upon waking in healthy individuals without sleep disorders.

<Test Method 2>
A placebo-controlled, double-blind, randomized, parallel-group comparative study was conducted to verify the effects of PHGG on morning sleepiness, sleep onset and maintenance, dreaming, fatigue recovery, and sleep duration in healthy elderly subjects. Healthy male and female subjects aged 60 years or older were enrolled.
Of the 91 screening cases, 66 healthy individuals who did not fall under the exclusion criteria were included. Exclusion criteria included those with a history of malignant tumors or heart disease, pacemaker users, those receiving treatment for arrhythmia, liver damage, kidney damage, diabetes, dyslipidemia, or hypertension, regular users of medicines or supplements, those with allergies, those with exercise habits (more than twice a week, more than 30 minutes per session, for more than a year), those infected with COVID-19, those participating in other clinical trials within 28 days prior to obtaining consent, and others deemed inappropriate by the investigator.
66 subjects were randomly divided into two groups, one of which was the test food group (33 subjects) and the other was the placebo group (33 subjects). The test group took 5g/day of PHGG from Example 1, and the placebo group took 5g/day of the placebo powdered food every day with breakfast for 12 weeks. Note that three subjects in the test group and two subjects in the placebo group dropped out midway through the study, so data from 30 and 31 subjects, respectively, were analyzed.

Statistical analyses were performed on POMS2 and OSA-MA scores at weeks 0, 8, and 12. POMS2 is a test that can quickly assess not only relatively long-lasting emotional states but also fluctuating, transient emotions. It includes seven factors: Anger-Hostility (AH), Confusion-Bewilderment (CB), Depression-Depression (DD), Fatigue-Apathy (FI), Tension-Anxiety (TA), Vitality-Energy (VA), and Friendliness (F), as well as TMD as an indicator of overall mood state. A score below 30 corresponds to "very low," 30-39 to "low," 40-59 to "average," 0-69 to "high," and >70 to "very high." Lower scores for TMD, AH, CB, DD, FI, and TA indicate better outcomes, while higher scores for VA and F indicate better outcomes.
The OSA-MA is a test that evaluates sleepiness upon waking, sleep onset and maintenance, dreaming, fatigue recovery, and sleep duration, and was conducted at home upon waking for three days prior to the test (the day of the test, the day before, and the day before that). The average values for the three days were used as the measurement value.
Tables 3 and 4 show the POMS2 score data. No significant differences were confirmed between the groups in each POMS2 score, but the actual measured values of VA after 8 weeks of intake and the change from baseline tended to be higher in the test food group than in the placebo group (both P = 0.066), suggesting that intake of guar gum hydrolysate improves vitality and energy.

Table 5 shows the mean (Mean), standard deviation (SD), median (Med), minimum (Min), maximum (Max), intergroup difference (Δ) and standard error (SE), minimum value of the 95% confidence interval (95% CI+), maximum value of the 95% confidence interval (95% CI+), and statistical analysis results for each OSA-MA score.
OSA-MA is a psychological scale that evaluates the internal phase of sleep upon awakening, with higher scores indicating better sleepiness. Of the OSA-MA scores, the effect of guar gum hydrolysate intake was confirmed for "morning sleepiness." After 8 weeks of intake, the actual measured values and the change from baseline were significantly higher in the test food group than in the placebo group, and after 12 weeks of intake, the actual measured values and the change tended to be higher in the test food group than in the placebo group (both P = 0.096). Actual score after 8 weeks (test food group: 20.1 ± 4.4 points, placebo group: 19.6 ± 6.0 points, difference between groups: 1.8 points [0.1, 3.6], P = 0.043), change 1 after 8 weeks (test food group: 1.8 ± 3.6 points, placebo group: -0.6 ± 3.9 points, difference between groups: 1.8 points [0.1, 3.6], P = 0.043), actual score after 12 weeks (test food group: 20.0 ± 4.2 points, placebo group: 19.9 ± 6.6 points, difference between groups: 1.5 points [-0.3, 3.3], P = 0.096), change 2 after 12 weeks (test food group: 1.7 ± 3.5 points, placebo group: -0.3 ± The mean mean score for sleep was 4.1 points, mean mean score for sleep was 1.5 points [-0.3, 3.3], P = 0.096). However, no significant differences were observed between the groups for other sleep measures.
Thus, the effect of improving alertness upon waking was observed in elderly healthy people aged 60 years or older, just as in healthy people aged 30 years or older but younger than 50 years.

As described above, according to this embodiment, a novel composition for increasing motivation and/or a novel composition for improving wakefulness upon waking up can be provided.

Claims (6)

A guar gum decomposition product having an average molecular weight of 1.0 x ¹⁰ to 2.0 x ¹⁰ , with 70% by mass or more of the product being within this average molecular weight range, and having a viscosity of 50 mPa·s or less in a 1% by mass aqueous solution when measured at 25°C and 60 rpm using a Brookfield viscometer,
The guar gum decomposition product is obtained by hydrolyzing and lowering the molecular weight of a galactomannan polysaccharide contained in guar-derived endosperm, which has a galactose to mannose content ratio (galactose:mannose) in the range of 1:1.3 to 1:2.1, using a microbial β-mannanase, and is a composition for increasing motivation after sleep in healthy individuals without sleep disorders, characterized in that it contains a dietary fiber content of at least 70% by mass as determined by an enzyme-HPLC method. A guar gum decomposition product having an average molecular weight of 1.0 x ¹⁰ to 2.0 x ¹⁰ , with 70% by mass or more of the product being within this average molecular weight range, and having a viscosity of 50 mPa·s or less in a 1% by mass aqueous solution when measured at 25°C and 60 rpm using a Brookfield viscometer,
The composition for improving alertness upon waking in healthy individuals without sleep disorders is characterized in that the guar gum decomposition product is obtained by hydrolyzing and lowering the molecular weight of a galactomannan polysaccharide contained in guar-derived endosperm, which has a galactose to mannose content ratio (galactose:mannose) in the range of 1:1.3 to 1:2.1, using a microbial β-mannanase , and contains at least 70% by mass of dietary fiber as determined by an enzyme-HPLC method. A food or drink for increasing motivation, comprising the composition for increasing motivation according to claim 1 . A motivation-increasing medicine containing the motivation-increasing composition according to claim 1 . A food or drink for improving awakening, comprising the composition for improving awakening according to claim 2 . A pharmaceutical product for improving wakefulness, comprising the composition for improving wakefulness according to claim 2 .