Mood improvers

Abstract

To provide a mood state improvement agent and a fatigue feeling improvement food for a healthy person, including collagen peptide.SOLUTION: A mood state improvement agent incudes as a primary component collagen peptide having an average molecular weight of 500-12,000, the collagen peptide decomposed by microorganism-derived protease. The collage peptide can, when orally administered to a healthy person who is self-aware of being liable to fall sick, improved, with statistically significant difference, fatigue-impotence (FI) evaluation and vitality-activity (VA) evaluation evaluated by POMS2.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to a mood-improving agent for healthy individuals, comprising collagen peptides. [Background technology]

[0002] Collagen is a structural protein found in skin, tendons, and cartilage. It is unique in that it contains repeating units of -(Gly-XY)n- (X and Y are any amino acids) and post-translationally modified hydroxyproline. Most collagens in vivo have a triple helix structure, consisting of three polypeptide chains with a molecular weight of approximately 100,000 bound together in a helical fashion. When degraded with enzymes, acids, or alkalis, collagen yields polypeptides with chain lengths and compositions that vary depending on the degree of degradation and the enzyme. For example, when gelatin is degraded with a protease derived from Clostridium, it produces polypeptides whose main component is -(Gly-XY)n- (X and Y are any amino acids), whereas when gelatin is degraded with an enzyme derived from ginger rhizome, it produces a peptide composition represented by the formula X-Hyp-Gly (X is any amino acid residue other than Gly, Hyp, or Pro) (Patent Document 1).

[0003] It has been reported that oral ingestion of collagen peptides decomposed with an enzyme derived from ginger rhizomes releases Pro-Hyp into the blood, which promotes the proliferation of hippocampal cells and exerts an antidepressant-like effect (Non-Patent Document 1).

[0004] Furthermore, with regard to collagen peptides, there have been reports of DPP-4 inhibitors (Patent Document 2), immunostimulators (Patent Document 3), bone formation promoters (Patent Document 4), angiotensin-converting enzyme inhibitors (Patent Document 5), and the like.

[0005] On the other hand, it is known that excessive work can cause various health problems, and the Ministry of Health, Labor and Welfare has set up a website where workers can self-check their accumulated fatigue levels (Non-Patent Document 2). Early detection of physical and mental fatigue can avoid overwork, prevent lifestyle-related diseases and depression, and improve quality of life. There are compositions for improving, maintaining, and / or improving attention function, whose active ingredient is an enzymatic hydrolysate of whey protein containing peptides with specific amino acid sequences (Patent Document 6), and foods for improving poor health that contain scallop mantle extract, improve vitality, suppress depression, and relieve fatigue (Patent Document 7). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 6075656 [Patent Document 2] International Publication No. 2013 / 065832 [Patent Document 3] International Publication No. 2016 / 076276 [Patent Document 4] Patent No. 6860877 [Patent Document 5] Patent No. 7048270 [Patent Document 6] Patent No. 7011984 [Patent Document 7] Patent No. 7105456 [Non-patent literature]

[0007] [Non-Patent Document 1] “Prolyl-hydroxyproline, a collagen-derived dipeptide, enhances hippocampal cell proliferation, which leads to antidepressant-like effects in mice”, The FASEB Journal 34 (4), 5715-5723, 2020-03 Wiley [Non-patent document 2] https: / / kokoro.mhlw.go.jp / fatigue-check / worker.html Summary of the Invention [Problem to be solved by the invention]

[0008] As mentioned above, there are various reports on the efficacy of collagen peptides. Non-Patent Document 1 reports antidepressant effects, but the relationship between collagen peptides and the improvement of mental fatigue and poor physical condition described in Patent Documents 6 and 7 is unclear. Even healthy individuals with no brain function problems can experience depression, not just those with dementia or depression. For example, fatigue can have both mental and physical causes, and mental fatigue manifests as somnolence (drowsiness) and lethargy. If collagen peptides derived from biological components could prevent or improve mental fatigue, they would be safe, maintain and improve work efficiency, and improve the quality of life of individuals by improving mood.

[0009] In view of the above-mentioned current situation, the present disclosure aims to provide an agent for improving the mood state of healthy people, a food product for improving fatigue in healthy people, etc., which contains collagen peptides. [Means for solving the problem]

[0010] The present inventors administered collagen peptides degraded with microbial proteases to healthy individuals who are prone to illness for eight weeks, and evaluated their mood states using POMS2 (Profile of Mood States 2nd Edition) (trademark). They found that the fatigue-lethargy (FI) and vigor-vitality (VA) scores improved with statistical significance compared to the placebo group, and thus completed the present disclosure.

[0011] That is, the present disclosure: One or more selected from the group consisting of the genus Rhizopus, the genus Aspergillus, the genus Bacillus, and the genus Streptomyces Average molecular weight of protease-degraded 2,000~8,000 Collagen peptides consisting only of , healthy people Fatigue-lethargy assessed by POMS2The present invention provides an agent for improving the above.

[0012] moreover, One or more selected from the group consisting of the genus Rhizopus, the genus Aspergillus, the genus Bacillus, and the genus Streptomyces Average molecular weight of protease-degraded 2,000~8,000 Collagen peptides consisting only of , healthy people Vitality-energy improver as assessed by POMS2 This provides: [Effects of the Invention]

[0014] According to the present disclosure One or more selected from the group consisting of the genus Rhizopus, the genus Aspergillus, the genus Bacillus, and the genus Streptomyces Average molecular weight of protease-degraded 2,000~8,000 Collagen peptides consisting only of , healthy people Improves fatigue, lethargy, vitality, and energy assessed by POMS2 is provided. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present disclosure provides: One or more selected from the group consisting of the genus Rhizopus, the genus Aspergillus, the genus Bacillus, and the genus Streptomyces Average molecular weight of protease-degraded 2,000~8,000 Collagen peptides consisting only of , healthy people Improves fatigue, lethargy, vitality, and energy assessed by POMS2 The present disclosure will be described in detail below.

[0016] The average molecular weight of the collagen peptide used in this disclosure is 500 to 12,000, preferably 1,000 to 10,000, more preferably 2,000 to 8,000, and particularly preferably 4,000 to 8,000. The average molecular weight refers to the weight-average molecular weight. Collagen has a "collagen-like sequence" represented by -(Gly-XY)n- (X and Y represent amino acids). It can be hydrolyzed with acid or alkali, or degraded with proteases derived from microorganisms such as Rhizopus, Aspergillus, Bacillus, and Streptomyces, as well as plant-derived proteases such as ginger rhizome enzyme. The peptide composition produced varies depending on the protease used. For example, Clostridium bacteria can produce collagen peptides primarily composed of the -(Gly-XY)n- (X and Y represent amino acids) sequence with an N-terminus of glycine by using an enzyme specific for cleaving between Y and Gly. On the other hand, when hydrolyzed with an enzyme derived from ginger rhizome, peptide compositions can be obtained, such as X-Hyp-Gly, X-Pro-Gly, or Gly-Pro-X (where X is an amino acid residue other than Gly, Hyp, or Pro), where the second amino acid residue from the C-terminus is Pro or Hyp. The collagen peptides used in this disclosure have been hydrolyzed with a microbial protease to achieve the above average molecular weight. Some low-molecular-weight collagen peptides are digestion-resistant and exhibit physiological activity when taken orally. As described in Non-Patent Document 1, when ginger rhizome-derived enzyme hydrolyzates are ingested, Pro-Hyp is present in the blood, which affects brain function and exerts antidepressant effects. We then compared the blood Pro-Hyp concentrations of humans who ingested 5 g of ginger rhizome-derived enzyme hydrolysate and microbial protease hydrolysate. 30 minutes after ingestion, the values ​​were 8.1±5.4 nmol / ml for the ginger rhizome-derived enzyme hydrolysate and 4.6±3.0 nmol / ml for the microbial protease hydrolysate, with a statistically significant difference (p<0.05) between the two. The Area Under the Curve (AUC) values ​​up to 6 hours after ingestion were also statistically significant (p<0.05) between the microbial protease hydrolysate and the ginger rhizome-derived enzyme hydrolysate.However, as shown in the examples below, it has been found that the above collagen peptides, which have been decomposed with microbial proteases, can improve the mood state, as assessed by the internationally used POMS2 (trademark), of healthy individuals who are prone to fatigue and illness, thereby reducing fatigue and improving vitality and energy.

[0017] The collagen peptide used in the present disclosure may be derived from any animal species, including fish such as tilapia, sea bream, and salmon, birds, pigs, cattle, and others, and may be extracted from any tissue such as fish scales, dermis, tendons, and bones. Preferably, it is derived from fish scales, pigs, cattle, or birds. While types I to XXVIII of collagen are known, any type may be used. Type I collagen is preferred. The isoelectric point of the collagen peptide varies depending on the production method, but in the present disclosure, the isoelectric point is preferably 7.0 to 9.5, more preferably 7.5 to 8.5.

[0018] In the present disclosure, "healthy individuals" refers to individuals who are free from illness or disease and are physically and mentally healthy. Additionally, "mood state improvers" refers to agents that reduce fatigue and improve motivation and vitality.

[0019] The mood improvers, fatigue-relieving foods for healthy individuals, and foods for improving and maintaining a positive mood for healthy individuals disclosed herein may contain flavorings, excipients, thickeners, sweeteners, plant extracts, and vitamins, provided that their effects are not impaired. Furthermore, the dosage form may be powder, granules, pills, capsules, tablets, liquids, suspensions, or any other form, provided that the stability of the collagen peptides is ensured. In the case of powders or granules, they are preferably soluble in water or hot water and do not gel when cooled.

[0020] In this disclosure, food refers to an edible state that can be directly used for consumption by animals, including humans. Therefore, the food may be the above-mentioned food as it is, or may be a food simply converted into a powder, granule, pellet, or other form. It may also be a liquid or jelly-like beverage obtained by adding water to the above-mentioned food and, if necessary, a thickener or flavoring agent, or a jelly obtained by solidifying the above-mentioned food with agar or gelatin.

[0021] The method of administration of the food for improving fatigue in healthy people and the food for improving and maintaining a positive mood in healthy people disclosed herein may be oral administration or tube administration. In this disclosure, "food" includes nutritional supplements such as supplements; nasal, enteral, and other tube-based nutritional preparations. When used as a food, there are no particular limitations on the other ingredients added to the food, provided that they are suitable for use as a food. Water, proteins, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, etc. may be blended as ingredients.

[0022] Examples of nutritional supplements include the above foods as they are, or the above food compositions processed into powder, granules, pellets, etc., and liquid or jelly-like products obtained by adding water or a thickener to the above foods.The above food compositions may also be added to any of the conventionally known supplements.

[0023] The intake amount, converted into the amount of collagen peptide, is 0.1 to 30 g per day, more preferably 2 to 10 g. Hydroxyproline is an amino acid characteristic of collagen, and when calculating the collagen peptide content, the amount of collagen peptide can be roughly calculated based on the amount of hydroxyproline. It may be taken in multiple divided doses per day.

[0024] The mood improver, food for improving fatigue in healthy people, and food for improving and maintaining a positive mood in healthy people disclosed herein may be taken before or after meals, between meals, or at any time, and may be mixed into food ingredients and cooked, and the cooked ingredients may be ingested, or sprinkled on cooked food ingredients and ingested.

[0025] The disclosed improving agents, fatigue-reducing foods for healthy individuals, and foods for improving and maintaining a positive mood for healthy individuals can maintain a healthy mood when administered to healthy individuals. They are also useful for individuals who experience mental fatigue due to pressure, lethargy, or other mental fatigue, as well as healthy individuals who are prone to illness. Mental fatigue manifests as drowsiness, lethargy, etc. Preventing or improving mental fatigue can improve mood and enhance the quality of daily life. [Example]

[0026] The present disclosure will now be described in detail with reference to examples, but these examples are not intended to limit the present disclosure in any way.

[0027] Example 1 Evaluation was conducted in a randomized, placebo-controlled, double-blind, parallel-group comparative study using the Japanese version of POMS2, commissioned to Ortho Medico Co., Ltd. In addition to the 65 questions in POMS2, an original questionnaire using the Likert scale method and a diary-based physical condition questionnaire were also added.

[0028] The subjects for this experiment were healthy individuals aged 20 or over who were prone to fatigue and illness. Participants were selected from those with relatively high levels of fatigue-lethargy (FI) at screening. The subjects for analysis consisted of 31 individuals in each of the test food group and placebo group, who were divided into two groups to avoid significant differences in age, gender, height, and IgE levels. Analysis was performed using PPS (Per Protocol Analysis Set) and FAS (Full Analysis Set).

[0029] The subjects were: (i) those currently undergoing treatment for or with a history of malignant tumors, heart failure, or myocardial infarction; (ii) those with a pacemaker or implantable cardioverter defibrillator; (iii) those undergoing treatment for arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, dyslipidemia, hypertension, or other chronic diseases; (iv) those who regularly consume foods for specified health uses, foods with functional claims, or other foods / drinks that are thought to have functional properties; (v) those who eat foods high in lactic acid bacteria, such as lactic acid bacteria drinks and fermented foods, two or more days a week; and (vi) those who consume foods high in collagen / gelatin (beef tendon, liver, offal / hormones, pig's feet, chicken thighs, chicken wings / skin, chicken cartilage, fish, etc.). The following were excluded from the study: (i) those who eat seafood (fish skin, conger eel, eel, monkfish, jelly, collagen hotpot, gelatin, gummy candy, marshmallows, etc.) two or more days a week; (vii) those who regularly take medicines (including herbal medicines) or supplements; (viii) those with allergies (to medicines or foods related to the test food), especially those who are allergic to fish, collagen, or gelatin; (ix) those who suffer from hay fever; (x) those who have received a vaccine for influenza or other infectious diseases within the year prior to the date of obtaining the consent form; (xi) those who are currently smoking or have stopped smoking within the year prior to the date of obtaining the consent form; and (xii) those who are pregnant, breastfeeding, or intending to become pregnant during the study period.

[0030] The test drug used in the test food group was collagen peptide granules (trade name "FCP-AG", derived from tilapia type I collagen, digested with microbial food-grade proteases (derived from Rhizopus, Aspergillus, Bacillus, and Streptomyces), average molecular weight 4,000-8,000), and the placebo used in the placebo group was dextrin powder. Both groups took 5g twice a day (after breakfast and dinner) dissolved in about half a glass of water or warm water. The intake period was 8 weeks.

[0031] Participants were asked to answer 65 questions from the POMS2 at screening, before the start of intake, and after 4 and 8 weeks of intake. Responses were calculated for each item using seven scales: Tension-Anxiety (TA), Depression-Dejection (DD), Anger-Hostility (AH), Vigor-Activity (VA), Fatigue-Inertia (FI), Confusion-Bewilderment (CB), and Friendliness (F), and were evaluated using a Total Mood Disturbance (TMD) score.

[0032] Measurement values ​​at each time point were compared between groups at each time point using a linear mixed model with the screening value as the baseline value, covariates, time point, group, interaction between time point and group, interaction between baseline value and time point, and study participant as factors.

[0033] The results of POMS2 were as follows: (1) The actual measured values ​​of fatigue and lethargy (FI) are shown in the table below. The test food group reduced FI values ​​over time, but after 8 weeks of intake, the FI values ​​were reduced more than the placebo group with a statistically significant difference (P=0.045).

[0034] [Table 1]

[0035] (2) The actual measured values ​​of fatigue and lethargy (FI) are shown in the table below. The test food group improved their VA values ​​over time, but after 8 weeks of intake, their VA values ​​improved more than the placebo group with a statistically significant difference (P=0.002).

[0036] [Table 2]

[0037] (3) The actual measured values ​​of POMS2, excluding FI and VA, at screening, at the start of intake, 4 weeks after intake, and 8 weeks after intake are shown below. The scores for TMD (Total Mood Disturbance), Anger-Hostility (AH), Confusion-Bewilderment (CB), Depression-Dejection (DD), and Tension-Anxiety (TA) tended to decrease over time, but no statistically significant differences were detected. Furthermore, the score for Friendliness (F) fluctuated, and no statistically significant differences were detected.

[0038] [Table 3]

[0039] [Table 4]

[0040] [Table 5]

[0041] [Table 6]

[0042] In addition, an original Likert-scale questionnaire was administered at screening, at the start of intake, and after four and eight weeks of intake. The seven questions included: 1. "Shoulder stiffness and back pain," 2. "Tend to be constipated," 3. "Tend to have diarrhea," 4. "Fatigue persists even after a night's sleep," 5. "Feel tired for no apparent reason," 6. "Skin condition is poor," and 7. "Hands tend to become rough." Participants were asked to respond on a six-point scale: 1. "Not at all applicable," 2. "Very not applicable," 3. "Not very applicable," 4. "Somewhat applicable," 5. "Very applicable," and 6. "Very applicable." The median, first quartile (Q1), and third quartile (Q3) of the measured values ​​were calculated and compared between groups using the Mann-Whitney U test. The results are shown in the table below. Eight weeks after the start of intake, a statistically significant difference (P<0.05) was detected between the placebo group and the test food group in the item "I can't get rid of fatigue even after a night's sleep."

[0043] [Table 7]

[0044] In addition, a diary-style physical condition questionnaire was conducted (1. "Feeling feverish," 2. "Runny nose," 3. "Nasal congestion," 4. "Sore throat," 5. "Cough," 6. "General fatigue," 7. "Muscle pain," 8. "Joint pain," 9. "Chills"). When the cumulative number of days each symptom occurred for each participant was compared between groups using a t-test, no statistical significance was detected for any of the symptoms.

[0045] (Summary) Looking at the results for individual items in the test food group, at the time of testing after 8 weeks of intake, the sub-items of VA, "7. Lively," "12. Positive mood," "55. Feeling good without worries," "57. Energetic," "60. Motivated," and "62. Active," showed significantly higher scores compared to the placebo group, while the sub-items of FI, "45. Tired" and "59. Exhausted," showed significantly lower scores compared to the placebo group. Furthermore, in the original questionnaire, the test food group showed significantly lower scores for "Fatigue doesn't go away even after a night's sleep" at the time of testing after 8 weeks of intake compared to the placebo group. These results suggest that ingestion of the test food reduced mood states related to fatigue and lethargy, and enhanced mood states related to vitality and energy, as well as fatigue recovery through sleep, thereby reducing subjective fatigue and the occurrence of cold symptoms.

[0046] The present disclosure allows various embodiments and modifications without departing from the broad spirit and scope of the present disclosure. Furthermore, the above-described embodiments are intended to illustrate the present disclosure and do not limit the scope of the present disclosure. That is, the scope of the present disclosure is defined by the claims, not the embodiments. Various modifications made within the scope of the claims and the meaning of equivalent disclosures are considered to be within the scope of the present disclosure.

Claims

1. An agent for improving fatigue and lethargy as assessed by POMS2 in healthy individuals, which consists solely of collagen peptides with an average molecular weight of 2,000 to 8,000 that have been degraded with one or more proteases selected from the group consisting of Rhizopus, Aspergillus, Bacillus, and Streptomyces.

2. An agent for improving vitality and vitality as assessed by POMS2 in healthy individuals, which consists solely of collagen peptides with an average molecular weight of 2,000 to 8,000 that have been degraded with one or more proteases selected from the group consisting of Rhizopus, Aspergillus, Bacillus, and Streptomyces.

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