Composition for improving mental health conditions and composition for improving decrease in activity level

Abstract

The present invention provides a composition for improving mental health conditions, a composition for improving motivation for activity, and a composition for improving decrease in activity level, each containing N-lactoylphenylalanine as an active ingredient.

Description

Composition for improving mental health status and composition for improving reduced activity level

[0001] The present invention relates to a composition for improving mental health status having N-lactylphenylalanine as an active ingredient, more specifically, a composition for improving or enhancing activity motivation, or a composition for improving reduced activity level due to aging. Further, the present invention relates to a method for improving mental health status or improving reduced activity level due to aging by administering N-lactylphenylalanine as an active ingredient.

[0002] N-lactylphenylalanine is a compound having a structure in which the amino group of phenylalanine and the carboxyl group of lactic acid are covalently bonded, having a structure represented by the following formula (1). N-lactylphenylalanine has previously been proposed for use as a component of a flavor added to foods (Patent Document 1). In recent years, however, it has been found that N-lactylphenylalanine is produced in the body during exercise in humans and other animals and has effects such as suppressing food intake and anti-obesity effects, and its use for treating metabolic diseases and the like has been proposed (Patent Documents 2 and 3).

[0003] International Publication No. 1997 / 004667 International Publication No. 2022 / 235557 US Patent Application Publication No. 2024 / 0122884

[0004] However, regarding the physiological effects of N-lactylphenylalanine to date, specific verification has not been sufficient for those other than the known food intake suppression effect and anti-obesity effect. Further, since N-lactylphenylalanine is decomposed in the digestive tract when orally administered, it is considered unsuitable for oral administration (Patent Document 3). In previous studies, sufficient examination has not been made on the physiological effects on living bodies, such as administration by injection. In particular, the action effects by oral administration have hardly been examined. Therefore, verification of new action effects of N-lactylphenylalanine, particularly new action effects by oral administration, is required.

[0005] The inventors of the present invention, in light of these problems, conducted diligent studies and, as a result, discovered new effects and efficacy of N-lactoylphenylalanine, leading to the present invention. That is, this application provides the following: [1] A composition for improving mental health, comprising N-lactoylphenylalanine as an active ingredient. [2] The composition according to 1, wherein the improvement of mental health is an improvement or enhancement of motivation for activity. [3] The composition according to 2, wherein the improvement of mental health is an improvement or enhancement of motivation for activity under a state of decreased activity due to aging. [4] A composition for improving decreased activity, comprising N-lactoylphenylalanine as an active ingredient. [5] The composition according to 4, wherein the decreased activity is a decrease in activity due to aging. [6] The composition according to either 4 or 5, wherein the improvement of decreased activity is an improvement or enhancement of motivation for activity. [7] The composition according to any one of 1 to 6, wherein the composition is for oral administration. [8] The composition according to any one of 1 to 6, wherein the composition is a food composition or a pharmaceutical composition. [9] A method for improving mental health, comprising administering N-lactoylphenylalanine as an active ingredient.

[10] The method according to 9, wherein the improvement in mental health is an improvement or enhancement of motivation to be active.

[11] The method according to 10, wherein the improvement in mental health is an improvement or enhancement of motivation to be active in a state of decreased activity due to aging.

[12] A method for improving decreased activity, comprising administering N-lactoylphenylalanine as an active ingredient.

[13] The method according to 12, wherein the decreased activity is a decrease in activity due to aging.

[14] The method according to either 12 or 13, wherein the improvement in decreased activity is an improvement or enhancement of motivation to be active.

[15] The method according to any one of 9 to 14, wherein the administration is oral administration.

[16] Foods for Specified Health Uses (including conditionally designated Foods for Specified Health Uses), Foods with Function Claims, Foods with Nutrient Function Claims, Foods for Special Dietary Uses, Nutritional Supplements, Rehabilitation Nutritional Foods, Health Supplements, or Oral Supplements containing N-lactoylphenylalanine as an active ingredient.

[17] Oral Pharmaceuticals containing N-lactoylphenylalanine as an active ingredient.[A1] The use of N-lactoylphenylalanine as an active ingredient in the manufacture of a composition for improving mental health. [A2] The use according to A1, wherein the improvement of mental health is an improvement or enhancement of motivation to be active. [A3] The use according to A2, wherein the improvement of mental health is an improvement or enhancement of motivation to be active under conditions of decreased activity due to aging. [A4] The use of N-lactoylphenylalanine as an active ingredient in the manufacture of a composition for improving decreased activity levels. [A5] The use according to A4, wherein the decreased activity is a decrease in activity due to aging. [A6] The use according to either A4 or A5, wherein the improvement of decreased activity is an improvement or enhancement of motivation to be active. [A7] The use according to any one of A1 to A6, wherein the composition is a composition for oral administration. [A8] The use according to any one of A1 to A6, wherein the composition is a food composition or a pharmaceutical composition. [B1] The use of N-lactoylphenylalanine or a composition containing it as an active ingredient for improving mental health or for non-therapeutic purposes. [B2] The use or non-therapeutic use described in B1, wherein the improvement in mental health is an improvement or enhancement of motivation to be active. [B3] The use or non-therapeutic use described in B2, wherein the improvement in mental health is an improvement or enhancement of motivation to be active in a state of reduced activity due to aging. [B4] The use or non-therapeutic use of N-lactoylphenylalanine or a composition containing it as an active ingredient for the improvement of reduced activity. [B5] The use or non-therapeutic use described in B4, wherein the reduced activity is a decrease in activity due to aging. [B6] The use or non-therapeutic use described in either B4 or B5, wherein the improvement of reduced activity is an improvement or enhancement of motivation to be active. [B7] The use or non-therapeutic use described in any one of B1 to B6, wherein the use of a composition containing N-lactoylphenylalanine as an active ingredient is a composition for oral administration. [B8] Use of a composition comprising N-lactoylphenylalanine as an active ingredient, wherein the composition is a food composition or a pharmaceutical composition, as described in any one of B1 to B6 or as a non-therapeutic use.[C1] A composition containing N-lactoylphenylalanine as an active ingredient, used for improving mental health. [C2] The composition according to C1, wherein the improvement in mental health is an improvement or enhancement of motivation to be active. [C3] The composition according to C2, wherein the improvement in mental health is an improvement or enhancement of motivation to be active in a state of decreased activity due to aging. [C4] A composition containing N-lactoylphenylalanine as an active ingredient, used for improving decreased activity levels. [C5] The composition according to C4, wherein the decreased activity level is a decrease in activity due to aging. [C6] The composition according to either C4 or C5, wherein the improvement in decreased activity levels is an improvement or enhancement of motivation to be active. [C7] The composition according to any one of C1 to C6, used as a composition for oral administration. [C8] The composition according to any one of C1 to C6, wherein the composition is a food composition or a pharmaceutical composition. [D1] Use of N-lactoylphenylalanine as an active ingredient in a composition for improving mental health. [D2] The use described in D1, wherein the improvement in mental health is an improvement or enhancement of motivation to be active. [D3] The use described in D2, wherein the improvement in mental health is an improvement or enhancement of motivation to be active in a state of reduced activity due to aging. [D4] The use of N-lactoylphenylalanine as an active ingredient in a composition for improving reduced activity levels. [D5] The use described in D4, wherein the reduced activity is a decrease in activity due to aging. [D6] The use described in either D4 or D5, wherein the improvement in reduced activity levels is an improvement or enhancement of motivation to be active. [D7] The use described in any one of D1 to D6, wherein the composition is a composition for oral administration. [D8] The use described in any one of D1 to D6, wherein the composition is a food composition or a pharmaceutical composition.

[0006] Administering a composition containing N-lactoylphenylalanine as the active ingredient can improve mental health. Furthermore, it can improve age-related decline in activity levels and enhance motivation, offering potential benefits in the treatment and prevention of various physical and mental illnesses.

[0007] This graph shows the average number of activities for each group at each time point during the rest period in the example study. This graph also shows the average number of activities for each group at each time point during the active period in the example study.

[0008] (First and Second Compositions) The first composition of this embodiment is a composition for improving mental health, comprising N-lactoylphenylalanine as an active ingredient. Furthermore, the second composition of this embodiment is a composition for improving age-related decline in activity levels, comprising N-lactoylphenylalanine as an active ingredient.

[0009] <Active Ingredient> [N-Lactylphenylalanine] The first and second compositions of this embodiment contain N-lactoylphenylalanine as an active ingredient. N-lactoylphenylalanine is a compound having the structure represented by formula (1) above, and may include N-lactoylphenylalanine or a pharmaceutically acceptable salt thereof, a salt acceptable as a food ingredient, and one or more pharmaceutically acceptable carriers or excipients thereof. The stereochemistry of the lactic acid residue in N-lactoylphenylalanine may be L-isomer or D-isomer, but in one embodiment, the L-isomer is preferred. Also, the stereochemistry of the phenylalanine residue may be L-isomer or D-isomer, but in one embodiment, the L-isomer is preferred.

[0010] N-lactoylphenylalanine can be produced from free amino acids by the action of lactoyltransferase of the lactobacillus species (Zhao CJ, Schieber A, Ganzle MG: Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review. Food Res Int 2016, 89(Pt 1):39-47). For example, it can be produced by fermentation by microorganisms and purified and separated from the fermented product, or fermented products containing N-lactoylphenylalanine produced by microbial fermentation (e.g., yogurt or fermented milk) can be used as is. It can also be produced by chemical synthesis, for example, by the method described in Patent Document 1.

[0011] <Uses> The first composition of this embodiment is a composition for improving mental health, in which N-lactoylphenylalanine is the active ingredient. Mental health, also known as mental well-being or mental health of the heart, is considered an important condition for living a vibrant and authentic life. Specifically, it is defined as being able to recognize and express one's own emotions (emotional health), being able to think appropriately according to the situation and solve problems realistically (intellectual health), and being able to build constructive and positive relationships with others and society (social health). This mental health state can be evaluated, for example, using the five items of the World Health Organization's (WHO) WHO-5 Mental Health Status Scale (1. Feeling cheerful and happy, 2. Feeling calm and relaxed, 3. Feeling motivated and active, 4. Feeling well-rested and refreshed). In addition, it can be evaluated using the MHC-SF-J (Geriatric Social Science, Vol. 43, No. 3, 2021.10) and the K10 scale (Journal of Industrial and Organizational Psychology, 2016, Vol. 30, No. 1, 81-8). This decline in mental health is a cause of mental and physical disorders. This decline in mental health is attributed to extrinsic factors such as stress from interpersonal relationships and social activities, and intrinsic factors such as senility, fatigue, poor physical condition (hormonal imbalances / changes, etc.), and physical disorders / diseases. The composition of this embodiment makes it possible to improve or prevent such a decline in mental health. In particular, the composition of this embodiment can be used to improve or enhance the decline in motivation (mental and psychological) to spontaneously engage in activities that consume more energy than being at rest, such as daily living activities (activities performed to carry out daily life, such as housework, work, commuting to work or school) and exercise (activities such as sports that are performed intentionally or planned with the aim of maintaining or improving physical fitness).

[0012] In other words, in this invention, "motivation to be active" refers to the feeling of actively and positively engaging in the above-mentioned activities, and "improvement of motivation to be active" refers to enhancing that feeling. Here, "improvement or enhancement of motivation to be active" in this embodiment may include bringing the motivation of a patient whose motivation to be active has decreased due to a mental illness closer to or restoring it to its pre-illness state, but preferably includes further enhancing the motivation of a person who does not have a mental illness but whose motivation to be active has decreased due to stress, etc., or a person whose motivation to be active has decreased due to physical weakness or decline caused by aging, etc., as described later, or a person who has normal motivation. Improvement of motivation to be active can be confirmed, for example, by extending or increasing the time or amount of spontaneous activity, increasing the frequency, time, intensity, duration or amount of exercise, and further by activating brain regions related to motivation.

[0013] Furthermore, the second composition of this embodiment is a composition for improving decreased activity levels, comprising N-lactoylphenylalanine as an active ingredient.

[0014] In this embodiment, "decreased activity level" includes, for example, a decrease in daily activity levels resulting from physical and mental fatigue or stress caused by recent changes in the work and living environment, or the advanced information society brought about by the development of the internet and information networks. In addition, another aspect of "decreased activity level" may include a decrease in activity levels in frail elderly individuals. This frail state in the elderly has attracted attention as a social problem, and the concept of "Frailty" has been proposed, mainly in the field of geriatrics, to describe the frail state of elderly individuals before they become dependent on care (Ferrucci L, et al. Am Geriatr Soc. 2004; 52: 625-34). Furthermore, the Japanese translation of "Frailty," "Frail," was published by the Japan Geriatrics Society in May 2014, and in this embodiment, "decreased activity level," more specifically "decreased activity level due to aging," may include "decreased activity level," an indicator that refers to the state of "frailty" that exists in the process of elderly individuals becoming dependent on care.

[0015] In response to these "decrease in activity levels," the composition of this embodiment makes it possible to improve or enhance this "decrease in activity levels." More specifically, the composition of this embodiment is a composition for improving motivation to be active or a composition for enhancing motivation to be active. For example, improvement or enhancement of motivation to be active by the composition of this embodiment leads to changes such as an increase in the frequency of exercise, an increase in the duration of exercise, or the performance of exercises that consume more energy, in other words, an increase in activity levels. Therefore, an increase in motivation to be active can be confirmed by an increase in activity levels during the time from waking up to going to bed. That is, activity levels can be measured as the total time of spontaneous activity or the total energy of spontaneous activity during the time from waking up to going to bed.

[0016] The composition of this embodiment brings about favorable mental and psychological effects on activity, and therefore, it can be expected to improve not only the frail state in the elderly but also the decline in mental health observed in old age. Furthermore, since the composition of this embodiment can increase the amount of activity, it can incidentally suppress muscle and bone deterioration and is expected to reduce the risk of needing long-term care. In particular, the composition of this embodiment exhibits an excellent effect in improving the amount of activity during the active period of daily life, that is, during the time of day when daily activities are taking place. For this reason, the composition of this embodiment can be used for the purpose of improving the amount of activity during the time of day when activities are taking place. Here, the time of day when activities are taking place is the time of day when energy consumption is relatively high, and in the case of humans, it corresponds to the time of day when daily activities are taking place from waking up to going to sleep, that is, during the daytime. For this reason, more specifically, the composition of this embodiment can be used for the purpose of increasing the amount of activity during the daytime.

[0017] <Target> The target age is not particularly limited, as it is intended for those experiencing a decline in mental health and motivation due to aging, such as fatigue and stress from daily life. The target may include, for example, newborns (within 28 days of birth); infants (under 1 year old); toddlers (1 to 6 years old); children (7 years and older, under 15 years old); adults (15 years and older); those 60 years and older; and those 65 years and older. Muscle mass begins to decline after peaking in the 20s and decreases by 1% per year after age 60, so targeting those 60 years and older is preferable. There is no upper limit, but it may be 100 years or younger, 90 years or younger, or 80 years or younger. In one aspect, the target may be middle-aged and elderly, and further, elderly. Elderly refers to those 65 years of age or older according to the WHO definition. Middle-aged refers to those 40 years and older but under 65, and further, those 45 years and older but under 65.

[0018] Furthermore, the composition of this embodiment can be used not only by individuals with a decline in mental health, individuals whose activity levels have decreased due to aging, etc., or individuals whose motivation to be active has decreased, but also by individuals with high mental health for the purpose of preventing a decline in mental health. More preferably, it is used by individuals with a decline in mental health, individuals whose activity levels have decreased, and / or individuals whose motivation to be active has decreased. When used as a food, it is preferable for individuals who do not have a mental illness but whose mental health has declined due to aging or stress, individuals whose activity levels have decreased, and / or individuals whose motivation to be active has decreased.

[0019] In one embodiment, the subject is a healthy subject. A healthy subject refers to a human or an animal other than a human, as described below, that has not been diagnosed with any disease. In another embodiment, the subject is a diseased subject. When the subject is a diseased subject, it is preferable that the above-mentioned state of "decreased activity level," "decreased motivation for activity," and "decreased mental health" are not due to symptoms of the disease.

[0020] The composition of this embodiment can be used to treat individuals with a decline in mental health, individuals with reduced activity levels, and / or individuals with reduced motivation. Furthermore, the composition of this embodiment may be used for therapeutic or non-therapeutic purposes.

[0021] (Therapeutic Uses) In this embodiment relating to therapeutic uses, treatment includes reducing the risk of onset, delaying the onset, prevention, therapy, stopping or delaying progression. Therapy includes curative therapy (therapy to remove the cause) and symptomatic therapy (therapy to improve symptoms). Actions for improvement or treatment include medical acts performed by physicians and nurses, midwives, etc., under the direction of a physician. Furthermore, prevention or reduction of the risk of onset includes recommending the intake of specific components and nutritional guidance (including nutritional guidance necessary for the recuperation of sick or injured persons, and nutritional guidance for maintaining and promoting health).

[0022] (Non-therapeutic Uses) In this embodiment relating to non-therapeutic uses, "treatment" does not include the prevention or treatment of disease, but includes maintaining a condition, temporarily improving a condition, or assisting in the improvement of a condition. Treatment includes non-therapeutic actions performed by food manufacturers, food distributors, etc. Furthermore, maintaining a condition and temporary improvement include recommending the intake of specific foods and nutritional guidance (including nutritional guidance necessary for the recuperation of sick or injured persons, and nutritional guidance for maintaining and promoting health). In other words, the composition of this embodiment can be used non-therapeuticly. Non-therapeutic means not intended to treat a disease. In one embodiment, the composition of this embodiment can be used by oral ingestion in the form of food, etc. (for example, as a food composition). In the above embodiment, the composition is not a medicine, but is provided in the form of, for example, a dietary supplement, health food, nutritional food, or supplement. Non-therapeutic use means, for example, being used for the purpose of maintaining the current condition, temporary improvement or relief, support, etc. In one embodiment relating to non-therapeutic uses, the composition of this embodiment can be used on healthy subjects without disease. In another embodiment, the composition of this embodiment can also be used for non-therapeutic purposes on subjects with disease. In the above embodiments, even if the subject is in a diseased state, the composition is provided as a food in accordance with the laws and regulations of each country regarding food labeling at the time of implementation (it is not a medicine). For example, the composition can also be used in the form of food or the like as a composition to support treatment. Here, support for treatment means a non-therapeutic use that is part of the treatment of a disease or illness or dietary management. Examples of support for treatment include use in a subject undergoing treatment for a disease or illness to supplement the therapeutic effect or provide nutritional support during treatment; use in a subject who has undergone treatment for a disease or illness to supplement the prognosis or provide nutritional support for maintaining and managing the health status after treatment; and use in a subject who is scheduled to undergo treatment for a disease or illness to enhance the effect of subsequent treatment or provide nutritional support before treatment. In these embodiments, the composition is not a medicine and is provided in the form of, for example, a dietary supplement, health food, nutritional food, or supplement.

[0023] <Composition> [Pharmaceutical composition or food composition, etc.] The composition of this embodiment may be a pharmaceutical composition or a food composition. Unless otherwise specified, pharmaceuticals and foods include not only those for humans but also those for non-human animals. Examples of non-human animals include mammals, birds, reptiles, amphibians, and fish. Non-human animals may also be commercial animals, research animals, or companion animals. The term "companion animal" refers to livestock or domestically raised animals that can easily satisfy physical, emotional, behavioral, and social needs as a household companion or by having close daily relationships with one or more humans. In one embodiment, species included in the definition of companion animals include dogs, canines, cats, felines, cattle, horses, goats, sheep, pigs, primates (such as monkeys), rabbits, ferrets, rodents (such as guinea pigs, hamsters, mice, and rats), and other small mammals. In another embodiment, the species included in the definition of companion animals are dogs, cats, horses, rabbits, ferrets, guinea pigs, and other small mammals, birds, small reptiles, fish, and domestic animals. The pharmaceutical compositions of this embodiment include drugs suitable for pharmaceutically acceptable modes of administration, such as oral preparations, injections, enteral preparations, inhalants, and topical preparations. The food compositions of this embodiment also include general foods, functional foods, and nutritional compositions, unless otherwise specified, as well as therapeutic diets (those that serve a therapeutic purpose, prepared based on a menu created by a dietitian or the like based on a diet prescription issued by a physician), semi-digested nutritional supplements, therapeutic diets, modified diets, care foods, therapeutic support foods, health foods, dietary supplements, and functional health foods. Unless otherwise specified, foods include not only solids but also liquids, such as beverages, drinks, liquid foods, and soups.Functional foods refer to foods that can impart specific functionalities to the living body, and encompass all health foods, such as Foods for Specified Health Uses (including conditionally designated FOSHU [Foods for Specified Health Uses]), Foods with Function Claims, Foods with Nutrient Function Claims, Foods for Special Dietary Uses, Nutritional Supplements, Rehabilitation Nutritional Foods, Health Supplements, Supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated preparations, capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon delivery capsules, etc.), and Beauty Foods (e.g., diet foods). In this embodiment, "functional foods" refers to foods that can impart specific health claims based on the food standards of Codex Alimentarius (FAO / WHO Joint Food Standards Committee). This invention encompasses health foods to which the claim applies, and the composition of this embodiment can exert the effects and efficacy (physiological or pharmacological effects) of N-lactoylphenylalanine on the body when administered orally. Therefore, it can be used as an orally administered pharmaceutical composition containing N-lactoylphenylalanine as an active ingredient, a Food for Specified Health Uses (including conditionally designated Foods for Specified Health Uses), a Food with Function Claims, a Health Functional Food including a Food with Nutrient Function Claims, a Food for Special Dietary Uses, a Nutritional Supplement, a Rehabilitation Nutrition Food, a Health Supplement, and an Orally Intake Supplement. When making health claims, the food regulations and laws of each country at the time of implementation shall take precedence. Furthermore, the food composition can be used for the non-therapeutic uses described above.

[0024] [Pharmaceutical Composition] The composition of this embodiment can be a pharmaceutical composition. Unless otherwise specified, the pharmaceutical composition includes not only those for humans but also those for animals other than humans. The provisions for animals other than humans are as described above. The pharmaceutical composition of this embodiment includes drugs suitable for pharmaceutically acceptable administration methods, such as oral preparations, injections, enteral preparations, inhalations, and topical preparations. Since the composition of this embodiment can exert the effects and efficacy (physiological or pharmacological effects) of N-lactoylphenylalanine on the body when administered orally, it can be used as an orally administered pharmaceutical composition containing N-lactoylphenylalanine as an active ingredient.

[0025] [Food Composition] The composition of this embodiment may be a food composition. Unless otherwise specified, the food composition includes not only those for humans but also those for animals other than humans. Examples of animals other than humans include mammals, birds, reptiles, amphibians, and fish. The same applies to animals other than humans as described above. Unless otherwise specified, the food composition of this embodiment includes general foods, functional foods, and nutritional compositions, and also includes therapeutic foods (those that serve a therapeutic purpose; prepared based on a menu created by a dietitian or the like based on a diet prescription issued by a doctor), semi-digested nutritional supplements, therapeutic diets, component-adjusted foods, nursing care foods, therapeutic support foods, health foods, dietary supplements, and functional health foods. Unless otherwise specified, the food includes not only solids but also liquids, such as beverages, drinks, liquid foods, and soups. Functional foods refer to foods that can impart specific functionalities to the living body, and encompass all health foods, such as Foods for Specified Health Uses (including conditionally designated FOSHU [Foods for Specified Health Uses]), Foods with Function Claims, Foods with Nutrient Function Claims, Foods for Special Dietary Uses, Nutritional Supplements, Rehabilitation Nutritional Foods, Health Supplements, Supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated preparations, capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon delivery capsules, etc.), and Beauty Foods (e.g., diet foods). In this embodiment, "functional foods" refers to foods that can impart specific health claims based on the food standards of Codex Alimentarius (FAO / WHO Joint Food Standards Committee). This invention encompasses health foods to which the claim applies, and the composition of this embodiment can exert the effects and efficacy (physiological or pharmacological effects) of N-lactoylphenylalanine on the body when administered orally. Therefore, it can be used as a Food for Specified Health Uses (including conditionally designated Foods for Specified Health Uses), a Food with Function Claims, a Food with Nutrient Function Claims, a Food for Special Dietary Uses, a Nutritional Supplement, a Rehabilitation Nutritional Food, a Health Supplement, or an Oral Supplement containing N-lactoylphenylalanine as an active ingredient. When making health claims, the food regulations and laws of each country at the time of implementation shall take precedence. Furthermore, the food composition can be used for the non-therapeutic uses described above.

[0026] [Administration Route, etc.] The composition of this embodiment may be administered orally, parenterally, for example, via tube (gastrostomy, jejunostomy), or nasally, but oral administration is preferred, and the composition of this embodiment can be used as an oral composition containing N-lactoylphenylalanine as the active ingredient. The composition can be administered to the subject repeatedly and can be administered to the subject continuously over a long period of time. The duration is not particularly limited, but in order to observe sufficient effects, it is preferable to administer it continuously for a relatively long period, for example, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, or 1 year or more. The composition may be administered daily, in advance when the risk is high, or when necessary. The composition may be administered as part of a meal, before meals, after meals, or between meals, or when a disease or condition that you want to improve with the composition occurs.

[0027] [Dosage and Content] The dosage of the composition of this embodiment may be any amount that produces the desired effect. The dosage can be set appropriately considering various factors such as the age, weight, and symptoms of the subject. The daily dosage of the composition may be 0.01 g or more as the amount of active ingredient (total amount if multiple active ingredients are included), preferably 0.015 g or more, more preferably 0.03 g or more, even more preferably 0.05 g or more, even more preferably 0.1 g or more, even more preferably 0.25 g or more, and even more preferably 0.3 g or more. The upper limit of the daily amount of active ingredient may be 20 g or less, 10 g or less, 9 g or less, 8 g or less, 7 g or less, 6 g or less, 5 g or less, 4 g or less, or 3 g or less, regardless of the lower limit. If the composition contains multiple active ingredients, the amount of active ingredient refers to the total amount of the active ingredients included. The drug may be administered once a day, or divided into multiple doses per day, for example, 2 to 10 times. The amount of active ingredient administered per dose can be, for example, 0.01 g or more, preferably 0.025 g or more, and more preferably 0.03 g or more. The upper limit of the amount of active ingredient per dose can be 10 g or less, 8 g or less, 6 g or less, 4 g or less, 3 g or less, or 2 g or less, regardless of the lower limit. The amount of active ingredient in the composition can be appropriately adjusted according to the form of the composition, the number of doses per day, etc., so as to achieve the desired dosage.

[0028] [Other components and additives] In relation to the present invention, the composition may contain other active ingredients and nutritional components that are acceptable as pharmaceuticals or foods. Examples of such components include lipids (e.g., milk fat, vegetable oils, medium-chain fatty acid-containing oils), proteins (e.g., milk protein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), heat-denatured whey protein, and enzyme-treated whey protein), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), and carbohydrates (gluco These include sugars, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin), electrolytes (e.g., sodium, potassium, calcium, magnesium), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acid), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, etc. The composition may also further contain additives that are acceptable as pharmaceuticals or foods. Examples of such additives include inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coatings, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavorings, acidulants, and natural products. More specifically, these include water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, acacia gum, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, etc.

[0029] [Dosage Form / Form] The pharmaceutical composition of this embodiment can be provided as various formulations or pharmaceutical compositions in combination with pharmaceutically acceptable carrier components or additives. For example, the drug of this embodiment can be used as granules, fine granules, powders, effervescent granules, tablets (uncoated tablets, coated tablets, film-coated tablets, sugar-coated tablets, thin-layer sugar-coated tablets, chewable tablets, effervescent tablets), capsules (soft capsules, hard capsules), oral liquids (elixirs, limonades), syrups, oral jellies, or film formulations, but preferably any dosage form suitable for oral administration, such as solid formulations like tablets, granules, powders, pills, and capsules; liquid formulations like liquids, suspensions, and syrups; gels, aerosols, etc.

[0030] When the composition of this embodiment is used as a food composition, it may be prepared in any form such as solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, or capsule. Furthermore, the food composition according to this embodiment can be in any form such as dairy products, supplements, confectionery, beverages, drinks, seasonings, processed foods, prepared dishes, or soups. More specifically, the composition of this embodiment can be in the form of liquid food, semi-liquid food, jelly, gel, powder, prepared milk powder, prepared liquid milk, baby food, infant food, milk powder / liquid milk for pregnant and lactating women, fermented milk, bars, mousse, chocolate, biscuits, ice cream, fermented milk, lactic acid bacteria beverages, dairy beverages, milk beverages, soft drinks, tablets, cheese, bread, biscuits, crackers, pizza crusts, food for the sick, nutritional foods, frozen foods, processed foods, etc. It can also be in the form of granules, powder, paste, concentrated liquid, etc., for administration by mixing with beverages or foods. Granules and powders can be in the form of cubes or sticks (packaged in single-serving portions). In relation to the present invention, "prepared powdered milk" refers to a product made by processing raw milk, cow's milk, special milk, or raw buffalo milk, or food products made from these as raw materials, or by using these as the main raw material, to which nutrients necessary for infants and young children are added and made into a powder, as defined in the "Ministerial Ordinance Concerning Standards for Ingredients of Milk and Dairy Products (hereinafter abbreviated as "Milk and Dairy Products Ordinance")." In relation to the present invention, "prepared liquid milk" refers to a product made by processing raw milk, cow's milk, special milk, or raw buffalo milk, or food products made from these as raw materials, or by using these as the main raw material, to which nutrients necessary for infants and young children are added and made into a liquid, as defined in the Milk and Dairy Products Ordinance. Prepared milk powder or prepared liquid milk (these are sometimes collectively referred to as prepared milk powders; and in explanations of prepared milk powders, prepared milk powder may be used as an example, but the explanation also applies to prepared liquid milk) can be for infants, follow-up (to supplement weaning foods), low birth weight infants, children, adults, pregnant and lactating women, breastfeeding women, the elderly, people with allergies, people with lactose intolerance, or people with congenital metabolic disorders. Preferred examples of prepared milk powders are those for infants, follow-up, low birth weight infants, and children.Regardless of which component is used, the food composition of the present invention shall be used in accordance with the food safety laws of each country, and shall be used at or below the intake level in which safety is guaranteed, or at or below the acceptable daily intake (ADI).

[0031] [Other] In the manufacture of the composition of this embodiment, the stage of compounding the active ingredient can be selected as appropriate. The compounding stage is not particularly limited as long as it does not significantly impair the properties of the active ingredient. For example, the active ingredient can be mixed with the raw materials. Alternatively, the active ingredient can be added at the final stage of manufacturing to produce a composition containing the active ingredient.

[0032] The composition of this embodiment may indicate its intended use (purpose), and in one embodiment, it may indicate the function of the composition or active ingredient, or how to use it based on that function. Examples of how to use it based on the function are as described above for function, action, and effect. In addition, in one embodiment, the composition of this embodiment may indicate that it is recommended for administration to a specific target. Examples of targets to be indicated are as described above for target. The indication may be explicit or implicit. Examples of explicit indications are direct markings on tangible objects such as the product itself, packaging, containers, labels, tags, etc., while examples of implicit indications (which can also be called tacit indications) include advertising and promotional activities by place or means, such as websites, stores, brochures, exhibitions, media seminars, books, newspapers, magazines, television, radio, mail, email, audio, etc.

[0033] In one embodiment, the recommendation to consume the composition is made on a personal basis. Such a recommendation can be made using documents addressed to the target (whether written or electronic), the target's tablet device, smartphone, personal computer, or social networking service (SNS).

[0034] (Method for improving mental health, etc.) This embodiment includes a method for improving mental health, which involves administering N-lactoylphenylalanine as an active ingredient, and is carried out by administering the first composition of this embodiment. Furthermore, the improvement of mental health is defined as an improvement or enhancement of motivation for activity, and moreover, the improvement of mental health is defined as an improvement or enhancement of motivation for activity in a state of decreased activity due to aging.

[0035] Furthermore, this embodiment also includes a method for improving decreased activity levels, which involves administering N-lactoylphenylalanine as an active ingredient, and is carried out by administering the second composition of this embodiment. Moreover, this method assumes that the decreased activity level is due to aging, and furthermore, that the improvement of the decreased activity level is an improvement or enhancement of motivation for activity. The administration method, target population, etc., are as described above. The present invention will be described in more detail below using examples. However, the technical scope of this embodiment is not limited to these examples.

[0036] (Example of test: Examination of improvement in activity level or motivation) Twenty 74-week-old male B6J mice (Jackson Laboratory Japan) were pre-fed for three weeks. Three weeks later (at 77 weeks of age), the motor function (coordination and motor learning ability) of each mouse was evaluated using the rotor rod test according to the publicly available literature (Yano et al. Exp Gerontol. 2017 Oct 15;97:29-37). The mice were divided into two groups of 10 each so that motor function and body weight were comparable between the groups. Subsequently, an N-lactoylphenylalanine administration test was started at 78 weeks of age. For the example group, N-lactoylphenylalanine (manufactured by Meiji Co., Ltd., with the L-form of the lactic acid residue (i.e., the same stereochemistry as L-lactic acid)) was administered daily via oral tube to each animal at a dose of 50 mg / kg / day (equivalent to a human equivalent dose of 4.1 mg / kg / day for a 60 kg human; the calculation method was based on the US FDA's Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers). For the comparative group, sterile water was administered daily instead of N-lactoylphenylalanine-containing water, in the same manner as the example group. After the start of administration, body weight and food intake were measured once a week. In addition, a wire hang test was performed at 5 weeks after the start of administration, a rotor rod test at 6 weeks after the start of administration, and activity levels were measured from 8 to 9 weeks after the start of administration.

[0037] <Activity Measurement> Activity levels were measured using ACTIMO-100N (Shin Factory Co., Ltd.). One mouse was placed in a measurement cage equipped with the measurement device, and after a one-day preliminary rearing period with a 12-hour light-dark cycle (light on (resting period): 7 am to 7 pm, lights off (active period): 7 pm to 7 am the next day), measurements were taken during the 24 hours leading up to the resting and active periods of the mice's activity. The measurement involved counting the number of times the sensor of the measurement device was blocked (activity count) at each time point (every hour; for example, if the start time was 7 am, the number of times from 7 am to 8 am was measured), and the activity count per hour was calculated. After calculation, the difference in activity counts between the example group and the comparative example group, as well as the time-to-time differences in activity counts during each of the resting and active periods, were evaluated using two-way ANOVA. Tables 1 and 2 and Figures 1 and 2 show the average number of activities per hour during the rest and activity phases. Note that the times in Tables 1 and 2 and Figures 1 and 2 refer to the time period from 7:00 (7 am) to 8:00 (8 am) in the case of 7:00 (7 am).

[0038]

[0039]

[0040] Tables 1 and 2 and Figures 1 and 2 show that the number of activities during the active phase increased in the example group compared to the comparative example group. Two-way ANOVA showed no statistically significant difference between the example group and the comparative example group during the resting phase (p > 0.05), but there was a statistically significant difference (p < 0.01) during the active phase. This indicates that N-lactoylphenylalanine in this embodiment has the effect of improving activity levels during the active phase. In particular, since this study used aged mice, which clearly had reduced activity levels, it was demonstrated that N-lactoylphenylalanine in this embodiment can improve reduced activity levels. In addition, N-lactoylphenylalanine is said to be unsuitable for oral administration because it is broken down in the gastrointestinal tract when administered orally (Patent Document 3). However, it has become clear that the composition of this embodiment can exert its effects when administered orally, and it has been found that it can be used as a food for specified health uses (including conditionally designated FOSHU [Foods for Specified Health Uses]), a food with functional claims, a health functional food including a nutrient function food, a food for special dietary uses, a nutritional supplement, a rehabilitation nutrition food, a health supplement, and an oral supplement containing N-lactoylphenylalanine as an active ingredient.

[0041] <Wire Hang Test> To further verify the effects of N-lactoylphenylalanine, a wire hang test was conducted at 5 weeks after the start of administration to examine whether there were differences in muscle strength between the example group and the comparative example group. In the wire hang test, a mouse was placed on a wire mesh and the mesh was inverted. The time from when the mouse clung to the wire mesh until it released its limbs and fell to the ground was measured, and the time to fall was corrected for body weight for evaluation (see https: / / pmc.ncbi.nlm.nih.gov / articles / PMC10667228 / for the calculation method). Based on the measured results, statistical analysis (Students' t test) was performed to examine whether there were differences between the example group and the comparative example group.

[0042] As a result of the examination, no significant difference was found between the experimental group and the comparative group in the muscle strength difference by the wire hang test (p > 0.05). Also, the rotor rod test was conducted at the 6th week from the start of administration, and the difference between the experimental group and the comparative group in the obtained results was similarly evaluated by statistical analysis (Students' t test). However, no statistical significant difference was found between the two groups in this test either (p > 0.05). Furthermore, when the body weights and food intakes in the experimental group and the comparative group measured every week after the start of administration were evaluated by two-way analysis of variance, no statistical significant difference was found between these two groups (both p > 0.05). From the above results, in the experimental group administered with the composition of this embodiment, while a significant improvement in the activity level was observed, no significant changes were found in muscle strength, body weight, motor function, and food intake. Thus, it was found that the activity level was improved by the desire for activity, that is, the improvement of the activity desire, rather than the change in the physical function. Therefore, it was shown that the composition containing N-lactylphenylalanine as an active ingredient of this embodiment has the effects of improving the activity level, improving, and enhancing the activity desire.

[0043] [Production Example 1 Tablet Candy] Using N-lactylphenylalanine, a tablet candy type food composition for muscle maintenance is produced according to a conventional method with the following formulation.

[0044] Granulated sugar 718 parts by mass Concentrated fruit juice 50 parts by mass Citric acid 60 parts by mass Flavor 20 parts by mass Gelatin 10 parts by mass N-lactylphenylalanine 100 parts by mass Calcium carbonate 15 parts by mass Magnesium oxide 5 parts by mass Potassium dihydrogen phosphate 22 parts by mass

[0045] [Production Example 2: Powdered Beverage] Using N-lactylphenylalanine, a beverage is produced according to the following formulation by a conventional method. Anhydrous crystalline glucose: 720 parts by mass Citric acid granules: 60 parts by mass Tartaric acid: 60 parts by mass Sodium bicarbonate granules: 55 parts by mass Flavor: 25 parts by mass N-lactylphenylalanine: 30 parts by mass Dolomite: 50 parts by mass

[0046] [Production Example 3: Beverage] Using N-lactylphenylalanine, the raw materials are mixed and dissolved according to the following formulation, sealed in a container, and heated at 90°C for 5 minutes to obtain a beverage. N-lactylphenylalanine: 2.9 parts by mass 5-fold concentrated peach juice: 2 parts by mass Sugar: 5 parts by mass Citric acid: 0.3 parts by mass Sodium citrate: 0.05 parts by mass Water: 89.75 parts by mass

[0047] [Production Example 4: Jelly Beverage] Using N-lactylphenylalanine, the raw materials are mixed and dissolved according to the following formulation, sealed in a container, and heated at 90°C for 5 minutes to obtain a jelly beverage. N-lactylphenylalanine: 2.9 parts by mass Granulated sugar: 15.0 parts by mass Fruit juice concentrate: 0.6 parts by mass Citric acid: 0.3 parts by mass Sodium citrate: 0.05 parts by mass Agar: 0.3 parts by mass Flavor: 0.008 parts by mass Water: 80.8 parts by mass

[0048] The present invention relates to a composition for improving mental health, comprising N-lactoylphenylalanine as an active ingredient. More specifically, it relates to a composition for improving or increasing decreased activity levels, or improving or increasing motivation for activity. In particular, it supports the maintenance and improvement of people's health by improving age-related decline in activity levels and increasing motivation for activity. Furthermore, the present invention provides pharmaceutical compositions, food compositions, and methods for producing them that support the maintenance and improvement of people's health. Moreover, the present invention can realize improvements in the health conditions of various people, ensure healthy lives, and promote welfare.

Claims

1. A composition for improving mental health, comprising N-lactoylphenylalanine as an active ingredient.

2. The composition according to claim 1, wherein the improvement in mental health is an improvement or enhancement of motivation to be active.

3. The composition according to claim 2, wherein the improvement in mental health is an improvement or enhancement of motivation to be active under conditions of reduced activity due to aging.

4. A composition for improving decreased activity levels, comprising N-lactoylphenylalanine as an active ingredient.

5. The composition according to claim 4, wherein the decrease in activity level is due to aging.

6. The composition according to any one of claims 4 or 5, wherein the improvement in the decrease in activity level is an improvement or increase in motivation to be active.

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