Composition for promoting development in children

Abstract

The present invention addresses the problem of defining physiological significance and functions such as the influence of nicotinamide mononucleotide (NMN) contained in breast milk on the development of children. A composition for improving the athletic ability of a child is provided comprising a precursor of NAD. The improvement in athletic ability is preferably any one selected from the group consisting of promotion of skeletal muscle development and improvement in activity. A composition for reducing triglyceride levels in the blood of a child is provided comprising a precursor of NAD. A composition for reducing the blood glucose level in a child is provided comprising a precursor of NAD. A composition for inhibiting fat accumulation in children is provided, comprising a precursor of NAD.

Description

Technical Field

[0001] This invention relates to compositions for improving children's athletic ability, compositions for lowering triglyceride levels in children's blood, compositions for lowering children's blood glucose levels, and compositions for inhibiting fat accumulation in children. This invention is useful in the fields of children's, especially infants', development, health, and nutrition, as well as in the manufacture of food and beverages for these purposes. Background Technology

[0002] β-Nicotinamide mononucleotide (NMN) is a precursor to nicotinamide adenine dinucleotide (NAD), which is essential for maintaining human life functions. It is a compound belonging to vitamin B3. To date, NAD has primarily been reported for its beneficial effects related to aging.

[0003] Regarding motor function, for example, reports have shown improved skeletal muscle function and increased spontaneous movement in older mice with high SIRT1 expression in the brain. SIRT1 plays an important role in the control of metabolic responses in various tissues through NAD-dependent enzymatic activity (Non-Patent Literature 1). Additionally, reports have shown significant improvements in walking speed and left-hand grip strength in older men who received daily administration of 250 mg NMN for 6 or 12 weeks (Non-Patent Literature 2). Patent Document 1 discloses a composition for preventing chemotherapy-induced neurotoxicity in a subject, comprising a compound that increases NAD+ levels in the subject, the chemotherapy-induced neurotoxicity including chemotherapy-induced cognitive impairment (CICI), wherein the subject is: i) a subject who has been exposed to a chemotherapy agent but has not yet developed CICI, or ii) a subject who is currently exposed to a chemotherapy agent, or iii) a subject who is planned to be exposed to a chemotherapy agent, and the compound that increases NAD+ levels is an NAD+ precursor selected from nicotinamide mononucleotide (NMN), nicotinic acid, nicotinamide, nicotinamide nucleoside (NR), nicotinic acid mononucleotide or nicotinic acid ribose, or salts thereof. As another aspect of Patent Document 1, a method for improving the neurological function and motor skills of a subject is disclosed, the method comprising the step of administering an effective amount of an agent to the subject, the agent increasing NAD+ levels in the subject. Patent Document 2 discloses a composition comprising a specific nicotinamide adenine dinucleotide (NAD) precursor, which is a composition for conferring health benefits to female mammals and / or their offspring. The composition is characterized by being administered orally, via a mucosal membrane (e.g., nasal), by inhalation, by injection, or topically (e.g., percutaneously) to the female mammal, from which the offspring orally ingest breast milk, thereby conferring the health benefits to the offspring. The health benefits conferred to the female mammal include reduced weight gain associated with pregnancy, promoted postpartum weight loss, and / or increased breast milk production during lactation. The health benefits conferred to the offspring include increased brain quality, improved physical function, prevention of age-related weight gain, and / or reduced anxiety. Patent Document 3 discloses a method for increasing the motor abilities of a subject, comprising the step of administering an effective amount of an NAD+ precursor to the subject.

[0004] In addition, regarding triglycerides, for example, it has been reported that in a trial of mice fed a high-fat diet and then given NMN, lipid metabolism was improved and the amount of triglycerides in the liver was reduced (Non-Patent Document 3). Patent Document 4 describes the administration of two capsules once daily for four weeks (28 days) to three subjects (over 50 years old) with high blood triglyceride levels. The administration consisted of hard capsules containing 20 mg of resveratrol and 20 mg of β-nicotinamide mononucleotide, and hard capsules containing 20 mg of resveratrol, 20 mg of β-nicotinamide mononucleotide, and 120 mg of nicotinamide. The results showed a reduction in triglyceride levels. Patent Document 5 describes an adiponectin secretion promoter, characterized by using β-nicotinamide mononucleotide or a pharmacologically acceptable salt thereof, and their solvates as active ingredients. It also describes that by promoting adiponectin secretion, it can treat or prevent obesity-related systemic metabolic disorders, particularly multi-organ insulin resistance. Patent document 6 describes a method for treating or preventing at least one physical state selected from the group consisting of oxidative stress, oxidative stress-related states, decreased glutathione levels, and states associated with decreased glutathione levels. The method includes administering an effective amount of a combination of nicotinamide adenine dinucleotide (NAD+) precursor and at least one ketone or ketone precursor to an individual in need of the combination. An example of a physical state is elevated triglyceride levels.

[0005] Furthermore, regarding blood glucose levels, for example, it has been reported that: by administering NMN, glucose tolerance impairment caused by prolonged high-fat diets in mice, both in the mother and after weaning, was improved (Non-Patent Literature 3 mentioned above); when NMN was administered, NAD+ levels in the intestines of model mice with reduced glucagon-like peptide-1 (GLP-1) production and diet-induced obesity mice were restored, and obesity-related metabolic disorders characterized by reduced ileal glucagon pro-expression and GLP-1 production, manifested as postprandial hyperglycemia, were restored (Non-Patent Literature 4). Patent Literature 7 describes a glucose uptake enhancer for muscle tissue containing a yeast extract containing β-NMN as an active ingredient. Additionally, Patent Literature 8 describes a pharmaceutical composition or health food composition, characterized by preferably containing nicotinamide mononucleotide and mogroside, and describes this composition as a composition for lowering blood glucose levels, promoting the growth and repair of pancreatic islet cells, and addressing hyperglycemia and / or diabetes.

[0006] In addition, regarding the inhibition of fat accumulation, for example, it has been reported that the glucose tolerance impairment caused by long-term high-fat diets in mice after weaning and maternal use was improved by the administration of NMN (see above Non-Patent Literature 3). Similarly, when NMN was administered to mice fed a high-fat diet, obesity-related metabolic disorders characterized by lipid metabolism and glucose tolerance were improved (see above Non-Patent Literature 4).

[0007] Patent document 7 describes a glucose absorption enhancer for muscle tissue containing a yeast extract with β-NMN as an active ingredient, and describes the agent as a preventative or ameliorative agent for diabetes and various complications such as obesity caused by diabetes. Patent document 8 describes a pharmaceutical composition or health food composition, characterized by preferably containing nicotinamide mononucleotide and mogroside, and describes the composition as being used to control fat accumulation and weight.

[0008] On the other hand, it has been reported that NMN synthesis in rat mammary glands is specifically increased during lactation (Non-Patent Literature 5). Furthermore, recent studies have found that human breast milk contains NAD+ metabolites, represented by nicotinamide, which are particularly rich in NMN (Non-Patent Literature 6). Additionally, it has been reported that, using an animal model, lactating male mice were orally administered nicotinamide nucleoside (NR) daily from day 2 to day 20 after birth, weaned on day 21, and fed a high-fat diet for 10 weeks from day 90. Mice administered NR showed beneficial effects on lipid and energy metabolism in adult skeletal muscle and liver compared to the control group (Non-Patent Literature 7).

[0009] Existing technical documents

[0010] Patent documents

[0011] Patent Document 1: International Publication WO2016 / 176437 (Japanese Patent No. 2018-514548, Japanese Patent No. 7193232)

[0012] Patent Document 2: International Publication WO2018 / 102426 (Japanese Patent No. 2020-504168, Japanese Patent No. 7136795)

[0013] Patent Document 3: International Publication WO2018 / 112541 (Japanese Patent Publication No. 2020-504722)

[0014] Patent Document 4: International Publication WO2016 / 158212 (Japanese Patent No. 6545256)

[0015] Patent Document 5: Japanese Patent Application Publication No. 2018-131418

[0016] Patent Document 6: International Publication WO2019 / 242982 (Japanese Patent Publication No. 2021-528372)

[0017] Patent Document 7: Japanese Patent Application Publication No. 2018-203691 (Japanese Patent No. 7093161)

[0018] Patent Document 8: International Publication WO2020 / 177153 (Japanese Patent Publication No. 2022-534165)

[0019] Non-patent literature

[0020] Non-patent literature 1: Satoh A et al, Cell Metab. 2013 Sep 3;18(3):416-30.

[0021] Non-patent literature 2: Igarashi M et al, NPJ Aging. 2022 May 1;8(1):5.

[0022] Non-patent literature 3: Uddin GM et al, Cells. 2020 Mar 25;9(4):791.

[0023] Non-patent literature 4: Nagahisa T et al, Endocrinology. 2022 Apr 1;163(4):bqac023.

[0024] Non-patent literature 5: AL Greenbaum et al, Biochem J 1 March 1968; 107 (1):55-62.

[0025] Non-patent literature 6: J Chromato B 2019; 1110-1111: 74-80

[0026] Non-patent literature 7: Alba Serrano et ai, Nutrients 2022, 14, 2259. Summary of the Invention

[0027] The problem the invention aims to solve

[0028] Although breast milk contains NMN, the physiological significance and function of NMN, such as its effects on children's development, are still unclear.

[0029] Solution for solving the problem

[0030] This invention provides the following content.

[0031] [1] A nutritional composition for children comprising a precursor of nicotinamide adenine dinucleotide (NAD), the composition being used to promote the development of children, the development of children being selected from any aspect of improved athletic ability, reduced blood triglycerides, reduced blood glucose levels, and inhibition of fat accumulation.

[0032] [2] The composition according to 1 is a composition for improving athletic ability, wherein the improvement of athletic ability is selected from any of the groups consisting of compositions that promote the development and activity of skeletal muscles.

[0033] [3] The composition according to 1 or 2 is a composition for improving athletic ability, the improvement of athletic ability being determined by selecting any one of the group consisting of increased muscle strength, increased spontaneous action volume and increased movement speed.

[0034] [4] The composition according to any one of 1 to 3, wherein promoting the development of the child is promoting the development of the child after weaning.

[0035] [5] The composition according to any one of 1 to 4, wherein promoting the development of children is promoting the development of children over 3 years of age.

[0036] [6] The composition according to any one of 1 to 5 is intended for consumption by infants or young children.

[0037] [7] The composition according to any one of 1 to 5 is intended for consumption by children during and before weaning.

[0038] [8] The composition according to any one of 1 to 7 is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0039] [9] The composition according to any one of 1 to 8, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0040]

[10] The composition according to any one of 1 to 9, wherein the concentration of NMN at the time of intake is 0.05 μg / mL or more.

[0041]

[11] The composition according to any one of 1 to 10 is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0042]

[12] A composition comprising a precursor of nicotinamide adenine dinucleotide (NAD), said composition for use in children during and before weaning, to promote development in children after weaning.

[0043]

[13] According to the composition of 12, the one that promotes the development of children is selected from any one of improving motor ability, reducing blood triglycerides, reducing blood glucose levels, and inhibiting fat accumulation.

[0044] This invention provides the following content.

[0045]

[101] A pediatric nutritional composition comprising a precursor of nicotinamide adenine dinucleotide (NAD), said composition being used in a method of promoting development in a child in any of the aspects selected from improved athletic performance, reduced blood triglycerides, reduced blood glucose levels, and inhibition of fat accumulation. Use of a precursor of nicotinamide adenine dinucleotide (NAD) in the manufacture of a pediatric nutritional composition for promoting development in a child, said development being selected from any of the aspects selected from improved athletic performance, reduced blood triglycerides, reduced blood glucose levels, and inhibition of fat accumulation. A method or non-therapeutic method comprising the step of administering to a subject a pediatric nutritional composition comprising a precursor of nicotinamide adenine dinucleotide (NAD), said method for promoting development in a child, said development being selected from any of the aspects selected from improved athletic performance, reduced blood triglycerides, reduced blood glucose levels, and inhibition of fat accumulation. The use or non-therapeutic use of a pediatric nutritional composition containing a precursor of nicotinamide adenine dinucleotide (NAD) for promoting development in children, for promoting any aspect of development selected from improvements in motor ability, reduction of blood triglycerides, reduction of blood glucose levels, and inhibition of fat accumulation.

[0046]

[102] The composition, use in manufacturing, method or non-therapeutic use according to 101 is used to improve athletic ability, the improvement of athletic ability being selected from any of the groups consisting of promoting skeletal muscle development and improving activity.

[0047]

[103] The composition, use in manufacturing, method or non-therapeutic use according to 101 or 102, is used to improve athletic ability, and the improvement in athletic ability is determined by selecting any one of the group consisting of increased muscle strength, increased spontaneous action volume and increased movement speed.

[0048]

[104] The composition, use in manufacture, method or non-therapeutic method, use or non-therapeutic use of any one of 101 to 103, wherein promoting the development of a child is promoting the development of a child after weaning.

[0049]

[105] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use according to any one of 101 to 104, wherein promoting the development of children is promoting the development of children over 3 years of age.

[0050]

[106] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use of any one of 101 to 105, wherein the composition is intended for ingestion by an infant or young child.

[0051]

[107] The composition, use in manufacture, method or non-therapeutic method, use or non-therapeutic use of any one of 101 to 105, wherein the composition is intended for consumption by children at or before weaning.

[0052]

[108] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use according to any one of 101 to 107, wherein the composition is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0053]

[109] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use according to any one of 101 to 108, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0054]

[110] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use according to any one of 101 to 109, wherein the NMN concentration at the time of intake of the composition is 0.05 μg / mL or more.

[0055]

[111] The composition, use in manufacturing, method or non-therapeutic method, use or non-therapeutic use according to any one of 101 to 110, wherein the composition is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0056]

[112] A precursor of nicotinamide adenine dinucleotide (NAD) or a composition comprising thereof, used in a method of administration to children at or before weaning to promote the development of children after weaning. Use of a precursor of nicotinamide adenine dinucleotide (NAD) in the manufacture of a composition for use in a method of administration to children at or before weaning to promote the development of children after weaning. A method or non-therapeutic method comprising the step of administering a precursor of nicotinamide adenine dinucleotide (NAD) to a subject for administration to children at or before weaning to promote the development of children after weaning. Use or non-therapeutic use of a precursor of nicotinamide adenine dinucleotide (NAD) for administration to children at or before weaning to promote the development of children after weaning.

[0057]

[113] The composition, use in manufacturing, method or non-therapeutic use according to 112, wherein promoting the development of children is selected from any one of improving motor ability, reducing blood triglycerides, reducing blood glucose levels, and inhibiting fat accumulation.

[0058] This invention provides the following content.

[0059]

[201] A composition for improving children’s athletic ability, comprising a precursor of nicotinamide adenine dinucleotide (NAD).

[0060]

[202] According to the composition of 201, the improvement in motor ability is selected from any one of the groups consisting of promoting skeletal muscle development and improving activity.

[0061]

[203] According to the composition of 201 or 202, the improvement in motor ability is determined by selecting any one of the group consisting of increased muscle strength, increased spontaneous action volume and increased movement speed.

[0062]

[204] The composition according to any one of 201 to 203, wherein improving a child’s motor skills is improving the motor skills of an infant or toddler.

[0063]

[205] The composition according to any one of 201 to 204, wherein improving the child's motor skills is improving the motor skills of a child after weaning.

[0064]

[206] The composition according to any one of 201 to 205 is intended for consumption by infants or young children.

[0065]

[207] The composition according to any one of 201 to 205 is intended for consumption by children during and before weaning.

[0066]

[208] The composition according to any one of 201 to 207 is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0067]

[209] The composition according to any one of 201 to 208, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0068]

[210] The composition according to 209, wherein the concentration of NMN at the time of intake is 0.05 μg / mL or more.

[0069]

[211] The composition according to 209 or 210 is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0070] The present invention also provides the following:

[0071]

[301] A composition for reducing triglyceride levels in the blood of children, comprising a precursor of nicotinamide adenine dinucleotide (NAD).

[0072]

[302] The composition according to 301, wherein lowering the blood triglyceride level in children is lowering the blood triglyceride level in infants or young children.

[0073]

[303] The composition according to 301 or 302, wherein reducing the blood triglyceride level in children is reducing the blood triglyceride level in children after weaning.

[0074]

[304] The composition according to any one of 301 to 303 is intended for consumption by infants or young children.

[0075]

[305] The composition according to any one of 301 to 303 is intended for consumption by children during and before weaning.

[0076]

[306] The composition according to any one of 301 to 305 is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0077]

[307] The composition according to any one of 301 to 306, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0078]

[308] The composition according to 307, wherein the concentration of NMN at the time of intake is 0.05 μg / ml or more.

[0079]

[309] The composition according to 307 or 308 is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0080] The present invention also provides the following:

[0081]

[401] A composition for lowering blood glucose levels in children, comprising a precursor of nicotinamide adenine dinucleotide (NAD).

[0082]

[402] The composition according to 401, wherein the decrease in blood glucose level in children is a decrease in blood glucose level in infants or young children.

[0083]

[403] The composition according to 401 or 402, wherein the decrease in blood glucose level in the child is a decrease in blood glucose level in a child after weaning.

[0084]

[404] The composition according to any one of 401 to 403 is intended for consumption by infants or young children.

[0085]

[405] The composition according to any one of 401 to 403 is intended for consumption by children during and before weaning.

[0086]

[406] The composition according to any one of 401 to 405 is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0087]

[407] The composition according to any one of 401 to 406, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0088]

[408] The composition according to 407, wherein the concentration of NMN at the time of intake is 0.05 μg / ml or more.

[0089]

[409] The composition according to 407 or 408 is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0090] The present invention also provides the following:

[0091]

[501] A composition for inhibiting fat accumulation in children, comprising a precursor of nicotinamide adenine dinucleotide (NAD).

[0092]

[502] The composition according to 501, wherein inhibiting fat accumulation in children is inhibiting fat accumulation in infants or young children.

[0093]

[503] The composition according to 501 or 502, wherein inhibiting fat accumulation in children is inhibiting fat accumulation in children after weaning.

[0094]

[504] The composition according to any one of 501 to 503 is intended for consumption by infants or young children.

[0095]

[505] The composition according to any one of 501 to 503 is intended for consumption by children during and before weaning.

[0096]

[506] The composition according to any one of 501 to 505 is any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

[0097]

[507] The composition according to any one of 501 to 506, wherein the precursor of NAD is nicotinamide mononucleotide (NMN).

[0098]

[508] The composition according to 507, wherein the concentration of NMN at the time of intake is 0.05 μg / ml or more.

[0099]

[509] The composition according to 507 or 508 is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

[0100] The effects of the invention

[0101] The composition of the present invention can contribute to children's healthy growth in the future by improving children's athletic ability, reducing children's blood triglyceride levels, lowering children's blood sugar levels, and inhibiting children's fat accumulation.

[0102] NMN, one of the active ingredients, is naturally found in breast milk, so it can safely provide targeted benefits to children.

[0103] According to the present invention, information is provided regarding the correlation between NMN intake during and prior to weaning and athletic performance, blood triglyceride levels, blood glucose levels, and fat accumulation.

[0104] One formulation is expected to be used in the treatment of diseases or conditions related to motor function in children. Another formulation is expected to be used in the treatment of diseases or conditions related to triglyceride levels in the blood of children. Another formulation is expected to be used in the treatment of diseases or conditions related to blood glucose levels in children. Another formulation is expected to be used in the treatment of diseases or conditions related to fat accumulation in children.

[0105] In addition, the compositions of the present invention are expected to be used to improve children's nutritional status and maintain / enhance their health. Attached Figure Description

[0106] Figure 1-1 Grip strength was measured 3 weeks after weaning. Ctrl: Control group; NMN: NMN group; n=20 for each group; values ​​are mean ± standard error. :p<0.05 Student's t-test vs Ctrl.

[0107] Figure 1-2 Spontaneous movement volume / average movement speed. An open field test was conducted 2 weeks after weaning to measure spontaneous movement volume and average movement speed. Ctrl: Control group, NMN: NMN group, n=20 for each group, values ​​are mean ± standard error. :p<0.05 Student's t-test vs Ctrl.

[0108] Figure 2 The value represents the triglyceride concentration in the blood. Plasma was separated from whole blood samples taken 2 weeks after weaning, and triglyceride concentration was measured. Ctrl: Control group (n=7), NMN: NMN group (n=5), values ​​are mean ± standard error.

[0109] Figure 3Blood glucose levels were measured by separating plasma from whole blood samples taken two weeks after weaning. Ctrl: Control group (n=7), NMN: NMN group (n=5), values ​​are mean ± standard error. :p<0.01 Student's-test vs Ctrl.

[0110] Figure 4 Relative weight of white adipose tissue. White adipose tissue weight was measured by dissection two weeks after weaning. Ctrl: Control group; NMN: NMN group; n=10 for each group; values ​​are mean ± standard error. :p<0.01 Student's t-test vsCtrl. Detailed Implementation

[0111] [Active Ingredients]

[0112] The composition of this embodiment contains a precursor of nicotinamide adenine dinucleotide (NAD) as the active ingredient. It should be noted that the active ingredient refers to a component that contributes to the intended purpose; in the context of functionally labeled foods, it is sometimes referred to as a functionally related ingredient.

[0113] In this invention, the precursor of NAD refers to NAD itself or substances that can be converted into NAD within an organism. NAD functions as a coenzyme for various dehydrogenases in organisms and can exist in both oxidized (NAD+) and reduced (NADH) states. In this invention, unless otherwise stated, references to NAD refer to both oxidized NAD+ and reduced NADH.

[0114] The precursor of NAD can be used in the composition in the form of only one or more.

[0115] In one embodiment, the composition comprises any of the compounds represented by the following general formula (I), namely nicotinamide mononucleotide derivatives, as a precursor of NAD.

[0116]

[0117] In the formula, R 1 and R 2Each acyl group has 6 to 16 carbon atoms, and the hydrocarbon group bonded to the carbonyl carbon is a straight-chain or branched saturated or unsaturated hydrocarbon group. Such a compound can be produced by acylation of NMN in a solvent containing more than 20% by mass of a strongly acidic liquid with a pKa value of less than 2.0, using any acylating agent selected from the group consisting of a carboxylic acid with 6 to 16 carbon atoms, a halide of the carboxylic acid, and an anhydride of the carboxylic acid, wherein the straight-chain or branched saturated or unsaturated hydrocarbon group is bonded to the carbonyl carbon (see WO2017 / 110317).

[0118] In one embodiment, the composition comprises any one selected from the group consisting of nicotinamide mononucleotide (NMN), nicotinic acid, nicotinamide (sometimes also called niacinamide), nicotinamide nucleoside, reduced nicotinamide nucleoside, β-trigonelline, nicotinic acid mononucleotide, nicotinic acid ribose, tryptophan, and their food- or pharmaceutically acceptable salts as a precursor of NAD.

[0119] In a preferred embodiment, the composition contains NMN or a salt thereof that is acceptable as a food or pharmaceutical preparation as a precursor to NAD.

[0120] NMN exists as an optical isomer in both α- and β-forms. However, in this invention, unless otherwise stated, when referring to NMN, we are referring to the β-form NMN (β-nicotinamide mononucleotide). NMN is an intermediate metabolite of NAD+.

[0121] Salts acceptable as food or medicine are any salt selected from the group consisting of nitrates, sulfates, carbonates, bicarbonates, halogen salts, formates, acetates, citrates, tartrates, oxalates, fumarates, salts of saturated or unsaturated fatty acids with 3 to 20 carbon atoms, salts of carnitine and its derivatives, salts of hydroxycitric acid and its derivatives, salts of ascorbic acid and its derivatives, salts of ascorbic acid phosphate and its derivatives, sodium salts, potassium salts, calcium salts, magnesium salts, zinc salts, and ammonium salts.

[0122] Precursors to NAD, NMN, nicotinic acid, nicotinamide, nicotinamide nucleoside, reduced nicotinamide nucleoside, β-trigonelline, nicotinic acid mononucleotide, nicotinic acid ribose, tryptophan, and their salts acceptable as food or pharmaceuticals can be manufactured by various methods. They can be synthesized or extracted from natural products containing the substance, cultures of yeast, etc.

[0123] [use]

[0124] The composition of this embodiment is used for any of the following: improving children's athletic ability, reducing children's blood triglyceride levels, reducing children's blood glucose levels, and inhibiting children's fat accumulation. It should be noted that, in relation to this invention, "any of the following" refers to both the quantity and type of the components being arbitrary.

[0125] Regarding this invention, unless otherwise stated, references to children are not limited to human children. Regarding this invention, references to age refer to human age, unless specifically stated or determined from the context to be the age of a particular animal. For example, when referring to age 3, it refers to 3 years old in humans; when referring to mice, it refers to approximately 4 weeks old, equivalent to 3 years old in humans. For the relationship between human and mouse ages, see S. Dutta, P. Sengupta. LifeSciences 152 (2016) 244-248. Regarding this invention, references to children, in the case of humans, refer to those under 18 years of age, including those before weaning, during weaning, and in the short period after weaning (e.g., from weaning to approximately 3 years of age), and also include infants.

[0126] The weaning period refers to the time during which children consume breast milk or its substitutes while also taking in other sources of nutrition. In humans, this period varies from person to person but typically ranges from 4-6 months to around 18 months after birth. It's important to note that "weaning period and before" refers to both the period before and after weaning, while "weaning period after" refers to the period following weaning, excluding the weaning period itself.

[0127] In this invention, when referring to the treatment of a disease or condition, it includes reducing the risk of onset, delaying onset, prevention, treatment, cessation of progression, and slowing of disease progression. Treatment includes medical actions performed by physicians for the purpose of treating the disease, as well as non-medical actions performed by persons other than physicians, such as dietitians, managed dietitians, health care professionals, midwives, nurses, clinical laboratory technicians, food manufacturers, and food distributors. Furthermore, treatment includes: recommendations for the administration or intake of specific foods, dietary guidance, health care guidance, nutritional guidance (including nutritional guidance for the recuperation of the injured and sick, and nutritional guidance for maintaining and improving health), dietary management, and guidance for diet-related nutritional improvements. The objects of treatment in this invention include humans (individuals) and non-human mammals (companion animals, etc.). Additionally, in this invention, "(conducting) intake" can be understood as "(conducting) administration." "(conducting) administration" refers not only to pharmaceutical compositions but also sometimes to food compositions.

[0128] (Function / Effect)

[0129] <Improvement of athletic ability>

[0130] In one embodiment, the composition is used to improve a child's motor skills.

[0131] According to the research of the inventors, mice that were given NMN during infancy, and more specifically, mice that were given NMN until day 21 after birth (the day of weaning), showed an increase in grip strength three weeks after weaning (calculated to be equivalent to 4.6 years in humans according to the aforementioned literature).

[0132] Therefore, in one manner, the composition is intended for consumption by children at any of the following periods: before weaning, during weaning, and a short period after weaning (e.g., after weaning to about 3 years of age), preferably for consumption by children at and before weaning (before and during weaning).

[0133] In another embodiment, the composition is used to improve the motor skills of children after the weaning period. For example, the composition is used to improve the motor skills of children selected from any period selected after weaning, a short period after weaning (e.g., after weaning to about 3 years old), or 3 to 5 years old. Preferably, the composition is used to improve the motor skills of children after weaning.

[0134] In a particularly preferred embodiment, the composition is intended for consumption by a child at a specific stage to improve the child's motor skills after that stage. For example, the composition is intended for consumption by a child at any stage selected from before weaning, during weaning, and a short period after weaning (e.g., after weaning to approximately 3 years of age), to improve the child's motor skills at any stage selected from after weaning, a short period after weaning (e.g., after weaning to approximately 3 years of age), and between 3 and 5 years of age. Preferably, the composition is intended for consumption by a child at or before weaning to improve the child's motor skills after weaning.

[0135] Improved motor skills include enhanced skeletal muscle development and increased mobility. Enhanced skeletal muscle development can be assessed by increased muscle strength. Mobility refers to an active state. Improved mobility can be assessed by, for example, an increase in spontaneous movement or an increase in average speed of movement. Improved mobility also includes cases resulting from enhanced brain function (central nervous system functions).

[0136] Improvements in motor skills can be evaluated through actions such as standing with support, walking with support, squatting, walking independently, walking with alternating limb swings, standing on one leg, climbing stairs, jumping with both feet, hanging with both hands, running, throwing, and kicking.

[0137] Improvements in athletic ability can also be assessed through tests such as the 25-meter sprint, standing long jump, pitching, continuous double-leg jumps, duration of body support, and catching. Further improvements can be evaluated through tests such as grip strength, sit-ups, sit-and-reach, repeated lateral jumps, 20-meter shuttle run, 50-meter sprint, standing long jump, and softball throwing.

[0138] In one embodiment, the composition of the present invention is used to maintain athletic ability, to effectively maintain improved athletic ability, and to assist in achieving these objectives.

[0139] In one embodiment, the composition of the present invention is used to treat a disease or condition related to mobility, which is expected to be improved by enhancing mobility.

[0140] <Lowering blood triglyceride levels>

[0141] In one manner, the composition is used to lower triglyceride levels in a child's blood. Blood triglycerides are sometimes also referred to as neutral fats.

[0142] Triglycerides are the main lipids and body fats found in foods such as meat, fish, and cooking oils; they are also simply called fats. Triglycerides are an important source of energy and are essential for the intake of fat-soluble vitamins and essential fatty acids. However, excessive intake can lead to obesity as body fat and cause lifestyle-related diseases. Generally, a blood triglyceride concentration of 150 mg / dL or higher is considered hypertriglyceridemia.

[0143] According to the research of the inventors, mice that were given NMN during infancy, and more specifically, mice that were given NMN until day 21 after birth (the day of weaning), tended to have lower blood triglyceride concentrations two weeks after weaning (calculated to be equivalent to 3.8 years in humans according to the above literature).

[0144] Therefore, in one manner, the composition is intended for consumption by children at any of the following periods: before weaning, during weaning, and a short period after weaning (e.g., after weaning to about 3 years of age), preferably for consumption by children at and before weaning (before and during weaning).

[0145] In another embodiment, the composition is used to reduce blood triglyceride levels in children after the period of ingestion. For example, the composition is used to reduce blood triglyceride levels in children selected from any period selected after weaning, a short period after weaning (e.g., from weaning to approximately 3 years of age), or from 3 to 5 years of age. Preferably, the composition is used to reduce blood triglyceride levels in children after weaning.

[0146] In a particularly preferred embodiment, the composition is intended for consumption by a child at a specific stage, reducing the child's blood triglyceride levels after that stage. For example, the composition is intended for consumption by a child selected from the period before weaning, during weaning, and a short period after weaning (e.g., after weaning to approximately 3 years of age), reducing the child's blood triglyceride levels at any stage selected from the period after weaning, a short period after weaning (e.g., after weaning to approximately 3 years of age), and between 3 and 5 years of age. Preferably, the composition is intended for consumption by a child at or before weaning, reducing the child's blood triglyceride levels after weaning.

[0147] A decrease in blood triglyceride levels can be measured, for example, using separated plasma and commercially available kits.

[0148] In one embodiment, the compositions of the present invention are used to maintain blood triglyceride levels, to maintain a state of reduced blood triglyceride levels, and to assist in achieving these objectives.

[0149] In one embodiment, the compositions of the present invention are used to treat a disease or condition associated with blood triglyceride levels, which is expected to be improved by lowering blood triglyceride levels.

[0150] <Lowering blood sugar levels>

[0151] In one embodiment, the composition is used to lower blood sugar levels in children.

[0152] Blood glucose level refers to the concentration of glucose in the blood. Carbohydrates and other dietary nutrients are digested and absorbed, becoming glucose which enters the bloodstream. A person's blood glucose level is maintained within a narrow range (approximately 70-100 mg / dL when fasting) through the action of insulin, glucagon, and other hormones. A persistently high blood glucose level is called hyperglycemia. If this state persists for a long time, it poses a risk of damaging blood vessels and leading to arteriosclerosis. Diabetes is a disease caused by insufficient insulin secretion or its inability to function effectively, resulting in chronically elevated blood glucose levels. In recent years, the number of children with type 2 diabetes has been steadily increasing; therefore, measures to lower and maintain blood glucose levels are expected to play an important role in preventing the onset of diabetes.

[0153] According to the research of the inventors, mice that were given NMN during infancy, and more specifically, mice that were given NMN until day 21 after birth (the day of weaning), had significantly lower blood glucose levels two weeks after weaning (calculated to be equivalent to 3.8 years in humans according to the above literature).

[0154] Therefore, in one manner, the composition is intended for consumption by children at any of the following periods: before weaning, during weaning, and a short period after weaning (e.g., after weaning to about 3 years of age), preferably for consumption by children at and before weaning (before and during weaning).

[0155] In another embodiment, the composition is used to lower blood glucose levels in children after the weaning period. For example, the composition is used to lower blood glucose levels in children selected from the period after weaning, a short period after weaning (e.g., from weaning to about 3 years old), or any period between 3 and 5 years old. Preferably, the composition is used to lower blood glucose levels in children after weaning.

[0156] In a particularly preferred embodiment, the composition is intended for consumption by a child at a specific stage, thereby lowering the child's blood glucose levels after that stage. For example, the composition is intended for consumption by a child at any stage selected from before weaning, during weaning, and a short period after weaning (e.g., after weaning to approximately 3 years of age), thereby lowering the child's blood glucose levels at any stage selected from after weaning, a short period after weaning (e.g., after weaning to approximately 3 years of age), and between 3 and 5 years of age. Preferably, the composition is intended for consumption by a child at or before weaning, thereby lowering the child's blood glucose levels after weaning.

[0157] A decrease in blood glucose levels can be measured, for example, using separated plasma and commercially available kits.

[0158] In one embodiment, the compositions of the present invention are used to maintain blood glucose levels, to effectively maintain a reduction in blood glucose levels, and to assist in achieving these objectives.

[0159] In one embodiment, the composition of the present invention is used to treat a disease or condition associated with blood glucose levels, which is expected to be improved by lowering blood glucose levels.

[0160] <Inhibition of Fat Accumulation>

[0161] In one embodiment, the composition is used to inhibit fat accumulation in children.

[0162] Generally speaking, when referring to fat in relation to the body, this includes visceral fat and subcutaneous fat. According to the research of the present invention, mice administered NMN during infancy had lower levels of white adipose tissue around the reproductive organs after weaning compared to control mice. Therefore, the compositions of the present invention are suitable for inhibiting the accumulation of fat, particularly visceral fat.

[0163] According to the research of the inventors, mice given NMN during infancy, and more specifically mice given NMN until day 21 after birth (the day of weaning), tended to have lower fat accumulation concentrations two weeks after weaning (calculated to be equivalent to 3.8 years in humans according to the aforementioned literature).

[0164] Therefore, in one manner, the composition is intended for consumption by children at any of the following periods: before weaning, during weaning, and a short period after weaning (e.g., after weaning to about 3 years of age), preferably for consumption by children at and before weaning (before and during weaning).

[0165] In another embodiment, the composition is used to inhibit fat accumulation in children after the weaning period. For example, the composition is used to inhibit fat accumulation in children selected from the period after weaning, a short period after weaning (e.g., from weaning to about 3 years old), or any period between 3 and 5 years old. Preferably, the composition is used to inhibit fat accumulation in children after weaning.

[0166] In a particularly preferred embodiment, the composition is intended for consumption by a child at a specific stage, inhibiting fat accumulation in that child after that stage. For example, the composition is intended for consumption by a child at any stage selected from before weaning, during weaning, and a short period after weaning (e.g., from weaning to approximately 3 years of age), inhibiting fat accumulation in that child at any stage selected from after weaning, a short period after weaning (e.g., from weaning to approximately 3 years of age), and between 3 and 5 years of age. Preferably, the composition is intended for consumption by a child at or before weaning, inhibiting fat accumulation in that child after weaning.

[0167] The amount of body fat or the degree of fat accumulation can be measured, for example, using CT scans or body fat scales (conductivity method / bioimpedance method). Additionally, it can be estimated using waist circumference measurements, which are reportedly roughly proportional to the accumulation of visceral fat.

[0168] In one embodiment, the compositions of the present invention are used to prevent fat accumulation, maintain a state of well-inhibited fat accumulation, and assist in achieving these objectives.

[0169] In one embodiment, the compositions of the present invention are used to treat diseases or conditions associated with fat accumulation, which are expected to be improved by inhibiting fat accumulation.

[0170] (object)

[0171] The composition of this embodiment is intended for consumption by children (under 18 years of age). Regarding this invention, unless otherwise stated, references to children include infants (under 1 year of age, including newborns under 1 month of age), toddlers (1 year and older but under 6 years of age), and adolescents (6 years and older but under 18 years of age).

[0172] One formulation is suitable for use by individuals who wish to improve athletic performance, or who have this need. Another formulation is also promising for the treatment of diseases or conditions related to athletic performance in children. One formulation is suitable for use by individuals who wish to lower blood triglyceride levels, or who have this need. Another formulation is also promising for the treatment of diseases or conditions related to blood triglyceride levels in children. One formulation is suitable for use by individuals who wish to lower blood glucose levels, or who have this need. Another formulation is also promising for the treatment of diseases or conditions related to blood glucose levels in children. One formulation is suitable for use by individuals who wish to inhibit fat accumulation, or who have this need. Another formulation is also promising for the treatment of diseases or conditions related to fat accumulation in children.

[0173] In one embodiment, the composition is intended for consumption by infants or toddlers at or before weaning. In another embodiment, the composition of the present invention is intended for any of the following: improvement of motor function, reduction of blood triglycerides, reduction of blood glucose levels, and inhibition of fat accumulation in infants or toddlers. In a particularly preferred embodiment, the composition of the present invention is intended for consumption by infants or toddlers at or before weaning, for subsequent effects on the child, selected from any of the following: improvement of motor function, reduction of blood triglycerides, reduction of blood glucose levels, and inhibition of fat accumulation.

[0174] In one manner, the composition is suitable for consumption by subjects who wish to be artificially fed rather than breastfed, or subjects who require artificial feeding. The composition is also suitable for consumption by animals other than humans.

[0175] [Composition]

[0176] (Dosage form / form)

[0177] The compositions of this embodiment can be prepared in any form, such as solid, liquid, mixture, suspension, emulsion, gel, or sol. The compositions of this embodiment can be formulated into synthesized nutritional compositions by mixing various components. Synthesized nutritional compositions are sometimes simply referred to as nutritional compositions. Nutritional compositions do not contain biosynthesized substances, such as breast milk. Regarding this invention, when referring to compositions (including nutritional compositions) as for children, it means substances intended for consumption by children, excluding substances intended for consumption by pregnant women and lactating women.

[0178] In a particularly preferred embodiment, the composition is in the form of formula milk powder, formula liquid milk, or breast milk substitute. Formula milk powder refers to a substance made by processing raw milk, cow's milk, or specialty cow's milk, or foods made from them, or by using them as the main ingredient, adding nutrients required by infants, and forming it into a powder form. Formula liquid milk refers to a substance made by processing raw milk, cow's milk, or specialty cow's milk, or foods made from them, or by using them as the main ingredient, adding nutrients required by infants, and forming it into a liquid form.

[0179] Formula milk powder, liquid formula milk, or breast milk substitutes can be used for infants, follow-up formula, low birth weight infants, children, adults, the elderly, people with allergies, people with lactose intolerance, or people with congenital metabolic disorders. In Japan, follow-up formula refers to products designed to ensure a balanced intake of nutrients required from weaning at approximately 9 months of age until around 3 years of age, representing infancy and early childhood.

[0180] In one method, the formula milk powder is dissolved at 5-17%, preferably 8-16%, and more preferably 12-15%. The formula milk powder can be packaged in single doses (e.g., for dissolving in hot water to prepare 200 ml of milk) in strips or cubic shapes.

[0181] The compositions of this embodiment can also be formulated into compositions for use as food or medicine, other than formula milk powder, formula liquid milk, or breast milk substitutes. Unless otherwise stated, food or medicine includes not only for human use but also for use in animals other than humans. Unless otherwise stated, food includes general food, functional food, infant food, nutritional compositions, and also therapeutic food (food for therapeutic purposes; food prepared based on a doctor's prescribed diet or a menu created by a nutritionist, etc.), dietary therapy food, formula food, nursing food, and therapeutic adjunctive food. Unless otherwise stated, food includes not only solids but also liquids, such as beverages, health drinks, liquid foods, and soups. Functional food refers to food that can impart specified functions to an organism, including foods for specific health purposes (including conditionally formulated foods for specific health purposes), functionally labeled foods, health function foods including nutritional functional foods, foods for special purposes, nutritional supplements, health supplements, nutritional supplements (e.g., tablets, coated tablets, sugar-coated tablets, capsules, liquid preparations, etc.), beauty foods (e.g., weight loss foods), and all other health foods. Additionally, regarding this invention, functional foods include health foods with health claims applicable to food standards based on the Codex Alimentarius Commission (FAO / WHO Joint Committee on Food Standards). Cosmetics include medicated cosmetics.

[0182] When the composition of the embodiments is a food, it can be made into any form such as a nutritional supplement, snack, beverage, health drink, seasoning, dairy product, processed food, side dish, soup, etc. Specifically, the composition of the present invention can be made into forms such as gummy candies, tablets, health drinks, fermented milk, milk beverages, dairy drinks, soft drinks, ice cream, cheese, bread, biscuits, thin crispy biscuits, pizza crust, formula milk powder, liquid food, food for patients, nutritional food, frozen food, processed food, etc. In addition, it can also be made into granules, powders, pastes, concentrates, etc. for mixing or diluting with beverages or food to prepare beverages, etc. Specifically, it can be made into syrups for adding to milk.

[0183] When the composition of this embodiment is a drug, examples of specific forms include chewable tablets, sublingual tablets, tablets, pills, capsules, granules, powders, liquids, suspensions, emulsions, syrups, liniments, lotions, gels, aerosols, sprays, ointments, creams, patches, mud dressings, eye drops, nasal drops, and suppositories.

[0184] (Content / Dosage of Active Ingredient)

[0185] The content and concentration of the NAD precursor in the composition of this embodiment (or the total content and concentration when using multiple NAD precursors) need only be an amount sufficient to achieve the target effect, and can be appropriately set considering various factors such as the subject's age, weight, and target effect. It should be noted that, in this invention, unless otherwise stated, the amount or concentration of the NAD precursor in the composition is expressed as the amount / concentration in NMN. When using a NAD precursor other than NMN as the active ingredient, it is sufficient to use a precursor of NAD with an equimolar amount / equimolar concentration of NMN. This conversion can be easily performed by those skilled in the art. It should be noted that the following description uses NMN as an example to illustrate the amount or concentration, but this description can be appropriately understood by those skilled in the art to apply to the use of NAD precursors other than NMN.

[0186] When the composition of this embodiment is a solid, such as formula milk powder, the amount of NMN per 100g of the composition can be 0.05mg or more, preferably 0.1mg or more, more preferably 0.5mg or more, and even more preferably 1mg or more. Alternatively, the amount of NMN per 100g of the composition can be 1.1mg or more, 1.5mg or more, 2mg or more, 2.5mg or more, 3mg or more, 4mg or more, 4.5mg or more, 5mg or more, 6mg or more, 7mg or more, 8mg or more, 9mg or more, or 10mg or more.

[0187] When the composition of this embodiment is a solid, such as formula milk powder, the upper limit of the NMN content per 100g of composition can be set to 200mg or less, 100mg or less, 50mg or less, or 10mg or less. From the viewpoint of being within the range of amounts normally contained in breast milk, the NMN content per 100g of composition can be set to 16.1mg or less, or 13mg or less.

[0188] When the composition of this embodiment is a liquid, such as a formulated liquid emulsion, the NMN concentration of the composition can be set to 0.025 μg / mL or more, preferably 0.05 μg / mL or more, more preferably 0.25 μg / mL or more, even more preferably 0.5 μg / mL or more, even more preferably 0.85 μg / mL or more, and even more preferably 1.7 μg / mL or more. Alternatively, it can be set to 1.8 μg / mL or more, 2 μg / mL or more, 2.2 μg / mL or more, 2.4 μg / mL or more, 2.6 μg / mL or more, 3 μg / mL or more, 3.5 μg / mL or more, 3.7 μg / mL or more, 4 μg / mL or more, 4.3 μg / mL or more, 4.6 μg / mL or more, 5 μg / mL or more, and 5.5 μg / mL or more.

[0189] When the composition of this embodiment is a liquid, such as a formulated liquid milk, the upper limit of the NMN concentration in the composition can be set to 340 μg / mL or less, 170 μg / mL or less, 85 μg / mL or less, 25 μg / mL or less, 17 μg / mL or less, or 5 μg / mL or less. From the viewpoint of being within the range of amounts typically contained in breast milk, the NMN concentration is preferably 8.1 μg / mL or less, and can be set to 6.0 μg / mL or less, or 3.1 μg / mL or less.

[0190] The NMN content in the composition of this embodiment can be designed considering the daily NMN dosage. The daily dose of NMN can be set to 0.013 mg or more, preferably 0.25 mg or more, more preferably 0.43 mg or more, and even more preferably 0.85 mg or more. In addition, the daily dose of NMN can be set to 0.9 mg or more, 1 mg or more, 1.2 mg or more, 1.6 mg or more, 2 mg or more, 3 mg or more, 6 mg or more, 6.3 mg or more, 6.6 mg or more, 7 mg or more, 7.5 mg or more, or 8 mg or more.

[0191] The upper limit of the daily dose of NMN can be set to below 170 mg, 85 mg, 43 mg, 13 mg, 8.5 mg, or 2.5 mg. From the viewpoint of being within the range of amounts typically found in breast milk, the preferred daily dose of NMN is 8.1 mg or less, and it can also be set to 6.0 mg or less.

[0192] Such a daily dose can be divided into multiple portions, for example, into 3 to 7 portions suitable for 3 to 7 intakes per day.

[0193] The composition of this embodiment can be ingested at any time of day. When the composition of this embodiment is formula milk powder, formula liquid milk, or breast milk substitute, it can be used for breastfeeding in the same way as in the case of breastfeeding.

[0194] It is believed that NAD concentration in the body exhibits diurnal variation, and based on the view that it increases during the active period, in one approach, it is considered preferable to ingest more of the composition in the morning, which corresponds to the start of the active period.

[0195] (Other ingredients, additives)

[0196] In addition to the NAD precursor, the composition of this embodiment may also contain other nutrients acceptable as food or pharmaceutical ingredients. For example, when the composition is in the form of formula milk powder, formula liquid milk, or breast milk substitute, as components other than NMN, it may contain proteins, lipids, cholesterol, carbohydrates, niacin, pantothenic acid, biotin, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, zinc, sodium, potassium, calcium, selenium, iron, copper, magnesium, phosphorus, lactoglobulin, α-lactalbumin, β-lactoglobulin, ARA (arachidonic acid), DHA (docosahexaenoic acid), linoleic acid, α-linolenic acid, phospholipids, fructooligosaccharides, inositol, β-carotene, chlorine, carnitine, taurine, nucleotides, etc.

[0197] In addition to the precursor of NAD, the compositions of the present invention may also contain other active ingredients and nutrients acceptable as food or medicine.

[0198] In addition, the composition of this embodiment may also contain additives acceptable as food or pharmaceutical additives. Examples of such additives include inactive carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavorings, acidulants, and natural products.

[0199] (usage)

[0200] The composition of this embodiment is for oral administration. It can be administered non-orally, for example, via a tube (gastrostomy, enterostomy, etc.), or via the nose, but oral administration is preferred.

[0201] The composition of this embodiment can be repeatedly ingested by the subject, and can also be continuously ingested for a long period of time. There is no particular limitation on the duration, but to fully confirm the effect, it is preferable to continue ingestion for a longer period, such as more than one week, more than two weeks, more than one month, more than three months, more than six months, or more than one year. NMN, as the active ingredient, is a substance with long-term consumption experience, and NMN is naturally present in breast milk; therefore, the composition of this embodiment is particularly suitable for long-term ingestion.

[0202] (other)

[0203] The composition of this embodiment can be used in conjunction with the intake of other ingredients, health foods / nutritional supplements, exercise, regular diet, etc. Furthermore, the composition of this embodiment can be used in combination with any of the following therapies: those that promote improved athletic performance, those that promote the reduction of triglycerides in the blood, those that promote the reduction of blood glucose levels, and those that promote the inhibition of fat accumulation.

[0204] Those skilled in the art can readily manufacture the composition of this embodiment using existing equipment. In the manufacture of the composition of this embodiment, the NMN compounding stage is not particularly limited as long as it does not significantly impair the properties of NMN.

[0205] When the composition of this embodiment is in the form of formula milk powder, formula liquid milk, or breast milk substitute, it can also be manufactured using conventional methods. For example, in the case of formula milk powder, it can be manufactured as follows: A mixture of whey protein, casein, soy protein, sugars (lactose, oligosaccharides), minerals, vitamins, and oils (as fatty acids, including ARA, DHA, linoleic acid, α-linolenic acid, etc.) is blended, dissolved, mixed, and purified. Then, it is sterilized, concentrated, homogenized, and subjected to drying processes such as spray drying to obtain formula milk powder. In this case, there are no particular restrictions on the NMN blending stage as long as it does not significantly impair the properties of NMN.

[0206] For products containing the composition of this embodiment, the function and intended use can be indicated, and information recommending specific individuals for consumption or intake can also be provided. This indication can be direct or indirect. Examples of direct indication include descriptions on the product itself, packaging, containers, labels, and signs. Examples of indirect indication include advertising / promotional activities conducted through websites, shops, brochures, exhibitions, media seminars, books, newspapers, magazines, television, radio, mail, emails, audio, and other venues or means. Examples of indicated functions and intended uses include "helps improve athletic performance," "helps maintain athletic performance," "helps lower triglyceride levels in the blood," "helps maintain triglyceride levels in the blood at a low level," "helps lower blood sugar levels," "helps maintain low blood sugar levels," "helps inhibit fat accumulation," "for infants under 6 months of age," "for infants," and "for toddlers."

[0207] Example

[0208] By administering NMN to infant mice, we investigated whether it affected post-weaning motor development, blood triglyceride levels, blood glucose levels, and the accumulation of white adipose tissue (lipid metabolism).

[0209] [Examples 1-4: Common Method]

[0210] 1) The gift

[0211] β-Nicotinamide Mononucleotide (NMN) was dissolved in distilled water at a concentration of 100 mg / mL before being administered to mice.

[0212] 2) Animals

[0213] Ten female C57BL / 6J mice, 13 days into their pregnancy, were purchased. The mice were kept individually in a breeding room with a room temperature of 22±2℃, humidity of 55±15%, a light cycle of 7:00~19:00, and a dark cycle of 19:00~7:00 until the pups were born. After birth, the mice were kept in a group with their pups until weaning, and the newborn pups were used for experiments.

[0214] 3) NMN administration

[0215] All pups were sexed on the third day after birth, and divided into two groups based on a roughly 50 / 50 male-to-female ratio within the litter: one receiving distilled water (subsequent control group) and the other receiving NMN (subsequent NMN group). For the NMN-treated groups, NMN was administered orally at a volume of 10 μL per pup per day from the third to the thirteenth day after birth. From the fourteenth to the twenty-first day (the day of weaning), NMN was administered orally at a volume of 5 mL / kg body weight (dose 500 mg / kg body weight). For the distilled water-treated groups, the same volume and frequency of administration were administered orally.

[0216] [Example 1: Effects on motor development after weaning]

[0217] (method)

[0218] 1) Grouping

[0219] On the day of weaning, the weight of all pups was measured. Males were divided into a control group and an NMN group, and females were also divided into a control group and an NMN group, for a total of 4 groups (n=10 in each group). After weaning, pups were fed according to standard feeding practices until the day their grip strength, spontaneous movement, and average moving speed were measured.

[0220] 2) Grip strength measurement

[0221] Three weeks after weaning, grip strength (forelimbs only) was measured in all individuals using a mouse / rat grip strength meter (MK-380CM / F, Muromachi Machinery Co., Ltd.). Ten measurements were performed on each individual, and the highest value was recorded. Grip strength values ​​were calculated using the individual's body weight as a correction.

[0222] 3) Measurement of spontaneous movement / average movement speed

[0223] Two weeks after weaning, all individuals underwent an open field test to measure spontaneous movement and average movement speed. Mice were placed in an open field test chamber (Shinfactory) and their free movement for 10 minutes was recorded. The spontaneous movement (total distance traveled) and average movement speed (average of movement speed excluding stationary states) were calculated from the obtained video using dedicated analysis software (SMART 3.0, Panlab).

[0224] (result)

[0225] 1) Grip strength

[0226] Compared with the control group, the grip strength of both females and males was higher in the NMN group. Figure 1-1 ).

[0227] 2) Spontaneous movement volume / average movement speed

[0228] Compared with the control group, the NMN group showed higher spontaneous movement and average movement speed when both males and females were compared together. Figure 1-2 ).

[0229] (Inspection)

[0230] NMN administration during infancy increased grip strength, spontaneous movement, and average walking speed after weaning. It has been reported that in mice with high expression of SIRT1 (Feldman JL, Dittenhafer-Reed KE, Denu JM. J Biol Chem. 2012; 287:42419-42427), skeletal muscle function and spontaneous movement were improved (see aforementioned Non-Patent Literature 1); and in clinical trials involving NMN intervention, motor ability was improved (see aforementioned Non-Patent Literature 2). Therefore, it is believed that in this experiment, the increased NAD+ levels in the brain and skeletal muscle due to NMN administration during infancy promoted skeletal muscle growth / development, thereby increasing muscle strength and thus improving motor ability.

[0231] (in conclusion)

[0232] This invention clarifies that administering NMN during infancy can improve motor abilities such as grip strength, spontaneous movement, and average speed after weaning. This invention contributes to elucidating the physiological significance of NMN contained in breast milk and is beneficial for the healthy growth and development of many children.

[0233] [Example 2: Effect on blood triglyceride levels after weaning]

[0234] (method)

[0235] 1) Grouping

[0236] On the day of weaning, the weight of the pups was measured. Males were divided into two groups: a control group (n=7) and an NMN group (n=5). After weaning, the pups were fed normally for two weeks, and plasma was separated from the blood obtained through whole blood sampling.

[0237] 2) Determination of triglyceride concentration

[0238] Triglyceride concentrations were determined using separated plasma and a kit (Triglyceride E-test Wako: No. 432-40201).

[0239] (result)

[0240] Blood triglyceride concentration

[0241] Compared with the control group, the NMN group showed a tendency to have lower blood triglyceride concentrations. Figure 2 ).

[0242] (Inspection)

[0243] Administration of NMN during infancy resulted in a reduction in blood triglyceride concentrations after weaning. It has been reported that administration of NMN to mice fed a high-fat diet improved lipid metabolism and reduced triglyceride levels in the liver (see Non-Patent Literature 3 above). Therefore, it is believed that in this study, the reduction in blood triglyceride concentrations may have been due to the effect of NMN administration during infancy on lipid metabolism.

[0244] (in conclusion)

[0245] It has been established that administering NMN during infancy reduces blood triglycerides after weaning. This invention contributes to elucidating the physiological significance of NMN in breast milk and is useful for the healthy growth and development of many children.

[0246] [Example 3: Effect on blood glucose levels after weaning]

[0247] (method)

[0248] 1) Grouping

[0249] On the day of weaning, the weight of the pups was measured. Males were divided into two groups: a control group (n=7) and an NMN group (n=5). After weaning, the pups were fed normally for two weeks, and plasma was separated from the blood obtained through whole blood sampling.

[0250] 2) Measurement of blood glucose levels

[0251] Using separated plasma, the blood glucose concentration (blood glucose level) was measured with a kit (Glucose II-Test Wako: No. 439-90901).

[0252] (result)

[0253] blood sugar level

[0254] Compared with the control group, the blood glucose level in the NMN group was significantly lower. Figure 3 ).

[0255] (Inspection)

[0256] Administering NMN during infancy resulted in low blood glucose levels after weaning. Studies have reported improved glucose tolerance and increased GLP-1 production in digestive tract tissues in mice fed a high-fat diet after NMN administration (Non-Patent Literature 3, 4). Therefore, it is believed that in this study, the effect of NMN administration during infancy on glucose tolerance (glucose metabolism) may have been due to its influence on blood glucose levels.

[0257] (in conclusion)

[0258] This invention clarifies that administering NMN during infancy can lower post-weaning blood sugar levels. It contributes to elucidating the physiological significance of NMN in breast milk and is beneficial for the healthy growth and development of many children.

[0259] [Example 4: Effects on the accumulation of white adipose tissue (lipid metabolism) after weaning]

[0260] (method)

[0261] Grouping, white fat weight determination

[0262] On the day of weaning, the weight of all pups was measured. Males were divided into a control group (n=7) and an NMN group (n=5), and females were also divided into a control group (n=3) and an NMN group (n=5), for a total of 4 groups. After weaning, the pups were fed normally for 2 weeks, then dissected, and the white adipose tissue around the reproductive organs was removed and weighed. The weight of the white adipose tissue was corrected for the individual's body weight to calculate the relative weight value.

[0263] (result)

[0264] White fat weight

[0265] Compared with the control group, the weight of white adipose tissue was lower in both females and males in the NMN group. Figure 4 ).

[0266] (Inspection)

[0267] Administration of NMN during infancy suppressed the accumulation of white adipose tissue after weaning. Studies have reported improvements in glucose tolerance and lipid metabolism, as well as increased GLP-1 production in digestive tract tissues, in mice fed a high-fat diet after NMN administration (see aforementioned non-patent literature 3, 4). Therefore, it is believed that in this study, the inhibition of white adipose tissue accumulation may have been due to the effects of NMN administration during infancy on glucose tolerance and lipid metabolism.

[0268] (in conclusion)

[0269] It has been established that administering NMN during infancy inhibits the accumulation of white fat after weaning. This invention contributes to clarifying the physiological significance of NMN contained in breast milk and is useful for the healthy growth and development of many children.

[0270] [Example of formula milk powder manufacturing]

[0271] For raw materials, NMN is added to the final product (in the case of formula milk powder dissolved at a concentration of 5-17% (w / v)) at a concentration of 0.1-100mg / 100g, for example 16.2-100mg / 100g. After dissolving, mixing, and purifying the milk using conventional methods, the raw materials are sterilized, concentrated, homogenized, and spray-dried to obtain formula milk powder.

[0272] Industrial availability

[0273] According to the present invention, a pharmaceutical composition or food composition, or a method for manufacturing a pharmaceutical or food, capable of continuously improving children's athletic ability in the future, can be provided. According to the present invention, a pharmaceutical composition or food composition, or a method for manufacturing a pharmaceutical or food, capable of continuously reducing children's blood triglyceride levels in the future, can be provided. According to the present invention, a pharmaceutical composition or food composition, or a method for manufacturing a pharmaceutical or food, capable of continuously reducing children's blood glucose levels in the future, can be provided. According to the present invention, a pharmaceutical composition or food composition, or a method for manufacturing a pharmaceutical or food, capable of continuously inhibiting children's fat accumulation in the future, can be provided. Furthermore, according to the present invention, it is expected to achieve nutritional improvements for numerous children, ensure healthy lives, and promote welfare.

Claims

1. A nutritional composition for children comprising a precursor of nicotinamide adenine dinucleotide (NAD), the composition being used to promote the development of children, said development being selected from any aspect of improved motor skills, reduced blood triglycerides, reduced blood glucose levels, and inhibition of fat accumulation.

2. The composition according to claim 1, wherein the composition is for improving athletic ability, and the improvement of athletic ability is selected from any group of compositions that promote the development and activity of skeletal muscles.

3. The composition according to claim 1, wherein the composition is for improving athletic ability, and the improvement in athletic ability is measured by selecting any one of the group consisting of increased muscle strength, increased spontaneous movement, and increased movement speed.

4. The composition according to claim 1, wherein, Promoting children's development means promoting the development of children after weaning.

5. The composition according to claim 1, wherein, Promoting children's development means promoting the development of children over 3 years old.

6. The composition according to any one of claims 1 to 5, for use in infants or young children.

7. The composition according to any one of claims 1 to 5, for use in children during and before weaning.

8. The composition according to any one of claims 1 to 5, wherein it is in any form selected from the group consisting of formula milk powder, formula liquid milk and breast milk substitute foods.

9. The composition according to any one of claims 1 to 5, wherein, The precursor to NAD is nicotinamide mononucleotide (NMN).

10. The composition according to claim 9, wherein, The concentration of NMN during ingestion is above 0.05 μg / mL.

11. The composition according to claim 9, which is in the form of formula milk powder and contains more than 0.1 mg of NMN per 100g.

12. A composition comprising a precursor of nicotinamide adenine dinucleotide (NAD), said composition for use in children during and before weaning to promote development in children after weaning.

13. The composition according to claim 12, wherein, Promoting children's development is selected from any one of the following: improving motor skills, lowering blood triglycerides, lowering blood glucose levels, and inhibiting fat accumulation.

Images