WO2017179707A1 - Combination for improving frailty - Google Patents

Combination for improving frailty Download PDF

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Publication number
WO2017179707A1
WO2017179707A1 PCT/JP2017/015316 JP2017015316W WO2017179707A1 WO 2017179707 A1 WO2017179707 A1 WO 2017179707A1 JP 2017015316 W JP2017015316 W JP 2017015316W WO 2017179707 A1 WO2017179707 A1 WO 2017179707A1
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WIPO (PCT)
Prior art keywords
combination
vitamin
zinc
present
milk protein
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PCT/JP2017/015316
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French (fr)
Japanese (ja)
Inventor
公一郎 角
欣也 芦田
高橋　毅
伊藤　裕之
省二 新開
諭 清野
Original Assignee
株式会社明治
地方独立行政法人 東京都健康長寿医療センター
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Publication of WO2017179707A1 publication Critical patent/WO2017179707A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum

Definitions

  • the present invention relates to a novel combination for improving flail.
  • Non-patent Document 1 A flail is an intermediate state proposed by the Japan Geriatrics Society between a healthy state and a state requiring nursing care (a state requiring support in daily life). "Frail” is a Japanese translation of Frailty, and Japanese translations such as "weak", “old age”, “weakness”, and “fragile” have been used so far.
  • a decrease in skeletal muscle mass due to aging can be cited as a central risk factor for flail (Non-patent Document 2).
  • it is known that mental health also affects the flail cycle that causes the flail to deteriorate in a chain, such as activity and nutrient intake (non-patented). Reference 2).
  • Non-Patent Document 6 it has been shown that ingestion of protein in combination with muscle strength training can effectively increase skeletal muscle mass not only in young people but also in elderly people.
  • Non-Patent Document 7 research is being conducted to increase the effect of muscle training by supplementing with an amino acid composition having an increased leucine content, which has a particularly strong protein synthesis stimulating action.
  • amino acids such as leucine are more expensive than proteins, and since they are inferior in flavor, it is not easy for elderly people to continue to take them.
  • Non-Patent Document 9 when the daily milk protein supplement was 15 g, protein supplementation did not contribute to the increase in muscle mass (Non-patent Document 8), and the effect was set at a high level of 30 g.
  • Patent Document 1 describes the use of whey protein or vitamin D as a nutritional intervention that helps prevent loss of muscle mass as a method of attenuating loss of functional status including exercise health and nutritional intervention. .
  • Patent Document 2 describes an amino acid composition for oral use for preventing or improving skeletal muscle loss in the elderly, containing L-leucine in a molar composition ratio of 35 to 57% in the total essential amino acids. .
  • Patent Document 3 describes an oral amino acid composition for preventing or improving skeletal muscle loss in the elderly, which contains L-leucine in a molar composition ratio of 35 to 66% in the total essential amino acids. .
  • Patent Document 4 discloses a muscle atrophy inhibitor containing zinc aspartate or magnesium aspartate as an active ingredient.
  • Patent Document 5 discloses a method of using a composition containing a protein substance in the manufacture of a medicament for the treatment of a subject suffering from insulin resistance, wherein the protein substance is at least 24% of the energy value. And at least 12% by weight or more of leucine based on the proteinaceous substance is described.
  • Patent Document 6 discloses a composition for increasing muscle containing a hydrolyzate of wheat protein.
  • Patent Document 7 discloses drinking water containing mineral components (excluding phosphorus), and by weight blending ratio, sodium 8.3, potassium 33.0, magnesium 3.1, calcium 3.8, iron 0. 3. A composition of 0.09 zinc is described.
  • Non-Patent Document 10 when middle-aged and older men were divided into four groups: a control group, a nutrition group, an exercise group, and an exercise + nutrition group, skim milk enriched with vitamin D as a nutritional intervention was ingested. There is no significant difference between the exercise group and the exercise + nutrition group, and it is described that vitamin D-enriched skim milk has no effect of further enhancing the skeletal muscle mass, strength, and function improvement effects of exercise.
  • Non-patent document 11 shows that IGF-1 involved in skeletal muscle synthesis is increased by ingesting protein to the frail elderly, and further ingesting zinc earlier compared to protein alone. It has been suggested that IGF-1 is elevated. There is no exercise intervention here.
  • Non-Patent Document 12 two groups of elderly people who require reduced muscle mass are subject to exercise. One is exercise only, and the other is exercise 3 times a week in addition to exercise. It has been described that when “active” was ingested for 3 months, skeletal muscle mass was not changed by exercise alone, but when penpal active was ingested, the muscle mass increased by 5.4%. It is described that penpal active contains 10 g of protein (BCAA content is 2.5 g), vitamin D 12.5 ⁇ g, zinc 28 mg, etc. per 125 mL (200 kcal) serving. Here, the subject is elderly people requiring care.
  • Non-Patent Document 13 the effects of a combined intervention program consisting of exercise, nutritional guidance, and hot spring bathing were compared with non-intervention groups for elderly people over 65 years old. It is described that the score is improving but the muscle mass is not improved.
  • Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial J Am Med Dir 71913 Sonja Kukuljan et al. Effect of resistance exercise and fortified milk on skeletal muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial. J Appl Physiol 2009; 107: 1864-1 A. Rodondi et al. Zinc increases the effect of essential amino acids-whey protein supplements in frail elderly. The Journal of Nutrition, Health & Aging 2009; 13 (6): 491-497 M Yamada et al. Nutritional supplementation during resistance training improved skeletal muscle mass in community-dwelling frail older adults. The Journal of Frailty & Aging 2012; 1 (2): 64-70 Sakurai et al. Study on effectiveness of combined intervention program using hot spring facilities -Study by randomized controlled trial-
  • An object of the present invention is to provide a novel combination for improving flail, which comprises milk protein and effectively improves flail.
  • the present inventors have found that flair can be effectively improved when ingested in combination with milk protein, zinc, and vitamin D.
  • a combination for improving flail comprising milk protein, zinc and vitamin D.
  • the combination according to (1) further comprising vitamin B12 and folic acid.
  • the combination according to (1) or (2), wherein the milk protein is whole milk protein.
  • the combination according to any one of (1) to (3), wherein the milk protein content is 1 to 15 g.
  • the combination according to any one of (1) to (4), wherein the zinc content is 1 to 40 mg.
  • a method for improving flail comprising the step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
  • the method according to (16), wherein the combination further comprises vitamin B12 and folic acid.
  • the method according to (16) or (17), wherein the milk protein is whole milk protein.
  • the method according to any one of (16) to (18), wherein the milk protein content in the combination is 1 to 15 g.
  • the method according to any one of (16) to (19), wherein the zinc content in the combination is 1 to 40 mg.
  • a method for improving mental health comprising a step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
  • a method for reducing the risk of flail comprising the step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
  • a method for reducing the risk of skeletal muscle mass reduction comprising a step of causing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
  • the following invention is provided.
  • (30) Use of milk protein, zinc and vitamin D in the manufacture of a combination for improving flail.
  • (31) The use according to (30), wherein the combination further comprises vitamin B12 and folic acid.
  • (32) The use according to (30) or (31), wherein the milk protein is a whole milk protein.
  • (33) The use according to any one of (30) to (32), wherein the milk protein content in the combination is 1 to 15 g.
  • (35) The use according to any one of (30) to (34), wherein the vitamin D content in the combination is 1 to 100 ⁇ g.
  • the following invention is provided.
  • (4) Milk protein, zinc and vitamin D for use in the manufacture of a combination for improving flail.
  • (45) The milk protein, zinc and vitamin D according to (44), wherein the combination further comprises vitamin B12 and folic acid.
  • (46) The milk protein, zinc and vitamin D according to (44) or (45), wherein the milk protein is a whole milk protein.
  • (47) The milk protein, zinc and vitamin D according to any one of (44) to (46), wherein the milk protein content in the combination is 1 to 15 g.
  • (48) The milk protein, zinc and vitamin D according to any one of (44) to (47), wherein the zinc content in the combination is 1 to 40 mg.
  • Milk protein, zinc and vitamin D for use in the production of a combination for improving skeletal muscle mass reduction.
  • Milk protein, zinc and vitamin D for use in the manufacture of a combination for improving mental health.
  • Milk protein, zinc and vitamin D for use in the manufacture of a combination for reducing the risk of flail.
  • Milk protein, zinc and vitamin D for use in the manufacture of a combination for reducing the risk of skeletal muscle mass loss.
  • the target flail can be remarkably improved by ingesting the combination of the present invention.
  • the subject's skeletal muscle mass reduction can be advantageously improved by ingesting the combination of the present invention.
  • a decrease in sensitivity to protein synthesis stimulation can be improved by ingesting the combination of the present invention.
  • the combination of this invention can improve mental health advantageously.
  • the combination of the present invention uses a milk protein that is relatively inexpensive and excellent in flavor as a protein source, and therefore provides a dose and / or flavor that can be easily incorporated into a daily meal.
  • the combination of the present invention is advantageous in that it reduces skeletal muscle loss when ingested by elderly people who practice exercises such as low to medium strength muscle strength training that are easy to continue. Furthermore, the combination of the present invention is advantageous in that it improves mental health when taken by elderly people who practice exercises such as low-to-medium strength training that are easy to continue. Furthermore, the combination of the present invention suppresses the flail cycle from both physical and mental aspects when ingested by elderly people who practice exercises such as low-to-medium strength strength training that are easy to continue This is advantageous in improving flail.
  • the combination for improving flail according to the present invention is characterized by containing milk protein, zinc, and vitamin D.
  • the combination for improving flail of the present invention may further contain vitamin B12 and folic acid.
  • the milk protein blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and examples thereof include whole milk protein, whey protein, casein, milk fat globule membrane protein, and the like. It is a whole milk protein.
  • the content of leucine in the milk protein is not particularly limited as long as the effect of the present invention is not hindered, but is preferably less than 10% by mass.
  • the form of the milk protein blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, the milk raw material may remain as it is, and the milk protein purified from the milk raw material may be used. Form may be sufficient.
  • milk raw materials include milk, skim milk, butter, unsalted butter, butter oil, cream, cream powder, butter milk, skim milk powder, whole milk powder, spinach milk, concentrated milk, skim milk concentrate, Concentrated whey, whey powder, milk protein concentrate, whey protein concentrate, lactose, or combinations thereof.
  • Milk raw materials or milk proteins purified from milk raw materials may be blended singly or in combination of two or more.
  • a milk raw material that is commercially available and distributed as a food raw material or food additive can be used as a milk protein.
  • the content of milk protein in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but as a content of the milk protein itself, a viewpoint of providing a tasty milk protein-containing combination at low cost. Therefore, it is preferably 1 to 15 g, more preferably 5 to 13 g, and still more preferably 9 to 12 g.
  • the milk protein content in the combination product of the present invention can be measured by, for example, the Kjeldahl method described in “Food Hygiene Inspection Guidelines, Physical and Chemical Editing” (supervised by the Ministry of Health and Welfare, Health Sanitation Bureau).
  • the form of zinc to be blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be contained in the combination in the form of a salt.
  • Specific examples of such zinc include zinc chloride, zinc sulfate, zinc gluconate, and yeast zinc. Preferred are zinc gluconate and yeast zinc, and more preferred is zinc gluconate.
  • zinc that is commercially available and distributed as a food additive, a preparation containing zinc, and the like can be used.
  • the content of zinc in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of zinc itself is preferably 1 to 40 mg, more preferably 4 to 20 mg. More preferably, it is 6 to 10 mg.
  • the zinc content in the combination of the present invention can be measured by, for example, the atomic absorption spectrophotometry described in “Food Hygiene Inspection Guidelines, RIKEN” (supervised by the Ministry of Health and Welfare, Health Sanitation Bureau).
  • vitamin D blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered.
  • Specific examples of such vitamin D include ergocalciferol (VD2), cholecalciferol (VD3), calcidiol, calcitriol, doxel calciferol, calcipotriene, preferably VD2, VD3, more preferably VD3.
  • vitamin D marketed and distributed as a food additive, a preparation containing vitamin D, and the like can be used.
  • the vitamin D content in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of vitamin D itself is preferably 1 to 100 ⁇ g, more preferably 2 to 20 ⁇ g. More preferably 3 to 8 ⁇ g.
  • the content of vitamin D in the combination of the present invention can be measured by, for example, HPLC method according to the procedure described in Takebayashi Jun et al. Vitamin 2011; 85 (12): 645-650.
  • the form of folic acid blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered.
  • Specific examples of such folic acid include folic acid, 5-methyltetrahydrofolic acid, methyl 5-methyltetrahydrofolate, and the like, with folic acid being preferred.
  • folic acid that is commercially available and distributed as a food additive, a preparation containing folic acid, and the like can be used.
  • the content of folic acid in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of folic acid itself is preferably 50 to 1000 ⁇ g, more preferably 70 to 500 ⁇ g, More preferably, it is 100 to 300 ⁇ g.
  • the content of folic acid in the combination product of the present invention can be measured, for example, by the microorganism quantification method described in the “Fiveth Supplement Japanese Food Standard Component Table Analysis Manual” (published by the National Printing Bureau).
  • vitamin B12 blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered.
  • Specific examples of such vitamin B12 include methylcobalamin, hydroxocobalamin, adenosylcobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin and the like, preferably cyanocobalamin.
  • vitamin B12 commercially available as a food additive and a preparation containing vitamin B12 can be used.
  • the content of vitamin B12 in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of vitamin B12 itself is preferably 0.1 to 100 ⁇ g, more preferably 1 to 50 ⁇ g, more preferably 5 to 20 ⁇ g.
  • the content of vitamin B12 in the combination of the present invention can be determined by, for example, microbiological quantification method (for food labeling standards (Notified on March 30, 2015, Table 139, Deputy Director of Consumer Affairs Agency) ( Http://www.caa.go.jp/foods/pdf/151224_tuchi4-betu2.pdf p121-123).
  • the mass ratio of zinc and vitamin D to zinc is preferably 1: 0.95 to 1: 1, more preferably 1: 0.97 to 1: 0. .9999, more preferably 1: 0.999 to 1: 0.9995.
  • the mass ratio of the sum of zinc and vitamin D to vitamin D is preferably 1: 0.00003 to 1: 0.5, more preferably 1: 0.0001 to 1: 0.01, and more preferably 1: 0.0005 to 1: 0.001.
  • the mass ratio of the sum of zinc and vitamin D to milk protein is preferably 1: 200 to 1: 8000, more preferably 1: 300 to 1: 5000, More preferably, it is 1: 500 to 1: 2000.
  • the mass ratio of zinc, vitamin D, vitamin B12, and folic acid to zinc is preferably 1: 0.5 to 1: 1, more preferably 1: 0. .6 to 1: 1, more preferably 1: 0.97 to 1: 1.
  • the mass ratio of zinc, vitamin D, vitamin B12 and folic acid to vitamin D is preferably 1: 0.00003 to 1: 0.05, more preferably It is 1: 0.0001 to 1: 0.01, more preferably 1: 0.0005 to 1: 0.001.
  • the mass ratio of zinc, vitamin D, vitamin B12 and folic acid to vitamin B12 is preferably 1: 0.00001 to 1: 0.05, more preferably It is 1: 0.00001 to 1: 0.01, more preferably 1: 0.001 to 1: 0.005.
  • the mass ratio of zinc, vitamin D, vitamin B12, and folic acid to folic acid is preferably 1: 0.001 to 1: 0.4, more preferably 1 : 0.005 to 1: 0.1, more preferably 1: 0.01 to 1: 0.03.
  • the mass ratio of the total of zinc, vitamin D, vitamin B12, and folic acid to milk protein is preferably 1: 200 to 1: 7000, more preferably 1: 500 to 1: 5000, more preferably 1: 1000 to 1: 2000.
  • the combination of the present invention may contain other vitamins such as vitamin A, vitamin E, vitamin B1, vitamin B2, niacin, vitamin B6, pantothenic acid, vitamin C, and / or other minerals together with the above ingredients, For example, sodium, calcium, iron, copper, selenium and the like may be further included.
  • the combination of the present invention is at least one selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, niacin, vitamin B6, pantothenic acid, vitamin C, sodium, calcium, iron, copper and selenium. For example, all of them.
  • the combination of the present invention may contain 150 to 1800 ⁇ g RE of vitamin A, preferably 300 to 900 ⁇ g RE, 7.5 to 90 mg, preferably 15 to 45 mg of vitamin E, and 0.8 to 0.8 of vitamin B1. 9.0 mg, preferably 1.5 to 4.5 mg, vitamin B2 1.0 to 12.0 mg, preferably 2.0 to 6.0 mg, niacin 8 to 96 mg NE, preferably 16 -48 mg NE, vitamin B6 2-30 mg, preferably 3-12 mg, pantothenic acid 3-36 mg, preferably 6-18 mg, vitamin C 100-800 mg, preferably 200-500 mg May be included.
  • the combination of the present invention may also contain, for example, 40-640 mg sodium, preferably 80-320 mg, 75-1400 mg calcium, preferably 150-700 mg, 1.5-30 mg iron, preferably It may contain 3.5-15 mg, 0.1-1.6 mg copper, preferably 0.2-0.8 mg, and 6-72 ⁇ g, preferably 12-36 ⁇ g selenium.
  • the combination of the present invention may further contain lipids, carbohydrates, proteins other than milk proteins, ash and the like.
  • the combination of the present invention may further comprise at least one selected from the group consisting of lipids, carbohydrates and proteins other than milk protein, and ash, such as all of them.
  • the combination of the present invention may contain 1 to 16 g, preferably 2 to 8 g of lipid, 5 to 80 g, preferably 10 to 40 g of carbohydrate, and 0.18 to 10 of protein other than milk protein. 0.0g, preferably 0.35 to 5.0g, and ash content 0.15 to 1.8g, preferably 0.3 to 0.9g.
  • the combination of the present invention can be provided as a combination of the above ingredients and optionally orally acceptable additives.
  • Orally acceptable additives include aqueous media such as water, solvents, solubilizers, lubricants, emulsifiers, tonicity agents, stabilizers, preservatives, preservatives, surfactants, regulators, chelates Agents, pH adjusters, buffers, excipients, thickeners, colorants, fragrances or fragrances.
  • the combination of the present invention can be prepared by a known method such as mixing, dissolving, dispersing, or suspending the above components.
  • the mixture, solution, dispersion, suspension, etc. of each of the above components may be subjected to homogenization treatment or sterilization treatment as long as the effects of the present invention are not hindered. Good.
  • the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be in the form of one composition or agent, and is composed of a combination of a plurality of compositions or agents. Also good. Moreover, the said combination may be comprised integrally or as a different body. Examples of the combination of the plural or separate compositions include, for example, a combination of a composition comprising milk protein and a composition comprising zinc and vitamin D, or a composition comprising milk protein. And a combination of zinc, vitamin D, vitamin B12 and a composition comprising folic acid.
  • the form of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, and may be solid, semi-solid or liquid, but is preferably solid or liquid, It is more preferable that it is liquid from the viewpoint of ease of intake and flavor.
  • the combination of the present invention is a combination of a plurality of compositions or agents, the form of each composition or each agent may be the same or different.
  • the volume of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, and may be, for example, 50 to 5000 mL, preferably 100 to 1000 mL, more preferably 100 to 500 mL, 200 to 400 mL is preferred.
  • the weight of the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be, for example, 50 to 5000 g, preferably 100 to 1000 g, more preferably 100 to 500 g. More preferably, it is 200 to 400 g.
  • capacitance or weight shows the sum total of the combination, when the combination of this invention is a combination of a some composition or agent.
  • the combination of the present invention is preferably provided as a unit of daily oral intake.
  • the daily oral intake of milk protein, zinc and vitamin D, or the daily oral intake of milk protein, zinc, vitamin D, vitamin B12 and folic acid in the combination of the present invention is as described above in the combination. It can be the same as the content of.
  • the combination of the present invention consists of units of daily oral intake and comprises 1 to 15 g of milk protein, 1 to 40 mg of zinc, and 1 to 100 ⁇ g of vitamin D. Or 1 to 15 g of milk protein, 1 to 40 mg of zinc, 1 to 100 ⁇ g of vitamin D, 0.1 to 100 ⁇ g of vitamin B12, and 50 to 1000 ⁇ g of folic acid.
  • the content of the above milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 and folic acid is preferably the content per 100 to 1000 mL of the combination of the present invention. More preferably, the content per 100 to 500 mL of the combination of the present invention, and still more preferably the content per 200 to 400 mL of the combination of the present invention.
  • the combination of the present invention is preferably provided in a package form.
  • the packaging form is not particularly limited, and examples thereof include packs and containers.
  • the container used can be provided in a normal form such as a molded container mainly composed of polyethylene terephthalate, a metal can, or a bottle.
  • the combination of the present invention when it is in a liquid state, it can be drunk without dilution, for example, by filling the container.
  • the surface of the packaging may be labeled with ingredients, dosage and usage, etc., with specific functions such as improving flail and reducing skeletal muscle mass. It may be attached. Suitable examples of such packaging forms include supplements, pharmaceutical preparations, foods, beverages and the like.
  • the display may be affixed to the combination of the present invention itself, or may be affixed to a container, packaging material or package insert containing the combination of the present invention.
  • the display includes information related to the combination of the present invention, such as flyers, brochures, pops, catalogs, posters, books, DVDs, storage media, electronic bulletin boards, advertisements on the Internet, etc. May be displayed / advertised to be effective.
  • the combination of the present invention can advantageously improve flail (also referred to as weakness, aging, weakness, or fragility). Therefore, according to one preferable aspect of the combination of the present invention, it is provided as a combination for improving flail (weakness, senility, weakness, or fragility) or reducing the risk of becoming flail or a condition requiring care.
  • the combination of the present invention can advantageously improve skeletal muscle mass reduction, it is also provided as a combination for sarcopenia improvement or skeletal muscle mass reduction or sarcopenia risk reduction.
  • the combination of the present invention is provided as a combination for improving mental health or improving mental health.
  • specific mental aspects (psychological symptoms) of flail include decreased motivation, depression, delirium, dementia, sleep disorder, anxiety disorder, withdrawal, fatigue, and the like.
  • the above-mentioned combination for improving mental health or improving mental health can improve mental health or improve psychological state. It is also provided as a combination for reducing the risk.
  • a method for improving flail which is an effective amount of milk protein, zinc, and vitamin D, or an effective amount of milk protein, zinc, vitamin D, vitamin B12, and folic acid.
  • a subject preferably ingested
  • a method is provided that includes ingesting a subject in need thereof.
  • the method is provided as a method for improving the decrease in skeletal muscle mass.
  • the method is provided as a method for improving mental health.
  • “improvement” not only includes the meaning of the improvement of the condition or symptom in the subject, or the reversal, prevention or delay of the progression of the condition or symptom, but also prepares in advance for the assumed deterioration, It also includes the meaning of “prevention” to prevent the occurrence of symptoms.
  • the “effective amount” can be set in the same manner as each component of the combination. Specifically, the “effective amount” means the content of milk protein, zinc, and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 in the unit of daily oral intake of the combination. And the content of folic acid and the like. And in the method of this invention, according to one aspect, the medical action with respect to a human is excluded.
  • the method for improving flail the method for improving the decrease in skeletal muscle mass, the method for improving the mental health level, etc., when the subject is a healthy person or a human who is flailed, is not treated except for medical practice.
  • Method. One method for determining whether or not the flared state is that Fried et al. Defined the frailty ((1) weight loss, (2) subjective fatigue, (3) decreased daily activities, (4) (Linda P. Fried et al., Frailty in Older Adults: Evidence for a Phenotype. J Gerontol A) Biol Sci Med Sci 2001; 56: M146-56).
  • the method of ingestion of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but preferably, tube ingestion (nasal ingestion, gastric fistula etc.), oral ingestion, is there.
  • Examples of the combination of the present invention include pharmaceuticals, quasi-drugs, supplements, cosmetics, foods and drinks such as foods or drinks including foods for specified health use, nutritional functional foods or functionally labeled foods, nutrition bars, jelly-forms
  • Examples include provision of foods and powdered beverages, and beverages are preferable from the viewpoint of ease of intake and flavor.
  • each component of the combination of the present invention may be ingested simultaneously by the subject, or may be ingested separately by the subject.
  • the constituents of the combination are preferably milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 and folic acid.
  • the usage of the combination of the present invention depends on the type of subject, age, gender, degree of flail, degree of skeletal muscle mass loss, or degree of mental health unless the effects of the present invention are disturbed. Those skilled in the art can appropriately set. Further, the daily intake of the combination of the present invention may be ingested by the subject once, or may be ingested by the subject multiple times. Therefore, the number of daily intakes as a combination of the present invention is 1 to 5 times a day, preferably 1 to 3 times a day, more preferably once a day. .
  • the timing of ingestion of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but it is not necessary to ingest before and after exercise, and can be ingested with a normal meal.
  • the combination of the present invention is a combination of a plurality of compositions
  • the plurality of compositions may be ingested simultaneously by the subject, or may be ingested separately by the subject.
  • the subject of the present invention is preferably a human, more preferably a healthy or flared human.
  • the age of the subject of the present invention is not particularly limited as long as the effect of the present invention is not hindered.
  • skeletal muscle mass reduction and / or improvement of flail in an elderly person for example, a human 65 years or older
  • it can be used particularly advantageously in improving mental health the elderly are preferred.
  • the subject of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the flail is improved and / or the skeletal muscle mass is reduced and / or the mental health is improved.
  • it is preferably a human who is exercising, and more preferably an elderly person who is exercising (for example, a human 65 years or older).
  • the exercise is preferably an exercise that can be easily continued, such as walking (especially rapid walking), jogging, running, swimming, strength training, and the like, and more preferably strength training.
  • the strength training is not particularly limited as long as the effects of the present invention are not hindered, but low to medium strength strength training is preferable from the viewpoint of continuity.
  • the low-to-medium strength training means, for example, training at a strength of 40 to 70% (low strength to medium strength) of the maximum lifting weight and / or 10-level omnibus resistance exercise scale (OMNI- RES) Question sheet (0 very easy-2 easy-4 slightly easy-6 slightly tight-8 tight-10 very tight (limit)) and the subject feels "slightly tight” (5-7) training is there.
  • Examples of the muscular strength training include training using its own weight, rubber band, and the like. Specific training contents include arm curls (biceps curl), shoulder lateral and front raises, pull downs, and rubber bands for the upper limbs. Rowing (rowing).
  • Targeting the trunk includes knee lift, knees, hip lifts, and front elbow bridge in the sitting position.
  • Each exercise is performed 20 times x 2 sets, and it is preferable to increase the load with a rubber band or the like so that it becomes an intensity that feels “slightly tight” individually.
  • a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid in the manufacture of a combination for improving flail Use is provided.
  • a combination of folic acid a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, in the manufacture of a combination for improving mental health.
  • a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid as a combination for improving flail Is provided.
  • a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin as a combination for improving mental health Provided as the use of a combination of B12 and folic acid.
  • Also according to another aspect of the present invention is the use of a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid for improving flail.
  • a combination of milk protein, zinc and vitamin D or milk protein, zinc, vitamin D, vitamin B12, and Use of a combination of folic acid is provided.
  • a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 for improving mental health. And the use of a combination of folic acid is provided.
  • a combination of milk protein, zinc, and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12, and folic acid is included in the combination.
  • a method for producing a combination for improving flail is provided.
  • a combination of milk protein, zinc and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid is incorporated in the combination. It is provided as a method for producing a combination for improving skeletal muscle mass reduction.
  • a combination of milk protein, zinc and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid is combined. It is provided as a method of producing a combination for improving mental health,
  • a combination of milk protein, zinc, and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12, and folic acid (active ingredient) for improving flail As)) is provided.
  • a combination of milk protein, zinc, and vitamin D, or milk protein, zinc, vitamin D, vitamin B12, and folic acid is used to improve the decrease in skeletal muscle mass.
  • a combination comprising (as active ingredients) is used to improve the decrease in skeletal muscle mass.
  • a combination comprising (as active ingredients) a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12, and Provided as a combination comprising (as an active ingredient) a combination of folic acid.
  • compositions can be carried out according to the description of the composition and method of the present invention.
  • Example 1 Production raw material water of test sample 1 , milk raw material (fat concentrated milk (manufactured by Meiji), cream (manufactured by Meiji), milk protein concentrate (manufactured by Fontera)), flavor, antioxidant
  • the agent vitamin E was blended and mixed thoroughly before homogenization.
  • the obtained solution was sterilized and then cooled to prepare a liquid test sample 1 (milk base).
  • the composition of test sample 1 is shown in Table 1.
  • Example 2 Production raw material water of test sample 2 was mixed with iron (sodium ferrous citrate (Sanferol): manufactured by Eisai Food Chemical Co., Ltd.), zinc (zinc gluconate (Hercious Zn): Fuso Chemical Industry Co., Ltd.) )), Folic acid (DSM Nutoritional Products), vitamin B12 (cyanocobalamin: DSM Nutoritional Products), vitamin D (cholecalciferol: DSM Nutoritional Products), mandarin orange, orange juice, ginseng juice, sweetener, flavoring, A pH adjusting agent and the like were blended and mixed thoroughly before homogenization. The obtained solution was sterilized and then cooled to prepare a liquid test sample 2. The composition of Test Sample 2 is shown in Table 2.
  • Test Example 1 Exercise / Nutrition Intervention Test for Healthy Elderly People 78 men and women of healthy elderly people (65 to 80 years old) were exercised (40 people, 7 of whom were male) and exercise + nutritional group (38 The group was divided into two groups: 5 people). Both groups were given a study consisting of exercise classes twice a week and daily exercise habits. The strength training conducted in this exercise class was performed using rubber bands and weights, gradually increasing the strength as needed so that the above-mentioned elderly felt “slightly tight” on the OMNI-RES questionnaire. Specific training contents include arm curls (biceps curl), shoulder lateral and front raises, pull downs, and rubber bands for the upper limbs. We performed rowing (rowing).
  • the leucine concentration in plasma was measured before and after the start of the above test and compared before and after the start of the test. Specifically, before and after the start of the above test, blood was collected from elderly people after fasting overnight to obtain plasma. The leucine concentration in the obtained plasma was measured by the HPLC / ESI-MS method according to the method of Shimbo et al. (Biomedical® Chromatography® 2010; 24 (7): 683-691).
  • the plasma leucine concentration before the start of the test and after the end of the test is shown in FIG.
  • the plasma leucine concentration before the start of the above test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 102.5 ⁇ 2.6%, exercise group: 94.5 ⁇ 2.0%).
  • the plasma leucine concentration after the end of the test was significantly lower than the plasma leucine concentration before the start of the test.
  • the exercise + nutrition group the plasma leucine concentration was maintained between before the start of the test and after the end of the test. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
  • lean body mass was measured by the double energy X-ray absorption method as an index of skeletal muscle mass, and compared before and after the start of the test.
  • the lean body mass before the start of the test and after the end of the test is shown in FIG. In FIG. 2, the lean body mass before the start of the above test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 100.5 ⁇ 0.3%, exercise group: 98.9 ⁇ 0.3%).
  • the lean body mass in the exercise group after the test was significantly lower than the lean body weight before the start of the test.
  • the exercise + nutrition group lean body mass was maintained between before and after the start of the test. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
  • Skeletal muscle index (SMI) before and after the start of the test was calculated and compared before and after the start of the test.
  • This SMI was calculated by the limb lean mass / (height) 2 which is generally used.
  • the limb lean mass was measured by the double energy X-ray absorption method.
  • FIG. 3 shows the SMI ratio after the end of the test when the SMI before the start of the test is 100%. Data show mean ⁇ standard error (exercise + nutrition group: 101.2 ⁇ 0.6%, exercise group: 98.8 ⁇ 0.4%). According to FIG. 3, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
  • Serum 25-hydroxyvitamin D (25- (OH) vitamin D) concentration is measured by radioimmunoassay (2-antibody method) using the serum obtained by the standard method before and after the start of the above test.
  • 25- (OH) vitamin D is one of vitamin D metabolites and is an indicator of vitamin D nutritional status.
  • the serum 25- (OH) vitamin D concentration before the start of the test and after the end of the test is shown in FIG. In FIG. 5, the serum 25- (OH) vitamin D concentration before the start of the test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 159.0 ⁇ 7.9%, exercise group: 131.7 ⁇ 7.0%). According to FIG. 5, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between exercise + nutrition group and exercise group was analyzed by Student's t-test.
  • Serum vitamin B12 concentration was measured by chemiluminescence enzyme immunoassay using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
  • the serum vitamin B12 concentration before the start of the above test and after the end of the above test is shown in FIG.
  • the serum vitamin B12 concentration before the start of the test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 123.5 ⁇ 5.4%, exercise group: 99.6 ⁇ 2.9%). According to FIG. 6, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
  • Serum folate concentration was measured by chemiluminescent enzyme immunoassay using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
  • the serum folate concentration before the start of the above test and after the end of the above test is shown in FIG.
  • the serum folic acid concentration before the start of the above test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 247.3 ⁇ 17.5%, exercise group: 114.4 ⁇ 4.5%). According to FIG. 7, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
  • Serum zinc concentration was measured by atomic absorption spectrometry using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
  • the serum zinc concentration before the start of the test and after the end of the test is shown in FIG. In FIG. 8, the serum zinc concentration before the start of the above test is 100%.
  • Data show mean ⁇ standard error (exercise + nutrition group: 97.3 ⁇ 1.7%, exercise group: 95.5 ⁇ 1.8%). According to FIG. 8, although the change is not significant in the exercise + nutrition group, the zinc concentration is significantly decreased in the exercise only group.
  • the statistically significant difference between before and after the start of the test was analyzed by a paired t test.
  • Test Example 1 As described above, in Test Example 1, it was confirmed that the concentration of 25- (OH) -vitamin D, vitamin B12, and folic acid in the blood increased significantly in the exercise + nutrition group compared to the exercise group. . In addition, it was confirmed that the decrease in blood zinc concentration was suppressed in the exercise + nutrition group.
  • Test Sample 1 and Test Sample 2 of the present invention can improve sarcopenia by incorporating them into life together with a level of strength training that they can continue. . Also, considering the results of the WHO-5 score, Test Sample 1 and Test Sample 2 of the present invention simultaneously improved sarcopenia and improved psychological state, and were shown to be effective as a method for improving flail. .

Abstract

The present invention provides a novel combination for improving frailty or a novel combination for suppressing reduction in skeletal muscle mass. More specifically, the present invention provides a combination for improving frailty or a combination for suppressing reduction in skeletal muscle mass, said combination comprising milk proteins, zinc and vitamin D.

Description

フレイル改善用組み合わせ物Combination for flail improvement 関連出願の参照Reference to related applications
　本特許出願は、２０１６年４月１４日に出願された日本国特許出願２０１６－０８１４５３号に基づく優先権の主張を伴うものであり、かかる先の特許出願における全開示内容は、引用することにより本明細書の一部とされる。 This patent application is accompanied by a claim of priority based on Japanese Patent Application No. 2016-081453 filed on Apr. 14, 2016, the entire disclosure of which is hereby incorporated by reference It is made a part of this specification.
　本発明は、新規なフレイル改善用組み合わせ物に関する。 The present invention relates to a novel combination for improving flail.
　世界的に社会の高齢化は大きな問題となっており、健康長寿を達成することが喫緊の課題となっている。高齢者の健康長寿が妨げられる要因の1つとして、年齢の増加と共にフレイルの比重が大きくなることが示唆されている（非特許文献１）。フレイルとは、日本老年医学会が提唱している、健常な状態と要介護状態（日常生活でサポートが必要な状態）の中間の状態のことである。「フレイル」はFrailtyの日本語訳であって、これまで、「虚弱」、「老衰」、「衰弱」、「脆弱」等の日本語訳も用いられてきた。フレイルの中心的なリスクファクターとして加齢による骨格筋量の減少（サルコペニア）が挙げられる（非特許文献２）。また、上述のサルコペニアのような身体的な側面に加え、精神的な健康度も活動量や栄養摂取量などフレイルを連鎖的に悪化させるフレイルサイクルに影響を及ぼすことが知られている（非特許文献２）。 The global aging of society has become a major problem, and achieving healthy longevity is an urgent issue. As one of the factors that hinder the health and longevity of the elderly, it has been suggested that the specific gravity of flail increases with age (Non-patent Document 1). A flail is an intermediate state proposed by the Japan Geriatrics Society between a healthy state and a state requiring nursing care (a state requiring support in daily life). "Frail" is a Japanese translation of Frailty, and Japanese translations such as "weak", "old age", "weakness", and "fragile" have been used so far. A decrease in skeletal muscle mass due to aging (sarcopenia) can be cited as a central risk factor for flail (Non-patent Document 2). In addition to the physical aspects such as sarcopenia described above, it is known that mental health also affects the flail cycle that causes the flail to deteriorate in a chain, such as activity and nutrient intake (non-patented). Reference 2).
　サルコペニアを予防する取り組みとしては運動療法と栄養的介入が中心的な役割を果たすと考えられている。骨格筋量は骨格筋におけるタンパク質合成と分解のバランスによって規定される。タンパク質合成の亢進には食事によるたんぱく質の摂取が主な役割を担っている。たんぱく質の摂食により、血中のアミノ酸濃度が増加し、骨格筋の合成が刺激される。この効果はとくにロイシンに顕著に認められる。高齢者においては、骨格筋のタンパク質分解は若齢者と同等であるが、食事（またはロイシン）によるタンパク質合成刺激に対する感受性が低下していること（anabolic resistance）が示唆されており（非特許文献３）、正味の骨格筋代謝が負となる。これがサルコペニアの一因であると考えられている（非特許文献４）。 運動 Exercise therapy and nutritional intervention are considered to play a central role in preventing sarcopenia. Skeletal muscle mass is defined by the balance of protein synthesis and degradation in skeletal muscle. Dietary protein intake plays a major role in enhancing protein synthesis. Protein intake increases blood amino acid levels and stimulates skeletal muscle synthesis. This effect is particularly noticeable with leucine. In elderly people, skeletal muscle proteolysis is similar to that in young people, but it is suggested that the sensitivity to protein synthesis stimulation by diet (or leucine) is reduced (anabolic resistance) (Non-patent literature) 3) Net skeletal muscle metabolism is negative. This is considered to be a cause of sarcopenia (Non-Patent Document 4).
　また、骨格筋に十分な強度の筋力トレーニングを負荷すると骨格筋のタンパク質合成と分解は共に亢進する。その際に十分な栄養があると、タンパク質合成が更に高まり、骨格筋代謝のバランスは正となる。そのため、筋力トレーニングを長期間にわたって継続すると骨格筋量は増大する。高齢者においても若齢者と同様に筋力トレーニングの有用性が認められており、高強度の筋力トレーニング（例えば８０％最大挙上重量を８～１２回/セット×２～３セット/週）は高齢者の骨格筋量減少を防止できることが示唆されている。一方、自体重やラバーバンドを用いた低～中強度の筋力トレーニングの効果は明確ではない（非特許文献５）。しかしながら、高齢者にとって高強度の筋力トレーニングを継続することは、身体的、精神的、環境的に難しいのが現状といえる。 Also, when sufficient strength training is applied to skeletal muscle, both skeletal muscle protein synthesis and degradation increase. If there is sufficient nutrition at that time, protein synthesis will increase further and the balance of skeletal muscle metabolism will be positive. Therefore, skeletal muscle mass increases when muscle strength training is continued for a long period of time. The effectiveness of strength training is recognized in the elderly as well as the young, and high-intensity strength training (for example, 80% maximum lifting weight 8-12 times / set x 2-3 sets / week) It has been suggested that skeletal muscle mass loss in the elderly can be prevented. On the other hand, the effect of low-to-medium strength muscle strength training using its own weight or rubber band is not clear (Non-Patent Document 5). However, it can be said that it is physically difficult for elderly people to continue high-intensity strength training physically, mentally, and environmentally.
　さらに、筋力トレーニングと組み合わせて、たんぱく質を摂取すると、若齢者のみならず高齢者においても効果的に骨格筋量を増加しうることが示されている（非特許文献６）。しかしながら、上述のように、高齢者ではanabolic resistanceが認められることから、若齢者と同様の利益を得るためには、若齢者以上のたんぱく質を摂取せねばならず、現実的ではない。そこで、特にタンパク質合成刺激作用の強いロイシン含量を高めたアミノ酸組成物を補給することで筋力トレーニングの効果を高めるとの研究が進められている（非特許文献７）。しかしながら、ロイシンなどのアミノ酸はたんぱく質と比較して高価であり、また、風味に劣ることから、高齢者が継続して摂取し続けるのは容易ではない。 Furthermore, it has been shown that ingestion of protein in combination with muscle strength training can effectively increase skeletal muscle mass not only in young people but also in elderly people (Non-Patent Document 6). However, as described above, since anabolic resistance is observed in the elderly, in order to obtain the same benefits as those of young people, it is necessary to ingest proteins higher than young people, which is not realistic. Therefore, research is being conducted to increase the effect of muscle training by supplementing with an amino acid composition having an increased leucine content, which has a particularly strong protein synthesis stimulating action (Non-patent Document 7). However, amino acids such as leucine are more expensive than proteins, and since they are inferior in flavor, it is not easy for elderly people to continue to take them.
　また、筋力トレーニングの効果を増強するために、たんぱく質源として比較的安価であり風味に優れた乳たんぱく質を利用することも知られているが、これまでの筋力トレーニングと乳たんぱく質補給を組み合わせた介入試験では、1日あたりの乳たんぱく質補給量が１５gでは筋肉量の増加にたんぱく質の補給は寄与せず（非特許文献８）、効果があったとされるのは３０gという高レベルで設定されたものである（非特許文献９）。 In addition, it is also known to use relatively inexpensive milk protein with excellent flavor as a protein source to enhance the effect of strength training, but it is an intervention that combines conventional strength training and milk protein supplementation. In the test, when the daily milk protein supplement was 15 g, protein supplementation did not contribute to the increase in muscle mass (Non-patent Document 8), and the effect was set at a high level of 30 g. (Non-Patent Document 9).
　一方で、近年、種々の健康増進機能を有する、たんぱく質やアミノ酸を含有する経口製品が報告されている。例えば、特許文献１には、運動健康法と栄養介入を含む機能状態の喪失を減弱する方法として、筋肉量の喪失予防を助ける栄養介入としてホエーたんぱく質またはビタミンＤなどを用いることが記載されている。 On the other hand, in recent years, oral products containing proteins and amino acids having various health promotion functions have been reported. For example, Patent Document 1 describes the use of whey protein or vitamin D as a nutritional intervention that helps prevent loss of muscle mass as a method of attenuating loss of functional status including exercise health and nutritional intervention. .
　また、特許文献２には、Ｌ－ロイシンを総必須アミノ酸中のモル組成比で３５～５７％含有する高齢者の骨格筋減少を防止または改善するための経口用アミノ酸組成物が記載されている。 Patent Document 2 describes an amino acid composition for oral use for preventing or improving skeletal muscle loss in the elderly, containing L-leucine in a molar composition ratio of 35 to 57% in the total essential amino acids. .
　また、特許文献３には、Ｌ－ロイシンを総必須アミノ酸中のモル組成比で３５～６６％含有する高齢者の骨格筋減少を防止または改善するための経口用アミノ酸組成物が記載されている。 Patent Document 3 describes an oral amino acid composition for preventing or improving skeletal muscle loss in the elderly, which contains L-leucine in a molar composition ratio of 35 to 66% in the total essential amino acids. .
　また、特許文献４には、アスパラギン酸亜鉛またはアスパラギン酸マグネシウムを有効成分とする筋萎縮抑制剤が記載されている。 Patent Document 4 discloses a muscle atrophy inhibitor containing zinc aspartate or magnesium aspartate as an active ingredient.
　また、特許文献５には、インスリン抵抗性を患う対象の処置の為の医薬の製造における、たんぱく性物質を含む組成物を使用する方法であって、該たんぱく性物質がエネルギー値の少なくとも２４％を与え、かつ、たんぱく性物質に基づき少なくとも１２重量％以上のロイシンを与えることが記載されている。 Patent Document 5 discloses a method of using a composition containing a protein substance in the manufacture of a medicament for the treatment of a subject suffering from insulin resistance, wherein the protein substance is at least 24% of the energy value. And at least 12% by weight or more of leucine based on the proteinaceous substance is described.
　また、特許文献６には、小麦たんぱく質の加水分解物を含有する、筋肉増加用組成物が記載されている。 Patent Document 6 discloses a composition for increasing muscle containing a hydrolyzate of wheat protein.
　また、特許文献７には、ミネラル成分（リンを除く）を含有する飲料水で、重量配合比で、ナトリウム８．３、カリウム３３．０、マグネシウム３．１、カルシウム３．８、鉄０．３、亜鉛０．０９である組成が記載されている。 Patent Document 7 discloses drinking water containing mineral components (excluding phosphorus), and by weight blending ratio, sodium 8.3, potassium 33.0, magnesium 3.1, calcium 3.8, iron 0. 3. A composition of 0.09 zinc is described.
　また、非特許文献１０には、中高年の男性を対照群、栄養摂取群、運動群、運動＋栄養摂取群の４群に分けて栄養介入としてビタミンＤを強化した脱脂乳を摂取させたところ、運動群と運動＋栄養群では大きな差異は認められず、ビタミンＤ強化脱脂乳に運動による骨格筋量、強度、機能改善効果を更に増強する効果はなかったことが記載されている。 In Non-Patent Document 10, when middle-aged and older men were divided into four groups: a control group, a nutrition group, an exercise group, and an exercise + nutrition group, skim milk enriched with vitamin D as a nutritional intervention was ingested. There is no significant difference between the exercise group and the exercise + nutrition group, and it is described that vitamin D-enriched skim milk has no effect of further enhancing the skeletal muscle mass, strength, and function improvement effects of exercise.
　また、非特許文献１１には、虚弱な高齢者に対したんぱく質を摂取させることにより、骨格筋合成に関与するＩＧＦ－１が増加し、更に亜鉛を摂取することでたんぱく質のみと比較して早期にＩＧＦ－１が高まることが示唆されている。ここで、運動介入はしていない。 Non-patent document 11 shows that IGF-1 involved in skeletal muscle synthesis is increased by ingesting protein to the frail elderly, and further ingesting zinc earlier compared to protein alone. It has been suggested that IGF-1 is elevated. There is no exercise intervention here.
　また、非特許文献１２には、２グループの筋量低下が認められる要介護高齢者を対象として、片方には運動のみ、もう片方には運動に加えて週３回、高機能流動食「ペンパルアクティブ」を３ヵ月摂取させたところ、運動のみでは骨格筋量が変化しなかったのに対し、ペンパルアクティブを摂取させると５．４％筋量が増加したことが記載されている。ペンパルアクティブは、１回分１２５ｍＬ（２００ｋｃａｌ）あたり、たんぱく質１０ｇ（ＢＣＡＡ含量は２．５ｇ）、ビタミンＤ　１２．５μｇ、亜鉛２８ｍｇ等を含むことが記載されている。ここで、対象は要介護高齢者である。 In Non-Patent Document 12, two groups of elderly people who require reduced muscle mass are subject to exercise. One is exercise only, and the other is exercise 3 times a week in addition to exercise. It has been described that when “active” was ingested for 3 months, skeletal muscle mass was not changed by exercise alone, but when penpal active was ingested, the muscle mass increased by 5.4%. It is described that penpal active contains 10 g of protein (BCAA content is 2.5 g), vitamin D 12.5 μg, zinc 28 mg, etc. per 125 mL (200 kcal) serving. Here, the subject is elderly people requiring care.
　また、非特許文献１３には、６５歳以上の高齢者を対象として運動、栄養指導、温泉入浴からなる複合介入プログラムの効果を非介入群と比較検討したところ、介入により身体機能やＷＨＯ－５スコアが改善傾向であるが、筋量は改善していないことが記載されている。 In Non-Patent Document 13, the effects of a combined intervention program consisting of exercise, nutritional guidance, and hot spring bathing were compared with non-intervention groups for elderly people over 65 years old. It is described that the score is improving but the muscle mass is not improved.
　以上のように、乳たんぱく質、亜鉛、およびビタミンＤを組み合わせて摂取すると、フレイルを効果的に改善させうる技術的手段は報告されていない。 As described above, no technical means that can effectively improve flail when ingested in combination with milk protein, zinc, and vitamin D has not been reported.
特表２０１２－５３３６２７号公報Special table 2012-533627 gazette 特開２０１２－１３１８１９号公報JP 2012-131819 A 特表２００８－５３４５９９号公報Special table 2008-534599 特表２０１２－１８０３４７号公報Special table 2012-180347 gazette 特開２０１３－１３９４７０号公報JP 2013-139470 A 特開２０１２－０６２３０９号公報JP 2012-062309 A 特開２０１１－２２５４７５号公報JP 2011-225475 A
　本発明は、乳たんぱく質を含んでなる、フレイルを効果的に改善させる新規なフレイル改善用組み合わせ物を提供することを目的とする。 An object of the present invention is to provide a novel combination for improving flail, which comprises milk protein and effectively improves flail.
　本発明者らは、乳たんぱく質、亜鉛、およびビタミンＤを組み合わせて摂取すると、フレイルを効果的に改善することを見出した。 The present inventors have found that flair can be effectively improved when ingested in combination with milk protein, zinc, and vitamin D.
　本発明によれば、以下の発明が提供される。
（１）乳たんぱく質、亜鉛およびビタミンＤを含む、フレイル改善用組み合わせ物。
（２）ビタミンＢ１２および葉酸をさらに含む、（１）に記載の組み合わせ物。
（３）乳たんぱく質が全乳たんぱく質である、（１）または（２）に記載の組み合わせ物。
（４）乳たんぱく質の含有量が１～１５ｇである、（１）～（３）のいずれか一つに記載の組み合わせ物。
（５）亜鉛の含有量が１～４０ｍｇである、（１）～（４）のいずれか一つに記載の組み合わせ物。
（６）ビタミンＤの含有量が１～１００μｇである、（１）～（５）のいずれか一つに記載の組み合わせ物。
（７）ビタミンＢ１２の含有量が０．１～１００μｇである、（２）～（６）のいずれか一つに記載の組み合わせ物。
（８）葉酸の含有量が５０～１０００μｇである、（２）～（７）のいずれか一つに記載の組み合わせ物。
（９）高齢者のための、（１）～（８）のいずれか一つに記載の組み合わせ物。
（１０）運動を行っているヒトのための、（１）～（９）のいずれか一つに記載の組み合わせ物。
（１１）組成物である、（１）～（１０）のいずれか一つに記載の組み合わせ物。
（１２）前記組成物が飲食品である、（１１）に記載の組み合わせ物。
（１３）前記飲食品が飲料である、（１２）に記載の組み合わせ物。
（１４）乳たんぱく質、亜鉛およびビタミンＤを含む、骨格筋量減少改善用組み合わせ物。
（１５）乳たんぱく質、亜鉛およびビタミンＤを含む、精神的健康度向上用組み合わせ物。 According to the present invention, the following inventions are provided.
(1) A combination for improving flail, comprising milk protein, zinc and vitamin D.
(2) The combination according to (1), further comprising vitamin B12 and folic acid.
(3) The combination according to (1) or (2), wherein the milk protein is whole milk protein.
(4) The combination according to any one of (1) to (3), wherein the milk protein content is 1 to 15 g.
(5) The combination according to any one of (1) to (4), wherein the zinc content is 1 to 40 mg.
(6) The combination according to any one of (1) to (5), wherein the content of vitamin D is 1 to 100 μg.
(7) The combination according to any one of (2) to (6), wherein the content of vitamin B12 is 0.1 to 100 μg.
(8) The combination according to any one of (2) to (7), wherein the content of folic acid is 50 to 1000 μg.
(9) The combination according to any one of (1) to (8) for elderly people.
(10) The combination according to any one of (1) to (9), for a human performing exercise.
(11) The combination according to any one of (1) to (10), which is a composition.
(12) The combination according to (11), wherein the composition is a food or drink.
(13) The combination according to (12), wherein the food or drink is a beverage.
(14) A combination for improving skeletal muscle mass reduction, comprising milk protein, zinc and vitamin D.
(15) A combination for improving mental health, comprising milk protein, zinc and vitamin D.
　また、本発明によれば、以下の発明が提供される。
（１６）乳たんぱく質、亜鉛およびビタミンＤを含む、組み合わせ物の有効量を対象に摂取させる工程を含む、フレイルを改善するための方法。
（１７）前記の組み合わせ物が、ビタミンＢ１２および葉酸をさらに含む、（１６）に記載の方法。
（１８）前記乳たんぱく質が全乳たんぱく質である、（１６）または（１７）に記載の方法。
（１９）前記の組み合わせ物中の乳たんぱく質の含有量が１～１５ｇである、（１６）～（１８）のいずれか一つに記載の方法。
（２０）前記の組み合わせ物中の亜鉛の含有量が１～４０ｍｇである、（１６）～（１９）のいずれか一つに記載の方法。
（２１）前記の組み合わせ物中のビタミンＤの含有量が１～１００μｇである、（１６）～（２０）のいずれか一つに記載の方法。
（２２）前記の組み合わせ物中のビタミンＢ１２の含有量が０．１～１００μｇである、（１７）～（２１）のいずれか一つに記載の方法。
（２３）前記の組み合わせ物中の葉酸の含有量が５０～１０００μｇである、（１７）～（２２）のいずれか一つに記載の方法。
（２４）高齢者のための、（１６）～（２３）のいずれか一つに記載の方法。
（２５）運動を行っているヒトのための、（１６）～（２４）のいずれか一つに記載の方法。
（２６）乳たんぱく質、亜鉛およびビタミンＤを含む、組み合わせ物の有効量を対象に摂取させる工程を含む、骨格筋量の減少を改善するための方法。
（２７）乳たんぱく質、亜鉛およびビタミンＤを含む、組み合わせ物の有効量を対象に摂取させる工程を含む、精神的健康度を向上させるための方法。
（２８）乳たんぱく質、亜鉛およびビタミンＤを含む、組み合わせ物の有効量を対象に摂取させる工程を含む、フレイルのリスクを低下させるための方法。
（２９）乳たんぱく質、亜鉛およびビタミンＤを含む、組み合わせ物の有効量を対象に摂取させる工程を含む、骨格筋量の減少のリスクを低下させるための方法。 Moreover, according to this invention, the following invention is provided.
(16) A method for improving flail, comprising the step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
(17) The method according to (16), wherein the combination further comprises vitamin B12 and folic acid.
(18) The method according to (16) or (17), wherein the milk protein is whole milk protein.
(19) The method according to any one of (16) to (18), wherein the milk protein content in the combination is 1 to 15 g.
(20) The method according to any one of (16) to (19), wherein the zinc content in the combination is 1 to 40 mg.
(21) The method according to any one of (16) to (20), wherein the vitamin D content in the combination is 1 to 100 μg.
(22) The method according to any one of (17) to (21), wherein the vitamin B12 content in the combination is 0.1 to 100 μg.
(23) The method according to any one of (17) to (22), wherein the content of folic acid in the combination is 50 to 1000 μg.
(24) The method according to any one of (16) to (23), for an elderly person.
(25) The method according to any one of (16) to (24), for a human performing exercise.
(26) A method for improving a decrease in skeletal muscle mass, comprising a step of causing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
(27) A method for improving mental health, comprising a step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
(28) A method for reducing the risk of flail, comprising the step of allowing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
(29) A method for reducing the risk of skeletal muscle mass reduction, comprising a step of causing a subject to take an effective amount of a combination comprising milk protein, zinc and vitamin D.
　また、本発明によれば、以下の発明が提供される。
（３０）フレイル改善用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。
（３１）前記の組み合わせ物が、ビタミンＢ１２および葉酸をさらに含む、（３０）に記載の使用。
（３２）前記乳たんぱく質が全乳たんぱく質である、（３０）または（３１）に記載の使用。
（３３）前記の組み合わせ物中の乳たんぱく質の含有量が１～１５ｇである、（３０）～（３２）のいずれか一つに記載の使用。
（３４）前記の組み合わせ物中の亜鉛の含有量が１～４０ｍｇである、（３０）～（３３）のいずれか一つに記載の使用。
（３５）前記の組み合わせ物中のビタミンＤの含有量が１～１００μｇである、（３０）～（３４）のいずれか一つに記載の使用。
（３６）前記の組み合わせ物中のビタミンＢ１２の含有量が０．１～１００μｇである、（３１）～（３５）のいずれか一つに記載の使用。
（３７）前記の組み合わせ物中の葉酸の含有量が５０～１０００μｇである、（３１）～（３６）のいずれか一つに記載の使用。
（３８）高齢者のための、（３０）～（３７）のいずれか一つに記載の使用。
（３９）運動を行っているヒトのための、（３０）～（３８）のいずれか一つに記載の使用。
（４０）骨格筋量減少改善用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。
（４１）精神的健康度向上用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。
（４２）フレイルのリスクの低下用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。
（４３）骨格筋量の減少のリスクの低下用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。 Moreover, according to this invention, the following invention is provided.
(30) Use of milk protein, zinc and vitamin D in the manufacture of a combination for improving flail.
(31) The use according to (30), wherein the combination further comprises vitamin B12 and folic acid.
(32) The use according to (30) or (31), wherein the milk protein is a whole milk protein.
(33) The use according to any one of (30) to (32), wherein the milk protein content in the combination is 1 to 15 g.
(34) The use according to any one of (30) to (33), wherein the zinc content in the combination is 1 to 40 mg.
(35) The use according to any one of (30) to (34), wherein the vitamin D content in the combination is 1 to 100 μg.
(36) The use according to any one of (31) to (35), wherein the content of vitamin B12 in the combination is 0.1 to 100 μg.
(37) The use according to any one of (31) to (36), wherein the content of folic acid in the combination is 50 to 1000 μg.
(38) The use according to any one of (30) to (37), for an elderly person.
(39) The use according to any one of (30) to (38), for a human performing exercise.
(40) Use of milk protein, zinc and vitamin D in the production of a combination for improving skeletal muscle mass reduction.
(41) Use of milk protein, zinc and vitamin D in the manufacture of a combination for improving mental health.
(42) Use of milk protein, zinc and vitamin D in the manufacture of a combination for reducing the risk of flail.
(43) Use of milk protein, zinc and vitamin D in the manufacture of a combination for reducing the risk of skeletal muscle mass loss.
　また、本発明によれば、以下の発明が提供される。
（４４）フレイル改善用組み合わせ物の製造に使用するための、乳たんぱく質、亜鉛およびビタミンＤ。
（４５）前記の組み合わせ物が、ビタミンＢ１２および葉酸をさらに含む、（４４）に記載の乳たんぱく質、亜鉛およびビタミンＤ。
（４６）前記乳たんぱく質が全乳たんぱく質である、（４４）または（４５）に記載の乳たんぱく質、亜鉛およびビタミンＤ。
（４７）前記の組み合わせ物中の乳たんぱく質の含有量が１～１５ｇである、（４４）～（４６）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（４８）前記の組み合わせ物中の亜鉛の含有量が１～４０ｍｇである、（４４）～（４７）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（４９）前記の組み合わせ物中のビタミンＤの含有量が１～１００μｇである、（４４）～（４８）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（５０）前記の組み合わせ物中のビタミンＢ１２の含有量が０．１～１００μｇである、（４５）～（４９）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（５１）前記の組み合わせ物中の葉酸の含有量が５０～１０００μｇである、（４５）～（５０）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（５２）高齢者のための、（４４）～（５１）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（５３）運動を行っているヒトのための、（４４）～（５２）のいずれか一つに記載の乳たんぱく質、亜鉛およびビタミンＤ。
（５４）骨格筋量減少改善用組み合わせ物の製造に使用するための、乳たんぱく質、亜鉛およびビタミンＤ。
（５５）精神的健康度向上用組み合わせ物の製造に使用するための、乳たんぱく質、亜鉛およびビタミンＤ。
（５６）フレイルのリスク低下用組み合わせ物の製造に使用するための、乳たんぱく質、亜鉛およびビタミンＤ。
（５７）骨格筋量の減少のリスク低下用組み合わせ物の製造に使用するための、乳たんぱく質、亜鉛およびビタミンＤ。 Moreover, according to this invention, the following invention is provided.
(44) Milk protein, zinc and vitamin D for use in the manufacture of a combination for improving flail.
(45) The milk protein, zinc and vitamin D according to (44), wherein the combination further comprises vitamin B12 and folic acid.
(46) The milk protein, zinc and vitamin D according to (44) or (45), wherein the milk protein is a whole milk protein.
(47) The milk protein, zinc and vitamin D according to any one of (44) to (46), wherein the milk protein content in the combination is 1 to 15 g.
(48) The milk protein, zinc and vitamin D according to any one of (44) to (47), wherein the zinc content in the combination is 1 to 40 mg.
(49) The milk protein, zinc and vitamin D according to any one of (44) to (48), wherein the content of vitamin D in the combination is 1 to 100 μg.
(50) The milk protein, zinc and vitamin D according to any one of (45) to (49), wherein the content of vitamin B12 in the combination is 0.1 to 100 μg.
(51) The milk protein, zinc and vitamin D according to any one of (45) to (50), wherein the content of folic acid in the combination is 50 to 1000 μg.
(52) The milk protein, zinc and vitamin D according to any one of (44) to (51) for elderly people.
(53) The milk protein, zinc and vitamin D according to any one of (44) to (52), for a human performing exercise.
(54) Milk protein, zinc and vitamin D for use in the production of a combination for improving skeletal muscle mass reduction.
(55) Milk protein, zinc and vitamin D for use in the manufacture of a combination for improving mental health.
(56) Milk protein, zinc and vitamin D for use in the manufacture of a combination for reducing the risk of flail.
(57) Milk protein, zinc and vitamin D for use in the manufacture of a combination for reducing the risk of skeletal muscle mass loss.
　また、本発明によれば、以下の発明が提供される。
（５８）上記組み合わせ物が一体的にまたは別体として構成されている、（１）に記載の組み合わせ物。 Moreover, according to this invention, the following invention is provided.
(58) The combination according to (1), wherein the combination is configured integrally or as a separate body.
　本発明によれば、本発明の組み合わせ物を対象に摂取させることにより、顕著に対象のフレイルを改善することができる。また、本発明の組み合わせ物を対象に摂取させることにより、対象の骨格筋量減少を有利に改善することができる。本発明によれば、本発明の組み合わせ物を対象に摂取させることにより、タンパク質合成刺激に対する感受性の低下を改善することができる。また、本発明の組み合わせ物は、精神的健康度を有利に向上することができる。また、本発明の組み合わせ物は、たんぱく質源として比較的安価であり風味に優れた乳たんぱく質を利用していることから、毎日の食事に無理なく組み込むことのできる用量および／または風味を提供することができる点で有利である。さらに、本発明の組み合わせ物は、継続することが容易な低～中強度の筋力トレーニング等の運動を実践する高齢者が摂取することで、骨格筋減少を改善する点で有利である。さらに、本発明の組み合わせ物は、継続することが容易な低～中強度の筋力トレーニング等の運動を実践する高齢者が摂取することで、精神的健康度を向上させる点で有利である。さらに、本発明の組み合わせ物は、継続することが容易な低～中強度の筋力トレーニング等の運動を実践する高齢者が摂取することで、身体的側面、精神的側面の両面からフレイルサイクルを抑制することでフレイルを改善する点で有利である。 According to the present invention, the target flail can be remarkably improved by ingesting the combination of the present invention. Moreover, the subject's skeletal muscle mass reduction can be advantageously improved by ingesting the combination of the present invention. According to the present invention, a decrease in sensitivity to protein synthesis stimulation can be improved by ingesting the combination of the present invention. Moreover, the combination of this invention can improve mental health advantageously. In addition, the combination of the present invention uses a milk protein that is relatively inexpensive and excellent in flavor as a protein source, and therefore provides a dose and / or flavor that can be easily incorporated into a daily meal. This is advantageous in that Furthermore, the combination of the present invention is advantageous in that it reduces skeletal muscle loss when ingested by elderly people who practice exercises such as low to medium strength muscle strength training that are easy to continue. Furthermore, the combination of the present invention is advantageous in that it improves mental health when taken by elderly people who practice exercises such as low-to-medium strength training that are easy to continue. Furthermore, the combination of the present invention suppresses the flail cycle from both physical and mental aspects when ingested by elderly people who practice exercises such as low-to-medium strength strength training that are easy to continue This is advantageous in improving flail.
運動群および運動＋栄養群における、運動・栄養介入試験の開始前および終了後の血漿ロイシン濃度変化を示すグラフである。It is a graph which shows the plasma leucine density | concentration change before the exercise | movement and a nutrition + nutrition group before the start of exercise / nutrition intervention test, and after completion | finish. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前および終了後の除脂肪体重を示すグラフである。It is a graph which shows the lean body weight before the start of exercise / nutrition intervention test in the exercise group and exercise + nutrition group, and after completion | finish. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前の骨格筋指数に対する終了後の骨格筋指数の比率を示すグラフである。It is a graph which shows the ratio of the skeletal muscle index after completion | finish with respect to the skeletal muscle index before the start of an exercise and a nutrition intervention test in an exercise group and an exercise | movement + nutrition group. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前および終了後のＷＨＯ－５精神的健康状態表のスコアを示すグラフである。It is a graph which shows the score of the WHO-5 mental health state table | surface before and after the completion | finish of the exercise / nutrition intervention test in an exercise group and an exercise + nutrition group. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前の血清２５－（ＯＨ）ビタミンＤ濃度に対する終了後の血清２５－（ＯＨ）ビタミンＤ濃度の比率を示すグラフである。It is a graph which shows the ratio of the serum 25- (OH) vitamin D density | concentration after completion | finish with respect to the serum 25- (OH) vitamin D density | concentration before the exercise | movement / nutrition intervention test in the exercise group and exercise + nutrition group. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前の血清ビタミンＢ１２濃度に対する終了後の血清ビタミンＢ１２濃度の比率を示すグラフである。It is a graph which shows the ratio of the serum vitamin B12 density | concentration after completion | finish with respect to the serum vitamin B12 density | concentration before the exercise | movement / nutrition intervention test in the exercise group and the exercise + nutrition group. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前の血清葉酸濃度に対する終了後の血清葉酸濃度の比率を示すグラフである。It is a graph which shows the ratio of the serum folate density | concentration after completion | finish with respect to the serum folate density | concentration before the exercise | movement / nutrition intervention test start in the exercise group and exercise + nutrition group. 運動群および運動＋栄養群における、運動・栄養介入試験の開始前および終了後の血清亜鉛濃度変化を示すグラフである。It is a graph which shows a serum zinc level change before the start of exercise / nutrition intervention test in the exercise group and exercise + nutrition group, and after completion | finish.
発明の具体的説明DETAILED DESCRIPTION OF THE INVENTION
　本発明のフレイル改善用組み合わせ物は、乳たんぱく質、亜鉛、およびビタミンＤを含有することを一つの特徴としている。本発明のフレイル改善用組み合わせ物は、さらに、ビタミンＢ１２および葉酸を含有してもよい。 The combination for improving flail according to the present invention is characterized by containing milk protein, zinc, and vitamin D. The combination for improving flail of the present invention may further contain vitamin B12 and folic acid.
　本発明の組み合わせ物に配合される乳たんぱく質は、本発明の効果を妨げない限り、特に限定されず、全乳たんぱく質、乳清たんぱく質、カゼイン、乳脂肪球皮膜たんぱく質などが挙げられ、好ましくは、全乳たんぱく質である。上記乳たんぱく質におけるロイシンの含量は、本発明の効果を妨げない限り特に限定されないが、１０質量％未満が好ましい。また、本発明の組み合わせ物に配合される乳たんぱく質の形態は、本発明の効果を妨げない限り、特に限定されず、乳原料のままであってもよく、乳原料から精製された乳たんぱく質の形態であってもよい。かかる乳原料の具体的な形態としては、牛乳、脱脂乳、バター、無塩バター、バターオイル、クリーム、クリームパウダー、バターミルク、脱脂粉乳、全脂粉乳、れん乳、濃縮乳、脱脂濃縮乳、濃縮ホエイ、ホエイ粉、ミルクプロテインコンセントレート、ホエイたんぱく濃縮物、乳糖、またはそれらの組み合わせなどが挙げられる。乳原料または乳原料から精製された乳たんぱく質は、単独で配合してもよく、２種以上を組み合わせて配合してもよい。本発明では、例えば、食品原料や食品添加剤として市販されて流通している乳原料を、乳たんぱく質として用いることができる。 The milk protein blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and examples thereof include whole milk protein, whey protein, casein, milk fat globule membrane protein, and the like. It is a whole milk protein. The content of leucine in the milk protein is not particularly limited as long as the effect of the present invention is not hindered, but is preferably less than 10% by mass. In addition, the form of the milk protein blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, the milk raw material may remain as it is, and the milk protein purified from the milk raw material may be used. Form may be sufficient. Specific forms of such milk raw materials include milk, skim milk, butter, unsalted butter, butter oil, cream, cream powder, butter milk, skim milk powder, whole milk powder, spinach milk, concentrated milk, skim milk concentrate, Concentrated whey, whey powder, milk protein concentrate, whey protein concentrate, lactose, or combinations thereof. Milk raw materials or milk proteins purified from milk raw materials may be blended singly or in combination of two or more. In the present invention, for example, a milk raw material that is commercially available and distributed as a food raw material or food additive can be used as a milk protein.
　本発明の組み合わせ物における乳たんぱく質の含有量は、本発明の効果を妨げない限り、特に限定されないが、乳たんぱく質そのものの含有量として、風味のよい乳たんぱく質含有組み合わせ物を安価に提供するという観点から、好ましくは１～１５ｇであり、より好ましくは５～１３ｇであり、さらに好ましくは、９～１２ｇである。本発明の組み合わせ物における乳たんぱく質の含有量は、例えば、「食品衛生検査指針　理化学編」（厚生省生活衛生局監修）に記載のケルダール法で測定することができる。 The content of milk protein in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but as a content of the milk protein itself, a viewpoint of providing a tasty milk protein-containing combination at low cost. Therefore, it is preferably 1 to 15 g, more preferably 5 to 13 g, and still more preferably 9 to 12 g. The milk protein content in the combination product of the present invention can be measured by, for example, the Kjeldahl method described in “Food Hygiene Inspection Guidelines, Physical and Chemical Editing” (supervised by the Ministry of Health and Welfare, Health Sanitation Bureau).
　本発明の組み合わせ物に配合される亜鉛の形態は、本発明の効果を妨げない限り、特に限定されず、塩の形態で組み合わせ物中に含有させてもよい。かかる亜鉛の具体的な形態としては、塩化亜鉛、硫酸亜鉛、グルコン酸亜鉛、酵母亜鉛などが挙げられるが、好ましくは、グルコン酸亜鉛、酵母亜鉛であり、より好ましくは、グルコン酸亜鉛である。本発明では、例えば、食品添加剤として市販されて流通している亜鉛や、亜鉛を含む製剤などを用いることができる。 The form of zinc to be blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be contained in the combination in the form of a salt. Specific examples of such zinc include zinc chloride, zinc sulfate, zinc gluconate, and yeast zinc. Preferred are zinc gluconate and yeast zinc, and more preferred is zinc gluconate. In the present invention, for example, zinc that is commercially available and distributed as a food additive, a preparation containing zinc, and the like can be used.
　本発明の組み合わせ物における亜鉛の含有量は、本発明の効果を妨げない限り、特に限定されないが、亜鉛そのものの含有量として、好ましくは１～４０ｍｇであり、より好ましくは４～２０ｍｇであり、さらに好ましくは６～１０ｍｇである。本発明の組み合わせ物における亜鉛の含有量は、例えば、「食品衛生検査指針　理化学編」（厚生省生活衛生局監修）に記載の原子吸光光度法で測定することができる。 The content of zinc in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of zinc itself is preferably 1 to 40 mg, more preferably 4 to 20 mg. More preferably, it is 6 to 10 mg. The zinc content in the combination of the present invention can be measured by, for example, the atomic absorption spectrophotometry described in “Food Hygiene Inspection Guidelines, RIKEN” (supervised by the Ministry of Health and Welfare, Health Sanitation Bureau).
　本発明の組み合わせ物に配合されるビタミンＤの形態は、本発明の効果を妨げない限り、特に限定されない。かかるビタミンＤの具体的な形態としては、エルゴカルシフェロール（ＶＤ２）、コレカルシフェロール（ＶＤ３）、カルシジオール、カルシトリオール、ドキセルカルシフェロール、カルシポトリエンなどが挙げられるが、好ましくは、ＶＤ２、ＶＤ３、より好ましくは、ＶＤ３である。本発明では、例えば、食品添加剤として市販されて流通しているビタミンＤや、ビタミンＤを含む製剤などを用いることができる。 The form of vitamin D blended in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered. Specific examples of such vitamin D include ergocalciferol (VD2), cholecalciferol (VD3), calcidiol, calcitriol, doxel calciferol, calcipotriene, preferably VD2, VD3, more preferably VD3. In the present invention, for example, vitamin D marketed and distributed as a food additive, a preparation containing vitamin D, and the like can be used.
　本発明の組み合わせ物におけるビタミンＤの含有量は、本発明の効果を妨げない限り、特に限定されないが、ビタミンＤそのものの含有量として、好ましくは１～１００μｇであり、より好ましくは２～２０μｇであり、さらに好ましくは３～８μｇである。本発明の組み合わせ物におけるビタミンＤの含有量は、例えば、ＨＰＬＣ法により、竹林　純他　ビタミン　2011；85(12)：645-650に記載の手順に従って測定することができる。 The vitamin D content in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of vitamin D itself is preferably 1 to 100 μg, more preferably 2 to 20 μg. More preferably 3 to 8 μg. The content of vitamin D in the combination of the present invention can be measured by, for example, HPLC method according to the procedure described in Takebayashi Jun et al. Vitamin 2011; 85 (12): 645-650.
　本発明の組み合わせ物に配合される葉酸の形態は、本発明の効果を妨げない限り、特に限定されない。かかる葉酸の具体的な形態としては、葉酸、5-メチルテトラヒドロ葉酸、5-メチルテトラヒドロ葉酸メチル葉酸塩などが挙げられるが、好ましくは、葉酸である。本発明では、例えば、食品添加剤として市販されて流通している葉酸や、葉酸を含む製剤などを用いることができる。 The form of folic acid blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered. Specific examples of such folic acid include folic acid, 5-methyltetrahydrofolic acid, methyl 5-methyltetrahydrofolate, and the like, with folic acid being preferred. In the present invention, for example, folic acid that is commercially available and distributed as a food additive, a preparation containing folic acid, and the like can be used.
　本発明の組み合わせ物における葉酸の含有量は、本発明の効果を妨げない限り、特に限定されないが、葉酸そのものの含有量として、好ましくは５０～１０００μｇであり、より好ましくは７０～５００μｇであり、さらに好ましくは１００～３００μｇである。本発明の組み合わせ物における葉酸の含有量は、例えば、「五訂増補日本食品標準成分表分析マニュアル」（国立印刷局発行）に記載の微生物定量法で測定することができる。 The content of folic acid in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of folic acid itself is preferably 50 to 1000 μg, more preferably 70 to 500 μg, More preferably, it is 100 to 300 μg. The content of folic acid in the combination product of the present invention can be measured, for example, by the microorganism quantification method described in the “Fiveth Supplement Japanese Food Standard Component Table Analysis Manual” (published by the National Printing Bureau).
　本発明の組み合わせ物に配合されるビタミンＢ１２の形態は、本発明の効果を妨げない限り、特に限定されない。かかるビタミンＢ１２の具体的な形態としては、メチルコバラミン、ヒドロキソコバラミン、アデノシルコバラミン、塩酸ヒドロキソコバラミン、酢酸ヒドロキソコバラミン、シアノコバラミンなどが挙げられるが、好ましくは、シアノコバラミンである。本発明では、例えば、食品添加剤として市販されて流通しているビタミンＢ１２や、ビタミンＢ１２を含む製剤などを用いることができる。 The form of vitamin B12 blended in the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered. Specific examples of such vitamin B12 include methylcobalamin, hydroxocobalamin, adenosylcobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin and the like, preferably cyanocobalamin. In the present invention, for example, vitamin B12 commercially available as a food additive and a preparation containing vitamin B12 can be used.
　本発明の組み合わせ物におけるビタミンＢ１２の含有量は、本発明の効果を妨げない限り、特に限定されないが、ビタミンＢ１２そのものの含有量として、好ましくは０．１～１００μｇであり、より好ましくは１～５０μｇであり、さらに好ましくは５～２０μｇである。本発明の組み合わせ物におけるビタミンＢ１２の含有量は、例えば、微生物学的定量法により、（食品表示基準について（平成27年3月30日消食表第139号，消費者庁次長通知　別添　栄養表示関係http://www.caa.go.jp/foods/pdf/151224_tuchi4-betu2.pdf　p121-123）に記載の手順に従って測定することができる。 The content of vitamin B12 in the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the content of vitamin B12 itself is preferably 0.1 to 100 μg, more preferably 1 to 50 μg, more preferably 5 to 20 μg. The content of vitamin B12 in the combination of the present invention can be determined by, for example, microbiological quantification method (for food labeling standards (Notified on March 30, 2015, Table 139, Deputy Director of Consumer Affairs Agency) ( Http://www.caa.go.jp/foods/pdf/151224_tuchi4-betu2.pdf p121-123).
　また、本発明の組み合わせ物において、亜鉛およびビタミンＤの合計と、亜鉛との質量比は、好ましくは１：０．９５～１：１であり、より好ましくは１：０．９７～１：０．９９９９であり、さらに好ましくは１：０．９９９～１：０．９９９５である。 In the combination of the present invention, the mass ratio of zinc and vitamin D to zinc is preferably 1: 0.95 to 1: 1, more preferably 1: 0.97 to 1: 0. .9999, more preferably 1: 0.999 to 1: 0.9995.
　また、本発明の組み合わせ物において、亜鉛およびビタミンＤの合計と、ビタミンＤとの質量比は、好ましくは１：０．００００３～１：０．５であり、より好ましくは１：０．０００１～１：０．０１であり、さらに好ましくは１：０．０００５～１：０．００１である。 In the combination of the present invention, the mass ratio of the sum of zinc and vitamin D to vitamin D is preferably 1: 0.00003 to 1: 0.5, more preferably 1: 0.0001 to 1: 0.01, and more preferably 1: 0.0005 to 1: 0.001.
　また、本発明の組み合わせ物において、亜鉛およびビタミンＤの合計と、乳たんぱく質との質量比は、好ましくは１：２００～１：８０００であり、より好ましくは１：３００～１：５０００であり、さらに好ましくは１：５００～１：２０００である。 In the combination of the present invention, the mass ratio of the sum of zinc and vitamin D to milk protein is preferably 1: 200 to 1: 8000, more preferably 1: 300 to 1: 5000, More preferably, it is 1: 500 to 1: 2000.
　また、本発明の組み合わせ物において、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の合計と、亜鉛との質量比は、好ましくは１：０．５～１：１であり、より好ましくは１：０．６～１：１であり、さらに好ましくは１：０．９７～１：１である。 In the combination of the present invention, the mass ratio of zinc, vitamin D, vitamin B12, and folic acid to zinc is preferably 1: 0.5 to 1: 1, more preferably 1: 0. .6 to 1: 1, more preferably 1: 0.97 to 1: 1.
　また、本発明の組み合わせ物において、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の合計と、ビタミンＤとの質量比は、好ましくは１：０．００００３～１：０．０５であり、より好ましくは１：０．０００１～１：０．０１であり、さらに好ましくは１：０．０００５～１：０．００１である。 In the combination of the present invention, the mass ratio of zinc, vitamin D, vitamin B12 and folic acid to vitamin D is preferably 1: 0.00003 to 1: 0.05, more preferably It is 1: 0.0001 to 1: 0.01, more preferably 1: 0.0005 to 1: 0.001.
　また、本発明の組み合わせ物において、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の合計と、ビタミンＢ１２との質量比は、好ましくは１：０．００００１～１：０．０５であり、より好ましくは１：０．００００１～１：０．０１であり、さらに好ましくは１：０．００１～１：０．００５である。 In the combination of the present invention, the mass ratio of zinc, vitamin D, vitamin B12 and folic acid to vitamin B12 is preferably 1: 0.00001 to 1: 0.05, more preferably It is 1: 0.00001 to 1: 0.01, more preferably 1: 0.001 to 1: 0.005.
　また、本発明の組み合わせ物において、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の合計と、葉酸との質量比は、好ましくは１：０．００１～１：０．４であり、より好ましくは１：０．００５～１：０．１であり、さらに好ましくは１：０．０１～１：０．０３である。 In the combination of the present invention, the mass ratio of zinc, vitamin D, vitamin B12, and folic acid to folic acid is preferably 1: 0.001 to 1: 0.4, more preferably 1 : 0.005 to 1: 0.1, more preferably 1: 0.01 to 1: 0.03.
　また、本発明の組み合わせ物において、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の合計と、乳たんぱく質との質量比は、好ましくは１：２００～１：７０００であり、より好ましくは１：５００～１：５０００であり、さらに好ましくは１：１０００～１：２０００である。 In the combination of the present invention, the mass ratio of the total of zinc, vitamin D, vitamin B12, and folic acid to milk protein is preferably 1: 200 to 1: 7000, more preferably 1: 500 to 1: 5000, more preferably 1: 1000 to 1: 2000.
　また、本発明の組み合わせ物は、上記成分と共に、他のビタミン、例えば、ビタミンＡ、ビタミンＥ、ビタミンＢ１、ビタミンＢ２、ナイアシン、ビタミンＢ６、パントテン酸、ビタミンＣなど、および／または他のミネラル、例えば、ナトリウム、カルシウム、鉄、銅、セレンなどをさらに含んでもよい。例えば、本発明の組み合わせ物は、ビタミンＡ、ビタミンＥ、ビタミンＢ１、ビタミンＢ２、ナイアシン、ビタミンＢ６、パントテン酸、ビタミンＣ、ナトリウム、カルシウム、鉄、銅およびセレンからなる群から選択される少なくとも１つ、例えばその全て、をさらに含んでもよい。例えば、本発明の組み合わせ物は、ビタミンＡを１５０～１８００μｇＲＥ、好ましくは３００～９００μｇＲＥ含んでもよく、ビタミンＥを７．５～９０ｍｇ、好ましくは１５～４５ｍｇ含んでもよく、ビタミンＢ１を０．８～９．０ｍｇ、好ましくは１．５～４．５ｍｇ含んでもよく、ビタミンＢ２を１．０～１２．０ｍｇ、好ましくは２．０～６．０ｍｇ含んでもよく、ナイアシンを８～９６ｍｇＮＥ、好ましくは１６～４８ｍｇＮＥ含んでもよく、ビタミンＢ６を２～３０ｍｇ、好ましくは３～１２ｍｇ含んでもよく、パントテン酸を３～３６ｍｇ、好ましくは６～１８ｍｇ含んでもよく、ビタミンＣを１００～８００ｍｇ、好ましくは２００～５００ｍｇ含んでもよい。本発明の組み合わせ物はまた、例えば、ナトリウムを４０～６４０ｍｇ、好ましくは８０～３２０ｍｇ含んでもよく、カルシウムを７５～１４００ｍｇ、好ましくは１５０～７００ｍｇ含んでもよく、鉄を１．５～３０ｍｇ、好ましくは３．５～１５ｍｇ含んでもよく、銅を０．１～１．６ｍｇ、好ましくは０．２～０．８ｍｇ含んでもよく、セレンを６～７２μｇ、好ましくは１２～３６μｇ含んでもよい。 The combination of the present invention may contain other vitamins such as vitamin A, vitamin E, vitamin B1, vitamin B2, niacin, vitamin B6, pantothenic acid, vitamin C, and / or other minerals together with the above ingredients, For example, sodium, calcium, iron, copper, selenium and the like may be further included. For example, the combination of the present invention is at least one selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, niacin, vitamin B6, pantothenic acid, vitamin C, sodium, calcium, iron, copper and selenium. For example, all of them. For example, the combination of the present invention may contain 150 to 1800 μg RE of vitamin A, preferably 300 to 900 μg RE, 7.5 to 90 mg, preferably 15 to 45 mg of vitamin E, and 0.8 to 0.8 of vitamin B1. 9.0 mg, preferably 1.5 to 4.5 mg, vitamin B2 1.0 to 12.0 mg, preferably 2.0 to 6.0 mg, niacin 8 to 96 mg NE, preferably 16 -48 mg NE, vitamin B6 2-30 mg, preferably 3-12 mg, pantothenic acid 3-36 mg, preferably 6-18 mg, vitamin C 100-800 mg, preferably 200-500 mg May be included. The combination of the present invention may also contain, for example, 40-640 mg sodium, preferably 80-320 mg, 75-1400 mg calcium, preferably 150-700 mg, 1.5-30 mg iron, preferably It may contain 3.5-15 mg, 0.1-1.6 mg copper, preferably 0.2-0.8 mg, and 6-72 μg, preferably 12-36 μg selenium.
　また、本発明の組み合わせ物は、脂質、炭水化物、乳たんぱく質以外のたんぱく質、灰分などをさらに含んでもよい。例えば、本発明の組み合わせ物は、脂質、炭水化物および乳たんぱく質以外のたんぱく質、灰分からなる群から選択される少なくとも１つ、例えばその全て、をさらに含んでもよい。例えば、本発明の組み合わせ物は、脂質を１～１６ｇ、好ましくは２～８ｇ含んでもよく、炭水化物を５～８０ｇ、好ましくは１０～４０ｇ含んでもよく、乳たんぱく質以外のたんぱく質を０．１８～１０．０ｇ、好ましくは０．３５～５．０ｇ含んでもよく、および灰分を０．１５～１．８ｇ、好ましくは０．３～０．９ｇ含んでもよい。 The combination of the present invention may further contain lipids, carbohydrates, proteins other than milk proteins, ash and the like. For example, the combination of the present invention may further comprise at least one selected from the group consisting of lipids, carbohydrates and proteins other than milk protein, and ash, such as all of them. For example, the combination of the present invention may contain 1 to 16 g, preferably 2 to 8 g of lipid, 5 to 80 g, preferably 10 to 40 g of carbohydrate, and 0.18 to 10 of protein other than milk protein. 0.0g, preferably 0.35 to 5.0g, and ash content 0.15 to 1.8g, preferably 0.3 to 0.9g.
　また、本発明の組み合わせ物は、上記成分と共に、所望により経口上許容可能な添加剤を配合した組み合わせ物として提供することができる。経口上許容可能な添加剤として、水などの水性媒体、溶剤、溶解補助剤、滑沢剤、乳化剤、等張化剤、安定化剤、保存剤、防腐剤、界面活性剤、調整剤、キレート剤、ｐＨ調整剤、緩衝剤、賦形剤、増粘剤、着色剤、芳香剤または香料などが挙げられる。 In addition, the combination of the present invention can be provided as a combination of the above ingredients and optionally orally acceptable additives. Orally acceptable additives include aqueous media such as water, solvents, solubilizers, lubricants, emulsifiers, tonicity agents, stabilizers, preservatives, preservatives, surfactants, regulators, chelates Agents, pH adjusters, buffers, excipients, thickeners, colorants, fragrances or fragrances.
　本発明の組み合わせ物は、上記の各成分を混合、溶解、分散、懸濁するなどの公知の手法により、調製することができる。また、本発明の組み合わせ物の調製においては、本発明の効果を妨げない限り、上記の各成分の混合物、溶解物、分散物、懸濁物などに、均質化処理や殺菌処理を施してもよい。 The combination of the present invention can be prepared by a known method such as mixing, dissolving, dispersing, or suspending the above components. In the preparation of the combination of the present invention, the mixture, solution, dispersion, suspension, etc. of each of the above components may be subjected to homogenization treatment or sterilization treatment as long as the effects of the present invention are not hindered. Good.
　また、本発明の組み合わせ物は、本発明の効果を妨げない限り、特に制限されず、１つの組成物または剤の形態であってもよく、複数の組成物または剤の組み合わせから構成されていてもよい。また、上記組み合わせ物は一体的にまたは別体として構成されていてもよい。上記複数または別体としての組成物の組み合わせとしては、例えば、乳たんぱく質を含んでなる組成物と、亜鉛およびビタミンＤを含んでなる組成物との組み合わせ、または、乳たんぱく質を含んでなる組成物と、亜鉛、ビタミンＤ、ビタミンＢ１２および葉酸を含んでなる組成物との組み合わせが挙げられる。 Further, the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be in the form of one composition or agent, and is composed of a combination of a plurality of compositions or agents. Also good. Moreover, the said combination may be comprised integrally or as a different body. Examples of the combination of the plural or separate compositions include, for example, a combination of a composition comprising milk protein and a composition comprising zinc and vitamin D, or a composition comprising milk protein. And a combination of zinc, vitamin D, vitamin B12 and a composition comprising folic acid.
　また、本発明の組み合わせ物の形態は、本発明の効果を妨げない限り、特に制限されず、固形状、半固形状または液状であってもよいが、固形状または液状であることが好ましく、摂取の簡便性、風味の観点から液状であることがより好ましい。本発明の組み合わせ物が複数の組成物または剤の組み合わせである場合には、各組成物または各剤の形態が同じであっても異なっても構わない。 Further, the form of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, and may be solid, semi-solid or liquid, but is preferably solid or liquid, It is more preferable that it is liquid from the viewpoint of ease of intake and flavor. When the combination of the present invention is a combination of a plurality of compositions or agents, the form of each composition or each agent may be the same or different.
　本願発明の組み合わせ物の容量は、本発明の効果を妨げない限り、特に限定されず、例えば、５０～５０００ｍＬとしてもよく、好ましくは１００～１０００ｍＬであり、より好ましくは１００～５００ｍＬであり、さらに好ましくは２００～４００ｍＬである。また、本願発明の組み合わせ物の重量は、本発明の効果を妨げない限り、特に限定されず、例えば、５０～５０００ｇとしてもよく、好ましくは１００～１０００ｇであり、より好ましくは１００～５００ｇであり、さらに好ましくは２００～４００ｇである。上記容量または重量は、本発明の組み合わせ物が複数の組成物または剤の組み合わせである場合には、その組み合わせの合計を示す。 The volume of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, and may be, for example, 50 to 5000 mL, preferably 100 to 1000 mL, more preferably 100 to 500 mL, 200 to 400 mL is preferred. The weight of the combination of the present invention is not particularly limited as long as the effects of the present invention are not hindered, and may be, for example, 50 to 5000 g, preferably 100 to 1000 g, more preferably 100 to 500 g. More preferably, it is 200 to 400 g. The said capacity | capacitance or weight shows the sum total of the combination, when the combination of this invention is a combination of a some composition or agent.
　また、本発明の組み合わせ物は、１日の経口摂取量の単位として提供することが好ましい。本発明の組み合わせ物における、乳たんぱく質、亜鉛およびビタミンＤの１日の経口摂取量、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２および葉酸の１日の経口摂取量は、上述した組み合わせ物中の含有量と同様とすることができる。 Also, the combination of the present invention is preferably provided as a unit of daily oral intake. The daily oral intake of milk protein, zinc and vitamin D, or the daily oral intake of milk protein, zinc, vitamin D, vitamin B12 and folic acid in the combination of the present invention is as described above in the combination. It can be the same as the content of.
　したがって、本発明の好ましい態様によれば、本発明の組み合わせ物は、１日の経口摂取量の単位からなり、乳たんぱく質１～１５ｇ、亜鉛１～４０ｍｇ、およびビタミンＤ　１～１００μｇを含んでなるか、または、乳たんぱく質１～１５ｇ、亜鉛１～４０ｍｇ、ビタミンＤ　１～１００μｇ、ビタミンＢ１２　０．１～１００μｇ、および葉酸５０～１０００μｇを含んでなる。また、上記の乳たんぱく質、亜鉛、およびビタミンＤ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の含有量は、好ましくは、本発明の組み合わせ物１００～１０００ｍＬ当たりの含有量であり、より好ましくは、本発明の組み合わせ物１００～５００ｍＬ当たりの含有量であり、さらに好ましくは、本発明の組み合わせ物２００～４００ｍＬ当たりの含有量である。 Therefore, according to a preferred embodiment of the present invention, the combination of the present invention consists of units of daily oral intake and comprises 1 to 15 g of milk protein, 1 to 40 mg of zinc, and 1 to 100 μg of vitamin D. Or 1 to 15 g of milk protein, 1 to 40 mg of zinc, 1 to 100 μg of vitamin D, 0.1 to 100 μg of vitamin B12, and 50 to 1000 μg of folic acid. Further, the content of the above milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 and folic acid is preferably the content per 100 to 1000 mL of the combination of the present invention. More preferably, the content per 100 to 500 mL of the combination of the present invention, and still more preferably the content per 200 to 400 mL of the combination of the present invention.
　また、本発明の組み合わせ物は、包装形態で提供することが好ましい。包装形態としては、特に限定されず、パックや容器などが挙げられる。この場合、使用される容器は、例えば、ポリエチレンテレフタレートを主成分とする成形容器や金属缶、瓶などの通常の形態で提供することができる。ここで、本発明の組み合わせ物が液状の場合、容器詰とすることにより、例えば、希釈せずに飲用できる。また、包装の表面には、成分の表示、用量や用法の表示などを付していてもよいし、フレイルを改善させる、骨格筋量の減少を改善させるなどの具体的な機能の表示などを付していてもよい。かかる包装形態の好適な例としては、サプリメント、医薬製剤、食品、飲料などが挙げられる。ここで、表示は、本発明の組み合わせ物自体に付したものであってもよいし、本発明の組み合わせ物を含有する容器、包装材または添付文書に付したものであってもよい。また、表示は、本発明の組み合わせ物の関連する情報として、チラシ、パンフレット、ポップ、カタログ、ポスター、書籍、ＤＶＤなどの記憶媒体、電子掲示板やインターネットなどでの広告などで、本発明の組み合わせ物が効果的であることを表示・広告するものであってもよい。 Also, the combination of the present invention is preferably provided in a package form. The packaging form is not particularly limited, and examples thereof include packs and containers. In this case, the container used can be provided in a normal form such as a molded container mainly composed of polyethylene terephthalate, a metal can, or a bottle. Here, when the combination of the present invention is in a liquid state, it can be drunk without dilution, for example, by filling the container. In addition, the surface of the packaging may be labeled with ingredients, dosage and usage, etc., with specific functions such as improving flail and reducing skeletal muscle mass. It may be attached. Suitable examples of such packaging forms include supplements, pharmaceutical preparations, foods, beverages and the like. Here, the display may be affixed to the combination of the present invention itself, or may be affixed to a container, packaging material or package insert containing the combination of the present invention. In addition, the display includes information related to the combination of the present invention, such as flyers, brochures, pops, catalogs, posters, books, DVDs, storage media, electronic bulletin boards, advertisements on the Internet, etc. May be displayed / advertised to be effective.
　本発明の組み合わせ物は、フレイル（虚弱、老衰、衰弱、または脆弱とも言われる）を有利に改善させることができる。したがって、本発明の組み合わせ物の好ましい一つの態様によれば、フレイル（虚弱、老衰、衰弱、または脆弱）改善用またはフレイルもしくは要介護状態となるリスクの低減のための組み合わせ物として提供される。また、本発明の組み合わせ物は、骨格筋量減少を有利に改善させることができることから、サルコペニア改善用または骨格筋量減少もしくはサルコペニアのリスクの低減のための組み合わせ物としても提供される。また、本発明の組み合わせ物の好ましい別の一つの態様によれば、本発明の組み合わせ物は、精神的健康度向上用または精神的健康の改善用組み合わせ物として提供される。また、フレイルの具体的な精神的側面（精神的症状）として、意欲低下、うつ状態、せん妄、認知症、睡眠障害、不安障害、閉じこもり、疲労感等が挙げられる。ここで、上記精神的健康度向上用または精神的健康の改善用組み合わせ物は、精神的健康度を向上、または、心理状態を改善できることから、フレイルの精神的症状改善用またはフレイルの精神的症状となるリスクの低減のための組み合わせ物としても提供される。 The combination of the present invention can advantageously improve flail (also referred to as weakness, aging, weakness, or fragility). Therefore, according to one preferable aspect of the combination of the present invention, it is provided as a combination for improving flail (weakness, senility, weakness, or fragility) or reducing the risk of becoming flail or a condition requiring care. In addition, since the combination of the present invention can advantageously improve skeletal muscle mass reduction, it is also provided as a combination for sarcopenia improvement or skeletal muscle mass reduction or sarcopenia risk reduction. According to another preferred embodiment of the combination of the present invention, the combination of the present invention is provided as a combination for improving mental health or improving mental health. In addition, specific mental aspects (psychological symptoms) of flail include decreased motivation, depression, delirium, dementia, sleep disorder, anxiety disorder, withdrawal, fatigue, and the like. Here, the above-mentioned combination for improving mental health or improving mental health can improve mental health or improve psychological state. It is also provided as a combination for reducing the risk.
　また、本発明の別の態様によれば、フレイルの改善方法であって、乳たんぱく質、亜鉛、およびビタミンＤの有効量、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の有効量を対象に服用（好ましくは、摂取）させることを含んでなる方法が提供され、それを必要とする対象に摂取させることを含んでなる方法が提供される。また、本発明の方法の好ましい別の一つの態様によれば、上記方法は骨格筋量の減少の改善方法として提供される。また、本発明の方法の好ましい別の一つの態様によれば、上記方法は精神的健康度の向上方法として提供される。ここで、「改善」とは、対象における状態もしくは症状の好転、または、状態もしくは症状の進行の逆転、防止もしくは遅延の意味を含むだけでなく、想定される悪化に対して事前に備え、状態または症状の発生を未然に防ぐ「予防」の意味も含む。また、「有効量」は、上記組み合わせ物の各構成成分と同様に設定することができる。具体的には、「有効量」とは、上記組み合わせ物の１日の経口摂取量の単位における、乳たんぱく質、亜鉛、およびビタミンＤの含有量、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の含有量などと同様に設定することができる。そして、本発明の方法では、一つの態様によれば、ヒトに対する医療行為を除くものである。例えば、上述の、フレイルの改善方法、骨格筋量の減少の改善方法、または、精神的健康度の向上方法等は、対象が健常者またはフレイル状態のヒトである場合、医療行為を除く非治療的方法とされる。なお、フレイル状態であるかを判定する1つの方法は、Friedらのフレイルティの定義（(1)体重減少、(2)主観的疲労感、(3)日常生活活動量の減少、(4)身体能力（歩行速度）の減弱、(5)筋力（握力）の低下のうち3項目以上にあてはまること）による（Linda P. Fried et al., Frailty in Older Adults: Evidence for a Phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: M146-56参照）。これは主に身体機能的なフレイルを判定する基準であるが、他に身体的フレイルだけでなく抑うつなどの心理的フレイルや社会的フレイルの要素を取り入れたEdmonton Scale（Roifson DB et al. Age Ageing 2006; 35: 526-9）、Groningen indicator(Schuurmans H et al. J Gerontol A Biol Sci 2004; 59: M926-926)、SOF index(Ensrud KE et al. Arch Intern Med 2008; 168: 382-9)による評価もある。
　また、本邦では新開らが15の質問のみでなる「介護予防チェックリスト」を作成しており、15点中、3～4点以上でFriedらの定義での虚弱者（フレイル状態のヒト）をある程度選抜できることを報告している（新開ら 日本公衛誌 2013; 60(5): 262-274）。
　フレイル状態であるかは、新開らの方法で判定できる。
　本発明のフレイルの改善方法、骨格筋量の減少の改善方法、精神的健康度の向上方法等は、本発明の組み合わせ物について、本明細書に記載された内容に従って実施することができる。 According to another aspect of the present invention, there is provided a method for improving flail, which is an effective amount of milk protein, zinc, and vitamin D, or an effective amount of milk protein, zinc, vitamin D, vitamin B12, and folic acid. Is provided to a subject (preferably ingested), and a method is provided that includes ingesting a subject in need thereof. According to another preferred embodiment of the method of the present invention, the method is provided as a method for improving the decrease in skeletal muscle mass. According to another preferred embodiment of the method of the present invention, the method is provided as a method for improving mental health. Here, “improvement” not only includes the meaning of the improvement of the condition or symptom in the subject, or the reversal, prevention or delay of the progression of the condition or symptom, but also prepares in advance for the assumed deterioration, It also includes the meaning of “prevention” to prevent the occurrence of symptoms. The “effective amount” can be set in the same manner as each component of the combination. Specifically, the “effective amount” means the content of milk protein, zinc, and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 in the unit of daily oral intake of the combination. And the content of folic acid and the like. And in the method of this invention, according to one aspect, the medical action with respect to a human is excluded. For example, the method for improving flail, the method for improving the decrease in skeletal muscle mass, the method for improving the mental health level, etc., when the subject is a healthy person or a human who is flailed, is not treated except for medical practice. Method. One method for determining whether or not the flared state is that Fried et al. Defined the frailty ((1) weight loss, (2) subjective fatigue, (3) decreased daily activities, (4) (Linda P. Fried et al., Frailty in Older Adults: Evidence for a Phenotype. J Gerontol A) Biol Sci Med Sci 2001; 56: M146-56). This is mainly a criterion for determining physical functional flile, but it is not only a physical flail but also an Edmonton Scale (Roifson DB et al. Age Aging) that incorporates psychological and social flail elements such as depression. 2006; 35: 526-9), Groningen indicator (Schuurmans H et al. J Gerontol A Biol Sci 2004; 59: M926-926), SOF index (Ensrud KE et al. Arch Intern Med 2008; 168: 382-9) There is also evaluation by.
In Japan, Shinkai et al. Has created a “care prevention checklist” consisting of only 15 questions. Out of 15 points, 3 to 4 points indicate frail people (flaried people) as defined by Fried et al. It has been reported that it can be selected to some extent (Shinkai et al. Japan Public Health Magazine 2013; 60 (5): 262-274).
Whether or not it is in a flared state can be determined by a newly opened method.
The method for improving flail, the method for improving the decrease in skeletal muscle mass, the method for improving mental health, etc. according to the present invention can be carried out according to the contents described in the present specification for the combination of the present invention.
　本発明の摂取の方法は、本発明の効果を妨げない限り、特に限定されないが、好ましくは、経管摂取（経鼻摂取、胃ろうなど）、経口摂取であり、より好ましくは、経口摂取である。本発明の組み合わせ物としては、医薬品、医薬部外品、サプリメント、化粧料、または、特定保健用食品、栄養機能食品もしくは機能性表示食品を含む食品または飲料等の飲食品、栄養バー、ゼリー状食品、粉末飲料での提供が挙げられ、摂取の簡便性、風味の観点から飲料が好ましい。 The method of ingestion of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but preferably, tube ingestion (nasal ingestion, gastric fistula etc.), oral ingestion, is there. Examples of the combination of the present invention include pharmaceuticals, quasi-drugs, supplements, cosmetics, foods and drinks such as foods or drinks including foods for specified health use, nutritional functional foods or functionally labeled foods, nutrition bars, jelly-forms Examples include provision of foods and powdered beverages, and beverages are preferable from the viewpoint of ease of intake and flavor.
　また、本発明の方法では、本発明の組み合わせ物の各構成成分を同時に対象に摂取させてもよく、別々に対象に摂取させてもよい。上記組み合わせ物の構成成分としては、好ましくは、乳たんぱく質、亜鉛およびビタミンＤ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２および葉酸とされる。 In the method of the present invention, each component of the combination of the present invention may be ingested simultaneously by the subject, or may be ingested separately by the subject. The constituents of the combination are preferably milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 and folic acid.
　本発明の組み合わせ物の摂取の用法は、本発明の効果を妨げない限り、対象の種類、年齢、性別、フレイルの程度、骨格筋量減少の程度、または、精神的健康度の程度に応じて、当業者が適宜設定することができる。また、本発明の組み合わせ物の１日の摂取量は、１回で対象に摂取させてもよく、複数回で対象に摂取させてもよい。したがって、本発明の組み合わせ物としての１日の摂取回数は、１日に１～５回であり、好ましくは、１日に１～３回であり、より好ましくは、１日に１回である。さらに、本発明の組み合わせ物の摂取のタイミングは、本発明の効果を妨げない限り、特に限定されないが、運動前後に摂取する必要はなく、普段の食事と併せて摂取することができる。また、本発明の組み合わせ物が複数の組成物の組み合わせである場合には該複数の組成物を同時に対象に摂取させてもよく、別々に対象に摂取させてもよい。 The usage of the combination of the present invention depends on the type of subject, age, gender, degree of flail, degree of skeletal muscle mass loss, or degree of mental health unless the effects of the present invention are disturbed. Those skilled in the art can appropriately set. Further, the daily intake of the combination of the present invention may be ingested by the subject once, or may be ingested by the subject multiple times. Therefore, the number of daily intakes as a combination of the present invention is 1 to 5 times a day, preferably 1 to 3 times a day, more preferably once a day. . Furthermore, the timing of ingestion of the combination of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but it is not necessary to ingest before and after exercise, and can be ingested with a normal meal. Moreover, when the combination of the present invention is a combination of a plurality of compositions, the plurality of compositions may be ingested simultaneously by the subject, or may be ingested separately by the subject.
　本発明の対象は、好ましくは、ヒトであり、より好ましくは、健常な状態、または、フレイル状態のヒトである。 The subject of the present invention is preferably a human, more preferably a healthy or flared human.
　また、本発明の対象の年齢は、本発明の効果を妨げない限り、特に限定されないが、高齢者（例えば、６５歳以上のヒト）の骨格筋量減少および／もしくはフレイルの改善、ならびに／または、精神的健康度の向上において特に有利に利用することができることから、好ましくは、高齢者である。 In addition, the age of the subject of the present invention is not particularly limited as long as the effect of the present invention is not hindered. However, skeletal muscle mass reduction and / or improvement of flail in an elderly person (for example, a human 65 years or older), and / or Since it can be used particularly advantageously in improving mental health, the elderly are preferred.
　さらに、本発明の対象は、本発明の効果を妨げない限り、特に限定されないが、運動を行っているヒトのフレイルの改善および／もしくは骨格筋量減少、ならびに／または、精神的健康度の向上において特に有利に利用することができることから、好ましくは、運動を行っているヒトであり、さらに好ましくは、運動を行っている高齢者（例えば、６５歳以上のヒト）である。ここで、上記運動は継続が容易な運動が好ましく、例えば、ウォーキング（特に速歩）、ジョギング、ランニング、水泳、筋力トレーニングなどが挙げられ、より好ましくは、筋力トレーニングである。
　上記筋力トレーニングは、本発明の効果を妨げない限り、特に限定されないが、継続性の観点から、低～中強度の筋力トレーニングが好ましい。ここで、低～中強度の筋力トレーニングとは、例えば、最大挙上重量の40～70％（低強度～中強度）の強度でのトレーニング、および／または、10段階omnibus resistance exercise scale(OMNI-RES)質問紙(0非常に楽～2楽～4やや楽～6ややきつい～8きつい～10非常にきつい（限界）)で対象が「ややきつい」と感じる（5～7）程度のトレーニングである。上記筋力トレーニングとしては、例えば、自体重、ラバーバンド等を用いたトレーニングが挙げられる。具体的なトレーニング内容としては、上肢を対象として、arm curls（二頭筋カール）、 shoulder lateral and front raises（ショルダー・ラテラル・アンド・フロント・ライズ）、 pull downs（プルダウン）、 およびラバーバンドを用いたrowing（ローイング）が挙げられる。下肢を対象として、立位でのstandard and split squat（スタンダード・アンド・スプリット・スクワット）、 lunges（ランジ）、 およびtoe and heel raises（トゥ・アンド・ヒール・ライズ）、座位でのadductions（アダクション）、 knee extensions（膝の進展）が挙げられる。体幹を対象として、座位でのknee lift（ニー・リフト）、crunches（腹筋運動）、 hip lifts（ヒップリフト）、およびfront elbow bridge（フロント・エルボー・ブリッジ）が挙げられる。各運動は20回×2セット実施し、個別に「ややきつい」と感じる強度になるようラバーバンドなどで負荷を上げることが好ましい。 Further, the subject of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but the flail is improved and / or the skeletal muscle mass is reduced and / or the mental health is improved. In particular, it is preferably a human who is exercising, and more preferably an elderly person who is exercising (for example, a human 65 years or older). Here, the exercise is preferably an exercise that can be easily continued, such as walking (especially rapid walking), jogging, running, swimming, strength training, and the like, and more preferably strength training.
The strength training is not particularly limited as long as the effects of the present invention are not hindered, but low to medium strength strength training is preferable from the viewpoint of continuity. Here, the low-to-medium strength training means, for example, training at a strength of 40 to 70% (low strength to medium strength) of the maximum lifting weight and / or 10-level omnibus resistance exercise scale (OMNI- RES) Question sheet (0 very easy-2 easy-4 slightly easy-6 slightly tight-8 tight-10 very tight (limit)) and the subject feels "slightly tight" (5-7) training is there. Examples of the muscular strength training include training using its own weight, rubber band, and the like. Specific training contents include arm curls (biceps curl), shoulder lateral and front raises, pull downs, and rubber bands for the upper limbs. Rowing (rowing). Standard and split squat in standing position, lunges, and toe and heel raises, and adductions in sitting position for lower limbs , Knee extensions. Targeting the trunk includes knee lift, knees, hip lifts, and front elbow bridge in the sitting position. Each exercise is performed 20 times x 2 sets, and it is preferable to increase the load with a rubber band or the like so that it becomes an intensity that feels “slightly tight” individually.
　また、本発明の別の態様によれば、フレイル改善用組み合わせ物の製造における、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用が提供される。また、本発明の使用の好ましい一つの態様によれば、骨格筋量減少改善用組み合わせ物の製造における、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用として提供される。また、本発明の使用の好ましい別の一つの態様によれば、精神的健康度向上用組み合わせ物の製造における、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用として提供される。 Also according to another aspect of the present invention, a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid in the manufacture of a combination for improving flail. Use is provided. According to one preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 in the manufacture of a combination for improving skeletal muscle mass reduction. , And the use of a combination of folic acid. According to another preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, in the manufacture of a combination for improving mental health Provided as the use of a combination of vitamin B12 and folic acid.
　また、本発明の別の態様によれば、フレイル改善用組み合わせ物としての、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用が提供される。また、本発明の使用の好ましい一つの態様によれば、骨格筋量減少改善用組み合わせ物としての、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用として提供される。また、本発明の使用の好ましい別の一つの態様によれば、精神的健康度向上用組み合わせ物としての、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用として提供される。 Also according to another aspect of the present invention, the use of a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid as a combination for improving flail Is provided. Further, according to one preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12, as a combination for improving skeletal muscle mass reduction, And the use of a combination of folic acid. According to another preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin as a combination for improving mental health Provided as the use of a combination of B12 and folic acid.
　また、本発明の別の態様によれば、フレイルの改善のための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用が提供される。また、本発明の使用の好ましい一つの態様によれば、骨格筋量減少の改善のための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用が提供される。また、本発明の使用の好ましい別の一つの態様によれば、精神的健康度の向上のための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせの使用が提供される。 Also according to another aspect of the present invention is the use of a combination of milk protein, zinc and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid for improving flail. Provided. Also according to a preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D or milk protein, zinc, vitamin D, vitamin B12, and Use of a combination of folic acid is provided. According to another preferred embodiment of the use of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12 for improving mental health. And the use of a combination of folic acid is provided.
　また、本発明の別の態様によれば、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを組み合わせ物中に配合することを特徴とする、フレイル改善用組み合わせ物の製造方法が提供される。また、本発明の製造方法の好ましい一つの態様によれば、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを組み合わせ物中に配合することを特徴とする、骨格筋量減少改善用組み合わせ物の製造方法として提供される。また、本発明の製造方法の好ましい別の一つの態様によれば、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを組み合わせ物中に配合することを特徴とする、精神的健康度向上用組み合わせ物の製造方法として提供される。 According to another aspect of the present invention, a combination of milk protein, zinc, and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12, and folic acid is included in the combination. A method for producing a combination for improving flail is provided. According to one preferred embodiment of the production method of the present invention, a combination of milk protein, zinc and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid is incorporated in the combination. It is provided as a method for producing a combination for improving skeletal muscle mass reduction. According to another preferred embodiment of the production method of the present invention, a combination of milk protein, zinc and vitamin D, or a combination of milk protein, zinc, vitamin D, vitamin B12 and folic acid is combined. It is provided as a method of producing a combination for improving mental health,
　また、本発明の別の態様によれば、フレイル改善のための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを（有効成分として）含む組み合わせ物が提供される。また、本発明の好ましい一つの態様によれば、骨格筋量の減少の改善のための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを（有効成分として）含む組み合わせ物として提供される。また、本発明の好ましい別の一つの態様によれば、精神的健康度を向上させるための、乳たんぱく質、亜鉛、およびビタミンＤの組み合わせ、または、乳たんぱく質、亜鉛、ビタミンＤ、ビタミンＢ１２、および葉酸の組み合わせを（有効成分として）含む組み合わせ物として提供される。 According to another aspect of the present invention, a combination of milk protein, zinc, and vitamin D or a combination of milk protein, zinc, vitamin D, vitamin B12, and folic acid (active ingredient) for improving flail As)) is provided. According to one preferred embodiment of the present invention, a combination of milk protein, zinc, and vitamin D, or milk protein, zinc, vitamin D, vitamin B12, and folic acid is used to improve the decrease in skeletal muscle mass. As a combination comprising (as active ingredients) According to another preferred embodiment of the present invention, a combination of milk protein, zinc and vitamin D, or milk protein, zinc, vitamin D, vitamin B12, and Provided as a combination comprising (as an active ingredient) a combination of folic acid.
　上記の使用、製造方法、組み合わせ物（組成物）の態様はいずれも、本発明の組成物や方法に関する記載に準じて実施することができる。 Any of the above-described uses, production methods, and combinations (compositions) can be carried out according to the description of the composition and method of the present invention.
　以下、実施例により、本発明をより具体的に説明するが、本発明の技術範囲は、これらの例示に限定されるものではない。なお、特に記載しない限り、本発明で用いられる全部のパーセンテージや比率は質量による。また、特に記載しない限り、本明細書に記載の単位や測定方法はJIS規格による。 Hereinafter, the present invention will be described more specifically by way of examples. However, the technical scope of the present invention is not limited to these examples. Unless otherwise specified, all percentages and ratios used in the present invention are based on mass. Unless otherwise specified, the units and measurement methods described in this specification are based on JIS standards.
例１：試験サンプル１の製造
　原料水に、乳原料（脱脂濃縮乳（(株)明治製）、クリーム（(株)明治製）、ミルクプロテインコンセントレート（フォンテラ社製））、香料、酸化防止剤（ビタミンE）を配合して十分に混合してから均質化した。この得られた溶液を殺菌してから冷却して、液状の試験サンプル１（乳ベース）を調製した。試験サンプル１の組成を表１に示した。 Example 1: Production raw material water of test sample 1 , milk raw material (fat concentrated milk (manufactured by Meiji), cream (manufactured by Meiji), milk protein concentrate (manufactured by Fontera)), flavor, antioxidant The agent (vitamin E) was blended and mixed thoroughly before homogenization. The obtained solution was sterilized and then cooled to prepare a liquid test sample 1 (milk base). The composition of test sample 1 is shown in Table 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
例２：試験サンプル２の製造
　原料水に、鉄（クエン酸第一鉄ナトリウム（サンフェロール）：エーザイフード・ケミカル(株)製）、亜鉛（グルコン酸亜鉛（ヘルシャスZn）：扶桑化学工業(株)製）、葉酸（DSM Nutoritional Products社製）、ビタミンＢ１２（シアノコバラミン：DSM Nutoritional Products社）、ビタミンＤ（コレカルシフェロール：DSM Nutoritional Products社）、みかん、オレンジ果汁、人参汁、甘味料、香料、ｐH 調整剤などを配合して十分に混合してから均質化した。この得られた溶液を殺菌してから冷却して、液状の試験サンプル２を調製した。試験サンプル２の組成を表２に示した。
Figure JPOXMLDOC01-appb-T000002
 Example 2: Production raw material water of test sample 2 was mixed with iron (sodium ferrous citrate (Sanferol): manufactured by Eisai Food Chemical Co., Ltd.), zinc (zinc gluconate (Hercious Zn): Fuso Chemical Industry Co., Ltd.) )), Folic acid (DSM Nutoritional Products), vitamin B12 (cyanocobalamin: DSM Nutoritional Products), vitamin D (cholecalciferol: DSM Nutoritional Products), mandarin orange, orange juice, ginseng juice, sweetener, flavoring, A pH adjusting agent and the like were blended and mixed thoroughly before homogenization. The obtained solution was sterilized and then cooled to prepare a liquid test sample 2. The composition of Test Sample 2 is shown in Table 2.
Figure JPOXMLDOC01-appb-T000002
試験例１：健常高齢者を対象とした運動・栄養介入試験
　健常な高齢者（６５歳～８０歳）の男女７８名を運動群（４０名、内男性７名）および運動＋栄養群（３８名、内男性５名）の２群に分けた。両群に対し、週２回の運動教室および日々の運動習慣励行からなる試験を実施した。この運動教室で実施した筋力トレーニングは、ラバーバンドや自重を利用し、上記高齢者自身がOMNI-RES質問紙で「ややきつい」と感じる程度に適宜強度を漸増して実施した。具体的なトレーニング内容としては、上肢を対象として、arm curls（二頭筋カール）、 shoulder lateral and front raises（ショルダー・ラテラル・アンド・フロント・ライズ）、 pull downs（プルダウン）、 およびラバーバンドを用いたrowing（ローイング）を実施した。下肢を対象として、standard and split squat（スタンダード・アンド・スプリット・スクワット）、 lunges（ランジ）、およびtoe and heel raises（トゥ・アンド・ヒール・ライズ）を立位で実施し、adductions（アダクション）、 knee extensions（膝の進展）を座位で実施した。体幹を対象として、座位でのknee lift（ニー・リフト）、crunches（腹筋運動）、 hip lifts（ヒップリフト）、およびfront elbow bridge（フロント・エルボー・ブリッジ）を実施した。各運動は20回×2セット実施し、個別に「ややきつい」と感じる強度になるようラバーバンドなどで負荷を上げた。また、上記筋力トレーニングは健常な高齢者においては比較的容易に継続が可能であることが確認された。試験後に、全体の８０％以上の高齢者がこれからも運動を続けていく自信があると回答した。
　運動＋栄養群の高齢者のみに対して、例１で製造した試験サンプル１および例２で製造した試験サンプル２を1日に1本ずつなるべく朝、昼の食事と併せて経口摂取させた。
　上記試験は３ヶ月続けられた。 Test Example 1: Exercise / Nutrition Intervention Test for Healthy Elderly People 78 men and women of healthy elderly people (65 to 80 years old) were exercised (40 people, 7 of whom were male) and exercise + nutritional group (38 The group was divided into two groups: 5 people). Both groups were given a study consisting of exercise classes twice a week and daily exercise habits. The strength training conducted in this exercise class was performed using rubber bands and weights, gradually increasing the strength as needed so that the above-mentioned elderly felt “slightly tight” on the OMNI-RES questionnaire. Specific training contents include arm curls (biceps curl), shoulder lateral and front raises, pull downs, and rubber bands for the upper limbs. We performed rowing (rowing). For the lower limbs, standard and split squat, lunges, and toe and heel raises are performed in an upright position, adductions (adduction), Knee extensions were performed in the sitting position. Knee lift, crunches, hip lifts, and front elbow bridge in the sitting position were performed on the trunk. Each exercise was carried out 20 times x 2 sets, and the load was increased with a rubber band etc. so that the intensity felt “slightly tight” individually. It was also confirmed that the strength training can be continued relatively easily in healthy elderly people. After the test, over 80% of the elderly responded that they were confident that they would continue to exercise.
Only elderly people in the exercise + nutrition group were orally ingested with test meal 1 produced in Example 1 and test sample 2 produced in Example 2 together with meals in the morning and noon as much as possible once a day.
The test was continued for 3 months.
　上記試験の開始前と終了後に血漿中のロイシン濃度を測定し、試験の開始前と終了後で比較した。具体的には、上記試験の開始前と終了後に、一晩絶食した後に高齢者の血液を採取し、血漿を得た。得られた血漿中のロイシン濃度をShimboらの方法（Biomedical Chromatography 2010; 24(7):683-691）に準じてＨＰＬＣ/ＥＳＩ-ＭＳ法にて測定した。 The leucine concentration in plasma was measured before and after the start of the above test and compared before and after the start of the test. Specifically, before and after the start of the above test, blood was collected from elderly people after fasting overnight to obtain plasma. The leucine concentration in the obtained plasma was measured by the HPLC / ESI-MS method according to the method of Shimbo et al. (Biomedical® Chromatography® 2010; 24 (7): 683-691).
　上記試験の開始前および上記試験の終了後の血漿ロイシン濃度を図１に示した。なお、図１では、上記試験の開始前の血漿ロイシン濃度を１００％としている。データは平均値±標準誤差を示す（運動＋栄養群：102.5±2.6%、運動群：94.5±2.0%）。
　その結果、運動群において、上記試験終了後の血漿ロイシン濃度は上記試験開始前の血漿ロイシン濃度に比べ有意に低下していた。一方、運動＋栄養群において、上記試験開始前と終了後との間の血漿ロイシン濃度は維持されていた。なお、上記試験開始前と終了後の間の統計学的有意差は対応のあるt検定で解析した。 The plasma leucine concentration before the start of the test and after the end of the test is shown in FIG. In FIG. 1, the plasma leucine concentration before the start of the above test is 100%. Data show mean ± standard error (exercise + nutrition group: 102.5 ± 2.6%, exercise group: 94.5 ± 2.0%).
As a result, in the exercise group, the plasma leucine concentration after the end of the test was significantly lower than the plasma leucine concentration before the start of the test. On the other hand, in the exercise + nutrition group, the plasma leucine concentration was maintained between before the start of the test and after the end of the test. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
　上記試験の開始前と終了後において、骨格筋量の指標として除脂肪体重（Ｌｅａｎ　Ｂｏｄｙ　Ｍａｓｓ）を二重エネルギーエックス線吸収法で測定し、試験の開始前と終了後で比較した。
　上記試験の開始前および上記試験の終了後の除脂肪体重を図２に示した。なお、図２では、上記試験の開始前の除脂肪体重を１００％としている。データは平均値±標準誤差を示す（運動＋栄養群：100.5±0.3%、運動群：98.9±0.3%）。
　その結果、試験終了後の運動群における除脂肪体重は、試験開始前の除脂肪体重に比べ有意に低下していた。一方、運動＋栄養群において、上記試験開始前と終了後との間の除脂肪体重は維持されていた。なお、上記試験開始前と終了後の間の統計学的有意差は対応のあるt検定で解析した。 Before and after the start of the above test, lean body mass was measured by the double energy X-ray absorption method as an index of skeletal muscle mass, and compared before and after the start of the test.
The lean body mass before the start of the test and after the end of the test is shown in FIG. In FIG. 2, the lean body mass before the start of the above test is 100%. Data show mean ± standard error (exercise + nutrition group: 100.5 ± 0.3%, exercise group: 98.9 ± 0.3%).
As a result, the lean body mass in the exercise group after the test was significantly lower than the lean body weight before the start of the test. On the other hand, in the exercise + nutrition group, lean body mass was maintained between before and after the start of the test. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
　上記試験の開始前と終了後における骨格筋指数（ＳＭＩ：Ｓｋｅｌｅｔａｌ　Ｍｕｓｃｌｅ　Ｉｎｄｅｘ）を算出し、試験の開始前と終了後で比較した。このＳＭＩは、一般的に用いられている、四肢除脂肪重量／（身長）２で算出した。また、四肢除脂肪重量は二重エネルギーエックス線吸収法で測定した。
　上記試験の開始前のＳＭＩを１００％とした場合の試験終了後のＳＭＩの比率を図３に示した。データは平均値±標準誤差を示す（運動＋栄養群：101.2±0.6%、運動群：98.8±0.4%）。図３によれば、運動＋栄養群が運動群と比較して有意に高かった。なお、運動＋栄養群と運動群との間の統計学的有意差はＷｅｌｃｈの検定で解析した。 Skeletal muscle index (SMI) before and after the start of the test was calculated and compared before and after the start of the test. This SMI was calculated by the limb lean mass / (height) 2 which is generally used. The limb lean mass was measured by the double energy X-ray absorption method.
FIG. 3 shows the SMI ratio after the end of the test when the SMI before the start of the test is 100%. Data show mean ± standard error (exercise + nutrition group: 101.2 ± 0.6%, exercise group: 98.8 ± 0.4%). According to FIG. 3, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
　さらに、上記試験の開始前と終了後の高齢者の精神的健康度を、世界保健機関が推奨する精神的健康度の指標であるＷＨＯ－５精神的健康状態表を用いて評価した。
　その結果、運動群ではＷＨＯ－５のスコアが変化しなかったのに対して、運動＋栄養群では有意にスコアの上昇が認められた（図４）。図４のデータはスコアの平均値を示す。ここで、スコアの上昇は心理的状況の好転を示す。なお、上記試験開始前と終了後の間の統計学的有意差は対応のあるt検定で解析した。 Furthermore, the mental health of the elderly before and after the start of the above test was evaluated using the WHO-5 Mental Health Status Table, which is an index of mental health recommended by the World Health Organization.
As a result, while the WHO-5 score did not change in the exercise group, a significant increase in the score was observed in the exercise + nutrition group (FIG. 4). The data in FIG. 4 shows the average score. Here, an increase in score indicates an improvement in the psychological situation. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
　上記試験の開始前と終了後に定法で得た血清を用いて、血清２５－ヒドロキシビタミンＤ（２５－（ＯＨ）ビタミンＤ）濃度を放射性免疫測定法（2抗体法）で測定し、試験の開始前と終了後で比較した。なお、２５－（ＯＨ）ビタミンＤはビタミンＤの代謝物の一つであり、ビタミンＤ栄養状態の指標である。
　上記試験の開始前および上記試験の終了後の血清２５－（ＯＨ）ビタミンＤ濃度を図５に示した。なお、図５では、上記試験の開始前の血清２５－（ＯＨ）ビタミンＤ濃度を１００％としている。
　データは平均値±標準誤差を示す（運動＋栄養群：159.0±7.9%、運動群：131.7±7.0%）。図５によれば、運動＋栄養群が運動群と比較して有意に高かった。なお、運動＋栄養群と運動群との間の統計学的有意差はＳｔｕｄｅｎｔのｔ検定で解析した。 Serum 25-hydroxyvitamin D (25- (OH) vitamin D) concentration is measured by radioimmunoassay (2-antibody method) using the serum obtained by the standard method before and after the start of the above test. Compared before and after. 25- (OH) vitamin D is one of vitamin D metabolites and is an indicator of vitamin D nutritional status.
The serum 25- (OH) vitamin D concentration before the start of the test and after the end of the test is shown in FIG. In FIG. 5, the serum 25- (OH) vitamin D concentration before the start of the test is 100%.
Data show mean ± standard error (exercise + nutrition group: 159.0 ± 7.9%, exercise group: 131.7 ± 7.0%). According to FIG. 5, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between exercise + nutrition group and exercise group was analyzed by Student's t-test.
　上記試験の開始前と終了後に定法で得た血清を用いて、血清ビタミンＢ１２濃度を化学発光酵素免疫測定法で測定し、試験の開始前と終了後で比較した。
　上記試験の開始前および上記試験の終了後の血清ビタミンＢ１２濃度を図６に示した。なお、図６では、上記試験の開始前の血清ビタミンＢ１２濃度を１００％としている。
　データは平均値±標準誤差を示す（運動＋栄養群：123.5±5.4%、運動群：99.6±2.9%）。図６によれば、運動＋栄養群が運動群と比較して有意に高かった。なお、運動＋栄養群と運動群との間の統計学的有意差はＷｅｌｃｈの検定で解析した。 Serum vitamin B12 concentration was measured by chemiluminescence enzyme immunoassay using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
The serum vitamin B12 concentration before the start of the above test and after the end of the above test is shown in FIG. In FIG. 6, the serum vitamin B12 concentration before the start of the test is 100%.
Data show mean ± standard error (exercise + nutrition group: 123.5 ± 5.4%, exercise group: 99.6 ± 2.9%). According to FIG. 6, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
　上記試験の開始前と終了後に定法で得た血清を用いて、血清葉酸濃度を化学発光酵素免疫測定法で測定し、試験の開始前と終了後で比較した。
　上記試験の開始前および上記試験の終了後の血清葉酸濃度を図７に示した。なお、図７では、上記試験の開始前の血清葉酸濃度を１００％としている。
　データは平均値±標準誤差を示す（運動＋栄養群：247.3±17.5%、運動群：114.4±4.5%）。図７によれば、運動＋栄養群が運動群と比較して有意に高かった。なお、運動＋栄養群と運動群との間の統計学的有意差はＷｅｌｃｈの検定で解析した。 Serum folate concentration was measured by chemiluminescent enzyme immunoassay using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
The serum folate concentration before the start of the above test and after the end of the above test is shown in FIG. In FIG. 7, the serum folic acid concentration before the start of the above test is 100%.
Data show mean ± standard error (exercise + nutrition group: 247.3 ± 17.5%, exercise group: 114.4 ± 4.5%). According to FIG. 7, the exercise + nutrition group was significantly higher than the exercise group. The statistically significant difference between the exercise + nutrition group and the exercise group was analyzed by Welch's test.
　上記試験の開始前と終了後に、定法で得た血清を用いて、血清亜鉛濃度を原子吸光分析法で測定し、試験の開始前と終了後で比較した。
　上記試験の開始前および上記試験の終了後の血清亜鉛濃度を図８に示した。なお、図８では、上記試験の開始前の血清亜鉛濃度を１００％としている。
　データは平均値±標準誤差を示す（運動＋栄養群：97.3±1.7%、運動群：95.5 ±1.8%）。図８によれば、運動＋栄養群では変化が有意でないが、運動のみ群では有意に亜鉛濃度が減少している。なお、上記試験開始前と終了後の間の統計学的有意差は対応のあるt検定で解析した。　 Serum zinc concentration was measured by atomic absorption spectrometry using serum obtained by a conventional method before and after the start of the above test, and compared before and after the start of the test.
The serum zinc concentration before the start of the test and after the end of the test is shown in FIG. In FIG. 8, the serum zinc concentration before the start of the above test is 100%.
Data show mean ± standard error (exercise + nutrition group: 97.3 ± 1.7%, exercise group: 95.5 ± 1.8%). According to FIG. 8, although the change is not significant in the exercise + nutrition group, the zinc concentration is significantly decreased in the exercise only group. The statistically significant difference between before and after the start of the test was analyzed by a paired t test.
　上述の様に、試験例１において、運動＋栄養群では、血中の２５－（ＯＨ）－ビタミンＤ、ビタミンＢ１２、および葉酸濃度が、運動群に比べ、有意に増加することが確認された。また、運動＋栄養群では、血中の亜鉛濃度の減少が抑制されることが確認された。 As described above, in Test Example 1, it was confirmed that the concentration of 25- (OH) -vitamin D, vitamin B12, and folic acid in the blood increased significantly in the exercise + nutrition group compared to the exercise group. . In addition, it was confirmed that the decrease in blood zinc concentration was suppressed in the exercise + nutrition group.
　血漿ロイシン濃度、除脂肪体重、骨格筋指数の結果から、本発明の試験サンプル１および試験サンプル２は自身が継続可能なレベルの筋力トレーニングとともに生活に取り入れることで、サルコペニアを改善できることが示唆された。また、ＷＨＯ－５のスコアの結果も考慮すると、本発明の試験サンプル１および試験サンプル２はサルコペニア改善と心理状態の改善を同時に成し遂げており、フレイルの改善法として有効であることが示された。 From the results of plasma leucine concentration, lean body mass, and skeletal muscle index, it was suggested that Test Sample 1 and Test Sample 2 of the present invention can improve sarcopenia by incorporating them into life together with a level of strength training that they can continue. . Also, considering the results of the WHO-5 score, Test Sample 1 and Test Sample 2 of the present invention simultaneously improved sarcopenia and improved psychological state, and were shown to be effective as a method for improving flail. .

Claims (22)

  1. 　乳たんぱく質、亜鉛およびビタミンＤを含む、フレイル改善用組み合わせ物。 Flail improving combination containing milk protein, zinc and vitamin D.
  2. 　ビタミンＢ１２および葉酸をさらに含む、請求項１に記載の組み合わせ物。 The combination according to claim 1, further comprising vitamin B12 and folic acid.
  3. 　乳たんぱく質が全乳たんぱく質である、請求項１または２に記載の組み合わせ物。 The combination according to claim 1 or 2, wherein the milk protein is whole milk protein.
  4. 　乳たんぱく質の含有量が１～１５ｇである、請求項１～３のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 3, wherein the milk protein content is 1 to 15 g.
  5. 　亜鉛の含有量が１～４０ｍｇである、請求項１～４のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 4, wherein the zinc content is 1 to 40 mg.
  6. 　ビタミンＤの含有量が１～１００μｇである、請求項１～５のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 5, wherein the content of vitamin D is 1 to 100 µg.
  7. 　ビタミンＢ１２の含有量が０．１～１００μｇである、請求項２～６のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 2 to 6, wherein the content of vitamin B12 is 0.1 to 100 µg.
  8. 　葉酸の含有量が５０～１０００μｇである、請求項２～７のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 2 to 7, wherein the content of folic acid is 50 to 1000 µg.
  9. 　高齢者のための、請求項１～８のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 8, for elderly people.
  10. 　運動を行っているヒトのための、請求項１～９のいずれか一項に記載の組み合わせ物。 10. The combination according to any one of claims 1 to 9, for a human performing exercise.
  11. 　組成物である、請求項１～１０のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 10, which is a composition.
  12. 　前記組成物が飲食品である、請求項１１に記載の組み合わせ物。 The combination according to claim 11, wherein the composition is a food or drink.
  13. 　前記飲食品が飲料である、請求項１２に記載の組み合わせ物。 The combination according to claim 12, wherein the food or drink is a beverage.
  14. 　骨格筋量減少改善用の、請求項１～１３のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 13, which is used for improving skeletal muscle mass reduction.
  15. 　精神的健康度向上用の、請求項１～１４のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 14, for improving mental health.
  16. 　前記組み合わせ物が一体的にまたは別体として構成されている、請求項１～１５のいずれか一項に記載の組み合わせ物。 The combination according to any one of claims 1 to 15, wherein the combination is configured integrally or as a separate body.
  17. 　フレイル改善用組み合わせ物の製造における、乳たんぱく質、亜鉛およびビタミンＤの使用。 Use of milk protein, zinc and vitamin D in the manufacture of a combination for improving flail.
  18. 　前記組み合わせ物が骨格筋量減少改善用組み合わせ物である、請求項１７に記載の使用。 The use according to claim 17, wherein the combination is a combination for improving skeletal muscle mass reduction.
  19. 　前記組み合わせ物が精神的健康度向上用組み合わせ物である、請求項１７または１８に記載の使用。 The use according to claim 17 or 18, wherein the combination is a combination for improving mental health.
  20. 　乳たんぱく質、亜鉛およびビタミンＤを有効量で対象に摂取させることを含んでなる、フレイルの改善方法。 A method for improving flail, comprising allowing a subject to ingest effective amounts of milk protein, zinc and vitamin D.
  21. 　骨格筋量の減少の改善方法である、請求項２０に記載の方法。 The method according to claim 20, which is a method for improving a decrease in skeletal muscle mass.
  22. 　精神的健康度の向上方法である、請求項２０または２１に記載の方法。 The method according to claim 20 or 21, which is a method for improving mental health.
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