WO2013080911A1 - Nutritional composition for improving intestinal flora - Google Patents

Nutritional composition for improving intestinal flora Download PDF

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Publication number
WO2013080911A1
WO2013080911A1 PCT/JP2012/080450 JP2012080450W WO2013080911A1 WO 2013080911 A1 WO2013080911 A1 WO 2013080911A1 JP 2012080450 W JP2012080450 W JP 2012080450W WO 2013080911 A1 WO2013080911 A1 WO 2013080911A1
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Prior art keywords
nutritional composition
milk
protein
milk protein
bacteria
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PCT/JP2012/080450
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French (fr)
Japanese (ja)
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真也 永渕
粂　久枝
健人 山地
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株式会社明治
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Priority to JP2013547137A priority Critical patent/JP6234227B2/en
Priority to IN3449DEN2014 priority patent/IN2014DN03449A/en
Priority to CN201280059104.9A priority patent/CN103957720B/en
Priority to SG11201402693VA priority patent/SG11201402693VA/en
Publication of WO2013080911A1 publication Critical patent/WO2013080911A1/en
Priority to HK14111191.8A priority patent/HK1197795A1/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
    • 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
    • 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
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C19/00—Cheese; Cheese preparations; Making thereof
    • A23C19/06—Treating cheese curd after whey separation; Products obtained thereby
    • A23C19/068—Particular types of cheese
    • A23C19/076—Soft unripened cheese, e.g. cottage or cream cheese
    • A23C19/0765—Addition to the curd of additives other than acidifying agents, dairy products, proteins except gelatine, fats, enzymes, microorganisms, NaCl, CaCl2 or KCl; Foamed fresh cheese products
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a nutritional composition for improving intestinal flora.
  • the intestinal environment is thought to be involved in various diseases and aging.
  • the number of bacteria of the genus Bifidobacterium is decreased, and it is said that the intestinal flora is disturbed.
  • the deterioration of the intestinal flora may promote aging.
  • Bad bacteria in the intestine produce harmful spoilage products (ammonia, amines, phenols, indoles, etc.). These spoilage products directly damage the intestinal tract and are partially absorbed by the body to promote aging throughout the life of the host, as well as the development of diseases such as cancer, myocardial infarction, and hypertension. Is involved.
  • Non-patent Document 1 Non-patent Document 1
  • Non-patent Document 3 the culture supernatant of propionic acid bacteria and lactic acid bacteria
  • Entererococcus genus the culture supernatant of propionic acid bacteria and lactic acid bacteria
  • Non-patent Document 3 fructooligosaccharides
  • these are nutritional compositions (liquid foods) for the purpose of supplementing nutrition, and none of them are known for the purpose of promoting the growth of good bacteria of the genus Bifidobacterium and / or Lactobacillus.
  • an object of the present invention is to provide a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus in the intestine (intestinal tract) at the same time as replenishing nutrition.
  • compositions comprising milk protein hydrolysates, fermented milk proteins, phospholipids, fats and oils containing oleic acid, and isomaltulose promote the growth of Bifidobacterium and / or Lactobacillus bacteria The effect was found and the present invention was completed.
  • the above-described nutritional composition was found to increase the number and occupancy of the genus Bifidobacterium and Lactobacillus without changing the total number of bacteria in the intestine. . From this result, it was found that the above nutritional composition promotes the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus. In addition, a decrease in pH in the cecum, an increase in the weight of cecal tissue and cecal contents, and an increase in the amount of organic acids in the cecal contents were confirmed. Therefore, the composition of the present invention is useful for improving the intestinal flora.
  • the present invention [1] Milk protein hydrolyzate and fermented milk protein as protein, fats and oils containing oleic acid as lipid, and milk phospholipid and / or soy lecithin, and isomaltulose as carbohydrate and / or Bifidobacterium genus and / or A nutritional composition for promoting the growth of the genus Lactobacillus, [2]
  • the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), ⁇ -lactalbumin, ⁇ -lactoglobulin and lactoferrin.
  • the nutritional composition according to the above [1], [3] The nutritional composition according to any one of [1] to [2] above, wherein the milk protein hydrolyzate is contained in an amount of 0.9 to 5.0 g per 100 ml of the nutritional composition.
  • Milk protein hydrolyzate may be obtained by hydrolyzing whey protein concentrate (WPC) and / or whey protein isolate (WPI) with an alcalase from Bacillus licheniformus and from porcine pancreas
  • WPC whey protein concentrate
  • WPI whey protein isolate
  • the nutritional composition according to any one of [1] to [3], obtained by hydrolysis with trypsin, [5] The hydrolyzate of milk protein according to any one of [1] to [4], wherein the permeate is a permeate obtained by treatment with an ultrafiltration membrane having a molecular weight cut off of 10,000.
  • Nutritional composition of the [6] The nutritional composition according to any one of [1] to [5] above, wherein the fermented milk protein is derived from cheese, [7] The nutritional composition according to [6], wherein the cheese is quark, [8] The nutritional composition according to any one of [1] to [7] above, wherein the fermented milk protein is contained in an amount of 0.5 to 6 g per 100 ml of the nutritional composition, [9] The nutritional composition according to any one of [1] to [8] above, wherein isomaltulose is contained in an amount of 4 to 15 g per 100 ml of the nutritional composition. [10] The nutritional composition according to any one of [1] to [9], wherein the lipid contains oleic acid in a proportion of 30% or more of the total fatty acid composition.
  • the nutritional composition of the present invention can improve the intestinal microflora at the same time as replenishing nutrition.
  • the nutritional composition of the present invention when used for liquid food, oral / enteral / tube feeding, etc., in addition to nutritional supplementation, the intestinal flora of those who have taken it can also be improved.
  • the composition of this invention can be ingested safely, it is suitable for the nutrition management in long-term medical treatment.
  • 2 is a graph showing the weight of the cecum and the pH in the cecum in Example 1.
  • the graph represents mean ⁇ SD. *: P ⁇ 0.05.
  • 2 is a graph showing the amount of short-chain fatty acids in the cecum contents in Example 1.
  • the graph represents mean ⁇ SD. *: P ⁇ 0.05.
  • 2 is a graph showing analysis results of Bifidobacterium genus and Lactobacillus genus in Example 1.
  • the graph represents mean ⁇ SD. *: P ⁇ 0.05.
  • the present invention relates to the following 1. To 3. And a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus.
  • Protein 2. 2. Lipid Carbohydrate The nutritional composition of the present invention contains, as protein, a hydrolyzate of milk protein and fermented milk protein. Includes fats and phospholipids containing oleic acid as lipids. Contains isomaltulose as a carbohydrate. Below, the structural component of the composition of this invention is demonstrated concretely.
  • milk protein hydrolyzate As raw milk protein, casein, whey protein (whey protein concentrate (WPC), whey protein isolate (WPI), ⁇ -lactalbumin ( ⁇ -La), ⁇ -lactoglobulin ( ⁇ -Lg)), at least one milk protein selected from milk protein concentrates (MPC, also referred to as total milk protein (TMP)) and mixtures thereof.
  • WPC whey protein concentrate
  • WPI whey protein isolate
  • ⁇ -La ⁇ -lactalbumin
  • ⁇ -Lg ⁇ -lactoglobulin
  • MPC also referred to as total milk protein (TMP)
  • Milk protein hydrolyzate will be explained by taking whey protein hydrolysis as an example.
  • Enzymes used to hydrolyze whey proteins are usually pepsin, trypsin and chymotrypsin, but research reports using plant-derived papain, bacteria and fungi-derived proteases (Food Technol., 48: 68-71,1994; Trends Food Sci. Technol., 7: 120-125, -1996; Food Proteins and Their Applications, pp. 443-472, 1997). Accordingly, these enzymes can be used in the present invention. Therefore, the composition of this invention contains what is obtained by hydrolyzing the above-mentioned milk protein by the at least 1 enzyme selected from the group which consists of these enzymes.
  • the activity of an enzyme that hydrolyzes whey protein varies greatly depending on its type. A person skilled in the art can select an optimum enzyme based on the activity of each enzyme. Pepsin degrades ⁇ -La and modified ⁇ -La, but does not degrade native ⁇ -Lg (Neth.hMilk dairy J., 47: 15-22, 1993). Trypsin degrades ⁇ -La slowly but hardly ⁇ -Lg (Neth.NetMilk dairy J., 45: 225-240, 1991). Chymotrypsin degrades ⁇ -La quickly, but slowly degrades ⁇ -Lg.
  • the functional properties of the milk protein can be altered over a wide range of pH and processing conditions (Enzymezyand Chemical Modification of proteins in Food proteins and their Applications, pp. 393-423, 1997, Marcel Dekker, Inc., New York, 1997; Food Technol., 48: 68-71, 1994).
  • peptides derived from milk protein various physiologically active peptides are known.
  • peptides derived from ⁇ s2-casein have been pointed out to destroy microorganisms (Rhodotorula rubra, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, Staphylococcus carnosus, Bacillus subtilis) that are not naturally present in the standard intestinal flora (Special Table 2000-507941).
  • the nutritional composition using only whey protein hydrolyzate as the protein source suppresses the growth of lactic acid bacteria and enterococci in the jejunum and ileum compared to the nutritional composition using only the undegraded whey protein as the protein source. It has been pointed out. However, no bifidobacteria were detected in any of the test groups (Japanese Patent Publication No. 2004-536143). Furthermore, ⁇ -casein-derived peptides and lactoferrin-derived peptides obtained from pepsin-treated milk proteins allow Bifidobacterium bifidum to grow relatively (preferentially) over E. coli in vitro. Has been pointed out (Japanese Patent Publication No. 2001-516570). However, specific experimental data is not disclosed.
  • Subtilis) -derived protease using a non-pH-stat method to hydrolyze to a degree of hydrolysis (DE) of 15-30% to obtain an ultrafiltration membrane permeate with a cut-off value exceeding 10,000 Japanese Patent No. 3167723
  • the milk protein hydrolyzate of the present invention includes those prepared by methods and techniques other than these patent documents.
  • a whey protein hydrolyzate can be prepared, for example, by a method including the following steps (1) to (5).
  • a whey protein isolate (WPI, Davisco) with a protein content of approximately 90% (w / w) as a dry product is added to distilled water so that the protein concentration is 8% (w / v). Dissolve to obtain an aqueous protein solution.
  • the aqueous solution is heat treated at 85 ° C. for 2 minutes to denature the protein.
  • the pH of the aqueous solution after the heat treatment can be about 7.5, for example.
  • Alcalase 2.4L (enzyme, Novozymes) was added at 2.0% (w / w) with respect to the concentration of the protein (substrate), and the aqueous solution was maintained at 55 ° C. for 3 hours for hydrolysis. Decompose.
  • PTN 6.0S enzyme, Novozymes Japan
  • a trypsin derived from swine was added at a concentration of 3.0% (w / w) with respect to the concentration of the protein (substrate), and the aqueous solution was 55%. Hydrolyze by holding at °C for 3 hours. That is, the total hydrolysis time can be, for example, 6 hours in total.
  • the pH of the aqueous solution at the end of these hydrolysis reactions can be, for example, about 7.0.
  • the hydrolyzate of whey protein is centrifuged (20,000 ⁇ g, 10 minutes) and then treated with an ultrafiltration (UF) membrane (Millipore Ultrafree-MC) having a molecular weight cut-off of 10,000.
  • UF ultrafiltration
  • the five parameters for optimization include preheating, enzyme to substrate ratio (E / S), pH, hydrolysis temperature, and hydrolysis time,
  • preheating 65 to 90 ° C.
  • E / S 0.01 to 0.2
  • pH 2 to 10
  • hydrolysis temperature 30 to 65 ° C.
  • hydrolysis time 3 to 20 hours.
  • enzymes used for protein hydrolysis include the following.
  • the following enzymes can be obtained through suppliers such as Novo Nordisk. 1) End-type protease, Bacillus, Licheniformus origin: Alcalase ⁇ B. lentus origin: Esperase ⁇ B. subtilis origin: Neutrase ⁇ Bacteria origin: Protamex ⁇ Pig pancreas origin: PTN (trypsin) 2) From exo-type protease, Aspergillus oryzae: Flavorzyme, from porcine or bovine viscera: Carboxypeptidase
  • the hydrolyzate of the milk protein of the present invention includes the protein hydrolyzate itself, a retentate treated with an ultrafiltration membrane (retentate) or a permeate (permeate), and similar activities required in the present invention.
  • Commercially available milk protein hydrolysates with for example, as the milk protein hydrolyzate of the present invention, the molecular weight cut-off is any one of 5000, 6000, 7000, 8000, 9000, 10000 as the lower limit (“more than or more than”), 15000, 20000, 25000, A retentate treated with an ultrafiltration membrane having a molecular weight between two points with an upper limit ( ⁇ less than or lower) of any one of 30000, preferably an ultrafiltration membrane having a molecular weight cut off of 10,000. Can be used.
  • Milk protein hydrolyzate content includes other ingredients (fermented milk protein, fats and oils containing oleic acid, milk phospholipids, soy lecithin, isomaltulose, etc.), pathology of enteral nutrition patients, It can be adjusted as appropriate according to symptoms, age, weight, application and the like.
  • the blended amount of the hydrolyzate of milk protein is 0.9 to 5.0 gm, preferably 0.9 to 3.0 g, more preferably 1.0 to 2.5 g, and still more preferably 1.2 to 2.0 g per 100 ml of the nutritional composition. Although it can illustrate, it is not limited to these ranges.
  • fermented milk protein As the origin of the fermented milk protein of the present invention, so-called fermented milk (domestic milk such as cow's milk, buffalo milk, goat milk, sheep milk, horse milk and / or partially skimmed milk, skimmed milk, reduced whole milk, reduced milk, etc. All of the liquid milk prepared by combining one or more milk raw materials such as skim milk, reduced partial skim milk, butter and cream with a starter such as lactic acid bacteria can be used. For example, fresh cheese, natural cheese, yogurt, whey cheese are included in the fermented milk protein of the present invention.
  • the cheese of the present invention is a product obtained by fermenting milk, buttermilk or cream with lactic acid bacteria, or removing whey (whey) from milk, buttermilk or cream, which is obtained by adding an enzyme to the cream, It does not matter whether solidification or aging occurs. Lactobacillus bulgaricus, Streptococcus thermophilus can be mainly used as a starter for producing fermented milk.
  • the nutritional composition of the present invention may be prepared using any fermented milk, but is preferably prepared using fresh cheese or yoghurt, more preferably quark or yoghurt.
  • Quark is a kind of non-ripe-molded (fresh) cheese, characterized by low fat content, refreshing flavor and sourness.
  • a general method for producing quark will be described below. First, skim milk is sterilized, then inoculated with 0.5 to 5% (w / w) of lactic acid bacteria starter (mainly Lactobacillus bulgaricus, Streptococcus thermophilus) and fermented. When the pH of the solution reaches 4.6, a curd is formed, and the whey is centrifuged using a quark separator, and then the obtained curd is cooled.
  • lactic acid bacteria starter mainly Lactobacillus bulgaricus, Streptococcus thermophilus
  • the total solid content is 17 to 19% (w / w)
  • the protein is 11 to 13% (w / w)
  • the fat is less than 1% (w / w)
  • what was solidified using the rennet is also included in the quark of the present invention.
  • Also included in the quark of the present invention are those obtained by adding and cultivating a mixed culture of Lactococcus belonging to Lactococcus, Cremoris and Leuconostoc species to skim milk and removing whey. Is done.
  • curd obtained by carrying out similarly to the said method with a cutter, heating the solution is also included by the fresh cheese of this invention.
  • lactic acid bacteria have a probiotic effect.
  • fresh cheese whey obtained by fermentation of lactic acid bacteria is known to have antibacterial effects against Escherichia coli, Vibrio parahaemolyticus, Bifidobacteria, Bacteroides, etc. (Japanese Patent Laid-Open No. 07-155103).
  • the blended amount of fermented milk protein is the blended amount of other ingredients (milk protein hydrolyzate, fat-containing fats and oils containing oleic acid, milk phospholipid, soy lecithin, isomaltulose, etc.) It can be adjusted as appropriate according to symptoms, age, weight, application and the like.
  • the amount of fermented milk protein may be 0.5 to 6 g, preferably 2 to 6 g, more preferably 2.5 to 4.5 g, per 100 g of the nutritional composition in terms of protein. It is not limited to these ranges.
  • milk also referred to as normal milk or mature milk
  • the origin of milk may be any animal such as cow, buffalo, goat, sheep, horse, human.
  • Lipid 2-1 Phospholipid in the present invention, a combination of milk phospholipid and soybean-derived lecithin or egg yolk lecithin can be used as the phospholipid. Alternatively, milk phospholipid, soybean-derived lecithin, or egg yolk lecithin may be used alone as the phospholipid. Preferred phospholipids of the present invention include, but are not limited to, milk phospholipid and / or soybean-derived lecithin, or milk phospholipid and / or egg yolk lecithin.
  • lecithin is used to refer to phosphatidylcholine in fields such as biochemistry, medicine and pharmacy, but commercially or industrially, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid and other phospholipids It is used as a general term for a mixture of The 7th edition of the Food Additives (1999) defines that lecithin is "obtained from oil seeds or animal raw materials, the main component of which is phospholipid".
  • the lecithin of the present invention includes these phospholipids used in a commercial or industrial sense.
  • Milk phospholipid consists of sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), lysophosphatidylcholine (LPC), and milk fat globule membrane (MFGM) is localized only.
  • SM sphingomyelin
  • PC phosphatidylcholine
  • PE phosphatidylethanolamine
  • PI phosphatidylinositol
  • PS phosphatidylserine
  • LPC milk fat globule membrane
  • MFGM milk fat globule membrane
  • Soy lecithin Soy lecithin is widely used in the food field as a natural food additive.
  • polyenephosphatidylcholine is also used as a medicine (indication: improvement of liver function in chronic liver disease, fatty liver, hyperlipidemia).
  • the so-called “natural” series of phospholipid products are usually ordered by the PC content in the product.
  • Various types of phospholipids that have been improved according to the use of phospholipids have been produced. Soy lecithin products are classified as shown in Table 2 for the sake of convenience, depending on the main PC content due to the purification and fractionation of soy lecithin (Yamama Fujikawa, Oil Chemistry, Vol. 40 (10), pp.951). -p58, 1991).
  • milk phospholipid and soybean lecithin may be used alone or in combination.
  • the amount of milk phospholipid and / or soy lecithin is the amount of other ingredients (milk protein hydrolyzate, fermented milk protein, fats and oils containing oleic acid, isomaltulose, etc.) It can be adjusted as appropriate according to symptoms, age, weight, application and the like.
  • the blending amount of milk phospholipid and / or soybean lecithin can be exemplified by a total of 0.01 to 0.5 g, 0.05 to 0.5 g, 0.1 to 0.5 g, 0.2 to 0.3 g per 100 mL of the nutritional composition. However, it is not limited to these ranges.
  • composition of the present invention contains an oil containing oleic acid as a lipid.
  • the Ministry of Health, Labor and Welfare has a desirable intake ratio of saturated fatty acids (SFA: palmitic acid, stearic acid, etc.): monounsaturated fatty acids (MUFA: oleic acid, etc.): polyunsaturated fatty acids (PUFA: linoleic acid, linolenic acid, etc.) It is recommended that the ratio of conventional 1: 1.5: 1 to 3: 4: 3 and the ratio of n-6 fatty acids: n-3 fatty acids be 4: 1.
  • oleic acid which is a monounsaturated fatty acid can be included in the nutritional composition of the present invention.
  • lipid sources rich in oleic acid include high oleic sunflower oil, rapeseed oil, olive oil, high oleic safflower oil, soybean oil, corn oil and palm oil.
  • nutritionally prepared fats and oils are mentioned as a lipid source containing oleic acid. Sunflower oil, rapeseed oil, olive oil, and mixtures with olive oil can also be used.
  • the amount of oleic acid is based on the amount of other ingredients (milk protein hydrolyzate, fermented milk protein, milk phospholipid, soy lecithin, isomaltulose, etc.), the condition, symptoms, age, weight, It can be appropriately adjusted depending on the application.
  • the blending amount of oleic acid can be exemplified by 25% or more, preferably 30% or more, more preferably 30 to 50% in the fatty acid composition of the nutritional composition of the present invention. It is not limited to.
  • polyunsaturated fatty acids such as DHA, EPA and arachidonic acid
  • medium chain fatty acids such as caprylic acid, capric acid and lauric acid
  • the ratio of saturated fatty acid: monounsaturated fatty acid: polyunsaturated fatty acid is increased. It can be adjusted to be close to 3: 4: 3.
  • isomaltulose can be mainly used as the sugar.
  • sugar alcohols sorbitol, xylitol, maltitol, etc.
  • honey granulated sugar, glucose, fructose, invert sugar and the like can be used.
  • Isomaltulose is a disaccharide in which glucose and fructose molecules are ⁇ -1,6-linked, and is a structural isomer of sucrose. 6-O- ( ⁇ -D-Glucopyranosyl) -D-fructose Also called maltulose or palatinose. It has a molecular weight of 342.297 and Cas. No. 13718-94-0 and is used for sweeteners. Isomaltulose is contained in very small amounts in honey and sugarcane. In addition, ⁇ -glucosyltransferase derived from Protaminobacter rubrum is allowed to act on sucrose to transfer ⁇ -1,2 linkages to ⁇ -1,6 linkages to produce isomaltulose.
  • isomaltulose is similar to that of sucrose, but the sweetness is about half that of sucrose. Orally ingested isomaltulose is degraded by isomaltase in the digestive tract, and is digested and absorbed into glucose and fructose in the same way as sucrose (Toshinao Aida, Journal of Japanese Society of Nutrition and Food, Vol. . 36 (3): 169-173, 1983).
  • isomaltose, panose, isomalttriose and the like that are digested with isomaltase compete with the digestion of isomaltulose, and it is said that digestive absorption is suppressed by ingesting isomaltulose ( Japanese Journal of Nutrition and Food, 36 (3), pp.169-173 (1983)).
  • the calorie of isomaltulose is 4kcal / g.
  • isomaltulose includes palatinose syrup, reduced palatinose or palatinose syrup.
  • Palatinose starch syrup is a starch syrup-like liquid substance mainly composed of oligosaccharides such as tetrasaccharide, hexasaccharide and octasaccharide produced by dehydration condensation of isomaltulose.
  • isomaltulose is highly selectively assimilated by the butyric acid bacterium Clostridium butyricum and promotes the growth of Clostridium butyricum (Takeo Mizutani, “Characteristics and utilization of palatinose oligosaccharides”, New Food Industry) Food Materials Research Group, 1991, Vol. 33, No. 2, pp. 9-16).
  • an aqueous solution prepared by dissolving a combination of a crystalline osmotic pressure regulator such as isomaltulose and a colloid osmotic pressure regulator such as dextrin and indigestible dextrin in water to adjust the osmotic pressure to 200 to 440 mOsm / L. It is also known to adjust the growth environment of useful bacteria by eliminating harmful bacteria (International Publication WO2004 / 067037).
  • the blending amount of isomaltulose is blended with other ingredients (milk protein hydrolyzate, fermented milk protein, fats and oils containing oleic acid, milk phospholipids, soybean lecithin, etc.) It can be adjusted as appropriate according to age, weight, use and the like. Specifically, the blending amount of isomaltulose can be exemplified by 4 to 15 g, preferably 5 to 7 g per 100 mL of the nutritional composition, but is not limited to these ranges.
  • the amount of heat of the nutritional composition of the present invention can be adjusted by appropriately adding proteins, lipids and carbohydrates.
  • heat amount of the nutrition composition of this invention can illustrate 50-150 kcal per 100 ml of nutrition composition, Preferably, it is 80-120 kcal, However It is not limited to these ranges.
  • the energy ratio of the protein, lipid, and carbohydrate to the whole nutritional composition in the nutritional composition of the present invention substantially conforms to the nutritional requirements of the sixth revised Japanese. Specific examples include 15 to 25% protein, 20 to 30% lipid, and 45 to 65% carbohydrates, but are not limited to these ranges.
  • the nutritional composition of the present invention may also contain dietary fiber.
  • Dietary fiber refers to a substance in food that is not hydrolyzed by human digestive enzymes, and is classified into water-soluble dietary fiber and insoluble dietary fiber based on its affinity for water.
  • indigestible oligosaccharides such as lactulose, lactitol, or raffinose can be used as water-soluble dietary fiber.
  • Physiological functions of indigestible oligosaccharides are known to reach the large intestine as undigested substances, contribute to the activation and proliferation of intestinal bifidobacteria, and have an improved intestinal environment, ie, an intestinal regulating effect. Yes.
  • water-soluble dietary fiber candidates pectin (protopectin, pectinic acid, pectinic acid), guar gum / enzymatic degradation product, tamarind seed gum and the like can be used.
  • high-molecular water-soluble dietary fiber includes soybean thickening polysaccharide, konjac glucomannan, alginic acid, low molecular alginic acid, psyllium, gum arabic, seaweed polysaccharide (cellulose, lignin-like substance, agar) , Carrageenan, alginic acid, fucodyne, laminarin), microbial gum (welan gum, curdlan, xanthan gum, gellan gum, dextran, pullulan, lambzan gum), other gums (seed-derived locust bean gum, tamarind gum, tara gum, sap-derived caraya gum, Polydextrose of low molecular weight water-soluble dietary fiber
  • Insoluble dietary fiber increases the mass of indigestibles in the large intestine and shortens the transit time. As a result, the number of defecations increases, resulting in an increase in stool volume.
  • Insoluble dietary fiber candidates include cellulose, hemicellulose, lignin, chitin, chitosan, soy bran, wheat bran, barley bran, pine fiber, corn fiber, beet fiber, oat bran, rye bran, pearl bran, rice bran, millet, millet Millet bran such as barnyard millet and sorghum, cereal bran (leguminous) bran, artificial grain bran such as buckwheat, sesame bran and okara.
  • the nutritional composition of the present invention includes water, protein, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, emulsifiers in addition to the proteins, lipids, carbohydrates, and dietary fibers. , Thickeners, stabilizers and the like can be used.
  • the protein examples include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, whey protein hydrolysate, ⁇ -casein, ⁇ -casein, ⁇ - Casein, ⁇ -lactoglobulin, ⁇ -lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein and other animal and vegetable proteins, their degradation products; butter, whey minerals, cream, whey, non-protein nitrogen And various milk-derived components such as sialic acid, phospholipid, and lactose. It may contain peptides such as casein phosphopeptides and lysines and amino acids.
  • saccharide examples include saccharides, processed starch (in addition to text phosphorus, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like.
  • lipids include animal oils such as lard and fish oil, fractionated oils thereof, hydrogenated oils and transesterified oils; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, Examples include vegetable oils such as hydrogenated oils and transesterified oils.
  • vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline.
  • minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium.
  • organic acid include malic acid, citric acid, lactic acid, tartaric acid, erythorbic acid, and the like.
  • ingredients that reduce fecal odor eg, champignon extract 5 mg to 500 mg (0.005% to 0.5%)
  • carotenoid preparations eg, ⁇ -carotene, ⁇ -carotene, lycopene, lutein, etc. 10 ⁇ g to 200 ⁇ g (0.00001% to 0.0002%)
  • an antioxidant catechin, polyphenol, etc.
  • Two or more of these components can be used in combination, and a synthetic product and / or a food containing a large amount thereof may be used.
  • the form of the food may be any form such as a solid, liquid, or gel.
  • the production of the nutritional composition of the present invention can be carried out by methods known in the art. After some or all of the raw materials have been prepared, homogenization is performed as necessary. Homogenization means homogenization by thoroughly mixing each prepared component, and the fat globules and coarse particles of other components are mechanically refined to prevent the rising and aggregation of fat and the like, and the nutritional composition It means making into a uniform emulsified state.
  • heat treatment or heat sterilization is performed.
  • heat sterilization conditions general food sterilization conditions can be used, and heat sterilization can be performed using a conventional apparatus. For example, sterilization of 62-65 ° C x 30 minutes, 72 ° C or more x 15 seconds or more, 72 ° C or more x 15 minutes or more, or 120-150 ° C x 1-5 seconds, or 121-124 ° C x 5-20 minutes, 105
  • sterilization at ⁇ 140 ° C. retort (pressure heating) sterilization, high-pressure steam sterilization, etc. can be used, it is not limited to these examples.
  • the heat sterilization can be preferably performed under pressure.
  • the composition of the present invention can be used for normalization and maintenance of intestinal flora.
  • the nutritional composition of the present invention is suitable for nutritional management of oral and enteral nutrition patients, the elderly, infants and the like, for example, as liquid food, oral and tube feeding, beverages, gel foods (especially so-called functional foods) and the like. Can be used.
  • the osmotic pressure of the nutritional composition of the present invention can be exemplified by an osmotic pressure of about 500 to 1000 mOsm / l, such as about 550 to 750 mOsm / l.
  • the range is not limited.
  • the pH of the nutritional composition of the present invention can be adjusted to 4.6 or less, preferably 3.0 to 4.3, more preferably 3.8 to 4.2, but is not limited to these ranges.
  • the intestinal environment is thought to be involved in various diseases and aging.
  • the number of bacteria of the genus Bifidobacterium is decreased, and it is said that the intestinal flora is disturbed.
  • the deterioration of the intestinal flora may promote aging.
  • Bad bacteria in the intestine produce harmful spoilage products (ammonia, amines, phenols, indoles, etc.), but these spoilage products directly damage the intestinal tract and are partially absorbed by the body,
  • diseases such as cancer, myocardial infarction and hypertension.
  • probiotics such as bifidobacteria and lactic acid bacteria
  • probiotics have also been reported to increase the number of bifidobacteria and lactic acid bacteria in the intestine, and to prevent the increase of harmful substance-producing bacteria (such as a decrease in Clostridium) due to a decrease in the intestinal pH. Yes.
  • Liquid foods and enteral nutrients are used by elderly people and various pathologies. Since the intestinal function of the ingestion target is not functioning sufficiently, there are many liquid foods and enteral nutrients with little addition of dietary fiber, and there are few liquid foods and enteral nutrients that take into account cecal fermentation. . Since general liquid foods and enteral nutrients do not contain dietary fiber or are insufficient in content, cecal fermentation of those who take them is insufficient.
  • the nutritional composition of the present invention contains fermented milk protein and dietary fiber to maintain cecal fermentation in the normal range, thereby increasing the cecal tissue weight and cecal content.
  • An increase in cecal content means an increase in intestinal flora and an increase in total short-chain fatty acid content.
  • the present invention provides a cecal tissue weight comprising a hydrolyzate of milk protein as protein and a fermented milk protein, an oil containing oleic acid as a lipid, and milk phospholipid and / or soy lecithin and isomaltulose as a carbohydrate.
  • the present invention provides a composition for promoting an increase in the amount of cecum and a composition for promoting an increase in the content of the cecum.
  • the nutritional composition of the present invention increases the number and occupation rate of Bifidobacterium genus and Lactobacillus genus in cecal contents and feces without changing the total number of bacteria in the intestine in in vivo tests using rats. Was confirmed. In addition, a decrease in pH in the cecum, an increase in the weight of the cecal tissue / cecal contents, and an increase in the amount of organic acids in the cecal contents were confirmed. Therefore, the composition of the present invention is useful for improving intestinal flora.
  • the invention also includes a hydrolyzate of milk protein and a fermented milk protein as protein, an oil containing oleic acid as lipid, and milk phospholipid and / or soybean lecithin, and isomaltulose as carbohydrate.
  • a composition for promoting a decrease in pH and a composition for promoting an increase in the amount of an organic acid in the intestine. Examples of the intestine include the small intestine, the large intestine, and the cecum.
  • the nutritional composition of the present invention is effective against various Bifidobacterium bacteria and Lactobacillus bacteria.
  • Bifidobacterium bacteria include Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis, and Bifidobacterium catenulatum.
  • Lactobacillus examples include Lactobacillus casei, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus murinus, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus gasseri, and Lactobacillus. Whether growth of Bifidobacterium bacteria or Lactobacillus bacteria has been promoted can be determined by methods known to those skilled in the art such as observation of bacterial colonies and real-time PCR.
  • the daily intake of the nutritional composition of the present invention in a pharmaceutical product or food / drink depends on the pathology, age, symptoms, weight, use of the subject, and whether the nutritional composition of the present invention is the only nutritional item. Since it differs, it is not specifically limited. Specifically, in the case of an adult, the intake per day may be 400 to 1600 ml, preferably 600 to 1600 ml, more preferably 800 to 1200 ml. For healthy adults, for example, up to 3000 ml per day may be taken. The intake amount can also be determined by the attending physician of the subject person. Moreover, you may use the nutrition composition of this invention together with the pharmaceutical and foodstuff which have the improvement effect of the intestinal microflora conventionally known.
  • fermented propionic acid bacteria examples include fermented propionic acid bacteria, DHNA (2,4-dihydroxy-2-naphthoic acid), ACNQ (2-amino-3-carboxy-l, 4-naphthoquinone), and fructooligosaccharides.
  • DHNA 2,4-dihydroxy-2-naphthoic acid
  • ACNQ 2-amino-3-carboxy-l, 4-naphthoquinone
  • fructooligosaccharides examples include fermented propionic acid bacteria, DHNA (2,4-dihydroxy-2-naphthoic acid), ACNQ (2-amino-3-carboxy-l, 4-naphthoquinone), and fructooligosaccharides.
  • ACNQ 2-amino-3-carboxy-l, 4-naphthoquinone
  • the nutritional composition of the present invention can be used in the form of any medicine or food or drink.
  • enteric bacteria can be obtained by directly administering the nutritional composition of the present invention as a pharmaceutical or by directly ingesting it as a special-purpose food such as a food for specified health use, a nutritional functional food, a nutritional supplement, a liquid food or a supplement. It is expected to improve the flora.
  • various foods milk, soft drinks, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crusts, prepared milk powder, liquid foods, special-purpose foods, regardless of the form of liquid, paste, solid, powder, etc. , Foods for the sick, nutritional foods, frozen foods, processed foods, and other commercially available foods).
  • a nutrient composition when the usage form of a nutrient composition is a powder, it can manufacture by using means, such as spray drying and freeze-drying, for example.
  • the nutritional composition of the present invention When used as a medicine or supplement, it can be administered in various forms.
  • the form include oral administration using tablets, capsules, granules, powders, syrups and the like.
  • These various preparations can be usually used in the pharmaceutical preparation technical field such as main agents and excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, coating agents and the like according to conventional methods. It can be formulated using known adjuvants for formulation. Further, it may contain an appropriate amount of calcium. Further, an appropriate amount of vitamins, minerals, organic acids, sugars, amino acids, peptides, etc. may be added.
  • the nutritional composition of the present invention comprises a hydrolyzate of milk protein and fermented milk protein as protein, an oil containing oleic acid as lipid, and / or milk phospholipid and / or soybean lecithin, and isomalt as a carbohydrate. It can also be expressed as a drug for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, including sucrose.
  • the present invention also relates to a method for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, comprising the step of orally administering the nutritional composition of the present invention to an animal. Mammals are examples of subjects to which the nutritional composition of the present invention is administered.
  • Mammals include humans and mammals other than humans, preferably humans and monkeys, more preferably humans.
  • the present invention provides a milk protein hydrolyzate and fermented milk protein as a protein and an oil or fat containing oleic acid as a lipid for use in promoting the growth of bacteria of either or both of the genus Bifidobacterium and Lactobacillus, And a nutritional composition comprising milk phospholipid and / or soybean lecithin, and isomaltulose as a carbohydrate.
  • the present invention relates to the use of proteins, lipids and carbohydrates in the manufacture of a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus.
  • the present invention also relates to the use of proteins, lipids and carbohydrates for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus.
  • the present invention also provides a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, which comprises a step of combining a pharmaceutically acceptable carrier with proteins, lipids and carbohydrates. It relates to a manufacturing method. Specific examples of proteins, lipids and carbohydrates have been described herein. It should be noted that all prior art documents cited in the present specification are incorporated herein by reference.
  • Example 1 Efficacy test using animals
  • Test sample A general liquid food having the composition shown in Tables 3 and 4 and the nutritional composition of the present invention were prepared, and sterilized (135 to 145 ° C. ⁇ 5 to 10 seconds) by retort (heat and pressure) and freeze-dried. Used as a test sample. The content of oleic acid contained in the nutritional compositions in the table was 39% in the fatty acid composition.
  • Control group Ingested lyophilized liquid food.
  • Test group Ingested lyophilized product of the nutritional composition of the present invention.
  • Necropsy was performed under ether anesthesia, and after blood sampling, the abdomen was opened, the cecum was taken out, the ileum side and the colon side were ligated with a thread, the weight of the cecum was measured, and frozen at -80 ° C. until measurement.
  • the supernatant was transferred to another microtube, and Carrez I (53.5 g of ZnSO4 ⁇ 7H2 0/100 ml) and Carrez II (17.2 g of K4 [Fe (CN) 6] 3H2O / 100 ml) were each 2.5 ⁇ g per 200 ⁇ l of supernatant. ⁇ l was added and stirred. Centrifuge at 4 ° C, 10000rpm for 10 minutes, transfer the supernatant to a filter-equipped microtube (0.22 ⁇ m), and centrifuge again at 4 ° C, 10000rpm for 10 minutes to measure the supernatant. A sample was used.
  • the organic acid in the measurement sample was quantified by a post-column pH buffered conductivity detection method using a conductivity detector (Niwa T., Nakao M., Hoshi S. et al. Effect of Dietary Fiber on Morphine-induced Constipation in Rats, Biosci. Biotechnol. Biochem., 66 (6), 1233-1240, 2002).
  • Detector Electrical conductivity detector (Shimadzu CDD-10A)
  • Bacterial DNA was extracted from the feces and cecal contents, and Bifidobacterium genus and Lactobacillus genus bacteria count (viable cell count + dead cell count) were measured by real-time PCR. Number / g)). In addition, the ratio of the number of bacteria of each bacterium to the total number of bacteria was calculated as an occupation ratio (%). Statistical analysis of the results was performed by Student's t-test (equal variance) or Welch's test (unequal variance).
  • FIG. 1 shows the weight of each group, such as the cecum, and the pH in the cecum. Cecal weight increased significantly (p ⁇ 0.05) in the test group compared to the control group. This increase was due to an increase in cecal tissue weight and cecal content. In addition, the test group showed a significantly lower (p ⁇ 0.05) pH in the cecum than the control group.
  • FIG. 2 shows the amount of short chain fatty acids in the cecum contents. Compared to the control, there was no significant difference in the test group, but there was a tendency for short-chain fatty acids to increase.
  • FIG. 3 the analysis result of the intestinal microflora of each group is shown.
  • the nutritional composition of the present invention can improve the intestinal flora. Specifically, the composition of the present invention promotes the growth of lactic acid bacteria of the genus Bifidobacterium and / or Lactobacillus, promotes an increase in intestinal weight, promotes an increase in the amount of organic acid in the intestinal contents, It is useful for promoting a decrease and promoting an increase in short chain fatty acids.

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Abstract

A nutritional composition comprising milk protein hydrolyzate, a cultured milk protein, a phospholipid, an oil containing oleic acid, and isomaltulose, wherein an intestinal flora improvement effect has been found. Specifically, this nutritional composition has been found to increase the bacteria count and occupancy of Bifidobacterium genus and Lactobacillus genus in the intestine, in in vivo tests using rats. From these results, this nutritional composition is understood to promote the propagation of the Bifidobacterium genus and/or the Lactobacillus genus of bacteria.

Description

腸内菌叢改善用栄養組成物Nutritional composition for improving intestinal flora
　本発明は、腸内菌叢を改善するための栄養組成物に関する。 The present invention relates to a nutritional composition for improving intestinal flora.
　腸内環境は様々な疾患や老化に関与していると考えられている。高齢者では、Bifidobacterium属の細菌数が減少して、腸内菌叢が乱れていると言われている。このような腸内菌叢の悪化では、老化を促進する可能性が指摘されている。腸管内の悪玉菌は有害な腐敗産物（アンモニア、アミン、フェノール、インドールなど）を産生する。これらの腐敗産物は腸管に直接的に障害を与えると共に、部分的に体内に吸収され、宿主の生涯に渡って老化を促進するだけでなく、ガン、心筋梗塞、高血圧などの疾患の発症にも関わっている。これに対して、腸管内のBifidobacterium属のような善玉菌は悪玉菌の増殖を阻害する。従って、腸管内のBifidobacterium属の細菌の存在は健康維持に役立ち、有用な腸内細菌として、宿主の生涯に渡って重要であることが示唆されている。つまり、腸管内のBifidobacterium属の細菌数の減少や消失は、不健全な状態を意味するのである（非特許文献１）。 The intestinal environment is thought to be involved in various diseases and aging. In the elderly, the number of bacteria of the genus Bifidobacterium is decreased, and it is said that the intestinal flora is disturbed. It has been pointed out that the deterioration of the intestinal flora may promote aging. Bad bacteria in the intestine produce harmful spoilage products (ammonia, amines, phenols, indoles, etc.). These spoilage products directly damage the intestinal tract and are partially absorbed by the body to promote aging throughout the life of the host, as well as the development of diseases such as cancer, myocardial infarction, and hypertension. Is involved. On the other hand, good bacteria such as the genus Bifidobacterium in the intestine inhibit the growth of bad bacteria. Therefore, it is suggested that the presence of Bifidobacterium in the intestinal tract is useful for maintaining health and is important as a useful intestinal bacterium for the life of the host. That is, a decrease or disappearance of the number of Bifidobacterium in the intestinal tract means an unhealthy state (Non-patent Document 1).
　ところで、経腸栄養患者では、腸管内のBifidobacterium属の細菌数が健常人に比べて少なく（非特許文献２、非特許文献３）、腸内菌叢が健常人に比べて悪化していると考えられている。このことから、経腸栄養患者の乱れた腸内菌叢を正常のそれに近づける必要がある。 By the way, in enteral nutrition patients, the number of bacteria of the genus Bifidobacterium in the intestinal tract is less than that of healthy people (Non-patent Documents 2 and 3), and the intestinal flora is worse than that of healthy people. It is considered. For this reason, it is necessary to bring the disturbed gut microbiota of enteral nutrition patients closer to normal.
　腸内菌叢を改善する効果のある食材には、Bifidobacterium属やLactobacillus属などのプロバイオティクスのほかに、プロピオン酸菌や乳酸菌（エンテロコッカス属、ラクトコッカス属）の培養上清（特許文献１）、フラクトオリゴ糖（非特許文献３）などが知られている。しかしながら、これらは栄養の補給を目的とした栄養組成物（流動食）そのもので、Bifidobacterium属および／またはLactobacillus属の善玉菌の増殖の促進を目的とするものは知られていない。 In addition to probiotics such as Bifidobacterium genus and Lactobacillus genus, the culture supernatant of propionic acid bacteria and lactic acid bacteria (Enterococcus genus, Lactococcus genus) is included as a food material effective in improving the intestinal flora (Patent Document 1). And fructooligosaccharides (Non-patent Document 3) are known. However, these are nutritional compositions (liquid foods) for the purpose of supplementing nutrition, and none of them are known for the purpose of promoting the growth of good bacteria of the genus Bifidobacterium and / or Lactobacillus.
特開平05-041995号公報Japanese Patent Laid-Open No. 05-041995
　本発明は、このような状況に鑑みてなされたものである。すなわち本発明の課題は、栄養を補給すると同時に、腸内（腸管内）のBifidobacterium属および／またはLactobacillus属の細菌の増殖を促進するための栄養組成物を提供することである。 The present invention has been made in view of such a situation. That is, an object of the present invention is to provide a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus in the intestine (intestinal tract) at the same time as replenishing nutrition.
　本発明者らは、上述の課題を解決するために鋭意検討した。その結果、乳タンパク質の加水分解物、発酵乳タンパク質、リン脂質、オレイン酸を含有する油脂、およびイソマルチュロースを含む栄養組成物が、Bifidobacterium属および／またはLactobacillus属の細菌の増殖を促進する効果を見出し、本発明を完成させた。 The present inventors diligently studied to solve the above-described problems. As a result, nutritional compositions comprising milk protein hydrolysates, fermented milk proteins, phospholipids, fats and oils containing oleic acid, and isomaltulose promote the growth of Bifidobacterium and / or Lactobacillus bacteria The effect was found and the present invention was completed.
　具体的には、ラットを用いたin vivo試験において、上述の栄養組成物が、腸内の総菌数を変化させることなく、Bifidobacterium属やLactobacillus属の細菌数および占有率を高めることを見出した。この結果から、上述の栄養組成物は、Bifidobacterium属および／またはLactobacillus属の細菌の増殖を促進することがわかった。また、盲腸内のpHの低下、盲腸組織・盲腸内容物の重量の増加、盲腸内容物の有機酸量の増加が確認された。従って、本発明の組成物は、腸内菌叢の改善に有用である。 Specifically, in an in vivo test using rats, the above-described nutritional composition was found to increase the number and occupancy of the genus Bifidobacterium and Lactobacillus without changing the total number of bacteria in the intestine. . From this result, it was found that the above nutritional composition promotes the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus. In addition, a decrease in pH in the cecum, an increase in the weight of cecal tissue and cecal contents, and an increase in the amount of organic acids in the cecal contents were confirmed. Therefore, the composition of the present invention is useful for improving the intestinal flora.
　すなわち、本発明は、
[１] タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および／または大豆レシチン、糖質としてイソマルチュロースを含む、Bifidobacterium属および／またはLactobacillus属の増殖を促進するための栄養組成物、
[２] 乳タンパク質が、カゼイン、乳タンパク質濃縮物（MPC）、ホエイタンパク質濃縮物（WPC）、ホエイタンパク質分離物（WPI）、α-ラクトアルブミン、β-ラクトグロブリンおよびラクトフェリンからなる群より選択される、前記[１]に記載の栄養組成物、
[３] 乳タンパク質の加水分解物が、栄養組成物１００ｍｌあたり０．９～５．０ｇ含まれる、前記[１]～[２]のいずれか１つに記載の栄養組成物、
[４] 乳タンパク質の加水分解物が、ホエイタンパク質濃縮物（WPC）および／またはホエイタンパク質分離物（WPI）をバシラス・リシェニフォルムス（Bacillus licheniformus）由来のアルカラーゼで加水分解およびブタ膵臓由来のトリプシンで加水分解して得られる、前記[１]～[３]のいずれか１つに記載の栄養組成物、
[５] 乳タンパク質の加水分解物が、分画分子量10,000の限外濾過膜で処理して得られる透過画分（パーミエイト）である、前記[１]～[４]のいずれか１つに記載の栄養組成物、
[６] 発酵乳タンパク質がチーズに由来する、前記[１]～[５]のいずれか１つに記載の栄養組成物、
[７] チーズがクワルクである、前記[６]に記載の栄養組成物、
[８] 発酵乳タンパク質が、栄養組成物１００ｍｌあたり０．５～６ｇ含まれる、前記[１]～[７]のいずれか１つに記載の栄養組成物、
[９] イソマルチュロースが、栄養組成物１００ｍｌあたり４～１５ｇ含まれる、前記[１] ～[８]のいずれか１つに記載の栄養組成物、
[１０] 脂質にオレイン酸が全脂肪酸組成の３０%以上の割合で含まれる、前記[１] ～[９]のいずれか１つに記載の栄養組成物、からなる。 That is, the present invention
[1] Milk protein hydrolyzate and fermented milk protein as protein, fats and oils containing oleic acid as lipid, and milk phospholipid and / or soy lecithin, and isomaltulose as carbohydrate and / or Bifidobacterium genus and / or A nutritional composition for promoting the growth of the genus Lactobacillus,
[2] The milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin, β-lactoglobulin and lactoferrin. The nutritional composition according to the above [1],
[3] The nutritional composition according to any one of [1] to [2] above, wherein the milk protein hydrolyzate is contained in an amount of 0.9 to 5.0 g per 100 ml of the nutritional composition.
[4] Milk protein hydrolyzate may be obtained by hydrolyzing whey protein concentrate (WPC) and / or whey protein isolate (WPI) with an alcalase from Bacillus licheniformus and from porcine pancreas The nutritional composition according to any one of [1] to [3], obtained by hydrolysis with trypsin,
[5] The hydrolyzate of milk protein according to any one of [1] to [4], wherein the permeate is a permeate obtained by treatment with an ultrafiltration membrane having a molecular weight cut off of 10,000. Nutritional composition of the
[6] The nutritional composition according to any one of [1] to [5] above, wherein the fermented milk protein is derived from cheese,
[7] The nutritional composition according to [6], wherein the cheese is quark,
[8] The nutritional composition according to any one of [1] to [7] above, wherein the fermented milk protein is contained in an amount of 0.5 to 6 g per 100 ml of the nutritional composition,
[9] The nutritional composition according to any one of [1] to [8] above, wherein isomaltulose is contained in an amount of 4 to 15 g per 100 ml of the nutritional composition.
[10] The nutritional composition according to any one of [1] to [9], wherein the lipid contains oleic acid in a proportion of 30% or more of the total fatty acid composition.
　本発明の栄養組成物は、栄養を補給すると同時に、腸内菌叢を改善することができる。例えば、本発明の栄養組成物を流動食、経口・経腸・経管栄養などに用いると、栄養の補給に加え、それを摂取した者の腸内菌叢をも改善することができる。また、本発明の組成物は、安全に摂取できるので、長期療養における栄養管理に適している。 The nutritional composition of the present invention can improve the intestinal microflora at the same time as replenishing nutrition. For example, when the nutritional composition of the present invention is used for liquid food, oral / enteral / tube feeding, etc., in addition to nutritional supplementation, the intestinal flora of those who have taken it can also be improved. Moreover, since the composition of this invention can be ingested safely, it is suitable for the nutrition management in long-term medical treatment.
実施例１における、盲腸等の重量、および盲腸内のpHを示すグラフである。グラフはmean±SDを表す。＊：p<0.05。2 is a graph showing the weight of the cecum and the pH in the cecum in Example 1. The graph represents mean ± SD. *: P <0.05. 実施例１における、盲腸内容物の短鎖脂肪酸量を示すグラフである。グラフはmean±SDを表す。＊：p<0.05。2 is a graph showing the amount of short-chain fatty acids in the cecum contents in Example 1. The graph represents mean ± SD. *: P <0.05. 実施例１における、Bifidobacterium属、Lactobacillus属の解析結果を示すグラフである。グラフはmean±SDを表す。＊：p<0.05。2 is a graph showing analysis results of Bifidobacterium genus and Lactobacillus genus in Example 1. The graph represents mean ± SD. *: P <0.05.
　以下、本発明を詳細に説明する。ただし、本発明は以下の好ましい実施態様に限定されず、本発明の範囲内で自由に変更できるものである。
　本発明は、以下の１．から３．を含む、Bifidobacterium属およびLactobacillus属の細菌の両方またはいずれか一方の細菌の増殖を促進するための栄養組成物に関する。
１．タンパク質
２．脂質
３．糖質
　本発明の栄養組成物は、タンパク質として、乳タンパク質の加水分解物および発酵乳タンパク質を含む。脂質としてオレイン酸を含有する油脂およびリン脂質を含む。糖質としてイソマルチュロースを含む。以下に、本発明の組成物の構成成分を具体的に説明する。 Hereinafter, the present invention will be described in detail. However, the present invention is not limited to the following preferred embodiments, and can be freely changed within the scope of the present invention.
The present invention relates to the following 1. To 3. And a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus.
1. Protein 2. 2. Lipid Carbohydrate The nutritional composition of the present invention contains, as protein, a hydrolyzate of milk protein and fermented milk protein. Includes fats and phospholipids containing oleic acid as lipids. Contains isomaltulose as a carbohydrate. Below, the structural component of the composition of this invention is demonstrated concretely.
1．タンパク質
1-1 乳タンパク質の加水分解物
　原料の乳タンパク質として、カゼイン、ホエイタンパク質（ホエイタンパク質濃縮物（WPC）、ホエイタンパク質分離物（WPI）、α-ラクトアルブミン（α-La）、β-ラクトグロブリン（β-Lg））、乳タンパク質濃縮物（MPC、総乳タンパク質(TMP)ともいう）から選択される少なくとも1つの乳タンパク質およびこれらの混合物を例示することができる。 1． protein
1-1 Milk protein hydrolyzate As raw milk protein, casein, whey protein (whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (Β-Lg)), at least one milk protein selected from milk protein concentrates (MPC, also referred to as total milk protein (TMP)) and mixtures thereof.
　乳タンパク質の加水分解物について、ホエイタンパク質の加水分解を例に説明する。ホエイタンパク質の加水分解に用いる酵素として通常、ペプシン、トリプシンおよびキモトリプシンがあるが、植物由来のパパイン、バクテリアや菌類由来のプロテアーゼを用いた研究報告（Food Technol., 48: 68-71,1994；Trends Food Sci. Technol., 7: 120-125, 1996；Food Proteins and Their Applications, pp. 443-472, 1997）もある。従って本発明においては、これらの酵素を使用することができる。よって本発明の組成物は、上述の乳タンパク質を、これらの酵素からなる群から選択される少なくとも１つの酵素によって加水分解することによって得られるものを含む。ホエイタンパク質を加水分解する酵素の活性は、その種類により大きく変動する。当業者であれば、各酵素の活性に基づき最適な酵素を選択することができる。ペプシンはα-Laおよび変性したα-Laを分解するが、未変性の（native）β-Lgを分解しない（Neth. Milk dairy J., 47: 15-22, 1993 ）。トリプシンはα-Laをゆっくりと分解するが、β-Lgをほとんど分解しない（Neth. Milk dairy J., 45: 225-240, 1991）。キモトリプシンはα-Laを速く分解するが、β-Lgをゆっくりと分解する。パパインはウシ血清アルブミン（BSA）およびβ-Lgを分解するが、α-Laを分解しにくく、α-Laには抵抗性がある（Int. Dairy Journal 6: 13-31, 1996a）。しかしながら、パパインはCaを結合していないα-Laを酸性のpHで完全に分解する（J.Dairy Sci., 76: 311-320, 1993）。 Milk protein hydrolyzate will be explained by taking whey protein hydrolysis as an example. Enzymes used to hydrolyze whey proteins are usually pepsin, trypsin and chymotrypsin, but research reports using plant-derived papain, bacteria and fungi-derived proteases (Food Technol., 48: 68-71,1994; Trends Food Sci. Technol., 7: 120-125, -1996; Food Proteins and Their Applications, pp. 443-472, 1997). Accordingly, these enzymes can be used in the present invention. Therefore, the composition of this invention contains what is obtained by hydrolyzing the above-mentioned milk protein by the at least 1 enzyme selected from the group which consists of these enzymes. The activity of an enzyme that hydrolyzes whey protein varies greatly depending on its type. A person skilled in the art can select an optimum enzyme based on the activity of each enzyme. Pepsin degrades α-La and modified α-La, but does not degrade native β-Lg (Neth.hMilk dairy J., 47: 15-22, 1993). Trypsin degrades α-La slowly but hardly β-Lg (Neth.NetMilk dairy J., 45: 225-240, 1991). Chymotrypsin degrades α-La quickly, but slowly degrades β-Lg. Papain degrades bovine serum albumin (BSA) and β-Lg, but is difficult to degrade α-La and is resistant to α-La (Int. Dairy Journal 6: 13-31, 1996a). However, papain completely degrades α-La not bound to Ca at an acidic pH (J. Dairy Sci., 76: 311-320, 1993).
　乳タンパク質の加水分解の程度をコントロールして、乳タンパク質を修飾することにより、広範囲のpHおよびプロセッシングの条件に亘って、乳タンパク質の機能的な特性を変更することができる（Enzyme and Chemical Modification of proteins in Food proteins and their Applications, pp. 393-423, 1997, Marcel Dekker, Inc., New York, 1997；Food Technol., 48: 68-71, 1994）。 By controlling the degree of milk protein hydrolysis and modifying the milk protein, the functional properties of the milk protein can be altered over a wide range of pH and processing conditions (Enzymezyand Chemical Modification of proteins in Food proteins and their Applications, pp. 393-423, 1997, Marcel Dekker, Inc., New York, 1997; Food Technol., 48: 68-71, 1994).
　ペプチド結合の加水分解では、荷電基数および疎水性の増加、低分子量化、ならびに分子の立体配置の修飾がもたらされる（J. Dairy Sci., 76: 311-320, 1993）。 乳タンパク質の機能的な特性の変化は加水分解度に大きく依存する。例えば、ホエイタンパク質の機能性に共通して見られる最大の変化は溶解性の増加と粘度の低下である。ホエイタンパク質の加水分解度が高い場合、その加水分解物では、しばしば、加熱しても沈澱せず、pH が3.5～4.0において溶解性が高くなる。また、その加水分解物では、無処置（intact）のタンパク質よりも、はるかに粘度が低くなる。これらの差異は特に、タンパク質の濃度が高い場合に顕著である。その他の影響としては、ゲル特性の変化、熱安定性の向上、乳化性および起泡安定性の低下などが挙げられる（Int. Dairy journal, 6: 13-31, 1996a；Dairy Chemistry 4, pp. 347-376, 1989；J. Dairy Sci., 79: 782-790, 1996）。 Hydrolysis of peptide bonds results in increased number of charged groups and hydrophobicity, lower molecular weight, and modification of molecular configuration (J. Dairy Sci., 76: 311-320, 1993). Changes in the functional properties of stalactite proteins are highly dependent on the degree of hydrolysis. For example, the greatest changes commonly seen in whey protein functionality are increased solubility and decreased viscosity. When the degree of hydrolysis of whey protein is high, the hydrolyzate often does not precipitate even when heated and becomes highly soluble at a pH of 3.5 to 4.0. Also, the hydrolyzate has a much lower viscosity than intact protein. These differences are particularly noticeable when the protein concentration is high. Other effects include changes in gel properties, improved thermal stability, reduced emulsifiability and foam stability (Int. Dairy journal, 6: 13-31, 1996a; Dairy Chemistry 4, pp. 347-376, 1989; J. Dairy Sci., 79: 782-790, 1996).
　乳タンパク質から派生して、さまざまな生理活性ペプチドが知られている。例えば、αs2-カゼイン由来のペプチドは、標準的な腸内細菌叢に自然に存在しない微生物（Rhodotorula rubra、大腸菌、Enterococcus faecium、Staphylococcus epidermidis、Staphylococcus carnosus、Bacillus subtilis）を破壊することが指摘されている（特表2000-507941号公報）。また、ホエイタンパク質の加水分解物のみをタンパク質源とする栄養組成物では、未分解のホエイタンパク質のみをタンパク質源とする栄養組成物と比べて、空腸・回腸の乳酸菌や腸球菌の増殖を抑制することが指摘されている。しかしいずれの試験群においても、ビフィズス菌は検出されていない（特表2004-536143号公報）。さらに、乳タンパク質のペプシン処理物から得られる、κ-カゼイン由来のペプチドおよびラクトフェリン由来のペプチドでは、in vitroにおいて、ビフィドバクテリウム・ビフィダムを大腸菌よりも相対的に（優先的に）成長させることが指摘されている（特表2001-516570号公報）。しかし具体的な実験データは開示されていない。 Derived from milk protein, various physiologically active peptides are known. For example, peptides derived from αs2-casein have been pointed out to destroy microorganisms (Rhodotorula rubra, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, Staphylococcus carnosus, Bacillus subtilis) that are not naturally present in the standard intestinal flora (Special Table 2000-507941). In addition, the nutritional composition using only whey protein hydrolyzate as the protein source suppresses the growth of lactic acid bacteria and enterococci in the jejunum and ileum compared to the nutritional composition using only the undegraded whey protein as the protein source. It has been pointed out. However, no bifidobacteria were detected in any of the test groups (Japanese Patent Publication No. 2004-536143). Furthermore, κ-casein-derived peptides and lactoferrin-derived peptides obtained from pepsin-treated milk proteins allow Bifidobacterium bifidum to grow relatively (preferentially) over E. coli in vitro. Has been pointed out (Japanese Patent Publication No. 2001-516570). However, specific experimental data is not disclosed.
　一方、乳タンパク質の加水分解物については、上記に例示した学術文献に加えて、数多くの調製方法などが開示された特許文献（公開特許公報および特許公報）が存在する。当業者であれば、これらの文献にしたがって乳タンパク質の加水分解物を調製することができる。例えば、
カゼインとホエイタンパク質を別々に加水分解してから、疎水性部分を吸着・除去した後に、両者を所定割合で混合する方法（日本特許第2,986,764号）、
ホエイタンパク質をバチルス属由来のプロテアーゼと放線菌由来のプロテアーゼにより加水分解した後に、酵素と不溶性の加水分解物を除去する方法（日本特許第3,222,638号）、
β-ラクトグロブリンを酵素で分解して、分岐鎖アミノ酸／芳香族アミノ酸のモル比が10重量%以上、芳香族アミノ酸が2.0重量%未満、平均分子量が数百～数千のペプチドの混合物を得る方法（日本特許第3,183,945号）、
ホエイタンパク質中のβ-ラクトグロブリンを選択的に酵素分解する方法（日本特許第2,794,305号）、あるいは
ホエイタンパク質をバシラス・リシェニフォルムス（B. licheniformis）由来のプロテアーゼおよび／または枯草菌（B. subtilis）由来のプロテアーゼにより、非－pH－スタット法を用いて、15～30%の加水分解度（DE）まで加水分解し、カットオフ値10,000を超える限外濾過膜の透過液を得る方法（日本特許第3167723号）
などを挙げることができるがこれらに限定されない。本発明の乳タンパク質加水分解物では、これらの特許文献以外の方法や技術で調製されたものも包含される。 On the other hand, regarding the hydrolyzate of milk protein, in addition to the academic literatures exemplified above, there are patent documents (open patent publications and patent publications) in which many preparation methods and the like are disclosed. One skilled in the art can prepare milk protein hydrolysates according to these references. For example,
A method of hydrolyzing casein and whey protein separately, adsorbing and removing the hydrophobic part, and then mixing both in a predetermined ratio (Japanese Patent No. 2,986,764),
A method for removing whey protein from proteases derived from Bacillus and actinomycetes and then removing the enzyme and insoluble hydrolyzate (Japanese Patent No. 3,222,638),
Degradation of β-lactoglobulin with an enzyme yields a mixture of peptides having a branched chain amino acid / aromatic amino acid molar ratio of 10% by weight or more, an aromatic amino acid content of less than 2.0% by weight, and an average molecular weight of several hundred to several thousand. Method (Japanese Patent No. 3,183,945),
A method of selectively degrading β-lactoglobulin in whey protein (Japanese Patent No. 2,794,305), or a protein derived from B. licheniformis and / or Bacillus subtilis (B. Subtilis) -derived protease using a non-pH-stat method to hydrolyze to a degree of hydrolysis (DE) of 15-30% to obtain an ultrafiltration membrane permeate with a cut-off value exceeding 10,000 ( (Japanese Patent No. 3167723)
However, it is not limited to these. The milk protein hydrolyzate of the present invention includes those prepared by methods and techniques other than these patent documents.
　本発明の好ましい態様として、ホエイタンパク質の加水分解物は、例えば下記（１）～（５）の工程を含む方法により調製することができる。
（１）乾燥物としてタンパク質の含量が約90 %（w/w）のホエイタンパク質の分離物（WPI、ダビスコ社）を、タンパク質の濃度が8 %（w/v）となるように蒸留水に溶解して、タンパク質の水溶液を得る。
（２）この水溶液を85℃、2分間で加熱処理して、タンパク質を変性させる。この加熱処理後の水溶液のpHは、例えば約7.5とすることができる。
（３）その後に、アルカラーゼ2.4L（酵素、ノボザイムス社）を、タンパク質（基質）の濃度に対して2.0 %（w/w）で添加し、その水溶液を55℃、3時間で保持して加水分解する。
（４）次に、豚由来のトリプシンである PTN 6.0S（酵素、ノボザイムズジャパン社）を、タンパク質（基質）の濃度に対して3.0 %（w/w）で添加し、その水溶液を55℃、3時間で保持して加水分解する。つまり、加水分解の時間は例えば合計6時間とすることができる。これらの加水分解の反応終了時の水溶液のpHは、例えば約7.0とすることができる。
（５）ホエイタンパク質の加水分解物は、遠心処理（20,000×g、10分間）した後に、分画分子量が10,000の限外濾過（UF）膜（ミリポア社ウルトラフリー-MC）で処理する。 As a preferred embodiment of the present invention, a whey protein hydrolyzate can be prepared, for example, by a method including the following steps (1) to (5).
(1) A whey protein isolate (WPI, Davisco) with a protein content of approximately 90% (w / w) as a dry product is added to distilled water so that the protein concentration is 8% (w / v). Dissolve to obtain an aqueous protein solution.
(2) The aqueous solution is heat treated at 85 ° C. for 2 minutes to denature the protein. The pH of the aqueous solution after the heat treatment can be about 7.5, for example.
(3) Thereafter, Alcalase 2.4L (enzyme, Novozymes) was added at 2.0% (w / w) with respect to the concentration of the protein (substrate), and the aqueous solution was maintained at 55 ° C. for 3 hours for hydrolysis. Decompose.
(4) Next, PTN 6.0S (enzyme, Novozymes Japan), a trypsin derived from swine, was added at a concentration of 3.0% (w / w) with respect to the concentration of the protein (substrate), and the aqueous solution was 55%. Hydrolyze by holding at ℃ for 3 hours. That is, the total hydrolysis time can be, for example, 6 hours in total. The pH of the aqueous solution at the end of these hydrolysis reactions can be, for example, about 7.0.
(5) The hydrolyzate of whey protein is centrifuged (20,000 × g, 10 minutes) and then treated with an ultrafiltration (UF) membrane (Millipore Ultrafree-MC) having a molecular weight cut-off of 10,000.
　タンパク質の加水分解物の調製方法では、最適化のための5つのパラメーターとして、予備加熱、酵素と基質の比率（E/S）、pH、加水分解の温度、および加水分解の時間などがあり、例えば、次の条件を挙げることができる。すなわち、予備加熱：65～90℃、E/S：0.01～0.2、pH：2～10、加水分解の温度：30～65℃、加水分解の時間：3～20時間である。 In the protein hydrolyzate preparation method, the five parameters for optimization include preheating, enzyme to substrate ratio (E / S), pH, hydrolysis temperature, and hydrolysis time, For example, the following conditions can be mentioned. That is, preheating: 65 to 90 ° C., E / S: 0.01 to 0.2, pH: 2 to 10, hydrolysis temperature: 30 to 65 ° C., hydrolysis time: 3 to 20 hours.
　タンパク質の加水分解に使用する酵素として、例えば次のものを挙げることができる。次の酵素は、例えばノボノルディスク社などの供給者を通じて入手することができる。
1) エンド型プロテアーゼ
・バシラス・リシェニフォルムス由来：アルカラーゼ（Alcalase）
・B. レントゥス（B. lentus）由来：エスペラーゼ
・枯草菌由来：ニュートラーゼ（Neutrase）
・バクテリア由来：プロタメックス
・豚膵臓由来：PTN（トリプシン）
2) エキソ型プロテアーゼ
・アスペルギルス・オリゼ（Aspergillus oryzae）由来：フレーバーザイム
・豚あるいはウシ内臓由来：カルボキシペプチダーゼ Examples of enzymes used for protein hydrolysis include the following. The following enzymes can be obtained through suppliers such as Novo Nordisk.
1) End-type protease, Bacillus, Licheniformus origin: Alcalase
・ B. lentus origin: Esperase ・ B. subtilis origin: Neutrase
・ Bacteria origin: Protamex ・ Pig pancreas origin: PTN (trypsin)
2) From exo-type protease, Aspergillus oryzae: Flavorzyme, from porcine or bovine viscera: Carboxypeptidase
　上記酵素の他に、動物由来のパンクレアチン、ペプシン、植物由来のパパイン、ブロメライン、微生物由来（例えば、乳酸菌、酵母、カビ、放線菌など）のエンドプロテアーゼおよびエキソプロテアーゼ、これらの粗精製物、菌体破砕物等を例示することができる。また、酵素の混合物として、バシラス・リシェニフォルムス由来のアルカラーゼと豚膵臓由来のPTN（トリプシン）の組み合わせがよく用いられる。 In addition to the above-mentioned enzymes, animal-derived pancreatin, pepsin, plant-derived papain, bromelain, microorganism-derived (for example, lactic acid bacteria, yeast, mold, actinomycetes, etc.) endoprotease and exoprotease, crudely purified products, bacteria Examples include crushed body and the like. Also, as a mixture of enzymes, a combination of Alcalase derived from Bacillus licheniformus and PTN (trypsin) derived from porcine pancreas is often used.
　本発明の乳タンパク質の加水分解物には、タンパク質の加水分解物そのもの、限外濾過膜で処理した保持液（リテンテイト）あるいは透過液（パーミエイト）、さらに、本発明で必要とされる同様の活性が有る市販の乳タンパク質の加水分解物が包含される。例えば、本発明の乳タンパク質加水分解物として、分画分子量が5000、6000、7000、8000、9000、10000のいずれかを下限（「～以上、又は、～より高い）、15000、20000、25000、30000のいずれかを上限（～以下、又は、～より低い）とする２点の間の分子量である限外濾過膜、好ましくは分画分子量が10000である限外濾過膜で処理した保持液を用いることができる。 The hydrolyzate of the milk protein of the present invention includes the protein hydrolyzate itself, a retentate treated with an ultrafiltration membrane (retentate) or a permeate (permeate), and similar activities required in the present invention. Commercially available milk protein hydrolysates with For example, as the milk protein hydrolyzate of the present invention, the molecular weight cut-off is any one of 5000, 6000, 7000, 8000, 9000, 10000 as the lower limit (“more than or more than”), 15000, 20000, 25000, A retentate treated with an ultrafiltration membrane having a molecular weight between two points with an upper limit (˜less than or lower) of any one of 30000, preferably an ultrafiltration membrane having a molecular weight cut off of 10,000. Can be used.
　乳タンパク質の加水分解物の配合量は、他の成分（発酵乳タンパク質、オレイン酸を含有する油脂、乳リン脂質、大豆レシチン、イソマルチュロースなど）の配合量、経腸栄養患者の病態、症状、年齢、体重、用途などにより適宜調整することができる。具体的には、乳タンパク質の加水分解物の配合量として、栄養組成物100 mL当たり0.9～5.0g 、好ましくは0.9～3.0g、より好ましくは1.0～2.5g、さらに好ましくは1.2～2.0gを例示することができるが、これらの範囲に限定されない。 Milk protein hydrolyzate content includes other ingredients (fermented milk protein, fats and oils containing oleic acid, milk phospholipids, soy lecithin, isomaltulose, etc.), pathology of enteral nutrition patients, It can be adjusted as appropriate according to symptoms, age, weight, application and the like. Specifically, the blended amount of the hydrolyzate of milk protein is 0.9 to 5.0 gm, preferably 0.9 to 3.0 g, more preferably 1.0 to 2.5 g, and still more preferably 1.2 to 2.0 g per 100 ml of the nutritional composition. Although it can illustrate, it is not limited to these ranges.
1-2 発酵乳タンパク質
　次に発酵乳タンパク質について説明する。本発明の発酵乳タンパク質の由来として、所謂、発酵乳（牛乳、水牛乳、ヤギ乳、羊乳、馬乳などの家畜乳および／または、これらの部分脱脂乳、脱脂乳、還元全乳、還元脱脂乳、還元部分脱脂乳、バター、クリームなどの乳原料を１種または２種以上で組み合わせて調製した液状乳を、乳酸菌などのスターターを用いて発酵させたもの全般）を用いることができる。 例えば、フレッシュチーズ、ナチュラルチーズ、ヨーグルト、ホエイチーズは、本発明の発酵乳タンパク質に包含される。また、本発明のチーズとは、乳、バターミルクもしくはクリームを乳酸菌で発酵させ、または乳、バターミルクもしくはクリームに酵素を加えてできた凝乳からホエイ（乳清）を除去したものをいい、固形化や熟成の有無について問わない。発酵乳を製造するスターターとして、Lactobacillus bulgaricus, Streptococcus thermophilusを主に用いることができるが、これらに限られず、例えば、Streptococcus lactis, Streptococcus cremoris, Streptococcus diacetilactis, Enterococcus faecium, Enterococcus fecalis, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus murinus, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus gasseri, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breveなどの乳酸菌やビフィズス菌を用いることもできる。その他、プロピオニバクテリウム属菌（Propionibacterium）などの発酵乳を製造する際に用いられる微生物を併用することができる。本発明の栄養組成物は、いずれの発酵乳を用いて調製してもよいが、好ましくは、フレッシュチーズまたはヨーグルト、より好ましくは、クワルク（quark）またはヨーグルトを用いて調製する。 1-2 Fermented milk protein Next, fermented milk protein will be explained. As the origin of the fermented milk protein of the present invention, so-called fermented milk (domestic milk such as cow's milk, buffalo milk, goat milk, sheep milk, horse milk and / or partially skimmed milk, skimmed milk, reduced whole milk, reduced milk, etc. All of the liquid milk prepared by combining one or more milk raw materials such as skim milk, reduced partial skim milk, butter and cream with a starter such as lactic acid bacteria can be used. For example, fresh cheese, natural cheese, yogurt, whey cheese are included in the fermented milk protein of the present invention. The cheese of the present invention is a product obtained by fermenting milk, buttermilk or cream with lactic acid bacteria, or removing whey (whey) from milk, buttermilk or cream, which is obtained by adding an enzyme to the cream, It does not matter whether solidification or aging occurs. Lactobacillus bulgaricus, Streptococcus thermophilus can be mainly used as a starter for producing fermented milk. Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus murinus, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus gasseri, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve, etc. In addition, microorganisms used in producing fermented milk such as Propionibacterium can be used in combination. The nutritional composition of the present invention may be prepared using any fermented milk, but is preferably prepared using fresh cheese or yoghurt, more preferably quark or yoghurt.
　フレッシュチーズには、カッテージ、クワルク、ストリング、ヌーシャテル、クリームチーズ、モツァレラ、リコッタ、マスカルポーネなどの数多くの種類がある。 クワルクは非熟成型（フレッシュ）チーズの一種であり、脂肪含量が低く、爽やかなフレーバーと酸味が特徴である。クワルクの一般的な製造法を以下に説明する。
　まずは脱脂乳を殺菌してから、乳酸菌のスターター（主にLactobacillus bulgaricus, Streptococcus thermophilus）を0.5～5 ％（w/w）で接種して発酵させる。その溶液のpHが4.6に達すると、カードが形成されるので、クワルクセパレーターを用いて、ホエイを遠心分離してから、その得られたカードを冷却する。本発明のクワルクの組成の一例として、例えば、全固形分が17～19 ％（w/w）、タンパク質が11～13 ％（w/w）、脂肪が1 ％（w/w）未満、炭水化物が2～8 ％（w/w）、乳糖が2 ％（w/w）未満を挙げることができる。その他、レンネットを用いて凝固させたものも、本発明のクワルクに包含される。また、ラクトコッカスに属するラクチス菌、クレモリス菌とロイコノストック属の菌種の混合培養液を脱脂乳に添加して培養し、ホエイを除去して得られたものも、本発明のクワルクに包含される。また、上記方法と同様にして得られたカードをカッターで切断した後に、その溶液を加温しながらホエイを分離して得られたものも、本発明のフレッシュチーズに包含される。 There are many types of fresh cheese such as cottages, quarks, strings, Neuchâtel, cream cheese, mozzarella, ricotta and mascarpone. Quark is a kind of non-ripe-molded (fresh) cheese, characterized by low fat content, refreshing flavor and sourness. A general method for producing quark will be described below.
First, skim milk is sterilized, then inoculated with 0.5 to 5% (w / w) of lactic acid bacteria starter (mainly Lactobacillus bulgaricus, Streptococcus thermophilus) and fermented. When the pH of the solution reaches 4.6, a curd is formed, and the whey is centrifuged using a quark separator, and then the obtained curd is cooled. As an example of the composition of the quark of the present invention, for example, the total solid content is 17 to 19% (w / w), the protein is 11 to 13% (w / w), the fat is less than 1% (w / w), the carbohydrate 2-8% (w / w) and lactose less than 2% (w / w). In addition, what was solidified using the rennet is also included in the quark of the present invention. Also included in the quark of the present invention are those obtained by adding and cultivating a mixed culture of Lactococcus belonging to Lactococcus, Cremoris and Leuconostoc species to skim milk and removing whey. Is done. Moreover, what was obtained by separating the whey after cutting the card | curd obtained by carrying out similarly to the said method with a cutter, heating the solution is also included by the fresh cheese of this invention.
　乳酸菌にプロバイオティクス効果があることは広く知られている。また、乳酸菌発酵で得られるフレッシュチーズのホエイには、大腸菌、腸炎ビブリオ菌、ビフィズス菌、バクテロイデスなどに対する抗菌効果を有することが知られている（特開平07-155103号公報）。 It is widely known that lactic acid bacteria have a probiotic effect. In addition, fresh cheese whey obtained by fermentation of lactic acid bacteria is known to have antibacterial effects against Escherichia coli, Vibrio parahaemolyticus, Bifidobacteria, Bacteroides, etc. (Japanese Patent Laid-Open No. 07-155103).
　発酵乳タンパク質の配合量は、他の成分（乳タンパク質加水分解物、オレイン酸を含有する油脂含有油脂、乳リン脂質、大豆レシチン、イソマルチュロースなど）の配合量、摂取対象者の病態、症状、年齢、体重、用途などにより適宜調整することができる。具体的には、発酵乳タンパク質の配合量として、タンパク質に換算して栄養組成物100 mL当たり0.5～6g、好ましくは2～6 g、より好ましくは2.5～4.5 gを例示することができるが、これらの範囲に限定されない。 The blended amount of fermented milk protein is the blended amount of other ingredients (milk protein hydrolyzate, fat-containing fats and oils containing oleic acid, milk phospholipid, soy lecithin, isomaltulose, etc.) It can be adjusted as appropriate according to symptoms, age, weight, application and the like. Specifically, the amount of fermented milk protein may be 0.5 to 6 g, preferably 2 to 6 g, more preferably 2.5 to 4.5 g, per 100 g of the nutritional composition in terms of protein. It is not limited to these ranges.
　日本国の乳及び乳製品の成分規格等に関する省令（昭和26年12月27日厚生省令第52号）では、乳等一般の成分規格及び製造の方法の基準として「分べん後５日以内の牛、山羊又はめん羊から乳を搾取してはならない」旨が定められている。つまり、この省令では初乳の乳製品への使用が制限されている。
　本発明において乳タンパク質の加水分解物や発酵乳タンパク質の調製に使用する乳は、乳（normal milk、あるいは成熟乳（mature milk）ともいう）を用いるのがより好ましい。乳の由来は、ウシ、水牛、ヤギ、ヒツジ、ウマ、ヒトなど、いずれの動物であってもよい。 According to the Ministerial Ordinance on Component Standards for Milk and Dairy Products in Japan (Ministry of Health and Welfare Ordinance No. 52 of December 27, 1951), “Standard cattle within five days after distribution” Do not milk milk from goats or sheep. " In other words, this ministerial ordinance restricts the use of colostrum in dairy products.
In the present invention, it is more preferable to use milk (also referred to as normal milk or mature milk) for the milk protein hydrolyzate or fermented milk protein preparation. The origin of milk may be any animal such as cow, buffalo, goat, sheep, horse, human.
2．脂質
2-1 リン脂質
　本発明においては、リン脂質として乳リン脂質と大豆由来レシチンあるいは卵黄レシチンの組み合わせを用いることができる。あるいは、リン脂質として乳リン脂質、大豆由来レシチン、卵黄レシチンを単独で使用してもよい。本発明の好ましいリン脂質として、乳リン脂質と大豆由来レシチンの両方またはいずれか一方、または、乳リン脂質と卵黄レシチンの両方またはいずれか一方を挙げることができるがこれらに限定されない。レシチンという用語は、生化学、医学、薬学などの分野ではホスファチジルコリンを指す用語として使用されているが、商業的あるいは工業的には、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジン酸および他のリン脂質の混合物の総称として使われている。食品添加物公定書第7版（1999）では、レシチンは、「油糧種子または動物原料から得られたもので、その主成分は、リン脂質である」、と定義されている。本発明のレシチンには、商業的あるいは工業的な意味において使用されるこれらのリン脂質も含まれる。 2． Lipid
2-1 Phospholipid In the present invention, a combination of milk phospholipid and soybean-derived lecithin or egg yolk lecithin can be used as the phospholipid. Alternatively, milk phospholipid, soybean-derived lecithin, or egg yolk lecithin may be used alone as the phospholipid. Preferred phospholipids of the present invention include, but are not limited to, milk phospholipid and / or soybean-derived lecithin, or milk phospholipid and / or egg yolk lecithin. The term lecithin is used to refer to phosphatidylcholine in fields such as biochemistry, medicine and pharmacy, but commercially or industrially, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid and other phospholipids It is used as a general term for a mixture of The 7th edition of the Food Additives (1999) defines that lecithin is "obtained from oil seeds or animal raw materials, the main component of which is phospholipid". The lecithin of the present invention includes these phospholipids used in a commercial or industrial sense.
乳リン脂質
　乳リン脂質は、スフィンゴミエリン(SM)、ホスファチジルコリン(PC)、ホスファチジルエタノールアミン（PE）、ホスファチジルイノシトール（PI）、ホスファチジルセリン（PS）、リゾホスファチジルコリン（LPC）からなり、乳脂肪球皮膜（MFGM）のみに局在している。乳リン脂質の特徴は、表1に示すように、大豆レシチンには含まれないSMを多量に含むことである。 Milk phospholipid Milk phospholipid consists of sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), lysophosphatidylcholine (LPC), and milk fat globule membrane (MFGM) is localized only. As shown in Table 1, the characteristic of milk phospholipid is that it contains a large amount of SM that is not contained in soybean lecithin.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
大豆レシチン
　大豆レシチンは天然の食品添加物として、食品分野で広く使われる。一方、ポリエンホスファチジルコリンは医薬品（適応：慢性肝疾患における肝機能の改善、脂肪肝、高脂質血症）としても使われている。
　いわゆる「天然系」の一連のリン脂質製品に関しては、通常、製品中のPC含量によって序列されている。リン脂質の用途に応じてグレートアップした各種のリン脂質が製造されている。大豆レシチン製品は、大豆レシチンの精製、分画による主なPC含量の違いにより、便宜的に表2のように分類されている（藤川琢馬、油化学 第40巻(10), pp.951-p58, 1991）。 Soy lecithin Soy lecithin is widely used in the food field as a natural food additive. On the other hand, polyenephosphatidylcholine is also used as a medicine (indication: improvement of liver function in chronic liver disease, fatty liver, hyperlipidemia).
The so-called “natural” series of phospholipid products are usually ordered by the PC content in the product. Various types of phospholipids that have been improved according to the use of phospholipids have been produced. Soy lecithin products are classified as shown in Table 2 for the sake of convenience, depending on the main PC content due to the purification and fractionation of soy lecithin (Yamama Fujikawa, Oil Chemistry, Vol. 40 (10), pp.951). -p58, 1991).
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　本発明において、乳リン脂質と大豆レシチンはそれぞれ単独で使用してもよく、また組み合わせて使用してもよい。乳リン脂質および／または大豆レシチンの配合量は、他の成分（乳タンパク質加水分解物、発酵乳タンパク質、オレイン酸を含有する油脂、イソマルチュロースなど）の配合量、摂取対象者の病態、症状、年齢、体重、用途などにより適宜調整することができる。具体的には、乳リン脂質および／または大豆レシチンの配合量として、栄養組成物100 mL当たり合計0.01～0.5 g、0.05～0.5 g、0.1～0.5 g、0.2～0.3 gを例示することができるが、これらの範囲に限定されない。 In the present invention, milk phospholipid and soybean lecithin may be used alone or in combination. The amount of milk phospholipid and / or soy lecithin is the amount of other ingredients (milk protein hydrolyzate, fermented milk protein, fats and oils containing oleic acid, isomaltulose, etc.) It can be adjusted as appropriate according to symptoms, age, weight, application and the like. Specifically, the blending amount of milk phospholipid and / or soybean lecithin can be exemplified by a total of 0.01 to 0.5 g, 0.05 to 0.5 g, 0.1 to 0.5 g, 0.2 to 0.3 g per 100 mL of the nutritional composition. However, it is not limited to these ranges.
2-2 その他の脂質
　本発明の組成物は、脂質としてオレイン酸を含有する油脂を含む。厚生労働省では、飽和脂肪酸（SFA：パルミチン酸、ステアリン酸など）：一価不飽和脂肪酸（MUFA：オレイン酸など）：多価不飽和脂肪酸（PUFA：リノール酸、リノレン酸など）の望ましい摂取比率を従来の1：1.5：1～3：4：3となるよう、また、n-6系脂肪酸：n-3系脂肪酸の比率が4：1となるよう勧告している。わが国において、MUFAの摂取比を1.5倍まで高めた食生活の実施は難しいということが勧告の理由の一つである。そこで、望ましい脂肪酸摂取比率（SMP比）を実現するために、脂質の脂肪酸組成中一価不飽和脂肪酸（MUFA）の含量を高めることが考えられる。そのために、一価不飽和脂肪酸であるオレイン酸を本発明の栄養組成物に含有せしめることができる。オレイン酸を多く含む脂質源としては、例えば、高オレイン酸のハイオレイックヒマワリ油、ナタネ油、オリーブ油、高オレイン酸ベニバナ油、大豆油、コーン油、パーム油などが挙げられる。またオレイン酸を含む脂質源として栄養調製油脂（日本油脂(株)）が挙げられる。ヒマワリ油、ナタネ油、オリーブ油、およびオリーブ油との混合物も用いることができる。 2-2 Other lipids The composition of the present invention contains an oil containing oleic acid as a lipid. The Ministry of Health, Labor and Welfare has a desirable intake ratio of saturated fatty acids (SFA: palmitic acid, stearic acid, etc.): monounsaturated fatty acids (MUFA: oleic acid, etc.): polyunsaturated fatty acids (PUFA: linoleic acid, linolenic acid, etc.) It is recommended that the ratio of conventional 1: 1.5: 1 to 3: 4: 3 and the ratio of n-6 fatty acids: n-3 fatty acids be 4: 1. One of the reasons for the recommendation is that in Japan, it is difficult to carry out a diet that increases the intake ratio of MUFA to 1.5 times. Therefore, in order to realize a desirable fatty acid intake ratio (SMP ratio), it is conceivable to increase the content of monounsaturated fatty acids (MUFA) in the fatty acid composition of lipids. Therefore, oleic acid which is a monounsaturated fatty acid can be included in the nutritional composition of the present invention. Examples of lipid sources rich in oleic acid include high oleic sunflower oil, rapeseed oil, olive oil, high oleic safflower oil, soybean oil, corn oil and palm oil. Moreover, nutritionally prepared fats and oils (Nippon Yushi Co., Ltd.) are mentioned as a lipid source containing oleic acid. Sunflower oil, rapeseed oil, olive oil, and mixtures with olive oil can also be used.
　オレイン酸の配合量は、他の成分（乳タンパク質加水分解物、発酵乳タンパク質、乳リン脂質、大豆レシチン、イソマルチュロースなど）の配合量、摂取対象者の病態、症状、年齢、体重、用途などにより適宜調整することができる。具体的には、オレイン酸の配合量として、本発明の栄養組成物の脂肪酸組成中25％以上、好ましくは30%以上、より好ましくは30～50%を例示することができるが、これらの範囲に限定されない。さらに、DHA、EPA、アラキドン酸などの多価不飽和脂肪酸、カプリル酸、カプリン酸、ラウリン酸などの中鎖脂肪酸を加えて、飽和脂肪酸：一価不飽和脂肪酸：多価不飽和脂肪酸の比率を3：4：3に近くなるように調整することができる。 The amount of oleic acid is based on the amount of other ingredients (milk protein hydrolyzate, fermented milk protein, milk phospholipid, soy lecithin, isomaltulose, etc.), the condition, symptoms, age, weight, It can be appropriately adjusted depending on the application. Specifically, the blending amount of oleic acid can be exemplified by 25% or more, preferably 30% or more, more preferably 30 to 50% in the fatty acid composition of the nutritional composition of the present invention. It is not limited to. In addition, polyunsaturated fatty acids such as DHA, EPA and arachidonic acid, medium chain fatty acids such as caprylic acid, capric acid and lauric acid are added, and the ratio of saturated fatty acid: monounsaturated fatty acid: polyunsaturated fatty acid is increased. It can be adjusted to be close to 3: 4: 3.
3．糖質および食物繊維
　本発明において、糖質として主にイソマルチュロースを使用することができる。その他の糖質としては、糖アルコール（ソルビトール、キシリトール、マルチトールなど）、ハチミツ、グラニュー糖、ブドウ糖、果糖、転化糖などを使用することができる。 3． Sugar and dietary fiber In the present invention, isomaltulose can be mainly used as the sugar. As other saccharides, sugar alcohols (sorbitol, xylitol, maltitol, etc.), honey, granulated sugar, glucose, fructose, invert sugar and the like can be used.
　イソマルチュロースは、ブドウ糖と果糖が１分子ずつα－１，６結合した二糖類で、ショ糖の構造異性体であり、６‐Ｏ‐（α‐Ｄ‐Ｇｌｕｃｏｐｙｒａｎｏｓｙｌ）‐Ｄ‐ｆｒｕｃｔｏｓｅあるいはイソマルツロース、パラチノースともいう。分子量342.297、Cas. No. 13718-94-0で、甘味料などに用いられている。イソマルチュロースは蜂蜜やサトウキビなどに非常に少量含まれている。また、スクロースにプロタミノバクター・ルブラム（Protaminobacter rubrum）起源の α-グルコシルトランスフェラーゼなどを作用させて、α－１，２結合をα－１，６結合に転移させて、イソマルチュロースを製造することもできる。イソマルチュロースの甘味はスクロースに似ているが、甘味度はスクロースの約半分である。経口的に摂取されたイソマルチュロースは、消化管内でイソマルターゼによって分解を受け、ショ糖と同様にグルコースとフルクトースに消化されて吸収される（合田敏尚ら、日本栄養・食糧学会誌, Vol. 36(3): 169-173, 1983）。他にイソマルターゼで消化を受けるイソマルトース、パノース、イソマルトトリオースなどは、イソマルチュロースの消化と競合するため、イソマルチュロースの摂取によって消化吸収が抑制されると言われている（日本栄養・食糧学会誌、36(3)、pp.169-173(1983)）。イソマルチュロースのカロリーは4kcal/gである。本発明において、イソマルチュロースは、パラチノースシロップ、還元パラチノースあるいはパラチノース水飴などを含む。パラチノース水飴は、イソマルチュロースの脱水縮合によって生じる四糖、六糖、八糖などのオリゴ糖を主成分とする水飴状の液状物である。 Isomaltulose is a disaccharide in which glucose and fructose molecules are α-1,6-linked, and is a structural isomer of sucrose. 6-O- (α-D-Glucopyranosyl) -D-fructose Also called maltulose or palatinose. It has a molecular weight of 342.297 and Cas. No. 13718-94-0 and is used for sweeteners. Isomaltulose is contained in very small amounts in honey and sugarcane. In addition, α-glucosyltransferase derived from Protaminobacter rubrum is allowed to act on sucrose to transfer α-1,2 linkages to α-1,6 linkages to produce isomaltulose. You can also The sweetness of isomaltulose is similar to that of sucrose, but the sweetness is about half that of sucrose. Orally ingested isomaltulose is degraded by isomaltase in the digestive tract, and is digested and absorbed into glucose and fructose in the same way as sucrose (Toshinao Aida, Journal of Japanese Society of Nutrition and Food, Vol. . 36 (3): 169-173, 1983). In addition, isomaltose, panose, isomalttriose and the like that are digested with isomaltase compete with the digestion of isomaltulose, and it is said that digestive absorption is suppressed by ingesting isomaltulose ( Japanese Journal of Nutrition and Food, 36 (3), pp.169-173 (1983)). The calorie of isomaltulose is 4kcal / g. In the present invention, isomaltulose includes palatinose syrup, reduced palatinose or palatinose syrup. Palatinose starch syrup is a starch syrup-like liquid substance mainly composed of oligosaccharides such as tetrasaccharide, hexasaccharide and octasaccharide produced by dehydration condensation of isomaltulose.
　イソマルチュロースが酪酸菌クロストリジウム・ブチリカムに高選択的に資化され、クロストリジウム・ブチリカムの生育を促進することは知られている（水谷武雄、"パラチノースオリゴ糖の特性と利用"、New Food Industry、食品資材研究会、１９９１年、第３３巻、第２号、ｐ．９－１６）。また、イソマルチュロースなどの晶質浸透圧調整剤、およびデキストリン・難消化デキストリンなどの膠質浸透圧調整剤の組み合わせを水に溶解して、浸透圧200～440mOsm/Lに調整した水溶液が腸内の有害菌を排除し有用菌の増殖環境を調整することも知られている（国際公開WO2004/067037号）。 It is known that isomaltulose is highly selectively assimilated by the butyric acid bacterium Clostridium butyricum and promotes the growth of Clostridium butyricum (Takeo Mizutani, “Characteristics and utilization of palatinose oligosaccharides”, New Food Industry) Food Materials Research Group, 1991, Vol. 33, No. 2, pp. 9-16). In addition, an aqueous solution prepared by dissolving a combination of a crystalline osmotic pressure regulator such as isomaltulose and a colloid osmotic pressure regulator such as dextrin and indigestible dextrin in water to adjust the osmotic pressure to 200 to 440 mOsm / L. It is also known to adjust the growth environment of useful bacteria by eliminating harmful bacteria (International Publication WO2004 / 067037).
　イソマルチュロースの配合量は、他の成分（乳タンパク質加水分解物、発酵乳タンパク質、オレイン酸を含有する油脂、乳リン脂質、大豆レシチンなど）の配合量、摂取対象者の病態、症状、年齢、体重、用途などにより適宜調整することができる。具体的には、イソマルチュロースの配合量として、栄養組成物100 mL当たり4～15 g好ましくは5～7 gを例示することができるが、これらの範囲に限定されない。 The blending amount of isomaltulose is blended with other ingredients (milk protein hydrolyzate, fermented milk protein, fats and oils containing oleic acid, milk phospholipids, soybean lecithin, etc.) It can be adjusted as appropriate according to age, weight, use and the like. Specifically, the blending amount of isomaltulose can be exemplified by 4 to 15 g, preferably 5 to 7 g per 100 mL of the nutritional composition, but is not limited to these ranges.
　本発明の栄養組成物は、適当にタンパク質、脂質、糖質を加えることにより、その熱量を調節することができる。本発明の栄養組成物の熱量は、栄養組成物100mlあたり50～150kcal、好ましくは、80～120 kcalを例示することができるが、これらの範囲に限定されない。
　また、本発明の栄養組成物における、タンパク質、脂質および糖質の栄養組成物全体に対するエネルギー比率は、第六次改定日本人の栄養所要量にほぼ準ずる。具体的に、タンパク質15～25%、脂質20～30%、糖質45～65 %を例示することができるが、これらの範囲に限定されない。 The amount of heat of the nutritional composition of the present invention can be adjusted by appropriately adding proteins, lipids and carbohydrates. The calorie | heat amount of the nutrition composition of this invention can illustrate 50-150 kcal per 100 ml of nutrition composition, Preferably, it is 80-120 kcal, However It is not limited to these ranges.
In addition, the energy ratio of the protein, lipid, and carbohydrate to the whole nutritional composition in the nutritional composition of the present invention substantially conforms to the nutritional requirements of the sixth revised Japanese. Specific examples include 15 to 25% protein, 20 to 30% lipid, and 45 to 65% carbohydrates, but are not limited to these ranges.
　本発明の栄養組成物は、食物繊維を含むこともできる。食物繊維は、ヒトの消化酵素によって加水分解されない食物中の物質を指し、水に対する親和性から、水溶性食物繊維および不溶性食物繊維に分類される。水溶性食物繊維として、難消化性オリゴ糖のラクツロース、ラクチトール、あるいはラフィノースなどを用いることができる。難消化性オリゴ糖の生理機能としては、未消化物のまま大腸に到達し、腸内ビフィズス菌の活性化および増殖に寄与し、腸内環境の改善すなわち整腸効果を有することが知られている。その他の水溶性食物繊維の候補として、ペクチン（プロトペクチン、ペクチニン酸、ペクチン酸）、グアーガム・酵素分解物、タマリンドシードガムなどを用いることができる。
　さらに、水溶性食物繊維の候補として、高分子水溶性食物繊維では、大豆増粘多糖類、こんにゃくグルコマンナン、アルギン酸、低分子アルギン酸、サイリウム、アラビアガム、海藻多糖類（セルロース、リグニン様物質、寒天、カラギーナン、アルギン酸、フコダイン、ラミナリン）、微生物ガム（ウエランガム、カードラン、キサンタンガム、ジェランガム、デキストラン、プルラン、ラムザンガム）、その他のガム（種子由来のローカストビーンガム、タマリンドガム、タラガム、樹液由来のカラヤガム、トラガントガム）など、低分子水溶性食物繊維のポリデキストロース、難消化性デキストリン、パインファイバー、マルチトールなどを用いることができる。 The nutritional composition of the present invention may also contain dietary fiber. Dietary fiber refers to a substance in food that is not hydrolyzed by human digestive enzymes, and is classified into water-soluble dietary fiber and insoluble dietary fiber based on its affinity for water. As water-soluble dietary fiber, indigestible oligosaccharides such as lactulose, lactitol, or raffinose can be used. Physiological functions of indigestible oligosaccharides are known to reach the large intestine as undigested substances, contribute to the activation and proliferation of intestinal bifidobacteria, and have an improved intestinal environment, ie, an intestinal regulating effect. Yes. As other water-soluble dietary fiber candidates, pectin (protopectin, pectinic acid, pectinic acid), guar gum / enzymatic degradation product, tamarind seed gum and the like can be used.
Furthermore, as water-soluble dietary fiber candidates, high-molecular water-soluble dietary fiber includes soybean thickening polysaccharide, konjac glucomannan, alginic acid, low molecular alginic acid, psyllium, gum arabic, seaweed polysaccharide (cellulose, lignin-like substance, agar) , Carrageenan, alginic acid, fucodyne, laminarin), microbial gum (welan gum, curdlan, xanthan gum, gellan gum, dextran, pullulan, lambzan gum), other gums (seed-derived locust bean gum, tamarind gum, tara gum, sap-derived caraya gum, Polydextrose of low molecular weight water-soluble dietary fiber such as tragacanth gum), indigestible dextrin, pine fiber, maltitol and the like can be used.
　不溶性食物繊維は、大腸での不消化物のカサを増やし、通過時間を短縮する。その結果排便回数が増し、便量の増加をもたらす。不溶性食物繊維の候補として、セルロース、ヘミセルロース、リグニン、キチン、キトサン、大豆ふすま、小麦ふすま、大麦ふすま、パインファイバー、コーンファイバー、ビートファイバー、オート麦ふすま、ライ麦ふすま、ハトムギふすま、米糠、キビ、アワ、ヒエ、モロコシなどの雑穀ふすま、菽穀（マメ科）ふすま、ソバなどの擬穀ふすま、ゴマふすま、おからなどが挙げられる。 Insoluble dietary fiber increases the mass of indigestibles in the large intestine and shortens the transit time. As a result, the number of defecations increases, resulting in an increase in stool volume. Insoluble dietary fiber candidates include cellulose, hemicellulose, lignin, chitin, chitosan, soy bran, wheat bran, barley bran, pine fiber, corn fiber, beet fiber, oat bran, rye bran, pearl bran, rice bran, millet, millet Millet bran such as barnyard millet and sorghum, cereal bran (leguminous) bran, artificial grain bran such as buckwheat, sesame bran and okara.
　本発明の栄養組成物は、前記のタンパク質、脂質、糖質、食物繊維の他に、水、タンパク質、糖質、脂質、ビタミン類、ミネラル類、有機酸、有機塩基、果汁、フレーバー類、乳化剤、増粘剤、安定化剤などを使用することができる。タンパク質としては、例えば全脂粉乳、脱脂粉乳、部分脱脂粉乳、カゼイン、ホエイ粉、ホエイタンパク質、ホエイタンパク質濃縮物、ホエイタンパク質分離物、ホエイタンパク質加水分解物、α―カゼイン、β―カゼイン、κ－カゼイン、β―ラクトグロブリン、α―ラクトアルブミン、ラクトフェリン、大豆タンパク質、鶏卵タンパク質、肉タンパク質などの動植物性タンパク質、これらの分解物；バター、ホエイ（乳清）ミネラル、クリーム、ホエイ、非タンパク態窒素、シアル酸、リン脂質、乳糖などの各種乳由来成分などが挙げられる。カゼインホスホペプチド、リジンなどのペプチドやアミノ酸を含んでいてもよい。糖質としては、例えば、糖類、加工澱粉（テキストリンのほか、可溶性澱粉、ブリティッシュスターチ、酸化澱粉、澱粉エステル、澱粉エーテルなど）、食物繊維などが挙げられる。脂質としては、例えば、ラード、魚油など、これらの分別油、水素添加油、エステル交換油などの動物性油脂；パーム油、サフラワー油、コーン油、ナタネ油、ヤシ油、これらの分別油、水素添加油、エステル交換油などの植物性油脂などが挙げられる。ビタミン類としては、例えば、ビタミンA、カロチン類、ビタミンB群、ビタミンC、ビタミンD群、ビタミンE、ビタミンK群、ビタミンP、ビタミンQ、ナイアシン、ニコチン酸、パントテン酸、ビオチン、イノシトール、コリン、葉酸などが挙げられ、ミネラル類としては、例えば、カルシウム、カリウム、マグネシウム、ナトリウム、銅、鉄、マンガン、亜鉛、セレンなどが挙げられる。有機酸としては、例えば、リンゴ酸、クエン酸、乳酸、酒石酸、エリソルビン酸などが挙げられる。また、便臭低減効果のある素材（例えば、シャンピニオンエキスを5 mg～500 mg(0.005%～0.5%)）、カロチノイド製剤（例えば、α-カロチン、 β-カロチン、リコピン、ルテインなどを含む製剤を10μg～200μg (0.00001%～0.0002%)）、抗酸化剤（カテキン、ポリフェノールなど）を含ませることもできる。これらの成分は、２種以上を組み合わせて使用することができ、合成品および／またはこれらを多く含む食品を用いてもよい。食品の形態としては、固体、液体、ゲル状などいずれの形態であってもかまわない。 The nutritional composition of the present invention includes water, protein, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, emulsifiers in addition to the proteins, lipids, carbohydrates, and dietary fibers. , Thickeners, stabilizers and the like can be used. Examples of the protein include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, whey protein hydrolysate, α-casein, β-casein, κ- Casein, β-lactoglobulin, α-lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein and other animal and vegetable proteins, their degradation products; butter, whey minerals, cream, whey, non-protein nitrogen And various milk-derived components such as sialic acid, phospholipid, and lactose. It may contain peptides such as casein phosphopeptides and lysines and amino acids. Examples of the saccharide include saccharides, processed starch (in addition to text phosphorus, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like. Examples of lipids include animal oils such as lard and fish oil, fractionated oils thereof, hydrogenated oils and transesterified oils; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, Examples include vegetable oils such as hydrogenated oils and transesterified oils. Examples of vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline. Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium. Examples of the organic acid include malic acid, citric acid, lactic acid, tartaric acid, erythorbic acid, and the like. In addition, ingredients that reduce fecal odor (eg, champignon extract 5 mg to 500 mg (0.005% to 0.5%)), carotenoid preparations (eg, α-carotene, β-carotene, lycopene, lutein, etc.) 10 μg to 200 μg (0.00001% to 0.0002%)) and an antioxidant (catechin, polyphenol, etc.) can also be included. Two or more of these components can be used in combination, and a synthetic product and / or a food containing a large amount thereof may be used. The form of the food may be any form such as a solid, liquid, or gel.
　本発明の栄養組成物の製造は、当業界において公知の方法で実施できる。前記原材料を一部または全てを調合した後に、必要に応じて均質化を行う。均質化とは、調合した各成分を十分混合することにより均質にし、また、脂肪球や他成分の粗大粒子を機械的に微細化して脂肪などの浮上・凝集を防止するとともに、栄養組成物を均一な乳化状態にすることをいう。 The production of the nutritional composition of the present invention can be carried out by methods known in the art. After some or all of the raw materials have been prepared, homogenization is performed as necessary. Homogenization means homogenization by thoroughly mixing each prepared component, and the fat globules and coarse particles of other components are mechanically refined to prevent the rising and aggregation of fat and the like, and the nutritional composition It means making into a uniform emulsified state.
　本発明の栄養組成物の製造においては加熱処理または加熱殺菌を行う。加熱殺菌条件は、一般的な食品の殺菌条件を用いることができ、慣用の装置を用いて加熱殺菌を行うことができる。例えば、62～65℃×30分、72℃以上×15秒以上、72℃以上×15分以上若しくは120～150℃×1～5秒の殺菌、または121～124℃×5～20分、105～140℃の滅菌、レトルト（加圧加熱）殺菌、高圧蒸気滅菌などを使用することができるが、これらの例に限定されない。加熱殺菌は、好ましくは加圧下で行うことができる。
　また、液状の栄養組成物を予め加熱滅菌した後、無菌的に容器に充填する方法（例えば、UHT滅菌法とアセプティック包装法を併用した方法）、液状の栄養組成物を容器に充填した後、容器とともに加熱滅菌する方法（例えば、オートクレーブ法）、缶容器や流動食や経口・経管栄養に用いる各種容器（いわゆるソフトバッグ、栄養バックなど）に充填しレトルト殺菌（例えば115～145℃で5～10秒）を行う方法、缶容器や流動食や経口・経管栄養に用いる各種容器（いわゆるソフトバッグ、栄養バックなど）に充填しレトルト殺菌した後に約140～145℃で約5～8秒間加熱殺菌後、冷却し、無菌充填を行う方法を例示することができるが、これらの例に限定されない。
　加熱処理または加熱殺菌によって、原料の発酵乳に由来するスターター（乳酸菌、ビフィズス菌、またはプロピオニバクテリウム属菌など）は死滅する。 In the production of the nutritional composition of the present invention, heat treatment or heat sterilization is performed. As heat sterilization conditions, general food sterilization conditions can be used, and heat sterilization can be performed using a conventional apparatus. For example, sterilization of 62-65 ° C x 30 minutes, 72 ° C or more x 15 seconds or more, 72 ° C or more x 15 minutes or more, or 120-150 ° C x 1-5 seconds, or 121-124 ° C x 5-20 minutes, 105 Although sterilization at ˜140 ° C., retort (pressure heating) sterilization, high-pressure steam sterilization, etc. can be used, it is not limited to these examples. The heat sterilization can be preferably performed under pressure.
In addition, after preliminarily heat-sterilizing the liquid nutritional composition, aseptically filling the container (for example, a method using a combination of the UHT sterilization method and the aseptic packaging method), filling the container with the liquid nutritional composition, Method of heat sterilization with containers (for example, autoclave method), can containers, liquid foods, various containers used for oral and tube feeding (so-called soft bags, nutrition bags, etc.) and retort sterilization (for example, at 115 to 145 ° C 5 ~ 10 seconds), filling in cans, liquid foods and various containers used for oral and tube feeding (so-called soft bags, nutrition bags, etc.) and sterilized by retort for about 5-8 seconds at about 140-145 ° C Although the method of cooling after heat sterilization and performing aseptic filling can be illustrated, it is not limited to these examples.
By the heat treatment or heat sterilization, starters (such as lactic acid bacteria, bifidobacteria, or Propionibacterium spp.) Derived from fermented milk as a raw material are killed.
　本発明の組成物は、腸内菌叢の正常化や維持のために用いることができる。本発明の栄養組成物は、例えば流動食や経口・経管栄養、飲料、ゲル状食品（特に、いわゆる機能性食品）などとして、経口・経腸栄養患者や高齢者、乳幼児などの栄養管理に用いることができる。 The composition of the present invention can be used for normalization and maintenance of intestinal flora. The nutritional composition of the present invention is suitable for nutritional management of oral and enteral nutrition patients, the elderly, infants and the like, for example, as liquid food, oral and tube feeding, beverages, gel foods (especially so-called functional foods) and the like. Can be used.
　本発明の栄養組成物の浸透圧は約500～1000 mOsm/l、例えば約550～750 mOsm/lの浸透圧を例示することができる。室温で測定する場合、栄養組成物の粘度は、20～100 cp（1cp = 0.001 Pa・s）、好ましくは25～60 cp、より好ましくは30～50 cpを例示することができるが、これらの範囲に限定されない。
　また、本発明の栄養組成物のpHは4.6以下、好ましくは3.0～4.3、より好ましくは3.8～4.2に調整することができるが、これらの範囲に限定されない。 The osmotic pressure of the nutritional composition of the present invention can be exemplified by an osmotic pressure of about 500 to 1000 mOsm / l, such as about 550 to 750 mOsm / l. When measured at room temperature, the viscosity of the nutritional composition may be 20 to 100 cp (1 cp = 0.001 Pa · s), preferably 25 to 60 cp, more preferably 30 to 50 cp. The range is not limited.
Further, the pH of the nutritional composition of the present invention can be adjusted to 4.6 or less, preferably 3.0 to 4.3, more preferably 3.8 to 4.2, but is not limited to these ranges.
　腸内環境は様々な疾患や老化に関与していると考えられている。高齢者では、Bifidobacterium属の細菌数が減少して、腸内菌叢が乱れていると言われている。このような腸内菌叢の悪化では、老化を促進する可能性が指摘されている。腸管内の悪玉菌は有害な腐敗産物（アンモニア、アミン、フェノール、インドールなど）を産生するが、これらの腐敗産物は腸管に直接的に障害を与えると共に、部分的に体内に吸収され、宿主の生涯に渡って老化を促進するだけでなく、ガン、心筋梗塞、高血圧などの疾患の発症にも関わっている。これに対して、腸管内のBifidobacterium属のような善玉菌は悪玉菌の増殖を阻害する。従って、腸管内のBifidobacterium属の乳酸菌の存在は健康維持に役立ち、有用な腸内細菌として、宿主の生涯に渡って重要であることが示唆されている。つまり、腸管内のBifidobacterium属の乳酸菌の減少や消失は、不健全な状態を意味するのである。
　ところで、経腸栄養患者では、腸管内のBifidobacterium属の細菌数が健常人に比べて少なく、経腸栄養患者では、腸内菌叢が健常人に比べて悪化していると考えられている。このことから、経腸栄養患者の乱れた腸内菌叢を正常に近づける必要がある。 The intestinal environment is thought to be involved in various diseases and aging. In the elderly, the number of bacteria of the genus Bifidobacterium is decreased, and it is said that the intestinal flora is disturbed. It has been pointed out that the deterioration of the intestinal flora may promote aging. Bad bacteria in the intestine produce harmful spoilage products (ammonia, amines, phenols, indoles, etc.), but these spoilage products directly damage the intestinal tract and are partially absorbed by the body, In addition to promoting aging throughout life, it is also involved in the development of diseases such as cancer, myocardial infarction and hypertension. On the other hand, good bacteria such as the genus Bifidobacterium in the intestine inhibit the growth of bad bacteria. Therefore, it is suggested that the presence of lactic acid bacteria belonging to the genus Bifidobacterium in the intestinal tract is useful for maintaining health and is important as a useful intestinal bacterium for the life of the host. In other words, the decrease or disappearance of Bifidobacterium lactic acid bacteria in the intestinal tract means an unhealthy state.
By the way, in enteral nutrition patients, the number of bacteria of the genus Bifidobacterium in the intestinal tract is less than that in healthy people, and in enteral nutrition patients, the intestinal flora is thought to be worse than in healthy people. For this reason, it is necessary to bring the disturbed intestinal flora of enteral nutrition patients close to normal.
　ビフィズス菌や乳酸菌などのプロバイオティクス投与が腸内における有機酸量の増加および腐敗産物の減少と関連することが多くの報告で示されている。また、プロバイオティクス投与により、腸内のビフィズス菌や乳酸菌が増加し、これに伴って腸内のpHが低下することによる有害物質産生細菌（Clostridiumの減少など）の増加阻止なども報告されている。 Many reports show that the administration of probiotics such as bifidobacteria and lactic acid bacteria is associated with an increase in the amount of organic acids and a decrease in spoilage products in the intestine. Probiotics have also been reported to increase the number of bifidobacteria and lactic acid bacteria in the intestine, and to prevent the increase of harmful substance-producing bacteria (such as a decrease in Clostridium) due to a decrease in the intestinal pH. Yes.
　流動食や経腸栄養剤は高齢者や様々な病態で使用されている。摂取対象者の腸管機能が充分機能していないことから、食物繊維の添加が少ない流動食や経腸栄養剤が多く、盲腸発酵に配慮した流動食や経腸栄養剤が少ないのが現状である。一般的な流動食や経腸栄養剤は食物繊維を含有しないか、含有量が不十分であるため、摂取した者の盲腸発酵が不十分となる。本発明の栄養組成物は発酵乳タンパク質や食物繊維を含有することで盲腸発酵を正常範囲に保ち、それによって盲腸組織重量の増加や盲腸内容物の増加をもたらす。盲腸内容物の増加は腸内菌叢の増加や総短鎖脂肪酸量の増加を意味する。短鎖脂肪酸は盲腸や大腸で吸収され、腸内の蠕動運動や盲腸や大腸の増殖の促進にも関与していることがわかっている。従って本発明は、タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および／または大豆レシチン、糖質としてイソマルチュロースを含む、盲腸組織重量の増加を促進するための組成物や盲腸内容物の増加を促進するための組成物を提供する。 Liquid foods and enteral nutrients are used by elderly people and various pathologies. Since the intestinal function of the ingestion target is not functioning sufficiently, there are many liquid foods and enteral nutrients with little addition of dietary fiber, and there are few liquid foods and enteral nutrients that take into account cecal fermentation. . Since general liquid foods and enteral nutrients do not contain dietary fiber or are insufficient in content, cecal fermentation of those who take them is insufficient. The nutritional composition of the present invention contains fermented milk protein and dietary fiber to maintain cecal fermentation in the normal range, thereby increasing the cecal tissue weight and cecal content. An increase in cecal content means an increase in intestinal flora and an increase in total short-chain fatty acid content. Short chain fatty acids are absorbed in the cecum and large intestine and are known to be involved in peristaltic movement in the intestine and the promotion of cecal and large intestine growth. Accordingly, the present invention provides a cecal tissue weight comprising a hydrolyzate of milk protein as protein and a fermented milk protein, an oil containing oleic acid as a lipid, and milk phospholipid and / or soy lecithin and isomaltulose as a carbohydrate. The present invention provides a composition for promoting an increase in the amount of cecum and a composition for promoting an increase in the content of the cecum.
　本発明の栄養組成物は、ラットを用いたin vivo試験において、腸内の総細菌数を変化させることなく、盲腸内容物や糞便中のBifidobacterium属、Lactobacillus属の細菌数や占有率を高めることが確認された。また、盲腸内のｐＨ低下や、盲腸組織・盲腸内容物の重量、盲腸内容物の有機酸量の増加が確認された。従って、本発明の組成物は、腸内菌叢改善に有用である。また本発明は、タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および／または大豆レシチン、糖質としてイソマルチュロースを含む、腸内のｐＨ低下を促進するための組成物や腸内の有機酸量の増加を促進するための組成物を提供する。腸としては小腸、大腸、盲腸などが挙げられる。
　本発明の栄養組成物は、様々なBifidobacterium属の細菌およびLactobacillus属の細菌に対して効果的である。Bifidobacterium属の細菌としてBifidobacterium longum、Bifidobacterium bifidum、 Bifidobacterium breve、Bifidobacterium animalis、Bifidobacterium lactis、Bifidobacterium infantis、Bifidobacterium catenulatumが挙げられる。またLactobacillus属の細菌としてLactobacillus casei、Lactobacillus helveticus、 Lactobacillus acidophilus、Lactobacillus rhamnosus、 Lactobacillus plantarum、Lactobacillus murinus、Lactobacillus reuteri、Lactobacillus brevis、Lactobacillus gasseri、Lactobacillus paracaseiが挙げられる。
　Bifidobacterium属の細菌やLactobacillus属の細菌の増殖が促進されたか否かは、細菌のコロニーの観察やリアルタイムPCRによる方法など当業者に公知の方法により判定することができる。 The nutritional composition of the present invention increases the number and occupation rate of Bifidobacterium genus and Lactobacillus genus in cecal contents and feces without changing the total number of bacteria in the intestine in in vivo tests using rats. Was confirmed. In addition, a decrease in pH in the cecum, an increase in the weight of the cecal tissue / cecal contents, and an increase in the amount of organic acids in the cecal contents were confirmed. Therefore, the composition of the present invention is useful for improving intestinal flora. The invention also includes a hydrolyzate of milk protein and a fermented milk protein as protein, an oil containing oleic acid as lipid, and milk phospholipid and / or soybean lecithin, and isomaltulose as carbohydrate. Provided are a composition for promoting a decrease in pH and a composition for promoting an increase in the amount of an organic acid in the intestine. Examples of the intestine include the small intestine, the large intestine, and the cecum.
The nutritional composition of the present invention is effective against various Bifidobacterium bacteria and Lactobacillus bacteria. Bifidobacterium bacteria include Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis, and Bifidobacterium catenulatum. Examples of bacteria belonging to the genus Lactobacillus include Lactobacillus casei, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus murinus, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus gasseri, and Lactobacillus.
Whether growth of Bifidobacterium bacteria or Lactobacillus bacteria has been promoted can be determined by methods known to those skilled in the art such as observation of bacterial colonies and real-time PCR.
　本発明の栄養組成物の医薬品または飲食品における一日当たりの摂取量は摂取対象者の病態、年齢、症状、体重、用途、および本発明の栄養組成物が栄養の唯一のものであるかなどによって異なるため、特に限定されない。具体的には、成人の場合一日当たり400～1600ml、好ましくは600～1600ml、より好ましくは800～1200mlの摂取量を例示することができる。健康な成人の場合、例えば一日当たり3000mlまで摂取してもよい。また、摂取量は、摂取対象者の担当医により決定することもできる。
　また、本発明の栄養組成物を従来知られる腸内菌叢の改善効果を有する医薬品や食品と併用して用いてもよい。具体的には、プロピオン酸菌発酵物、DHNA(2,4-dihydroxy-2-naphthoic acid)、ACNQ(2-amino-3-carboxy-l,4-naphthoquinone)、フラクトオリゴ糖などを挙げることができるが、これらの例に限定されない。 The daily intake of the nutritional composition of the present invention in a pharmaceutical product or food / drink depends on the pathology, age, symptoms, weight, use of the subject, and whether the nutritional composition of the present invention is the only nutritional item. Since it differs, it is not specifically limited. Specifically, in the case of an adult, the intake per day may be 400 to 1600 ml, preferably 600 to 1600 ml, more preferably 800 to 1200 ml. For healthy adults, for example, up to 3000 ml per day may be taken. The intake amount can also be determined by the attending physician of the subject person.
Moreover, you may use the nutrition composition of this invention together with the pharmaceutical and foodstuff which have the improvement effect of the intestinal microflora conventionally known. Specific examples include fermented propionic acid bacteria, DHNA (2,4-dihydroxy-2-naphthoic acid), ACNQ (2-amino-3-carboxy-l, 4-naphthoquinone), and fructooligosaccharides. However, it is not limited to these examples.
　本発明の栄養組成物は医薬品または飲食品いずれの形態でも利用することができる。例えば、本発明の栄養組成物を医薬品として直接投与することにより、または特定保健用食品などの特別用途食品、栄養機能食品、栄養補助食品、流動食やサプリメントとして直接摂取することにより、腸内菌叢を改善することが期待される。また、液状、ペースト状、固形、粉末などの形態を問わず、各種食品（牛乳、清涼飲料、発酵乳、ヨーグルト、チーズ、パン、ビスケット、クラッカー、ピッツァクラスト、調製粉乳、流動食、特別用途食品、病者用食品、栄養食品、冷凍食品、加工食品その他の市販食品など）に添加し、これを摂取してもよい。また、栄養組成物の使用形態が粉末の場合、例えば噴霧乾燥、凍結乾燥などの手段を用いることにより製造することができる。 The nutritional composition of the present invention can be used in the form of any medicine or food or drink. For example, enteric bacteria can be obtained by directly administering the nutritional composition of the present invention as a pharmaceutical or by directly ingesting it as a special-purpose food such as a food for specified health use, a nutritional functional food, a nutritional supplement, a liquid food or a supplement. It is expected to improve the flora. In addition, various foods (milk, soft drinks, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crusts, prepared milk powder, liquid foods, special-purpose foods, regardless of the form of liquid, paste, solid, powder, etc. , Foods for the sick, nutritional foods, frozen foods, processed foods, and other commercially available foods). Moreover, when the usage form of a nutrient composition is a powder, it can manufacture by using means, such as spray drying and freeze-drying, for example.
　本発明の栄養組成物を医薬品またはサプリメントとして使用する場合には、種々の形態で投与することができる。その形態として、例えば、錠剤、カプセル剤、顆粒剤、散剤、シロップ剤などによる経口投与を挙げることができる。これらの各種製剤は、常法に従って主剤および賦形剤、結合剤、崩壊剤、滑沢剤、矯臭剤、溶解補助剤、懸濁剤、コーティング剤などの医薬の製剤技術分野において通常使用しうる、既知の製剤化のための補助剤を用いて製剤化することができる。また、適当量のカルシウムを含んでいてもよい。さらに適当量のビタミン、ミネラル、有機酸、糖類、アミノ酸、ペプチド類などを添加してもよい。 When the nutritional composition of the present invention is used as a medicine or supplement, it can be administered in various forms. Examples of the form include oral administration using tablets, capsules, granules, powders, syrups and the like. These various preparations can be usually used in the pharmaceutical preparation technical field such as main agents and excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, coating agents and the like according to conventional methods. It can be formulated using known adjuvants for formulation. Further, it may contain an appropriate amount of calcium. Further, an appropriate amount of vitamins, minerals, organic acids, sugars, amino acids, peptides, etc. may be added.
　本発明の栄養組成物は、タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および大豆レシチンの両方またはいずれか一方、糖質としてイソマルチュロースを含む、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進するための薬剤と表現することもできる。
　また本発明は、本発明の栄養組成物を動物に経口投与する工程を含む、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進する方法に関する。本発明の栄養組成物が投与される対象としては哺乳動物が挙げられる。哺乳動物としてはヒト及びヒト以外の哺乳動物が挙げられ、好ましくはヒトやサルが挙げられ、より好ましくはヒトが挙げられる。
　また本発明は、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進に使用するための、タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および／または大豆レシチン、糖質としてイソマルチュロースを含む栄養組成物に関する。あるいは本発明は、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進するための栄養組成物の製造における、タンパク質、脂質および糖質の使用に関する。また本発明は、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進のための、タンパク質、脂質および糖質の使用に関する。また本発明は、タンパク質、脂質および糖質と薬学的に許容される担体を配合する工程を含む、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進のための栄養組成物の製造方法に関する。タンパク質、脂質および糖質の具体例は本明細書に説明した。
　なお本明細書において引用された全ての先行技術文献は、参照として本明細書に組み入れられる。 The nutritional composition of the present invention comprises a hydrolyzate of milk protein and fermented milk protein as protein, an oil containing oleic acid as lipid, and / or milk phospholipid and / or soybean lecithin, and isomalt as a carbohydrate. It can also be expressed as a drug for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, including sucrose.
The present invention also relates to a method for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, comprising the step of orally administering the nutritional composition of the present invention to an animal. Mammals are examples of subjects to which the nutritional composition of the present invention is administered. Mammals include humans and mammals other than humans, preferably humans and monkeys, more preferably humans.
Further, the present invention provides a milk protein hydrolyzate and fermented milk protein as a protein and an oil or fat containing oleic acid as a lipid for use in promoting the growth of bacteria of either or both of the genus Bifidobacterium and Lactobacillus, And a nutritional composition comprising milk phospholipid and / or soybean lecithin, and isomaltulose as a carbohydrate. Alternatively, the present invention relates to the use of proteins, lipids and carbohydrates in the manufacture of a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus. The present invention also relates to the use of proteins, lipids and carbohydrates for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus. The present invention also provides a nutritional composition for promoting the growth of bacteria of the genus Bifidobacterium and / or Lactobacillus, which comprises a step of combining a pharmaceutically acceptable carrier with proteins, lipids and carbohydrates. It relates to a manufacturing method. Specific examples of proteins, lipids and carbohydrates have been described herein.
It should be noted that all prior art documents cited in the present specification are incorporated herein by reference.
　以下、本発明に関して実施例を挙げて説明するが、本発明は、これにより限定されるものではない。 Hereinafter, although an example is given and explained about the present invention, the present invention is not limited by this.
[実施例１：動物を用いた有効性試験]
（被検試料）
　表３および表４に示す配合の一般流動食および本発明の栄養組成物を調製し、これをレトルト（加熱加圧）殺菌(135～145℃×5～10秒)したものを凍結乾燥して被検試料として用いた。なお、表中の栄養組成物に含まれるオレイン酸の含有量は、脂肪酸組成中39%であった。
　対照群：一般流動食の凍結乾燥物を摂取。
　試験群：本発明の栄養組成物の凍結乾燥物を摂取。 [Example 1: Efficacy test using animals]
(Test sample)
A general liquid food having the composition shown in Tables 3 and 4 and the nutritional composition of the present invention were prepared, and sterilized (135 to 145 ° C. × 5 to 10 seconds) by retort (heat and pressure) and freeze-dried. Used as a test sample. The content of oleic acid contained in the nutritional compositions in the table was 39% in the fatty acid composition.
Control group: Ingested lyophilized liquid food.
Test group: Ingested lyophilized product of the nutritional composition of the present invention.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
（動物実験）
　6週齢雄性SDラット（日本SLC）を、体重を指標に対照群および試験群の２群（各群n=6）に群分けして、同日（day0）より被検試料を18日間または22日間自由摂取させた。この間、飲料水も自由摂取させた。被検試料の摂取開始から18日目（day18）または22日目(day22）に剖検を行った。糞は剖検日の朝に採取した。剖検はエーテル麻酔下で行い、心臓採血の後、開腹して盲腸を取り出し、回腸側と結腸側を糸で結紮した後、盲腸重量を測定し、-80℃で測定まで凍結保存した。 (Animal experimentation)
Six-week-old male SD rats (Japan SLC) were divided into two groups (each group n = 6) of the control group and the test group using the body weight as an index, and the test samples were collected on the same day (day 0) for 18 days or 22 days. Ad libitated daily. During this time, drinking water was also taken freely. Necropsy was performed on the 18th day (day 18) or 22nd day (day 22) from the start of ingestion of the test sample. Feces were collected on the morning of autopsy. Necropsy was performed under ether anesthesia, and after blood sampling, the abdomen was opened, the cecum was taken out, the ileum side and the colon side were ligated with a thread, the weight of the cecum was measured, and frozen at -80 ° C. until measurement.
（測定）
・盲腸内のpH：凍結した盲腸を解凍し、盲腸内容物が入った状態の盲腸にラコムテスターpH計（アズワン（株））を挿入して、pHを測定した。
・盲腸組織重量・盲腸内容物重量：盲腸内のpHを測定後、直ちに盲腸組織と盲腸内容物を分離して秤量した。
・盲腸内容物の短鎖脂肪酸量：盲腸内容物を集め均一に混合した。200mgの盲腸内容物に400μlのミリＱ水を添加し、超音波破砕機でホモジナイズして均一にした後、４℃、10000rpmで10minの条件で遠心分離を行った。上清を別のマイクロチューブに移し、上清200μl当たり、Carrez I（53.5g of ZnSO4・7H2 0/100ml）、Carrez II（17.2g of K4 ［Fe(CN)6］3H2O/100ml）を各2.5μl加え攪拌した。4℃、10000rpm、10分の条件で遠心分離を行い、上清をフィルター付きマイクロチューブ（0.22μm）に移し、再度、4℃、10000rpm、10分の条件で遠心分離を行い、上清を測定試料とした。測定試料中の有機酸を、電気伝導度検出器を用いた、ポストカラムpH緩衝化電気伝導度検出法によって定量した（Niwa T., Nakao M., Hoshi S. et al. Effect of Dietary Fiber on Morphine-induced Constipationin Rats, Biosci. Biotechnol. Biochem., 66(6), 1233-1240, 2002）。
　検出器：電気伝導度検出器(島津 CDD-10A)
　カラム：有機酸分析用ポリマーカラムICSep ICE-PRE-ORH-801
　6.5mmI.D.×300mm（東京化学工業（株））
　有機酸分析用ガードカラムカートリッジICSep ICE-ORH-801
　4.0mmI.D.×20mm（東京化学工業（株））
　カラムの温度：55℃
　移動相：5mM p-トルエンスルホン酸水溶液、0.5ml/min
　反応液：5mM p-トルエンスルホン酸と100μM EDTA(2Na)を含む
　20mM Bis-Tris水溶液、0.5ml/min
・腸内菌叢の解析：
　盲腸内容物には凍結乾燥処理を施した。
　糞便および盲腸内容物乾燥物から細菌のDNAを抽出して、Bifidobacterium属、Lactobacillus属の細菌数（生菌数＋死菌数）をリアルタイムPCRにて測定し、細菌数の対数値(log10 (細菌数/g))を求めた。また、総細菌数に対する各細菌の菌数の割合を占有率（％）として算出した。
　結果の統計解析は、Student's t-test（等分散）またはWelchの検定（不等分散）で行った。 (Measurement)
-PH in the cecum: The frozen cecum was thawed, and the pH was measured by inserting a Lacom Tester pH meter (As One Co., Ltd.) into the cecum containing the cecal contents.
-Cecal tissue weight-Cecal content weight: After measuring the pH in the cecum, the cecal tissue and cecal content were immediately separated and weighed.
-Short chain fatty acid content of cecal contents: The cecal contents were collected and mixed uniformly. 400 μl of milli-Q water was added to 200 mg of cecum contents, homogenized with an ultrasonic crusher, and then homogenized, followed by centrifugation at 4 ° C. and 10,000 rpm for 10 min. The supernatant was transferred to another microtube, and Carrez I (53.5 g of ZnSO4 · 7H2 0/100 ml) and Carrez II (17.2 g of K4 [Fe (CN) 6] 3H2O / 100 ml) were each 2.5 μg per 200 μl of supernatant. μl was added and stirred. Centrifuge at 4 ° C, 10000rpm for 10 minutes, transfer the supernatant to a filter-equipped microtube (0.22μm), and centrifuge again at 4 ° C, 10000rpm for 10 minutes to measure the supernatant. A sample was used. The organic acid in the measurement sample was quantified by a post-column pH buffered conductivity detection method using a conductivity detector (Niwa T., Nakao M., Hoshi S. et al. Effect of Dietary Fiber on Morphine-induced Constipation in Rats, Biosci. Biotechnol. Biochem., 66 (6), 1233-1240, 2002).
Detector: Electrical conductivity detector (Shimadzu CDD-10A)
Column: ICSep ICE-PRE-ORH-801 polymer column for organic acid analysis
6.5mm ID × 300mm (Tokyo Chemical Industry Co., Ltd.)
Guard column cartridge for organic acid analysis ICSep ICE-ORH-801
4.0mmI.D. × 20mm (Tokyo Chemical Industry Co., Ltd.)
Column temperature: 55 ° C
Mobile phase: 5 mM p-toluenesulfonic acid aqueous solution, 0.5 ml / min
Reaction solution: 20 mM Bis-Tris aqueous solution containing 5 mM p-toluenesulfonic acid and 100 μM EDTA (2Na), 0.5 ml / min
・ Intestinal flora analysis:
The cecum contents were lyophilized.
Bacterial DNA was extracted from the feces and cecal contents, and Bifidobacterium genus and Lactobacillus genus bacteria count (viable cell count + dead cell count) were measured by real-time PCR. Number / g)). In addition, the ratio of the number of bacteria of each bacterium to the total number of bacteria was calculated as an occupation ratio (%).
Statistical analysis of the results was performed by Student's t-test (equal variance) or Welch's test (unequal variance).
（結果）
　図１に、各群の盲腸等の重量、および盲腸内のpHを示す。盲腸重量が対照群に比べ、試験群で有意に(p<0.05)増加した。この増加は盲腸の組織重量と盲腸内容物の増加によるものであった。また、対照群に比べ、試験群は盲腸内pHが有意に(p<0.05)低値を示した。
　図２に、盲腸内容物の短鎖脂肪酸量を示す。対照に比べ、試験群で有意な差は認められなかったが短鎖脂肪酸が増加する傾向を示した。
　図３に、各群の腸内菌叢の解析結果を示す。Bifidobacterium属の細菌数および占有率は糞便と盲腸内容物とも、試験群は対照群に対して有意に(p<0.05)増加した。盲腸内容物のLactobacillus属の細菌数および占有率も、試験群は対照群に対して有意に(p<0.05)増加した。なお、糞便と盲腸内容物の総細菌数に両群間でほとんど変化はなかった（data not shown）。
　また、試験期間中の体重および摂餌量についても、両群間で有意な差を認めなかった。以上の結果から、本発明の栄養組成物が、栄養を補給すると同時にBifidobacterium属および／またはLactobacillus属の増殖を促進したことがわかった。 (result)
FIG. 1 shows the weight of each group, such as the cecum, and the pH in the cecum. Cecal weight increased significantly (p <0.05) in the test group compared to the control group. This increase was due to an increase in cecal tissue weight and cecal content. In addition, the test group showed a significantly lower (p <0.05) pH in the cecum than the control group.
FIG. 2 shows the amount of short chain fatty acids in the cecum contents. Compared to the control, there was no significant difference in the test group, but there was a tendency for short-chain fatty acids to increase.
In FIG. 3, the analysis result of the intestinal microflora of each group is shown. The number and occupancy of Bifidobacterium were significantly (p <0.05) higher in the test group than in the control group for both feces and caecal contents. The number and occupancy of Lactobacillus bacteria in the cecum contents also increased significantly (p <0.05) in the test group compared to the control group. In addition, there was almost no change in the total number of bacteria in feces and cecal contents between the two groups (data not shown).
In addition, there was no significant difference between the two groups regarding body weight and food consumption during the test period. From the above results, it was found that the nutritional composition of the present invention promoted the growth of the genus Bifidobacterium and / or Lactobacillus simultaneously with the supplementation of nutrition.
　本発明の栄養組成物は、腸内菌叢を改善することができる。具体的には、本発明の組成物は、Bifidobacterium属および／またはLactobacillus属の乳酸菌の増殖の促進、腸重量の増加の促進、腸内容物の有機酸量の増加の促進、腸内のpHの低下の促進、短鎖脂肪酸の増加の促進などに有用である。 The nutritional composition of the present invention can improve the intestinal flora. Specifically, the composition of the present invention promotes the growth of lactic acid bacteria of the genus Bifidobacterium and / or Lactobacillus, promotes an increase in intestinal weight, promotes an increase in the amount of organic acid in the intestinal contents, It is useful for promoting a decrease and promoting an increase in short chain fatty acids.

Claims (10)

  1. タンパク質として乳タンパク質の加水分解物および発酵乳タンパク質、脂質としてオレイン酸を含有する油脂、ならびに乳リン脂質および大豆レシチンの両方またはいずれか一方、糖質としてイソマルチュロースを含む、Bifidobacterium属およびLactobacillus属の両方またはいずれか一方の細菌の増殖を促進するための栄養組成物。 Milk protein hydrolysates and fermented milk proteins, fats and oils containing oleic acid as lipids, and / or milk phospholipids and / or soy lecithin, and isomaltulose as the carbohydrate, Bifidobacterium and Lactobacillus A nutritional composition for promoting the growth of bacteria of both or either genus.
  2. 乳タンパク質が、カゼイン、乳タンパク質濃縮物（MPC）、ホエイタンパク質濃縮物（WPC）、ホエイタンパク質分離物（WPI）、α-ラクトアルブミン、β-ラクトグロブリンおよびラクトフェリンからなる群より選択される、請求項1に記載の栄養組成物。 The milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin, β-lactoglobulin and lactoferrin. Item 2. The nutritional composition according to Item 1.
  3. 乳タンパク質の加水分解物が、栄養組成物１００ｍｌあたり０．９～５．０ｇ含まれる、請求項１または２に記載の栄養組成物。 The nutritional composition according to claim 1 or 2, wherein the milk protein hydrolyzate is contained in an amount of 0.9 to 5.0 g per 100 ml of the nutritional composition.
  4. 乳タンパク質の加水分解物が、ホエイタンパク質濃縮物（WPC）および／またはホエイタンパク質分離物（WPI）をバシラス・リシェニフォルムス（Bacillus licheniformus）由来のアルカラーゼで加水分解およびブタ膵臓由来のトリプシンで加水分解して得られる、請求項１～３のいずれか１項に記載の栄養組成物。 Milk protein hydrolysates hydrolyze whey protein concentrate (WPC) and / or whey protein isolate (WPI) with alcalase from Bacillus licheniformus and with trypsin from porcine pancreas The nutritional composition according to any one of claims 1 to 3, obtained by decomposition.
  5. 乳タンパク質の加水分解物が、分画分子量10,000の限外濾過膜で処理して得られる透過画分（パーミエイト）である、請求項１～４のいずれか１項に記載の栄養組成物。 The nutritional composition according to any one of claims 1 to 4, wherein the milk protein hydrolyzate is a permeate obtained by treatment with an ultrafiltration membrane having a molecular weight cut-off of 10,000.
  6. 発酵乳タンパク質がチーズに由来する、請求項１～５のいずれか１項に記載の栄養組成物。 The nutritional composition according to any one of claims 1 to 5, wherein the fermented milk protein is derived from cheese.
  7. チーズがクワルクである、請求項６に記載の栄養組成物。 The nutritional composition according to claim 6, wherein the cheese is quark.
  8. 発酵乳タンパク質が、栄養組成物１００ｍｌあたり０．５～６ｇ含まれる、請求項１～７のいずれか１項に記載の栄養組成物。 The nutritional composition according to any one of claims 1 to 7, wherein the fermented milk protein is contained in an amount of 0.5 to 6 g per 100 ml of the nutritional composition.
  9. イソマルチュロースが、栄養組成物１００ｍｌあたり４～１５ｇ含まれる、請求項１～８のいずれか１項に記載の栄養組成物。 The nutritional composition according to any one of claims 1 to 8, wherein isomaltulose is contained in an amount of 4 to 15 g per 100 ml of the nutritional composition.
  10. 脂質にオレイン酸が全脂肪酸組成の３０%以上の割合で含まれる、請求項１～９のいずれか１項に記載の栄養組成物。 The nutritional composition according to any one of claims 1 to 9, wherein the lipid contains oleic acid in a proportion of 30% or more of the total fatty acid composition.
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