WO2013080911A1 - 腸内菌叢改善用栄養組成物 - Google Patents

腸内菌叢改善用栄養組成物 Download PDF

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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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nutritional composition
milk
protein
milk protein
bacteria
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PCT/JP2012/080450
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English (en)
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 IN3449DEN2014 priority Critical patent/IN2014DN03449A/en
Priority to HK14111191.8A priority patent/HK1197795B/xx
Priority to JP2013547137A priority patent/JP6234227B2/ja
Priority to CN201280059104.9A priority patent/CN103957720B/zh
Priority to SG11201402693VA priority patent/SG11201402693VA/en
Publication of WO2013080911A1 publication Critical patent/WO2013080911A1/ja

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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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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 OR TREATMENT 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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CN115551873A (zh) * 2020-03-13 2022-12-30 帝斯曼知识产权资产管理有限公司 调节胃肠道微生物代谢途径和代谢物的方法
JP2023519172A (ja) * 2020-03-13 2023-05-10 ディーエスエム アイピー アセッツ ビー．ブイ． 胃腸微生物代謝経路及び代謝物を調節する方法
WO2022184772A1 (en) * 2021-03-02 2022-09-09 Arla Foods Amba Immunogenic protein hydrolysate with reduced allergenicity
CN115053929A (zh) * 2022-05-23 2022-09-16 江西人之初乳品营养有限公司 一种适合脂肪肝人群的配方奶粉及其制备
CN115053929B (zh) * 2022-05-23 2024-04-23 江西人之初乳品营养有限公司 一种适合脂肪肝人群的配方奶粉及其制备

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