JP4307475B2 - Infant nutrition composition - Google Patents

Description

  The present invention relates to a nutritional composition for infants, which contains RNA and polyamine, and has a gastrointestinal maturation promoting action. By ingesting the nutritional composition for infants of the present invention, maturation and development of the immature digestive tract during infancy can be promoted, and the digestive absorption ability can be improved, which is useful as a medicine or food.

RNA is a polynucleotide in which a nucleotide containing a base component such as adenine or cytosine forms a single chain polymer with a phosphodiester bond, and is involved in protein synthesis in all cells in the body. Yes. RNA is also contained in breast milk at a high concentration, and there is an interest in the physiological role for infants. Orally ingested RNA is considered to be broken down into nucleotides and nucleosides and absorbed by the action of nucleases and phosphatases in the digestive tract. Therefore, as for the physiological action of RNA, an immunostimulatory action, lipid metabolism improvement / promotion, and brain function improving action can be expected as in the case of nucleotides.
ADKulkarni et al. Have reported that breeding mice with a diet supplemented with RNA increases resistance to infection and improves immunity (Journal of Parenteral and Enteral Nutrition, 10, 169-171 (1986)). . Hamada et al. Have also shown that feed supplemented with RNA suppresses diarrhea in young animals and promotes growth (Japanese Patent Laid-Open No. 43-28059). Despite having such an action, the conventional nutritional composition for infants using milk as a main ingredient hardly contained RNA. In addition, some infant formulas containing nucleotides have been found, but infants taking breast milk are taking not only nucleotides but also RNA and taking artificial milk. It may be necessary to fortify RNA into milk powder to meet the infant's requirements.

Polyamines, on the other hand, are linear aliphatic hydrocarbons having two or more primary amino groups, such as putrescine, spermidine, and spermine, which stabilize nucleic acids, promote nucleic acid synthesis, activate protein synthesis, Physiological actions such as histone acetylation, protein phosphorylation promoting action, and cell membrane stabilization action are known. Recently, effects of promoting cell proliferation and differentiation have also been reported. In particular, polyamines taken orally have been reported to mature the gastrointestinal mucosa (Buts JP et al., Digestive Diseases and Science, 38, 1091 (1993); Grant, AL et al., J. Anim. Sci). , 68, 363 (1990); Dufour, C. et al., Gastroenterology, 95, 112 (1988)). It has also been reported that polyamines taken orally are quickly taken into the body and used in tissues (Bardocz, S. et al., J. Nutr. Biochem., 4,66 (1993)).
On the other hand, examples of use in foods include a method for producing konjac (Japanese Patent Laid-Open No. 6-38690) that promotes the absorption of proteins, which reduces the odor of konjac and does not adversely affect when cooked with other foods. Nutritional compositions (Japanese Patent Laid-Open No. 6-305,956) and the like for the purpose of maintaining good growth and health. Examples of using polyamines as pharmaceuticals include a method for inhibiting gastric acid secretion and an ingesting composition for inhibiting gastric acid secretion (Kai 58-131914) and an immunostimulant (Japanese Patent Laid-Open No. 59-98015 and special patents). Kaihei 2-223514) is known. As described above, various effects are known for polyamines, and since their importance has begun to be recognized in recent years, it is desirable from the nutritional point of view to strengthen a nutritional composition with a low polyamine content. Conceivable. However, like RNA, the nutritional composition mainly made from milk contained almost no polyamine.

  In recent years, infant formulas have been provided with products that are much closer in terms of ingredients compared to breast milk, which is the ultimate goal, due to improved technology. However, in terms of functionality, many problems still remain as compared with breast milk, and a formula milk powder that more closely approximates breast milk is desired. Conventional formulas have no suitable ingredients, and the need for RNA or polyamines in infancy has not been fully recognized, so these ingredients can be combined or strengthened in infant nutrition at the same time. It never happened.

JP 43-028059 A Japanese Patent Laid-Open No. 06-038690 Japanese Patent Application Laid-Open No. 06-305956 JP 58-131914 A JP 59-098015 A Japanese Patent Laid-Open No. 02-223514 Journal of Parenteral and Enteral Nutrition, 10, 169-171 (1986) Buts J.P. et al., Digestive Diseases and Science, 38, 1091 (1993) Grant, A.L. et al., J. Anim.Sci., 68, 363 (1990) Dufour, C. Et al., Gastroenterology, 95, 112 (1988) Bardocz, S. et al., J. Nutr. Biochem., 4, 66 (1993)

  In view of the situation as described above, the present inventors have intensively studied polyamines or RNAs, and as a result, found that adding both substances within a specific range significantly promotes maturation or development of the infant's digestive tract. It was. In addition, as a result of intensive research on the problems of conventional infant formulas, the present inventors have developed a milk powder that is functionally more similar to breast milk by adding polyamine and RNA simultaneously. Therefore, this invention makes it a subject to provide the nutrition composition for infants which has a digestive tract maturation promotion effect containing RNA and a polyamine.

  The present invention relates to a nutritional composition for infants, which contains RNA and polyamine, and has a gastrointestinal maturation promoting action. Specifically, the present invention relates to an infant nutritional composition comprising 1 mg to 200 mg of RNA and 10 μg to 2000 μg of polyamine per 100 g of solids of the composition. At this time, the polyamine is at least two selected from the group consisting of spermine, spermidine, putrescine, or cadaverine, and spermine is 10 to 90%, spermidine is 10 to 90%, and putrescine is 0 to 90%. , And / or 0 to 20% cadaverine. By ingesting the nutritional composition for infants of the present invention, maturation and development of the immature digestive tract during infancy can be promoted, and the digestive absorption capacity can be improved, which is useful as a medicine or food.

  From the above results, the present invention provides a nutritional composition for infants, which contains RNA and polyamine, and has a gastrointestinal maturation promoting action. By ingesting the nutritional composition for infants of the present invention, maturation and development of the immature digestive tract during infancy can be promoted, and the digestive absorption capacity can be improved, which is useful as a medicine or food.

  The RNA and polyamine in the present invention are characterized by containing 1 mg to 200 mg of RNA and 10 μg to 2000 μg of polyamine per 100 g of the solid of the composition. At this time, if the amount of each component is less than these amounts, the effect does not appear, and since the content in the breast milk is about this level, it is not preferable to contain more than this because it approximates the breast milk. As the polyamine in the present invention, at least two selected from the group consisting of spermine, spermidine, putrescine, or cadaverine are used. In particular, it is preferable to blend three types of spermine, spermidine, and putrescine. The composition ratio of the polyamine is preferably 10 to 90% spermine, 10 to 90% spermidine, 0 to 90% putrescine, and / or 0 to 20% cadaverine. The RNA source used in the present invention is not particularly limited as long as it is used as a food. Preferred examples include fish larvae or yeast. Further, the polyamine source to be added is not particularly limited as long as it is similarly used as a food. For example, an animal organ or a baby.

  The nutritional composition for infants in the present invention includes infant formulas, formulas for low birth weight infants, follow-up milks, formulas for infants with allergic diseases, etc., and proteins, lipids, carbohydrates, vitamins and minerals It is configured as a main component. In addition, you may contain the component which can be further mix | blended with the infant nutrition composition. Protein sources include milk protein fractions such as casein, whey protein concentrate (WPC), whey protein isolate (WPI), αs-casein, β-casein, α-lactalbumin, and β-lactoglobulin. Alternatively, plant proteins such as soybean protein and wheat protein, and peptides or amino acids obtained by enzymatic degradation of these to various degrees of degradation can be used. Fat sources include milk fat, lard, beef tallow, or animal oil such as fish oil including bonito oil, tuna oil, etc., or soybean oil, rapeseed oil, corn oil, coconut oil, palm oil, palm kernel oil, safflower oil Vegetable oils such as sesame oil, linseed oil, evening primrose oil, MCT, or cottonseed oil, and fractionated oils, hydrogenated oils, transesterified oils, and the like can be used. As the sugar source, lactose, maltose, glucose, sucrose, dextrin, 6'-galactosyl lactose, fructooligosaccharide, oligosaccharide such as lactulose, artificial sweetener, soluble polysaccharide, or starch can be used. Vitamin and mineral sources include “CODEX Standards for Special Use Foods Including Infant Foods and Related Sanitation Work Rules, CAC / VOL.IX-1st Edition and Supplement 1,2,3,4” (issued by the Japan International Dairy Federation, 1993), "1993 edition of designated food additive manual (revised 31st edition) (published by Food and Science Co., Ltd., 1993)" or "notification of food additive / food material natural product manual (12th edition)" Among the minerals and vitamins described in (published by Food and Science, 1992), those usable for infant foods can be used. Examples of vitamins include vitamins A, B, C, D, E, K, folic acid, pantothenic acid, β-carotene, nicotinic acid amide, etc., and minerals include calcium, magnesium, iron , Copper, zinc, iodine, manganese, selenium and the like. The blending ratio of protein, fat, carbohydrate, vitamin, and mineral is 5 to 50% by weight, 5 to 50% by weight, 20 to 80% by weight, 0.005 to 5% by weight, and 0.005, respectively, per solid. 5% by weight is preferred.

  The nutritional composition thus obtained increases the digestive absorption function of nutrient components, prevents allergen permeation, exhibits various functions inherent in the digestive tract, and further increases the activity of natural killer cells and macrophages. Such effects as immunostimulating effects such as activation of desaturase, increase in the amount of DHA and arachidonic acid in the brain, and increase in in vivo phospholipids can be expected. Furthermore, the effect of simultaneous intake of RNA and polyamine can be further enhanced by other substances such as arginine, β-carotene, ganglioside, sialic acid, lactoferrin, arachidonic acid, DHA and the like.

(Example)
The present invention will be described in more detail with reference to the following examples, which are merely illustrative and the present invention is not limited thereto.

Preparation of milk powder containing RNA and polyamine
Skim milk 96 kg, whey protein concentrate (WPC; Danish Protein) 3 kg and lactose 17.6 kg are added and dissolved, and water-soluble vitamin components (vitamins B1, B6, B12, C, niacin, folic acid, pantothenic acid) , Biotin, choline, inositol, etc.) and mineral components (calcium carbonate, potassium chloride, magnesium sulfate, sodium ferrous citrate, copper sulfate, zinc sulfate, etc.) 0.4 kg each and yeast RNA (purity about 50%) 100 g, in accordance with a polyamine preparation method (Japanese Patent Laid-Open No. 8-232809), 36 g of a polyamine preparation prepared from salmon shiroko and fat-soluble vitamins (vitamins A, D, E, K, β-carotene, etc.) Dissolved, linoleic acid, γ-linolenic acid, arachidonic acid, α-linolenic acid, EPA (eicosapentaene Acid), DHA (docosahexaenoic acid), and homogenized by mixing prepared fat 9.56kg including cholesterol. The obtained solution was sterilized, concentrated by a conventional method, and dried to obtain 120 kg of milk powder. The formula prepared by dissolving this powdered milk in warm water to a solid content of 13% contained about 5 mg / 100 ml of RNA and about 120 μg / 100 ml of polyamine.

Preparation of milk powder containing RNA and polyamine ・ 2
Dissolve 760 g of whey powder and 20 g of lactose in 3 kg of hot water, 20 g of water-soluble vitamins and mineral components similar to those in Example 1, 20 g of yeast RNA (purity of about 50%), and a method for preparing polyamine (specialty) Polyamine preparation 30 mg, skim milk powder 740 g prepared from salmon milk obtained according to Kaihei No. 8-238094), and 478 g of prepared fat in which the same fat-soluble vitamin component as in Example 1 was dissolved were added and homogenized. The obtained solution was sterilized, concentrated by a conventional method, and dried to obtain 2 kg of milk powder. The product prepared by dissolving this milk powder in warm water contained about 0.13 mg / 100 ml of RNA and about 1.3 g / 100 ml of polyamine.

Composition of the nutritional composition for infants of the present invention The typical composition (per 100 ml) of the nutritional composition for infants in the present invention is shown in the following table. Further, ganglioside, arachidonic acid, lactoferrin, lactulose, galactooligosaccharide, cholesterol and the like may be blended as other components not described.

(Test Example 1)
Intestinal Maturation Promoting Effect The intestinal maturation promoting effect was tested according to the following method. That is, according to the method of Hall et al. (Science, 109, 1313-1315, 1975), cannulation was performed on SD rats (5 days old), and artificial nursing was performed. The artificial milk used at this time was prepared according to the composition of rat milk (Dymsza et al., Journal of Nutrition, 84, 100, 1964.). The amount of artificial milk fed was such that the artificial lactating rats showed weight gain similar to that of the mother nursing rats. From 5 days to 10 days of age, the breast milk was raised with the above-described artificial milk, and 11 days to 14 days of age were divided into 4 groups, which were used as a control group and an addition group. The same artificial milk was given to the control group as it was, and the additive group was given artificial milk to which RNA alone, polyamine alone, and RNA and polyamine were added, respectively. RNA was added at 5 mg / 100 ml, and polyamine was added at 120 μg / 100 ml. At the age of 15 days, the mice were sacrificed by whole blood collection under ether anesthesia, and the small intestine was removed. Under ice temperature, the small intestinal mucosa was scraped from the small intestine with a glass cover and suspended in cold physiological saline, and then the small intestinal mucosa fraction was prepared with a homogenizer. The lactase and maltase disaccharide degrading enzyme activities in this small intestinal mucosa fraction were measured according to the method of Dahlqvist et al. (Anal. Biochem., 7, pp18-25 (1964)). That is, lactose and maltose were used as substrates, mixed with 50 μl of the substrate solution and 50 μl of the small intestinal mucosa fraction, and incubated at 37 ° C. for 30 minutes. After incubation, 20 μl of the reaction solution is collected, and the amount of glucose released and decomposed by the enzyme of the small intestinal mucosa is measured using a glucose measurement kit (Wako Pure Chemical Industries, Ltd.). It was. In this method, maturation of intestinal cells can be confirmed by a decrease in tissue lactase activity and an increase in maltase activity. The results are shown in FIGS. In the group containing only RNA, there was almost no difference compared to the control group, but in the group where RNA and polyamine were added at the same time, the decrease in lactase activity, which is an index of maturation, and the case where polyamine was added alone, and An increase in maltase activity was observed. It was confirmed that the maturation of intestinal mucosa was synergistically promoted by the interaction of RNA and polyamine.

(Test Example 2)
Intestinal maturation promoting effect In the same manner as in Test Example 1, SD rats (5 days of age) were cannulated and subjected to artificial nursing. The groupings were a control group (artificial milk administration group), an RNA addition group, a polyamine addition group, an RNA and polyamine addition group. RNA was added to 2.5 mg / 100 ml and polyamine was added to 60 μg / 100 ml artificial milk. The test substance was administered from 5 to 14 days of age. At the age of 15 days, it was sacrificed by whole blood sampling under ether anesthesia, and the small intestine was extracted and used as a specimen. The total wet weight of the specimen was measured, and a histological search (villus height and gland depth) was performed. The results are shown in FIGS. When RNA or polyamine was administered alone, it was not very effective compared to the control group, but it was confirmed that administration of RNA and polyamine simultaneously promoted maturation of the intestinal tract due to the synergistic effect of both. It was done.

The lactase activity (%) in the small intestine in each administration group in Test Example 1 is shown. The maltase activity (%) in the small intestine in each administration group in Test Example 1 is shown. The whole wet weight (mg / cm) of the small intestine in each administration group in Test Example 2 is shown. The height of the villi of the small intestine and the depth of the gland (μm) in each administration group in Test Example 2 are shown.

Claims (2)

RNA and at least two or more polyamines selected from the group consisting of spermine, spermidine, putrescine, or cadaverine, containing 10 to 90% of the spermine, 10 to 90% of the spermidine, and 0 to 90 of the putrescine % And / or said cadaverine is 0-20%, The nutrition composition for infants which has a digestive tract maturation promotion effect | action characterized by the above-mentioned .   The nutritional composition for infants according to claim 1, comprising 1 mg to 200 mg of RNA and 10 µg to 2000 µg of polyamine per 100 g of solids of the composition.