KR20090097945A - Agent for facilitating the development of brain in infant comprising milk-derived phospholipid and food composition comprising the same - Google Patents

Abstract

Disclosed is an agent for facilitating the development of the brain in an infant, which comprises an effective amount of a milk-derived phospholipid or a sphingomyelin. Also disclosed is a food composition for improving the nervimotion and/or the learning function in an infant, which comprises the agent. For direct intake, the agent preferably comprises at least 0.027 wt% of a milk-derived phospholipid or at least 0.005 wt% of a sphingomyelin.

Description

Infant brain development promoter containing phospholipid derived from milk and food composition containing same {Agent for facilitating the development of brain in infant comprising milk-derived phospholipid and food composition comprising the same}

The present invention aims to improve the growth and development of the brain of premature infants, in particular psychomotor and learning functions, especially phospholipids derived from sphingomyelin and docosahexaenoic acid (Docosa hexaenoic acid; DHA). It relates to an infant brain development accelerator containing. The present invention also relates to a food composition containing the infant brain development accelerator.

Essential fatty acids, such as ω-3 fatty acids, have a great effect on the living body, and in particular, contribute greatly to the growth and development of the fetus and newborn baby. In general, it is known that fatty acid transport from the mother to the fetus is rarely performed in the first trimester, and that fatty acids are transferred to the fetus through the placenta at the end of pregnancy. Fatty acids are said to be actively absorbed into the brain of fetuses and newborns in the late pregnancy and early postpartum to improve cognition and visual development. However, in premature infants, the low amount of fatty acids transferred from the mother and the low ability of the fatty acid biosynthesis of the child itself may cause a deficiency of DHA, which plays an important role in the development of the brain and nervous system.

It is also known that myelination (myelination) of the fetus occurs later in pregnancy. However, in the case of premature infants, myelination is often inadequate, and in combination with the deficiency state of DHA described above, there are cases in which it is disadvantageous in terms of neurodevelopment (Non Patent Literature 1).

On the other hand, phospholipids are known to have a great influence on infants in maturity. In particular, regarding phospholipids derived from milk, the effect of raising the DHA content in the body (Patent Document 1), the effect of treating intestinal motor dysfunction disease by developing the intestinal plexus (Patent Document 2), and promoting the maturation and development of the digestive tract The effect (patent document 3) etc. which are made are already reported. Moreover, the effect of promoting myelination in the optic nerve during development is also known (Non Patent Literature 2).

Non-Patent Document 1: Kyoko Tanaka. Infant psychopsychological behavior development and fatty acids. Footsteps in Medicine, 218: 403-407, 2006

[Non-Patent Document 2] Oshida et al., Effects of dietary sphingomyelin on control nervous system myelination in developing rats. Pediatric Res, 53: 589-593, 2003

Patent Document 1: Japanese Patent Application Laid-Open No. 2001-128642

Patent Document 2: Japanese Patent Laid-Open No. 2003-252765

Patent Document 3: Japanese Patent Laid-Open No. 2000-250563

Disclosure of Invention

Problems to be Solved by the Invention

Among the phospholipids, in particular, phospholipids derived from breast milk and milk (hereinafter also referred to as milk phospholipids) have different characteristics from phospholipids derived from soybean and egg yolk. In particular, it differs in that it contains a large amount of phospholipid called sphingomyelin (henceforth abbreviated as "SM"). This sphingomyelin is present in cell membranes such as cranial nerve tissue, and is considered to have a myelin formation promoting action, in particular, as a major component of myelin.

However, in premature babies such as those described above, particularly in low birth weight infants whose early nutrition is known to have a significant impact on later development, oral intake of sphingomyelin plays a role in neurodevelopment, particularly psychomotor development. It is still unclear.

Means to solve the problem

As a result of the present inventors' diligence regarding the above-mentioned problem, the composition containing milk derived phospholipid and DHA was administered to a premature infant, and Bayley infant development test (The Bayley Scales of Infant) was compared with administration of a composition containing egg yolk lecithin and DHA. The development, Fagan test (Fagan test of infant intelligence), and visual evoked potential (VEP) tests have been found to show improvement in developmental indicators, and the present invention has been completed. In the composition containing the milk-derived phospholipid and DHA, and the composition containing egg yolk lecithin and DHA, the amount of DHA was the same.

Therefore, the object of the present invention can be attained by an infant brain development accelerator which contains a milk-derived phospholipid, which contains a lot of sphingomyelin.

One aspect of the present invention is an infant brain development accelerator containing an effective amount of milk derived phospholipids. The infant brain development promoter of the present invention may contain an effective amount of docosahexaenoic acid.

The infant brain development accelerator is taken as it is. It may be manufactured for direct intake, or may be manufactured as a shape (concentrate, dried product, etc.) to be ingested after appropriately adjusting with water, hot water, milk (milk, human breast milk, etc.) at the time of ingestion. In the case of direct intake, the milk-derived phospholipid is contained at least 0.027% by weight, and when DHA is blended, the docosahexaenoic acid is preferably contained at least 0.008% by weight. Moreover, when mix | blending at least 0.005 weight% of said sphingomyelin and DHA, it is also preferable to contain at least 0.008 weight% of said docosahexaenoic acid.

In addition, in the case of ingestion (concentrate, dried product, etc.) after proper adjustment with water, hot water, milk (milk, human breast milk, etc.) at the time of ingestion, the effective amount of phospholipid derived from milk is at least 0.15% by weight, DHA When mix | blending, it is preferable that the effective amount of docosahexaenoic acid is at least 0.05 weight%. Moreover, as content of sphingomyelin, at least 0.03 weight% is preferable, and when mix | blending DHA, it is also preferable to contain at least 0.05 weight% of said docosahexaenoic acid. In addition, in this invention, "weight%" means "w / w%" unless there is particular notice.

Infants in the present invention are preferably any of premature infants, low birth weight infants, very low birth weight infants, and very low birth weight infants.

In another aspect of the present invention, there is provided a food composition for improving infant psychomotor and / or learning function, which contains the infant brain development accelerator. In this case, it is preferable that the food composition is any one of powdered milk powder, concentrate for beverage preparation, and dried product for beverage preparation.

The present invention specifically provides the following.

(1) Infant brain development accelerator prepared by combining phospholipids containing at least 0.005% by weight of sphingomyelin at the time of ingestion,

(2) the infant brain development promoter according to the above (1), wherein the phospholipid is derived from milk;

(3) the infant brain development promoter according to the above (1) or (2), wherein the sphingomyelin is derived from milk;

(4) The infant brain development promoter according to any one of (1) to (3), wherein the phospholipid derived from milk is at least 0.027% by weight at the time of ingestion,

(5) The infant development promoter according to any one of (1) to (4) above, wherein the amount of sphingomyelin in the product is at least 0.03% by weight, and the amount of sphingomyelin is at least 0.005% by weight when ingested.

(6) The infant development promoter according to any one of the above (1) to (4), which is formulated so that the milk-derived cognitive mass in the product is at least 0.15% by weight and the milk-derived cognitive mass is at least 0.027% by weight. ,

(7) The infant development promoter according to any one of the above (1) to (6), which contains at least 0.008% by weight of docosahexaenoic acid at the time of ingestion,

(8) The infant development promoter according to any one of (5) to (7), wherein the product contains at least 0.05% by weight of docosahexaenoic acid,

(9) The infant brain development accelerator according to any one of the above (1) to (8), wherein the infant is any one of premature infants, low birth weight infants, very low birth weight infants, and ultra low birth weight infants.

(10) a food composition for improving infant psychomotor and / or learning function, comprising the infant brain development promoter according to any one of (1) to (9) above;

(11) the food composition for improving infant mental exercise and / or learning function according to the above (9), wherein the food composition is any one of formula powder, concentrate for beverage preparation, and dried product for beverage preparation,

(12) Infant brain development accelerators containing sphingomyelin to be added to food and adjusted to at least 0.005% by weight of sphingomyelin in food when ingested;

(13) The infant according to the above (11), which further contains docosahexaenoic acid and is added to the food and adjusted to at least 0.008% by weight of docosahexaenoic acid in the food at the time of ingestion. Brain development accelerator,

(14) a method for promoting brain development in infants, characterized by administering sphingomyelin or phospholipid derived from sphingomyelin;

(15) a method for improving psychomotor and / or learning function in infants, characterized by administering sphingomyelin or phospholipid derived from sphingomyelin;

(16) The method according to the above (14) or (15), wherein the infant is any one of the group consisting of premature infants, low birth weight infants, very low birth weight infants, and very low birth weight infants;

(17) use of sphingomyelin or sphingomyelin for the production of infant brain development promoters,

(18) the use of sphingomyelin or sphingomyelin for the production of food compositions for improving infant psychomotor and / or learning functions,

(19) The use according to the above (17) or (18), wherein the infant is any of the group consisting of premature infants, low birth weight infants, very low birth weight infants, and ultra low birth weight infants.

Effects of the Invention

By improving the infant brain development accelerator and the infant psychomotor and / or learning function improving food composition according to the configuration of the present invention, improving the development and learning function of the brain of premature infants, especially low birth weight infants, which have not been known so far It became possible. The purpose can be achieved by a convenient means of ingesting the pharmaceutical or food composition, and the effect is unpredictable.

In addition, the milk-derived phospholipid as a raw material and DHA are relatively easy to obtain, and it is possible to manufacture the pharmaceutical or food composition of the present invention having the above characteristics easily and inexpensively.

Brief description of the drawings

FIG. 1 is a visual generation potential diagram in which the time (latency) from the pattern stimulus (left side of chart) to the peak of a sound wave at 16 Hz is measured in a VEP test. The horizontal axis represents time.

2 is a graph showing the content of arachidonic acid as a composition analysis result of red blood cell fatty acid. Values at 4 weeks (4 weeks) and 8 weeks (8 weeks) after birth (before) are shown.

3 is a graph showing the content of DHA as a composition analysis result of red blood cell fatty acids. Values at 4 weeks (4 weeks) and 8 weeks (8 weeks) after birth (before) are shown.

4 is a graph showing the plasma sphingomyelin concentration as a result of the composition analysis of plasma phospholipids. Values are shown immediately after (before) birth, at 2 weeks (2 weeks), at 4 weeks (4 weeks), at 6 weeks (6 weeks), and at 8 weeks (8 weeks).

FIG. 5 is a graph showing MDI, PDI, and BRS index scores of Bayley infant development test at 6 months of fertilization.

Fig. 6 is a graph showing the Fagan score at 3 months and 6 months of age at the Fagan test.

FIG. 7 is a graph showing the time (msec) of VEP inspection at 3 months and 6 months of age.

Implement the invention  Best form for

EMBODIMENT OF THE INVENTION Hereinafter, although this invention is demonstrated in detail, this invention is not limited to the individual form described below.

The "phospholipid" in this invention may be a single phospholipid component, or the mixture which consists of several phospholipid components may be sufficient as it. Preferable examples of the "phospholipid" in the present invention are phospholipids containing sphingomyelin, and more preferably "milk derived phospholipids". In the present invention, "milk derived phospholipid" refers to a phospholipid mixture prepared from animal milk. In general, milk-derived phospholipids include phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and in particular, unlike phospholipids derived from soybean or egg yolk, they are characterized by containing a large amount of sphingomyelin ( Matsumoto Nobuyoshi, Takemasa Mutsuko, Morita Tetsuro, Kawasaki Journal of Medical Welfare Vol.15 No 1 2005 209-216). This sphingomyelin is present in cell membranes such as cranial nerve tissue, and is considered to have a myelin formation promoting action, in particular, as a major component of myelin.

In the milk-derived phospholipid used in the present invention, milk as a raw material can be used in addition to the milk of various livestock such as cattle, goats, sheep, horses, buffaloes, and the like.

The milk-derived phospholipid used in the present invention can be prepared by extracting it from raw oil (for example, milk). In particular, in the case of milk, a phospholipid having a phospholipid composition close to that of human breast milk (hereinafter sometimes referred to as "milk") can be produced.

Moreover, it is also possible to use a commercial item as milk derived phospholipid. Commercially available products such as Dairy Incredibles of New Zealand (for example, milk complex lipid products having a phospholipid content of 40.6% or 85.3%), New Zealand, Bay Milk Products (trade name: ALPHA LIPID), Sphingo Myelin content 20% by weight) and the like.

In the present invention, the milk-derived phospholipid can be used as a composition containing it. As said composition, the phospholipid fraction extracted from the milk component and not refine | purified to the grade of the said product etc. is mentioned. Specific examples include a composite lipid fraction prepared by fractionation from milk or buttermilk, butter serum, or a concentrate thereof.

Docosahexaenoic acid (DHA) used for this invention is n-3 type polyunsaturated fatty acid which has a C22 and a carbon-carbon unsaturated bond 6, and is also represented by "22: 6, n = 3". Also known as Cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid. Molecular weight 328, Cas. No. 6217-54-5, antithrombotic action, blood lipid lowering action, etc. are known. It is widely distributed in the cerebral cortex synaptic membrane and photoreceptors of the eye, and its content increases in the development stages of the central nerve and myelin. (Editing by Ooki Michinori, Chemical Metabolism, Tokyo Chemical Co., Ltd., pp.95 (1994) )). It can be seen that DHA is contained in a lot of fish oil, but recently, microorganisms such as marine microorganisms, such as Labyrinthula (Lavirintula, Traustochytrium), and single cells, have also been known as sources of DHA. In the present invention, the DHA may be used as it is in a state contained in fish oil, microorganisms, or the like, or may be purified. In addition, although chemical synthesis and microbial synthesis can also be used, it is not limited to these examples.

The milk-derived phospholipid content in the infant brain development promoter of the present invention may be appropriate. However, in general, the product for direct intake is 0.027% by weight or more, preferably 0.027-0.95 weight, as the milk-derived phospholipid at the time of ingestion. It is good to contain 0.005 weight% or more, preferably 0.006-0.95 weight% as% or SM. When DHA is blended, the DHA content is preferably 0.008% by weight or more, preferably 0.009% by weight or more in the product.

In addition, the infant brain development accelerator of the present invention can also be used as an aspect of a product (concentrate, dried product, etc.) to be ingested after being properly adjusted with water, hot water, milk (milk, human breast milk, etc.) at the time of ingestion. In this case, it can be prepared so that the amount of sphingomyelin in a product is at least 0.03 weight%, and at the time of ingestion, the amount of sphingomyelin is at least 0.005 weight%. Alternatively, the milk-derived phosphate mass in the product may be at least 0.15% by weight, and at the time of ingestion, the milk-derived phosphate mass may be at least 0.027% by weight. In addition, when mix | blending DHA, it is preferable to set it as 0.05 weight% or more in a product with respect to DHA content.

In addition, food composition for improving infant mental exercise and / or learning function, such as infant formula containing infant infant brain development promoter of the present invention, 0.150% by weight or more, preferably 0.170 to 0.95 wt%, or 0.030 wt% or more as SM, preferably 0.035 to 0.95 wt%. In addition, when mix | blending DHA, it is preferable to set it as 0.055 weight% or more in a product, and, as for DHA content, it is more preferable to set it as 0.060 weight% or more.

In the food composition for improving infant psychomotor and / or learning functions, such as infant formula for infants-schoolchildren containing the infant brain development promoter of the present invention, concentrates for beverage preparations, and dry matters for beverage preparations, phospholipids derived from milk in the product It is preferable to contain 0.300% by weight or more, preferably 0.320 to 0.95% by weight, or 0.060% by weight or more, and preferably 0.065 to 0.95% by weight as SM. In addition, when mix | blending DHA, it is preferable to set it as 0.050 weight% or more in a product, Preferably it is 0.060 weight% or more about DHA content.

Preferred specific examples of the infant brain development promoter of the present invention include infant formula prepared by enhancing sphingomyelin. General formula for infants is formulated so that milk is a main ingredient, but the composition of the protein is different from that of milk as a raw material in order to bring the composition closer to human breast milk. For example, the ratio of casein and whey protein is about 6: 4 for milk and about 2: 8 for formula. In addition, the composition of the whey protein is also changed to be different from milk. Β-lactoglobulin in milk is likely to be an allergen. For this reason, the formula powder which increased the alpha-lacto albumin and lowered the ratio of (beta) -lactoglobulin relatively, the formula powder which hydrolyzed the whole or all the whey protein, the formula milk which mixed the specific refined protein, or (beta) Formulated milk powders that selectively decompose only lactoglobulin are commercially available.

In the process of preparing such formula, sphingomyelin originally contained in milk is often lost. For this reason, in order to expect the effect as an infant brain development promoter of this invention, it is necessary to strengthen sphingomyelin in general formula.

The daily intake of the infant brain development accelerator of the present invention is not particularly limited because it varies depending on the age, symptoms, development, weight, etc. of the ingestor, 0.1 to 10000 mg / kg body weight can be ingested, preferably 0.1 to 1000 mg / kg body weight, more preferably 1 to 300 mg / kg body weight. In particular, when the ingestor is an infant, it is preferable to consume at least 35 mg / kg body weight as milk-derived phospholipid or at least 7 mg / kg body weight as SM. It is also preferable to take at least 10 mg / kg body weight as DHA. In the case where the ingestor is children or school children, it is preferable to consume 70 mg or more per person as phospholipid derived from milk or 14 mg or more per person as SM. In addition, it is preferable to take 10 mg or more per person as DHA.

Infant brain development accelerators of the present invention can be used to improve the mental exercise and learning functions used in infants, children, school children and the like. Especially, it is preferable to use for infants, and it is more preferable also to use for infants, low birth weight infants, very low birth weight infants, and very low birth weight infants. The premature infant referred to in the present invention refers to a child whose birth weight is low due to the lack of gestational days, and the low birth weight infant refers to a child whose birth weight is less than 2500 g. Among low birth weight infants, particularly low birth weight infants refer to children whose birth weight is less than 1500 g and ultra low birth weight infants are less than 1000 g birth weight. In addition, a pregnant woman or an elderly person may be ingested.

In addition, the present invention, as another aspect of the infant brain development accelerator, "Infant brain development accelerator containing sphingomyelin for adding to food, adjusted to at least 0.005% by weight of sphingomyelin in food when ingested (Hereinafter referred to as "the sphingomyelin-containing infant brain development promoter of the present invention"). The sphingomyelin-containing infant brain development promoter of the present invention is a composition for enhancing sphingomyelin by addition to general food and drink of infants. For example, by adding the sphingomyelin-containing infant brain development promoter of the present invention to general formula, it is possible to strengthen the amount of sphingomyelin of the general formula. Furthermore, it is also possible to further contain docosahexaenoic acid and to add it to a foodstuff and to adjust so that docosahexaenoic acid in the foodstuff at the time of ingestion may be at least 0.008 weight%.

When the infant brain development promoter of the present invention is used as a medicine or the food composition of the present invention as a supplement or a treat for infants and school children, it can be administered in various forms. As the form thereof, for example, oral administration by tablets, coated tablets, capsules, granules, powders, solutions, syrups, emulsions and the like can be given. These various preparations are prepared according to the conventional methods of pharmaceutical preparations such as excipients, binders, disintegrants, lubricants, coloring agents, copulation agents, dissolution aids, suspensions, coating agents, etc. It can be formulated using a known adjuvant commonly used in the field. Moreover, you may add the additional component (vitamin, mineral, organic acid, sugar, amino acid, peptide, etc.) which are mentioned later according to the objective. As the ingestion method, any method such as oral intake, cerebral intake, intravenous administration, enteral nutrition method, central vein nutrition method, or the like may be used.

The food composition of the present invention is a food or beverage type composition containing the infant brain development accelerator of the present invention. The food composition of this invention can be manufactured and used suitably according to a conventional method. The form may be any of a solid form (powder, granules and the like), a paste form, a liquid form or a suspension form, and may be a milk powder or a milk product using various components such as sweeteners, acidulants, vitamins, and nutrients. In particular, it is suitable for the premature infants, low birth weight infants, very low birth weight (VLBW) children, and very low birth weight (ELBW) children, especially those who need to promote brain function development. Moreover, it can also be used as infant milk powder for infant formula, concentrate for beverage preparation, and dry matter for beverage preparation. It may also be added to ordinary milk powder, milk products, beverages, foods, formulas, etc. and may be used as additives or concentrates for enhancing milk-derived phospholipids or sphingomyelin and DHA. Alternatively, it may be directly taken as a supplement derived from milk-derived phospholipids or sphingomyelin and DHA, tablets, syrups, syrups, beverages, concentrates, drinks, formulas, and the like. In addition, the ingestion method may be any method such as oral ingestion or cervical ingestion.

The food composition containing the infant brain development promoter of this invention can contain the general component used for the normal food composition. For example, the present invention is not limited to these, but water, proteins, sugars, vitamins, minerals, organic acids, organic bases, fruit juices, flavors and the like can be used as other components. As the protein, for example, whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin animal and vegetable proteins such as α-lactoalbumin, lactoferrin, soy protein, egg protein, and hexaprotein, and these hydrolysates; Various milk-derived components, such as butter, whey mineral, cream, whey, nonprotein nitrogen, sialic acid, and lactose, are mentioned. Examples of the saccharide include sugars, processed starch (except dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), plant fibers, and the like. As other lipids, For example, animal fats and oils, such as these fractionation oil, hydrogenated oil, and transesterified oil; And vegetable oils such as palm oil, safflower oil, corn oil, rapeseed oil, palm oil, fractionated oils thereof, hydrogenated oil, and transesterified oils. As vitamins, for example, 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, folic acid Etc. As minerals, calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, etc. are mentioned, for example. As an organic acid, malic acid, citric acid, lactic acid, tartaric acid, etc. are mentioned, for example. These components can be used in combination of 2 or more type, You may use synthetic | combination goods and / or food containing many.

According to the Bayley infant development test, Fagan test, and visual developmental development test of the very low birth weight infant in the examples described below, the infant brain development accelerator of the present invention is used for the development of various developmental indicators such as mental, exercise, and intelligence All have been shown to have an improving effect. From this fact, it can be said that the infant brain development accelerator of the present invention is useful for improving mental exercise and learning function of the infant.

In addition, all the prior art documents referred in this specification are integrated in this specification as a reference.

Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to these specific examples.

Examination Schedule

Eighteen cases of very low birth weight infants (mean gestational age 30.3 weeks, mean birth weight 1107 g) were divided into nine cases of the test group (sphingomyelin enriched milk group) and nine cases of the control group (control milk group), which are shown in Table 1. Test milk containing the ingredients (control oil, sphingomyelin (SM) fortified oil) was taken in each group.

In Table 1, total phospholipid shows the content of phospholipid contained in each test milk. About 65% of the total phospholipids are derived from raw materials such as whey. In addition, about 35% of the total phospholipids are derived from reinforcing phospholipids (eg yolk lecithin or milk phospholipids) shown in Table 1.

The enhanced phospholipid source of the test milk of the test group was a milk phospholipid containing a lot of SM, and the yolk lecithin containing little SM was used as the enhanced phospholipid source of the test milk of the control group. Table 2 shows the composition of total phospholipids contained in each test milk. As can be seen from Tables 1 and 2, the SM fortified oil (infant brain development promoter) according to the present invention is characterized by a high ratio of SM in phospholipids.

In mammals, water was added to the SM fortified oil and the control oil of the composition of Table 1, and the crude oil was prepared at a crude oil concentration of 15 w / v%. Mammals were given priority to breast milk, and deficiencies were randomly supplemented with SM fortified milk (SM 20 w / w% in total phospholipids) or control (SM 13 w / w% in total phospholipids). Specifically, mammals were started within 24 hours of birth, and 0.5 to 1.0 ml / time was injected into the nasal gastric tube 8 times a day, and if the gastric residual amount did not exceed the injection amount, the amount was increased by 4 to 8 ml / day. . Immediately after birth, blood was collected at 2, 4, 6, and 8 weeks of age to analyze the composition of plasma phospholipids (sphingomyelin) and erythroid fatty acids (arachidonic acid, DHA). In addition, Fagan test and VEP test were performed at 3 and 6 months of fertilization, and Bayley infant development test was performed at 6 months of fertilization (correction age refers to the age after conception, ie conception age). In addition, during the test period, the presence or absence of complications, weight gain rate, and breast milk retention rate were also observed. Here, "mammal milk rate" means the ratio of breast milk to the total amount of milk (breast milk, control milk or SM fortified milk) ingested by the VLBW child during the entire test period.

<Evaluation method>

(1) The Bayley Scales of Infant Development

This test is a comprehensive developmental diagnostic method for children aged 0 to 3 years. It consists of three areas: psychological development indicators (MDI), psychomotor development indicators (PDI), and behavioral assessment (BRS). There are 178 items for the MDI and 111 items for the PDI, and these tasks are actually performed on the child and scored. In addition, the BRS evaluates 30 items, such as concentration and coordination, from expressions of the child's behavior during the test.

In MDI, the sensitivity and discrimination of sensitivity and discrimination of infants, the degree of responsiveness, the acquisition of homeostasis of objects, the situation of memory, learning and problem-solving ability, the situation of language and communication, the ability to synthesize and classify, and extractive thinking Evaluate Psychological measures are represented as psychological development indicators (MDI).

In PDI, body control, coordination of muscle movement, fine manipulation of fingers, and the ability of exercise are evaluated. On this scale, the movement of the body and the basic development of the control of the body can be seen in accordance with the development of the central nerve.

MDI and PDI are standard scores with an average of 100 and a standard deviation of 15. The BRS determines that the highest score is 100, 26-100 is normal, 11-25 is borderless, and 10 or less is inadequate (see Kobayashi's Noboru Supervised Infant Development Manual, Bunkodo, 121-135, 2000). .

Infants' behavior records identify and assess the child's specific behavioral features at the time of examination. Evaluate overall behavior, including relationships, emotions, motivation, specific senses, and interests.

The inventors conducted these tests in accordance with Bayley et al. (Bayley N. Manual for the Bayley Scales of Infant Development. The Psychological Corporation, New York, 1969). In practice, using the Bayley Scale for Infant Development Second editiont, purchased from The Psychological Corporation Harcourt Brace and Company (UK), the subject was placed on the mother's lap with the examiner for about 30 to 40 minutes. It was. The results were entered on the record sheet of the regulations and the index scores (MDI, PDI, BRS) were calculated from the conversion tables indicated in the manual (O'Connor, et al. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids. : a prospective, randomized controlled trial.Pediatrics, 108: 359-371, 2001).

(2) Fagan test of infant intelligence

This test causes the child to look at the face for a certain period of time, causing a phenomena, and then substituting the other face at the same time to determine which picture the child is looking at (mirror preference). Purification is the process of coding in the brain by looking at new things and cognizing and remembering them. The novelty preference (新奇 選好) is the process of coding more novel. The speed of purifying phenomena and mystery preferences have been shown to predict the development of intelligence (Kyoko Tanaka. Infant psychopsychiatric behavior development and fatty acids. Footsteps in medicine, 218: 403-407, 2006).

The inventors performed this test in accordance with Fagan et al. (Fagan JF et al. The Fagan Test of Infant Intelligence. Infant Test Corporation, Cleveland, 1986). In fact, using the Fagan tees kit purchased from Infantest (USA), the subject was face-to-face with the examiner on the mother's knee, and the test was performed for about 20 minutes. The test consists of 10 tasks, one of which is to be purified and novel. The stimuli presented are all face photographs (infants, adult women, and adult men), and the examiner records from the pinhole of the stage presenting the photographs the computer's eye movements. The results used% looking time to novel target, which is the ratio of watch time to stimulation of stimulation (O'Connor, et al. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.Pediatrics, 108: 359-371, 2001).

(3) Visual evoked potentials (VEP) testing

This is a neurophysiological test that measures the rate of nerve transmission through the optic nerve. The process of myelinization was assessed by measuring the moment (msec) due to pattern stimulation at 16 Hz (Tanaka Kyoko. Infant psychopsychiatric behavioral development and fatty acids. Footsteps of medicine, 218: 403-407, 2006).

In practice, the subject was watched 1 m forward on the mother's knee and the potential change was recorded from three electrodes attached to the head. A moving picture of a checkerboard pattern was projected onto the monitor, and the lead electrode was attached to the left and right sides of the top 3 cm of the posterior head nodules, and the reference electrode was attached to the top 6 cm from the root portion and recorded. As shown in Fig. 1, the time from the 16 Hz pattern stimulus (left side of the chart) to the peak of the speech wave (temporary) was measured and compared (Kos-Pietro S, et al. Maturation of human visual evoked). potential: 27 weeks conceptional age to 2 years. Neuropediatrics: 318-323, 1997).

<Result>

No significant difference was found between the two groups in the presence of complications, weight gain, and breast milk retention (Table 3).

In addition, significant differences were not recognized in fatty acid composition analysis results including arachidonic acid (AA) and docosahexaenoic acid (DHA) (FIGS. 2 and 3). On the other hand, in the analysis of the composition of plasma phospholipids, in the SM-enriched group, the plasma SM concentrations at 4 and 6 weeks of age were significantly higher than those of the control group (p <0.01: un-paired Student's t test) (4 weeks 27.6%). vs 16.3%, 6 weeks 23.1% vs 16.0%) (FIG. 4). In addition, the BRS score and Fagan test of Bayley test at 6 months of age were significantly higher (p <0.05: un-paired Student's t test) in the SM-enriched group (Bayley 85.1 vs 55.1, Fagan 53.4 vs). 48.2) (FIGS. 5 and 6). In the VEP test, only a short time (3 months: 110.5 msec, 6 months: 104.2 msec) was significant (p <0.05: paired Student's t test) at 6 months of fertilization in the SM-enriched group. (FIG. 7).

From these results, we observed differences in various developmental indicators of mental, exercise, and intelligence, and myelination of the nerves by the difference in phospholipids, even though the levels of DHA in the body were equal by administering the milk and brain development promoter of the present invention. Could. That is, the first synergistic effect was found in the combination of milk derived phospholipid and DHA.

The infant brain development accelerator and infant psychomotor and / or learning function improving food composition of the present invention can improve the development and learning function of the brain of premature infants, especially low birth weight infants, which have not been known so far. The object can be achieved by a very simple means of ingesting the medicament or composition of the present invention, and the effect is unpredictable. In addition, milk-derived phospholipids and DHA, which are raw materials, are relatively easy to obtain, and it is possible to manufacture pharmaceuticals, food compositions, and the like having the above characteristics easily and inexpensively.

Claims (19)

Infant brain development promoter prepared by incorporating phospholipids containing at least 0.005% by weight of sphingomyelin upon ingestion. The method of claim 1, Infant brain development promoter wherein the phospholipid is derived from milk. The method according to claim 1 or 2, Infant brain development promoter of the sphingomyelin derived from milk. The method according to any one of claims 1 to 3, Infant brain development promoter having at least 0.027% by weight of phospholipid derived from milk. The method according to any one of claims 1 to 4, Infant development promoter prepared so that the amount of sphingomyelin in the product is at least 0.03% by weight, and at the time of ingestion, the amount of sphingomyelin is at least 0.005% by weight, The method according to any one of claims 1 to 4, The infant development promoter which is prepared so that the milk-derived cognitive mass in a product may be at least 0.15 weight%, and at the time of ingestion, it will be at least 0.027 weight%. The method according to any one of claims 1 to 6, An infant development promoter containing at least 0.008% by weight of docosahexaenoic acid at the time of ingestion. The method according to any one of claims 5 to 7, Infant development promoter containing at least 0.05% by weight of docosahexaenoic acid in the product. The method according to any one of claims 1 to 8, Infant brain development promoter, characterized in that any one of premature infants, low birth weight infants, very low birth weight infants, ultra-low birth weight infants. A food composition for improving infant mental exercise and / or learning function, comprising the infant brain development accelerator according to any one of claims 1 to 9. The method of claim 9, Food composition for infants mental exercise and / or learning function improvement, characterized in that any one of the formula, powdered beverage concentrate, and dried beverage preparation. An infant brain development promoter containing sphingomyelin, added to food, for adjusting so that the sphingomyelin in food at least 0.005% by weight upon ingestion. The method of claim 11, An infant brain development accelerator, which further contains docosahexaenoic acid and is added to foods so as to be adjusted to at least 0.008% by weight of docosahexaenoic acid in the food at the time of ingestion. A method for promoting brain development of an infant, comprising administering sphingomyelin or sphingomyelin-derived phospholipids. A method of improving psychomotor and / or learning function in infants, characterized by administering sphingomyelin or phospholipids derived from milk comprising sphingomyelin. The method according to claim 14 or 15, Infants are any one of the group consisting of premature infants, low birth weight infants, very low birth weight infants, and very low birth weight infants. Use of Lactose-derived phospholipids comprising sphingomyelin or sphingomyelin for the production of infant brain development promoters. Use of sphingomyelin or sphingomyelin for milk-derived phospholipids for the preparation of food compositions for infant psychomotor and / or learning function enhancement. The method of claim 17 or 18, Infants are any one of the group consisting of premature infants, low birth weight infants, very low birth weight infants, and very low birth weight infants.

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