CN101636167B - Agent for facilitating the development of brain in infant comprising milk-derived phospholipid and food composition comprising the same - Google Patents
Agent for facilitating the development of brain in infant comprising milk-derived phospholipid and food composition comprising the same Download PDFInfo
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Abstract
本发明提供含有有效量的乳来源的磷脂或鞘磷脂的婴幼儿脑发育促进剂以及含有该婴幼儿脑发育促进剂的用于提高婴幼儿神经运动和/或学习功能的食品组合物。该婴幼儿脑发育促进剂用于直接摄取时，优选含有至少0.027重量％的乳来源的磷脂或至少0.005重量％的鞘磷脂。The present invention provides an infant brain development promoter containing an effective amount of milk-derived phospholipid or sphingomyelin and a food composition containing the infant brain development promoter for improving neuromotor and/or learning functions of infants. When the brain development promoter for infants is used for direct ingestion, it is preferable to contain at least 0.027% by weight of milk-derived phospholipids or at least 0.005% by weight of sphingomyelin.
Description
Technical field
The present invention relates to the g and D of premature infant's brain, especially nervimotion and learning functionality rise to purpose, contain the abundant milk-derived phospholipid of sphingomyelins particularly and the infant brain growth accelerant of docosahexenoic acid (DHA).The invention still further relates to the food compositions that contains this infant brain growth accelerant.
Background technology
ω-3 is that essential fatty acid such as fatty acid is big to the influence of organism, particularly concerning the people, to its fetus and neonatal growth, grow and have very big contribution.Known parent transports fatty acid to fetus hardly usually at first half period of gestation, at latter half of gestation, transports fatty acid through Placenta Hominis to fetus.It is believed that at above-mentioned latter half of gestation and puerperal in early days, fetus and neonatal brain actively absorb fatty acid, and cognition and visual development function are improved.If but the premature infant, because above-mentioned fatty acid from parent is few, premature infant's self fatty acid synthesis capability is low again, the deficiency state of the DHA that therefore might occur particularly in brain and neural growth, playing an important role.
In addition, also known to latter half of gestation, the neural myelin that fetus can be taken place forms (Myelination).If but the premature infant, in most cases myelin forms insufficiently, and the deficiency state with above-mentioned DHA works mutually sometimes, aspect neurodevelopment, becomes unfavorable situation (non-patent literature 1).
On the other hand, present known phospholipid is big to the influence of the infant in the maturation.Particularly milk-derived phospholipid it is reported that it has the effect (patent documentation 1) of DHA content in the raising body, treats the effect (patent documentation 2) of the Insufficient disease of intestinal movement, the maturation in facilitating digestion road and the effect (patent documentation 3) of growing etc. through the intestinal plexus nervorum is grown.In addition, the also known effect (non-patent literature 2) that the myelin formation that promotes developmental optic nerve is arranged.
Patent Document 1: Tian Zhonggong child. Infants Full Developmental と psychological operations fatty acids. Medical Full Ayumi ,218:403-407, 2006
Non-patent literature 2: オ シ ダ etc., Effects of dietary sphingomyelin on control nervous system myelination in developing rats.Pedatric Res, 53:589-593,2003 years
Patent documentation 1: TOHKEMY 2001-128642 description
Patent documentation 2: TOHKEMY 2003-252765 description
Patent documentation 3: TOHKEMY 2000-350563 description
Summary of the invention
In the phospholipid, particularly from the phospholipid of breast milk and milk (below be also referred to as newborn phospholipid), has the characteristic that is different from from the phospholipid of Semen sojae atricolor and egg yolk.Particularly has following difference: contain the phospholipid that is called sphingomyelins (following abbreviate as sometimes " SM ") in a large number.This sphingomyelins is present in the cell membrane of cranial nerve tissue etc., and particularly it is the main component of myelin, thinks that it has the effect that promotes that myelin forms.
But, for the early stage nutrition of above-mentioned premature infant, especially known puerperal to after growth have the low birth weight infant of material impact, the oral uptake of sphingomyelins is grown neurodevelopment, particularly nervimotion and is had what kind of effect and it be unclear that.
To above-mentioned problem; The inventor concentrates on studies; The result finds: after the premature infant being contained the compositions of milk-derived phospholipid and DHA; Compare with the compositions that contains Ovum Gallus domesticus Flavus lecithin and DHA; In Bayley infant development inspection (The Bayley Scales of InfantDevelopment), Fagan test (Fagan test of infant intelligence), visual evoked potential (VEP:visual evoked potential) inspection, visible developmental index improves, thereby has accomplished the present invention.In the above-mentioned compositions that contains milk-derived phospholipid and DHA with contain in the compositions of Ovum Gallus domesticus Flavus lecithin and DHA, DHA measures identical.
Therefore, the object of the invention can be reached through the infant brain growth accelerant that contains the milk-derived phospholipid that particularly contains sphingomyelins in a large number.
One aspect of the present invention relates to the infant brain growth accelerant of the milk-derived phospholipid that contains effective dose.Infant brain growth accelerant of the present invention can also contain the docosahexenoic acid of effective dose.
Above-mentioned infant brain growth accelerant can be processed with the direct picked-up of the original state picked-up shape with preparation, and water, hot water, milk (milk, lacto etc.) wait the preparation (concentrate, dry thing etc.) that absorbs after the suitably modulation in the time of also can being formed in picked-up.When using preparation, preferably contain the milk-derived phospholipid of at least 0.027 weight %, under the situation that cooperates DHA, preferably contain the above-mentioned docosahexenoic acid of at least 0.008 weight % for directly absorbing.In addition, also preferably contain the above-mentioned sphingomyelins of at least 0.005 weight %, under the situation that cooperates DHA, preferably contain the above-mentioned docosahexenoic acid of at least 0.008 weight %.
In addition; If water, hot water, milk (milk, lacto etc.) etc. are suitably modulated the preparation (concentrate, dry thing etc.) of back picked-up during picked-up; Then the effective dose of preferred milk-derived phospholipid is at least 0.15 weight %; Under the situation that cooperates DHA, the effective dose of docosahexenoic acid preferably is at least 0.05 weight %.In addition,, preferably be at least 0.03 weight %, under the situation that cooperates DHA, preferably contain the above-mentioned docosahexenoic acid of at least 0.05 weight % as the content of sphingomyelins.Wherein, short of specified otherwise among the present invention, " weight % " is meant " w/w% ".
About infant of the present invention, be preferably any one in premature infant, low birth weight infant, very low birth weight infant and the ULBW.
Another aspect of the present invention provides the food compositions that is used to improve infant nervimotion and/or learning functionality that contains above-mentioned infant brain growth accelerant.At this moment, food compositions be preferably formula milk, brew with concentrate and brew with in the dry thing any.
The present invention provides following technical scheme particularly:
(1) a kind of infant brain growth accelerant, it contains the sphingomyelins of at least 0.005 weight % when picked-up, and through cooperating phospholipid to make.
(2) the infant brain growth accelerant described in above-mentioned (1), wherein, above-mentioned phospholipid is milk-derived.
(3) the infant brain growth accelerant described in above-mentioned (1) or (2), wherein, above-mentioned sphingomyelins is milk-derived.
(4) like each described infant brain growth accelerant in above-mentioned (1) to (3), wherein, milk-derived phospholipid is at least 0.027 weight % when picked-up.
(5) like each described infant brain growth accelerant in above-mentioned (1) to (4), wherein, the sphingomyelins amount in the product is at least 0.03 weight %, and is modulated into when picked-up sphingomyelins amount and is at least 0.005 weight %.
(6) each described infant brain growth accelerant in above-mentioned (1) to (4), wherein, the milk-derived phospholipid amount in the product is at least 0.15 weight %, and is modulated into when picked-up milk-derived phospholipid amount and is at least 0.027 weight %.
(7), wherein, when picked-up, contain the docosahexenoic acid of at least 0.008 weight % like each described infant brain growth accelerant in above-mentioned (1) to (6).
(8) like each described infant brain growth accelerant in above-mentioned (5) to (7), wherein, in product, contain the docosahexenoic acid of at least 0.05 weight %.
(9) like each described infant brain growth accelerant in above-mentioned (1) to (8), it is characterized in that infant is any one in premature infant, low birth weight infant, very low birth weight infant and the ULBW.
(10) a kind of food compositions that is used to improve infant nervimotion and/or learning functionality is characterized in that, contains each described infant brain growth accelerant in the claim (1) to (9).
(11) food compositions that is used to improve infant nervimotion and/or learning functionality described in above-mentioned (10) is characterized in that, food compositions is formula milk, brew with concentrate and brew with in the dry thing any.
(12) a kind of infant brain growth accelerant that contains sphingomyelins, the sphingomyelins when it is used for adding food to and is modulated into picked-up in the food is at least 0.005 weight %.
(13) the infant brain growth accelerant described in above-mentioned (12) is characterized in that, further contain docosahexenoic acid, it adds in the food, and the docosahexenoic acid that is modulated in when picked-up food is at least 0.008 weight %.
(14) a kind of brain development promotion method of infant is characterized in that, gives sphingomyelins or contains the milk-derived phospholipid of sphingomyelins.
(15) method that improves of a kind of nervimotion that makes infant and/or learning functionality is characterized in that, gives sphingomyelins or contains the milk-derived phospholipid of sphingomyelins.
(16) method described in above-mentioned (14) or (15), wherein, infant is any one in premature infant, low birth weight infant, very low birth weight infant and the ULBW.
(17) a kind of sphingomyelins or the purposes of milk-derived phospholipid in making the infant brain growth accelerant that contain sphingomyelins.
(18) a kind of sphingomyelins or the milk-derived phospholipid that contains sphingomyelins are used for improving the purposes of the food compositions of infant nervimotion and/or learning functionality in manufacturing.
(19) purposes described in above-mentioned (17) or (18), wherein, infant is any one in premature infant, low birth weight infant, very low birth weight infant and the ULBW.
Utilize infant brain growth accelerant and the food compositions that is used to improve infant nervimotion and/or learning functionality of the formation of the invention described above, unknown effect promptly improves the growth and the learning functionality of the brain of premature infant, particularly low birth weight infant before can reaching.Through absorbing the so easy method of above-mentioned medicament or food compositions, can achieve the goal, and its effect is unexpected.
In addition, be easier to obtain, therefore can make medicament of the present invention with above-mentioned characteristic or food compositions etc. easy and at an easy rate as milk-derived phospholipid, the DHA ratio of raw material.
Description of drawings
Fig. 1 measures the visual evoked potential figure that the time (incubation period) till the peak of pictorial stimulus (chart left end)～negative ripple of 16Hz obtains in VEP inspection.The transverse axis express time.
Fig. 2 is the composition analysis result of erythrocyte membrane fat acid, is the figure of the arachidonic content of expression.Expression is the value of birth back (before the test), birth back 4 weeks (4 week), birth back 8 weeks (8 week) just.
Fig. 3 is the composition analysis result of erythrocyte membrane fat acid, is the figure of the content of expression DHA.Expression is the value of birth back (before the test), birth back 4 weeks (4 week), birth back 8 weeks (8 week) just.
Fig. 4 is the composition analysis result of blood plasma phospholipid, is the figure of expression blood plasma sphingomyelins concentration.Expression is the value of birth back (before the test), birth back 2 weeks (2 week), birth back 4 weeks (4 week), birth back 6 weeks (6 week), birth back 8 weeks (8 week) just.
Fig. 5 is the figure of MDI, PDI and the BRS index score of the expression Bayley infant development inspection of correcting 6 months monthly ages.
Fig. 6 is the figure of Fagan score at 3 months rectification monthly ages and 6 months of expression Fagan test.
Fig. 7 is the figure that the incubation period (msec) that the VEP at 3 months monthly ages and 6 months checks is corrected in expression.
The specific embodiment
The present invention below at length is described, but the invention is not restricted to the modes of the following stated.
" phospholipid " among the present invention can be independent phospholipid composition, also can be the mixture that is formed by multiple phospholipid composition.As " phospholipid " among the present invention, preferred example is the phospholipid that contains sphingomyelins, more preferably " milk-derived phospholipid ".So-called among the present invention " milk-derived phospholipid " is meant, by the synthetic mixture of phospholipids of animal milk.Typically, in addition to containing milk-derived phospholipid phosphatidylcholine (PC), phosphatidylethanolamine (PE), the particular its compatibility with soy or egg yolk phospholipids different sources,? Having this characteristic contains large amounts of sphingomyelin (Matsumoto, Yoshinobu, Takemasa Chikako, Tetsuro Morita, Kawasaki Medical Welfare Society Vol.15? Nol? 2005209-216).This sphingomyelins is present in the cell membrane of cranial nerve tissue etc., and particularly it is the main component of myelin, is considered to it and has the effect that promotes that myelin forms.
About the milk-derived phospholipid that uses among the present invention,, except the milk that can use various domestic animals such as cattle, goat, sheep, horse, Babalus bubalis L., can also use breast milk as raw material milk.
The milk-derived phospholipid that uses among the present invention can extract from raw material milk (for example milk) and make.Particularly milk can be made phospholipid and form and the proximate phospholipid of lacto (following abbreviate as sometimes " breast milk ").
In addition, as milk-derived phospholipid, can also use commercially available article.As commercially available article; Can use New Zealand Dairy Ingredients Company products (for example content of phospholipid is milk complex lipid product of 40.6% or 85.3% etc.) or New Zealand Bay Milk Products Company products (trade name ALPHALIPID, sphingomyelin content are 20 weight %) etc.
In addition, in the present invention,, can use with the form of the compositions that contains it as milk-derived phospholipid.As said composition, can enumerate from milk composition and to extract but be not refined to the phospholipid fraction of the degree of the said goods etc.Particularly, can give an example and from milk or buttermilk, butter serum, separate the complex lipid component that makes or its concentrate etc.
The docosahexenoic acid that uses among the present invention (DHA) is that carbon number is 22, n-3 with 6 carbon-to-carbon unsaturated bonds is a polyunsaturated fatty acid, also is expressed as " 22:6, n=3 ".Be also referred to as cis-4,7,10,13,16, the 19-docosahexenoic acid.Molecular weight is 328, and Cas.No. is 6217-54-5, and known its has anti thrombotic action, effect for reducing blood fat etc.In the body, mainly located in the cerebral cortex synaptic membranes, eye photoreceptors in the central nervous system, myelin developmental stages, and its content increased (Big Wood Road is ら compilation, chemical event code, Tokyo Chemical colleagues issuance, pp.95 (1994 )).Known DHA contains in fish oil in a large number, and in recent years, Marine microorganism Labyrinthuleas class (Labyrinthuliidae section, thraustochytriale section (Thraustochtriidae)), microorganism such as unicellular are also as the supply source of DHA and known.In the present invention, DHA can directly adopt the DHA that contains the state in microorganism etc., perhaps also can adopt refining DHA.In addition, can also adopt through chemosynthesis, the synthetic DHA that obtains of microorganism, but be not limited to these examples.
Milk-derived content of phospholipid in the infant brain growth accelerant of the present invention suitably gets final product; Under the common situation, directly absorbing in the product of usefulness the milk-derived phospholipid during for picked-up; Can contain more than the 0.027 weight %, preferably contain 0.027～0.95 weight %; For SM, can contain more than the 0.005 weight %, preferably contain 0.006～0.95 weight %.In addition, under the situation that cooperates DHA, about DHA content, making it is more than the 0.008 weight % in product, is preferably more than the 0.009 weight %.
Water, hot water, milk (milk, lacto etc.) etc. were suitably modulated the form of the product (concentrate, dry thing etc.) of back picked-up when in addition, infant brain growth accelerant of the present invention can also be formed in picked-up.At this moment, the sphingomyelins amount in the product is at least 0.03 weight %, and the sphingomyelins amount is at least 0.005 weight % in the time of can being modulated into picked-up.In addition, the milk-derived phospholipid amount in the product is at least 0.15 weight %, and milk-derived phospholipid amount is at least 0.027 weight % in the time of can being modulated into picked-up.In addition, under the situation that cooperates DHA,, preferably be more than the 0.05 weight % in product about DHA content.
In addition; Formula milk of using at the infant that contains infant brain growth accelerant of the present invention etc. is used for improving the food compositions of infant nervimotion and/or learning functionality; In the product; For milk-derived phospholipid, can contain more than the 0.150 weight %, preferably contain 0.170～0.95 weight %; In addition,, can contain more than the 0.030 weight %, preferably contain 0.035～0.95 weight % for SM.In addition, under the situation that cooperates DHA,, preferably be more than the 0.055 weight % in product, more preferably more than the 0.060 weight % about DHA content.
The formula milk of using in child～school age population of containing infant brain growth accelerant of the present invention, brew is used for improving infant nervimotion and/or learning functionality with dry thing etc. with concentrate, brew food compositions; In the product; For milk-derived phospholipid; Can contain more than the 0.300 weight %, preferably contain 0.320～0.95 weight %; In addition,, can contain more than the 0.060 weight %, preferably contain 0.065～0.95 weight % for SM.In addition, under the situation that cooperates DHA,, preferably be more than the 0.050 weight % in product, more preferably more than the 0.060 weight % about DHA content.
As the preferred object lesson of infant brain growth accelerant of the present invention, can enumerate the infant of having strengthened sphingomyelins and use formula milk.The regular convention formula milk powder that infant uses is primary raw material with milk, but becomes to be grouped into lacto approaching in order to make, and makes great efforts according to making protein form and make as the different mode of the milk of raw material.For example the ratio of casein and lactalbumin is about 6: 4 in the milk, and is about 2: 8 in the formula milk.In addition, the composition of lactalbumin is also changed, make them different with milk.The beta lactoglobulin that contains in the milk is prone to become anaphylactogen.Therefore, commercially available formula milk have the ALA amount is increased and formula milk that the ratio of beta lactoglobulin descends relatively, with the lactalbumin part of the whole or all the formula milk that obtains of hydrolysis, cooperated specific refining proteinic formula milk, or the formula milk that only optionally the beta lactoglobulin decomposition obtained etc.
In making the process of this formula milk, in most cases the sphingomyelins that contains of milk itself can lose.Therefore, in order to expect effect, need in common formula milk, strengthen sphingomyelins as infant brain growth accelerant of the present invention.
The daily intake of infant brain growth accelerant of the present invention is according to the difference of the monthly age of taking the photograph taker, symptom, development degree, body weight etc. and difference; Therefore not special the qualification; Can absorb 0.1～10000mg/kg body weight; Preferred picked-up 0.1～1000mg/kg body weight is more preferably absorbed 1～300mg/kg body weight.Particularly when taking the photograph taker and be infant, preferably absorb above milk-derived phospholipid of 35mg/kg body weight or the above SM of 7mg/kg body weight.As DHA, preferably absorb more than the 10mg/kg body weight.When taking the photograph taker for child～pupil, for milk-derived phospholipid, preferably everyone absorbs more than the 70mg; For SM, preferably everyone absorbs more than the 14mg.In addition, for DHA, preferably everyone absorbs more than the 10mg.
Infant brain growth accelerant of the present invention can be used for infant, child, pupil etc., realizes that nervimotion and learning functionality improve.Wherein, be preferred for infant, more preferably be used for premature infant and low birth weight infant, very low birth weight infant, the ULBW of infant.The so-called premature infant of the present invention is meant because of the not enough neonate that causes the low neonate of birth weight, low birth weight infant to be meant the not enough 2500g of birth weight of gestational age.In the low birth weight infant, very low birth weight infant points out to give birth to the neonate of underweight 1500g especially, and ULBW is meant the neonate of the not enough 1000g of birth weight.In addition, pregnant and lying-in women and advanced age the person also can be used as the picked-up object.
In addition; Among the present invention; Another form as the infant brain growth accelerant provides " be used for adding food to and the sphingomyelins that is modulated in when picked-up food is at least 0.005 infant brain growth accelerant weight %, that contain sphingomyelins " (below be called " the sphingomyelins infant brain growth accelerant that contains of the present invention ").The sphingomyelins infant brain growth accelerant that contains of the present invention is to be used for adding to the compositions of the full diet article of infant with the reinforcement sphingomyelins.For example, through in common formula milk, adding the sphingomyelins infant brain growth accelerant that contains of the present invention, can when picked-up, strengthen the sphingomyelins amount of regular convention formula milk powder.In addition, can also contain docosahexenoic acid, add in the food, and the docosahexenoic acid that is modulated in when picked-up food is at least 0.008 weight %.
When infant brain growth accelerant of the present invention is used with nutritional supplement or sugar-tablet (tablet confectionary) as baby～pupil as medicine or with food compositions of the present invention, can give with various forms.As its form, for example can enumerate per os such as tablet, coated tablet, capsule, granule, powder, solution, syrup, emulsion and give.Above-mentioned various preparation; Can adopt common method, in constituent of the present invention, use in the pharmaceutical preparations technology fields such as excipient, binding agent, disintegrating agent, lubricant, coloring agent, drug flavoring, cosolvent, suspending agent, coating materials normally used known adjuvant to process preparation as principal agent.In addition, according to expectation, the supplementary element of stating after can also adding (vitamin, mineral, organic acid, saccharide, aminoacid, peptide class etc.).In addition, as its acquisition method, can be arbitrary methods such as oral feeding method, warp pipe alimentation, intravenous feeding, enteral nutrition method, central vein nutrition method.。
Food compositions of the present invention is the Foods or drinks based composition that contains infant brain growth accelerant of the present invention.Food compositions of the present invention can suitably be made according to common method and use.As its form; Can be in solid-state (powder, graininess etc.), pasty state, liquid state or the suspension any; If use various one-tenth such as sweet taste material, acid flavoring, vitamin agent, nutritional labeling to assign to process milk powder or milk product, then be suitable for special needs such as infant, particularly premature infant, low birth weight infant, ELBW (VLBW) youngster, ULBW (ELBW) youngster and promote the object that brain function is grown.In addition, also can be used as formula milk, brew concentrate, the brew that child～pupil uses uses with dry thing.In addition, can also process and be used for adding to ordinary powdered milk, milk product, beverage, food, slop etc. and come the phospholipid in fortified milk source or additive or the concentrated solution of sphingomyelins and DHA.Perhaps, can also process the nutritional supplement, sugar-tablet, malt sugar, syrup, beverage, concentrated solution, beverage, the slop that contain milk-derived phospholipid or sphingomyelins and DHA and wait directly picked-up.In addition, as its acquisition method, can be arbitrary methods such as oral feeding method, warp pipe alimentation.
In the food compositions that contains infant brain growth accelerant of the present invention, can contain the general composition that in common food compositions, uses.For example, though be not limited to these, the present invention can assign to water, protein, saccharide, vitamins, minerals, organic acid, organic base, fruit juice, perfumery etc. to use as other one-tenth.As protein, for example can enumerate of animal or plant nature protein, their hydrolyzate such as whole milk powder, defatted milk powder, partially skimmed milk powder, casein, whey powder, lactalbumin, Lactalbumin concentrate, lactalbumin isolate, alpha-casein, beta-casein, κ-casein, beta lactoglobulin, ALA, lactoferrin, soybean protein, egg albumen, meat albumen; Various milk-derived one-tenth such as butter, whey mineral, butter, milk surum, non-albumen attitude nitrogen, sialic acid, lactose grade.As sugar, can enumerate saccharide, producing starch (except that cyclodextrin, also having soluble starch, British starch, Oxytarch, starch ester, starch ether etc.), dietary fiber etc.As other lipid, for example can enumerate Adeps Sus domestica, fish oil etc., their distillate oil, hydrogenated oil and fat, ester exchange wet goods animal raw fat; Petiolus Trachycarpi oil, safflower oil, Semen Maydis oil, Oleum Brassicae campestris, Oleum Cocois, their distillate oil, hydrogenated oil and fat, ester exchange wet goods vegetative grease etc.As vitamins; For example can enumerate vitamin A, carotenoid, vitamin B complex, vitamin C, vitamin D family, vitamin E, vitamin K family, Citrin, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, folic acid etc.; As minerals, for example can enumerate calcium, potassium, magnesium, sodium, copper, ferrum, manganese, zinc, selenium etc.As organic acid, for example can enumerate malic acid, citric acid, lactic acid, tartaric acid etc.These compositions can make up more than 2 kinds and to use, and also can use composite and/or contain the food of these compositions in a large number.
Through after state Bayley infant development inspection, Fagan test, the visual evoked potential inspection of the very low birth weight infant object among the embodiment, show that infant brain growth accelerant of the present invention has the effect of various developmental indexs such as comprehensive improvement nerve, motion, intelligence and neural myelin formation.We can say that thus infant brain growth accelerant of the present invention improves useful to the nervimotion and the learning functionality of infant.
Need to prove that the existing document of all that quote in this description all is incorporated in this description as a reference.
Embodiment
Below, come to explain particularly the present invention based on embodiment, but the invention is not restricted to these concrete examples.
< test arrangement >
18 routine very low birth weight infants (mean gestational age is that 30.3 weeks, average birth weight are 1107g) are divided into 9 routine test group (sphingomyelins reinforce-milk suckling group) and 9 routine matched groups (contrasting milk suckling group), let the test that each group picked-up contains composition shown in the table 1 use milk (contrast milk, sphingomyelins (SM) reinforce-milk).
Table 1
| Every 100g | Matched group (contrast milk suckling group) | Test group (SM reinforce-milk suckling group) |
| Protein (g) lipid (g) energy (kcal) | 13.4 17.3 467 | 13.4 17.3 467 |
| Total phospholipids (mg) is strengthened with phospholipid cholesterol (mg) beta-carotene (μ g) DHA (mg) EPA (mg) arachidonic acid (mg) | 200 Ovum Gallus domesticus Flavus lecithins 80 70 100 30 50 | 200 |
| Nucleotide (mg) selenium (μ g) | 14 7 | 14 7 |
In the table 1, total phospholipids is represented the content of each test with the phospholipid that contains in the milk integral body.About 65% from raw materials such as milk surums in the total phospholipids.In addition, in the total phospholipids about 35% from the reinforcement shown in the table 1 with phospholipid (Ovum Gallus domesticus Flavus lecithin or newborn phospholipid).
The test of test group is the newborn phospholipid that contains a large amount of SM with the reinforcement phospholipid source of milk, and the test of matched group is adopted the Ovum Gallus domesticus Flavus lecithin that contains SM hardly with the reinforcement phospholipid source of milk.Table 2 is depicted as the composition of each test with the total phospholipids that contains in the milk.Table 1, table 2 show: the characteristics of SM reinforce-milk of the present invention (infant brain growth accelerant) are that the ratio of the SM in the phospholipid is high.
Table 2
| Test is with each constituent concentration in the total phospholipids that contains in the milk | Unit | Matched group (contrast milk suckling group) | Test group (SM reinforce-milk suckling group) |
| PE (PHOSPHATIDYL ETHANOLAMINE) | w/ |
20 | 18 |
| PC (phosphatidylcholine) | w/w％ | 29 | 22 |
| SM (sphingomyelins) | w/w％ | 13 | 20 |
| PS (Phosphatidylserine) | w/ |
20 | 16 |
| PI (phosphatidylinositols) | w/w％ | 11 | 12 |
| Others (other) | w/ |
7 | 12 |
During suckling, it is the milk of 15w/v% that the SM reinforce-milk of the composition of table 1 adopts interpolation water to be modulated into milk concentration with contrast milk.The preferential breast milk of suckling, insufficient part then use SM reinforce-milk (SM is 20w/w% in the total phospholipids) or contrast milk (SM is 13w/w% in the total phospholipids) to replenish at random.Particularly, since 24 hours puerperal with interior suckling, inject 0.5～1.0ml/ time through nasogastric tube, 8 times on the 1st, need only the stomach residual quantity and be not higher than injection rate, then carry out increment successively by 4～8ml/ day.Just taking a blood sample the composition of analysed for plasma phospholipid (sphingomyelins) and erythrocyte membrane fat acid (arachidonic acid, DHA) after birth back, the birth 2,4,6,8 weeks.Correct 3 months monthly ages and 6 months enforcement Fagan test and VEP inspection, carrying out Bayley infant development inspection (the rectification monthly age is meant the monthly age after becoming pregnant, i.e. expression is become pregnant the monthly age) at 6 months monthly ages of rectification then.In addition, at duration of test, observation has or not complication, weight increase rate, breast-fed rate.Here, " breast-fed rate " is meant, the shared ratio of breast milk in total milk amount of VLBW picked-up during the whole test (breast milk or contrast milk or SM reinforce-milk).
< evaluation methodology >
(1) Bayley infant development inspection (The Bayley Scales ofInfant Development)
This inspection be with about 0 years old to 3 years old be the comprehensive growth method of diagnosis of object, constitute by these 3 fields of MDI (MDI), psychomotor developmental index (PDI), behavior observation scales (BRS).MDI has 178 problems, and PDI has 111 problems, and the child is implemented these problems practically, and provides score.In addition, BRS shows 30 projects such as estimating concentration power and harmony according to child's the action in the inspection.
Among the MDI, situation, language and alternative situation, ability, the abstract thinking comprehensive and classification of acquisition, mnemonic learning and the problem resolving ability of the permanent property of the acuteness and the property distinguished of the perception-intellectual of infant, reactive degree, object are evaluated.The psychology yardstick is represented with the mode of MDI (MDI).
Among the PDI, fine operation, motor capacity that health control, muscular movement are regulated, pointed are evaluated.Adopt this yardstick, know and move with the corresponding health of the growth of nervus centralis and the basic growth of health control.
MDI and PDI are 100 to be meansigma methods, to be the standard score of standard deviation with 15.BRS highest score 100,26-100 normal zone ,11-25 as the boundary zone, 10 the following decision was poor (see small Linden? Supervision. Infants Development Education Evaluation ma Uni ア Hikaru, Man Kwong Tong ,121-135, 2000).
In infant behavior record, hold the distinctive behavior characteristics of child during inspection and evaluate.All behaviors such as inter personal contact, emotion aspect, motivation, distinctive sensation, care are evaluated.
The inventor carries out above-mentioned inspection according to the method (Bayley N.Manual for the Bayley Scales ofInfant Development.The Psychological Corporation, New York, 1969) of Bayley etc.In the reality; The Bayley Scale for Infant Development Second edition that employing is bought from The Psychological Corporation Harcourt Brace andCompany (UK); Make object be sitting in the above-knee of mother and face-to-face, checked with about 30～40 minutes with the inspection implementer.In the paper used for recording of regulation, write down the result,, calculate index score (MDI according to the conversion table of record in the handbook (マ ニ ユ ア Le mentioned above); PDI; BRS) (O ' Connor, et al.Growthand development in preterm infants fed long-chain polyunsaturated fatty acids:a prospective, randomized controlled trial.Pediatrics; 108:359-371,2001).
(2) Fagan test (Fagan test of infant intelligence)
This inspection is to cause habituation phenomenon (familiarization phenomenon) through making the child watch face photo certain hour attentively; Then; Different face photos is side by side shown in pairs, measure the child and can watch which photo (novel preference rate (ratio of preference forunprecedentedness)) attentively.The habituation phenomenon is meant seeing that new things encode in brain, thus the process of understanding and memory.Novel preference is meant the process of curiosity coding more.Phenomenon has been shown by customary speed and novelty preference rate can foresee their mental development (Tian Zhonggong child. Infants Full mental action Developmental と fatty acids. Medical Full Ayumi ,218:403-407, 2006).
The inventor is according to the method (Fagan JF et al.The Fagan Test of InfantIntelligence.Infant Test Corporation, Cleveland, 1986) of Fagan etc., and implementing should inspection.In the reality, adopt the Fagan Test Kit that buys from Infantest company (USA), make object be sitting in the above-knee of mother and face-to-face, checked with about 20 minutes with the examiner.Inspection is made up of 10 problems, and one of them problem is made up of habituation test and novel test.The stimulation of showing all is face photo (baby, adult female, an adult male), and the examiner observes from the pin hole of the object stage that shows photo, with the moving recording of child's sight line in computer.The result adopt ratio to the fixation time of novel stimulus be novel preference rate (%looking time to novel target) (O ' Connor; Et al.Growth and development in preterm infants fed long-chainpolyunsaturated fatty acids:a prospective; Randomized controlled trial.Pediatrics; 108:359-371,2001).
(3) VEP (visual evoked potential figure: inspection Visual evoked potentials)
This inspection is a kind of neuro physiology inspection, measures the neurotransmission speed through optic nerve.Graphic determination 16Hz stimulation induced latency (msec), evaluation of the degree of myelination (Tian Zhonggong child. Infants Full mental action Developmental と fatty acids. Medical Full Ayumi ,218:403-407, 2006).
In the reality, make object be sitting in the above-knee of mother and watch the monitor in 1m the place ahead attentively, write down potential change according to 3 electrodes being satisfied with head.Monitor shows the animation of checkerboard pattern, and 3cm installs leadout electrode in the 3cm side to the left and right above nodular from occiput, and reference for installation electrode above apart from the 6cm of nasion portion carries out record.As shown in Figure 1; Time (incubation period) till the peak of pictorial stimulus (figure left end)～negative ripple of mensuration 16Hz; Compare research (Kos-Pietro S; Et al.Maturation of human visual evoked potential:27weeks conceptional age to 2years.Neuropediatrics:318-323,1997)
< result >
Between two groups, do not see and have or not, have significant difference (table 3) aspect the weight increase rate, breast-fed rate in complication.
[table 3]
| ? | Matched group (9 example) | Test group (SM reinforce-milk suckling group) (9 example) |
| The weight increase rate chronic lung disease patent ductus arteriosus retinopathy of prematurity intracranial hemorrhage necrotic enteritis in breast-fed |
72.4％ 57.9％ 222.5％ 3 4 1 0 0 | 78.8％ 62.4％ 184.3％ 0 2 2 0 0 |
In addition, in the result etc. of fatty acid compositional analysis who with arachidonic acid (AA), docosahexenoic acid (DHA) is representative, also unknown significance difference (Fig. 2 and Fig. 3).On the other hand; In the composition analysis of blood plasma phospholipid; In SM reinforce-milk group; 4 weeks of birth back are compared with matched group with the blood plasma SM concentration in 6 weeks, and (p＜0.01:un-paired Student ' stest) the high value (4 all 27.6%vs16.3%, 6 all 23.1%vs16.0%) that demonstrates significance (Fig. 4).In addition; In the BRS score and Fagan test of the Bayley inspection when correcting 6 months monthly ages, SM reinforce-milk group is compared (p＜0.05:un-paired Student ' s test) that demonstrate significance high value (Bayley85.1vs55.1, Fagan53.4vs48.2) (Fig. 5 and Fig. 6) with matched group.In addition, in VEP inspection, only in SM reinforce-milk group, correct 6 months monthly ages and compared, significance ground incubation period (p＜0.05:paired Student ' s test) shortening (3 months: 110.5msec, 6 months: 104.2msec) (Fig. 7) with 3 months.
Can know from these results, through giving infant brain growth accelerant of the present invention, although intravital DHA concentration equate because the difference of phospholipid, can be observed difference thereby form at the myelin of various developmental indexs such as nerve, motion, intelligence and nerve.That is, in milk-derived phospholipid and DHA combination, found high synergy first.
Infant brain growth accelerant of the present invention and the food compositions that is used to improve infant nervimotion and/or learning functionality can reach unknown in the past effect, promptly can improve the growth and the learning functionality of the brain of premature infant, particularly low birth weight infant.Can achieve the goal through absorbing the so very easy method of medicament of the present invention or compositions, and its effect is unexpected.In addition, be easier to obtain, therefore can make medicament with above-mentioned characteristic or food compositions etc. easy and at an easy rate as milk-derived phospholipid, the DHA ratio of raw material.
Claims (15)
1. the purposes of milk-derived phospholipid in the brain development promoter of making premature infant, low birth weight infant, very low birth weight infant or ULBW that contains sphingomyelins; Wherein, said growth accelerant contains the sphingomyelins of at least 0.005 weight % when picked-up.
2. purposes as claimed in claim 1, wherein, milk-derived phospholipid is at least 0.027 weight % when picked-up.
3. purposes as claimed in claim 1, wherein, the sphingomyelins amount that said growth accelerant is modulated in the product is at least 0.03 weight %, and the sphingomyelins amount during picked-up is at least 0.005 weight %.
4. purposes as claimed in claim 1, wherein, the milk-derived phospholipid amount that said growth accelerant is modulated in the product is at least 0.15 weight %, and the milk-derived phospholipid amount during picked-up is at least 0.027 weight %.
5. like each described purposes in the claim 1 to 4, wherein, said growth accelerant contains the docosahexenoic acid of at least 0.008 weight % when picked-up.
6. like each described purposes in the claim 1 to 4, wherein, said growth accelerant contains the docosahexenoic acid of at least 0.05 weight % in product.
7. the purposes of sphingomyelins in the brain development promoter of making premature infant, low birth weight infant, very low birth weight infant or ULBW; Wherein, Said growth accelerant adds in the food, and the sphingomyelins that is modulated in when picked-up food is at least 0.005 weight %.
8. purposes as claimed in claim 7 is characterized in that said growth accelerant further contains docosahexenoic acid, and it adds in the food, and the docosahexenoic acid that is modulated in when picked-up food is at least 0.008 weight %.
9. the milk-derived phospholipid that contains sphingomyelins is used for improving the purposes of food compositions of nervimotion and/or the learning functionality of premature infant, low birth weight infant, very low birth weight infant or ULBW in manufacturing; Wherein, said compositions contains the sphingomyelins of at least 0.005 weight % when picked-up.
10. purposes as claimed in claim 9, wherein, milk-derived phospholipid is at least 0.027 weight % when picked-up.
11. purposes as claimed in claim 9, wherein, the sphingomyelins amount that said compositions is modulated in the product is at least 0.03 weight %, and the sphingomyelins amount during picked-up is at least 0.005 weight %.
12. purposes as claimed in claim 9, wherein, the milk-derived phospholipid amount that said compositions is modulated in the product is at least 0.15 weight %, and the milk-derived phospholipid amount during picked-up is at least 0.027 weight %.
13. like each described purposes in the claim 9～12, wherein, said compositions contains the docosahexenoic acid of at least 0.008 weight % when picked-up.
14. like each described purposes in the claim 9～12, wherein, said compositions contains the docosahexenoic acid of at least 0.05 weight % in product.
15. purposes as claimed in claim 9, wherein, said compositions is formula milk, brew with concentrate and brew with in the dry thing any.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006354897 | 2006-12-28 | ||
| JP354897/2006 | 2006-12-28 | ||
| PCT/JP2007/075288 WO2008081934A1 (en) | 2006-12-28 | 2007-12-28 | Agent for facilitating the development of brain in infant comprising milk-derived phospholipid and food composition comprising the same |
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| CN101636167A CN101636167A (en) | 2010-01-27 |
| CN101636167B true CN101636167B (en) | 2012-10-03 |
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| JP (1) | JP5959137B2 (en) |
| KR (1) | KR20090097945A (en) |
| CN (1) | CN101636167B (en) |
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| WO (1) | WO2008081934A1 (en) |
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| BRPI0919192A2 (en) | 2008-09-02 | 2015-08-18 | Nutricia Nv | Use of lipid, nutritional composition, and process for producing a nutritional composition |
| WO2010068086A1 (en) | 2008-12-11 | 2010-06-17 | N.V. Nutricia | Nutritional compositions with large lipid globule size |
| JP6043064B2 (en) * | 2009-06-16 | 2016-12-14 | 株式会社明治 | A milk-derived composition for pregnant women that prevents the risk of reduced birth weight in babies |
| US20120309716A1 (en) * | 2010-02-03 | 2012-12-06 | Kao Corporation | Motor Function Improver |
| WO2011115476A1 (en) | 2010-03-17 | 2011-09-22 | N.V. Nutricia | Infant nutrition for improving fatty acid composition of brain membranes later in life |
| SE536599C3 (en) * | 2012-04-10 | 2017-01-10 | Hero Ag | Nutritional composition with low calorie and low protein content |
| US20160263033A1 (en) | 2013-11-01 | 2016-09-15 | N.V. Nutricia | Lipid composition for improving body composition during catch-up growth |
| CN108135242A (en) | 2015-10-15 | 2018-06-08 | N·V·努特里奇亚 | Infant formula with specific lipid structure for healthy growth |
| EP4205560A1 (en) * | 2015-12-14 | 2023-07-05 | Société des Produits Nestlé S.A. | Nutritional compositions and infant formulas to promote myelination in the brain |
| JP7088829B2 (en) | 2016-04-13 | 2022-06-21 | 株式会社明治 | Composition for improving brain function for newborns |
| MY196605A (en) | 2016-12-09 | 2023-04-20 | Nutricia Nv | Nutritional Composition for Improving Cell Membranes |
| CN112042750B (en) * | 2020-09-09 | 2022-04-05 | 北京三元食品股份有限公司 | A kind of infant formula milk powder rich in milk fat globule membrane protein, phospholipids and oligosaccharides and preparation method thereof |
| CN114145347A (en) * | 2021-11-30 | 2022-03-08 | 内蒙古伊利实业集团股份有限公司 | Phospholipid composition capable of improving learning and memory ability and application thereof |
| CN114711295A (en) * | 2022-04-29 | 2022-07-08 | 安徽东荣堂生物科技有限公司 | Complementary food nutrition supplement food |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001128642A (en) * | 1999-11-02 | 2001-05-15 | Meiji Milk Prod Co Ltd | A food composition containing a milk-derived phospholipid. |
| JP2003252765A (en) * | 2002-02-28 | 2003-09-10 | Snow Brand Milk Prod Co Ltd | Agent for treatment of intestinal movement insufficiency |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01279827A (en) * | 1988-05-02 | 1989-11-10 | Taiyo Fishery Co Ltd | Cerebral function improver, learning ability enhancer, mneme enhancer, preventive agent or remedy for dementia or functional food having cerebral functional improving effect |
| JP4568464B2 (en) * | 2001-11-07 | 2010-10-27 | 雪印乳業株式会社 | Memory disorder prevention and treatment |
| JP4535662B2 (en) * | 2002-04-10 | 2010-09-01 | 太陽化学株式会社 | Brain function improving composition |
| US10086009B2 (en) * | 2005-05-23 | 2018-10-02 | Massachusetts Institute Of Technologies | Compositions containing pufa and/or uridine and methods of use thereof |
| JP2007246404A (en) * | 2006-03-14 | 2007-09-27 | Snow Brand Milk Prod Co Ltd | Learning ability-improving agent |
| US20080003330A1 (en) * | 2006-06-30 | 2008-01-03 | Ricardo Rueda | Infant formulas for early brain development |
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2007
- 2007-12-28 KR KR1020097015502A patent/KR20090097945A/en not_active Ceased
- 2007-12-28 CN CN2007800518292A patent/CN101636167B/en not_active Expired - Fee Related
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001128642A (en) * | 1999-11-02 | 2001-05-15 | Meiji Milk Prod Co Ltd | A food composition containing a milk-derived phospholipid. |
| JP2003252765A (en) * | 2002-02-28 | 2003-09-10 | Snow Brand Milk Prod Co Ltd | Agent for treatment of intestinal movement insufficiency |
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| JP5959137B2 (en) | 2016-08-02 |
| CN101636167A (en) | 2010-01-27 |
| JPWO2008081934A1 (en) | 2010-04-30 |
| KR20090097945A (en) | 2009-09-16 |
| HK1140427A1 (en) | 2010-10-15 |
| WO2008081934A1 (en) | 2008-07-10 |
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