JPH06205640A - Processed milk powder for baby nursing effective for improving state of feces - Google Patents

Abstract

PURPOSE:To obtain a processed milk powder for baby nursing, causing remarkably suppressed trouble of the deterioration of feces state caused by the conventional processed milk powder for baby nursing, absolutely free from defects and problems and suitable for the nutrition of baby. CONSTITUTION:This milk powder for improving the feces state of baby contains docosahexaenoic acid and beta-carotene or docosahexaenoic acid, beta-carotene and lactoferrins and, as necessary, whey protein or whey protein and proteins other than when protein are decomposed with an enzyme and are contained therein. Yellow feces same as that of the baby fed with breast is discharged from a baby fed with this processed milk powder and there is no problem in the growth of baby.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention contains docosahexaenoic acid and β-carotene, or docosahexaenoic acid, β-carotene and lactoferrin, and optionally contains an enzymatic decomposition product of whey protein, and further, if necessary. According to another aspect, the present invention relates to a powdered infant formula for improving fecal properties, which comprises an enzymatic degradation product of all proteins other than whey protein.

In this specification, percentages are expressed by weight unless otherwise specified, and μg% means solid content 1
The value is in μg of the weight of the substance contained per 00 g, and the mg% is the value in mg of the weight of the substance contained per 100 g of the solid content. In addition, lactoferrin is
Lactoferrin, apolactoferrin, metal-saturated lactoferrin derived from milk of mammals such as cows, hydrolysates thereof, peptides of SEQ ID NO: 1 to SEQ ID NO: 31, peptides containing peptides of SEQ ID NO: 1 to SEQ ID NO: 31, or these It is a mixture of two or more.

[0003]

2. Description of the Related Art As a substitute for breast milk to be administered to infants who cannot receive breast milk or infants who are short of breast milk for various reasons, infant formula (hereinafter sometimes simply referred to as formula). Has been developed. Conventionally, infant formula has been developed for the purpose of satisfying nutritional requirements based on recent pediatric nutrition, based on the nutritional components in breast milk, but it is required as a milk substitute instead of satisfying nutritional components. Due to insufficient physiological function, studies have been conducted on the function of breast milk biochemically. As a result, a formula has been developed that not only prevents the deficiency of nutritional components but also positively mixes components that are expected to have certain physiological effects. As an example, it is contained in breast milk and is said to be involved in the infant's nervous system.
Docosahexaenoic acid (hereinafter sometimes abbreviated as DHA), which is a 3-series highly unsaturated fatty acid, and lactoferrin as a protective factor against infection have been developed.

On the other hand, since the state of the baby's feces serves as an indicator of the health of the baby, attention has been paid to the relationship between the baby's fecal properties and health. That is, because of the emulsification
Or, to satisfy the required amount, modified milk powder fortified with iron, modified milk powder with an increased ratio of whey protein to casein protein (that is, increased ratio of whey protein) to improve protein quality , Etc. are commercially available, but it is known that the frequency of the color of stool becomes green in infants who ingest these formulas [Journal
Journal of Pediatric Gas
troenterology and Nutrition), Vol. 4, p. 771, 1985].

These facts exemplify that the modified milk powder has not reached the level of the breast milk in various points, and an urgent improvement is desired. As a method for solving the problem of green stool in infants, for example, an attempt has been made to improve green stool by blending 2 to 5% of fructooligosaccharide in the formula powder (Japanese Patent Laid-Open No. 3-266937). It is disclosed that even if fructooligosaccharide is added to powdered milk at a ratio of 2 to 5%, green stool will be produced in about 1 in 5 cases.

[0006] Furthermore, lactoferrin is, in vivo,
It is a natural iron-binding protein contained in tears, saliva, peripheral blood, milk, etc., and is known to show an antibacterial action against harmful microorganisms such as Escherichia coli, Candida and Clostridium [Journal] Of Pediatrics (Journa
l of Pediatrics), Volume 94, Page 1: 1979
Year]. Also, 0.5 to 3 for Staphylococcus and Enterococcus
It is known to have an antibacterial effect at a concentration of 0 mg / ml [Nonnecke, BJ & Smith, KL; Journal;
of Dairy Science) Volume 67, 606 Page: 19
1984], but the relationship between lactoferrins and green stool has not been known at all.

[0007]

Among the characteristics of feces, it is the color of stool that is significantly different from breast-fed infants and artificially-fed infants, and frequently. That is, as described above, breast-fed babies have a large number of bowel movements, soft stools, and yellow stools, whereas artificially fed infants have a smaller number of stools compared to breast-feeding babies, have firm stools, and have a green color tone. Is often the case. This green-colored stool is the most frequent problem in parenting counseling, but is not necessarily a pathological condition. The color tone of stool is affected by the components of the milk powder and the redox state in the intestinal tract, but there is no problem that the stool becomes green with the passage of time after defecation.

[0008] As described above, the fecal color is green, and the secretion ratio of bilirubin and biliverdin, which are bile pigments secreted from the gallbladder, and the direct and indirect changes of the substances in the intestinal tract due to oxidation or reduction. This is because. Therefore, in infants administered with formula powder in which a large amount of substances (such as iron) that affect the redox of the intestinal contents are present, the frequency of feces showing green color increases. Further, it is known that in the iron-fortified infant formula, when the ratio of whey protein to the constituent proteins is enhanced, the tendency of feces to show a greener color is enhanced. Similarly, from a nutritional point of view, it is also known that when a highly unsaturated fatty acid such as DHA is added to the modified milk powder, the redox property of the intestinal contents is changed, so that the tendency of green stool is enhanced.

[0009] Therefore, as a result of intensive research to solve the above-mentioned problems, the present inventors have found that DHA-enriched formula powders, which are preferably added in infant nutrition, are β
-Carotene or β-carotene and lactoferrin are blended, and if necessary, 40% or more of whey protein is treated with an enzyme to form a decomposed product (mixture of peptide and amino acid) to obtain a conventional powdered milk. It was found that the feces can be remarkably improved as compared with. That is, β-carotene alone or a combination of β-carotene and lactoferrin imparts stability to changes in redox of intestinal contents by addition of DHA, and whey protein was enhanced. It has been found that, in the modified milk powder, at least 40% of the whey protein is treated with an enzyme to form a decomposed product, whereby the tendency of fecal greening can be reduced.

An object of the present invention is to provide a milk powder suitable for infant nutrition, which does not have the above-mentioned drawbacks and problems found in conventional milk powder.

[0011]

The first invention of the present invention for solving the above-mentioned problems is a infant formula for improving stool performance, which comprises DHA and β-carotene.

A second invention of the present invention which solves the above-mentioned problems, is a baby formula for improving stool performance, which comprises DHA, β-carotene and lactoferrin,
Is.

Further, according to the present invention, DHA is contained in a proportion of at least 0.1% (by weight) of fats and oils, β-carotene is contained in a proportion of at least 40 μg%, and lactoferrins. Is lactoferrin,
Apolactoferrin, metal-saturated lactoferrin, hydrolysates thereof, peptides of SEQ ID NO: 1 to SEQ ID NO: 31, peptides containing peptides of SEQ ID NO: 1 to SEQ ID NO: 31, or a mixture of two or more thereof; Contains at least 20 mg% whey protein if necessary at least 40%
It is also a desirable embodiment that the protein is enzymatically decomposed at a ratio of (weight), and if necessary, all proteins other than whey protein are enzymatically decomposed.

Next, the present invention will be described in detail.

DHA to be added to infant formula in the present invention
Any of substances derived from natural products such as animals and microorganisms and substances synthesized chemically or biochemically can be used, and commercially available products can also be used. The content of DHA in breast milk is greatly influenced by the dietary content of the mother and varies widely among individuals, but 0.75 ± 0.33% per fat (average in normal milk (lactation period 15 to 30 days) in Japanese). Values ± standard deviation, Journal of Japanese Society of Pediatric Nutrition and Gastroenterology, Vol. 6, page 123, 1992). This is 95% of the breast milk surveyed
0.09% to 1.41% of DHA in the above milk fat
It means that it was contained, and the added amount of DHA to the powdered milk is preferably within these contents. Furthermore, excessive intake of highly unsaturated fatty acids increases the amount of vitamin E required in the living body (edited by Ichiro Hara, “Nutrition and Diseases of Fats and Oils”, p. 355, Saishobo, 1990), so addition of excess amount is preferred. Absent.

In the present invention, β-carotene added to the powdered milk is a substance derived from a natural product such as a microorganism or plant,
Any chemically synthesized substance or biochemically synthesized substance can be used, and a commercially available product may be used. Although no harmful effect due to excessive intake of β-carotene is known, the addition amount thereof is at least 50 μg% in the first invention and at least 40 in the second invention from the test examples described below.
μg%, β-carotene content of Japanese breast milk 12 μg
/ 100 ml (solid content 12%), that is, solid content 100
It is preferably 100 μg per gram (100 μg%. “Fourth Edition Japanese Food Standard Ingredient Table” edited by Science and Technology Agency Resource Research Committee, Ministry of Finance Printing Bureau, November 25, 1982) or less.

In the present invention, the lactoferrin to be added to the powdered milk is commercially available lactoferrin, colostrum of mammals (eg, human, cow, sheep, goat, horse, etc.), transitional milk, normal milk, terminal milk, or the like. Non-fat milk which is a processed product of milk, normal method (for example, ion exchange chromatography) from whey and the like, lactoferrin separated therefrom, hydrochloric acid, apolactoferrin deferred with citric acid, apolactoferrin iron, copper, Metal saturated or partially saturated lactoferrin chelated with a metal such as zinc or manganese, a hydrolyzate thereof, a peptide of SEQ ID NO: 1 to SEQ ID NO: 31, a mixture of two or more thereof, and the like, which are commercially available or publicly known. Any of those prepared by the above method can be used.

The hydrolyzate of lactoferrin can be obtained by a known method of hydrolyzing lactoferrin with an acid or an enzyme, for example. That is, in the case of performing hydrolysis with an acid, lactoferrin is made into an aqueous solution, an inorganic acid or an organic acid is added thereto, and the mixture is heated to a predetermined temperature for a predetermined time for hydrolysis. When the enzyme is used for hydrolysis, lactoferrins are made into an aqueous solution, the pH of the enzyme used is adjusted to an optimum pH, enzymes such as pepsin and trypsin are added, and the mixture is kept at a predetermined temperature for a predetermined time for hydrolysis. After hydrolysis, the enzyme is inactivated by a conventional method. The degradation product obtained by hydrolysis with an acid or an enzyme is a mixture of degradation products containing peptides having antibacterial properties and having various molecular weights.

Reaction liquid obtained by hydrolysis with the above-mentioned acid or enzyme (solution of hydrolyzate of lactoferrin)
Is cooled by a conventional method and, if necessary, neutralized by a conventional method,
It can be desalted, decolorized, and optionally fractionated by a conventional method, and the resulting solution can be used as it is as a concentrated solution as a concentrated solution or as a powder by drying it.

Further, the peptides of SEQ ID NO: 1 to SEQ ID NO: 31 are obtained by hydrolyzing lactoferrins with an acid or an enzyme, and obtaining a peptide-containing fraction from a mixture of the degradation products by a known separation means such as liquid chromatography. Method,
Alternatively, the amino acid sequence of the peptide obtained as described above is determined by a known method (for example, a method using a gas phase sequencer), and a peptide containing the amino acid sequence is determined by a known method (for example, peptide automatic synthesis). It can be prepared by a method of obtaining a desired peptide by synthesizing by a method using an apparatus or the like, or by synthesizing a peptide having homology with the peptide thus obtained by a known synthesis method. You can also do it.

The peptide prepared as described above is
As illustrated in the sequence listing below, peptides including the peptides of SEQ ID NOs: 1 to 31 can also be used in the present invention in the same manner.

In the present invention, as is apparent from Test Example 2 described later, when lactoferrins are added to the powdered milk powder at a ratio of at least 20 mg%, preferably 40 mg% or more in the second invention, the effect of preventing green stools is improved. Is improved.

The whey protein used in the present invention and the protein other than whey protein may be enzymatically decomposed by any known method, but the degree of decomposition changes the color tone of stool.

The degree of decomposition of these proteins is expressed as a percentage of the amount of non-protein nitrogen determined by the formol titration method with respect to the amount of total nitrogen determined by the Kjeldahl method. Therefore, for example, the value expressed as the percentage of the non-protein nitrogen content determined by the formol titration method with respect to the total nitrogen content of whey protein or proteins other than whey protein is 4 whey protein.
Even if it exceeds 0%, or even if it reaches 100% with proteins other than whey protein, if it contains other undegraded whey protein or proteins other than whey protein, it is degraded. The degree is 40% or less or 100% or less, respectively.

In the present invention, as is clear from Test Example 1 and Test Example 2 described below, the degree of decomposition of whey protein is
In the first invention, when it is at least 50%, and when it is at least 40% in the second invention, the green stool prevention effect is improved.

Further, in the present invention, from the viewpoint of prevention of allergy, even in the case of the modified milk powder containing the protein as the protein source, the peptide in which all of the proteins are enzymatically decomposed, Test Example 3 described later is used.
As is clear from the above, it has a green stool prevention effect.

The raw material of the powdered milk thus prepared is manufactured by the same method as the conventional powdered milk, and the obtained powdered milk is administered to an infant by the same method as the conventional powdered milk. be able to. In addition, it has been confirmed by a test that at this time, no side effect which is considered to be caused by this infant formula is caused.

Next, the present invention will be described in detail by showing test examples.

Test Example 1 This test was conducted to examine the effects of the amount of β-carotene added and the degree of whey protein degradation on stool color.

Test Method Components other than DHA, β-carotene, and enzymatic decomposition products of whey protein had the same composition as that of commercially available powdered milk (manufactured by Company A).
Formulated milk powder was prepared in which the amounts of HA and β-carotene added and the degree of enzymatic decomposition of whey protein were changed as shown in Table 1, and the milk powder was ingested by an infant, and the color tone of feces was visually observed.

Test Results The results of this test are shown in Table 1. From the results of Table 1, DHA is 0.10% or 1.41% with respect to fats and oils.
When added, if the amount of β-carotene added is 50 μg% or more, the color of feces is green-yellow to yellow-green, and if the degree of enzymatic decomposition of whey protein is 50% or more, the color of feces is yellow-green. ~ It was observed to be yellow. DHA,
When the type and amount of β-carotene and the whey protein degradation degree were changed and tested, almost the same results were obtained.

[0032]

[Table 1] (Test Example 2) This test was carried out in order to examine the influence of the amount of β-carotene and lactoferrin added and the degree of whey protein degradation on the color tone of feces.

Test Method Components other than DHA, β-carotene, whey protein hydrolyzate and lactoferrin hydrolyzate had the same composition as commercially available powdered milk (manufactured by Company A), and DHA, β-carotene and lactoferrin hydrolyzate were added. A modified milk powder was prepared in which the amount and the degree of whey protein decomposition were changed as shown in Table 2, and the milk powder was ingested by an infant, and the color of feces was visually observed.

Test Results The results of this test are shown in Table 2. From the results of Table 2, DHA is 0.10% or 1.41% with respect to fats and oils.
When added, the addition amount of lactoferrin degradation product is 20 mg
% Or more and the amount of β-carotene added is 40 μg% or more, the color of feces is green-yellow to yellow-green, and the degree of decomposition of whey protein is 40% or more, the color of feces is yellow. It was observed that the color was green to yellow, and when the amount of the lactoferrin degradation product added was 40 mg% or more, the effect of preventing green stool was further improved. Although not shown in Table 2, the results of observing the properties of feces at the same time showed that when β-carotene and a lactoferrin degradation product were added, the proportion of watery stools and loose stools was increased depending on the addition amount. A tendency was observed that it was declining.

The test was carried out by changing the types and amounts of DHA, β-carotene and lactoferrin, and the degree of whey proteolysis, but almost the same results were obtained.

[0036]

[Table 2] (Test Example 3) This test was carried out in order to investigate the effect of the amount of β-carotene added and the degree of decomposition of whey protein and proteins other than whey protein on fecal color.

Test Method Components other than DHA, β-carotene, lactoferrin hydrolyzate, whey protein hydrolyzate, and protein hydrolyzate other than whey protein have the same composition as commercially available milk powder (manufactured by A),
DHA, lactoferrin hydrolyzate, β-carotene content, whey protein and the degree of degradation of proteins other than whey protein were changed as shown in Table 3 to prepare a modified milk powder, which was then ingested by an infant to give feces. The color tone and properties of were observed with the naked eye.

Test Results The results of this test are shown in Table 3. From the results of Table 3, the addition amount of lactoferrin degradation product was 40 mg%, when DHA was added 0.30% or 1.00% to fats and oils, the addition amount of β-carotene was 40 μg% or more, and milk If the degree of decomposition of the clear protein is 40% or more, it is recognized that the color of the feces is yellowish green to yellow. In this case, the color of the feces has almost no effect on the degree of decomposition of proteins other than whey protein. I didn't receive it.

Although not shown in Table 3, the observation of the properties of feces at the same time revealed that β-carotene,
When the lactoferrin hydrolyzate was added, the proportion of watery feces and loose feces tended to decrease depending on the amount added.

Therefore, it has been confirmed that the same effect of improving feces can be expected also in the modified milk powder in which all the contained proteins have been enzymatically decomposed, which has been attracting attention from the viewpoint of allergy prevention in recent years.

The test was conducted by changing the types and amounts of DHA, β-carotene, and lactoferrin, and the degree of degradation of whey protein and proteins other than whey protein, but almost the same results were obtained.

[0042]

[Table 3] Reference Example 1 50 mg of commercially available beef lactoferrin (manufactured by Sigma) was dissolved in 0.9 ml of purified water, and the pH was adjusted to 0.1 with hydrochloric acid of 0.1 standard.
Adjusted to 5, then commercial pig pepsin (manufactured by Sigma) 1 m
g, and hydrolyzed at 37 ° C. for 6 hours. Then 0.
Adjust the pH to 7.0 with 1 standard sodium hydroxide, and
The enzyme was inactivated by heating at 0 ° C for 10 minutes, cooled to room temperature, and centrifuged at 15,000 rpm for 30 minutes to obtain a transparent supernatant. 100 μl of this supernatant was added to TSK gel ODS-
After high-performance liquid chromatography using 120T (manufactured by Toso Co., Ltd.), 10 samples were injected at a flow rate of 0.8 ml / min.
20 minutes with 0.05% TFA (trifluoroacetic acid)
% Acetonitrile, then 0.05% T for 30 minutes
Elute with a gradient of 20-60% acetonitrile containing FA, collect fractions eluting between 24-25 minutes,
Vacuum dried. This dried product was dissolved in purified water at a concentration of 2% (weight / volume), and again TSK gel ODS-120T.
(Manufactured by Tosoh Corporation), and subjected to high performance liquid chromatography at a flow rate of 0.8 ml / min for 10 minutes after injection of the sample.
Elute with 24% acetonitrile containing 05% TFA, then elute with a gradient of 24-32% acetonitrile containing 0.05% TFA for 30 minutes, 33.5-35.
Fractions eluting during 5 minutes were collected. The above operation was repeated 25 times and dried in vacuum to obtain about 1.5 mg of antibacterial peptide.

The above antimicrobial peptide was hydrolyzed with 6N hydrochloric acid, and the amino acid composition was analyzed by an ordinary method using an amino acid analyzer. The same sample was subjected to Edman degradation 25 times using a gas phase sequencer (manufactured by Applied Biosystems) to determine the sequence of 25 amino acid residues. In addition, a disulfide bond analysis method using DTNB (5,5-dithio-bis (2-nitrobenzoic acid)) [Analytic Biochemistry (Analytic
al Biochemistry), 67, 493, 1975.
Year] confirmed the existence of disulfide bonds.

As a result, this peptide consists of 25 amino acid residues, the 3rd and 20th cysteine residues are disulfide-bonded, and the 3rd cysteine residue leads to N
It was confirmed to have the amino acid sequence of SEQ ID NO: 26 in which two amino acid residues were bound to the -terminal side and 5 amino acids were bound to the C-terminal side from the 20th cysteine residue, respectively. .

Reference Example 2 Using a peptide automatic synthesizer (Pharmacia LKB Biotechnology, LKBBiolynx4170), Shepard et al. [Journal of Chemical Society Parkin I (Journal of Chemical Societ
y Perkin I), p. 538, 1981], and antibacterial peptides were synthesized as follows.

N, N-dicyclohexylcarbodiimide was added to an amino acid whose amine functional group was protected by a 9-fluorenylmethoxycarbonyl group to produce the desired anhydride of the amino acid, and this Fmoc-amino acid anhydride was synthesized. Using. In order to produce a peptide chain, Fmoc-asparagine anhydride corresponding to the C-terminal asparagine residue is immobilized on Ultrosin A resin (Pharmacia LKB Biotechnology) via its carboxyl group using dimethylaminopyridine as a catalyst. did. Then, this resin was washed with dimethylformamide containing piperidine to remove the protecting group of the amine functional group of the C-terminal amino acid, and then the Fmoc-arginine anhydride corresponding to the second position from the C-terminal of the amino acid sequence was added to the C-terminal. Coupling to the deprotected amine functionality of arginine immobilized on the resin via the terminal amino acid residue. In the same manner, glutamine, tryptophan, glutamine, and phenylalanine were sequentially fixed in the same manner.
After completion of coupling of all amino acids and formation of a peptide chain having a desired amino acid sequence, 94% TFA, 5
% Of phenol and 1% of ethanediol were used to remove protective groups other than acetamidomethyl and peptides to remove the peptides, the peptides were purified by high performance liquid chromatography, and the solution was concentrated and dried. Then, a peptide powder was obtained.

The amino acid composition of the obtained peptide was analyzed by an ordinary method using an amino acid analyzer, and SEQ ID NO: 1 was used.
It was confirmed to have 0 amino acid sequence.

Reference Example 3 3 kg of commercially available bovine lactoferrin (manufactured by Oleofina Co., Belgium) was dissolved in 57 l of purified water, and p was added with 1 standard hydrochloric acid.
After adjusting H to 3.0, 90 g of commercially available pig pepsin (manufactured by Sigma) was added and hydrolyzed at 37 ° C. for 4 hours. Then adjust the pH to 7.0 with 1 standard sodium hydroxide, inactivate the enzyme by heating at 80 ° C for 10 minutes, cool to room temperature, and centrifuge with a continuous centrifuge to obtain a clear supernatant liquid. Got The supernatant was concentrated and then freeze-dried to obtain about 2.8 kg of bovine lactoferrin degradation product.

Reference Example 4 20 kg of commercially available whey powder (manufactured by Domo) was added to 180 l of tap water.
, PH was adjusted to 8.0 with 1 standard sodium hydroxide, 80 g of commercially available trypsin (manufactured by Novo Nordisk Bioindustry) was added, and the mixture was hydrolyzed at 37 ° C. for 12 hours and then at 10 ° C. at 10 ° C. The enzyme was inactivated by heating for 1 minute, cooled to room temperature, and the precipitate was removed by continuous centrifugation to obtain a transparent supernatant. The supernatant was concentrated to 30% and spray-dried to obtain about 17 kg of a whey protein hydrolyzate having a degree of decomposition of about 50%.

Reference Example 5 2800 g of commercially available casein (manufactured by Nippon Protein Co., Ltd.)
A 10% sodium hydroxide solution was dissolved in warm water adjusted to pH 7.3 to prepare an 18% concentration casein solution.
After heat sterilizing this solution by a conventional method, it is allowed to cool to room temperature,
After adjusting the pH to 9.0 with 10% sodium hydroxide,
28 g of commercially available pancreatin F (manufactured by Amano Pharmaceutical Co., Ltd.) and 28 g of papain (manufactured by Amano Pharmaceutical Co., Ltd.) were added, hydrolyzed at 45 ° C. for 16 hours, heated at 90 ° C. for 10 minutes to inactivate the enzyme, and then brought to room temperature. After cooling, the precipitate was removed by filtration through Celite, and the transparent filtration liquid was concentrated and spray-dried to obtain 1955 g of casein hydrolyzate.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

[0052]

【Example】

Example 1 To 200 kg of raw material milk, 2.8 desalted whey powder (manufactured by Domo Co.)
kg, whey protein hydrolyzate produced by the same method as in Reference Example 3.6 kg, adjusted fat (manufactured by NOF Corporation) 1
8.7 kg, DHA (manufactured by NOF Corporation) 25.65 g, β
-Carotene (manufactured by Nippon Roche) 48 mg, lactose (manufactured by Megre Co.) 43.7 kg, vitamins (manufactured by Tanabe Seiyaku Co., Ltd.) 22
g, 550 g of minerals (manufactured by Tomita Pharmaceutical Co., Ltd.) were added and standardized, the milk preparation was homogenized, sterilized at 121 ° C. for 2 seconds, and then the sterilized milk preparation was concentrated and spray-dried to obtain about 90 kg of powdered milk powder. It was

This modified milk powder contained 0.1% DH per fat and oil.
It contained A and 50 μg% β-carotene. When this infant formula was ingested by an infant, the tendency of feces to turn green was reduced.

Example 2 200 kg of raw material milk, 31 kg of desalted whey, and a decomposition degree of 65
% Whey protein hydrolyzate produced by the same method as in Reference Example 4 except that the content is 10%, lactose (manufactured by Megre Co., Ltd.) 40.5 kg, vitamins (manufactured by Tanabe Seiyaku Co., Ltd.) 21
g, and 552 g of minerals (manufactured by Tomita Pharmaceutical Co., Ltd.) were standardized, the milk preparation was homogenized, sterilized at 121 ° C. for 2 seconds, and then the sterilized milk preparation was concentrated and sterilized into a concentrated milk preparation (Japan). 18.7 kg of oil and fat company, 362 g of DHA (manufactured by Nippon Oil and Fat Company), β-carotene (manufactured by Nippon Roche Company) 9
6 mg was added and spray-dried to obtain about 91 kg of modified milk powder.

This modified milk powder contained 1.41% D per fat and oil.
It contained HA and 100 μg% β-carotene.
When this infant formula was ingested by an infant, the tendency of feces to turn green decreased.

Example 3 350 kg of raw material milk was added with 4.9 desalted whey powder (manufactured by Domo).
kg, whey protein hydrolyzate 6.3k produced by the same method as Reference Example 4, except that the degree of degradation is 80%
g, adjusted fat (manufactured by NOF CORPORATION) 32.7 kg, DHA
(Nippon Yushi Co., Ltd.) 44.89 g, β-carotene (Nippon Roche) 84 mg, lactoferrin (Oleofina) 73 g, lactose (Megreh) 76.5 kg, vitamins (Tanabe Seiyaku) 38.5 g , And 963 g of minerals (manufactured by Tomita Pharmaceutical Co., Ltd.) were added, the composition was standardized, the obtained milky lotion was homogenized, sterilized at 121 ° C. for 2 seconds, and the sterilized milky lotion was concentrated and spray-dried to prepare. Powdered milk 146kg
Got

This modified milk powder contained 0.1% DH per fat and oil.
A, 50 μg% β-carotene and 52 mg% lactoferrins were contained. When this infant formula was ingested by an infant, the tendency of feces to turn green decreased, and the tendency of watery stools and loose stools decreased.

Example 4 To 280 kg of raw material milk was added 43.4 kg of desalted whey and 5.18 kg of a whey protein hydrolyzate produced by the same method as in Reference Example 4 except that the degree of decomposition was 50%. , Lactose (manufactured by Megre Co.) 56.7 kg, vitamins (manufactured by Tanabe Seiyaku Co., Ltd.) 29.5 g, and minerals (manufactured by Tomita Seiyaku Co., Ltd.) 77
3 g was added to standardize the composition, the obtained milky lotion was homogenized, sterilized at 121 ° C. for 2 seconds, the sterilized milky lotion was concentrated, and sterilized adjusted fat (manufactured by NOF Corporation) 26.1 kg,
DHA (manufactured by Nippon Oil & Fats Co., Ltd.), 507 g, β-carotene (manufactured by Nippon Roche), 134 mg, and 54 g of the peptide of SEQ ID NO: 10 manufactured by the same method as in Reference Example 2 were spray-dried to obtain about 126 kg of modified milk powder.

The prepared milk powder contained 1.41% D per fat and oil.
It contained HA, 100 μg% β-carotene, and 60 mg% lactoferrins. When this infant formula was ingested by an infant, the tendency of feces to turn green decreased, and the tendency of watery stools and loose stools decreased.

Example 5 43.4 kg of desalted whey was added to 280 kg of raw material milk, 56.7 kg of lactose (manufactured by Megre Co.), 29.5 g of vitamins (manufactured by Tanabe Seiyaku Co., Ltd.), and minerals (Tomita Pharmaceutical Co., Ltd.) Made) 7
73 g was added, the composition was standardized, the obtained milky lotion was homogenized, sterilized at 121 ° C. for 2 seconds, the sterilized milky lotion was concentrated, and sterilized adjusted fat (manufactured by NOF Corporation) 26.1 k
g, DHA (manufactured by NOF Corporation), 507 g, β-carotene (manufactured by Nippon Roche), 134 mg, and 81 g of the peptide of SEQ ID NO: 26 manufactured by the same method as in Reference Example 1, and spray-dried to obtain about 126 kg of the powdered milk. It was

This prepared milk powder contained 1.41% D per fat and oil.
It contained HA, 100 μg% β-carotene, and 40 mg% lactoferrins. When this infant formula was ingested by an infant, the tendency of feces to turn green decreased, and the tendency of watery stools and loose stools decreased.

Example 6 To 280 kg of raw material milk, 43.4 kg of desalted whey was added, 56.7 kg of lactose (manufactured by Megre Co.), 29.5 g of vitamins (manufactured by Tanabe Pharmaceutical Co., Ltd.), and minerals (Tonda Pharmaceutical Co., Ltd.). Made) 7
73 g was added, the composition was standardized, the obtained milky lotion was homogenized, sterilized at 121 ° C. for 2 seconds, the sterilized milky lotion was concentrated, and sterilized adjusted fat (manufactured by NOF Corporation) 26.1 k
g, DHA (manufactured by NOF Corporation) 254 g, β-carotene (manufactured by Nippon Roche) 100 mg, and 75 g of a lactoferrin hydrolyzate produced by the same method as in Reference Example 3.
It was spray-dried together with it to obtain about 126 kg of modified milk powder.

The prepared milk powder contained 0.7% DH per fat and oil.
A, 75 μg% of β-carotene and 56 mg% of lactoferrins were contained. When this infant formula was ingested by an infant, the tendency of feces to turn green decreased, and the tendency of watery stools and loose stools decreased.

Example 7 14.6 kg of soluble polysaccharide (manufactured by Showa Sangyo Co., Ltd.), 46 kg of purified lactose (manufactured by Megre Co.), 40 kg of whey protein hydrolyzate manufactured by the same method as in Reference Example 4, and Reference Example 5 7 kg of casein hydrolyzate produced by the same method, 40 kg of adjusted fat (manufactured by NOF Corporation), 100 g of DHA (manufactured by NOF Corporation), β-carotene (manufactured by Nippon Roche) 150
mg, vitamins (manufactured by Tanabe Seiyaku Co., Ltd.) 35 g, and minerals (manufactured by Tomita Seiyaku Co., Ltd.) 920 g were mixed and dissolved to homogenize 1
Sterilized at 20 ° C for 2 seconds. Then, the sterilized milk preparation was concentrated and spray-dried together with 60 g of the hydrolyzate of lactoferrin produced by the same method as in Reference Example 3 to prepare about 1
Obtained 45 kg.

All the proteins contained in this modified milk powder were enzymatically decomposed, and this modified milk powder contained 0.2
3% DHA, 102 μg% β-carotene, 40 mg
% Lactoferrin degradation product was contained. When this infant formula was ingested by an infant, the tendency of feces to turn green decreased, and the tendency of watery stools and loose stools decreased.

[0066]

The effects of the present invention are as follows. 1) The stool of an infant who ingests the infant formula of the present invention becomes yellow stool similar to that of an infant who ingests breast milk. 2) The infant formula of the present invention has no problem in the growth of infants.

[0067]

[Sequence list]

SEQ ID NO: 1 Sequence length: 11 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys. Sequence: Lys Xaa Xaa Xaa Xaa Gln Xaa Xaa Met Lys Lys 1 5 10

SEQ ID NO: 2 Sequence length: 11 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Lys Xaa Xaa Xaa Xaa Gln Xaa Xaa Met Arg Lys 1 5 10

SEQ ID NO: 3 Sequence length: 6 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Arg Xaa Xaa Xaa Xaa Arg 1 5

SEQ ID NO: 4 Sequence length: 6 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Lys Xaa Xaa Xaa Xaa Arg 1 5

SEQ ID NO: 5 Sequence length: 6 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Lys Xaa Xaa Xaa Xaa Lys 1 5

SEQ ID NO: 6 Sequence length: 6 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Arg Xaa Xaa Xaa Xaa Lys 1 5

SEQ ID NO: 7 Sequence length: 5 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Arg Xaa Xaa Xaa Arg 1 5

SEQ ID NO: 8 Sequence length: 5 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Lys Xaa Xaa Xaa Arg 1 5

SEQ ID NO: 9 Sequence length: 5 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Arg Xaa Xaa Xaa Lys 1 5

SEQ ID NO: 10 Sequence length: 6 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Phe Gln Trp Gln Arg Asn 15

SEQ ID NO: 11 Sequence length: 5 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence: Phe Gln Trp Gln Arg 1 5

SEQ ID NO: 12 Sequence length: 4 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Gln Trp Gln Arg 1

SEQ ID NO: 13 Sequence length: 3 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Trp Gln Arg 1

SEQ ID NO: 14 Sequence length: 5 Sequence type: Amino acid Topology-: Linear sequence type: Peptide sequence: Arg Arg Trp Gln Trp 15

SEQ ID NO: 15 Sequence length: 4 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence: Arg Arg Trp Gln 1

SEQ ID NO: 16 Sequence length: 4 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Trp Gln Trp Arg 1

SEQ ID NO: 17 Sequence length: 3 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Gln Trp Arg 1

SEQ ID NO: 18 Sequence length: 6 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Leu Arg Trp Gln Asn Asp 15

SEQ ID NO: 19 Sequence length: 5 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Leu Arg Trp Gln Asn 1 5

SEQ ID NO: 20 Sequence length: 4 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Leu Arg Trp Gln 1

SEQ ID NO: 21 Sequence length: 3 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence: Arg Trp Gln 1

SEQ ID NO: 22 Sequence length: 20 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: Cys No. 2 and Cys No. 19 in the following sequence
Cys has a disulfide bond. Sequence: Lys Cys Arg Arg Trp Gln Trp Arg Met Lys Lys Leu Gly Ala Pro 1 5 10 15 Ser Ile Thr Cys Val 20

SEQ ID NO: 23 Sequence length: 20 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: Cys * in the following sequence prevents disulfide bond formation, 1 shows cysteine in which a thiol group is chemically modified. Sequence: Lys Cys * Arg Arg Trp Gln Trp Arg Met Lys Lys Leu Gly Ala Pro 1 5 10 15 Ser Ile Thr Cys * Val 20

SEQ ID NO: 24 Sequence length: 20 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: Cys No. 2 and No. 19 in the following sequence
Cys has a disulfide bond. Sequence: Lys Cys Phe Gln Trp Gln Arg Asn Met Arg Lys Val Arg Gly Pro 1 5 10 15 Pro Val Ser Cys Ile 20

SEQ ID NO: 25 Sequence length: 20 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: Cys * in the following sequence prevents disulfide bond formation, 1 shows cysteine in which a thiol group is chemically modified. Sequence: Lys Cys * Phe Gln Trp Gln Arg Asn Met Arg Lys Val Arg Gly Pro 1 5 10 15 Pro Val Ser Cys * Ile 20

SEQ ID NO: 26 Sequence length: 25 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Cys 3 and 20
Cys has a disulfide bond. Sequence: Phe Lys Cys Arg Arg Trp Gln Trp Arg Met Lys Lys Leu Gly Ala 1 5 10 15 Pro Ser Ile Thr Cys Val Arg Arg Ala Phe 20 25

SEQ ID NO: 27 Sequence length: 11 Sequence type: Amino acid Topology :: Linear Sequence type: Peptide Sequence: Lys Thr Arg Arg Trp Gln Trp Arg Met Lys Lys 1 5 10

SEQ ID NO: 28 Sequence length: 38 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: Cys 16 and 33 in the following sequence are disulfides Are connected. Sequence: Lys Asn Val Arg Trp Cys Thr Ile Ser Gln Pro Glu Trp Phe Lys 1 5 10 15 Cys Arg Arg Trp Gln Trp Arg Met Lys Lys Leu Gly Ala Pro Ser 20 25 30 Ile Thr Cys Val Arg Arg Ala Phe 35

SEQ ID NO: 29 Sequence length: 32 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Cys 10 and 27 are disulfides Are connected. Sequence: Thr Ile Ser Gln Pro Glu Trp Phe Lys Cys Arg Arg Trp Gln Trp 1 5 10 15 Arg Met Lys Lys Leu Gly Ala Pro Ser Ile Thr Cys Val Arg Arg 20 25 30 Ala Phe

SEQ ID NO: 30 Sequence length: 47 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, the sequence length 36 is 9, 26 Of the peptide having Cys at position No. 35 and No. 35 and Cys at position No. 26 and Cys at position No. 26 have a disulfide bond,
A peptide having a sequence length of 11 and having Cys at position 10 has a disulfide bond with Cys at position 10. Sequence: Val Ser Gln Pro Glu Ala Thr Lys Cys Phe Gln Trp Gln Arg Asn 1 5 10 15 Met Arg Lys Val Arg Gly Pro Pro Val Ser Cys Ile Lys Arg Asp 20 25 30 SerPro Ile Gln Cys Ile 35 Gly Arg Arg Arg Arg Arg Ser Val Gln Trp Cys Ala 1 5 10

SEQ ID NO: 31 Sequence length: 5 Sequence type: Amino acid Topology-: Linear Sequence type: Peptide Sequence characteristics: In the following sequence, Xaa represents any amino acid residue except Cys . Sequence: Lys Xaa Xaa Xaa Lys 15

Claims (8)

[Claims] 1. A baby formula for improving stool performance, which comprises docosahexaenoic acid and β-carotene. 2. A baby formula for improving fecal properties, which comprises docosahexaenoic acid, β-carotene and lactoferrins. 3. The infant formula as claimed in claim 1 or 2, wherein docosahexaenoic acid is contained in a proportion of at least 0.1% (by weight) of the fats and oils contained therein. 4. At least 40 μg% of β-carotene.
The infant formula for improving fecal properties according to claim 1 or 2, which is contained in a proportion of 5. The lactoferrin is lactoferrin,
Selected from the group consisting of apolactoferrin, metal-saturated lactoferrin, hydrolysates thereof, peptides of SEQ ID NO: 1 to SEQ ID NO: 31, peptides containing peptides of SEQ ID NO: 1 to SEQ ID NO: 31, and mixtures of two or more thereof. The infant formula prepared to improve the fecal property according to any one of claims 2 to 4. 6. The lactoferrin is at least 20 m
The infant formula as claimed in any one of claims 2 to 5, which is contained in a proportion of g%. 7. The method according to claim 1, wherein the whey protein is enzymatically decomposed at a rate of at least 40% (by weight).
The infant formula for improving the stool property according to [4]. 8. The infant formula as claimed in claim 1, wherein a protein other than the whey protein is enzymatically decomposed.