JPH0517368A - Antiallergic breast milk-enriching composition - Google Patents

Abstract

PURPOSE:To obtain a nutritional supplementary composition for premature baby having antiallergic effect, containing nutrients necessary for premature baby at a prescribed amount to be added to mother's milk. CONSTITUTION:An antiallergic composition capable of enriching mother's milk using a mixture consisting of 40-80wt.% hydrolyzate of whey protein having at least 70wt.% purity and being <=10<-4> in antigenic residual activity measured by ELISA suppression assay (Enzyme-linked immunosorbent assay) by the use of an anti-serum against whey protein and 60-20wt.% hydrolyzate of casein having at least 80wt.% purity and being <=10<-4> in antigenic residual activity measured by ELISA using anticasein serum as the nitrogen sources, and further containing prescribed amounts of fats, saccharides, minerals, vitamins, etc., at a ratio of <=5wt.% based on the final product.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention has a low antigenicity, is effective in the prevention of dietary allergies, and is suitable for supplementing the nutrition of premature infants fed with breast milk, and is an antiallergic fortified milk composition. Regarding things.

[0002]

2. Description of the Related Art Conventionally, feeding of premature babies has mainly been carried out using artificial milk. However, in recent years, it has become clear that the colostrum of breast milk contains a large amount of immune substances, and it has been actively recommended to give breast milk to premature infants.

Further, in the 1980s, a detailed analysis of the components of breast milk was carried out, and the mother's milk that gave birth to an immature baby (hereinafter referred to as "premature infant milk") was found to be the milk of a mother who gave birth to a mature baby (hereinafter referred to as mature baby milk). It is revealed that the concentration of protein, sodium and chlorine is higher and that of lactose is lower than that of (1). Has been found to be optimal.

However, as a result of a more detailed analysis of breast milk, it was found that premature baby milk 2 to 4 weeks after the start of lactation had the same main nutrient content as that of mature baby milk, When breastfeeding premature babies, potential nutritional deficiencies became a concern. Moreover, nutrient deficiency is a serious problem for very small premature infants who show rapid growth from 2 to 4 weeks after the start of lactation. As a result of lack of protein, calcium, phosphorus, sodium, iron, etc., hypoproteinemia,
Signs such as rickets, hyponatremia, anemia, poor weight gain, etc. may occur.

From the above viewpoints, as a method of utilizing the advantages of breast milk nutrition and complementing the nutrients, fortifiers containing various nutrients (hereinafter referred to as breast milk enhancers) are added to breast milk and administered to premature infants. An attempt was made. Ronnholm [Pediatrics, No. 7
7, p. 649, 1986], Schanl
er) [Journal of Pediatrics (Journal
of Pediatrics), 107, 437, 1985.
Year], Hagelberg [Acta Paediatrica Scandina
vica), 71, 597, 1982], Kawaguchi et al. (Journal of the Newborn Society of Japan, 23, 640, 198).
(7 years) reported that good results were obtained by feeding premature infants with premature infant milk supplemented with protein obtained from breast milk.

Although it is clear that not only premature babies but also babies, milk proteins are qualitatively preferable to cow milk proteins, but in reality, commercialization of breast milk proteins is difficult in many respects, and recently it has been difficult. Protein obtained from milk is used as a raw material for breast milk fortifying compositions. Modanlow, etc. [Journal of Pediatric Gastroenterology and Nutriti
on), Vol. 5, p. 762, 1986], a mixture of milk-derived whey and casein is added to breast milk in a non-hydrolyzed state and a premature infant is fed at a standard feeding rate. ,
Permitted to improve physical development and biochemistry of blood.
Recently, Hayashi et al. (25th Annual Meeting of Japanese Society of Neonatal, Tokyo, 19
(1989) also reported that milk protein-enriched breast milk was effective in the care of premature infants.

There are various ways of thinking about the nutritional requirements of premature babies, especially very small premature babies, and many problems still remain today. Among them, the American Academy of Pediatrics' view that "close to the same level as intrauterine development" has received much support, but in all of the above reports, the administration of breast milk containing a breast milk enhancer The internal level of growth was maintained without any problems, and no metabolic abnormality was observed.

On the other hand, it is well known that dietary allergies due to dietary proteins such as milk, egg and soybean may occur in infancy, and there are many reports on milk proteins. Previous reports have been limited to full-term babies and no studies of premature babies have been conducted, but recently it has been demonstrated that milk allergies can occur in premature babies. Lucas
Etc. [British Medical Journal (British
Medical Journal), vol. 289, p. 1254, 19
1984] divided premature babies into a group that was given milk powder for premature infants (hereinafter simply referred to as “milk powder”) and a breast milk administration group, and collected peripheral venous blood to test milk and anti-IgE antibodies. The histamine release rate by in vitro challenge was measured. As a result, it was found that histamine release rate was high in the milk powder administration group in any of the challenges, and that the milk powder administration caused a potential anaphylactic sensitization. Furthermore, Lucas et al. [British Medical Journal Vol. 300, No. 837]
Page, 1990] divided premature babies into breast-fed and milk-fed groups and investigated the incidence of allergic symptoms in both groups. In atopic families, the allergic disease rate was significantly higher in the milk-fed group. Admitted.

[0009]

As described above, it has been clinically clarified not only at the laboratory level that the potential sensitization of milk protein to anaphylaxis can occur even in premature infants. In the conventional breast milk fortified composition, the antiallergic property was not considered at all.

The present invention is a nutritional supplement composition for premature babies to be added to breast milk, which has low antigenicity, can be administered to premature babies without fear of food allergy, and is excellent in nutritional physiology of premature babies. The purpose is to provide things.

[0011]

In view of the above-mentioned circumstances, the inventors of the present invention have anti-allergic properties that are low in antigenicity, effective in preventing food allergies, and excellent in nutritional physiology of premature infants. The present invention has been completed by conducting intensive research to develop a breast milk-enhancing composition.

The present invention for solving the above-mentioned problems is characterized in that the nutritional supplement composition for premature infants added to breast milk contains at least the nitrogen source and fat described in the following (a) and (b). An anti-allergic breast milk-enriched composition comprising: (a) a nitrogen source: a whey protein hydrolyzate having a purity of at least 70% (by weight; the same applies hereinafter unless otherwise specified), which is an anti-whey protein serum. ELISA (Enzyme:
linked immunosorbent assay) The residual antigen activity measured by the inhibition test method (hereinafter referred to as the ELISA test method) is 1
A hydrolyzate of 0 ^-4 or less (hereinafter simply referred to as whey protein hydrolyzate) and a hydrolyzate of casein having a purity of at least 80%, which are measured by an ELISA test method using anti-casein serum. (B) Fat: 5% or less of the solid content of the final product, with a hydrolyzate having a residual antigen activity of 10 ^-4 or less (hereinafter simply referred to as casein hydrolyzate).

The whey protein hydrolyzate and casein hydrolyzate used as raw materials for the antiallergic composition of the present invention are produced as follows.

The whey protein hydrolyzate is a whey protein hydrolyzate having a purity of at least 70%, preferably 90% or more, which is separated and purified from whey or the like by a conventional method (for example, ultrafiltration or ion exchange method). Is dissolved in water or purified water at a concentration of 10% or less, the pH is adjusted to 6.5-10, and a commonly used proteolytic enzyme is added, followed by hydrolysis by a conventional method and heating to lose the enzyme. Activate or remove the enzyme by ultrafiltration, and the residual antigen activity is 10 ^-4.
The following whey protein hydrolyzate is obtained.

As the proteolytic enzyme used for hydrolysis, any of animal-derived enzymes such as pancreatin, plant-derived enzymes such as papain, microorganism-derived enzymes such as bacteria and mold, and the like can be used. An example of a particularly desirable mode is as follows. The enzyme used is trypsin as a main component, and pancreatin containing chymotrypsin and exopeptidase, papain, and Aspergillus oryzae (Aspergillus oryzae).
oryzae) -derived endopeptidase, or Bacillus subtilis-derived endopeptidase, and the like are preferable. Any of these enzymes may be a commercially available product.

The units of activity of these enzymes are defined as follows. Milk Casein [Hammarste
n). 1 unit of the enzyme activity showing the color reaction with the Folin reagent of allyl amino acid corresponding to 1 μg of tyrosine at 30 ° C. for 1 minute at 30 ° C. (hereinafter, this unit is referred to as PUN unit) Is displayed. The amount of these enzymes used is 20 w / w pancreatin per whey protein.
0-2000 PUN units, preferably 300-1000 PUN units, Papain 250-2000 PUN units, preferably 300-1000 PU
N units, Aspergillus oryza
e) endopeptidase from 200-2000 PUN units, preferably 300-1000 PUN units, Bacillus subtilis
lus subtilis) derived endopeptidase 200-2000PU
N units, preferably 300 to 1000 PUN units are suitable.

To the aqueous solution of whey protein, a predetermined amount of the enzyme is added according to the amount of whey protein, and the temperature is 45 to 52 ° C.
It is hydrolyzed for 3 to 24 hours, preferably 6 to 20 hours. Then, the enzyme is inactivated by heat treatment or the enzyme is removed by ultrafiltration treatment. The heat treatment is appropriately performed at 70 ° C. for 10 minutes to 140 ° C. for 2 seconds. The ultrafiltration treatment is a fractionated molecular weight 1 that allows the enzyme to permeate and the peptide to permeate to facilitate recovery.
It takes place in the range of 5,000 to 2,000. Then, it is filtered with Celite or the like, and spray-dried or freeze-dried to obtain a whey protein hydrolyzate. The whey protein hydrolyzate thus obtained has an antigen residual activity of 10 ⁻⁴ or less.

The casein hydrolyzate is prepared by separating and purifying by a conventional method. Casein having a purity of at least 80%, preferably 90% or more is dissolved in water at a concentration of 12% and the pH is adjusted to 7 to 8.5.
And add the commonly used proteolytic enzyme,
It is hydrolyzed by a conventional method to obtain a casein hydrolyzate having an antigen residual activity of 10 ⁻⁴ or less.

The proteolytic enzyme used is an animal-derived enzyme such as pancreatin, a plant-derived enzyme such as papain, or a microorganism-derived enzyme such as bacteria or mold, either alone or in a mixture.

A particularly preferable embodiment is as follows. The enzyme used is trypsin as a main component, and pancreatin containing chymotrypsin and exopeptidase, papain, and Aspergillus oryzae (Aspergillus oryzae).
oryzae) -derived endopeptidase, or Bacillus subtilis-derived endopeptidase, and the like are preferable. Any of these enzymes may be a commercially available product. The units of activity of these enzymes are as defined above. The amounts of these enzymes used are 200-2000 PUN units of pancreatin, preferably 300-1000 PUN units, and 250- papain per gram of casein.
2000 PUN units, preferably 300 to 1000 PUN units, endopeptidase from Aspergillus oryzae 200 to 2000 PUN units, preferably 300 to 10
00PUN units, Bacillus subtilis
From 200 to 2000 PUN units of endopeptidase from origin, preferably 300 to 1000 PUN units are suitable.

[0021] To the aqueous solution of casein, a predetermined amount of the enzyme is added according to the amount of casein, and the mixture is added at a temperature of 45 to 52 ° C for 3 to
The hydrolysis is carried out for 24 hours, preferably 6-20 hours.
Then, the enzyme is inactivated by heat treatment or the enzyme is removed by ultrafiltration treatment. The heat treatment is appropriately performed at 70 ° C. for 10 minutes to 140 ° C. for 2 seconds. Ultrafiltration treatment is a fractionated molecular weight that is easy to collect because it allows peptides to permeate without allowing the enzyme to permeate.
It takes place in the range of 15,000 to 2,000. Then, it is filtered with Celite or the like, and spray-dried or freeze-dried to obtain a whey protein hydrolyzate. The whey protein hydrolyzate thus obtained has an antigen residual activity of 10 ⁻⁴ or less.

Next, the production of the milk fortified composition will be described. The anti-allergic-milk enhancing composition of the present invention is a liquid,
Although it may be in the form of powder, the following is an example of a particularly desirable mode for producing a powder product. Ratio of whey protein hydrolyzate and casein hydrolyzate produced as described above (whey protein hydrolyzate / casein hydrolyzate)
Is 80/20 to 40/60 (particularly preferably 60/40 to 45/55), and the protein (equivalent amount) occupies in the total solids of the final product.
Weigh each hydrolyzate at a rate of 10 to 40%, dissolve it in water at a concentration of 5 to 15%, add the specified amount of minerals, heat to 40 to 65 ° C, and then add the final product solid content. 5% or less of a predetermined amount of fat, sugar, and vitamins are mixed, emulsified by a high-pressure homogenizer, and heat-sterilized by a conventional method,
Dry to obtain a breast milk fortified composition.

Regarding the fat content of the final product, deficiency is not a problem in premature babies, so 5% or less, preferably 1 to 2 as a fat-soluble vitamin carrier.
%. The fat to be used may be any fat as long as it is an edible fat and oil, but fats and oils containing a large amount of medium chain fatty acids which are said to be well absorbed even by premature infants are particularly desirable.

The obtained anti-allergic breast milk-enriched composition is added to breast milk at a ratio of 1 to 10% in terms of solid content of the anti-allergic breast milk-enriched composition per 100 ml of breast milk and administered to premature infants. .

According to the test described below, the antiallergic mother's milk-enhancing composition of the present invention obtained as described above is effective in preventing allergies and is excellent in amino acid balance. It is nutritionally superior because it contains a certain amount of nutrients.

Next, the present invention will be described in detail by showing test examples.
In addition, the following antigen residual activity, amino acid composition,
And the general component composition was measured by the following method. (1) Method for measuring residual antigen activity It was measured by the ELISA test method as follows. 96-well plate (made by Nunc) coated with whey protein,
After washing, a mixture of rabbit anti-whey protein serum and hydrolyzate sample is supplied to the plate holes to react, and after washing, alkaline phosphatase-labeled goat anti-rabbit IgG antibody (Zemed Laboratory) is reacted, and then After washing, sodium p-nitrophenylphosphate was added, and after 30 minutes, the reaction was stopped by adding 5N sodium hydroxide, and the reaction product was measured by a microplate reader (Journal of Japanese Society of Pediatric Allergy, Volume 1). , Page 36, 1987). (2) Measuring method of amino acid composition For amino acids other than tryptophan, cysteine and methionine, the sample was hydrolyzed with 6N hydrochloric acid at 110 ° C for 24 hours, and tryptophan with barium hydroxide.
After alkaline decomposition at 110 ° C for 22 hours, cysteine and methionine were treated with formic acid, hydrolyzed with 6N hydrochloric acid at 110 ° C for 18 hours, and analyzed with an amino acid analyzer (Hitachi: 835 type) to determine the amino acid composition. I asked. (3) General component composition Protein, fat, carbohydrate, ash, and water can be measured by the official method (December 27, 1952, Ministry of Health and Welfare Ordinance No. 52 “Ministerial Ordinance Concerning Component Standards of Milk and Dairy Products” (Ii) (7) Testing method for component specifications of milk, etc.). Test Example 1 This test was conducted to examine the relationship between residual antigen activity and allergic property of whey protein degradation products. (1) Preparation of samples Using various whey proteins and enzymes, the following eight types of whey protein hydrolysates having various antigenic properties were prepared. Sample 1: Whey protein having a purity of 75% was dissolved in water at a concentration of 10% and adjusted to pH 8.0 with sodium hydroxide, and then pancreatin (Amano Pharmaceutical Co., Ltd.) was added to the whey protein at 1%. Was added at a rate of 50 ° C., hydrolyzed at 50 ° C. for 2 hours, and heat treated at 85 ° C. for 10 minutes. This solution was filtered using Hyflo Super Cell and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−3.5 . Sample 2: Whey protein with a purity of 75% was dissolved in water at a concentration of 10% and adjusted to pH 8.0 with sodium hydroxide, and then pancreatin (manufactured by Amano Pharmaceutical Co., Ltd.) was added to the whey protein at 3%. Was added at a ratio of 5%, hydrolyzed at 50 ° C. for 6 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−4.5 . Sample 3: Whey protein having a purity of 75% was dissolved in water at a concentration of 10%, adjusted to pH 7.0 with sodium hydroxide, and papain (manufactured by Nagase Seikagaku Co., Ltd.) was added to the whey protein at 3%. %, Added, reacted at 50 ° C. for 6 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^-5 . Sample 4: Whey protein having a purity of 75% was dissolved in water at a concentration of 10%, adjusted to pH 7.5 with sodium hydroxide, and then actinase (manufactured by Kaken Pharmaceutical Co., Ltd.) was added to the whey protein at 1%. %, Added, hydrolyzed at 50 ° C. for 2 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ⁻⁴ . Sample 5: Whey protein having a purity of 90% was dissolved in water at a concentration of 10% and adjusted to pH 7.5 with sodium hydroxide, and then pancreatin (Amano Pharmaceutical Co., Ltd.) was added to the whey protein at 1%. Was added at a ratio of 5 ° C., hydrolyzed at 50 ° C. for 6 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−3.5 . Sample 6: Whey protein with a purity of 90% was dissolved in water at a concentration of 10% and adjusted to pH 7.5 with sodium hydroxide, and then pancreatin (manufactured by Amano Pharmaceutical Co., Ltd.) was added to the whey protein at 3%. Was added at a ratio of 5 ° C., hydrolyzed at 50 ° C. for 6 hours, and heated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−4.5 . Sample 7: Whey protein having a purity of 90% was dissolved in water at a concentration of 10%, adjusted to pH 7.0 with sodium hydroxide, and papain (manufactured by Nagase Seikagaku Co., Ltd.) was added to the whey protein at 3%. %, Added, hydrolyzed at 50 ° C. for 6 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ⁻⁴ . Sample 8: Whey protein having a purity of 90% was dissolved in water at a concentration of 10%, adjusted to pH 7.5 with sodium hydroxide, and then actinase (manufactured by Kaken Pharmaceutical Co., Ltd.) was added to the whey protein 3 times. %, Added, hydrolyzed at 50 ° C. for 6 hours, and heat-treated at 85 ° C. for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^-5 . (2) Test method The allergic property was measured as follows. After birth 3
A group of 5 week-old male guinea pigs was used as a group and the samples were weighed at 100
50 mg / g was orally administered continuously for 3 weeks. After 3 weeks, a 10% solution of whey protein with a purity of 90% or more was infused intravenously, the onset of anaphylactic shock was observed, and the allergenicity was judged according to the following criteria, and the average value of each group was calculated. And the allergic property value was determined. In addition, the same test was carried out for the group to which the unhydrolyzed whey protein was administered and the group to which no whey protein was administered.

Allergic 3 Shock death due to anaphylaxis.

Allergic 2 shock is induced but not fatal.

Allergenicity 1 Weak symptoms such as nasal rubbing and piloerection.

Allergic property 0 No particular change was observed. (3) Test results The results of this test are shown in Table 1. As is clear from Table 1, the whey protein hydrolyzate having an antigen residual activity of 10 ⁻⁴ or less was found to have no allergenicity.

[0031]

[Table 1] Test Example 2 This test was conducted to investigate the relationship between residual antigenic activity and allergenicity of casein hydrolysates. (1) Preparation of Samples The following four types of casein hydrolysates that retain various antigenicities were prepared using various caseins and enzymes. Sample 1: Edible lactic acid casein having a purity of 85% (made by Newland Daily Board) was dispersed in water at a concentration of 10%,
Dissolve while adjusting the pH to 8.0 with sodium hydroxide, add pancreatin (manufactured by Amano Pharmaceutical Co., Ltd.) at a ratio of 1% to edible lactic acid casein, and hydrolyze it at 50 ° C for 2 hours to obtain 85 ° C.
The enzyme was inactivated by heating for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−3.5 . Sample 2: 85% pure edible lactic acid casein (made by Newland Daily Board) was dispersed in water at a concentration of 10%,
Dissolve while adjusting the pH to 8.0 with sodium hydroxide, add pancreatin (manufactured by Amano Pharmaceutical Co., Ltd.) at a ratio of 1% to edible lactate casein, hydrolyze it at 50 ° C for 6 hours, and 85 ° C.
The enzyme was inactivated by heating for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ^−4.5 . Sample 3: Edible lactic acid casein having a purity of 85% (Newland Daily Board) was dispersed in water at a concentration of 10%,
Dissolve while adjusting the pH to 7.0 with sodium hydroxide, add papain (made by Nagase Seikagaku Co., Ltd.) at a ratio of 1% to edible lactic acid casein, hydrolyze at 50 ° C for 6 hours, and 85 ° C.
The enzyme was inactivated by heating for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ⁻⁴ . Sample 4: Edible lactic acid casein having a purity of 85% (made by Newland Daily Board) was dispersed in water at a concentration of 10%,
Dissolve while adjusting the pH to 7.5 with sodium hydroxide, and add actinase (Kaken Pharmaceutical Co., Ltd.) at a ratio of 1% to edible lactate casein, hydrolyze at 50 ° C for 6 hours, and at 85 ° C.
The enzyme was inactivated by heating for 10 minutes. This solution was filtered using a hyfloss parcel and freeze-dried to obtain a sample. The residual antigenic activity of this degradation product was 10 ⁻⁴ . (2) Test method The allergic property was tested in the same manner as in Test Example 1 except that the above-mentioned 4 kinds of samples and edible lactic acid casein were used. (3) Test results The results of this test are shown in Table 2. As is clear from Table 2, the casein hydrolyzate having a residual antigenic activity of 10 ⁻⁴ or less was found to have no allergenicity.

[0032]

[Table 2]

[0033]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples. Example 1 13.6 kg of a whey protein hydrolyzate having a residual antigenic activity of 10 ⁻⁴ (hydrolysis protein equivalent 79.4%) obtained by hydrolyzing a whey protein having a purity of 75% in the same manner as in Sample 3 of Test Example 1. And 8.2 kg of a casein hydrolyzate having a residual antigenic activity of 10 ⁻⁴ (protein equivalent 87.4%) obtained by hydrolyzing casein having a purity of 85% in the same manner as in Sample 3 of Test Example 2 was dissolved in 140 kg of water. , 5kg of water dissolved in a predetermined amount of minerals, heated to 60 ℃, vegetable fat 2.0kg, malt dextrin 66.4kg, sugar 6.6kg,
And a predetermined amount of vitamins are mixed, and this mixed solution is sufficiently emulsified with a high-pressure homogenizer and sterilized at 120 ° C for 2 seconds.
It was spray-dried to obtain about 97 kg of a powdered anti-allergic milk-fortified composition. The ratio of the whey protein hydrolyzate to the total protein equivalent of the obtained powdery antiallergic breast milk-enriched composition was 60%, and the ratio of casein hydrolyzate was 40%.
Met. Table 3 shows the analysis values of the general component composition measured by the above-mentioned official method and the amino acid composition measured by the above method.

[0034]

[Table 3] Example 2 21.2 kg of a whey protein hydrolyzate with a residual antigenic activity of 10 ⁻⁵ (protein equivalent 85.1%) obtained by hydrolyzing a whey protein having a purity of 90% in the same manner as in Sample 3 of Test Example 1. And 13.7 kg of a casein hydrolyzate having a residual antigenic activity of 10 ^-4 (protein equivalent 87.4%) obtained by hydrolyzing casein having a purity of 85% by the same method as in Sample 3 of Test Example 2 was dissolved in 140 kg of water. , 5kg of water, added a certain amount of minerals, heated to 60 ℃, vegetable fat 1.0kg, malt dextrin 55.5kg, sugar 5.5kg
, And a predetermined amount of vitamins, and the mixture was sufficiently emulsified with a high-pressure homogenizer, sterilized at 120 ° C for 2 seconds, spray-dried, and about 97 kg of a powdered anti-allergic milk enriched composition. Got

The ratio of the whey protein hydrolyzate to the total protein equivalent of the obtained powdery anti-allergic breast milk-enriched composition was 60%, and the ratio of casein hydrolyzate was 40%. In addition, the general component composition measured by the above-mentioned official method,
The analytical values of the amino acid composition measured by the above method are shown in Table 4.

[0036]

[Table 4] Example 3 15.9 kg of a whey protein hydrolyzate having a residual antigenic activity of 10 ⁻⁵ (protein equivalent 85.1%) obtained by hydrolyzing a whey protein having a purity of 90% in the same manner as in Sample 3 of Test Example 1. And 18.9 kg of a casein hydrolyzate having a residual antigenic activity of 10 ⁻⁴ (protein equivalent 87.4%) obtained by hydrolyzing casein with a purity of 85% in the same manner as in Sample 3 of Test Example 2 was dissolved in 140 kg of water. , 5kg of water, added a certain amount of minerals, heated to 60 ℃, vegetable fat 1.0kg, malt dextrin 55.5kg, sugar 5.5kg
, And a predetermined amount of vitamins, and the mixture was sufficiently emulsified with a high-pressure homogenizer, sterilized at 120 ° C for 2 seconds, spray-dried, and about 97 kg of a powdered anti-allergic milk enriched composition. Got

The whey protein hydrolyzate was 45% and the casein hydrolyzate was 55% with respect to the total protein equivalent of the obtained powdery anti-allergic breast milk-enriched composition. In addition, the general component composition measured by the above-mentioned official method,
The analytical values of the amino acid composition measured by the above method are shown in Table 5.

[0038]

[Table 5]

[0039]

The effects of the present invention are as follows. (1) Since the anti-allergic breast milk-enriched composition of the present invention has substantially no allergenicity, it can be used for nutritional supplementation of premature infants having dietary allergic diseases. (2) Since the anti-allergic breast milk-enriched composition of the present invention has substantially no allergic property, it can be used for prevention of dietary allergic in premature infants having an allergic predisposition.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical indication location // A23L 1/29 8114-4B (72) Inventor Mikio Kajikawa 118 Minamibogaoka, Asahi-ku, Yokohama-shi, Kanagawa Morinaga Kibogaoka Dormitory (72) Inventor Takahiro Tsuchiyama 118 Minami Kibogaoka, Asahi-ku, Yokohama, Kanagawa Morinaga Kibogaoka Dormitory

Claims (2)

[Claims] 1. A nutritional supplement composition for premature infants to be added to breast milk, which contains at least the nitrogen source and fat described in the following (a) and (b).
(A) Nitrogen source: a whey protein hydrolyzate having a purity of at least 70% (by weight), and an ELISA (Enzyme linked immunosorbentassay) inhibition test method using anti-whey protein serum A hydrolyzate having an antigen residual activity of 10 ^-4 or less as measured by a method and a hydrolyzate of casein having a purity of at least 80% (by weight), which is an ELISA using an anti-casein serum (ELISA: Enzyme linked immunosorbent assay). ) A mixture with a hydrolyzate having an antigen residual activity of 10 ⁻⁴ or less measured by an inhibition test method (b) fat: 5% (weight) or less of the final product solid content. 2. The anti-allergic agent according to claim 1, wherein the nitrogen source is a mixture of whey protein hydrolyzate having 40 to 80% (by weight) and casein hydrolyzate having 60 to 20% (by weight). Sexual milk enriched composition.