JP3418200B2 - Hypoallergenic nutrition composition - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention uses a milk-derived κ-casein glycomacropeptide (hereinafter abbreviated as GMP) as a nitrogen source, and if necessary, amino acids, peptides,
The present invention relates to a nutritional composition having a low allergenicity, which contains a protein to improve its amino acid composition.

[0002]

2. Description of the Related Art Allergy, particularly food allergy, is an allergic disease that frequently occurs in infancy, and in recent years, its tendency to increase is remarkable. At present, the only basic treatment for food allergies is the removal of food allergens from the diet. The three major food allergens in Japan are milk, egg and soybean. However, they are protein-rich, inexpensive foods that are ingested frequently by the Japanese people, and their removal from the diet poses serious problems nutritionally or economically, food allergic patients and their Cause to family. Especially milk in infancy,
The removal of eggs and soybeans from the diet poses a major nutritional problem because it is in a strong growing season. Therefore, there is a strong social demand for a nutritious alternative that has no or low allergenicity to be given to patients with food allergies.

In the case of such food allergies, goat milk, animal meat milk, soybean milk, etc. have been used as an alternative food containing no causative allergen. However, these have various drawbacks described below.

Not only is goat milk unsuitable for infants, who account for the majority of food allergic patients, but also because goat milk protein has cross-reactivity with cow milk protein, In particular, it has been reported that it is not preferable to give this to infant patients (published by RAVEN RRESS Robert.
N. Hamburger edition “Food Intole
race in Infinity Allergol
Ogy, Immunology, and Gastro
enterology ”Vol. 1, pp. 253-2
65 (1989)).

[0005] In addition, although milk prepared from animal meat as a raw material is also manufactured and sold, animal meat allergic patients are not desired to give the animal meat because these animal meat also have cross-reactivity with milk protein. It has been reported (ibid.).

Further, in foreign countries such as Europe and America,
Soy milk has been recommended as an alternative to milk. But,
In Japan, food-allergic patients are often soybean-allergic because of the dietary habits unique to Japan, and because food soybean protein itself has a high allergenicity, food-allergic patients who are not soybean-allergic patients are soybean-allergic. It has been pointed out that continuous intake often causes soybean allergy (Yamashita et al. (1987) Pediatrics MOOK No. 48 pp. 228-241).

Therefore, at present, nutritional compositions containing amino acids or peptides as nitrogen sources are being sold. However, they also have the following drawbacks. That is, the formulas and nutritional compositions containing only free amino acids as the nitrogen source do not theoretically contain proteins having allergenicity, but have an unpleasant taste and odor derived from free amino acids and have a long duration. In addition to preventing intake over a period of time, it also has a high osmotic pressure, resulting in poor digestion and absorption (Nonomura et al. (1989) Allergic Clinical. 9. pp.
1035).

[0008] In addition, a milk prepared by hydrolyzing a protein derived from milk or soybean with an enzyme and having a reduced allergenicity is manufactured and sold. However, these formulas have unpleasant tastes and odors derived from amino acids and peptides produced by protein hydrolysis, which makes it difficult to take for a long period of time, and the allergenicity is not always removed. To alleviate the problem of taste, it is necessary to weaken the degree of protein hydrolysis, but in that case, allergenicity remains high.
On the contrary, if the protein is highly hydrolyzed in order to reduce the allergenicity, the taste is deteriorated (Arita et al. (1989) Allergy Clin. 9.pp1030).

[0009]

[Problems to be Solved by the Invention] A nutritional composition having a low allergenicity as a suitable substitute for providing food allergic patients including milk allergy has a low allergenicity or a sufficiently low allergenicity. It should have a good flavor, high nutritional value, good digestion and absorption properties, and enable long-term continuous use. However, the above requirements have mutually contradictory properties to be simultaneously realized within the scope of the prior art, and a nutritional composition or hypoallergenic milk having all of them has not existed until now. The absence of such nutritional composition is a serious problem in health and hygiene of food allergy patients, which has been increasing in Japan in recent years, and the present invention provides a novel nutritional composition with low allergenicity, which has never existed before. By doing so, the problem is solved.

[0010]

[Means for Solving the Problems] The inventors of the present invention have conducted extensive studies to develop a nutritional composition having a low allergenicity or an allergenicity that satisfies all the above-mentioned requirements. It was found that GMP has no allergenicity, and the present invention was accomplished by producing a nutritional composition using this as a nitrogen source. That is, the present invention relates to a nutritional composition for a low allergen having a low allergen property, which contains GMP derived from milk as a nitrogen source. The hypoallergenicity in the present invention means that the allergenicity is low or the allergenicity is not present.

GMP is a known sialic acid-binding peptide produced when rennet or pepsin is allowed to act on milk κ casein, and is disclosed by Tanimoto et al. (JP-A-2-2765).
42) or Dosako et al. (JP-A-63-28419).
A large amount can be prepared from milk by the method of Japanese Patent No. 9).

GMP is a tasteless, odorless, stable to heat, and extremely soluble substance. Since it is made of casein as a raw material, whey such as β-lactoglobulin, which is often a problem in milk allergy, is present. Contains no protein. Further, GMP has a high molecular weight of about 9000, which is higher than that of free amino acids and peptides.
Not only the osmotic pressure per unit amount of nitrogen is low, but also GM
When preparing a nutritional composition containing lipids using P as a raw material, GMP has the same action as a surfactant, and therefore reduces the problem of lipid emulsification that is encountered when using peptides or free amino acids as raw materials. be able to. The above characteristics, in producing a nutritional composition with low allergenicity,
It will be a great advantage. Furthermore, as a major characteristic, GMP
Has an excellent infection-protecting ability against microorganisms and viruses, so that a nutritional composition using this as a raw material can also be expected to have an infection-protecting effect.

Next, the amino acid composition of GMP is shown in Table 1.

[Table 1]

GMP is deficient in or low in some essential amino acids. Therefore, in the case of short-term use, it is possible to form a nutritional composition having a low allergenicity by using only GMP as the only nitrogen source, but when preparing a nutritional composition to be used for a long term in consideration of nutritional value. Includes at least 1 selected from the group consisting of a mixture of free amino acids, peptides and proteins so that the amino acid balance is suitable for the age of the target food allergy patient.
It is necessary to add an appropriate source of amino acids to obtain an appropriate amino acid composition.

The nutritional composition thus obtained can be used as a milk powder, an enteral nutritional agent, a tube nutritional agent, a dietary supplement, and the like. In this case, a free amino acid mixture, a peptide, a protein, a carbohydrate, a lipid, an emulsifier, vitamins, minerals, etc. may be appropriately added while taking care not to cause an excessive increase in osmotic pressure or an increase in allergenicity. I can. In particular, when administered to infants, it is necessary to mix and enhance the following amino acid with GMP according to the amino acid composition of human milk so that an amino acid equivalent to or similar to the amino acid composition of human milk can be taken. desirable.
L-leucine, L-lysine, methionine, L-cysteine, L-cystine, phenylalanine, L-tyrosine,
L-tryptophan, L-arginine, L-histidine, L-valine, L-isoleucine and glycine

The nutritional composition thus prepared is
An unprecedented new type of low allergenic nutritional composition that has good taste, no allergenicity, high nutritional value and digestive absorption, and has the protective ability against infection of GMP. Becomes

[0017]

EXAMPLES Next, the present invention will be described more specifically by showing examples. Example 1 1 kg of WPC derived from cheese whey was dissolved in 50 l of water at 50 ° C., and 35% hydrochloric acid was added to adjust the pH to 3.5. This solution was subjected to UF with a UF membrane having a molecular weight cut off of 20,000.
Device (module: DDS 36 type, ultrafiltration membrane: DD
The solution was passed through S company 61 pp). Liquid temperature 50 ℃, operating pressure 0.4
The operation was performed at MPa to obtain concentrated liquid 101 and permeated liquid 40 l. To this permeate, add 10 ml of 25% NaOH solution and p
After setting to H7, UF treatment was performed again using the same UF device under the same conditions to obtain 5 l of a concentrated liquid. A diafiltration (DF) was performed while maintaining the liquid volume at 5 L while adding deionized water. Since the electric conductivity of the concentrated solution became constant when the amount of water added reached 25 l, the water addition was stopped and further concentrated to obtain 0.2 l of the desired concentrated liquid. The GMP concentrate thus obtained was sprayed at a pressure of 1.0 kg / c.
m ^2, spray dried exhaust air temperature 80 ° C. (spray-drying apparatus: Yamato Scientific Co., Pal bis Mini Spray) to, GMP powder 18
g was obtained.

10 g of GMP obtained by the above method
Then, 2.8 g of the free amino acid mixture having the composition shown in Table 2 was mixed to prepare a GMP amino acid mixture. This GM
A mixture of 10 g of P-amino acid mixture, 60.5 g of a mixture of sucrose, a soluble polysaccharide and a sugar consisting of tapioca starch, 3.5 g of a mineral mixture and 2.2 g of a vitamin mixture were added to 700 ml of warm water.
Dissolved in ml. To this, 27.8 g of purified vegetable fat was mixed and homogenized. The obtained solution was sterilized, concentrated by a conventional method, and dried to obtain 100 g of milk powder. When this powdered milk was dissolved in warm water so as to have a solid content of 13%, it had good solubility, had no separation of fat, had good taste, and had the same level as ordinary infant formula. It had an osmotic pressure.

[0019]

[Table 2]

For the purpose of removing fat from the milk powder thus obtained and more accurately obtaining data for evaluation of the allergenicity due to the nitrogen source, the powdered milk was dissolved in warm water at 100 mg / ml, and 5000 rpm was added. After centrifuging for 30 minutes, the lower layer was collected and used as skim milk. 200 μl of this skim milk
10% of DTP (Chiba Serum Research Institute Pertussis, Tetanus, Diphtheria 3 vaccine)
To 10 week-old female slc: ddY mice, 0.5 ml was intraperitoneally administered per mouse. Thereafter, every other week, the above-mentioned skim milk was intraperitoneally administered 6 times at a ratio of 5 μl / 0.5 ml physiological saline / mouse. Three days after the final sensitization, blood was collected from the heart and serum was collected. Although the GMP-specific antibody was detected by the immune double diffusion method (Octalony method),
No GMP-specific antibody could be detected in any of the mice.

Example 2 Powdered milk obtained in the same manner as in Example 1 was used as skimmed milk in the same manner as in Example 1, and 100 μl thereof was added to 10 ml of DTP.
0.5 ml of 9 ml of slc / ddY female mice 4 weeks old was intraperitoneally administered, and then 100 μm of the skim milk was added.
l / 0.5 ml saline / mouse was intraperitoneally administered 6 times every other week, and blood was collected in the same manner as in Example 1,
Serum was obtained. An attempt was made to detect a GMP-specific antibody by the double immunodiffusion method, but no specific antibody was detected in any mouse.

Example 3 Powdered milk obtained in the same manner as in Example 1 was used as skimmed milk in the same manner as in Example 1, and 200 μl thereof was dissolved and mixed in 10 ml of DTP to give 9 slw / ddY mouse females 4 weeks old. 0.
5 ml each was intraperitoneally administered twice at 1-week intervals, and 1 week later, intraperitoneally administered at a ratio of skim milk 200 μl / 0.5 ml physiological saline / mouse, and 3 days later, blood was collected in the same manner as in Example 1, Serum was obtained. GMP by immune double diffusion
An attempt was made to detect a specific antibody, but no specific antibody was detected in any mouse.

Example 4 Powdered milk obtained in the same manner as in Example 1 was used as skimmed milk in the same manner as in Example 1 and 200 μl thereof was dissolved and mixed in 10 ml of DTP to give 9 slc / ddY mouse females 4 weeks old. 0.
Administer 5 ml intraperitoneally and skim milk every other week 2
It was intraperitoneally administered three times at a ratio of 00 μl / 0.5 ml physiological saline / mouse, and 3 days after the final sensitization, blood was collected in the same manner as in Example 1 to obtain serum. An attempt was made to detect a GMP-specific antibody by the double immunodiffusion method, but no specific antibody was detected in any mouse.

Example 5 Caseinate acid and GM prepared as in Example 1.
A modified AIN-76 purified feed (according to the formulation by Oriental Yeast Co., Ltd.) having a composition as shown in Table 3 was prepared using the P-amino acid mixture as a nitrogen source, and 10 mice per group (BALB / c, 3 weeks old). Male) for 5 weeks,
Weight gain over time was measured. The results are shown in Fig. 1. The figure shows the changes over time in the average body weight of the mice in each group. As is clear from the figure, the weight gain of the GMP amino acid mixture group is better than that of the casein diet group.

[0025]

[Table 3]

[0026]

INDUSTRIAL APPLICABILITY As described above, the present invention uses a milk-derived non-allergenic GMP as a nitrogen source, so that a hypoallergenic nutritional composition can be obtained. Furthermore, in the present invention, GMP derived from milk is mixed with free amino acids, peptides, proteins, etc.
By improving the defects of the amino acid composition peculiar to MP, it has good taste, has no allergenicity, has high nutritional value and digestive absorbability, and has the ability of GMP to prevent infection. It was possible to provide a new type of nutritional composition having low allergenicity, which is not available in the market.

[Brief description of drawings]

1 shows a growth curve of a mouse when a diet containing a GMP amino acid mixture according to Example 5 and a normal casein diet were administered to the mouse.

[Explanation of symbols]

●-● GMP amino acid mixture feed administration group □-□ Casein feed administration group

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Tadashi Iwata               Saitama Prefecture Kawagoe City Oita 6083 No. 7 Kawagoe               Green Park L1-207                (56) Reference JP-A-2-276542 (JP, A)                 JP-A-63-233911 (JP, A)                 JP-A-63-284133 (JP, A)                 JP-A-49-124244 (JP, A)                 JP-A-52-94453 (JP, A)                 JP-A-52-139735 (JP, A)                 Dairy Cooperative Material, Vol. 40 (1990) 117               -129 pages

Claims (4)

(57) [Claims] 1. A nutritional composition for low allergen , comprising a milk-derived κ-casein glycomacropeptide as a nitrogen source. 2. A nutritional composition for a low allergen , comprising a milk-derived κ-casein glycomacropeptide and at least one selected from the group consisting of amino acids, peptides and proteins as a nitrogen source. 3. L-leucine, L-lysine, methionine, L-containing κ-casein glycomacropeptide derived from milk and at least one selected from the group consisting of amino acids, peptides and proteins as a nitrogen source. By enhancing at least one amino acid selected from the group consisting of cysteine, L-cystine, phenylalanine, L-tyrosine, L-tryptophan, L-arginine, L-histidine, L-valine, L-isoleucine and glycine Nutritional composition for low allergen 4. The nutritional composition for hypoallergen is milk powder.
The nutritional set for hypoallergen according to claim 1.
Adult