DD297304A5 - PROTEIN, PEPTIDE AND AMINO-ACID MIXTURES WITH OPTIMIZED AMINOSA-ACID COMPOSITION AND THEIR USE FOR THE PREPARATION OF BREW AND BIRTH SEED FOODS AND ADDITIVES TO WOMEN'S MILK - Google Patents

Abstract

Protein, peptide and amino acid mixtures of optimised amino acid composition are provided which can be used as the protein base for the preparation of additives for women's milk and as a protein base for producing milk foods for prematurely born babies and other infants. The mixtures according to the invention contain 18 essential amino acids in a defined ratio, this ratio being calculated and selected on the basis of the nutritive protein content of women's milk.

Description

Field of application of the invention

The invention relates to protein, peptide and amino acid mixtures with optimized amino acid composition and their use for the production of preterm and infant formulas and of supplements for women's milk.

Characteristic of known prior art

The amino acid requirement of the infant is usually derived by type and amount from the amino acid composition of breast milk. The basis for this is the total protein contained therein. Breast milk is therefore used by a number of official bodies (FAO / WHO, ESPGAN) as the basis for assessing protein quality (chemical score) in infant formulas (1,2,3). Since the amino acids in the milk of women from different proteins with different amino acid composition, of which z. B. the immunoglobulin A and lactoferrin leave the gastrointestinal tract virtually undigested (4,5,6), the infant is not all the amino acids of breast milk for the synthesis of endogenous protein available. Therefore, the total amino acid composition of breast milk does not reflect the ideal amino acid pattern for the Chemical Score and is therefore not optimal as a basis for evaluating breast milk.

So far, it has been customary to orient the protein quality of industrially produced infant formulas and infant formula on the total protein of the milk of women (amino acid composition, chemical score). Conventional or known foods for infants and premature babies were therefore compiled on the basis of this Chemical Score. However, in infants and preterm infants fed on such known diets, serum amino acid imbalances and elevated urea levels, compared to those of breastfed infants, have often been observed. These imbalances are characterized by high threonine, methionine, valine, isoleucine, leucine, phenylalanine and tyrosine levels and are based on the nutritionally poorly balanced amino acid composition of conventional infant formulas, which as a protein base usually cow's milk protein with a specific casein, whey protein Ratio, e.g. 80/20 or 40/60 or 60/40.

Children fed with such known diets thus differ markedly from breastfed children with regard to the physiology of their amino acid metabolism, with a tendency to serum amino acid imbalances and high levels of uric acid. For the sake of clarity, it should be noted at this point that the known diets contain sufficient fats and carbohydrates for energy production and that the statements made here in connection with the amino acids are subject to this condition.

In premature babies and young infants, abundant protein also causes relatively severe renal stress, which can be clinically demonstrated by increased excretion of amino acids and their metabolites in the urine (aminoaciduria, special cystinuria, methioniuria, sulphate excretion).

In addition, preterm infants have a significantly higher protein requirement compared to those born in infants, which is usually derived from fetal protein storage during the 26th or 36th week of gestation. Assuming an 80% protein utilization, Pohlandt and Kupferschmid (7) calculated a requirement of 2.7 g / kg / day for the 30th to 31st postconceptional week and 1.3 g / kg / day for the 38th week. This need can not be covered by milk of women (protein content approx. 1%), which leads above all to a too slow growth of the infant.

To meet the specific needs of the premature infant, special premature baby foods with a high energy density and a relatively high protein content based on cow's milk protein with a casein / whey protein ratio of 40/60 and a protein content of 1.5 to 2.1% developed.

In addition, so-called "human milk engineering" has become more important in recent years, with women's milk being supplemented with isolated women's milk protein, but for understandable reasons, this is difficult to achieve in preterm infants and infants in intensive care units.

Object of the invention

The object of the present invention is to provide a protein and amino acid base which can be used for the production of foods and in particular infant formulas or of additives to breast milk for the purpose of premature infant feeding. This makes it possible to optimally cover the amino acid requirements of premature babies and infants in a qualitative and quantitative manner.

-3- 297 304 Darling of the essence of the invention

The object of the present invention is to provide improved protein, peptide and amino acid mixtures with optimized To provide amino acid composition used in the preparation of foods and in particular Infant milks or for the production of supplement in breast milk for the purpose of premature baby feeding

can be used.

This problem is solved by the teaching of the claims. It has now surprisingly been found that in the diet of infants with the above, known

However, imbalances of serum amino acids do not occur when adapted or partially adapted diets are observed

Infants are fed with a diet whose amino acid composition is the so-called nutritional protein content

the woman's milk corresponds. The amino acid composition of the protein used in this diet according to the invention,

Peptide and amino acid mixture was thus in contrast to the previous practice for the assessment of protein quality

as well as the optimization associated with infant milk formulas not based on the amino acid composition of the total human milk protein, but on the basis of the so-called nutritive protein content of the breast milk.

It has also been found, surprisingly, that for the preparation of the protein, peptide and Amino acid mixtures (hereinafter only the term amino acid mixtures is used, but for a

such protein, peptide and amino acid mixture is) can use amino acids in free form. If _o example, do not see or be very difficult to achieve the desired amino acid composition by mixing different, available commercially for example proteins, proteins and / or peptides, one can amino acids in free

Add form to achieve that these amino acid mixtures claimed the amino acids listed in the Area included. According to the invention, an amino acid mixture with the following amino acid composition is thus provided:

amino acids g / 100g total amino acids Aspartic acid + asparagine 7.69 to 10.41 threonine 3.62 to 4.90 serine 3.33 to 4.51 Glutamic acid + glutamine 15.71 to 21.25 proline 8.70 to 11.76 glycine 1.27 to 1.73 alanine 2.53 to 3.43 Cystine + cysteine 1.45 to 2.17 valine 4.56 to 6.16 methionine 1.42-2.12. isoleucine 5.58 to 7.54 leucine 9.04 to 12.24 tyrosine 3.98 to 5.38 phenylalanine 3.19 to 4.31 histidine 2.49 to 3.37 lysine 6.56 to 8.88 arginine 1.93 to 2.69 tryptophan 1.72 to 2.32

The mixture according to the invention must contain the amino acids in such a form that they are digestible for the infant

are. In other words, only such proteins, peptides and hydrolyzates etc. are considered in the composition of the inventive mixtures which are broken down into smaller "units" (if required) in the infant's gastrointestinal tract and then resorbed Those proteins etc. which can not be broken down by the infant into a resorbable form and thus excreted are thus disregarded The above table therefore refers only to those amino acids which are present in "resorbable form".

In order to avoid the imbalances mentioned above, it is important that all listed amino acids in the

claimed claimed in the invention food are present in the inventive area. Of course, these imbalances need not necessarily and to a great extent occur when one of the listed amino acids in one.

Quantity is present, which is slightly outside the specified range. However, such imbalances can already then

very pronounced S6in, if only one amino acid is present in an amount which is considerably outside the stated range.

For the production of the amino acid mixtures according to the invention, one will of course try for reasons of cost,

as little as possible to use free amino acids, since the latter are more expensive than common proteins used for the dietetc. The free amino acids are therefore used to complete a mixture of proteins, etc., and thus to optimize so that the mixture has the desired amino acid composition.

A prerequisite for the optimization of protein mixtures is that of all raw materials used in the development of Mixtures are used, the amino acid composition either known from the outset or by Analysis has been determined. In principle, each protein is characterized by its own amino acid composition. Its biological value

depends essentially on the relative amounts of the occurring amino acids. From proteins with different biological value can be obtained by mixing nutritionally high-quality products. Usually

is thereby added to a protein with the limiting amino acid X, a protein that contains just this amino acid X in high concentration.

The amino acid data are obtained by known analytical methods by z. B. the raw material samples hydrolyzed with 6molarer hydrochloric acid with the exclusion of atmospheric oxygen for 16 h. Cystine and methionine are additionally determined after performance with performic acid, as well as tryptophan separately by a known conventional HPLC method (Inoue et al., Anal. Biochem. 1983, Vol. 132, pp. 468-480).

The following amino acids are included in the calculation for optimization: a) essential L-amino acids: threonine, cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine and tryptophan; b) nonessential L-amino acids: aspartic acid, serine, glutamic acid, proline, glycine, alanine and arginine.

In carrying out the necessary calculations, of course, must be satisfied the fact that some raw materials are not made up only of amino acids. The same applies to combining the raw materials to produce the mixture according to the invention.

As used herein, the term "protein, peptide and amino acid mixtures" refers to mixtures based on proteins, peptides, hydrolyzates, etc., and pure amino acids, so that proteins, peptides and hydrolyzates may be present alone or together may contain different proteins and / or peptides For the purpose of optimization, amino acids may be present in pure form In other words, the amino acids present in these mixtures after preparation of the mixtures according to the invention need not necessarily be derived from a protein or peptide or a component thereof The optimized amino acid composition, of course, refers to the sum of the total of the amino acids present in a mixture, and the mixtures according to the invention are in question here the amino acids preferably in the claim 2 listed amounts.

As already mentioned above, an essential idea of the present invention is that the mixtures according to the invention with respect to their amino acid composition corresponds to the amino acid composition of the so-called nutritive protein content of the breast milk approximately. This amino acid composition according to the nutritional protein content is shown in Table I at the end of the description. The proteins which belong to this nutritive protein fraction are essentially caseins, α-lactalbumin and serum albumin. Commercially available proteins or peptides and commercially available proteinaceous raw materials, such as cow's milk, cow's milk proteins, isolated cow's milk protein fractions, protein hydrolysates, peptides and L-amino acids, may serve as raw materials for the mixtures according to the invention. Other animal and vegetable proteins, such as soy protein, goat's milk protein, beef protein, etc. can also be used.

He.indungsgemäß thus cow milk proteins, isolated cow's milk protein fractions, protein hydrolysates, peptides and / or L-amino acids and other animal and vegetable proteins, such as soy protein, goat's milk protein, beef protein, etc. with peptides (including from hydrolysates) and / or L-amino acid in different weight ratios are combined in such a way that a product with nutritionally optimal for baby nutritionally optimal amino acid pattern and high biological value corresponding to the nutritional protein content of the breast milk or any other reference protein.

The mixtures according to the invention with an optimized amino acid composition can be used according to the invention as an additive for protein fortification of breast milk or as a basis for the preparation of premature infant and infant foods.

In the clinical trial it has been shown that the amino acid patterns in the blood of infants fed with breastmilk plus a supplement which corresponds in its amino acid composition to the nutritive portion of breastmilk are balanced and those of children fed with breastmilk plus breastmilk protein enrichment , correspond. The corresponding results of this clinical examination are explained in more detail below. This can not be achieved with conventional infant and premature infant formula. As a rule, appropriately nourished children have unbalanced amino acid patterns in the blood, which indicates imbalances and is an indication of too much stress on the immature child's kidney.

The inventively developed mixtures have a physiologically extracted amino acid composition, avoid, as shown, unphysiological metabolic stress and lead to good prosperity of children and a balanced metabolism.

The use of the mixtures according to the invention as a basis for industrially manufactured preterm and infant milk formulas has been clinically proven and leads to the physiological thriving of children. Hei is to have the balanced metabolism, especially the blood amino acid levels, which correspond to those breast milk-fed infants more than those fed with conventional infant and premature baby milk formulas.

The technical and chemical-physical properties of the protein mixtures according to the invention should be such as to form a food which is sufficiently soluble and can be administered without difficulty, together with breast milk or industrially produced premature baby and infant formulas. Amino acids and protein concentrate in powder form can be mixed dry and granulated. However, it has been shown in practice that such mixtures are unstable, can tend to segregate and, above all, are usually poorly soluble.

The invention therefore also provides a process for the preparation of additives (supplements) for breast milk as well as premature infant and baby food based on a protein, peptide and amino acid mixture provided according to the invention, wherein the mixtures provided according to the invention, optionally together with vitamins, trace elements, Minerals, fats (eg., Milk fat, vegetable fat) and / or carbohydrates (eg., Lactose, maltodextrin, starch) and suitable emulsifiers in a liquid medium, for example water and / or lean / whole milk, dissolves or dispersed and / or emulsified and then subjected to a heat treatment. The subsequent drying of the mixture has the result that all components are homogeneously distributed and subsequent segregation is no longer possible.

One proceeds in particular so that one pre-dissolves the components of the formulations in a corresponding amount of water or

disparates, setting a dry matter of 40 to 50%. In the predetermined amount of water is ⁰ to 60 Cerwärmt to 80, dissolved or dispersed one after the other protein concentrates, L-amino acids, the mineral and other

Ingredients of the formulations (compare the examples) and stirred with an intensive mixer homogeneous and lump-free. The mixture can be heated to 95 ^° C. and sterilized by means of UHT treatment in order to obtain a flawless bacteriological To maintain the quality of the final product. This is followed by a homogenization of the approach and then a Spray-drying the concentrate using spray-drying equipment with both nozzles and disks

can be brought.

The spray-dried powder is homogeneous, easy to dose, slightly soluble, does not segregate and can be packed immediately. The Durability of the powder thus obtained is good and is at least two years. The powder can in another Be granulated or instantized. Supplements (supplements) for breast milk, preterm and infant formulas are manufactured in

the way that the appropriate amounts of protein concentrate and / or skimmed milk or whole milk are first dispersed in water at 60-8O ⁰ C, it being assumed that a dry matter of 30-50%. Thereafter, the L-amino acids, carbohydrates (eg lactose, maltodextrins, starch) and minerals are successively added and stirred in without lumps.

Conveniently, an intensive agitator is used for the preparation of the approach. The emulsifiers are in the fat

pre-dissolved; The heated to 60-80 ⁰ C fats are added to the approach and stirred in evenly. Subsequently, the vitamins are dissolved in the batch. The finished batch is homogenized (100-200 bar) and processed with spray driers into powder.

The powders thus obtained can be instantized in further steps. The production of ready-to-use, liquid premature babies and baby milk formulas follows a similar course Scheme. The specification of water or milk is designed so that the corresponding concentration of the dry matter

between 12-16%.

Instead of intact proteins, hydrolyzed proteins (e.g., whey protein hydrolysates, casein hydrolysates, Soy protein hydrolyzates, collagen hydrolysates) are used to prepare protein mixtures of optimal biological value

manufacture. As a result, it is possible according to the invention to also produce hypoallergenic protein mixtures and protein masterbatches for producing hypoallergenic infant foods.

When calculating the amino acid values of the mixtures according to the invention, the following should be considered. In general, the amino acid value analyzed for a protein or peptide is expressed in g and expressed as 100 g

per protein or peptide. Now, however, the relative amino acid composition is different for each protein or peptide. In addition, contain 100g of protein or peptide more than 100g of amino acids, as in the splitting of the Peptidbzw. Water is incorporated so that the sum of the protein or peptide amino acid is greater than 100g. For example, the sum of amino acids in cow's milk protein is about 110 g and serum albumin about 108 g, and there are also proteins and peptides in which 100 g of protein or peptide contains 125 g and more amino acids.

In order to take this circumstance into account, the calculation of the amino acid values based on the total amino acids takes place

based on the expressed in g molecular weights of the free amino acids minus the molecular weight of water. The calculation of the total amino acids is based on the reduced by the water content

Molecular weights of the respective amino acids. However, if the values are not related to the total amino acids or the sum of the amino acids (eg g / 100g Amino acids), but on a food or other product, then those values are assumed that are not

are reduced by the molecular weight of water. In other words, the molecular weight of the free amino acid, including the water content, is included in the calculation.

If, by the way, amino acids are mentioned, this naturally refers to the L-amino acids. Clinical Trials with Optimized Protelium / Amino Acid Composition Diets The following is a more detailed explanation of the clinical examination already mentioned above, which is carried out using inventive Mixtures was performed.

1) Protein supplement for the fortification of breast milk for the nutrition of preterm infants and small-for-date-children

In the study, premature babies were fed human milk supplemented with an amino acid optimate supplement

was. As a control group preterm infants were used, in which the human milk with isolated proteins from human milk enriched.

The amino acid-optimized supplement had the following composition:

Protein (N χ 6.38) 20.1% carbohydrates 70.4% fat 0.6% minerals 8.4% vitamins 0.5%

Throughout the duration of the study (25 days), optimal growth was achieved with a weight gain averaging 17.3 g / kg / d, a length increase of 1.1 cm / week and an increase in head circumference of 0.9 cm / week. Comparable values were measured in the control group.

The optimized supplement, in addition to the very good growth of infants, also resulted in plasma amino acid levels comparable to the plasma levels of children receiving breast milk supplemented with breast milk proteins. The following Table 1 shows a comparison of the plasma amino acid levels of the two nutritional groups.

Table 1: plasma amino acid levels of premature babies in pmol%; A: human milk + optimized supplement; B: human milk + isolated human milk proteins

A B

9.1 ± 1.7 1.3 ± 0.1

9.3 ± 1.9 23.2 ± 1.5 14.8 ± 1.8

8.2 ± 1.3 16.7 ± 2.2

51.7 ± 3.2 27.4 ± 6.7

18.8 ± 2.0 27.7 ± 6.4

2.5 ± 0.2 15.8 ± 1.8

4.4 ± 0.7

3.0 ± 0.4

7.1 ± 1.1 11.1 ± 1.6 18.6 ± 4.3

5.0 ± 0.9 14.4 ± 3.5 20.0 ± 2.8

8.4 ± 1.6

9.0 ± 1.3

2) Premature baby food with optimized protein / amino acid mixture (liquid) The food described here was developed for premature babies who can not or can not be sufficiently nourished with breast milk.

In one study, premature babies were nourished with this food, comparing the growth, plasma amino acid levels, and energy and nitrogen balances with children fed exclusively with human milk.

The amino acid-optimized diet had the following main components:

taurine 9.3 ± 2.4 aspartic acid 1.2 ± 0.3 hydroxyproline 8.4 ± 2.2 threonine 16.9 ± 4.3 serine 13.0 ± 2.7 asparagine 5.7 ± 1.4 glutamic acid 10.8 ± 1.2 glutamine 38.1 ± 17.6 proline 21.8 ± 7.8 glycine 17.2 ± 3.8 alanine 26.8 ± 10.4 citrulline 1.9 ± 0.7 valine 12.9 ± 3.0 cystine 3.4 ± 1.1 methionine 2.5 ± 0.6 isoleucine 6.9 ± 1.3 leucine 10.6 ± 2.3 tyrosine 12.0 ± 4.4 phenylalanine 5.3 ± 0.7 ornithine 9.1 ± 3.8 lysine 14.0 ± 4.7 histidine 7.8 ± 1.5 arginine 7.0 ± 2.9

Protein (N χ 6.25) 1.67% carbohydrates 4.40% fat 4.00% water 86.00%

Table 2 shows a comparison of weight gains, length growth, and increases in head circumference of the preterm neonates examined.

Table 2: Weight gain, length growth, increase in Kophmfanges; A: optimized premature baby food B: human milk

A B

increase in weight

(g / kg / d) 16.3 17.0

linear growth

(cm / week) 1.8 1.3

Increase in head circumference

(cm / week) 1.1 0.9

Both energy and nitrogen balances led to very similar results for both groups.

With the optimized premature infant formula plasma amino acid levels could be achieved, which were comparable to those of human milk-fed premature babies.

In the following, preferred mixtures according to the invention are described in more detail by way of examples.

example 1

Protein supplementation for the enrichment of breast milk for the nutrition of premature babies and small-for-date children.

1.1. composition 4.786% g / 100g g / 100g demineralized whey protein product amino acids (Protein Content (N x 6.38) -: 76% 4.616% 1.02 8.79 sodium caseinate 0.136% 0.58 4.91 (Protein Content (N x 6.38) -: 90% 0.315% 0.53 4.37 L-histidine 0.398% 2.06 18,02 L-isoleucine 0.339% 1.20 10.09 L-leucine 0.078% 0.19 1.44 L-lysine-L-glutamate 0.145% 0.38 3.02 L-tryptophan 0.364% 0.21 1.93 L-VaMn 0.058% 0.62 5.23 Magnesium L-aspartate 0.204% 0.24 2.10 L-cystine 0.048% 0.76 6.53 L-glutamic acid 0.485% 1.22 , 0.48 L-glycine 0.170% 0.51 4.58 L-proline 0.068% 0.41 3.64 L-tyrosine 0.067% 0.33 2.91 L-phenylalanine 0.830% 0.86 7.52 taurine 6.000% 0.30 2.68 common salt 0.500% 0.22 2.00 calcium glycerophosphate 80.393% 11.64 100.24 » vitamin mix 100.000% Maltodextrin III 5) b) Amino acid analysis (g / 100g product, g / 100g amino acids) Aspartic acid + asparagine threonine serine Glutamic acid + glutamine proline glycine alanine Cystine + cysteine valine methionine isoleucine leucine tyrosine phenylalanine histidine lysine arginine tryptophan

*) Deviation from 100 due to analytic conditions badingt

1.3. manufacturing

Batch size: 100 kg powder

In a heatable container with intensive agitator, z. B. Ultraturrax, Y-Stral, about 451 water to 60-8O ⁰ C warmed.

Successively demineralized whey protein and sodium caseinate are stirred in and dispersed without lumps.

Thereafter, successively L-histidine, L-isoleucine, L-leucine, L-lysine L-glutamate, L-tryptophan, L-VaMn, magnesium L-aspartate, L-cystine, L-glutamic acid, L-glycine, L -Proline, L-tyrosine, L-phenylalanine and taurine added to the batch.

The water-soluble L-amino acids are conveniently pre-dissolved in slightly warm water. This gives a better distribution in the approach.

After complete dissolution of all components or dispersion, the addition of common salt (pre-dissolved in some warm water), calcium glycerophosphate, maltodextrin and vitamin mix.

After completion, lump-free dissolution, the concentrate is heated to 90-95 ° C (z. B. means saddle Beer superheater) cooled to 65-7O ⁰ C and then homogenized at 60-100bar.

The homogenate is between stacked in a heated tank at about 65-7O ⁰ C and then immediately spray-dried and sieved (z. B. Algaier sieve).

The powder thus obtained is taken in sacks or containers and packed in bags or cans.

Further instentization and / or granulation processes can be connected.

Example 2

Protein supplementation for the enrichment of women's milk for the nutrition of premature babies.

2.1 Composition 76% 1.745% Eutmixed whey protein 90% 6.509% (F'rotein content-fN χ 6.38) -: sodium caseinate 93% 2.121% (Protein content- (N χ 6.38) -: 0.064% 1-lactalbumin 0.280% yrotinine content (N χ 6.38) -: 0.280% L-histidine 0.120% L-isoleucine 0.055% L-leucine 0.600% L-valine 0.409% Magnesium L-aspartate 0.040% L-glutamic acid 0.082% L-proline 0.067% L-tyrosine 0.830% alanine 6.000% taurine o, roo% common salt 80.298% calcium glycerophosphate 100,000% vitamin mix Maltodextrin (DE5) 100 g 3g · 2.2. analysis 10.2 g 0.31 g a) Type analysis: 80.9 g 2.43 g Protein (N x 6.38) 3.0g 0.09 g (MitAminosäuren-N) 0.2 g 0.01g carbohydrates 3.0 g 0.09 g ash fat water

* Dosage: to 100ml milk for women = Sg product

b) Amino acid analysis (g / 100g product, g / 100g amino acids)

g / 100g g / 100g

Product amino acids

Aspartic acid + asparagine 1.17 9.02 threonine 0.55 4.16 serine 0.58 4.28 Glutamic acid + glutamine 2.31 18,09 proline 1.34 10.08 glycine 0.23 1.56 alanine 0.42 2.98 Cystine + cysteine 0.22 1.81 valine 0.69 5.20 methionine 0.26 2.04 isoleucine 0.85 6.54 leucine 1.37 10.54 tyrosine 0.57 4.58 phenylalanine 0.51 4.06 histidine 0.38 3.00 lysine 1.00 7.82 arginine 0.32 2.56 tryptophan 0.25 2.03 13.02 100.36

2.3. manufacturing

The procedure is as described in Example 1. Example 3 Hydrolyzate '/ Amino Acids Mixture as an easily digestible additive to women's milk for the nutrition of premature babies and as

Hypoallergenic additive to breast milk for infants.

3.1. composition : 90% 5.125% enzymatic hydrolyzate of whey protein 5.388% (Protein Content (N x 6.38) -: 0.075% : 79% 0.113% enzymatic hydrolyzate of casein 0.213% (Protein Content (N x 6.38) -: 0.325% Glutathione, reduced 0.250% L-histidine 0.088% L-isoleucine 0.038% L-leucine 0.266% L-lysine-L-glutamate 0.438% L-tryptophan 0.188% L-valine 0.038% Magnesium L-aspartate 0.067% L-proline 0.830% L-tyrosine 6.000% L-phenylalanine 0.500% taurine 80.058% common salt 100 g 100.000% calcium glycerophosphate vitamin mix 10.3 g 3g · Maltodextrin (DE5) 83,1g 3.0g 0.31 g 3.2. analysis 0.6 g 2.49 g a) Type analysis: 3.0 g 0.09 g Protein (Nx6,38) 0.02 g (MitAminosäuren-N) 0.09 g carbohydrates ash fat water

'Dosage: on 100ml of breast milk = 3g product

b) Amino acid analysis (g / 100g product, g / 100g amino acids)

g / 100g g / 100g

Product amino acids

Aspartic acid + asparagine 1.00 8.84 threonine 0.48 4.17 serine 0.51 4.32 Glutamic acid + glutamine 2.02 18.13 proline 1.18 10.18 glycine 0.19 1.48 alanine 0.36 2.94 Cystine + cysteine 0.21 1.99 valine 0.61 5.27 methionine 0.22 1.98 isoleucine 0.74 6.52 leucine 1.19 10.49 tyrosine 0.51 4.69 phenylalanine 0.41 3.73 histidine 0.33 2.98 lysine 0.88 7.89 arginine 0.28 2.57 tryptophan 0.23 2.14 11.35 100.30

3.3. manufacturing

The procedure is as described in Example 1. Example 4 Frühgebohrenennahrung with optimized Lweiß- / Aminosäuremischung (liquid)

4.1. composition : 36.5% i.t.). 0.960% milk fat 3.000% 0.040% Vegetable fats (eg corn oil, soya oil) 3.540% Emulsifier (lecithin) 22.520% demineralized whey powder 0.140% (Protein content- (N χ 6.38) -: 4.228% : 13.5% 0.012% Skimmed milk (dry matter: 9.0%) 0.027% (Protein content- (N χ 6.38) -, 0.031% lactose 0.013% Maltodextrin (DE 5) 0.008% L-histidine 0.002% L-isoleucine 0.021% L-leucine 0.007% L-lysine-L-glutamate 0.006% L-tryptophan 0.051% L-valine 0.014% L-aspartic acid 0.007% L-cystine L-glutamic acid L-proline 100 g 0.141% L-tyrosine 1.4 g 0.050% taurine 0.056% Mineralstoffmix 7.1g 65.125% (Copper sulphate, zinc sulphate, 0.4 g 100.000% Potassium iodate, manganese sulfate) 4.0 g • vitamin mix calcium glycerophosphate water 4.2. analysis a) Type analysis: Protein (N x 6.38) (MitAminosäuren-N) carbohydrates ash fat

b) Amino acid analysis (g / 100g product, g / 100g amino acids)

g / 100g g / 100g score

Product amino acids

Aspartic acid + asparagine 0.144 8.97 threonine 0.077 4.70 serine 0,075 4.47 Glutamic acid + glutamine 0.286 18.08 proline 0.163 9.91 glycine 0.028 1.53 alanine 0.054 3.10 Cystine + cysteine 0.027 1.79 valine 0.086 5.24 methionine 0.032 2.02 isoleucine 0.103 6.40 leucine 0.167 10.37 tyrosine 0,070 4.54 phenylalanine 0,060 3.85 histidine 0,045 2.86 lysine 0,120 7.58 arginine 0,040 2.60 tryptophan 0.031 2.03 1608 100.06

Manufacturing Method: Premature baby food, liquid 234.80 kg Batch size: 1000 kg 0.40 kg Whole milk with 4.1% milk fat 30.00 kg (corresponding to 9,6kg milkfat and skimmed milk 35.40 kg with 20,268kg skimmed milk solids) 1,40 kg emulsifier 42.28 kg vegetable fat 0.12 kg demineralized whey powder 0.27 kg lactose 0.31 kg maltodextrin 0.13 kg L-histidine 0.08 kg L-isoleucine 0.02 kg L-leucine 0.21 kg L-lysine-L-glutamate 0.07 kg L-tryptophan 0.06 kg L-valine 0.51 kg L-aspartic acid 0.14 kg L-cystine 0.07 kg L-glutamic acid 1,41kg L-proline 0.50 kg L-tyrosine 0.56 kg taurine 651,26kg Mineralstoffmix 1000.00 kg vitamin mix Calcium hydrogen phosphate water

500.0 kg of water are placed in a heatable tank with intensive agitator and preheated to 70 ° C. Thereafter 234,8kg whole milk, adjusted to 4.1% fat content, added to the water and heating the mixture to 7O ⁰ C heated. Thereafter, 35.4 kg of demineralized whey powder are stirred in and completely dissolved. 1.4kg of lactose are added to the batch and dissolved. After that, one after another is added:

0.12 kg L-histidine 0.27 kg L-isoleucine 0.31 kg L-leucine 0.13 kg L-lysine L-glutamate 0.08 kg L-tryptophan 0.02 kg L-valine 0.21 kg L Aspartic acid O, O7kgL lysine 0.06kg L-glutamic acid 0.51kg L-proline 0.14kg L-tyrosine 0.07kg taurine

The water-soluble L-amino acids are placed in 50 ° C warm water (about 20 liters per L-amino acid) and then added to the batch. Thereafter, 0.56 kg of calcium hydrogen phosphate are dispersed in the batch. Dissolve 0.4 kg of emulsifier in 30 kg of hot vegetable oil (about 50-55 "C), stir in the fat, mix in the mixture of minerals and vitamins, and adjust to 1000 kg with water.

The approximately 7O ⁰ C warm homogeneous mixture is homogenized at 180 bar, interposed and cooled to 6-8 ⁰ C. After analytical control of the fat and protein content, the batch is UHT-heated and the milk aseptically bottled in cans or in glass bottles. Alternatively, the cooled milk is bottled in glass bottles and terminally sterilized.

Example 5

Adapted infant milk formula with optimized protein / amino acid mixture (liquid)

5.1. composition 2.160% Mi Ohfett 1.440% Vegetable fats (eg corn oil, soya oil) 0.040% Emulsifier (lecithin) demineralized whey powder 3.290% (Protein content - (N x 6.38) -: 13.5%) Skimmed milk (dry matter: 9.0%) 20.910% (Protein Content (N x 6.38) -: 6.5% i.T.) 0.690% lactose 0.011% L-histidine 0.025% L-isoleucine

L-leucine 100 g 0.029% L-lysine-L-glutamate 1.3g 0.012% L-tryptophan 0.007% L-valine 7.2g 0.002% L-Asparaglnsäure 0.2 g 0.019% L-cystine 3.6 g 0.006% L-Giutaminsäure 0.005% L-proline 0.047% L-tyrosine 0.013% taurine 0.007% vitamin mix 0.160% water 71.127% 100.000% 5.2. analysis a) Type analysis Protein (N x 6.38) (RnitAminosäuren-N) carbohydrates Ash fat

b) Amino acid analysis (g / 100g product, g / 100g amino acids)

g / 100g g / 100g

Product 'Amino Acids

Aspartic acid + asparagine 0.132 8.88 5.3. Production process: Mammalian milk formula, liquid 237.00 kg threonine 0.072 4.75 Batch size: 1000 kg 0.40 kg serine 0,069 4.44 Cream with 9.36% milkfat content 14,40 kg Glutamic acid + glutamine 0.265 18,09 32,90 kg proline 0,151 9.91 6,90 kg glycine 0.026 1.54 (with 18.828kg skimmed milk dry substance) 0,11kg alanine 0,050 3.10 emulsifier 0.25kg Cystine + cysteine 0.024 1.73 vegetable fat 0.29 kg valine 0,080 5.26 demineralized whey powder 0.12 kg methionine 0,030 • 2.05 lactose 0.07 kg isoleucine 0.096 6.44 L-histidine 0.02 kg leucine 0.156 10.47 i.-isoleucine 0,19kg tyrosine 0,065 4.55 L-leucine 0.06 kg phenylalanine 0,055 3.81 L-lysine-L-glutamate 0.05 kg histidine 0,041 2.82 L-tryptophan 0.47 kg lysine 0.112 7.64 L-valine 0.13 kg arginine 0,038 2.65 L-aspartic acid 0.07 kg tryptophan 0.028 1.99 L-cystine 1.60 kg 1,490 100.11 L-glutamic acid 704.97 kg L-proline 1000.00 kg L-tyrosine taurine vitamin mix water

500 kg of water were pumped into a heatable tank with agitator and warmed to 70 ° C. 237 kg of milk containing 9.1% milk fat (cream) and 18.828 kg lean skimmed milk are added and the batch is warmed to 70 ° C. As in Example 4, demineralized whey powder, lactose, the L-amino acids, the taurine and the emulsifier / fat mixture are added in the same way and stirred homogeneously. Thereafter, the addition of the vitamin mixture and water addition takes place ad 1000 kg mixture

The mixture is homogenized at 180 bar, cooled to 6-8 ⁰ C, filled into vials and sterilized.

Example 6 Adapted infant milk formula with optimized protein / amino acid mixture as spray product

6.1. composition .) 17.540% g / 100g g / 100g milk fat 11.200% product amino acids Vegetable fats (eg corn oil, soya oil) 0.500% 0.98 8.91 Emulsifier (lecithin) 0.53 4.73 demineralized whey powder 24.420% 0.51 4.46 (Protein Content (N x 6.38) -: 13.5% 1.96 18.05 Skimmed milk powder 13.920% 1.13 9.96 (Protein content (N χ 6.38) -: 36.5% i.T 29.360% 0.19 1.51 lactose 0.083% 0.37 3.14 L-histidine 0.188% 0.19 1.79 L-isoleucine 0.215% 0.59 5.22 L-leucine 0.090% 0.22 2.06 L -. 'Ysin L-glutamate 0.056% 0.71 6.43 L-tryptophan 0.014% 1.15 10.42 L-VaMn 0.146% 0.48 4.53 L-aspartic acid 0.049% 0.41 3.82 L-cystine 0.042% 0.31 2.85 L-glutamic acid 0.354% 0.83 7.60 L-proline 0.098% 0.28 2.64 L-tyrosine 0.025% 0.21 2.01 taurine 0.500% 11.05 100.13 vitamin mix Mineral blend 0.500% (Trace elements, Zn, Mn, Cu, J) 0.400% calcium carbonate 0.300% potassium chloride 100.000% 6.2. analysis g / 100ml a) Type analysis: 100g (13% solution) 1.2g Protein (N x 6.38) 9.3 g (MitAminosäuren-N) 7.5 g Carbohydrates 57.8g 0.3g Ash 2.3g 3.7 g Fat 28.6 g - Water 2.0 g b) Amino acid analysis (g / 100g product, g / 100g amino acids) Aspartic acid + asparagine threonine serine Glutamic acid + glutamine proline glycine alanine Cystine + cysteine valine methionine isoleucine leucine tyrosine phenylalanine histidine lysine arginine tryptophan

G.3. manufacturing Batch size: 100 kg

172.2kg of cream (with 10.2% milk fat and 13.92kg skimmed milk dry substance) are served in a heatable tank

Stirred and heated to 70 ° C. With vigorous stirring are successively demineralized whey powder, lactose, the L-amino acids, taurine, Potassium chloride (in about 10 liters of hot water (60 ⁰ C) pre-dissolved), calcium carbonate and the mineral mixture

admitted and completely dissolved. 0.5 kg emulsifier are dissolved in 11.2 kg hot vegetable fat mixture (50-60 ⁰ C) and added to the batch. Thereafter, the vitamin mixture is stirred.

The finished batch is heated to 70-75 ⁰ C and homogenized at 180bar. Thereafter, the concentrate over a Heater heated to 95 ° C, cooled to 70 ° C and spray dried. Example 7 Infant milk formula with optimized protein-Mminosäurenmischung as Sprühpndukt for hypoallergenic diet

7.1. composition : 79% dn, Cu, J) 26.297% 2.000% Vegetable fats (eg corn oil, soya oil) : 90% Emulsifier (lecithin) 5.857% whey protein hydrolyzate (Protein content- (N χ 6.38) -: 6.157% casein hydrolyzate 100 g 36.800% (Protein Content (N x 6.38) -: 14, d00% Lactose, milk protein-free 11.7 g 3.000% Maltodextrin (DE5) 0.086% Strength 54.6 g 0.129% Glutathione (reduced) 3.4g 0.243% L-histidine 28.3 g 0.371% L-isoleucine 2.0 g 0.286% L-leucine 0,1C0% L-lysine-L-glutamate 0.043% L-tryptophan 0.304% L-VaMn 0.500% Magnesium L-aspartate Mineral mixture (calcium, phosphorus, 0.214% L-proline Trace elements z. Fe, Zn, f 0.043% L-tyrosine citric acid 0.310% L-phenylalanine tri-potassium citrate vitamin mix potassium chloride 1.400% 0.190% 7.2. analysis 0.270% a) Type analysis: 0.600% 100.000% Protein (Nx6,38) (MitAminosäuren-N) g / 100ml carbohydrates (13% solution) ash 1.5g fat water 7.1g 0.4g 3.7 g -

b) Amino acid analysis (g / 100g product, g / 100g amino acids)

g / 100g g / 100g

Product amino acids

Aspartic acid + asparagine 1.14 8.83 threonine 0.55 4.19 serine 0.58 4.31 Glutamic acid + glutamine 2.31 18.17 proline 1.34 10.13 glycine 0.22 1.50 alanine 0.41 2.93 Cystine + cysteine 0.24 1.99 valine 0.70 5.30 methionine 0.25 1.97 isoleucine 0.85 6.57 leucine 1.36 10.51 tyrosine 0.58 4.68 phenylalanine 0.47 3.75 histidine 0.37 2.93 lysine 1.01 7.94 arginine 0.32 2.57 tryptophan 0.26 2.12 12.96 100.38

7.3. manufacturing

Batch size: 100 kg In 100 liters of hot water (about 70-75 ⁰ C) are dissolved with vigorous stirring in succession: lactose, maltodextrin, Starch, whey protein hydrolyzate, casein hydrolyzate, reduced glutathione, L-amino acids, potassium chloride (in approx. 5 liters

60 ° C warm water pre-dissolved), tri-potassium citrate (in about 5 liters of hot water-60 ° C pre-dissolved), citric acid (in approx.

3 liters of hot water-60 ⁰ C-pre-dissolved) and the mineral mixture.

The emulsifiers are completely dissolved in the hot melted fat (50-60 ° C) and the mixture is added to the batch

added. Thereafter, the vitamin mixture is added and completely dissolved.

The batch is heated to 70-75 ⁰ C and homogenized with 180-200 bar. Thereafter, the concentrate is in a Heater heated to 95 ⁰ C and then spray dried. Table I Amino acid composition according to the nutritive protein content of breast milk (g / 100g total amino acids)

aspartic acid 9.05 threonine 4.26 serine 3.92 glutamic acid 18.48 proline 10.23 glycine 1.50 alanine 2.98 cystine 1.81 valine 5.36 methionine 1.77 isoleucine 6.56 leucine 10.64 tyrosine 4.68 phenylalanine 3.75 histidine 2.93 lysine 7.72 Arßinin 2.34 tryptophan 2.02

1. Commission of European Communities

Luxembourg 1983, EUR 8753

2nd Report of a Joint FAO / WHO Ad Hoc Expert Committee Rome 1973, WHO Technical Report Series No.

3. ESPGAN Committee on Nutrition Guidelines on Infant Nutrition Acta Paediat Scand Suppl. 262.1977

4. Bindels, J.G., and Harzer, G. Ernährungs-Umschau 32 (1985) 223-224

5. Ogra, S.S., Weintraub, D., and Ogra, P.L. J. Immunol. 119 (1977) 245-248

6. Hambraeus, L., Fransson, G.B., and Lonnerdal, B. Lancet Il (1984) 167-168

7. Pohlandt, F., and Kupferschmidt, C. Klin.Päd.19 (1985) 164-166

8. Heinson, S.A.Α., Anderson, G.H., and Bryan, M.H. Am.J.CIin.Nutr.33 (1980) 811-815

9. Hibberd, C, Brooke, O.G., Carter, N.D., and Wood, C.J. Human. Nutr.35 (1981) 189-198

10. Sann, L., Bienvenu, F., Lahet, C., Bienvenu, J., and Bethenof, M. Acta. Paediat. Scand. 70 (1981) 115-116

Claims (6)

1. Protein, peptide and amino acid mixtures based on proteins which are digestible for the infant and, if appropriate, their hydrolyzates and free amino acids having the following amino acid composition: Amino acids g / 100g Total amino acids * Aspartic acid + asparagine 7.69-10.41 Threonine 3.62-4.90 Serine 3.33-4.51 Glutamic acid + glutamine 15.71-21.25 proline 8.70-11.76 Glycine 1.27-1.73 Alanine 2.53-3.43 Cystine + cysteine 1.45-2.17 Valine 4,56-6,16 Methionine 1.42-2.12 Isoleucine 5.58-7.54 Leucine 9,04-12,24 Tyrosine 3.98-5.38 Phenylalanine 3,19-4,31 Histidine 2,49-3,37 Lysine '- · 6,56-8,88 Arginine 1.99-2.69 Tryptophan 1.72-2.32 * calculated on the basis of the molecular weight (s) of the amino acid (s) each minus the molecular weight of water 2. Protein, peptide and Aminosäurenmischungerr according to claim 1 having the following amino acid composition: Amino acids g / 100g total amino acids Aspartic acid + asparagine 7.95-9.72 threonine 3.92-4.90 Serine 3.87-4.50 Glutamic acid + glutamine 16,34-20,70 Proline 9.16-11.20 Glycine 1.35-1.65 Alanine 2.70-3.31 Cystine + cysteine 1.58-2.01 Valine 4,70-5,73 Methionine 1,74-2,12 Isoleucine 5.97-7.29 Leucine 9.42-11.51 Tyrosine 4,14-5,06 Phenylalanine 3.40-4.15 Histidine 2.67-3.27 Lysine 6,83-8,34 Arginine 2.30-2.69 Tryptophan 1.84-2.26 3. protein, peptide and amino acid mixtures according to claim 1 or 2, characterized in that it contains commercially available proteins or peptides and commercially available proteinaceous raw materials such as cow's milk, cow's milk proteins, isolated cow's milk protein fractions, protein hydrolysates, peptides and optionally free L-amino acids. 4. protein, peptide and amino acid mixtures according to at least one of claims 1 to 3, characterized in that they contain soy protein, goat's milk protein and / or beef protein. 5. Use of the protein, peptide and amino acid mixtures according to any one of claims 1 to 4 as a protein base for the preparation of additives to breast milk and as a protein base for the production of preterm and other infant formulas and infant formulas. 6. A process for the preparation of additives for breast milk and preterm and infant formulas based on a protein, peptide and amino acid mixture according to one of claims 1 to 4, characterized in that the raw materials in the calculated proportions, optionally together with vitamins, Trace elements, minerals, fats, carbohydrates and / or geeigreten emulsifiers in water and / or skimmed / whole milk dissolves or dispersed and / or emulsified and the liquid mixture optionally pasteurized or sterilized, homogenized and, if a powder should be produced! , spray-dried.