NZ756828B2

NZ756828B2 - Lactoferrin and sialic acid-modulated milk powder and preparation method thereof

Info

Publication number: NZ756828B2
Application number: NZ756828A
Authority: NZ
Inventors: Yang Yanyu
Original assignee: Unipharm Healthy Manufacturing Co Limited
Filing date: 2019-08-29
Publication date: 2021-08-03

Abstract

The invention relates to a milk powder and a preparation method and use thereof, in particular to a milk powder containing lactoferrin and sialic acid, a preparation method thereof and use thereof. It belongs to the field of food, especially dairy technology. A lactoferrin and sialic acid-prepared milk powder according to the present invention, which is composed of the following materials in parts by weight, and the ratio of the components and parts by weight is: 400-600 parts of instant whole milk powder, and 400-450 parts of instant skim milk powder, 500-700 parts of whey protein powder, 0.5-2 parts of taurine, 300-350 parts of anhydrous glucose, 120-130 parts of oligofructose, furthermore including: 1-3 parts of lactoferrin 20-40 parts of sialic acid. The product of the invention provides nutrition mainly by the combination of lactoferrin and sialic acid, supplemented by other nutrients, so that the nutrition of the milk powder is more perfect, and the method of mixing powder is studied, so that the final product is more uniform and beneficial to human body absorption and Utilize, while avoiding the problem of affecting the quality of the final product due to uneven mixing. ilk powder according to the present invention, which is composed of the following materials in parts by weight, and the ratio of the components and parts by weight is: 400-600 parts of instant whole milk powder, and 400-450 parts of instant skim milk powder, 500-700 parts of whey protein powder, 0.5-2 parts of taurine, 300-350 parts of anhydrous glucose, 120-130 parts of oligofructose, furthermore including: 1-3 parts of lactoferrin 20-40 parts of sialic acid. The product of the invention provides nutrition mainly by the combination of lactoferrin and sialic acid, supplemented by other nutrients, so that the nutrition of the milk powder is more perfect, and the method of mixing powder is studied, so that the final product is more uniform and beneficial to human body absorption and Utilize, while avoiding the problem of affecting the quality of the final product due to uneven mixing.

Description

TITLE Lactoferrin and sialic acid-modulated milk powder and preparation method thereof TECHNICAL FIELD The invention relates to a milk powder and a preparation method and use thereof, in particular to a milk powder containing lactoferrin and sialic acid, a preparation method thereof and use thereof. It belongs to the field of food, especially dairy technology.

BACKGROUND OF THE INVENTION Sialic acid, N-acetylneuraminic acid, has the molecular formula C11H19NO9. N- acetylneuraminic acid is the most widely distributed in nature, mainly glycoproteins, glycolipids or animal cell membranes or secretions. In a glycoprotein or a glycolipid, since the keto group at the 2-position forms a glycosidic bond, it is located at the non-reducing end of the sugar side chain, and its anionic charge or a unique chemical structure makes it have various physiological specificities. In the natural world, from the virus to the animal, the enzyme which is hydrolyzed to remove the terminal N-acetylneuraminic acid (neuraminidase) has been identified by the treatment of this enzyme. For example, this sugar residue constitutes a binding site of an influenza virus of a red blood cell membrane, and plays a major role in the mutual recognition of plasma glycoproteins and hepatocytes or the recognition mechanism of lymphocytes to the circulation pathway. Although the biosynthetic pathway is somewhat different in animals and bacteria, it is subjected to N- acetylmannosamine or its 6-phosphate, which is catalyzed by a specific pyrophosphatase to react with CTP to form CMP-N-acetylneuraminic acid. After that, the sugar chain is incorporated by a glycosyl transfer reaction.

Studies have shown that sialic acid has important biological functions in the growth and development of infants, including: improving the memory and intelligence of infants; anti-recognition; antiviral effects; inhibiting leukocyte adhesion and anti-inflammatory effects. However, infant formula containing sialic acid produced in the existing industry has a large loss of sialic acid during production, transportation, and storage. Studies have shown that sialic acid has important biological functions in the growth and development of infants, including: improving the memory and intelligence of infants; anti-recognition; antiviral effects; inhibiting leukocyte adhesion and anti-inflammatory effects. However, there is no industrial production of infant formula containing sialic acid, and there is no complete formula and process.

Sialic acid is a kind of natural saccharide compound widely present in biological systems. It is an essential nutrient for human brain cognitive development and has important biological functions such as cell recognition, survival, reproduction, biofilm flow, and endocytosis. Wait. The supply of exogenous sialic acid can increase the concentration of gangliosides in the brain of animals and increase the learning ability of animals, especially cognitive levels. Studies have shown that mouse cubs have obstacles in cognition and behavior when sialic acid intake is insufficient, and cognitive ability is significantly improved after sialic acid supplementation is sufficient; small consumption of sialic acid formula containing high dose is small Pigs have significantly better learning and memory skills than pigs who consume regular formula. Therefore, the researchers believe that early sialic acid intake after birth can lay the foundation for long-term cognitive development.

In clinical studies, Dida et al. confirmed by double-blind trial that supplementation of high sialic acid milk to infants aged 0-6 months can increase serum ganglioside levels and promote cognitive development. The current study found that milk-source sialic acid is high in casein glycomacropeptide (CGMP) produced during the process of rennet agglutination.

In addition to providing a large amount of sialic acid to the human body, this bioactive peptide also promotes the proliferation of bifidobacteria, inhibits the infection of viruses and toxins, inhibits allergic reactions, and serves as a nutritious food for patients with phenylketonuria (PKU).

In addition, breast milk is rich in nutrients, such as high quality such as lactoferrin, which is beneficial to enhance the resistance of infants and young children.

However, there are many breast milk shortages in reality, which requires the selection of other products to help increase the immunity of infants and young children. At present, the most common formula on the market is formula milk powder, there are many brands, such as Nestle, Abbott, etc., and according to different needs, there are a variety of functional infant formula milk powder, and meet the growth cycle of infants of different ages. The basic nutrients needed. However, most of the formula milk powder on the market lacks some beneficial ingredients in breast milk, and it is difficult to truly improve the immunity of infants and young children and promote the growth and development.

Therefore, many companies and scholars are committed to developing a formula that is closer to the nutritional components of breast milk to improve the immunity of infants and young children.

Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional glycoprotein in transferrin. Lactoferrin is a globular glycoprotein with a molecular weight ranging from 76 to 80 kDa and widely present in various exudates such as milk, saliva, tears, and snivel. Lactoferrin is also present in metaphase neutrophils and is secreted by some acinar cells. Lactoferrin can be extracted from milk or obtained using recombinant DNA techniques. Human colostrum has the highest lactoferrin concentration, followed by human milk, with the lowest concentration in milk (150 mg/l).

Lactoferrin is one of the components of the human immune system. It has antibacterial activity and is part of the innate defense, mainly in the mucosa. Lactoferrin protects infants from pathogens such as bacteria. Lactoferrin also interacts with DNA and RNA, polysaccharides and heparin and exhibits certain physiological functions in these receptor-ligand complexes.

Lactoferrin is involved in the transmembrane transport of iron and controls the balance and secretion of iron ions in the blood. It is found in the milk, plasma and neutrophils of humans and other mammals and is the secretion of mammals such as saliva, gall bladder, tears and pancreas, the main proteins in the composition. The concentration of lactoferrin in milk varies from 7 g/L in human colostrum to 1 g/L in mature milk.

X-ray diffraction indicates that lactoferrin is a polypeptide chain comprising about 700 amino acids and two homologous globular domains: N-ring and C-loop. The N-loop corresponds to the 1-33rd amino acid residue in the peptide chain, and the C-loop corresponds to the 345-692 amino acid residues, and the two domains are joined at both ends by a short-chain alpha-helix. Each loop consists of two subdomains (subdomains): N1, N2 and C1, C2 and contains an iron binding site and a glycosylation site. The degree of glycosylation of lactoferrin may vary, so the molecular weight of lactoferrin varies from 76 to 80 kDa. The stability of lactoferrin is related to its degree of glycosylation.

Lactoferrin is a basic protein with an isoelectric point of 8.7, which exists in two forms: holo-lactoferrin rich in iron form and apo-lactoferrin without iron form. The two have different tertiary structures: apo-lactoferrin is characterized by an "open" N-ring and a "closed" C-ring, while the holo-lactoferrin rings are "closed". Each lactoferrin molecule reversibly binds two irons, zinc, copper or other metal ions. The two binding sites are located in two protein globular domains, respectively. Each ion binds to six ligands: four from the ligand in the peptide chain (2 tyrosine residues, 1 histidine residue and 1 aspartate residue) and 2 carbonates or Bicarbonate ion.

Lactoferrin forms a red complex with iron; its affinity for iron is 300 times higher than that of transferrin. Affinity increases in weakly acidic media. It is shown that lactoferrin not only involves the transport of iron, zinc, and copper ions, but also regulates the absorption of these ions. The presence of zinc and copper ions in the solution does not affect the iron binding capacity of lactoferrin and may even increase.

Lactoferrin exists in different forms of polymer in plasma and exudates: monomeric to tetrameric. Lactoferrin is more likely to be present in the body and in the form of a polymer, especially when the concentration is high. Studies have found that tetramers are the predominant form of lactoferrin under physiological conditions.

The oligomeric form of lactoferrin depends mainly on the concentration of the protein, while the formation of the poly-polymeric form is strongly influenced by Ca . In the 2+ −10 −11 presence of Ca , when the concentration is 10 ～10 M, lactoferrin mainly exists as a −9 −10 monomer; but when the concentration is increased to 10 ～10 M, the monomer will be converted into a tetramer form. In general, the concentration of lactoferrin in the blood is between the monomer and tetramer transition concentrations, so that lactoferrin has a polymerized state of monomer and tetramer in the blood. Many of the functional properties of lactoferrin depend on its oligomeric form. For example, lactoferrin monomers bind tightly to DNA, while tetramer forms do not.

Lactoferrin can alter the spatial conformation of the virus, causing the virus to lose its ability to bind to human host cell receptors. Lactoferrin forms a protective layer on the surface of the receptor, preventing the adhesion of viruses and human cells.

According to research at home and abroad in recent years, exogenous supplemental lactoferrin can play a very good role in antiviral. In addition, a large number of academic papers have shown that sialic acid can act as a viral inhibitor. Therefore, lactoferrin combined with sialic acid is a good antiviral agent.

The combination of lactoferrin and sialic acid helps to strengthen immunity and make babies grow healthier.

Chinese patent application CN108029768A discloses an infant formula containing lactoferrin and probiotics, which simultaneously adds probiotics and lactoferrin to infant formula, and regulates the intestinal flora of infants and young children through probiotics.

Lactoferrin protects against the invasion of external microorganisms. However, a professor at the Children's Hospital Medical Center in Cincinnati, Ohio, and his research team demonstrated that red blood cells (CD71+ cells) expressing CD71 receptors can suppress the immune response in 6-day-old mice. They also found that CD71+ cells in human cord blood also have unique immunosuppressive properties, but CD71+ cells in adult mice do not have these characteristics, suggesting that immunosuppressive properties are restricted to newborns. The researchers also pointed out that although the immune system of newborns is inhibited, the growth of probiotics can be improved. It can be seen that the probiotics of newborns are sufficient to achieve self-sufficiency, and the addition of new probiotics is likely to cause their own probiotics to breed and disorder, which has a negative effect on the growth of newborns.

CN109007037A A composition for enhancing infant immunity and a product thereof, comprising 30-60 parts by weight of milk powder, 0.05-2 parts of lactoferrin, 5-30 parts of concentrated whey protein, 5 parts by weight -15 parts of prebiotic, 20-50 parts of desalted whey powder, 1-5 parts of lactalbumin, 0.1-2 parts of N-acetylneuraminic acid and 0.003- 0.05 parts of folic acid compound. However, according to this ratio, lactoferrin and N- acetylneuraminic acid are not the best use of the human body. The key is the loss in the digestive tract of the body. At the same time, the molecular distance between the two is too far to be used by the human body at the same time.

The current problem is that lactoferrin and sialic acid supplemented at the same time, and there is no stable composition that specifically maintains the two components, because both are very good nutritional supplements, and the current products are simultaneously mixed, most of the products supplemented with two supplements are concentrated on infant formula, which causes great loss in the production process, and there is an unreasonable absorption in the human body.

STATEMENT OF INVENTION The object of the present invention is to invent a milk powder containing lactoferrin and sialic acid, a preparation method thereof and use thereof, which not only can meet the nutritional needs of the human body, but also have high utilization rate while maintaining product stability.

The lactoferrin and sialic acid-prepared milk powder of the present invention, which is composed of the following materials in parts by weight, the ratio of the components and parts by weight: 400-600 parts of instant whole milk powder, 400-450 of instant skim milk powder Parts, 500-700 parts of whey protein powder, 0.5-2 parts of taurine, 300-350 parts of anhydrous glucose, 120-130 parts of oligofructose, furthermore including: 1-3 parts of lactoferrin, 20-40 parts of saliva acid.

Wherein, preferably, 500 parts of instant whole milk powder, 420 parts of instant skim milk powder, 600 parts of whey protein powder, 1 part of taurine, 320 parts of anhydrous glucose, 127 parts of oligofructose, wherein: 2 parts of protein and 30 parts of sialic acid.

The above milk powder further comprises 0.1 to 0.5 parts by weight of the composite trace element and 0.1 to 0.3 parts by weight of the complex vitamin.

The above milk powder further comprises 0.3 parts by weight of a composite trace element and 0.2 parts by weight of a multivitamin.

The above composite trace elements, the compound composition and the ratio by weight are: calcium 300-973.5 mg, phosphorus 150-649 mg, magnesium 30-106.2 mg, potassium 375-1121 mg, iron 3.5-14.75 mg, zinc 3-10.62 mg, sodium 125-413 mg, iodine 62.5-354 μg, copper 210-737.5 μg, manganese 6.25-737.5 μg.

The above-mentioned multivitamins are compounded in composition and weight ratio: the components and weight ratios are: vitamin A 1165.5-4224.1 IU, vitamin D3 250- 885 IU, vitamin E 12.5-35.4 IU, vitamin C 62.5-221.25 Mg, vitamin K 25-177μg, vitamin B1 350-2124μg, vitamin B2 475-2802.5μg, vitamin B6 225-1239μg, vitamin B12 0.625-3.54μg, niacin 1.8-11.06mg, pantothenic acid 2375-14012.5μg, folic acid 62.5- 354 μg, biotin 10- 53.1 μg.

The above formulation also includes from 0.5 to 2 parts by weight of cationic colloid.

The above product is prepared by the following method: the cationic colloid may be a composition, and the preferred composition is: A combination of carrageenan, guar gum, and propylene glycol alginate, the ratio of the three preferred combinations of colloids is (1-2): (1-2): (1-2); The ratio by weight of modified starch, locust bean gum, konjac gum and guar gum is (1-2): (1-2): (1-2): (1-2); The ratio by weight of carrageenan, xanthan gum, pectin and guar gum is (1-2): (1- 2): (1-2): (1-2); The ratio by weight of xanthan gum, locust bean gum, konjac gum and carrageenan is (1-2): (1-2): (1-2): (1-2); The ratio by weight of dextrin, carrageenan, xanthan gum, and sodium alginate is (1- 2): (1-2): (1-2): (1-2).

Firstly, set the temperature of the heatable three-dimensional mixer to 50-60℃. After -20 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer and mix for 10-20 minutes. Heat to 65℃, add a part of the gel, mix for 20-30 minutes, then add the remaining colloid, continue mixing for 20-30 minutes, then reduce the temperature to 40-45℃, then mix for 10-20 minutes, then wait for a while The temperature is lowered to room temperature to obtain a sialic acid and lactoferrin composition; the other powder adjuvant may be further added to the composition, and further mixed for 30-40 minutes, and the mixing is finished. Then we get milk powder product of the present invention.

It is foreseeable that in the process of mixing, there will be a certain proportion of protein molecules at 60-65℃, the chain of its folded structure will unfold, but the proportion of protein is very low, so this loss is negligible, and when the temperature At the time of the decline, a part of the protein is reversible and will return to the original structure; and at this temperature, most of the functional groups of the protein molecule can still maintain the original function.

In addition, gel particles protect them from heat by encapsulating the protein molecules inside.

Preferably, the weight of the previously added colloid is preferably from one third to one half of the total weight, and after many trials, the dispersion of the final product is optimal in this ratio range.

Wherein, a more preferred mixture of sialic acid and lactoferrin is added in a batchwise manner, that is, half of the weight of sialic acid is first added, and after completely mixing with lactoferrin, the time ranges from about 10 to 30 minutes, and then The remaining half by weight of sialic acid was added before the addition of the colloid and mixing was continued for about 5-10 minutes. The advantage of this is that it further solves the problem of the taste of sialic acid mentioned above. After adding half of the mixture and mixing evenly, add half of the mixture, and the uniformity of the mixture should be continuously increased to about 3-5%.

Mixing two small amounts of raw materials in advance is good, in this way which helps the final powder mix evenly, providing the opportunity to combine sialic acid and lactoferrin molecules. At 50-60℃, sialic acid and lactoferrin are not destroyed. However, the molecular motion will be strengthened, and the mixing rate and bonding rate will be improved; Here we emphasize that the above-mentioned colloids, the most commonly used in actual production, are the preferred colloidal composition and weight ratio we mentioned, namely: carrageenan, guar gum, propylene glycol alginate combination, more selective The production use ratio is 1:1:1. Of course, using the ratio (1-2) as above: (1-2): (1-2) is also effective.

In the present invention, the best choice of carrageenan is: K-type carrageenan (also known as kappa-carrageenan, also known as carrageenan) and type I carrageenan (iota carrageenan) because they are only soluble in 40-70 ℃ between hot water and hot milk.

Moreover, they only gel in the presence of certain cations. This means that we can produce two types of milk powders with different textures by using excipients with cations (eg Ca, Mg).

In addition, one of the most important properties that distinguish carrageenan from other hydrocolloids is its ability to interact with milk proteins. The high reactivity of carrageenan with milk is due to the strong electrostatic interaction between the negatively charged ester sulfate groups in the carrageenan molecule and the strong positive charge of the bovine cheese protein micelles. Another form of interaction is through the linkage established between the ester sulfate group of carrageenan and the carboxylic acid residue of the amino acid constituting the protein. The reactivity with proteins depends on many factors such as the concentration of carrageenan, the type of protein, temperature, pH value and isoelectric point of the protein. The ability of carrageenan to complex with milk proteins combined with its hydrogel properties makes it an effective ingredient in stable and gelled dairy products.

Quality requirements for carrageenan: 80% by particle size distribution through 200 mesh, moisture content below 15%, pH value 7.0-10.0.

The other two colloids should also be 80% through 200 mesh and moisture content below 15%.

In order to better quantitatively compare the method of the present invention with the conventional mixing method in the prior art, the inventors tested 15 sets of comparative data, and the products of the conventional mixed mode by the method of heating mixing and stepwise addition of the present invention. The range of uniformity improvement is between 9.6-11.2%; Mixing uniformity and weighing accuracy, system stability is called the three performance indicators of the batching system. The uniformity of the batch material not only affects the performance index of the subsequent process equipment, but also directly relates to the quality of the final product. Especially in the infant formula industry, the uniformity of the ingredients directly affects the nutritional balance. If the ingredients are mixed unevenly, it may cause poisoning.

Following the idea of this method, the inventors further found that cooling after mixing directly can cause a slight agglomeration, which will have a certain impact on the use of the product. After further experiments, the inventor has obtained a favorable effect to improve the problem. The method is, the way of mixing and cooling down at the same time.

This product can be packed in carton or plastic bottles, or in glass bottles or tinplate.

Research and analysis: The inventors have found that the colloid is charged, and in the presence of a charge, the composition of the present invention can be very well combined in proportion to the parts by weight, and at the same time, the loss in the mixed production process is very small due to the presence of the colloid; The reason for the colloidal attraction is that the particles present in the colloid are exactly the micelles, and the colloid is composed of micelles. The micelle is composed of a rubber core, an adsorption layer and a diffusion layer. The rubber core is agglomerated by many molecules or other particles. It has strong adsorption capacity, and there is an electric double layer, that is, an adsorption layer and a diffusion layer, on the periphery of the rubber core. In layman's terms, the colloid nucleus adsorbs ions with a certain charge, forming colloidal particles, and the charged colloidal particles can further adsorb oppositely charged ions. The ion layer in the colloidal particles is called the adsorption layer, and the ion layer adsorbed by the colloidal particles is called the diffusion layer. Since the colloidal particles have a large surface area, the adsorption capacity is strong, and the adsorbed ions and its tightly bound are difficult to separate, so that the charged colloidal particles in the colloid can be stably present. The ability of the colloidal particles to adsorb oppositely charged ions is relatively small, and the adsorbed ions are easily separated. The micelles are electrically neutral. Therefore, the rubber particles are charged, while the colloid is electrically neutral. Description: The charging of the rubber particles can be either adsorption or ionization.

After long-term research by the inventors, it was found that 20-50 sialic acid polymers can bind to a point on lactoferrin, and under the action of charged colloid, the combination is very stable and combined in physical state, which not only does not affect human body absorption, Moreover, it is also a very important invention of the present invention to protect the sialic acid and lactoferrin from being destroyed during processing. After the concept of the invention, the inventor has conducted several tests and tested each test. The mixed product is sent for inspection. According to the loss of the two components, which kind of colloid and processing method is better, it is concluded that due to the existence of colloidal charge, the combination of sialic acid and lactoferrin is very good, which is beneficial to the human body. Utilize, while protecting both from damage, increasing end-use rates140.

Another advantage of the present invention is that the two compositions are used in advance in the presence of a colloid to form a composition for separate use, which facilitates dispersion in the product at the time of use, which is advantageous for the stability of the produced product and avoids use due to uneven mixing. Uneven distribution of nutrients occurs.

According to the above analysis and description, the product of the invention provides nutrition mainly by the combination of lactoferrin and sialic acid, supplemented by other nutrients, so that the nutrition of the milk powder is more perfect, and the method of mixing powder is studied, so that the final product is more Uniformity is beneficial to the absorption and utilization of the human body, and at the same time avoids the problem of affecting the quality of the final product due to uneven mixing.

DETAILED DESCRIPTION OF THE INVENTION The embodiments of the present invention are intended to be illustrative, and not to limit the scope of the present invention. Any slight difference in nutrient composition due to the difference in milk source should not be used as a reason for the inconsistency between the embodiment of the present invention and the specification, so the present invention aims to protect the purpose of adding nutrients, rather than to make the ratio particularly strict. The ground is limited to a specific value.

Embodiment 1 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 50℃. After 20 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 20 minutes, heat to 65℃, and add Part of the colloid, mix for 30 minutes, then add the remaining colloid, continue mixing for 30 minutes, then reduce the temperature to 45℃, mix for another 20 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; Additional powder adjuvant can be added to this composition, mixed for another 40 minutes, and the mixing is finished.

According to parts by weight, it consists of the following components: 400 parts of instant whole milk powder, 400 parts of instant skim milk powder, 500 parts of whey protein powder, 0.5 parts of taurine, and anhydrous. There are 300 parts of glucose and 120 parts of oligofructose, including 1 part of lactoferrin and 20 parts of sialic acid.

The above milk powder further comprises 0.1 parts by weight of a composite trace element and 0.1 parts by weight of a multivitamin.

A combination of carrageenan, guar gum, and propylene glycol alginate, the ratio of the three combined colloids is 1:1:1.

Embodiment 2 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 60℃. After 5 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 10 minutes, heat to 65℃, and add Part of the colloid, mix for 20 minutes, then add the remaining colloid, continue mixing for 30 minutes, then reduce the temperature to 45℃, mix for another 20 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 30 minutes, and the mixing is finished.

According to the parts by weight, it is composed of the following components: the ratio of the composition component and the weight component is: 600 parts of instant whole milk powder, 450 parts of instant skim milk powder, 700 parts of whey protein powder, 2 parts of taurine, 350 parts of anhydrous glucose, 130 parts of oligofructose, furthermore, including 3 parts of lactoferrin and 40 parts of sialic acid.

The above milk powder further comprises 0.5 parts by weight of a composite trace element and 0.3 parts by weight of a multivitamin.

The combination of modified starch, locust bean gum, konjac gum and guar gum, the weight ratio of the three combined colloids is 1:1:1:1.

Embodiment 3 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 55℃. After 10 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 15 minutes, heat to 65℃, and add Part of the colloid, mix for 25 minutes, then add the remaining colloid, continue mixing for 25 minutes, then reduce the temperature to 42℃, then mix for 15 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 35 minutes, and the mixing is finished.

According to parts by weight, it consists of the following components: 500 parts of instant whole milk powder, 420 parts of instant skim milk powder, 600 parts of whey protein powder, 1 part of taurine, 320 parts of anhydrous glucose, 125 parts of oligofructose, and further include: 2 parts of lactoferrin and 30 parts of sialic acid.

The combination of carrageenan, xanthan gum, pectin and guar gum, the weight ratio of the three combined colloids is 1:1:1:1.

Embodiment 4 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 55℃. After 10 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 15 minutes, heat to 65℃, and add Part of the colloid, mix for 25 minutes, then add the remaining colloid, continue mixing for 25 minutes, then reduce the temperature to 42℃, then mix for 15 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 35 minutes, and the mixing is finished.

According to parts by weight, it consists of the following components: 500 parts of instant whole milk powder, 420 parts of instant skim milk powder, 600 parts of whey protein powder, 1 parts of taurine, 320 parts of anhydrous glucose, 125 parts of oligofructose, furthermore, including 2 parts of lactoferrin and 30 parts of sialic acid.

Embodiment 5 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 55℃. After 10 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 15 minutes, heat to 65℃, and add Part of the colloid, mix for 25 minutes, then add the remaining colloid, continue mixing for 25 minutes, then reduce the temperature to 42℃, then mix for 15 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 35 minutes, and the mixing is finished.

Embodiment 6 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 55℃. After 10 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 15 minutes, heat to 65℃, and add Part of the colloid, mix for 25 minutes, then add the remaining colloid, continue mixing for 25 minutes, then reduce the temperature to 42℃, then mix for 15 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 35 minutes, and the mixing is finished.

Embodiment 7 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 50℃. After 20 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 10 minutes, heat to 65℃, and add Part of the colloid, mix for 30 minutes, then add the remaining colloid, continue mixing for 20 minutes, then reduce the temperature to 45℃, mix for another 10 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 40 minutes, and the mixing is finished.

According to parts by weight, it consists of the following components: 600 parts of instant whole milk powder, 450 parts of instant skim milk powder, 700 parts of whey protein powder, 0.5 parts of taurine, 300 parts of anhydrous glucose, 120 parts of oligofructose, furthermore, including 1 parts of lactoferrin and 20 parts of sialic acid.

The combination of carrageenan, xanthan gum, pectin and guar gum, the weight ratio of the three combined colloids is 2:1:1:1.

Embodiment 8 The preparation method of the lactoferrin and sialic acid-prepared milk powder of the present invention is as follows: First set the temperature of the heatable three-dimensional mixer to 55℃. After 20 minutes, wait until the temperature distribution in the mixer is even. Add sialic acid and lactoferrin to the mixer, mix for 20 minutes, heat to 65℃, and add Part of the colloid, mix for 25 minutes, then add the remaining colloid, continue mixing for 25 minutes, then reduce the temperature to 45℃, mix for another 20 minutes, wait for a while, then lower the temperature to room temperature, that is, get sialic acid and lactate Protein composition; additional powder adjuvant can be added to this composition, mixed for another 40 minutes, and the mixing is finished.

According to parts by weight, it consists of the following components: 450 parts of instant whole milk powder, 420 parts of instant skim milk powder, 580 parts of whey protein powder, 0.9 parts of taurine, 330 parts of anhydrous glucose, 125 parts of oligofructose, furthermore, including 1 part of lactoferrin and 20 parts of sialic acid.

The combination of carrageenan, xanthan gum, pectin and guar gum, the weight ratio of the three combined colloids is 1:2:2:2.

Embodiment 9 The method and ratio are the same as in the first embodiment, wherein: The composite trace elements mentioned above have a composition and a ratio by weight of calcium 973.5 mg, phosphorus 649 mg, magnesium 106.2 mg, potassium 1121 mg, iron 14.75 mg, zinc 10.62 mg, sodium 413 mg, iodine 354 μg, copper 737.5 μg, manganese 737.5μg.

The above-mentioned multivitamin, the compounding component and the ratio by weight are: vitamin A 4224.1IU, vitamin D3 885 IU, vitamin E 35.4 IU, vitamin C 221.25 mg, vitamin K 177 μg, vitamin B1 2124 μg, vitamin B2 2802.5 μg, vitamin B6 1239 μg, vitamin B12 3.54 μg, nicotinic acid 11.06 mg, pantothenic acid 14012.5 μg, folic acid 354 μg, biotin 53.1 μg.

Embodiment 10 The method and ratio are the same as in the embodiment 2, wherein: The composite trace elements described above are compounded in a composition and a ratio by weight: calcium 300 mg, phosphorus 150 mg, magnesium 30 mg, potassium 375 mg, iron 3.5 mg, zinc 3 mg, sodium 125 mg, iodine 62.5 μg, copper 210 μg, manganese 6.25 μg. .

The above-mentioned multivitamin, the compounding component and the ratio by weight are: vitamin A 1165.5IU, vitamin D3 250 IU, vitamin E 35.4 IU, vitamin C 62.5 mg, vitamin K 25 μg, vitamin B1 350 μg, vitamin B2 475 μg, vitamin B6 225 μg, vitamin B12 0.625 μg, niacin 1.8 mg, pantothenic acid 2375 μg, folic acid 62.5 μg, biotin 10 μg.

Embodiment 11 The method and ratio are the same as in the third embodiment, wherein: The above composite trace elements, the compound composition and the ratio by weight are: calcium 300 mg, phosphorus 649 mg, magnesium 30 mg, potassium 1121 mg, iron 3.5 mg, zinc 10.62 mg, sodium 125 mg, iodine 354 μg, copper 210 μg, manganese 737.5 μg.

The above-mentioned multivitamin, the compounding component and the ratio by weight are: vitamin A 1165.5IU, vitamin D3 885 IU, vitamin E 12.5 IU, vitamin C 221.25 mg, vitamin K 25 μg, vitamin B1 2124 μg, vitamin B2 475 μg, vitamin B6 1239 μg, vitamin B12 0.625 μg, nicotinic acid 11.06 mg, pantothenic acid 2375 μg, folic acid 354 μg, biotin 10 μg.

Embodiment 12 The method and ratio are the same as in the embodiment 4, wherein: The above composite trace elements, the compound composition and the ratio by weight are: 650 mg of calcium, 450 mg of phosphorus, 60 mg of magnesium, 750 mg of potassium, 6.7 mg of iron, 5.5 mg of zinc, 300 mg of sodium, 210 μg of iodine, 470 μg of copper, 230 μg of manganese.

The above-mentioned multivitamins are compounded in composition and weight ratio: vitamin A 2600 IU, vitamin D3 685 IU, vitamin E 26 IU, vitamin C 142 mg, vitamin K 86 μg, vitamin B1 1420 μg, Vitamin B2 1120 μg, vitamin B6 650 μg, vitamin B12 2.25 μg, niacin 6.8 mg, pantothenic acid 4500 μg, folic acid 420 μg, biotin 35 μg.

Embodiment 13 The method and ratio are the same as in the embodiment 5, wherein: The composite trace elements mentioned above have a composition and a ratio by weight of calcium 973.5 mg, phosphorus 649 mg, magnesium 30 mg, potassium 375 mg, iron 3.5 mg, zinc 10.62 mg, sodium 413 mg, iodine 354 μg, copper 210 μg, manganese. 6.25 μg.

The above-mentioned multivitamin, the compounding component and the ratio by weight are: vitamin A 1165.5IU, vitamin D3 250 IU, vitamin E 35.4 IU, vitamin C 221.25 mg, vitamin K 177 μg, vitamin B1 2124 μg, vitamin B2 2802.5 μg, vitamin B6 1239 μg, vitamin B12 3.54 μg, nicotinic acid 11.06 mg, pantothenic acid 2375 μg, folic acid 354 μg, biotin 53.1 μg.

Embodiment 14 The method and ratio are the same as in the embodiment 6, wherein: The above composite trace elements, the compound composition and the ratio by weight are: calcium 900 mg, phosphorus 185 mg, magnesium 65 mg, potassium 720 mg, iron 7.5 mg, zinc 6.45 mg, sodium 235 mg, iodine 150 μg, copper 550 μg, manganese 365 The above-mentioned multivitamin, the compounding component and the ratio by weight are: vitamin A 4224.1IU, vitamin D3 885 IU, vitamin E 35.4 IU, vitamin C 221.25 mg, vitamin K 177 μg, vitamin B1 350 μg, vitamin B2 475 μg, vitamin B6 225 μg, vitamin B12 0.625 μg, niacin 1.8 mg, pantothenic acid 2375 μg, folic acid 354 μg, biotin 53.1 μg.

Embodiment 15 The method and ratio are the same as in the embodiment 7, wherein: The composite trace elements described above are compounded in a composition and a ratio by weight: calcium 552 mg, phosphorus 486 mg, magnesium 73 mg, potassium 658 mg, iron 5.3 mg, zinc 6.8 mg, sodium 320 mg, iodine 160 μg, copper 550 μg, manganese 550 μg .

The above-mentioned multivitamins are compounded in composition and weight ratio: the components and weight ratios are: vitamin A 1165.5-4224.1 IU, vitamin D3 250-885 IU, vitamin E 12.5-35.4 IU, vitamin C 62.5-221.25 Mg, vitamin K 25-177μg, vitamin B1 350- 2124μg, vitamin B2 475-2802.5μg, vitamin B6 225-1239μg, vitamin B12 0.625-3.54μg, niacin 1.8-11.06mg, pantothenic acid 2375-14012.5μg, folic acid 62.5- 354 μg, biotin 10- 53.1 μg.

Test experiment for an embodiment of the present invention 1. Nutritional ingredient testing Detection method: sialic acid was detected by high performance liquid chromatography, the detection conditions were C18 (250mm × 4.6mm, 5um) column; column temperature 30 ° C; fluorescence detector excitation Wavelength 373nm, emission wavelength 448nm; flow rate 1mL / min; injection volume is 10μL; mobile phase selected as methanol: acetonitrile: ultrapure water, ratio 8:9:84.

Test results: The product powders of the examples all meet the requirements of national standards. 2. Water activity and Bifidobacterium live bacterial count detection: Test Results: The products produced in the examples of the present invention have higher nutrient levels and lower low water activity, and can better ensure the stability of nutrients. 3. In vitro animal simulation experiment Detection method: 40 Kunming mice (male) with an average body weight of 20±0.05g were selected and divided into 4 groups, 12 in each group, and 4 groups of mice were: Group 1 was fed the milk powder of Example 9; 2 groups were fed the milk powder of Example 12; 3 groups were fed the milk powder of Example 15; 4 groups were fed with commercially available infant formula; Forty-eight mice were acclimated for one week and fasted for 48 hours with free access to water. Then quantitatively inject the milk powder with a concentration of about 37%, each 0.5mL, and then slaughter 10 of each group at 2h at the time point, quickly open the abdominal cavity, remove the stomach, duodenum, and place the small intestine saved in ice box. 1) Determination of fat digestibility The digestive tract was washed with physiological saline, gastric juice and intestinal juice were collected in physiological saline, and the fat content in each sample was measured by acid hydrolysis method, and the obtained fat content was the digestibility than the total fat content of the upper gavage emulsion. 2) Determination of lactose digestibility The digestive tract was washed with physiological saline, gastric juice and intestinal fluid were collected in physiological saline, and the lactose content of each sample was measured by the Rein-Kinong method, and the obtained lactose content was the digestibility of the total lactose content of the upper gavage emulsion. 3) Determination of protein digestibility The digestive tract was washed with physiological saline, gastric juice and intestinal juice were collected in physiological saline, and the protein content of each sample was determined by Kjeldahl method. The protein content obtained was the digestibility of the total protein content of the upper gavage emulsion.

Test results: Compared with the existing milk powder, the product obtained by the composition of the invention has higher fat digestibility, lactose digestibility and protein digestibility, and can better ensure the absorption of nutrients in the premature infants whose intestines are not fully developed.

Digestibility test results Lactose Digestibility Fat Digestibility (％) Protein Digestibility (％) embodiment 9 78.5 92.8 81.2 embodiment 12 78.2 93.5 78.8 embodiment 15 79.3 93.2 79.4 Comparative 62.8 72.1 72.5 embodiment Because lactoferrin has many biological activities such as antibacterial, anti-oxidation and anti-cancer, adding lactoferrin to infant formula or baby food can help infants and young children to resist microorganisms such as Escherichia coli, reduce common diseases such as diarrhea caused by viruses, and improve their immunity. The formulation of this patent application is more beneficial to the immune and nervous systems and promotes the growth of visceral mature and healthy visceral microflora.

The following experiments are carried out to verify the effect.

The first is an enhanced immunity test. A sample prepared in Example 1 was used as an experimental example, and a skim milk powder containing an equal amount of lactoferrin was used as a comparative example according to Example 1.

The experimental animals were selected from the same quality mice, 81 male and female, and were randomly divided into three groups. Each group was randomly divided into three groups for testing.

According to the food intake of the test mice, the maximum dose was designed to be g/d, fed directly, and fed continuously for 30 days. The MTT method was used to induce the transformation of mouse spleen lymphocytes induced by ConA; the hemagglutinin assay was performed by hemagglutination method; the antibody-producing cells were detected by Jerne modified slide method; and the mouse peritoneal macrophages phagocytized chicken red blood cells were tested by semi-in vivo method.

The experimental results are shown in the following table: Table 1 Effect of sample group on serum blood lysin anti-volume number in mice dose Number of experimental Optical density difference animals Experimental example 9 228.80±11.46 Comparative example 9 191.31±14.39 It can be seen from Table 1 that the experimental example has an obvious effect of increasing the blood solubilization anti-volume number compared with the mouse of the comparative example.

Table 2 Effect of sample on mouse antibody-producing cells dose Number of experimental Antibody-producing cell animals number（106） Experimental example 9 398.62±39.15 Comparative example 9 226.41±62.95 From Table 2, it can be seen that the experimental example has an effect of increasing the number of antibody-producing cells as compared with the mouse of the comparative example.

Table 3 Effect of sample group on the ability of mouse peritoneal macrophages to phagocytose chicken red blood cells dose Number of experimental Percentage of Phagocytic index animals phagocytosis（%） Experimental 9 35.92±9.19 1.63±0.56 example Comparative 9 23.98±6.86 1.01±0.39 example It can be seen from Table 3 that the peritoneal macrophages have superior phagocytic index to chicken red blood cells compared with the control mice.

WHAT

Claims

WE CLAIM IS

1. A lactoferrin and sialic acid-modulated milk powder, composed of (by weight): 400-600 parts of instant whole milk powder, instant skim milk powder 400-450 parts, 500- 700 parts of whey protein powder, 0.5-2 parts of taurine, 300-350 parts of anhydrous glucose, 120-130 parts of oligofructose, lactoferrin 1-3 Parts, sialic acid 20-40 parts, and 0.5 to 2 parts by weight of a cationic colloid, wherein the cationic colloid is eather: carrageenan, guar gum, and propylene glycol alginate, in a ratio of (1-2): (1-2): (1-2) by weight; modified starch, locust bean gum, konjac gum and guar gum, in a ratio of (1-2): (1-2): (1- 2): (1-2) by weight; carrageenan, xanthan gum, pectin and guar gum, in a ration of (1-2): (1-2): (1-2): (1-2) by weight; xanthan gum, locust bean gum, konjac gum and carrageenan, in a ratio of (1-2): (1-2): (1- 2): (1-2) by weight; or dextrin, carrageenan, xanthan gum, and sodium alginate, in a ratio of (1-2): (1-2): (1-2): (1-2) by weight.

2. The prepared milk powder according to claim 1, the ratio of the constituent components and parts by weight is: 500 parts of instant whole milk powder, instant skim milk powder 420 parts, 600 parts of whey protein powder, 1 part of taurine, 320 parts of anhydrous glucose, and 127 parts of oligofructose, including 2 parts of lactoferrin and 30 parts of sialic acid.

3. The prepared milk powder according to claim 1 or 2, wherein the milk powder further comprises 0.1 to 0.5 parts by weight of a composite trace element and 0.1 to 0.3 parts by weight of a multivitamin.

4. The milk powder according to claim 3, wherein the milk powder further comprises 0.3 parts by weight of a composite trace element and 0.2 parts by weight of a multivitamin.

5. The prepared milk powder according to claim 3 or 4, wherein the composite trace element has a compound composition and a weight ratio of calcium: 300-973.5 mg, phosphorus 150-649 mg, and magnesium 30 -106.2 mg, potassium 375-1121 mg, iron 3.5- 14.75 mg, zinc 3-106.62 mg, sodium 125-413 mg, iodine 62.5-354 μg, copper 210-737.5 μg, and manganese 6.25-737.5 μg.

6. The prepared milk powder according to claim 3 or 4, wherein the ratio by weight of the multivitamin are: vitamin A 1165.5-4224.1 IU, Vitamin D 250-885 IU, vitamin E 12.5-35.4 IU, vitamin C 62.5-221.25 mg, vitamin K 25-177 μg, vitamin B1 350-2124μg, vitamin B 475-2802.5 μg, vitamin B 225-1239 μg, vitamin B 0.625- 3.54 μg, niacin 1.8-11.06 mg, 6 12 pantothenic acid 2375-14012.5 μg, folic acid 62.5-354 μg, biotin 10-53.1 μg.