CN111903766A

CN111903766A - Infant formula milk powder and preparation method thereof

Info

Publication number: CN111903766A
Application number: CN202010793714.8A
Authority: CN
Inventors: 李拖平; 李苏红; 孙玥; 孙晓; 李文杰
Original assignee: Shenyang Agricultural University
Current assignee: Shenyang Agricultural University
Priority date: 2020-08-10
Filing date: 2020-08-10
Publication date: 2020-11-10

Abstract

The invention provides infant formula milk powder which is characterized by comprising the following components in parts by weight: the infant formula milk powder is a milk-based formula, and lactose-N-disaccharide I and human milk oligosaccharide are added. The invention also provides a preparation method of the infant formula milk powder. The formula milk powder disclosed by the invention is added with lactose-N-disaccharide I and human milk oligosaccharide, so that the components of the formula milk powder are closer to breast milk, and the formula milk powder can be used as infant antiallergic formula milk powder.

Description

Infant formula milk powder and preparation method thereof

Technical Field

The invention belongs to the technical field of infant formula food, and particularly relates to infant formula milk powder added with lactose-N-disaccharide I and human milk oligosaccharide and a preparation method thereof.

Background

All over the world, infant feeding regimes have similar characteristics. The superiority of some of the nutrients in breast milk undoubtedly makes it the best source of nutrition for newborns. Traditionally, breast milk is the only nutrient before an infant can eat solid food. Breast feeding is an important basis for infant nutrition. Breast milk can provide all nutrients necessary for the growth and development of infants, thereby realizing the optimal growth, development and health of infants. For infants, breast milk is the best nutritional product for growth and development.

Although breast feeding may be advocated by many health organizations, most infants within 1 year of age receive formula powder feeding at specific times throughout the world. About 1/3 infants are unable to obtain breast feeding globally due to physical constitution, environment, disease, occupation, society, etc. In rapidly developing countries such as china, breast-feeding is not available in even higher rates. The pure breast feeding proportion of China is extremely low, and the common milk powder is lack of antibiotics and active substances and cannot meet the sufficient nutritional requirements of infants. The Chinese breast feeding influence factor survey report issued by the foundation of Chinese development research shows that the proportion of early contact and early milk start after birth of infants is only 11 percent and is far lower than the world average level of 45 percent. For office workers, 86% of infants with salary can have less than 6 months of vacation. The proportion of the nursing room set in the workplace is only 19 percent, and the requirement of continuous breast feeding after the baby mother resumes work is far from being met.

Cow milk contains 85-88% of water, fat, protein, lactose, minerals and vitamins. In order to prolong the shelf life of milk products and to adjust the production and consumption disharmony, manufacturers use concentration and drying processes to remove most of the water from milk or milk-processed products, and produce so-called powdered milk, also called powdered milk.

Until the 19 th century, the replacement of breast feeding with infant formula was not studied. In 1838, the German scientist Johann Simon performed a comprehensive analysis of the nutritional content of cow's and breast milk. In 1865, the german chemist Justus von Liebig invented a milk formula with cow milk as raw material and wheat, malt flour and potassium bicarbonate as additives, and this milk formula was the infant formula which was patented and marketed the earliest.

The formula milk powder close to breast milk in composition has important significance for nutrition and health of infants. Modern infant formula is a breast milk substitute produced industrially and designed specifically for infants. The infant formula milk powder is a powdery product which is prepared by taking milk and milk protein products as main raw materials, adding a proper amount of vitamins, minerals and/or other auxiliary materials and only using a physical method for production and processing, and is suitable for normal infants. The infant formula milk powder is an infant food which takes cow milk as a main raw material and simulates breast milk by adjusting components, and can meet the growth and development and nutritional requirements of infants under 3 years old as a substitute of the breast milk. The milk-based infant formula milk powder and the functional formula milk powder are important components of milk powder products, and compared with ready-to-drink products, the milk powder products are easy to adjust in nutritional composition, long in storage period and more suitable for special nutritional requirements of infants. Infant formula powders can be classified into infant formula powders (suitable for eating at 0-6 months), larger infant formula powders (suitable for eating at 6-12 months) and infant formula powders (suitable for eating at 12-36 months), depending on their suitability for different months.

Breast milk has significant advantages over infant formula. The breast milk is the most suitable and perfect natural food for infants, is specially designed for infants, and has the nutritional ingredients which change along with the growth and development of the infants. Breast milk contains immune factors and digestible whey proteins, and is a good source of taurine (essential for bile, eye and brain function). Breast milk contains digestible lipids, which are essential for brain development. Lactose in breast milk promotes the growth of acid-forming bacteria and enhances the absorption of calcium and other mineral elements. In addition, the content of sodium and zinc in the breast milk with good quality is low, iron and calcium exist in a form easy to absorb, the absorption rate of iron in the breast milk reaches 50%, and the absorption rate of iron in food is only 2% -30%. The nutrients in the breast milk are particularly suitable for the growth and development requirements of the infants in the aspects of quantity, proportion, biological activity and the like, and the breast-fed infants have good intelligence and physical development and strong resistance. Research shows that breast feeding can enhance the immunity of infants, promote intelligence, reduce the occurrence of sudden infant death, reduce obesity in childhood, reduce the probability of suffering from allergic diseases and the like, and the benefit brought by the breast feeding to the adult stage can be extended.

The infant formula milk powder is close to breast milk to the maximum extent, and whether the feeding effect of the infant formula milk powder is consistent with the breast milk feeding effect or not is the golden standard for testing the infant formula milk powder. Despite the lack of perfection of current infant formulas, there has been significant progress and improvement in the history of breast milk replacement development, and the composition and quality of infant formulas is still in constant perfection. Recent rapid development of infant formula has been mainly reflected in the reduction or elimination of potential allergens and the maximum proximity to human milk.

In 1899, the French doctor Tissier isolated bifidobacteria from the faeces of breast-fed infants, and found that bifidobacteria are associated with the frequency and nutrition of diarrhea in infants, and thus, extensive studies on intestinal microecology systems were initiated. The bifidobacterium is one of the most main physiological beneficial bacteria in human intestinal tracts, plays an important role in maintaining the microecological balance of the intestinal tracts, and has multiple physiological functions of resisting infection, resisting tumors, activating immunity, delaying senescence, inducing apoptosis, nourishing and the like in vivo. As one of indexes for testing the health of organisms, the bifidobacterium plays an important role in promoting the growth and development of infants, regulating nutrition, preventing diarrhea and constipation, improving immunity, preventing infection and the like.

The method of feeding has a major influence on the relative proportion of established flora in the gut, usually a higher proportion of bifidobacteria in the gut of breast-fed infants than in artificially fed infants of the same age, which have a more complex flora composition, which means that breast-fed infants are at a lower risk of intestinal, respiratory and urinary tract infections. Experiments show that the bifidobacteria in intestinal tracts of breast-fed infants born for 6-8 days account for 98% of the total bacteria, and the bifidobacteria in intestinal tracts of artificially fed infants account for only 61%. Although infant food formulations have been improved in recent years, it is less common to achieve the same benefits of bifidobacteria in the gut as breast-fed infants. These observations, however, demonstrate that diets can affect the composition of the gut microbiota, and that the results may also affect health. This is the basis for dietary intervention that is now very popular.

The gut microbiota uses substrates from food (i.e. non-digestible oligosaccharides, dietary fibres, non-digestible proteins that enter the gut) and endogenous substrates such as mucin (which is the major glycoprotein that makes up the outer mucosal layer of the gut) to maintain growth. The huge flora in the intestine is absolutely anaerobic and energy is obtained by fermentation. The two main fermentation substrates are non-digestible carbohydrates from the diet (i.e. resistant starch, non-starchy polysaccharides and fibres from plants and non-digestible oligosaccharides) and proteins not digested by the small intestine. Among them, the fermentation of carbohydrates is the most advantageous for obtaining energy, which results in a gradient utilization of the matrix in the intestinal tract. The main substrate on which bacteria depend for growth is dietary carbohydrates. Lactose and oligosaccharides such as fructooligosaccharides, galactooligosaccharides enter the colon. The degree to which the gut flora degrades these carbohydrates varies considerably, as do the non-digestible oligosaccharides that enter the large intestine, such as fructooligosaccharides, galactooligosaccharides, etc., which are preferentially utilized by bifidobacteria.

Recent medical research proves that the intestinal flora is closely related to human health. When beneficial bacteria in human body are dominant in quantity, the health of human body can be kept, and when beneficial bacteria in microecosystem in intestinal tract of human body are in disadvantage, and harmful bacteria such as putrefactive bacteria occupy the wind, the flora balance is destroyed, and disease can be caused.

The definition of probiotic (probiotic) is "a live microbial dietary supplement beneficial to the health of the host". Probiotics are "non-pathogenic, viable microorganisms, made from single or mixed cultures, that when applied to humans or animals, produce beneficial effects on the host by improving the balance of gut microorganisms and their performance when sufficient doses are achieved. Probiotics are a group of beneficial microflora which can colonize in the intestinal tract, maintain the balance of intestinal flora, stimulate the immune tissue of the intestinal mucosa and have main influence on the intestinal mucosa immunity. Current research focuses on the effect of probiotics on immune regulation, commonly referred to as lactobacilli and bifidobacteria.

In 1995, professor Gibson in the united kingdom named prebiotics, substances that selectively promote the growth of probiotics such as bifidobacteria. Since the 20 th century and 80 th century Japan discovered the prebiotic effect of fructo-oligosaccharide, other various functional oligosaccharides were developed and produced industrially in large quantities.

Prebiotics are defined as "nondigestible food ingredients that can beneficially affect the host by selectively stimulating the growth or activity of one or a few bacteria in the colon, thereby promoting host health". Such activated bacteria should be naturally beneficial, such as bifidobacteria and lactic acid bacteria. Prebiotics have this effect provided they must withstand digestion prior to entering the colon, and preferably remain undigested throughout the large intestine until the beneficial effects are achieved. The prebiotics are indigestible food components, which are not digested and absorbed by small intestine but directly reach large intestine after being ingested, and are selectively utilized as carbon sources by physiologically active microorganisms in the large intestine to promote the growth and activity of the physiologically active microorganisms, so that the prebiotics have health effect on hosts. Bifidobacteria are by far the major dominant flora that can be stimulated by all prebiotics.

The oligosaccharide (oligosaccharide), also called oligosaccharide or oligooligosaccharide, is a straight-chain or branched-chain carbohydrate compound formed by connecting 2-10 same or different monosaccharide units through glycosidic bonds. Oligosaccharides are widely present in the natural world, such as breast milk and colostrum of various animals, and are also present in small amounts in free form or in sugar-bound form in plants, and recently, they have been receiving attention because of their physiological effects on the digestive tract.

The prebiotics are mainly functional oligosaccharides, have the sweetness of 30-60 percent of that of cane sugar, are healthy sugar, are not absorbed after eating, do not increase the blood sugar, do not cause obesity and also do not cause decayed teeth. In recent years, low molecular weight oligosaccharides have gained much attention because, in addition to being non-starch polysaccharides, they are the most convenient carbon source for colonic bacteria, which after ingestion are not digested in the small intestine and enter the ileum and caecum in an intact state, where most or part of them can be utilized as substrates by resident bacteria in the colon, resulting in a decrease in pH and the production of short chain fatty acids, which effect can lead to a reduction in pathogenic bacteria. Research shows that eating oligosaccharide with prebiotic function can stimulate the propagation of inherent beneficial bacteria in vivo, promote the balance of flora, regulate immunity and promote health. Fructooligosaccharides naturally present in food products are well-studied prebiotics.

Prebiotics are particularly suitable for the growth and activation of bifido-and lactic-bacteria and are included as beneficial microorganisms because some species of this group have therapeutic and prophylactic effects on infants and adults. Bifidobacteria have a particularly great influence on weaning infants, for example it helps to prevent the development of diseases in infants and to inhibit infection by intestinal pathogens in the gut. Similarly, if bifidobacteria are reduced, it may account for at least part of the susceptibility of the elderly to disease, and thus there is a strong link between the reduced resistance to disease origin in the elderly and the reduction in the number of bifidobacteria and the production of naturally occurring resistant factors. The ability of the intestinal flora to cope with pathogenic bacteria is substantially reduced due to the reduction of bifidobacteria.

Prebiotics can stimulate the growth of a limited number of bacteria, resulting in a change in the balance between microbiota in the large intestine. The effect of prebiotics on flora regulation was also seen in human feeding experiments, with galacto-and fructo-oligosaccharides increasing bifidobacteria in faeces. If the selectively stimulated bacteria are of probiotic nature, the health efficacy of ingestion of prebiotics is similar to that of probiotics. In addition, prebiotic dietary supplements act not only to increase the number of lactic acid bacteria, but also to regulate the metabolism of the microorganism. It was found that galacto-and fructo-oligosaccharides cause an increase in bifidobacteria in vivo similar to breast-fed infants, that an increase in the number of bifidobacteria and lactobacilli protects the gut from infections and allergies, and that this effect persists until after infancy.

Although people try to supplement beneficial bacteria in human bodies by using probiotic preparations (bifidobacteria, lactic acid bacteria and the like) to improve flora balance and improve immune function, live bacteria are difficult to kill by gastric acid, bile and the like after entering esophagus and can enter the large intestine for a few times. With the development of probiotic products (e.g. maintaining high viable counts, avoiding pollution), prebiotics have been developed with the aim of selectively enhancing the human indigenous flora by non-living food ingredients, thereby overcoming the loss of probiotic survival rate. A large number of research results prove that the prebiotics can promote the propagation of inherent probiotics in the intestines, adjust the microecological balance of the intestines, generate organic acid to acidify the pH value of the intestines, and inhibit the growth of harmful bacteria and the generation of toxins when being eaten. In addition, ingestion of prebiotics helps prevent diarrhea and constipation, regulate the body's immune function, lower blood lipids and cholesterol, and promote the absorption of nutrients.

Galacto-oligosaccharides (GOS) are oligosaccharides containing galactose and are Glu-alpha-1, 4[ beta-Gal-1, 6 [)]_nThe oligosaccharide in the form, wherein n is 2 to 5. Galacto-oligosaccharides are produced from milk syrup by converting the transgalactosylation activity of beta-galactosidase. The commercial galacto-oligosaccharide consists of 2-8 monosaccharides, wherein the main galacto-oligosaccharide is disaccharide and trisaccharide, the monosaccharides in the galacto-oligosaccharide are mainly connected by beta-1, 4 glycosidic bonds and beta-1, 6 glycosidic bonds, and a small amount of beta-1, 3 glycosidic bonds and beta-1, 2 glycosidic bonds are also available.

Certain strains of breast milk can colonize the gut during childhood and act as probiotics, and human milk oligosaccharides are good media for these probiotics. The human milk oligosaccharide is beneficial to the health of human intestinal tracts, promotes the proliferation of beneficial bacteria in the intestinal tracts and prevents the colonization of exogenous pathogenic bacteria. These probiotics affect not only the ability of the infant to fight pathogenic bacteria, but also the use of energy and the development of obese shapes. There is increasing evidence that human colonic microorganisms are beneficial to the nutrition and health of the host. Especially for the highly sensitive stages of infancy, it is important to improve gut health by adjusting the diet.

The lactooligosaccharide can promote the proliferation of beneficial bacteria, promote the division and secretion of B lymphocyte, induce the mRNA expression of various substances with immunological activity (such as interferon and interleukin), enhance the activity of macrophage, promote the absorption of antioxidant trace elements such as Zn, Ca, Se and the like, and improve the immunological function of the organism. After the lacto-oligosaccharide promotes a large amount of beneficial bacteria such as lactic acid bacteria and the like to grow and proliferate in intestinal tracts, the lactic acid bacteria can synthesize nutrient substances required by human growth, such as B vitamins, vitamin K, nicotinic acid and amino acid.

Human Milk Oligosaccharides (HMOs for short), also called breast Milk Oligosaccharides, Human Milk Oligosaccharides, and breast Milk Oligosaccharides. Human milk oligosaccharides are second only to lactose and fat in human breast milk, the 3 rd largest solid component, which has been found to have important biological functions. The content of the human milk oligosaccharide in human colostrum is up to 20-25 g/L, and the content of mature breast milk is reduced to 5-20 g/L.

Human milk oligosaccharides consist of 5 basic saccharide units: d-glucose (Glc), D-galactose (Gal), N-acetylglucosamine (GlcNAc), L-fucose (Fuc) and sialic acid (Sia). The human milk oligosaccharides all contain lactose (Gal-beta-1, 4-Glc) at the reducing end, and on the basis of the reducing end, the oligosaccharide chains are extended by connecting beta-1, 3 or beta-1, 6 bonds with lacto-N-disaccharide I (Gal-beta-1, 3-N-GlcNAc, type I chain structure) or N-acetamido lactose (Gal-beta-1, 4-N-GlcNAc, type II chain structure) to form a core structure such as lacto-N-tetraose, lacto-N-neotetraose and lacto-N-hexaose. On the basis of the core structure, sugar chains can be modified with different numbers of fucose and sialic acid to form a wide variety of oligosaccharide structures.

Human milk oligosaccharides are primary prebiotics that stimulate the development of bifidogenic intestinal flora in the gut of breast-fed infants. Bifidus factor effects of fructo-oligosaccharides and galacto-oligosaccharides are comparable to human milk oligosaccharides, but evidence showing that human milk oligosaccharides have an increased effect in the gut beyond the effect on bifidobacteria is increasing. It can block the adhesion of pathogenic bacteria on the straw film of intestine and the development of intelligence.

Human milk oligosaccharides may produce local or systemic potential health benefits for breast-fed infants, and infant formulas fortified with these functional ingredients are beneficial to the physical health of the infant. Human breast milk contains a large number of abundant complex oligosaccharides that are not readily digestible by infants but are available to the infant's intestinal microbiota, and these oligosaccharides are often associated with bifidobacteria, together contributing to a more abundant intestinal microbiota in healthy infants. Many of the benefits of human milk are attributed to oligosaccharides, which not only have the effect of combating intestinal pathogenic microbial infection and maintaining intestinal ecological balance, but also bind toxins, stimulate bifidobacterial growth and competitively exclude pathogenic bacteria.

Human milk oligosaccharides have high biological activity, are important active factors in breast milk, are natural molecules which are well recognized to have high potential in the fields of nutrition and biomedical application, and play an extremely important role in the healthy growth of infants. The human milk oligosaccharide is an important prebiotic in breast milk, is not damaged by gastric acid of a human body, is not decomposed by digestive enzyme, can directly reach the large intestine, stimulates the growth of beneficial flora (bifidobacteria and lactobacilli) in the intestinal tract, indirectly inhibits the growth of harmful flora, and maintains the microecological balance of the intestinal tract. The oligosaccharide is a free receptor of bacteria in the intestinal tract, can be combined with escherichia coli in the intestinal tract, and can block and prevent the escherichia coli from colonizing the intestinal mucosa. The oligosaccharide is also fermented and decomposed into short-chain fatty acid by intestinal bacteria, and the short-chain fatty acid can be effectively absorbed and utilized by epithelial cells of the intestinal tract of the infant, can promote the growth of the epithelial cells and the intestinal peristalsis, maintain the acidic environment of the intestinal tract, and inhibit the propagation of escherichia coli. Human milk oligosaccharides may also affect the intestinal epithelial cell response of infants, thereby indirectly affecting the immune system of infants. The galacto-oligosaccharide and the fructo-oligosaccharide added in the existing infant formula milk powder cannot imitate the function of human milk oligosaccharide.

Lacto-N-disaccharide I (Lacto-N-biose I, LNB for short), also called galactose beta-1, 3-N-acetylglucosamine (Gal-beta-1, 3-GlcNAc), Lacto-N-disaccharide. lacto-N-disaccharide I is the core building block of human milk oligosaccharides and is a specific bifidus factor.

Since lacto-N-disaccharide I is an important structural component in human milk oligosaccharides, many researchers have attempted to synthesize lacto-N-disaccharide I. Patent application CN 1207135a discloses a method for preparing lacto-N-disaccharide I using microbial culture broth. Synthesis of lactose-N-disaccharide I was carried out by Veter A et al using a multienzyme synthesis method (Veter A et al, registered glycosylation-associated synthesis of lactose-N-biose I (Gal. beta.1-3 GlcNAc) and 3' -silyl-lacto-N-biose I (NeuAc. alpha.2-3 Galb1-3GlcNAc), Eur. J.biochem,2000,267: 942-949). However, while the milligram fraction of the natural oligosaccharide extract lacto-N-disaccharide I is commercially available for chemical analysis, no synthetic lacto-N-disaccharide I is commercially available to date.

According to the analysis of Chaturvedi P et al, breast milk has an oligosaccharide content of about 7.2g/L, a 2 '-fucosyllactose content of about 2.43g/L, a lacto-N-fucosylpentaose content of about 1.91g/L, a 3' -fucosyllactose content of about 0.86g/L, a lacto-N-tetraose content of about 0.55g/L, a lacto-N-difucohexaose content of about 0.50g/L, a lacto-N-difucosyltetraose content of about 0.43g/L, and a lacto-N-neotetraose content of about 0.17g/L (Chaturvedi P et al, fused human milk lipids, vitamin E index derivatives and over the core of milk. Glycobiology,2001,11(5): 365-.

2 '-fucosyllactose can be produced by fermentation, i.e. glucose and lactose are fermented to 2' -fucosyllactose and other carbohydrates, which are purified/filtered, evaporated, and dried to give these powders, which contain lactose and other human milk oligosaccharides. The human milk oligosaccharide 2' -fucosyllactose can now be produced for use in the production of infant formula or as a dietary supplement, making it accessible to the nutrition of breast milk.

Lacto-N-tetraose (LNT for short) is a neutral oligosaccharide present in human colostrum. The lacto-N-tetraose is converted from lacto-N-trisaccharide II by the human enzyme β -1, 3-N-acetylglucosamine aminotransferase 2. lactose-N-tetrasaccharide is a human milk oligosaccharide core type with very rich content in human breast milk, and the scientifically verified effect of lactose-N-tetrasaccharide can reduce pathogenic bacteria colonization and infection caused by metabolic toxins. Meanwhile, lacto-N-tetraose can promote intestinal health balance by supporting the proliferation of bifidobacteria.

Lacto-N-neotetraose (Lacto-N-neotetraose, LNnT for short) is one of the oligosaccharides present in human milk. Studies have shown that the concentration of lacto-N-neotetraose is about 0.54g/L in human colostrum and drops to 0.2g/L in mature breast milk. The lacto-N-neotetraose acts as a bacterial receptor for pneumococci, and can be used to recognize the receptor specificity of glycosyltransferases, the substrate specificity of glycosidases, and the structure of antigenic determinants. In addition, lacto-N-neotetraose is a core structural element of more complex oligosaccharides in glycolipids and glycoproteins (erythrobioside esters, 6-sialyl-lacto-N-neotetraose, etc.) having various physiological activities.

Most of functional milk powder for promoting intestinal health is added with prebiotics, and can assist in balancing intestinal flora and improving intestinal function. The functional characteristics of the formula milk can be more similar to those of breast milk by supplementing prebiotic components in the formula milk. Prebiotics are foods that are not digested and absorbed by the body and selectively promote the growth and viability of a limited number of bacteria in the intestinal tract. Studies have shown that the intestinal flora plays an important role in the immune response of the local and systemic system. Emerging theories suggest that early nutritional intervention may lead to body immunological features by modifying the gut microflora in a way that alters the microbiological characteristics, thereby producing a clinical effect. The clinical interest is to promote the potential anti-allergic reaction of the organism by controlling the intestinal flora, and the method plays an important role in preventing atopic diseases. The composition of the intestinal flora of healthy individuals and patients with anaphylaxis is analyzed, and the results show that the microbial patterns of the healthy individuals and the patients with anaphylaxis are different.

Today, the market is full of the full complement of infant formula, leaving parents and doctors with no choice, especially when allergy is a concern. Generally, allergy is a specific reaction to an allergen, a harmless substance, which is characterized by the ability to induce a specific lgE response. Food allergy is an adverse immune response that occurs repeatedly upon sustained exposure to a given food, unlike adverse reactions to food, such as food intolerance, pharmacological reactions and toxin elicitation. The most common allergies in infants are allergic dermatitis, asthma, allergic rhinoconjunctivitis, and food allergies. Infants are vulnerable groups and allergies to infant formula sometimes result in emergency hospitalization. An increasing number of infants worldwide suffer from allergic diseases and there is a concern about how to prevent or reduce the risk of allergy during critical periods. Allergic reactions in infants to food are ubiquitous and are associated with food composition. Food allergies may occur at an early stage and may occur frequently. Therefore, prevention should be performed as early as possible. Nutritional prevention after delivery can reduce food allergies and a range of infant illnesses during infancy.

People have the highest concern about the prevalence of food allergies in young children. The biggest reason reported is that many infants are no longer breastfed but are fed with infant formula for short or long term supplementation or single feeding, or are changed from breastfeeding to powder feeding after weaning. Although any food may trigger an allergic reaction, there are foods that are more likely to cause food allergy in most infants, such as cow's milk protein, eggs, peanuts, walnuts, soy (mainly for infants) and wheat, from which 85% to 90% of diagnosed food allergy is caused. The relative frequency of development of different allergens varies with the feeding regime of the infant. Generally, foods containing polypeptides or proteins may cause allergic reactions. Approximately 2.5% of newborns have hypersensitivity to cow's milk before the age of 1 year, and approximately 80% of these children will be accompanied by this hypersensitivity until the age of 5 years. About 60% of cow's milk allergy is caused by immunoglobulin (lgE). Nearly 25% of infants will be accompanied by this hypersensitivity reaction to age 20, while 35% of these children may suffer from other food allergies. Infant nutrition and other environmental factors have profound effects on infant allergies.

It is a general consensus that the increased incidence of allergic disease in infants and young children means that it is becoming more and more important to produce commercial healthy, effective "anti-allergic" foods. The addition of acidic and neutral oligosaccharides to the formula powder provides effective early prevention, which is also effective in infants with low risk of allergy. The formulation reduces airway hypersensitivity immediately after birth and even later in life. Studies have shown that infant formula mixed with short chain neutral galacto-oligosaccharides and long chain oligosaccharides can reduce the incidence of allergic dermatitis in the first 6 months of life of the newborn, which can indicate that the primary mechanism of action of immunomodulation is achieved by the intestinal flora. They fed healthy term infants with a history of allergies to parents and consumed formula milk powder supplemented with prebiotics (8g/L galacto-oligosaccharides/polyfructose) and placebo (8g/L maltodextrin) between 6 months and 2 years of age. During this period, the allergic symptoms in infants of the galactooligosaccharide/polyfructose group were significantly reduced. Early oligosaccharide dietary intervention recipes have a prophylactic effect on allergies and infections.

More and more infant formulas are supplemented with prebiotics. Prevention of allergic reactions by means of dietary intervention, the use of prebiotics to modulate the infant's intestinal flora and thus promote a healthy maturation of the immune system, including desensitization processes to oral tolerance to food antigens. It is now generally accepted that the gut microflora plays an important role in the establishment of the immune system after birth of an infant and that a number of methods are used to modulate the gut microflora and thereby influence the development of allergic symptoms. Studies have shown that early oligosaccharide prebiotic diets can prevent allergies and infections. This protection exceeds the intervention period, suggesting that the mechanism of action may be due to a change in gut flora affecting the immunomodulating effect.

Studies on the use of lacto-N-disaccharide have been rarely reported. Lipping et al, in patent application CN 106589012 a, disclose that mouse feeding experiments show that lacto-N-disaccharide can specifically proliferate bifidobacterium enterobacter and suggest that lacto-N-disaccharide can be added as prebiotic in food products.

Disclosure of Invention

The invention aims to provide nutrition-enriched infant formula milk powder added with lactose-N-disaccharide I and human milk oligosaccharide and a preparation method thereof.

In the infant formula milk powder, the content of lactose-N-disaccharide I can be 0.01-2.5%, and the content of human milk oligosaccharide can be 0.01-2.5%.

The lacto-N-disaccharide I (LNB) of the invention can be synthesized by an enzymatic method. The enzymatic synthesis of lacto-N-disaccharide I can be carried out, for example, by using sucrose and N-acetylglucosamine as raw materials, and converting them into human milk oligosaccharide synthetases such as epimerase, uridine phosphate acyltransferase, lactobiose phosphorylase, and sucrose phosphorylase. The four synthetase genes can be cloned in bifidobacteria and constructed in food-grade engineering bacteria (Escherichia coli/Bacillus subtilis).

In the infant formula milk powder of the present invention, the human milk oligosaccharide may include one or more than two of human milk oligosaccharides such as 2 '-fucosyllactose, lacto-N-fucosylpentaose, 3' -fucosyllactose, lacto-N-tetraose, lacto-N-difucohexaose, lacto-N-difucosyltetraose, lacto-N-neotetraose, and the like.

The lacto-N-tetraose of the present invention may be obtained commercially or may be biosynthesized. For example, lactose-N-trisaccharide is synthesized from lactose and N-acetylglucosamine as raw materials by using glucose-1-phosphatase, β -1, 3-N-acetylglucosamine transferase and UDP-glucose hexose phosphate uridyltransferase, and then galactose is introduced into the non-reducing end of a lactose-N-trisaccharide acceptor by using lactose-N-trisaccharide as a substrate and sucrose as raw materials by using galactose and UDP-galactose epimerase, thereby obtaining lacto-N-tetrasaccharide.

The invention also discloses the infant formula milk powder added with the lactose-N-disaccharide I and the human milk oligosaccharide, which comprises the following raw materials in percentage by weight: 25-40 parts of full-cream milk powder, 25-35 parts of desalted whey powder, 3-15 parts of vegetable oil, 10-25 parts of lactose, 0.015-2.5 parts of lactose-N-disaccharide I, 0.015-2.5 parts of human milk oligosaccharide, 3-5 parts of galacto-oligosaccharide, 5-15 parts of 1, 3-dioleate-2-palmitic triglyceride, 0.05-0.35 part of casein phosphopeptide, 0.4-1 part of compound vitamin, 0.3-1 part of compound mineral substance, 0.01-0.03 part of nucleotide, 0.5-0.8 part of L-carnitine, 0-0.04 part of taurine, 0.02-1 part of arachidonic acid (ARA), 0.02-1 part of docosahexaenoic acid (DHA) and 0.01-1.5 parts of milk fat globule membrane.

In the infant formula milk powder, the vegetable oil comprises, by weight, 25-35 parts of coconut oil, 36-48 parts of corn oil, 12-22 parts of high-oleic acid sunflower seed oil, 8-12 parts of soybean oil and 10-20 parts of low-erucic acid rapeseed oil.

In the infant formula milk powder, the compound vitamins comprise the following raw materials, by weight, 7-15 parts of vitamin A, 3-7 parts of vitamin D, 5-10 parts of vitamin E, 0.8-4.6 parts of vitamin K, 4.6-8 parts of vitamin B, 1.2-2.8 parts of folic acid, 50-60 parts of vitamin C and 0.8-3 parts of lutein.

In the infant formula milk powder, the compound mineral matter comprises the following raw materials, by weight, 0-45 parts of tricalcium phosphate, 0.1-0.5 part of anhydrous copper sulfate, 8-12 parts of potassium chloride, 0.06-3 parts of potassium iodate, 10-15 parts of ferrous sulfate, 10-20 parts of magnesium chloride, 0-0.5 part of manganese sulfate, 0-0.5 part of sodium selenite, 1-5 parts of zinc oxide and 25-45 parts of sodium citrate.

In the infant formula milk powder, the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

The invention also discloses application of the infant formula milk powder as infant antiallergic formula milk powder. The infant formula milk powder has the beneficial effect of antianaphylaxis and can be used as the infant antianaphylaxis formula milk powder.

The invention also discloses a preparation method of the infant formula milk powder, which comprises the following steps:

1) preparing materials: weighing whole milk powder, desalted whey powder, lactose, taurine, compound mineral matters and compound vitamins according to a set proportion, mixing and dissolving the whole milk powder, the desalted whey powder, the lactose, the taurine, the compound mineral matters and the compound vitamins by using purified water at 45-60 ℃, fully stirring the mixture, and fully and uniformly mixing the mixture with vegetable oil, 1, 3-dioleoyl-2-palmitic acid triglyceride and milk fat globule membrane after uniformly stirring the mixture;

2) homogenizing;

3) sterilizing;

4) and (3) drying: spray drying the sterilized materials to prepare milk powder, and sieving the milk powder with a 20-mesh sieve to prepare base powder;

5) mixing: premixing lactose-N-disaccharide I, human milk oligosaccharide, galacto-oligosaccharide, L-carnitine, nucleotide, casein phosphopeptide, docosahexaenoic acid and arachidonic acid which are weighed according to a preset proportion, and then fully and uniformly mixing the mixture with base powder.

In the preparation method, the homogenizing refers to homogenizing the uniformly mixed material by using a high-pressure homogenizer, wherein the homogenizing condition can be that the homogenizing temperature is 50-65 ℃, and the homogenizing pressure is 12-24 MPa.

In the preparation method, the sterilization condition can be that the materials are sterilized at the temperature of 80-94 ℃, and the sterilization time is 25-50 s.

In the preparation method, the spray drying process conditions can be that the spray pressure is 12MPa to 20MPa, the temperature of the concentrated material is 40 ℃ to 65 ℃, the air inlet temperature is 165 ℃ to 195 ℃, and the air exhaust temperature is 80 ℃ to 95 ℃.

Specifically, the present invention is as follows:

1. an infant formula milk powder is characterized in that: the infant formula milk powder is a milk-based formula, and lactose-N-disaccharide I and human milk oligosaccharide are added.

2. The infant formula powder according to item 1, characterized in that: the content of the lacto-N-disaccharide I is 0.01-2.5%.

3. The infant formula powder according to item 1, characterized in that: the content of the human milk oligosaccharide is 0.01-2.5%.

4. Infant formula powder according to item 2, characterized in that: the content of the human milk oligosaccharide is 0.01-2.5%.

5. The infant formula powder according to item 4, characterized in that: the infant formula milk powder comprises the following raw materials in parts by weight: 25-40 parts of full-cream milk powder, 25-35 parts of desalted whey powder, 3-15 parts of vegetable oil, 10-25 parts of lactose, 0.015-2.5 parts of lactose-N-disaccharide I, 0.015-2.5 parts of human milk oligosaccharide, 3-5 parts of galactooligosaccharide, 5-15 parts of 1, 3-dioleate-2-palmitic triglyceride, 0.05-0.35 part of casein phosphopeptide, 0.4-1 part of compound vitamin, 0.3-1 part of compound mineral substance, 0.01-0.03 part of nucleotide, 0.5-0.8 part of L-carnitine, 0-0.04 part of taurine, 0.02-1 part of arachidonic acid, 0.02-1 part of docosahexaenoic acid and 0.01-1.5 part of milk fat globule membrane.

6 the infant formula powder according to item 5, characterized in that: the vegetable oil comprises, by weight, 25-35 parts of coconut oil, 36-48 parts of corn oil, 12-22 parts of high-oleic acid sunflower oil, 8-12 parts of soybean oil and 10-20 parts of low-erucic acid rapeseed oil.

7. Infant formula powder according to item 5, characterized in that: the compound vitamin comprises the following raw materials, by weight, 7-15 parts of vitamin A, 3-7 parts of vitamin D, 5-10 parts of vitamin E, 0.8-4.6 parts of vitamin K, 4.6-8 parts of vitamin B, 1.2-2.8 parts of folic acid, 50-60 parts of vitamin C and 0.8-3 parts of lutein.

8. Infant formula powder according to item 5, characterized in that: the compound mineral comprises the following raw materials, by weight, 0-45 parts of tricalcium phosphate, 0.1-0.5 part of anhydrous copper sulfate, 8-12 parts of potassium chloride, 0.06-3 parts of potassium iodate, 10-15 parts of ferrous sulfate, 10-20 parts of magnesium chloride, 0-0.5 part of manganese sulfate, 0-0.5 part of sodium selenite, 1-5 parts of zinc oxide and 25-45 parts of sodium citrate.

9. Infant formula powder according to item 5, characterized in that: the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

10. The infant formula powder according to item 6, characterized in that: the compound vitamin comprises the following raw materials, by weight, 7-15 parts of vitamin A, 3-7 parts of vitamin D, 5-10 parts of vitamin E, 0.8-4.6 parts of vitamin K, 4.6-8 parts of vitamin B, 1.2-2.8 parts of folic acid, 50-60 parts of vitamin C and 0.8-3 parts of lutein.

11. The infant formula powder according to item 6, characterized in that: the compound mineral comprises the following raw materials, by weight, 0-45 parts of tricalcium phosphate, 0.1-0.5 part of anhydrous copper sulfate, 8-12 parts of potassium chloride, 0.06-3 parts of potassium iodate, 10-15 parts of ferrous sulfate, 10-20 parts of magnesium chloride, 0-0.5 part of manganese sulfate, 0-0.5 part of sodium selenite, 1-5 parts of zinc oxide and 25-45 parts of sodium citrate.

12. The infant formula powder according to item 6, characterized in that: the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

13. The infant formula powder according to item 7, characterized in that: the compound mineral comprises the following raw materials, by weight, 0-45 parts of tricalcium phosphate, 0.1-0.5 part of anhydrous copper sulfate, 8-12 parts of potassium chloride, 0.06-3 parts of potassium iodate, 10-15 parts of ferrous sulfate, 10-20 parts of magnesium chloride, 0-0.5 part of manganese sulfate, 0-0.5 part of sodium selenite, 1-5 parts of zinc oxide and 25-45 parts of sodium citrate.

14. The infant formula powder according to item 7, characterized in that: the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

15. The infant formula powder according to item 8, characterized in that: the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

16. The infant formula powder according to any one of claims 1 to 15, characterized in that: the human milk oligosaccharide comprises one or more than two of 2 '-fucosyllactose, lacto-N-fucosylpentaose, 3' -fucosyllactose, lacto-N-tetraose, lacto-N-difucohexaose, lacto-N-difucosyltetraose and lacto-N-neotetraose.

17. Use of the infant formula of any one of claims 1 to 16 as an infant antiallergic formula.

18. The method of making the infant formula of any one of claims 5 to 15, comprising the steps of:

2) homogenizing;

3) sterilizing;

19. The method of preparing an infant formula according to item 18, wherein: and homogenizing the uniformly mixed materials by using a high-pressure homogenizer under the homogenizing condition that the homogenizing temperature is 50-65 ℃ and the homogenizing pressure is 12-24 MPa.

20. The method of preparing an infant formula according to item 18, wherein: the sterilization condition is that the materials are sterilized at the temperature of 80-94 ℃, and the sterilization time is 25-50 s.

21. The method of preparing an infant formula according to item 18, wherein: the technological conditions of the spray drying are that the spray pressure is 12MPa to 20MPa, the temperature of the concentrated material is 40 ℃ to 65 ℃, the air inlet temperature is 165 ℃ to 195 ℃, and the air exhaust temperature is 80 ℃ to 95 ℃.

22. The method of preparing an infant formula according to item 19, wherein: the sterilization condition is that the materials are sterilized at the temperature of 80-94 ℃, and the sterilization time is 25-50 s.

23. The method of preparing an infant formula according to item 19, wherein: the technological conditions of the spray drying are that the spray pressure is 12MPa to 20MPa, the temperature of the concentrated material is 40 ℃ to 65 ℃, the air inlet temperature is 165 ℃ to 195 ℃, and the air exhaust temperature is 80 ℃ to 95 ℃.

24. The method of preparing an infant formula according to item 20, wherein: the technological conditions of the spray drying are that the spray pressure is 12MPa to 20MPa, the temperature of the concentrated material is 40 ℃ to 65 ℃, the air inlet temperature is 165 ℃ to 195 ℃, and the air exhaust temperature is 80 ℃ to 95 ℃.

The invention has the following advantages: the lactose-N-disaccharide I and the human milk oligosaccharide which are suitable for growth and development of infants are added into the infant formula milk powder provided by the invention, so that the effects of proliferating probiotics, improving the balance of intestinal flora and promoting the health of intestinal tracts can be better achieved. The invention ensures that the infant formula milk powder is close to breast milk to a great extent.

Drawings

FIG. 1 shows total IgE levels in sera of sensitized mice.

Detailed Description

The present invention will be described in detail and specifically with reference to the following examples in order to better understand the present invention, but the scope of the present invention is not limited by the following examples. Any changes and modifications, and any equivalents made to the invention without departing from the spirit thereof are intended to be covered by the scope of the invention.

Experimental Material

1. Preparation of lacto-N-disaccharide I

10mM sucrose, 10mM uridine diphosphate glucose, 10mM N-acetylglucosamine (analytically pure, Dingguo organism), 5U sucrose phosphorylase, 5U UDP-glucose hexose phosphate uridyltransferase, 5U UDP-glucose epimerase, 100U lactose-N-disaccharide phosphorylase and 100mM phosphate buffer (analytically pure, Dingguo organism) (pH 6-7) are placed in the same reaction system, the reaction system reacts for 5 days at 30 ℃, the enzyme in the reaction system is removed, and the lactose-N-disaccharide I is obtained by concentration and crystallization. The molecular weight of the lactose-N-disaccharide I product is 383 by the detection of an ultrahigh pressure liquid chromatography-time-of-flight mass spectrometer (Agilent technologies, Inc.), and the structure of the lactose-N-disaccharide I product is confirmed to be lactose-N-disaccharide I by nuclear magnetic resonance detection. The yield of lacto-N-disaccharide I is up to 80%.

2. Preparation of lacto-N-tetraose

100mM N-acetylglucosamine, 100mM lactose, 1mU glucose-1-phosphatase, 1mU beta-1, 3-N-acetylglucosamine transferase and 1mU UDP-glucose hexose phosphate uridyltransferase were placed in the same reaction system and reacted at 30 ℃ for 2 days to obtain lactose-N-trisaccharide.

100mM sucrose, 1mU sucrose synthase, 0.1mM uridine diphosphate, 1mU UDP-galactose epimerase, 1mU beta-galactosyltransferase, and 100mM lactose-N-trisaccharide were placed in the same reaction system and reacted at 30 ℃ for 2 days to obtain lactose-N-tetrasaccharide.

Examples

Example 1

Preparing common infant formula milk powder, wherein the milk powder comprises the following raw materials in percentage by weight: 25.93% of whole milk powder, 33.52% of desalted whey powder, 14.17% of vegetable oil, 10.14% of lactose, 3.42% of galacto-oligosaccharide, 8.31% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.59% of compound vitamin, 0.67% of compound mineral, 0.03% of nucleotide, 0.58% of L-carnitine, 0.03% of taurine, 0.62% of arachidonic acid, 0.64% of docosahexaenoic acid and 0.03% of milk fat globule membrane.

The vegetable oil comprises the following components in percentage by mass: 30% of coconut oil, 40% of corn oil, 10% of high oleic acid sunflower oil, 10% of soybean oil and 10% of low erucic acid rapeseed oil.

The compound vitamin comprises the following components in percentage by mass: 11.32% of vitamin A, 6.2% of vitamin D, 8.8% of vitamin E, 3.57% of vitamin K, 6.03% of vitamin B, 1.46% of folic acid, 59.72% of vitamin C and 2.7% of lutein.

The compound mineral comprises the following components in percentage by mass: 30.11% of tricalcium phosphate, 0.12% of anhydrous copper sulfate, 8.86% of potassium chloride, 1% of potassium iodate, 13.08% of ferrous sulfate, 10.84% of magnesium chloride, 0.16% of manganese sulfate, 0.36% of sodium selenite, 2.54% of zinc oxide and 32.93% of sodium citrate.

Wherein the nucleotide comprises the following components in percentage by mass: 51.5% of cytidylic acid, 13.1% of adenylic acid, 6.6% of guanylic acid, 19.6% of uridylic acid and 9.2% of inosinic acid.

The common infant formula milk powder is prepared by the following method, and specifically comprises the following steps:

(1) preparing materials: weighing whole milk powder, desalted whey powder, lactose, taurine, compound mineral matters and compound vitamins according to a set proportion, mixing and dissolving with purified water of 55 ℃, fully stirring, and fully and uniformly mixing with vegetable oil, 1, 3-dioleoyl-2-palmitic acid triglyceride and milk fat globule membrane;

(2) homogenizing: homogenizing the uniformly mixed materials by a high-pressure homogenizer at the temperature of 50 ℃ and the pressure of 12 MPa;

(3) and (3) sterilization: sterilizing the homogenized material at 92 ℃ for 35 s;

(4) spray drying: the sterilized materials are sprayed and dried to prepare milk powder, and the process conditions are as follows: spraying at 18MPa, concentrating at 55 deg.C, introducing air at 180 deg.C, and exhausting at 94 deg.C, and sieving with 20 mesh sieve;

(5) mixing: pre-mixing galacto-oligosaccharide, L-carnitine, nucleotide, casein phosphopeptide, docosahexaenoic acid and arachidonic acid which are weighed according to a preset proportion, and then fully and uniformly mixing the mixture with base powder;

(6) and (6) packaging.

Example 2

Preparing an infant formula milk powder added with lactose-N-disaccharide I and human milk oligosaccharide, wherein the milk powder comprises the following raw materials in percentage by weight: 25.93% of full-fat milk powder, 33.52% of desalted whey powder, 14.17% of vegetable oil, 10.14% of lactose, 2.072% of lactose-N-disaccharide I, 1.048% of human milk oligosaccharide, 3.42% of galacto-oligosaccharide, 8.31% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.59% of compound vitamin, 0.67% of compound mineral substance, 0.03% of nucleotide, 0.58% of L-carnitine, 0.03% of taurine, 0.62% of arachidonic acid, 0.64% of docosahexaenoic acid and 0.03% of milk fat globule membrane.

The human milk oligosaccharide comprises the following components in percentage by mass: 37.5% 2' -fucosyllactose, 62.5% lacto-N-tetraose.

The infant formula milk powder added with the lacto-N-disaccharide I and the human milk oligosaccharide is prepared by the following method, and specifically comprises the following steps:

(5) mixing: premixing lactose-N-disaccharide I, human milk oligosaccharide, galacto-oligosaccharide, L-carnitine, nucleotide, casein phosphopeptide, docosahexaenoic acid and arachidonic acid which are weighed according to a predetermined proportion, and then fully and uniformly mixing the premixed lactose-N-disaccharide I, the human milk oligosaccharide, the galacto-oligosaccharide, the L-carnitine, the nucleotide, the casein phosphopeptide, the docosahexaenoic acid and the arachidonic acid;

(6) and (6) packaging.

Example 3

This example prepares a larger infant formula powder with added lacto-N-disaccharide I and human milk oligosaccharide, which is composed of the following raw materials in percentage by weight: 32.74% of whole milk powder, 30.38% of desalted whey powder, 9.02% of vegetable oil, 14.25% of lactose, 0.066% of lactose-N-disaccharide I, 0.054% of human milk oligosaccharide, 4.17% of galacto-oligosaccharide, 6.15% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.41% of compound vitamin, 0.44% of compound mineral substance, 0.03% of nucleotide, 0.78% of L-carnitine, 0.03% of taurine, 0.33% of arachidonic acid, 0.45% of docosahexaenoic acid and 0.5% of milk fat globule membrane.

The human milk oligosaccharide comprises the following components in percentage by mass: 45% 2' -fucosyllactose, 35% lacto-N-tetraose, 20% lacto-N-neotetraose.

The vegetable oil comprises the following components in percentage by mass: 34% of coconut oil, 34% of corn oil, 12% of high oleic acid sunflower oil, 8% of soybean oil and 12% of low erucic acid rapeseed oil.

The compound vitamin comprises the following components in percentage by mass: 12.79% of vitamin A, 5.5% of vitamin D, 8.98% of vitamin E, 2.27% of vitamin K, 6.88% of vitamin B, 2.25% of folic acid, 59.7% of vitamin C and 1.63% of lutein.

The compound mineral comprises the following components in percentage by mass: 9.78% of tricalcium phosphate, 0.35% of anhydrous copper sulfate, 11.03% of potassium chloride, 2.6% of potassium iodate, 14.82% of ferrous sulfate, 14.9% of magnesium chloride, 0.17% of sodium selenite, 2.66% of zinc oxide and 43.69% of sodium citrate.

Wherein the nucleotide comprises the following components in percentage by mass: 49.5% of cytidylic acid, 15.1% of adenylic acid, 7.8% of guanylic acid, 19% of uridylic acid and 8.6% of inosinic acid.

The infant formula milk powder added with the lactose-N-disaccharide I and the human milk oligosaccharide is prepared by the following method, and specifically comprises the following steps:

(1) preparing materials: weighing whole milk powder, desalted whey powder, lactose, taurine, compound mineral matters and compound vitamins according to a set proportion, mixing and dissolving with purified water of 45 ℃, fully stirring, and fully and uniformly mixing with vegetable oil, 1, 3-dioleoyl-2-palmitic acid triglyceride and milk fat globule membrane;

(2) homogenizing: homogenizing the uniformly mixed materials by a high-pressure homogenizer at the temperature of 55 ℃ and the pressure of 18 MPa;

(3) and (3) sterilization: sterilizing the homogenized material at 80 deg.C for 50 s;

(4) spray drying: the sterilized materials are sprayed and dried to prepare milk powder, and the process conditions are as follows: spraying milk powder with spraying pressure of 12MPa, concentrating material temperature of 65 deg.C, air inlet temperature of 165 deg.C, air exhaust temperature of 80 deg.C, and steam supply pressure of 0.9MPa, and sieving with 20 mesh sieve;

(6) and (6) packaging.

Example 4

This example prepares a powdered milk formula for infants added with lacto-N-disaccharide I and human milk oligosaccharide, which comprises the following raw materials by weight: 39.1% of whole milk powder, 27.63% of desalted whey powder, 5.98% of vegetable oil, 13.8% of lactose, 0.04% of lactose-N-disaccharide I, 0.06% of human milk oligosaccharide, 4.27% of galacto-oligosaccharide, 6.22% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.41% of compound vitamin, 0.43% of compound mineral substance, 0.03% of nucleotide, 0.78% of L-carnitine, 0.03% of taurine, 0.42% of arachidonic acid, 0.53% of docosahexaenoic acid and 0.07% of milk fat globule membrane.

The human milk oligosaccharide comprises the following components in percentage by mass: 30.7% 2' -fucosyllactose, 49.3% lacto-N-tetraose, 14.9% lacto-N-fucosylpentaose, 5.1% lacto-N-difucohexaose.

The vegetable oil comprises the following components in percentage by mass: 30% of coconut oil, 35% of corn oil, 12% of high oleic acid sunflower oil, 8% of soybean oil and 15% of low erucic acid rapeseed oil.

The compound vitamin comprises the following components in percentage by mass: 13.29 percent of vitamin A, 6.5 percent of vitamin D, 9.48 percent of vitamin E, 4.27 percent of vitamin K, 6.88 percent of vitamin B, 1.85 percent of folic acid, 56.1 percent of vitamin C and 1.63 percent of lutein.

The compound mineral comprises the following components in percentage by mass: 23.68% of tricalcium phosphate, 0.35% of anhydrous copper sulfate, 8.03% of potassium chloride, 2.37% of potassium iodate, 12.32% of ferrous sulfate, 13.9% of magnesium chloride, 4.66% of zinc oxide and 34.69% of sodium citrate.

Wherein the nucleotide comprises the following components in percentage by mass: 52.9 percent of cytidylic acid, 11.3 percent of adenylic acid, 5.8 percent of guanylic acid, 21.7 percent of uridylic acid and 8.3 percent of inosinic acid.

(1) preparing materials: weighing whole milk powder, desalted whey powder, lactose, taurine, compound mineral matters and compound vitamins according to a set proportion, mixing and dissolving the whole milk powder, the desalted whey powder, the lactose, the taurine, the compound mineral matters and the compound vitamins by using purified water at 60 ℃, fully stirring the mixture, and fully and uniformly mixing the mixture with vegetable oil, 1, 3-dioleoyl-2-palmitic acid triglyceride and milk fat globule membrane after uniformly stirring the mixture;

(2) homogenizing: homogenizing the uniformly mixed materials by a high-pressure homogenizer at 65 ℃ and 24 MPa;

(3) and (3) sterilization: sterilizing the homogenized material at 94 deg.C for 25 s;

(4) spray drying: the sterilized materials are sprayed and dried to prepare milk powder, and the process conditions are as follows: spraying milk powder with 20-mesh screen under the conditions of spraying pressure of 20MPa, concentrated material temperature of 40 deg.C, air inlet temperature of 195 deg.C, air exhaust temperature of 95 deg.C and steam supply pressure of 0.8 MPa;

(6) and (6) packaging.

Example 5

Preparing infant formula milk powder added with human milk oligosaccharide, wherein the milk powder comprises the following raw materials in percentage by weight: 25.93% of full-fat milk powder, 33.52% of desalted whey powder, 14.17% of vegetable oil, 10.14% of lactose, 1.048% of human milk oligosaccharide, 3.42% of galactooligosaccharide, 8.31% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.59% of compound vitamin, 0.67% of compound mineral, 0.03% of nucleotide, 0.58% of L-carnitine, 0.03% of taurine, 0.62% of arachidonic acid, 0.64% of docosahexaenoic acid and 0.03% of milk fat globule membrane.

The compound mineral comprises the following components in percentage by mass: 25.11 percent of tricalcium phosphate, 0.12 percent of anhydrous copper sulfate, 9.86 percent of potassium chloride, 1 percent of potassium iodate, 14.08 percent of ferrous sulfate, 10.84 percent of magnesium chloride, 0.16 percent of manganese sulfate, 0.36 percent of sodium selenite, 2.54 percent of zinc oxide and 35.93 percent of sodium citrate.

The infant formula milk powder added with the human milk oligosaccharide is prepared by the following method, and specifically comprises the following steps:

(5) mixing: premixing human milk oligosaccharide, galacto-oligosaccharide, L-carnitine, nucleotide, casein phosphopeptide, docosahexaenoic acid and arachidonic acid which are weighed according to a preset proportion, and then fully and uniformly mixing the mixture with base powder;

(6) and (6) packaging.

Example 6

Preparing a formula milk powder for children added with lactose-N-disaccharide I, wherein the milk powder comprises the following raw materials in percentage by weight: 25.93% of whole milk powder, 33.52% of desalted whey powder, 14.17% of vegetable oil, 10.14% of lactose, 2.072% of lactose-N-disaccharide I, 3.42% of galactooligosaccharide, 8.31% of 1, 3-dioleate-2-palmitic acid triglyceride, 0.2% of casein phosphopeptide, 0.59% of compound vitamin, 0.67% of compound mineral, 0.03% of nucleotide, 0.58% of L-carnitine, 0.03% of taurine, 0.62% of arachidonic acid, 0.64% of docosahexaenoic acid and 0.03% of milk fat globule membrane.

The compound mineral comprises the following components in percentage by mass: 31.11 percent of tricalcium phosphate, 0.12 percent of anhydrous copper sulfate, 9.86 percent of potassium chloride, 1 percent of potassium iodate, 10.08 percent of ferrous sulfate, 10.84 percent of magnesium chloride, 0.16 percent of manganese sulfate, 0.36 percent of sodium selenite, 2.54 percent of zinc oxide and 33.93 percent of sodium citrate.

The infant formula milk powder added with the lactose-N-disaccharide I is prepared by the following method, and specifically comprises the following steps:

(5) mixing: premixing lactose-N-disaccharide I, galacto-oligosaccharide, L-carnitine, nucleotide, casein phosphopeptide, docosahexaenoic acid and arachidonic acid which are weighed according to a preset proportion, and then fully and uniformly mixing the premixed lactose-N-disaccharide I, the galacto-oligosaccharide, the L-carnitine, the nucleotide, the casein phosphopeptide, the docosahexaenoic acid and the arachidonic acid;

(6) and (6) packaging.

Example 7

The effect of the infant formula milk powder with added lacto-N-disaccharide I and human milk oligosaccharide in alleviating the symptoms of cow's milk protein allergy is specifically verified below.

Experimental Material

The mice are purchased from Beijing Huafukang biotech GmbH, and are 6-8 weeks old healthy SPF female mice, the breeding environment temperature is 20 +/-3 ℃, the artificial light illumination is carried out for 12 hours every day, the ventilation is free, and the mice can eat and drink water freely.

Mouse immunoglobulin E (IgE) ELISA kits, purchased from Shanghai enzyme-linked Biotechnology, Inc.

Experimental methods

Mouse sensitization model establishment

The healthy SPF mice 48 were randomly selected as experimental groups, and were divided into a blank control group, an allergy model control group, and an experimental group, each group consisting of 6 mice. Allergic model control group and experimental group mice were infused with 0.2 mL/mouse allergen beta-lactoglobulin (1mg/mL) and immune adjuvant cholera toxin (10. mu.g/mL) on days 1, 7, 14 and 21, respectively, from the start of the experiment; the blank control group was drenched with 0.2 mL/tube of physiological saline. The experimental group is respectively drenched with prescribed formula milk powder (200mg/mL) from day 1, 0.2mL each time, and 3 times per day through mouth and stomach irrigation; the blank control group and the allergy model control group were infused with the same volume of physiological saline. On day 28, the allergy model control group and the experimental group mice were gavaged with 0.2 mL/mouse of 50mg/mL beta-lactoglobulin, and sensitization was stimulated. After 1h of challenge, orbital bleeds were performed in all treatment groups. The steps are strictly operated according to the requirements of a mouse ELISA kit, and the IgE level in serum is detected under the wavelength of 450 nm.

The experimental groups mice were numbered as follows:

group a, regular infant formula powder of example 1 was consumed. lactose-N-disaccharide I and human milk oligosaccharide are not added in the raw materials of the common infant formula milk powder;

group B, taking the infant formula of example 2. The infant formula of example 2 is a formula supplemented with lacto-N-disaccharide I and human milk oligosaccharides, the other ingredients being the same as the formula described in example 1;

group C, consumption of infant formula powder of example 3. The infant formula of example 3 is a formula supplemented with lacto-N-disaccharide I and human milk oligosaccharides;

group D, consumption of infant formula of example 4. The infant formula of example 4 is a formula supplemented with lacto-N-disaccharide I and human milk oligosaccharides;

group E, consumption of infant formula of example 5. The infant formula of example 5 is a formula with the addition of human milk oligosaccharides, without the addition of lacto-N-disaccharide I;

group F, taking the infant formula of example 6. The infant formula of example 6 was a formula with lacto-N-disaccharide I added, without human milk oligosaccharides.

Results of the experiment

FIG. 1 shows total IgE levels in sera of sensitized mice. As can be seen from fig. 1, the total IgE concentration in β -lactoglobulin-sensitized serum was significantly increased compared to the blank control. The serum total IgE concentration of mice in the formulation groups (group B, group C, group D, group E, group F) to which lacto-N-disaccharide I and/or human milk oligosaccharide was added was significantly reduced compared to the allergy model control and the general formulation group a, indicating that the addition of lacto-N-disaccharide I and/or human milk oligosaccharide milk powder could alleviate allergy.

In addition, after sensitization, the mice in the allergy model control group and the common formula group A showed watery stool symptoms, and the watery stool symptoms of the mice in the formula groups (group B, group C, group D, group E and group F) added with lacto-N-disaccharide I and/or human milk oligosaccharide disappeared.

Claims

2. The infant formula powder according to claim 1, characterized in that: the content of the lactose-N-disaccharide I is 0.01-2.5%, and the content of the human milk oligosaccharide is 0.01-2.5%.

3. The infant formula powder according to claim 2, characterized in that: the infant formula milk powder comprises the following raw materials in parts by weight: 25-40 parts of full-cream milk powder, 25-35 parts of desalted whey powder, 3-15 parts of vegetable oil, 10-25 parts of lactose, 0.015-2.5 parts of lactose-N-disaccharide I, 0.015-2.5 parts of human milk oligosaccharide, 3-5 parts of galactooligosaccharide, 5-15 parts of 1, 3-dioleate-2-palmitic triglyceride, 0.05-0.35 part of casein phosphopeptide, 0.4-1 part of compound vitamin, 0.3-1 part of compound mineral substance, 0.01-0.03 part of nucleotide, 0.5-0.8 part of L-carnitine, 0-0.04 part of taurine, 0.02-1 part of arachidonic acid, 0.02-1 part of docosahexaenoic acid and 0.01-1.5 part of milk fat globule membrane.

4. The infant formula powder according to claim 3, characterized in that: the vegetable oil comprises, by weight, 25-35 parts of coconut oil, 36-48 parts of corn oil, 12-22 parts of high-oleic acid sunflower oil, 8-12 parts of soybean oil and 10-20 parts of low-erucic acid rapeseed oil.

5. The infant formula powder according to claim 3, characterized in that: the compound vitamin comprises the following raw materials, by weight, 7-15 parts of vitamin A, 3-7 parts of vitamin D, 5-10 parts of vitamin E, 0.8-4.6 parts of vitamin K, 4.6-8 parts of vitamin B, 1.2-2.8 parts of folic acid, 50-60 parts of vitamin C and 0.8-3 parts of lutein.

6. The infant formula powder according to claim 3, characterized in that: the compound mineral comprises the following raw materials, by weight, 0-45 parts of tricalcium phosphate, 0.1-0.5 part of anhydrous copper sulfate, 8-12 parts of potassium chloride, 0.06-3 parts of potassium iodate, 10-15 parts of ferrous sulfate, 10-20 parts of magnesium chloride, 0-0.5 part of manganese sulfate, 0-0.5 part of sodium selenite, 1-5 parts of zinc oxide and 25-45 parts of sodium citrate.

7. The infant formula powder according to claim 3, characterized in that: the nucleotide comprises the following raw materials, by weight, 45-55 parts of cytidylic acid, 10-20 parts of adenylic acid, 5-15 parts of guanylic acid, 15-25 parts of uridylic acid and 5-15 parts of inosinic acid.

8. The infant formula powder according to any one of claims 1 to 7, characterized in that: the human milk oligosaccharide comprises one or more than two of 2 '-fucosyllactose, lacto-N-fucosylpentaose, 3' -fucosyllactose, lacto-N-tetraose, lacto-N-difucohexaose, lacto-N-difucosyltetraose and lacto-N-neotetraose.

9. Use of the infant formula of any one of claims 1 to 8 as an infant antiallergic formula.

10. Process for the preparation of an infant formula according to any one of claims 3 to 7, comprising the steps of:

2) homogenizing: homogenizing the uniformly mixed materials by using a high-pressure homogenizer;

3) sterilizing;