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CN114128767B - Milk protein partially hydrolyzed hypoallergenic infant formulas containing breast milk oligosaccharides - Google Patents

Milk protein partially hydrolyzed hypoallergenic infant formulas containing breast milk oligosaccharides Download PDF

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Publication number
CN114128767B
CN114128767B CN202111450898.9A CN202111450898A CN114128767B CN 114128767 B CN114128767 B CN 114128767B CN 202111450898 A CN202111450898 A CN 202111450898A CN 114128767 B CN114128767 B CN 114128767B
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infant formula
powder
protein
milk
total
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CN114128767A (en
Inventor
李艳杰
刘彪
李威
孔小宇
吴春梅
王雯丹
吉塞拉·阿德里安娜·怀斯
司徒文佑
王燕霞
周名桥
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Inner Mongolia Yili Industrial Group Co Ltd
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Inner Mongolia Yili Industrial Group Co Ltd
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
    • A23C9/203—Dietetic milk products not covered by groups A23C9/12 - A23C9/18 containing bifidus-active substances, e.g. lactulose; containing oligosaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1522—Inorganic additives, e.g. minerals, trace elements; Chlorination or fluoridation of milk; Organic salts or complexes of metals other than natrium or kalium; Calcium enrichment of milk
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1526—Amino acids; Peptides; Protein hydrolysates; Nucleic acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1528—Fatty acids; Mono- or diglycerides; Petroleum jelly; Paraffine; Phospholipids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/156—Flavoured milk preparations ; Addition of fruits, vegetables, sugars, sugar alcohols or sweeteners
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/158—Milk preparations; Milk powder or milk powder preparations containing additives containing vitamins or antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Dairy Products (AREA)

Abstract

The present invention provides a milk protein partially hydrolyzed hypoallergenic infant formula comprising milk oligosaccharides. In particular, the present invention provides an infant formula comprising breast milk oligosaccharides including lactose-N-tetraose, the total content of lactose-N-tetraose in the infant formula being 14.2-2273.0mg/100g powder, or 0.02-3.0g/L on a milk basis, based on the total mass of the infant formula; and the total protein content in the infant formula is 9-20 g/100g based on the total mass of the infant formula, the total protein comprises hydrolyzed milk protein, the degree of hydrolysis is 8-23, and the protein with the molecular weight distribution of 3000dal or less accounts for more than 80% of the total protein. The invention also provides a preparation method and related application of the infant formula.

Description

Milk protein partially hydrolyzed hypoallergenic infant formulas containing breast milk oligosaccharides
Technical Field
The invention relates to a hypoallergenic infant formula, in particular to a milk protein partial hydrolysis hypoallergenic infant formula containing breast milk oligosaccharide, a preparation method and related applications thereof, and belongs to the technical field of infant special medical hypoallergenic foods.
Background
In recent years, the incidence of food allergy (food hypersensitivity/allergy, FH/FA) has been on the rise year by year, and has become a focus of research. Among infant food allergies, cow milk and egg allergies are the most common. Milk proteins are the most commonly used protein source for common infant formulas. CMPA refers to adverse reactions of the body on milk proteins mediated by immune mechanisms, and can be mediated by IgE, non-IgE or a mixture of the two. Symptomatically, non-IgE mediated light-moderate CMPA is more prone to gastrointestinal symptoms, most commonly irritable, i.e. intestinal cramps; in addition, vomiting, diarrhea, etc.; skin symptoms include itching, erythema, nonspecific rash, overt eczema, and the like. IgE-mediated CMPA skin symptoms are more prominent, and are manifested by acute itching, erythema, urticaria, angioedema, acute diffuse atopic eczema; gastrointestinal symptoms include vomiting, diarrhea, abdominal pain/intestinal cramps; respiratory symptoms are acute rhinitis and/or conjunctivitis, whereas non-IgE mediated CMPA rarely develops respiratory symptoms within 1 year of age.
Current avoidance therapy is used as a guideline for children with milk protein allergy. The process uses a milk protein deep hydrolysis formula (eHF) for diagnosis and treatment, and uses a milk protein partial hydrolysis formula (pHF) and an integral protein formula for home reintroduction test. However, clinical studies have shown that long-term consumption of deeply hydrolyzed formulas, circumventing the whole diet, can result in slow growth and development of infants to some extent. Moreover, long-term use of hydrolysis formulations places a significant economic burden on the child's home. Clinical data indicate that the milk protein allergy population has a higher proportion of tolerance than the whole protein formulation when reintroduced, thereby moving earlier from the deep hydrolysis formulation to the partial hydrolysis formulation. It is interesting that infants improve symptoms by deep hydrolysis of milk proteins and then switch from a milk protein partially hydrolyzed to an integrin formulation as soon as possible.
On the other hand, intestinal leakage (leak gun) refers to a phenomenon in which intestinal permeability increases to cause intestinal harmful substances such as bacteria and toxins to pass through intestinal mucosa into other tissues, organs and blood circulation in the human body. Intestinal permeability is related to intestinal barrier function, and normal intestinal permeability depends on the integrity of the intestinal mucosal barrier. Intestinal mucosal barriers are a complex multi-layer system that includes physical barriers, chemical barriers, biological barriers, and immune barriers. The physical barrier of the intestinal tract serves as a first line of defense against the external environment and occupies a central position in the structure of the intestinal tract, and is composed of intestinal epithelial cells and intercellular junctions. Intestinal cell permeability is largely divided into transepithelial or transcellular and paracellular. Paracellular permeability is dependent on transport through the interstitial space between cells. The intercellular junctions include tight junctions, adhesive junctions, desmosomes, etc., of which the most important is the tight junctions, which are located at the top of the outer membrane of the intestinal epithelium, are of a narrow band-like structure to block the intercellular spaces, thereby preventing macromolecular substances such as bacteria and toxins in the intestinal lumen from entering the blood circulation through the intercellular spaces. The tight junctions between cells have a high dynamic stability, and their permeability determines the barrier function of the whole intestinal epithelial cells, and are regulated by intracellular and extracellular signals, and can be affected by diet, diseases, stress, etc. The intestinal chemical barrier is mainly composed of a mucus layer which alters the sites of intestinal microorganisms and prevents them from directly contacting the host intestinal tissue cells. In addition, some substances produced in the intestinal tract such as bile salts, mucopolysaccharides, lysozyme and glycoproteins may also act as a chemical barrier. The intestinal biological barrier is a microecological system with dynamic stability formed by intestinal symbiotic bacteria and a host, the intestinal symbiotic bacteria are attached to a mucous membrane layer on the surface of the intestinal canal of the host, a microbial barrier formed by bacteria is formed, and the colonisation and the multiplication of pathogenic bacteria are inhibited through mechanisms such as competitive adhesion and the like. In the intestinal tract immune barrier, the related lymphoid tissues of the intestinal tract play a role in playing a role in resisting pathogen invasion, wherein lymphocytes, macrophages and the like play a role in playing a role in resisting pathogen invasion, and in effector molecules of intestinal tract immunity, secretory immunoglobulin A (sIgA) plays a key role, is produced in the lamina propria of the intestinal tract and secreted into the intestinal cavity after being processed by intestinal epithelial cells, can block adhesion of antigens such as bacteria, toxins, viruses and the like on the mucous membrane, and plays a role in clearing the antigens. The interaction of these barriers allows the intestinal tract to maintain a permeability balance, preventing the loss of water and electrolytes and the entry of antigens and microorganisms into the body, while allowing the exchange of molecules between the body and the environment and the absorption of nutrients in the food.
Intestinal leakage caused by abnormal intestinal barrier function is a major potential cause of many health problems, especially microbial toxins produced by metabolism of flora in the intestinal tract or other toxin substances entering with food, enter the blood circulation through the intestinal wall with increased permeability ("intestinal leakage"), cause various autoimmune symptoms by stimulating the autoimmune system, or poison internal organs, and thus cause various diseases. Compared with infants fed by breast milk, infants not fed by breast milk are unsound in intestinal development, and intestinal leakage is easier to occur.
In the current most infant special medical milk proteolytic formula milk powder in the market, the prebiotic source is fructo-oligosaccharide or galacto-oligosaccharide, or no prebiotic is added, so that the problem that the integrity of intestinal epithelium is improved, the intestinal leakage cannot be prevented or reduced, and the allergic infant can not be promoted to endure the whole protein formula as soon as possible cannot be solved.
Thus, there is a need for solutions that improve the intestinal health of infants.
Disclosure of Invention
It is an object of the present invention to provide an infant formula that improves the intestinal health of infants.
It is a further object of the present invention to provide a method for preparing said infant formula.
It is a further object of the present invention to provide the use of said infant formula.
The inventor finds that the breast milk oligosaccharide lactose-N-tetraose (LNT) alone or in combination with other breast milk oligosaccharides can be used for preventing or improving intestinal leakage or intestinal barrier injury, is beneficial to improving intestinal permeability and intestinal barrier among cells and improving gaps among cells, and is particularly beneficial to maintaining intestinal health of infants. Thus, the addition of breast milk oligosaccharides including lactose-N-tetraose to an infant formula in the present invention provides an infant formula that prevents intestinal leakage to promote intestinal health.
In particular, in one aspect, the present invention provides an infant formula comprising breast milk oligosaccharides including lactose-N-tetraose, the total content of lactose-N-tetraose in the infant formula being 14.2-2273.0mg/100g powder, or 0.02-3.0g/L on a milk basis, based on the total mass of the infant formula;
and the total protein content in the infant formula is 9-20 g/100g based on the total mass of the infant formula, the total protein comprises hydrolyzed milk protein, the degree of hydrolysis is 8-23, and the protein with the molecular weight distribution of 3000dal or less accounts for more than 80% of the total protein.
lactose-N-tetraose is a representative substance of oligosaccharides based on core sugar chains and free of fucosyl or sialyl groups, which are generally commercially available as prepared by microbial fermentation and have the same structure as lactose-N-tetraose found in human milk.
According to a specific embodiment of the invention, the amount of lactose-N-tetraose in the infant formula of the invention is 70.9-1515.3mg/100g powder, or 0.1-2.0g/L on a milk basis; preferably 70.9-757.7mg/100g of powder or 0.1-1.0g/L in terms of milk.
According to a specific embodiment of the present invention, the infant formula of the invention wherein the breast milk oligosaccharide further comprises 3'-sialyllactose (3' -sialylactose, 3'-SL or 3 SL), the amount of 3' -sialylactose to be used in the infant formula is 14.2-1515.3mg/100g powder, or 0.02-2.0g/L on a milk basis, based on the total mass of the infant formula. Preferably, the amount of 3' -sialyllactose in the infant formula is 70.9-454.6mg/100g powder, or 0.1-0.6g/L on a milk basis; more preferably 70.9-227.3mg/100g of powder or 0.1-0.3g/L in terms of milk.
3' -sialyllactose, which is a trisaccharide structure formed by sialic acid and lactose, is a representative substance of sialyl oligosaccharides. The 3 '-sialyllactose commercial products in the prior art are mostly prepared by a microbial fermentation method, and have the same structure as the 3' -sialyllactose found in human milk.
According to a specific embodiment of the present invention, the infant formula of the present invention, in which the mass ratio of lactose-N-tetraose to 3' -sialyllactose in the breast milk oligosaccharide is (3-5): 1. the study of the invention shows that the breast milk oligosaccharide composition can prevent or improve intestinal leakage or intestinal barrier injury more remarkably, is beneficial to improving the intestinal permeability and the intestinal barrier among cells and improving the gap among cells, and is particularly beneficial to maintaining the intestinal health of infants.
According to a specific embodiment of the present invention, the infant formula of the invention further comprises 2'-fucosyllactose (2' -Fucosyl lactose,2'-FL or 2 FL), the 2' -fucosyllactose being used in the infant formula in an amount of 14.2-3182.2mg/100g meal, or 0.02-4.2g/L in terms of milk, based on the total mass of the infant formula. Preferably, the amount of 2' -fucosyllactose in the infant formula is 70.9-1818.4mg/100g meal, or 0.1-2.4g/L in terms of milk; more preferably 70.9-1515.3mg/100g of powder or 0.1-2.0g/L in terms of milk.
2' -fucosyllactose is a trisaccharide structure formed by fucose and lactose, and is a representative substance of fucosyl oligosaccharides. The commercial material is typically prepared by microbial fermentation and has the same structure as the oligosaccharides found in human milk.
According to a specific embodiment of the present invention, the total content of breast milk oligosaccharides in the infant formula of the present invention is below 4000mg/100g powder.
In some embodiments of the invention, the infant formula of the invention wherein the breast milk oligosaccharide consists of (1-4) in mass ratio: 1 with lactose-N-tetraose. Such a breast milk oligosaccharide composition may significantly inhibit or reduce the production of branched fatty acids in the gut, especially in infants not receiving breast milk (formula fed infants), may significantly reduce the production of branched fatty acids such as isovaleric acid in the gut, may further reduce the production of distal colonic isobutyric acid, reduce the pH of the gut, be utilized by the gut flora as a prebiotic in the gut system and produce gas, and/or regulate the production of beneficial short chain fatty acids in the gut system, including formic acid, acetic acid, propionic acid, butyric acid and/or lactic acid.
In some embodiments of the invention, the infant formula of the invention wherein the breast milk oligosaccharide consists of (3-5) in mass ratio: (1.5-2.5): 1, lactose-N-tetraose and 3' -sialyllactose. The studies of the present invention show that such a breast milk oligosaccharide composition can be used for improving the intestinal immune response, in particular for improving the immune response activity of differentiation of intestinal monocytes into macrophages. In some embodiments of the invention, the improvement of the immune response activity of monocytes differentiated into macrophages is the improvement of the immune response activity of monocytes differentiated into macrophages in response to stimulation or the prevention of the reduction of the immune response activity of monocytes after trained differentiation into macrophages. In particular, in the human intestinal tract, the flora metabolic disorder can generate toxins such as lipopolysaccharide with abnormal concentration, and the breast milk oligosaccharide composition can promote the immune response activity of macrophages to the stimulation of the toxins. In addition, monocytes may have reduced immune response activity upon differentiation into macrophages upon stimulation (i.e., trained conditions) by some enterotoxins, and the breast milk oligosaccharide compositions of the invention may prevent the reduction of immune response activity and even further enhance immune response activity. According to some embodiments of the invention, the immune response activity is characterized in the present invention by measuring the amount of secreted TNF- α after differentiation of monocytes to macrophages. Experiments prove that the breast milk oligosaccharide composition can promote the secretion of TNF-alpha when the breast milk oligosaccharide composition is used for responding to stimulus (such as lipopolysaccharide stimulus) after monocytes are differentiated into macrophages.
According to a specific embodiment of the present invention, the infant formula of the present invention uses commercially available food grade milk oligosaccharide raw materials as the raw material for providing milk oligosaccharide.
According to a specific embodiment of the present invention, the infant formula of the present invention is intended to reduce the high risk of allergy to milk proteins to infants, thus requiring that the major component (more than 80%) of the total protein be hydrolysed milk proteins and that the degree of hydrolysis be 8-23 and that the protein having a molecular weight distribution of 3000dal or less be more than 80% of the total protein.
The infant formula of the present invention may comprise one or more of hydrolyzed whey protein powder, hydrolyzed casein powder, hydrolyzed milk protein powder, and hydrolyzed milk fat globule membrane protein as the starting materials for providing total protein.
According to a specific embodiment of the present invention, the infant formula of the present invention has a fat content of 15 to 29g/100g, based on the total mass of the infant formula; the carbohydrate content is 50-58 g/100g.
The infant formula of the invention may comprise, as the starting materials, a milk fat-containing base material and may further comprise vegetable oils which may comprise one or more of sunflower oil, corn oil, soybean oil, canola oil, coconut oil, palm oil, walnut oil, preferably sunflower oil, corn oil and soybean oil, the addition of which provides the fat component to the product on the one hand and linoleic acid on the other hand, and also alpha-linolenic acid on the other hand. In addition, the fat-providing raw material may optionally include a raw material OPO structured fat added for providing 1, 3-dioleoyl-2-palmitoleic acid triglyceride. More preferably, the infant formula comprises, based on 1000 parts by weight of the infant formula: 0-150 parts by weight of sunflower seed oil; corn oil 0-40 weight portions; 0-80 parts by weight of soybean oil; 0 to 140 parts by weight of OPO structural fat.
According to a specific embodiment of the invention, the infant formula of the invention wherein the carbohydrate is derived partly from lactose and partly from non-lactose sources such as pregelatinized starch, maltodextrin, solid corn syrup, glucose syrup. I.e. infant formulas according to the invention, the carbohydrate-providing raw material comprises, in addition to lactose-containing base raw material, raw lactose and pre-hydrolysed and gelatinized starch. Preferably, the raw materials of the formula powder comprise, based on 1000 parts by weight: lactose 0-580 weight portions and non-lactose material 0-580 weight portions. The specific addition amount of lactose may be adjusted within the range.
According to a specific embodiment of the invention, the infant formula of the invention further comprises one or more of nutrients, DHA, ARA, nucleotides, lactoferrin, probiotics. Preferably, the infant formula comprises, based on 1000 parts by weight, the following raw materials: 8-15 parts by weight of DHA and 14-28 parts by weight of ARA; 0 to 0.7 weight portion of lactoferrin; 7-50 parts by weight of compound nutrients comprising calcium powder, vitamins and minerals.
According to the specific embodiment of the invention, the compound nutrient is a combination of nutrient components meeting the national standard, and different additive amounts are used according to different formulas. The infant formula of the present invention may optionally employ any one or any combination of the following compounded nutrient ingredients if desired with the addition of nutrients. Preferably, the compound nutrient at least comprises compound vitamins, calcium powder and mineral nutrition packages, and the dosages of the components are as follows:
1) A compound vitamin, wherein each gram of compound vitamin comprises the following components:
taurine: 140-340 mg
Vitamin a: 1700-5800 mu gRE
Vitamin D: 25-70 mu g
Vitamin B 1 ：2000～6800μg
Vitamin B 2 ：3000～6900μg
Vitamin B 6 ：1700～4000μg
Vitamin B 12 ：8～20μg
Vitamin K 1 ：200～700μg
Vitamin C: 0-700 mg
Vitamin E: 10-70 mg alpha-TE
Nicotinamide: 10000-41550 mug
Folic acid: 350-920 mu g
Biotin: 70-245 mug
Pantothenic acid: 7100-25230 mu g
Inositol: 0-250mg
L-carnitine: 0-60mg
2) Mineral two, in every gram of mineral two:
sodium: 40-100 mg
Potassium: 200-500 mg
2) Mineral three, in every gram of mineral two:
calcium: 200-500 mg
Phosphorus: 75-300 mg
3) Mineral one, per gram of mineral one:
iron: 20-110 mg
Zinc: 23-90 mg
Copper: 2000-4180 mug
Iodine: 500-995 mug
Selenium: 0-200 mu g
Manganese: 0-579 mug
4) The compound magnesium chloride is contained in each gram of magnesium chloride bag:
magnesium: 80-170 mg
5) Choline chloride in a bag per gram of Choline chloride
Choline: 300-950 mg
The base material of the compound nutrient is preferably lactose, solid corn syrup or L-sodium ascorbate. Based on 1000 weight parts of the milk protein partial hydrolysis formula powder containing the breast milk oligosaccharide, the addition amount of the compound nutrient is 7-52 weight parts, wherein the compound vitamin nutrition package is preferably 2-4 weight parts, the mineral secondary nutrition package is preferably 2-16 weight parts, the mineral tertiary nutrition package is preferably 0.5-20 weight parts, the mineral primary nutrition package is preferably 0.5-3 weight parts, the magnesium chloride is 0-3.5 weight parts, the choline chloride is 0-4.5 weight parts, and the base material of each nutrition package is preferably lactose or L-sodium ascorbate.
In order to ensure the utilization efficiency of nutrients, the invention selects stable nutrient dosage forms.
The content of each component of the compound nutrient is the content of the nutrient components in other raw materials of the milk powder which are not included in order to strengthen the addition amount of the nutrient substances,
according to a specific embodiment of the invention, in the infant formula of the invention, the probiotic is bifidobacteria. Preferably, the bifidobacterium is added in an amount of 0.1 to 0.2 parts by weight based on 1000 parts by weight of the infant formula; and more preferably 0.18 to 0.2 parts by weight. More preferably, the content of bifidobacteria per part by weight of the bifidobacteria powder is 3X 10 10 CFU or more.
According to some preferred embodiments of the present invention, an infant formula of the present invention comprises the following raw materials:
7-50 parts by weight of compound nutrients comprising calcium powder, vitamins and minerals;
DHA 2-15 weight portions;
3-22 parts by weight of ARA;
0 to 0.2 part by weight of bifidobacterium.
It will be appreciated that the particular amounts of the ingredients in the infant formulas of the present invention should be determined by adjusting the ingredients to meet the desired specifications for the formula product. In the infant formulas of the present invention, product performance indicators not specifically described or listed should be performed in accordance with the national standards of infant formulas (infant formulas) and the specifications of the relevant standards and regulations.
In the infant formula of the invention, all the raw materials are commercially available, and the raw materials are selected to meet the requirements of relevant standards. In addition, the expressions "compound" and "combine" are used for convenience of description, and do not mean that the components must be mixed together before application. All raw materials should be added and used on the premise of meeting related regulations.
In another aspect, the present invention also provides a method of preparing the infant formula, the method comprising:
the infant formula is prepared by mixing the breast milk oligosaccharide with other ingredients in the infant formula using a wet or dry manufacturing process. The preparation process mainly comprises the following steps: proportioning, homogenizing, concentrating, sterilizing, spray drying and dry mixing to obtain the finished product. In the invention, the breast milk oligosaccharide can be mixed together during the mixing process, and can also be added during the post-mixing or dry mixing process. The specific process conditions can be carried out by referring to conventional methods in the field of formula milk powder production.
According to a specific embodiment of the present invention, the method of preparing an infant formula of the present invention comprises:
1) Powder adding: the various powder raw materials are metered according to the formula and then are uniformly added into a powder preparation tank for storage through an air-assisted system.
2) Vacuum powder suction: various powder raw materials in the powder preparation tank are sucked into the vacuum mixing tank through the vacuum system.
3) Melting and oil preparing: the oil and fat specified in the formula are put into an oil melting room according to the formula requirement, the temperature of the oil melting room is kept at 50-90 ℃, and after the oil is melted, the oil is pumped into a mixed oil storage tank according to the formula proportion requirement through an oil pump and a flowmeter.
4) And (3) storing the mixed oil: the mixed oil is stored in an oil storage tank in a heat preservation way at the temperature of 40-50 ℃ for less than 12 hours to prevent fat oxidation.
5) Weighing: and pumping the mixed oil into a mixing tank through an oil pump according to the formula requirement.
6) Nutrient dissolution and addition: respectively adding calcium powder, mineral substances and vitamins, respectively, dissolving with 100-200 kg of purified water, respectively, adding into a wet mixing tank, and flushing an adding tank and a pipeline with 100kg of purified water after each time.
7) Breast milk oligosaccharide dissolution addition: and (3) dissolving part of the mixed liquor in the step (6) for the raw material of the breast milk oligosaccharide, and then adding the dissolved mixed liquor into a mixing tank to obtain the mixed liquor containing the breast milk oligosaccharide.
8) And (3) filtering: the mixed feed liquid is filtered by a filter screen to remove physical impurities possibly carried in the raw materials.
9) Homogenizing: homogenizing the mixed feed liquid by a homogenizer, wherein the primary pressure of homogenization is 105+/-5 bar, and the primary pressure of homogenization is 32+/-3 bar, mechanically treating the fat globules, and dispersing the fat globules into uniform fat globules.
10 Cooling and storing: the homogenized feed liquid enters a plate heat exchanger for cooling: cooling to below 20 ℃, temporarily storing in a pre-storing cylinder, entering the next working procedure within 6 hours, and starting the stirrer according to the set requirement.
11 Concentration sterilization: during production, double-effect concentration is used, the sterilization temperature is more than or equal to 83 ℃, and the sterilization time is 25 seconds. The discharge concentration is 48% -52% of dry matter.
12 Concentrated milk storage, pre-heating filtration, spray drying: the concentrated milk is temporarily stored in a concentrated milk balance tank. Preheating to 60-70 ℃ by a scraper preheater, filtering the preheated material by a filter with the aperture of 1mm, pumping the material into a drying tower by a high-pressure pump for spray drying, and agglomerating the fine powder on the top of the tower or a fluidized bed according to requirements. Air inlet temperature: 165-180 deg.c, exhaust temperature 75-90 deg.c, high pressure pump pressure 160-210 bar, and negative tower pressure-4 to-2 mbar.
13 Fluidized bed drying and cooling: and (3) the powder from the drying tower is subjected to fluidized bed (primary) secondary drying and then is cooled to 25-30 ℃ by the fluidized bed (secondary), so that the milk powder main material is obtained.
14 Split charging: when DHA, ARA, lactoferrin and bifidobacterium are contained in the formula, weighing, sealing and packaging the DHA, the ARA, the lactoferrin and the bifidobacterium according to the formula requirement.
15 Dry blending): and uniformly mixing the weighed DHA, ARA, lactoferrin, bifidobacterium and the milk powder main material in a dry mixer.
16 Screening powder: the granularity of the milk powder is uniform through the vibrating screen, and the powder slag is scrapped.
17 Powder discharge: and (3) receiving powder by using a sterilized powder collecting box, and conveying the powder from a powder outlet room to a powder feeding room.
18 Powder) is added: and pouring the milk powder into a powder storage tank on a size packaging machine according to the packaging requirement.
19 Packaging: 800 g automatic packaging machine nitrogen filling package. The oxygen content is lower than 1% when nitrogen is filled. 900 g of iron can is automatically filled with nitrogen and packaged, and the oxygen content is lower than 5%.
20 Boxing: packaging the packaged small bags into a paper box, adding a powder spoon at the same time, and sealing by a box sealing machine.
21 Inspection of the finished product: sampling and checking the packaged product according to a checking plan.
22 Warehousing and storing: the qualified products are stored in warehouse, and the storage is required at normal temperature, and the humidity is less than or equal to 65%.
In another aspect, the invention also provides the use of the infant formula as a food for improving the intestinal health of infants and increasing the tolerance of the products. In particular, the improvement of intestinal health in infants includes preventing intestinal leakage and/or improving immune responses. The preventing intestinal leakage includes improving intercellular intestinal permeability and/or intestinal barrier, and/or reducing intercellular gaps. The improving the immune response comprises improving the immune response activity of monocytes to differentiate into macrophages, and/or the improving the immune response comprises increasing the amount of TNF- α secreted in response to stimulation after the monocytes differentiate into macrophages.
The infant formula food disclosed by the invention has the effects of reducing the high risk of milk protein allergy, discomfort of gastrointestinal function, intestinal leakage of infants and the like, can promote the health of intestinal microenvironment, increase the tolerance of products, and can shorten the use time of hydrolyzed formulas for infants and use the whole protein formula as soon as possible.
Drawings
FIG. 1 shows the effect of breast milk oligosaccharides according to the invention on the molecular transport of FD 4.
FIG. 2 shows the effect of breast milk oligosaccharides on the immune response of monocyte-differentiated macrophages in the present invention.
Detailed Description
In order to more clearly understand the technical features, objects and advantages of the present invention, the technical solutions of the present invention will now be described in detail with reference to specific examples, which should be understood to be only illustrative of the present invention and not limiting the scope of the present invention.
Unless specifically defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the relevant art. In the examples, the raw materials of each breast milk oligosaccharide were obtained from Jennewein, a supplier, and the content of the breast milk oligosaccharide was measured by a method conventional in the art. The operating conditions not specified in detail in the examples were carried out according to the usual procedures in the art.
Example 1
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80% of 120 kg of hydrolyzed whey protein powder (hydrolysis degree 8), 115 kg of lactose, 435 kg of solid corn syrup, 120 kg of high oleic sunflower seed oil, 40 kg of corn oil, 50 kg of soybean oil, 80 kg of OPO structural fat, 0.16 kg of breast milk oligosaccharide (LNT), 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The infant formula of this example was prepared as follows:
1) Powder adding: the various powder raw materials are metered according to the formula and then are uniformly added into a powder preparation tank for storage through an air-assisted system.
2) Vacuum powder suction: various powder raw materials in the powder preparation tank are sucked into the vacuum mixing tank through the vacuum system.
3) Melting and oil preparing: the oil and fat specified in the formula are put into an oil melting room according to the formula requirement, the temperature of the oil melting room is kept at 50-90 ℃, and after the oil is melted, the oil is pumped into a mixed oil storage tank according to the formula proportion requirement through an oil pump and a flowmeter.
4) And (3) storing the mixed oil: the mixed oil is stored in an oil storage tank in a heat preservation way at the temperature of 40-50 ℃ for less than 12 hours to prevent fat oxidation.
5) Weighing: and pumping the mixed oil into a mixing tank through an oil pump according to the formula requirement.
6) Nutrient dissolution and addition: respectively adding calcium powder, mineral substances and vitamins, respectively, dissolving with 100-200 kg of purified water, respectively, adding into a wet mixing tank, and flushing an adding tank and a pipeline with 100 kg of purified water after each time.
7) Breast milk oligosaccharide dissolution addition: and (3) dissolving part of the mixed liquor in the step (6) for the breast milk oligosaccharide, and then adding the dissolved mixed liquor into a mixing tank to obtain the mixed liquor containing the breast milk oligosaccharide.
8) And (3) filtering: the mixed feed liquid is filtered by a filter screen to remove physical impurities possibly carried in the raw materials.
9) Homogenizing: homogenizing the mixed feed liquid by a homogenizer, wherein the primary pressure of homogenization is 105+/-5 bar, and the primary pressure of homogenization is 32+/-3 bar, mechanically treating the fat globules, and dispersing the fat globules into uniform fat globules.
10 Cooling and storing: the homogenized feed liquid enters a plate heat exchanger for cooling: cooling to below 20 ℃, temporarily storing in a pre-storing cylinder, entering the next working procedure within 6 hours, and starting the stirrer according to the set requirement.
11 Concentration sterilization: during production, double-effect concentration is used, the sterilization temperature is more than or equal to 83 ℃, and the sterilization time is 25 seconds. The discharge concentration is 48% -52% of dry matter.
12 Concentrated milk storage, pre-heating filtration, spray drying: the concentrated milk is temporarily stored in a concentrated milk balance tank. Preheating to 60-70 ℃ by a scraper preheater, filtering the preheated material by a filter with the aperture of 1mm, pumping the material into a drying tower by a high-pressure pump for spray drying, and agglomerating the fine powder on the top of the tower or a fluidized bed according to requirements. Air inlet temperature: 165-180 deg.c, exhaust temperature 75-90 deg.c, high pressure pump pressure 160-210 bar, and negative tower pressure-4 to-2 mbar.
13 Fluidized bed drying and cooling: and (3) the powder from the drying tower is subjected to fluidized bed (primary) secondary drying and then is cooled to 25-30 ℃ by the fluidized bed (secondary), so that the milk powder main material is obtained.
14 Split charging: and weighing DHA, ARA and bifidobacteria by powder workshop personnel according to the formula requirement, sealing bags and subpackaging.
15 Dry blending): and uniformly mixing the weighed DHA, ARA, bifidobacteria and the milk powder main materials in a dry mixer.
16 Screening powder: the granularity of the milk powder is uniform through the vibrating screen, and the powder slag is scrapped.
17 Powder discharge: and (3) receiving powder by using a sterilized powder collecting box, and conveying the powder from a powder outlet room to a powder feeding room.
18 Powder) is added: and pouring the milk powder into a powder storage tank on a size packaging machine according to the packaging requirement.
19 Packaging: 800 g automatic packaging machine nitrogen filling package. The oxygen content is lower than 1% when nitrogen is filled. 900 g of iron can is automatically filled with nitrogen and packaged, and the oxygen content is lower than 5%.
20 Boxing: packaging the packaged small bags into a paper box, adding a powder spoon at the same time, and sealing by a box sealing machine.
21 Inspection of the finished product: sampling and checking the packaged product according to a checking plan.
22 Warehousing and storing: the qualified products are stored in warehouse, and the storage is required at normal temperature, and the humidity is less than or equal to 65%.
In the product, the protein content is 9.6g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85% of the total protein), the fat content is 29g/100g, the carbohydrate content is 55g/100g, and the lactose-N-tetraose content is 15mg/100g of powder.
Example 2
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80%200 kg of hydrolyzed whey protein powder (hydrolysis degree 15), 500 kg of lactose, 90 kg of high oleic sunflower seed oil, 10 kg of corn oil, 50 kg of soybean oil, 110 kg of OPO structural fat, 2.8 kg of breast milk oligosaccharide (LNT), 38 kg of compound nutrient, 3 kg of DHA, 6 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 16g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85% of the total protein), the fat content is 26g/100g, the carbohydrate content is 50g/100g, and the lactose-N-tetraose content is 270mg/100g of powder.
Example 3
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80% of 160 kg of hydrolyzed whey protein powder (degree of hydrolysis 15), 530 kg of solid corn syrup, 60 kg of high oleic sunflower seed oil, 20 kg of corn oil, 70 kg of soybean oil, 140 kg of OPO structural fat, 7.8 kg of breast milk oligosaccharide (LNT), 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.2 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 11.2g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85 percent of the total protein), the fat content is 29g/100g, the carbohydrate content is 53g/100g, and the lactose-N-tetraose content is about 750mg/100g of powder.
Example 4
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80% of 120 kg of hydrolyzed whey protein powder (hydrolysis degree 8), 115 kg of lactose, 435 kg of solid corn syrup, 120 kg of high oleic sunflower seed oil, 40 kg of corn oil, 50 kg of soybean oil, 80 kg of OPO structural fat, 0.12 kg of breast milk oligosaccharide (LNT+3' -SL) composition, 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 9.6g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85 percent of the total protein), the fat content is 29g/100g, the carbohydrate content is 55g/100g, and the lactose-N-tetraose content is 85.7mg/100g of powder; the content of 3' -sialyllactose is 21.4mg/100g powder;
example 5
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80%200 kg of hydrolyzed whey protein powder (hydrolysis degree 15), 500 kg of lactose, 90 kg of high oleic sunflower seed oil, 10 kg of corn oil, 50 kg of soybean oil, 110 kg of OPO structural fat, 8.7 kg of breast milk oligosaccharide (LNT+3' -SL) composition, 38 kg of compound nutrient, 3 kg of DHA, 6 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 16g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85 percent of the total protein), the fat content is 26g/100g, the carbohydrate content is 50g/100g, and the lactose-N-tetraose content is about 680mg/100g of powder; 3' -sialyllactose content is 170mg/100g powder;
example 6
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80%155 kg of hydrolyzed whey protein powder (hydrolysis degree 15), 530 kg of solid corn syrup, 60 kg of high oleic sunflower seed oil, 20 kg of corn oil, 70 kg of soybean oil, 140 kg of OPO structural fat, 9.6 kg of breast milk oligosaccharide (LNT+3' -SL) composition, 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.2 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 11.2g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85 percent of the total protein), the fat content is 29g/100g, the carbohydrate content is 53g/100g, and the lactose-N-tetraose content is about 751mg/100g of powder; the 3' sialyllactose content was about 188mg/100g powder.
Example 7
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80% of 120 kg of hydrolyzed whey protein powder (hydrolysis degree 8), 115 kg of lactose, 435 kg of solid corn syrup, 120 kg of high oleic sunflower seed oil, 40 kg of corn oil, 50 kg of soybean oil, 80 kg of OPO structural fat, 1.1 kg of breast milk oligosaccharide (2 '-FL+LNT+3' -SL) composition, 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 9.6g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85% of the total protein), the fat content is 29g/100g, and the carbohydrate content is 55g/100g. The 2 '-fucosyllactose content in the product was about 57mg/100g, the lactose-N-tetraose content in the product was about 28.5mg/100g, and the 3' -sialyllactose content in the product was about 14.2mg/100g.
Example 8
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80%200 kg of hydrolyzed whey protein powder (hydrolysis degree 15), 500 kg of lactose, 90 kg of high oleic sunflower seed oil, 10 kg of corn oil, 50 kg of soybean oil, 110 kg of OPO structural fat, 20 kg of breast milk oligosaccharide (2 '-FL+LNT+3' -SL) composition, 38 kg of compound nutrient, 3 kg of DHA, 6 kg of ARA, 0.1 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 16g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85% of the total protein), the fat content is 26g/100g, and the carbohydrate content is 50g/100g. The amount of 2 '-fucosyllactose in the product was about 1113mg/100g, the amount of lactose-N-tetraose was about 557mg/100g, and the amount of 3' -sialyllactose was about 278mg/100g.
Example 9
The raw material composition of the infant formula of this example is as follows (1000 kg is produced):
80% of hydrolyzed whey protein powder (degree of hydrolysis 15) 150 kg, 530 kg of solid corn syrup, 60 kg of high oleic sunflower seed oil, 20 kg of corn oil, 70 kg of soybean oil, 140 kg of OPO structural fat, 28 kg of breast milk oligosaccharide (2 '-FL+LNT+3' -SL) composition, 38 kg of compound nutrient, 9 kg of DHA, 18 kg of ARA, 0.2 kg of bifidobacterium and 0.65 kg of nucleotide.
Wherein the compound nutrients comprise about 3.0 kg of compound vitamin nutrition package, about 2.0 kg of choline chloride nutrition package, about 12 kg of calcium powder nutrition package, 16 kg of sodium potassium nutrition package, about 2 kg of mineral nutrition package and about 3.0 kg of magnesium chloride nutrition package, and the base material of each nutrition package is solid corn syrup.
The product preparation process is as in example 1.
In the product, the protein content is 11.2g/100g (the protein with the molecular weight distribution of less than 3000dal accounts for more than 85% of the total protein), the fat content is 29g/100g, and the carbohydrate content is 53g/100g. The amount of 2 '-fucosyllactose in the product was about 1515mg/100g, the amount of lactose-N-tetraose was about 757mg/100g, and the amount of 3' -sialyllactose was about 378mg/100g.
Experimental results of improving intestinal leakage of Breast milk oligosaccharide
1. Experiments to improve paracellular permeability
The experiment examines the influence of different HMO and the composition thereof on the epithelial function of the small intestine under normal conditions, and the intestinal permeability and the intestinal barrier (improving paracellular permeability) among cells are improved through the indexes such as intestinal barrier, FD4 (fluorescein isothiocyanate dextran; FITC labeled dextran) molecular transport condition and the like.
Normal (non-invasive) conditions
Caco-2 cells were cultured in DMEM medium of transwell system for 21 days to simulate the small intestine epithelial cell layer. The test HMO or HMO composition (final concentration in the culture system 0.1 mg/mL) was added and cultured for 24 hours, followed by addition of FD4 molecules (final surface concentration 250 ug/mL) and further culture. FD4 molecule transport was measured at 24 hours of continued culture, and three times as biological replicates. A control group of DMEM medium without any HMO or HMO composition tested was also provided.
Data analysis
Statistical analysis of the molecular transport permeability data of FD4 was performed with two-tailed paired T-test. If there is a significant difference between the two groups, and p <0.05, the two groups are denoted by asterisks. Two asterisks indicate p <0.01. Three asterisks indicate p <0.001.
Experimental results
The results are shown in FIG. 1. LNT group, mass ratio 4:1 and 3'-SL significantly reduces FD4 molecular transport (P < 0.05), indicating that the LNT, LNT and 3' -SL compositions of the invention improve intercellular intestinal permeability (reduce intercellular intestinal permeability), promote intestinal barrier, and analyze the effects mainly due to the reduced intercellular gap and the improved intercellular tightness, thereby increasing the tightness of the paracellular transport pathway and effectively reducing intestinal leakage.
Tcda challenge experiments
The experiment examines the influence of HMO compositions with different proportions (the mass ratio of LNT to 3' -SL is 2:1 and 4:1 respectively) on the epithelial function of small intestine under the invasion condition of microbial toxin clostridium difficile toxin A (Clostridium difficile toxin A, tcDA), and the trans-membrane resistance TEER index is measured through the TcDA invasion experiment.
Caco-2 cells were cultured in DMEM medium of transwell system for 21 days to simulate the small intestine epithelial cell layer. The HMO composition to be tested (final concentration in the culture system 0.1 mg/mL) was added and cultured for 24 hours, then TcDA (final surface concentration 200 ug/mL) was added and the culture continued. The transmembrane resistance TEER was measured at 0, 3 hours after addition of TcDA for further culture, and three times as biological replicates. A control group of DMEM medium without any HMO or HMO composition tested was also provided.
Data analysis
For data of transmembrane resistance TEER, statistical analysis was performed using Tukey's multiple comparison test. If there is a significant difference between the two groups, and p <0.05, the two groups are denoted by asterisks. Two asterisks indicate p <0.01. Three asterisks indicate p <0.001.
Experimental results
Table 1 shows the effect of measuring transmembrane resistance after three hours of incubation with toxin A, LNT and 3' -SL compositions on transmembrane resistance.
TABLE 1
As can be seen from the results of the intestinal barrier test for three hours, the mass ratio was 2: the lnt+3' -SL composition of 1 significantly reduced the transmembrane resistance compared to the control, whereas the mass ratio of the present invention is 4: the lnt+3'-SL composition of 1 did not significantly reduce the transmembrane resistance, and demonstrated a trend of synergistic effect between the LNT and 3' -SL compositions of the specific ratio range of the present invention.
Experimental results of efficacy of Breast milk oligosaccharide composition in improving monocyte differentiation into macrophage immune response
The effect of HMOs on the activity of monocytes to differentiate into macrophages was examined by acclimating and activating monocytes.
Harvesting and culture of monocytes
The experimental conditions for specific blood sample collection and culture are as follows:
monocytes were isolated from blood samples of multiple healthy adult donors using the manufacturer's recommended procedure using the quatemacs system and CD14 microbeads magnetic bead sorting kit (Miltenyi Biotec, leiden, the netherlands). Written consent was obtained from the donor prior to blood collection.
Cultivation of monocytes: in RPMI 1640-Glutamax medium (Gibco, brisivisk, netherlands) supplemented with 10% fetal bovine serum (FBS, hyclone, emermeh, netherlands), 1% MEM nonessential amino acids (Gibco Brisivisk, netherlands), 1% sodium pyruvate (Lonza, buradar, netherlands), 1% penicillin/streptomycin (Sigma, st. Louis, misuri, U.S.A.), 1X 10 6 The concentration of cells/2 ml/well was cultured in 24-well plates.
Immune response activity studies included pretreatment of monocytes and immune response challenge testing performed 6 days later. The specific operation is as follows:
Monocytes were recovered from liquid nitrogen, after 1 day of recovery, the following group of experiments were performed, and all HMO feed in this experiment were from Jennewein:
HMO group: different HMO samples (different HMO monomers or HMO compositions in different proportions, wherein the proportions of monomers in the HMO composition are in mass ratio) were added to the monocyte medium at a final concentration of 0.1mg/mL, incubated with monocytes for 24 hours, after which the fresh medium was changed (washed out of the HMO samples) and incubation was continued for 6 days to differentiate the monocytes into macrophages. Then, lipopolysaccharide (final concentration of lipopolysaccharide in the medium 10 ng/mL) was added for 24 hours, and the secreted TNF-. Alpha.was measured from the supernatant.
Control group 1 (lipopolysaccharide group): the monocytes were pretreated with lipopolysaccharide, i.e., lipopolysaccharide was added to the monocyte medium at a final concentration of 0.1mg/mL, co-cultured with the monocytes for 24 hours, and then cultured for 6 days with fresh medium (washed out of LPS) to differentiate the monocytes into macrophages. Then, lipopolysaccharide (final concentration of lipopolysaccharide in the medium 10 ng/mL) was added for 24 hours, and the secreted TNF-. Alpha.was measured from the supernatant. The purpose of the control pre-treatment with the pre-lipopolysaccharide was to reduce the ability of monocytes to respond to subsequent re-stimulation, which is expected to reduce the response of monocytes to the second lipopolysaccharide stimulation.
Control group 2 (medium group): monocytes were cultured in medium without any test substances added for 7 days to differentiate monocytes into macrophages. Then, lipopolysaccharide (final concentration of lipopolysaccharide in the medium 10 ng/mL) was added for 24 hours, and the secreted TNF-. Alpha.was measured from the supernatant. Experimental methods refer to the method reported by Bekking et al (2016,Clinical and Vaccine Immunology), which uses ELISA (enzyme-linked immunosorbent assay) and a TNF-alpha specific kit to determine TNF-alpha, and the ELISA assay wavelength is 450nm, and uses Plate Reader Spark apparatus to determine the absorbance, spark sequence number is 200903777, and Spark control application sequence number is V3.1.
Data analysis
Macrophage immune response data were statistically analyzed using one way ANOVA. If there is a significant difference between the two groups, and p <0.05, the two groups are denoted by asterisks. Two asterisks indicate p <0.01. Three asterisks indicate p <0.001.
Experimental results
The experimental results are shown in fig. 2. The mass ratio is 4:2: 2' -FL of 1: LNT: the group of 3' -SL breast milk oligosaccharide compositions showed a significant elevation of TNF- α secretion (p < 0.05) in the monocyte trained model.
In addition, as the test results of the lipopolysaccharide group showed that lipopolysaccharide reduced the immune response, the lipopolysaccharide group was found to have a significant effect in reducing the immune response compared to the culture medium group without any test substance.

Claims (8)

1. Use of an infant formula for the preparation of a food product having an effect of improving the intestinal permeability and/or intestinal barrier between cells and/or reducing the gap between cells, wherein the infant formula comprises breast milk oligosaccharides consisting of lactose-N-tetraose and 3 '-sialyllactose in a mass ratio of lactose-N-tetraose to 3' -sialyllactose of 4:1, the total content of lactose-N-tetraose in the infant formula is 14.2-2273.0 mg/100g powder, based on the total mass of the infant formula, or 0.02-3.0 g/L on a milk basis;
and, based on the total mass of the infant formula, the total protein content in the infant formula is 9-20 g/100g, the total protein comprises hydrolyzed milk protein, the degree of hydrolysis is 8-23, and the protein with the molecular weight distribution of 3000dal or less accounts for 80% or more of the total protein.
2. Use according to claim 1, wherein the amount of 3' -sialyllactose applied in the infant formula is 14.2-1515.3 mg/100g powder, based on the total mass of the infant formula, or 0.02-2.0 g/L on milk basis.
3. Use of an infant formula for the preparation of a food product having an improved immune response, wherein the infant formula comprises breast milk oligosaccharides consisting of, in mass ratio, 4:2:1, 2 '-fucosyllactose, lacto-N-tetraose and 3' -sialyllactose; said improving an immune response comprises improving the immune response activity of monocytes to differentiate into macrophages, and/or said improving an immune response comprises increasing the amount of TNF- α secreted in response to a stimulus after differentiation of monocytes into macrophages;
the total content of lactose-N-tetraose in the infant formula is 14.2-2273.0 mg/100g powder, based on the total mass of the infant formula, or 0.02-3.0 g/L on a milk basis; the amount of 2' -fucosyllactose used in infant formulas is 14.2-3182.2 mg/100g powder or 0.02-4.2 g/L on a milk basis;
and, based on the total mass of the infant formula, the total protein content in the infant formula is 9-20 g/100g, the total protein comprises hydrolyzed milk protein, the degree of hydrolysis is 8-23, and the protein with the molecular weight distribution of 3000dal or less accounts for 80% or more of the total protein.
4. Use according to claim 3, wherein the total content of breast milk oligosaccharides in the infant formula is below 4000 mg/100g powder.
5. Use according to claim 1 or 3, wherein the fat content is 15-29 g/100g based on the total mass of the infant formula; the carbohydrate content is 50-58 g/100g.
6. Use according to claim 1 or 3, wherein the infant formula further comprises one or more of DHA, ARA, nucleotides, lactoferrin, probiotics.
7. Use according to claim 1 or 3, wherein the infant formula is prepared according to a preparation method comprising:
the infant formula is prepared by mixing the breast milk oligosaccharide with other ingredients in the infant formula using a wet or dry manufacturing process.
8. The use according to claim 7, wherein the raw materials for providing total protein in the raw materials of the infant formula comprise one or more of hydrolysed whey protein powder, hydrolysed casein powder, hydrolysed milk protein powder, hydrolysed milk fat globule membrane proteins.
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