TW201233340A - Human milk oligosaccharides for modulating inflammation - Google Patents

Abstract

Disclosed are nutritional compositions including human milk oligosaccharides that can be administered to preterm infants, term infants, toddlers, and children for reducing inflammation and the incidence of inflammatory diseases.

Description

201233340 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to human milk (HMO) for regulating inflammation of infants, young children or children. More specifically, the present invention relates to human milk fortifiers, preterm and term infant formulas and child formulas comprising HMO which reduce inflammation and thereby prevent and/or treat inflammatory conditions and diseases. The present application claims the benefit of U.S. Provisional Application No. 61/428,860, filed on Jan. 31, 2010, which is hereby incorporated by reference. [Prior Art] The inflammatory response attempts to restore and maintain internal stability after infection, antigenic attack, or physical, chemical or traumatic injury. Although the inflammatory response is generally considered a beneficial response to the injury, it may have an adverse physiological response if the immune system is not properly regulated. Specifically, 'unregulated oxidation and related inflammation are the main causes of tissue damage and clinically important diseases in preterm and term infants. This is largely due to the immature function of the natural immune system in infants, especially premature babies. Breastfeeding is associated with infant growth, gastrointestinal and immune system development, and growth and maturity balance, thereby protecting infants from infection and inflammatory diseases. In addition to sources of antioxidants such as vitamins A, C, E and selenium, breast milk appears to contain endogenous antioxidants such as superoxide dismutase, glutathione peroxidase and catalase or other non-enzymatic antibodies. Oxidants such as glutathione, lactoferrin and more. In addition, breast milk includes HMO, which not only acts as a pathogen receptor analog, but also by infant intestinal epithelial cells and/or associated 161,308. Doc 201233340 Apoptotic cell population activates immune factors. The function of these breast milk components to act as antioxidants and immunomodulators not only includes protecting breast milk lipids from peroxidation, but can also help to modulate inflammatory responses to infection or other damage. Not all babies are acceptable for human breast milk. In addition, there are currently no vaccines available for the prevention of inflammatory diseases. Therefore, it would be beneficial to develop safe and effective prophylactic or therapeutic methods, particularly for infants. Accordingly, it would be desirable to provide nutritional compositions, particularly synthetic infant formulas, which can produce nutritional benefits including improved growth and development of the immune system. In addition, it may be beneficial for the right nutritional composition to modulate inflammation and enhance immunity against microbial infections, including bacterial and viral infections, and other inflammatory diseases. SUMMARY OF THE INVENTION The present invention relates to a nutritional composition for reducing infant 'children's or children's inflammation, including synthetic infant formula, synthetic child formula, and synthetic child formula, including at least one of 11] A combination of one or more of polyunsaturated fatty acids (LCPUFA), antioxidants, and/or nucleotides, and methods of using such compositions. One embodiment is a synthetic child formula for regulating respiratory virus-induced inflammation. The synthetic children's formula comprises a mixture of 3'-sialyllactose and 6,-sialyllactose at a concentration of from about 1 mg/m]L to about 20 mg/mL. The content of the 3-saliva 8 lactose is about Q. 001 mg/mL to less than 0. 15 mg/mL. Another embodiment is a method of reducing the need for an infant's infant or child's inflammatory disease. The method comprises administering to the infant, toddler or child a concentration of 161308. Doc 201233340 degrees is about 0. Lactose_N neotetrasaccharide from 001 mg/mL to about 〇·2 mg/mL. Another embodiment relates to a method of inhibiting the growth of respiratory viruses in infants, young children or children. The method comprises identifying an infant, a child or a child having at least one of a respiratory tract fusion virus, a type 3 human parainfluenza virus, and a influenza A virus, and administering to the infant, toddler or child a concentration of about 0. 001 mg/mL to about 0. A combination of 2 mg/mL lactose_N_neotetraose. It has been found that specific combinations of specific HMOs such as 3,-sialyllactose, 6,-sialyllactose and other HMOs as described herein, as well as hm〇 as described herein, are highly effective in suppressing infants, young children and children. Inflammation, and in particular by reducing human immune cells to produce some key cytokines without increasing viral load, which can lead to faster recovery from infection to suppress viral-induced inflammation in infants, young children and children, including respiratory fusion viruses , human parainfluenza and influenza A. Surprisingly, it was determined that hm〇 showed the desired repression effect even at very low concentrations, including concentrations below the concentration seen in breast milk. Furthermore, it was unexpectedly found that 6'-sialyllactose is immunomodulatory even in the absence of virus and induces the production of cytokines derived from monocytes. "Also found that although the biological response is usually between 30 and 6 There is a 'minimum period of time' and therefore the in vitro procedure generally uses 3 to 60 minutes of incubation, but pre-treatment of the cells for 24 hours will better reflect the pre-exposure of HMOs that are received from breast milk every day for breastfed infants. In addition, it has been found that fucosylated HMO alone (including 3,-fucosyllactose) or in combination with sialic acid is highly effective in inhibiting respiratory viruses. Very 161,308. Doc 201233340 To 3'-fucosyllactose and sialic acid are still effective at low concentrations. Furthermore, it has been found that when a particular HMO is combined with a long-chain polyunsaturated fatty acid and/or carotenoid, it acts synergistically on the respiratory virus. These synergistic actions suppress viral inducing inflammatory cytokines, and in particular interferon-inducible peptone (ΙΡ-ΙΟ). Other components including antioxidants (such as vitamin A and vitamin E) or nucleotides may also be added to the combination of HMO and long chain polyunsaturated fatty acids and/or carotenoids. It has also been found to include 'acidic/sialylation (eg 6'-sialyllactose) and/or neutral/fucosylation (eg 2,-fucosyllactose) and/or n-acetylglucoside ( For example, a combination of LNnT) can prevent the development of necrotic enteritis. Again, these HMOs have been found to reduce oxidative stress in infants. [Embodiment] The nutritional compositions and methods described herein use a combination of HMO or HMO alone with a long chain polyunsaturated fatty acid and/or an antioxidant, particularly a guurin and/or a nucleotide, to control and reduce Many diseases and conditions associated with inflammation. The nutritional compositions described herein include synthetic infant formulas comprising a combination of HMO or HMO. These and other features of the nutritional compositions and methods are described in detail below, as well as a number of variations and additions. Some of the terms 0 "retort packaging" and "fetort sterilization" are described herein. It is used interchangeably and, unless otherwise specified, refers to the usual operation of filling a container with a nutrient solution, most typically a metal can or other similar package, and then subjecting the liquid-filled package to the necessary heat sterilization step to form Sterilized and pressurized packaging nutrient solution 161308. Doc 201233340 Product ° Unless otherwise specified, the term "aseptic packaging" as used herein refers to the manufacture of a packaged product without relying on the above-described pressurized packaging steps, wherein the nutrient solution and package are separately sterilized prior to filling, The sterilized, aseptically packaged nutrient solution product is then combined under sterile or aseptic processing conditions. As used herein, the terms "fat" and "oil" are used interchangeably to refer to a lipid material derived from a plant or animal or from a plant or animal, unless otherwise specified. These terms also include synthetic lipid materials as long as the synthetic materials are suitable for oral administration to humans. As used herein, the term "human milk oligosaccharide" or "HMO" generally refers to a plurality of complex carbohydrates present in human breast milk, which may be in an acidic or neutral form, and refer to its precursors, unless otherwise specified. body. Exemplary non-limiting human milk oligosaccharides include 3,-sialyllactose, 6,-sialyllactose, 3'-fucosyllactose, 2, fucosyllactose, and lactose_N_neotetraose. Examples The inhuman human milk oligosaccharide precursors include sialic acid and/or fucose. As used herein, the term "storing" means that the nutritional product is packaged at 18-24 ° C for at least 3 months (including from about 6 months to about 24 months and is also included). Keep the commodity stable after about 12 months to about 18 months. As used herein, the "nutritional formulation" or "nutritional composition" is used interchangeably and unless otherwise specified, refers to synthetic formulas including s nutrient, nutrient powder, nutrient solids, nutrient solids, nutrient half. Liquids, nutritional supplements and any other nutritious food known in the art 161308. Doc 201233340 ° Nutritional powder can be reconstituted to form a nutrient solution, which contains one or more of fat, protein and f-water compounds and is suitable for human oral consumption. The term "nutritional formula" or "nutritional composition" does not include human breast milk. Unless otherwise specified, $, as used herein, the term "nutrient solution" means a nutritional product in ready-to-drink liquid form, a concentrated form, and a nutrient prepared by restoring the nutritional powder described herein prior to use. liquid. Unless otherwise stated; t, as used herein, the term "nutritional powder" refers to a nutritional product in a flowable or self-contained form that can be reconstituted prior to consumption: water or another aqueous liquid and includes spray drying Powder mixed with dry blend/dry blend. Unless otherwise specified, (d) as used herein, the term "nutritional semi-solid" refers to a nutrient production of a property (such as rigidity) between a solid and a liquid - examples of semi-solids include pudding, gelatin, and facial enamel. Unless otherwise specified, the term "nutrient hemi-liquid" is used as a buttoning property (such as flow properties) as used herein. Nutrition between liquids and solids ^ Some examples of semi-liquids include milk gels (thlck shake) and liquid condensation unless otherwise specified, otherwise (four) months or less. Such as:: = "baby" "system child" refers to the person born in the family born 36 weeks ago, the term "early term "child" is used unless otherwise specified, as used herein to refer to Three years old. Unless otherwise specified, this document refers to persons over the age of three to twelve. Use, the term "child" is 161308. Doc 201233340 The term "newborn" as used herein, unless otherwise specified, refers to a person from birth to four weeks. As used herein, the terms "infant formula" or "synthetic infant formula" are used interchangeably and refer to liquid and solid, and semi-liquid and semi-solid human milk substitutes or substitutes suitable for infant consumption, unless otherwise specified. . Synthetic formulations include components having a semi-purified or purified source. The term "semi-purified" or "purified" as used herein, unless otherwise specified, refers to a material that has been prepared by purifying a natural material or by synthesis. The term "infant formula" or "synthetic infant formula" does not include human breast milk. As used herein, the term "synthetic children's formula", as used herein, refers to liquid and solid and semi-liquid and semi-solid human (four) substitutes or substitutes suitable for infants or young children up to 36 months (3 years old). Things. Synthetic formulations include components having a semi-purified or purified source. Unless otherwise specified, the term "semi-purified" or "purified" as used herein refers to a material that has been prepared by purification of natural materials or by synthesis. The term "synthetic child nutrition formula" does not include human breast milk. Unless otherwise specified, the term "synthetic child formula" as used herein is suitable for liquid and solid and semi-liquid and semi-solid human milk substitutes or substitutes for children up to 12 years of age. Synthetic formulations include components having a semi-purified or purified source. The term "semi-purified" & "purified" as used herein, unless otherwise specified, refers to a material that has been prepared by purifying a natural material or by synthesis. The term "synthetic child nutrition formula" does not include human breast milk. Sf· “Premature babies are dispensed unless otherwise specified” or as used herein 161308. Doc 201233340 方" means liquid and solid nutritional products suitable for consumption in premature babies. As used herein, the term "human milk fortifier", as used herein, refers to liquid and solid nutritional products suitable for mixing with a breast milk or premature infant formula or infant formula for consumption by premature or term infants. Unless otherwise specified, 'as used herein, the term "absence of a virus" or "absent a virus" with respect to the induction of a cytokine derived from a monocyte refers to an individual ("absence of a virus" or "absent a virus") For example, infants have no virus or have a virus that is less than the amount required to cause an immune response; that is, 'less than the body's natural immune response increases the amount of cytokines and other immune factors required to produce. The term "inflammatory disease" as used herein, unless otherwise specified, refers to any disease, disorder, or condition characterized by inflammation. The term "infectiously mediated inflammatory disease" as used herein, unless otherwise specified, refers to an inflammatory disease associated with or induced by a microbial infection, including viral and bacterial infections. As used herein, the terms "susceptible" and "at risk", as used herein, mean minimal resistance to a condition or disease, including a genetic predisposition, a family history of the condition or disease. And/or have its symptoms. Unless otherwise specified, the terms "modulating" or "modulating (m〇dulati〇n)" or "modulating" as used herein mean the intended action on a selected feature. Unless otherwise specified, the term "sickness growth" or "bacterial growth" as used herein refers to the production, proliferation, or re-creation of a virus or bacterium. Doc 201233340 system. Unless otherwise stated, all percentages and parts are as used herein by weight of the total composition. Unless otherwise stated, all such weights are based on the active ingredient content with respect to the listed ingredients and therefore do not include solvents or by-products that may be included in commercially available materials. The "numerical range" as used herein is intended to include a sub-set of the number, whether or not specifically disclosed. In addition, such numerical ranges should be construed as providing a phantom for the claims of any number or number of subsets within the range. For example, the disclosure should be considered as support: to 8 3 to 7, 5 to 6, 1 To 9, 3. 6 to 4_6, 3. 5 to 9. 9 equal range. References to singular features or limitations of the present invention are intended to include the corresponding plural features or limitations, and vice versa, unless the context or the context of the invention is otherwise clearly indicated. All combinations of methods or process steps, as used herein, may be performed in any order, unless otherwise indicated or referred to in the context of the combination. The nutritional compositions and methods can comprise, consist of, or consist essentially of, the essential elements of the compositions and methods described herein, and any other or optionally existing elements described herein or otherwise used in the application of a nutritional product. composition. Product Form The nutritional compositions of the present invention may be formulated and administered in the form of any known or otherwise suitable oral product. Any solid, liquid, semi-solid, semi-liquid or powder product form (including combinations or variations thereof) is suitable for use herein, limited to 161308. Doc 201233340 The condition is a form such as 13⁄4 that allows the safe and effective delivery of a basic ingredient as defined herein to an individual. The nutritional compositions of the present invention comprise one or more Hm(R) as described herein. Such compositions may include one or more HMOs alone or in combination with other immunopotentiating factors, including but not limited to long chain polyunsaturated acids (LCPUFA), nucleotides and antibodies as discussed below. Oxidizing agents such as carotenoids and vitamins. The nutritional composition can be in the form of any product comprising the ingredients described herein, and it is safe and effective for oral administration. The nutritional composition can be formulated to include only the ingredients described herein, or can be modified to contain as appropriate a plurality of different product forms. The nutritional composition of the present invention is suitably formulated into a dietary product form, which is defined herein as an embodiment comprising the ingredients of the present invention in the form of the following product. It contains at least one of fat, protein and carbohydrate, and preferably contains vitamins, minerals or a combination thereof. The nutritional composition will comprise; HMO, which is suitably combined with at least one of protein, fat, vitamins and minerals to produce a nutritional composition. The nutritional composition can be formulated to contain a sufficient variety and amount of nutrients to provide a unique, primary or supplemental source of nutrition, or to provide a particular nutritional product for an individual suffering from a particular disease or condition or a target nutritional benefit as described below. . Specific non-limiting examples of product forms suitable for use with the HMO-containing compositions as disclosed herein include, for example, liquid and powdered dietary supplements suitable for use in infants and children, liquid and powdered human milk fortifiers, liquids 161308. Doc 201233340 and powdered preterm formula, liquid and powder infant formula, liquid and powder and semi-element formula, liquid and powder children formula, liquid and powder infant formula and liquid and powder larger infant formula (f 〇ll〇w_ 〇n formulas). Nutrient solutions Nutrient solutions include concentrated and ready-to-eat nutrient solutions. These nutrient solutions are most commonly formulated as suspensions or emulsions, although other liquid forms are also within the scope of the present invention. A nutritional emulsion suitable for use may be an aqueous emulsion comprising protein, fat and carbohydrate. Such emulsions are generally in the form of a flowable or potable liquid at about to about 25 ° C and are typically in the form of an oil-in-water, water-in-oil or complex aqueous emulsion 'but such emulsions most often have a continuous aqueous phase and a discontinuous oil In the form of an oil-in-water emulsion. The nutritional emulsion can be and is generally stable to storage. The nutritional emulsion typically contains up to about 95% by weight water, including from about 50% to about 95%, also from about 60% to about 90%, and also from about 70% to about 85% water, by weight of the nutritional emulsion. Nutritional emulsions can have a variety of product densities, but most typically have a density greater than about 1. 03 g/mL 'includes greater than about 1. 04 g/mL, including greater than about 1. 055 g/mL 'includes about 1. 06 g/mL to about 1_12 g/mL, and also includes about 1. 085 g/mL to about 1. 10 g/mL. The nutritional emulsion can have a caloric density suitable for the nutritional needs of the end user, although in most cases the emulsion typically comprises at least 19 kcal/fl oz (660 kcal/liter), more typically about 20 kcal/fl oz (675 -680 kcal / liter) to about 25 kcal / fl oz (820 kcal / liter), and even more usually about 2 〇 kcal / fl oz (675-680 kcal / liter) to about 24 kcal / fl 〇z (800-810 thousand 161308. Doc -13- 201233340 Cards/L)) The 22-24 kcal/fl oz formula is most commonly used for premature or low birth weight infants and 20-21 kcal/fl oz (675-680) Formulas up to 700 kcal/litre are most commonly used for term infants. In some embodiments, the emulsion may have a caloric density of from about 50 Å to 00 kcal per liter, including from about 15 千 kcal to about 5 kcal per liter. In some specific embodiments, the emulsion may have a caloric density of 25 or 50 or 75 or 100 kcal/liter of beta. The pH of the nutritional emulsion may be about 3. 5 to about 8, but most preferably in the range of from about 4.6 to about 7.5, including from about 5 5 to about 7 3, including from about 6 2 to about 7. 2. Although the serving size of the nutritional emulsion can vary depending on a number of variables, typically each amount is typically at least about i mL, or even at least about 2 mL, or even at least about 5 mL, or even at least about 丨〇mL. , or even at least about 25 mL, including from about 4 mL to about 250 mL, and from about 10 mL to about 24 mL, in the range of from about 1 mL to about 3 mL. Nutritional Solids The nutritional solids can be in any solid form & but generally in the form of a flowable or substantially flowable particulate composition or at least a particulate composition. Particularly suitable forms of solid product for manufacture include spray drying, coalescence and/or dry blending; final compositions. The compositions can be readily taken and measured with a spoon or similar device and can be readily reconstituted by the intended user with a suitable aqueous liquid (usually water) to form a nutritional combination for immediate oral or enteral use. Things. In this case, "immediately" is generally meant to be within about 48 hours, most typically within about 24 hours, preferably immediately after recovery. 16130S. Doc 201233340 Nutritional powders can be reconstituted with water prior to use to a caloric density suitable for the end user's nutritional needs, although in most cases the powders are reconstituted with water to form at least 19 kcal/fl oz (660 kcal/liter), More typically about 20 kcal/fl oz (675-680 kcal/liter) to about 25 kcal/fl oz (820 kcal/liter), and even more typically about 20 kcal/fl 〇z (675-680 kcal) / liter) to a composition of about 24 kcal / fl oz (800-810 kcal / liter). In general, the 22-24 kcal/fl oz formula is most commonly used in premature or low birth weight infants, and the 20-21 kcal/fl oz (675-680 to 700 kcal/litre) formula is most commonly used for term infants. In some embodiments, the reconstituted powder may have a caloric density of from about 50 to 100 kcal/liter to about 660 kcal/liter, including from about 15 kcal/liter to about 500 kcal/liter. In some particular embodiments, the emulsion may have a heat density of 25 or 50 or 75 or 100 kcal/liter. Human Milk Oligosaccharide (HMO) The nutritional composition of the present invention comprises at least one HMO, and in many embodiments includes two or two, a combination of upper HMOs. Oligosaccharides are one of the major components of human breast milk and contain an average of 1 gram of neutral oligosaccharide per liter and 1 gram of acid oligosaccharide per liter. The composition of human milk oligosaccharides is complex and more than 2 different oligosaccharide-like structures are known. The HMO can be included in the nutritional composition, alone or in some embodiments, in combination with other immune enhancing factors (e.g., LCPUFAs, antioxidants, nucleotides, etc.) as described herein. HMOs may be isolated or enriched from milk secreted by mammals, including but not limited to a wide range of human, bovine, ovine, porcine or goat species. HMO may also be fermented by microorganisms, enzymatically, chemically synthesized or The combination is produced. 161308. Doc 201233340 HMO suitable for use in a nutritional composition may include an acidic oligosaccharide, a neutral oligo-sound, a glucoside oligosaccharide, and a ημ〇 precursor, which may be used individually or in combination in the compositions of the present invention. Specific non-limiting examples include: sialic acid (i.e., free sialic acid, sialic acid binding to lipids, sialic acid binding protein); D. glucose (Glc); D-galactose (Gal); Ν-acetylglucose Amine (GlcNAc); L-fucose (Fuc); fucosyl oligosaccharide (also known as lactose-N-codaripentin I; lactose·Ν-fucod pentasaccharide π; 2'-fucosyl Lactose; 3'-fucosyllactose 'lactose-Ν-fucod pentasaccharide; lactose-Ν-diarophora hexose I, and lactose difucosa tetrasaccharide; non-fucosylated, non-saliva Acidified oligo (ie lactose-Ν-tetraose and lactose-Ν_new tetrasaccharide); sialic acid oligosaccharide (ie 3,_sialic acid-3-fucosyl lactose; disial acid monofucose) Lactose _ Ν _ new hexasaccharide; monofucose-based monosialo-lactose _ Ν _ octasaccharide (sialo Lea); sialyllactose-N-fucohexaose π; disial lactose _N_fuc Pentasaccharide π ; single fucosyl di saliva Lactic acid lactose·Ν-tetraose); and sialic acid fucosyl oligosaccharide (ie 2'-sialyllactose; 2-sialyl lactosamine; 3,_sialyl lactose; 31-sialyl lactosamine; 6, sialyl lactose; 6, sialyl lactosamine, sialyllactose-Ν-neotetraose c; monosialo-lactose _ Ν _ hexaose; disialyl lactose hexose I; monosialo-lactose _ Ν _New hexose glucoside; monosialo-lactose-Ν-new hexasaccharide 二; disial lactose·N-new hexasaccharide; disialo-lactose-Ν-tetraose; disialo-lactose·Ν_hexaose 11; Sialyl lactose, tetrasaccharide a; disialyl lactose·Ν_hexaose; and sialic acid lactose _ν·tetrasaccharide 匕. A variant in which the reducing end of glucose (Glc) is replaced by N-acetylglucosamine (for example, 2'-fucosyl-N-acetylglucosamine (2, _FLNac) is 2,_fucosyllactose The variant) also applies. These HMOs are more fully described in U.S. Patent Application 161,308. Doc • 16 · 201233340, No. 2009/0098240, which is incorporated herein in its entirety by reference. Other suitable examples of HMOs which may be included in the compositions of the present invention include lactose-N-fucos pentasaccharide V, lactose-N-hexaose, p-lactose-N-hexaose, lactose-N-six hexose, pair - lactose-N-six hexose, monofucosyl lactose-N-hexasaccharide II, isomerized fucosylated lactose-N-hexasaccharide (1), isomerized fucosylated lactose-N- Hexaose (3), isomeric fucosylated lactose-N-hexasaccharide (2), difucosyl-p-lactose-N-sixhexose, difucosyl-p-lactose-N -hexaose, difucosyllactose-N-hexaose, lactose-N-new octasaccharide, p-lactose-N-octasaccharide, iso-lactose-N-octasaccharide, lactose-N-octasaccharide, single Fucosyl lactose-new octasaccharide, monofucosyl lactose-N-octasaccharide, difucosyl lactose-N-octasaccharide I, difucosyllactose-N-octasaccharide II, Eryan Alginose lactose-N-new octasaccharide II, difucosyllactose-N-new gossip I, lactose-N-decasaccharide, trifucosyl lactose-N-new octasaccharide, trifucose Lactose-N-octasaccharide, trifucosyl-iso-lactose-N-octasaccharide, lactose-N-dwarf-hexasaccharide II, sialic acid-lactose-N-tetraose a, sialic acid-lactose -N-tetraose b, sialic acid-lactose-N-tetraose c. Sialic acid-fucosyl-lactose-N-tetraose I, sialic acid-fucosyl-lactose-N-tetraose II and disialo-lactose-N-tetraose and combinations thereof. Particularly suitable nutritional compositions include at least one of the following HMO or HMO precursors: sialic acid (SA); 3'-sialyllactose (3'SL); 6--sialyllactose (6, SL); '-fucosyllactose (2'FL); 3'-fucosyllactose (3'FL); lactose-N-tetraose and lactose-N-neotetraose (LNnT), especially 6'SL with 3'SL combination; 3'FL and SA combination; 2'FL and 3'FL combination; 2'FL, 3'SL and 6'SL combination; 3'SL, 3'FL and LNnT combination; And a combination of 6'SL, 2'FL and LNnT. 161308. Doc -17- 201233340 Other exemplary combinations include: SA, 3'SL, 6'SL, 3'FL, 2'FL and LNnT; 3'SL, 6, SL, 3'FL, 2'FL and LNnT; SA , 6'SL, 3, FL, 2, FL and LNnT; SA, 3'SL ' 3'FL, 2, FL and LNnT; SA, 3'SL, 6, SL, 2'FL and LNnT; SA, 3 'SL, 6'SL, 3, FL and LNnT; SA, 3'SL, 6'SL, 3'FL and 2, FL; SA and 3'SL; SA and 6'SL; SA and 2'FL; SA And LNnT; SA, 3'SL and 6'SL; SA, 3'SL and 3'FL; SA, 3'SL and 2'FL; SA, 3'SL and LNnT; SA, 6'SL and 3'FL SA, 6'SL and 2'FL; SA, 6'SL and LNnT; SA, 3, FL and 2'FL; SA, 3, FL and LNnT; SA, 2'FL and LNnT; SA, 3, SL , 6, SL and 3, FL; SA, 3'SL, 6'SL and 2'FL; SA, 3'SL, 6, SL and LNnT; SA, 3, SL, 3'FL and 2'FL; SA , 3'SL, 3TL and LNnT; SA, 3'SL > 2, FL and LNnT; SA, 6'SL, 3'FL and 2'FL; SA, 6, SL, 2'FL and LNnT; SA, 6, SL, 3'FL and LNnT; SA, 3, FL, 2, FL and LNnT; SA, 6'SL, 2'FL and LNnT; SA, 3, SL, 3'FL, 2, FL and LNnT; SA, 6'SL, 3'FL, 2, FL and L NnT; SA, 3, SL, 6'SL, 3'FL and LNnT; SA, 3'SL, 3'FL, 2'FL and LNnT; SA, 3'SL, 6'SL, 2'FL and LNnT; 3'SL, 6'SL > 3'FL and 2, FL; 3'SL > 6, SL, 2, FL and LNnT; 3, SL, 3, FL, 2, FL and LNnT; 3'SL, 6'SL, 3, FL and LNnT; 3'SL '6'SL and 3'FL; 3'SL, 3'FL and 2'FL; 3, SL, 2, FL and LNnT; 3'SL, 6' SL and 2'FL; 3'SL '6'SL and LNnT; 3'SL and 3, FL; 3, SL and 2'FL; 3'SL and LNnT; 6'SL and 3'FL; 6'SL with 2, FL; 6'SL and LNnT; 6, SL, 3'FL and LNnT; 6'SL, 3, FL, 2'FL and LNnT; 3'FL, 2, FL and LNnT; 3'FL and LNnT; • 18 - 161308. Doc 201233340 and 2, FL and LNnT. The HMO is present in the nutritional composition in a total amount of ruthenium (mg of hMO per ml of composition) in the following composition: at least about 1 mg/mL in the nutritional composition, including at least about 〇. 〇1 mg/mL, including about 〇1 mg/mL to about 20 mg/mL' including about 〇. 〇1 mg/mL to about 20 mg/niL, including about 0. 01 mg/mL to about 10 mg/mL, including about 0. 01 mg/mL to about 5 mg/mL, including about 0. 001 mg/mL to about 1 mg/mL, including about o. Ooi mg/mL to about 0. 23 mg/mL, including about 〇. 〇1 mg/mL to about mg 23 mg/mL total ΗΜΟ» In general, the amount of HM 营养 in the nutritional composition will depend on the amount of HMO present and the other components in the nutritional composition. In a particular embodiment, when the nutritional product is a nutritional powder, the total concentration of HMO in the nutritional powder is about 〇. 〇〇〇5〇/0 to about 5〇/0, including approximately 〇1〇/. Up to about 1% (based on the weight of the nutritional powder). In another specific embodiment, when the nutritional product is a ready-to-feed nutrient solution, the total concentration of HMO in the ready-to-feed nutrient solution is about 〇. 〇001% to approximately 〇5〇0/〇, including approximately 0_001. /〇 to about 0. 15%, including about 0. 01% to about 〇 1〇%, and further includes about 0. 01% to about 0. 03〇/. (based on the weight of the ready-to-eat nutrient solution). In another specific embodiment, when the nutritional product is a concentrated nutrient solution, the total concentration of HMO in the concentrated nutrient solution is about 0. 0002% to about 0.60%, including about 0. 002% to about 0. 30%, including about 0. 02% to about 〇. 2〇. /〇, and further includes about 0. 02°/. To about 0. 06% (based on the weight of the concentrated nutrient solution). In a particular embodiment, the nutritional composition comprises a neutral human milk source of about 0. 001 mg/mL to approximately 20 mg/mL, including 〇. 〇1 mg/mL to about 20 mg/mL' includes about o. Ooi mg/mL to less than 2 mg/mL, and includes about I61308. Doc 19 201233340 0. 01 mg/mL to less than 2 mg/mL » In some embodiments, hydrazine is used in combination to provide the desired immunopotentiating effect. By way of example, s 'in one embodiment, the nutritional composition comprises 6, and the combination with 3 SL' has a total amount of from about 〇_〇〇1 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to about 20 mg/mL, including about o. Ooi mg/mL to less than 0. 23 mg/mL 'includes approximately 〇. 〇1 mg/mL to less than 〇23 mg/mL, including about 0. 001 mg/mL to less than 0. 15 mg/mL, and includes about 〇. 〇1 mg/mL to less than 〇.  1 5 mg/mL nutritional composition. In another embodiment, the nutritional composition comprises a combination of 6'SL and 3, SL, and the total amount of ruthenium is about 0. 001 mg/mL to approximately 20 mg/mL ’ package. Circumference 〇. 〇1 mg/mL to about 20 mg/mL, and includes greater than 0. 65 mg/mL to approximately 20 mg/mL. In another embodiment, the 'nutritional composition comprises a 3'SL and 6'SL weight ratio of from about 1:20 to about 20:1 ' including from about 1:1 〇 to about 1 〇:1, and including about 1:2 To about 2:1. In a particular embodiment, the nutritional composition comprises alone 6, SL or 6, SL in combination with other bismuth in an amount of about o. Ooi mg/mL to about 20 mg/mL, including about 〇. 〇1 mg/mL to about 20 mg/mL, including about 0. 001 mg/mL to less than 0. 25 mg/mL, including approximately 0. 01 mg/mL to less than 0. 25 mg/mL, including greater than 〇. 4 mg/mL to about 20 mg/mL, and includes about 0. 1 mg/mL to about 0. 5 mg/mL. In one embodiment, when the nutritional composition comprises 6'SL, the total amount of HMO in the nutritional composition comprises at least about 88% (based on the total weight of the HMO) 6, SL, including about 88% (based on the total weight of the hydrazine) ) to about 96% (based on the total weight of ruthenium), including about 88% (based on the total weight of ruthenium) to about 100 ° /. (based on the total weight of ΗΜΟ) and includes approximately 100°/. (based on the total weight of the ΗΜΟ) 6'SL. 161308. Doc • 20· 201233340 In another embodiment, the nutritional composition comprises a combination of 3, SL or 3'SL and other HMOs in an amount of about 0. 001 mg/mL to about 20 mg/mL 'includes about 0. 01 mg/mL to about 20 mg/mL' includes about 0. 001 mg/mL to less than 0. 15 mg/mL, including about 〇. 〇1 mg/mL to less than 0. 15 mg/mL' and includes greater than 0. 25 mg/mL to approximately 20 mg/mL. In one embodiment, when the nutritional composition comprises 3, SL, the total amount of HMO in the nutritional composition comprises at least about 85% (based on the total weight of the HMO) 3'SL' comprises about 85% (based on the total weight of the HMO) ) to about 88 ° /. (based on the total weight of the HMO), including approximately 85°/. (based on the total weight of the HMO) to about 100% (based on the total weight of the HMO) and including about 1 〇〇 ° /. (in terms of total HMO) 3'SL » In a particular embodiment, the nutritional composition comprises a combination of LNnT or LNnT alone and other HMOs in an amount of about 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to about 20 mg/mL, including about 0,001 mg/mL to less than 0. 2 mg/mL, including about 〇·〇1 mg/mL to less than 0. 2 mg/mL, including about 0. 001 mg/mL to about 0. 1 mg/mL, and includes greater than 0. From 32 mg/mL to about 20 mg/mL. In another specific embodiment, the nutritional composition comprises a combination of 3'FL or 3'FL alone and other HMOs in an amount of about 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to approximately 20 mg/mL' includes approximately o. Ooi mg/mL to less than 1 mg/mL, including about 0. 01 mg/mL to less than 1 mg/mL and includes greater than 1. 7 mg/mL to approximately 20 mg/mL. In a particular embodiment, the nutritional composition comprises a combination of 3'FL and SA having a total HMO of from about 0.00 1 mg/mL to about 20 mg/mL, including from about 0 mg to about 20 mg. /mL. In one embodiment, the nutritional composition 161308. Doc -21 · 201233340 Includes 0. 001 mg/mL to less than 1 mg/mL, including 0. From 1 mg/mL to less than 1 mg/mL of 3'FL and about 1 mg/mL of SA. In another embodiment, the nutritional composition comprises a combination of 2'FL or 2'FL alone or other HMO in an amount of about 0. From 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to about 20 mg/mL, including about 0. 001 mg/mL to less than 2 mg/mL, including about 0. 01 mg/mL to less than 2 mg/mL, including about 0. 001 mg/mL to about 1 mg/mL, and includes about 0. 01 mg/mL to about 0. 001 mg/mL. In another embodiment, the nutritional composition comprises a combination of 2'FL or 2'FL alone and other HMOs in an amount of about 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to approximately 20 mg/mL and includes greater than 2. 5 mg/mL to approximately 20 mg/mL. In a particular embodiment, the nutritional composition comprises a combination of 2TL and 3'FL having a total HMO of 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to approximately 20 mg/mL. In another embodiment, the nutritional composition comprises a combination of 6'SL, 2'FL, and LNnT, the total amount of HMO being about 0. 00 1 mg/mL to about 20 mg/mL, including from about 0. 01 mg/mL to about 20 mg/mL. Long-chain polyunsaturated fatty acid (LCPUFA) In addition to the above HMO, the nutritional product of the present invention may include LCPUFA. The LCPUFA is included in the nutritional composition to provide nutritional support, as well as to reduce oxidative stress and enhance the growth and functional development of the intestinal epithelium and related immune cell populations. In some embodiments, the nutritional composition comprises a combination of one or more HMOs with one or more LCPUFAs such that the composition provides synergistic benefits to the end user, such as a synergistic regulation of antiviral immune response and suppression of inflammation. Doc -22- 201233340 The same benefits. In some embodiments, the HMO used in combination with the LCPUFA to provide a synergistic effect is an acidic HMO. Exemplary LCPUFAs for use in nutritional compositions include, for example, omega-3 LCPUFAs and omega-6 LCPUFAs. Specific LCPUFAs include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), arachidonic acid (ARA), linoleic acid, and linolenic oil. Acid (alpha linoleic acid) and gamma-linolenic acid derived from oil sources such as vegetable oil, marine plankton, fungal oil and fish oil. In a particular embodiment, the LCPUFA is derived from fish oil such as menhaden, shoe fish, suspected fish, squid, flounder, gold grab fish or herring oil. Particularly preferred LCPUFAs for use in nutritional compositions with HMO include DHA, ARA, EPA, DPA, and combinations thereof. In order to reduce the potential side effects of high dose LCPUFA in the nutritional composition, the LCPUFA content preferably does not exceed 3% by weight of the total fat content of the nutritional composition, including less than 2% by weight of the total fat content, and includes less than the total fat content. 1% by weight. The LCPUFA may be in the form of a free fatty acid, a triglyceride, a diglyceride, a monoglyceride, a phospholipid, an esterified form or one or more of the above. Provided as a mixture, preferably in the form of triglyceride S. The nutritional composition as described herein will typically comprise a total concentration of about 〇. 01 mM to about 10 mM and includes about 〇. L 1 mM to about 1 mM LCPUFA. Alternatively, the nutritional composition comprises a total concentration of about 0. 001 g / L to about 1 g / L of LCPUFA 〇 161308. Doc • 23· 201233340 In one embodiment, the nutritional composition comprises a total long bond omega-6 fatty acid at a concentration of from about 100 mg/L to about 425 mg/L or from about 12 mg to about 53 mg per 100 kcal and/or A total long chain omega 3 fatty acid is included at a concentration of from about 40 mg/L to about 185 mg/L or from about 5 mg to about 23 mg per 100 kcal. In a particular embodiment, the ratio of long chain omega-6 fatty acids to long chain omega-3 fatty acids in the nutritional composition is in the range of from about 2:1 to about 3:1, preferably about 2. 5:1. In a particular embodiment, the nutritional composition comprises a concentration of about 0. 025 mg/mL to about 0. 130 mg/mL or about 3 mg to about 16 mg of DHA per 100 kcal. In another embodiment, the nutritional composition comprises a concentration of from about 〇8〇 mg/mL to about 0. 250 mg/mL or about 10 mg to about 31 mg of ARA per 100 kcal. In another embodiment, the nutritional composition comprises a combination of DHA and ARA such that the ratio of DHA to ARA is in the range of from about 1:4 to about 1:2. Antioxidants Additionally, the nutritional composition may comprise one or more antioxidants in combination with HM(R) (and optionally LCPUFAs and/or nucleotides) to provide nutritional support, as well as reduce oxidative stress. In some embodiments, nutrition The combination of the composition package and the antioxidant is such that the composition provides synergistic benefits to the end user, such as a synergistic benefit of modulating the antiviral immune response and suppressing inflammation. In some embodiments, HMO is used in combination with a carotenoid (and specifically lutein beta-carotene 'zeaxanthin and/or lycopene) to provide synergy. Any of the antioxidants suitable for administration via sigma may be used in the camp of the present invention: 'including, for example, vitamin A, vitamin bismuth, vitamin C, allo alcohol, tocopherol, and carotenoid (including For example, lutein, β-胡萝萄161308. Doc -24- 201233340 Prime, zeaxanthin and lycopene and combinations thereof). As described above, the technology used in the nutritional composition

Your oxidizing agent can be used alone with HMO or in combination with ΗΜΟ and LCPUFA and/or nucleotides. In a particular embodiment, the antioxidants used in the nutritional compositions include: carotenoids, especially carotenoids, lycopene, zeaxanthin and/or beta-caulon. The combination. A nutritional composition comprising such combinations as selected and defined herein can be used to modulate the levels of inflammation and/or C-reactive protein in preterm and term infants. Generally preferably, the nutritional composition comprises at least one of lutein, lycopene, zeaxanthin and beta-carotene to provide a total amount of carotenoids of from about 0.001 pg/mL to about 10 pg/ mL. More specifically, the nutritional composition comprises lutein in an amount from about 0.001 pg/mL to about 1 pg/mL, including from about 1 gg/mL to about 5 pg/mL, including from about 0.001 gg/mL to about 〇 〇19〇pg/mL, including from about 0.001 pg/mL to about 〇.014〇pg/mL, and also includes from about 0.044 pg/mL to about 5 pg/mL lutein. It is also generally preferred that the nutritional composition comprises from about p·〇〇1 pg/mL to about 1 〇gg/mL, including from about o.ooi pg/mL to about 5 pg/mL, about 〇·〇〇1 pg/ mL to about 0.013 〇 gg/mL, including from about 0.001 pg/mL to about 0.0075 pg/mL, and also including about 0.0185

Kg/mL to about 5 pg/mL lycopene. It is also generally preferred that the nutritional composition comprises from about 1 pg/mL to about 10 gg/mL, including from about 1 pg/mL to about 5 pg/mL, from about 0.001 final gram to about 0.025 pg/mL, including约〇_〇01 M^g/mL to about 〇.〇11 pg/mL, and also includes from about 0.034 pg/mL to about 5 pg/mL β-carotene. It will be appreciated that any combination of such amounts of beta-carotene, lutein, zeaxanthin and lycopene may be included in the camp of the invention 16I308.doc • 25-201233340. The situation is included in a nutritional composition as described herein. Any or all of the carotenoids included in the nutritional compositions described herein may be derived from natural sources or artificially synthesized. Each carotenoid in the selected combination may be obtained from any known or otherwise suitable source of material for use in the nutritional composition, and each may be provided individually or together, or in any combination, and from many sources, Sources include multivitamin premixes such as those containing other vitamins or minerals in combination with one or more carotenoids as described herein. Non-limiting examples of some suitable sources of lutein, lycopene, beta-carotin or combinations thereof include LycoVit® lycopene (available from BASF, Mount Olive, NJ), Lyc-0-Mato® tomato The extract is in the form of oil, powder or beads (available from LycoRed Corp., Orange, NJ), beta-carotene, lutein or lycopene (available from DSM Nutritional Products, Parsippany, NJ), FloraGLO® leaf yellow (gambling from Kemin Health, Des Moines, ΙΑ), Xangold® natural lutein ester (between Cognis, Cincinnati, 〇H) and Lucarotin® beta-carotene (available from BASF, Mount Olive, NJ). Nucleotide In addition to HMO, the nutritional composition of the present invention may additionally comprise a nucleotide and/or a nucleotide precursor selected from the group consisting of a nucleoside, a purine, a pyrimidine, a ribose, and a deoxyribose. The nucleotide may be in the form of monophosphate, dicapric acid or triphosphate. The nucleotide can be a ribonucleotide or a deoxyribose core: g: acid. Nucleotides can be monomeric, dimeric or polymeric (including RNA and DNA) nucleotides. The nucleotide may be present in the nutritional composition in free acid form or in the form of a salt, preferably a monosodium salt. In some embodiments, the 'nutritional composition includes 161308.doc -26·201233340 HMO in combination with nucleotides such that the composition provides synergistic benefits to the end user' such as modulating an antiviral immune response and suppressing inflammation and/or Synergistic Benefits of Improving Intestinal Barrier Integrity. The incorporation of nucleotides into the nutritional compositions of the present invention improves intestinal barrier integrity and/or maturity, which is beneficial for intestinal dysplasia and thus intestinal barrier maturation. Slow premature and full-term children. The nucleosides and/or nucleosides suitable for use in the nutritional composition include one or more of the following: 5·-mono-acid cytidine, 5,-monophosphate uridine, 5,-monophosphate adenosine, 51- 1-monophosphate guanosine monophosphate and / or 5 · _ monophosphate muscle bitter, more preferably heart monophosphate, 5'_monophosphate uridine, 5,-monophosphate adenosine, 5, _ monophosphate bird popular 5'-inosine monophosphate. Nucleotides are at least about 5 mg/L, including at least about 1 mg/L, including from about 10 mg/L to about 200 mg/L, including from about 42 mg/L to about 1〇2 mg/L, and include A total amount of nucleotides of at least about 72 mg/L of the nutritional product is present in the nutritional product. In a particular embodiment, when the nutritional composition is a nutritional powder, the amount of nucleotides can be at least about 0.007% 'including from about 78% to about 0.1556%' and includes about 0.056% (in nutritional powder) By weight, or at least about 0.007 grams per 1 gram of nutritional powder, including from about 78 grams to about 0.1556 grams, and including about 0.056 grams of nucleotide acid. In another particular embodiment, 'when a nutritional composition In the case of a ready-to-eat nutrient solution, the content of 'nucleotide acid is at least about 0.001%' including about 1% to about 0.017%% and includes about 0.071% by weight of the nutrient solution, or per 100 grams. The ready-to-feed nutrient solution is at least about 0.001 grams, including about 1 gram of 161308.doc 27·201233340 to about 0.0197 grams and includes about 0.0071 grams of nucleotides. In another particular embodiment, when the nutritional composition is a concentrated nutrient solution, the amount of nucleotides is at least about 〇.〇019%, including from about 0 0019% to about 0.0382%, and includes about 〇.〇138% (by weight of the nutrient solution), or at least about 0.0019 grams per 1 gram of concentrated nutrient solution, including from about 0.0019 grams to about 0.03 82 grams, and including about 0.0138 grams of nucleotides. Giant Nutrients A nutritional composition comprising HMO can be formulated to include at least one of a protein, a fat, and a carbohydrate. In many embodiments, the nutritional composition will include HMO and proteins, carbohydrates, and fats. Although the total concentration or amount of fat, protein and carbohydrate can be determined by the type of product (ie human milk fortifier, preterm formula, infant formula, etc.), product form (ie nutrient solids, powder, ready-to-feed liquid or concentrated liquid) and The desired dietary requirements of the user vary, but such concentrations or amounts are most commonly included within one of the following embodiments, including any other essential fat, protein, and/or carbohydrate component as described herein. For liquid preterm and term infant formulas, the carbohydrate concentration is typically in the range of from about 5% to about 4%, including from about 7% to about 30%, based on the weight of the preterm or term infant formula, including From about 1% to about 25%; the fat concentration is most typically in the range of from about 1% to about 3%, including from about 2% to about 15%, by weight of the preterm or term infant formula, and includes From about 3% to about 1%; and the protein concentration is most typically in the range of from about 0.5% to about 30%, including from about 1% to about 15%, by weight of the preterm or term infant formula, and also includes From about 2% to about 1%. I61308.doc •28· 201233340 For liquid human milk fortifiers, the carbohydrate concentration is most typically in the range of from about 10% to about 75%, including from about 10% to about 50%, by weight of the human milk fortifier, including From about 20% to about 40%; by weight of the human milk fortifier, the fat concentration is most typically in the range of from about 10% to about 40%, including from about 15% to about 37%, and also includes from about 18% to about 30%; and the protein concentration is most typically in the range of from about 5% to about 40%, including from about 10% to about 30%, and also from about 15% to about 25%, by weight of the human milk fortifier. The amount of carbohydrate, fat and/or protein in any of the liquid nutritional compositions described herein can also be characterized in a manner other than the percentage of the total calories of the liquid nutritional composition, or an alternative thereto, as shown in the table below. These macronutrients for use in the liquid nutritional compositions of the present invention are most typically formulated in any of the calorie ranges (Examples A-F) described in the following table (the term "about" is added before each value). Nutrient as a percentage of total calories Example A Example B Example C Carbohydrate 0-98 2-96 10-75 Protein 0-98 2-96 5-70 Fat 0-98 2-96 20-85 Example D EXAMPLE E Example F Carbohydrate 30-50 25-50 25-50 Protein 15-35 10-30 5-30 Fat 35-55 1-20 2-20 In a specific example, a liquid infant formula (ie, food type and Concentrated liquids include the following examples wherein the protein component can comprise from about 7.5% to about 25% of the caloric content of the formula; the carbohydrate component can comprise from about 35% to about 50% of the total caloric content of the infant formula; and the fat The components may comprise from about 30% to about 60% of the total caloric content of the infant formula. These ranges are provided as examples only and are not intended to be limited. 161308.doc •29- 201233340 Other suitable ranges are shown in the table below (the term "about" is added before each value). Nutrients accounted for % of total calories. Example G Example 实施 Example I Carbohydrate: 20-85 30-60 35-55 Fat: 5-70 20-60 25-50 Protein: 2-75 5-50 7-40 When the nutritional product is a powdered preterm or term infant formula, the protein component is present in an amount of from about 5% to about 35%, including from about 8% to about 12%, by weight of the preterm or term infant formula. And includes from about 10% to about 1 2 ° /. The fat component is present in an amount of from about 1% to about 35% by weight of the formula of the premature or term infant, including about 25°/. Up to about 30%, and including from about 26% to about 28%; and the carbohydrate component is present in an amount from about 30% to about 85%, including from about 45% to about 60% by weight of the preterm or term infant formula %, including about 50% to about 55%. For powdered human milk fortifiers, the protein component is present in an amount of from about 1% to about 55% by weight of the human milk fortifier, including from about 10% to about 50%. And comprising from about 10% to about 30%; the fat component is from about 1% to about 30% by weight of the human milk fortifier, including from about 1% to about 25%, and including from about 1% to about 20%; and the carbohydrate component is present in an amount of from about 15% to about 75%, including from about 15% to about 60%, including from about 20% to about 50%, by weight of the human milk fortifier. The total amount or concentration of fat, carbohydrate and protein in the powdered nutritional composition of the present invention will vary depending on the choice of composition and the dietary or medical needs of the intended user. Other suitable examples of macronutrient concentrations are described below. 161308.doc 30·201233340 Examples. In this case, the total amount or concentration refers to all sources of fat, carbohydrate and protein in the powdered product. For powdered nutritional compositions, the total amount or concentration is most commonly and preferably formulated in any of the ranges set forth in the following table (the term "about" is added before each value). Nutrients account for % of total calories. Example J Example 实施 Example L Carbohydrate 1_85 30-60 35-55 Fat 5-70 20-60 25-50 Protein 2-75 5-50 7-40 Fat In addition to the above LCPUFA The nutritional composition of the present invention may comprise other sources of fat. Other fat sources suitable for use herein include any fat or fat source suitable for use in oral nutritional products and compatible with the essential elements and characteristics of such products. For example, in one particular embodiment, the other fat is derived from a short chain fatty acid. Non-limiting examples of fats or sources thereof suitable for use in the nutrient calves described herein include coconut oil, branch coconut oil, soybean oil, corn oil, eucalyptus oil, safflower oil, safflower safflower oil Oleic acid (EMERS〇L 6313 oleic acid, Cognis Oleochemicals, Malaysia), MCT oil (medium chain triglyceride), sunflower oil, high oleic sunflower oil, palm and palm kernel oil, palm olein ( Palm olein), rapeseed oil, marine oil (marine, fish oil, fungal oil, algae oil, cottonseed oil, and combinations thereof. Protein The nutritional composition of the present invention may further comprise a protein as appropriate, and is suitable for use in an oral nutritional composition. And any of the protein sources of these products are suitable for use in nutritional compositions. Non-limiting examples of proteins or sources thereof suitable for nutrient production include hydrolysis, part A source of hydrolyzed or non-hydrolyzed protein or protein, which may be derived from any known or otherwise suitable source, such as milk (eg casein, whey), animal (eg meat, fish) , steroids (eg, rice, corn), plants (eg, soybeans), or combinations thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates, casein isolates, highly hydrolyzed as described herein Brass protein, whey protein, road protein or road protein dance, whole cow milk, partial or complete skim milk, soy protein isolate 'soy protein concentrate, etc.. In the embodiment, the nutritional composition includes the source Protein source for human and/or bovine-derived milk proteins. Carbohydrates The nutritional products of the present invention may, in a step-by-step manner, comprise any carbon water suitable for use in oral nutritional products and compatible with the essential elements and characteristics of such products. Compounds Non-limiting for carbohydrates or sources thereof for use in the nutritional products described herein (4) may include maltodextrin, hydrolyze or modify the flour or corn house powder: glucose polymer, corn syrup, corn syrup solid胄, derived from water-breaking compounds of rice, carbohydrates derived from cowpea, carbohydrates derived from horse-aged potatoes, cassava, sugar, glucose, Sugar, lactose, high fructose sugar Yu seeking polyethylene, honey, sugar alcohol (e.g. maltitol fucose alcohols, sorbitol), artificial sweetener, such as Li _ factors, (iv) alanine ethyl clock, sweet chrysanthemum), and combinations thereof. The water-repellent compound required by the main body of *&amp;, is the low dextrose equivalent (DE) maltodextrin. 161308.doc -32· 201233340 Other ingredients as the case may exist The nutritional composition of the present invention may include other groups as the case may exist - the production may be altered. The physical, chemical, aesthetic, or processing characteristics of σ or when used as a target population, act as a drug or other nutrient component. Many of such optional ingredients are known or otherwise suitable for use in medical foods or other nutritional products or pharmaceutical dosage forms and may also be used in the compositions herein, with the proviso that Oral administration is safe and compatible with the essential and other ingredients in the selected product form. Non-limiting examples of such optional ingredients include preservative emulsifiers, buffers, fructooligosaccharides, galactooligosaccharides, polydextrose (tetra), and other probiotics (prebi〇tics), Probiotics, pharmaceutically active agents, anti-inflammatory agents, other nutrients, colorants, flavoring agents, thickening agents and stabilizers, emulsifiers, lubricants, and the like, as described herein. The nutritional composition may further comprise a sweetener, preferably comprising at least one sugar alcohol such as maltitol, erythritol, sorbitol, xylitol, mannitol 'isomalt and lactitol' and also preferably At least one artificial or high-potency sweetener such as potassium acesulfame, aspartame, sucralose 'saccharin, stevia and tagatose. Such sweeteners, especially combinations of sugar alcohols and artificial sweeteners, are particularly suitable for formulating liquid beverage embodiments of the present invention having the desired advantageous profile. These sweetener combinations are particularly effective in masking the unpleasant taste sometimes associated with the addition of vegetable proteins to liquid beverages. The concentration of sugar alcohol present in the nutritional product, as appropriate, may be in the range of at least about 0.01%, including from about 1% to about 10%, and also from about 1% to about 6%. The artificial sweetener concentration 161308.doc •33·201233340 degrees may be in the range of about 0.01% 'including about 0.05% to about 5%', including about 0.1% to about 1.0, based on the weight of the nutritional product. %. A flow or anti-caking agent can be included in the nutritional composition as described herein to delay the agglomeration or agglomeration of the powder over time and to facilitate easy flow of the powder embodiment from its container. Any known flow or anti-caking agent known or otherwise suitable for use in nutritional powders or product forms is suitable for use herein, non-limiting examples of which include tricalcium phosphate, citrate and combinations thereof The concentration of the agent or anti-caking agent varies depending on the product form, other selected ingredients, the desired flow properties, etc., but is usually in the range of from about 〇i% to about 4% by weight of the nutritional composition, including About 0.5〇/. Up to about 2〇/0. Stabilizers can also be included in the nutritional composition. Any stabilizer known or otherwise suitable for use in the nutritional compositions is also suitable for use herein, some non-limiting examples of which include gums such as triterpene. The stabilizer may comprise from about 0.1% to about 5.0% by weight of the nutritional composition, including from about 5% to about 3%, including from about 0.7% to about 1.5%. The nutritional composition may further comprise any of a variety of other vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin D, refractory E, vitamin κ, thiamine, riboflavin, 哆 哆Alcohol, vitamin B! 2, carotenoids (such as β-carotene, zeaxanthin, lutein, arbutin), acid, folic acid, pantothenic acid, biotin, vitamin C, biliary, inositol, Salts and derivatives and combinations thereof. The nutritional composition may further comprise a sweeper of various other additional minerals, non-limiting examples of which include L magnesium, iron m sodium, potassium, molybdenum, chromium, vapors, and combinations thereof. 161308.doc • 34· 201233340 Method of Manufacture The nutritional composition of the present invention can be prepared by any known or otherwise effective manufacturing technique for preparing a solid or liquid form of the selected product. Many of these techniques are known for use in the absence of a product, such as a nutrient solution or a nutritional powder, and which can be readily applied by a general practitioner to the nutritional compositions described herein. Thus, the nutritional compositions of the present invention can be prepared by any of a variety of known or otherwise effective methods of formulation or manufacture. In a suitable manufacturing method, for example, at least three separate pastes are prepared, including a protein in-fat 'PIF slurry, a carbohydrate mineral (ch〇min) slurry, and a water-in-protein (protein_in_water). , piw) slurry. The slurry is heated and mixed with oil (such as rapeseed oil, corn oil, etc.), followed by continuous addition of heat and stirring to add an emulsifier (such as lecithin), fat-soluble vitamins and a part of total protein (such as milk protein concentrate, etc.) The formation of ^ cHO_MIN slurry is formed by adding the following to water under heating and stirring: minerals (such as potassium citrate, dipotassium arsenate, sodium citrate, etc.), traces and ultra-trace minerals (TM/ UTM premix), thickener or suspending agent (eg crystalline cellulose, gellan gum, carrageenan). The resulting CH〇_MIN slurry is kept under continuous heating and stirring for 10 minutes, followed by the addition of other minerals (such as chlorination, carbonation, potassium peroxide, etc.) and/or carbohydrates (eg, Hm〇, fructooligosaccharides, Sucrose, corn syrup, etc.). The PIW slurry is then formed by mixing with the rest of the protein, if present, under heating and mixing. The slurry is then pushed together under heat scrambling and the pH is adjusted to 6.6-7.0, and then the composition is subjected to a high temperature short time (HTST) treatment during which the composition is heat treated, emulsified and homogenized. Then let it cool. Add 161308.doc -35- 201233340 Add water 'gluten and ascorbic acid, adjust the pH to the desired range 'if necessary' and add water to achieve the desired total solids content if necessary. The composition is then aseptically packaged to form a sterile packaged nutritional emulsion. The emulsion can then be further diluted, heat treated and packaged to form a ready-to-serve or concentrated liquid, or it can be heat treated and subsequently processed and packaged into a reconstitutable powder, such as spray dried, dry blended, coalesced powder. The nutritional solids such as spray dried nutritional powder or dry mixed nutritional powder are prepared by any collection of known or otherwise effective techniques suitable for the preparation and formulation of nutritional powders. For example, when the nutritional powder is a spray-dried nutritional powder, the spray-drying step can likewise include any spray drying technique known or otherwise suitable for use in the manufacture of nutritional powders. Many different spray drying methods and techniques are known for use in the nutritional field, all of which are suitable for use in the manufacture of the spray dried nutritional powder herein. A method of preparing a spray-dried nutritional powder comprises forming and homogenizing an aqueous slurry or liquid comprising pre-digested fat and optionally protein, carbohydrate and other fat sources, followed by spray drying the slurry or liquid Produces a spray-dried nutritional powder. The method may further comprise the steps of spray drying, dry mixing or otherwise adding other nutrient ingredients, including any one or more of the ingredients described herein, to the spray dried nutritional powder. Other suitable methods for the preparation of nutritional products are described, for example, in U.S. Patent No. 6,365,218 (Borschel et al.), U.S. Patent No. 6,589,576 (Borschel et al.), and U.S. Patent No. 6,300,096 (. </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> The nutritional compositions described can be used for one or more of the diseases or conditions discussed herein, or can be used to provide one or more of the benefits described herein to premature babies, infants, toddlers, and children&apos;. Premature infants, infants, young children or children of the composition may actually have or suffer from the disease or condition, or may be susceptible to the disease or condition or at risk of developing the disease or condition (ie, 'actually possible' Not yet suffering from a disease or condition, but compared to the general population, due to certain conditions, family history, etc., is at risk of being sick.) Whether premature, infant, toddler or child actually suffers A disease or condition, or at risk of a disease or condition, or susceptible to a disease or condition, premature infants, infants, young children or children are classified as "needs" in this article to help combat and fight disease or condition. Premature infants, infants, young children or children may actually have respiratory tract inflammation or may be at risk of respiratory inflammation due to, for example, family history or other medical conditions (susceptible to respiratory inflammation). Regardless of premature infants, infants, young children Or the child actually has a disease or condition, or is at risk of or at risk of a disease or condition, and uses the nutritional composition described herein to help premature infants, infants, young children or children in this The invention is based on the above, as some method embodiments of the invention relate to a subset or subclass of a particular identified individual (ie, "need" to help with one or more specific diseases or specific diseases described herein a subset or subclass of individuals, so not all premature babies, infants, young children, and children are premature infants as described herein for certain diseases or conditions. A subset or subclass of infants, toddlers, and children" 161308.doc -37- 201233340 A nutritional composition as described herein comprising a single HMO or a combination of HMO and one or more other components to provide for reducing, for example, the respiratory tract A nutritional source of inflammation (eg, respiratory fusion virus-induced inflammation), intestinal inflammation, and inflammation of nasopharyngeal inflammation. The nutritional composition of the present invention can also provide optimal development and growth and maturation of the gastrointestinal and immune systems of infants. Balance, thereby enhancing the infant's ability to resist microbial infections and modulate the inflammatory response to infection (eg, increase phagocytosis and increase production of active oxides). ^ The nutritional composition also provides for the growth and maturation of infant intestinal epithelial cells. In a particular embodiment, administration of a nutritional composition comprising guanidine and nucleotides of the invention further activates the immune activity of neonatal intestinal epithelial cells or activates immune activity by its intestinal epithelial cells. In addition, the use of strontium in the nutritional composition reduces the growth of respiratory viruses (e.g., RS V2 human parainfluenza virus and influenza A virus), thereby reducing viral-induced upper respiratory tract infections. Thus, the use of HMO alone or in combination with other immune enhancing factors in nutritional products (such as a formula) is now possible to provide infants with alternatives or supplements that more closely mimic the benefits of breast milk. Together with the improvement in the growth and maturation of the infant's immune system as described above, the use of the nutritional composition of the invention also acts as an immunomodulator, thereby reducing infections in infants, young children and children (such as respiratory virus-induced infections) Induced inflammation, especially RSV-induced inflammation, and other infection-mediated inflammatory diseases. The addition of sputum may further increase the glutathione content in the body and blood of the infant and, in particular embodiments, the premature infant. 161308.doc -38· 201233340 'HMO reduces oxidative stress when used in combination with LCPUFA and/or antioxidants, especially with carotenoids', which are oxidized biomolecules (such as lipid peroxides and their decomposition products), protein carbonyls And metabolic diseases in which the production and accumulation of damaged Dna are increased. The results of oxidative stress range from improper metabolism to inflammation and cell and tissue death. Therefore, the incidence of inflammatory diseases such as necrotic enteritis (NEC) is further reduced by reducing the incidence of unregulated inflammation and oxidation in infants, reducing damage to tissue lining and cell death. In addition to the benefits discussed above, it has been found that nutritional products including HMO can modulate the production of cytokines derived from monocytes from infants, even in the absence of virus. The production of this cytokine leads to an improvement in immunity to further prevent microbial infection and reduce virus growth. In a specific embodiment, the cytokines derived from monocytes produced by administering the nutritional composition of the present invention include, for example, interleukin-1, interleukin-8, interleukin-Ια, intermediaries. White pigment _ ΐ β, interleukin _ lra and combinations thereof. Another benefit of using HMO in the Lvyang composition is that HM〇 has been found to regulate the production of IP-10, which is a chemotactic factor that plays an important role in the inflammatory response to viral infections. Specifically, t, clinical RSV in children There was a positive correlation between the severity of infection and serum IP-10 levels. Therefore, reducing the ιρ_ι〇 signal can reduce the severity of RSV infection. In a particular embodiment, IP-10 production was reduced to levels seen in the uninfected control group. Along with IP-ίο reduction, HM0 has been found to reduce platelet neutrophil globulin complex (PNC) formation, which is present in human blood and consists of at most unstimulated neutrophils. Because it exists in the form of aggregates 161308.doc •39·201233340, it has a large ability to initiate an inflammatory process and can increase the production of active oxides. Therefore, a reduction in the formation of PNC can result in a decrease in oxidative stress and inflammation in infants. EXAMPLES The following examples illustrate specific embodiments and/or features of the nutritional compositions of the present invention. The examples are provided for illustrative purposes only and are not to be construed as limiting the invention, as many variations may be present without departing from the spirit and scope of the invention. All exemplified amounts are by weight based on the total weight of the composition, unless otherwise specified. Exemplary compositions are stable nutritional compositions prepared according to the methods of manufacture described herein such that, unless otherwise specified, each exemplary composition includes sterile processing examples and pressurized packaging examples. Examples 1-5 Examples 1 - 5 illustrate ready-to-feed nutritional emulsions of the present invention, the ingredients of which are listed in the table below. Unless otherwise specified, all ingredient amounts are listed in kilograms per 1 kilogram of batch product. Ingredient Example 1 Example 2 Example 3 Example 4 Example 5 Water sufficient amount sufficient amount sufficient sufficient amount of concentrated skim milk 86.64 86.64 86.64 86.64 86 64 Lactose 54.80 54.80 54.80 54.80 54.80 High oleic acid safflower oil 14.10 14.10 14.10 14.10 14.10 Soybean oil 10.6 10.6 10.6 10.6 10.6 Coconut oil 10.1 10.1 10.1 10.1 10.1 3'Sialyl lactose (3'SL) 0.0948 0.090 0.085 9.479 9.005 Hemi-oligosaccharide (GOS) 8.63 8.63 8 63 8.63 8 63 Whey protein concentrate 6.40 6.40 6 40 6 40 6 40 Potassium citrate 478.9 r 478.9 g 478.9 g 478.9 g 478.9 g 161308.doc 201233340

Calcium carbonate 448.28 g 448.28 g 448.28 g 448.28 r 448.28 g Soy lecithin 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g Stabilizer 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g ARA oil 368.01 g 368.01 g 368.01 g 368.01 g 368.01 r Glycoside/chloride premix 293.26 g 293.26 g 293.26 g 293.26 g 293.26 g potassium chloride 226.45 g 226.45 g 226.45 g 226.45 g 226.45 g ascorbic acid 445.94 g 445.94 g 445.94 g 445.94 g 445.94 g vitamin mineral mixture 142.88 g 142.88 g 142.88 g 142.88 g 142.88 g DHA oil 137.8 g 137.8 g 137.8 g 137.8 g 137.8 g Carrageenan 180.0 r 180.0 g 180.0 g 180.0 r 180.0 g Magnesium chloride 55.0 g 55.0 g 55.0 g 55.0 g 55.0 g Ferrous sulfate 58.0 g 58.0 g 58.0 g 58.0 g 58.0 g Choline chloride 53.9 g 53.9 g 53.9 g 53.9 g 53.9 g Vitamin A, D3, E, IQ premix 47.4 g 47.4 g 47.4 g 47.4 g 47.4 g Lime acid 29.77 g 29.77 g 29.77 g 29.77 g 29.77 g Mixed type caraway «prima premix 26.40 g 26.40 g 26.40 g 26.40 g 26.40 g sodium chloride AN AN AN AN AN L-meat test 3.31 g 3.31 g 3.31 g 3.31 g 3.31 g Tricalcium phosphate 15.65 g 15.65 g 15.65 g 15.65 g 15.65 g Potassium dihydrogen phosphate 13.67 g 13.67 g 13.67 g 13.67 g 13.67 g Riboflavin 2.42 g 2.42 g 2.42 g 2.42 g 2.42 g Potassium hydroxide AN AN AN AN AN AN = Illustrative Examples 6-10 Examples 6-10 illustrate ready-to-feed nutritional emulsions of the present invention, the ingredients of which are listed in the table below. Unless otherwise specified, all ingredient quantities are listed in kilograms per 1000 kg batch of product. Ingredients Example 6 Example 7 Example 8 Example 9 Example 10 Water sufficient amount sufficient amount sufficient amount sufficient amount concentrated skim milk 86.64 86.64 86.64 86.64 86.64 lactose 54.80 54.80 54.80 54.80 54.80 161308.doc -41 - 201233340

High oleic safflower oil 14.10 14.10 14.10 14.10 14.10 Soybean oil 10.6 10.6 10.6 10.6 10.6 Coconut oil 10.1 10.1 10.1 10.1 10.1 61 sialyllactose (6'SL) 0.0948 0.0901 0.0853 9.479 9.0047 galactooligosaccharide (GOS) 8.63 8.63 8.63 8.63 8.63 Whey Protein Concentrate 6.40 6.40 6.40 6.40 6.40 Potassium Citrate 478.9 g 478.9 g 478.9 g 478.9 g 478.9 g Calcium Carbonate 448.28 g 448.28 g 448.28 g 448.28 g 448.28 g Soy lecithin 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g Stabilizer 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g ARA oil 368.01 g 368.01 g 368.01 g 368.01 g 368.01 g nucleotide/gasification premix 293.26 g 293.26 g 293.26 g 293.26 g 293.26 g potassium 226.45 g 226.45 g 226.45 g 226.45 g 226.45 g ascorbic acid 445.94 g 445.94 g 445.94 g 445.94 g 445.94 g vitamin and mineral mixture 142.88 g 142.88 g 142.88 g 142.88 g 142.88 g DHA oil 137.8 g 137.8 g 137.8 g 137.8 g 137.8 g carrageenan 180.0 g 180.0 g 180.0 g 180.0 g 180.0 g magnesium nitride 55.0 g 55.0 g 55.0 g 55.0 g 55.0 g ferrous sulfate 58.0 g 58.0 g 58.0 g 58.0 s 58.0 g gasified choline 53.9 g 53.9 g 53.9 g 53.9 g 53.9 g Vitamin A, D3, E, K, premix 47.40 g 47.40 g 47.40 g 47.40 g 47.40 g Citric acid 29.77 g 29.77 g 29.77 g 29.77 g 29.77 g mixed type carotenoid premix 26.40 g 26.40 g 26.40 g 26.40 g 26.40 g sodium chloride AN AN AN AN AN L-meat test 3.31 g 3.31 g 3.31 g 3.31 g 3.31 g tricalcium phosphate 15.65 g 15.65 g 15.65 g 15.65 g 15.65 g potassium dihydrogen phosphate 13.67 g 13.67 g 13.67 g 13.67 g 13.67 g riboflavin 2.42 g 2.42 g 2.42 g 2.42 g 2.42 g potassium hydroxide AN AN AN AN AN AN=11-15 as needed Examples 11-1 5 illustrate concentrated liquid emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise specified, all ingredients are listed in kilograms per 1/4 kg batch of 161308.doc -42 - 201233340.

Ingredient Example 11 Example 12 Example 13 Example 14 Example 15 Water sufficient amount sufficient amount sufficient sufficient amount of concentrated skim milk 157.67 157.67 157.67 157.67 157.67 lactose 108.66 108.66 108.66 108.66 108.66 high oleic safflower oil 26.82 26.82 26.82 26.82 26.82 soybean oil 20.16 20.16 20.16 20.16 20.16 Hazelnut oil 19.24 19.24 19.24 19.24 19.24 3' sialyllactose (3'SL) 0.1896 0.1802 0.1706 18.958 18.009 galactooligosaccharide (GOS) 17.67 17.67 17.67 17.67 17.67 whey protein concentrate 12.20 12.20 12.20 12.20 12.20 citric acid Potassium 1.277 1.277 1.277 1.277 1.277 Calcium carbonate 996.1 g 996.1 g 996.1 g 996.1 g 996.1 g Soy lecithin 685.0 g 685.0 g 685.0 g 685.0 g 685.0 g Monoglyceride 685.0 g 685.0 g 685.0 g 685.0 g 685.0 g ARA oil 684.2 g 684.2 g 684.2 g 684.2 g 684.2 g nucleotide/gasification premix 568.9 g 568.9 g 568.9 g 568.9 g 568.9 g potassium carbonate 429.7 g 429.7 g 429.7 g 429.7 g 429.7 g ascorbic acid 293.8 g 293.8 g 293.8 g 293.8 g 293.8 g Vitamin and mineral mixture 276.9 g 276.9 g 276.9 g 276.9 g 276.9 g DHA oil 256.1 g 25 6.1 g 256.1 g 256.1 g 256.1 g Carrageenan 200.0 g 200.0 g 200.0 g 200.0 g 200.0 g Magnesium sulfide 173.3 r 173.3 g 173.3 g 173.3 g 173.3 g Ferrous sulfate 112.7 g 112.7 g 112.7 g 112.7 g 112.7 g Gasification Cholesterol 104.8 g 104.8 g 104.8 g 104.8 g 104.8 g Vitamin A, D3, E, premix 86.90 g 86.90 g 86.90 g 86.90 g 86.90 g Citric acid 57.50 g 57.50 g 57.50 g 57.50 g 57.50 g Mixed carotenoid pre Mixture 41.90 g 41.90 g 41.90 g 41.90 g 41.90 g gasification nano 23.50 g 23.50 g 23.50 g 23.50 g 23.50 g L-meat test 6.40 g 6.40 g 6.40 g 6.40.g 6.40 g tricalcium phosphate AN AN AN AN AN Phosphate II Potassium hydrogen hydroxide AN AN AN AN AN Potassium hydroxide AN AN AN AN AN 161308.doc -43- 201233340 AN = as needed Examples 16-20 Examples 16-20 illustrate the ready-to-feed nutritional emulsion of the present invention, the ingredients of which are listed in the following table . Unless otherwise specified, all ingredients are listed in kilograms per 1000 kg batch. Ingredient Example 16 Example 17 Example 18 Example 19 Example 20 Water sufficient amount sufficient amount sufficient sufficient amount of concentrated skim milk 86.64 86.64 86.64 86.64 86.64 Lactose 54.80 54.80 54.80 54.80 54.80 High oleic acid safflower oil 14.10 14.10 14.10 14.10 14.10 Soybean oil 10.6 10.6 10.6 10.6 10.6 Coconut oil 10.1 10.1 10.1 10.1 10.1 HMO mixture 0.0948 0.0901 0.0853 9.479 9.0047 Θ sialyllactose (6'SL) 0.0316 0.0300 0.0284 3.159 3.002 2'fucosyllactose (2'FL) 0.0316 0.0300 0.0284 3.159 3.002 Lactose - N-neotetraose (LNnT) 0.0316 0.0300 0.0284 3.159 3.002 Semi-milk sugar (GOS) 8.63 8.63 8.63 8.63 8.63 Whey protein concentrate 6.40 6.40 6.40 6.40 6.40 Potassium citrate 478.9 g 478.9 g 478.9 g 478.9 g 478.9 g Calcium carbonate 448.28 g 448.28 g 448.28 g 448.28 g 448.28 g soy egg bowl 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g stabilizer 355.74 g 355.74 g 355.74 g 355.74 g 355.74 g ARA oil 368.01 g 368.01 g 368.01 g 368.01 g 368.01 g nucleoside Acid/gasification premix 293.26 g 293.26 g 293.26 g 293.26 g 293.26 g gasified potassium 226.45 g 2 26.45 g 226.45 g 226.45 g 226.45 g ascorbic acid 445.94 g 445.94 g 445.94 g 445.94 g 445.94 g vitamin and mineral mixture 142.88 g 142.88 g 142.88 g 142.88 g 142.88 g DHA oil 137.8 g 137.8 g 137.8 g 137.8 g 137.8 g carrageenan 180.0 g 180.0 g 180.0 g 180.0 g 180.0 g Magnesium sulfide 55.0 g 55.0 g 55.0 g 55.0 r 55.0 g Ferrous sulfate 58.0 g 58.0 g 58.0 g 58.0 g 58.0 g 161308.doc • 44- 201233340

Choline chloride 53.9g 53.9 g 53.9 g 53.9 g 53.9 g Vitamin A, D3, E, Κι premix 47.40 g 47.40 g 47.40 g 47.40 g 47.40 g Citric acid 29.77 g 29.77 g 29.77 g 29.77 g 29.77 g Mixed type Carrot «premix 26.40 g 26.40 g 26.40 g 26.40 g 26.40 g gasification nano AN AN AN AN AN L-meat test 3.31 g 3.31 g 3.31 g 3.31 g 3.31 g tricalcium phosphate 15.65 g 15.65 g 15.65 g 15.65 g 15.65 g Potassium dihydrogen phosphate 13.67 g 13.67 g 13.67 g 13.67 g 13.67 g Riboflavin 2.42 g 2.42 g 2.42 g 2.42 g 2.42 g Potassium hydroxide AN AN AN AN AN AN=Examples 21-25 Examples 21-25 The concentrated liquid emulsion of the present invention is illustrated, the ingredients of which are listed in the following table. Unless otherwise specified, all ingredient quantities are listed in kilograms per 1000 kg batch of product. Ingredient Example 21 Example 22 Example 23 Example 24 Example 25 Water sufficient amount sufficient amount sufficient sufficient amount of concentrated skim milk 157.67 157.67 157.67 157.67 157.67 lactose 108.66 108.66 108.66 108.66 108.66 high oleic safflower oil 26.82 26.82 26.82 26.82 26.82 soybean oil 20.16 20.16 20.16 20.16 20.16 Oyster oil 19.24 19.24 19.24 19.24 19.24 HMO mixture 18.957 18.009 17.061 19.905 20.853 6' sialyllactose (6'SL) 6.319 6.003 5.687 6.635 6.951 2'fucosyllactose (2TL) 6.319 6.003 5.687 6.635 6.951 Lactose - N-neotetraose (LNnT) 6.319 6.003 5.687 6.635 6.951 galactooligosaccharide (GOS) 17.67 17.67 17.67 17.67 17.67 Whey protein concentrate 12.20 12.20 12.20 12.20 12.20 Potassium citrate 1.277 1.277 1.277 1.277 1.277 Calcium carbonate 996.1 g 996.1 g 996.1 g 996.1 g 996.1 g Soy lecithin 685.0 g 685.0 g 685.0 g 685.0 g 685.0 g 161308.doc •45· 201233340

Monoglyceride 685.0 g 685.0 g 685.0 g 685.0 g 685.0 g ARA oil 684.2 g 684.2 g 684.2 g 684.2 g 684.2 g nucleotide/vapor compound premix 568.9 g 568.9 r 568.9 g 568.9 g 568.9 g gasification potassium 429.7 g 429.7 g 429.7 g 429.7 g 429.7 g ascorbic acid 293.8 g 293.8 g 293.8 g 293.8 g 293.8 g vitamin mineral mixture 276.9 g 276.9 g 276.9 g 276.9 g 276.9 g DHA oil 256.1 g 256.1 g 256.1 g 256.1 g 256.1 g carrageenan 200.0 g 200.0 g 200.0 g 200.0 g 200.0 g Magnesium sulfide 173.3 g 173.3 g 173.3 g 173.3 g 173.3 g Ferrous sulfate 112.7 g 112.7 g 112.7 g 112.7 g 112.7 g Gasified choline 104.8 g 104.8 g 104.8 g 104.8 g 104.8 g Vitamin A, D3, E, hydrazine, premix 86.90 g 86.90 g 86.90 g 86.90 g 86.90 g citric acid 57.50 g 57.50 g 57.50 g 57.50 g 57.50 g mixed type carotenoid 15 premix 41.90 g 41.90 g 41.90 g 41.90 g 41.90 g gasification nano 23.50 g 23.50 g 23.50 g 23.50 g 23.50 g L-meat test 6.40 r 6.40 g 6.40 g 6.40 g 6.40 g tricalcium phosphate AN AN AN AN AN Potassium dihydrogen phosphate AN AN AN AN AN Hydroxide Potassium AN AN AN AN AN AN= Examples 26-30 Examples 26-30 illustrate the need human milk fortifier of the present invention is a liquid, the ingredients listed in the table below. Unless otherwise specified, all ingredients are listed in kilograms per 1000 kg batch. Ingredient Example 26 Example 27 Example 28 Example 29 Example 30 Water sufficient amount sufficient sufficient sufficient amount of skim milk 353 353 353 353 353 corn syrup solid 85.3 85.3 85.3 85.3 85.3 medium chain triglyceride 53.2 53.2 53.2 53.2 53.2 whey Protein Concentrate 47.2 47.2 47.2 47.2 47.2 HMO Mixture 18.957 18.009 17.061 19.905 20.853 161308.doc •46· 201233340 6 Liquoric Acid Lactose (6'SL) 6.319 6.003 5.687 6.635 6.951 2' Fucosyllactose (2'FL) 6.319 6.003 5.687 6.635 6.951 Lactose-N-neotetraose (LNnT) 6.319 6.003 5.687 6.635 6.951 Calcium phosphate 25.5 25.5 25.5 25.5 25.5 Ascorbic acid 5.6 5.6 5.6 5.6 5.6 Potassium citrate 3.1 3.1 3.1 3.1 3.1 Magnesium gas 2.8 2.8 2.8 2.8 2.8 Citric acid Sodium 1.4 1.4 1.4 1.4 1.4 Gasification sodium 1.4 1.4 1.4 1.4 1.4 Soy lecithin 609 g 609 g 609 g 609 g 609 g M-inositol 500 g 500 g 500 g 500 g 500 g in the scented amine 400 g 400 g 400 g 400 g 400 g ARA oil 313 g 313 g 313 g 313 g 313 g tocopherol acetate 31〇g 31〇g 31〇g 31〇g 31〇g zinc sulfate 300 s 300 g 300 g 300 g 300 g calcium pantothenate 182 g 182 g 182 g 182 g 182 g ferrous sulfate 133 g 133 g 133 r 133 g 133 g DHA oil 116 g 116 g 116 g 116 g 116 g palmitate vitamin A 100 g 100 S 100 g 100 g 100 g copper sulfate 51.0 g 51.0g 51.0 g 51.0 g 51.0 g thiamine hydrochloride 50.0 g 50.0 g 50.0 g 50.0 g 50.0 g riboflavin 47.0 g 47.0 g 47.0 g 47.0 g 47.0 g hydrochloric acid sterol 27.0 g 27.0 g 27.0 g 27.0 g 27.0 g vitamin D3 20.0 g 20.0 g 20.0 g 20.0 g 20.0 R Folic acid 3.5 g 3-5 g 3.5 g 3.5 g 3.5 g Biotin 3.4 g 3.4 g 3.4 g 3.4 g 3.4 g Manganese sulfate 1.5 g 1.5 g 1.5 g 1.5 g 1.5 g Leaf green醌1.2 g 1.2 g 1.2 g 1.2 g 1.2 g cyanocobalamin 100 mg 100 mg 100 mg 100 mg 100 mg sodium benzoate 43.0 mg 43.0 mg 43.0 mg 43.0 mg 43.0 mg Examples 31-35 Examples 31-35 illustrate the invention Spray-dried nutritional powders, the ingredients of which are listed in the table below. Unless otherwise specified, all ingredients are listed in kilograms per 1000 metrics of 161,308.doc -47 to 201233340 kg.

Ingredient Example 31 Example 32 Example 33 Example 34 Example 35 Concentrated skim milk 698.5 698.5 698.5 698.5 698.5 Lactose 386.0 386.0 386.0 386.0 386.0 High oleic acid safflower oil 114.4 114.4 114.4 114.4 114.4 Soybean oil 85.51 85.51 85.51 85.51 85.51 Coconut oil 78.76 78.76 78.76 78.76 78.76 3 'Sialyl lactose (3'SL) 0.3792 0.3604 0.3412 37.916 36.0188 galactooligosaccharide (GOS) 69.50 69.50 69.50 69.50 69.50 Whey protein concentrate 51.08 51.08 51.08 51.08 51.08 Potassium citrate 9.168 9.168 9.168 9.168 9.168 Calcium carbonate 4.054 4.054 4.054 4.054 4.054 Soy lecithin 1.120 1.120 1.120 1.120 1.120 ARA oil 2.949 2.949 2.949 2.949 2.949 nucleotide/gasification premix 2.347 2.347 2.347 2.347 2.347 vaporized potassium 1.295 1.295 1.295 1.295 1.295 Ascorbic acid 1.275 1.275 1.275 1.275 1.275 Vitamin mineral mixture 1.116 1.116 1.116 1.116 1.116 DHA oil 1.113 1.113 1.113 1.113 1.113 Magnesium vapor 1.038 1.038 1.038 1.038 1.038 Gasification sodium 579.4 g 579.4 g 579.4 g 579.4 g 579.4 g Ferrous sulfate 453.6 g 453.6 g 453.6 g 453.6 g 453.6 g Gasification 432.1 g 432.1 g 432.1 g 432.1 g 432.1 g Vitamin A, D3, E, K! Premix 377.2 g 377.2 g 377.2 g 377.2 g 377.2 g ascorbyl phthalate 361.3 g 361.3 g 361.3 g 361.3 g 361.3 g Mixed Carotenoid premix 350.1 g 350.1 g 350.1 g 350.1 g 350.1 g mixed tocopherol 159.2 g 159.2 g 159.2 g 159.2 g 159.2 g L- meat test 26.30 g 26.30 g 26.30 g 26.30 g 26.30 g riboflavin 3.181 g 3.181 g 3.181 g 3.181 g 3.181 g Tricalcium phosphate 0-5.23 0-5.23 0-5.23 0-5.23 0-5.23 Potassium dihydrogen phosphate 0-5.23 0-5.23 0-5.23 0-5.23 0-5.23 Potassium hydroxide AN AN AN AN AN AN = as needed 161308.doc -48· 201233340 Example 36 In this example, the effect of purified human milk oligosaccharide (HMO) on inhibition of viral infectivity in vitro was analyzed. Three respiratory viruses with a uniform viral dose of about 500 units per milliliter to about 1,000 units per milliliter: (1) respiratory syncytial virus (RSV); (2) human parainfluenza virus (HPIV3); or (3) One of the Η1Ν1 influenza viruses is co-cultured with one of the following: to prepare samples: (1) 3'-sialyllactose (3'SL); (2) 6'-sialyllactose (63L); 3) 3'-fucosyllactose (3'FL); (4) 21-fucosyllactose (2'FL); (5) lactose-N-neotetraose (LNnT); or (6) The concentration of sialic acid (SA) «HMO is 1 mg/mL or 10 mg/mL. The antiviral activity of various HMOs against respiratory viruses was evaluated and the results are shown in the following table: HMO IC50 (mg HMO/mL) RSV HPIV3 H1N1 Influenza 3SL &gt;10 &gt;10 〜5 6'SL &gt;10 &gt;10 〜 10 3FL ~ 5 ~ 2 ~ 5 2, FL &gt; 10 &gt; 10 ~ 10 LNnT &gt; 10 NT &gt; 10 SA NT ~ 2 ~ 5 NT = Untested results show a concentration of 1 mg / ML (IC50 about 2 5 mg/ML): TFL has antiviral activity against all three respiratory viruses. This result was unexpected because previously published reports showed that only the sialylated oligomer form provided anti-viral activity. SA significantly inhibited HPIV3 and H1N1 viruses at a concentration of 1 mg/mL. The H1N1 influenza virus was also inhibited by 3'SL at a concentration of 1 mg/mL. 161308.doc •49- 201233340 Example 37 In this example, the ability of various HMOs to block the infectivity of the H1N1 influenza virus in vitro was analyzed. Viral infectivity was assessed by observing cytopathic effect (CPE) and quantifying viral lesion formation units. To form a viral material, the H1N1 influenza virus was purchased from ATCC (VR 1469) and expanded in Madin Darby Canine Kidney (MDCK) epithelial cells (ATCC CCL_34). The cell free supernatant was frozen in aliquots to maintain the viral material. Cell CpE was observed during initial virus culture and expansion to form viral material. To quantify viral infectivity, immunocytochemical focal unit formation (FFU) analysis was performed using commercially available mouse monoclonal antibodies against viral nucleoproteins coupled to biotinylated anti-mouse IgG secondary antibodies. To observe virally infected cell lesions, streptavidin was performed using streptavidin HRp (ABC, from Vector Laboratories, lnc.). Although the total number of viral lesions is proportional to the concentration of the infectious virus, the lesions are quite large and scattered, and there are many individual infected cells that do not form lesions, especially at higher viral concentrations. Because this makes the quantification of viral infectivity difficult and time consuming, it helps to reduce the Brownian movement of the virus in the entire cell layer by changing the virus concentration and by applying the sputum veruy medium (〇verUy medium). To further improve the FFu analysis. The use of tragacanth improves the analysis by reducing the number of individual infected cells while still allowing the formation of easily observable lesions. Although the lesions vary in size, some of which are quite large, they are still easily quantified by grid technology during calculations and are proportional to viral concentration or potency. 161308.doc -50- 201233340 After the test, the assay was applied to various HMOs to analyze the ability to block the infectivity of the H1N1 virus. Specifically, HMO at concentrations of 0.01 mg/mL, 0.1 mg/mL, 1.0 mg/mL, and 10 mg/mL were added to the inoculated virus suspension, incubated at 37 ° C for 1 hour, and then added to the MDCK single. In layer cells. This mixture was allowed to bind to the cell layer for thirty minutes at 37 °C. The cell layer is then washed and the cells are incubated for a further 18-24 hours, then fixed and subjected to immunocytochemical staining. The results are shown in Figure 1. As shown in Figure 1, 3'FL, 3'SL and SA each inhibited viral infectivity by more than 90% when used at a concentration of 10 mg/mL. 2'FL and 6'SL inhibited the infectivity by about 60% at 10 mg/mL. Example 38 In this example, the effect of a nutritional composition comprising various HMOs on reducing the oxidative stress of premature piglets was evaluated. Preterm piglets were collected by caesarian section (CS) with 92% surviving. Piglets received total parenteral nutrition (TPN) for 48 hours. After 48 hours, TPN was stopped and the piglets were randomized into three groups: Formulation group (π=7), Enfamil® Lacto-Free, Mead Johnson, Evansville, IN; Treatment group (n=9), arrogant Enfamil® Lacto-Free was supplemented with a combination of 400 mg/L 6'SL, 1500 mg/L 2'FL and 200 mg/L LNnT; and a colostrum group (n=5) fed bovine colostrum. Piglets were fed their respective feeds at a rate of 120 mL per kg of body weight for the next 48 hours. The piglet is then euthanized earlier after 48 hours of enteral nutrition (EN) or if the piglet develops a sign of necrotizing enteritis. Blood was collected via a umbilical artery catheter and plasma was separated from blood and stored at -70 °C until 161308.doc -51 - 201233340. Commercially available assays (NwLSS glutathione analysis #NWK-GSH01 ' Northwest Life Science Specialties, Vancouver, before the feeding time (time 〇) and 6 hours, 12 hours, 24 hours, 36 hours and 48 hours after feeding) WA) measures the concentration of glutathione (GSH) in the plasma taken from piglets. The results are shown in Fig. 2". As shown in Fig. 2, the concentration of gsh in the plasma from the control group decreased from time 0 to 6 hours after the feeding. "GSH was still low in the control group 24 hours after εν. In contrast, piglets fed a composition containing the HMO combination have a plasma GSH content pattern comparable to that of the colostrum. Example 39 In this example, the ability of 3'SL, 6'SL and LNnT to reduce viral-induced inflammation in vitro was demonstrated. Specifically, '3 SL or 6SL at a concentration of 〇·1 mg/mL, 0.2 mg/mL or 〇·5 mg/mL was added to fresh peripheral blood mononuclear cells at 37 C, 5% C〇2 Incubate to pre-treat cells for approximately 24 hours. LNnT at a concentration of 0.1 mg/mL, 0.2 mg/mL or 1 mg/mL was added to fresh peripheral blood mononuclear cells and incubated at 37t, 5% C〇2 to pre-treat the cells for about 24 hours. Lactose was included as a carbohydrate control group. A matched control group of endotoxin concentrations was included to distinguish the effects of the ingredients from the inherently low levels of endotoxin. Then, some variables were incubated with the RSV of 〇.1 at 37t, 5% C〇2 for about 1 hour. The uninfected control variables were incubated with the medium for about 1 hour at 37 ° C, 5%. After about an hour, add fresh medium alone or fresh medium containing appropriate concentrations of 3, SL, 6, sl, 161308.doc · 52· 201233340 LNnT, lactose or endotoxin to appropriate tubes at 37 ° C, 5 The cells were incubated for 48 hours at % C〇2. Supernatants were collected 24 and 48 hours after infection. The cytokines in the supernatant were measured for each variable at 24 and 48 hours to assess the effect of HMO on the early immune response against RSV. Cytokines were measured using a custom Bio-Plex human cytokine kit from Bio-Rad. The results of interferon-inducible protein 10 (IP-10, also known as CXCL 10) are shown in Figures 3 and 4 (for 3, SL and 6, SL) and in Figures 5 and 6 (for LNnT). IP·10 is a CXC chemokine that attracts, binds to, and activates the CXCR3 receptor on natural killer cells and memory T cells. IP-10 is expressed by monocytes and many other cells and is induced by interferon. The severity of RSV clinical disease in children (eg, by the following measurements: length of hospitalization, fever, and number of days needed to supplement 〇2) and serum IP There is a positive correlation between -1 〇. Therefore, reducing the IP_1 信号 signal can reduce the severity of the RSV disease experienced. The IP-10 results for 3'SL and 6, SL are detailed in Figures 3 and 4 and show some variability in donor response, but surprisingly, 6, SL significantly down-regulates the viral infection variables of the two donors. In the IP-10. It should be noted that 6, SL is able to reduce 11 &gt; 1 〇 to the level seen in the uninfected control group. 3'SL is not valid in donor b, but RSV induced IP_10 is down-regulated in donor E. These data show that 3, both pores and 6'SL block Rsv-induced Ip_1〇, but 6, SL is more effective for underground adjustment of ιρ_ι〇. The results also indicate that lower than (6 mg of M mg/mL and content of more than 0.5 mg/mL can effectively reduce the IP-1 of some individuals. The results of IP_10 are detailed in Figures 5 and 6 and are shown for Some variability in response, but surprisingly, LNnT significantly down-regulated 1P-10 in the 161308.doc-53-201233340 viral infection variable of both donors. It should be noted that 'LNnT can reduce ip-1 至 to The amount seen in the uninfected control group. The results also indicate that between 0.2 mg LNnT/mL and 1 mg LNnT/mL and greater than 1 mg/mL can effectively reduce the IP-10 of some individuals. The inclusion of the unit concentration control clearly indicates that the reduction in IP-10 is not due to the presence of very low levels of endotoxin in LNnT. In Figures 7 and 8, the cytokine results are also surprisingly shown, 6,51 ^ Increase the level of interleukin-1 (IL_1 〇) in a dose-dependent manner in the presence or absence of RSV. The IL-10 results for LNnT are shown in Figures 9 and 1〇. The surprising thing is that LNnT Increased IL-10 concentration in a dose-dependent manner in the presence or absence of RSV. IL-10 is produced by activated CD8+ T cells. It is produced by CD4+ T cells after antigen-specific and multi-strain activation, and by monocytes after bacterial lipopolysaccharide-activated cells. The inclusion of matched endotoxin unit concentration control group clearly inferred that ip-io increased and Not attributable to 6, very low levels of endotoxin in SL*LNnT. Surprisingly, 'the discovery of pretreatment with 6,SL, 3, SL or LNnT for 24 hours is effective in reducing inflammation caused by RSV. If the measurement is reduced by 1?_1〇, it is shown that 6, SL and LNnT are more effective in suppressing virus-induced inflammation than 3, SL. In addition, 'Show 6, SL is immunomodulatory in the absence of virus because The inclusion of 6'SL induces and/or improves the production of cytokines derived from monocytes such as IL-10, ΜιΡ·ιρ, interferon-7, IL_8, ILla, 仏邛 and L Ira. 3, SL is also immunomodulatory in the presence or absence of virus 'because 3, SL inclusion can induce and / or improve cytokines derived from monocytes (such as MIP-Ιβ, interferon 丫, More than _8 and 161308.doc •54- 201233340 IL-lra). Surprising LNnT is also immunomodulatory in the presence or absence of virus 'because the inclusion of LNnT induces and/or ameliorates cytokines derived from monocytes (such as IL_1 〇, mip_ 1 β, CU-γ, IL) -8, IL-la, IL-Ιβ and IL-lra) production. Example 40 In this example, the analysis reduced the combination of inflammatory cytokine ratio _8, SL and 63L in vitro. Specifically, '3'SL and 6,SL at a concentration of 0.1 mg/mL, 0.2 mg/mL or 0.5 mg/mL are added individually or at a total concentration of 〇2 mg/mL, 0.4 mg/mL or 1.0 mg. The combination of /mL (combination 1 = 1 part 3181^ and 1 part 6 SL, combination 2 = 1 part 3'SL and 2 parts 6'SL) was added to fresh peripheral blood mononuclear cells (PBMC) and at 37. (:, 5% C〇2 was incubated to pre-treat cells for about 24 hours. Including lactose as a carbohydrate control group, including matching endotoxin unit concentration control group to distinguish the component action from the inherently low content of endotoxin. After 24 hours', then some variables were incubated with RSV with an infection magnification (MOI) of 0.1 at 37 ° C, 5% C 〇 2 for about 1 hour. Uninfected at 37 ° C, 5% C 〇 2 The control variables were incubated with the medium for about 1 hour. After about 1 hour, fresh medium alone or fresh medium containing appropriate concentrations of 3'SL or 6'SL, either individually or in combination, was added to the appropriate variables' at 37°. CB, 5% C〇2 was incubated for 48 hours. The supernatant was collected at 24 and 48 hours after infection, divided into aliquots and stored frozen at -7 〇〇c for post-mortem analysis. For 48 hours, the cytokines in the supernatant were assayed for each variable to assess the effect of 3'SL and/or 6'SL on the early immune response against RSV. Custom Bio-Plex human cells from Bio-Rad were used. I61308.doc, 55· 201233340 Measure the cytokines in the prime group. Interleukin-8 (IL-8) results Shown in Figure 11. IL-8 is produced by stimulated monocytes, macrophages, and fibroblasts and is a chemokine of all migratory immune cells. IL-8 activates neutrophils and enhances reactive oxygen species. Metabolism. IL-8 strongly binds to red blood cells in vivo, and once bound, it no longer activates neutrophils. IL-8 is an inflammatory cytokine, therefore, it is generally necessary to reduce the content of IL-8. The combination of 3, SL and 6, SL improves the kinetics of the IL-8 reaction in the presence or absence of RSV. Individually, in the presence of rsv, increasing concentrations of 3'SL and 6SL can increase IL-8. 2 and to a certain extent, the combination of 1 and HMO increases the agricultural level and decreases the concentration of IL-8. Therefore, it can be inferred that inflammation can be reduced by administering a combination of 3'SL and 6'SL. Example 41 In this example In the presence or absence of ph〇rbai myristate acetate (PMA), the extracellular activity of peripheral blood mononuclear cells (PBMC) in uninfected and RSV-infected cells was reduced. The ability of oxygen species (ROS). On day 0, fresh human PBMC were isolated from whole blood. 〇.! 2/FL of mg/mL, 0.2 mg/mL or 1 mg/mL was added to PBMC and incubated for about 24 hours at 37 C, 5% C 〇 2. On day 1, the cell supernatant was removed and PBMCs were incubated with a separate medium or medium plus respiratory syncytial virus (RSV) with a infection magnification (MOI) of 1 at 37 ° C, 5% C 〇 2 for about 1 hour. After about 1 hour, fresh medium alone or medium containing the appropriate concentration of 2'FL was added to an appropriate test tube, and cells were incubated at 37 ° C, 5% C02 for 147308.doc • 56 · 201233340 for 48 hours. On day 3, 20% (3.5 χ 105 cells) of PBMC cultures were removed to analyze the production of reactive oxygen species derived from NADPH oxidase using the chemiluminescent probe isoluminol. The separated cells were evenly divided into two tubes having a reaction mixture containing isoluminol and horseradish peroxidase. One tube was treated with phorbol 12-tetradecanoate 13-acetate to induce activation of the NADPH oxidase complex. Chemiluminescence generated by reactive oxygen species was monitored by a luminometer over a period of 60 minutes. Active oxygen production was quantified by integrating the area under the curve over a 60 minute period. The remaining PBMC supernatant and cell lysate were separately collected, aliquoted and stored frozen at -70 °C for later analysis. As shown by the results in Figure 12B, 2'FL suppresses the release of extracellular reactive oxygen species (ROS) from uninfected (0.1-0.2 mg 2' in the absence of phorbol myristate acetate (PMA). FL/mL) and infected cells (0.1-1.0 mg 2'FL/mL). Furthermore, as shown by the results in Figure 12A, 2'FL suppresses uninfected in the presence of 卩]\48 (0.1-1.〇111§2 under 1^1111〇 and infected (0.1-0.2 mg 2 'FL/mL) ROS in PBMC. Repression of ROS reduces RSV-induced oxidative stress damage to lung and other tissues. Example 42 In this example, the combination of 2'FL and 6'SL is shown to reduce IP in vitro. 1〇 (the marker of viral inflammation). Specifically, fresh human peripheral blood mononuclear cells (PBMC) were isolated from whole blood on day 0. 2'FL alone (concentration 0.1 mg/mL, 0.2 mg) /mL, 0.5 mg/mL or 1 mg/mL) or 2'FL and 6'SL (concentration 0.05 161308.doc -57- 201233340 mg/mL, 0.1 mg/mL, 0·2 mg/mL or 1 mg /mL) The combination was added to PBMC and incubated at 37 ° C, 5% CO 2 for about 24 hours. On day 1, the cell supernatant was removed and PBMC was treated at 37 ° C, 5% C 〇 2 The medium or medium alone is supplemented with respiratory syncytial virus (RSV) with an infection rate (MOI) of 1 for about 1 hour. After about 1 hour, fresh medium alone or with appropriate concentration of 2'FL and/or 6' will be used. The medium of SL is added to an appropriate test tube, and Cells were incubated at 37 ° C, 5% C 〇 2 for 48 hours. On day 3, the supernatant was collected (48 hours after infection). At 48 hours, the Luminex human cytokine kit was used to measure the supernatant for each variable. Cytokines to assess the effect of HMO on early immune responses to RSV. Surprisingly, 'as shown in Figure 13, 2, the combination of FL and 6, SL reduces the synergy of IP·1 54 by 54%. Interferon-inducible protein! 〇 (Ip_丨〇, also known as CXCL10) is a CXC chemokine that attracts 'binding and activates CXCR3 receptors on natural killer cells and memory tau cells. Ιρ_1〇 is composed of monocytes and Many other cells behave and are induced by interferon. There is a positive correlation between the severity of RSV clinical disease in children (eg, by the following measurements: length of hospitalization, fever, and days requiring 02 supplementation) and serum IP_1〇. Decrease/may indicate a decrease in the severity of the Rsv disease experienced. It can be concluded from the fact that by administering 2, the combination of well and 6, SL can reduce the severity of the RSV disease experienced. [Simple description of the diagram] The picture shows the truth Figure 1-3 shows the infectivity of MDCK cells in the presence of various ίίΜΟ. Figure 2 is a graph depicting the glutathione from piglets measured in Example 38. 161308.doc -58-201233340 A plot of the pulp content. Figure 3 is a graph depicting the IP-10 content produced by administration of 3, SL and 6, SL as measured in Clarity &amp; Figure 4 is a graph depicting the enthalpy of the IP-10 content produced by the administration of 3, SL and 6, SL as measured in Example 39. Figure 5 is a graph showing the content of IP-1〇 produced by the administration of LNnT as measured in Example 39. Figure 6 is a plot of the effect of administration of LNnT as measured in Example 39. A map of IP-10 content. Figure 7 is a graph depicting the IL-10 content produced by administration of 3'SL and 6, SL as measured in Example 39. Figure 8 is a graph depicting the IL-10 content produced by administration of 3'SL and 6'SL as measured in Example 39. Figure 9 is a graph depicting the content of 10 produced by administration as measured in Example 39. Figure 10 is a graph depicting the IL-10 content produced by administration of L Ν η τ as measured in Example 39. Figure 11 is a graph of IL-8 content produced by administration of 3, SL and/or 6, SL as measured in Example 40. Figures 12A and 12B are graphs depicting the degree of chemical luminescence produced by administration of 2, FL in the presence or absence of phorbol myristate acetate (PMA) as measured in Example 41. Figure 13 is a graph depicting the percent reduction in IP-io produced by administration of 211 and 6'SL, either alone or in combination, as measured in Example 42. I61308.doc •59-

Claims (1)

201233340 VII. Scope of Application: 1. A synthetic children's formula for regulating respiratory virus-induced inflammation. The synthetic children's formula contains 3'-sialyllactose at a concentration of about 0.001 mg/mL to about 20 mg/mL. A mixture with 6,-sialyllactose wherein the content of the 3'-sialyllactose is from about o.ooi mg/mL to less than 0.15 mg/mL. 2. A synthetic child formula according to claim 1, which comprises o.ooi mg/mL to a mixture of 3'-sialyllactose and 6'-sialyllactose β of less than 0.23 mg/mL. A synthetic child formula comprising a mixture of 3'-sialyllactose and 6'-sialyllactose from 〇〇〇i mg/mL to less than 0.15 mg/mL. 4. The synthetic children formula of claim 1 which comprises a mixture of 3'-sialyllactose and 6'-sialyllactose greater than 65.65 mg/mL to 20 mg/mL. 5. The synthetic children's formula of claim 1, wherein the 6, sialic lactose is present at a concentration of from 0.001 mg/mL to less than 0.25 mg/mL. 6. For the synthetic children's formula of Item 1, the 6, sialic lactose is present at a concentration greater than 〇.4 mg/mL to 20 mg/mL. 7. A method of reducing inflammation in an infant, a child or a child. The method comprises administering to the infant, toddler or child a lactose comprising a concentration of from about 1 mg/mL to about 2 mg/mL. A composition of sugar. A method of β, wherein the lactose neotetrasaccharide is present at a concentration of from about 〇〇丄.〇〇丄 mg/mL to about 〇丨mg/mL. 9. The method of claim 7, wherein the inflammatory condition is inflammation of the respiratory tract. The method of claim 7, wherein the inflammatory condition is selected from the group consisting of respiratory tract virus-induced inflammation, enteritis, nasopharyngitis, and combinations thereof. 161308.doc 201233340 11. 12. 13. 14. 15. The method of claim 7, wherein the composition further comprises from 0.001 mg/mL to less than 25 mg/mL 6, sialyllactose. The method of claim 7, wherein the composition further comprises from 0.001 mg/mL to less than 0.15 mg/mL of 3,-sialyllactose. The method of claim 7, wherein the composition further comprises 3'-sialyllactose and 6'- in a weight ratio of 3,-sialyllactose to 6'-sialyllactose of from about 1:20 to about 20:1. Sialyl lactose. The method of claim 7, wherein the composition further comprises 3,-sialyllactose and 6' in a weight ratio of 3,-sialyllactose to 6'-sialyllactose of from about 1·2 to about 2:1. - Sialyl lactose. A method of inhibiting the growth of respiratory viruses in infants, young children or children, the method comprising administering to the infant, toddler or child a lactose-indole-neotetraose comprising a concentration of from about 1 mg/mL to about 0.2 mg/mL Compositions. 161308.doc