TW201233343A - Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof - Google Patents

Abstract

Disclosed are nutritional compositions including human milk oligosaccharides in combination with long chain polyunsaturated fatty acids and/or carotenoids that can be administered to preterm infants, term infants, toddlers, and children for reducing inflammation and the incidence of inflammatory diseases.

Description

201233343 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to human milk oligosaccharide (HMO) for regulating inflammation of infants, young children or children. More specifically, the present invention relates to human milk comprising HM〇.  Fortifying agents, preterm and term infant formulas and formulas for children that reduce inflammation and thereby prevent and/or treat inflammatory conditions and diseases. The present application claims the benefit of U.S. Provisional Application Serial No. 61/428, 861, 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, Lu's unregulated oxidative and related inflammation is the main cause of premature infants 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 increased development of the baby's respiratory, gastrointestinal and immune systems and a balance between growth and maturity, thereby protecting the infant from infection and inflammatory diseases. .  In addition to sources of antioxidants such as vitamins A, C, strontium and selenium, breast milk appears to contain endogenous antioxidants such as superoxide dismutase, glutathione peroxidase and catalase or other non-enzymatic antibodies. Oxidizing agents such as cholestyramine, lactoferrin and polyphenols. In addition, 'breast milk includes HMO, which not only acts as a pathogen receptor analog, but also by infant intestinal epithelial cells and/or related 161309. Doc 201233343 Epidemic 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 prevention or treatment methods, especially 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 would be beneficial if the nutritional composition modulates inflammation and enhances immunity against microbial infections, including bacterial and viral infections, and other inflammatory diseases. SUMMARY OF THE INVENTION The present invention relates to nutritional compositions for reducing inflammation in infants, young children, or children, including synthetic infant formulas, synthetic children's formulations, and synthetic children's formulations, including at least one HM alone or with long chains. A combination of one or more of saturated fatty acids (LCPUFA), antioxidants, and/or nucleotides, and methods of using such compositions. One embodiment is a synthetic child formula comprising human milk oligosaccharide and about 0. 025 mg/mL to about 〇. 13 〇 mg/mL long chain polyunsaturated fatty acids. Another embodiment is a synthetic child formula comprising human milk oligosaccharide and about 0. 001 pg/mL to about 1 〇 pg/mL carotenoid. Another embodiment is a method of reducing inflammation in infants, young children or children in need thereof. The method of shai comprises administering to the infant, toddler or child a human milk oligosaccharide and about 0. 025 mg/mL to about 0. 130 mg/mL long chain polyunsaturated fat 161309. Doc 201233343 Acid composition. Another embodiment is a method of reducing inflammation in infants, young children or children in need. The method comprises administering to the infant, toddler or child a human milk supplement and about 0. A composition of 001 Kg/mL to about 10 pg/mL carotenoid. It has been discovered that certain HMOs, such as 3,-sialyllactose, 6, sialyllactose, and other HMOs as described herein, as well as specific combinations of HMOs as described herein, are highly effective in suppressing infants, toddlers, and children. It is generally inflamed' and especially suppresses the virus-induced inflammation of infants, young children and children, including respiratory syncytia virus, human parainfluenza and influenza A, by reducing some of the key cytokines produced by human immune cells without increasing viral load. Causes faster recovery from infection. Surprisingly, it has been determined that Hm 〇 shows the desired repression, even at very low concentrations, including concentrations below that found in breast milk. Further, it has been unexpectedly found that 6,-sialyllactose is immunomodulatory even in the absence of virus and induces the production of cytokines derived from monocytes. It has also been found that although the biological response usually occurs within a period of 3 to 6 minutes, and therefore the in vitro procedure generally uses 3 to 6 minutes of culture, the 24-hour pretreatment of the cells provides a closer measure of breast milk. Infants receive pre-exposure to HMO every day from breast milk. In addition, fucosylated HMOs (including 3'-fucosyllactose) have been found to be highly effective in inhibiting respiratory viruses, either alone or in combination with sialic acid. Even at low concentrations, 3'-fucosyllactose and sialic acid are effective. Furthermore, it has been found that when a particular HMO is combined with a long chain polyunsaturated fatty acid and/or a carotenoid, it acts synergistically against respiratory viruses (including RSV). These synergistic actions suppress viral-induced inflammatory cell stimulating 161309. Doc 201233343 素, and especially interferon-induced protein 〇 (lP-l〇). 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, sialyllactose) and/or neutral/fucosylation (eg, 2'-fucosyllactose) and/or n-acetylglucoside (eg, LNnT). The HMO combination prevents 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 long chain polyunsaturated fatty acids and/or antioxidants, particularly carotenoids and/or nucleobens, to control and reduce inflammation. Many diseases and conditions. 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 many variations and additions depending on the circumstances. The terms "ret〇rt packaging" and "retort sterilizing" are used interchangeably herein and, unless otherwise specified, refer to the following common operations: filling a container with a nutrient solution, most commonly A metal can or other similar package is then subjected to the necessary heat sterilization step to form a sterilized, pressurized packaged nutrient solution product. As used herein, the term "aseptic packaging", as used herein, refers to the manufacture of an i-package without relying on the above-described pressurized packaging steps. σ, wherein the nutrient solution and the package are separately sterilized prior to filling, and then combined under sterile or aseptic processing conditions to form a sterilized, sterile package 161309. Doc 201233343 Contains nutrient solution products. "Unless otherwise stated, the terms "(4)" and "oil" are used interchangeably to mean a substance derived from a plant or animal or processed from a plant or animal. These terms also include a substance of interest, as long as These synthetic substances are suitable for oral administration to humans. As used herein, the term "human milk oligo-J or HMO", as used herein, generally refers to a plurality of complex carbohydrates present in human breast milk that may be in acidic or neutral form and refer to their precursors. . Illustrative: Restricted human milk oligosaccharides include 3,-sialyllactose, 6,_sialyllactose, fucosyl sugar, 2·-fucosyllactose, and lactose_N_neotetraose. Exemplary human lactose precursors include sialic acid and/or fucose. As used herein, the term "storage stable" as used herein means that the nutritional product is packaged at 18-24 t, followed by storage for at least 3 months (including from about 6 months to about 24 months and also including about 12). Keep the commodity stable after months to about a month. As used herein, the terms "nutritional formulation" or "nutritional composition" are used interchangeably and, unless otherwise specified, refer to synthetic formulations, including nutrient solutions, nutritional powders, nutritional solids, nutrient semi-solids, nutritive semi-liquids, Nutritional supplements and any other nutritious foods known in the art. The nutritional powder can be reconstituted to form a nutrient solution, each of which contains one or more of fat, protein and carbohydrates and is suitable for human oral consumption. The term "nutritional formula" or "nutritional composition" does not include human breast milk. The term "nutrient solution" as used herein, unless otherwise specified, is intended to be in the form of a ready-to-drink liquid form, a concentrated form of a nutritional product, and by 161309. Doc 201233343 The nutrient solution prepared by restoring the nutrient powder described herein before use. ::Additional Regulations 'Otherwise, as used herein, the term "nutrition powder" is a nutritional product in a flowable or self-contained form that can be reconstituted before consumption or in addition to aqueous liquids and includes spray drying. Powder mixed with dry blend/dry blend. The term "nutrient semi-solid" as used herein, unless otherwise specified, refers to a nutritional product having a property (such as rigidity) between a solid and a liquid. Some examples of semi-solids include pudding, gelatin and dough. Unless otherwise specified, 'the term "nutritional semi-liquid" as used herein refers to a nutritional product having a property (such as flow properties) between a liquid and a solid... some half (four) examples include a thiekshake and a liquid gel . The term "infant" as used herein, unless otherwise specified, refers to a person who is _month or less than seven months. As used herein, the term "premature baby" refers to a person born before the slave mother 36 weeks ago. The term "young child" as used herein, unless otherwise specified, refers to a person who is one year old to three years old. &amp; Unless otherwise stated, the term "child" as used herein refers to a person between the ages of three and twelve. Unless otherwise specified, the term "newborn" as used herein 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, semi-liquid, solid and semi-solid human milk substitutes or substitutes suitable for infant food use, unless otherwise specified. 161309. Doc 201233343 Synthetic formulations include components with semi-purified or purified sources. 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. The term "synthetic child formula" as used herein, unless otherwise specified, means a liquid, semi-liquid, solid and semi-solid human milk substitute or replacement 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. As used herein, the term "synthetic children's formula", as used herein, is a liquid, semi-liquid, solid and semi-solid human milk substitute or substitute suitable for use by children up to 12 years of age. 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 "synthetic child nutrition formula" does not include human breast milk. As used herein, the term "premature formula", as used herein, refers to liquid and solid nutritional products suitable for consumption in preterm infants. The term "human milk fortifier" as used herein, unless otherwise specified, refers to liquid and solid nutritional products suitable for mixing with breast milk or preterm formula or infant formula for consumption by premature or term infants. Unless otherwise specified, as used herein, with regard to induction, 161309. Doc 201233343 'Original; the term cytokine of monocytes "absence of Vlrus_i or "absent a virus" means that an individual (such as an infant) has no virus or has a virus that is less than The amount required to elicit an immune response; that is, 'less than the amount required for the body's natural immune response to produce cytokines and other immune factors. The term "inflammatory:" or inflammatory condition 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. The term "susceptible" and at risk, as used herein, unless otherwise specified, means that it has minimal resistance to a condition or disease, including a genetic predisposition, a family history of the condition or disease, And / or have their symptoms. The term "odulating" or "modulating (m〇dulati〇n)" or "modulating" as used herein, unless otherwise specified, refers to the intended action on the selected feature. The term "viral" or "bacterial growth" as used herein, unless otherwise specified, refers to the production, proliferation, or elimination of viruses or bacteria unless otherwise used, as used herein, all percentages, parts, and ratios. Based on the weight of the total composition. All such weights, unless otherwise specified, 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. 161309. Doc 201233343 As used herein, the range of values is intended to include a <RTI ID=0.0> </ RTI> number of each number and number within the range, whether or not specifically disclosed. In addition, such numerical ranges are to be construed as providing support for any number or number of claims within the scope. For example, the disclosure of '丨 to (7) should be considered as support.  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 clearly dictates otherwise. All combinations of methods or process steps can 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, as well as any other or optionally elements described herein or otherwise suitable for use in the application of a nutritional product. . "Product form The nutritional composition of the present invention may be formulated and administered in any form known or otherwise suitable for oral administration. Any solid, liquid, semi-solid and semi-liquid or .  Powder product forms, including combinations or variations thereof, are suitable for use herein.  The conditions are such that the form allows the safe and effective delivery of the essential ingredients as defined herein to the individual. The nutritional compositions of the present invention comprise one or more HM(R) as described herein. Such compositions T include singly- or multiple HM oximes or combinations thereof with other immunopotentiating factors, including but not limited to the lengths as discussed below. Doc 201233343 Chain polyunsaturated acids (LCPUFA), nucleotides and antioxidants 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. Such embodiments comprising the ingredients of the invention in the form of a product comprising at least one of fat, protein and carbohydrate, and preferably also containing vitamins, minerals or combinations thereof. The nutritional composition will comprise at least 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 amount and amount of nutrients to provide the sole, primary or supplementary 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 calves forms suitable for use with compositions containing HMO as disclosed herein include, for example, liquid and powdered dietary supplements suitable for use in infants and children, liquid and powdered human milk fortifiers , liquid and powder 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llow_〇n formulas). Nutrient Solution Nutrient solution includes concentrated and ready-to-eat nutrient solution. These nutrient solutions are most commonly adjusted 161309. Doc • 12- 201233343 Formulated as a suspension or emulsion, although other liquid forms are within the scope of the 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 a temperature of from about 1 ° C 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 are most often in the form of a continuous aqueous phase and An oil-in-water emulsion in the form of a discontinuous oil phase. The nutritional emulsion can be and is generally stable to storage. The nutritional emulsion typically contains up to about 95% by weight water, based on the weight of the nutritional emulsion, including from about 50% to about 95°/. It also includes from about 60% to about 90%, and also includes from about 70% to about 85% water. 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 ι·〇4 g/mL, including greater than about 1. 055 g/mL, including about ΐ·〇6 g/mL to about 1. 12 g/mL, and also includes about 1. 085 g/mL to about 1. 1 〇 g/mL. The nutritional emulsion can have a caloric density suitable for the end user's nutritional needs' 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 (82 〇 kcal / liter), and even more usually about 2 〇 kcal / fl 〇 z (675-680 kcal / liter) to 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 20-21 kcal/fl oz (675_680 to 700 kcal/litre) formula is most commonly used. Full term. In some embodiments, the emulsion may have a caloric density of from about 5 〇 1 〇〇 kcal / liter to about 660 kcal / liter ' including from about 150 kcal / liter to about 500 kcal / liter. 161309. Doc 13 201233343 In some particular embodiments, the emulsion may have a caloric density of 25 or 50 or 75 or 100 kcal/liter. The pH of the nutritional emulsion may range from about 3 · 5 to about 8, but is most preferably about 4. 5 to about 7. Within the scope of 5, including about 5. 5 to about 7. 3, including 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 1 mL, or even at least about 2 mL, or even at least about 5 mL, or even at least about 1 mL. , or even at least about 25 mL, including from about 1 mL to about 300 mL, including from about 4 mL to about 250 mL, and including from about 1 mL to about 240 mL. Nutritional Solids The nutritional solids can be in any solid form, but are typically in the form of a flowable or substantially flowable particulate composition or at least a particulate composition. Particularly suitable nutritional solid product forms include spray dried, coalesced and/or dry blended powder compositions. The compositions can be easily taken and measured with a spoon or similar device and can be easily 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, 'immediate use of j means generally within about 48 hours, most usually within about 24 hours, preferably immediately after recovery. Nutritional powder can be reconstituted with water before use until adjusted to end user nutrition The required heat density '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 〇z (675-680 kcal / liter ) to approximately 25 kcal/fl 〇z (820 kcal / liter) &gt; even more typically about 20 kcal/fl oz (675-680-^-liter) to 161309. Doc •14· 201233343 A composition of approximately 24 kcal/fl 〇z (800-810 kcal/liter). In general, the 22 24 kcal/fl 〇Z formula is more commonly used in preterm or low birth weight infants and 2〇_ 21 kcal/fl OZ (675-680 to 700 kcal/litre) formula is more commonly used in term infants. In some embodiments, the reconstituted powder may have a caloric density of from about 5 〇 -1 千 kcal / liter to about 660 kcal / liter, including from about 15 〇 kcal / liter to about 500 kcal / liter. In some particular embodiments, the emulsion may have a caloric 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 HM oxime and, in many embodiments, a combination of two or more HMOs. Oligosaccharides are one of the major components of human milk and contain an average of gram grams of neutral oligosaccharides per liter and gram of acid oligosaccharides per liter. The composition of human milk oligosaccharides is complex and more than 2 different widow-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. HMO can be isolated or enriched from milk secreted by mammals. 'These mammals include, but are not limited to, human, bovine, ovine, porcine or goat species. HMO can also be fermented by microorganisms, enzymatically, chemically synthesized or The combination is produced. HM(R) suitable for use in nutritional compositions can include acidic oligosaccharides, oligosaccharides, n-6 glucosylated oligosaccharides, and HM oxime precursors. Specific non-limiting examples of HMOs that may be included individually or in combination in the compositions of the present invention include: sialic acid (i.e., free sialic acid, sialic acid that binds to lipids, sialic acid that binds to proteins); D-glucose (Glc) ; D-galactose (Gal); N-acetylglucose 16l309. Doc 201233343 Amine (GlcNAc); L-fucose (L-FUC); D-fucose (D_Fuc); fucosyl oligosaccharide (also known as lactose-N-fuco-pentasaccharide I; lactose-N- Fucod pentasaccharide II; 2·-fucosyllactose; 3'-fucosyllactose; lactose_N_fucod pentasaccharide; lactose-N-diatomium hexasaccharide I; and lactose Tetrasaccharide); non-fucosylated, non-sialylated oligosaccharide (ie lactose-N-tetraose and lactose_N-neotetraose); sialic acid oligosaccharide (ie 3'-sialic acid-3- Fucosyllactose; disialo-monofucosyl lactose-N-six hexose; monofucosyl monosiallyl lactose-N-octasaccharide (sialic acid Lea); sialyl lactose hexasaccharide ; disialo-lactose-N-fuco-pentaose II; monofucosyl disiallyl lactose _n•tetrasaccharide; and sialic acid fucosyl oligosaccharide (ie 2'-sialyllactose; 2 - sialyl lactosamine; 3'-sialyllactose; 3'-sialyl lactosamine; 6'-sialyllactose; 6'-sialyl lactosamine; sialyllactose-N-neotetraose c; monosialic acid Lactose-N-hexaose; disialyl lactose-N-hexasaccharide I; monosialo-lactose-N-six hexose I; monosialyllactose-N-six hexose II Disialyllactose-N-new hexasaccharide; disialo-lactose-N-tetraose; disialo-lactose-N-hexasaccharide II; sialyl lactose tetrasaccharide a; disialo-lactose-N-hexasaccharide I ; and sialyllactose-N·tetraose b). A variant in which the reducing end of glucose (Glc) is replaced by N-acetylglucosamine (for example, 2·-fucosyl-N-ethylglucamine (2'-FLNac) is 2'·fucosyl Variants of lactose are also suitable. Such hms are more fully described in U.S. Patent Application Serial No. 2009/0098240, the disclosure of which is incorporated herein in its entirety. 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-galactose hexose, lactose-N-six hexose, p-lactose- N-new hexasaccharide, monofucosyl lactose _N•hexaose π, isomerized fucosylated milk 161309. Doc • 16· 201233343 Sugar-N-hexaose (1), isomerized fucosylated lactose-N-hexaose (3), isomerized fucosylated lactose-N-hexaose (2), two Fucosyl-p-lactose-N-sixaose, difucosyl-p-lactose-N-hexaose, difucosyllactose-N-hexaose, lactose-N-new octasaccharide, --Lactose-N-octasaccharide, iso-lactose-N-octasaccharide, lactose-N-octasaccharide, monofucosyl lactose-new octasaccharide, monofucosyl lactose-N-octasaccharide, Eryan Alginose lactose-N-octasaccharide I, difucosyllactose-N-octasaccharide II, difucosyl lactose-N-new octasaccharide II, difucosyllactose-N-new octasaccharide I, lactose-N-decasaccharide, trifucosyl lactose-N-new octasaccharide, tricalcium glucosyl lactose-N-octasaccharide, tri-steamed glycosyl-iso-lactose-N-octasaccharide, lactose- N-diatoms-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. 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 161309. Doc -17- 201233343 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, 3'FL and LNnT; SA, 3'SL ' 2'FL A LNnT; SA, 6'SL &gt; 3, FL and 2'FL; SA, 6'SL &gt; 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 LNnT; 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 &gt; 3,FL and 2,FL ; 3' SL &gt; 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 With LNnT; 6'SL and 3'FL; 6'SL and 2'FL; 6'SL and LNnT; 6'SL, 3'FL and LNnT; 6,SL, 3'FL, 2'FL and LNnT; 'FL, 2'FL and LNnT; 3'FL and LNnT; and 2'FL and LNnT ° HMO are present in the nutritional composition in the total amount of HMO (mg of HMO per ml of composition) in the following composition: nutrition At least about 0 in the composition. 001 mg/mL, including at least about 0. 01 mg/mL, including about 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to about 20 mg/mL, including about 161309. Doc 201233343 0·01 mg/mL to about 10 mg/mL, including about 〇. (H mg/mL to approximately 5 mg/mL, including approximately o. Ooi mg/mL to about 1 mg/mL, including about 0. 01 mg/mL to about 1 mg/mL, including about 0. 001 mg/mL to about 0. 23 mg/mL, including approximately 0. 01 mg/mL to approximately 〇·23 mg/mL total HMO. Generally, the amount of mash in the nutritional composition will depend on the particular ημ〇 present and the amount of other components in the nutritional composition. In a specific embodiment, when the nutritional product is a nutritional powder, the total concentration of lanthanum in the nutritional powder is about 0. 0005% to about 5%, including about 0. 01% to about 1% (based on the weight of the nutritional powder). In another specific embodiment, when the nutritional product is a ready-to-eat nutrient solution, the total concentration of bismuth in the ready-to-feed nutrient solution is about ο. Οοορ/. To approximately 〇〇 5〇〇/0, including approximately 0. 001% to about 0. 15°/. ‘includes approximately 0. 01% to about no%, and further includes about 0. 01% to about 0,03% (based on the weight of the ready-to-feed nutrient solution). In another specific embodiment, when the nutritional product is a concentrated nutrient solution, the total concentration of lanthanum in the concentrated nutrient solution is about 0. 0002% to about 〇·6〇%, including about 0. 002% to about 0. 30%, including about 0. 02% to about 0. 20%, 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 about 0. 001 mg/mL to about 20 mg/mL' includes 0. 01 mg/mL to about 20 mg/mL, including about 0. 001 mg/mL to less than 2 mg/mL, and includes about 〇. A neutral human milk oligosaccharide in an amount of from 1 mg/mL to less than 2 mg/mL. In some embodiments, HMO is used in combination to provide the desired immunopotentiating effect. For example, in one embodiment, the nutritional composition comprises 6, in combination with 3'SL, the total amount of HMO is about o. Ooi mg/mL to about 20 161309. Doc •19· 201233343 mg/mL’ includes approximately 0. 01 mg/mL to about 20 mg/mL, including about 0. 001 mg/mL to about 0. 23 mg/mL 'includes approximately 0. 01 mg/mL to about 0. 23 mg/mL' includes about 0. 001 mg/mL to less than 〇·ΐ5 mg/mL and includes from about 0,01 mg/mL to less than o. i 5 mg/mL nutritional composition. In another embodiment, the nutritional composition comprises 6, a combination of SL and 3, SL, the total amount of ημο is about 0. 001 mg/mL to about 20 mg/mL' includes about 0. 01 mg/mL to approximately 20 mg/mL and includes greater than 0. 65 mg/mL to approximately 20 mg/mL. In another embodiment, the 'nutritional composition comprises a weight ratio of from about 2:2 to about 2:1, including from about 1:10 to about 10:1 and including from about 1:2 to about 2:1, 3] 1 and 6, sl. In a particular embodiment, the nutritional composition comprises alone 6, SL4 6, SL in combination with other HMOs, in an amount from about 0 〇〇i mg/mL to about 20 mg/mL' including about 〇·〇ι mg/ From 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' includes 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 HMO) ) to about 96% (based on the total weight of HMO) 'includes about 88 ° /. (based on the total weight of HMO) to about 1% by weight (based on the total weight of HMO)' and includes about 100% (based on the total weight of HMO) 6, SL. In another embodiment t, the nutritional composition comprises 3, SL or 3, SL in combination with other HMOs in an amount of about o. Ooi 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. 15 mg/mL, including about 0. 01 mg/mL to less than 〇·15 mg/mL, and 161309. Doc -20· 201233343 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, including about 85% (based on the total weight of the HMO) ) to about 88 ° /. (based on the total weight of the HMO), including about 85% (based on the total weight of the HMO) to about 100% (based on the total weight of the HMO), and including about 100% (based on the total weight of the HMO) 3'SL. In a particular embodiment, the nutritional composition comprises LNnT or LNnT alone in combination with 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 0. 01 mg/mL to less than 0. 2 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 about 20 mg/mL, including about 0. 001 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 3TL and SA, the total amount of HMO being about 0. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to approximately 20 mg/mL. In one embodiment, the nutritional composition comprises about 0. 001 mg/mL to less than 1 mg/mL, including 0. 01 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 2TL 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 small 16l309. Doc -21 - 201233343 at 2 mg/mL, including approximately 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 approximately 1 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 about 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 2'FL and 3'FL, the total amount of HMO being 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. 001 mg/mL to about 20 mg/mL, including about 0. 01 mg/mL to approximately 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 includes a combination of one or more HMOs with one or more LCPUFAs to provide synergistic benefits to the end user, such as a synergistic benefit of modulating an antiviral immune response and suppressing inflammation. 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), 161309. Doc -22- 201233343 Meta-tetraenoic acid (ARA), linoleic acid, linoleic acid (alpha linoleic acid) and γ- derived from oil sources (such as vegetable oil, marine plankton, fungal oil and fish oil) Sub-linolenic acid. In a particular embodiment, the LCpuFA is derived from fish oil, such as menhaden, squid, squid, squid, squid, or herring oil, especially in combination with HMO for use in nutritional compositions. Good LCPUFAs 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 provided in the form of a free fatty acid, a triglyceride form, a diglyceride form, a monoglyceride form, a phospholipid form, an esterified form, or a mixture of one or more of the foregoing, preferably a triglyceride. The form is provided. The nutritional composition as described herein will typically comprise a total concentration of about 0. 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. LCPUFA from 001 g/L to approximately 1 g/L. In one embodiment, the nutritional composition comprises a total long bond 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 (〇-6 fatty acids and/or additionally comprising a concentration of about 40 mg/L to about 185 mg/L or about 5 mg to about 23 mg of total long chain omega-3 fatty acids per 100 kcal. In a particular embodiment, the long chain omega-6 fatty acids and long chain omega in the nutritional composition · 3 fatty acids 16l309. Doc 23· 201233343 The ratio is in the range of 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. From 025 mg/mL to about mo mg/mL or from about 3 mg to about 16 mg of DHA per 1 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 per 100 kcal. In another embodiment, the nutritional composition comprises a ratio such that 〇ηα to ARA is in the range of from about 1:4 to about 1:2. A combination of DHA and ARA. Antioxidants Additionally, the nutritional composition may comprise a combination of one or more antioxidants and Hm(R) (and optionally LCPUFA and/or nucleotides) to provide nutritional support and to reduce oxidative stress. In some embodiments, the nutritional composition comprises a combination of HMO and an antioxidant such that the composition provides synergistic benefits to the end user, such as synergistic benefits of modulating the antiviral immune response and suppressing inflammation. In some embodiments, HMO is used in combination with carotenoids (and in particular lutein, beta-cain, zeaxanthin, and/or lycopene to provide synergy) may include suitable for oral administration Any of the antioxidants for use in the nutritional compositions of the present invention, including, for example, vitamin A, vitamins, vitamins c' retinol, tocopherols, and carotenoids (including, for example, lutein, carotene, corn gluten And lycopene and combinations thereof). As described above, the antioxidant used in the nutritional composition can be used alone or in combination with HMO and LCPUFA and/or nucleoside acid. In a particular embodiment, the antioxidant used in the nutritional composition comprises a carotenoid, especially a carotenoid lutein, lycopene, zeaxanthin 161309. Doc •24- 201233343 and / or a combination of beta-carotene. 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, arbutin, zeaxanthin and beta-carotene to provide a total amount of about 〇. Carotenoids from 1 gg/mL to about 10 pg/mL. More specifically, the nutritional composition contains about 0. 001 pg/mL to about 10 pg/mL, including about o. Ooi pg/mL to about 5 pg/mL, including about 0. 001 pg/mL to about 0. 0190 pg/mL' includes approximately 0. 001 pg/mL to about 0. 0140 pg/mL, and also includes lutein in an amount from about 0 '〇44 pg/mL to about 5 pg/mL. It is also generally preferred that the nutritional composition comprises about 〇. 〇〇i pg/mL to about 10 pg/mL, including about 0. 001 pg/mL to, about 5 pg/mL, 'about 0. 001 pg/mL to about 0. 0130 gg/mL, including about o. Ooi pg/mL to about 〇〇〇75 call/mL, and also includes about 0. 0185 pg/mL to about 5 pg/mL lycopene. Generally, preferably, the nutritional composition comprises from about 1 pg/mL to about 1 〇 pg/mL, including from about gg/mL to about 5 pg/mL, about 〇. 0〇1 gg/mL to approximately 〇 〇25 gg/mL, including approximately 0. 001 pg/mL to about 0·011 wmL, and also includes about 34 tons of lanthanum to about 5 pg/mL of beta carotene. It will be appreciated that any combination of such amounts of p-carotene, lutein, zeaxanthin and scutellarin may be included in the present invention. In. Other carotenoids may optionally be included in the nutritional compositions 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. In a particular embodiment, the nutritional composition comprises - in combination with sorrel. 161309. Doc -25- 201233343 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 a variety of sources, including sources of 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-carotene or combinations thereof include Ly+coVit® saffronin (available from BASF, Mount Olive, NJ), Lyc-0-Mato® Tomato extract in oil, powder or beads (gamd from LycoRed Corp., Orange, NJ), beta-carotene, lutein or saffron (purchased from DSM Nutritional Products, Parsippany, NJ), FloraGLO ® lutein (available from Kemin Health, Des Moines, IA), Xangold® natural lutein ester (purchased from Cognis, Cincinnati, OH) and Lucarotin® beta-carotene (available from BASF, Mount Olive, N.) J). Nucleotides In addition to HMO, the nutritional composition of the present invention may additionally comprise a nucleotide and/or nucleotide precursor selected from the group consisting of nucleosides, purine bases, pyrimidine bases, ribose and deoxyribose. The nucleotide may be in the form of a monophosphate, diphosphate or triphosphate. The nucleotide can be a ribonucleotide or a deoxyribonucleotide. 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 a combination of hydrazine and nucleotides such that the composition provides synergistic benefits to the end user, such as modulating an antiviral immune response and suppressing inflammation and/or improving intestinal barrier integrity. Synergy benefits. 161309. Doc -26- 201233343 Nucleotide incorporated into the nutritional composition of the present invention can improve the integrity and/or maturity of the intestinal barrier, which is beneficial to the insufficient development of the intestinal flora and thus the slower maturation of the intestinal barrier Premature and full-term children. Nucleotides and/or nucleosides suitable for use in a nutritional composition include one or more of the following: 5'-monophosphate cytidine, 5,-monophosphate uridine, 5,-monophosphate, glucoside, 5 '-1-monophosphate guanosine and/or 5'-inosine monophosphate, more preferably 5,_monosodium cytidine, 5·. monophosphate urinary abundance, 5·_ adenosine monophosphate, 5,_ The nucleotides of guanosine monophosphate and 5'-monosenoate include 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 about 42 The total amount of nuclear acid from mg/L to about 102 mg/L and including at least about 72 mg/L of nutritional product is present in the nutritional product. In a particular embodiment, when the nutritional composition is a nutritional powder, the content of the nucleotide acid can be at least about 0. 007% ‘includes approximately 0078% to approximately 0. 1556%, and includes about 0. 056% (based on the weight of the nutritional powder), or at least about 0% per 1 gram of nutritional powder. 007 grams, including about 0. 0078 grams to about 0. 1556 grams, and includes about 0. 056 grams of nucleotides. In another specific embodiment, when the nutritional composition is a ready-to-feed nutrient solution *, the nucleotide content is at least about 0. 001%, including about 0. 001% to about.  0. 0197% ' and includes about 0. 0071% (based on the weight of the nutrient solution), or at least about 0 mg per 100 grams of ready-to-feed nutrient solution. 001 grams, including about 0. 001 grams to about 0. 0197 grams, and includes about 0. 0071 grams of nucleotides. In another specific embodiment, when the nutritional composition is a concentrated nutrient solution, the content of nucleotides is at least about 0. 0019%, including about 0. 0019°/. To about 161309. Doc •27· 201233343 0. 0382% ’ and includes about 〇. 〇 138. /. (based on the weight of the nutrient solution), or at least about 0 per 100 grams of concentrated nutrient solution. 0019 grams, including about 0. 0019 grams to about 0. 0382 grams, and includes about 〇. 〇 138 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 needs of the user vary, but such concentrations or amounts are most commonly within one of the following ranges of implementation, including any other essential fat, protein and/or carbohydrate component as described herein for liquid preterm infants And term infant formula, wherein the carbohydrate concentration is most typically in the range of from about 5% to about 40% by weight of the preterm or term infant formula, including from about 7% to about 30%, including from about 10% to about 25%; the fat concentration is most typically in the range of from about 1% to about 3〇〇/〇, including from about 2% to about 15%, and also includes about 3% to the weight of the preterm or term infant formula. About 1〇〇/0; and the protein concentration is usually about 0. by weight of the premature or term formula. It is in the range of 5% to about 30%, including about 1 〇/0 to about 15%, and also includes about 2% to about 1 〇〇/0. For liquid human milk fortifiers, the carbohydrate concentration is most typically in the range of from about 10% to about 75% by weight of the human milk fortifier, including from about 10% to about 50%, including about 20% to About 40%; the weight of human milk fortifier I61309. Doc •28·201233343, fat concentration is most usually in the range of about 10% to about 40%, including about 15% to about 37%, and also includes about 18.8% to about 30%; 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 agent. 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 following table. 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 (plus the term "about" 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 Water-Reducing Compound 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 in which the protein component can comprise about 7. 5% to about 25%; the carbohydrate component may comprise from about 35% to about 50% of the total caloric content of the infant formula; and the fat component 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 limiting. Other suitable ranges are shown in the table below (at each value 161309. Doc -29- 201233343 preceded by the term "about". 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 including from about 10% to about 12%; the fat component is present in an amount of from about 10% to about 35%, including from about 25% to about 30%, and including about 26% by weight of the preterm or term infant formula Up to about 28%; and the carbohydrate component is present in an amount of from about 30% to about 85%, including from about 45% to about 60%, including from about 50% to about 55%, by weight of the preterm or term infant formula . For powdered human milk fortifier, 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 including from about 10% to about 30%; The fat component is present in an amount of from about 1% to about 30% by weight of the human milk fortifier. , comprising from about 1% to about 25%, and including from about 1% to about 20%; and the carbohydrate component is from about 15% to about 75% by weight of the human milk fortifier, including about 15% to About 60%, including about 20% to about 50%. 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. The other suitable conditions for the macronutrient concentration are described below. Doc -30- 201233343 Example. In this case, total or indifference refers to the source of fat, carbohydrates and protein in the powdered product. For powdered nutritional compositions, the total amount or concentration is the most common and preferably the following table describes the formulation (adding the term "about" before each value to the total calories of the total calories EXAMPLE J Example K --- Example 1L Carbohydrate 1-85 ~ 30-60 —— — 35-55 Fat 5-70 — One — 20-60 25-50 Protein 2-75 5-50 7-40 Fat In addition to the LCPUFA described above, the nutritional compositions of the present invention may comprise other sources of fat. Other sources of fat suitable for use herein include any fat suitable for use in oral nutritional products and compatible with the essential elements and characteristics of such products. Or fat. For example, in a 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 nutritional products described herein include coconut oil, branches Coconut oil, soybean oil, corn oil, thief/yellow, red 彳 b oil 'shang oleic safflower oil, oleic acid (emers〇l 6313 oil 酉, Cognis Oleochemicals, Malaysia) ' MCT oil (medium chain triglyceride) Ester), sunflower oil, high oleic sunflower seeds Oil, palm and palm kernel oil, palm olein, rapeseed oil, marine oil, fish oil, fungal oil, seaweed oil, cottonseed oil, and combinations thereof. Protein The nutritional combination of the present invention The substance may further contain protein as appropriate. Suitable for 161309. Doc •31· 201233343 Used in oral nutritional compositions and in combination with the basic elements and characteristics of the products of Hexing·Hao#. The source of 彳 protein is suitable for use in nutritional compositions. : a non-limiting, non-limiting, partially hydrolyzed or non-hydrolyzed protein f or protein source for a protein or source thereof in a nutritional product, which may be derived from any known or otherwise suitable source of rice, such as milk (eg casein, Whey), animals (eg meat, fish), cereals (eg rice, corn), plants (eg soybean) or combinations thereof. Non-limiting examples of such Kesi proteins include milk protein isolates as described herein - milk protein concentrates, albumin isolates, highly hydrolyzed road proteins, whey proteins, glutinin or bristle protein feed, whole cattle Etiquette, partial or complete skim milk, A soy protein isolate, soy protein concentrate, and the like. In a particular embodiment, the nutritional composition comprises a protein source derived from human and/or bovine derived milk proteins. Carbohydrates The nutritional products of the present invention may include, in a stepwise manner, any carbohydrate compound suitable for use in oral nutritional products and compatible with the essential elements and characteristics of such products. Non-limiting examples of carbohydrates or sources thereof suitable for use in the nutritional products described herein can include malt-, hydrolyzed or modified temple flour or corn starch, glucose polymer, corn sugar poly, corn sugar-destroyed solids, From carbohydrates in rice, carbohydrates from cowpea, carbohydrates from Mafeng, cassava, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohol (eg maltitol, red algae) Sugar alcohol, sorbitol), artificial sweeteners (such as sucralose, potassium sulfamate, stevia) and combinations thereof. Especially the required carbohydrate is low dextrose equivalent 161309. Doc •32· 201233343 (DE) Maltodextrin Other ingredients present as the case may further comprise other optional components which may alter the physical, chemical, aesthetic or processing characteristics of the product or Acts as a drug or other nutrient component when used in a target population. 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 preservatives, emulsifiers, buffers, fructooligosaccharides, galactooligosaccharides, polydextrose ((10) plus·e), and other beneficial bacteria plus calories... , probiotics, pharmaceutically active agents, anti-inflammatory agents, other nutrients, colorants, flavoring agents, thickening agents and stabilizers, emulsifiers, lubricants, etc. 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, isomaltose and lactitol, and also Good includes at least an artificial or door-effect sweetener such as B-hydrochloric acid, aspartame, susceptin, saccharin, stevia and tagatose. Such sweeteners, especially combinations of sugar alcohol tray artificial sweeteners, are particularly suitable for formulating liquid beverage embodiments of the invention having the desired advantageous profile. Such sweetener combinations are particularly effective in masking sometimes with liquid beverages. Add the inappropriate taste associated with the plant jelly protein. In the nutritional products, the concentration of sugar alcohol in the product can be 0. Within the range of 01%, including 0 10/ sΊ. l/o to about 10%, and also includes about 1% to about 161309. Doc -33- 201233343 6%. The artificial sweetener concentration, as the case may be, may be about 0. Within the range of 01%, including approximately 5% to approximately 5%, including approximately 0. 1% to about 1. 0%. 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 a nutritional powder or product form is suitable for use herein, non-limiting examples of which include tricalcium phosphate, citrate, and combinations thereof. The concentration of the flow or anti-caking agent in the nutritional composition will vary depending on the product form 'other selected ingredients, desired flow characteristics, etc., but is usually from about 1% to about 4% by weight of the nutritional composition. Within the scope, including about 0. 5% to about 2 〇 / 〇. Stabilizers can also be included in the nutritional composition. Any stabilizer known or otherwise suitable for use in a nutritional composition is also suitable for use herein, some non-limiting examples of which include gums such as triterpene. The stabilizer may comprise from about 5% by weight of the nutritional composition (M% to about 5. 0%, including about 5% to about 3%, including about 0. 7% to about 1. 5〇/〇. The nutritional composition may further comprise any of a variety of other dimensions, non-limiting examples of which include vitamin A, vitamin I vitamin E, vitamin k, thiamine, riboflavin &quot; ratio. Polyol, vitamin Bu, carotenoids (such as carotenoids, zeaxanthin, chlorophyll _ sucrose), money, folic acid, pantothenic acid, biotin, vitamin K, test, inositol, its salts and derivatives And their combinations.

The nutritional composition may further comprise a phase of various other additional minerals, non-limiting examples of which include H, iron, and H 161309.doc • 34· 201233343 sodium, potassium, molybdenum, chromium, vapors, and combinations thereof. Method of Manufacture The nutritional compositions 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 any of the product forms, such as nutrient solutions or nutritional powders, 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.) To form. Ch〇_min The slurry is formed by adding the following to water under heating and stirring: minerals (such as potassium citrate, dipotassium hydrogen phosphate, 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 heating and stirring for 10 minutes, followed by the addition of other minerals (such as potassium chloride, magnesium carbonate, potassium iodide, etc.) and/or carbohydrates (eg HM0, fructooligosaccharides, sucrose, corn) Syrup, etc.). The PIW slurry is then formed by mixing with the rest of the protein, if present, under heat and agitation. The resulting slurry is then blended together under heat and agitation and the pH is adjusted to 6.6-7.0, followed by high temperature short-time (HTST) treatment of the composition, where 161309.doc -35 - 201233343 :::: combination The material is heat treated, emulsified and homogenized, and then allowed to cool. Add cold vitamins and ascorbic acid, adjust the pH to the desired level, if necessary, and add water to achieve the desired total solids content. The composition is then aseptically packaged to form a sterile packaged nutritional emulsion. The emulsion may then be diluted, heat treated and packaged to form a ready-to-eat or concentrated liquid, or it may 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 a collection of any known or otherwise effective techniques for preparing and formulating nutritional powders. By way of example, D, 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 field of nutrition' all of which are suitable for use in the manufacture of spray dried nutritional powders 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 preparing 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.), U.S. Patent No. 63,69,8 (Carls. Patent Application No. 200301187 〇 3 A1 (Nguyen et al.), 161309.doc • 36·201233343 The descriptions are hereby incorporated by reference herein in its entirety in its entirety herein. Methods of Use The nutritional compositions as described herein can be used to address 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 infants, infants, toddlers, and children. Premature infants, infants, young children or children using the nutritional compositions described herein may actually have or suffer from the disease or condition, or may be predisposed to or at risk of developing a disease or condition ( That is, there may not be a disease or a condition in reality, but it is at a high risk of illness due to certain conditions, family history, etc. compared with the general population.) Whether premature, infant, toddler or child actually Premature infants, infants, young children or children are classified as "needs" in this article to help them cope with and fight diseases or conditions. They are at risk of disease or condition, or at risk of disease or condition. . For example, premature infants, infants, young children, or children may actually have respiratory tract inflammation or may be at risk of developing respiratory tract infection (susceptible to respiratory tract inflammation) due to, for example, family history or other medical conditions. Help preterm infants with the nutritional composition described herein, whether the premature infant, infant, toddler or child actually has the disease or condition, or is only in the wind, disease or condition of the wind or is susceptible to the disease or condition Infants, toddlers or children are within the scope of the invention. Based on the above 'because some method embodiments of the present invention are related to a subset or subclass of a particular fine solid (ie, "need" to help a subset or individual of individuals for the particular disease or particular condition described herein. Class), so not all premature babies, infants, young children, and children are a subset or subclass of infants, toddlers, and children as described in this article for 161309.doc •37· 201233343 in certain preterm infants as described in certain diseases or conditions. Inside. A nutritional composition as described herein comprises a combination of HMO alone or HMO with one or more other components to provide inflammation for reducing intestinal inflammation and nasopharyngeal inflammation, such as respiratory tract inflammation (eg, respiratory fusion virus-induced inflammation). Source of nutrition. The HMO-containing nutritional composition of the present invention can also provide optimal development and growth and maturation balance of the infant's gastrointestinal and immune systems, 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 the intestinal epithelial cells of the infant. In a particular embodiment, administration of a nutritional composition comprising HMO and nucleotides of the invention further activates the immunological activity of neonatal intestinal epithelial cells or activates immunological activity by its intestinal epithelial cells. In addition, the use of HMO in nutritional compositions can reduce the growth of respiratory viruses (such as RSV, type 2 human parainfluenza virus and influenza A virus), thus reducing viral-induced upper respiratory tract infections. Therefore, by nutritional products (such as infant formula) Using a combination of HMO or HMO alone with other immune enhancing factors, it is now possible to provide infants with alternatives or supplements that more closely mimic the benefits of breast milk. The use of the nutritional composition of the present invention together with the improvement of the growth and maturation of the infant's immune system as described above 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. 161309.doc • 38 · 201233343 The addition of ημο further increases the amount of glandular peptide in the body and blood of infants and, in certain embodiments, preterm infants. When used in combination with LCPUFA and/or antioxidants, especially with carotenoids, hydrazine reduces oxidative stress, which is the production of oxidized biomolecules (such as lipid persulfides and their breakdown products), protein carbonyls, and oxidized damaged DNA. And accumulate increased metabolic conditions. 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 comprising 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 particular 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 _ i ra and combinations thereof. Another benefit of using HMO in nutritional compositions is that HM(R) has been found to regulate the production of IP-10, a chemokine that plays an important role in the inflammatory response to viral infections. Specifically, there is a positive correlation between the severity of clinical Rsv infection in children and serum IP-10 levels. Therefore, reducing Ip_1〇 4a can reduce the severity of RSV infection. In a particular embodiment, IP-10 production is reduced to levels seen in the uninfected control group. Along with the IP-10 reduction, HM0 has been found to reduce platelet preference white 16I309.doc -39- 201233343 blood cell complex (PNC) formation 'its presence in human blood and up to 25% unstimulated neutrophil Composition of white blood cells. Since pnc exists in the form of aggregates, it has a large ability to initiate an inflammatory process and can increase the production of active oxides. Therefore, a decrease in PNC formation 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 stated. Exemplary compositions are storage stable nutritional compositions prepared according to the manufacturing methods 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 following table. Unless otherwise specified, all ingredient quantities are listed in kilograms per 1000 kg batch of 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 161309.doc -40· 201233343 31 sialyllactose (3'SL) 0.0948 0.090 0.085 9.479 9.005 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 Soybean egg fat 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 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 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 carbide 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 gasification test 53.9 g 53.9 g 53.9 g 53.9 g 53.9 g Vitamin A, D3, E, Κι premix 47.4 g 47.4 g 47.4 g 47.4 g 47.4 g Citric acid 29.77 g 29.77 g 29.77 g 29.77 g 29.77 g mixed type caraway «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 = 161309 .doc .41 . 201233343 Examples 6-10 Examples 6-10 illustrate ready-to-feed nutritional emulsions of the present invention, 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 6 Example 7 Example 8 Example 9 Example 10 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 Ovum oil 10.1 10.1 10.1 10.1 10.1 6'Sialyl lactose (6'SL) 0.0948 0.0901 0.0853 9.479 9.0047 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 Citric acid Potassium 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 sulfide 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 Gasification choline 53.9 g 53.9 g 53.9 g 53.9 g 53.9 g 161309.doc -42- 201233343 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 carotenoid premix 26.40 g 26.40 g 26.40 g 26.40 g 26.40 g gasification nano AN, AN AN AN AN L-carnitine 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=Example 11- 15 Examples 11-15 illustrate concentrated liquid emulsions of the present invention, 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 11 Example 12 Example 13 Example 14 Example 1S 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 Coconut oil 19.24 19.24 19.24 19.24 19.24 31 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 161309.doc • 43- 201233343 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 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 chloride 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 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 chloride 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, K! 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 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 g 6.40 g 6.40 g 6.40 g 6.40 g tricalcium phosphate AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN AN The ingredients are listed in the table below. 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 Hazelnut oil 10.1 10.1 10.1 10.1 10.1 HMO mixture 0.0948 0.0901 0.0853 9.479 9.0047 6'SL 0.0316 0.0300 0.0284 3.159 3.002 2'FL 0.0316 0.0300 0.0284 3.159 3.002 LNnT 0.0316 0.0300 0.0284 3.159 3.002 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/vapor 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 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 55.0 g 55.0 g 55.0 g 55.0 g 55.0 g 161309.doc -45- 201233343

Ferrous sulfate 58.0 g 58.0 g 58.0 g 58.0 g 58.0 g gasification test 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 Lemon 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 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 dihydrogenate 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 = as needed Examples 21-25 Examples 21-25 illustrate concentrated liquid emulsions of the 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. 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 Hazelnut oil 19.24 19.24 19.24 19.24 19.24 HMO mixture 18.957 18.009 17.061 19.905 20.853 6,SL 6.319 6.003 5.687 6.635 6.951 2'FL 6.319 6.003 5.687 6.635 6.951 LNnT 6.319 6.003 5.687 6.635 6.951 161309.doc -46- 201233343 Sugar (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 Soybean egg squama 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/vapor former premix 568.9 g 568.9 g 568.9 g 568.9 g 568.9 g chlorination 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, Κι pre Mixture 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 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 g 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 Potassium hydroxide AN AN AN AN AN AN= 161309. Doc-47·201233343 Examples 26-30 Examples 26-30 illustrate human milk fortifier liquids 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 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 6'SL 6.319 6.003 5.687 6.635 6.951 2'FL 6.319 6.003 5.687 6.635 6.951 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 hydride 2.8 2.8 2.8 2.8 2.8 Sodium citrate 1.4 1.4 1.4 1.4 1.4 Sodium nitride 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 Nicotinamide 400 g 400 g 400 g 400 g 400 g ARA oil 313 g 313 g 313 g 313 g 313 g tocopheryl acetate 310 g 310 g 310 g 310 g 310 g zinc sulfate 300 g 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 g 133 g 133 g 161309.doc -48- 201233343 DHA oil 116g 116g 116g 116g 116g palmitic acid vitamin A 100 g 100 g 100 g 100 g 100 g copper sulfate 51.0 g 51.0 g 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 g 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 chlorophyll 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 citrate 43.0 mg 43.0 mg 43.0 mg 43.0 mg 43.0 mg Examples 31-35 Examples 31-35 illustrate spray-dried nutritional powders of the present invention, the ingredients of which are listed in the following table. Unless otherwise specified, all ingredient quantities are listed in kilograms per 1000 kg of bulk product. 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 Norse 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 161309.doc -49 - 201233343 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 Potassium chloride 1.295 1.295 1.295 1.295 1.295 Ascorbic acid 1.275 1.275 1.275 1.275 1.275 Vitamin and 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 nano 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 gas choline 432.1 g 432.1 g 432.1 g 432.1 g 432.1 g vitamin A, D3, hydrazine, hydrazine] premix 377.2 g 377.2 g 377.2 g 377.2 g 377.2 g ascorbyl palmitate 361.3 g 361.3 g 361.3 g 361.3 g 361.3 g mixed type 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 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 tract fusion virus (RSV); 161309.doc -50- 201233343 (2) Human parainfluenza virus (HPIV3); or (3) one of the H1N1 influenza viruses is co-cultured with one of the following HMOs to prepare a sample: (1) 3'-sialyllactose (3'SL); (2) 6--saliva Lactose (6'SL); (3) 3·-fucosyllactose (3TL); (4) 2·-fucosyllactose (2'FL); (5) Lactose-N-neotetraose (LNnT); or (6) The addition of sialic acid (SA) 〇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 3'SL &gt;10 &gt;10 〜5 6'SL &gt;10 &gt; 10~10 3'FL~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 ( The 3'FL with IC50 of about 2-5 mg/ML) has antiviral activity against all three respiratory viruses. This result was unexpected because previously published reports showed that only the sialylated polymeric 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. 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 161309.doc -51 - 201233343. To form a viral material, the H1N1 influenza virus was gambling from ATCC (VR 1469) and amplified in Madin Darby Canine Kidney 'MDCK epithelial cells (ATCC ccl_34). The cell free supernatant was cold washed 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 formation unit (FFU) analysis was performed using a commercially available mouse monoclonal antibody against a viral nucleoprotein coupled to a biotinylated anti-mouse IgG primary antibody. To observe the virally infected cell lesions, (d) Streptavidin HRp (ABC, from Vector Laboratories, Inc.) was developed. Although the total number of viral lesions is directly proportional to the infective virus influx, 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's indifference and by applying the covering medium of the gum (4) coffee medium. To further improve the ffu analysis. The use of tragacanth can improve the analysis by reducing the number of individual infected cells, while still allowing the formation of (4) disease I lesions of different sizes, which are still large, but still easy to use by using the tree during calculation Techniques are quantified and proportional to viral concentration or potency. After the test, the assay was applied to various HM〇 to analyze the ability to block the infectivity of the mNi virus. Specifically, concentrations of 0.01 mg/mL, 0.1 mg/mL, ΐ·〇mg/mL, and 1〇mg/mI^HM〇 were added to the inoculated virus suspension' for 1 hour at 37CT, followed by addition to MDCK. Single layer fine 161309.doc •52- 201233343 in the cell. This mixture was allowed to bind to the cell layer for thirty minutes at 37 C. The cell layer is then washed&apos; and the cells are incubated for an additional 18-24 hours, then fixed and subjected to immunocytochemical staining. The results are shown in the figure. As shown in Figure 1, when the concentration used was 1 〇 mg/mL, 3, FL, 3ISL and SA each inhibited viral infectivity by more than 9%. 2, fl and 6, SL inhibits the infectivity by about 6〇〇/0 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) at 92% gestation. The pigs received total parenteral nutrition (TpN) for 48 hours. After 48 hours 'stop TPN and randomize piglets into three groups: Formulation group (η 7) 'Fake food Enfamil® Lacto-Free, constructed from Mead Johnson, Evansville, IN; treatment group (n=9) 'Meal Enfamil ® Lacto-Free 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. The piglets were fed their respective feeds at a rate of i2 〇 mL per kg of body weight for the next 48 hours. Then, after 48 hours of enteral nutrition (EN), or if the pig develops the symptoms of necrotic enteritis, the piglet is euthanized earlier. The ▲• liquid is collected through the umbilical artery catheter, and the it slurry is separated from the gold liquid. Store at -7 (TC until analysis). Use just before the feeding time (time 〇) and 6 hours, 12 hours, 24 hours, 36 hours and 48 hours after feeding, using commercially available assays (NWLSS glutathione analysis #NWK -GSH01,Northwest Life Science Specialties, 161309.doc -53· 201233343

Vancouver, WA) measures the concentration of glutathione (GSH) in the plasma taken from piglets. The results are shown in Figure 2. As shown in Figure 2, the concentration of gSH in the plasma from the control group decreased from time 至 to 6 hours after feeding. GSH was still low 24 hours after EN in the control group. 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 is illustrated. Specifically, 3, SL or 6, SL, at a concentration of 0.1 mg/mL, 〇 2 mg/mL or 〇 5 mg/mL, was added to fresh peripheral blood mononuclear cells at 37 C, 5 °/. Incubate under C 〇 2 to pre-treat the cells for about 24 hours. LNnT at a concentration of 〇·1 mg/mL, 0.2 mg/mL or 1 mg/mL· was added to fresh peripheral blood mononuclear cells at 37. (:, 5% C 〇 2 incubation 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. At 5% C〇2, some variables were incubated with rSV with an infection magnification (MOI) of 0.1 hr. The uninfected control variables were incubated with the medium for about 丨 hours. After about 丨 hours, Add fresh medium alone or fresh medium containing appropriate concentrations of 3, sl, 6, sl, LNnT, lactose or endotoxin to appropriate tubes and incubate the cells for 48 hours at 37 C, 5% C 〇 2. The supernatant was collected for the hour. At 24 and 48 hours, the cytokine in the supernatant was assayed for each variable. 161309.doc •54·201233343 was used to assess the effect of HMO on the early immune response against RSV. Use from Bio-Rad The custom Bio-Plex human cytokine kit measures cytokines. The results of interferon-inducible protein 10 (ΙΡ·10' also known as CXCL 10) are shown in Figures 3 and 4 (for 3, SL and 6, SL) ) and Figures 5 and 6 (for LNnT) ΙΡ_10 is a CXC chemokine that attracts, binds to, and activates CXCR3 receptors on natural killer cells and memory T cells. IP-10 is expressed by mono- and other cells and is induced by interferon. RSV clinical disease in children Severity (eg, by the following measurements: length of hospitalization, duration of fever, and number of days needed to supplement 〇2) is positively correlated with serum IP-10. Therefore, reducing IP_10 signaling can reduce the severity of RSV disease experienced. The results of 3'8!^ and 6'81^卩-10 are detailed in Figures 3 and 4 and show some variability in the donor response, but surprisingly the '6'SL significantly down-regulates two donors. 1 to 10 in the viral infection variable. It should be noted that 6,81^ can reduce 1卩-1〇 to the level seen in the uninfected control group. 3'SL is ineffective in donor B, but in the donor The IP-10 induced by RSV was down-regulated in E. These data showed that 3, SL and 6'SL all inhibited RSV-induced IP-10, but 6, SL was more effective to down-regulate ip_10. The results also showed that it was lower than 0.1 mg/mL. 6, SL content and content greater than 0.5 mg / mL can effectively reduce the IP - 1 〇 of some individuals. LNnT IP-1 〇 knot Details are shown in Figures 5 and 6 and show some variability in the donor response, but surprisingly, LNnT significantly down-regulates IP-10 in the viral infection variables of both donors. It should be noted that LNnT enables ip_ 1〇 decreased to the level seen in the uninfected control group. The results also indicate that the content between 〇.2 mg LNnT/mL and 1 mg LNnT/mL and greater than 1 mg/mL can effectively reduce some individuals ΙΡ_1〇 . The matched endotoxin concentration is clearly indicated by the inclusion of 161309.doc -55- 201233343. The reduction in ip_ 1 并不 is not due to the extremely low levels of endotoxin in LNnT. In Figures 7 and 8, the cytokine results also surprisingly show that 6, a few increases the level of interleukin 1 (IL 10) 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. Surprisingly, 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, produced by CD4+ T cells after antigen specificity and activation of multiple strains, and produced by monocytes after activation of cells by bacterial lipopolysaccharide. The inclusion of the matched endotoxin unit concentration control clearly concluded that the increase in ιρ·ιο was not attributable to the presence of very low levels of endotoxin in 6, red or [&gt;111. The surprisingly s&lt;s&gt;'s found that pretreatment with 6' SL, 3' SL or LNnT for 24 hours effectively reduced inflammation caused by RSV. In addition, reducing the measured by *Ip_1〇 showed that 6 S L and LNnT were more effective in suppressing viral-induced inflammation than 31SL. In addition, 'Show 6'SL is immunomodulatory in the absence of virus, because the inclusion of 6'SL can induce and/or ameliorate cytokines derived from monocytes (such as IL-10, ΜΙΡ_1β, interferon-γ, IL). -8, IL-la, IL-Ιβ and IL-lra) production. Surprisingly, 3'sL is also immunomodulatory in the presence or absence of virus 'because 3, SL inclusions can induce and/or improve cytokines derived from monocytes (such as MIP-Ιβ, interferon) 1. The production of Jiang _8 and IL-lra). Surprisingly, LNnT is also immunomodulatory in the presence or absence of virus, as the inclusion of LNnT induces and/or ameliorates cytokines derived from monocytes (such as IL-10, ΜΙΡ·ΐβ, interferon). Production of -γ, IL-8, IL-la, IL-Ιβ and IL-1ra). 161309.doc • 56· 201233343 Example 40 In this example, 'Note 2, the combination of FL and lycopene reduces the ability of virus replication in vitro. Specifically, on Day-Day, the (:^1113 monolayer was inoculated in a 24-well dish to the third day with a number sufficient to reach 951〇〇% confluence. On the third day, a separate concentration of 0.5 pg/mL was added. 2'FL of 1 pg/mL or 5 gg/mL or lycopene at a concentration of 〇·5 pg/mL, 1 gg/mL or 5 pg/mL or a concentration of 〇5 Mg/mL, 1 eg /mL or a combination of 5 pg/mL of tetrahydrofuran (THF) and incubated at 37 ° C, 5% C 〇 2 for about 24 hours. THF is the solvent used to dissolve lycopene' and is therefore included to distinguish Solvent-treated control group. On day 1 'The cell supernatant was removed and the monolayer was added to the medium or medium alone at 37 eC, 5% C〇2 plus a respiratory fusion virus with a multiplicity of infection (MOI) of 1. RSV) - incubated for about 1 hour. After about 1 hour, add fresh medium alone or medium containing the appropriate concentration of 2'FL and lycopene or 2'FL and THF to the appropriate wells' and at 37 ° C, Cells were incubated for 48 hours at 5% c〇2. On day 3, supernatants and cell lysates were collected separately, aliquoted and stored frozen at -7 (TC for later analysis.) by TaqMan qRTPCR Cell lysates were analyzed to assess viral replication by measuring the number of RSV NS1 replicas. As shown in Figure 11, 'in some combinations xanthene and 10 is called 2, FL+0 5 is called erythromycin; and 0.1 and 1 Kg 2, FL+1 gg lycopene) The combination of 2'FL and lycopene showed a synergistic effect, which resulted in significant inhibition of viral load as measured by the RSV ns 1 copy. In addition, as shown in Figure 1 It can be seen that the 2'FL alone shows a moderate concentration-dependent decrease of RSV NS1. 161309.doc -57· 201233343 Surprisingly, 'at the selected concentration 2, the combination of FL and lycopene can substantially inhibit RSV in vitro. Replication Example 41 In this example, the ability of 2'FL in combination with lycopene to reduce ιρ_ 1 〇 (a marker of viral inflammation) in vitro is demonstrated. Specifically, s, the concentration is 0.1 mg/mL, 0.2 mg/ 2'FL in mL or 1 mg/mL with lycopene at a concentration of 0.5 pg/mL, 1.0 pg/mL or 5.0 pg/mL or a concentration of 0.5 pg/mL, 1·〇pg/mL or 5.0 pg/mL The combination of THF is added to fresh human peripheral blood mononuclear cells (pBMC) and incubated at 37 C, 5 ° C. About 24 hours. THF is the solvent used to dissolve the ruthenin, and is therefore included in the control group to distinguish the solvent. After about 24 hours, then some variables will be given at 37, 5% C 〇 2 Incubation was carried out for about 1 hour with an rsv with an infection magnification (MOI) of 1. Uninfected control variables were incubated with the medium for about 1 hour at 3 7 C, 5 ° / 〇 C 〇 2 . After about 1 hour, fresh medium alone or medium containing appropriate concentrations of 2 FL and argonin or 2'FL and THF was added to the appropriate variables, and pBMC 48 was incubated at 37 ° C, 5% C 〇 2 hour. The supernatant was collected 48 hours after infection. At 48 hours, the Luminex human cytokine kit was used to measure the cytokines in the supernatant for each variable to assess the effect on the early immune response to RSV. Interferon-inducible protein 1〇 (ΙΡ-1〇, also known as CXCL10) is a CXC chemokine that attracts, binds to, and activates cxcR3 receptors 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 amount 161309.doc •58-201233343: length of hospitalization, fever, and days of need to supplement 〇2) is positively correlated with serum IP-10. Thus, a decrease in Ip_i0 may indicate a decrease in the severity of the RSV disease experienced. Surprisingly, as shown in Figure 12, the combination of 2'FL and lycopene resulted in a stepwise concentration-dependent down-regulation of IP-10. Although the effect of using 2'FL at lower lycopene concentrations is evident, it is tested for 2'FL· and 5.0 pg/mL· at concentrations of 〇^ mg/mL, 0.2 mg/mL or 1 mg/mL. The combination of the highest sucrose concentration shows the strongest decrease in IP_1(). Thus, it can be inferred that the combination of 2&apos;FL and lycopene can reduce the severity of the rSV disease experienced&apos; especially at a lycopene concentration of 5.0 pg/mL. Example 42 In this example, the combination of 2'FL, 3'FL and paclitaxel was demonstrated to reduce the ability of 1 P-10 (a marker of viral inflammation) in vitro. Specifically, 'will be alone or in combination 2, FL (concentration of 〇.1 mg/mL), 3'SL (concentration of 0.1 mg/mL), and lycopene (concentration of 〇5 ton / 〇 ^, j 〇 Pg/mL or 5 pg/mL) or tetrahydrofuran (THF) (concentration 〇.5 pg/m) L, i 〇pg/mL or 5 gg/mL) (as shown in Figure 13) was added to Fresh human peripheral blood mononuclear cells (PBMC) and at 37. (:, 5% C 〇 2 incubation to pre-treat cells for about 24 hours. THF is the solvent used to dissolve swain, and therefore includes the THF concentration control to distinguish the solvent. After about 24 hours, then at 37 C, 5 ° /. C02, some variables and infection magnification (Μοι) was iiRsv for about 1 hour. The uninfected control variables were incubated with the medium for about 1 hour at 37eC, 5% C〇2. After 1 hour, fresh medium alone or with appropriate concentrations: 2, FL, 3, SL and lycopene; 2, FL; 16I309.doc • 59· 201233343 3'SL; 2'FL and 3'SL; Or THF medium was added to the appropriate variables, and PBMCs were incubated for 48 hours at 37 ° C, 5% C 〇 2. The supernatant was collected 48 hours after infection at 48 hours using the Luminex Human Cytokines kit for The cytokines in the supernatant were assayed to assess the effect of HMO on the early immune response to RSV. Interferon-inducible protein 10 (IP-10, also known as CXCL10) attracts, binds to and activates natural killer cells and CXC chemokine of CXCR3 receptor on memory T cells. ip·1 〇 by single core Cells and many other cells behave and are 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) is positive between serum IP-10 Therefore, a decrease in ΐρ· 1 可 can indicate a decrease in the severity of the RSV disease experienced. Surprisingly, 2, the combination of FL, 3, SL and lycopene leads to an increase with the dose of lycopene. IP_1() is down-regulated (see Figure 13). Using the highest lycopene concentration tested (5.〇pg/mL), a synergistic reduction in IP-10 is seen for 2'FL, 3'SL and lycopene ( 86〇/0 is reduced. Therefore, it can be inferred that the combination of 2'FL, 3'SL and lycopene can have a synergistic effect in reducing the severity of the rsv disease experienced by 1. [Simplified illustration] Figure 1 A graph depicting the H1N1 viral infectivity of MDCK cells in the presence of various HMOs as tested in Example 37. Figure 2 is a graph depicting the blood letrin content of glutathione from piglets as measured in Example 38. Figure 3 is a graph depicting the administration of 3, SL and 6 as measured in Example 39. Figure 7 is a graph showing the IP-10 content of 161309.doc -60-201233343 produced by SL. Figure 4 is a graph depicting the IP-10 content produced by the administration of 3'SL and 6'SL as measured in Example 39. Figure 5 is a graph depicting the IP-10 content produced by administration of LNnT as measured in Example 39. Figure 6 is a graph depicting IP-1 produced by administration of LNnT as measured in Example 39. The map of the 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 IL-10 content produced by administration of LNnT as measured in Example 39. Figure 10 is a graph depicting the IL-10 content produced by administration of LNnT as measured in Example 39. Figure 11 is a graph depicting the amount of RSV NS1 replica produced by administration of 2'FL and/or lycopene as measured in Example 40. Figure 12 is a graph depicting the IP-10 content produced by administration of 2'FL and lycopene as measured in Example 41. Figure 13 is a graph depicting the percent reduction of ιρ_10 produced by 2'FL, 3'SL, and lycopene, either individually or in combination, as measured in Example 42. 161309.doc

Claims (1)

201233343 VII. Patent Application Range: 1. A synthetic children's formula comprising human milk oligosaccharide and a long chain polyunsaturated fatty acid of from about 0.025 mg/mL to about 0.130 mg/mL. 2. The synthetic child formula of claim 1, wherein the human milk oligosaccharide is selected from the group consisting of: 6'-sialyllactose, 2'-fucosyllactose, and combinations thereof, and the long chain The polyunsaturated fatty acid is selected from the group consisting of linoleic acid, linoleic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, docosapentaenoic acid, and combinations thereof. 3. The synthetic children formula of claim 2, wherein the long chain polyunsaturated fatty acid is docosahexaenoic acid. 4. The synthetic child formula of claim 2, wherein the human milk oligosaccharide is 6,-sialyllactose. 5_ The synthetic child formula of claim 4, wherein the 6,-sialyllactose is present at a concentration of from about 0.001 mg/mL to about 20 mg/mL. 6. The synthetic child formula of claim 5, wherein the 6,-sialyllactose is present at a concentration of from about 0.001 mg/mL to less than 0.25 mg/mL. 7. The synthetic child formula of claim 5, wherein the 6,-sialyllactose is present at a concentration greater than 0.4 mg/mL to 20 mg/mL. 8. A synthetic child formula comprising human milk oligosaccharide and from about 0.001 pg/mL to about 10 pg/mL carotenoid. 9. The synthetic children formula of claim 8 wherein the carotenoid is present at a concentration of from about 0.001 gg/mL to about 5 gg/mL. 10. The synthetic children formula of claim 8, wherein the human milk oligosaccharide is selected from the group consisting of 6'-sialyllactose, 2·-fucosyllactose, and combinations thereof, and 161309.doc 201233343 The glucosinolate is selected from the group consisting of lutein, erythropoietin, beta-carotene, and combinations thereof. 11. A method of reducing inflammation in an infant, a child or a child, the method comprising administering to the infant, child or toddler a human milk oligosaccharide comprising from about 25 mg/mL to about 0.130 mg/mL long chain polyunsaturated fatty acid Composition. 12. The method of claim 11, wherein the human milk oligosaccharide is selected from the group consisting of 6, sialyllactose, 2_fucosyllactose, and combinations thereof, and the long chain polyunsaturated fatty acid system A group consisting of linoleic acid, linoleic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, docosapentaenoic acid, and combinations thereof is selected. 13. The method of claim 11, wherein the long chain polyunsaturated fatty acid is docosahexaenoic acid. 14. The method of claim 11, wherein the human milk oligosaccharide is 6'-sialyllactose. 15. The method of claim 14, wherein the 6, sialic lactose is present at a concentration of about 〇 (n mg/mL to about 20 mg/mL. I61309.doc