HK1161840B - Nutritional composition to promote healthy development and growth - Google Patents

Description

Nutritional composition for promoting healthy development and growth

Technical Field

The present invention relates generally to the field of nutritional compositions. In particular, the present invention relates to a nutritional composition which provides improved digestibility compared to conventional compositions.

Background

It is well accepted that developing infants require a source of calcium as part of a nutritionally complete diet. Human breast milk provides sufficient calcium to supply the nutritional needs. However, calcium supplementation is often required in nutritional compositions used as the sole source of nutrition for infants to provide the required amount of calcium. Typically, this calcium supplement is added in the following form: calcium lactate, calcium sulfate, calcium chloride, calcium citrate, calcium phosphate, calcium D-gluconate, calcium aspartate, calcium propionate, or a combination thereof.

Although the above calcium salts are generally sufficient to provide bioavailable calcium, the carbohydrate portion of the above calcium salts is not considered to have a beneficial prebiotic effect (prebiotic effect) that may be desirable after dissociation.

In addition, other factors present in human breast milk are thought to be beneficial to the developing body. For example, functional proteins, such as transforming growth factor-beta (TGF- β), play an important role in many processes required for health and development in infants and children, as well as adults.

More specifically, TGF-. beta.is a generic term for a family of polypeptides, members of which have multifunctional regulatory activity. Three differentially regulated mammalian isoforms, termed TGF-beta 1, TGF-beta 2, and TGF-beta 3, play important roles in a variety of processes in developing infants, children, and adults. TGF- β is known as a 25-kDa homodimeric cytokine that regulates pleiotropic (pleiotropic) function both in the immune system and systemically, expressed both in several cell types of the intestinal mucosa, including lymphocytes, epithelial cells, macrophages and stromal cells, and by T-cells, neutrophils, macrophages, epithelial cells, fibroblasts, platelets, osteoblasts, osteoclasts and other cells. Additionally, TGF- β is present in human breast milk and may affect multiple aspects of infant health and development.

It would therefore be advantageous to provide a nutritional formula that provides a combination of nutrients designed to promote healthy development and growth, particularly in infants. A calcium source should be included in the nutritional formula that provides sufficient bioavailable calcium and has buffering properties more similar to human milk than traditional calcium compounds, and also advantageously has a prebiotic effect. Furthermore, the nutritional formula should be well tolerated in animals, especially human infants, and should not produce or cause excessive gas, abdominal distension, bloating or diarrhea.

Description of the invention

Briefly, in one embodiment, the present invention is directed to a nutritional composition comprising: a lipid or fat, a protein source, a source of long chain polyunsaturated fatty acids (including docosahexaenoic acid (DHA)), a source of supplemental calcium which, upon dissociation, provides a carbohydrate moiety with prebiotic function and has equivalent calcium bioavailability compared to lactate, sulfate, chloride, citrate or saccharate salts of calcium; in a preferred embodiment, the supplemental calcium source comprises calcium gluconate. In a particular embodiment, the calcium source consists solely of calcium gluconate. In some embodiments of the nutritional compositions of the present invention, the supplemental calcium source comprises a level of up to about 2.5% by weight. In other embodiments, the supplemental calcium source in the nutritional composition is at a level of up to about 2.0% by weight. In still other embodiments, the supplemental calcium source comprises at least about a 1.0 wt.% level. The term "supplemental calcium source" as used herein means a source of calcium that is added to the nutritional composition, in the form of a salt. The term does not include calcium inherent in the other components of the nutritional composition.

The present invention also relates to a nutritional composition comprising:

a. up to about 7g/100kcal of fat or lipid, more preferably from about 3 to about 7g/100kcal of fat or lipid;

b. up to about 5g/100kcal of a protein source, more preferably from about 1 to about 5g/100kcal of a protein source;

c. about 5 to about 100mg/100kcal of a source of long chain polyunsaturated fatty acids (including DHA), more preferably about 10 to about 50mg/100kcal of a source of long chain polyunsaturated fatty acids (including DHA); and

d. up to about 2.5% by weight of a supplemental calcium source that, upon dissociation, provides prebiotic function and has equivalent bioavailability compared to lactate, sulfate, chloride, citrate, or saccharate salts of calcium. In some embodiments, the nutritional composition includes from about 0.015(pg/μ g) ppm to about 0.1(pg/μ g) ppm TGF- β, more preferably from about 0.0225(pg/μ g) ppm to about 0.075(pg/μ g) ppm TGF- β.

In yet another embodiment, the present invention relates to a nutritional composition with improved digestibility, comprising: a lipid or fat, a protein source, a source of long chain polyunsaturated fatty acids including docosahexaenoic acid (DHA), up to about 2.5 wt% of a calcium source including at least 20% calcium gluconate, and optionally TGF- β.

Best mode for carrying out the invention

The technical problem to be solved by the invention is as follows: novel nutritional compositions are provided that can be readily digested, providing biochemical and/or physiological benefits. In an embodiment of the invention, the nutritional composition comprises a lipid or fat, a protein source, a source of long chain polyunsaturated fatty acids including docosahexaenoic acid (DHA), and a source of supplemental calcium which, upon dissociation, provides a carbohydrate moiety with prebiotic (prebiotic) function. In certain embodiments, the calcium source comprises calcium gluconate. More specifically, the compositions disclosed herein comprise:

a. up to about 7g/100kcal of fat or lipid, more preferably from about 3 to about 7g/100kcal of fat or lipid;

b. up to about 5g/100kcal of a protein source, more preferably from about 1 to about 5g/100kcal of a protein source;

c. about 5 to about 100mg/100kcal of a source of long chain polyunsaturated fatty acids (including DHA), more preferably about 10 to about 50mg/100kcal of a source of long chain polyunsaturated fatty acids (including DHA);

d. up to about 2.5% by weight of a supplemental calcium source that, upon dissociation, provides a carbohydrate moiety with prebiotic function; the supplemental calcium source preferably has equivalent calcium bioavailability compared to the lactate, sulfate, chloride, citrate or saccharate salt of calcium, and advantageously comprises at least 20% calcium gluconate.

In some embodiments, the nutritional composition may be an infant formula. The term "infant" (infant) as used herein refers to a person not older than 12 months of age. The term "infant formula" applies to compositions in liquid or powdered form that can meet the nutritional needs of an infant as a human milk substitute. In the united states, the contents of infant formulas are dictated by federal regulations set forth at 21c.f.r. § 100, 106 and 107. These regulations define macronutrient, vitamin, mineral, and other component levels to try to mimic the nutritional and other characteristics of human breast milk. The term "toddler" (young child or young child) as used herein refers to a person older than 12 months and up to 3 years of age (36 months). The term "child" (child) as used herein refers to a person over the age of 3 years and less than adolescence.

The composition may be administered to a preterm infant receiving the infant formula. The term "preterm infant" (or prematurity infant) as used herein refers to an infant born after less than 37 weeks of gestation.

The composition may, but need not, be nutritionally complete. One skilled in the art will recognize that "nutritional completeness" varies with a number of factors including, but not limited to, age, clinical status, and dietary intake of the subject to which the term is applied. Generally, "nutritionally complete" means that the nutritional compositions of the invention provide all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy in sufficient quantities for normal growth. The term "essential" (when used with respect to a nutritional ingredient) refers to any nutritional ingredient that cannot be synthesized by the body in an amount sufficient for normal growth and maintenance of health, and therefore must be provided by the diet. The term "conditionally essential" for nutritional ingredients refers to nutritional ingredients that must be provided by the diet in the event that the body does not have access to sufficient amounts of precursor compounds for in vivo synthesis to occur.

By definition, a composition that is "nutritionally complete" for a preterm infant must provide all of the carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy in qualitatively and quantitatively sufficient amounts for the growth of the preterm infant. By definition, a composition that is "nutritionally complete" for a term infant must provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of the term infant. One skilled in the art will recognize that "term infant" refers to an infant born at least 37 weeks after gestation, typically 37 to 42 weeks after gestation. By definition, a composition that is "nutritionally complete" for a child must provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of a child given a particular age and stage of development.

The nutritional composition may be provided in any form known in the art, including a powder, gel, suspension, paste, solid, liquid concentrate, or ready-to-use composition. In a preferred embodiment, the nutritional composition is an infant formula, in particular an infant formula suitable for use as the sole source of nutrition for an infant. In another embodiment, the nutritional composition is a formula suitable for use as the sole source of nutrition for preterm infants.

In a preferred embodiment, the nutritional compositions disclosed herein may be administered enterally. As used herein, "enteral" means through or in the gastrointestinal or digestive tract, and "enteral administration" includes oral feeding, intragastric feeding, administration through the pylorus, or any other means of introduction into the digestive tract.

The fat or lipid source suitable for use in the practice of the present invention may be of any kind known or used in the art, including but not limited to: animal sources such as milk fat (milk fat), butter, milk fat (butter fat), egg yolk lipids; aquatic sources such as fish oil, seal oil (marine oil), single cell oil (single cell oil); vegetable and vegetable oils, such as corn oil, canola oil, sunflower oil, soybean oil, palm olein, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil, linseed (linseed) oil, cottonseed oil, high oleic safflower oil, palm stearin, palm kernel oil, wheat germ oil; medium chain triglyceride oils and emulsions and esters of fatty acids; and any combination thereof.

Milk protein sources useful in the practice of the present invention include, but are not limited to: milk protein powder, milk protein concentrate, milk protein isolate, skim milk solids, skim milk powder, whey protein isolate, whey protein concentrate, sweet whey, acid whey, casein, acid casein, caseinate (e.g., sodium caseinate, sodium calcium caseinate, calcium caseinate), and any combination thereof.

In one embodiment, the protein is provided as an intact protein. In other embodiments, the protein is provided as a combination of both intact and partially hydrolyzed protein, with a degree of hydrolysis between about 4% and 10%. In another embodiment, the protein source may be supplemented with glutamine-containing peptides.

In a particular embodiment of the invention, the whey: the casein ratio approximates that found in human breast milk. In one embodiment, the protein source comprises from about 40% to about 80% whey protein. In another embodiment, the protein source may comprise about 20% to about 60% casein.

In some embodiments of the invention, the supplemental calcium source in the nutritional composition comprises calcium gluconate alone or in combination with a calcium source selected from the group consisting of: calcium lactate, calcium sulfate, calcium chloride, calcium citrate, calcium phosphate, calcium D-gluconate, calcium aspartate, calcium propionate, and combinations thereof. In a particular embodiment of the invention, the only supplemental calcium source in the nutritional composition comprises calcium gluconate.

By dissociation, the carbohydrate portion of the supplemental calcium source (e.g., calcium gluconate) provides a prebiotic effect due to conversion to short chain fatty acids in the gut. While not wishing to be bound to this or any other hypothesis, it is believed that the gluconate dissociated from the calcium gluconate may provide an enhanced prebiotic effect due to the greater solubility of the calcium gluconate and its ability to act as a fermentable substrate for the selected visceral flora to ultimately produce short chain fatty acids. In addition, the use of calcium gluconate as a supplemental calcium source in nutritional compositions may also provide other physiologically important benefits to formula-fed infants, including but not limited to: a softer clot is formed in the human viscera by acidification; smaller clots in the human viscera are formed by acidification; increased digestibility; softer stools; the rate of gastric emptying is increased, more like breast-fed infants; short chain fatty acid profiles are produced in formula-fed infants similar to those produced in breast-fed infants; the beneficial bacteria count and species increase in the gut of formula-fed infants while providing calcium bioavailability equivalent to other supplemental calcium sources typically used in infant formulas.

In one embodiment of the invention, the nutritional composition may comprise one or more probiotics (probiotic). The term "probiotic" means a microorganism that exerts beneficial effects on the health of the host. In this embodiment, any probiotic known in the art may be acceptable as long as the desired results are achieved. In particular embodiments, the probiotic may be selected from the group consisting of Lactobacillus, Lactobacillus rhamnosus GG, Bifidobacterium (Bifidobacterium species), Bifidobacterium longum (Bifidobacterium longum) and Bifidobacterium animalis subsp.

If probiotics are included in the composition, the amount of probiotics may be about 10⁴To about 10¹⁰Colony forming units (cfu) per kilogram of body weight were varied between days. In yet another embodiment, the amount of probiotic may be in the range of about 10⁶To about 10⁹cfu per kg body weight was varied between days. In yet another embodiment, the amount of probiotic may be at least about 10⁶cfu per kg body weight per day.

In one embodiment, the probiotic(s) may be viable or non-viable. The term "viable" (viable) as used herein refers to living microorganisms. The term "non-viable" (non-viable) or "non-viable probiotic" refers to non-viable probiotic microorganisms, their cellular components and/or metabolites. Such non-viable probiotic bacteria may be heat-killed (heat-kill) or otherwise inactivated, but retain the ability to beneficially affect the health of the host. The probiotics useful in the present invention may be naturally occurring, synthetically or developed by genetic manipulation of organisms, whether such new resources are now known or later developed.

In particular embodiments, the nutritional composition may also comprise one or more prebiotics (prebiotics). The term "prebiotic" as used herein refers to an indigestible food ingredient that exerts a benefit on the health of the host. Such health benefits may include, but are not limited to: selectively stimulating the growth and/or activity of one or a limited amount of beneficial visceral bacteria, stimulating the growth and/or activity of ingested probiotic microorganisms, selectively reducing visceral pathogens, and favorably influencing the distribution of visceral short chain fatty acids. Such prebiotics may be naturally occurring, synthetically or developed through genetic manipulation of organisms and/or plants, whether such new resources are now known or later developed. Prebiotics useful in the present invention may include oligosaccharides, polysaccharides and other prebiotics, including fructose, xylose, soy (soya), galactose, glucose and mannose. More specifically, the prebiotic useful in the present invention may include lactulose (lactulose), lactosucrose (lactulose), raffinose, xylooligosaccharide (gluco-oligosaccharide), inulin, polydextrose (polydextrose), polydextrose powder, fructooligosaccharide (fruto-oligosaccharide), isomaltooligosaccharide (isomalto-oligosaccharide), soybean oligosaccharide, lactosucrose, xylooligosaccharide (xylooligosaccharide), chitooligosaccharide (chito-oligosaccharde), oligomannose (mano-oligosaccharide), gum arabic oligosaccharide (aribo-oligosaccharide), sialyloligosaccharide (sialyl-oligosaccharide), fucooligosaccharide (fuco-oligosaccharide), galactooligosaccharide (galacto-oligosaccharide), and gentio-oligosaccharide (gentio-oligosaccharide).

In one embodiment, the total amount of prebiotic present in the nutritional composition may be from about 1.0g/L to about 10.0g/L of the composition. As noted, the total amount of prebiotic present in the nutritional composition may be from about 2.0g/L to about 8.0g/L of the composition. At least 20% of the prebiotics should comprise galactooligosaccharides.

In addition to galactooligosaccharides, the prebiotic ingredient may also comprise polydextrose (polydextrode PDX). If polydextrose is used as a prebiotic, the amount of polydextrose in the nutritional composition, in one embodiment, may be in the range of from about 1.0g/L to about 4.0 g/L.

The amount of galactooligosaccharides in the nutritional composition may, in one embodiment, be from about 0.2mg/100Kcal to about 1.0mg/100 Kcal. In another embodiment, the amount of galactooligosaccharide in the nutritional composition may be from about 0.1mg/100Kcal to about 0.5mg/100 Kcal. If polydextrose is used as a prebiotic, the amount of polydextrose in the nutritional composition, in one embodiment, may be in the range of from about 0.1mg/100Kcal to about 0.5mg/100 Kcal. In another embodiment, the amount of polydextrose may be about 0.3mg/100 Kcal. In a specific embodiment, galactooligosaccharides and polydextrose are supplemented to the nutritional composition in a total amount of about 0.6mg/100 Kcal.

The nutritional formula of the present invention contains a source of long chain polyunsaturated fatty acids (LCPUFAs) including docosahexaenoic acid (DHA). Other suitable LCPUFAs include, but are not limited to, alpha-linoleic acid, gamma-linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), and arachidonic acid (ARA).

In one embodiment, the nutritional composition is supplemented with DHA and ARA simultaneously. In this embodiment, the weight ratio of ARA to DHA may be from about 1:3 to about 9: 1. In one embodiment of the invention, the ratio is from about 1:2 to about 4: 1.

The amount of long chain polyunsaturated fatty acids in the nutritional composition may vary from about 5mg/100Kcal to about 100mg/100Kcal, more preferably from about 10mg/100Kcal to about 50mg/100 Kcal.

The nutritional composition may be supplemented with oils containing DHA and ARA using standard methods known in the art. For example, DHA and ARA may be added to the formulation by replacing an equal amount of oil (e.g., high oleic sunflower oil) typically present in formulations. As another example, oils containing DHA and ARA may be added to the formula by replacing an equal amount of the remaining total fat mixture that is typically present in formulas that do not contain DHA and ARA.

When used, the sources of DHA and ARA may be any known in the art, such as seal oil, fish oil, single cell oil, egg yolk lipids, and brain lipids. In some embodiments, the DHA and ARA are derived from single cell Martek oil, DHASCOOr a variant thereof. DHA and ARA may be in natural form as long as the residue of the LCPUFA source does not cause any substantial detrimental effect on the infant. Alternatively, DHA and ARA may be used in refined form.

In one embodiment of the invention, the sources of DHA and ARA are single cell oils as taught in U.S. Pat. Nos. 5,374,567, 5,550,156, and 5,397,591, the disclosures of which are incorporated herein by reference in their entirety. The present invention is not limited to these oils.

In a particular embodiment, the compositions of the present invention are milk-based nutritional compositions that can provide biochemical and physiological benefits. As is known in the art, milk proteins contain two main components: acid-soluble whey proteins and acid-insoluble casein, the latter representing about 80% of the total protein content in milk. Upon entering the acidic environment of the stomach, casein precipitates and complexes with minerals, forming semi-solid clots of varying size and hardness. The body digests smaller, softer clots more easily than larger, harder clots. Clot formation can be an important consideration in the development of nutritional compositions, including but not limited to infant formulas, medical foods, and preterm formulas. In one embodiment of the invention, the composition of the invention provides a nutritional composition having softer and less coagulum than standard infant formula.

As discussed above, the nutritional compositions of the present invention also comprise TGF- β. In a specific embodiment of the invention, the level of TGF-. beta.in the compositions of the invention is from about 0.0150 (pg/. mu.g) ppm to about 0.1 (pg/. mu.g) ppm. In another embodiment, the level of TGF- β in a composition of the invention is from about 0.0225(pg/μ g) ppm to about 0.0750(pg/μ g) ppm.

In a specific embodiment of the invention, the level of TGF- β in the compositions of the invention is from about 2500pg/mL to about 10,000pg/mL of the composition, more preferably from about 3000pg/mL to about 8000 pg/mL.

In one embodiment, the ratio of TGF- β 1 to TGF- β 2 in the compositions of the invention is in the range of from about 1:1 to about 1:20, more particularly, in the range of from about 1: 5 to about 1: 15.

In some embodiments, the biological activity of TGF- β in the nutritional composition is increased by the addition of a bioactive-enhanced whey fraction. Any bioactive whey fraction known in the art may be used in this embodiment, provided that the desired results are obtained. In one embodiment, the bioactive whey fraction may be a whey protein concentrate. In a particular embodiment, the whey protein concentrate may be Salibra800, obtained from Glanbia Nutritions. In another embodiment, the Whey protein concentrate may be Nutri Whey 800, available from DMVInternational. In yet another embodiment, the whey protein concentrate may be Salibra-850, available from Glanbia Nutritionals. In yet another embodiment, the whey protein concentrate may be Prolacta lactalis WPI90, available from lactplus industries u.s.a., Inc. In a further embodiment, the whey protein concentrate may be provided by MGNutritionals.

In some embodiments, the compositions of the present invention may elicit oral tolerance. The term "oral tolerance" as used herein means that the cellular and/or humoral immune response to an antigen is specifically inhibited by the prior administration of the antigen via the oral route. Oral tolerance affects the responsiveness of the local immune system of the intestinal mucosa itself, thus preventing hypersensitivity reactions to food proteins that might otherwise cause severe inflammatory reactions in the gut. The development of oral tolerance is an important component in proper mucosal immune function. Oral antigens, like food, food proteins or commensal bacteria (commensal bacteria), are often processed in a manner that results in modulation of the immune response. This response does not harm the host and results in a systemic low-response (hypo-responsiveness) when subsequently challenged orally with the same food antigen. Oral tolerance is thus established. However, oral tolerance may also be lost in response to the development and pathogenesis of several immunologically-based diseases, including inflammatory bowel disease, Crohn's disease, and ulcerative colitis. In a particular embodiment, the binding of TGF- β of the invention to prebiotics may synergistically help to elicit oral tolerance to antigens in an environment where oral tolerance has previously been lost. In some embodiments, the initiation of oral tolerance may be enhanced by administration of the compositions of the present invention. In other embodiments, oral tolerance achieved in a subject may be maintained by administering a composition of the invention.

The following examples describe various embodiments of the present specification. Other embodiments within the scope of the claims will be apparent to those skilled in the art from consideration of the specification or practice of the invention disclosed herein. It is intended that the specification, together with the examples, be considered as exemplary only with the spirit and scope of the invention being indicated by the claims which follow the examples. In the examples, all percentages are given on a weight basis unless otherwise indicated.

Example 1

This example illustrates another embodiment of the powdered infant formula of the present invention.

Components

Analysis of composition

	Gram (per 100g)	Gram (per 100mL under routine dilution)	Heat distribution
				Protein	10.84	1.47	8.34
Fat	28.57	3.89	49.50
				Carbohydrate compound	54.87	7.46	42.16
Ash of	2.70	0.37
				Moisture content	3.02	89.9
Calories of	510	69.4

Nutrient composition

Nutrient composition	Amount (per 100 calories)
		Calories of	100
Protein, g	2.1
		Fat, g	5.6
Carbohydrate, g	10.6
		Ash, g	0.6
Water, mL (conventional dilution)	133
		Linoleic acid, mg	900
Alpha-linolenic acid, mg	85
		Arachidonic acid, mg	25

Nutrient composition	Amount (per 100 calories)
		Docosahexaenoic acid, mg	17
Vitamin A, IU	300
		Vitamin D, IU	60
Vitamin E, IU	2
		Vitamin K, mcg	8
Thiamine, mcg	80
		Riboflavin, mcg	140
Vitamin B6，mcg	60
		Vitamin B12，mcg	0.3
Nicotinic acid, mcg	1000
		Folic acid, mcg	16
Pantothenic acid, mcg	500
		Biotin, mcg	3
The vitamin C is added into the mixture of the vitamin C,mg	12
		choline, mg	24
Inositol, mg	6
		Taurine, mg	6
Carnitine, mg	2
		Calcium, mg	78
Phosphorus, mg	43
		Magnesium, mg	8
Iron, mg	1.8
		Zinc, mg	1
Manganese, mcg	15
		Copper, mcg	75
Iodine, mcg	10
		Sodium, mg	27

Nutrient composition	Amount (per 100 calories)
		Potassium, mg	108
Chloride, mg	63
		Selenium, mcg	2.8
Galacto-oligosaccharides	0.6
		AMP equivalent, mg	0.5
CMP equivalent, mg	2.5
		GMP equivalent, mg	0.3
UMP equivalent, mg	0.9
		Nucleoside equivalent, mg	4.2

To prepare 1 liter of standard diluted (20kcal/fl.oz.) product, 136 grams of powder was mixed with 895.2 grams of water. To prepare a 1 quart standard dilution product, 128.7 grams of the powder was mixed with 847.2 grams of water.

The infant formula described in this example contained approximately 4g/L galacto-oligosaccharides and had an ARA level of 25mg/100kcal upon reconstitution. The formula contains 5.6g fat per 100kcal to achieve a fat content similar to human milk. The formulation also has a low buffer strength (buffer strength).

All pH adjustments for this infant formula were performed using potassium hydroxide solution. The specific gravity of the formulation was 1.03117.

Example 2

This example illustrates one embodiment of the powdered infant formula of the present invention.

Components

Analysis of composition

	Gram (per 100g)	Gram (per 100mL under routine dilution)	Heat distribution
				Protein	10.84	1.47	8.50
Fat	28.57	3.89	50.67
				Carbohydrate compound	54.87	7.46	40.83
Ash of	2.70	0.37
				Moisture content	3.02	89.9
Calories of	508	69.1

Nutrient composition

Nutrient composition	Amount (per 100 calories)
		Calories of	100
Protein, g	2.1
		Fat, g	5.6
Carbohydrate, g	10.6
		Ash, g	0.6
Water, mL (conventional dilution)	133
		Linoleic acid, mg	900
Alpha-linolenic acid, mg	85
		Arachidonic acid, mg	25
Docosahexaenoic acid, mg	17
		Vitamin A, IU	300
Vitamin D, IU	60
		Vitamin E, IU	2
Vitamin K, mcg	8
		Thiamine, mcg	80
Riboflavin, mcg	140
		Vitamin B6，mcg	60
Vitamin B12，mcg	0.3
		Nicotinic acid, mcg	1000
Folic acid, mcg	16
		Pantothenic acid, mcg	500
Biotin, mcg	3
		Vitamin C, mg	12
Choline, mg	24
		Inositol, mg	6
Taurine, mg	6
		Carnitine, mg	2

Nutrient composition	Amount (per 100 calories)
		Calcium, mg	78
Phosphorus, mg	43
		Magnesium, mg	8
Iron, mg	1.8
		Zinc, mg	1
Manganese, mcg	15
		Copper, mcg	75
Iodine, mcg	10
		Sodium, mg	27
Potassium, mg	108
		Chloride, mg	63
Selenium, mcg	2.8
		Polydextrose	0.3
Galacto-oligosaccharides	0.3
		AMP equivalent, mg	0.5
CMP equivalent, mg	2.5
		GMP equivalent, mg	0.3
UMP equivalent, mg	0.9
		Nucleoside equivalent, mg	4.2

To prepare 1 liter of standard diluted (20kcal/fl.oz.) product, 136 grams of powder was mixed with 895.2 grams of water. To prepare a 1 quart standard dilution product, 128.7 grams of the powder was mixed with 847.2 grams of water.

Upon reconstitution, the infant formula described in this example contained about 2g/L of galacto-oligosaccharide and 2g/L of polydextrose. The infant formula has an ARA level of 25mg/100 kcal. The formula contains 5.6g fat per 100kcal to achieve a fat content similar to human milk. The formulation also has low buffer strength.

All pH adjustments for this infant formula were performed using potassium hydroxide solution. The specific gravity of the formulation was 1.03117.

Example 3

This example illustrates a comparison of calcium carbonate to calcium gluconate in an infant formula meeting the calcium needs of newborn pigs with and without oligosaccharide supplementation. In this study, feeding of calcium carbonate in the diet was compared with feeding of calcium gluconate with and without oligosaccharide supplementation.

Twenty-eight primary pigs 1 to 15 days old were used in this example. The formula was provided to the pigs 3 times a day in equal amounts by a gravity-fed teat feeding system (feeding speed designed to grow similar to sows fed piglets). The diet was formulated to be nutritionally equivalent and to contain 1.3% calcium, which was intentionally slightly higher than the nutritional needs of the pigs.

A significant effect of the calcium source (P < 0.01) on growth performance was observed. Pigs receiving the calcium carbonate containing formula had a higher rate of weight gain, feed intake and efficiency of weight gain compared to pigs receiving calcium gluconate. Thus, calcium gluconate can have a weight-management effect by regulating weight gain and food consumption.

Although there was no significant difference in plasma calcium or phosphorus concentrations among any of the initial test groups, pigs fed the calcium gluconate formulation had higher (P < 0.01) plasma calcium concentrations and lower (P < 0.01) plasma inorganic phosphorus concentrations on days 5 and 10 of feeding. However, by the end of the study, there was no longer a significant difference in plasma calcium concentrations based on dietary calcium sources, although plasma inorganic phosphorus was still significantly lower (P < 0.01) in pigs fed calcium gluconate-containing formulas.

At the completion of the study, the calcium source had no significant effect on the length, fresh weight, dry weight or ash weight of the radius and ulna of the swine. However, the maximum load that can be tolerated by these bones of calcium gluconate-fed pigs in the 3-point flexion test (3-point flexible testing) is significantly greater (P < 0.05). In addition, there is a tendency for the calcium gluconate-fed pigs to have a higher% bone ash (P < 0.06).

All references cited in this specification, including but not limited to all papers, publications, patents, patent applications, presentations, texts, reports, manuscripts, manuals, books, web records, journal articles, periodicals, and the like, are hereby incorporated by reference in their entirety. The discussion of the references herein is intended merely to be a generalization of the art to which the authors assert and no admission is made that any reference constitutes prior art. Applicants reserve the right to challenge the accuracy and pertinence of the cited references.

Although the description of the preferred embodiments of the present invention has used specific terms, devices and methods, such description is for illustrative purposes only. The words used are words of description rather than of limitation. It will be understood that changes and variations may be made by those of ordinary skill in the art without departing from the spirit or scope of the present invention, which is set forth in the following claims. Moreover, it should be understood that aspects of the various embodiments may be interchanged both in whole or in part. For example, while methods for manufacturing commercial sterile liquid nutritional supplement products are available according to the exemplified methods, other uses are contemplated. Therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained herein.

Claims (12)

1. A nutritional composition for infants or children comprising:

a. a lipid or fat;

b. a protein source;

c. a source of long chain polyunsaturated fatty acids comprising docosahexaenoic acid; and

d. up to 2.5 wt.% of a supplemental calcium source, wherein at least 20% of the supplemental calcium source comprises calcium gluconate; and

e. 0.015 to 0.1 (pg/. mu.g) ppm of TGF-. beta.s.

2. The nutritional composition of claim 1, wherein the source of long chain polyunsaturated fatty acids further comprises arachidonic acid.

3. The nutritional composition of claim 2, wherein the ratio of arachidonic acid to docosahexaenoic acid is from 1:3 to 9: 1.

4. The nutritional composition of claim 1, wherein the lipid or fat comprises a level of up to 7g/100 kcal.

5. The nutritional composition of claim 1, wherein the protein source comprises a level of up to 5g/100 kcal.

6. The nutritional composition of claim 1, wherein the supplemental calcium source consists only of calcium gluconate.

7. The nutritional composition of claim 1, further comprising 0.2 to 1.5mg/100 kcal of prebiotic composition, wherein the prebiotic composition comprises at least 20% oligosaccharide, which comprises galacto-oligosaccharide.

8. The nutritional composition of claim 7, wherein the prebiotic composition further comprises polydextrose.

9. The nutritional composition of claim 1, further comprising at least one probiotic.

10. The nutritional composition of claim 9, wherein the probiotic is selected from the group consisting of: bifidobacterium, Lactobacillus, and combinations thereof.

11. The nutritional composition of claim 1, wherein the TGF- β level is 2500pg/mL to 10,000 pg/mL.

12. The nutritional composition of claim 1, wherein the ratio of TGF- β 1 to TGF- β 2 is 1:1 to 1: 20.