WO2012009426A1

WO2012009426A1 - High tolerance infant formula including hydrolyzed protein

Info

Publication number: WO2012009426A1
Application number: PCT/US2011/043838
Authority: WO
Inventors: Chron-Si Lai; Paul W Johns; Steven R Davis; Hawley K Linke; Marlene W Borschel; Benjamin D Travis; Richard T Ponce Jr
Original assignee: Abbott Laboratories
Current assignee: Abbott Laboratories
Priority date: 2010-07-13
Filing date: 2011-07-13
Publication date: 2012-01-19
Anticipated expiration: 2013-01-13

Abstract

Disclosed are high tolerance infant formulas including hydrolyzed proteins, such as hydrolyzed whey protein and hydrolyzed casein protein. The high tolerance formulas reduce the incidence of loose and discolored stools in infants, and may also reduce gas and spit up. The high tolerance formulas include a hydrolyzed protein, a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, and a substantially indigestible fermentable carbohydrate. Methods of use of the high tolerance infant formula are also disclosed.

Description

HIGH TOLERANCE INFANT FORMULA INCLUDING HYDROLYZED PROTEIN

FIELD OF THE DISCLOSURE

[0001] The present disclosure relates to an improved tolerance infant formula. More particularly, the present disclosure relates to an improved tolerance infant formula including a hydrolyzed protein, a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, and a substantially indigestible fermentable carbohydrate.

BACKGROUND OF THE DISCLOSURE

[0002] Infant formulas are widely commercially available. Conventional infant formulas typically contain fat, carbohydrate, protein, vitamins, and minerals, and potentially other nutritionally beneficial components. Conventional infant formulas may be based on one of three general types of protein: (1) intact protein; (2) hydrolyzed protein; and/or (3) free amino acids.

[0003] For some infants, formulas based on hydrolyzed proteins, such as hydrolyzed whey protein or hydrolyzed casein protein, are required due to allergies or other conditions of the infant that limit the types of protein that they can ingest safely and comfortably. Although hydrolyzed proteins can be used in infant formulas as an alternative to other proteins, in many cases the hydrolyzed protein is not well tolerated by the infant, especially when the hydrolyzed protein has a degree of hydrolysis of 7 or higher. Intolerance is a non-immune system associated reaction and may be evidenced by behavior or stool or feeding pattern changes, such as increased spit-up or vomiting, an increased number of stools, more watery stools, black stools, and increased fussiness. Intolerance is most often indicated by gastrointestinal symptoms (e.g., stool patterns and gas) as well as behavior characteristics (e.g., acceptance of formula, fussing and crying).

[0004] To combat the tolerance issue, some hydrolyzed protein-containing infant formulas have conventionally been formulated with palm oil to increase the firmness of stools.

Although palm oil docs provide some stool-firming effect, it can cause adverse effects on fat and calcium digestibility, which can lead to a lower bone mineralization rate in the infant. [0005] As such, there is a need for well tolerated infant formulas that are based on hydrolyzed protein. Additionally, it would be very beneficial if the hydrolyzed protein-based infant formula improved tolerance without providing any adverse effects on the nutritional value of the infant formula.

SUMMARY OF THE DISCLOSURE

[0006] The present disclosure is directed to high tolerance infant formulas that include hydrolyzed protein. In some embodiments, the hydrolyzed protein is a hydrolyzed whey protein or hydrolyzed casein protein. The infant formula improves tolerance and improves stool consistency and color.

[0007] The present disclosure is specifically directed to an infant formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7.

[0008] The present disclosure is further specifically directed to a method of decreasing the incidence of loose stool in an infant. The method comprises administering to an infant a formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7.

[0009] The present disclosure is further specifically directed to a method of improving formula tolerance in an infant. The method comprises administering to an infant a formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, the hydrolyzed protein comprising at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7.

[0010] It has been unexpectedly found that a hydrolyzed protein-containing high tolerance infant formula can be prepared by including a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein. Surprisingly, it was discovered that the inclusion of the substantially indigestible fermentable carbohydrate in the formula substantially increased the tolerance of the hydrolyzed protein-containing formula.

[0011 ] Additionally, it has further been discovered that very high levels of hydrolyzed protein, including levels of up to 100% by weight of the total protein, can be included in the high tolerance infant formula in combination with the substantially indigestible fermentable carbohydrate without decreasing the tolerance of the formula.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0012] The high tolerance infant formulas of the present disclosure generally comprise a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and hydrolyzed protein. Additionally, the high tolerance infant formulas generally comprise fat. These and other essential or optional elements or limitations of the high tolerance infant formulas and methods of the present disclosure are described in detail hereinafter.

[0013] The term "infant formula" as used herein, unless otherwise specified, refers to a nutritional composition designed for infants, including pre-term and full term infants up to one year in age, which contains sufficient nutrients such as proteins, carbohydrates, lipids, vitamins, and minerals to potentially serve as a supplemental, primary, or sole source of nutrition.

[0014] All percentages, parts and ratios as used herein, are by weight of the total formulation, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified.

[0015] Numerical ranges as used herein arc intended to include every number and subset of numbers within that range, whether specifically disclosed or not. Further, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 2 to 8, from 3 to 7, from 5 to 6, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.

[0016] All references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.

[0017] All combinations of method or process steps as used herein can be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.

[0018] The various embodiments of the high tolerance infant formulas of the present disclosure may also be substantially free of any optional or selected essential ingredient or feature described herein, provided that the remaining high tolerance infant formula still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term "substantially free" means that the selected high tolerance infant formula contains less than a functional amount of the optional ingredient, typically less than 0.1% by weight, and also including zero percent by weight of such optional or selected essential ingredient.

[0019] The high tolerance infant formulas and corresponding manufacturing methods of the present disclosure can comprise, consist of, or consist essentially of the essential elements and limitations of the disclosure as described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful in the high tolerance infant formula.

Product Form

[0020] The high tolerance infant formulas of the present disclosure may be formulated in any known or otherwise suitable product form for oral or parenteral administration, with powdered, ready-to-feed, and concentrated liquid formulations being particularly suitable. Oral product forms arc preferred and include any solid, liquid, or powder formulation suitable for use herein, provided that such a formulation allows for safe and effective oral delivery of the essential and other selected ingredients from the selected product form.

[0021 ] The high tolerance infant formulas of the present disclosure may have any caloric density suitable for the targeted infants, or provide such a density upon reconstitution of a powder embodiment or upon dilution of a liquid concentrate embodiment. For example, most common caloric densities for the infant formula embodiments of the present disclosure are generally at least about 19 kcal/fl oz (660 kcal/liter), more typically from about 20 kcal/fl oz (675-680 kcal/liter) to about 25 kcal/fl oz (820 kcal/liter), even more typically from about 20 kcal/fl oz (675-680 kcal/liter) to about 24 kcal/fl oz (800-810 kcal/liter). Generally, the 22-24 kcal/fl oz formulas are more commonly used in preterm or low birth weight infants, and the 20- 21 kcal/fl oz (675-680 to 700 kcal/liter) formulas are more often used in term infants.

Low Glvcemic Carbohydrate

[0022] The high tolerance infant formulas of the present disclosure include a low glycemic carbohydrate as part of the carbohydrate component of the formula. As used herein, "low glycemic carbohydrate" refers to carbohydrates that are slow digesting and cause a slower rise in blood sugar as compared to a glucose solution. Infants have a much less mature carbohydrate digesting system as compared to adults and a slow digesting carbohydrate for an infant may not be a slow digesting carbohydrate for an adult. For example, cooked starch is a low glycemic carbohydrate for infants, but not for adults.

[0023] It has been shown that low glycemic carbohydrates increase the amount of postprandial glucose dependent insulinotropic polypeptide (GIP). GIP has been suggested to act as a paracrine to induce Glucagon like peptides (GLP) secretion. GLP-2 derived from GLP is an intestine gut maturation hormone. GLP-1, another hormone derived from GLP is known to retard the transit of food through the gastrointestinal tract by reducing the amplitude of GI contraction, thus allowing more time for the infant to digest and absorb nutrients and improve tolerance by reducing spit-up and firming stools.

[0024] Generally, any low glycemic carbohydrate suitable for inclusion in infant formula can readily be utilized in the high tolerance infant formulas of the present disclosure.

Suitable examples of low glycemic carbohydrates include starch, cooked starch, rice starch, lightly hydrolyzed starch, dextrin, low dextrose equivalent (DE) maltodextrin, DEI maltodextrin, DE3 maltodextrin, lactose, galactose, and combinations thereof.

[0025] The high tolerance infant formula includes the low glycemic carbohydrate in an amount of from about 10% (by weight) to about 40% (by weight), including from about 20% (by weight) to about 40% (by weight), and also including about 30% (by weight) of the total carbohydrate component in the high tolerance formula.

Substantially Digestible Fructose-Containing Carbohydrate

[0026] The high tolerance infant formulas of the present disclosure include a substantially digestible fructose-containing carbohydrate as part of the carbohydrate component of the formula.

[0027] Generally, any substantially digestible fructose-containing carbohydrate suitable for inclusion in infant formula can readily be utilized in the high tolerance infant formulas of the present disclosure. Suitable examples of substantially digestible fructose-containing

carbohydrates include fructose, high fructose corn syrup, sucrose, palatinose and other sucrose isomers, and combinations thereof.

[0028] The high tolerance infant formula includes the substantially digestible fructose- containing carbohydrate in an amount of from about 5% (by weight) to about 40% (by weight), including from about 5% (by weight) to about 15% (by weight), and also including about 10% (by weight) of the total carbohydrate component in the high tolerance formula.

Substantially Indigestible Fermentable Carbohydrate

[0029] The high tolerance infant formulas of the present disclosure include a substantially-indigestible fermentable carbohydrate as part of the carbohydrate component of the formula. Although substantially-indigestible fermentable carbohydrates have traditionally been thought to increase loose stool in infants, it has been surprisingly discovered that when used in combination with the other components as described herein, the substantially-indigestible fermentable carbohydrate actually increases the firmness of the stool of the infant. [0030] The substantially-indigestible carbohydrate is generally selected from the group consisting of long chain fructooligosacchandes, short chain fructooligosacchandes (generally referred to as fructooligosacchandes), galactose-containing oligosaccharides (generally referred to as galactooligosaccharides), inulin, hydrolyzed inulin, gum arabic, and combinations thereof.

[0031 ] Fructooligosacchandes (FOS), which are also known as fructooligosaccharide- bascd prebiotics, are saccharides comprising β-l inked fructose units, which are preferably linked by β(2,1) and/or β(2,6) glycosidic linkages. Examples of suitable fructooligosaccharidcs include inulin, levari, and graminan. In general, inulin, levan, and graminan differ in the amount of branching that is present in their fructose chains and in the types of bonds connecting the individual ructose units. For example, levans generally consist of chains of fructose units that are typically connected by a β(2-6) bond. Although levans may occur as linear chain

carbohydrates, they are more typically composed of branched fructose chains. In contrast, inulins generally consist of linear chains of fructose units that are typically connected by β(2-1) linkages. Graminans, or mixed type fructans, may comprise both β(2-1) and β(2-6) linkage bonds between fructose units. The fhictooligosaccharide of the present disclosure may, in some embodiments, contain a β(2,1) glycosidic linked glucose at the reducing end. As noted herein, the fructooligosacchandes may be short chain fructooligosacchandes, long chain

fructooligosacchandes, or combinations of short chain and long chain fructooligosaccharidcs.

[0032] Fructooligosaccharidcs may be found widely distributed in nature. For example, inulin may be found as a plant storage carbohydrate, and is common to plants of the Composite family. Inulin may be derived from a variety of plants, such as Jerusalem artichoke and Dahlia tuber, and is a major constituent of some herbs, such as burdock root, dandelion root,

elecampane root, chicory root, and codonopsis, among others. Fructooligosacchandes are also commercially available as, for example, Raftilose® (Orafti), Ac ti light (Beghin-Meiji), or Synergy 1® (Orafti) among others.

[0033] The fhictooligosaccharide of the present disclosure will typically have a degree of polymerization of from 2 to about 20. Preferably the fructooligosaccharide has a degree of polymerization of from 2 to about 10, or even from 2 to 7. It should be understood that not all fructooligosaccharidcs present in a composition of the present disclosure need to have the same degree of polymerization. For instance, the term "fructooligosaccharide" or "FOS" may also refer to a mixture of fructooligosaccharides having varying chain lengths; that is, long chain lengths and/or short chain lengths.

[0034] Galactose-containing oligosaccharides, commonly referred to as

galactooligosaccharides (GOS) are indigestible oligosaccharides containing one or more galactose molecule and one molecule of glucose connected through β(1,4) and/or \l,6) glycosidic bonds. The GOS used in the compositions of the present disclosure may be selected from β-galactooligosaccharides, a-galactooligosaccharides, and (arabino-) galactans. In some embodiments, the GOS may be a trans-galactooligosaccharide (TOS). The GOS may be represented by the formula: [galactose]„-glucose, wherein n is an integer between 1 and 20, and preferably is selected from 2, 3, 4, 5, 6, 7, 8, 9, or 10. The term "galactooligosaccharide" or "GOS" may also refer to a mixture of galactooligosaccharides having different chain lengths; that is, long chain lengths and/or short chain lengths. Galactooligosaccharides are also commercially available as, for example, Vivinal® GOS (75% total solids, 60% of total solids GOS; Friesland) and GOS (Clasado).

[0035] The high tolerance infant formula includes the substantially-indigestible fermentable carbohydrate an amount of from about 1.4% (by weight) to about 15.0% (by weight), including from about 1.4% (by weight) to about 14.1% (by weight), and also including from about 2.0% to about 10.0% (by weight) of the total carbohydrate component in the high tolerance formula.

Hydrolyzed Protein

[0036] The high tolerance infant formulas of the present disclosure include a hydrolyzed protein as part of the protein component of the formula.

[0037] The hydrolyzed protein component of the high tolerance formula comprises at least 50% by weight, including at least 60% (by weight), including at least 70% (by weight), including at least 80% (by weight), including at least 90% (by weight) and also including 100% by weight of the total protein component of the high tolerance infant formula. [0038] The hydrolyzed protein component of the high tolerance formula comprises hydrolyzed protein that has a degree of hydrolysis of at least 7, including at least 8, at least 9, at least 10, and including from 9-1 1.

[0039] The hydrolyzed protein included in the high tolerance formula is any hydrolyzed protein suitable for use in infant formulas including, for example, hydrolyzed whey protein, hydrolyzed casein protein, hydrolyzed soy protein, hydrolyzed wheat protein, hydrolyzed com protein, hydrolyzed fish protein, hydrolyzed vegetable protein, hydrolyzed pea protein, and combinations thereof.

[0040] Particularly suitable hydrolyzed proteins include hydrolyzed whey protein, hydrolyzed casein protein, and combinations thereof. One particularly suitable hydrolyzed whey protein is a hydrolyzed sweet whey protein, such as that commercially available from Hilmar Ingredients (Hilmar, California) under the designation Hilmar 8350 Whey Protein Hydrolysate.

Macronntrients

[0041 ] The high tolerance infant formulas of the present disclosure comprise carbohydrate, fat, and protein macronutrients of sufficient types and amounts, to meet the nutritional needs of infants, including premature infants. The concentration of these

macronutrients in the various embodiments of the present disclosure includes the ranges described hereinafter.

[0042] Many different sources and types of proteins, fats and carbohydrates are known and can be used in the high tolerance infant formula in addition to the components described above, provided that the selected nutrients arc safe and effective for oral administration and are compatible with the essential and other added ingredients.

[0043] Proteins suitable for use in the high tolerance infant formulas of the present disclosure, in addition to the hydrolyzed protein component as described above, include hydrolyzed, partially hydrolyzed or non-hydrolyzed proteins or protein sources, and can be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn), vegetable (e.g., soy), or combinations thereof. The proteins for use herein can also include, or be entirely or partially replaced by, free amino acids known for use in nutritional compositions, non-limiting examples of which include tryptophan, glutamine, tyrosine, methionine, cysteine, arginine, and combinations thereof. Other (nonprotein) amino acids typically added to nutritional compositions include carnitine and taurine. In some cases, the D-forms of the amino acids are considered as nutritionally equivalent to the Informs, and isomer mixtures are used to lower cost (for example, D,L-methionine).

[0044] Fats suitable for use in the high tolerance infant formulas of the present disclosure include coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, marine oils, cottonseed oils, long-chain polyunsaturated fatty acids such as arachidonic acid ( ARA), docosahexacnoic acid (DHA), and eicosapentaenoic acid (EPA), and combinations thereof.

[0045] In addition to these food grade oils, structured lipids may be incorporated into the high tolerance infant formulas. Structured lipids are predominantly triacylglycerols containing mixtures of medium and long chain fatty acids on the same glycerol nucleus.

[0046] Carbohydrates in addition to carbohydrates described above may be included in the high tolerance infant formula. Additional carbohydrates suitable for use in the high tolerance infant formulas of the present disclosure may be simple, complex, or variations or combinations thereof. Non-limiting examples of suitable carbohydrates include hydrolyzed or modified starch or cornstarch, corn syrup, corn syrup solids, rice-derived carbohydrate, glucose, fructose, lactose, high fructose com syrup, indigestible oligosaccharides (e.g., fhictooligosaccharidcs), soluble or insoluble fiber, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), and combinations thereof.

[0047] The concentration or amount of fat, protein, and carbohydrate in the high tolerance infant formulas of the present disclosure may vary considerably depending upon the particular product form (i.e., powder, ready-to-feed liquid, or concentrated liquid) and targeted dietary needs. These macronutrients arc most typically formulated within any of the caloric ranges (embodiments A-F) described in the following table (each numerical value is preceded by the term "about"). Nutrient % Total Embodiment A Embodiment B Embodiment C

Calories

Carbohydrate 0-98 2-96 10-75

Protein 0-98 2-96 5-70

Fat 0-98 2-96 20-85

Embodiment D Embodiment E Embodiment F

Carbohydrate 30-50 25-50 25-50

Protein 15-35 10-30 5-30

Fat 35-55 1-20 2-20

[0048] The high tolerance infant formula includes those embodiments in which the protein component may comprise from about 7.5% to about 25% of the caloric content of the formula; the carbohydrate component may comprise from about 35% to about 50% of the total caloric content of the infant formula; and the lipid 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. Additional suitable ranges are noted in the following table (each numerical value is preceded by the term "about").

Optional Ingredients

[0049] The high tolerance infant formulas may further comprise other optional components that may modify the physical, chemical, aesthetic or processing characteristics of the products or serve as pharmaceutical or additional nutritional components when used in a targeted population. Many such optional ingredients are known or otherwise suitable for use in nutritional products and may also be used in the compositions herein, provided that such optional ingredients are safe and effective for administration and are compatible with the essential and other selected components in the compositions.

[0050] Non-limiting examples of such other optional ingredients include preservatives, anti-oxidants, buffers, pharmaceutical actives, sweeteners, colorants, flavors, flavor enhancers, thickening agents and stabilizers, emulsifying agents, lubricants, and so forth.

[0051 ] The high tolerance infant formulas may further include one or more minerals, non-limiting examples of which include phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, iodine, calcium, potassium, chromium, chromium picolinate, molybdenum, selenium, and combinations thereof.

[0052] The high tolerance infant formulas may also include one or more vitamins, non- limiting examples of which include carotenoids (e.g., beta-carotene, zcaxanthin, lutein, lycopene), biotin, choline, inositol, folic acid, pantothenic acid, choline, vitamin A, thiamine (vitamin Bl), riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6),

cyanocobalamin (vitamin B12), ascorbic acid (vitamin C), vitamin D, vitamin E, vitamin K, and various salts, esters or other derivatives thereof, and combinations thereof.

Methods of Use

[0053] The high tolerance infant formulas of the present disclosure may be used to decrease the incidence of loose stool, gas, and/or spit up in infants that require, or benefit from, an infant formula including hydrolyzed protein due to allergies or other reasons. The high tolerance infant formulas of the present disclosure may also be used to improve the color (i.e., less black stools) of an infant's stools. The high tolerance infant formulas can be administered to any infant, preterm or full term, that can benefit from an infant formula including hydrolyzed protein that has high tolerance.

[0054] In one embodiment, the present disclosure includes methods directed to decreasing the incidence of loose stools in an infant, particularly an infant that benefits from an infant formula based on hydrolyzed protein. The method includes administering to the infant a formula including a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7. Particular infants that may benefit from this method include those infants with allergies related to cow's milk protein or protein other than hydrolyzed protein.

[0055] In another embodiment, the present disclosure includes methods directed to improving infant formula tolerance in an infant, particularly an infant that benefits from an infant formula based on hydrolyzed protein. The method includes administering to the infant a formula including a low glycemic carbohydrate, a substantially digestible fructose-containing

carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7. Particular infants that may benefit from this method include those infants with allergies related to cow's milk protein or protein other than hydrolyzed protein.

Manufacture

[0056] The high tolerance infant formulas of the present disclosure may be prepared by any known or otherwise effective technique suitable for making and formulating a powdered infant formula, a ready-to-feed infant formula, or a concentrated infant formula that is diluted prior to use, variations of which may depend upon variables such as the exact selected product form, ingredient combination, packaging and container selection, and so forth, for the desired high tolerance infant formula. Such techniques and variations for any given formula are easily determined and applied by one of ordinary skill in the nutritional formulation or manufacturing arts based on the disclosure herein. [0057] The high tolerance infant formulas of the present disclosure, including the exemplified formulas described hereinafter, can therefore be prepared by any of a variety of known or otherwise effective formulation or manufacturing methods. These methods most typically involve the initial formation of an aqueous slurry, sometimes prepared from a number of preliminary slurries, containing carbohydrates, proteins, lipids, stabilizers or other formulation aids, vitamins, minerals, or combinations thereof. The slurry is emulsified, pasteurized, homogenized, and cooled. Various other solutions, mixtures, or other materials may be added to the resulting emulsion before, during, or after further processing. This emulsion can then be further diluted, heat-treated, and packaged to form a ready-to-feed or concentrated liquid, or it can be heat-treated and subsequently processed and packaged as a reconstitutablc powder, e.g., spray dried, dry mixed, agglomerated.

[0058] Other suitable methods for making nutritional formulas are described, for example, in U.S. Pat. No. 6,365,218 (Borschel, et al.), U.S Patent 6,589,576 (Borschel, et al.), U.S. Pat. No. 6,306,908 (Carlson, et al.), U.S. Patent Application 20030118703 Al (Nguyen, et al.), which descriptions are incorporated herein by reference.

EXAMPLES

[0059] The following examples illustrate specific embodiments and/or features of the high tolerance infant formulas of the present disclosure. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure. All exemplified amounts are weight percentages based upon the total weight of the formulation, unless otherwise specified.

Example 1

[0060] In this Example, the effect of various carbohydrate systems in partially hydrolyzed protein-based infant formulas (Tables 1-3 or commercially available palm oil- containing infant formula) on stool consistency were tested in a human infant clinical trial.

Infant stool consistencies from infants fed one of the three formulas were recorded by the mothers using a 5 point scale system where: l=watery stool; 2=loose/mushy stool; 3= soft stool;

4=formed stool; and 5= hard stool. The results are shown in Table 4. Table 1 : Formulation including hydrolyzed protein and sucrose

Table 2: Formulation including hydrolyzed protein, sucrose and rice starch

Ingredient Amount per 1000 lb 0b)

Sodium Chloride 2.00

Water SolublcVitamin Mix 1.50

DHA Oil 1.12

Choline Chloride 0.68

Oil Soluble Vitamin Mix 0.40

Ferrous Sulfate 0.32

L-Camittne 0.1 1

Ascorbyl Palmitate 0.08

Tocopherol 0.08

Potassium Iodide 0.508(g)

Table 3: Formulation including hydrolyzed protein, sucrose, rice starch and GOS

Table 4

[0061] As shown in Table 4, infants fed the formulation including hydrolyzed protein, sucrose, rice starch, and GOS produced a firmer stool consistency as compared to infants fed the formulations including hydrolyzed protein and sucrose or hydrolyzed protein, sucrose, and rice starch during the 14 days of feeding. It was found that the inclusion of GOS in combination with the hydrolyzed protein, sucrose, and rice starch increased stool consistency, which is surprising as it has previously been found that the inclusion of GOS in infant formulas softened stools.

[0062] Additionally, while the infants fed the commercially available palm oil- containing infant formula also produced firm stools, it is known that the use of palm olein oil for increasing the firmness of stools, can adversely affect fat and calcium digestibility, which can lead to a lowered bone mineralization rate as noted above. The formulation including the hydrolyzed protein, sucrose, rice starch, and GOS had almost as firm stools as the commercially available palm oil-containing infant formula, and will not adversely affect calcium digestibility. Examples 2-6

[0063] Examples 2-6 illustrate exemplary high tolerance infant formulas of the present disclosure, the ingredients of which are listed in Table 5 below. All ingredient amounts are listed as pounds per ~1000 pound batch of product, unless otherwise specified. The high tolerance infant formulas of Examples 2-6 may be prepared according to conventional processing techniques as described herein.

Table 5

Ingredients Example 2 Example 3 Example4 Example 5 Example 6

Maltodcxtrin 232.02 205.02 140.02 127.02 147.02

Rice Starch 171.90 171.90 206.90 136.9 171.90

Whey Protein 157.75 157.75 157.75 157.75 157.75

Hydrolysate

High Oleic 1 12.14 1 12.14 1 12.14 1 12.14 1 12.14

Safflower Oil

Sucrose 98.62 90.62 85.62 98.62 98.62

Soy Oil 81.30 81.30 81.30 81.30 81.30

Coconut Oil 82.87 82.87 82.87 82.87 82.87

GOS 35.00 70.0 105.0 140.0 120.0

Calcium Citrate 13.76 13.76 13.76 13.76 13.76

Potassium 1 1.67 1 1.67 1 1.67 1 1.67 1 1.67

Phosphate

Monobasic

Tri Calcium 6.25 6.25 6.25 6.25 6.25

Phosphate

Potassium 3.59 3.59 3.59 3.59 3.59

Chloride

ARA Oil 2.94 2.94 2.94 2.94 2.94

Ascorbic Acid 2.63 2.63 2.63 2.63 2.63

Magnesium 2.35 2.35 2.35 2.35 2.35 Chloride

Nucleotide 2.40 2.40 2.40 2.40 2.40

Premix

Potassium 2.23 2.23 2.23 2.23 2.23

Citrate

Sodium Chloride 2.00 2.00 2.00 2.00 2.00

Water Soluble 1.50 1.50 1.50 1.50 1.50

Vitamin Premix

DHA Oil 1.09 1.09 1.09 1.09 1.09

Choline 0.67 0.67 0.67 0.67 0.67

Chloride

Oil Soluble 0.40 0.40 0.40 0.40 0.40

Vitamin Premix

Ferrous Sulfate 0.32 0.32 0.32 0.32 0.32

L-Carnitine 0.1 1 0.1 1 0.1 1 0.1 1 0.1 1

Ascorbyl 0.08 0.08 0.08 0.08 0.08 Palmitate

Tocopherol 0.08 0.08 0.08 0.08 0.08

Potassium 0.500 (g) 0.500 (g) 0.500 (g) 0.500 (g) 0.500 (g) Ingredients Example 2 Example 3 Example 4 Example 5 Example 6

Iodide

Example 7

[0064] In this Example, the effect of the carbohydrate system of a highly hydrolyzed protein based formula on stool consistency in two week old piglets was tested. One sample includes xanthan gum, which is known to improve tolerance in infant formula by firming stools, and the second includes DEI maltodextrin (a low glycemic carbohydrate) in place of the xanthan gum.

[0065] The two week old piglets were randomized and housed in individual metabolic cages on day 1. During this adaptation period (7 days), the piglets were fed a commercial highly hydrolyzed protein based infant formula dispensed in a spill proof container. The piglets were fed three times a day and they are given 30 minutes to consume the feed. The feed was then removed after 30 minutes. The piglets were fed the two study formula for 2 weeks after the adaptation an training period (Table 6 and 7). Daily feed intake was recorded and the stool consistencies were recorded by the pig handlers. The stool consistency was categorized using the following scoring system : l=watery stool (no solid particle, diarrhea); 2.0=Ioose/mushy stool (pancake batter like texture); 2.5=loose/mush stool (unformed stool, pudding like texture); 3.0=soft stools that have grainy oat meal texture; 3.5= soft stools that retain shape but not firm enough to retain cracks on the surface; 4.0=formed stools that retain small cracks on the surface; 4.5=formed stools that exhibits defined and very visible cracks on the surface; and 5.0= dry lumps of stools.

[0066] The stools were analyzed for the following characteristics: percentage of watery stool, percentage of loose or mushy stool, percentage of soft stools, percentage of formed stool, and percentage of hard stools. The mean rank stool consistency was also calculated (average of averaged daily stool score). The results are shown in Table 8.

Table 6: Formulation 1

Ingredient -Amount per 1000 lb 0b)

Casein Hydrolysate 176.37

Maltodextrin 169.99

High Oleic Safflower Oil 103.06

Sucrose 69.21

L-Cystine 2-HCI 2.07

Table 7: Formulation 2

Ingredient -Amount per 1000 lb (lb)

L-Carnitine 0.1 1

Tocopherol 0.12

Potassium Iodide 0.0007

Corn Starch 30.42

Maltodextrin 145.65

L-Cystine 2-HCI 2.07

Table 8

[0067] As shown in Table 8, the two samples produced similar characteristics in the stool consistency. Accordingly it is shown that the addition of the low glycemic

carbohydrate, DEI maltodextrin, produces nearly the same stool firming effect as xanthan gum.

Claims

WHAT IS CLAIMED IS:

1. An infant formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable

carbohydrate, and a hydrolyzed protein, the hydrolyzed protein comprising at least 50% by weight of the total protein and having a degree of hydrolysis of at least 7.

2. The infant formula as set forth in claim 1 , wherein the hydrolyzed protein is selected from the group consisting of whey protein hydrolysate, partially hydrolyzed sodium caseinate, casein hydrolysate, hydrolyzed soy protein, hydrolyzed wheat protein, and hydrolyzed corn protein.

3. The infant formula as set forth in claim 1, wherein the low glycemic carbohydrate is selected from the group consisting of starch, rice starch, lightly hydrolyzed starch, dextrin, low DE maltodextrin, DEI maltodextrin, DE3 maltodextrin, lactose, galactose, and combinations thereof.

4. The infant formula as set forth in claim 1, wherein the low glycemic carbohydrate comprises from about 10% (by weight) to about 40% (by weight) of the total carbohydrates in the formula.

5. The infant formula as set forth in claim 1, wherein the substantially digestible fructose-containing carbohydrate is selected from the group consisting of fructose, high fructose com syrup, sucrose, palatinose, sucrose isomers, and combinations thereof.

6. The infant formula as set forth in claim 1, wherein the substantially digestible fructose-containing carbohydrate comprises from about 5% (by weight) to about 40% (by weight) of the total carbohydrates in the formula.

7. The infant formula as set forth in claim 1, wherein the substantially indigestible fermentable carbohydrate is selected from the group consisting of galactooligosaccharidcs, fructooligosaccharides, inulin, hydrolyzed inulin, gum Arabic, and combinations thereof.

8. The infant formula as set forth in claim 1 , wherein the substantially indigestible fermentable carbohydrate comprises from about 1.4% (by weight) to about 15% (by weight) of the total carbohydrates in the formula.

9. A method of decreasing the incidence of loose stool in an infant, the method comprising administering to an infant a formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, wherein the hydrolyzed protein comprises at least 50% by weight of the total protein and has a degree of hydrolysis of at least 7.

10. The method as set forth in claim 9, wherein the hydrolyzed protein is selected from the group consisting of whey protein hydrolysate, partially hydrolyzed sodium caseinate, casein hydrolysate, hydrolyzed soy protein, hydrolyzed wheat protein, hydrolyzed corn protein, and combinations thereof.

11. The method as set forth in claim 9, wherein the low glycemic carbohydrate is selected from the group consisting of starch, rice starch, lightly hydrolyzed starch, dextrin, low DE maltodextrin, DEI maltodextrin, DE3 maltodextrin, lactose, galactose, and combinations thereof.

12. The method as set forth in claim 9, wherein the low glycemic carbohydrate comprises from about 10% (by weight) to about 40% (by weight) of the total carbohydrates in the formula.

13. The method as set forth in claim 9, wherein the substantially digestible fructose- containing carbohydrate is selected from the group consisting of fructose, high fructose com syrup, sucrose, palatinose, sucrose isomers, and combinations thereof.

14. The method as set forth in claim 9, wherein the substantially digestible fructose- containing carbohydrate comprises from about 5% (by weight) to about 40% (by weight) of the total carbohydrates in the formula.

15. A method of improving formula tolerance in an infant, the method comprising administering to an infant a formula comprising a low glycemic carbohydrate, a substantially digestible fructose-containing carbohydrate, a substantially indigestible fermentable carbohydrate, and a hydrolyzed protein, the hydrolyzed protein comprising at least 50% by weight of the total protein and having a degree of hydrolysis of at least 7.