IMPROVING THE LONG TERM SAFETY OF

POWDERED INFANT FORMULAS

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and any benefit of U.S. Provisional Application No. 61/726,275, filed November 14, 2012, the entire contents of which are incorporated by reference in its entirety.

FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to compositions and methods for creating an effective antimicrobial barrier in powdered nutritional compositions, and particularly, powdered infant formulas, to reduce the risk of microbial contaminants in the powdered nutritional compositions that can further be amplified once reconstituted with an aqueous liquid. More particularly, powdered nutritional compositions are prepared by incorporating caprylic acid-enriched coconut oil prior to reconstitution to inhibit the growth of pathogenic bacteria, such as Cronobacter sakazakii (C. sakazakii), in the compositions.

BACKGROUND OF THE DISCLOSURE

[0003] Adult, pediatric, and infant manufactured nutritional compositions comprising a targeted selection of nutritional ingredients are well known and widely available, some of which may provide a sole source of nutrition, while others may provide a supplemental source. These nutritional compositions include nutritional powders that can be reconstituted with water or other aqueous liquid. These nutritional powders may be dryblended nutritional powders that include dry ingredients blended together or spray dried nutritional powders that may optionally include one or more dryblended components.

[0004] Powdered infant formulas are especially popular for providing nutrition early in life and their use continues to increase around the world. These powdered infant formulas are particularly convenient as the powdered formulas can be easily stored and transported, later to be reconstituted to provide liquid formula.

[0005] One potential drawback of some powdered infant formulas is their susceptibility to microbial contamination. The genus Cronobacter, which contains at least 16 biogroups of the emerging opportunistic pathogen, C sakazakii, primarily affects infants, and occasionally immunocompromised and/or elderly patients. These microorganisms are part of the normal flora in any type of processing environment, including food factories and homes. For example, C. sakazakii is known to survive for at least two years in powdered infant formulas. It is not currently possible to completely eliminate this group of microorganisms from the environment, and various previous attempts to reduce levels of Cronobacter spp. have not been successful. Initially, powdered formulas, and in particular powdered infant formulas, are typically not commercially prepared as sterile products. Further, improper handling during preparation (e.g., reconstitution) and feeding of the formulas allows for the amplification of any bacteria present in the formulas.

[0006] Accordingly, there is a continuing need in the art for methods of improving the safety of powdered nutritional compositions, and in particular, powdered infant formulas. Particularly, it would be advantageous if formulas could be prepared to incorporate ingredients that could inhibit the growth of pathogenic bacteria, such as C. sakazakii, commonly found in powdered infant formulas. It would additionally be advantageous if the antimicrobial ingredient was an ingredient that provides additional nutritional benefits. SUMMARY OF THE DISCLOSURE

[0007] The present disclosure is directed to powdered nutritional compositions and methods of preparing powdered nutritional compositions having improved safety and reduced risk of microbial contaminants. More particularly, the methods inhibit the growth of opportunistic pathogenic bacteria, and specifically the growth of Cronobacter sakazakii, in powdered nutritional compositions. To improve the safety and reduce the risk of microbial contaminants, a caprylic acid-enriched coconut oil is utilized in the compositions.

[0008] One embodiment of the present disclosure is directed to a method of inhibiting the growth of pathogenic bacteria in a powdered nutritional composition. The method comprises incorporating caprylic acid-enriched coconut oil into the powdered nutritional composition.

[0009] Another embodiment of the present disclosure is directed to a method of inhibiting the growth of Cronobacter sakazakii in a powdered nutritional composition. The method comprises incorporating caprylic acid-enriched coconut oil into the powdered nutritional composition.

[0010] Another embodiment of the present disclosure is directed to a powdered nutritional composition comprising caprylic acid-enriched coconut oil.

[0011] Another embodiment of the present disclosure is directed to a powdered infant formula comprising caprylic acid-enriched coconut oil.

[0012] It has been unexpectedly found that caprylic acid enriched coconut oil can be introduced into powdered nutritional compositions prior to reconstitution to inhibit the growth of pathogenic bacteria. Particularly, the presence of caprylic acid in powdered nutritional compositions inhibits the growth of C. sakazakii, thereby creating an effective antimicrobial barrier to reduce the risk of microbial contaminants and improve the safety of the powdered nutritional compositions. As caprylic acid can safely and readily be used in nutritional compositions, this antimicrobial barrier approach can have broad applicability in various powdered nutritional products. DETAILED DESCRIPTION OF THE DISCLOSURE

[0013] The powdered nutritional compositions and methods of the present disclosure utilize a caprylic acid-enriched coconut oil to inhibit the growth of pathogenic bacteria, and particularly, the growth of C. sakazakii. The methods described in the present disclosure address and overcome the longstanding problem of controlling microbial contamination in powdered nutritional compositions. Although prior methods of reducing microbial infection in nutritional compositions, and particularly, in powdered infant formulas, have been available, these methods have had limited success as powdered formulas are typically improperly handled during preparation, reconstitution and feeding, thus requiring reconstitution of the formulas with relatively hot (~70°C) water to avoid growth and amplification of the bacteria present in the powdered formulas. By creating an effective antimicrobial barrier in the powdered nutritional composition, that is, prior to reconstitution, presence of bacteria is reduced such to reduce the risk of microbial contamination created during subsequent reconstitution.

[0014] The methods described herein offer a new alternative means for reducing the microbial load of powdered nutritional compositions by incorporating caprylic acid-enriched coconut oil into the powdered nutritional composition prior to reconstitution. Conveniently, the methods of the present disclosure can easily be utilized with a variety of powdered nutritional products. As such, the present disclosure provides for an easy and cost effective means of improving the safety of powdered nutritional compositions, and particularly, of powdered infant formulas.

[0015] These and other optional elements or limitations of the methods and nutritional compositions prepared by the methods of the present disclosure are described in detail hereafter.

[0016] The terms "nutritional formulation" or "nutritional composition" as used herein, are used interchangeably and, unless otherwise specified, refer to nutritional liquids, nutritional powders, nutritional bars, nutritional supplements, and any other nutritional food product as known in the art. The nutritional powders may be reconstituted to form a nutritional liquid. The nutritional formulation or nutritional composition may include at least one of fat, protein and carbohydrate, and is suitable for oral consumption by a human.

[0017] The term "nutritional liquid" as used herein, unless otherwise specified, refers to nutritional products in ready-to-drink liquid form, concentrated form, and nutritional liquids made by reconstituting the nutritional powders described herein prior to use.

[0018] The terms "powdered nutritional" or "nutritional powder" as used herein, are used interchangeably and, unless otherwise specified, refer to nutritional formulations in flowable or scoopable form that can be reconstituted with water or another aqueous liquid prior to consumption and include both spray dried and dry mixed/dryblended powders.

[0019] The term "infant formula" as used herein, unless otherwise specified, refers to solid infant formulas and toddler formulas, wherein infant formulas are intended for infants up to 1 year of age and toddler formulas are intended for children from about 1 year of age to about 10 years of age. The formulas include components that are of semi-purified or purified origin. As used herein, unless otherwise specified, the terms "semi-purified" or "purified" refer to a material that has been prepared by purification of a natural material or by synthesis. The term "infant formula" does not include human breast milk.

[0020] The term "preterm infant formula" as used herein, unless otherwise specified, refers to solid nutritional compositions suitable for consumption by a preterm infant. The term "preterm infant" as used herein, refers to a person born prior to 36 weeks of gestation.

[0021] The terms "adult formula" and "adult nutritional product" as used herein, are used interchangeably to refer to formulas for generally maintaining or improving the health of an adult, and includes those formulas designed for adults who have, are susceptible to, or are at risk of specific diseases and conditions. [0022] The terms "fat" and "oil" as used herein, unless otherwise specified, are used interchangeably to refer to lipid materials derived or processed from plants or animals.

[0023] The term "inhibit growth" as used herein, refers to preventing the growth and amplification of, inactivating, and/or even killing microbes present in the powdered nutritional compositions. The terms "inactivate" or "inactivating" as used herein, refer to altering microbes such to put the microbes in a non-viable state; that is, a state in which the microbial cells are non-culturable and are metabolically inactive.

[0024] The terms "microbe" or "microorganism" as used herein, are used herein interchangeably to refer to organisms having a single cell, cell clusters or no cell at all, and include, for example, bacteria, fungi, archaea, and protists, which can cause disease.

[0025] All percentages, parts and ratios as used herein, are by weight of the total composition, 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.

[0026] 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.

[0027] 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.

[0028] The various embodiments of the powdered nutritional compositions prepared using the methods of the present disclosure may also be substantially free of any optional or selected essential ingredient or feature described herein, provided that the remaining powdered nutritional composition 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 powdered nutritional compositions contain 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.

[0029] The powdered nutritional compositions and corresponding methods of the present disclosure can comprise, consist of, or consist essentially of the essential elements of the disclosure as described herein, as well as any additional or optional element described herein or otherwise useful in powdered nutritional composition applications.

Powdered Nutritional Compositions

[0030] The powdered nutritional compositions of the present disclosure including the caprylic acid-enriched coconut oil may be formulated and administered in any known or otherwise suitable powdered product form. Any powdered product form is suitable for use herein, provided that such form allows for safe and effective oral delivery to the individual of the essential ingredients and any optional ingredients, as also defined herein.

[0031] The powdered nutritional compositions of the present disclosure are preferably formulated as dietary powdered product forms, which are defined herein as those embodiments comprising the essential ingredients of the present disclosure in a powdered form that then contains at least one of fat, protein, and carbohydrate, and preferably also contains vitamins, minerals, or combinations thereof. The nutritional compositions will comprise caprylic acid-enriched coconut oil, desirably in combination with at least one of protein, carbohydrate, vitamins, and minerals, to produce a nutritional combination.

[0032] The powdered nutritional composition may be formulated with sufficient kinds and amounts of nutrients to provide a sole, primary, or supplemental source of nutrition, or to provide a specialized nutritional composition for use in individuals afflicted with specific diseases, disorders, or conditions or with a targeted nutritional benefit as described below.

[0033] The powdered nutritional compositions are typically in the form of flowable or substantially flowable particulate compositions, or at least particulate compositions. Particularly suitable nutritional solid product forms include spray dried, agglomerated and/or dryblended powder compositions. The compositions can easily be scooped and measured with a spoon or similar other device, and can easily be reconstituted by the intended user with a suitable aqueous liquid, typically water, to form a nutritional composition for immediate oral or enteral use. In this context, "immediate" use generally means within about 48 hours, most typically within about 24 hours, preferably right after reconstitution.

[0034] Specific non-limiting examples of product forms prepared using the methods as disclosed herein include, for example, powdered human milk fortifiers, powdered preterm infant formulas, powdered infant formulas, powdered elemental and semi-elemental formulas, powdered pediatric formulas, powdered toddler formulas, powdered adult formulas, and powdered medicinal formulas.

[0035] The nutritional powders may be reconstituted with water prior to use to a caloric density tailored to the nutritional needs of the ultimate user, although in most instances the powders are reconstituted with water to form compositions comprising at least 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. In some embodiments, the reconstituted powder may have a caloric density of from about 50-100 kcal/liter to about 2000 kcal/liter, including from about 150 kcal/liter to about 500 kcal/liter. In some specific embodiments, the emulsion may have a caloric density of 25, or 50, or 75, or 100 kcal/liter. Caprylic Acid-Enriched Coconut Oil

[0036] The powdered nutritional compositions of the present disclosure include caprylic acid, typically through incorporation into the composition of a caprylic acid-enriched coconut oil. Caprylic acid is an eight-carbon saturated fatty acid known by the systematic name octanoic acid, and has the formula

It is found naturally in the milk of various mammals, and it is a minor constituent of coconut oil and palm kernel oil. Caprylic acid, as well as its monoglyceride, monocaprylin, is used in the treatment of some bacterial infections. Due to its relatively short chain length, it has no difficulty in penetrating fatty cell wall membranes, and thus, is effective in combating certain bacteria.

[0037] Typically, coconut oil is an edible oil extracted from the kernel or meat of matured coconuts harvested from the coconut palm (Cocos nucifera).

Throughout the tropical world, it has provided the primary source of fat in the diets of millions of people for generations. Conventional coconut oil includes caprylic acid in an amount of about 8% by weight.

[0038] The caprylic acid-enriched coconut oil for use in the powdered nutritional compositions of the present disclosure includes at least 9% by weight caprylic acid, including at least 15% by weight caprylic acid, including at least 20% by weight caprylic acid, including at least 25% by weight caprylic acid, and including at least 30% by weight caprylic acid. In suitable embodiments, the caprylic acid- enriched coconut oil comprises from 10% to about 99% by weight caprylic acid, including from about 20% to about 25% by weight caprylic acid, and including from about 28% to about 33% by weight caprylic acid. In one particularly suitable embodiment, the caprylic acid-enriched coconut oil includes about 30% by weight caprylic acid. [0039] The powdered nutritional composition includes from about 1% to about 15% by weight caprylic acid-enriched coconut oil, including from about 3% to about 11% by weight, including from about 4% to about 9% by weight, and including from about 5% to about 8% by weight caprylic acid-enriched coconut oil.

[0040] Typically, the powdered nutritional composition provide an individual with from about 0.9 grams to about 11 grams caprylic acid in one liter, including from about 2 grams to about 9 grams, and including from about 4 grams to about 7 grams caprylic acid in one liter.

[0041] Suitable caprylic acid-enriched coconut oils for use in the powdered nutritional compositions are commercially available from Peter Cremer North America, LP (Cincinnati, Ohio) and Twin Rivers Technologies, Inc. (Quincy, Massachusetts).

Macronutrients

[0042] The powdered nutritional compositions including the caprylic acid- enriched coconut oil may be formulated to additionally include at least one of fat (in addition to the coconut oil), protein and carbohydrate. In many embodiments, the powdered nutritional compositions will include the caprylic acid-enriched coconut oil in combination with protein, carbohydrate and additional fat.

[0043] Although total concentrations or amounts of the fat, protein, and carbohydrates may vary depending upon the product type (i.e., human milk fortifier, preterm infant formula, infant formula, toddler formula, pediatric formula, follow-on formula, adult nutritional, etc.) and targeted dietary needs of the intended user, such concentrations or amounts most typically fall within one of the following embodied ranges, inclusive of any other essential fat, protein, and/or carbohydrate ingredients as described herein.

[0044] For the powdered preterm or term infant formulas, the protein component is present in an amount of from about 5% to about 35%, including from about 8% to about 12%, and including from about 10% to about 12% by weight of the preterm or term infant formula; the fat component (including both the caprylic acid- enriched coconut oil and any other fat sources) is present in an amount of from about 10% to about 35% , including from about 25% to about 30%, and including from about 26% to about 28% by weight of the preterm or term infant formula; 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.

[0045] For powdered human milk fortifiers, the protein component is present in an amount of from about 1% to about 55%, including from about 10% to about 50%, and including from about 10% to about 30% by weight of the human milk fortifier; the fat component (including both the caprylic acid-enriched coconut oil and any other fat sources) is present in an amount of from about 1% to about 30%, including from about 1% to about 25%, and including from about 1% to about 20% by weight of the human milk fortifier; and the carbohydrate component is present in an amount of from about 15% to about 75%, including from about 15% to about 60%, including from about 20% to about 50% by weight of the human milk fortifier.

[0046] For powdered adult nutritionals, the protein component is present in an amount of from about 10% to about 90%, including from about 30% to about 80%, and including from about 40% to about 75% by weight of the adult nutritional; the fat component (including both the caprylic acid-enriched coconut oil and any other fat sources) is present in an amount of from about 0.5% to about 20%, including from about 1% to about 10%, and including from about 2% to about 5% by weight of the adult nutritional; and the carbohydrate component is present in an amount of from about 5% to about 40%, including from about 7% to about 30%, including from about 10% to about 25% by weight of the adult nutritional.

[0047] The total amount or concentration of fat, carbohydrate, and protein, in the powdered nutritional compositions of the present disclosure can vary

considerably depending upon the selected composition and dietary or medical needs of the intended user. Additional suitable examples of macronutrient concentrations are set forth below. In this context, the total amount or concentration refers to all fat, carbohydrate, and protein sources in the powdered composition. For powdered nutritional compositions, such total amounts or concentrations are most typically and preferably formulated within any of the embodied ranges described in the following table (each numerical value is preceded by the term "about').

Fat

[0048] The powdered nutritional compositions of the present disclosure may optionally comprise any source or sources of fat (in addition to the caprylic acid- enriched coconut oil). Suitable additional sources of fat for use herein include any fat or fat source that is suitable for use in an oral nutritional composition and is compatible with the essential elements and features of such composition. For example, in one specific embodiment, the fat is derived from long chain

polyunsaturated fatty acids (LCPUFAs).

[0049] Exemplary LCPUFAs for use in the nutritional compositions include, for example, ω-3 LCPUFAs and ω-6 LCPUFAs. Specific LCPUFAs include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (ARA), linoleic acid, linolenic acid (alpha linolenic acid) and gamma-linolenic acid derived from oil sources such as plant oils, marine plankton, fungal oils, and fish oils. In one particular embodiment, the LCPUFAs are derived from fish oils such as menhaden, salmon, anchovy, cod, halibut, tuna, or herring oil. Particularly preferred LCPUFAs for use in the nutritional compositions with the caprylic acid-enriched coconut oil include DHA, ARA, EPA, and combinations thereof.

[0050] In order to reduce potential side effects of high dosages of LCPUFAs in the nutritional compositions, the content of LCPUFAs preferably does not exceed 3% by weight of the total fat content, including below 2% by weight of the total fat content, and including below 1% by weight of the total fat content in the nutritional composition.

[0051] The LCPUFA may be provided as free fatty acids, in triglyceride form, in diglyceride form, in monoglyceride form, in phospholipid form, or as a mixture of one or more of the above, preferably in triglyceride form. In another specific embodiment, the fat is derived from short chain fatty acids.

[0052] Additional non-limiting examples of suitable fats or sources thereof (in addition to the caprylic acid-enriched coconut oil) for use in the nutritional compositions described herein include fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, high oleic safflower oil, oleic acids (EMERSOL 6313 OLEIC ACID, Cognis Oleochemicals, Malaysia), MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, marine oils, fish oils, fungal oils, algae oils, cottonseed oils, and combinations thereof.

Protein

[0053] The powdered nutritional compositions of the present disclosure may optionally further comprise proteins. Any protein source that is suitable for use in oral nutritional compositions and is compatible with the essential elements and features of such compositions is suitable for use in the nutritional compositions.

[0054] Non-limiting examples of suitable proteins or sources thereof for use in the nutritional compositions include hydrolyzed, partially hydrolyzed or non- hydrolyzed proteins or protein sources, which may 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. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates, casein protein isolates, extensively hydrolyzed casein, whey protein, sodium or calcium caseinates, whole cow milk, partially or completely defatted milk, soy protein isolates, soy protein concentrates, and so forth. [0055] In one embodiment, the protein source is a hydrolyzed protein hydrolysate. In this context, the terms "hydrolyzed protein" or "protein hydrolysates" are used interchangeably herein and include extensively hydrolyzed proteins, wherein the degree of hydrolysis is most often at least 20%, including from 20% to about 80%, and also including from about 30% to about 80%, even more preferably from about 40% to about 60%. The degree of hydrolysis is the extent to which peptide bonds are broken by a hydrolysis method. The degree of protein hydrolysis for purposes of characterizing the extensively hydrolyzed protein component of these embodiments is easily determined by one of ordinary skill in the formulation arts by quantifying the amino nitrogen to total nitrogen ratio (AN/TN) of the protein component of the selected liquid formulation. The amino nitrogen component is quantified by USP titration methods for determining amino nitrogen content, while the total nitrogen component is determined by the Tecator Kjeldahl method, all of which are well known methods to one of ordinary skill in the analytical chemistry art.

[0056] Suitable hydrolyzed proteins may include soy protein hydrolysate, casein protein hydrolysate, whey protein hydrolysate, rice protein hydrolysate, potato protein hydrolysate, fish protein hydrolysate, egg albumen hydrolysate, gelatin protein hydrolysate, combinations of animal and vegetable protein hydrolysates, and combinations thereof. Particularly preferred protein hydrolysates include whey protein hydrolysate and hydrolyzed sodium caseinate.

[0057] When used in the nutritional compositions, the protein source may include at least 20% (by weight total protein) protein hydrolysate, including from about 30% to 100% (by weight total protein) protein hydrolysate, and including from about 40% to about 80% (by weight total protein) protein hydrolysate, and including about 50% (by weight total protein) protein hydrolysate. In one particular embodiment, the nutritional composition includes 100% (by weight total protein) protein hydrolysate.

Carbohydrate [0058] The powdered nutritional compositions of the present disclosure may further optionally comprise carbohydrates that are suitable for use in an oral powdered nutritional composition and are compatible with the essential elements and features of such compositions.

[0059] Non-limiting examples of suitable carbohydrates or sources thereof for use in the powdered nutritional compositions described herein may include maltodextrin, hydrolyzed or modified starch or cornstarch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, pea-derived carbohydrates, potato-derived carbohydrates, tapioca, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), artificial sweeteners (e.g., sucralose, acesulfame potassium, stevia) and combinations thereof. A particularly desirable carbohydrate is a low dextrose equivalent (DE) maltodextrin.

[0060] Other suitable carbohydrates include any dietary fiber suitable for use in a powdered nutritional composition, including soluble and insoluble fiber, especially fructooligosaccharides and/or galactooligosaccharides.

Other Optional Ingredients

[0061] The powdered nutritional compositions of the present disclosure may further comprise other optional components that may modify the physical, chemical, aesthetic or processing characteristics of the compositions or serve as pharmaceutical or additional nutritional components when used in the targeted population. Many such optional ingredients are known or otherwise suitable for use in medical food or other nutritional products or pharmaceutical dosage forms and may also be used in the compositions herein, provided that such optional ingredients are safe for oral administration and are compatible with the essential and other ingredients in the selected product form.

[0062] Non-limiting examples of such optional ingredients include preservatives, emulsifying agents, buffers, pharmaceutical actives, anti-inflammatory agents, additional nutrients as described herein, colorants, flavors, thickening agents and stabilizers, emulsifying agents, lubricants, and so forth. [0063] A flowing agent or anti -caking agent may be included in the powdered nutritional compositions as described herein to retard clumping or caking of the powder over time and to make a powder embodiment flow easily from its container. Any known flowing or anti-caking agents that are known or otherwise suitable for use in a nutritional powder or product form are suitable for use herein, non-limiting examples of which include tricalcium phosphate, silicates, and combinations thereof. The concentration of the flowing agent or anti-caking agent in the powdered nutritional composition varies depending upon the product form, the other selected ingredients, the desired flow properties, and so forth, but most typically range from about 0.1% to about 4%, including from about 0.5% to about 2%, by weight of the powdered nutritional composition.

[0064] A stabilizer may also be included in the powdered nutritional compositions. Any stabilizer that is 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 xanthan gum. The stabilizer may represent from about 0.1% to about 5.0%, including from about 0.5% to about 3%, including from about 0.7% to about 1.5%, by weight of the powdered nutritional composition.

[0065] Additionally, the powdered nutritional compositions may comprise one or more antioxidants to provide nutritional support, as well as to reduce oxidative stress. Any antioxidants suitable for oral administration may be included for use in the powdered nutritional compositions of the present disclosure, including, for example, vitamin A, vitamin E, vitamin C, retinol, tocopherol, and carotenoids.

[0066] In one specific embodiment, the antioxidants for use in the powdered nutritional compositions include carotenoids such as lutein, zeaxanthin, lycopene, beta-carotene, and combinations thereof, and particularly, combinations of the carotenoids lutein, lycopene, and beta-carotene. Nutritional compositions containing these combinations, as selected and defined herein, can be used to modulate inflammation and/or levels of C-reactive protein in preterm and term infants. [0067] The powdered nutritional compositions may further comprise any of a variety of other vitamins or related nutrients, non-limiting examples of which include vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B 12, niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts and derivatives thereof, and combinations thereof.

[0068] The powdered nutritional compositions may further comprise any of a variety of other additional minerals, non-limiting examples of which include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, chloride, and combinations thereof.

[0069] The powdered nutritional compositions of the present disclosure may additionally comprise nucleotides and/or nucleotide precursors selected from the group consisting of nucleoside, purine base, pyrimidine base, ribose and deoxyribose to improve intestinal barrier integrity and/or maturation. This is particularly desirable when the powdered nutritional composition is a powdered infant formula. The nucleotide may be in monophosphate, diphosphate, or triphosphate form. The nucleotide may be a ribonucleotide or a deoxyribonucleotide. The nucleotides may be monomeric, dimeric, or polymeric (including RNA and DNA). The nucleotide may be present in the powdered nutritional composition as a free acid or in the form of a salt, preferably a monosodium salt.

[0070] Suitable nucleotides and/or nucleosides for use in the powdered nutritional compositions include one or more of cytidine 5'-monophosphate, uridine 5'-monophosphate, adenosine 5 '-monophosphate, guanosine 5 '-1 -monophosphate, and/or inosine 5'-monophosphate, more preferably cytidine 5'-monophosphate, uridine 5'-monophosphate, adenosine 5 '-monophosphate, guanosine 5 '-monophosphate, and inosine 5 '-monophosphate.

Methods of Manufacture

[0071] The powdered nutritional compositions of the present disclosure may be prepared by any known or otherwise effective manufacturing technique for preparing nutritional powders and can easily be applied by one of ordinary skill in the art to the powdered nutritional compositions described herein.

[0072] The powdered nutritional compositions of the present disclosure can therefore be prepared by any of a variety of known or otherwise effective formulation or manufacturing methods. In one suitable manufacturing process, for example, at least three separate slurries are prepared, including a protein-in-fat (PIF) slurry, a carbohydrate-mineral (CHO-MIN) slurry, a protein-in-water (PIW) slurry. The PIF slurry is formed by heating and mixing the oil (e.g., caprylic acid-enriched coconut oil, etc.) and then adding an emulsifier (e.g., lecithin), fat soluble vitamins, and a portion of the total protein (e.g., milk protein concentrate, etc.) with continued heat and agitation. The CHO-MIN slurry is formed by adding with heated agitation to water: minerals (e.g., potassium citrate, dipotassium phosphate, sodium citrate, etc.), trace and ultra trace minerals (TM/UTM premix), thickening or suspending agents (e.g. avicel, gellan, carrageenan). The resulting CHO-MIN slurry is held for 10 minutes with continued heat and agitation before adding additional minerals (e.g., potassium chloride, magnesium carbonate, potassium iodide, etc.), and/or carbohydrates (e.g., GOS, HMOs, fructooligosaccharide, sucrose, corn syrup, etc.). The PIW slurry is then formed by mixing with heat and agitation the remaining protein, if any.

[0073] The resulting slurries are then blended together with heated agitation and the pH adjusted to 6.6-7.0, after which the composition is subjected to high- temperature short-time (HTST) processing during which the composition is heat treated, emulsified and homogenized, and then allowed to cool. Water soluble vitamins and ascorbic acid are added, the pH is adjusted to the desired range if necessary, flavors are added, and water is added to achieve the desired total solid level. The composition is then heat-treated and subsequently processed and packaged as a reconstitutable powder, e.g., spray dried, drymixed, agglomerated.

[0074] For example, when the nutritional powder is a spray dried nutritional powder, the spray drying step may likewise include any spray drying technique that is known for or otherwise suitable for use in the production of nutritional powders. Many different spray drying methods and techniques are known for use in the nutrition field, all of which are suitable for use in the manufacture of the spray dried nutritional powders herein.

[0075] One method of preparing the spray dried nutritional powder comprises forming and homogenizing the slurries comprising fat (including the caprylic acid-enriched coconut oil), and optionally protein, carbohydrate, and other sources of fat as described above, and then spray drying the slurries to produce a spray dried nutritional powder. The method may further comprise the step of spray drying, drymixing, or otherwise adding additional nutritional ingredients, including any one or more of the ingredients described herein, to the spray dried nutritional powder.

[0076] Other suitable methods for making powdered nutritional

compositions are described, for example, in U.S. Pat. No. 6,365,218 (Borschel, et al.), U.S. Patent No. 6,589,576 (Borschel, et al.), U.S. Pat. No. 6,306,908 (Carlson, et al.), U.S. Patent Application No. 20030118703 Al (Nguyen, et al.), which descriptions are incorporated herein by reference to the extent that they are consistent herewith.

Methods of Use

[0077] The methods of the present disclosure provide for the creation of an effective antimicrobial barrier to reduce the risk of microbial contamination of powdered nutritional compositions. Cronobacter is a gram-negative, rod-shaped, pathogenic bacterium. Cronobacter has been associated with the use of powdered infant formula and is a cause of invasive infection in infants with historically high case fatality rates (40-80%). Particularly, in infants, it can cause bacteraemia, meningitis and necrotizing enterocolitis. All Cronobacter species have been linked retrospectively to clinical cases of infection in either adults or infants and therefore all species should be considered as opportunistic pathogens. However, multilocus sequence typing has shown that the majority of neonatal meningitis cases in the past 30 years, across 6 countries, have been associated with only one genetic lineage of the species C. sakazakii, and therefore this clone appears to be of greatest concern with infant infections. The methods of the present disclosure are directed to inhibiting the growth of opportunistic pathogen, and particularly, of C. sakazakii in powdered nutritional compositions, and in particular embodiments, in powdered infant formulas.

[0078] The powdered nutritional compositions including caprylic acid- enriched coconut oil may be administered to a subset of individuals in need of powdered nutritional compositions with improved safety. Some individuals that are in specific need of safer powdered nutritional compositions having reduced risk of microbial contamination may include immunocompromised preterm infants, infants, pediatrics, teens, adults or older adults (adults age 50 and over), preterm infants, infants, pediatrics, teens, adults or older adults who experience, are susceptible to, or at an elevated risk of diseases and conditions, associated with a suppression in immunity (e.g., cancer, HIV, AIDS, diabetes, etc.), preterm infants and infants who experience, are susceptible to, or at an elevated risk of necrotizing enterocolitis, and the like. Preterm infants, infants, pediatrics, teens, adults, and older adults may be susceptible to or at elevated risk for experiencing these diseases and conditions due to family history, age, environment, and/or lifestyle. Based on the foregoing, because some of the method embodiments of the present disclosure are directed to specific subsets or subclasses of identified individuals (that is, the subset or subclass of individuals "in need" of assistance in addressing one or more specific conditions noted herein), not all individuals will fall within the subset or subclass of individuals as described herein for certain diseases or conditions.

[0079] The individual desirably consumes at least one serving of the powdered nutritional composition daily, and in some embodiments, may consume two, three, or even more servings per day. Each serving is desirably administered as a single, undivided dose, although the serving may also be divided into two or more partial or divided servings to be taken at two or more times during the day. The methods of the present disclosure include continuous day after day administration, as well as periodic or limited administration, although continuous day after day administration is generally desirable. The methods of the present disclosure are preferably applied on a daily basis, wherein the daily administration is maintained continuously for at least 3 days, including at least 5 days, including at least 1 month, including at least 4 weeks, including at least 8 weeks, including at least 2 months, including at least 6 months, desirably for at least 18-24 months, desirably as a long term, continuous, daily, dietary supplement.

EXAMPLES

[0080] The following examples illustrate specific embodiments and/or features of the powdered nutritional compositions prepared using the methods 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 composition, unless otherwise specified.

[0081] The exemplified compositions are powdered nutritional compositions that may be prepared in accordance with the manufacturing methods described herein, such that each exemplified powdered nutritional composition has a reduced risk of microbial contamination.

Examples 1-5

[0082] Examples 1-5 illustrate powdered infant formulas of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch, unless otherwise specified.

Calcium Carbonate 3.41 3.41 3.41 3.41 3.41

ARA Oil 2.96 2.96 3.11 3.11 3.11

Magnesium Chloride 2.88 2.88 2.85 2.85 2.85

Nucleotide Premix 2.62 2.62 2.62 2.62 2.62

Ascorbic Acid 1.59 1.59 1.59 1.59 1.59

Water-soluble Vitamin Premix 1.43 1.43 1.43 1.43 1.43

DHA oil 1.17 1.17 1.23 1.23 1.23

L-cystine Dihydrochloride 1.10 1.10 1.10 1.10 1.10

Choline Chloride 910.00 g 910.00 g 910.03 g 910.03 g 910.03 g

Ascorbyl Palmitate 858.50 g 858.50 g 858.70 g 858.70 g 858.70 g

Sodium Chloride 796.70 g 796.70 g 752.82 g 752.82 g 752.82 g

Ferrous Sulfate 453.50 g 453.50 g 454.01 g 454.01 g 454.01 g

Vitamin ADEK Premix 350.75 g 350.75 g 351.17 g 351.17 g 351.17 g

Mixed Carotenoids 0.00 0.00 187.39 g 187.39 g 187.39 g

Mixed Tocopherols 158.30 g 158.30 g 158.03 g 158.03 g 158.03 g

L- carnitine 107.80 g 107.80 g 107.81 g 107.81 g 107.81 g

Beta-carotene 11.95 g 11.95 g 0.00 0.00 0.00

Vitamin A Palmitate 8.06 g 8.06 g 8.07 g 8.07 g 8.07 g

Riboflavin 5.40 g 5.40 g 5.40 g 5.40 g 5.40 g

Potassium Iodide 1.01 g 1.01 g 1.47 g 1.47 g 1.47 g

Potassium Hydroxide As needed As needed As needed As needed As needed