Nutritional products including a novel fat system including monoglycerides

ES 2 552 525 T3

DESCRIPTION

Nutritious products that include a fat system that includes free fatty acids

Disclosure field

The present disclosure relates to nutritional products comprising predigested fat and to methods of using the nutritional products. More specifically, the present disclosure relates to products for infants, children, and pediatric patients that comprise a fatty acid component that provides nutritional benefits including an improvement in digestion, tolerance, and absorption of nutrients as well as a reduction in the incidence of necrotizing enterocolitis, colic, and short bowel syndrome.

Disclosure background

Nutritional liquids and powders, including formula for infants and pediatric individuals, that comprise a targeted selection of nutrients are well known and widely available, some of which may provide a single nutritional source, while others may provide a supplemental source. These nutritional sources include powders that can be reconstituted with water or other aqueous liquids, as well as concentrated, ready-to-drink nutritional liquids such as milk- or protein-based emulsions. These nourishing liquids are especially helpful when formulated with selected nourishing ingredients.

Although breast milk is generally recognized as the best nutrition for newborns, not all mothers can breastfeed successfully. Human milk replacers (infant formulas) can provide complete nutrition, and have been shown to meet the normal growth needs of the infant and the nutritional needs of development. Unfortunately, a small percentage of newborns who are fed infant formula may experience gastrointestinal (GI) intolerance problems, including loose stools, gas, necrotizing enterocolitis, colic, and the like.

The problem of GI intolerance may be due at least in part to incomplete digestion and absorption of nutrients by the infant. To solve this tolerance problem, some infant formulas exclude lactose as an ingredient, while others substitute hydrolyzed protein for intact milk protein to reduce burning in an infant's digestive system.

Additionally, some formula-fed newborns have a much lower rate of fat absorption than breast-fed infants. This discrepancy in the rate of fat absorption decreases as infants mature. Newborns are presumably deficient in lipase, and thus do not digest or absorb fat in the same way as breastfed infants, who receive lipase in breast milk.

A digestive system for preterm infants is less developed than that of a full-term infant, because it additionally needs more nutrients (calories) than term infants to accelerate growth and development. Medium chain triglycerides (MeT oil) are easy to digest and absorb, and have been included in preterm preparations to improve the fat, protein, and calcium absorption of the formula. The medium chain fatty acids included in the medium chain triglycerides, however, are not used to resynthesize triglycerides to form chylomicrons after the MeT oil is digested and absorbed. Like many lipid soluble nutrients, such as carotenoids and vitamins A, D, E, and K, they are believed to pack into chylomicrons prior to entering the systemic circulation, the benefit provided by MeT oil on the absorption of lipid soluble nutrients, which is also important for growth and development, it may be more limited.

Although attempts have been made in the past to solve the GI and other problems listed above, it would be desirable to provide formula for infants and for pediatric individuals that can provide similar nutritional benefits to breast milk, and also provide good tolerance, digestion and absorption of water-insoluble hydrophobic nutrients as well as reduction in the incidence of ailments such as necrotizing enterocolitis, colic, and short bowel syndrome. Additionally, it would be beneficial if these preparations could be free of stabilizers, and especially free of carrageenan. Dietary supplements and nutritional products comprising predigested fats which may be in the form of fatty acids are described in, for example, WO2011 / 128626; EP 1 688 049, and US 7 045 143.

Disclosure summary

The present disclosure is directed to nutritional products, and specifically to infant formulas, which include predigested fats that include a fatty acid-containing component. The nutritional products of the present invention comprise proteins, carbohydrates and a fat system, said fat system comprising from 10% by weight to 60% by weight of an unsaturated free fatty acid component, where the nutritional product is

ES 2 552 525 T3 selects between a liquid emulsion or a reconstitutable powder in a liquid emulsion. These compositions can be used advantageously to provide an improvement in the tolerance, digestion and absorption of nutrients, including water insoluble / lipid soluble nutrients, and to reduce the incidence of necrotizing enterocolitis, colic, and short bowel syndrome. In some embodiments, the fatty acid component may be provided in the form of calcium or magnesium salts of the fatty acid, thereby providing the added benefit of additional nutrients.

It has been discovered that nutritional products such as formula for infants, children, and pediatric individuals that include a predigested fat, such as the monoglycerides and fatty acids described herein, can reduce the total burning in the digestive system of fats. of the infant to improve the infant's fat digestion and absorption, including the absorption of water-insoluble / lipid-soluble nutrients. Specifically, absorption of predigested fat in the proximal small intestine stimulates eeK secretion, which promotes pancreatic alpha cell maturation and secretion of digestive enzymes. Likewise, the secretion of GLP-1 and GLP-2 is stimulated, which also promotes the maturation of the intestine.

Surprisingly, the use of predigested fat and the subsequent secretion of CCK and GLP-1 delay GI transit and stimulate pancreatic enzyme secretion to allow more complete digestion and absorption of nutrients. The reduction in the amount of nutrients that penetrate the infant's colon results in reduced colonic fermentation, which is part of the cause of gas and loose stool problems. In addition, it has been discovered that the use of a predigested fat can reduce the incidence of necrotizing enterocolitis, colic, and / or short bowel syndrome.

Furthermore, it has been discovered that the acidic component of the unsaturated fat in predigested fat can react with calcium or magnesium sources and the resulting salts formed are surprisingly bioavailable. Along with the provision of a good source of calcium or magnesium, these calcium or magnesium salts are also surprisingly soft, in contrast to fatty acids which are generally bitter and impart a strong burning sensation to the throat. Additionally, it has been discovered that calcium or magnesium salts of fatty acids surprisingly act to stabilize nutritional emulsions, since they do not form a sediment that is difficult to disperse in the emulsion of the type of many insoluble calcium salts that are prone. Thus, in many embodiments, the inclusion of calcium or magnesium salts of fatty acids as part of the predigested fat can eliminate the need for stabilizers, such as carrageenans.

Brief description of the drawings

FIGS. 1A and 1B show a picture of a control emulsion and an experimental emulsion as prepared in Example 19.

FIG. 2 is a diagram showing the effect of diet on stool consistency.

Detailed description of the disclosure

The nutritional products described herein comprise predigested fat. By reducing burning in the digestive system of infants, children, or older children, numerous benefits are achieved while providing a stable bioavailable product. These and other essential characteristics of nutritional products, as well as some of the many optional variations and additions, are described in detail hereinafter.

The terms flexible packaging and flexible packaging with sterilization are used interchangeably in the present document, and unless otherwise specified, they refer to a common practice of filling a container, more usually it can be a metal container or other similar , with a nutritional liquid and then subjecting the liquid filled container to the heat sterilization step necessary to form nutritional liquid product in a sterilized flexible container.

The term aseptic packaging, as used herein, unless otherwise specified, refers to the manufacture of a packaged product without relying on the flexible packaging step described above, where the nutritional liquid and the package are sterilized. separately prior to filling, and then combined under sterile or aseptic processing conditions to form a sterile, aseptically packaged nutritional liquid product.

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. These terms also include synthetic lipid materials as long as such synthetic materials are suitable for oral administration to humans.

The term storage stable as used herein, unless otherwise specified, refers to a nutritional product that remains commercially stable after being packaged and then stored at 18-24 ° C for at least 3 months, between approximately 6 months and

ES 2 552 525 T3 approximately 24 months, and also including between approximately 12 months and approximately 18 months.

The terms nutritional formulation or nutritional product or nutritional composition as used herein, are used interchangeably and, unless otherwise specified, refer to liquid and solid (including semi-liquid and semi-solid) human milk fortifiers, preterm infant formula. liquid and solid, liquid and solid infant formula, liquid and solid follow-on formula, liquid and solid pediatric formula, and liquid and solid children's preparations. The solids can be powders that can be reconstituted to form a nutritional liquid, all of which comprise one or more of fat, protein, and carbohydrate and are suitable for oral consumption by a human.

The term nutritional liquid as used herein, unless otherwise specified, refers to nutritional products in ready-to-drink liquid form, in concentrated form, and nutritional liquids prepared by reconstituting the nutritional powders described herein above. of use.

The term "nutritional powder" as used herein, unless otherwise specified, refers to nutritional products in fluidized or granulable form that can be reconstituted with water or other aqueous liquids before consumption and include spray-dried and mixed powders. dry / dry mixed powders.

The term infant as used herein, unless otherwise specified, refers to a person 12 months or younger. The term "premature infant" as used herein refers to a child delivered before 36 weeks gestation.

The term child as used herein, unless otherwise specified, refers to a person over one year of age to three years of age.

The term older child as used herein, unless otherwise specified, refers to a person older than three years of age to twelve years of age.

The term "predigested fat" as used herein, unless otherwise specified, refers to a fatty acid component that contains a fatty acid.

The term infant formula as used herein, unless otherwise specified, refers to liquid and solid nutritional products suitable for consumption by an infant as the primary source of nutrition.

The term preterm infant formula as used herein, unless otherwise specified, refers to liquid and solid nutritional products suitable for consumption by a preterm infant as the primary source of nutrition.

The term human milk fortifier as used herein, unless otherwise specified, refers to liquid and solid nutritional products suitable for mixing with human milk or a preterm infant formula or an infant formula for consumption by a preterm or term infant.

The term "fatty acid-containing monoglyceride" as used herein, unless otherwise specified, refers to a glyceride consisting of a fatty acid chain covalently attached to a glycerol molecule through an ester bond to one. from the Sn-1 (α), Sn-2 (β), or Sn-3 (α ') position of the glycerol molecule.

The term "fatty acid component", as used herein, unless otherwise specified, refers to free fatty acids or fatty acid salts such as calcium or magnesium salts of fatty acids from a source that has less 20% (by weight) of total myristic, palmitic, and stearic acid.

The term "lipid-soluble nutrient" as used herein, unless otherwise specified, refers to water-insoluble nutrients, such as oil-soluble (lipid-soluble) vitamins (e.g., vitamins A, D, E , and K), carotenoids (eg, lutein, beta-carotene, lycopene, etc.), glycolipids (gangliosides), sterols, and phytochemicals.

The term "substantially free" means that the selected nutritional product contains less than a functional amount of the optional ingredient, typically less than 1%, including less than 0.5%, including less than 0.1%, and also including zero percent. , by weight of said optional or selected ingredient.

Nutritional products and methods may comprise, consist of, or consist essentially of the elements of the products described herein, as well as any additional or optional elements described.

ES 2 552 525 T3 herein or otherwise useful in nutritional product and method applications.

Product shape

The predigested fat-containing nutritional products and associated methods of the present disclosure may be formulated and administered in any oral product form known or otherwise suitable. Any solid, semi-solid, liquid, semi-liquid, or powder form, including combinations or variations thereof, are suitable for use herein, provided that such forms allow oral, safe and effective administration to the individual of the ingredients as also defined herein.

The nutritional products of the present disclosure include predigested fat as described herein. The products can optionally include monoglycerides containing fatty acids or a fatty acid component in combination with other sources of fat as indicated below.

Products can include any form of product that comprises the ingredients described herein, and that is safe and effective for oral administration. Nutritional products can be formulated to include only the ingredients described herein, or they can be modified with optional ingredients to form a number of different product forms.

The nutritional products of the present disclosure are formulated in the form of a food product, which is defined herein as those embodiments that comprise the ingredients of the present disclosure in a product form that further contains at least one of fat, protein, and carbohydrate, and preferably also contains vitamins, minerals, or their combinations. In many embodiments, the product will comprise predigested fat in combination with proteins, carbohydrates, vitamins, and minerals to produce a nutritious product.

Nutritional powders may be formulated with sufficient types and amounts of nutrients to provide a single primary or supplemental source of nutrition, or to provide a specialized nutritional product for use in individuals suffering from specific diseases or conditions or with nutritional benefit. directed to an end.

Non-specific examples of product forms suitable for use with predigested fat as described herein include, for example, powdered and liquid human milk fortifiers, powdered and liquid preterm infant formulas, liquid infant formulas. and powders, liquid and powdered elemental and semi-elemental preparations, liquid and powdered pediatric preparations, and liquid and powdered infant formulas.

Nutritious liquids

Nutritional liquids include concentrated, ready-to-drink nutritious liquids. These nutritive liquids are most commonly formulated as suspensions or emulsions.

Nutritional emulsions suitable for use can be aqueous emulsions comprising proteins, fats, and carbohydrates. These emulsions are generally fluidizable or drinkable liquids at between about 1 ° C to about 25 ° C and are typically in the form of oil-in-water, water-in-oil, or complex aqueous emulsions, although such emulsions are usually in the form of oil emulsions. in water having a continuous aqueous phase and a discontinuous oil phase.

Nutritional emulsions can and usually are semi-stable. Nutritional emulsions typically contain up to about 95% by weight of water, including from about 50% to about 95%, also including from about 60% to about 90%, and also including from about 70% to about 88%, water. by weight of nutritional emulsions. Nutritional emulsions can thus have a variety of product densities, but more typically have a density greater than about 1.03 g / ml, including more than about 1.04 g / ml, including more than about 1.055 g. / ml, including from about 1.06 g / ml to about 1.12 g / ml, and also including from about 1.085 g / ml to about 1.10 g / ml.

Nutritional emulsions can have a caloric density adjusted to the nutritional needs of the end user, although in most cases the emulsions comprise at least 19kcal / fl oz (660 kcal / liter), more typically about 20 kcal / fl oz ( 675-680 kcal / liter) to about 25 kcal / fl oz (820 kcal / liter), even more typically from about 20 kcal / fl oz (675-680 kcal / liter) to about 24 kcal / fl oz (800-810 kcal / liter). In general, 22-24 kcal / fl oz (740-810 kcal / liter) formulas are most commonly used in preterm or low birth weight infants, and 20-21 kcal / fl oz (675-680 at 700 kcal / liter) are most often used in full-term newborns. In some embodiments, the emulsion may have a caloric density of between about 100 kcal / liter to about 660 kcal / liter, including from about 150 kcl / liter to about 500 kcal / liter.

ES 2 552 525 T3

The nutritional emulsion may have a pH ranging from about 3.5 to about 8, but is more advantageously in a range from about 4.5 to about 7.5, including from about 5.5 to about 7.3, including from about 6.2 to about 7.2.

Although the serving size for the nutritional emulsion can vary depending on numerous variables, a typical serving size is generally at least about 2 ml, or even at least about 5 ml, or even at least about 10 ml, or even at least about 2 ml. minus about 25 ml, including ranges from about 2 ml to about 300 ml, including from about 4 ml to about 250 ml, and including from about 10 ml to about 240 ml.

As indicated above, nutritional products can also be in the form of a semi-liquid, including those forms that have intermediate properties, such as flow properties, between liquids and solids. Illustrative semi-liquids include thick shakes and liquid gels.

Nutritive solids

The nutritive solids can be in any solid form but are usually 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 compositions, or dry-mixed powders. The compositions can be easily picked up and measured with a spoon or other similar device, where the compositions can be easily reconstituted by the intended user with a suitable aqueous liquid, usually water, to form a nutritional formulation for immediate oral or enteric use. In this context, immediate use generally means in about 48 hours, more usually in about 24 hours, preferably after reconstitution.

Nutritional powders can be reconstituted with water prior to use at a caloric density adjusted to the nutritional needs of the end user, although in most cases, powders are reconstituted with water to form compositions comprising at least 19kcal / floz (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 (800810 kcal / liter). In general, 22-24 kcal / fl oz (740-810 kcal / liter) formula is most commonly used in preterm or low birth weight infants, and 20-21 kcal / fl oz (675- 680 to 700 kcal / liter) are most often used in full-term newborns. In some embodiments, the reconstituted powder may have a caloric density of between about 50 kcal / liter to about 660 kcal / liter, including from about 100 kcal / liter to about 500 kcal / liter.

As indicated above, nutritional products can also be in the form of a semi-solid, including those forms that have intermediate properties, such as rigidity, between solids and liquids. Some examples of semisolids include puddings, jellies, and pasta.

Predigested fat system

Fatty acid component

The nutritional products of the present disclosure include fatty acids that comprise a fatty acid component as part of the predigested fatty system. The fatty acid component comprises from 10% by weight to 60% by weight of an unsaturated free fatty acid component. Fatty acids are normal metabolites in the body, notably formed during the breakdown of fat (triglycerides, diglycerides, cholesterol esters, and certain phospholipids).

Any beneficial fatty acid in the nutritional product can be included in the nutritional products as part of the predigested fat system. In one embodiment, the fatty acid is an unsaturated free fatty acid. In some embodiments that include unsaturated free fatty acids, the total amount of unsaturated free fatty acids with a chain length of more than 14 carbon atoms is less than 15% by weight. Illustrative fatty acids suitable for inclusion in the nutritional products described herein include, but are not limited to, arachidonic acid, linolenic acid, docosahexanoic acid, stearidonic acid, oleic acid, eicosenoic acid, acidic mead, erucic acid, acid nervónico, and its mixtures and combinations. Particularly preferred fatty acids include arachidonic acid, linoleic acid, linolenic acid, docosahexaenoic acid, and oleic acid.

The fatty acid component for inclusion in the predigested system includes those derived from oils such as vegetable oils, marine oils, fish oils, algae oil, fungal oils, animal fats, fractionated animal fats, and combinations thereof. Suitable vegetable oils include, for example, olive oil, canola oil, corn oil, soybean oil, and combinations thereof. In one embodiment, when an animal fat is used, the fatty acids are obtained by enzymatic hydrolysis of lard or tallow and the level of palmitic acid and stearic acid in the resulting fatty acid mixture is reduced to less

ES 2 552 525 T3 of 20% of the total fatty acids, including less than 2% of the total fatty acids. In another embodiment, at least part of the fatty acids are obtained from soybean oil or tree resin. Once obtained from the oil source, the fatty acids are substantially free of monoglycerides, diglycerides, and triglycerides.

In general, the fatty acids will be obtained from an oil source that contains less than about 20% (by weight) palmitic acid and / or stearic acid and / or myristic acid. In some embodiments, the fatty acids are obtained from an oil source that contains less than about 15% (by weight), including less than about 10% (by weight), including less than about 5% (by weight), and including less than 2% (by weight) palmitic acid and / or stearic acid and / or myristic acid.

In a specific embodiment, the fatty acids are obtained from an oil source that contains less than about 20% (by weight), including from about 10% (by weight) to about 15% (by weight) of palmitic acid and / or stearic acid and / or myristic acid. In another specific embodiment, the nutritional product includes palmitic acid in an amount of less than about 10% (by weight) of the total fatty acids.

In some embodiments, the nutritional products can include the fatty acids in salt form; that is, fatty acids can be added to nutritional products as fatty acid salts. In a suitable embodiment, the fatty acids are added to the nutritional product in the form of calcium salts of fatty acids, magnesium salts of fatty acids, or a combination thereof.

One skilled in the art can prepare the fatty acid salts based on the disclosure herein. In a suitable process, emulsions including calcium salts of C10-C24 fatty acids can be prepared by first preparing the fatty acid salts using some starting sources of calcium mixed with at least one source of C10-C24 fatty acids. More specifically, in one method, a starting source comprising C10-C24 fatty acids in a mixture of triglycerides or free forms can be formed by contact with calcium hydroxide and / or calcium carbonate and / or calcium phosphate. In another method, C10-C24 fatty acids in a triglyceride mixture or in free form can be prepared by contacting hydrated CaCl2 or Ca (AcO) 2 at a pH of 6 to about 7.5.

The above methods can be carried out under an inert atmosphere, for example with N2 or argon. In other examples, any of the described methods can be carried out in an ambient atmosphere (eg, where the reaction is not carried out in an atmosphere with a low oxygen content).

The source comprising the C10-C24 fatty acids and the calcium source can be mixed by any method known in the art. Mixing is not understood to imply a particular mixing result, such as dissolving any component to a particular level or forming any particular composition, such as a homogeneous mixture, although such mixtures can be produced and some components can be dissolved by mixing. Mixing can be vigorous and can be carried out manually or by a mechanical device such as, but not limited to, a static mixer, a magnetic stirrer, a stirrer, a spindle, or a rotating device. Mixing can be carried out by forcing or bubbling a gas through the mixture or by sonication.

Mixing of the C10-C24 fatty acid source with a calcium source can be carried out for at least 1 minute. Mixing can also be carried out for at least 1, 5, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 minutes, where any of the indicated values ​​may form a higher or lower endpoint as appropriate.

Mixing can be carried out at various temperatures, but normally the method takes place at an elevated temperature. The precise elevated temperature may depend on the particular starting sources of C10-C24 fatty acids or calcium and the amounts of calcium being used. Suitable temperatures at which mixing can be carried out include, but are not limited to, from about 4 to about 100 ° C, from about 10 to about 100 ° C, from about 15 to about 100 ° C, or from about 20 to about 70 ° C.

Sources comprising C10-C24 fatty acids or calcium can also be heated prior to mixing. Said preheating step can be carried out at any of the temperatures or temperature ranges described herein.

In some embodiments, the mixing of C10-C24 fatty acids and calcium can be carried out under reduced pressure. A suitable pressure is less than or equal to about 1 Torr (1 mm Hg) or less than or equal to about 0.1 Torr (0.1 mm Hg).

In a desirable embodiment, the calcium salts of C10-C24 fatty acids are prepared by adding free C10-C24 unsaturated fatty acids and a source of calcium, such as Ca (OH) 2, CaCl2, CaCO3, Ca-citrate or a mixture of these salts, to form an oil mixture. More specifically, the fatty acids dissolve in a hot aqueous solution (eg, having a temperature of between about 40 to about 80 ° C). I know

ES 2 552 525 T3 can adjust the pH of the solution normally to a pH of about 10-11, using KOH or NaOH. Calcium is then added to the solution containing dissolved fatty acids. Normally, the fatty acids and calcium are allowed to settle for 10 minutes to ensure a complete reaction between the fatty acids and the calcium ions. The mixture is then homogenized to form the oil mixture.

In another desirable embodiment, a mixture of calcium salts of fatty acids including fatty acids from fish oil, seaweed oil, fungal oil, and soybean oil is prepared as part of a predigested fat system. Fish oil, seaweed oil, fungal oil, and soybean oil are mixed together and hydrolyzed by potassium hydroxide with a nitrogen blanket. A source of calcium, such as calcium chloride, is then added to the mixture to react with the fatty acids to produce insoluble calcium salts of fatty acids. Insoluble fatty acid salts can be isolated by filtering, and washed with water prior to vacuum drying.

It has now been surprisingly found that although fatty acid salts, such as calcium salts of fatty acids, are generally insoluble in nutritional products, they do not settle in solution to form a hard sediment layer to redisperse. In this way, the use of calcium and / or magnesium salts of fatty acids allows better administration of calcium / magnesium and, in many embodiments, can eliminate the need for additional stabilizers, such as carrageenans, such that the product can be substantially or completely free of carrageenan.

Accordingly, the use of fatty acid salts allows for improved bioavailability of calcium and / or magnesium and fatty acids compared to products using calcium phosphate or calcium carbonate in the calcium source.

Furthermore, the use of the fatty acid salts in the nutritional products of the present disclosure has been found to provide bioavailable fatty acids such as arachidonic acid (ARA) and the like, which have been shown to enhance the growth of infants. The use of the predigested fat also provides a creamy nutritious product with improved product stability and longer shelf life.

Nutritional products include unsaturated free fatty acids or their salts in an amount of 10% to 60% (by weight) of the fatty component included in the nutritional product, including at least about 15%, including at least about 20%, including about 10% to about 60%, including from about 15% to about 40%, and including from about 15% to about 35%, including about 10%, including about 15%, including about 20%, including about 25%, including about 30%, including about 35%, and further including about 40%, or even about 50%, or even about 60%, by weight of the included fat component in the nutritional product.

In some embodiments, the nutritional products include a mixture of a fatty acid component and fatty acid-containing monoglycerides. In these embodiments, the nutritional product contains the mixture in an amount of at least 10% (by weight) of the fat component included in the nutritional product, including at least about 15%, including at least about 20%, including about 10%. to about 40%, including from about 20% to about 65%, including from about 25% to about 50%, including from about 15% to about 30%, and including from about 15% to about 25%, including about 10%, including about 15%, including about 20%, including about 25%, including about 30%, including about 35%, and further including about 40% or even about 50%, or even about 60%, or even about 70%, or even about 80%, or even about 90%, or even about 100% by weight of the fat component included in the nutritional product.

In other embodiments, nutritional products include a fatty acid component, fatty acid-containing monoglycerides, or combinations thereof in an amount of at least 0.2% (by weight), including at least 1% (by weight), including minus 2% (by weight), and including at least 5% (by weight) of total dry matter in the nutritional product.

Macronutrients

Although the total concentrations or amounts of the fat, protein, and carbohydrates may vary depending on the type of product (i.e., a human milk fortifier, an infant formula, etc.), the form of the product (i.e. nutrient solid, powder, ready-to-drink liquid, or concentrated liquid) and the dietary needs of the intended user, such concentrations or amounts are more typically in one of the following encompassed ranges, inclusive of any other essential fat, protein, and / or carbohydrates as described herein.

For liquid products prepared for preterm and term infants, the carbohydrate concentrations of

ES 2 552 525 T3 carbon more typically range from about 5% to about 40%, including from about 7% to about 30%, including from about 10% to about 25%, by weight of the preterm or term infant formula; Fat concentrations (including predigested fat and any other fat sources) most typically range from about 1% to about 30%, including from about 2% to about 15%, and also including from about 3% to about 10%, in weight of preterm or term infant formula; and protein concentrations more typically range from about 0.5% to about 30%, including from about 1% to about 15%, and also including from about 2% to about 10%, by weight of preterm infant formula or finished.

For carbohydrates in human milk fortifying liquid products, concentrations typically range, most typically, from about 10% to about 75%, including from about 10% to about 50%, including from about 20% to about 50%. about 40%, by weight, of the human milk fortifier; Fat concentrations (including predigested fat and any other fat sources) most typically range from about 10% to about 40%, including from about 15% to about 37%, and also including from about 18% to about 30%, in weight of human milk fortifier; and protein concentrations more typically range from about 5% to about 40%, including from about 10% to about 30%, and also including from about 15% to about 25%, by weight of the human milk fortifier.

The level or amount of carbohydrates, fats, and / or proteins in the liquid nutritional products can also be characterized in addition to or alternatively as a percentage of the total calories in the nutritional products shown in the following Table. These macronutrients for the liquid nutritional products of the present disclosure are most commonly formulated in any of the caloric ranges (embodiments AF) described in the following Table (each numerical value is preceded by the term "about").

<td>Nutrient% Cal. Totals</td><td>Embodiment A</td><td>Embodiment B</td><td>Embodiment C</td>

<td>Carbohydrates</td><td> 0-98</td><td> 2-96</td><td> 10-75</td>

<td>Protein</td><td> 0-98</td><td> 2-96</td><td> 5-70</td>

<td>Grease</td><td> 0-98</td><td> 2-96</td><td> 20-85</td>

<td></td><td>Embodiment D</td><td>Embodiment E</td><td>Embodiment F</td>

<td>Carbohydrates</td><td> 30-50</td><td> 25-50</td><td> 25-50</td>

<td>Protein</td><td> 15-35</td><td> 10-30</td><td> 5-30</td>

<td>Grease</td><td> 35-55</td><td> 1-20</td><td> 2-20</td>

In a specific example, liquid infant formulations (ready-to-feed concentrated liquids) include those embodiments where the protein component can comprise between about 7.5% to about 25% of the caloric content of the formula; the carbohydrate component may comprise between about 35% to about 50% of the total caloric content of the infant formula; and the fat component can comprise between about 30% to about 60% of the total caloric content of the preparation. These ranges are provided as examples only, and are not intended to be limiting. Additional suitable ranges are reported in the following Table (each numerical value is preceded by the term "about").

<td>Nutrient% Cal. Totals</td><td>Embodiment G</td><td>Embodiment H</td><td>Embodiment I</td>

<td>Carbohydrates:</td><td> 20-85</td><td> 30-60</td><td> 35-55</td>

<td>Grease:</td><td> 5-70</td><td> 20-60</td><td> 25-50</td>

<td>Protein:</td><td> 2-75</td><td> 5-50</td><td> 7-40</td>

When the nutritional product is a powdered formula for preterm or term infants, the protein component is present in an amount 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 is present in an amount 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%, and including from about 50% to about 55% by weight of the preterm or term infant formula. .

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

ES 2 552 525 T3 fat component is present in an amount 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%, and including from about 20% to about 50% by weight of the human milk fortifier.

The total amount of fat, carbohydrate, and protein concentration in the powdered nutritional products of the present disclosure can vary considerably depending on the product selected and the dietary or medical needs of the intended user. Additional suitable examples of macronutrient concentrations are shown below. In this context, the total amount or concentration refers to all sources of fat, carbohydrates, and proteins in the powdered product. For powdered nutritional products, such total amounts or concentrations are most normally and preferably formulated in any of the encompassed ranges described in the following Table (all numbers are approximately leading).

<td>Nutrient% Cal. Totals</td><td>Embodiment J</td><td>Embodiment K</td><td>Embodiment L</td>

<td>Carbohydrates</td><td> 1-85</td><td> 30-60</td><td> 35-55</td>

<td>Grease</td><td> 5-70</td><td> 20-60</td><td> 25-50</td>

<td>Protein</td><td> 2-75</td><td> 5-50</td><td> 7-40</td>

Grease

In addition to predigested fat, the nutritional products of the present disclosure may comprise an additional source or sources of fat (the total amount of fat being referred to herein as the fat component or fat system of the nutritional product). Additional sources of fat suitable for use herein include any source of fat that is suitable for use in an oral nutritional product and is compatible with the elements and characteristics of such products.

Non-limiting examples of additional fats or their sources suitable for use in the nutritional products described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, coconut oil. high oleic safflower, oleic acids (OLEIC ACID EMERSOL 6313), 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. In one embodiment, suitable fats or their sources include oils or oil blends that include long chain polyunsaturated fatty acids (LCPUFA), preferably LC-PUFA having four or more double bonds. Some specific non-limiting polyunsaturated acids for inclusion include, for example, docosahexaenoic acid (DHA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and the like.

In general, the predigested fat described herein is included in the nutritional product in combination with one, two, three, four, or more additional fat sources. In one embodiment, monoglycerides (desirably in the form of monoglycerol palmitate), fatty acids (desirably in the form of calcium salts), a high oleic oil, and coconut oil are combined together to provide the fatty component in a nutritious product. In this embodiment, the monoglycerides are present in an amount of between about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23%, and about 25% by weight of the fatty component, the fatty acids are unsaturated free fatty acids, and said unsaturated free fatty acids are present in an amount of between 10% to 60% including about 10%, about 15%, about 20%, and about 25% by weight of the fatty component, the high oleic oil is present in an amount from about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 25%, and about 30% by weight of the fat component, and the coconut oil is present in an amount of between about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25% by weight of the fat component.

In another embodiment, monoglycerides containing fatty acids (desirably in the form of monoglycerol palmitate), a fatty acid component (desirably in the form of calcium salts), a high oleic safflower oil, and coconut oil are combined. they combine together to provide the fat component in a nutritious product. In this embodiment, the monoglycerides are present in an amount of between about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23%, and about 25%. % by weight of the fatty component, the fatty acids are unsaturated free fatty acids, and

ES 2 552 525 T3 said unsaturated free fatty acids are present in an amount from about 1% to about 60% including from about 10% to about 30%, including about 10%, about 15%, about 20%, and about 25%. By weight of the fat component, the high oleic oil is present in an amount from about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 25%, and about 30% by weight of the fat component, and the coconut oil is present in an amount of between about 1% to about 40%, including about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25% by weight of the fat component.

In another embodiment, monoglycerides containing fatty acids (desirably in the form of monoglycerol palmitate), a fatty acid component (desirably in the form of calcium salts), a high oleic safflower oil, coconut oil, oil that contains DHA, and oil containing ARA combine together to provide the fat component in a nutritious product. In this embodiment, the monoglycerides are present in an amount of from about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23%, and about 25% by weight of the fatty component, the fatty acids are unsaturated free fatty acids present in an amount of 10 to 60%, including about 10% to about 30%, including about 10%, about 15%, about 20%, and about 25% by weight of the fat component, the high oleic oil is present in an amount from about 1% to about 40%, including from about 10% to about 30% , including about 10%, about 15%, about 20%, about 25%, and about 30% by weight of the fat component, and coconut oil is present in an amount of between about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25%. % by weight of the fat component. The DHA-containing oil is present in an amount of about 1% to about 10%, including about 5% by weight of the fat component and the ARA-containing oil is present in an amount of about 1% to about 10%, including about 5% by weight of the fat component.

Protein

The nutritional products of the present disclosure may optionally further comprise protein in addition to predigested fat. Any protein source that is suitable for use in oral nutritional products and is compatible with the elements and characteristics of such products is suitable for use in combination with predigested fat.

Non-limiting examples of suitable proteins or their sources for use in nutritional products include hydrolyzed, partially hydrolyzed or non-hydrolyzed proteins or protein sources, which may be obtained from any known or otherwise suitable source such as milk (e.g. casein , whey), animal (for example, meat, fish), cereals (for example, rice, corn), vegetables (for example, soy) or their combinations. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates as described herein, casein protein isolates, extensively hydrolyzed casein, whey proteins, sodium or calcium caseinates, whole cow's milk. , partially or fully skimmed milk, soy protein isolates, soy protein concentrates, and so on.

Carbohydrates

The nutritional products of the present disclosure may optionally further comprise any carbohydrates that are suitable for use in an oral nutritional product and are compatible with the elements and characteristics of said products.

Non-limiting examples of carbohydrates or their sources for use in the nutritional products described herein may include maltodextrin, hydrolyzed or modified cornstarch or starch, glucose polymers, corn syrup, corn syrup solids, hydrates from rice derived carbohydrates, pea derived carbohydrates, potato derived carbohydrates, tapioca, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (eg maltitol, erythritol, sorbitol), artificial sweeteners (eg sucralose, acesulfame potassium, stevia), and combinations thereof.

Other optional ingredients

The nutritional products of the present disclosure may comprise other optional components that can modify the physical, chemical, aesthetic or processing characteristics of the products or serve as pharmaceutical or additional nutritional components when used in a target population. Many such optional ingredients are known or otherwise suitable for use in a medical food or other products.

ES 2 552 525 T3 nutritional or dosage forms and may also be used in the compositions herein, provided that said optional ingredients are safe for oral administration and are compatible with the ingredients in the selected product form.

Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifying agents, buffers, fructooligosaccharides, galactooligosaccharides, prebiotics, pharmaceutical actives, additional nutrients as described herein, colorants, flavors, thickening and stabilizing agents, emulsifying agents, lubricants, and so on.

The nutritional products may further comprise a sweetening agent, preferably further including at least one sugar alcohol such as maltitol, erythritol, sorbitol, xylitol, mannitol, isomalt, and lactitol, and also preferably including at least one artificial or high potency sweetener. such as acesulfame K, aspartame, sucralose, saccharin, stevia, and tagatose. These sweetening agents, especially as a combination of a sugar alcohol and an artificial sweetener, are especially useful in formulating the liquid beverage embodiments of the present disclosure that have a desirable flavor profile. These sweetener combinations are especially effective in masking off-flavors sometimes associated with the addition of plant protein to a liquid beverage. The optional sugar alcohol concentrations in the nutritional product can range from at least about 0.01%, including from 0.1% to about 10%, and also including from about 1% to about 6%, by weight of the nutritional product. Optional artificial sweetener concentrations can range from about 0.01%, including from about 0.05% to about 5%, also including from about 0.1% to about 1.0%, by weight of the nutritional product.

A flow agent or anti-caking agent may be included in the nutritional products described herein to retard clumping and caking of the powder over time and to make a powder embodiment flow easily from its container. Suitable for use herein are any known flowability or anti-caking agents known or otherwise suitable for use in a powder or nutritional product form, non-limiting examples of which include tricalcium phosphate, silicates, and combinations thereof. . The concentration of the flow agent or anti-caking agent in the nutritional product varies depending on the form of the product, the other ingredients selected, the desired flow properties, and so on, but more typically they range from about 0.1% to about 4%, including from about 0.5% to about 2%, by weight of the nutritional product.

A stabilizer can also be included in nutritional products. Any stabilizer that is known or otherwise suitable for use in a nutritional product is also suitable for use herein, some non-limiting examples of which include carrageenans and 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 nutritional product.

The nutritional product compositions may further comprise any of a variety of different vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B12, carotenoids (e.g. example, beta-carotene, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, their salts and derivatives, and their combinations.

The nutritional products can further comprise any of a variety of different minerals, non-limiting examples of which include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, chloride, and combinations thereof. Furthermore, in some embodiments, the nutritional products may be free of carrageenans.

Manufacturing methods

The nutritional products of the present disclosure can be prepared by any known manufacturing technique or otherwise effective to prepare the selected product in solid or liquid form. Many such techniques are known for any given product form such as liquids or powders and can easily be applied by one of ordinary skill in the art to the nutritional products described herein.

The nutritional products of the present disclosure can therefore be prepared by any of a variety of known or otherwise effective products or manufacturing methods. In a suitable manufacturing process, for example, at least three separate suspensions are prepared, including a protein-in-fat (PlF) suspension, a carbohydrate-mineral (CHO-MIN) suspension, and a protein-in-water suspension. (PIW). The PlF suspension is formed by heating and mixing the oil (for example, monoglycerides and / or fatty acids, oil containing fatty acids, canola oil, corn oil, etc.) and then adding

ES 2 552 525 T3 an emulsifier (eg, lecithin), water soluble vitamins, and a portion of the total protein (eg, milk protein concentrate, etc.) with continued heat and stirring. The CHO-MIN suspension is formed by adding with stirring and heating to water: minerals (for example, potassium citrate, dipotassium phosphate, sodium citrate, etc.), trace and ultra-trace minerals (premix of tM / uT), and / or thickening or suspending agents (eg, avicel, gellans, carrageenans). The resulting CHO-MIN suspension is held for 10 minutes with continued heat and stirring before adding additional minerals (e.g., potassium chloride, magnesium carbonate, potassium iodide, etc.), and / or carbohydrates (e.g. , fructooligosaccharides, sucrose, corn syrup, etc.). The PIW suspension is then formed by mixing the remaining protein, if applicable, with heat and stirring.

In a specific embodiment of the present disclosure, all or part of the predigested fat included in the nutritional product can be added to the CHO-MIN suspension, which contains less than 5% (by weight of the CHO-MIN suspension) of fat in the form of triglycerides. In this embodiment, at least 5% (by weight) of the total fat present in the nutritional products is in the form of predigested fat and is added to the suspension.

CHO-MIN. In some embodiments, at least 5% (by weight), including at least 10% (by weight), including at least 20% (by weight), including at least 30% (by weight), including at least 40% (by weight). ), including 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 including 100% (by weight) of the total predigested fat included in the nutritional product is added to the CHO-MIN suspension. In a particular embodiment, lipid soluble nutrients, such as carotenoids or vitamins A, D, E, and K, are dissolved in the predigested fat before the predigested fat is added to the CHO-MIN suspension or during the manufacture of CHOMIN suspension. By adding the predigested fat to the CHO-MIN suspension as opposed to the PIF suspension, the finished nutritional composition can be improved.

The resulting suspensions are then mixed together with stirring and heat and the pH adjusted to 6.6-7.0, after which the composition is subjected to high temperature short time processing (HTST) during which time 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, the flavors are added, and water is added to achieve the desired total solids level. The composition is then aseptically packaged to form an aseptically packaged nutritional emulsion. This emulsion can also be filled and then sterilized to form a ready-to-drink or concentrated liquid, or it can be spray-dried, dry-mixed, and / or agglomerated.

The nutritional powder, such as a spray-dried nutritional powder or a dry-blended nutritional powder, can be prepared by any group of known or otherwise effective techniques suitable for preparing and formulating a nutritional powder.

For example, when the nutritional powder is a spray-dried nutritional powder, the spray-drying step includes 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 nutritional field, all of which are suitable for use in making the spray dried nutritional powders herein.

One method of preparing the dry nutritional powder by spraying comprises forming and homogenizing an aqueous or liquid suspension comprising predigested fat, and optionally protein, carbohydrates, and other sources of fat, and then spray drying the suspension or liquid to produce a dry nutrient powder by spraying. The method may further comprise the step of spray drying, dry mixing, or otherwise adding additional nutritional ingredients, including any one or more of the ingredients described herein, to the spray dried nutritional powder.

Other suitable methods for preparing nutritional products are described, for example, in US Patent 6,365,218 (Borschel, et al.), US Patent 6,589,576 (Borschel, et al. ), US Patent 6,306,908 (Carlson, et al.), and US Patent Application 20030118703 A1 (Nguyen, et al.), the disclosures of which are incorporated herein by reference to the extent that they are consistent with it.

Methods of use

In accordance with the present disclosure, and as further described below, the nutritional products described herein can be used for numerous purposes, including, for example, improving digestion, improving nutrient absorption, enhancing tolerance, decrease the incidence of necrotizing enterocolitis, decrease the incidence of colic, and decrease the incidence of short bowel syndrome. The individual (infant, child, or older child) using the nutritional products described herein may actually have or suffer from the described disease or illness (i.e., may actually have health problems).

ES 2 552 525 T3 digestion, nutrient absorption and / or tolerance or you may actually have necrotizing enterocolitis, colic, or short bowel syndrome), or you may be susceptible to, or at risk for, disease or illness (that is You may not actually have the disease or illness yet, but you are at high risk compared to the general population of suffering from it due to certain pathologies, family history etc.) Whether the individual actually has the disease or ailment, or is at risk of or susceptible to the disease or ailment, the individual is hereby classified as in need of assistance in treating with and combining the disease or disease. For example, an infant may actually have necrotizing enterocolitis or may be at risk for necrotizing enterocolitis (susceptible to necrotizing enterocolitis) due to premature birth. Similarly, in another example, an infant may actually have tolerance and / or digestion and / or nutrient absorption problems, or may be at risk of (susceptible to) suffering from one or more of these ailments due to having other diseases. or ailments, or a family history of such problems. Whether the individual actually has the disease or ailment, or is only at risk for or is susceptible to suffering from the disease or ailment, it is within the scope of the present disclosure to assist the individual with the nutritional products described herein.

Based on the foregoing, as some of the method embodiments of the present disclosure are directed at specific subsets or subclasses of identified individuals (i.e., the subset or subclass of individuals in need of assistance in dealing with one or more specific diseases or specific ailments indicated in this document), not all individuals can benefit from all the methods of the embodiments described herein as well as not all individuals will be included in the subset or subclass of individuals that are described herein for certain diseases or conditions.

The nutritional products described herein desirably comprise predigested fat in combination with one or more additional fat sources to provide a nutritional source for infants, children, and older children to improve digestion and absorption of nutrients. Specifically, similar to the digestion of breastfed infants, as the fat source is at least partially digested before entering the duodenum, more time is allowed for the infant to absorb nutrients, particularly in the intestines, and the fat is reduced. amount of nutrients entering the infant's colon, thus resulting in fewer nutrients that can ferment and produce gas, which can result in reduced tolerance of a product. Thus, by using a predigested fat source such as monoglycerides and / or fatty acids in a nutritional product, such as infant formula, it is now possible to provide infants with an alternative, or supplement, to breast milk that mimics more narrowly its benefits.

Along with the enhanced absorption of nutrients as described above, it has been found that the use of predigested fat in a nutritional product also facilitates the formation of micelles when administered with one or more water-insoluble hydrophobic compounds, such as soluble vitamins in oil (lipid soluble) (vitamins A, D, E, and K), carotenoids (eg, lutein, beta-carotene lycopene, etc.), glycolipids (gangliosides), sterols, and phytochemicals. The formation of these micelles allows insoluble hydrophobic compounds to dissolve in digestion, which is a stage for absorption by the intestinal villi. Also, the predigested fat will be used to re-synthesize triglycerides to form chylomicrons. Chylomicrons transport the water-insoluble hydrophobic compounds in the lymph, where the circulation transports the insoluble hydrophobic compounds to the target organs and / or tissues to produce the desired physiological effects.

In addition to the benefits described above, nutritional products that include predigested fat have been found to stimulate the production of cholecystokinin (CCK) in the duodenum, which stimulates the production of pancreatic lipase. This production results in additional digestion of nutrients and reduces contractions of the upper gastrointestinal tract, allowing more time for absorption. In this way, the use of predigested fat in nutritional products reduces the total amount of nutrients that enter the colon, which can ferment and produce gas and a bloated sensation. Thus, the use of predigested fats in nutritional products can improve tolerance by improving digestion and absorption of nutrients with less gas. This can be particularly important in infants, as tolerance can be a problem in some infants.

Along with stimulation of CCK production, predigested fat has also been found to induce secretion of intestinal growth hormone, glucagon-like peptide 2 (GLP-2). GLP-2 can enhance the maturation of the infant's gut, resulting in better digestion and absorption of nutrients.

It has further been found that the nutritional products described herein that comprise predigested fat can be used to provide a nutritional source for infants, children, or older children that can reduce the incidence of necrotizing enterocolitis (NEC), colic, and / or short bowel syndrome.

Furthermore, in embodiments where the nutritional product is manufactured by a process where at least a portion of the predigested fat (or in some embodiments all of the predigested fat) is added to the carbohydrate-mineral suspension as opposed to the protein in In the fat suspension, the resulting stability of the nutritional product (generally in the form of a nutritional emulsion) can be improved.

ES 2 552 525 T3

Examples

The following examples illustrate the specific embodiments and / or characteristics of the nutritional products of the present disclosure. The examples are provided for illustrative purposes only and should not be construed as limitations on the present disclosure, as many variations are possible without departing from the spirit and scope of the disclosure. All amounts illustrated are percentages by weight based on the total weight of the composition, unless otherwise specified.

Illustrative compositions are freestanding nutritional products prepared in accordance with the manufacturing methods described herein, such that each illustrative product, unless otherwise specified, includes an aseptically processed embodiment and a flexible packaged embodiment.

Nutritional liquid embodiments are aqueous oil-in-water emulsions that are packaged in 240 ml plastic containers and remain physically stable for 12-18 months after formulation / packaging at storage temperatures ranging from 1 to 25 ° C.

EXAMPLES 1-4 (for information)

Examples 1-4 illustrate lactose-free infant nutrition emulsions of the present disclosure, the ingredients of which are shown in the following Table. All ingredient quantities are listed as kilograms per 1000 kilograms of product batch, unless otherwise specified.

<td>Ingredient</td><td>Example 1</td><td>Example 2</td><td>Example 3</td><td>Example 4</td>

<td>Water</td><td>cs</td><td>cs</td><td>cs</td><td>cs</td>

<td>Maltodextrin</td><td> 53</td><td> 43,3</td><td> 50</td><td> 60</td>

<td>Saccharose</td><td> 16,5</td><td> 25</td><td> 19,2</td><td> 16,38</td>

<td>Milk protein isolate</td><td> 15,65</td><td> 15,65</td><td> 15,65</td><td> 15,65</td>

<td>Corn oil</td><td> 12</td><td> 12</td><td> 12</td><td> 12</td>

<td>High oleic safflower oil</td><td> 10</td><td> 10</td><td> 10</td><td> 10</td>

<td>Monoglycerol palmitate</td><td> 10</td><td> 9</td><td> 8</td><td> 7</td>

<td>C10-C24 Fatty Acid Calcium Salt</td><td> 6,0</td><td> 7</td><td> 8</td><td> 9</td>

<td>Coconut oil</td><td> 2</td><td> 2</td><td> 2</td><td> 2</td>

<td>Fungal oil</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Lecithin</td><td> 0,1</td><td> 0,1</td><td> 0,1</td><td> 0,1</td>

<td>Dibasic potassium phosphate</td><td> 0,96</td><td> 0,96</td><td> 0,96</td><td> 0,96</td>

<td>Potassium chloride</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Ascorbic acid</td><td> 0,235</td><td> 0,235</td><td> 0,235</td><td> 0,235</td>

<td>Carrageenan</td><td> 0,150</td><td> 0,150</td><td> 0,150</td><td> 0,150</td>

<td>Potassium hydroxide</td><td> 0,136</td><td> 0,136</td><td> 0,136</td><td> 0,136</td>

<td>Premix TM / UTM</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td>

<td>Vitamin A, D, Premix E</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td>

<td>Aqueous solution Vitamin premix</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td>

<td>Potassium iodide</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td>

<td>Chromium chloride</td><td> 0,000217</td><td> 0,000217</td><td> 0,000217</td><td> 0,000217</td>

EXAMPLES 5-8 (for information)

Examples 5-8 illustrate lactose-based nutritional emulsions of the present disclosure, the ingredients of which are shown in the following Table. All ingredient quantities are listed as kg per 1000 kg batch of product, unless otherwise specified.

<td>Ingredient</td><td>Example 5</td><td>Example 6</td><td>Example 7</td><td>Example 8</td>

<td>Water</td><td>cs</td><td>cs</td><td>cs</td><td>cs</td>

<td>Lactose</td><td> 58</td><td> 66</td><td> 71</td><td> 63</td>

ES 2 552 525 T3

<td>Ingredient</td><td>Example 5</td><td>Example 6</td><td>Example 7</td><td>Example 8</td>

<td>Skimmed milk powder</td><td> 25</td><td> 10</td><td> 0</td><td> 16</td>

<td>Milk protein concentrate</td><td> 6,4</td><td> 13</td><td> 18</td><td> 10,5</td>

<td>High oleic safflower oil</td><td> 14</td><td> 14</td><td> 14</td><td> 14</td>

<td>Coconut oil</td><td> 6,2</td><td> 6,2</td><td> 6,2</td><td> 6,2</td>

<td>Monoglycerol palmitate</td><td> 10</td><td> 8</td><td> 6</td><td> 4</td>

<td>C10-C24 fatty acids</td><td> 5,5</td><td> 7,5</td><td> 9,5</td><td> 11,5</td>

<td>Fructooligosaccharides / Galactooligosaccharides</td><td> 9</td><td> 9</td><td> 9</td><td> 9</td>

<td>Fungal oil</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Dibasic potassium phosphate</td><td> 0,96</td><td> 0,96</td><td> 0,96</td><td> 0,96</td>

<td>Calcium hydroxide</td><td> 0,78</td><td> 1,07</td><td> 1,36</td><td> 1,64</td>

<td>Potassium chloride</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Ascorbic acid</td><td> 0,235</td><td> 0,235</td><td> 0,235</td><td> 0,235</td>

<td>Carrageenan</td><td> 0,150</td><td> 0,150</td><td> 0,150</td><td> 0,150</td>

<td>Potassium hydroxide</td><td> 0,136</td><td> 0,136</td><td> 0,136</td><td> 0,136</td>

<td>Premix TM / UTM</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td>

<td>Vitamin A, D, E premix</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td>

<td>Aqueous solution Vitamin premix</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td>

<td>Potassium iodide</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td>

<td>Chromium chloride</td><td> 0,000217</td><td> 0,000217</td><td> 0,000217</td><td> 0,000217</td>

EXAMPLES 9-12 (for information)

Examples 9-12 illustrate nutritional emulsions of the present disclosure, the ingredients of which are shown in the following Table. All ingredient quantities are listed as kilograms per 1000 kilograms of product batch, unless otherwise specified.

<td>Ingredient</td><td>Example 9</td><td>Example 10</td><td>Example 11</td><td>Example 12</td>

<td>Water</td><td>cs</td><td>cs</td><td>cs</td><td>cs</td>

<td>Corn Syrup Solids</td><td> 53</td><td> 43,3</td><td> 50</td><td> 60</td>

<td>Saccharose</td><td> 16,5</td><td> 25</td><td> 19,2</td><td> 16,38</td>

<td>Soy protein isolate</td><td> 19,5</td><td> 19,5</td><td> 19,5</td><td> 19,5</td>

<td>Corn oil</td><td> 12</td><td> 12</td><td> 12</td><td> 12</td>

<td>High oleic safflower oil</td><td> 10</td><td> 10</td><td> 10</td><td> 10</td>

<td>Monoglycerol palmitate</td><td> 10</td><td> 9</td><td> 8</td><td> 7</td>

<td>C10-C24 fatty acids</td><td> 6,0</td><td> 7</td><td> 8,0</td><td> 9</td>

<td>Fungal oil</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>L-cystine</td><td> 2,3</td><td> 2,3</td><td> 2,3</td><td> 2,3</td>

<td>L-Tyrosine</td><td> 1,1</td><td> 1,1</td><td> 1,1</td><td> 1,1</td>

<td>Calcium hydroxide</td><td> 0,09</td><td> 1,0</td><td> 1,1</td><td> 1,2</td>

<td>L-Tryptophan</td><td> 0,66</td><td> 0,66</td><td> 0,66</td><td> 0,66</td>

<td>Dibasic potassium phosphate</td><td> 0,96</td><td> 0,96</td><td> 0,96</td><td> 0,96</td>

<td>Potassium chloride</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Ascorbic acid</td><td> 0,235</td><td> 0,235</td><td> 0,235</td><td> 0,235</td>

<td>Carrageenan</td><td> 0,150</td><td> 0,150</td><td> 0,0</td><td> 0,0</td>

<td>Potassium hydroxide</td><td> 0,136</td><td> 0,136</td><td> 0,136</td><td> 0,136</td>

<td>Premix TM / UTM</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td>

<td>Vitamin A, D, E premix</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td>

<td>Aqueous solution Vitamin premix</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td>

<td>Potassium iodide</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td>

ES 2 552 525 T3

EXAMPLES 13-16 (for information)

Examples 13-16 illustrate hydrolyzed protein based on the infant nutritional emulsions of the present disclosure, the ingredients of which are shown in the following Table. All ingredient quantities are listed as kilograms per 1000 kilograms of product batch, unless otherwise specified.

<td>Ingredient</td><td>Example 13</td><td>Example 14</td><td>Example 15</td><td>Example 16</td>

<td>Water</td><td>cs</td><td>cs</td><td>cs</td><td>cs</td>

<td>Saccharose</td><td> 42</td><td> 42</td><td> 42</td><td> 42</td>

<td>Starch</td><td> 21,8</td><td> 21,8</td><td> 21,8</td><td> 21,8</td>

<td>Hydrolyzed protein</td><td> 22,2</td><td> 22,2</td><td> 22,2</td><td> 22,2</td>

<td>High oleic safflower oil</td><td> 13,7</td><td> 13,7</td><td> 13,7</td><td> 13,7</td>

<td>MCT oil</td><td> 6</td><td> 6</td><td> 6</td><td> 6</td>

<td>Monoglycerol palmitate</td><td> 10</td><td> 9</td><td> 8</td><td> 7</td>

<td>C10-C24 fatty acids</td><td> 11</td><td> 9,5</td><td> 8</td><td> 6,5</td>

<td>Coconut oil</td><td> 5</td><td> 7,5</td><td> 9</td><td> 11,5</td>

<td>Fungal oil</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Calcium hydroxide</td><td> 1,6</td><td> 1,29</td><td> 1,1</td><td> 0,93</td>

<td>L-Methionine</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Dibasic potassium phosphate</td><td> 0,96</td><td> 0,96</td><td> 0,96</td><td> 0,96</td>

<td>Potassium chloride</td><td> 0,3</td><td> 0,3</td><td> 0,3</td><td> 0,3</td>

<td>Ascorbic acid</td><td> 0,235</td><td> 0,235</td><td> 0,235</td><td> 0,235</td>

<td>Carrageenan</td><td> 0,0</td><td> 0,0</td><td> 0,150</td><td> 0,150</td>

<td>Potassium hydroxide</td><td> 0,136</td><td> 0,136</td><td> 0,136</td><td> 0,136</td>

<td>Premix TM / UTM</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td><td> 0,1684</td>

<td>Vitamin A, D, E premix</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td><td> 0,0758</td>

<td>Aqueous solution Vitamin premix</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td><td> 0,0728</td>

<td>Potassium iodide</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td><td> 0,00022</td>

EXAMPLE 17

In this Example the absorption and related bioavailability of calcium salts of C10C24 fatty acids were evaluated.

Thirty rats were randomly assigned to one of three diets (Diet 1, Diet 2, and Diet 3) containing variable protein and fat. Diets 1-3 are the same as those used in AOAC method 906.48, except that Diets 1-3 are higher in fat and include maltodextrin as the carbohydrate source. Diet 1 contains 10% by weight of protein available as acidic casein and 23.6% by weight of fat available as an oil blend containing 30% by weight of coconut oil, 30% by weight of soybean oil, and 40% by weight of high oleic safflower oil (HOSO). The nutritional profiles of Diets 2 and 3 are identical to the nutritional profile of Diet 1 except that the proteins, fat, carbohydrates and minerals are mixed, homogenized and spray dried. Diet 3 differs from Diet 2 only in that the HOSO oil is replaced by the calcium salts of the fatty acids from high oleic safflower oil and the tricalcium phosphate is replaced with potassium phosphate in such a way that the overall nutrient and mineral profiles of Diet 2 and Diet 3 are the same. The calcium salts and fatty acids of HOSO provide 100% of the calcium in the diet.

The rats were fed one of Diet 1, Diet 2, or Diet 3 for a period of 4 weeks. Food / protein uptake and weight gain at the end of the feeding trial were used to calculate feed conversion (grams of weight gain / grams of food uptake) and protein efficacy ratio (grams of increase in weight / grams of protein ingested) (PER). If the caloric value (i.e. calories / grams of substance) of the calcium salt of HOSO fatty acids is significantly lower than that of HOSO due to poor absorption, then Diet 3 rats would be expected to gain as much less weight as they consume more feed to maintain growth, both of which result in lower feed conversion and PER.

Results shown in the table below indicate that Diet 3 rats have the same conversion

ES 2 552 525 T3 of food or PER than the control, indicated that the caloric value of the calcium salt of the fatty acid HOSO is not different from the oil HOSO. Thus, the calcium salts of the fatty acid HOSO are shown to be highly bioavailable.

<td></td><td>Protein efficacy ratio</td><td>Feed conversion</td>

<td>Diet 1 (Control 1)</td><td> 2,83 ± 0,28*</td><td> 0,29 +/-0,03</td>

<td>Diet 2 (Control 2)</td><td> 3,16 +/-0,17</td><td> 0,31 +/-0,02</td>

<td>Diet 3 (calcium salt of the fatty acid)</td><td> 3,32 +/- 0,27</td><td> 0,37 +/-0,03</td>

<td colspan="3">* Standard deviation (n = 10)</td>

EXAMPLE 18

In this Example, the absorption of soybean fatty acid salts was analyzed in 10-day-old pigs.

Sixteen piglets were randomized into two groups and housed individually in metabolic cages and trained to take nutritious emulsions from a bowl in 30 minutes. After one week of training in a commercial ready-to-drink hydrolyzed protein-based preparation, the pigs were fed both a commercial hydrolyzed protein-based powder preparation (Control) that included tricalcium phosphate and calcium carbonate as a source of calcium, or an emulsion (Experimental emulsion) that included calcium salts of soybean fatty acids as a source of calcium. Protein source and level, fat level, and mineral profiles are identical for the Control and Experimental Emulsion. The Experimental Emulsion, however, includes soybean fatty acids in place of soybean oil in the Control and includes calcium hydroxide as part of the calcium mineral system to neutralize soybean fatty acids. The potassium phosphate level of the experimental Emulsion was adjusted to correspond to the phosphorus content of the Control. Calcium from soy fatty acids provides 100% of the calcium in the experimental emulsion.

Apparent fat and calcium digestibility were calculated based on the following preparations after two weeks of feeding:

Apparent fat digestibility = ((fat intake - fecal fat) / fat intake) * 100

Apparent calcium digestibility = ((calcium intake - fecal calcium) / calcium intake) * 100

Dry matter digestibility = ((dry matter intake - fecal dry matter) / dry matter intake) * 100

A decrease in feed conversion (weight / feed uptake) and a decrease in fat, calcium, and dry matter digestibility of the experimental Emulsion would indicate that the calcium salts of soy fatty acids from the Experimental Emulsion are highly absorbed. wrong, and, thus, that the caloric value and the bioavailability of calcium are lower for the experimental Emulsion compared to the Control.

As shown in the following table, the feed conversion, the fat digestibility and the dry matter digestibility of the experimental Emulsion do not differ significantly from that of the Control, indicating that the calcium salts of the soy fatty acids of the Emulsion experimental are highly absorbed and bioavailable for neonatal pigs. In addition, the apparent calcium digestibility data shown below indicates that the calcium salts of the soy fatty acids in the Experimental Emulsion are more bioavailable than the calcium included in the Control (i.e., tricalcium phosphate and calcium carbonate). .

<td></td><td>Apparent fat digestibility</td><td>Feed conversion (Grams of weight gain per 1 gram of feed (dry matter))</td><td>Apparent calcium digestibility</td><td>Digestibility of dry material apparent</td>

<td>Control</td><td> 97,6 +/-1,0</td><td> 0,82 ± 0,14*</td><td> 81,8 +/-7,2</td><td> 97,8 +/-0,7</td>

<td>Emulsion experiences</td><td> 97,6 +/-1,4</td><td> 0,80 +/-0,15</td><td> 91,3 +/-3,3</td><td> 98,0 +/-1,0</td>

<td colspan="5">* Standard deviation (n = 10)</td>

EXAMPLE 19

In this Example the emulsifying properties of the calcium salts of fatty acids were analyzed.

A first emulsion (Control Emulsion) was prepared by shearing 18 g of soybean oil at 130 ° F (54.44 ° C) containing monoglycerol palmitate (5% oil by weight) and 430 mg of Ca (as tricalcium phosphate) with 500 ml of water using a high shear benchtop mixer. A second emulsion (Calcium Fatty Acid Emulsion) containing an identical level of calcium and fat (12 g of soybean oil plus 6 g of soybean fatty acids) as the Control Emulsion was prepared by: (1) fatty acid dispersion soybeans in oil in water at a temperature of about 130 ° F (54.44 ° C); (2) adding 430 mg of ca as calcium chlorides; (3)

ES 2 552 525 T3 adjusting the pH of the solution to about 7.0 using KOH; and (4) shearing the mixture using a high shear benchtop mixer.

The Control Emulsion and the Calcium Fatty Acid Emulsion were allowed to settle for a period of three weeks to test for separation of the emulsion. After a single overnight period, the Control Emulsion exhibits a visible phase separation that includes a creamy layer on top of the emulsion. (See Figure 1A). In contrast, after three weeks of storage, the calcium fatty acid emulsion has only a slightly detectable, but not very visible, soapy layer of calcium on top of the emulsion with the emulsion remaining in one phase. There is no visible calcium sediment on the bottom of the Calcium Fatty Acid Emulsion (See Figure 1B).

These results indicate that calcium salts of fatty acids are effective emulsifiers and are capable of providing a source of calcium for a nutritive emulsion that will not substantially settle out of solution. This allows for an emulsion product with improved stability and longer half-life.

EXAMPLE 20

In this Example, the fat absorption amount and the calcium absorption amount of two separate test formulations and a control formulation were measured in 10-day-old pigs.

The first test formulation (Formulation 1) includes palm olein oil in the fat system, the second test formulation (Formulation 2) includes predigested fat in the fat system, and the control formulation (Formulation 3) includes low oil content. in palmitic acid in the fatty system. The following Table lists the components of the fat systems of the three formulations.

<td>Nutrient (grams)</td><td>Formulation 1 (Palm olein oil formulation)</td><td>Formulation 2 (Predigested fat formulation)</td><td>Formulation 3 (Control Formulation that includes oil with a low content of palmitic acid)</td>

<td>Coconut oil</td><td> 37,2</td><td> 0</td><td> 84,1</td>

<td>Oil of high safflower oleic</td><td> 62,8</td><td> 108</td><td> 111,9</td>

<td>Soy fatty acids</td><td> 0</td><td> 56,9</td><td> 0</td>

<td>ARA oil</td><td> 3,03</td><td> 3,03</td><td> 3,03</td>

<td>DHA oil</td><td> 1,52</td><td> 1,52</td><td> 1,52</td>

<td>Palmitate monoglycerol</td><td> 0</td><td> 65,4</td><td> 0</td>

<td>Lecithin</td><td> 1,12</td><td> 1,12</td><td> 1,12</td>

<td>Palm olein</td><td> 122,7</td><td> 0</td><td> 0</td>

<td>Soy oil</td><td> 57,1</td><td> 0</td><td> 83,8</td>

All three formulations are prepared having nearly identical mineral and nutrient profiles. The fatty acid profile of Formulations 1 and 2 mimics the fatty acid profile of human milk. Calcium hydroxide is included in Formulation 2 (in an amount sufficient to chelate free fatty acids) as a source of calcium, which reacts with soybean fatty acids to form calcium salts of insoluble fatty acids. This reaction eliminates the sensation of bitterness and burning in the throat imparted by free fatty acids. Furthermore, the level of potassium phosphate in Formulation 2 is increased to correspond to the level of phosphorus in Formulations 1 and 3. The calcium salt used in Formulations 1 and 3 is a calcium phosphate.

60 pigs older than 10 days (plus or minus two days) were randomized to receive either Formulation 1, Formulation 2, or Formulation 3. The pigs were housed individually in metabolic cages and fed five times a day for three weeks. after four days of training and adaptation. Fecal debris from day two to day eight was collected and analyzed for calcium absorption and fat absorption. Calcium absorption was calculated as the amount of calcium in the stool divided by the amount of calcium in the diet, multiplied by 100. Fat absorption was calculated as the amount of fat in the stool divided by the amount of fat in the diet, multiplied by 100. The results are shown in the following Table:

<td rowspan="2"></td><td colspan="2">Fat absorption Calcium absorption</td>

<td> (%)</td><td> (%)</td>

<td>Formulation 1 (palm olein)</td><td> 92,3 ± 3,9</td><td> 88,9 ± 4,7</td>

<td>Formulation 2 (predigested fat)</td><td> 98,2 ± 0,7</td><td> 93,1 ± 2,4</td>

ES 2 552 525 T3

<td></td><td>Fat absorption (%)</td><td>Calcium absorption (%)</td>

<td>Formulation 3 (control: fatty system with a low concentration of palmitic acid)</td><td> 98,0 ± 1,4</td><td> 90,7 ± 3,5</td>

As the results in the Table above indicate, the use of a predigested fat system allows an infant formula to mimic the fatty acid profile of human milk without the adverse effects on calcium and fat absorption as has been experienced with the system. fatty from palm olein oil. The fat and calcium absorption rates of Formula 2 (the predigested fat formulation) are at least as good as those of the formula with a low concentration of palmitic acid. These findings illustrate that calcium salts of soy fatty acids are widely available in neonatal pigs.

EXAMPLE 21

In this example, the postprandial increase in CCK production (ABC) and motilin production (ABC) were evaluated in the pigs of Example 20.

At the conclusion of the fat and calcium absorption analysis described in Example 20, the pigs given Formulation 2 (predigested fat formulation) or Formulation 3 (control formulation including a low concentration of palmitic acid) were fed for 12 hours, and fasting blood was drawn to isolate plasma. The pigs were allowed to recover for two hours and then 250 ml of both Formulation 2 and Formulation 3 were administered. Postprandial blood samples were drawn at 30 and 60 minutes after feeding and assayed for CCK and motilin. The postprandial increase in CCK (area under the curve) and motilin (AUC) was calculated. The results are shown in the table below.

<td rowspan="2"></td><td colspan="2">Formulation 2 (formulation of</td><td rowspan="2">Formulation 3 (Control: formulation with a low concentration of palmitic acid) (pg / ml * min)</td>

<td>predigested fat) * min)</td><td>(pg / ml</td>

<td>Postprandial increase in CCK secretion (area under the curve)</td><td colspan="2"> 1935±1464</td><td> 1046±754</td>

<td>Motilin AUC (postprandial increase)</td><td colspan="2"> 483±253</td><td> 839±403</td>

The data in the table above show that replacing triglycerides with predigested fat (monoglycerol palmitate plus soybean fatty acids) stimulates postprandial secretion of CCK, which has been shown to stimulate secretion of pancreatic digestive enzymes, enhances contraction of the gallbladder, and slows the transit from the mouth to the cecum. Thus, formulations with predigested fats can stimulate more digestible enzyme secretion and slow GI transit to allow greater digestion and absorption of nutrients. In this way, formulations that include predigested fat can improve tolerance to the preparation since undigested nutrients can cause excess colonic fermentation that produces gas, diarrhea, and stomach distension.

Furthermore, the data in the table above show that substituting digested fat for triglycerides (monoglycerol palmitate plus soybean fatty acids) reduces postprandial motilin secretion. Infants with colic have been shown to have a lower postprandial CCK level but a higher postprandial motilin level. This imbalance between postprandial gut hormones produces GI contractions in the infant, resulting in abdominal pain. The data in the table above show that the inclusion of predigested fat enhances the postprandial CCK level in an infant but reduces the level of motilin, thereby reducing hormonal imbalance to relieve GI contractions, abdominal pain, and colic.

EXAMPLE 22

In this example, the pigs of Example 20 were used to study the effect of various fat systems on palmitic acid and palmitic acid Sn-2 levels of chylomicron triglycerides.

The 1 hour postprandial blood sample was drawn from each pig and plasma was isolated, frozen in liquid nitrogen, and stored in a -80 ° C freezer. Total lipids were extracted from plasma using Folch solvent. Triglycerides were isolated by thin layer chromatography. The table below shows plasma triglyceride palmitic acid and Sn-2 palmitic acid from Formulation 1 (palm olein formulation) and Formulation 2 (predigested fat formulation). Chylomicron triglycerides and Sn-2 palmitic acid from pigs fed these two formulations are also shown in the table.

ES 2 552 525 T3

<td rowspan="2">Triglycerides in plasma of human infants breastfed</td><td>I Sn-2 I</td><td> 25,5</td>

<td>Triglycerin</td><td>LO OJ</td>

<td rowspan="2">Triglycerides in plasma from pigs fed the Formulation 2</td><td>Sn-2 |</td><td> 14,4</td>

<td>Triglycerin</td><td> 18,5</td>

<td rowspan="2">Formulation 2: (Fat predigested)</td><td>I Sn-2 I</td><td> 5,2</td>

<td>Triglycerin</td><td> 21,4</td>

<td rowspan="2">Triglycerides in plasma from pigs fed the Formulation 1</td><td>I Sn-2 I</td><td> 10,6</td>

<td>Triglycerides</td><td> 18,3</td>

<td rowspan="2">Formulation 1: (Palm Olea)</td><td>I Sn-2 I</td><td> 5,8</td>

<td>Triglycerides</td><td> 23,3</td>

<td></td><td></td><td>Palmitic acid level (%)</td>

ES 2 552 525 T3

As shown in the table above, plasma triglycerides from pigs fed predigested fat preparations have significantly higher plasma triglyceride Sn-2 palmitic acid content than pigs fed palm olein preparation. The palmitic acid / palmitic acid Sn-2 ratios of triglycerides in plasma are approximately 1.7 and 1.3, respectively, for Formulation 1 and Formulation 2, and this ratio is known to be approximately 1.1 for breastfed infants. Thus, these data indicate that the predigested fat formulation better mimics human milk than the palm olein fat formulation.

EXAMPLE 23

In this Example the pigs of Example 20 are used to study the effect of various fat systems on blood levels of lutein.

Plasma was extracted from a 1 hour postprandial blood sample from each pig using a solvent of chloroform and methanol in a 2: 1 ratio. The solvent was removed and the resulting lipids were poured out and analyzed for lutein using standard methods. The table below shows the lutein level of pigs fed Formulation 1 (palm olein formulation), Formulation 2 (predigested fat formulation), and Formulation 3 (formulation with a low concentration of palmitic acid) in mg of lutein. per mg of lipids.

<td></td><td>Formulation 1: (Palm Olein)</td><td>Formulation 2: (Predigested fat)</td><td>Formulation 3: (Low concentration of palmitic acid)</td>

<td>Lutein level</td><td>N / A *</td><td>0.765 pg</td><td>0.539 pg</td>

<td colspan="4">* The lutein level of Formulation 1 is too low to measure.</td>

As shown in the table above, pigs fed formulations that include predigested fat have increased lutein absorption compared to pigs fed formulations of palm olein or a low concentration of palmitic acid.

EXAMPLE 24

In this Example Formulation 2 (predigested fat formulation) and Formulation 3 (formulation with a low concentration of palmitic acid) of Example 20 were used to study the effects of various fat systems on lutein levels in micelles.

Formulation 2 and Formulation 3 are reconstituted with water (133 g of powder formulation per 1.0 L of water), and HCl is added to adjust the pH of the reconstituted formulations to 4.5. The reconstituted formulations are digested for 1 hour at room temperature by adding 1.00 ml of USP pepsin (56 mg / ml) to 40 ml of the reconstituted formulation. The pH of the reconstituted formulations is adjusted to 7.0 after digestion with pepsin and then a mixture of 28 mg of pancreatin amylast USP / protease, 28 mg of pancreatin lipase USP, and 108 mg of bile extracts is added to the digested formulations. with pepsin. The formulations are further digested at room temperature for 2 hours and centrifuged (31,000 g at 20 ° C for 3 hours). The digested formulations form an oil / cream plug, an aqueous phase, and a sediment layer. The aqueous phase is extracted for lutein analysis from micelles, which act as transporters during absorption of lutein in aqueous light. The following table shows the lutein level of micelles per kg of digested formulation.

<td></td><td>Formulation 2 digested: (Predigested fat)</td><td>Digested Formulation 3: (Low concentration of palmitic acid)</td>

<td>Lutein in micelles (pg)</td><td>0.598 pg</td><td>0.246 pg</td>

As shown in the table above, the amount of micelle lutein found in the digested formulation that includes predigested fat was more than twice the amount of micelle lutein found in the digested formulation that includes a low concentration of palmitic acid, thus indicating that the use of predigested fat can increase the absorption of lutein.

EXAMPLE 25

In this Example the ability of predigested fat to reduce the incidence of loose stool was tested.

Thirty weaned rats were fed a hydrolyzed protein-based infant powder formula comprising MCT oil as 30% of the fat source for a four-day adaptation period. At the end of the adaptation period, the rats were randomly assigned to two groups and fed both a Control Formulation (powdered infant formula with a low concentration of palmitic acid) and a Test Formulation (infant formula that contains predigested fat). The nutrient profile of the Control Formulation and the Test Formulation are identical. The rats were allowed free access to the

ES 2 552 525 T3 food and water for a period of five days, and the amount of food ingested and body weight were recorded daily.

Although there are no significant differences in food uptake or weight gain between the two groups, there is a significant difference in stool consistency. Rat stool consistency was scored using a 0-5 point system for at least two days of feeding. The score is based on the severity and consistency of the adhesion of the feces on a blotter sheet at the bottom of the cage. A score of 0 indicates normal stools and a score of 5 indicates watery diarrhea. As shown in Fig. 2, rats fed the Control Formulation (containing the MCT oil) produced looser stools than rats fed the Test Formulation (containing the predigested fat).

EXAMPLE 26

In this example, the ability of predigested fat to reduce the incidence of necrotizing enterocolitis (NEC) was tested.

Preterm pigs (92% gestation) delivered by cesarean section were immediately transferred to an incubator with oxygen (37 ° C), and a vascular catheter was placed in the umbilical artery. The pigs were given three injections (4, 6, and 7 ml / kg body weight) of maternal plasma via the vascular catheter during the first 24 hours. Total parenteral nutrition (TPN) was provided at a rate of 4-6 ml / kg / hour for 24 hours. Pigs were then randomized to receive both the Control Formulation and a PDF Formulation at a rate of 5 ml / kg / hour via an orogastric tube. The Control Formulation and the PDF Formulation are identical with the exception of the fat systems of the above. Specifically, the fat system in the Control Formulation includes vegetable oil, and the fat system in the PDF Formulation includes 30% monoglycerol palmitate, 20% soybean fatty acids, 26% high oleic safflower oil, 14% coconut oil, and 10% tributyrin. The Control Formulation and the PDF Formulation include 100 g of protein, 47 g of fat, and 50 g of corn syrup per liter of formulation. Pigs were euthanized after 36 hours of enteric feeding and necropsy was performed to assess the severity of NEC lesions using a 1-5 scoring system with a score of 1 indicating that there were no signs of NEC. The results are shown in the table below.

<td></td><td colspan="2">Block 1</td><td colspan="2">Block 2</td>

<td></td><td>Control formulation (n = 5)</td><td>PDF formulation (n = 3)</td><td>Formulation control (n = 5)</td><td>PDF formulation (n = 3)</td>

<td>Early death by NEC</td><td> 2</td><td> 0</td><td> 3</td><td> 1</td>

<td>NEC detected at necropsy</td><td> 2</td><td> 1</td><td> 0</td><td> 0</td>

<td>Total NEC</td><td> 4</td><td> 1</td><td> 3</td><td> 1</td>

As shown in the table above, five of the ten pigs (50%) that were fed the Control Formulation died of NEC before the conclusion of the enteric feeding period, but only one of the pigs (16.7%) fed with the PDF Formulation he died of NEC before the conclusion of the enteric feeding period. In addition, it was determined that seven of the ten pigs (70%) fed with the Control Formulation had NEC at the conclusion of the enteric feeding period, while it was determined that only two of the six pigs (33%) that were fed the PDF formulation had NEC at the conclusion of the enteric feeding period. In this way, it can be concluded that by replacing a vegetable oil fatty system with a fatty system that includes predigested fat, the incidence of NEC can be decreased.