Nutritional products including a novel fat system including monoglycerides.

(54) Title: NUTRITIONAL PRODUCTS THAT INCLUDE A NOVEL FAT SYSTEM THAT INCLUDES MONOGLYCERIDES.

(54) Title: NUTRITIONAL PRODUCTS INCLUDING A NOVEL FAT SYSTEM INCLUDING MONOGLYCERIDES.

(57) Summary

The present invention relates to a nutritional product comprising proteins, carbohydrates, and a fat system, the fat system comprising at least 10% by weight of monoglycerides containing fatty acids, wherein at least 70% of fatty acids in monoglycerides they are in the Sn-1 position, and where the nutritional product is selected from a liquid emulsion or a powder that can be reconstituted as a liquid emulsion.

(57) Abstract

Dlsclosed are nutrltlonal formulations ¡ncludlng predlgested fats that can be administered to preterm infants, infants, toddlers, and chlldren for ¡mprovlng tolerance, digestion, and absorptlon of nutrlents and for reduclng the ¡ncldence of necrotlzlng enterocolitis, collc, and short bowel syndrome. The predlgested fats Include fatty acld-contalnlng monoglycerides and / or a fatty acid component.

Institute

Mexican Property

Industrial

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PATENT TITLE NO. 344271

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Owner (s): ABBOTT LABORATORIES

Address: 100 Abbott Park Road, Dept. 0377 AP6A-1, Abbott Park, Illinois, 60064, USA

Name: NUTRITIONAL PRODUCTS THAT INCLUDE A NOVEL FAT SYSTEM THAT INCLUDES MONOGLYCERIDES.

Classification: lnt.CI.8: A23L33 / 115; A23L33 / 12; A61P1 / 00

Inventor (s): CHRON-SI LAI

REQUEST

Number: Intemactonals filing date

MX / a / 2013/007691 V December 21, 2011

PRIORITY

<td>Country:</td><td>Date:</td><td>Nu ipfNrp »:</td>

<td>US</td><td>December 29, 2010</td><td> 61/428,168</td>

<td>US</td><td>December 29, 2010</td><td> 61/428,173</td>

<td>US</td><td>December 29, 2010</td><td> 61/428,176</td>

<td>US</td><td>December 29, 2010</td><td> 61/428,177</td>

<td>US</td><td>December 29, 2010</td><td> 61/428,185</td>

Validity: Twenty years

Veiicimicmto Date: December 21, 2031 the patent of reference? Is granted based on articles 1 ·. 2nd fraction V, 6 = ration III, and 58 of the Industrial Property Law.

In accordance with article 23 of the Industrial Property Law, the patent will be valid for twenty years, non-extendable, counted from the date of filing of the international application and I will be subject to the payment of the fee to maintain the rights in force.

Whoever subscribes to this title does so based on the provisions of articles 6, sections III and 7, bis 2 of the Industrial Property Law (Official Journal of the Federation (DOF) 06/27/1991, amended on 02 / 08/1994, 10/25/1986, 12/26/1987, 05/17/1999, 01/26/2004, 06/16/2005, 01/25/2006, 06/05/2009 / 06/01 / 2010, 06/18/2010, 06/28/2010, 01/27/2012 and 04/09/2012): Articles 1, 3 »section V, subsection a), 4 and 12, sections I and III of the Regulation of the Mexican Institute of Industrial Property (DOF 14/12/1999, amended on 07/01/2002, 07/15/19) 2004, 07/28/2004 and 09/07/2007); Articles 1, 3, 4, 5, section V, subsection a), 16 sections I and III and 30 of the Organic Statute of the Mexican Institute of Industrial Property (DOF) 12/27/1999, amended on 10/10/2002, 07/29/2004, 08/04/2004 and 09/13/2007); 1, 3 and 5 paragraph a) of the Agreement that delegates powers to the Deputy Directors General, Coordinator, Divisional Directors, Heads of Regional Offices, Divisional Deputy Directors, Departmental Coordinators and other subordinates of the Mexican Institute of Industrial Property. (DOF 12/15/1999, amended on 02/04/2000, 07/29/2004, 08/04/2004 and 09/13/2007).

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MEXICAN INSTITUTE OF INDUETRAL PROPERTY

NUTRITIONAL PRODUCTS THAT INCLUDE A SYSTEM OF

NOVEL FAT INCLUDING MONOGLYCERIDES

Cross reference with related requests

This application claims the benefit of the North American provisional application No. 61 / 428,168 filed on December 29, 2010; US provisional application No. 61 / 428,173 filed on December 29, 2010; US provisional application No. 61 / 428,176 filed on December 29, 2010, US provisional application No. 61 / 428,177 filed on December 29, 2010; and US Provisional Application No. 61 / 428,185 filed on December 29, 2010, the descriptions of which are incorporated by reference in their entirety.

Field of the Invention

The present disclosure relates to nutritional products comprising predigested fat and to methods for the use of nutritional products. More particularly, the present disclosure relates to products for infants, children, and pediatric products comprising monoglycerides containing fatty acid and / or fatty acid component that provide nutritional benefits including improved digestion, tolerance and absorption of nutrients, as well as reduction in the incidence of necrotizing enterocolitis, colic and short bowel syndrome.

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MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

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Invention of the Invention

Nutritional liquids and powders, including infant and pediatric formulas, that comprise a specific selection of nutrients that are well known and widely available, some of which may provide a single source of nutrition, while others may provide a supplemental source. These nutritional products 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 nutritional liquids are especially useful when formulated with selected nutritional ingredients.

Although breast milk is generally recognized as the best nutrition for newborns, not all mothers can successfully breastfeed. Breast milk substitutes (infant formulas) can provide complete nutrition, and have been proven to meet the child's normal growth and developmental nutritional needs. Unfortunately, a small percentage of formula-fed newborn babies may experience gastrointestinal (Gl) intolerance problems, including diarrhea, gas, necrotizing enterocolitis, colic, and the like.

The problem of gastrointestinal intolerance may be at least in part due to incomplete digestion of nutrients and absorption in the infant. To deal with this problem of

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ingredient, while others replace intact milk protein with hydrolyzed protein for a baby's digestion system.

Also, some newborns have a much higher fat absorption rate than breastfed babies. This difference in fat absorption rate decreases as children get older. Presumably, newborns are lipase deficient, and therefore do not digest and absorb fat, as do breastfed babies who receive lipase in breast milk.

The digestion system of a premature newborn is less developed than that of a term newborn, however they need more nutrients (calories) than term infants to promote growth and development. Medium Chain Triglycerides (MCT Oil) are easy to digest and absorb, and have been included in formulas for premature babies to improve fat, protein and calcium absorption. The medium chain fatty acids included in the medium chain triglycerides, however, are not used to resynthesize the triglycerides to form chylomicrons after the MCT oil is digested and absorbed. Like many lipid soluble nutrients, such as carotenoids and vitamins A, D, E, and K, they are believed to be

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C i LA PUOPI INDUSTR> INDUSTRIAL packaged in chylomicrons before entering the systemic circulation, the benefit provided by MCT oil in the absorption of soluble lipid nutrients, which is also important for growth and development, may be more 5 limited.

Although attempts have been made in the past to resolve Gl and other problems set forth above, it would be desirable to provide infant and pediatric formulas that can provide nutritional benefits similar to breast milk, and also provide good tolerance, digestion and absorption of hydrophobic nutrients. insoluble in water, as well as a reduction in the incidence of conditions such as necrotizing enterocolitis, colic, and short bowel syndrome. Furthermore, it would be beneficial if these formulas could be free of 15 stabilizers, and specifically free of carrageenan.

Brief Description of the Invention

The present disclosure refers to nutritional products, and specifically infant formulas, which include predigested fat containing monoglycerides containing fatty acid and / or a fatty acid component. These nutritional compositions can be used advantageously to provide increased tolerance, digestion, and absorption of nutrients, including water-insoluble / lipid-soluble nutrients, and to reduce the incidence of necrotizing enterocolitis, colic, and short bowel syndromes. In some modalities, the

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Fatty Acid Component may be in foriTra 'efe acid-graee or provided as calcium or magnesium salts of the fatty acid, providing the added benefit of additional nutrients.

One embodiment is a fat system of a nutritional product that includes at least 10% by weight of fatty acid-containing monoglycerides. At least 70% of the fatty acid in the monoglycerics is in the Sn-1 position.

Another embodiment is an infant formula that includes at least 10% by weight of fatty acid-containing monoglycerides. At least 70% of the fatty acid in the monoglycerides are in the Sn-1 position.

Nutritional products such as infant formulas for young children and pediatric formulas including predigested fat, such as monoglycerides and fatty acids described in this document, have been found to reduce the overall fat load on the digestive system of a child to improve fat digestion and infant absorption, including absorption of water-insoluble / lipid-soluble nutrients. Specifically, the absorption of predigested fat in the proximal part of the small intestine stimulates the secretion of CCK, which promotes the maturation of alpha cells in the pancreas and the secretion of digestive enzymes. In addition, GLP-1 and GLP-2 secretion is stimulated, further promoting intestinal maturation.

Surprisingly, the use of

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a and the subsequent secretion of COK and GLP-1 retarTFoél and stimulates the secretion of pancreatic enzymes to allow the digestion of nutrients and more complete absorption. The reduction in the amount of nutrients entering the baby's colon results in reduced fermentation in the colon, which is part of the cause of loose stool and gas problems. Furthermore, it has been found that the use of predigested fat can reduce the incidence of necrotizing enterocolitis, colic, and / or short bowel syndrome.

Furthermore, it has been found that the unsaturated fatty acid component of the predigested fat can react with sources of calcium or magnesium and the resulting formed salts are surprisingly bioavailable. In addition to providing a good source of calcium or magnesium, these calcium or magnesium salts are also surprisingly mild, in contrast to fatty acids that are generally bitter and impart a strong burning sensation to the throat. Furthermore, it has been found that magnesium or calcium fatty acid salts surprisingly act to stabilize nutritional emulsions, as they do not form a hard to disperse settlement in the emulsion as many insoluble calcium salts are prone to do. As such, in many embodiments, the inclusion of magnesium or calcium fatty acid salts as part of the predigested fat can eliminate the need for stabilizers, such as carrageenan.

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Brief description of the Drawings ................

Figures 1A and 1B show a drawing of a control emulsion and an experimental emulsion according to the preparation of Example 19.

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

Detailed description of the invention

The nutritional products described herein comprise predigested fat. In many embodiments, the products include fatty acid-containing monoglycerides and a fatty acid component such that the predigested fat system includes two components. By reducing the burden on the child, or the child's digestive system, a number of benefits are realized while providing a stable and bioavailable product. These and other features of nutritional products, as well as some of the many optional variations and additions, are described in detail below.

The terms replica packaging and replica sterilization are used interchangeably throughout this document, and unless otherwise specified, it refers to the common practice of filling a container, more typically a metal can or other similar package, with a nutrient liquid. and then the liquid-filled container is subjected to the heat sterilization step necessary to form a sterilized nutritional liquid product, replicated.

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

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, including from about 6 months to about 24 months, and also including from about 12 months to about 18 months.

The terms nutritional formulation or product

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DE The frc «koa r \. . ._I1t „. . ,. . . III XpUSTRtAl •ⁱ»£“ £ 25 ** nutritional or nutritional composition as used here are used interchangeably and, at least to the contrary, “they refer to liquid and solid fortifiers of human milk (including semi-liquids and semi-solids), liquid and solid formulas for premature infants, liquid and solid infant formulas, follow-up liquid and solid formulas, liquid and solid pediatric formulas, and liquid and solid infant formulas. Solids can be powders that can be reconstituted to form a nutritional liquid, they all comprise one or more of the following; fat, protein and carbohydrates 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, concentrated form, and nutritional liquids, made by reconstitution of nutritional powders described in this document. Before its use.

The term nutritional powder, as used herein, unless otherwise specified, refers to easy-to-handle or fluid nutritional products that can be reconstituted with water or another aqueous liquid prior to consumption and includes powders dried by spray and dry / dry grind mixes.

The term baby, as used herein, unless

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to the contrary, it refers to a person 12 months or younger. The term premature baby as used here refers to a baby born before 36 weeks of gestation.

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

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

The term "predigested fat" as used herein, unless otherwise specified, refers to monoglycerides containing fatty acid and / or a fatty acid component.

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

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

The term fortifying human milk, as used herein, unless otherwise specified, is

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refers to liquid and solid nutritional products suitable for mixing with breast milk or formula for premature infants or infant formula for consumption by a premature or full-term newborn.

The term fatty acid-containing monoglyceride as used herein, unless otherwise specified, refers to a glyceride consisting of a fatty acid chain covalently linked to a glycerol molecule via an ester bond in one of the glycerol Sn-1 (a), Sn-2 (β), or Sn-3 (a ') molecule positions ·

The term "fatty acid component" as used herein, unless otherwise specified, refers to free fatty acids or fatty acid salts such as magnesium or calcium fatty acid salts derived from a source having less 20% (by weight) of calcium or 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 (eg, vitamins A, D , E, and K), carotenoids (eg, lutein, beta-carotene, lycopene, etc.,), glycolipids (gangliosides), sterols, and phytochemicals.

The numerical ranges as used here are intended to include each number and subset of numbers within that range, either specifically described or

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numerical ranges should be interpreted '| lli I | ij _L Support for a claim directed to any number or subset of numbers in description from 1 to 10 is due from 2 to 8, from 3 to 7, from 5 to 6, successively.

All references to that range. For example, an interpret that supports a range from 1 to 9, 3.6-4.6, 3.5-9.9, and thus the unique features or limitations of the present invention should include the corresponding plural feature or limitation, and vice versa, unless specified the opposite or clearly implied to the contrary by the context to which reference is made.

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

The various modalities of the nutritional products of the present disclosure may also be substantially free of any optional or selected ingredients or characteristics described herein, provided that the remaining nutritional product still contains all the required ingredients or characteristics as described herein. In this context, and unless otherwise specified, the term substantially libr means that the selected nutritional product contains functional optional ingredient,

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less than a quantity

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typically less than 1%, even less than 0.5%, even less than 0.1%, and even also zero percent, by weight, of such selected or optional ingredients.

Nutritional products and methods may comprise, consist of, or consist essentially of the elements of the products as described herein, as well as any additional or optional elements described herein or otherwise useful in the nutritional product and applications. of the method.

Product form

The nutritional products containing predigested fat and related methods of the present disclosure can be formulated and administered in any known suitable oral product form or other form. Any solid, semi-solid, liquid, semi-liquid, or powder form, including combinations or variations thereof, are suitable for use in this invention, as long as these forms allow for safe and effective oral administration to the individual of the ingredients as defined herein. .

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

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continuation.

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The products may include any form of product that comprises the ingredients described herein, and that is safe and effective for oral administration. The nutritional products described, or can be modified with optional ingredients to form a product.

The nutritional products of the present invention are preferably formulated as dietary product forms, which are defined as modalities comprising the ingredients of the present invention in a product form containing at least one of the following: fat, protein, and carbohydrates and Preferably, it also contains vitamins, minerals, or combinations thereof. In many modalities, the product will comprise predigested fat in combination with protein, carbohydrates, vitamins, and minerals to produce a nutritional product.

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

Specific non-limiting examples of product forms

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Suitable for your describe, include, liquid and powder ^Df MransnAB OUSTRIA For use with pre-digested fat as for example, human milk fortifiers liquid and powdered formulas for premature babies, liquid and powdered infant formulas, liquid and powdered semi-elemental and elemental formulas, liquid and powdered pediatric formulas and formulas for children, liquid and powder.

Nutritional Fluids

Nutritional liquids include both concentrated nutritional liquids and ready-to-drink liquids.

These nutritional liquids are most typically formulated in the form of suspensions or emulsions.

Nutritional emulsions suitable for use can be aqueous emulsions that contain protein, fat and carbohydrates. These emulsions are generally fluid or drinkable liquids from about 1 ° C to about 25 ° C and are typically in the form of oil-petticoat, water-in-oil, or complex aqueous emulsions, although such emulsions are more typically in the form of emulsions. oil-in-water that have a continuous aqueous phase and a discontinuous oil phase.

Nutritional emulsions can be and typically are stable. Nutritional emulsions typically contain up to about 95% by weight of water, including from about 50% to about 95%, including

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Nutritional emulsions may have a caloric density tailored to the nutritional needs of the end user, although in most cases emulsions generally contain at least 19 kcal / fluid ounce (660 kcal / liter), more typically about 20 kcal / fluid ounce (675-680 kcal / liter) to approximately 25 kcal / fluid ounce (820 kcal / liter), even more typically from about 20 kcal / fluid ounce (675-680 kcal / liter) to about 24 kcal / fluid ounce (800-810 kcal / liter). In general, formulas with 22-24 kcal / fluid ounce (740-810 kcal / liter) are most often used in premature or low birth weight babies, and formulas with 20-21 kcal / fluid ounce (675 at 680 to 700 kcal / liter) are most often used in term-born children. In some embodiments, the emulsion may have a caloric density of approximately 100 kcal / liter at

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approximately 660 kcal / liter, even from approximately

150 kcal / liter to approximately 500 kcal / liter.

The nutritional emulsion can have a pH ranging from about 3.5 to about 8, but is more advantageously in a range from about

4.5 approximately

7.5, including from

5.5 approximately

7.3, including from approximately

6.2 approximately

7.2.

Although the serving size of the nutritional emulsion may vary depending on a number of variables, a typical serving size is generally at least about 2 ml, or even at least about 5 ml, or even at menbs approximately 10 ml, or even at least approximately 25 ml, including the interval from approximately 2 ml to approximately 300 ml, including from approximately 4 ml to approximately 250 ml, and that includes from approximately 10 ml to approximately 240 ml.

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

Nutritional Solids

> Nutritional solids can be in any solid form, but are typically in the form of compositions n iMPIftiSI

INSTITUTE fluid or substantially fluid particles> ® ^_]«° J ^_TOsuch '* JSJ! EJ? üs particle compositions. Particularly suitable nutritional solid forms of nrnrin ^ i ?? · include spray-dried or dry-mixed compositions. The compositions can be easily measured with a spoon or other similar device, where the compositions can be easily reconstituted by the intended user with a suitable aqueous liquid, typically water, to form a nutritional formulation for immediate oral or enteral use. In this context, immediate use generally means within about 48 hours, more typically within about 24 hours, preferably just after reconstitution.

Nutritional powders can be reconstituted with water before use at a caloric density tailored to the nutritional needs of the end user, although in most cases the powders are reconstituted with water to form compositions comprising at least 19 kcal / fluid ounce (660 kcal / liter), more typically from about 20 kcal / fluid ounce (675-680 kcal / liter) to about 25 kcal / fluid ounce (820 kcal / liter), even more typically d from about 20 kcal / fluid ounce (675-680 kcal / liter) to about 24 kcal / fluid ounce (800-810 kcal / liter). In general, formulas with 22-24 kcal / fluid ounce (740-810 kcal / liter) are most often used in very young or

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Low birth weight, and formulas with 20-21 kcal / fluid ounce (675-680-700 kcal / liter) are most often used in term-born infants. In some embodiments, the reconstituted powder can have a caloric density of from about 50 kcal / liter to about 660 kcal / liter, including from about 100 kcal / liter to about 500 kcal / liter.

As noted above, nutritional products may also be in the form of a semi-solid that includes those forms that are intermediate in properties, such as stiffness, between solids and liquids. Some examples include jellies, puddings, and pasta.

Predigested fat system

A. Monoglycerides that contain fatty acid

In some embodiments, the nutritional products of the present invention include fatty acid-containing monoglycerides, also known as monoacylglycerols, alone or in combination with a fatty acid component as described below. Monoglycerides are normal metabolites in the body that are formed during the breakdown of triglycerides and diglycerides. As noted, fatty acid-containing monoglycerides can be included in nutritional products in combination with a fatty acid component, such as fatty acids and / or salts of fatty acids as described below, or may be included in nutritional products in a fatty.

The monoglycerides that

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Containing fatty acid suitable for use in nutritional products can include fatty acids that have a chain length of 4 to 22 carbon atoms, including fatty acids that have a chain length of 14 to 20 carbon atoms, and even palmitic acid (16 carbon atoms). Particularly preferred are monoglycerides in which at least 70% of the fatty acids in the monoglycerides are in the Sn-1 position, including monoglycerol palmitate that has at least about 70% palmitic acid residues in the Sn- position. 1 (also known as the alpha position), including at least about 80% in the Sn-1 position, and including from about 85% to about 100% in the Sn-1 position. Furthermore, in some embodiments, the monoglycerides included in the nutritional products described herein may include traces of diglycerides, free glycerol, and / or free fatty acids. As used herein, the term "traces" means amounts not greater

10% by weight, but more commonly less than 7.5% by weight.

In a specific embodiment, the (and optionally as discussed below) are partially or fully provided to the product through the use of

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origeri'Tnimaí, monoglycerides and fatty acids can be added to the nutritional product by pancreatic lipase.

Alternatively, lard or tallow can be hydrolyzed prior to incorporation into the nutritional product to produce monoglycerides and fatty acids, which can be introduced into the nutritional product. Lard, tallow, or lard or hydrolyzed tallow can provide part or all of the monoglycerides and / or fatty acids in the nutritional product.

In another embodiment, the monoglycerides in the nutritional product are partially or totally derived from oils, such as vegetable oils, marine oils, fish oils, algae oil, mushroom oils, tree resin oils, and combinations thereof. Suitable vegetable oils include, for example, olive oil, caneola oil, corn oil, palm oil, soybean oil, and combinations thereof.

Fatty acid-containing monoglycerides are present in foodstuffs in amounts of at least about 10% by weight of the fat component included in the nutritional product, in particular at least about 15% by weight of the fat component included in the nutritional product , including at least

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approximately 20% by weight of the nutritional component of g't '&amp; S'auin ucto, including 15% to 25%, and including approximately 10%, including approximately 15%, including approximately 20%, including approximately 25%, including approximately 30 %, and further including about 35%, or even 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 a specific embodiment, when the nutritional product is a nutritional powder that includes a fat component of about 28% (by weight of the nutritional powder), the monoglycerides containing fatty acids are present at a level of about 10% (by weight of the fat component), or approximately 2.8 grams of acid fatty acid-containing monoglycerides for every 100 grams of nutritional powder.

In another specific embodiment, when the nutritional product is a ready-to-drink nutritional liquid that includes a fat component of approximately 3.67% (by weight of the ready-to-drink nutritional liquid), the monoglycerides containing fatty acid are present at a level of approximately 10% (by weight of the fat component), or about 0.367 grams of

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MEXICAN INSTITUTE

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fatty acids for every 100 grams of nutrition liquid when ready to drink.

In another specific embodiment, when the nutritional product is a concentrated liquid nutritional product that includes a fat component of approximately 7.34% (by weight of the concentrated liquid nutritional product), the monoglycerides containing fatty acids are present at a level of approximately 10% (by weight of fat component), or approximately 0.734 grams of fatty acid-containing monoglycerides for every 100 grams of concentrated liquid nutritional product.

In addition to providing numerous benefits described above, fatty acid-containing monoglycerides have also been found to have antiviral and / or antibacterial activity in nutritional products. Specifically, the presence of fatty acid-containing monoglycerides in nutritional products has been found to kill pathogens and / or slow their replication.

B, Fatty Acid Component

In addition to, or in place of, the fatty acid-containing monoglycerides described above, the nutritional products of the present invention may include a fatty acid component comprising fatty acids as a part of the predigested fat system. Fatty acids are normal metabolites

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in the body in particular formed during the decomposition of fat (triglycerides, diglycerides, cholesterol esters and certain phospholipids). This fatty acid component is separate and distinct from the fatty acid-containing monoglycerides discussed above.

Any beneficial fatty acid in a nutritional product can be included in nutritional products as part of the predigested fat system. In one embodiment, the fatty acid is a free unsaturated fatty acid. In some embodiments including 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. Exemplary 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, mead, erucic acid, nervonic acid, and mixtures and combinations thereof. Particularly preferred fatty acids include arachidonic acid, linoleic acid, linolenic acid, docosahexanoic acid, and oleic acid.

The fatty acid component for inclusion in the predigested fat system includes those derived from oils such as vegetable oils, marine oils, fish oils, seaweed oil, mushroom oils, animal fats, fractionated animal fats, and combinations thereof. .

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<img file="MX344271B_D0028.tif" />

I wnrwro MEXICANO Μ THE INDUSTRIAL PROPERTY

Suitable vegetable oils include, for example, olive oil, cane oil, corn oil, soybean oil, and combinations thereof. In one embodiment, when animal fat is used, the fatty acids are derived from the enzymatic hydrolysis of lard or tallow and the level of palmitic and stearic acid in the resulting fatty acid mixture is reduced to less than 20% of the total fatty acids, including less than 2% of total fatty acids. In other embodiments, at least some of the fatty acids are derived from soybean oil or tree resin. Once derived from the oil source, fatty acids are substantially free of monoglycerides, diglycerides, and triglycerides.

Fatty acids are generally derived from a source oil 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 derived from a source oil that contains less than about 15% (by weight), including less than about 10% (by weight), including less than about 5% (by weight), including less 2% (by weight) palmitic acid and / or stearic acid and / or myristic acid.

In a specific embodiment, the fatty acids are derived from a source oil that contains less than about 20% (by weight), including from about 10% (by weight) to about 15% (by weight) palmitic acid and / or

<img file="MX344271B_D0029.tif" />

IMPI MEXICAN INSTITUTE OF THE MONTH Stearic acid and / or myristic acid. In another modality ^ 'é ^^ e the nutritional product includes palmitic acid err a¹ eaiilidyd of less than about 10% (by weight) of the total fatty acids.

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

The fatty acid salts can be prepared by one skilled in the art based on the present description. In a suitable process, emulsions that include calcium salts of fatty acids Ci₀-C₂4 They can first be prepared by preparing fatty acid salts by using various starting sources of calcium mixed with at least one source of fatty acids C₁₀-C₂₄. More particularly, in one method, a starting source comprising fatty acids C₁₀-C₂₄ in a triglyceride or free-form mixture it can be formed by contact with calcium hydroxide and / or calcium carbonate and / or calcium phosphate. In another method, Ci fatty acids₀-C₂₄ in a triglyceride mixture or in free form can be made by contact with CaCI₂ hydrated or Ca (AcO)₂ at a pH of 6 to about d 7.5.

IMPI • MEXICAN NSTnVTO DE LA MONEDAD industrial

The above methods can be carried out under an inert atmosphere eg under N atmosphere₂ or argon, in other examples, described methods can be carried out under an ambient atmosphere (for example, where the reaction is not carried out under a low-atmosphere

The source comprising fatty acids C₁₀-C₂₄ and the calcium source can be mixed by any of the methods known in the art. Mixing is not intended to imply a particular result of mixing, such as dissolution of the components at a particular level or formation of a particular composition, such as homogeneous mixing, although such mixtures may occur and some of the components are can dissolve by mixing. The mixing can be vigorous and can be done or by a mechanical device such as, but not limited to, a static mixer, a magnetic stirrer, a stirrer, centrifuge, or rotary device. Mixing can be accomplished by forcing or bubbling a gas through the mixture or by sonication.

The mixture of the fatty acid source C₁₀-C₂₄ mixing with a source of calcium can also be done 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 ​​can form an upper or lower end point, as appropriate.

IMPIf

MBXICANG INSTITUTE f

THE PROPERTY 1

INDUSTRIAL

Mixing can be done at various temperatures, but generally the method is carried out at an elevated temperature. The precise elevated temperature may depend on the particular starting sources of fatty acids C₁₀-C₂₄ or calcium and amounts of the same that are used. Suitable temperatures at which the described 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 containing C fatty acids₁₀-C₂₄ or calcium can also be heated before mixing. Such a pre-heating step can be performed at any of the temperatures or temperature ranges described herein.

In some embodiments, the C fatty acid mixture₁₀-C₂₄and calcium can be performed under reduced pressure. Adequate pressure is less than or equal to about 1 Torr or less than or equal to about 0.1 Torr.

In a desirable embodiment, the calcium salts of fatty acids Ci₀-C₂₄ They are prepared by adding Ci unsaturated free fatty acids₀-C₂₄ and a source of calcium, such as Ca (OH)₂, CaCI₂, CaCO₃, Ca-citrate or a mixture of these salts, to form an oil mixture. More particularly, the

ÍMPI ^ 5 'NSTTTUTO MEXICANO' '/ LÍCTgCiS ·.

The fatty acids are dissolved in a ca'IWñYé aqueous solution (for example, which has a temperature of approx. The pH of the solution can be adjusted, generally to a pH of about 10-11, using KOH or NaOH. Calcium is then added to the solution containing dissolved fatty acid. Typically, the fatty and calcium acids were allowed to stand 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 fatty acid calcium salts including fatty acids from fish oil, algae oil, fungal oil, and soybean oil is prepared as part of the predigested fat system. Fish oil, algae oil, fungal oil, and soybean oil are mixed together and hydrolyzed with potassium hydroxide under a nitrogen atmosphere. A source of calcium, such as calcium chloride, is then added to the mixture to react with the fatty acids to produce insoluble calcium fatty acid salts. Insoluble fatty acid salts can be isolated by filtration, and washed with water before drying under vacuum.

It has surprisingly been 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 difficult sediment layer.

<img file="MX344271B_D0030.tif" />

from redisp rsar. Therefore, the use of magnesium / calcium salts of fatty acids allows a better delivery of calcium / magnesium and, in many modalities, can eliminate the need for additional stabilizers, such as carrageenan, in such a way that the product can be substantial or completely free of carrageenan.

Consequently, the use of fatty acid salts allows the bioavailability of calcium and / or magnesium and that of fatty acids compared to products that use calcium phosphate or calcium carbonate in the calcium source.

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

Nutritional products generally include fatty acids or fatty acid salts in an amount of at least about 10% (by weight) of the fatty component included in the nutritional product, including at least about 15%, including at least about 20%, including from about 10% to about 60%, including from about 15% to about 40%, and Including from about 15% to about 35%, including

IMPI

MEXICAN INSTITUTE approx ^ n / SSE ^

<img file="MX344271B_D0031.tif" />

including approximately 15%, including next 20% claimant, including approximately 25%, including approximately 30%, including approximately 35%, further including approximately 40%, or even approximately 50%, or even approximately 60%, or even approximately 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 some embodiments, nutritional products include a mixture of a fatty acid component and fatty acid-containing monoglycerides. In these embodiments, the food product contains the mixture in an amount of at least 10% (by weight) of the fatty component included in the nutritional product, including at least approximately approximately approximately approximately approximately

15%, including

<td>I less</td><td>; approximately</td><td> 20%,</td><td>including</td><td>of</td>

<td>10% a</td><td>approximately</td><td> 40%,</td><td>including</td><td>of</td>

<td>20 a</td><td>approximately</td><td> 65%,</td><td>including</td><td>d</td>

<td>25% a</td><td>approximately</td><td> 50%,</td><td>including</td><td>of</td>

<td>15% a</td><td>approximately</td><td> 30%,</td><td colspan="2">and that includes</td>

from about 15% to about 25%, including about 10%, including about 15%, including about 20%, including about

25%, including approximately 30%, including approximately 35%, and which also includes approximately

40% even about 50%,

IMPI

Mixican INSTITUTE even

<img file="MX344271B_D0032.tif" />

60%, even approximately 70%,

80%, even about 90%, even about

100% by weight of the fat component included in the nutritional product.

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

Nutrient Macro

Although total concentrations or amounts of fat, protein, and carbohydrates may vary depending on the type of product (i.e., human milk fortifier, infant formula, etc.), the form of the product (i.e., nutritional solid, powder , ready-to-drink liquid or concentrated liquid) and the specific dietary needs of its recipients, such concentrations or amounts are typically within one of the following incorporated ranges, including any other fat, protein, and / or carbohydrate ingredients described in this document.

For liquid infant formula products for preterm and full-term infants, the concentrations

ΙΜΡΙ ^ 5 '«ΉΤΤυΤΟ MIRICA NO

OF The carbohydrate nOMFOAO most typically ranges from about 40% to about 40%, including from about 7% to about 30%, including from about 10% to about 25%, by weight of formula for premature infants. or born in term; fat concentrations (including both predigested fat and any other fat source) 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 %, by weight of formula for preterm or term infants, and protein concentrations most 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 the formula for preterm or term infants.

For liquid human milk fortifying carbohydrate products, concentrations most typically range from about 10% to about 75%, including from about 10% to about 50%, including from about 20% to about 40%, by weight of the milk fortifier. human fat concentrations (including both predigested fat and any other fat source) most typically range from about 10% to about 40%, including from about 15% to

IMPI

MEXICAN INSTITUTE

FROM LA FROFISDAL

INDUSTRIAL of approximately approximately 37%, and also including

18% to about 30%, by weight of

<img file="MX344271B_D0033.tif" />

human milk fortifier; 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 liquid nutritional products can also be characterized in addition to, or alternatively, as a total percentage of calories in nutritional products as set forth in the following Table. These macronutrients of the liquid nutritional products of the present disclosure are most typically formulated within any of the caloric ranges (AF modalities) described in the following table (each numerical value is preceded by the term approximately).

<td>Total% of lime. of the nutrient</td><td>Mode A</td><td>Mode B</td><td>Mode C</td>

<td>Carbohydrate</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>Mode A</td><td>Mode B</td><td>Mode C</td>

<td>Carbohydrate</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 formulas

<img file="MX344271B_D0034.tif" />

(both ready-to-eat and liquid with those modalities in which the python can comprise from about 7.5% to about 25% of the caloric content of the formula; the carbohydrate component can comprise from about 35% to about 50% of the caloric content total infant formula, and the fat component may comprise from about 30% to about 60% of the total caloric content of infant formula. These ranges are provided only as examples, and are not intended to be limiting. Additional suitable ranges are indicated in the following Table (each numerical value is preceded by the term approximately).

<td>Total% of lime. of the nutrient</td><td>G mode</td><td>Mode H</td><td>Mode 1</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 of from about 5% to about 35%, including from about 8% to about 12%, including from about 10 % to about 12% by weight of the formula for preterm or term infants, the fat component is present in about 35%, including amount of approxi

<img file="MX344271B_D0035.tif" />

<img file="MX344271B_D0036.tif" />

ΓΜ THE PROPERTY

INDUSTRIAL approximately 25% to approximately 30%, including from next to next * 2 6% to approximately 28% by weight of the formula for premature or term infants and the carbohydrate component is present in an amount from about 30% to about 85%, including from about 45% to about 60%, including from about 50% to about 55% by weight of the formula for preterm or term infants.

For human milk powder fortifiers, the protein component is present in an amount of from about 1% to about 55%, including from about 10% to about 50%, including from about 10% to about 30% by weight of the fortifier. of human milk; the fat component is present in an amount of from about 1% to about 30%, including from about 1% to about 25%, and including from about 1% to about 20% by weight of the human milk fortifier; and the carbohydrate component is present in an amount of from about 15% to about 75%, including from about 15% to about 60%, and including from about 20% to about 50% by weight of the human milk fortifier.

<img file="MX344271B_D0037.tif" />

ÍMPIí ^ '•' ^ πτυτφΜίΛίρΛΝΟ

The total amount or concentration of fat, carbohydrate and protein in the powdered nutritional products of the present invention can vary considerably depending on the selected product and the dietary or medical needs of the target user. Additional suitable examples of macronutrient concentrations are set forth below. In this context, the total amount or concentration refers to all the fats, carbohydrates and protein sources in the powdered product. For nutritional powder products, the total amounts or concentrations are most typically and preferably formulated in any of the ranges of the modalities described in the following table (the numbers are approximately opposite).

<td>Total% of lime. of the nutrient</td><td>Mode J</td><td>K mode</td><td>L mode</td>

<td>Carbohydrate</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

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

IMPI

MUtICAMO INSTITUTE OF INDUSTRIAL PROPERTY

<img file="MX344271B_D0038.tif" />

Non-limiting examples of additional suitable fats or sources thereof for use in the nutritional products described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, oil. safflower with high oleic content, oleic acids (oleic acid EMERSOL 6313), MCT oil (medium chain triglycerides), sunflower oil, sunflower oil with high oleic content, palm kernel and palm kernel oils, palm olein, cane oil, marine oils, fish oils, mushroom oils, algae oils, cottonseed oils, and combinations thereof. In one embodiment, fats or suitable sources thereof including oils and oil mixtures, including long-chain polyunsaturated fatty acids (PUFA-CL), preferably LCPUFA having four or more double bonds. Some specific non-limiting polyunsaturated acids for inclusion include, for example, docosahexanoic acid (DHA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and the like.

Generally, the predigested fat here 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 (preferably in the form of calcium salts), a high oleic oil, and coconut oil are

TMPIj ^ a,. .,. INSTtTUTQMtMCANP combine together to provide the comp £ $ ^ ffi £ e in a nutritional product. In this embodiment, monoyii ^ ériflTiia-cr 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 fat component, the fatty acids are present in an amount of about 1% to about 40%, 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 of 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 from 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, the fatty acid-containing monoglycerides (desirably in the form of monoglycerol palmitate), a

IMPI ^

MEXICAN INSTITUTE V¡¡ ^ gCf9.

PROPERTY n fatty acid component (desirably in forr ^ a ^ tf ^ sa recres calcium), a high oloioe safflower oil and coconut oil combine together to provide the fat component in a nutritional product. In this embodiment, 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 wt% of the fat component, fatty acids 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%, and about 25% by weight of the fat component, the high oleic oil is 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 25%, and about 30% by weight of the fat component, and coconut oil is present in an amount of from 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 d I

In another embodiment, the monoglycerides that contain fat component acidfiS.

IMPI

MEXICAN INSTITUTE

OF industrial RROFIEDAD

<img file="MX344271B_D0039.tif" />

fatty (desirably in the form of monoglycerol palmitate), a component of fatty acid (desirably in the form of calcium salts), a safflower oil with high oleic content, a coconut oil contains ARA, component of the oil containing DHA, and oil that combine together to provide fat in a nutritional 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 fat component, the fatty acids 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%, and about 25% by weight of the fat component, the high oleic oil is present in an amount of about 1% to about 40%, including 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 about 1% to

<img file="MX344271B_D0040.tif" />

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. DHA-containing oil is present in an amount of about 1% to about 10%, including about 5% by weight of the fat component, and ARA-containing oil is present in an amount of about 1% to about 10%, including about 5% by weight of the fat component.

In another embodiment, the fatty component comprises about 38% (by weight) of high oleic safflower oil, about 17% (by weight) of coconut oil, about 23% (by weight), monoglycerin palmitate, about 20 % (by weight) of fatty acid calcium salts, approximately 0.5% (by weight) of oil containing DHA, and approximately 1.0% (by weight) of oil containing ARA.

Protein

The nutritional products of the present disclosure may optionally comprise protein and predigested fat. Any source of protein 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.

IMPI

JWTTHJTÜ MEXICANO O * ΙΛ INDUSTRIAL MLORBDAD

<img file="MX344271B_D0041.tif" />

Non-limiting examples of suitable protein or sources thereof for use in nutritional products include hydrolyzed, partially hydrolyzed proteins, or unhydrolyzed proteins or protein sources, which can be derived from any known or otherwise suitable source, such as milk (eg casein, whey), animal (eg meat, fish), cereal (eg rice, corn), vegetables (eg soy) or combinations thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates as described herein, casein protein isolates, extensively hydrolyzed casein, whey protein, sodium or calcium caseinates, whole milk from cow, partially or totally skimmed milk, soy protein isolates, soy protein concentrates and so on.

Carbohydrate

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

Non-limiting examples of carbohydrates or suitable sources thereof for use in the nutritional products described herein may include

IMPIfé maltodextrin, starch or corn starch γβ 'INDUSTRIAL * modified, glucose polymers, corn syrup, corn syrup solids, carbohydrates derived from peas, carbohydrates derived from peas, carbohydrates derived from potatoes, tapioca, sucrose, glucose, fructose , lactose, high fructose corn syrup, honey, sugar alcohols (for example, maltitol, erythritol, sorbitol), artificial sweeteners (for example, sucralose, acesulfame potassium, stevia) and combinations thereof.

Other optional ingredients

The nutritional products of the present invention may further comprise other optional components that can modify the physical, chemical, aesthetic or transformation characteristics of the products or serve as additional or pharmaceutical nutritional components when used in the target population. Many of these optional ingredients are known or otherwise suitable for use in medical foods or other nutritional products or pharmaceutical dosage forms and may also be used in the compositions herein, provided that such optional ingredients are safe for oral administration and are compatible with the ingredients in the selected form of the product.

Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifying agents,

IMPI instituto mexicah ^

OF THE

INDUSTRIAL ga lactool igosaccharides,

<img file="MX344271B_D0042.tif" />

buffers, fructooligosaccharides, prebiotics, pharmaceutical active substances?

additional nutrients, as described herein, colorants, flavors, thickening and stabilizing agents, emulsifying agents, lubricants, and so on.

sweetening agent, preferably including at least one sugar such as maltitol, erythritol, sorbitol, xylitol, mannitol, isomaltose and lactitol, and which also preferably includes at least one artificial or high potency sweetener, such as acesulfame K, saccharin, stevia and tagatosa. These especially as a combination of aspartame, sucralose, sweetening agents, a sugar alcohol and an artificial sweetener, are especially useful in formulating the liquid beverage modalities of the present disclosure that have a desirable favorable profile. These combinations of sweeteners are especially effective in masking undesirable flavors sometimes associated with adding vegetable protein to a liquid drink. Optional sugar alcohol concentrations in the nutritional product can range from at least 0.01%, including 0.1% to approximately 10%, and also including from approximately 1% to approximately 6%, by weight of the nutritional product. Concentrations of optional artificial sweeteners can range from about 0.01%, including from about 0.05% to

IMPI

MEXICAN INSTITUTE approximately

<img file="MX344271B_D0043.tif" />

also about

0.1% to aprnyimxUmaaia .. 1 0% by weight of the nutritional product.

An anti-caking agent or anti-caking agent may be included in described herein to retard lump formation by caking the powder with making a container flowing powder embodiment.

Any known or otherwise suitable anti-caking agent or anti-caking agent for use in a nutritional powder or product form are suitable for use in this invention, non-limiting examples of which include tricalcium phosphate, silicates, and combinations thereof. The concentration of the anti-caking agent or anti-caking agent in the nutritional product varies depending on the form of the product, the other selected ingredients, the desired flow properties, and so on, but more typically they vary 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 known or otherwise suitable stabilizer for use in a nutritional product is also suitable for use in this invention, some non-limiting examples of which include carrageenan and gums such as

MEXICAN INSTITUTE

DE LA PRORWAD O * represetTfáY * '*^Ldes

<td>xanthan gum.</td><td>The e</td>

<td>approximately</td><td> 0.1%</td>

<td>approximately</td><td> 0.5%</td>

<td>approximately</td><td> 0.7%</td>

<td>nutrition product</td><td>to the.</td>

about to

aa

5.0%, iiiiiuyarrOT?

approximately approximately

The compositions

3%, including nutritional products, may further comprise any of a variety of other vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin Bi₂, carotenoids (eg, beta-carotene, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, salts and derivatives thereof, and combinations thereof.

Nutritional products may further comprise any of a variety of other additional non-limiting examples of which include calcium phosphorous magnesium, iron, zinc, manganese, copper, sodium, potassium molybdenum, chromium, chloride, and combinations thereof.

In addition, in some modalities, nutritional products may be free of carrageenan.

Manufacturing method

The nutritional products of the present invention can be prepared by any known or otherwise effective manufacturing technique to prepare the selected solid product in liquid form. Many of these techniques are known for any form of

IMPI® 'NSTrnrro mixicanq I heard LA BROBISDAn industrial given product, such as nutritional liquids or powders and can be applied * with fa c 11 i'd δ to nutritional products described here.

The nutritional products of the present disclosure can therefore be prepared by any of a variety of known or otherwise effective product or manufacturing methods. In a suitable manufacturing process, for example, at least three separate suspensions are prepared, including a protein-in-fat suspension (PIF), a carbohydrate-mineral in-water suspension (PIW). The (CHO-MIN) and a suspension of protein PIF suspension is formed by heating and fatty, oil-containing fatty acid, cane oil, corn oil, etc.) and subsequently the addition of an emulsifier (eg lecithin) , fat soluble vitamins, and a serving of total protein (eg, milk protein concentrate, etc.) with heat and continuous stirring. The CHO-MIN suspension is formed by adding with heated stirring to the water: minerals (for example, potassium citrate, dipotassium phosphate, sodium citrate, etc.), trace and ultra trace minerals (premix TM / UTM), and / or thickener or suspending agents (eg Avicel, gellan, carrageenan). The resulting CHO-MIN suspension was held for 10 minutes with heat and continuous stirring before adding minerals.

<img file="MX344271B_D0044.tif" />

Additional IMPIs (for example, potassium chloride ^^ tJ ^ tS ^ Se magnesium, potassium iodide, etc.) and / or carbohydrates (for example, fructooligosaccharide, sucrose, corn syrup, etc.). The PIW suspension is then formed by mixing with heat

In a specific embodiment of the present disclosure, all or a portion of predigested fat included in the nutritional product can be added to the CHOMIN cell suspension containing less than 5% (by weight of the CHO-MIN suspension) of fat in triglyceride form. In this embodiment, at least 5% (by weight) of the total fat present in the nutritional product is in the form of predigested fat and added to the CHO-MIN cell suspension. 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 CHOMIN cell suspension. In a particular embodiment, lipid soluble nutrients, such as mixed carotenoids or vitamins A, D, E, and K, are dissolved in the predigested fat before the predigested fat that is added to the CHO-MIN cell suspension or during the

IMPI

MEXICAN NTOTVTO

<img file="MX344271B_D0045.tif" />

manufacture of CHO-MIN suspension. By measuring the predigested fat to the suspension of ^ iniac how-mim &lt;? Η as opposed to the PIF suspension, the stability of the finished nutritional composition can be improved.

The resulting suspensions were then mixed together with stirring with heating and the pH was adjusted to 6.6-7.0, after which the composition undergoes high-temperature short-time processing (HTST) during which the composition is heat-treated, emulsifies and homogenizes, and then allowed to cool. Vitamins soluble in water and ascorbic acid are added, the pH is adjusted to the desired range, if necessary, flavors are added and water is added to reach the desired total level of solids. The composition is packaged aseptically to form an aseptically packaged nutritional emulsion. This emulsion can also be filled and then sterilized to form a ready-to-use liquid or concentrate or it can be spray dried, dry mixed and / or agglomerated.

The nutritional solid, such as a spray-dried powder or dry-mixed nutritional powder, can be prepared by any collection of known or otherwise effective techniques suitable for the manufacture and formulation of a nutritional powder.

For example, when the nutritional powder is a spray-dried nutritional powder, the spray-drying step may also include any spray-drying technique that is known or otherwise.

IMPI

<img file="MX344271B_D0046.tif" />

INDUSTRIAL

<img file="MX344271B_D0047.tif" />

for use in the production of nutritional powders. Many different methods known for their suitability for spraying and drying techniques are use in the field of nutrition, all are use in the manufacture of spray dried nutritional powders herein.

One method of preparing the spray-dried nutritional powder comprises the formation and homogenization of an aqueous or liquid suspension comprising pre-digested fat and optionally proteins, carbohydrates, and other sources of fat, and then the suspension or liquid is spray-dried to produce a spray-dried nutritional powder. The method may further comprise the step of spray drying, dry mixing or otherwise adding additional dry nutritional ingredients, including one or more of the ingredients described herein to the spray dried nutritional powder.

Other suitable methods for manufacturing products

<td colspan="4">nutritional for example in</td><td>the</td><td>Patent</td><td>North American</td><td>Not</td>

<td> 6,365,218</td><td>(Borschel</td><td>and</td><td>cabbage.),</td><td>the</td><td>patent</td><td>North American</td><td>Not</td>

<td> 6,589,576</td><td>(Borschel</td><td>and</td><td>cabbage.)</td><td>the</td><td>patent</td><td>North American</td><td>Not</td>

<td> 6,306,908</td><td>(Carlson</td><td>and</td><td>cabbage.),</td><td>and</td><td>the so</td><td colspan="2">Patent legality</td>

North American 20030118703 A1 (Nguyen et al.), the disclosures of which are incorporated herein by reference to the extent that they are compatible herein.

with the present description, and as described

IVI 'all use

Agree

IMPI

ΙΙΉΓΓΠΤΓΓΟ MKJCANO OS THE INDUSTRIAL MEOMSDAD

<img file="MX344271B_D0048.tif" />

In detail below, the nutritional products described herein can be used for a number of purposes, including, for example, improving digestion, improving nutrient absorption, improving tolerance, decreasing the incidence of necrotizing enterocolitis, decreasing the incidence of colic, and decreasing the incidence of short bowel syndrome. The individual (infant, toddler, or child) using the food products described in this document may actually have or be affected by the described disease or condition (i.e., may actually have digestion, nutrient absorption, and / or tolerance problems or who may have necrotizing enterocolitis, colic, or short bowel syndrome), or may be susceptible to, or at risk of contracting, the disease or condition (i.e. They may not actually have the disease or condition yet, but are at high risk compared to the general population for contracting it due to certain conditions, family history, etc.). If the individual actually has the disease or condition, or is at risk or susceptible to the disease or condition, the individual is classified herein as in need of help in treating and fighting the disease or condition. For example, a child who may have necrotizing enterocolitis or may be at risk for necrotizing enterocolitis (susceptible to necrotizing enterocolitis) due to early birth.

<img file="MX344271B_D0049.tif" />

in another example, a baby may actually have tolerance and / or digestion and / or nutrient absorption problems, or may be at risk of (susceptible to) getting one or more of these conditions due to other diseases or conditions, or a family history of those problems. Whether the person actually has the disease or condition, or is only at risk of, or susceptible to contracting the disease or condition, it is within the scope of this description to assist the person with the nutritional products described in this document.

Based on the above, because some of the method modalities of the present description are directed to specific subsets or subclasses of identified individuals (i.e., the subset or subclass of individuals in need of help in the treatment of one or more specific diseases or specific conditions mentioned here), not all individuals can benefit from the method modalities described in this document as not all individuals will fall within the subset or subclass of individuals as described in this document for certain diseases or conditions.

Nutritional products as described herein comprise desirably predigested fat in combination with one or more additional fat sources to provide a nutritional source for infants, toddlers

<img file="MX344271B_D0050.tif" />

improve digestion and absorb nutrients. Specifically, similar to the digestion of breast-fed babies, as the fat source is at least partially digested before entering the duodenum, more time is allowed for nutrients to be absorbed by the baby, particularly in the intestines, and the amount of nutrients entering the child's colon is reduced, resulting in fewer nutrients that can ferment and produce gas, which can result in reduced tolerance of a product. As such, by utilizing 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 more closely mimics the benefits of it.

Along with improved nutrient absorption, as described above, the use of predigested fat within a nutritional product has been found to also facilitate micelle formation when administered with one or more water-insoluble hydrophobic compounds, such as oil. soluble (lipid soluble) vitamins (vitamins A, D, E, and K), carotenoids (eg, lutein, lycopene, beta-carotene, etc.), glycolipids (gangliosides), sterols, and phytochemicals. The formation of these micelles allows the hydrophobic insoluble compounds to dissolve in digestion, which is a step in

ΙΜΡΙ

MFXICzHD INSTITUTE

DIUHtOrmMD

IHBUSTR1A1

<img file="MX344271B_D0051.tif" />

absorption by the villi of the intestine. Additionally, the predigested fat is used to resynthesize triglycerides to form chylomicrons. Chylomicrons carry the water-insoluble hydrophobic compounds in the lymph, where the circulation transports the insoluble hydrophobic compounds to specific organs and / or tissues to produce desired physiological effects.

In addition to the benefits discussed above, nutritional products including 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 the digestion of nutrients and reduces contractions of the upper gastrointestinal tract, allowing more time for absorption. Therefore, the use of predigested fat in nutritional products reduces the total amount of nutrients entering the colon, which can be fermented and produces gas and a bloated sensation. As such, the use of predigested fats in nutritional products can improve tolerance by improving digestion and nutrient absorption with less gas. This can be especially important in children, as tolerance can be a problem in some children.

Along with the production of stimulatory CCK, predigested fat has also been found to induce secretion of int stinal growth hormone, I peptide-2 similar to

IMPI glucagon (GLP-2). GLP-2 can improve the Mexican iNfrmrro of ENDUSTUAL fkoeiedad maturation of the baby's intestine, resulting in better digestion and absorption of nutrients.

Furthermore, it has been found that nutritional products, such as those described here, comprising predigested fat can be used to provide a source of nutrition for infants, toddlers, or children that can reduce the incidence of necrotizing enterocolitis (NEO), colic, and / or short bowel syndrome.

Furthermore, in modalities in which the food product is manufactured by a process in which at least a portion of predigested fat (or in some modalities all of the predigested fat) is added to the suspension of carbohydrates and minerals as opposed to protein in fat suspension, the resulting stability of the nutritional product (generally in the form of a nutritional emulsion) can be improved.

EXAMPLES

The following examples illustrate specific modalities and / or characteristics of the nutritional products of the present description. The examples are given for the purpose of illustration only and should not be construed as a limitation of the present description, as many variations thereof are possible without departing from the spirit and scope of the description. All quantities shown are percentages by weight based

IMPI in the total weight of the composition, unless otherwise eSfp ^^ | ^ «e ^ g. . _______

The exemplified compositions are stable nutritional products prepared in accordance with the manufacturing methods described herein, such that each product that is exemplified, unless otherwise specified, includes an aseptically processed modality and a retort packaged modality.

Nutritional liquid modalities 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

Examples 1-4 illustrate the lactose-free infant nutritional emulsions of the present disclosure, the ingredients of which are listed in the Table below. All ingredient quantities are listed in kg per 1000 kg of product batch, unless otherwise specified.

<img file="MX344271B_D0052.tif" />

IMPI

ICυΤΟ MEXICANO DE LA MONEDAD fNDUmiAL

<td rowspan="2">Ingr di nt</td><td rowspan="2">Example 1</td><td rowspan="2">Example 2</td><td>Ei mDlQj--</td><td>Eiemolo 4</td>

<td></td><td></td>

<td>Water</td><td>cbp</td><td>cbp</td><td>cbp</td><td>cbp</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>Safflower oil with high oleic content</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>Fatty Acid Calcium Acid Salt₁₀-C₂4</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>Mushroom 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, E premix</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td>

<td>Water soluble 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 illustrate nutritional emulsions based on

IMPI mrrnuroMüucAHo nt LA raOMSOAD INOUSTIUAl

<img file="MX344271B_D0053.tif" />

EXAMPLES 5-8 of lactose of the present description, the ingredients of which are listed in the following table. All ingredient quantities are listed in kg per 1000 kg of product batch, 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>cbp</td><td>cbp</td><td>cbp</td><td>cbp</td>

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

<td>Dry fat-free milk</td><td> 25</td><td> 10</td><td> 0</td><td> 16</td>

<td>Whey 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>Fatty acids C₁₀-C₂₄</td><td> 5.5</td><td> 7.5</td><td> 9.5</td><td> 11.5</td>

<td>Fructolugosaccharides / Galac to-oligosaccharides</td><td> 9</td><td> 9</td><td> 9</td><td> 9</td>

<td>Mushroom 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>TM / UTM premix</td><td> 0.1684</td><td> 0.1684</td><td> 0.1684</td><td> 0.1684</td>

<td>Vitamin premix ADE</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td>

<td>Water soluble 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

Examples 9-12 ^I*^{, T}m7P¿Í^Micano Dt Ι.Λ Mqn_sdad'NW'STIUI

<img file="MX344271B_D0054.tif" />

Illustrated infant nutritional emulsions based on soy ingredients are listed in ingredient amounts of the present disclosure, of which the Table below. All are listed in kg per 1000 kg 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>cbp</td><td>cbp</td><td>cbp</td><td>cbp</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>Monogli cerol palmitate</td><td> 10</td><td> 9</td><td> 8</td><td> 7</td>

<td>Fatty acids C₁₀-C₂₄</td><td> 6.0</td><td> 7</td><td> 8.0</td><td> 9</td>

<td>Mushroom 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 premix ADE</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td>

<td>Water soluble 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>

IMPI

EXAMPLE 13-16

Examples 13-16 illustrate emulsions

MEXICAN INSTANT OF INDUSTRIAL PROPERTY

<img file="MX344271B_D0055.tif" />

nutritional sources based on hydrolyzed proteins for infants of the present description, whose ingredients are listed in the following table. All ingredient quantities are listed in kg per 1000 kg 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>cbp</td><td>cbp</td><td>cbp</td><td>cbp</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>Safflower oil with high oleic content</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>Fatty acids C₁₀-C₂₄</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>Mushroom 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-Meionin</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 premix ADE</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td><td> 0.0758</td>

<td>Vitamin premix soluble in water</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 in rats are evaluated with calcium salts of fatty acid C₁₀-C₂4.

Thirty rats were randomly assigned to one of the three diets (Diet 1, Diet 2 and Diet 3) containing different proteins and fats. Diets 1-3 are the same as those used in AOAC method 906.48, with the exception that or

diets 1-3 have a higher fat level and include maltodextrin as a carbohydrate source. Diet 1 contains

10% by weight of protein available as acid 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 oil of high oleic safflower (HOSO). The nutritional profiles of diets 2 and 3 are identical to the nutritional profile of diet 1, except that proteins, fats, carbohydrates, and minerals are mixed, homogenized, and spray dried. Diet 3 differs from diet 2 only in that HOSO oil is replaced by high-oleic safflower fatty acid calcium salts of calcium and tricalcium phosphate is replaced with potassium phosphate in such a way that the nutritional profiles and General minerals from Diet 2 and 3 are the same. Whole Ca-HOSO fatty acid salts provide 100% calcium in the diet.

IMPIg

MSJUCANG INSTITUTE Γ ^ ί

OF THE CV PROPERTY

INDUSTRIAL

Rats are fed one of Diet 1, Diet 2, Diet 3 over a period of 4 weeks. The feed / protein consumption and weight gain at the end of the feeding test is used for the calculation of feed conversion (gram of weight gain / gram of feed intake) and the protein efficiency ratio (gram of weight gain / gram of ingested protein) (PER). If the caloric value (i.e. calories / gram of substance) of the calcium salt of fatty acid HOSO is significantly less than that of HOSO due to malabsorption, then rats on diet 3 should be expected to either gain They will lose less weight or consume food to maintain their growth, both of which will result in a lower feed conversion and PER.

The results shown in the table below indicate that rats on diet 3 have the same feed conversion or PER as the control, indicating that the caloric value of HOSO fatty acid calcium salt is no different than HOSO oil. As such, HOSO fatty acid calcium salts are shown to be highly bioavailable.

<td></td><td>Protein efficiency rate</td><td>Food conversion</td><td>n</td>

<td>Diet 1 (Control 1)</td><td> 2.83+/-0.28*</td><td colspan="2"> 0.29 +/- 0.03</td>

<td>Diet 2 (Control 2)</td><td> 3.16+/-0.17</td><td colspan="2"> 0.31 +/- 0.02</td>

<td>Diet 3 (fatty acid calcium salt)</td><td> 3.32+/-0.27</td><td colspan="2"> 0.37 +/- 0.03</td>

<td>* Standard deviation (n = 1</td><td colspan="3"> 0)</td>

EXAMPLE 18

In this example, the absorption is analyzed

IMPI ^ ητυτοΜ «· &lt;^

<img file="MX344271B_D0056.tif" />

EC

THE INDUSTRIAL PROPERTY

<img file="MX344271B_D0057.tif" />

fatty soy in 10-day pigs.

they were housed individually in metabolic cages and trained to take nutritional emulsions from a container within 30 minutes. After one week of formation of a ready-to-eat hydrolyzed protein-based formula, pigs are fed a commercial hydrolyzed protein powder (Control) formula including tricalcium phosphate and calcium carbonate as the source of calcium, or an emulsion (Experimental emulsion) including calcium salts of soy fatty acids as the calcium source. Protein source and level, fat level and mineral profiles are identical for Control and Experimental Emulsion. The Experimental Emulsion, however, includes soy fatty acids instead 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 is adjusted to match the phosphorus content of the control. Soybean calcium fatty acids provide 100% of the calcium in the Experimental Emulsion.

The apparent digestibility of fat and calcium are calculated based on the following formulas after two weeks of feeding:

Fat apparent digestibility = ((fat consumption65

<img file="MX344271B_D0058.tif" />

INSTITUTO MEXICANO M LA MWMtDAt industrial fecal fat) / fat consumption) * 100

Apparent digestibility of calcium = ((calcium intake, fecal calcium) / calcium intake) * 100

Dry matter digestibility = ((dry matter consumption

- fecal dry matter) / dry matter consumption) * 100

A decreased conversion of feed (weight / feed intake) and decreased fat, calcium, and dry matter digestibility of the experimental emulsion would indicate that the soy fatty acid calcium salts of the Experimental Emulsion are poorly absorbed, and by therefore, the caloric value and bioavailability of calcium are lower for the Experimental Emulsion compared to the control.

As shown in the table below, feed conversion, fat digestibility and dry matter digestibility of the experimental emulsion did not differ significantly from that of the control indicating that the fatty acid soybean calcium salts of the Experimental emulsions are absorbed and highly bioavailable for neonatal pigs. Furthermore, the apparent calcium digestibility data shown below indicates that the calcium salts of soy fatty acids from the experimental emulsion are more bioavailable than the calcium included in the control (i.e. tricalcium phosphate and calcium carbonate) .

IMPI

MEXICAN INSTITUTE

SAY FAOPltTY

INDUSTRIAL

<img file="MX344271B_D0059.tif" />

<td></td><td>Fat apparent digestibility</td><td>Feed conversion (Gram weight gain / gram feed (dry material))</td><td>Apparent calcium digestibility</td><td>Apparent digestibility of ca material</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>Experimental emulsion</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>

* Standard deviation (N = 10)

EXAMPLE 19

In this example, the emulsifying properties of calcium salts of fatty acids are analyzed.

A first emulsion (Control Emulsion) is prepared by cutting 18 g of soybean oil at 130 ° F containing monoglycerol palmitate (5% oil by weight) and 430 mg of Ca (as tricalcium phosphate) with 500 ml of water using a high speed table cutting mixer. A second io emulsion (calcium fatty acid emulsion) containing an identical level of calcium and fat (12 g of soybean oil, plus 6 g of soy fatty acids) as the control emulsion is prepared by: (1 ) dispersion of soybean fatty acid in oil in water at a temperature of about 130 ° F; (2) addition of 430 mg of Ca as calcium chlorides; (3) adjusting the pH of the solution to approximately 7.0 with KOH, and (4) cutting the mixture using a high-cut benchtop mixer.

Both the Control Emulsion and the Fatty Acid Emulsion • TOHTWTO MlfcCANO

D £ LA HtOMKMD industrial Calcium were left to stand for a period of three weeks to analyze the separation of emulsions. 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 Fatty Acid Calcium Emulsion exhibits only a slightly detectable layer of calcium soap on top of the emulsion with the remaining emulsion in one phase. There are no visible calcium deposits at the bottom of the Fatty Acid Calcium Emulsion (see Figure 1B).

These results indicate that the fatty acid calcium salts are effective emulsifiers and are capable of providing a source of calcium to a nutritional emulsion that does not substantially conform out of solution. This allows an emulsion product with improved stability and a longer shelf life.

EXAMPLE 20

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

The first test formulation (Formulation 1) includes palm olein oil in the fat system, the second test formulation (Formulation 2) includes predigested fat

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INSTITUTO MEXICANO ΟΪ UA PROPERTY in the fat system and the control formulation (FornHfflSWbn

<img file="MX344271B_D0060.tif" />

includes palmitic acid oil of low content ηlΓStSrteww of fat. The components of the fat systems of the three formulations are shown in the Table below.

<td>Nutrients (grams)</td><td>Formulation 1 (Palm olein oil formulation)</td><td>Formulation 2 (Predigested fat formulation)</td><td>Formulation 3 (Control Formulation that includes palmitic acid oil)</td>

<td>Coconut oil</td><td> 37.2</td><td> 0</td><td> 84.1</td>

<td>Safflower oil with high oleic content</td><td> 62.8</td><td> 108</td><td> 111.9</td>

<td>Fatty acid oil</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>Monoglycerol palmitate</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 from nearly identical nutrient and mineral profiles. The fatty acid profile of Formulations 1 and 2 mimics the fatty acid profile of breast milk. Calcium hydroxide was included in Formulation 2 (in an amount sufficient to chelate all free fatty acid) as a source of calcium, which reacts with soy fatty acids to form insoluble calcium fatty acid salts. This reaction eliminates bitterness and the burning sensation in the

INDUSTRIAL throat imparted by free fatty acids. Furthermore, the level of potassium phosphate in Formulation 2 is raised to match the phosphorous level of Formulations 1 and 3. The calcium salt used in formulations 1 and 3 is calcium phosphate.

Sixty 10-day pigs (plus or minus two days) are 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 materials from the second day to day eighteen were collected and analyzed for calcium absorption and fat absorption. Calcium absorption is calculated as the amount of calcium in the stool divided by the amount of calcium in the diet, multiplied by 100. Fat absorption is 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 Table below.

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

<td>Formulation 3 (control: low palmitic acid fat system)</td><td> 98.0 + 1.4</td><td> 90.7 ±3.5</td>

As the results show in the table above. '^ TO ^ o

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INSTITUTO MSXICANO DE LA MOPIBDAD a pre-digested fat system allows a foriWül &lt;S IIIfdIIlll 'psid to mimic the fatty acid profile of breast milk without the adverse effects on fat and calcium absorption as experienced with an oil fat system of palm olein. The fat and calcium absorption rates of the Formula (predigested fat formulation) are at least as good as those of the low palmitic acid formula. These results illustrate that the calcium salts of soy fatty acids are highly bioavailable in neonatal pigs.

EXAMPLE 21

In this example, the postprandial increase in CCK production (AUC) and motilin production (AUC) are evaluated for the pigs in Example 20.

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

<img file="MX344271B_D0061.tif" />

show in the table below.

<td></td><td>Formulation 2 (predigested fat formulation) (pg / mL * min)</td><td>Formulation 3 (Control: low palmitic acid formulation) (pg / mL * min)</td>

<td>Postprandial increase in CCK secretion (area under the curve)</td><td> 1935 + 1464</td><td> 1046 + 754</td>

<td>Motilin AUC (postprandial increase)</td><td> 483+253</td><td> 839+403</td>

The data in the table above shows that replacing triglycerides with predigested fat (monoglycerol palmitate plus soy fatty acids) stimulates postprandial secretion of CCK, which has been shown to stimulate secretion of digestive enzymes from pancreas, improve contraction of the gallbladder, and slow the transit of the mouth to the blind. As such,

<td>formulations</td><td>with predigested fat they can stimulate the</td>

digestible enzyme secretion and slow Gl transit to allow

<td>more digestion</td><td>and nutrient absorption. Therefore, the</td>

<td>formulations,</td><td>including predigested fat, can improve</td>

<td>tolerance to</td><td>formula because undigested nutrients can</td>

causing excessive fermentation in the colon to produce gas, diarrhea and bloating.

<td>Also,</td><td>the data in the table above shows that the</td>

replacement of triglycerides with predigested fat (palmitate of

IMPI ♦ NSTTniTO MEXICANO t »E LA FHOEIBOAD monoglycerol plus soy fatty acids) reduces the sebWft'fón

<img file="MX344271B_D0062.tif" />

postprandial motilin. Colic TOtrtsretaTitee ooo has been shown to have a lower postprandial CCK level but a higher postprandial level of motilin. This imbalance between postprandial intestinal hormones causes gastrointestinal contractions in a baby, causing abdominal pain. The data in the table above shows that the inclusion of predigested fat improves a baby's postprandial CCK level, but reduces the level of motilin, thus reducing hormonal imbalance to alleviate gastrointestinal contractions, abdominal pain, and colic.

EXAMPLE 22

In this Example, the pigs of Example 20 are used to study the effect of different fat systems on triglyceride palmitic acid chylomicrons and palmitic acid levels Sn-2.

The 1 hour postprandial blood sample from each pig is drawn and plasma isolated, frozen with liquid nitrogen, and stored in a -80 ° C freezer. The total lipids from the plasma are extracted using the Folch solvent. Triglycerides were isolated by thin layer chromatography. The following table shows the Sn-2 palmitic triglyceride and palmitic acid plasma from Formulation 1 (palm olein formulation) and Formulation 2 (predigested fat formulation). Chylomicron triglyceride and palmitic acid Sn-2 from c rdos

<img file="MX344271B_D0063.tif" />

MEXICAN INSTITUTE fed with these two formulations are shown ^^ SBfBbfi

<img file="MX344271B_D0064.tif" />

the board.

<td></td><td colspan="2">Formulation 1: (Palm olein)</td><td colspan="2">Plasma triglyceride from pigs fed Formulation 1</td><td colspan="2">Formulation 2: (Predigested fat)</td><td colspan="2">Plasma triglyceride from pigs fed Formulation 2</td><td colspan="2">Plasma triglyceride of baby fed human milk</td>

<td></td><td>Triglyceride</td><td>Sn- two</td><td>Triglyceride</td><td>Sn- two</td><td>Triglyceride</td><td>Sn -two</td><td>Triglyceride</td><td>Sn- two</td><td>Triglyceride</td><td>Sn- two</td>

<td>Palmitic acid level (%)</td><td> 23.3</td><td> 5.8</td><td> 18.3</td><td> 10.6</td><td> 21.4</td><td> 5.2</td><td> 18.5</td><td> 14.4</td><td> 25</td><td> 25.5</td>

As shown in the table above, predigested fat plasma plasma triglycerides from formula fed pigs have a higher plasma triglyceride Sn-2 palmitic acid content than pigs fed palm olein formula. The ratios of palmitic acid to plasma triglyceride / palmitic acid Sn-2 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. As such, these data indicate that the predigested fat formulation mimics breast milk better than the palm olein fat formulation does.

EXAMPLE 23

In this Example, the pigs in Example 20 are used^-

MEXICAN INSTITUTE

OF THE PROPERTY

<img file="MX344271B_D0065.tif" />

study the effect of different fat systems on levels of

Plasma from the 1 hour postprandial blood sample from each pig is extracted using a 2: 1 chloroform and methanol solvent. The solvent is removed and the resulting lipids are pooled and analyzed for lutein using conventional methods. The table below shows the lutein level of pigs fed Formulation 1 (olein formulation), Formulation 2 (predigested fat formulation) and Formulation 3 (low palmitic acid formulation) in mg lutein per mg lipid .

<td></td><td>Formulation 1: (Palm olein)</td><td>Formulation 2; (Predigested fat)</td><td>Formulation 3: (Low palmitic acid)</td>

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

<td>* Lutein level c</td><td colspan="3">e Formulation 1 is too low to measure.</td>

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

EXAMPLE 24

In this example, Formulation 2 (predigrated fat formulation) and Formulation 3 (palmitic acid formulation of

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FROM Ottscg PROPERTY

INDUSTRIAL low content) of Example 20 are used to study the effects of different fat systems on the lutein levels of micelles.

Formulation 2 and Formulation 3 and are reconstituted with water (133 g of powdered formulation per 1.0 L of water), and HCI 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 subsequently a mixture of 28 mg of pancreatin amylase USP / protease, 28 mg of pancreatin lipase USP and 108 mg of bile extract is added to the digested formulations. with pepsin. The formulations are further digested at room temperature for 2 hours and centrifuged (31,000g 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 removed for analysis of micellar lutein, which act as carriers during the absorption of lutein into the aqueous lumen. The table below shows the level of micellar lutein per kg of the digested formulation.

<td></td><td>Digested Formulation 2 (Predigested Fat)</td><td>Digested formulation 3: (Low palmitic acid)</td>

<td>Micellar lutein (pg)</td><td>0.598 pg</td><td>0.246 pg</td>

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OC THE MLOHtDAO industrial table above, the cantklaArfteJ ^^ Egjjj ^ the digested formulation that includes twice the amount of lutein

<img file="MX344271B_D0066.tif" />

As shown in the micellar found in the predigested fat, more micellar was found in the digested formulation including low palmitic acid, indicating that the use of the predigested fat may increase the absorption of lutein.

EXAMPLE 25

In this example, the ability of predigested fat to reduce the incidence of loose stool is analyzed.

Thirty weaned rats are fed a hydrolyzed protein based infant formula powder, comprising MCT oil as 30% by weight of the fat source for a four day adaptation period. At the end of the adaptation period, rats were randomized into two groups and fed either a control formulation (powdered infant formula with low palmitic acid) or a test formulation (infant formula containing predigested fat). The nutritional profile of the control formulation and the test formulation are identical. Rats had free access to food and water over a period of five days, and the amount of food eaten and body weight were recorded daily.

Although there is no significant difference in food intake or weight gain between the two groups, there is a significant difference in stool consistency. Consistency of rat faeces was obtained using a μ

IW1 MEXICAN TUTO

Cf LA rXOHEOAD O industrial V last two days of scoring system 0-5 in feed.

The score is based on the severity and that of the feces that are attached to a cage transfer sheet. A score of 0 indicates that the stool is normal and a score of 5 watery diarrhea. As the picture shows. 2, rats fed the control formulation (containing MCT oil) produced looser stools than rats fed the test formulation (containing predigested fat).

EXAMPLE 26

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

Pigs born before term (92% gestation) and by cesarean section are immediately transferred to an oxygenated incubator (37 ° C), and a vascular catheter is placed in an umbilical artery. Pigs are given three injections (4, 6, and 7 ml / kg body weight) of maternal plasma through the vascular catheter during the first 24 hours. Total parental nutrition (TPN) is provided at a rate of 4-6 ml / kg / hour for 24 hours. Pigs are then randomly assigned to receive either a control formulation or a PDF formulation at a rate of 5 ml / kg / hour through an orogastric tube. The Control Formulation and the PDF Formulation are identical with

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MEXICAN INSTITUTE OF LA MORTHAGE except fat systems in the '' Wísmcrsv Specifically, the fat system in the formOTíTCróTI T! Tí CUllliul includes vegetable oil, and the fat system in the PDF formulation includes 30% by weight palmitate of monoglycerol, 20% by weight of soybean fatty acids, 26% by weight of high oleic safflower oil, 14% by weight of coconut oil, and 10% by weight of tributyrin. Both 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 enteral feeding and necropsy was performed to assess the severity of NEC lesions using a 1-5 scoring system with a score of 1 indicating 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>Formulation PDF (n = 3)</td><td>Control formulation (n = 5)</td><td>Formulation PDF (n = 3)</td>

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

<td>NEC detected at autopsy</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>

<img file="MX344271B_D0067.tif" />

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As shown in the table above, five pigs (50%) fed the control formulation died of NEC before the end of the enteral feeding period, but only one of the six pigs (16.7%) fed the Formulation PDF died of NEC before the conclusion of the enteral feeding period. Furthermore, seven of the ten pigs (70%) fed the control formulation were determined to have NEC at the end of the enteral feeding period, while only two of the six pigs (33%) fed the PDF formulation were determined that they had NEC at the conclusion of the enteral feeding period. Therefore, it can be concluded that by replacing a vegetable oil fat system with a fat system including predigested fat, the incidence of NEC can be decreased.

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