TW201306753A - Improved rate of protein digestion in a low calorie infant formula - Google Patents

Abstract

The present disclosure is directed to low calorie infant formulas, and in particular, low calorie infant formulas that have a low buffering capacity, exhibit an increased rate of protein hydrolysis and digestion, and have an improved tolerance, as compared to full calorie infant formulas. Also disclosed are low calorie liquid infant formulas that have a reduced (i.e., ''low'') micronutrient content on a per volume basis, and exhibit an overall improvement in the physical properties of the formula, as compared to low calorie liquid infant formulas having a higher micronutrient content.

Description

Low calorie infant formula that promotes protein digestibility

The present invention relates to low calorie infant formulas and, in particular, low calorie infant formulas having low buffering capacity, exhibiting increased protein hydrolysis and digestibility, and improved tolerance compared to the full calorie infant formula. It also reveals a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and an overall improvement in the physical properties of the formulation (including lighter color and stability) Sexual improvement) low calorie liquid infant formula.

The present application claims the benefit of U.S. Provisional Application Serial No. 61/428,827, filed on December 30, 2010, the disclosure of which is hereby incorporated by reference.

There are many types of well-known and widely available infant nutrition formulas. These infant formulas contain a variety of nutrients designed to meet the nutritional needs of the baby's growth, and typically include fats, carbohydrates, proteins, vitamins, minerals, and other nutrients that help optimize the growth and development of the baby.

However, breast milk is generally considered to be the best source of nutrition for newborns. Human breast milk is known to provide excellent immunological benefits to breastfed infants. Therefore, most infant formulas are designed to be closer to breast milk in terms of composition and function.

It is also known that the composition of human breast milk changes during the first few weeks after delivery. Human breast milk is called colostrum during the first 5 days after birth and is called transitional milk during the 6th to 14th day after birth and is subsequently referred to as mature milk. The corresponding human breast milk composition is significantly different during each lactation phase. For example, colostrum and transition milk have lower caloric density and higher protein and lower carbohydrate concentrations than mature milk. The vitamin and mineral concentrations in the three defined human milk groups are also different.

Some commercially available infant formulas are similar in composition but not identical to mature human breast milk and are used in newborns as well as larger infants. It has previously been recognized that feeding of newborns should be focused on promoting infant growth and that growth can be optimally achieved by feeding the infant with a commercial infant formula having nutrient and energy content similar to mature milk.

Recently, attempts have been made to formulate infant formulas for neonates that have lower energy content and therefore provide less calories during the first weeks or months of life compared to the calories provided by conventional full calorie infant formula feeding. Previous attempts to formulate infant formulas with low energy content involved reducing the amount of one or more macronutrients (eg, protein, fat, carbohydrates) per unit volume while maintaining micronutrient levels similar to those found in whole calorie infant formulas. . However, the combination of macronutrient reduction and high micronutrients produces a formulation with weak physical properties. For example, such formulations are generally darker in color, have increased settling problems and are more easily separated during the shelf life than full calorie formulations.

In addition, some infant formula-fed newborns can experience gastrointestinal intolerance (GI) intolerance problems, including soft stools, fart, and cough. GI intolerance problems can be attributed, at least in part, to digestion and absorption of nutrients (eg, proteins) in infants. To address this intolerance problem, some infant formulas exclude lactose as a component, while other infant formulas replace the intact milk protein with hydrolyzed proteins to reduce the burden on the baby's digestive system.

Some formula-fed infants may also experience more gastrointestinal infections than breastfed infants. One explanation for this phenomenon is the low buffering capacity of human breast milk. Human breast milk is known to have lower acid buffering properties than cow's milk and infant formula based on cow's milk. The low buffering capacity of human breast milk can make the natural gastric acidity of the baby more effective in inactivating the pathogens that are orally ingested.

There is therefore a need to provide a low calorie liquid infant formula with improved physical properties such as lighter color and improved stability compared to previously known low calorie infant formulas. There is also a need to provide infant formulas that have low buffering capacity (similar to breast milk) and that also have increased protein hydrolysis and digestibility and excellent tolerance to provide other benefits to the infant.

This invention relates to low calorie liquid infant formulas having improved physical properties. These formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and an overall improvement in the physical properties of the product (including lighter color and Stability improvement). Low calorie liquid and powder infant formulas having low buffering capacity, increased protein hydrolysis and digestibility, and/or improved formulation tolerance are also disclosed as compared to conventional full calorie infant formulas. The low calorie formula of the present invention provides sufficient nutrients for neonatal growth and development when administered to a newborn during the first few weeks of life.

Thus, in one embodiment, the invention relates to a method of improving protein digestion in infants. The method comprises administering an infant formula having an infant energy content of from about 200 to less than 600 kcal/liter.

In another embodiment, the invention is directed to a method of improving protein digestion in an infant. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having an energy of from about 200 to less than 600 kcal/liter of formula content. At least 65% of the micronutrient is included in the infant formula in an amount of from about 30% to about 80% by weight of the conventional micronutrient, per unit volume.

In another embodiment, the invention is directed to a method of improving protein digestion in an infant. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having an energy of from about 200 to about 360 kcal/liter of formula content. At least 45% of the micronutrient is included in the infant formula in an amount of from about 30% to about 65% by weight of the conventional micronutrient, per unit volume.

In another embodiment, the invention is directed to a method of improving protein digestion in an infant. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having an energy of from about 360 to less than 600 kcal/liter of formula content. At least 30% of the micronutrients are included in the infant formula in an amount of from about 55% to about 80% by weight of the conventional micronutrient, per unit volume.

In another embodiment, the invention is directed to a method of improving protein absorption in an infant. The method comprises administering an infant formula having an infant energy content of from about 200 to less than 600 kcal/liter.

It has been surprisingly found that if a sufficient amount of one or more micronutrients in a low calorie formulation is substantially matched to the micronutrient in the full calorie formula per kilocalories rather than in unit volume, then a low calorie with improved physical properties can be formulated. Liquid infant formula. Therefore, these formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and the overall physical properties of the product are improved (including lighter colors) And stability improvement).

Low calorie liquid or powdered infant formulas have also been found to have lower cushioning capacity than conventional full calorie infant formulas, and in some embodiments, have a lower buffering capacity than human milk. Therefore, the low calorie infant formula of the present invention can be used to adjust the gastric acidity of an infant, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of an infant, and promote the growth of beneficial microorganisms. It has also been found that the low calorie infant formula of the present invention exhibits increased protein hydrolysis and digestibility as compared to conventional full calorie infant formula, and thus has improved formulation tolerance.

The low calorie liquid infant formula disclosed herein can have low micronutrient content (in unit volume) and improved physical properties compared to conventional infant formulas having higher micronutrient content. In addition, the method of the present invention utilizes a low-calorie liquid and a powdered infant formula to regulate the gastric acidity of the infant, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of the infant and promote the growth of beneficial microorganisms, improve protein hydrolysis and digestibility, and improve formulation tolerance. These and other and optionally optional features of the infant formula and method of the present invention, as well as a variety of other optional variations and additions, are described in detail below.

The term "retort" and "retort sterilized" are used interchangeably herein and, unless otherwise indicated, are meant to fill a container with a nutrient liquid (such as a liquid infant formula) (most commonly a metal can). Or other similar packaging) and then subjecting the liquid-filled package to the necessary heat sterilization step to form a common operation of the sterilization-sterilized nutrient liquid product.

As used herein, the terms "aseptic" and "aseptic sterilized" are used interchangeably and, unless otherwise indicated, means that the packaged product is manufactured without relying on the sterilization sterilization step described above, wherein the individual is independently prior to filling. The nutritional liquids and packages are sterilized and then combined under sterile or aseptic processing conditions to form a sterilized, aseptically packaged nutritional liquid product.

The terms "nutritional formula" or "nutritional product" or "nutritional composition" as used herein are used interchangeably and refer to nutrient liquids, nutrient semi-liquids, nutritive solids, nutrient semi-solids, nutrient powders, nutrition, unless otherwise stated. Supplements and any other nutritious foods known in the art. The nutritional solids and powders can be reconstituted to form a nutritional liquid, which all contain one or more of fats, proteins, and carbohydrates, and are suitable for oral consumption by humans. The nutritional formula can include an infant formula.

The term "nutritional liquid" as used herein, unless otherwise indicated, refers to a ready-to-drink liquid form, a concentrated form of a nutritional product, and a nutritional liquid produced by restoring the nutritional powder described herein prior to use.

The term "nutritional powder" as used herein, unless otherwise indicated, refers to a nutritional product in a flowable or extractable form that can be reconstituted with water or another aqueous liquid prior to consumption and includes spray drying and dry mixing/drying. Blend the powder.

The term "nutritional semi-liquid" as used herein, unless otherwise indicated, refers to a form in which properties (such as flow properties) are between liquid and solid, examples of which include thick shakes and liquid gels.

The term "nutritional semi-solid" as used herein, unless otherwise indicated, refers to a form in which a property such as rigidity is between a solid and a liquid, examples of which include pudding, gelatin, and dough.

The term "infant" as used herein, unless otherwise indicated, refers to a child 12 months of age or younger than 12 months of age. The term "premature baby" as used herein refers to an infant born before the 36-week gestation period. The term "term infant" as used herein refers to an infant born at 36 weeks of gestation or after 36 weeks of gestation.

The term "neonatal" as used herein, unless otherwise indicated, refers to an infant who is younger than about 3 months, including infants from zero to about two weeks old. Newborns can be term infants or premature babies.

The term "infant formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional products suitable for consumption by infants. Unless otherwise stated herein, the term "infant formula" is intended to encompass both term infant formula and preterm formula.

The term "preterm formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional products suitable for consumption by preterm infants.

The term "micronutrient" as used herein refers to a small amount of essential material required by an organism. Non-limiting examples include vitamins, minerals, and the like.

The term "full calorie infant formula" as used herein refers to an infant formula in which the caloric density or energy content of the formulation is not reduced compared to the caloric density or energy content conventionally included in infant formulas. Typically, the full calorie infant formula will have an energy content of at least 600 kcal/L, or even at least 660 kcal/L, and more typically at least 676 kcal/L, including 600 kcal/L to 800 kcal/L.

The term "low calorie infant formula" as used herein refers to an infant formula that has a lower energy content per unit volume than a full calorie infant formula.

When referring to the micronutrient content of an infant formula, the term "high micronutrient" or "high micronutrient content" means that at least 80% of the micronutrients in the infant formula are almost the same amount as the micronutrients conventionally included in the infant formula ( For most micronutrients, usually within about 82%).

All percentages, parts and ratios as used herein are by weight of the total composition, unless otherwise indicated. All such weights, when referring to the recited ingredients, are based on the active level and therefore do not include solvents or by-products that may be included in the commercially available materials, unless otherwise stated.

The numerical ranges as used herein are intended to include a In addition, the numerical ranges should be considered as supporting the claim of any value or subset of values within the range. For example, the descriptions 1 to 10 should be considered to support ranges of 2 to 8, 3 to 7, 5 to 6, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, and the like.

All references to the singular features or limitations of the invention are intended to include the corresponding plural features or limitations, and vice versa, unless otherwise indicated.

All combinations of methods or process steps as used herein may be performed in any order, unless otherwise indicated or clearly contradicted by the context in which the reference combination is made.

The various embodiments of the infant formulas and methods of the present invention may also be substantially free of any optional ingredients or features selected as described herein, with the proviso that the remaining infant formula still contains all of the desired ingredients described herein. Or feature. In this context and unless otherwise indicated, the term "substantially free" means that the selected infant formula contains less than 1% by weight (including less than 0.5% by weight, including less than 1% by weight, including less than the functional amount, optionally included. Less than 0.1% by weight and also including 0% by weight) of the optional or selected ingredients.

The infant formula and method of the present invention may comprise the elements of the products and methods described herein as well as any other or optionally selected elements described herein or otherwise suitable for use in a nutritional infant formula application, as described herein. The elements of the products and methods, as well as any other or optional elements described herein or otherwise suitable for use in a nutritional infant formula application, consist essentially of or consist essentially of the elements of the products and methods described herein and or described herein or Any other or optional element that is otherwise suitable for use in nutritional infant formula applications.

Product form

The infant formula of the present invention can be formulated and administered in any known or other suitable oral product form. Any solid, semi-solid, liquid, semi-liquid or powder form, including combinations or variations thereof, is suitable for use in the present invention, provided that such forms are safe and effective for oral delivery of the essential ingredients as defined herein to the individual.

Specific non-limiting examples of product forms suitable for use in the products and methods disclosed herein include, for example, liquid and powder preterm formulas, liquid and powder term infant formulas, and liquid and powder elements and semi-element formulations.

The infant formula of the present invention is preferably formulated in the form of a dietary product, which is defined herein as an embodiment comprising the essential ingredients of the present invention and in the form of a product comprising at least one of a fat, a protein and a carbohydrate.

Infant formulas can be formulated with sufficient types and amounts of nutrients to provide a unique, primary or additional source of nutrients, or to provide specific nutritional products for infants suffering from a particular disease or condition or to provide targeted nutritional benefits.

The infant formula of the present invention needs to be formulated for use in newborns, including term newborns and premature newborns. Infant formulas are preferably formulated for feeding newborns during the first few weeks of life and are better for feeding newborns between 0 and 2 weeks of age. In one embodiment, the infant formula is formulated for feeding the newborn in the first two days after birth. This formula is referred to herein as "Day 1-2 Formulation" or "Day 1-2 Infant Formulation". In other embodiments, the infant formula is formulated for feeding the newborn during the 3-9th day after birth. This formula is referred to herein as "Day 3-9 Formulation" or "Day 3-9 Infant Formulation". It is to be understood that the infant formula formulated on Days 1-2 of the present invention is not limited to being administered only during the first two days after birth, and in some embodiments, larger infants may also be administered. Similarly, infant formulas administered on days 3-9 are not limited to administration only during days 3-9 postnatal, while in some embodiments infants of other ages may be administered.

Nutrient liquid

Nutrient liquids include concentrated nutrient liquids and ready-to-serve nutrient liquids. These nutrient liquids are most often formulated as suspensions, emulsions or as clear or substantially clear liquids.

Suitable nutritional emulsions can be aqueous emulsions containing proteins, fats and carbohydrates. The emulsions are typically in the form of a flowable or potable liquid at from about 1 ° C to about 25 ° C and are typically in the form of an oil-in-water, water-in-oil or complex aqueous emulsion, but such emulsions most typically have a continuous aqueous phase and A continuous oil phase in the form of an oil-in-water emulsion.

The nutrient liquid can be and is generally stable for storage. The nutritional liquid typically contains up to about 95% by weight water, from about 50% to about 95% by weight, also from about 60% to about 90% by weight, and also from about 70% to about 85% by weight, based on the weight of the nutritional liquid. water. The nutritional liquid can have a variety of product densities, but the density is most typically greater than about 1.03 g/mL, including greater than about 1.04 g/mL, including greater than about 1.055 g/mL, including from about 1.06 g/mL to about 1.12 g/mL, and Also included is from about 1.085 g/mL to about 1.10 g/mL.

The pH of the nutritional liquid can range from about 3.5 to about 8, but is preferably in the range of from about 4.5 to about 7.5, including from about 5.5 to about 7.3, including from about 6.2 to about 7.2.

Although the amount of nutrient liquid consumed can vary depending on a variety of variables, typical consumption levels are typically at least about 2 milliliters, or even at least about 5 milliliters, or even at least about 10 milliliters, or even at least about 25 milliliters, including from about 2 mL to about A range of 300 mL, including from about 100 mL to about 300 mL, from about 4 mL to about 250 mL, from about 150 mL to about 250 mL, from about 10 mL to about 240 mL, and from about 190 mL to about 240 mL.

Nutritional powder

The nutritional powder is in the form of a flowable or substantially flowable particulate composition, or at least in the form of a particulate composition. Particularly suitable nutritional powder forms include spray dried, coalesced or dry blended powder compositions or combinations thereof, or powders prepared by other suitable methods. The composition can be easily taken and measured with a spoon or other similar device, wherein the composition can be easily reconstituted with a suitable aqueous liquid (usually water) to form a nutritional liquid (such as an infant formula) for immediate oral or enteral use. . In this case, "immediate" use generally means use within about 48 hours of recovery, most typically within about 24 hours, preferably immediately after recovery or within 20 minutes of recovery.

Energy content

The infant formula of the present invention has a low energy content compared to conventional term and preterm formulas (as used herein interchangeably with the term "caloric density"). In particular, the infant formula of the present invention provides from about 200 kcal/L to less than 600 kcal/L (including from about 200 kcal/L to about 500 kcal/L, and more specifically from about 250 kcal/L to about 500 kcal/ L) The heat density or energy content. The infant formula of Days 1-2 of the present invention provides from about 200 kcal/L to about 360 kcal/L (including from about 200 kcal/L to about 350 kcal/L, also including from about 250 kcal/L to about 350 kcal/L, A heat density or energy content of from about 250 kcal/L to about 310 kcal/L, and more specifically about 250 kcal/L or about 270 kcal/L. The 3-9 day infant formula of the present invention provides from about 360 kcal/L to less than 600 kcal/L (including from about 370 kcal/L to less than 600 kcal/L, also including from about 360 kcal/L to about 500 kcal/L, A heat density or energy content of from about 390 kcal/L to about 470 kcal/L, and more specifically about 406 kcal/L or about 410 kcal/L. Compared to the infant formula of the present invention, the conventional full-term and preterm formula (also referred to herein as "full calorie infant formula") has a significantly higher caloric density or energy content, typically in the range of 600 kcal/L to 880 kcal/L. Inside.

When the infant formula of the present invention is in powder form, it is intended to restore the powder prior to use to achieve the above described caloric density and other nutritional requirements as described herein. Likewise, when the infant formula of the present invention is in the form of a concentrated liquid, it is intended to dilute the concentrate prior to use to achieve the desired caloric density and nutritional requirements. The infant formula can also be formulated as a ready-to-feed liquid that has the required caloric density and nutritional requirements.

The infant formula of the present invention requires administration to the infant according to the methods described in detail herein, and in detail the newborn. The methods can include feeding the infant formula according to the daily formula intake described herein.

The energy component of an infant formula is most often provided by a combination of fat, protein, and carbohydrate nutrients. The protein may comprise from about 4% to about 40% total calories, including from about 10% to about 30%, and also from about 15% to about 25%; the carbohydrate may comprise less than 40% total calories, including from about 5% to about 37% Also included is less than about 36%, and also includes from about 20% to about 33%; and the fat may comprise the remaining formula calories, most typically less than about 60% calories, including from about 30% to about 60%. Other illustrative amounts are set forth below.

Micronutrients

In some embodiments, in addition to low energy content, the infant formula of the present invention is also characterized by a low micronutrient content (in terms of unit volume).

As previously described, previous attempts to formulate infant formulas with low energy content have involved reducing the levels of one or more macronutrients (eg, protein, fat, carbohydrates) while maintaining micronutrient content and being found in a full calorie infant formula. The content is approximate (in terms of unit volume). For example, one liter of one or more macronutrients in a 1 liter lower calorie formula is reduced compared to a one liter full calorie formula, but the amount of micronutrients is roughly the same as that found in a 1 liter full calorie formula (for most Micronutrients, usually within at least about 82%). However, the combination of macronutrient reduction and high micronutrients produces a formulation with weak physical properties. For example, such formulations are generally darker in color, have increased settling problems and are more easily separated during the product shelf life than the full calorie formulation.

It has now been surprisingly found that low caloric liquids with improved physical properties can be formulated if the amount of micronutrients in the low calorie formula is substantially in compliance with the total calorie formula per kilocalorie (kcal) rather than unit volume. Baby formula. For example, a 100 kcal low calorie formula will contain micronutrients in substantially the same amount (for most micronutrients, typically within about 80%) as found in a 100 kcal all-calorie formulation. In this example, the micronutrient content of the low calorie formula will be formulated in 100 kcal. The low calorie liquid infant formula formulated per kcal has a reduced (ie "low") micronutrient content (in terms of unit volume, ie compared to the same volume full calorie formula), and the overall physical appearance of the formulation is improved overall , including lighter color and improved stability.

Accordingly, in some embodiments, the present invention is directed to low calorie, low micronutrient infant formulas. As used herein, the term "low micronutrient" or "low micronutrient content" when referring to an infant formula means that the amount of at least a portion of the micronutrient included in the infant formula is lower than the corresponding micronutrient conventionally included in the infant formula. Quantity (in unit volume). It should be understood that the amount of all micronutrients included in the infant formula may not necessarily be lower than the conventional micronutrient amount (in terms of unit volume) to achieve the infant formula as a low micronutrient infant formula. It is sufficient to reduce a portion of the micronutrients in the infant formula as compared to conventional amounts in unit volume.

"Micro-nutrient quantities or "native amounts" in the infant formula refer to the amount of standard micronutrients required by the industry-approved infant formula to achieve proper growth and development of the baby (in unit volume) meter). The conventionally selected micronutrient amounts (in unit volume) which may be included in the infant formula are set forth in Table A (i.e., Dietary Formulation) and Table B (Reconstituted Powder Formulation) below.

Table A: Ready-to-eat formula

Table B: Reconstituted Powder Formulation

Exemplary non-limiting micronutrients that may be included in conventional infant formulas include vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, biotin. , vitamin C, choline, inositol, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, sodium, potassium, chloride, fluoride, selenium and combinations thereof. Some exemplary conventional infant formulas can include a combination of copper, phosphorus, iron, calcium, and zinc. Some other exemplary conventional infant formulas may include a combination of copper, iron, and phosphorus.

In a particular embodiment, at least two of copper, phosphorus, iron, calcium, and zinc are about 5% less, or even about 10% smaller, or even about 20% smaller than the amounts set forth in Tables A and B above. , or even about 30% smaller, or even about 50% smaller, or even about 75% smaller, or even about 80% smaller, or even about 90% smaller in the low micronutrient formulation. In another particular embodiment, the iron and copper are about 5% less, or even about 10% smaller, or even about 20% smaller, or even about 30% smaller, or even less than 30%, or even less than the amounts set forth in Tables A and B above. Amounts of about 50%, or even about 75%, or even about 80%, or even about 90%, are present in low micronutrient formulations.

It should be understood that Tables A and B do not contain a complete list of suitable micronutrients that may be included in the infant formula of the present invention. In addition, the low micronutrient infant formula of the present invention need not include each of the micronutrients listed in Tables A and B. The present invention encompasses infant formulas comprising any of the micronutrients listed in Tables A and B and/or any combination of one or more of the other micronutrients known in the art to be included in an infant formula. The standard or conventional levels of these and other micronutrients (in terms of 100 kcal) can be readily determined by reference to European and/or US infant formula rules and standards.

When determining whether the micronutrient content (in terms of unit volume) in the infant formula is lower than the conventional content, the amount of "corresponding micronutrient" should be compared. In this case, "corresponding micronutrient" means the same micronutrients present in the infant formula being evaluated. For example, if the infant formula contains micronutrients such as calcium, phosphorus, and magnesium, the amount of the micronutrients in the infant formula and the amount of calcium, phosphorus, and magnesium conventionally included in the infant formula should be compared to determine the infant formula. Is the amount of micronutrients less "lower"?

The amount of micronutrients included in the low micronutrient infant formula of the present invention can be expressed as a percentage of the corresponding corresponding micronutrient amount per unit volume. For example, in some embodiments of the invention, a low micronutrient infant formula is provided wherein the micronutrients are included in the infant formula in an amount of from about 30% to about 80% of the amount of the corresponding micronutrient (in terms of unit volume) And comprising from about 30% to about 65%, from about 55% to about 80%, from about 40% to about 70%, from about 40% to about 50%, and from about 60% to about 70% of the amount of the corresponding micronutrient ( All in terms of unit volume). Typically, at least 65% of the micronutrients in the low micronutrient infant formula of the present invention comprise at least 75%, at least 80%, at least 90% and 100% micronutrients in an amount of from about 30% to about 80% of the conventional micronutrient amount. The amount is included in the infant formula (in unit volume).

In some embodiments, a low micronutrient infant formula is provided, wherein the micronutrient is included in the infant formula (in unit volume) in an amount from about 30% to about 65% of the amount of the corresponding micronutrient, including conventionally corresponding micronutrients From about 35% to about 60%, from about 40% to about 50%, from about 40% to about 45%, and especially about 40% by weight of the nutrient (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 45% micronutrient, including at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% micronutrient in a conventionally appropriate amount. Amounts from about 35% to about 60% of the amount of nutrients are included in the infant formula (in unit volume). In other embodiments, at least 10% of the micronutrient in the low micronutrient infant formula comprises at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the micronutrient by about 40 of the conventional micronutrient amount. Amounts from about % to about 50% are included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, the first 1-2 day infant formula.

In other embodiments, a low micronutrient infant formula is provided wherein the micronutrient is included in the infant formula (in unit volume) in an amount from about 55% to about 80% of the amount of the corresponding micronutrient, including conventionally corresponding micronutrients From about 60% to about 75%, from about 60% to about 70%, from about 60% to about 65%, and especially about 60% by weight of the nutrient (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 30% micronutrient, including at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% micronutrient in a conventionally appropriate amount. Amounts from about 55% to about 80% of the amount of nutrients are included in the infant formula (in unit volume). In other embodiments, at least 10% of the micronutrient in the low micronutrient infant formula comprises at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the micronutrient by about 60 of the conventional micronutrient amount. Amounts from % to about 70% are included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula.

In some embodiments wherein the micronutrients comprise minerals, the minerals are included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 80% of the amount of the corresponding minerals, including It is known that the amount of the corresponding mineral is from about 30% to about 65%, from about 55% to about 80%, from about 40% to about 70%, from about 40% to about 50%, and from about 60% to about 70% (both in units) Volume meter). Typically, at least 10%, including at least 45%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 90%, and 100% minerals in the low micronutrient infant formula of the present invention are An amount of from about 30% to about 80% of the amount of the corresponding mineral is known to be included in the infant formula (in unit volume).

In other embodiments, the mineral is included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 65% of the amount of the corresponding mineral, including the amount of the corresponding mineral. From about 35% to about 60%, from about 40% to about 50%, from about 40% to about 45%, and especially about 40% (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 10% minerals, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% minerals. It is customary to include from about 30% to about 65% of the amount of the corresponding mineral in the infant formula (in unit volume). In other embodiments, at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% of the minerals in the low micronutrient infant formula are known as corresponding minerals. Amounts from about 40% to about 50% of the amount of the substance are included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, the first 1-2 day infant formula.

In other embodiments, the mineral is included in the low micronutrient infant formula (in unit volume) in an amount from about 55% to about 80% of the amount of the corresponding mineral, including the amount of the corresponding mineral. From about 60% to about 75%, from about 60% to about 70%, from about 60% to about 65%, and especially about 60% (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% minerals, as is conventional. Amounts from about 55% to about 80% of the amount of the corresponding mineral are included in the infant formula (in unit volume). In other embodiments, at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% of the minerals in the low micronutrient infant formula are known as corresponding minerals. Amounts from about 60% to about 70% of the amount of the substance are included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula.

In some embodiments wherein the micronutrient comprises a vitamin, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 80% of the conventional vitamin amount, including the conventional vitamin amount. From about 30% to about 65%, from about 55% to about 80%, from about 40% to about 70%, from about 40% to about 50%, and from about 60% to about 70% (both in unit volume). Typically, at least 45%, including at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, and 100% of the vitamins of the low micronutrient infant formula of the present invention are conventionally known as vitamins. Amounts from about 30% to about 80% are included in the infant formula (in unit volume).

In other embodiments, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 65% of the conventional vitamin amount, including about 35% to about the conventional vitamin amount. 60%, from about 40% to about 50%, from about 40% to about 45% and especially about 40% (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 10% vitamins, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% vitamins. Amounts from about 30% to about 65% of the corresponding vitamin amount are included in the infant formula (in unit volume). In other embodiments, at least 10% of the vitamins in the low micronutrient infant formula, including at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the vitamins are from about 40% to about 10% of the conventional vitamins. A 50% amount is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, the first 1-2 day infant formula.

In other embodiments, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount from about 55% to about 80% of the conventional vitamin amount, including about 60% to about 10% of the conventional vitamin amount. 75%, from about 60% to about 70%, from about 60% to about 65%, and especially about 60% (both in unit volume). In such embodiments, at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% of the vitamins in the low micronutrient infant formula are conventionally corresponding. Amounts from about 55% to about 80% of the amount of vitamin are included in the infant formula (in unit volume). In other embodiments, at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, and at least 90% of the vitamins in the low micronutrient infant formula are about 60 of the conventional vitamin amount. Amounts from % to about 70% are included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula.

Suitable micronutrients that may be included in the infant formula of the present invention include vitamins or related nutrients, minerals, and combinations thereof. Non-limiting examples of suitable vitamins include vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, pyridoxine, vitamin B5, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamins C, choline, inositol, ascorbic acid, salts and derivatives thereof, and combinations thereof.

Non-limiting examples of suitable minerals that may be included in the infant formula of the present invention include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, sodium, potassium, molybdenum, chromium, chloride, fluoride, selenium. And their combinations.

Any infant formula can be formulated with the low micronutrient content disclosed herein, including autoclave sterilization and aseptic sterilization of ready-to-eat nutrient liquids, concentrated nutrient liquids, and nutritional powders.

Macronutrients

In addition to the micronutrients described herein, the infant formula of the present invention may also comprise one or more macronutrients. Macronutrients include proteins, fats, carbohydrates, and combinations thereof. The macronutrients suitable for use herein include any protein, fat, carbohydrate or source thereof known or otherwise suitable for use in an oral nutritional product, the restriction being that the macronutrient can be safely and effectively administered orally to the infant and otherwise Compatible with other ingredients in the infant formula.

Although the total concentration or amount of protein, fat and carbohydrate may vary depending on the product form (eg, powder or ready-to-feed liquid) and the intended dietary requirements of the intended user, such concentrations or amounts generally fall within the specific ranges described in the table below. In one of the terms (each term is preceded by the term "about"), including any other essential fat, protein and/or carbohydrate component described herein. For the powder examples, the content in the table below is the amount after the powder is reconstituted.

The total concentration or amount of protein, fat, and carbohydrate may also vary depending on whether the infant formula is a 1-2 day formulation or a 3-9 day formulation. The concentrations of protein, fat and carbohydrate in Formulations 1-2 and Days 3-9 are most often formulated in any of the specific ranges described in the table below (the terms are added before each value) "), including any other essential fat, protein and/or carbohydrate ingredients described herein. For the powder examples, the content in the table below is the amount after recovery.

Alternatively or additionally, the amount or amount of carbohydrate, fat and protein in the infant formula (whether in powder formula or ready-to-feed liquid or concentrated liquid) may also be characterized as the percentage of total calories in the infant formula. The macronutrients in the infant formula of the present invention are most often formulated in any of the ranges of calories described in the table below (each term is preceded by the term "about").

protein

In addition to the micronutrients described herein, the infant formula of the present invention may also comprise a protein. Any known or otherwise suitable protein or protein source may be included in the infant formula of the present invention with the proviso that the proteins are suitable for feeding infants and especially newborns.

Non-limiting examples of suitable proteins or sources thereof for use in an infant formula include hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from any known or other suitable source, such as milk (eg, casein, whey) ), animals (eg, meat, fish), cereals (eg, rice, maize), plants (eg, soybeans), or combinations thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates, casein isolates, highly hydrolyzed casein, whey proteins, casein sodium or casein calcium, whole fat milk as described herein. , partially or completely skim milk, soy protein isolate, soy protein concentrate, and the like. The protein used herein may also include free amino acids known for use in nutritional products or may be replaced, in whole or in part, by free amino acids known for use in nutritional products, such non-limiting free amino acids. Examples include L-alanine, L-aspartic acid, L-glutamic acid, glycine, L-histamine, L-isoleucine, L-leucine, L-phenylalanine, L- Proline, L-serine, L-threonine, L-proline, L-tryptophan, L-glutamic acid, L-tyrosine, L-methionine, L- Cysteine, taurine, L-arginine, L-carnitine, and combinations thereof.

fat

In addition to the micronutrients described herein, the infant formula of the present invention may also comprise a source of fat. Suitable fat sources for use in the infant formula disclosed herein include any fat or fat source suitable for use in oral nutritional products and compatible with the elements and characteristics of such products, with the proviso that the fats are suitable for feeding infants.

Non-limiting examples of suitable fats or sources thereof for use in the infant formulas described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, high oleic safflower oil, high GLA safflower oil, oleic acid, MCT oil (medium chain triglyceride), sunflower oil, high oleic sunflower oil, structured triglyceride, palm oil and palm kernel oil, palm olein ), rapeseed oil, linseed oil, borage seed oil, evening primrose oil, black currant seed oil, source of genetic oil, aquatic oil (eg tuna, sardines), fish oil, fungal oil, algae oil, cottonseed oil and Its combination. In one embodiment, a suitable fat or source thereof includes oil and oil blends, including long chain polyunsaturated fatty acids (LC-PUFA). Some non-limiting specific polyunsaturated acids that may be included include, for example, docosahexaenoic acid (DHA), eicosatetraenoic acid (ARA), eicosapentaenoic acid (EPA), linoleic acid (LA). ) and its analogues. Sources of non-limiting eicosatetraenoic acid and docosahexaenoic acid include aquatic oils, oils derived from eggs, fungal oils, algae oils, and combinations thereof.

Carbohydrate

The infant formula of the present invention may comprise any carbohydrate suitable for use in an oral nutritional product, such as an infant formula, and compatible with the elements and characteristics of such products.

Non-limiting examples of carbohydrates or sources thereof suitable for use in the infant formulas described herein may include maltodextrin; hydrolyzed, whole or modified starch or corn starch; glucose polymer; corn syrup; corn syrup solids Carbohydrate derived from rice; rice syrup; carbohydrate derived from pea; carbohydrate derived from potato; cassava; sucrose; glucose; fructose; lactose; high fructose corn syrup; honey; sugar alcohol (eg maltitol, red Alginitol, sorbitol); artificial sweeteners (eg, sucralose, acesulfame potassium, stevia); indigestible oligosaccharides, oligosaccharides (FOS); In one embodiment, the carbohydrate may comprise maltodextrin having a DE value of less than 20.

Other optional ingredients

The infant formula of the present invention may further comprise other optional ingredients which may improve the physical, chemical, aesthetic or processing characteristics of the product or act as a pharmaceutical or other nutritional component when used in the target population. A variety of such optional ingredients are known or otherwise suitable for use in pharmaceutical or other nutritional products or pharmaceutical dosage forms and may also be used in the compositions herein, with the proviso that the ingredients selected as such may be safe. It is administered orally and is compatible with the necessary and other ingredients in the selected product form.

Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, fructooligosaccharides, galactooligosaccharides, human milk oligosaccharides and other probiotics, pharmaceutically active , other nutrients, colorants, fragrances, thickeners and stabilizers, emulsifiers, lubricants, carotenoids (eg, beta-carotene, zeaxanthin, lutein, lycopene described herein) ) and so on.

The powdered infant formula described herein can include a flow or anti-caking agent to delay the agglomeration or agglomeration of the powder over time and to facilitate the flow of the powder embodiment from its container. Any flow or anti-caking agent known or otherwise suitable for use in a nutritional powder or product form may be suitable for use herein, non-limiting examples of which include tricalcium phosphate, citrate, and combinations thereof. The concentration of the flow agent or anti-caking agent in the nutritional product will vary depending on the product form, other selected ingredients, desired flow properties, etc., but is most typically in the range of from about 0.1% to about 4% by weight of the nutritional product, including about 0.5. From % by weight to about 2% by weight.

Stabilizers may also be included in the infant formula. Any stabilizer known or otherwise suitable for use in a nutritional product is also suitable for use herein, some non-limiting examples of which include gums such as triterpene. The stabilizer may comprise from about 0.1% to about 5.0% by weight of the infant formula, including from about 0.5% to about 3% by weight, including from about 0.7% to about 1.5% by weight.

stability

The low calorie, low micronutrient liquid infant formula of the present invention advantageously exhibits physical property improvements, including stability improvements, as compared to low calorie, high micronutrient formulations. Physical stability issues with liquid infant formulas typically occur when the formulation is stored for long periods of time prior to use. During this time, components of the formulation, such as fat, are typically separated from the aqueous component. The components of the infant formula may also settle from the suspension to form a sediment at the bottom of the formula container. Although this phase separation and sinking can be corrected by shaking the formulation to remix the formulation components, the phase separation and sinking typically cause the consumer's acceptance of the product to be greatly reduced.

It has been found that the micronutrient content of low calorie liquid infant formula can affect the stability of infant formula. In particular, the low calorie, low micronutrient liquid infant formula of the present invention advantageously exhibits less sedimentation and less separation during the formulation shelf life than the low calorie, high micronutrient formulation.

Protein load

A variety of measurements can be used to verify the stability of a liquid infant formula. For example, one method is to determine the stability of a liquid infant formula by measuring the protein loading. The protein loading can be expressed as the percentage of protein in the cream layer formed by high speed centrifugation of the infant formula (grams of protein per 100 grams of cream layer). Techniques suitable for determining protein loading are described in detail in the examples of the present disclosure.

The stability of liquid infant formula emulsions generally increases with increasing protein loading. It has been found that the low-calorie, low-micronutrient sterilizer-sterilized liquid infant formula has a higher protein load than the low-calorie, high-micronutrient sterilizer-sterilized liquid infant formula. This was observed in both the 1-2 day sterilization autoclave infant formula and the 3-9 day sterilization autoclave infant formula.

Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has increased protein loading compared to a low calorie, high micronutrient infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilized, ready-to-eat (RTF) formulation. In embodiments wherein the low calorie, low micronutrient liquid infant formula is the 1-2 day infant formula, the infant formula will typically have a protein loading of at least about 5.0%, including from about 5.0% to about 7.0%, about 5.5%. To about 6.5%, from about 5.7% to about 6.1% and especially about 5.9%.

In embodiments wherein the low calorie, low micronutrient liquid infant formula is a 3-9 day infant formula, the infant formula will typically have a protein loading value of at least about 6.0%, including from about 6.0% to about 8.0%, about 6.5%. To about 7.5%, from about 6.7% to about 7.1%, and especially about 6.9%. The low-calorie, low-micro nutrient liquid infant formula is preferably sterilized by sterilization.

Particle size

Another measure that can be used to verify the stability of a liquid infant formula is the particle size distribution and average particle size of the particles present in the infant formula. The particle size distribution and average particle size can be determined using any technique known in the art. One technique described in the examples of the present disclosure involves the use of a light scattering machine (e.g., Beckman Coulter LS 13 320) that uses a multi-wavelength source to measure the particle size distribution of particles suspended in a liquid infant formula sample. Other suitable techniques can also be used.

The stability of liquid infant formula emulsions generally increases with decreasing particle size. It has been found that the low-calorie, low-micro nutrient of the present invention has a larger number of small particles than the low-calorie, high-micronutrient 1-2 day sterilization-sterilized liquid infant formula. The average particle size of the particles present in the formulation is small.

Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has a smaller average particle size in the formulation than a low calorie, high micronutrient liquid infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilization-sterilized RTF formulation, and more preferably a 1-2 day sterilization-sterilized liquid infant formula. In embodiments wherein the low calorie, low micronutrient liquid infant formula is the 1-2 day infant formula, the average particle size of the particles present in the infant formula will typically range from about 0.1 μm to about 1.0 μm, including from about 0.15 μm to It is about 0.8 μm and about 0.15 μm to about 0.7 μm.

Generally, for the low calorie, low micronutrient 1-2 day liquid infant formula of the present invention, at least about 50% (including from about 50% to about 100% and from about 50% to about 70%) of the granules present in the infant formula The particle size (diameter) will be from about 0.15 μm to about 0.8 μm.

Cream separation speed (Creaming Velocity)

Another measure that can be used to verify the stability of a liquid infant formula is the rate of cream separation. The cream separation rate measures the rate at which the particles move in the liquid sample (in this case, the infant formula) and predicts the ability of the infant formula to form a cream layer after standing or centrifugation for a long period of time. The separation rate of the cream can be calculated using the following equation:

among them:

v _cream is the separation speed of _cream

ρ _fluid is the formula density

ρ _particle is the particle density

η is the formula viscosity

R is the average particle size

g is the acceleration of gravity.

The stability of a liquid infant formula emulsion generally increases as the cream separation speed decreases. It has been found that the low-calorie, low-micro nutrient of the present invention has a lower emulsion separation rate than the low-calorie, high-micronutrient 1-2 day sterilization-sterilized liquid infant formula.

Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has a low cream separation rate compared to a low calorie, high micronutrient infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilization-sterilized RTF formulation, and more preferably a 1-2 day sterilization-sterilized liquid infant formula. In embodiments in which the low calorie, low micronutrient liquid infant formula is the 1-2 day infant formula, the infant formula may have an emulsification separation rate of typically about 5.0 cm/day or less than 5.0 cm/day, including about 1.0 cm/ It is about 5.0 cm/day, about 3.0 cm/day to about 3.5 cm/day, and especially about 3.2 cm/day.

colour

The low calorie, low micronutrient liquid infant formula of the present invention also advantageously exhibits color improvements as compared to low calorie, high micronutrient formulations.

Liquid infant formulas contain a variety of nutrients that may interact during formulation, processing, and storage. These interactions can distort the color of the formula to gray, beige or other similar discoloration. Such discoloration usually causes consumers to greatly reduce the acceptance of the product, and consumers usually prefer bright, white products.

One technique that can be used to assess the color characteristics of an infant formula is the Agtron color score. The Aegis scoring system used herein was measured by a conventional technique using an Agtron 45 spectrophotometer (available from Agtron Inc., Reno, Nevada). Aegis is divided into measurements of the percentage of energy (light) reflected from the surface of each infant formula. The stronger or brighter the surface color of the formula, the higher the Aegis score. These scores range from 0 (black) to 100 (white).

It has been found that the micronutrient content of low calorie liquid infant formula can affect the color of the formula. In particular, the low calorie, low micronutrient liquid infant formula of the present invention has a brighter, whiter color (as defined by the Aegis score) compared to the low calorie, high micronutrient formula. This was observed in both sterilized and sterile sterilized low-calorie, low-micronutrient liquid formulations. The color improvement of low calorie, low micronutrient liquid infant formulas was also observed not only after the blending, but also after a long period of time (in some cases, at least 9 months after product formulation).

Therefore, in one aspect, the present invention relates to a low-calorie, low-micronutrient 1-2 day liquid infant formula, which is formulated to have at least about 45, including about 45, after formulation (within 1 day of blending). Up to about 60 and about 47 to about 55. The formulation is preferably a sterilization autoclave RTF formulation. In other embodiments, the formulation is divided into at least about 40, including from about 40 to about 50, for two months after formulation; the Aegles is divided into at least about 37, including about 40 to four months after formulation. Approximately 50; Aegis is divided into at least about 37, including about 37 to about 50, for six months after deployment; and the Aegean score of at least about 35, including about 35 to about 45, after nine months of blending.

In another aspect, the present invention relates to a low calorie, low micronutrient 3-9 day liquid sterilizing infant sterilized infant formula, wherein the formulated Aige Zhuang is divided into at least about 42, including about 42 to about 55 and about 45 to about 52. In other embodiments, the formulation is divided into at least about 40, including from about 40 to about 50, for three months after formulation; and the Aegles is divided into at least about 40, including about 40, for six months after deployment. To about 50.

In another aspect, the present invention is directed to a low-calorie, low-micronutrient 3-9 day liquid aseptically sterilized infant formula having a blended Aegis score of at least about 58, including from about 58 to about 65 and about 60. To about 62. In other embodiments, the formulation is divided into at least about 55, including from about 55 to about 62, for two months after formulation; the Aegles is divided into at least about 55, including about 55 to six months after deployment. Approximately 60; and nine months after the blending, the Aegis score is at least about 52, including about 52 to about 55.

Buffering capacity

The low calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits improved cushioning capacity as compared to a full calorie formulation.

It is believed that human breast milk contains certain factors that promote the development of a beneficial intestinal bacterial community (specifically, Bifidobacterium ), which prevents the proliferation of pathogenic microorganisms. The growth of Bifidobacterium in the intestinal tract of the baby is promoted by the physicochemical properties of human breast milk, especially its high lactose content, which is the source of Bifidobacterium, its low protein content and its low buffering capacity. In addition, the low buffering capacity of human milk allows the natural acidity in the infant's gastrointestinal tract (GI) to more effectively inactivate the orally ingested pathogen. In some cases, the infant formula may have a relatively high buffering capacity, which may not fully benefit the growth of the bifidobacteria and may potentially affect the natural acidity of the infant's gastrointestinal tract. Therefore, some formula-fed infants may experience more gastrointestinal infections than breastfed infants.

It has been found that the buffering capacity of the infant formula is related to the energy content of the formula. Specifically, it has been found that the buffering capacity of infant formulas decreases with decreasing energy content. Thus, the low calorie infant formula of the present invention advantageously has an improved (i.e., lower) cushioning capacity compared to a full calorie infant formula, and in some embodiments, has a lower buffering capacity than human milk. Thus, the low calorie infant formula of the present invention can be used to modulate gastric acidity in infants, particularly neonates, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of infants, promote the growth of beneficial microorganisms such as bifidobacteria, and increase the inactivation of orally ingested pathogens. Effectiveness.

Buffering capacity generally refers to the ability of a liquid to resist changes in pH. There are a variety of measures used to indicate the buffering capacity of the infant formula of the present invention. For example, the buffering capacity of an infant formula is expressed by the amount of increase in hydrogen ion concentration ([H+]) after the addition of hydrochloric acid (HCl) to the infant formula (or to the reconstituted formula of the powder infant formula embodiment). Specifically, buffer capacity is expressed as an increase in [H+] after adding 5 mmol of HCl to a 100 mL formulation, or after adding 5.50 mmol HCl to a 100 mL formulation (or adding 2.75 mmol HCl to a 50 mL formulation) The increase in [H+] is expressed.

The buffering capacity of the low calorie infant formula of the present invention (expressed as [H+] after adding 5 mmol of HCl to a 100 mL formulation) can be at least about 2.0 mM, including at least about 5.0 mM, at least about 7.0 mM, at least about 10.0 mM. At least about 13.0 mM and at least about 17.0 mM, and/or from about 2.0 mM to about 25.0 mM, including from about 5.0 mM to about 21.0 mM and from about 10.0 mM to about 21.0 mM. The infant formula can be a reconstituted powder formulation (sterilized or sterile) and can be formulated on days 1-2 or days 3-9. In one embodiment, the low calorie infant formula is a 3-9 day formulation and its buffering capacity (expressed as [H+] after adding 5 mmol of HCl to the 100 mL formulation) is at least about 2.0 mM, including at least about 5.0 mM At least about 7.0 mM and at least about 9.0 mM, and/or from about 2.0 mM to about 13.0 mM, including from about 8.0 mM to about 11.0 mM. In another embodiment, the low calorie infant formula is a 1-2 day formulation and its buffering capacity (expressed as [H+] after adding 5 mmol of HCl to the 100 mL formulation) is at least about 8.0 mM, including at least about 10.0 mM, at least about 13.0 mM, at least about 17.0 mM, and at least about 20.0 mM, and/or from about 8.0 mM to about 25.0 mM, including from about 8.0 mM to about 21.0 mM, from about 13.0 mM to about 20.0 mM and from about 17.0 mM to about 20.0 mM.

Alternatively, the buffering capacity of the infant formula can be expressed as a decrease in the pH of the formula after the addition of HCl to the infant formula (or to the reconstituted formula of the powder infant formula embodiment). Specifically, buffering capacity can be expressed as a decrease in pH after adding 5.50 mmol HCl to a 100 mL formulation (or adding 2.75 mmol HCl to a 50 mL formulation).

Thus, in one embodiment, the low calorie infant formula of the present invention is a powdered infant formula and its post-recovery buffering capacity (represented as a decrease in the pH of the formulation after the addition of 5.50 mmol of HCl to the 100 mL reconstituted formulation) is at least About 4.20, including at least about 4.50 and at least about 4.80. In another embodiment wherein the low calorie infant formula is a sterilized autoclaved RTF formulation, the buffering capacity (represented as a decrease in the pH of the formulation after the addition of 2.75 mmol of HCl to the 50 mL formulation) is at least about 4.20, including at least about 4.30. . In yet another embodiment wherein the low calorie infant formula is a sterile sterilized RTF formulation, the buffering capacity (represented as a decrease in pH of the formulation after the addition of 5.50 mmol HCl to the 100 mL formulation) is at least about 4.60, including at least about 4.70.

Another measure of buffer capacity is the buffer strength. Unless otherwise stated, the buffer strength of the infant formula of the present invention can be expressed as required to reduce the pH of the 50 mL formulation (or the reconstituted formulation of the powdered infant formula embodiment) from the initial pH (eg, 6.0) to pH 3.0. The volume of 0.1 M HCl. As used herein, the term "low buffer strength" means a buffer strength of about 18 mL or less. The buffer strength (when indicated) is also expressed herein as the milliliter of HCl required to reduce the pH of the 100 mL formulation from 6.0 to 3.0 and the pH of the 50 mL formulation from 6.0 to 3.0. The molar amount of HCl.

The buffer strength of the low calorie infant formula of the present invention (expressed as the pH of the 0.1 mL HCl required to reduce the pH of the 50 mL formulation (or the reconstituted formula of the powder infant formula) from the initial pH to pH 3.0) It is about 18 mL or less, including about 14 mL or less, and/or includes from about 9 mL to about 18 mL, including from about 10 mL to about 14 mL and from about 14 mL to about 18 mL. In one embodiment, the low calorie infant formula is a 3-9 day formulation with a buffer strength of about 18 mL or less, including from about 14 mL to about 18 mL and from about 16 mL to about 17 mL. In another embodiment, the low calorie infant formula is a 1-2 day formulation and has a buffer strength of about 14 mL or less, including from about 9 mL to about 14 mL and from about 10 mL to about 11 mL. The buffer strength of human milk is usually in the range of 9 mL to 18 mL. The low calorie infant formula of the present invention advantageously has a buffer strength comparable to or lower than that of human milk.

Protein hydrolysis and digestion

The low calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits faster protein hydrolysis and digestibility as compared to the full calorie formulation.

Two factors that determine the nutritional quality of food proteins are digestibility and bioavailability. Generally, the protein content of an infant formula is higher than the protein content found in breast milk. Infant formulas are typically prepared with higher protein content to address the hypothetical problem of lower protein digestibility.

In addition, in some cases, the methods used during infant formula preparation may have potential nutritional effects, such as reducing the solubility and/or digestibility of the protein in the formulation. For example, in some cases, some prolonged heat treatments for preparing concentrated liquids and ready-to-eat infant formulas may potentially reduce protein digestibility. Due to exposure to heat, protein denaturation or aggregation may, in some cases, alter its digestibility. Treatment of dairy products at elevated temperatures may also increase the reaction of the amino acid with the sugar, known as the Maillard reaction. In some cases, such reactions may reduce the bioavailability of the amino acid by limiting the proximity of the proteolytic enzyme. Therefore, some formula-fed babies may experience some absorption of nutrients (and especially proteins). Thus, infant formulas with improved protein digestion will be particularly beneficial for newborns with known levels of digestive enzymes such as pepsin and intestinal pancreatic enzymes that are lower than those of older infants and adults.

It has been found that the degree of protein digestion in infant formula (which may be used interchangeably herein with the term "hydrolysis") (which may be used interchangeably herein with the term "rate") is related to the energy content of the formulation. Specifically, it has been found that the digestibility of the protein present in the infant formula increases as the energy content of the formula decreases. The low calorie infant formula of the present invention advantageously has improved (e.g., faster) protein digestibility compared to a full calorie infant formula. This improves the infant's tolerance to infant formula and improves the absorption of nutrients (and especially proteins).

There are many types of measures used to indicate protein digestibility or degree. For example, the digestibility or degree of protein in the infant formula of the present invention is the protein molecular weight of the protein after in vitro gastrointestinal digestion or in vitro trypsinization using pepsin and trypsin (amylase/protease/lipase). (MW) said. A decrease in the median MW of the protein indicates a faster digestibility and an increased degree of digestion. The procedure for such digestion is illustrated in the examples.

In some embodiments, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after in vitro gastrointestinal digestion as described herein) is about 950 Daltons (Da) or Below 950 Daltons, including below 925 Da or 925 Da, below 850 Da or 850 Da, below 800 Da or 800 Da and below 790 Da or 790 Da. For the 3rd-9th day formulation of the present invention, the protein digestibility or extent (expressed as the median MW protein after in vitro gastrointestinal digestion as described herein) is typically from about 700 Da to about 950 Da. For Day 1-2 formulations, the protein digestibility or extent (expressed as the median MW of protein after in vitro gastrointestinal digestion as described herein) is typically below about 825 Da or 825 Da, including about 800 Da or 800. Below Da, about 780 Da or 780 Da or less, about 750 Da or 750 Da or less and about 720 Da or 720 Da or less. The protein digestibility or degree of the formulation on Day 1-2 is typically from about 700 Da to about 800 Da.

For the 3-9th day formulation, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after 71 minutes of in vitro trypsinization as described herein) is about 800 Da or Below 800 Da, including below about 775 Da or 775 Da and below about 750 Da or 750 Da, and especially from about 725 Da to about 775 Da. For Day 1-2 formulations, the protein digestibility or extent (expressed as the median MW protein value after 71 minutes of in vitro trypsinization as described herein) is typically about 750 Da or less than 750 Da, including about 725 Da or below 725 Da, below 700 Da or 700 Da and below about 690 Da or 690 Da, and especially about 675 Da or 675 Da or less to about 700 Da or less.

The protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after 60 minutes of in vitro trypsinization as described herein) is about 1000 Da or less, including about 950 Da. Or below 950 Da, below 900 Da or 900 Da, below about 850 Da or 850 Da, below about 825 Da or 825 Da and below about 810 Da or 810 Da, and especially from about 775 Da to about 825 Da.

The protein digestibility or extent can also be expressed as the percentage of total protein having a MW greater than 5000 Da after in vitro parenteral digestion or in vitro trypsinization as described herein. A smaller percentage means faster digestibility and increased digestion. For powder formulations, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as a percentage of total protein having a MW greater than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 13.5% or less. It includes about 12.0% or less, about 11.0% or less, about 9.0% or less and about 6.0% or less, and especially about 5.0% to about 13.5%. In an embodiment wherein the infant formula is autoclaved, the protein digestibility or extent (expressed as a percentage of total protein having a MW greater than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 8.0% or less. , comprising about 7.0% or less, about 6.0% or less, about 5.0% or less, about 4.0% or less, and about 3.0% or less, and further comprising about 2.0% to About 6.0%. In embodiments wherein the infant formula is aseptically sterilized, the protein digestibility or extent (expressed as a percentage of total protein having a MW greater than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 9.0% or less. It includes about 7.0% or less, about 6.0% or less, about 5.0% or less, about 3.0% or less, and further including about 2.0% to about 5.0%.

The rate or extent of protein digestibility can also be expressed by the amount of insoluble protein present in the infant formula after in vitro gastrointestinal digestion as described herein. Techniques for determining the insoluble protein content are set forth in the examples of the present invention. A smaller amount of insoluble protein indicates a faster digestibility and an increased degree of digestion.

The protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the amount of insoluble protein present in the formulation after in vitro parenteral digestion as described herein) is about 150 mg/L or 150 mg/L. Below, including below about 110 mg/L or 110 mg/L, below about 75 mg/L or 75 mg/L, below about 50 mg/L or 50 mg/L and below about 25 mg/L or 25 mg/L And especially from about 20 mg/L to about 110 mg/L.

As discussed herein, processing an infant formula and treating the dairy product, particularly at elevated temperatures, can increase the reaction of the amino acid with the sugar, known as the Mena reaction. These reactions reduce the bioavailability of the amino acid by limiting the accessibility of the proteolytic enzyme. It has now been found that the Mena reaction in the low calorie infant formula of the present invention is less aggressive than the full calorie formulation. This can be illustrated by determining the amount of Mena reaction marker in the infant formula after digestion. Specifically, it has been found that the low-calorie infant formula of the present invention has a Meena reaction label valerine content lower than the full calorie formula after in vitro gastrointestinal digestion as described herein.

Thus, in one aspect, the invention provides an infant formula comprising about 2.5 or less, including about 1.5 or less, about 1.0 or less, and about 0.90, after in vitro digestion, as described herein. The Mena reaction label proline is in an amount of 0.90 or less and especially about 0.7 to about 1.0 (mg/100 g product).

Preparation

The infant formula of the present invention can be prepared by any of the known or other preparative techniques effective for preparing the solid or liquid form of the selected product. A variety of such techniques are known for use in any given product form (such as a nutritional liquid or powder) and can be readily applied to the infant formula described herein by those of ordinary skill in the art.

Thus, the infant formula of the present invention can be prepared by any of a variety of known or otherwise effective methods of formulation or preparation. For example, in one suitable method of preparation, at least two separate slurries are prepared, subsequently blended together, heat treated, standardized, and finally sterilized to form a Sterilized Sterilized Infant Formula or aseptically processed and filled to form Sterile sterilized infant formula. Alternatively, the slurries can be blended together, heat treated, normalized, second heat treated, evaporated to remove water and spray dried to form a powdered infant formula.

The resulting slurry can include a carbohydrate-mineral (CHO-MIN) slurry and a protein-in-oil/PIO slurry. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides, etc.) in hot water with agitation, followed by the addition of minerals (eg potassium citrate, magnesium chloride, potassium chloride, sodium chloride, chlorination) Choline, etc.) to form CHO-MIN. The resulting CHO-MIN slurry was maintained under continuous heating and moderate agitation until it was subsequently blended with other prepared slurries.

By heating and mixing oils (such as high oleic safflower oil, soybean oil, coconut oil, monoglyceride, etc.) and emulsifiers (such as soy lecithin), and then adding oil-soluble vitamins under continuous heating and stirring, Mixing carotenoids, proteins (eg, milk protein concentrates, milk protein hydrolysates, etc.), carrageenan (if present), calcium carbonate or tricalcium phosphate (if present), and ARA oil and DHA oil (in some embodiments) Medium) to form a PIO slurry. The resulting PIO slurry was maintained under continuous heating and moderate agitation until it was subsequently blended with other prepared slurries.

The water is heated and then combined with the CHO-MIN slurry, skim milk (if present) and PIO slurry with sufficient agitation. The pH of the resulting blend was adjusted to 6.6-7.0 and the blend was maintained under moderate heating agitation. In some embodiments, ARA oil and DHA oil are added at this stage.

The composition is then processed by high temperature short time (HTST) during which the composition is heat treated, emulsified and homogenized, and then cooled. Water soluble vitamins and ascorbic acid are added, pH is adjusted to the desired range if necessary, perfume (if present) is added and water is added to obtain the desired total solids content. For sterile sterilized infant formulas, the emulsion is subjected to a second heat treatment via a sterile processor, cooled and then aseptically packaged into a suitable container. For sterilized infant formula, the emulsion is packaged in a suitable container and finally sterilized. In some embodiments, the emulsion may be further diluted, heat treated, and packaged to form the desired ready-to-eat or concentrated liquid, or may be heat treated and then processed and packaged as a reconstitutable powder (eg, spray dried, dry mixed, coalesced) ).

A spray dried powder infant formula or a dry mixed powder infant formula can be prepared by any known or other effective technique set suitable for the preparation and formulation of nutritional powders. For example, when the powdered infant formula is a spray dried nutritional powder, the spray drying step can similarly include any spray drying technique known or otherwise suitable for preparing nutritional powders. A variety of different spray drying methods and techniques are known for use in the field of nutrition, all of which are suitable for use in preparing the spray dried powder infant formula herein. After drying, the finished powder can be packaged in a suitable container.

Instructions

The low calorie infant formula of the present invention can be administered orally to infants, including term infants, premature infants, and/or newborns. A low-calorie infant formula can be administered to premature infants, term infants, and/or neonates as a source of infant nutrition and/or can be used to address one or more of the diseases or conditions discussed herein, or can be used to provide one or more of the articles herein. The benefits described. Either of these groups may actually be afflicted with a disease or condition, or may be at risk for a disease or condition (due to family history, etc.), may be sensitive to the disease or condition, or may require treatment/control/ Reduce a disease or condition. Infant formula will usually be administered daily at an intake that is suitable for the age of the infant. Thus, because some of the method embodiments disclosed herein pertain to certain subgroups or subcategories of infants (eg, infants in need of treatment or control of a disease or condition) and are generally not related to a standard infant population, not all infants may All method embodiments disclosed herein benefit from the examples.

For example, the methods of the invention can include administering one or more low calorie formulations of the invention to an infant at an average intake as described herein. In some embodiments, the amount of formula in which the newborn is increasing is provided during the first few weeks of life. The equivalent is most typically in the range of up to about 100 ml/day during the first day of life; an average of up to about 200 to about 700 ml/day during the remainder of the three-month neonatal feeding period, including 200 to about 600 ml/day and also includes about 250 to about 500 ml/day. It should be understood, however, that this amount may vary significantly from a particular newborn and its unique nutritional needs during the first weeks or months of life and the particular nutrient and caloric density of the infant formula being administered.

In some embodiments, the method of the present invention may be directed to the first few weeks or months of life (preferably during at least the first week of life, more preferably at least the first two weeks of life and including up to about 3 of life) Newborns of the month). Thereafter, the infant can be converted to a conventional infant formula (alone or in combination with human milk).

The methods described herein can include administering two or more different infant formulas to an infant. For example, a baby low calorie 1-2 day infant formula can be administered on the first two days after birth and then a low calorie 3-9 day infant formula can be administered on days 3-9 after birth. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth.

Unless otherwise stated, the infant formula used in the methods described herein is a nutritional formula and can be in any product form, including ready-to-feed liquids, concentrated liquids, reconstituted powders, and the like. In embodiments where the infant formula is in powder form, the method may further comprise reconstituting the powder with an aqueous vehicle (most typically water or human milk) to form the desired caloric density, followed by oral or enteral feeding of the infant. The powder formulation is reconstituted with sufficient water or other suitable fluid, such as human milk, to produce the desired caloric density and the amount of feed required to feed a baby. The infant formula may also be sterilized by sterilization or sterilization prior to use.

Other embodiments are described in more detail below.

nutrition

In one aspect, the invention relates to a method of providing nutrition to an infant. The method comprises administering to the infant one or more of the low calorie, low micronutrient infant formulas of the invention. Such methods can include daily administration of an infant formula, including administration in a daily intake as described above. In some embodiments, the infant is a newborn.

As noted above, any of the low calorie, low micronutrient infant formulas of the present invention can be used in this method. Specifically, the low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 80% of the amount of the corresponding micronutrient. Included in infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 80% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Day 3-9.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula), and then a low calorie infant formula (with high or low micronutrient content) with an energy content of about 360 kcal/L to less than 600 kcal/L from day 3 to day 9 after birth ( For example, the 3rd-9th formula). The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth.

Buffering capacity

The buffering capacity of the infant formula has been found to correlate with the energy content of the formula. Specifically, it has been found that the buffering capacity of infant formulas decreases with decreasing energy content. Thus, the low calorie infant formula of the present invention advantageously has an improved (i.e., lower) cushioning capacity compared to a full calorie infant formula, and in some embodiments, has a lower buffering capacity than human breast milk. Therefore, the low-calorie infant formula of the present invention can be used to increase the gastric acidity of infants, especially newborns, and to regulate the growth of gastrointestinal flora of infants, including controlling (eg, reducing) the growth of pathogenic microorganisms in the gastrointestinal tract of infants, promoting the growth of beneficial microorganisms in the gastrointestinal tract of infants, and increasing The effectiveness of inactivating pathogens that are orally ingested.

Without wishing to be bound by any particular theory, the pH value of the gastrointestinal tract of breast-fed infants is more acidic than that of a full-calorie-fed infant, thereby contributing to the deactivation of pathogenic ingested pathogens and providing a more suitable natural presence. An environment conducive to the growth of gastrointestinal flora. This is due, at least in part, to the low buffering capacity of human breast milk. Because the buffering capacity of the low calorie infant formula of the present invention is comparable to or lower than that of human breast milk, the gastric acidity of the infants fed by the low calorie infant formula disclosed herein will be more closely similar to those seen in breastfed infants.

Thus, in one aspect, the invention is directed to increasing the acidity of the gastric juice of an infant (e.g., by lowering the pH of the gastric juice) to about the same extent as breastfed infants. The method comprises identifying an infant with reduced gastric acidity and administering to the infant any of the low calorie infant formulas of the invention. The baby is preferably a newborn.

The term "gastric acidity" refers to the degree of acidity in the stomach and can be measured using pH. For example, gastric acidity increases as the pH of the stomach contents decreases. As used herein, the term "lower gastric acidity" means that the gastric acidity of an infant is lower than the gastric acidity normally seen in breastfed infants. Infants with reduced gastric acidity can be identified as having a reduced or lower rate of pathogen community formation in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to the extent typically found in breastfed infants.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L to about 500 kcal/L.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of increasing the acidity of gastric juice in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 80% of the amount of the corresponding micronutrient. Included in infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 80% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Day 3-9.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another embodiment, the invention relates to a method of modulating the growth of beneficial gastrointestinal flora in an infant. The method comprises identifying an infant whose gastrointestinal flora is unbalanced and administering to the infant any of the low calorie infant formulas of the invention. The baby is preferably a newborn.

For the purposes of the present invention, gastrointestinal flora growth can be modulated by promoting the growth of microorganisms that are beneficial to GI health and/or controlling the growth of pathogenic microorganisms. The growth of pathogenic microorganisms can be controlled by inhibiting, inhibiting, killing, inactivating, destroying or otherwise impeding the growth of pathogenic microorganisms such that the growth rate of such microorganisms is slowed or stopped. Infants with unbalanced GI flora growth include levels of one or more pathogenic microorganisms in the gastrointestinal tract of infants that are higher than those normally found in breastfed infants and/or one or more beneficial microbial components in the gastrointestinal tract of infants are generally lower than those commonly found in breastfed infants. The content of the baby. These infants can be identified by a lower rate of formation of pathogenic bacteria in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to a similar extent as is commonly found in breastfed infants, resulting in a GI environment that promotes the growth of beneficial microorganisms and controls the growth of pathogenic microorganisms.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to about 500 kcal/L formulation.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of modulating the growth of a gastrointestinal flora of an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

Beneficial microorganisms are microorganisms that maintain the gastrointestinal tract and exhibit physiological, immunomodulatory and/or antimicrobial effects such that they are found to be capable of preventing and treating GI diseases and/or conditions. Non-limiting examples of beneficial microorganisms include any one or more of the following microorganisms: Genus Lactobacillus , including L. acidophilus , L. amylovorus , Lactobacillus brevis ( L. brevis ), L. bulgaricus , L. casei spp. Casei , L. casei spp. Rhamnosus , Lactobacillus crispa ( L. crispatus ), L. delbrueckii ssp. Lactis , L. fermentum , L. helvaticus , L. johnsonii , L. paracasei , L. pentosus , L. plantarum , L. reuteri , and L. sake ; double fork Genus Bifidobacterium , including B. animalis , B. bifidum , B. breve , B. infantis and Longgen Bifidus (B. longum); Pediococcus (genus Pediococcus), package Lactic small cocci (P. acidilactici); Propionibacterium (genus Propionibacterium), including propionic acid acnes (P. acidipropionici), freudenreichii (P. freudenreichii), Jane Propionibacterium acnes (P. jensenii And P. theonii ; and genus Streptococcus , including S. cremoris , S. lactis , and S. thermophilus . ; and its combination.

Non-limiting examples of pathogenic microorganisms that can be grown by the methods disclosed herein include any one or more of the following pathogenic microorganisms: bacteria, such as genus Clostridum , including C. difficile . Escherichia coli / E. coli ; Vibrio sp .; Salmonella sp .; Shigella sp .; Camphylobacter sp .; gas production list Aeromonas sp .; Staphylococcus sp .; Pseudomonas sp .; and parasites such as Giardia sp .; and Cryptosporidium ( Cryptosporidium sp. ); and combinations thereof.

Protein digestion and hydrolysis

The digestibility and extent of protein in infant formula have been found to correlate with the energy content of the formula. Specifically, it has been found that the digestibility of the protein in the infant formula increases as the energy content of the formula decreases. Thus the low calorie infant formula of the present invention advantageously has improved (e.g., faster) digestibility compared to a full calorie infant formula. The low calorie infant formula of the present invention can therefore be used to improve formulation tolerance, protein digestion and nutrient (and especially protein) absorption in infants and especially neonates.

Thus, in one aspect, the invention relates to a method of improving protein digestion in infants. The method comprises identifying an infant undergoing protein insufficiency and administering to the infant any of the low calorie infant formulas of the invention. The baby is preferably a newborn.

As used herein, the term "improving protein digestion" includes increasing the rate of digestion (or hydrolysis) of a protein present in an infant formula and/or increasing the degree of digestion of the protein in the infant formula when contacted with a digestive enzyme. This protein digestion improvement can be determined using any of the metrics described herein, including, for example, the median weight of the protein after digestion, the percentage of total protein in the molecular weight after digestion greater than 5000 Daltons, and/or the presence in the formulation after digestion. The amount of protein dissolved.

As used herein, the term "protein insufficiency" means that the amount of protein actually present in the nutritional product consumed by the infant is less than the amount of protein normally digested by the breastfed infant. Infants undergoing protein insufficiency may exhibit signs of formulation intolerance and may therefore be identified using any of the formulation intolerance symptoms described herein. Infants who experience protein insufficiency can also be identified by diarrhea, soft stools, fart and/or bloating. Protein digestibility and extent are improved upon administration of the low calorie infant formula of the present invention.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation and/or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of improving protein digestion in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 80% of the amount of the corresponding micronutrient. Included in infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 80% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Day 3-9.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another embodiment, the invention is directed to a method of improving protein absorption in an infant. The method comprises identifying an infant experiencing protein insufficiency; and administering to the infant any of the low calorie infant formulas of the invention. An infant undergoing protein insufficiency can be identified using any of the criteria described herein for identifying infants undergoing protein insufficiency.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of improving protein absorption in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

Tolerance

The invention is also directed to a method of improving the tolerance of an infant formula in an infant. Infant formulation intolerance is a non-immune system-related response that can be confirmed by behavioral or fecal or eating patterns, such as increased cough or vomiting, increased frequency of bowel movements, more watery stools, increased black stools and crying . Infant formulation intolerance is most often associated with gastrointestinal symptoms (eg, fecal morphology, fart, cough) and behavioral characteristics (eg, formula acceptance, crying, and shouting). Infants with formulation intolerance may also experience gastroesophageal reflux.

It has been unexpectedly found that infants are more tolerant to infant formulas with lower energy content than full calorie formulas. Specifically, it has been found that low-calorie infant formulas exhibit faster protein hydrolysis and digestibility, produce less Mena reaction products (which cannot be broken down and absorbed) and have faster gastric emptying compared to the full-calorie formula. rate. When the gastric emptying is faster, the gastroesophageal reflux can be reduced and the formulation tolerance can be improved.

Thus, the low calorie infant formula of the present invention can be used to reduce the frequency of infant fart and/or cough. The low calorie infant formula of the present invention can also be used to increase the gastric emptying rate of an infant and to reduce the amount of the Mena reaction product produced by the edible formulation as compared to the full calorie infant formula.

A low-calorie infant formula can be administered to any infant (preterm or term) and in particular any infant who can benefit from an infant formula that has a low energy content and is also highly tolerant. In some embodiments, the neonate is administered a low calorie infant formula of the invention.

Thus, in one aspect, the invention is also directed to a method of improving the tolerance of an infant's infant formula. The method comprises identifying an infant suffering from infant formula intolerance and administering to the infant any one or more of the low calorie infant formulas of the invention. Infants with infant formula intolerance may include infants with one or more of the symptoms of formulation intolerance. These symptoms include (but are not limited to) fecal or eating patterns, such as increased cough or vomiting; increased frequency of bowel movements; more watery stools; black stools; increased crying, shouting, fart; and unwilling to consume formula. Some or all of the formulation intolerance symptoms may be reduced or eliminated upon administration of the low calorie infant formula of the present invention.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation or a 3-9 day formulation. In one embodiment, the low calorie infant formula has an energy content of from about 200 to about 600 kcal/liter of formula.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of improving infant formula tolerance in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 80% of the amount of the corresponding micronutrient. Included in infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 80% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Day 3-9.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another embodiment, the invention is directed to a method of inhibiting gastroesophageal reflux in a baby. The method comprises identifying an infant suffering from a gastroesophageal reflux and administering to the infant any one or more of the low calorie infant formulas of the invention. The baby is preferably a newborn.

When gastroesophageal reflux (GER) occurs, the stomach contents flow back into the esophagus and out of the mouth, causing nausea, cough and/or vomiting. Symptoms of GER include cough, vomiting, coughing, irritability, poor eating, bloody stools, and combinations thereof. When a GER occurs, the baby may also cough, shout or be nervous. For the purposes of the present invention, the term "inhibiting gastroesophageal reflux" is intended to include treating, preventing, and/or reducing the incidence of GER and/or at least one of its symptoms. Without wishing to be bound by any particular theory, it is believed that the low calorie infant formula of the present invention has a faster gastric emptying rate (i.e., the rate at which the contents pass through the stomach) as compared to the full calorie formulation, which causes a decrease in gastroesophageal reflux.

As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1-2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation.

The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation on Day 1-2 of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of inhibiting gastric esophageal reflux in an infant comprising administering to the infant any one or more of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested as described above.

In another aspect, the invention relates to a method of increasing the rate of gastric emptying in an infant comprising administering to the infant any one or more of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations.

The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 10th day after birth. The amount of micronutrients included in the formulation may be any of the above amounts. Formulations for administration to infants will usually be administered daily as ingested as described above.

Set

Furthermore, the present invention provides a kit comprising two or more low calorie infant formulas of the invention.

For example, in some embodiments, the kit can include at least one Day 1-2 formulation and at least one Day 3-9 formulation. Preferably, the kit will contain a sufficient amount of Day 1-2 formulation to provide adequate nutrition for the baby during the first two days of life, and a sufficient amount of Day 3-9 formulation to provide the baby at least 3-9 days after birth. nutrition. The infant formula included in the kit can be in any suitable form including, for example, a ready-to-feed liquid, a concentrated liquid, a powder, or a combination thereof. The kit can include low calorie, low micronutrient formulations and/or low calorie, high micronutrient formulations.

The kit may further include a kit instruction manual as the case may be. For example, the instructions may describe how to use the formula, for example, to indicate that the formula should be administered on days 1-2 after the first two days of birth and that the formula should be administered on days 3-9 after birth; the formula can be described The daily dosing schedule; and/or can describe how to practice any of the methods described in this disclosure. The instructions may further describe how to restore any powder infant formula included in the kit as appropriate.

In addition to the infant formula and optionally instructions, the kit may also include other components, such as one or more baby bottles of various sizes, one or more bottle liners of various sizes, bottle nipples and the like. Things.

Instance

The following examples illustrate specific embodiments and/or features of the infant formulas and methods of the present invention. The examples are provided for illustrative purposes only and are not to be considered as limiting the invention, and various changes may be made without departing from the spirit and scope of the invention. All exemplified amounts are by weight based on the total weight of the composition, unless otherwise stated.

Unless otherwise stated, the sterilization kettle sterilization and aseptic sterilization formulations prepared according to the preparation methods described herein are ready-to-eat liquid formulations.

Example 1-8

In these examples, 2 ounces of the 1-2 day infant formula with high or low micronutrient content and the 3rd-9 day infant formula were prepared. The ingredients used to prepare the formulations are set forth in Tables 1 and 2 below.

Table 1: Formula 1-2 days

Table 2: Days 3-9 Formulation

The formulation is prepared by preparing at least two separate slurries which are then blended together, heat treated, standardized and finally sterilized. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 74 ° C - 79 ° C, followed by the addition of citric acid, magnesium chloride, potassium chloride, potassium citrate, choline chloride and chlorine Sodium is used to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained at 49 ° C - 60 ° C with moderate agitation until it was subsequently blended with other prepared slurries.

The oil-coated protein slurry was prepared by combining high oleic safflower oil, coconut oil, monoglyceride and soy lecithin with stirring and heating to 66 ° C - 79 ° C. After standing for 10-15 minutes, add soybean oil, oil-soluble vitamin premix, mixed carotenoid premix, carrageenan, vitamin A, calcium citrate, dicalcium phosphate, ARA to the slurry. Oil, DHA oil and whey protein concentrate. The resulting oil slurry was maintained under moderate agitation at 49 ° C to 60 ° C until it was subsequently blended with other prepared slurries.

The water is heated to 49 ° C - 60 ° C and then combined with the carbohydrate-mineral slurry, skim milk and oil-in-oil slurry with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was maintained under moderate agitation at 49 °C - 60 °C.

The resulting blend was heated to 74 ° C - 79 ° C, emulsified to 900-1100 psig via a single stage homogenizer and then heated to 144 ° C - 147 ° C for about 5 seconds. The heated blend was passed through a flash cooler to bring the temperature down to 88 °C - 93 °C and then passed through a plate cooler to further reduce the temperature to 74 °C - 85 °C. The cooled blend was then homogenized at 2900-3100/400-600 psig, held at 74 °C - 85 °C for 16 seconds and then cooled to 2 °C - 7 °C. Obtain samples for analytical testing. The mixture was kept under stirring at 2 ° C to 7 ° C.

A water soluble vitamin (WSV) solution and an ascorbic acid solution are separately prepared and added to the treated blend slurry. Vitamin solution is prepared by adding the following ingredients to water under stirring: potassium citrate, ferrous sulfate, WSV premix, L-carnitine, copper sulfate, vitamin B2, inositol and nucleotide-choline premix Things. The ascorbic acid solution is prepared by adding potassium hydroxide and ascorbic acid to water in an amount sufficient to dissolve the ingredients. The pH of the ascorbic acid solution is then adjusted to 5-9 with potassium hydroxide.

The pH of the blend was adjusted with potassium hydroxide to a specified pH range of 7.1-7.6 (depending on the product) to obtain optimum product stability. The finished product is then filled into a suitable container and finally sterilized.

Example 9-11

In these examples, 32 ounces of sterile sterilized Day 3-9 infant formula with high or low micronutrient content were prepared. The ingredients used to prepare the formulations are set forth in Table 3 below.

Formulations were prepared by preparing at least two separate slurries, then blending them together, heat treating, normalizing, and then performing aseptic processing and filling. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 74 ° C - 79 ° C, followed by the addition of citric acid, magnesium chloride, potassium chloride, potassium citrate, choline chloride and chlorine Sodium sulphate (minerals vary depending on the formulation) to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained at 49 ° C - 60 ° C with moderate agitation until it was subsequently blended with other prepared slurries.

The oil-coated protein slurry was prepared by combining high oleic safflower oil, coconut oil, monoglyceride and soy lecithin with stirring and heating to 66 ° C - 79 ° C. After standing for 10-15 minutes, add soybean oil, oil-soluble vitamin premix, mixed carotenoid premix, carrageenan, calcium citrate, calcium hydrogen phosphate, ARA oil, DHA to the slurry. Oil and whey protein concentrate. The resulting oil slurry was maintained under moderate agitation at 49 ° C to 60 ° C until it was subsequently blended with other prepared slurries.

The water is heated to 49 ° C - 60 ° C and then combined with the carbohydrate-mineral slurry, skim milk and oil-in-oil slurry with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was maintained under moderate agitation at 49 °C - 60 °C.

The resulting blend was heated to 74 ° C - 79 ° C, emulsified to 900-1100 psig via a single stage homogenizer and then heated to 144 ° C - 147 ° C for about 5 seconds. The heated blend was passed through a flash cooler to bring the temperature down to 88 °C - 93 °C and then passed through a plate cooler to further reduce the temperature to 74 °C - 85 °C. The cooled blend was then homogenized at 2900-3100/400-600 psig, held at 74 °C - 85 °C for 16 seconds and then cooled to 2 °C - 7 °C. Obtain samples for analytical testing. The mixture was kept under stirring at 2 ° C to 7 ° C.

A water soluble vitamin (WSV) solution and an ascorbic acid solution are separately prepared and added to the treated blend slurry. Vitamin solutions were prepared by adding the following ingredients to the water with stirring: potassium citrate, ferrous sulfate, WSV premix, L-carnitine, vitamin B2, inositol, and nucleotide-choline premix. The ascorbic acid solution is prepared by adding potassium hydroxide and ascorbic acid to water in an amount sufficient to dissolve the ingredients. The pH of the ascorbic acid solution is then adjusted to 5-9 with potassium hydroxide.

The blend pH was adjusted with potassium hydroxide to a pH range of 6.8-7.0 for optimum product stability. The standardized blend is then subjected to a second heat treatment via a sterile processor. The blend was preheated to 63 °C - 74 °C and homogenized at 200 psig. The blend was further heated to 141 ° C - 144 ° C and passed through a holding tube. The heated blend was cooled to reduce the temperature to 74 °C - 85 °C and then homogenized at 1200 / 200 psig. The blend was further cooled to 16 ° C to 27 ° C and then aseptically filled into a suitable container at 21 ° C.

Example 12-15

In these examples, a 1-2 day infant formula with a high or low micronutrient content and a 3-9 day infant formula are prepared. The ingredients used to prepare the formulations are set forth in Table 4 below.

The formulation is prepared by preparing at least two separate slurries which are then blended together, heat treated, normalized, second heat treated, evaporated to remove water and finally spray dried. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 60-71 ° C, followed by magnesium chloride, potassium chloride, potassium citrate, choline chloride, and sodium chloride ( The minerals vary depending on the formulation to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained at 49 ° C - 60 ° C with moderate agitation until it was subsequently blended with other prepared slurries.

By combining high oleic safflower oil, soybean oil and coconut oil at 49 ° C - 60 ° C, followed by the addition of ascorbyl palmitate, mixed tocopherol, soy lecithin, oil-soluble vitamin premix, whey protein concentrate A whey protein hydrolysate (in some cases), a carotenoid premix, and calcium carbonate (and/or tricalcium phosphate) to prepare a protein-packed protein slurry. The resulting oil slurry was maintained under moderate agitation at 38 °C - 49 °C until it was subsequently blended with other prepared slurries.

The water, carbohydrate-mineral slurry, skim milk and oil-in-oil slurry were combined with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was maintained under moderate agitation at 49 °C - 60 °C. ARA oil and DHA oil were added after pH adjustment and prior to processing.

The resulting blend was heated to 71 ° C - 77 ° C, emulsified to a maximum of 300 psig via a single stage homogenizer and then heated to 82 ° C - 88 ° C for about 5 seconds. The heated blend was passed through a flash cooler to bring the temperature down to 77 °C - 82 °C and then passed through a plate cooler to further reduce the temperature to 71 °C - 77 °C. The cooled blend was then homogenized at 2400-2600/400-600 psig, held at 74 °C - 85 °C for 16 seconds and then cooled to 2 °C - 7 °C. Obtain samples for analytical testing. The mixture was kept under stirring at 2 ° C to 7 ° C.

A water soluble vitamin (WSV) solution and an ascorbic acid solution are separately prepared and added to the treated blend slurry. Vitamin solutions are prepared by adding the following ingredients to water under stirring: potassium citrate, ferrous sulfate, WSV premix, L-carnitine, vitamin B2 and nucleotide-choline premix (specific ingredients) Different things) The ascorbic acid solution is prepared by adding potassium hydroxide and ascorbic acid to water in an amount sufficient to dissolve the ingredients. The pH of the ascorbic acid solution is then adjusted to 5-9 with potassium hydroxide.

The pH of the blend was adjusted with potassium hydroxide to a pH range of 6.60-6.90 for optimum product stability. The normalized blend is then subjected to a second heat treatment. The blend was initially heated to 66 °C - 82 °C and then further heated to 118 °C - 124 °C for about 5 seconds. The heated blend is then passed through a flash cooler to bring the temperature down to 71 °C - 82 °C. After heat treatment, the blend evaporates to a density of 1.15 - 1.17 g/mL.

The evaporated blend was passed through a spray dryer to achieve a moisture content of 2.5% in the finished powder. The finished powder is then coalesced together with water into a binder solution. The finished product is then packaged into a suitable container.

Example 16

In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula was evaluated. Specifically, the buffering capacity and buffering strength of various 1-2 day infant formulas and 3-9 day infant formulas of the present invention are determined and compared to commercially available powdered infant formulas, commercially available ready-to-eat 2 oz. The formulation, commercial ready-to-eat 32 ounce sterile sterile control infant formula and human milk buffer capacity and buffer strength were compared. The ingredients used to prepare the control formulation are set forth in Table 5 below.

Control Formulation 1 was prepared as described in Examples 12-15 above; Control Formulation 2 was prepared as described in Examples 1-8 above and Control Formulation 3 was prepared as described in Examples 9-11 above.

Determination of the buffering capacity and buffering strength of a variety of Day 1-2 ready-to-eat (RTF) Sterilization Sterilization or Reconstituted Powder Formulations and Day 3-9 RTF Sterilization, RTF Sterile or Reconstituted Powder Formulations and Control Formulations 1-3 And the buffer capacity and buffer strength of human milk are compared. Specifically, the buffer strength of the formulation (or human milk) was determined by adding 0.5 mL of an aliquot of 0.10 M HCl to 50 mL of each formulation (or a reconstituted formulation in the case of a powder formulation) at 1 minute intervals. . The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the amount of 0.10 M HCl milliliter required to reduce the pH of the 50 mL formulation to 3.0. The buffering capacity of the formulation (or human milk) was determined by adding 5.00 mmol of HCl to 100 mL of each formulation (or a reconstituted formulation in the case of a powder formulation). The buffering capacity is reported as the increase in [H+] after the addition of HCl. The results are shown in Table 6 below and Figures 1 and 2.

As can be seen from these results, the buffering capacity of the formulation decreases as the energy content decreases. The buffer capacity of Formulations 1-2 days with an energy content of 270 kcal/L was lowest in all test formulations. The buffer strength of human milk has been reported to be in the range of 9.0 to 18.0 with an average of 13.5. As can be seen from the results set forth in Table 6 and Figures 1 and 2, the buffer strength of the formulation on Days 1-2 is comparable to or below the buffer strength of the human milk tested.

The formulation of the present invention, and in particular the reduced buffering capacity and cushioning strength of the Formula 1-2 day, provides physiological benefits to the infant. In particular, reduced buffering capacity and strength can help achieve a more favorable distribution of intestinal microflora and increase the effectiveness of inactivation of orally ingested intestinal pathogens.

Example 17

In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula was evaluated. Specifically, the buffer capacity and buffer strength of the powdered infant formula of Days 1-2 (Formulation 13) and Days 3-9 (Formulation 15) of the present invention after reconstitution were determined and compared with commercially available powdered infant formula (control formula) 1) Comparison of buffering capacity and buffering strength after recovery.

Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of formula plus 240 mL of water, and Control Formulation 1 was reconstituted using 35.0 g of formula plus 240 mL of water. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding an aliquot of 1.00 mL of 0.500 M HCl to a 100 mL recovery formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the milliliter of HCl required to reduce the pH of the 100 mL recovery formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5.50 mmol HCl to 100 mL of each reconstituted formulation. The buffering capacity is reported as the amount of increase in [H+] after the addition of HCl and the amount of pH reduction after the addition of HCl. The results are shown in Table 7 below and in Figures 3-6.

As can be seen from the results described in Table 7 and Figure 3-6, the buffer strength and buffering capacity of the formulation on Days 1-2 and Days 3-9 (such as the decrease in pH and the increase in [H+]) Both were significantly lower than the buffer strength and buffering capacity of the control formulation. Formulations 1-2 days with an energy content of 250 kcal/L had the lowest buffering capacity and buffer strength in all tested formulations, indicating that buffer strength and buffering capacity decreased with decreasing energy content.

Example 18

In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula was evaluated. Specifically, the buffer capacity and buffer strength of 2 ounces of the infant formula (Formulation 3) of Sterilization Sterilization of the present invention were measured and buffered with 2 ounces of commercially available Sterilization Control Infant Formula (Control Formula 2). And buffer strength is compared.

The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 0.50 mL of an aliquot of 0.500 M HCl to 50 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the milliliter of HCl required to reduce the pH of the 50 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 2.75 mmol HCl to 50 mL of each formulation. The buffering capacity is reported as the amount of [H+] increase after adding HCl and the amount of pH reduction after adding HCl. The results are shown in Table 8 below.

As can be seen from the results in Table 8, the buffer strength and buffering capacity of the formulation on Day 1-2 (as measured by pH reduction and [H+] increase) are significantly lower than the buffer strength and buffer of the control formulation. The ability to show that the low-calorie 1-2 day sterilization pot sterilization formulation of the present invention has a buffer strength and a buffering capacity lower than that of the conventional full-calorie infant formula.

Example 19

In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula was evaluated. Specifically, the buffer capacity and buffer strength of 32 ounces of the Aseptic Sterilization Day 3-9 infant formula (Formulation 11) of the present invention were determined and buffered and buffered with 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3). The strength is compared.

The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 1.00 mL of an aliquot of 0.500 M HCl to 100 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the milliliter of HCl required to reduce the pH of the 100 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5.50 mmol HCl to 100 mL of each formulation. The buffering capacity is reported as the amount of [H+] increase after adding HCl and the amount of pH reduction after adding HCl. The results are shown in Table 9 below.

As can be seen from the results in Table 9, the buffer strength and buffering capacity of the formulation on days 3-9 (such as the decrease in pH and the increase in [H+]) were significantly lower than the buffer strength and buffer of the control formulation. The ability to demonstrate the buffer strength and buffering capacity of the low calorie 3-9 day sterile sterilization formulation of the present invention is lower than the buffer strength and buffering capacity of the conventional full calorie infant formula.

Example 20

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, the degree of proteolysis of the reconstituted powdered infant formula (Formulation 13) of the present invention and the reconstituted powdered infant formula 3-9 of the present invention (Formulation 15) after intestine digestion in vitro is determined. And compared to the degree of protein hydrolysis of the reconstituted powder control infant formula (Control Formula 1).

Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of formula plus 240 mL of water, and Control Formulation 1 was reconstituted using 35.0 g of formula plus 240 mL of water. The digest is prepared by in vitro digestion of the reconstituted formula. Specifically, the pH of each 40 mL of the reconstituted formulation was adjusted to 4.5 using 6 M HCl. 1.00 mL of USP pepsin (prepared in water at 56 mg/mL) was added to the formulation and the resulting mixture was stirred at room temperature for 1 hour. The pH of the mixture was adjusted to 7.2 using 10 N NaOH. Next, 4.00 mL of USP trypsin amylase/protease (prepared in water at 6.94 mg/mL) was added plus USP trypsin lipase (prepared in water at 6.94 mg/mL) and the mixture was stirred at room temperature for 2 hours. The resulting digest was centrifuged at 31,000 x g for 4 hours at 20 °C.

Use Superdex The supernatant was analyzed by HPLC on a peptide 10/300 GL gel filtration column (Amersham Biosciences). Specifically, 5 mg of supernatant was added to 1 mL of mobile phase solution (700 mL Milli-Q) Water, 300 mL acetonitrile, 1.00 mL TFA) and the solution was run at Superdex at ambient temperature. On the column (flow rate: 0.4 ml / min; detection: UV at 205 nm; injection: 10 μL; run time: 80 minutes) to determine the median molecular weight of the protein in the digest and the molecular weight in the digest is greater than 5000 Dao The amount of protein (% of total protein). These measurements are an indicator of the extent of protein digestion. The presence of insoluble proteins in the agglomerates produced by centrifugation of the digests was also tested using acid hydrolysis/amino acid profiles using conventional methods. The results are shown in Table 10 below and in Figures 7-9.

As can be seen from these results, the protein hydrolysis in Formulations 1-2 and Days 3-9 was more extensive than the control formulation. In addition, all three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content.

Example 21

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, the degree of protein hydrolysis of the 2 ounce infant formula (Formulation 3) of the sterilization sterilizer of the present invention after gastrointestinal digestion in vitro and the 2 ounce commercial sterilization sterilized control infant formula (Control Formula 2) was determined. The degree of protein hydrolysis is compared.

The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 31,000 x g for 4 hours at 20 °C. Use Superdex using the procedure described in Example 20 above Peptide 10/300 GL gel filtration column (Amersham Biosciences) The supernatant was analyzed by HPLC and the median molecular weight of the protein in the digest and the amount of protein with a molecular weight greater than 5000 Daltons in the digest (% of total protein) were determined. ). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 11 below.

The presence of the Mena reaction label proline in the digest was also tested using acid hydrolysis and HPLC. These results are also shown in Table 11 below.

As can be seen from these results, the protein hydrolysis in the formulation on Days 1-2 was more extensive than in the control formulation. All three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. In addition, the Meline reaction marker methionine content of the formulation on Day 1-2 was lower than the control formulation. These results show that the low calorie 1-2 day autoclave sterilization formulation of the present invention is less sensitive to the Mena reaction than the conventional full calorie infant formula.

Example 22

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, the degree of protein hydrolysis of 32 ounces of the sterile sterile 3-9 day infant formula of the present invention (Formulation 11) after in vitro gastrointestinal digestion was determined and compared to 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3). The degree of protein hydrolysis was compared.

The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 31,000 x g for 4 hours at 20 °C. Use Superdex using the procedure described in Example 20 above The peptide 10/300 GL gel filtration column (Amersham Biosciences) was used to analyze the supernatant by HPLC, and the median value of the molecular weight (MW) of the protein in the digest and the amount of protein having a molecular weight greater than 5000 Daltons in the digest (%) Total protein percentage). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 12 below.

As can be seen from these results, the protein hydrolysis in Formulations 3-9 was more extensive than the control formulation. All three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content.

Example 23

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, the degree of protein hydrolysis after trypsinization of the 1-2 day powder infant formula (Formulation 13) of the present invention and the restored 3-9 day powder infant formula (Formulation 15) of the present invention are determined, The degree of protein hydrolysis after trypsinization was compared to the recovered commercial powdered infant formula (Control Formula 1).

Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of formula plus 240 mL of water, and Control Formulation 1 was reconstituted using 35.0 g of formula plus 240 mL of water. The digest is prepared by trypsinizing the reconstituted formula. Specifically, 9.00 mL of 0.05 M NaH ₂ PO ₄ (pH 7.5) was added to 9.00 mL of each formulation in a 20 mL vial. 2.00 mL of porcine pancreatin (prepared at 4.0 g/L in pH 7.5 buffer) was added to the formulation and the vials were placed in a 37 ° C water bath for 71 minutes. After 71 minutes, 1.5 mL of the mixture aliquot was transferred into a HPLC autosampler vial and the vial was crimped. The sealed vial was placed in a 100 ° C heating module for 5 minutes to stop trypsin digestion. 0.400 mL of the resulting digest was diluted with 1.00 mL of 8.30/6.00/0.02 (v/v) water/acetonitrile/trifluoroacetic acid. The diluted digest was centrifuged at 14,000 x g for 5 minutes at room temperature. Use Superdex using the procedure described in Example 20 above The peptide 10/300 GL gel filtration column (Amersham Biosciences) was used to analyze the supernatant by HPLC, and the median value of the molecular weight (MW) of the protein in the digest and the amount of protein having a molecular weight greater than 5000 Daltons in the digest (%) Total protein percentage). The results are shown in Table 13 below and Figures 10 and 11.

As can be seen from these results, the protein hydrolysis in Formulations 1-2 and Days 3-9 was more extensive than the control formulation. In addition, both digestion indices (median protein MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content.

Example 24

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, determine the degree of protein hydrolysis of the 2 ounce infant formula (Formulation 3) of the sterilization of the 1-2 days of the present invention before and after trypsin digestion and compare the baby formula with 2 ounces of commercially available sterilization kettle (control formula) 2) Comparison of the degree of protein hydrolysis before and after trypsinization.

Digests were prepared by trypsinization of the formulation using the same procedure as described in Example 23, except that the infant formula/pancreatin mixture was maintained in a 37 °C water bath for only 60 minutes. The diluted digest was centrifuged at 14,000 x g for 5 minutes at room temperature. Use Superdex Peptide 10/300 GL gel filtration column (Amersham Biosciences) was used to analyze the supernatant before digestion and the sample of the infant formula by HPLC using the procedure set forth in Example 20 above, and to determine the molecular weight of the protein in the infant formula prior to digestion. Value and protein median molecular weight after trypsin digestion for 60 minutes. The results are shown in Table 14 below.

As can be seen from these results, the rate of protein hydrolysis in the low calorie 1-2 day formulation was faster compared to the control formulation. In addition, the median MW after pancreatic digestion for 60 minutes was directly proportional to the caloric density of the infant formula, indicating that protein digestibility was inversely related to energy content.

Example 25

In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis is assessed. Specifically, the 1-2 day powder infant formula (Formulation 12) or the 3-9 day powder infant formula (Formulation 14) of the present invention, 2 ounces of the 1-2 day sterilization sterilized infant of the present invention are determined. Formulations (Formulations 1 and 2) or Days 3-9 Sterilization Sterilized Infant Formula (Formulation 5) and 32 ounces of the 3rd Days Sterile Sterilized Infant Formula (Formulation 9) of the Invention in Trypsin Digestion (Powder) or Living Body The extent of protein hydrolysis after exo-GI digestion (liquid) and the reconstituted commercial powder control infant formula (Control Formula 1), 2 ounces of commercially available Sterilization Control Infant Formula (Control Formula 2) and 32 ounces of commercially available aseptic sterilization controls The degree of protein hydrolysis of the formulation (Control Formula 3) was compared.

Formulation 12 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 14 was reconstituted using 21.4 g of formula plus 240 mL of water, and Control Formulation 1 was reconstituted using 35.0 g of formula plus 240 mL of water. The digest is prepared by trypsinizing the formulation (or reconstituted formulation) using the same procedure as described above. Use Superdex using the procedure described in Example 20 above The peptide 10/300 GL gel filtration column (Amersham Biosciences) was used to analyze the supernatant by HPLC, and the median value of the molecular weight (MW) of the protein in the digest and the amount of protein having a molecular weight greater than 5000 Daltons in the digest (%) Total protein percentage). The results are shown in Table 15 below.

As can be seen from these results, the protein hydrolysis in Formulations 1-2 and Days 3-9 was more extensive than the control formulation. In addition, both digestion indicators (protein median MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content.

Example 26

In this example, the effect of micronutrient content on the stability of the emulsion on the 1-2 day sterilization autoclave formulation and the 3-9 day sterile sterile infant formula was evaluated. Specifically, compare 32 ounces of high stability (Formulation 11) or low (Formulation 9) micronutrient content to the 3-9 day sterile sterilized infant formula for emulsion stability and 2 ounces with high (Formulation 3) or low (Formulation 1) The emulsion stability of the sterilized infant formula for the first 1-2 days of micronutrient content.

The emulsion stability was determined using the protein loading (expressed as the percentage of protein in the cream layer formed after high speed centrifugation of the formulation). The protein loading of each formulation was determined by pouring a 36-38 gram formulation into a tared 50 mL centrifuge tube and capping the centrifuge tube. The capped centrifuge tube was then placed in a JA-20 fixed angle rotator (Beckman Coulter, P/N 334831) and the rotator was placed in a Beckman J2-HS centrifuge (Beckman Coulter). The sample was centrifuged at 31,000 x g for 8 hours at 20 °C. After centrifugation, a cream layer was formed on the sample. The cream layer was transferred to a tared beaker and its weight recorded. The supernatant was poured into a separate beaker and the centrifuge tube was weighed again to determine the aggregate weight.

The amount of protein in the cream layer was determined using an acid hydrolysis/amino acid assay technique. The results are set forth in Table 16 below.

The protein loading value is an indicator of emulsion stability. Specifically, emulsion stability generally increases with increasing protein loading values. As can be seen from the above results, the protein loading value in the 1-2 day sterilization pot sterilization formula (ie, Formula 1) with low micronutrient content is higher than the 1-2 day sterilization kettle sterilization formula with high micronutrient content. The protein loading value in Formulation 3. These results show an increase in emulsion stability in the 1-2 day sterilization autoclave formulation with a low micronutrient content compared to comparable formulations with high micronutrient content. There was no significant difference in protein loading between the aseptically sterilized formulations of high micronutrient content and the aseptically sterilized formulations of low micronutrient content.

Example 27

In this example, the effect of micronutrient content on emulsion stability of the Sterilization Sterilization Formulation on Days 3-9 was evaluated. Specifically, compare the emulsion stability of a 2 ounce sterilized infant formula for a 3-9 day high (Formulation 8) or low (Formulation 6) micronutrient content.

The emulsion stability was determined using the protein loading (expressed as the percentage of protein in the cream layer formed after high speed centrifugation of the formulation). The protein loading of each formulation was determined using the procedure set forth in Example 26. The amount of cream layer (by weight of the total product) and the amount of protein in the cream layer (based on the weight of the total product) were also calculated. The results are set forth in Table 17 below.

As can be seen from these results, the protein loading value in Formulation 6 with a low micronutrient content is higher than the protein loading value in the high micronutrient formulation (i.e., Formulation 8). Formulation 6 also formed a larger cream layer than Formulation 8 and the percentage of protein in the cream layer (by weight of the total product) was higher. These results show an increase in emulsion stability in the 3-9 day autoclave sterilization formulation with a low micronutrient content compared to comparable formulations with high micronutrient content. Low micronutrient content Day 3-9 Sterilization Sterilization Formulation (ie Formulation 6) also has a higher protein loading than the low micronutrient content Day 1-2 Sterilization Sterilization Formulation (see Formulation 1, Example 26) The value and therefore the stability of the emulsion increases.

Example 28

In this example, the effect of micronutrient content on the color of the Sterilization Sterilization Formulation on Days 1-2 and Days 3-9 and the sterile sterilization formulation on Days 3-9 was evaluated.

The color quality of the formula was evaluated using the Aegis color method. The Aegis color method uses a spectrophotometer to measure the percentage of light reflected from the sample from 0 (black) to 100 (white). Bright color infant formulas (which are typically preferred by consumers) have a higher Aegean color score, while darker formulas have a lower score. The Aegean color scores of the low and high micronutrient content sterilization sterilization and aseptic sterilization formulations of the present invention measured over a plurality of time periods are set forth in Table 18 below (Sterilization Sterilization Formulation) and Table 19 (Days 3-9) Sterile sterilization formula).

Table 18: Sterilization Sterilization Formula

Table 19: Sterile Sterilization Formula 3-9

As can be seen from these results, the 1-2 day infant formula with low micronutrient content has a higher Aegis color than the 1-2 day infant formula with high micronutrient content. Score and therefore have a brighter color appearance. Similar results were obtained on the 3-9th Sterilization Sterilization Formula and the 3-9 Day Sterile Sterilization Formula, where the low micronutrient content formulation had a higher Aegis color score than the comparable formula with high micronutrient content. Even after prolonged periods of time (in some cases up to 9 months after product formulation), color improvements in low micronutrient formulations compared to comparable high micronutrient formulations were observed. These results show that the infant formula of the present invention having a low micronutrient content has a brighter and lighter color appearance than a comparable formulation having a high micronutrient content.

Example 29

In this example, the effect of micronutrient content on the particle size distribution of the formulation on day 1-2 of sterilization and the separation rate of the emulsifiable concentrate was evaluated.

Specifically, the particle size distribution of the 2 ounce formulation of the 1-2 day sterilization of the sterilizer with high micronutrient content (Formulation 3) or low micronutrient content (Formulation 1) was determined using a Beckman Coulter LS 13 320 light scattering machine. The results are shown in Figure 12.

As can be seen from Figure 12, the majority of the particles in the 1-2 day sterilization autoclave formulation (Formulation 1) have a size between about 0.1 μm and about 0.8 μm, and a small portion of the particles are between about 1 Between μm and about 8 μm. In contrast, the high micronutrient 1-2 day autoclave sterilization formulation (Formulation 3) has a particle size distribution more evenly ranging from about 0.1 μm to about 7 μm.

The average particle size of each formulation was determined from the particle size distribution and used to calculate the cream separation speed for each formulation. Specifically, calculate the separation rate of the cream using the following equation:

among them:

v _cream is the separation speed of _cream

ρ _fluid is the formula density

ρ _particle is the particle density

η is the formula viscosity

R is the average particle size

g is the acceleration of gravity.

The density of particles (e.g., oil droplets) was calculated by measuring the total surface area of the particles in a unit sample (100 mL) using a Beckman Coulter LS 13 320 light scattering machine. The volume of protein attached to the surface of the oil droplets is then measured using ultracentrifugation. The average thickness of the protein layer applied to each oil droplet is then divided by the volume of protein divided by the total surface area of the oil droplets. The average particle density was then calculated using a protein density of 1.41 (Fischer et al., Protein Science (2004), Vol. 13 (10), pp. 2825-2828).

The R ² values of each formulation and the cream separation speed are shown in Table 20.

Table 20: Particle size and emulsification separation speed of sterilization preparation in the sterilization machine on the first 1-2 days

As can be seen from this table, the average particle size of the low-micronutrient 1-2 day sterilization pot sterilization formula (Formulation 1) is smaller than the average particle size of the high-micronutrient 1-2 day sterilization pot sterilization formula (Formulation 3). Since the smaller particle size can indicate product stability, these results show that the low micronutrient of the present invention has a product stability greater than that of a comparable high nutrient content in the 1-2 day sterilization autoclave formulation.

The cream separation rate measures the rate at which particles (e.g., droplets) move through the liquid sample (in this case, the infant formula) and predicts the ability of the infant formula to form a cream layer. As can be seen from Table 20, the low micronutrient content on the first 1-2 days of the sterilization of the sterilization formula of the sterilization process is less than the high micronutrient content on the first 1-2 days of the sterilization process of the sterilization process. These results show that the low micronutrient content of the present invention on day 1-2 of the autoclave sterilization formulation has a reduced ability to form a cream layer compared to a comparable high micronutrient formulation and thus improved physical stability.

1 is a graph showing the buffer strength of various low calorie 1-2 day and 3-9 day infant formulas as compared to the control full calorie formula and human milk as discussed in Example 16.

2 is a graph showing the buffering capacity of various low calorie 1-2 day and 3-9 day infant formulas as compared to the control full calorie formula and human milk as discussed in Example 16.

3 is a graph showing the effect of adding HCl on the pH of the low calorie 1-2 day and 3-9 day reconstituted powder infant formula as compared to the control full calorie formulation as discussed in Example 17.

4 is a graph showing the buffer strength of the low calorie 1-2 day and 3-9 day reconstituted powder infant formula as compared to the control full calorie formulation as discussed in Example 17.

Figure 5 is a graph showing the buffering capacity of a low-calorie 1-2 day and 3-9 day reconstituted powdered infant formula as compared to a control full-calorie formulation as discussed in Example 17, such as adding 5.50 milligrams to a 100 mL formulation. A graph of molar HCl followed by a decrease in pH).

Figure 6 is a graph showing the buffering capacity of a low-calorie 1-2 day and 3-9 day reconstituted powdered infant formula as compared to a control full-calorie formulation as discussed in Example 17, such as adding 5.50 milligrams to a 100 mL formulation. A graph of the molars of HCl followed by [H+] increase).

Figure 7 is a graph showing the protein molecular weight (MW) of the reconstituted powder infant formula for low calorie days 1-2 and days 3-9 after in vitro parenteral digestion as compared to the control full calorie formulation as discussed in Example 20. A chart of values.

Figure 8 is a graph showing the MW greater than 5000 Da in the infant formula for low calorie 1-2 days and 3-9 days after intestine digestion in vitro compared to the control total calorie formulation as discussed in Example 20. A graph of total protein percentage.

Figure 9 is a graph showing the low-calorie 1-2 and 3-9 reconstituted powdered infant formula in protein pellets after high speed centrifugation after in vitro gastrointestinal digestion as compared to the control full calorie formulation as discussed in Example 20. A chart of the amount of insoluble (hard to digest) protein.

Figure 10 is a graph showing the median MW of the protein of the reconstituted powder infant formula for low calorie days 1-2 and days 3-9 after 71 minutes of trypsinization as compared to the control full calorie formulation as discussed in Example 23. chart.

Figure 11 is a graph showing the MW greater than 5000 Da in the low-calorie 1-2 and 3-9 reconstituted powder infant formulas after 71 minutes of trypsinization as compared to the control full-calorie formulation as discussed in Example 23. A graph of the percentage of total protein.

Figure 12 is a graph showing the particle size distribution of the 1-2 day formulation with high micronutrient content (Formulation 3) or low micronutrient content (Formulation 1) sterilized by autoclave as discussed in Example 29.

(no component symbol description)

Claims (20)

A method of improving protein digestion in an infant comprising administering to the infant an infant formula having an energy content of from about 200 to less than 600 kcal/liter. The method of claim 1, wherein the infant is a newborn. The method of claim 1, wherein the infant formula is a 1-2 day infant formula having an energy content of from about 200 to about 360 kcal/liter of formula. The method of claim 3, further comprising administering to the infant the 1-2 day infant formula during the first two days after birth and administering the infant to an energy content of about 360 to less than 3 to 9 days after birth. The 3rd-9th infant formula for the 600 kcal/litre formula. A method of improving protein digestion in an infant, the method comprising administering to the infant a low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having about The energy content of the formula of 200 to less than 600 kcal/liter, wherein at least 65% of the micronutrient is included in the infant formula in an amount of from about 30% to about 80% by weight of the conventional micronutrient amount per unit volume. The method of claim 5, wherein the infant is a newborn. A method for improving protein digestion in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having An energy content of from about 200 to about 360 kcal/liter of formula, wherein at least 45% of the micronutrient per unit volume is included in the infant formula in an amount from about 30% to about 65% of the amount of the corresponding micronutrient . The method of claim 7, wherein the infant is a newborn. The method of claim 7, wherein the infant formula is the 1-2 day infant formula. The method of claim 9, further comprising administering the infant to the infant formula 1-2 on the first two days after birth and administering the infant to an energy content of about 360 to less than 600 on days 3 to 9 after birth. The 3rd-9th infant formula for the kilocalorie/liter formula. The method of claim 10, wherein the 3-9 day infant formula is a low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, wherein At least 30% of the micronutrient per unit volume is included in the 3-9 day infant formula in an amount from about 55% to about 80% of the amount of the corresponding micronutrient. A method of improving protein digestion in an infant, the method comprising administering to the infant a low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having about The energy content of the formula of 360 to less than 600 kcal/liter, wherein at least 30% of the micronutrient per unit volume is included in the infant formula in an amount from about 55% to about 80% of the amount of the corresponding micronutrient. The method of claim 12, wherein the infant is a newborn. The method of claim 12, wherein the infant formula is a 3-9 day infant formula. The method of claim 14, further comprising administering to the infant a 1-2 day infant formula having an energy content of from about 200 to about 360 kcal/liter during the first two days of life and from 3 to 9 after birth. The baby is given the 3-9 day infant formula for the baby. A method of improving protein absorption in an infant comprising administering to the infant an infant formula having an energy content of from about 200 to less than 600 kcal/liter. The method of claim 16, wherein the infant is a newborn. The method of claim 16, wherein the infant formula is a 1-2 day infant formula having an energy content of from about 200 to about 360 kcal/liter of formula. The method of claim 18, further comprising administering the infant to the infant formula 1-2 on the first two days after birth and administering the infant to an energy content of from about 360 to less than 600 on days 3 to 9 after birth. The 3rd-9th infant formula for the kilocalorie/liter formula. The method of claim 16, wherein the infant formula has an energy content of from about 200 to about 400 kcal/liter of formula.