RU2795167C2 - Composition of breast milk fortifier - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: group of inventions relates to composition of human breast milk fortifier and its use. Human breast milk fortifier composition contains the following: copper, selenium, zinc, alpha-lactalbumin, casein, lactoferrin, alpha-tocopherol, gamma-tocopherol, nicotinic acid, retinol, DFSLTHN, FSLTNH3, GSLT6, LnNT, LNT, 6'-SL and SLTNTC. Also a package containing the said composition is disclosed and the use of the said composition to optimize growth and development or to maintain healthy growth in preterm, extremely low birth weight (ELBW) and/or very low birth weight (VLBW) infants, as well as to prevent and/or treat a condition selected from the following group: growth and/or developmental failure, growth retardation, infection, lung disease, developmental delays, blindness, and/or metabolic bone disease.

EFFECT: invention provides an optimized composition of a breast milk fortifier for premature babies.

17 cl, 4 dwg, 2 tbl, 2 ex

Description

Technical field

The present invention relates to a human breast milk fortifier composition, more particularly to a human milk fortifier composition providing one or more specific nutrients in amounts deficient in the breast milk of women who have given birth to a premature infant. In particular, the present invention relates to a fortifier composition formulated as a breast milk supplement at the birth of a premature infant, for use during the infant's hospital stay and after the infant has left (i.e., after discharge). In addition, the invention relates to the use of said breast milk fortifier composition.

Prerequisites for the creation of the invention

Babies are born at different stages of development. For example, preterm or preterm infants, which are infants born before term, ie. before the 37th week of pregnancy, may have a low birth weight. Other babies are small for their gestational age, ie. they may, for example, be born at term but have a small body weight, such as less than 2500 grams. These infants are generally at risk of stunting and increased risk of growth and development failure, and their nutrition after birth and during their stay in the NICU (neonatal intensive care unit) is carefully designed and monitored.

Nzegwu et al. [“Post discharge nutrition and the VLBW infants: to supplement or not supplement?”, Clin. 41 (2014), 463–474, noted that nutritional assessment begins at birth through anthropometric assessment to provide information on intrauterine growth, and continues until discharge from the hospital to assess postnatal growth. Indeed, many studies have highlighted the importance of early feeding of very low birth weight (LBWB <1500 g) and extremely low birth weight (LBWB <1000) infants for their short and long term growth and development.

Breast milk is generally accepted as the preferred source of enteral nutrition for preterm infants. In any case, breast milk from both preterm and term infants is insufficient to meet the special nutritional needs of infants with LLD, so breast milk fortifiers are used to meet the growing nutritional needs of these infants during their hospital stay. Breastfeeding during hospital stay has additional and significant benefits for preterm infants, such as reduced risk of NEC (necrotizing enterocolitis) and sepsis, improved gastrointestinal tolerance, and improved neurological outcomes.

Nutrition after hospital discharge requires more attention in any case, as it has been shown that preterm and especially extremely preterm infants are at higher risk of stunting at discharge, and that undergrowth is subsequently associated with worse neurodevelopmental outcomes.

The use of human milk fortifiers while in the NICU addresses the problem that breast milk does not fully meet the nutritional needs of preterm infants, but raises questions about the best nutritional option for these infants after discharge.

There are several approaches to post-discharge nutrition: infants can, for example, be fed post-discharge standard or preterm infant formula, breastfeeding, or breast milk fortified with standard high-calorie, multi-nutrient fortifiers, depending on nutritional status. and growth dynamics of the infant.

Current data on post-discharge nutrition in any case suggests that feeding with post-discharge formula or standard high-calorie, multi-nutrient fortifier results in minimal improvements in growth and neurological outcomes in some cases. This may be due to the fact that preterm infants are able to regulate their intake in accordance with the calorie intake; the higher the caloric content, the lower the intake (Teller et al, 2016), so that increasing the energy content of the diet (for example, when using breast milk fortified with existing high-calorie, multi-nutrient fortifiers) may ultimately lead to overall insufficient intake of essential nutrients.

On the other hand, other nutrients also remain in breast milk (option for preterm infants at discharge [Nzegwu et al., “Post discharge nutrition and the VLBW infants: to supplement or not supplement?”, Clin. Perinatol 41 (2014), 463–474] as well as for those who gained an acceptable weight for age after conception at discharge [ESPGHAN, 2006, Journal of Pediatric Gastroenterology and Nutrition, 42: 596–603].

Accordingly, there continues to be a need to identify ideal feeding solutions tailored to the nutritional needs of infants born preterm or with LLWB/LWB at discharge or after hospital discharge.

Thus, it is an object of the present invention to provide a human milk fortifier composition for use at discharge and post-discharge from the hospital for preterm infants with LBNR or LBNR, and containing the correct amounts of certain nutrients (which are deficient in mothers' breast milk). such premature infants or infants with LLD).

Furthermore, it is an object of the present invention to provide a human milk fortifier composition for use at or after discharge from the hospital for preterm infants with LBWR or HBWR that contains the correct amounts of certain nutrients and provides a high nutrient-to-energy ratio. .

Statement of the Invention

To meet the above needs, breast milk samples from mothers of full-term postmenstrual age infants corresponding to typical discharge dates for preterm/LWGR infants were analyzed and compared with breastmilk samples from mothers of preterm or LWGR infants of the same postmenstrual age.

Surprisingly, it was found that at the time of discharge, breast milk received by a premature baby is depleted in alpha-lactalbumin, casein and lactoferrin compared to milk received by a full-term baby of the same postmenstrual age. Similarly, at discharge, the milk of a premature infant is deficient in certain micronutrients (zinc, selenium, vitamin E, vitamin A) and some human milk oligosaccharides (HMOs) when compared to the milk of a term infant of the same postmenstrual age.

Based on the results obtained, the inventors have developed a breast milk fortifier for mothers who have given birth to premature infants or infants with LVR or CLVR, for use at the time of discharge or after the infant is discharged from the hospital. The fortifiers of the present invention are designed to make up for the deficiency found and to ensure that infants born preterm, with LVR or LLVR, and who are breastfed at discharge, receive nutrition consistent with that of a full-term infant of the same postmenstrual age with exclusively breastfeeding, which remains the gold standard for nutrition and maintenance of proper growth and (neurological) development up to 6 months after full-term babies are born. It is assumed that at the time of discharge, the growth of preterm infants with LBGR or LBGR actually follows the same growth curve as for term or normal weight infants of the same postmenstrual age, so that their nutritional requirements are at least comparable.

The fortifiers of the present invention further provide a high nutrient to energy ratio compared to currently available standard fortifiers. Thus, the fortifiers of the present invention are expected to have a limited effect on total infant milk intake and therefore may supplement preterm breast milk with the missing essential nutrients with little impact on total milk intake.

Thus, one aspect of the invention relates to a human milk fortifier composition containing at least one mineral delivery ingredient, in particular certain amounts of copper, selenium and/or zinc.

In another aspect, the invention relates to a human milk fortifier composition comprising at least one protein delivery ingredient, in particular certain amounts of alpha-lactalbumin, caseins and/or lactoferrin.

In yet another aspect, the invention relates to a human milk fortifier composition comprising at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

In another additional aspect, the invention relates to a human milk fortifier composition containing at least one ingredient that provides delivery of human milk oligosaccharides, in particular, certain amounts of difucosyllacto-N-hexaose-a (DFLNHa or DFSLTNH), monofucosyl-lacto-N-hexaose- III (MFLNH-III or FSLTNH3), 6'-galactosyl lactose (6'-GL or GSLT6), lacto-N-neotetraose (LNnT or LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'- SL) and/or sialyllacto-N-tetraose-c (LSTc or SLTNTC).

In another additional aspect, the present invention relates to a human milk fortifier composition comprising at least one ingredient that provides delivery of human milk oligosaccharides, in particular, certain amounts of difucosyl lacto-N-hexaose-a (DFSLTNH), monofucosyl lacto-N-hexaose-III (FSLTNH3), 6'-galactosyl lactose (GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL) and/or sialyllacto-N-tetraose-c (LSTc or SLTNTC); at least one mineral delivery ingredient, in particular certain amounts of copper, selenium and/or zinc; at least one ingredient that provides the delivery of proteins, in particular, certain amounts of alpha-lactalbumin, caseins and/or lactoferrin; and at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

In yet another aspect, a human milk fortifier composition is provided comprising at least one ingredient selected from the group consisting of copper providing ingredients; ingredients providing selenium; ingredients providing zinc; amino acid providing ingredients, eg alpha-lactalbumin, caseins and/or lactoferrin providing ingredients; ingredients providing alpha-tocopherol; ingredients providing gamma-tocopherol; ingredients providing nicotinic acid; ingredients providing retinol; ingredients providing DFSLTHN; ingredients providing FSLTNH3; ingredients providing 6'-SL; ingredients providing LnNT; ingredients providing LNT; ingredients providing 6'-SL; and ingredients providing SLTNTC; or their mixtures.

In yet another aspect, the present invention relates to said human milk fortifier composition for use in fortifying human milk, e.g., the breast milk of mothers who have given birth to preterm infants, LBWL, or LBWL infants at or after discharge from the hospital of a prematurely born BWBL infant. or KNVR.

In yet another aspect, the present invention relates to the use of said human milk fortifier composition for fortifying the breast milk of mothers who have given birth to preterm infants, LBWL, or LBWL infants at or after discharge from the hospital of a preterm, LBWB, or BHBF infant.

In another aspect, the present invention provides a human milk fortifier composition for use in the prevention and/or treatment of a condition selected from the group consisting of growth and/or developmental failure, growth retardation, infection, lung disease, developmental delays, blindness, and/or fractures. bones.

In another aspect of the present invention, the use of a human milk fortifier is provided for optimizing the growth and development of a preterm infant with LBW and/or LBW.

Yet another aspect of the present invention is to provide a package containing said human milk fortifier composition, wherein the package is a single dosing device or a multiple dosing device.

As a rule, various aspects of the invention can be combined and combined in any way possible within the scope of the invention. These and other aspects, elements and/or advantages of the invention will be apparent from the embodiments described below and explained with reference to them.

Hereinafter, the present invention will be described in more detail.

Detailed description of the invention

Definitions

Prior to a more detailed description of the present invention, the following terms and conventions will be defined.

Numerical ranges herein are intended to include all numbers and subsets of numbers contained within that range, whether specifically disclosed or not. In addition, these numerical ranges should be considered as confirmation of a claim that refers to any number or subset of numbers within this range. For example, the description "from 1 to 10" should be considered as confirming the range "from 1 to 10" (including 1 and 10), "from 2 to 8", "from 3 to 7", "from 1 to 9", "from 3.6 to 4.6", "3.5 to 9.9", etc. All references to features or limitations of the present invention in the singular shall include the corresponding feature or limitation in the plural, and vice versa, unless otherwise noted or unless the context in which the reference is made expressly implies otherwise.

The term "and/or" used in the context of "X and/or Y" should be interpreted as "X" or "Y" or "X and Y".

All technical and scientific terms used in this document, unless otherwise defined, have the generally accepted meaning understood by the ordinary person skilled in the art.

In the context of the present invention, the term "ingredient" or "ingredients" means an edible substance or mixture of substances, including at least one substance capable of delivering nutrients to the human body, or essentially consisting of it.

In the context of the present invention, the term “nutrient X providing ingredient” or “nutrient X providing ingredients” means an edible substance and/or a mixture of substances comprising at least one substance capable of delivering said nutrient X to the body. person, or essentially consisting of him.

In the context of the present invention, the term "ingredient providing nutrient X in the amount of Y" or "ingredients providing nutrient X in the amount of Y" means an edible substance and/or a mixture of substances, including at least one substance capable of delivering the specified nutrient X into the human body in the specified amount of Y, or essentially consisting of it.

In the context of the present invention, the term "ingredient providing Y amount of nutrient X/100 ml fortified breast milk" or "ingredients providing Y amount of nutrient X/100 ml fortified breast milk" means an edible substance and/or a mixture of substances comprising at least one substance capable of delivering said nutrient X to a human body in said amount Y when fortified with 100 ml of breast milk with a composition containing such ingredient and administered to a subject, or essentially consisting of it.

The term "infant" in the context of the present invention means a child under the age of 2 years; preferably the infant is a child under 12 months of age, eg under 9 months of age, eg under 6 months of age.

In the context of the present invention, the infant may be any term infant or premature infant. In one embodiment of the invention, the infant is selected from the group of preterm infants and term infants.

The term "term infant" refers to infants born at term or at a gestational age of 37 weeks or more.

The term "premature infant" refers to infants born at a gestational age of less than 37 weeks.

In the context of the present invention, the term "birth weight" means the first value of the weight of the fetus or newborn obtained after birth.

In the context of the present invention, the term "low birth weight" means a birth weight of less than 2500 g (up to and including 2499 g).

In the context of the present invention, the term "very low birth weight" means a birth weight of less than 1500 g (up to and including 1499 g).

In the context of the present invention, the term "extremely low birth weight" means a birth weight of less than 1000 g (up to and including 999 g).

The term "low birth weight infants" refers to infants weighing less than 2.5 kg at birth.

The term "very low birth weight infants" refers to infants weighing less than 1.5 kg at birth.

The term "very low birth weight infants" refers to infants weighing less than 1.0 kg at birth.

The term "infant small for gestational age" refers to infants having a birth weight more than 2 standard deviations below the mean reference birth weight on the gestational growth chart or having a birth weight below the 10th percentile of population weight data, obtained for infants of the same gestational age. The term "infants small for their gestational age" includes infants small at birth due to constitutive or genetic origin or due to intrauterine growth retardation.

In the context of the present invention, the term "gestational age" means an indicator of the duration of pregnancy and represents the time elapsed from the first day of the last normal menstrual period until the date of delivery.

If the date of the last normal menstrual period is not known, the gestational age is determined based on the best clinical judgment. Gestational age is usually expressed in completed weeks (for example, events occurring between 280 and 286 completed days after the start of the last normal menstrual period are considered to have occurred at 40 weeks of gestation).

For the purposes of calculating gestational age from the date of the first day of the last normal menstrual period to the date of delivery, it should be taken into account that the first day is considered day zero and not day one; so days 0–6 correspond to "full week zero"; days 7-13 - "full week one"; and the 40th week of actual pregnancy is synonymous with "full week 39".

In the context of the present invention, the term "chronological age" means the time elapsed since birth, and it can be measured in days, weeks, months and/or years.

In the context of the present invention, the term "postmenstrual age" means the cumulative time since the first day of the last menstrual period before birth (gestational age) and the time since birth (chronological age). Postmenstrual age is usually described as the number of weeks.

A schematic representation of age terminology used in the perinatal period is shown in FIG. 1.

In the context of the present invention, the term "perinatal period" refers to the period that begins at 22 completed weeks (154 days) of pregnancy (the time when a normal birth weight is 500 g) and ends seven completed days after birth.

In the context of the present invention, the term "newborn period" means the period that begins at the time of birth and ends 28 completed days after birth.

In the context of the present invention, the term "at discharge" and/or "at discharge from the hospital" refers to the moment when an infant born prematurely with LLVR or LVR is discharged from the hospital.

In one embodiment, the discharge of such infants from the hospital occurs between 36 and 50 weeks, such as between 36 and 48 weeks postmenstrual age.

The term "infant formula" in this document refers to a nutritional composition intended for infants as defined in the Codex Alimentarius (Code STAN 72-1981) and to special foods for infants (including foods for special medical purposes) as defined in the Codex Alimentarius (Codex STAN 72-1981). It also refers to a food specifically intended for consumption by infants during the first months of life and meeting the nutritional needs of this category of persons (Article 2(c) of European Commission Directive 91/321/EEC 2006/141/EC of 22 December 2006 about infant formulas and mixtures for feeding children). Infant formulas include initial infant formulas and complementary formulas. In general, initial formula is intended for infants from birth as a substitute for breast milk, and infant formula at the next level or for formula-fed infants from 6 months onwards.

"Milk formula for children from 1 to 3 years" (or GUM) is given after one year and beyond. Essentially, it is a milk-based drink adapted to the specific nutritional needs of young children. It is a nutritional composition that is used to feed children from 12 months to 2-3 years in combination with other foods.

The term "liquid" as used herein encompasses any aqueous or oil based composition, such as a fluid, oil, emulsion, or gel.

As used herein, the term "optimize" includes improvement or enhancement.

The composition of the present invention, including many of the embodiments described herein, may include, consist of, or essentially consist of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein. , or otherwise applicable in infant formula.

Concentrator

In the context of the present invention, the term "fortifier" refers to a composition that contains one or more nutrients with nutritional value for infants. In one embodiment, the fortifier according to the present invention contains at least one nutrient selected from the group consisting of minerals, vitamins, milk protein and human milk oligosaccharides.

The term "milk fortifier" means any composition used to fortify or supplement one of breast milk, infant formula, infant formula for 1 to 3 years of age, or breast milk fortified with other nutrients.

The term "breast milk fortifier" means any composition used to fortify or supplement breast milk or breast milk fortified with other nutrients. Accordingly, the human milk fortifier of the present invention may be administered after being dissolved in breast milk, breast milk fortified with other nutrients, or it may be administered as a separate composition.

When administered as a separate composition, the human milk fortifier of the present invention may also be referred to as a "supplement". In one embodiment, the human milk fortifier of the present invention is a supplement.

The "human milk fortifier" of the present invention is intended to be administered to infants born prematurely, with very low birth weight (LBW) or extremely low birth weight (LBW).

In one embodiment, the human milk fortifier of the present invention is intended to be administered to infants born preterm, very low birth weight (LBW) or very low birth weight (LBW) from the time such infants are discharged from the hospital, typically , in the period from 36 to 50 weeks, for example from 38 to 48 weeks of postmenstrual age.

In one embodiment, the human milk fortifier of the present invention is intended to be administered to infants born preterm, very low birth weight (LBW) or very low birth weight (LBW) from the time such infants are discharged from the hospital, typically , in the period from 36 to 50 weeks, for example from 38 to 48 weeks of postmenstrual age, until they reach the postmenstrual age of 9 months and/or body weight of 8 kilograms.

In one embodiment, the human milk fortifier of the present invention is intended to be administered to infants born preterm, very low birth weight (LBW) or very low birth weight (LBW) from the time such infants are discharged from the hospital, typically , in the period from 38 to 43 weeks, for example from 38 to 42 weeks of postmenstrual age.

In another embodiment, the human milk fortifier of the present invention is for administration to infants born preterm, very low birth weight (LBW) or extremely low birth weight (LBW) between 38 and 43 weeks postmenstrual age.

The milk fortifier may, for example, be in the form of a powder, tablet, capsule, lozenge or liquid, as long as it is suitable as a nutritional composition for an infant.

In one embodiment, the human milk fortifier of the present invention may be in the form of a powder or liquid, such as a solution or suspension in water.

In one embodiment, the human milk fortifier may further comprise protective hydrocolloids (such as gums, proteins, modified starches), binders, film forming agents, encapsulating agents/materials, wall/shell materials, matrix compounds, coatings, emulsifiers, surfactants. substances, solubilizing agents (oils, fats, waxes, lecithins, etc.), adsorbents, carriers, fillers, auxiliary compounds, dispersing agents, wetting agents, processing aids (solvents), anti-caking agents, taste masking agents, weighting agents, gelling agents; and gelling agents. The human milk fortifier may also contain traditional pharmaceutical additives and excipients, excipients and diluents, including, without limitation, water, gelatin of any origin, vegetable gums, lignin sulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers , emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.

Human milk fortifier compositions in liquid form have a number of distinct advantages. For example, liquid formulations may be more convenient when combined with packaging that dispenses calibrated droplets of a specific weight or volume. In some embodiments, liquid human milk fortifier compositions may be packaged in unit doses so that calibrated drops of a defined mass or volume can be administered while avoiding contamination of the remaining liquid due to handling and subsequent use.

In addition, liquid formulations are easier to mix with compositions to be fortified, while powder may in some cases form lumps.

In another embodiment, the milk fortifier according to the present invention may be administered as a separate composition.

Additionally, the supplement may contain an organic or inorganic carrier material suitable for enteral or parenteral administration, as well as vitamins, minerals, trace elements and other micronutrients in accordance with the recommendations of government authorities, such as European Commission Directive 2006/141 / EC of December 22 2006 on infant formula and complementary formula.

In one embodiment, the human milk fortifier of the present invention contains one of the nutrients described below, or combinations thereof.

In another embodiment, the human milk fortifier of the present invention consists of one of the nutrients described below, or combinations thereof.

Minerals

In one aspect, the present invention relates to a human milk fortifier composition containing at least one mineral delivery ingredient, in particular certain amounts of copper, selenium and/or zinc.

Copper

In one embodiment, a human milk fortifier composition is provided that contains at least one copper delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides copper in an amount in the range of 5 to 30 μg/100 ml, preferably 8 to 28 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing copper in an amount in the range of 5 to 30 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In Another Embodiment, Fortifier Composition In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that are capable of providing copper in an amount in the range of 1.25 to 7.50 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing copper in an amount in the range of 1 to 6 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide copper in an amount in the range of 79 to 253 micrograms, or 87 to 238 micrograms, or 107 to 202 micrograms.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, the ingredients capable of providing copper are selected from the group consisting of copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, and mixtures thereof. .

As one of skill in the art will appreciate, different ingredients can provide varying amounts of copper in the composition of the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of copper based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide copper in the composition in an amount in the range of 5 to 30 micrograms, copper sulfate in an amount in the range of 13 to 75 micrograms can be used.

Selenium

In one embodiment, a human milk fortifier composition is provided that contains at least one selenium delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides selenium in an amount in the range of 0.1 to 10 μg/100 ml, preferably 0.3 to 8 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing selenium in an amount in the range of 0.1 to 10 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing selenium in an amount in the range of 0.0025 to 0.25 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing selenium in an amount in the range of 0.002 to 0.2 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing selenium in an amount in the range of 1 to 7 micrograms, or 2 to 6 micrograms, or 2 to 5 micrograms.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing selenium are selected from the group consisting of sodium selenite, sodium selenate, sodium hydroselenite, and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of selenium in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of selenium based on the supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide selenium in the composition in an amount ranging from 0.1 to 10 micrograms, sodium selenate can be used in an amount ranging from 0.2 to 24 micrograms.

Zinc

In one embodiment, a human milk fortifier composition is provided that contains zinc delivery ingredients.

In one embodiment, the fortifier composition of the present invention provides zinc in an amount in the range of 50 to 550 μg/100 ml, preferably 100 to 500 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing zinc in an amount in the range of 50 to 550 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing zinc in an amount in the range of 12.5 to 137.5 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing zinc in an amount in the range of 10 to 110 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing zinc in an amount in the range of 50 to 550 micrograms, preferably 100 to 500 micrograms.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing zinc in an amount in the range of 1220 to 3880 micrograms, or 1340 to 3640 micrograms, or 1640 to 3090 micrograms.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing zinc are selected from the group consisting of zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate, and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of zinc in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of zinc based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide copper in the composition in an amount ranging from 50 to 550 micrograms, zinc sulfate can be used in an amount ranging from 123 to 1358 micrograms.

Squirrels

In another aspect, the invention relates to a human milk fortifier composition containing at least one protein delivery ingredient, in particular alpha-lactalbumin, caseins and/or lactoferrin.

Alpha lactalbumin

In one embodiment, a human milk fortifier composition is provided that contains ingredients to deliver appropriate amounts of alpha-lactalbumin.

In one embodiment, the fortifier composition of the present invention provides alpha-lactalbumin in an amount in the range of 25 to 180 mg/100 ml, preferably 30 to 150 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-lactalbumin in an amount ranging from 25 to 180 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-lactalbumin in an amount in the range of 6.25 to 45 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-lactalbumin in an amount in the range of 5 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing alpha-lactalbumin in an amount in the range of 25 to 180 mg, preferably 30 to 150 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing alpha-lactalbumin in an amount ranging from 0.4 to 1.31, or 0.45 to 1.23 g, or 0.55 to 1 .05

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing alpha-lactalbumin are selected from the group consisting of: milk (e.g., whole or skimmed milk powder), whey protein (e.g., isolates or concentrates), any other source of milk powder, and mixtures thereof.

In one further embodiment, ingredients capable of providing alpha-lactalbumin are selected from the group consisting of skimmed milk (such as, for example, skimmed cow's milk powder), whey protein (such as, for example, whey protein powder), milk powder (such as, for example, milk protein isolate) and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of alpha-lactalbumin in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of alpha-lactalbumin based on the supplier's specifications for the particular ingredient would be routine work for one of skill in the art.

For example, to provide alpha-lactalbumin in the composition in an amount in the range of 25 to 180 mg, whey protein powder in an amount in the range of 116 to 835 mg can be used.

Caseins

In one embodiment, a human milk fortifier composition is provided that contains at least one casein delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides caseins in an amount in the range of 01 to 500 mg/100 ml, preferably 20 to 400 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing caseins in an amount in the range of 10 to 500 mg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing caseins in an amount ranging from 2.5 to 125 mg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing caseins in an amount ranging from 2 to 100 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing caseins in an amount in the range of 01 to 500 mg, preferably 20 to 400 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing caseins in an amount ranging from 0.82 to 2.60 g, or from 0.90 to 2.44 g, or from 1.10 to 2. 07

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing caseins are selected from the group consisting of: milk (e.g., whole or skimmed milk powder), whey protein (e.g., isolates or concentrates), any other source of milk powder, and mixtures thereof.

In one further embodiment, the ingredients that are capable of providing caseins are selected from the group consisting of: fresh whole or skimmed milk, skimmed milk (such as, for example, skimmed cow's milk powder), whole milk (such as, for example, cow's whole milk powder). milk), whey protein (such as, for example, whey protein powder), powdered milk (such as, for example, milk protein isolate), cream (such as, for example, pasteurized cream), buttermilk (such as, for example, milk powder). buttermilk), caseinates (such as, for example, calcium, potassium and/or sodium caseinate), acid casein and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide different amounts of caseins in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of caseins based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

For example, to provide alpha-casein in the composition in an amount in the range of 1 to 500 mg, skimmed milk powder in an amount in the range of 4 to 1779 mg can be used.

lactoferrin

In one embodiment, a human milk fortifier composition is provided that contains at least one lactoferrin delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides lactoferrin in an amount in the range of 10 to 500 mg/100 ml, preferably 20 to 400 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing lactoferrin in an amount in the range of 10 to 500 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing lactoferrin in an amount ranging from 2.5 to 125 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing lactoferrin in an amount in the range of 10 to 500 mg, preferably 20 to 400 mg.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing lactoferrin in an amount in the range of 2 to 100 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing lactoferrin in an amount ranging from 0.50 to 1.58 g, or from 0.55 to 1.58 g, or from 0.67 to 1, 26

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Lactoferrin can be purified from milk or obtained recombinantly. Human colostrum has the highest concentration of lactoferrin, followed by milk and then cow's milk.

In one embodiment, ingredients capable of providing lactoferrin are commercially available and are selected from the group consisting of: purified or synthesized lactoferrin, whey protein isolate, whey protein concentrate, and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide different amounts of caseins in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of caseins based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

For example, to provide lactoferrin in a composition in an amount ranging from 10 to 500 mg, a whey protein isolate (e.g., Vitalarmor® GF-100 whey protein isolate containing 47% lactoferrin) can be used in an amount ranging from 21 to 1065 mg.

Alternative sources of amino acids

The amounts of alpha-lactalbumin, caseins and/or lactoferrin, which according to the authors of the present invention are absent in the analyzed milk obtained from preterm infants, are ultimately responsible for the intake of less certain amino acids in such milk obtained from preterm infants, compared with mother's milk, received by term infants of the same postmenstrual age.

Accordingly, as will be appreciated by one of skill in the art, the human milk fortifier of the present invention may, in one embodiment, contain alternative ingredients capable of delivering such amino acids in the desired amount.

Such ingredients may be selected from the group consisting of: milk proteins (e.g. derived from cow, goat and/or donkey milk, etc.), vegetable proteins (e.g. soy), hydrolysates derived from milk and/or vegetable proteins, peptides, free amino acids and mixtures thereof.

In one additional embodiment of the present invention, the breast milk fortifier may include a mixture of ingredients capable of delivering the missing amino acids in the required amounts; moreover, such a mixture contains at least two ingredients selected from the group consisting of alpha-lactalbumin, caseins, lactoferrin, milk proteins (for example, obtained from cow, goat and/or donkey milk, etc.), vegetable proteins (for example , soy), hydrolysates derived from milk and/or vegetable proteins, peptides, free amino acids and mixtures thereof.

In one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient that delivers human milk oligosaccharides, in particular certain amounts of difucosyllacto-N-hexaose-a (DFSLTNH), monofucosyllacto-N-hexaose-III (FSLTNH3 ), 6'-galactosyl lactose (GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL) and/or sialyl lacto-N-tetraose-c (LSTc or SLTNTC); at least one ingredient that provides the delivery of minerals, in particular, certain amounts of copper, selenium and/or zinc; at least one ingredient that provides delivery of amino acids, in particular, certain amounts of alpha-lactalbumin, caseins, lactoferrin, milk proteins (for example, obtained from cow, goat and/or donkey milk, etc.), vegetable proteins (for example, soy), hydrolysates derived from milk and/or vegetable proteins, peptides, free amino acids and mixtures thereof; and at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

It should be understood that all specific embodiments and combinations of nutrients described in the context of the present invention with reference to ingredients providing proteins (alpha-lactalbumin, caseins and/or lactoferrin), mutatis mutandis, will refer to the embodiments described below, where ingredients providing certain amino acids are used as alternative sources of starting compounds for protein synthesis.

In one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient that delivers human milk oligosaccharides, in particular certain amounts of difucosyllacto-N-hexaose-a (DFSLTNH), monofucosyllacto-N-hexaose-III (FSLTNH3 ), 6'-galactosyl lactose (GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL) and/or sialyl lacto-N-tetraose-c (LSTc or SLTNTC); at least one ingredient that provides the delivery of minerals, in particular, certain amounts of copper, selenium and/or zinc; at least one ingredient providing delivery of amino acids, in particular certain amounts of Glu (glutamic acid), ingredients providing Pro (proline); ingredients providing His (histidine); ingredients providing Ile (isoleucine); ingredients providing Leu (leucine); ingredients providing Lys (lysine); ingredients providing Met (methionine); and ingredients providing Trp (tryptophan); or mixtures thereof; and at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

In one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient that delivers human milk oligosaccharides, in particular certain amounts of difucosyllacto-N-hexaose-a (DFSLTNH), monofucosyllacto-N-hexaose-III (FSLTNH3 ), 6'-galactosyl lactose (GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL) and/or sialyl lacto-N-tetraose-c (LSTc or SLTNTC); at least one mineral delivery ingredient, in particular certain amounts of copper, selenium and/or zinc; at least one amino acid delivery ingredient, in particular certain amounts of isoleucine (Ile) providing ingredients; leucine providing ingredients (Leu), methionine providing ingredients (Met); and proline providing ingredients (Pro); or mixtures thereof; and at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

In one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient that delivers human milk oligosaccharides, in particular certain amounts of difucosyllacto-N-hexaose-a (DFSLTNH), monofucosyllacto-N-hexaose-III (FSLTNH3 ), 6'-galactosyl lactose (GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL) and/or sialyl lacto-N-tetraose-c (LSTc or SLTNTC); at least one mineral delivery ingredient, in particular certain amounts of copper, selenium and/or zinc; at least one ingredient providing delivery of amino acids, in particular certain amounts of essential amino acids, i.e. histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), threonine (Thr), tryptophan (Trp) and valine (Val) or mixtures thereof; and at least one vitamin delivery ingredient, in particular certain amounts of total tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

Based on the experiments carried out by the inventors of the present invention, the results of which are shown in FIG. 4, in one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient selected from the group consisting of isoleucine (Ile) providing ingredients; leucine providing ingredients (Leu); ingredients providing methionine (Met); and proline providing ingredients (Pro).

In another embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient selected from the group consisting of Glu (glutamic acid) providing ingredients; ingredients providing Pro (proline); ingredients providing His (histidine); ingredients providing Ile (isoleucine); ingredients providing Leu (leucine); ingredients providing Lys (lysine); ingredients providing Met (methionine); and Trp (tryptophan) providing ingredients.

In another embodiment, the present invention provides a human milk fortifier composition comprising ingredients providing essential amino acids, i.e. histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe ), threonine (Thr), tryptophan (Trp), and valine (Val).

Glutamic acid

In one embodiment, a human milk fortifier composition is provided that contains at least one glutamic acid delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides glutamic acid in an amount in the range of 5 to 100 mg/100 ml, such as 10 to 90 mg/100 ml, such as 30 to 80 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing glutamic acid in an amount in the range of 5 to 100 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing glutamic acid in an amount in the range of 1.25 to 25 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing glutamic acid in an amount in the range of 1 to 20 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing glutamic acid in an amount in the range of 170 to 560 mg, or 190 to 520 mg, or 230 to 440 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing glutamic acid are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of glutamic acid in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of glutamic acid based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Proline

In one embodiment, a human milk fortifier composition is provided that contains at least one proline delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides proline in an amount in the range of 5 to 60 mg/100 ml, such as 10 to 50 mg/100 ml, such as 15 to 40 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing proline in an amount in the range of 5 to 60 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing proline in an amount in the range of 1.25 to 15 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing proline in an amount in the range of 1 to 12 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing proline in an amount in the range of 105 to 350 mg, or 118 to 325 mg, or 140 to 275 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing proline are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of proline in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of proline based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Histidine

In one embodiment, a human milk fortifier composition is provided that contains at least one histidine delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides histidine in an amount in the range of 1 to 30 mg/100 ml, such as 2 to 25 mg/100 ml, such as 3 to 20 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing histidine in an amount in the range of 1 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing histidine in an amount in the range of 0.25 to 7.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing histidine in an amount in the range of 0.2 to 6 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing histidine in an amount in the range of 30 to 120 mg, or 35 to 105 mg, or 45 to 90 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing histidine are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of histidine in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of histidine based on the supplier's specifications for the specific ingredient would be routine work for one of skill in the art.

Isoleucine

In one embodiment, a human milk fortifier composition is provided that contains at least one isoleucine delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides isoleucine in an amount ranging from 1 to 30 mg/100 ml, such as 2 to 25 mg/100 ml, such as 3 to 20 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing isoleucine in an amount in the range of 1 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing isoleucine in an amount in the range of 0.25 to 7.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing isoleucine in an amount in the range of 0.2 to 6 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing isoleucine in an amount in the range of 60 to 200 mg, or 65 to 190 mg, or 80 to 160 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing isoleucine are commercially available.

As one of skill in the art will appreciate, different ingredients can provide different amounts of isoleucine in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of isoleucine based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Leucine

In one embodiment, a human milk fortifier composition is provided that contains at least one leucine delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides leucine in an amount in the range of 1 to 100 mg/100 ml, such as 5 to 80 mg/100 ml, such as 10 to 70 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing leucine in an amount in the range of 1 to 100 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing leucine in an amount in the range of 0.25 to 25 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing leucine in an amount in the range of 0.2 to 20 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide leucine in an amount in the range of 130 to 420 mg, or 140 to 400 mg, or 170 to 335 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing leucine are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of leucine in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of leucine based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Lysine

In one embodiment, a human milk fortifier composition is provided that contains at least one lysine delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides lysine in the range of 1 to 60 mg/100 ml, such as 5 to 50 mg/100 ml, such as 10 to 40 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing lysine in an amount in the range of 5 to 50 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing lysine in an amount in the range of 1.25 to 12.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing lysine in an amount in the range of 1 to 10 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing lysine in an amount in the range of 85 to 290 mg, or 90 to 270 mg, or 115 to 230 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing lysine are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of lysine in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of lysine based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Methionine

In one embodiment, a human milk fortifier composition is provided that contains at least one methionine delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides methionine in an amount in the range of 0.1 to 20 mg/100 ml, such as 0.5 to 15 mg/100 ml, such as 1 to 10 mg/100 ml, enriched breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing methionine in an amount in the range of 0.5 to 15 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing methionine in an amount in the range of 0.125 to 3.75 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing methionine in an amount in the range of 0.1 to 3 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing methionine in an amount in the range of 15 to 65 mg, or 20 to 60 mg, or 25 to 50 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing methionine are commercially available.

As one of skill in the art will appreciate, different ingredients can provide different amounts of methionine in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of methionine based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

Tryptophan

In one embodiment, a human milk fortifier composition is provided that contains at least one tryptophan delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides tryptophan in an amount in the range of 0.5 to 30 mg/100 ml, such as 1 to 25 mg/100 ml, such as 2 to 20 mg/100 ml, enriched human breast milk. milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing tryptophan in an amount in the range of 0.5 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing tryptophan in an amount in the range of 0.125 to 7.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing tryptophan in an amount in the range of 0.1 to 6 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide tryptophan in an amount in the range of 30 to 100 mg, or 32 to 95 mg, or 40 to 80 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing tryptophan are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of tryptophan in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of tryptophan based on the supplier's specifications for a particular ingredient would be routine work for one of skill in the art.

Essential amino acids

In one embodiment, a human milk fortifier composition is provided that contains ingredients to deliver essential amino acids. In one embodiment, the human milk fortifier composition of the present invention contains isoleucine (Ile), leucine (Leu), methionine (Met) delivery ingredients.

In one embodiment, the human milk fortifier composition of the present invention contains ingredients to deliver histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), threonine (Thr), tryptophan (Trp) and valine (Val).

In one embodiment, the fortifier composition of the present invention provides essential amino acids in an amount in the range of 10 to 600 mg/100 ml, such as 50 to 500 mg/100 ml, such as 80 to 350 mg/100 ml, of fortified human breast milk. .

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing essential amino acids in an amount in the range of 10 to 600 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing essential amino acids in an amount ranging from 2.5 to 150 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing essential amino acids in an amount ranging from 2 to 120 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing essential amino acids in an amount in the range of 700 to 2300 mg, or 750 to 2200 mg, or 950 to 1850 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing essential amino acids are commercially available.

As one of skill in the art will appreciate, different ingredients can provide different amounts of essential amino acids in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of essential amino acids based on the supplier's specifications for a particular ingredient would be routine work for one skilled in the art.

vitamins

In yet another aspect, the invention relates to a human milk fortifier composition containing ingredients to ensure the delivery of appropriate amounts of vitamins, in particular tocopherol (alpha and/or gamma tocopherol), retinol and/or nicotinic acid.

total tocopherol

In one embodiment, a human milk fortifier composition is provided that contains at least one total tocopherol delivery ingredient.

Total tocopherol includes alpha-tocopherol, gamma-tocopherol, or mixtures thereof.

In one embodiment, the fortifier composition of the present invention provides total tocopherol in an amount in the range of 5 to 1800 μg/100 ml, preferably 10 to 1700 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing total tocopherol in an amount in the range of 5 to 1800 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing total tocopherol in an amount in the range of 1.25 to 450 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing total tocopherol in an amount in the range of 1 to 360 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing total tocopherol in an amount in the range of 5 to 1800 micrograms, preferably 10 to 1700 micrograms.

In one embodiment, ingredients capable of providing total tocopherol are selected from the group consisting of: D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate; conjugate of DL-alpha-tocopheryl succinate with polyethylene glycol-1000; and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide different amounts of total tocopherol in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of total tocopherol based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

Alpha tocopherol

In one embodiment, a human milk fortifier composition is provided that contains at least one alpha-tocopherol delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides alpha-tocopherol in an amount in the range of 5 to 1800 µg/100 ml, preferably 10 to 1700 µg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-tocopherol in an amount ranging from 1.25 to 450 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing alpha-tocopherol in an amount ranging from 1 to 360 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing alpha-tocopherol in an amount ranging from 5 to 1800 micrograms, preferably from 10 to 1700 micrograms.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing alpha-tocopherol in an amount ranging from 2.39 to 7.60 mg, or from 2.64 to 7.13 mg, or from 3.21 to 6.06 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, the ingredients capable of providing alpha tocopherol are selected from the group consisting of: D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, conjugate DL-alpha-tocopheryl succinate with polyethylene glycol-1000 and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of alpha-tocopherol in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of alpha-tocopherol based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide alpha-tocopherol in the composition in an amount ranging from 5 to 1800 µg, DL-alpha-tocopheryl acetate can be used in an amount ranging from 7 to 2682 µg.

Gamma tocopherol

In one embodiment, a human milk fortifier composition is provided that contains at least one gamma-tocopherol delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides gamma-tocopherol in an amount in the range of 0.1 to 50 μg/100 ml, preferably 0.2 to 40 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing gamma-tocopherol in an amount in the range of 0.1 to 50 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing gamma-tocopherol in an amount in the range of 0.025 to 12.5 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing gamma-tocopherol in an amount in the range of 0.02 to 10 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing 0.1 to 50 micrograms, preferably 0.2 to 40 micrograms of gamma-tocopherol.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing gamma-tocopherol in an amount ranging from 0.04 to 0.13 mg, or from 0.05 to 0.13 mg, or from 0.06 to 0.11 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of gamma tocopherol in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of gamma tocopherol based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide gamma-tocopherol in the composition in an amount ranging from 0.02 to 10 µg, antioxidants can be used in an amount ranging from 0.071 to 36 µg.

A nicotinic acid

In one embodiment, a human milk fortifier composition is provided that contains at least one nicotinic acid delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides nicotinic acid in an amount in the range of 0.5 to 18 μg/100 ml, preferably 1 to 15 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing nicotinic acid in an amount in the range of 0.5 to 18 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing nicotinic acid in an amount in the range of 0.125 to 4.5 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing nicotinic acid in an amount in the range of 0.1 to 3.6 μg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing nicotinic acid in an amount ranging from 0.5 to 18 micrograms, preferably from 1 to 15 micrograms.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide nicotinic acid in an amount ranging from 2.44 to 7.74 micrograms, or from 2.68 to 7.26 micrograms, or from 3.27 to 6 .17 mcg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing nicotinic acid are selected from the group consisting of: nicotinic acid, nicotinamide, and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of nicotinic acid in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of nicotinic acid based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide nicotinic acid in the composition in an amount in the range of 0.5 to 18 µg, nicotinamide in an amount in the range of 0.5 to 18 µg can be used.

Retinol (Vitamin A)

In one embodiment, a human milk fortifier composition is provided that contains at least one retinol delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides retinol in an amount in the range of 1 to 250 μg/100 ml, preferably 5 to 200 μg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing retinol in an amount in the range of 1 to 250 µg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing retinol in an amount in the range of 0.25 to 62.5 µg/g of fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing retinol in an amount in the range of 0.2 to 50 μg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing retinol in an amount in the range of 1 to 250 micrograms, preferably 5 to 200 micrograms.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing retinol in an amount ranging from 0.24 to 0.75 mg, or from 0.26 to 0.70 mg, or from 0.32 to 0. 60 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

In one embodiment, ingredients capable of providing retinol are selected from the group consisting of: retinol, retinyl acetate, retinyl palmitate, and mixtures thereof.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of retinol in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of retinol based on the specification provided by the supplier for a particular ingredient would be routine work for one skilled in the art.

For example, to provide vitamin A (retinol) in the composition in an amount ranging from 1 to 250 µg, retinyl acetate can be used in an amount ranging from 1 to 295 µg.

breast milk oligosaccharides

In one embodiment, a human milk fortifier composition is provided that contains at least one ingredient that delivers human milk oligosaccharides, specifically difucosyl lacto-N-hexaose-a (DFSLTNH or DFLNHa), monofucosyl lacto-N-hexaose-III (MFLNH- III or FSLTNH3), 6'-galactosyl lactose (6'-GL or GSLT6), lacto-N-neotetraose (LnNT), lacto-N-tetraose (LNT), 6'-sialyllactose (6'-SL), or sialyl lactose N-tetraose-c (sialyllacto-N-tetraose-c or LSTc or SLTNTC) or mixtures thereof.

In all descriptions, the following abbreviations can be used to identify the structures of oligosaccharides given in the table below:

Abbreviation(s) Name (structure)

6'-GL or GSLT6 6'-galactosyl lactose (β-D-Gal-(1→6)-β-D-Gal-(1→4)-D-Glc) 6'-SL 6'-sialyllactose (α-Neu5Ac-(1→6)-β-D-Gal-(1→4)-D-Glc) LNT Lacto-N-tetraose (β-D-Gal-(1→3)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-D-Glc) LNnT or LnNT Lacto-N-neotetraose (β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-D-Glc) LSTc or SLTNTC Siallylacto-N-tetraose-c or siallylacto-N-tetraose-c
(α-Neu5Ac-(1→6)-β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-D-Glc ) MFLNH-III or FSLTNH3 Monofucosyllacto-N-hexaose-III
(β-D-Gal(1→4)-[α-L-Fuc(1→3)-]-β-D-GlcNAc(1→6)-[β-D-Gal-(1→3)- β-D-GlcNAc-(1→3)-]-β-D-Gal-(1→4)-D-Glc) DFLNHa or DFSLTNH Difucosyllacto-N-hexaose-a
(α-L-Fuc-(1→2)-β-D-Gal-(1→3)-β-D-GlcNAc-(1→3)-[β-D-Gal(1→4)-β -D-[α-L-Fuc(1→3)-]GlcNAc(1→6)-]-β-D-Gal-(1→4)-D-Glc)

Difucosyllacto-N-hexaose-a (DFSLTNH)

In one embodiment, a human milk fortifier composition is provided that contains at least one DFSLTNH delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides DFSLTNH in an amount in the range of 5 to 25 mg/100 ml, preferably 8 to 15 mg/100 ml, of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing DFSLTNH in an amount ranging from 5 to 25, such as 8 to 15 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing DFSLTNH in an amount ranging from 1.25 to 6.25, such as 2 to 3.75 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing DFSLTNH in an amount ranging from 1 to 5, eg 1.6 to 3 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing DFSLTNH in an amount in the range of 5 to 25 mg, preferably 8 to 15 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide DFSLTNH in an amount in the range of 40 to 128 mg, or 44 to 120 mg, or 54 to 102 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing DFSLTHN are commercially available (eg DFSLTHN or DFLNHa: CAS: 64396-27-6, supplied by Carbosynth in 90% purity).

As one of skill in the art will appreciate, different ingredients can provide varying amounts of DFSLTNH in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of DFSLTNH based on the supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide DFLNHa in the composition in an amount in the range of 5 to 25 mg, a DFLNHa ingredient containing 90% DFLNHa in an amount in the range of 5.56 to 27.8 mg can be used.

Monofucosyllacto-N-hexaose-III (FSLTNH3 or MFLNH-III)

In one embodiment, a human milk fortifier composition is provided that contains at least one FSLTNH3 delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides FSLTNH3 in an amount in the range of 0.5 to 35 mg/100 ml, preferably 5 to 20 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing FSLTNH3 in an amount ranging from 0.5 to 35, such as 5 to 10 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing FSLTNH3 in an amount in the range of 0.125 to 8.75, such as 1.25 to 5 mg/g, of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing FSLTNH3 in an amount in the range of 0.1 to 7, such as 1 to 4 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing FSLTNH3 in an amount in the range of 0.5 to 35 mg, preferably 5 to 20 mg.

In one embodiment, the liquid human fortifier of the present invention contains ingredients providing FSLTNH3 in an amount in the range of 45 to 145 mg, or 50 to 135 mg, or 61 to 115 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing FSLTNH3 are commercially available (eg MFLNH-III is supplied by Dextra).

As one of skill in the art will appreciate, different ingredients can provide varying amounts of FSLTNH3 in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of FSLTNH3 based on the supplier's specific ingredient specification would be routine work for one skilled in the art.

For example, to provide MFLNH-III in the composition in an amount ranging from 0.5 to 35 mg, an MFLNH-III ingredient containing 90% MFLNH-III can be used in an amount ranging from 0.56 to 38 .9 mg.

6'-Galactosyl lactose (GSLT6)

In one embodiment, a human milk fortifier composition is provided that contains at least one GSLT6 delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides GSLT6 in an amount in the range of 0.1 to 10 mg/100 ml, preferably 1 to 5 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing GSLT6 in an amount ranging from 0.1 to 10, such as 1 to 5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing GSLT6 in an amount ranging from 0.025 to 2.50, such as 0.25 to 2.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing GSLT6 in an amount in the range of 0.02 to 2, such as 0.2 to 1 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing GSLT6 in an amount in the range of 0.1 to 10 mg, preferably 1 to 5 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide GSLT6 in an amount in the range of 21 to 68 mg, or 23 to 64 mg, or 28 to 54 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing GSLT6 are commercially available (eg Vivinal GOS or Clasado GOS).

As one of skill in the art will appreciate, different ingredients can provide varying amounts of GSLT6 in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of 6'GL based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide 6'GL in the composition in an amount in the range of 0.1 to 10 mg, a trans-galactooligosaccharide (GOS) ingredient containing 12 g/100 g of 6'GL in an amount in the range from 0.83 to 83 mg.

Lacto-N-neotetraose (LnNT or LNnT)

In one embodiment, a human milk fortifier composition is provided that contains at least one LNnT delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides LnNT in an amount in the range of 0.1 to 25 mg/100 ml, preferably 1 to 10 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing LnNT in an amount ranging from 0.1 to 25, such as 1 to 10 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing LnNT in an amount ranging from 0.025 to 6.25, such as 0.25 to 2.5 mg/g, of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing LnNT in an amount ranging from 0.02 to 5, eg 0.2 to 22 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing LnNT in an amount in the range of 0.1 to 25 mg, preferably 1 to 10 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide LnNT in an amount in the range of 47 to 151 mg, or 52 to 142 mg, or 64 to 120 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing LnNT are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of LNnT in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of LNnT based on the specification of the particular ingredient supplied by the supplier would be routine work for one skilled in the art.

For example, to provide LnNT in the composition in an amount in the range of 0.1 to 25 mg, an LnNT ingredient containing 90% LnNT in an amount in the range of 0.11 to 27.8 mg can be used.

Lacto-N-tetraose (LNT)

In one embodiment, a human milk fortifier composition is provided that contains at least one LNT delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides LNT in an amount in the range of 0.5 to 55 mg/100 ml, preferably 5 to 30 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing LNT in an amount ranging from 0.5 to 55, such as 5 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing LNT in an amount ranging from 0.125 to 13.75, such as 1.25 to 7.5 mg/g, of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing LNT in an amount ranging from 0.1 to 11, eg 1 to 6 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing LNT in an amount in the range of 0.5 to 55 mg, preferably 5 to 30 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide LNT in an amount in the range of 87 to 279 mg, or 96 to 262 mg, or 118 to 222 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing LNT consumption are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of LNT in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide a claimed amount of LNT based on a supplier's specification for a particular ingredient would be routine work for one skilled in the art.

For example, to provide lacto-N-tetraose (LNT) in the composition in an amount ranging from 0.5 to 55 mg, a lacto-N-tetraose ingredient containing 95% LNT can be used in an amount ranging from 0.53 to 57.9 mg.

6'-Sialyl lactose (6'-SL)

In one embodiment, a human milk fortifier composition is provided that contains at least one 6'-SL delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides 6'-SL in an amount in the range of 5 to 355 mg/100 ml, preferably 15 to 35 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing 6'-SL in an amount ranging from 5 to 55, such as 15 to 35 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing 6'-SL in an amount ranging from 1.25 to 13.75, such as 3.75 to 8.75 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing 6'-SL in an amount ranging from 1 to 11, eg 3 to 7 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing 6'-SL in an amount ranging from 5 to 355 mg, preferably 15 to 35 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients providing 6'-SL in an amount ranging from 132 to 421 mg, or from 146 to 395 mg, or from 178 to 336 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing 6'-SL are commercially available.

As one of skill in the art will appreciate, different ingredients can provide varying amounts of 6'-SL in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of 6'-SL based on the supplier's specification for a particular ingredient would be routine work for one of skill in the art.

For example, to provide 6'-SL in the composition in an amount ranging from 5 to 355 mg, 6'-O-sialyllactose sodium can be used in an amount ranging from 5.2 to 367.3 mg.

Sialyl lacto-N-tetraose-c (SLTNTC or LSTc)

In one embodiment, a human milk fortifier composition is provided that contains at least one SLTNTC delivery ingredient.

In one embodiment, the fortifier composition of the present invention provides SLTNTC in an amount in the range of 1 to 60 mg/100 ml, preferably 1 to 30 mg/100 ml of fortified breast milk.

In one embodiment, the human milk fortifier composition contains ingredients that are capable of providing SLTNTC in an amount ranging from 1 to 60, eg 1 to 30 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 1 g per 100 ml of fortified breast milk.

In another embodiment, the human milk fortifier composition contains ingredients that are capable of providing SLTNTC in an amount in the range of 0.25 to 15, such as 2.5 to 7.5 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 4 g per 100 ml of fortified breast milk.

In yet another embodiment, the human milk fortifier composition contains ingredients that are capable of providing SLTNTC in an amount ranging from 0.2 to 12, eg 2 to 6 mg/g of the fortifier. In this embodiment, the recommended single dose of the fortifier is 5 g per 100 ml of fortified breast milk.

In one embodiment, the liquid human milk fortifier composition contains ingredients that are capable of providing SLTNTC in an amount in the range of 1 to 60 mg, preferably 1 to 30 mg.

In one embodiment, the liquid human milk fortifier of the present invention contains ingredients that provide SLTNTC in an amount in the range of 139 to 443 mg, or 153 to 415 mg, or 187 to 353 mg.

In such an embodiment, the liquid human milk fortifier may be administered as a separate formulation and the amount of nutrient is divided into 1, 2, 3, 4, 5, or 6 single doses per day. For example, the amount of a nutrient may be divided into 1, 3, or 6 single doses per day.

Ingredients capable of providing SLTNTC are commercially available.

As will be appreciated by one of skill in the art, different ingredients may provide varying amounts of SLTNTC in a composition according to the present invention, depending on the nature and amount of the ingredient used. However, calculating the amount of ingredient needed to provide the claimed amount of SLTNTC based on the specification of the particular ingredient provided by the supplier would be routine work for one skilled in the art.

For example, to provide LSTc intake in the composition in an amount in the range of 1 to 60 mg, the sodium salt of LSTc in an amount in the range of 1.02 to 61.3 mg can be used.

Specific Embodiments

In one embodiment, the present invention provides a human milk fortifier composition comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper, such as copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

zinc providing ingredients, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin, for example milk (eg whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing casein, for example milk (eg whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- lactoferrin providing ingredients, eg purified or synthesized lactoferrin, whey protein isolate, whey protein concentrate or mixtures thereof;

- ingredients providing alpha tocopherol, such as D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000 or their mixtures;

- ingredients providing gamma-tocopherol;

- ingredients providing nicotinic acid, for example nicotinic acid, nicotinamide or mixtures thereof;

retinol providing ingredients, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof;

- ingredients providing DFSLTHN, eg difucosyllacto-N-hexaose-a;

- FSLTNH3 providing ingredients, eg monofucosyllacto-N-hexaose-III;

- GSLT6 providing ingredients, eg 6'-galactosyl lactose;

- LnNT-providing ingredients, such as lacto-N-neotetraose;

- ingredients that provide LNT, such as lacto-N-tetraose;

- 6'-SL providing ingredients, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And

- ingredients providing SLTNTC, for example sialyllacto-N-tetraose-c;

or their mixtures.

In another embodiment, the present invention provides a breast milk fortifier comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 5 to 30 µg/g, or from 1.5 to 7.50 µg/g, or from 1 to 6 µg/g fortifier, e.g. copper (II) carbonate, citrate copper (II), copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 0.1 to 10 µg/g, or from 0.0025 to 25 µg/g, or from 0.002 to 0.2 µg/g of fortifier, e.g. sodium selenite, sodium selenate , sodium hydroselenite or mixtures thereof;

- ingredients providing zinc in an amount ranging from 50 to 550 µg/g, or from 12.5 to 137.5 µg/g, or from 10 to 110 µg/g fortifier, e.g. zinc acetate, zinc chloride, citrate zinc, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 25 to 180 mg/g, or from 6.25 to 45 mg/g, or from 5 to 30 mg/g of a fortifier, e.g. milk (e.g. whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of a fortifier, e.g. milk (e.g. whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier, e.g. purified or synthesized lactoferrin, whey protein isolate , whey protein concentrate or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/g, or from 1.25 to 450 µg/g, or from 1 to 360 µg/g of fortifier, for example D-alpha-tocopherol, DL -alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.1 to 50 µg/g, or from 0.025 to 12.5 µg/g, or from 0.02 to 10 µg/g of fortifier;

- ingredients providing nicotinic acid in an amount ranging from 0.5 to 18 µg/g, or from 0.25 to 4.25 µg/g, or from 0.1 to 3.6 µg/g of fortifier, for example nicotinic acid, nicotinamide or mixtures thereof;

- ingredients providing retinol in an amount ranging from 1 to 250 µg/g, or from 0.25 to 62.5 µg/g, or from 0.2 to 50 µg/g of fortifier, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof;

- ingredients providing DFSLTHN in an amount ranging from 5 to 25 mg/g, or from 1.25 to 6.25 mg/g, or from 1 to 5 mg/g of an enricher, such as difucosyllacto-N-hexaose-a ;

- ingredients providing FSLTNH3 in an amount ranging from 0.5 to 35 mg/g, or from 0.125 to 8.75 mg/g, or from 0.1 to 7 mg/g of an enricher, such as monofucosyllacto-N-hexaose -III;

- ingredients providing GSLT6 in an amount ranging from 0.1 to 10 mg/g, or from 0.025 to 2.5 mg/g, or from 0.02 to 2 mg/g of an enricher, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/g, or from 0.025 to 6.25 mg/g, or from 0.02 to 5 mg/g of an enricher, such as lacto-N-neotetraose ;

- ingredients providing LNT in an amount ranging from 0.5 to 55 mg/g, or from 0.125 to 13.75 mg/g, or from 0.1 to 11 mg/g of a fortifier, such as lacto-N-tetraose ;

- ingredients providing 6'-SL in an amount ranging from 5 to 55 mg/g, or from 1.25 to 13.75 mg/g, or from 1 to 11 mg/g of an enricher, for example 6'-sialyllactose or sodium salt of 6'-sialyllactose; And

- ingredients providing SLTNTC in an amount ranging from 1 to 60 mg/g, or from 0.25 to 15 mg/g, or from 0.2 to 12 mg/g of an enricher, for example sialyllacto-N-tetraose-c ;

or their mixtures.

In one embodiment, a breast milk fortifier composition is provided comprising:

- ingredients providing zinc in an amount in the range of 50 to 550 µg/g, or 12.5 to 137.5 µg/g, or 10 to 110 µg/g fortifier, e.g. zinc acetate, zinc chloride, citrate zinc, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate, or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 25 to 180 mg/g, or from 6.25 to 45 mg/g, or from 5 to 30 mg/g of a fortifier, e.g. milk (e.g. whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk source or mixtures thereof;

- ingredients providing caseins in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g fortifier, for example milk (for example, whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/g, or from 1.25 to 450 µg/g, or from 1 to 360 µg/g fortifier, e.g. D-alpha-tocopherol, DL -alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000, or mixtures thereof;

- ingredients providing LNT in an amount ranging from 0.5 to 55 mg/g, or from 0.125 to 13.75 mg/g, or from 0.1 to 11 mg/g of fortifier, such as lacto-N-tetraose ;

- ingredients providing 6'-SL in an amount ranging from 5 to 55 mg/g, or from 1.25 to 13.75 mg/g, or from 1 to 11 mg/g of an enricher, for example 6'-sialyllactose .

In a further embodiment, a human milk fortifier is provided further comprising ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/g, or 0.025 to 6.25 mg/g, or 0.02 to 5 mg /g enricher, such as lacto-N-neotetraose.

Breast milk fortifier as a separate composition (or supplement)

In some embodiments of the present invention, the human milk fortifier can be administered as a separate composition (without being dissolved/reconstituted in breast milk or in breast milk already fortified with other nutrients). In such embodiments, infants' daily requirement for the claimed nutrients of the present invention may be provided in a single dose or in the form of a supplement that may be offered over one or more feeding attempts.

Based on the results of the clinical studies shown in FIG. 3 regarding recommended milk intake and average body weight for different postmenstrual ages, the researchers calculated the deficient amounts of each nutrient established at discharge (eg, 38 to 43 weeks postmenstrual age) on a daily basis.

In the time period covering the period from the 38th to the 43rd week of postmenstrual age, the range of missing amounts of alpha-lactalbumin on a daily basis (from 0.41 to 1.31 g) was calculated as follows. The lower end of the range is calculated from the missing amount of alpha-lactalbumin in the breast milk of mothers of preterm infants (as shown in Fig. 3, 1.07 g/l) given a daily intake of 170 ml/kg body weight (Amez et al, JPGN , 2010:50: 200-7) and correlating it with the body weight of newborn girls in the 3rd percentile at 38 weeks (Fenton and Kim BMC Pediatrics 2013, 13:59). On the other hand, the upper end of the range is calculated based on the missing amount of alpha-lactalbumin in breast milk of mothers of preterm infants (as shown in Fig. 3, 1.07 g/l) given a daily intake of 210 ml/kg body weight (Lucas et al, ADC, 1992-67-691-2) and correlating it with the body weight of newborn girls in the 97th percentile at 43 weeks (Fenton and Kim BMC Pediatrics 2013, 13:59).

Based on the same inputs (missing amounts of a particular nutrient in the breast milk of mothers of preterm infants, average daily intake per kg of body weight, and body weight at a particular postmenstrual age), one skilled in the art will also be able to consider different ways of calculating such ranges for daily missing amounts of claimed nutrients.

In a further embodiment, the present invention provides a breast milk fortifier comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 79 to 253 micrograms, or from 87 to 238 micrograms, or from 107 to 202 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 1 to 7 μg, or from 2 to 6 μg, or from 2 to 5 μg, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

- ingredients providing zinc in an amount ranging from 1220 to 3880 µg, or from 1340 to 3640 µg, or from 1640 to 3090 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.4 to 1.31, or from 0.45 to 1.23 g, or from 0.55 to 1.05 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.82 to 2.60 g, or from 0.90 to 2.44 g, or from 1.10 to 2.07 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.50 to 1.58 g, or from 0.55 to 1.58 g, or from 0.67 to 1.26 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 2.39 to 7.60 mg, or from 2.64 to 7.13 g, or from 3.21 to 6.06 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.04 to 0.13 mg, or from 0.05 to 0.13 mg, or from 0.06 to 0.11 mg;

- ingredients providing nicotinic acid in an amount ranging from 2.44 to 7.74 micrograms, or from 2.68 to 7.26 micrograms, or from 3.27 to 6.17 micrograms, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.24 to 0.75 mg, or from 0.26 to 0.70 mg, or from 0.32 to 0.60 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures;

- ingredients providing DFSLTHN in an amount ranging from 40 to 128 mg, or from 44 to 120 mg, or from 54 to 102 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 45 to 145 mg, or from 50 to 135 mg, or from 61 to 115 mg, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 47 to 151 mg, or from 52 to 142 mg, or from 64 to 120 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 87 to 279 mg, or from 96 to 262 mg, or from 118 to 222 mg, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 132 to 421 mg, or from 146 to 395 mg, or from 178 to 336 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And

- ingredients providing SLTNTC in an amount ranging from 139 to 443 mg, or from 153 to 415 mg, or from 187 to 353 mg, for example sialyllacto-N-tetraose-c;

or their mixtures.

In another embodiment, the present invention provides a human milk fortifier comprising at least one mineral providing ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 79 to 253 micrograms, or from 87 to 238 micrograms, or from 107 to 202 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 1 to 7 μg, or from 2 to 6 μg, or from 2 to 5 μg, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

- ingredients providing zinc in an amount ranging from 1220 to 3880 µg, or from 1340 to 3640 µg, or from 1640 to 3090 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof.

In another embodiment, the present invention provides a human milk fortifier comprising at least one protein providing ingredient selected from the group consisting of:

- ingredients providing alpha-lactalbumin in an amount ranging from 0.4 to 1.31, or from 0.45 to 1.23 g, or from 0.55 to 1.05 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.82 to 2.60 g, or from 0.90 to 2.44 g, or from 1.10 to 2.07 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.50 to 1.58 g, or from 0.55 to 1.58 g, or from 0.67 to 1.26 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof.

In another embodiment, the present invention provides a human milk fortifier comprising at least one vitamin providing ingredient selected from the group consisting of:

- ingredients providing alpha-tocopherol in an amount ranging from 2.39 to 7.60 mg, or from 2.64 to 7.13 g, or from 3.21 to 6.06 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.04 to 0.13 mg, or from 0.05 to 0.13 mg, or from 0.06 to 0.11 mg;

- ingredients providing nicotinic acid in an amount ranging from 2.44 to 7.74 micrograms, or from 2.68 to 7.26 micrograms, or from 3.27 to 6.17 micrograms, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.24 to 0.75 mg, or from 0.26 to 0.70 mg, or from 0.32 to 0.60 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures.

In another embodiment, the present invention provides a human milk fortifier comprising at least one ingredient providing human milk oligosaccharides and selected from the group consisting of:

- ingredients providing DFSLTHN in an amount ranging from 40 to 128 mg, or from 44 to 120 mg, or from 54 to 102 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 45 to 145 mg, or from 50 to 135 mg, or from 61 to 115 mg, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 47 to 151 mg, or from 52 to 142 mg, or from 64 to 120 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 87 to 279 mg, or from 96 to 262 mg, or from 118 to 222 mg, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 132 to 421 mg, or from 146 to 395 mg, or from 178 to 336 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And

- ingredients providing SLTNTC in an amount ranging from 139 to 443 mg, or from 153 to 415 mg, or from 187 to 353 mg, for example sialyllacto-N-tetraose-c.

In another embodiment, the present invention provides a breast milk fortifier comprising:

- ingredients providing zinc in an amount ranging from 1220 to 3880 micrograms, or from 1340 to 3640 micrograms, or from 1640 to 3090 micrograms, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.4 to 1.31, or from 0.45 to 1.23 g, or from 0.55 to 1.05 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk source or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.82 to 2.60 g, or from 0.90 to 2.44 g, or from 1.10 to 2.07 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 2.39 to 7.60 mg, or from 2.64 to 7.13 g, or from 3.21 to 6.06 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing LnNT in an amount ranging from 47 to 151 mg, or from 52 to 142 mg, or from 64 to 120 mg, for example lacto-N-neotetraose.

In an additional embodiment, the breast milk fortifier according to the present invention further comprises:

- ingredients providing LNT in an amount ranging from 87 to 279 mg, or from 96 to 262 mg, or from 118 to 222 mg, for example lacto-N-tetraose.

In the embodiments described above, the human milk fortifier is provided in the form of a separate composition that is administered to the infant once a day.

In another further embodiment, the present invention provides a breast milk fortifier comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 26 to 84 micrograms, or from 29 to 79 micrograms, or from 35 to 67 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 0.33 to 2.33 micrograms, or from 0.66 to 2 micrograms, or from 0.66 to 1.66 micrograms, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

- ingredients providing zinc in an amount ranging from 406 to 1293 µg, or from 447 to 1213 µg, or from 546 to 1030 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.13 to 0.44 or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.27 to 0.87 g, or from 0.30 to 0.81 g, or from 0.37 to 0.69 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.17 to 0.53 g, or from 0.18 to 0.53 g, or from 0.22 to 0.42 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 0.80 to 2.53 mg, or from 0.88 to 2.38 mg, or from 1.07 to 2.02 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.013 to 0.04 mg, or from 0.016 to 0.04 mg, or from 0.02 to 0.037 mg;

- ingredients providing nicotinic acid in an amount ranging from 0.81 to 2.58 µg, or from 0.89 to 2.42 µg, or from 1.09 to 2.06 µg, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.08 to 0.25 mg, or from 0.08 to 0.23 mg, or from 0.10 to 0.20 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures;

- ingredients providing DFSLTHN in an amount ranging from 13 to 43 mg, or from 14 to 40 mg, or from 18 to 34 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 15 to 48 mg, or from 16 to 45 mg, or from 20 to 39 mg, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 15 to 51 mg, or from 17 to 47 mg, or from 21 to 40 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 29 to 93 mg, or from 32 to 87 mg, or from 39 to 74 mg, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 44 to 140 mg, or from 48 to 132 mg, or from 59 to 112 mg, for example 6'-sialyllactose or sodium salt of 6'-sialyllactose; And

- ingredients providing SLTNTC in an amount ranging from 46 to 148 mg, or from 51 to 138 mg, or from 62 to 118 mg, for example sialyllacto-N-tetraose-c;

or their mixtures.

In another embodiment, the present invention provides a human milk fortifier comprising at least one mineral providing ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 26 to 84 micrograms, or from 29 to 79 micrograms, or from 35 to 67 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 0.33 to 2.33 micrograms, or from 0.66 to 2 micrograms, or from 0.66 to 1.66 micrograms, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

- ingredients providing zinc in an amount ranging from 406 to 1293 µg, or from 447 to 1213 µg, or from 546 to 1030 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof.

In another embodiment, the present invention provides a human milk fortifier comprising at least one protein providing ingredient selected from the group consisting of:

- ingredients providing alpha-lactalbumin in an amount ranging from 0.13 to 0.44 or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.27 to 0.87 g, or from 0.30 to 0.81 g, or from 0.37 to 0.69 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.17 to 0.53 g, or from 0.18 to 0.53 g, or from 0.22 to 0.42 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof.

In another embodiment, the present invention provides a human milk fortifier comprising at least one vitamin providing ingredient selected from the group consisting of:

- ingredients providing alpha-tocopherol in an amount ranging from 0.80 to 2.53 mg, or from 0.88 to 2.38 g, or from 1.07 to 2.02 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.013 to 0.04 mg, or from 0.016 to 0.04 mg, or from 0.02 to 0.037 mg;

- ingredients providing nicotinic acid in an amount ranging from 0.81 to 2.58 µg, or from 0.89 to 2.42 µg, or from 1.09 to 2.06 µg, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.08 to 0.25 mg, or from 0.08 to 0.23 mg, or from 0.10 to 0.20 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures.

In another embodiment, the present invention provides a human milk fortifier comprising at least one ingredient providing human milk oligosaccharides and selected from the group consisting of:

- ingredients providing DFSLTHN in an amount ranging from 13 to 43 mg, or from 14 to 40 mg, or from 18 to 34 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 15 to 48 mg, or from 16 to 45 mg, or from 20 to 39 mg, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 15 to 51 mg, or from 17 to 47 mg, or from 21 to 40 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 29 to 93 mg, or from 32 to 87 mg, or from 39 to 74 mg, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 44 to 140 mg, or from 48 to 132 mg, or from 59 to 112 mg, for example 6'-sialyllactose or sodium salt of 6'-sialyllactose; And

- ingredients providing SLTNTC in an amount ranging from 46 to 148 mg, or from 51 to 138 mg, or from 62 to 118 mg, for example sialyllacto-N-tetraose-c.

In another embodiment, the present invention provides a breast milk fortifier comprising at least one ingredient selected from the group consisting of:

- ingredients providing zinc in an amount ranging from 406 to 1293 µg, or from 447 to 1213 µg, or from 546 to 1030 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.13 to 0.44 or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.27 to 0.87 g, or from 0.30 to 0.81 g, or from 0.37 to 0.69 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 0.80 to 2.53 mg, or from 0.88 to 2.38 mg, or from 1.07 to 2.02 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing LnNT in an amount ranging from 15 to 51 mg, or from 17 to 47 mg, or from 21 to 40 mg, for example lacto-N-neotetraose.

In a further embodiment, the present invention provides a breast milk fortifier further comprising:

- ingredients providing LNT in an amount ranging from 29 to 93 mg, or from 32 to 87 mg, or from 39 to 74 mg, for example lacto-N-tetraose.

In the embodiments described above, the human milk fortifier is provided in the form of a separate composition that is administered to the infant three times a day.

In a further embodiment, the present invention provides a human milk fortifier composition according to claim 1, comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 39.5 to 127 µg, or from 43 to 119 µg, or from 53 to 101 µg, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate ), copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 0.5 to 4 μg, or from 1 to 3 μg, or from 1 to 2.5 μg, for example sodium selenite, sodium selenate, sodium hydroselenite or mixtures thereof;

- ingredients providing zinc in an amount ranging from 610 to 1940 µg, or from 670 to 1820 µg, or from 820 to 1545 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.2 to 0.66, or from 0.22 to 0.62 g, or from 0.27 to 0.53 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.41 to 1.30 g, or from 0.45 to 1.22 g, or from 0.55 to 1.04 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.25 to 0.79 g, or from 0.27 to 0.79 g, or from 0.33 to 0.63 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 1.19 to 3.80 mg, or from 1.32 to 3.57 mg, or from 1.60 to 3.03 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.02 to 0.07 mg, or from 0.025 to 0.07 mg, or from 0.03 to 0.06 mg;

- ingredients providing nicotinic acid in an amount ranging from 1.22 to 3.87 micrograms, or from 1.34 to 3.63 micrograms, or from 1.63 to 3.08 micrograms, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.12 to 0.37 mg, or from 0.13 to 0.35 mg, or from 0.16 to 0.30 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures;

- ingredients providing DFSLTHN in an amount ranging from 20 to 64 mg, or from 22 to 60 mg, or from 27 to 51 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 22 to 73 mg, or from 25 to 68 mg, or from 30 to 58 mg, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 10 to 34 mg, or from 11 to 32 mg, or from 14 to 27 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 23 to 76 mg, or from 26 to 71 mg, or from 32 to 60 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 43 to 140 mg, or from 48 to 131 mg, or from 59 to 111 mg, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 66 to 211 mg, or from 73 to 198 mg, or from 89 to 168 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And

- ingredients providing SLTNTC in an amount ranging from 68 to 222 mg, or from 76 to 208 mg, or from 93 to 177 mg, for example sialyllacto-N-tetraose-c;

or their mixtures.

In another embodiment, the present invention provides a human milk fortifier composition comprising at least one mineral providing ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 13 to 42 µg, or from 14 to 40 µg, or from 17 to 34 µg, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof;

- ingredients providing selenium in an amount ranging from 0.165 to 1.165 µg, or from 0.33 to 1 µg, or from 0.33 to 0.84 µg, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof;

- ingredients providing zinc in an amount ranging from 203 to 647 micrograms, or from 223 to 606 micrograms, or from 273 to 515 micrograms, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

or their mixtures.

In a further embodiment, the present invention provides a human milk fortifier composition comprising at least one protein providing ingredient selected from the group consisting of:

- ingredients providing alpha-lactalbumin in an amount ranging from 0.06 to 0.22, or from 0.07 to 0.21 g, or from 0.09 to 0.17 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.13 to 0.44 g, or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof;

- ingredients providing lactoferrin in an amount ranging from 0.08 to 0.27 g, or from 0.09 to 0.27 g, or from 0.11 to 0.21 g, for example, purified or synthesized lactoferrin, isolate whey protein, whey protein concentrate or mixtures thereof;

or their mixtures.

In a further embodiment, the present invention provides a human milk fortifier composition comprising at least one vitamin providing ingredient selected from the group consisting of:

- ingredients providing alpha-tocopherol in an amount ranging from 0.40 to 1.27 mg, or from 0.44 to 1.19 mg, or from 0.54 to 1.01 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing gamma-tocopherol in an amount ranging from 0.006 to 0.02 mg, or from 0.008 to 0.02 mg, or from 0.01 to 0.018 mg;

- ingredients providing nicotinic acid in an amount ranging from 0.40 to 1.29 µg, or from 0.44 to 1.21 µg, or from 0.54 to 1.03 µg, for example nicotinic acid, nicotinamide or their mixtures;

- ingredients providing retinol in an amount ranging from 0.04 to 0.13 mg, or from 0.04 to 0.12 mg, or from 0.05 to 0.10 mg, for example retinol, retinyl acetate, retinyl palmitate or their mixtures;

or their mixtures.

In a further embodiment, the present invention provides a human milk fortifier composition comprising at least one human milk oligosaccharide providing ingredient selected from the group consisting of:

- ingredients providing DFSLTHN in an amount ranging from 6 to 22 mg, or from 7 to 20 mg, or from 9 to 17 mg, for example difucosyllacto-N-hexaose-a;

- ingredients providing FSLTNH3 in an amount ranging from 7 to 24 mg, or from 8 to 23 mg, or from 10 to 20 mg/g, for example monofucosyllacto-N-hexaose-III;

- ingredients providing GSLT6 in an amount ranging from 10 to 34 mg, or from 12 to 32 mg, or from 14 to 27 mg, for example 6'-galactosyl lactose;

- ingredients providing LnNT in an amount ranging from 7 to 26 mg, or from 8 to 24 mg, or from 10 to 20 mg, for example lacto-N-neotetraose;

- ingredients providing LNT in an amount ranging from 15 to 47 mg, or from 16 to 44 mg, or from 18 to 37 mg/g, for example lacto-N-tetraose;

- ingredients providing 6'-SL in an amount ranging from 22 to 70 mg, or from 24 to 61 mg, or from 28 to 56 mg, for example 6'-sialyllactose or sodium salt of 6'-sialyllactose; And

- ingredients providing SLTNTC in an amount ranging from 23 to 74 mg, or from 25 to 69 mg, or from 31 to 59 mg, for example sialyllacto-N-tetraose-c;

or their mixtures.

In a further embodiment, the present invention provides a breast milk fortifier comprising:

- ingredients providing zinc in an amount ranging from 203 to 647 micrograms, or from 223 to 606 micrograms, or from 273 to 515 micrograms, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof;

- ingredients providing alpha-lactalbumin in an amount ranging from 0.06 to 0.22, or from 0.07 to 0.21 g, or from 0.09 to 0.17 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk source or mixtures thereof;

- ingredients providing caseins in an amount ranging from 0.13 to 0.44 g, or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk source or mixtures thereof;

- ingredients providing alpha-tocopherol in an amount ranging from 0.40 to 1.27 mg, or from 0.44 to 1.19 mg, or from 0.54 to 1.01 mg, for example D-alpha- tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof;

- ingredients providing LnNT in an amount ranging from 7 to 26 mg, or from 8 to 24 mg, or from 10 to 20 mg, for example lacto-N-neotetraose;

or mixtures thereof.

In a further embodiment, the present invention provides a breast milk fortifier further comprising

- ingredients providing LNT in an amount in the range of 15 to 47 mg, or 16 to 44 mg, or 18 to 37 mg/g, such as lacto-N-tetraose.

In the embodiments described above, the human milk fortifier is provided in the form of a single composition that is administered to the infant six times a day.

Other Ingredients

In one embodiment of the present invention, the human milk fortifier composition of the present invention contains no ingredients other than those that provide at least one nutrient selected from the group consisting of the aforementioned minerals, vitamins, milk proteins, and human milk oligosaccharides.

In such an embodiment, the human milk fortifier composition of the present invention has the added benefit of a high nutrient to energy ratio and/or low energy value. Because of this limited caloric contribution to human milk fortified according to the present invention, it is not anticipated that there will be a subsequent need to adjust intakes for infants receiving such fortified breast milk so that the maximum possible nutrient intake can be achieved and the deficiencies of certain nutrients can be fully replenished. in breast milk of mothers of premature infants compared with full-term ones.

In such an embodiment, the human milk fortifier of the present invention provides a calorie content per 100 ml of fortified human milk in an amount ranging from 0 to 4.57 kcal.

In one embodiment, the human milk fortifier of the present invention has a calorie content in the range of 0 to 4.57 kcal/g of fortifier, such as in the range of 0 to 2.5 kcal/g of fortifier. In such an embodiment, the single dose of fortifier is 1 g of fortifier/100 ml of fortified milk.

In another embodiment, the human milk fortifier of the present invention has a calorie content in the range of 0 to 1.1 kcal/g of fortifier. In such an embodiment, the single dose of fortifier is 4 g of fortifier/100 ml of fortified milk.

In a further embodiment, the human milk fortifier of the present invention has a calorie content in the range of 0 to 0.9 kcal/g of fortifier. In such an embodiment, the single dose of fortifier is 5 g of fortifier/100 ml of fortified milk.

In another embodiment, the human milk fortifier composition according to the present invention may also optionally contain other additional and various nutrients, such as carbohydrates, probiotics, lipids, other vitamins or minerals.

If necessary, the composition according to the present invention may contain emulsifiers and/or stabilizers such as lecithin, mono- and diglyceride esters, monoglycerides, citric acid diglycerides, and the like. This is especially true if the composition is presented as a combination of oils and an aqueous liquid, such as an emulsion.

The composition may also optionally contain other substances that may have a beneficial effect, such as nucleotides, nucleosides, and the like, in amounts normally found in nutritional compositions intended for feeding infants.

Other optional ingredients may be ingredients that are commonly known for use in foods and nutritional products, in particular infant formulas or infant formula fortifiers, provided such optional materials are compatible with the essential ingredients described herein, are safe and effective. when used as intended and unnecessarily, do not otherwise impair the performance of the product.

Non-limiting examples of such optional ingredients include preservatives, probiotics, antioxidants, buffers, colors, flavors, thickeners, stabilizers, and other adjuvants or processing aids.

Use of a breast milk fortifier

The quality and quantity of various nutrients an infant receives can affect various indicators of health.

All milk proteins, breast milk oligosaccharides, minerals and vitamins are considered essential for optimal growth and development of the infant. Thus, optimizing their quality and content in infant nutrition (especially for infants born preterm, with LBGR and/or LBGR), as provided in the context of the present invention, can prevent growth and developmental failure (including the prevention and/or treatment of stunted growth , infections, lung disease, suboptimal nutritional status, anemia, (neurological) developmental delays, blindness, and metabolic bone disease) and may promote optimal growth and development.

In one embodiment, the present invention provides a human milk fortifier composition for use in fortifying the human milk of mothers who have given birth to preterm infants at the time of discharge from the hospital of the premature infant and thereafter.

In another embodiment, the present invention provides a human milk fortifier composition for use in fortifying the breast milk of mothers who have given birth to infants with LHWR or LHWR, at the time of discharge from the hospital of the infant born with LWHR or LHWF, and thereafter.

Premature infants are indeed particularly at risk for developmental delay, infection, lung disease, suboptimal nutritional status, anemia, delayed (neurological) development, blindness, and metabolic bone disease after discharge from the hospital.

In a further aspect, the present invention provides a human milk fortifier composition for use in the prevention and/or treatment of a condition selected from the group consisting of growth retardation, infection, lung disease, developmental delays, blindness, and/or metabolic bone disease.

In yet another embodiment, the present invention provides a human milk fortifier composition for use in the prevention and/or treatment of a condition selected from the group consisting of growth and/or developmental failure, growth retardation, infection, lung disease, developmental delays, blindness and/or metabolic bone disease; for administration at the time of discharge (and after discharge) from the hospital to an infant born prematurely with LVR or LVR.

Receipt

The composition in accordance with the present invention can be obtained by any suitable method. For example, the composition can be obtained by mixing the ingredients together in appropriate ratios. If emulsifiers are used, they can be included in the mixture at this stage. Vitamins and minerals can be added at this stage, but are usually added later to prevent thermal decomposition. Water, preferably reverse osmosis water, can then be mixed in to form a liquid mixture.

Yet another further aspect of the invention relates to a package containing a composition according to the invention, which is a single dosing device or a multiple dosing device.

In a specific embodiment of the invention, the package is a syringe, pouch, stick pack or vial.

It should be noted that the embodiments and elements described in the context of one aspect of the present invention are also applicable to other aspects of the invention.

All patent and non-patent references cited in this application are hereby incorporated by reference in their entirety.

The present invention will be further described in detail in the following non-limiting examples.

Experimental section

Example 1. Comparison of breast milk of mothers who gave birth prematurely with milk of mothers who gave birth at term

The present study compared the composition of breast milk of preterm mothers with the composition of breast milk of full-term mothers for several nutrients. Comparisons were made over a period of 38 to 48 weeks post-menstrual age in infants.

Methods used to analyze breast milk

Minerals

Copper (Cu), Selenium (Se) and Zinc (Zn) were analyzed according to the following method: A 0.7 ml aliquot of breast milk was transferred into PFA vials and mineralized using a CEM microwave digestion system using nitric acid (HNO ₃ )/peroxide hydrogen (H ₂ O ₂ ). Mineralized samples were transferred to PE tubes and diluted to 15 ml with Millipore purified water. The samples were then re-diluted after adding germanium (Ge) and tellurium (Te) as an internal standard and analyzed using inductively coupled plasma mass spectrometry (ICP-MS, Nexion 300 D, Perkin Elmer). A quality control (QC) sample was included in the analysis.

vitamins

B vitamins were analyzed by the method described in Redeuil et al (2017) A Novel Methodology for the Quantification of B-Vitamers in Breast Milk. J Anal Bioanal Tech 8: 352. doi: 10.4172:2155–9872.1000352.

Vitamin A (carotenoids) and vitamin E (tocopherols) were analyzed according to the following method: vitamin E (α-tocopherol and γ-tocopherol), provitamin A carotenoids (β-carotene and β-cryptoxanthin), and other carotenoids, e.g. lycopene, lutein and zeaxanthin, in breast milk were extracted by protein precipitation in ethanol and liquid-to-liquid extraction with a mixture of n-hexane and ethyl acetate containing butylated hydroxytoluene (BHT). The extracts were then evaporated to dryness under a stream of nitrogen. The dried extracts were re-dissolved in a mixture of isooctane and ethyl acetate and analyzed by UHPLC-UV-PD, Waters Acquity UPLC; column Thermo Hypersil GOLD Silica, 1.9 µm, 200 x 2.1 mm). The analytes were quantitated using authentic standards of rac-tocol (Matreya LLC, 1797; CAS no. 119-98-2) and trans-β-apo-8'-carotenal (Sigma-Aldrich, 10810; CAS no. 1107-26- 2).

OGM (Austin et al. (2018) Quantitative determination of non-lactose milk oligosaccharides. Analytica Chimica Acta 1010: 86. doi: 10.1016/j.aca.2017.12.036):

Oligosaccharides. Maltotriose was purchased from Sigma-Aldrich. Laminarithriasis was purchased from Carbosynth Limited (Compton, UK). A-tetrasaccharide (A-Tetra), 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT or LnNT), lacto -N-neohexaose (LNnH), 3'-sialyllactose (3-'SL), 6'-sialyllactose (6'-SL), lacto-N-fucosylpentaose-I (LNFP-I), LNFP-V, lacto-N α-neofucosylpentaose-V (LNnFP-V) and lacto-N-neodifucosylhexaose (LNnDFH) were purchased from Elicity SA (Crollet, France). 3'-Galactosyl lactose (3'GL), 6'-galactosyl lactose (6'GL or GSLT6), 4'-galactosyl lactose (4'GL), lacto-N-difucosylhexaose-I (LNDFH-I), difucosyllacto-N-hexaose -a (DFLNHa or DFSLTNH), disialyl lacto-N-tetraose (DSLNT), monofucosyllacto-N-hexaose-III (MFLNH-III or FSLTNH3), LNFP-II, LNFP-III, sialyl lacto-N-tetraose-a (LSTa) , LSTb, LSTc and lacto-N-hexaose (LNH) were purchased from Dextra Laboratories Ltd (Reading, UK)

Sample preparation. A milk sample or a mixed standard solution (50 µl) was transferred to a microtube (1.5 ml) and a laminatriose solution (0.5 mM, 50 µl) was added. After mixing, an aliquot (20 µl) was transferred to another microtube (1.5 ml) and 2AB labeling reagent (2AB (0.35 M) and sodium cyanoborohydride (1 M) in DMSO/acetic acid (7/3) was added, 200 µl). After mixing, the sample or standard was heated at 65°C for 2 hours. The mixture was then cooled at 4°C for 10 min, after which a mixture of water/acetonitrile (25/75, 0.6 ml) was added. Particles were removed by centrifugation (10,000 × g, 5 min), after which samples or standards were injected into the LC system.

liquid chromatography. A 3000-RS Ultra High Performance Liquid Chromatography (UHPLC) system with an RF-2000 fluorometer (PD) and a 2-way 10-channel high pressure switching valve was used (all equipment manufactured by Thermo Fisher Scientific, Waltham, USA). The columns were Acquity BEH Glycan (1.7 µm, 2.1 x 150 mm) and VanGuard BEH amide (1.7 µm, 2.1 x 50 mm), both from Waters Corporation (Milford, USA). The guard column was installed between the injector and the 10-way valve. After injection, the sample was sent to a guard column with a stream bled to waste to remove excess labeling reagents (0-2.3 min gradient in the table below), then the flow was directed through an analytical column and the oligosaccharides were eluted using an ammonium formate gradient (see .table below). The flow rate was 0.5 ml/min-1 and the column temperature was kept constant at 55°C. Detection was performed using a fluorimeter with an excitation wavelength of 330 nm and an emission wavelength of 420 nm.

Time (min) % acetonitrile % ammonium formate (50 mM) Valve position 0 95 5 Waste 2.3 95 5 Waste 2.5 90 10 Analysis 4.9 90 10 Analysis 32.1 82 18 Analysis 48.1 80.5 19.5 Analysis 61.5 78.0 22.0 Analysis 89.0 74.6 25.4 Analysis 89.5 thirty 70 Analysis 92.0 thirty 70 Analysis 93.0 90 10 Analysis 98.0 90 10 Analysis 99.0 95 5 Waste 100 95 5 Waste

Squirrels

Individual human milk proteins were analyzed using the LabChip system as described by Affolter M, et al. (2016) Temporal Changes of Protein Composition in Breast Milk of Chinese Urban Mothers and Impact of Caesarean Section Delivery. Nutrients 2016, 8, 504; doi:10.3390.

Amino acids

Amino acids were analyzed by the AccQ-Tag method offered by Waters (Waters Corporation, Milford, Massachusetts, USA). First, the proteins were hydrolyzed with 6 M HCl for 24 h at 110°C. Phenol (0.1%) was added to avoid tyrosine halogenation. After hydrolysis and neutralization, the amino acids were derivatized with 6-aminoquinolyl-N-hydroxysuccinylcarbamate (AQC) and then separated using reverse phase UPLC with UV detection at 260 nm. During acid hydrolysis, glutamine (Gln) and asparagine (Asn) are converted to glutamic acid (Glu) and aspartic acid (Asp), thus the values for Glu are the combined values for Glu and Gln, and the values for Asp are the combined values for Asp and Asn.

Statistical analysis

All analyzes were performed using statistical software R version 3.2.3.

In this particular analysis, all observations from the entire study period are pooled (maximum 12 observations for preterm infants and maximum 8 for term infants).

To compare the two groups (PRETERM and TERM), a mixed linear model was used in which the group and mode of delivery were considered fixed effects. Intra-individual variability was taken into account by assigning subjects to random effects. The main comparison is between PRETERM and TERM infants. An adjustment for mode of delivery is introduced because it is an effect that makes it difficult to interpret urgency status given that a higher proportion of preterm infants are delivered by caesarean section. The HMO concentration was modeled with a logarithmic transformation because the distribution is usually skewed and according to the Box-Cox and QQ plots, a logarithmic transformation seems to be appropriate. The transformation was not carried out only for 2'FL, since the distribution in this case could be considered normal.

results

The amounts of several human milk proteins, vitamins, minerals and oligosaccharides in the breast milk of preterm mothers were found to be statistically significantly different compared to the milk of full term mothers at the corresponding postmenstrual age of 38 to 48 weeks.

The results obtained for these nutrients are shown in FIG. 2.

For each nutrient, the results presented in FIG. 2 are the average values recorded for the period from 38 to 48 weeks postmenstrual age. It should be noted that only those nutrients were included in the table for which the difference in mean values for term and preterm infants was statistically significant (p<0.05).

In addition, in FIG. 3 shows the results of the same analysis carried out for the period from 38 to 43 weeks. Based on the data in this table, it is clear that preterm infants who are breastfed by their mothers have especially high requirements for certain nutrients during this period.

For each nutrient, the results presented in FIG. 3 are the average values recorded for the period from 38 to 43 weeks postmenstrual age. It should be noted that only those nutrients were included in the table for which the difference in mean values for term and preterm infants was statistically significant (p<0.05).

In FIG. 4 shows the results of an amino acid analysis performed on breast milk samples taken between 38 and 42 weeks postmenstrual age (samples from 74 term mothers and 29 premature mothers). This analysis was performed to identify alternative ingredients that could compensate for the lack of certain proteins (alpha-lactalbumin, caseins, lactoferrin) in the breast milk of mothers of preterm infants, as explained above.

The results show that in the milk of mothers who gave birth to premature babies, there is a nutritional deficiency in the following amino acids that need to be replenished: Glu (glutamic acid), Pro (proline), His (histidine), Ile (isoleucine), Leu (leucine), Lys (lysine), Met (methionine), Trp (tryptophan).

The amino acids for which the difference between term and preterm mean was clearly statistically significant (p<0.05) are: Ile, Leu, Met, Pro.

Amino acid analysis also revealed a statistically significant difference between the mean of term and preterm infants for the sum of essential amino acids [His, Ile, Leu, Lys, Met, Phe (phenylalanine), Thr (threonine), Trp, Val (valine)].

The given data reflects the information known to the inventors at the time of filing the application.

Due to the significantly lower levels in the milk of mothers of preterm infants of the nutrients shown in FIG. 2, a preterm infant who is exclusively breastfed, as a result, at the time of discharge from the hospital (between 38 and 48 weeks) receives significantly less of these nutrients compared to a full-term infant of the corresponding postmenstrual age who is exclusively breastfed. Since preterm infants already face challenges early in life, a balanced diet is essential, and the results of this study demonstrate the need for fortified breast milk of mothers of preterm infants to compensate for nutritional deficiencies at discharge and promote growth and development. development of these preterm infants.

Example 2

Table 1 below shows an example of a human milk fortifier composition according to the present invention. The recommended single dose for the fortifier described below is 1 g of fortifier per 100 ml of fortified breast milk.

Nutrient Content in enricher alpha lactalbumin 92 mg Caseins 148 mg lactoferrin 72 mg copper 17 mcg Selenium 0.33 mcg Zinc 229 mcg total tocopherol 334 mcg alpha tocopherol 330 mcg gamma tocopherol 4 mcg Vit. A/retinol 35 mcg A nicotinic acid 2.30 mcg DFSLTNH 12 mg FSLTNH3 14 mg GSLT6 3 mg LnNT 7 mg LNT 22 mg 6-SL 26 mg SLTNTC 23 mg Other Ingredients Bringing the composition to a total weight of 1 g

The composition according to the present invention can be given to an infant at the time of discharge from the hospital as a breast milk fortifier.

The composition is particularly suitable for feeding a premature infant as a supplement to breast milk at discharge or after discharge, for example at postmenopausal age from 36 weeks to 9 months.

The composition according to the present invention may be formulated with numerous variations without departing from the scope of the invention as defined in the claims.

The present invention also provides the following embodiments:

a) A breast milk fortifier composition containing at least one ingredient selected from the group consisting of:

- ingredients providing copper;

- ingredients providing selenium;

- ingredients providing zinc;

- ingredients providing alpha-lactalbumin;

- ingredients providing casein;

- ingredients providing lactoferrin;

- ingredients providing alpha-tocopherol;

- ingredients providing gamma-tocopherol;

- ingredients providing nicotinic acid;

- ingredients providing retinol;

- ingredients providing DFSLTHN;

- ingredients providing FSLTNH3;

- ingredients providing 6'-SL;

- ingredients providing LnNT;

- ingredients providing LNT;

- ingredients providing 6'-SL; And

- ingredients providing SLTNTC;

or their mixtures.

b) A human milk fortifier composition according to embodiment a) for dissolution in breast milk, comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount in the range of 5 to 30 µg/100 ml, for example 8 to 28 µg/100 ml of fortified breast milk;

- ingredients providing selenium in an amount in the range of 0.1 to 10 µg/100 ml, for example 0.3 to 8 µg/100 ml of fortified breast milk;

- ingredients providing zinc in an amount in the range of 50 to 550 µg/100 ml, for example 100 to 500 µg/100 ml of fortified breast milk;

- ingredients providing alpha-lactalbumin in an amount in the range of 25 to 180 mg/100 ml, for example 30 to 150 mg/100 ml of fortified breast milk;

- ingredients providing casein in an amount in the range of 10 to 500 mg/100 ml, for example 20 to 400 mg/100 ml of fortified breast milk;

- ingredients providing lactoferrin in an amount in the range of 10 to 500 mg/100 ml, for example 20 to 400 mg/100 ml of fortified breast milk;

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/100 ml, for example from 10 to 1700 µg/100 ml of fortified breast milk;

- ingredients providing gamma-tocopherol in an amount ranging from 0.1 to 50 µg/100 ml, for example from 0.2 to 40 µg/100 ml, of fortified breast milk;

- ingredients providing nicotinic acid in an amount ranging from 0.5 to 18 µg/100 ml, for example from 1 to 15 µg/100 ml, of fortified breast milk;

- ingredients providing retinol in an amount in the range of 1 to 250 μg/100 ml, for example 5 to 200 μg/100 ml of fortified breast milk;

- ingredients providing DFSLTHN in an amount in the range of 5 to 25 mg/100 ml, eg 8 to 15 mg/100 ml of fortified breast milk;

- ingredients providing FSLTNH3 in an amount in the range of 0.5 to 35 mg/100 ml, eg 5 to 20 mg/100 ml of fortified breast milk;

- ingredients providing GSLT6 in an amount in the range of 0.1 to 10 mg/100 ml, eg 1 to 5 mg/100 ml of fortified breast milk;

- ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/100 ml, for example from 1 to 10 mg/100 ml, of fortified breast milk;

- ingredients providing LNT in an amount in the range from 0.5 to 55 mg/100 ml, for example from 5 to 30 mg/100 ml, enriched breast milk;

- ingredients providing 6'-SL in an amount ranging from 5 to 355 mg/100 ml, for example 15 to 35 mg/100 ml of fortified breast milk; And

- ingredients providing SLTNTC in an amount in the range of 1 to 60 mg/100 ml, eg 1 to 30 mg/100 ml of fortified breast milk;

or their mixtures.

c) A human milk fortifier composition according to embodiment a) or b) for dissolution in breast milk, comprising at least one mineral providing ingredient selected from the group consisting of:

- ingredients providing copper in an amount in the range of 5 to 30 µg/100 ml, for example 8 to 28 µg/100 ml of fortified breast milk;

- ingredients providing selenium in an amount in the range of 0.1 to 10 µg/100 ml, for example 0.3 to 8 µg/100 ml of fortified breast milk;

- ingredients providing zinc in an amount in the range of 50 to 550 µg/100 ml, for example 100 to 500 µg/100 ml of fortified breast milk;

or their mixtures.

d) A human milk fortifier composition according to embodiment a) or b) for dissolution in breast milk, comprising at least one milk protein providing ingredient selected from the group consisting of:

- ingredients providing alpha-lactalbumin in an amount in the range of 25 to 180 mg/100 ml, for example 30 to 150 mg/100 ml of fortified breast milk;

- ingredients providing casein in an amount in the range of 10 to 500 mg/100 ml, for example 0.02 to 0.4 µg/100 ml of fortified breast milk;

- ingredients providing lactoferrin in an amount in the range of 10 to 500 mg/100 ml, for example 20 to 400 mg/100 ml of fortified breast milk;

or their mixtures.

e) A human milk fortifier composition according to embodiment a) or b) for dissolution in breast milk, comprising at least one vitamin providing ingredient selected from the group consisting of:

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/100 ml, for example from 10 to 1700 µg/100 ml of fortified breast milk;

- ingredients providing gamma-tocopherol in an amount ranging from 0.1 to 50 µg/100 ml, for example from 0.2 to 40 µg/100 ml, of fortified breast milk;

- ingredients providing nicotinic acid in an amount ranging from 0.5 to 18 µg/100 ml, for example from 1 to 15 µg/100 ml, of fortified breast milk;

- ingredients providing retinol in an amount in the range of 1 to 250 μg/100 ml, for example 5 to 200 μg/100 ml of fortified breast milk;

or their mixtures.

f) A human milk fortifier composition according to embodiment a) or b) for dissolution in breast milk, comprising at least one ingredient providing human milk oligosaccharides and selected from the group consisting of:

- ingredients providing DFSLTHN in an amount in the range of 5 to 25 mg/100 ml, eg 8 to 15 mg/100 ml of fortified breast milk;

- ingredients providing FSLTNH3 in an amount in the range of 0.5 to 35 mg/100 ml, eg 5 to 20 mg/100 ml of fortified breast milk;

- ingredients providing GSLT6 in an amount in the range of 0.1 to 10 mg/100 ml, eg 1 to 5 mg/100 ml of fortified breast milk;

- ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/100 ml, for example from 1 to 10 mg/100 ml, of fortified breast milk;

- ingredients providing LNT in an amount in the range from 0.5 to 55 mg/100 ml, for example from 5 to 30 mg/100 ml, enriched breast milk;

- ingredients providing 6'-SL in an amount ranging from 5 to 355 mg/100 ml, for example 15 to 35 mg/100 ml of fortified breast milk; And

- ingredients providing SLTNTC in an amount in the range of 1 to 60 mg/100 ml, eg 1 to 30 mg/100 ml of fortified breast milk;

or their mixtures.

g) A human milk fortifier composition according to embodiment a) comprising at least one ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 5 to 30 µg/g, or from 1.5 to 7.50 µg/g, or from 1 to 6 µg/g of fortifier;

- ingredients providing selenium in an amount ranging from 0.1 to 10 µg/g, or from 0.0025 to 25 µg/g, or from 0.002 to 0.2 µg/g of fortifier;

- ingredients providing zinc in an amount ranging from 50 to 550 µg/g, or from 12.5 to 137.5 µg/g, or from 10 to 110 µg/g of fortifier;

- ingredients providing alpha-lactalbumin in an amount ranging from 25 to 180 mg/g, or from 6.25 to 45 mg/g, or from 5 to 30 mg/g of fortifier;

- ingredients providing caseins in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier;

- ingredients providing lactoferrin in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier;

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/g, or from 1.25 to 450 µg/g, or from 1 to 360 µg/g of fortifier;

- ingredients providing gamma-tocopherol in an amount ranging from 0.1 to 50 µg/g, or from 0.025 to 12.5 µg/g, or from 0.02 to 10 µg/g of fortifier;

- ingredients providing nicotinic acid in an amount ranging from 0.5 to 18 µg/g, or from 0.25 to 4.25 µg/g, or from 0.1 to 3.6 µg/g of fortifier;

- ingredients providing retinol in an amount ranging from 1 to 250 µg/g, or from 0.25 to 62.5 µg/g, or from 0.2 to 50 µg/g of fortifier;

- ingredients providing DFSLTHN in an amount ranging from 5 to 25 mg/g, or from 1.25 to 6.25 mg/g, or from 1 to 5 mg/g of fortifier;

- ingredients providing FSLTNH3 in an amount ranging from 0.5 to 35 mg/g, or from 0.125 to 8.75 mg/g, or from 0.1 to 7 mg/g of fortifier;

- ingredients providing GSLT6 in an amount ranging from 0.1 to 10 mg/g, or from 0.025 to 2.5 mg/g, or from 0.02 to 2 mg/g of fortifier;

- ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/g, or from 0.025 to 6.25 mg/g, or from 0.02 to 5 mg/g of fortifier;

- ingredients providing LNT in an amount ranging from 0.5 to 55 mg/g, or from 0.125 to 13.75 mg/g, or from 0.1 to 11 mg/g of fortifier;

- ingredients providing 6'-SL in an amount ranging from 5 to 55 mg/g, or from 1.25 to 13.75 mg/g, or from 1 to 11 mg/g of fortifier; And

- ingredients providing SLTNTC in an amount ranging from 1 to 60 mg/g, or from 0.25 to 15 mg/g, or from 0.2 to 12 mg/g of fortifier;

or their mixtures.

h) A human milk fortifier composition according to embodiments a) to g), comprising at least one mineral providing ingredient selected from the group consisting of:

- ingredients providing copper in an amount ranging from 5 to 30 µg/g, or from 1.5 to 7.50 µg/g, or from 1 to 6 µg/g of fortifier;

- ingredients providing selenium in an amount ranging from 0.1 to 10 µg/g, or from 0.0025 to 25 µg/g, or from 0.002 to 0.2 µg/g of fortifier;

- ingredients providing zinc in an amount ranging from 50 to 550 µg/g, or from 12.5 to 137.5 µg/g, or from 10 to 110 µg/g of fortifier;

or their mixtures.

i) A human milk fortifier composition according to embodiments a) to g), comprising at least one milk protein providing ingredient selected from the group consisting of:

- ingredients providing alpha-lactalbumin in an amount ranging from 25 to 180 mg/g, or from 6.25 to 45 mg/g, or from 5 to 30 mg/g of fortifier;

- ingredients providing caseins in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier;

- ingredients providing lactoferrin in an amount ranging from 10 to 50 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier;

or their mixtures.

l) A human milk fortifier composition according to embodiments a) to g), comprising at least one vitamin providing ingredient selected from the group consisting of:

- ingredients providing alpha-tocopherol in an amount ranging from 5 to 1800 µg/g, or from 1.25 to 450 µg/g, or from 1 to 360 µg/g of fortifier;

- ingredients providing gamma-tocopherol in an amount ranging from 0.1 to 50 µg/g, or from 0.025 to 12.5 µg/g, or from 0.02 to 10 µg/g of fortifier;

- ingredients providing nicotinic acid in an amount ranging from 0.5 to 18 µg/g, or from 0.25 to 4.25 µg/g, or from 0.1 to 3.6 µg/g of fortifier;

- ingredients providing retinol in an amount ranging from 1 to 250 µg/g, or from 0.25 to 62.5 µg/g, or from 0.2 to 50 µg/g of fortifier;

or their mixtures.

m) A human milk fortifier composition according to embodiments a) to g), comprising at least one human milk oligosaccharide providing ingredient selected from the group consisting of:

- ingredients providing DFSLTHN in an amount ranging from 5 to 25 mg/g, or from 1.25 to 6.25 mg/g, or from 1 to 5 mg/g of fortifier;

- ingredients providing FSLTNH3 in an amount ranging from 0.5 to 35 mg/g, or from 0.125 to 8.75 mg/g, or from 0.1 to 7 mg/g of fortifier;

- ingredients providing GSLT6 in an amount ranging from 0.1 to 10 mg/g, or from 0.025 to 2.5 mg/g, or from 0.02 to 2 mg/g of fortifier;

- ingredients providing LnNT in an amount ranging from 0.1 to 25 mg/g, or from 0.025 to 6.25 mg/g, or from 0.02 to 5 mg/g of fortifier;

- ingredients providing LNT in an amount ranging from 0.5 to 55 mg/g, or from 0.125 to 13.75 mg/g, or from 0.1 to 11 mg/g of fortifier;

- ingredients providing 6'-SL in an amount ranging from 5 to 55 mg/g, or from 1.25 to 13.75 mg/g, or from 1 to 11 mg/g of fortifier; And

- ingredients providing SLTNTC in an amount ranging from 1 to 60 mg/g, or from 0.25 to 15 mg/g, or from 0.2 to 12 mg/g of fortifier;

or their mixtures.

n) The human milk fortifier composition according to any of embodiments a) or g) to m), which is in the form of a powder for dissolving in breast milk.

o). A human milk fortifier composition according to any embodiment of a) or g) to m) for use in human milk fortification or fortified human milk.

p) The use of a human milk fortifier according to any of embodiments a) to o) to optimize the growth and development of a premature infant with HRH and/or HRH.

q) A human milk fortifier composition according to any embodiment of a) to o) for use in maintaining healthy growth and development of preterm infants with LHR and/or HHCR at the time of hospital discharge.

r) A human milk fortifier composition according to any of a) to o) or q) for use in the prevention and/or treatment of a condition selected from the group consisting of growth and/or development failure, growth retardation, infection, disease lung, developmental delays, blindness and/or metabolic bone disease.

s) A package containing a human milk fortifier composition according to any one of a) to o) or q), which is a single dosing device or a multiple dosing device.

All options described in the above description should be interpreted as illustrative and not in a limiting sense.

Claims (134)

1. A human breast milk fortifier composition comprising: - copper; - selenium; - zinc; - alpha-lactalbumin; - casein; - lactoferrin; - alpha-tocopherol; - gamma-tocopherol; - nicotinic acid; - retinol; - DFSLTHN; - FSLTNH3; - GSLT6; - LNT; - LNT; - 6'-SL; And - SLTNTC. 2. A human breast milk fortifier composition according to claim 1, wherein the composition contains: - copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof; - sodium selenite, sodium selenate, sodium hydroselenite or mixtures thereof; - zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof; - milk (eg whole or skimmed milk), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - purified or synthesized lactoferrin, whey protein isolate, whey protein concentrate or mixtures thereof; - D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000 or mixtures thereof; - nicotinic acid, nicotinamide or mixtures thereof; - retinol, retinyl acetate, retinyl palmitate or mixtures thereof; - difucosyllacto-N-hexaose-a; - monofucosyllacto-N-hexaose-III; - 6'-galactosyl lactose; - lacto-N-neotetraose; - lacto-N-tetraose; - 6'-sialyllactose or sodium salt of 6'-sialyllactose; and/or - sialillacto-N-tetraose-s. 3. The composition of the breast milk fortifier according to claim 1 or 2 for dissolution in breast milk, containing: - copper in an amount in the range of 5 to 30 µg/100 ml, for example 8 to 28 µg/100 ml of fortified breast milk; - selenium in an amount ranging from 0.1 to 10 µg/100 ml, for example from 0.3 to 8 µg/100 ml, of fortified breast milk; - zinc in an amount in the range of 50 to 550 µg/100 ml, for example 100 to 500 µg/100 ml of fortified breast milk; - alpha-lactalbumin in an amount ranging from 25 to 180 mg/100 ml, for example from 30 to 150 mg/100 ml of fortified breast milk; - casein in an amount ranging from 10 to 500 mg/100 ml, for example from 20 to 400 mg/100 ml, enriched breast milk; - lactoferrin in an amount ranging from 10 to 500 mg/100 ml, for example from 20 to 400 mg/100 ml of fortified breast milk; - alpha-tocopherol in an amount ranging from 5 to 1800 µg/100 ml, for example from 10 to 1700 µg/100 ml, of fortified breast milk; - gamma-tocopherol in an amount ranging from 0.1 to 50 μg/100 ml, for example from 0.2 to 40 μg/100 ml, of fortified breast milk; - nicotinic acid in an amount ranging from 0.5 to 18 µg/100 ml, for example from 1 to 15 µg/100 ml, of fortified breast milk; - retinol in an amount in the range of 1 to 250 μg/100 ml, for example 5 to 200 μg/100 ml of fortified breast milk; - DFSLTHN in an amount in the range of 5 to 25 mg/100 ml, eg 8 to 15 mg/100 ml of fortified breast milk; - FSLTNH3 in an amount in the range of 0.5 to 35 mg/100 ml, eg 5 to 20 mg/100 ml of fortified breast milk; - GSLT6 in an amount ranging from 0.1 to 10 mg/100 ml, for example from 1 to 5 mg/100 ml of fortified breast milk; - LnNT in an amount ranging from 0.1 to 25 mg/100 ml, for example from 1 to 10 mg/100 ml of fortified breast milk; - LNT in an amount in the range of 0.5 to 55 mg/100 ml, eg 5 to 30 mg/100 ml of fortified breast milk; - 6'-SL in an amount ranging from 5 to 355 mg/100 ml, for example from 15 to 35 mg/100 ml, fortified breast milk; And - SLTNTC in an amount ranging from 1 to 60 mg/100 ml, for example from 1 to 30 mg/100 ml, of fortified breast milk. 4. The composition of the breast milk fortifier according to claim 1, containing: - copper in an amount ranging from 5 to 30 µg/g, or from 1.5 to 7.50 µg/g, or from 1 to 6 µg/g of enrichment agent, e.g. copper (II) carbonate, copper (II) citrate ), copper (II) gluconate, copper (II) sulfate, copper (II) complex with lysine, or mixtures thereof; - selenium in an amount ranging from 0.1 to 10 µg/g, or from 0.0025 to 25 µg/g, or from 0.002 to 0.2 µg/g of an enricher, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof; - zinc in an amount ranging from 50 to 550 µg/g, or from 12.5 to 137.5 µg/g, or from 10 to 110 µg/g of fortifier, e.g. zinc acetate, zinc chloride, zinc citrate, gluconate zinc, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof; - alpha-lactalbumin in an amount ranging from 25 to 180 mg/g, or from 6.25 to 45 mg/g, or from 5 to 30 mg/g of a fortifier, for example milk (for example, whole or skimmed milk), whey protein (eg isolates or concentrates), milk powder source or mixtures thereof; - caseins in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g fortifier, e.g. milk (e.g. whole or skimmed milk), milk protein whey (eg isolates or concentrates), milk powder sources or mixtures thereof; - lactoferrin in an amount ranging from 10 to 500 mg/g, or from 2.5 to 125 mg/g, or from 2 to 100 mg/g of fortifier, e.g. purified or synthesized lactoferrin, whey protein isolate, protein concentrate whey or mixtures thereof; - alpha-tocopherol in an amount ranging from 5 to 1800 µg/g, or from 1.25 to 450 µg/g, or from 1 to 360 µg/g fortifier, for example D-alpha-tocopherol, DL-alpha- tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate polyethylene glycol-1000 conjugate, or mixtures thereof; - gamma-tocopherol in an amount ranging from 0.1 to 50 µg/g, or from 0.025 to 12.5 µg/g, or from 0.02 to 10 µg/g of fortifier; - nicotinic acid in an amount ranging from 0.5 to 18 µg/g, or from 0.25 to 4.25 µg/g, or from 0.1 to 3.6 µg/g of a fortifier, for example nicotinic acid, nicotinamide or mixtures thereof; - retinol in an amount ranging from 1 to 250 µg/g, or from 0.25 to 62.5 µg/g, or from 0.2 to 50 µg/g of an enricher, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof ; - DFSLTHN in an amount ranging from 5 to 25 mg/g, or from 1.25 to 6.25 mg/g, or from 1 to 5 mg/g of an enricher, for example difucosyllacto-N-hexaose-a; - FSLTNH3 in an amount ranging from 0.5 to 35 mg/g, or from 0.125 to 8.75 mg/g, or from 0.1 to 7 mg/g of an enricher, for example monofucosyllacto-N-hexaose-III; - GSLT6 in an amount ranging from 0.1 to 10 mg/g, or from 0.025 to 2.5 mg/g, or from 0.02 to 2 mg/g of an enricher, for example 6'-galactosyl lactose; - LnNT in an amount ranging from 0.1 to 25 mg/g, or from 0.025 to 6.25 mg/g, or from 0.02 to 5 mg/g of an enricher, such as lacto-N-neotetraose; - LNT in an amount ranging from 0.5 to 55 mg/g, or from 0.125 to 13.75 mg/g, or from 0.1 to 11 mg/g of an enricher, for example lacto-N-tetraose; - 6'-SL in an amount ranging from 5 to 55 mg/g, or from 1.25 to 13.75 mg/g, or from 1 to 11 mg/g of an enricher, for example 6'-sialyllactose or sodium salt 6'-sialyllactose; And - SLTNTC in an amount ranging from 1 to 60 mg/g, or from 0.25 to 15 mg/g, or from 0.2 to 12 mg/g of an enricher, for example sialyllacto-N-tetraose-c. 5. The composition of the breast milk fortifier according to claim 1, containing: - copper in an amount ranging from 79 to 253 micrograms, or from 87 to 238 micrograms, or from 107 to 202 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper sulfate ( II), a complex of copper (II) with lysine or mixtures thereof; - selenium in an amount ranging from 1 to 7 μg, or from 2 to 6 μg, or from 2 to 5 μg, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof; - zinc in an amount ranging from 1220 to 3880 µg, or from 1340 to 3640 µg, or from 1640 to 3090 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof; - alpha-lactalbumin in an amount ranging from 0.4 to 1.31, or from 0.45 to 1.23 g, or from 0.55 to 1.05 g, for example milk (for example, whole or skimmed milk ), whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - caseins in an amount ranging from 0.82 to 2.60 g, or from 0.90 to 2.44 g, or from 1.10 to 2.07 g, for example milk (for example, whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - lactoferrin in an amount ranging from 0.50 to 1.58 g, or from 0.55 to 1.58 g, or from 0.67 to 1.26 g, for example, purified or synthesized lactoferrin, whey protein isolate , whey protein concentrate or mixtures thereof; - alpha-tocopherol in an amount ranging from 2.39 to 7.60 mg, or from 2.64 to 7.13 g, or from 3.21 to 6.06 mg, for example D-alpha-tocopherol, DL -alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000, or mixtures thereof; - gamma-tocopherol in an amount ranging from 0.04 to 0.13 mg, or from 0.05 to 0.13 mg, or from 0.06 to 0.11 mg; - nicotinic acid in an amount ranging from 2.44 to 7.74 μg, or from 2.68 to 7.26 μg, or from 3.27 to 6.17 μg, for example nicotinic acid, nicotinamide or mixtures thereof; retinol in an amount ranging from 0.24 to 0.75 mg, or from 0.26 to 0.70 mg, or from 0.32 to 0.60 mg, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof; - DFSLTHN in an amount ranging from 40 to 128 mg, or from 44 to 120 mg, or from 54 to 102 mg, for example difucosyllacto-N-hexaose-a; - FSLTNH3 in an amount ranging from 45 to 145 mg, or from 50 to 135 mg, or from 61 to 115 mg, for example monofucosyllacto-N-hexaose-III; - GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose; - LnNT in an amount ranging from 47 to 151 mg, or from 52 to 142 mg, or from 64 to 120 mg, for example lacto-N-neotetraose; - LNT in an amount ranging from 87 to 279 mg, or from 96 to 262 mg, or from 118 to 222 mg, for example lacto-N-tetraose; - 6'-SL in an amount ranging from 132 to 421 mg, or from 146 to 395 mg, or from 178 to 336 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And - SLTNTC in an amount ranging from 139 to 443 mg, or from 153 to 415 mg, or from 187 to 353 mg, for example sialyl lacto-N-tetraose-c. 6. The composition of the breast milk fortifier according to claim 1, containing: - copper in an amount ranging from 26 to 84 micrograms, or from 29 to 79 micrograms, or from 35 to 67 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper sulfate ( II), a complex of copper (II) with lysine or mixtures thereof; - selenium in an amount ranging from 0.33 to 2.33 µg, or from 0.66 to 2 µg, or from 0.66 to 1.66 µg, for example sodium selenite, sodium selenate, sodium hydroselenate or mixtures thereof ; - zinc in an amount ranging from 406 to 1293 µg, or from 447 to 1213 µg, or from 546 to 1030 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof; - alpha-lactalbumin in an amount ranging from 0.13 to 0.44 or from 0.15 to 0.41 g or from 0.18 to 0.35 g, for example milk (for example whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - caseins in an amount ranging from 0.27 to 0.87 g, or from 0.30 to 0.81 g, or from 0.37 to 0.69 g, for example milk (for example, whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - lactoferrin in an amount ranging from 0.17 to 0.53 g, or from 0.18 to 0.53 g, or from 0.22 to 0.42 g, for example, purified or synthesized lactoferrin, whey protein isolate , whey protein concentrate or mixtures thereof; - alpha-tocopherol in an amount ranging from 0.80 to 2.53 mg, or from 0.88 to 2.38 mg, or from 1.07 to 2.02 mg, for example D-alpha-tocopherol, DL -alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000, or mixtures thereof; - gamma-tocopherol in an amount ranging from 0.013 to 0.04 mg, or from 0.016 to 0.04 mg, or from 0.02 to 0.037 mg; - nicotinic acid in an amount ranging from 0.81 to 2.58 μg, or from 0.89 to 2.42 μg, or from 1.09 to 2.06 μg, for example nicotinic acid, nicotinamide or mixtures thereof; retinol in an amount ranging from 0.08 to 0.25 mg, or from 0.08 to 0.23 mg, or from 0.10 to 0.20 mg, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof; - DFSLTHN in an amount ranging from 13 to 43 mg, or from 14 to 40 mg, or from 18 to 34 mg, for example difucosyllacto-N-hexaose-a; - FSLTNH3 in an amount ranging from 15 to 48 mg, or from 16 to 45 mg, or from 20 to 39 mg, for example monofucosyllacto-N-hexaose-III; - GSLT6 in an amount ranging from 21 to 68 mg, or from 23 to 64 mg, or from 28 to 54 mg, for example 6'-galactosyl lactose; - LnNT in an amount ranging from 15 to 51 mg, or from 17 to 47 mg, or from 21 to 40 mg, for example lacto-N-neotetraose; - LNT in an amount ranging from 29 to 93 mg, or from 32 to 87 mg, or from 39 to 74 mg, for example lacto-N-tetraose; - 6'-SL in an amount ranging from 44 to 140 mg, or from 48 to 132 mg, or from 59 to 112 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And - SLTNTC in an amount ranging from 46 to 148 mg, or from 51 to 138 mg, or from 62 to 118 mg, for example sialyllacto-N-tetraose-c. 7. The composition of the breast milk fortifier according to claim 1, containing: - copper in an amount ranging from 13 to 42 micrograms, or from 14 to 40 micrograms, or from 17 to 34 micrograms, for example copper (II) carbonate, copper (II) citrate, copper (II) gluconate, copper sulfate ( II), a complex of copper (II) with lysine or mixtures thereof; - selenium in an amount ranging from 0.165 to 1.165 μg, or from 0.33 to 1 μg, or from 0.33 to 0.84 μg, for example sodium selenite, sodium selenate, sodium hydroselenite or mixtures thereof; - zinc in an amount ranging from 203 to 647 µg, or from 223 to 606 µg, or from 273 to 515 µg, for example zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc lactate, zinc oxide, zinc sulfate, zinc carbonate or mixtures thereof; - alpha-lactalbumin in an amount ranging from 0.06 to 0.22 or from 0.07 to 0.21 g or from 0.09 to 0.17 g, for example milk (for example whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - caseins in an amount ranging from 0.13 to 0.44 g, or from 0.15 to 0.41 g, or from 0.18 to 0.35 g, for example milk (for example, whole or skimmed milk) , whey protein (eg isolates or concentrates), powdered milk sources or mixtures thereof; - lactoferrin in an amount ranging from 0.08 to 0.27 g, or from 0.09 to 0.27 g, or from 0.11 to 0.21 g, for example, purified or synthesized lactoferrin, whey protein isolate , whey protein concentrate or mixtures thereof; - alpha-tocopherol in an amount ranging from 0.40 to 1.27 mg, or from 0.44 to 1.19 mg, or from 0.54 to 1.01 mg, for example D-alpha-tocopherol, DL -alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, DL-alpha-tocopheryl succinate, DL-alpha-tocopheryl succinate conjugate with polyethylene glycol-1000, or mixtures thereof; - gamma-tocopherol in an amount ranging from 0.006 to 0.02 mg, or from 0.008 to 0.02 mg, or from 0.01 to 0.018 mg; - nicotinic acid in an amount ranging from 0.40 to 1.29 μg, or from 0.44 to 1.21 μg, or from 0.54 to 1.03 μg, for example nicotinic acid, nicotinamide or mixtures thereof; - retinol in an amount ranging from 0.04 to 0.13 mg, or from 0.04 to 0.12 mg, or from 0.05 to 0.10 mg, for example retinol, retinyl acetate, retinyl palmitate or mixtures thereof; - DFSLTHN in an amount ranging from 6 to 22 mg, or from 7 to 20 mg, or from 9 to 17 mg, for example difucosyllacto-N-hexaose-a; - FSLTNH3 in an amount ranging from 7 to 24 mg, or from 8 to 23 mg, or from 10 to 20 mg/g, for example monofucosyllacto-N-hexaose-III; - GSLT6 in an amount ranging from 10 to 34 mg, or from 12 to 32 mg, or from 14 to 27 mg, for example 6'-galactosyl lactose; - LnNT in an amount ranging from 7 to 26 mg, or from 8 to 24 mg, or from 10 to 20 mg, for example lacto-N-neotetraose; - LNT in an amount ranging from 15 to 47 mg, or from 16 to 44 mg, or from 18 to 37 mg/g, for example lacto-N-tetraose; - 6'-SL in an amount ranging from 22 to 70 mg, or from 24 to 61 mg, or from 28 to 56 mg, for example 6'-sialyllactose or 6'-sialyllactose sodium salt; And - SLTNTC in an amount ranging from 23 to 74 mg, or from 25 to 69 mg, or from 31 to 59 mg, for example sialyllacto-N-tetraose-c. 8. Composition breast milk fortifier according to any one of paragraphs. 1-7 having a calorific value ranging from 0 to 4.57 kcal/g of fortifier. 9. The composition of the breast milk fortifier according to any one of paragraphs. 1 or 4-7, which is in powder form. 10. The composition of the breast milk fortifier according to any one of paragraphs. 1 or 4-8 which is in the form of a liquid, such as a solution or suspension in water. 11. The use of the breast milk fortifier composition according to any one of paragraphs. 1-7 to optimize the growth and development of an infant born prematurely with extremely low birth weight (ELBW) and/or very low birth weight (VLBW). 12. The use of a breast milk fortifier composition according to any one of paragraphs. 1-10 to support healthy growth in preterm infants with LVR and/or LVR at the time of discharge from the hospital. 13. The use of a breast milk fortifier composition according to any one of paragraphs. 1-10 for the prevention and/or treatment of a condition selected from the group consisting of growth and/or development failure, growth retardation, infection, lung disease, developmental delays, blindness, and/or metabolic bone disease. 14. A package containing a breast milk fortifier composition according to any one of paragraphs. 1-10, which is a single dosing device or a multiple dosing device. 15. The use of the breast milk fortifier composition according to claim 12 to support the healthy growth of infants born prematurely with LLWR and/or BHWR at the time of discharge from the hospital, and it is administered to infants born prematurely with LBW and/or BHWR during the period postmenstrual age from 38 to 48 weeks, for example during the period of postmenstrual age from 38 to 43 weeks or from 38 to 42 weeks. 16. The use of a breast milk fortifier composition according to any one of paragraphs. 1-4 for breast milk fortification. 17. The use of a breast milk fortifier composition according to any one of paragraphs. 1 or 5-7 as an additive for administration as a separate composition.

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