STABLE AQUEOUS COMPOSITION COMPRISING OLIGOSACCHARIDES.

Abstract

The present invention relates to a stable aqueous composition comprising oligosaccharides having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition ranges from 5.5 to 6.5.5.

Description

STABLE AQUEOUS COMPOSITION COMPRISING QUOGOSACCHARIDES FIELD OF INVENTION The present invention relates to a stable aqueous composition comprising oligosaccharides having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3. The invention further relates to the use of such aqueous composition as a milk fortifier or supplement for infants, in particular, infants born by cesarean section, premature infants, or infants who are small for gestational age and / or who had a low or very low birth weight (LWB or VLBW). The invention further relates to a method for preventing isoflavonization of the glucose unit at the reducing end of such oligosaccharides during heat treatment in aqueous compositions. BACKGROUND OF THE INVENTION Breast milk is recommended for all infants. However, in some cases, breastfeeding is inadequate or unsuccessful for medical reasons, or the mother chooses not to breastfeed. Infant formulas were developed for these situations. In addition, fortifiers and supplements have been developed to enrich breast milk or infant formula with specific ingredients. The importance of oligosaccharides contained in human breast milk (human milk oligosaccharides, HMQs) is well recognized in the scientific community as key to supporting digestive health, intestinal and / or mucosal maturation, and / or immune maturation in infants. Consequently, when an infant's diet lacks such nutrients (because the infant receives infant formulas that do not contain HMOs) or when the amount of HMOs in the human breast milk or formula the infant receives is inadequate for their needs, a composition that provides HMOs in the form of a supplement to be administered to the infant or dissolved in their feed would be desirable. In particular, an aqueous liquid composition comprising HMO would be necessary. Aqueous liquid compositions for whole nutrition must be microbiologically safe. Often, oligosaccharides cannot be sufficiently concentrated in an aqueous solution to achieve a microbiologically safe low water activity, because the resulting high density does not allow for easy application of the feed due to high viscosity and because many oligosaccharides begin to crystallize in a high-density solution. To address the problem, aseptic filling or retort sterilization can be implemented, but such procedures cause, during heat treatment, the isomerization of the oligosaccharide-reducing terminal monosaccharides. Consequently, an aqueous liquid composition comprising HMO is necessary that does not incur isomerization of the reducing terminal monosaccharides of oligosaccharides when subjected to heat treatments. Additionally, storage frequently alters the structure and function of oligosaccharides and, consequently, the quality of oligosaccharide products in aqueous compositions over time. Therefore, an aqueous liquid composition comprising HMO and exhibiting stability for oligosaccharides over time is required. Furthermore, an aqueous liquid composition comprising HMD must be characterized by respecting infant physiology when such composition is administered, either as a standalone supplement or dissolved in human breast milk. For example, an overly acidic pH in the aqueous solution is unsuitable for administration to infants. This is particularly relevant when the recipient of the aqueous solution is a premature infant, one who is small for gestational age, and / or who had a low or very low birth weight (LWB or VLBW). Therefore, an aqueous liquid composition comprising HMO is necessary that does not alter infant physiology such as acid-base balance to avoid acidosis when such a composition is administered. Accordingly, one object of the present invention is to identify a solution for preventing the isomerization of the reducing terminal monosaccharides of oligosaccharides in aqueous compositions. Furthermore, another object of the present invention is to prevent the degradation of oligosaccharides in aqueous compositions during storage. Additionally, another object of the present invention is to provide an aqueous liquid composition comprising HMOs that do not alter infant physiology when administered. BRIEF DESCRIPTION OF THE INVENTION The inventors discovered, surprisingly, that mild acidification, to a pH that can vary from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, of an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end stabilized such oligosaccharide against isophosphate formation. Very surprisingly, the levo acidification also prevented hydrolysis during storage. Accordingly, in one aspect, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another aspect, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, for use as a milk fortifier or supplement for infants, particularly infants who were born by cesarean section, who were born prematurely or who are small for gestational age and / or who had a low or very low birth weight (LWB or VLBW). In another aspect, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, for use in supporting digestive health, intestinal and / or mucosal maturation, and / or immune maturation in infants, particularly infants born by cesarean section, who were born prematurely or who are small for gestational age and / or who had a low or very low birth weight (LWB or VLBW). In an additional aspect, the present invention further provides the use of an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition ranges from 5.6 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, as a milk fortifier or supplement for infants, in particular infants who were born by cesarean section or who were born prematurely, or who are small for gestational age and / or who had a low or very low birth weight (LWB or VLBW). In an additional aspect, the present invention provides a method for preventing isomization in aqueous compositions during the heat treatment of oligosaccharides having a glucose unit at the reducing end, such method comprising: a) Provide an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end; b) Adjust the pH of the aqueous composition to a value that varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2; c) Optionally, subject the aqueous composition to a heat treatment. In another aspect, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 6.9 to 6.2, which is packaged in a single-dose unit BRIEF DESCRIPTION OF THE FIGURES The additional features and advantages of the present invention are described in, and will be evident from, the description of the embodiments, which are set forth below with reference to the figures in which: Figure 1 reports the analysis of fructose isomers of 2'FL and LNnT, as well as the degradation products of 2'FL and LNnT during the sterilization and storage process as described in Example 1. Figure 2 reports the analysis of Example 2 to determine 2FL (Figure 2a), LNnT (Figure 2d), the fructose isomers of the added 2'FL (indicated as FL lactutose in the graphs, Figure 2d) and of the added LNnT (indicated as LNnT isomer in the graphs, Figure 2e). as well as the bed for its degradation products (lactose, Figure 2c). Figure 3 reports the pH values ​​over time for the oligosaccharide solutions of Example 2 (starting respectively at pH 6 and 7), DETAILED DESCRIPTION OF THE INVENTION Definitions Within the context of the present invention, the term “monosaccharide” refers to carbohydrates containing from 3 to 6 carbon atoms. They can be polyhydroxy aldehydes or polyhydroxy ketones, depending on whether they comprise either an aldehyde or a ketone group, along with -OH substituted carbons in a chain. Polyhydroxy aldehydes are called “aldoses.” Polyhydroxy ketones are called “celloses.” Non-limiting examples of 6-carbon monosaccharides (hexose) are: allose, altrose, glucose, mannose, gulose, idase, galactose, latose, psilose, fructose, sorbose, and tagatose. Non-limiting examples of 5-carbon monosaccharides (pentose) are: ribose, arabinose, xylose, lyxose, ributose, and xylulose. In the context of the present invention, the term “oligosaccharide” indicates a linear or branched saccharide polymer containing a small amount (typically two out of ten) of simple sugars (5 or 6 member monosaccharides as defined above). Within the context of the present invention, the term “reducing end” for the oligosaccharide unit identifies the terminal monosaccharide with a free 5 anomeric carbon that does not participate in a glycosidic bond. Within the context of the present invention, the term “anomeric carbon” identifies the carbonyl carbon of a monosaccharide in its acyclic form. Depending on the position assumed by the -OH group attached to the anomeric carbon when the monosaccharide is in cyclic form (chair conformation), the configuration of said carbon is defined as ά (alpha) or β (beta) if the -OH group is axial or equatorial, respectively. In the context of the present invention, the term "oligosaccharide having a glucose unit at the reducing end" identifies an oligosaccharide molecule as defined above that has a glucose unit at the reducing end. Non-limiting examples of such oligosaccharides are: a) Certain “fucose-based oligosaccharides” based on lactose, that is, an oligosaccharide that has at least one fucose residue and a glucose at the reducing end. Some examples are 2'-FL (2' fucosyl lactose), 3-FL (3-fucosyl lactose), difucosyl lactose (DEL, also known as 2' LDFT, Laotodifucosyltetraose), lacto-N-fucopentaose (e.g., laolo-N-fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, laotoN-fucopentaose V), lacto-N-fucohexaose, lacto-N-difucohexaose L, fucosyl lacto-N-hexaose, fucosyl lacto-N-neohexaose, difucosyl lacto-N-hexaose II, difucosyl lacto-N-neohexaose II, and any combination of these. b) Certain “digosaccharide(s)” based on lactose, that is, an oligosaccharide having at least one residue of α-acetylagatosam and / or N-acetylagatosam and a glucose at the reducing end. Some examples are LNT (lacto-N-tetraose), para-lacto-N-neohexaose (para-LNnH), LMnT (lacto-N-neotetraose) or any combination thereof. Other examples are lacto-N-hexose, lacto-N-neohexaose, para-lacto-N-hexaose, para-lacto-N-neohexaose, lacto-N-octaose, lacto-N-neooctaose, isolato-N-octaose, para-lacto-N-octaose and lacto-N-octaose. c) Certain lactose-based “sialyl oligosaccharides”, that is, an oligosaccharide that has at least one sialic acid residue. It has an acidic nature. Some examples are 3'-SL (3' sialyl lactose) and 6'-SL (6' sialyl lactose). In the context of the present invention, the term “oligosaccharide having a glucose unit at the reducing end” also includes salts of such oligosaccharides. Similarly, when referring to specific oligosaccharides derived from human tissue, the salts of such oligosaccharides are also included within the scope of that terminology. In the context of the present invention, the expressions “fucosylated oligosaccharides comprising an α'-fucosyl epitope” and “2-fucosylated oligosaccharides” encompass fucosylated oligosaccharides with a certain homology of form since they contain an α'-fucosyl epitope; therefore, a certain homology of function can be expected. In the context of the present invention, the expression “at least one fucosylated oligosaccharide” and “at least one N-acetylated oligosaccharide” means “at least one 5.10 fusified oligosaccharide type” and “at least one N-acetyl oligosaccharide type”. In the context of the present invention, the term “aqueous compositions” identifies liquid compositions that may be solutions and / or dispersions of at least one oligosaccharide in an aqueous medium. In the context of the present invention, the term “isomerization” indicates the process where the three-dimensional arrangement of atoms in a molecule changes, producing a new molecule with the same number of atoms but with a different structure. In the context of the present invention, the term “pH modulator” indicates a substance that has the ability to affect (i.e., decrease, increase, or stabilize) the pH of an aqueous solution. Non-limiting examples of pH modulators are strong and mild acids (organic or inorganic), acidic oligosaccharides, strong and mild bases (organic or inorganic), and regulators (organic or inorganic). inorganics).Non-limiting examples of organic acids are: citric acid, phosphoric acid, lactic acid, and sialic acid. Non-limiting examples of inorganic bases are: potassium hydroxide (KOH) and sodium hydroxide (NaOH). Non-limiting examples of acidic oligosaccharides are sialic acid [1-acetylneuraminic acid (Neu5Ac)] and antico acids (glucuronic acid, galacturonidase). In the context of the present invention, the term “regulator” or “regulating agent” indicates a substance that has the ability to stabilize the pH of an aqueous solution within a certain narrow pK range. Regulating agents may be combined and / or dissolved in water to provide a buffer solution, which is also included within the scope of the term “regulator” and / or “regulating agent.” Non-limiting examples of regulating agents are citric acid, acetic acid, and phosphate salts (sodium or potassium). Non-limiting examples of solutions. Regulators are: Phosphate regulator (based on 2 phosphate salts, for example, monobasic sodium phosphate and dibasic sodium phosphate) and phosphate-citrate regulator (for example, McIlvaine regulator - based on citric acid and disodium phosphate). In the context of the present invention, the term “fortifying” refers to a composition comprising one or more nutrients that have a nutritional benefit for infants. The term “milk fortifier” means any composition used to fortify or supplement human breast milk, infant formula, growing-up milk, or human breast milk fortified with other nutrients. Accordingly, the human milk fortifier of the present invention may be administered after dissolution in human breast milk, infant formula, growing-up milk, or human breast milk fortified with other nutrients, or may be administered as a standalone composition. When administered as a standalone composition, the human milk fortifier of the present invention may be further identified as a 'supplement'. In one embodiment, the milk fortifier of the present invention is a supplement. The term “human breast milk fortifier” means any composition used to fortify or supplement human breast milk, or human breast milk fortified with other nutrients. In the context of the present invention, the expression “composition having a pH that varies from value X to value Y” identifies compositions that have a pH range that has a specified value within the indicated range (the extremes X and Y of the range are included), as well as compositions that have a pH that varies within the indicated range (the extremes X and Y of the range are included). Modalities of the invention Qlaogaglndos In one embodiment, the aqueous composition according to the present invention comprises two or more oligosaccharides having a glucose unit at the reducing end. In one embodiment, the aqueous composition according to the present invention comprises two oligosaccharides having a glucose unit at the reducing end. In one embodiment, the aqueous composition according to the present invention comprises three oligosaccharides having a glucose unit at the reducing end. In one embodiment, the aqueous composition according to the present invention comprises five oligosaccharides having a glucose unit at the reducing end. In one embodiment, the aqueous composition according to the present invention comprises six oligosaccharides having a glucose unit at the reducing end. In one embodiment, the aqueous composition according to the present invention comprises seven oligosaccharides having a glucose unit at the 20-end. In one embodiment, in the aqueous composition according to the present invention, the at least one oligosaccharide having a glucose unit at the reducing end is selected from the group consisting of: 2FFL, 3-SL, β-SL, DFL, LNnT, LNT, and 3-FL. In another embodiment, in the aqueous composition according to the present invention, the ai less an oligosaccharide having a glucose unit at the reducing end is selected from the group consisting of: 2-FL, 3'-SL, 6-SL, DFL, LNnT and LNT. In one embodiment, the aqueous composition according to the present invention comprises two oligosaccharides having a glucose unit at the reducing S-terminus and selected from the group consisting of: S'-FL, 3-FL, S'-SL, 6-SL, ÓFU LNnT and LNT, for example, being 2-FL and LNnT. In one embodiment, the present invention provides an aqueous composition as defined above comprising 2-FL and LNnT in a 10:1 ratio. In another embodiment, the present invention provides an aqueous composition as defined above comprising 2'-FL and LNnT in a 2:1 ratio. In one embodiment, the aqueous composition according to the present invention comprises three oligosaccharides having a glucose unit at the reducing end and selected from the group consisting of 2-FL, 3-FL, 3'-SL, 6'-SL, DFL, LNnT and LNT. In one embodiment, the present invention provides an aqueous composition as defined above comprising 2LFL, DFL and LNT in a ratio of 10:1:3-33, In one embodiment, the aqueous composition according to the present invention comprises five atagasaccharides having a glucose unit at the reducing end and selected from the group consisting of: 2'-FL, 3-FL, 3'-SL, 0SL, DFL, LNnT and LNT, for example, 2'-FL, 3'-SL, 6'-SL, DFL and LNT. In another embodiment, the present invention provides an aqueous composition 25 as defined above comprising 2'-FL, DFL, LNT, 5'-SL and 3'-SL in a ratio of 10:1:3.33:17; 1,2, In one embodiment, the aqueous composition according to the present invention comprises six ols having a glucose unit at the reducing end and selected from the group consisting of: 2-6, 3-FL, S'-SL, 6''-SL, DEL, δ LNnTy LNT, for example, 2-FL, S'-SL, 6-SL, DEL and LNT In one embodiment, the present invention provides an aqueous composition as defined above comprising 2'-FL, DFL, LNT, LNnT, 6'-SL and 3* SL in a ratio of 10:1: 3.33: 1.1: 17: 1.2. In one embodiment, the aqueous composition according to the present Invention comprises seven oligosaccharides having a glucose unit at the reducing end and being 2-FL, 3-FL, 3-SL, 6'-SL, DFL, LNnT and LNT, In another embodiment, the present invention provides an aqueous composition as defined above comprising Z-FL, DEL, 3-FL, LNT, LNnT, Ó'-SL and 3'-SL in a ratio of 10:1:2.5:3.33:1.1:17:1.2, pH range In one embodiment, the aqueous composition according to the invention has a pH ranging from 5.5 to 6.5. In an additional embodiment, the aqueous composition according to the invention has a pH ranging from 5.8 to 6.3. In another embodiment, the aqueous composition according to the invention has a pH ranging from 5.9 to 6.2, In another embodiment, the aqueous composition according to the invention has a pH of approximately 6, pH modulators As the expert in the technique can understand, the pH of the composition The aqueous composition can also be affected by the intrinsic acidity / basicity of the composition's ingredients and can then be modulated by using an appropriate pH modulator. For example, human tissue oligosaccharides added in crystalline form can contribute to an acidic pH if the material contains residual acetic acid from the crystallization process. This acidic pH can be adjusted and stabilized within the pH range according to the invention by using suitable pH modulators. In one embodiment, the aqueous composition according to the invention has a pH ranging from 5.5 to 5.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, which is achieved by adding one or more pH modulators. In one embodiment, the pH modulator is an organic acid. Any organic acid can be used as a technical aid to generate stable oligosaccharide solutions.Preferably, citric acid, sialic acid [also known as N-acetylneuraminic acid (Neu5Ac)], melic acid, or lactic acid can be used. In another embodiment, the pH modulator is an acidic oligosaccharide. In this case, oligosaccharides containing sialic acid (N-acetylneuraminic acid, NeuSAc) or oligosaccharides containing uronic acids (glucuronic acid, 20 25) can be used. Typical examples are pectin-derived oligosaccharides for oligosaccharides containing uronic acid. Advantageously, if the oligosaccharides containing sialic acid [N-acetylneuraminic acid (Neu5Ac)] are part of the oligosaccharide mixture in the compositions according to the invention, the acidic oligosaccharide itself can be used to acidify and stabilize the solution so that the acidic oligosaccharide... It also plays the role of a pH modulator. Typical examples are 3' and 6'-sialyl lactose for oligosaccharides containing sialic acid. In another form, the pH modulator is an inorganic base, for example, KOH or NaOH. In one embodiment, the pH modulator further consists of or comprises a buffering agent, for example, a phosphate buffer or a phosphate-citrate buffer (also known as a McHvaine buffer, based on a mixture of citric acid and disodium phosphate). As can be inferred from the data reported in Figure 3, Example 2, surprisingly, there is a natural decrease in the pH levels of the aqueous compositions of the invention. It is understood that the pH must remain relatively stable within certain values ​​during storage to ensure that the aqueous composition comprising HMO remains suitable for administration to infants, particularly premature infants, and to respect their physiology. Consequently, the option of including a regulating agent in the composition offers the additional advantage of allowing the pH to remain stable over time. Aqueous compositions In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 0 or from 5.9 to 6.2, In one embodiment, the present invention provides an aqueous composition comprising at least an oligosaccharide having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of the aqueous composition ranges from 5.5 to 6.5. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of said aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being 2'-FL and LNnT. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6, for example, from 5.8 to 6.3 or from 5.9 to 6.2, In a further embodiment, the present invention provides an aqueous 25 uornposKinn comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a 5-glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being 2-FL, 3'-SL, 6'-SL, DFL, and LNT. In another additional embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 4.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another additional embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, a pH modulator, a regulating agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another additional embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a unit of glucose at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being 2-FU, 3-SL, 6-SL, DFL, LNnT, and LNT. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the at least one oligosaccharide. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2.In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end, a pH modulator, and a buffering agent, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition comprises no other nutrients besides the oligosaccharide. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition comprises no other nutrients besides the oligosaccharide. In another embodiment, the present invention provides an aqueous composition 25 comprising two oligosaccharides having a glucose unit at ai. extreme reducing agent, a pH modulator and wherein the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise other nutrients besides oligosaccharides. In another embodiment, the present invention provides an aqueous composition 5 comprising two oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of the aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In another embodiment, the present invention provides an aqueous composition W comprising two oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides are 2-FL and LNnT, and the composition does not comprise any nutrients other than the oligosaccharides. In an additional embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition comprises no other nutrients besides the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being 2'-FL, 3-SL, 6-SL, DFL and LNT, and the composition comprising no other nutrients besides the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 8.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, a pH modulator, and wherein the pH of such aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, 25 and the composition does not comprise any other nutrients besides the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.5 to 6.2. The oligosaccharides are 2'-FL, 3'-SL, 6'-SL, DEL, LNnT, and LNT, and the composition comprises no other nutrients besides the oligosaccharides. In one embodiment, the present invention provides an aqueous composition comprising at least one omega-3 saccharide having a glucose unit at the reducing end and a concentration ranging from 5 to 50% w / w of the composition. In another embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition. In another additional embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and a concentration ranging from 10 to 30% w / w of the composition. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5. In another embodiment, the present invention provides: an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 36% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being 2'~FL and LNnT. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In an additional embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of the aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end, a pH modulator, a buffering agent, and wherein the pH of the aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of said aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. The oligosaccharides are 2-FL, 3-SL, 6-81, DFL, and LNT. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of said aqueous composition ranges from 4.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of said aqueous composition varies from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 36% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end and a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5. For example, from 5.8 to 6.3 or from 5.9 to 6.2. The oligosaccharides are 2-FL, 3-SL, 6'-SL, DFL, LNnT, and LNT. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the at least one oligosaccharide. In one embodiment, the present invention provides an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5. for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not include any nutrients other than the oligosaccharide. In one embodiment, the present invention provides an aqueous composition comprising at least an oligosaccharide having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharide. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of said aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharides. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharides. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In another embodiment, the present invention provides an aqueous composition comprising two oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides being g^FL and LNnT, and the composition comprising no other nutrients besides the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In a further embodiment, the present invention provides an aqueous composition comprising five oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6, for example, from 5.8 to 0 or from 5.9 to 6.2. The oligosaccharides are 2-F, 3-F, 6-F, DFL, and LNT, and the composition comprises no other nutrients besides the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, wherein the pH of said aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any other nutrients besides the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, and the composition does not comprise any nutrients other than the oligosaccharides. In another further embodiment, the present invention provides an aqueous composition comprising six oligosaccharides having a glucose unit at the reducing end at a concentration ranging from 8 to 35% w / w of the composition, a pH modulator, a buffering agent, and wherein the pH of such aqueous composition ranges from 5.5 to 6.5, for example, from 5.8 to 6.3 or from 5.9 to 6.2, the oligosaccharides are 2'-FU, 3-SL, 6MSL DFL, LNhT and LNT, and the composition does not comprise any other nutrients besides these oligosaccharides. Format Being in liquid form, aqueous compositions according to the present invention offer some particular advantages. For example, they can be more conveniently packaged to deliver calibrated drops of a specific weight or volume. In some embodiments, the aqueous compositions of the present invention can be packaged in individual doses so that calibrated drops of a certain weight or volume are supplied while preventing contamination of the remaining liquid due to handling and subsequent uses. In one embodiment, the aqueous liquid composition according to the present invention is presented in single-dose units packaged in plastic material. In one embodiment, said plastic material is flexible and compressible. In one embodiment, said plastic material may be polypropylene (PP) or polyethylene (PE). In one embodiment, the polypropylene may be low-density polyethylene (LDPE) or high-density polyethylene (HQPE). Furthermore, aqueous compositions are easy to mix with compositions to be fortified, whereas powder compositions may, in some cases, form lumps. Supplements In one embodiment, the aqueous composition according to the present invention and described above is a supplement. In such embodiment, the aqueous composition of the invention is administered as a standalone composition and is packaged in individual doses. Fortifiers In one embodiment, the aqueous composition according to the present invention is a milk fortifier. In this embodiment, the aqueous composition of the invention can be packaged in individual doses. Experimental section Method for the quantitative determination of 2'FL vLNnT Austin, et al., Molecules, 23 (20181 2650) An internal oligosaccharide standard (laminaritriose) is mixed with the oligosaccharide solution, and the oligosaccharides are fluorescently labeled by reacting 2-synthranilic acid amide (2AB) with the reducing end of OS via the formation of a Schiff base. The double bond is then reduced by reaction with sodium cyanoborohydride to produce a stable OS-2AB derivative. The labeled samples are diluted with acetonitol (AON) before the 1S injection into an ultra-high performance liquid chromatography (UHPLC) system equipped with hydrophilic interaction liquid chromatography (HILIC) analytical and capture columns. The labeled OS are detected using a fluprimeter. Oligosaccharide concentrations are determined from a standard curve using the relative response of the oligosaccharide (OS) to the internal standard (laminaritriose). Example 1 The oligosaccharides Z'fucosyl-lactose (2'FL) and iácio-N-neotetraose (Lto se The two solutions were mixed in a 2:1 (w / w) ratio and diluted in water to a final concentration of 10% (w / v). The solutions were acidified to pH 6 with citric acid and subjected to ultra-high temperature (UHT) treatment followed by aseptic filling of small single-dose bottles. The solutions were analyzed before and after filling the bottles, as well as after different storage times at 37°C (accelerated storage condition). The analysis was performed using HPLC with a gel column Amida-80 TSK (150 mm x 4.6 mm, particle size: 3 µm) was used for detection with a charged aerosol detector. For the fructose isomers of the added ZFL and LNnT, as well as their degradation products (fucose, lactose, and lacto-N-triose), quantification was performed using the relative response of the oligosaccharide to a standard curve. The fructose isomers of fucose, lactose, 2FL, LNnT, 2-fucosyl-Otulose, and LNnT were used as standards. The lacto-MuriQse content was calculated using the LNnT calibration curve. The results are reported in Figure 1. All data are expressed as % of added oligosaccharides. The results indicate that at pH 6, very limited formation of such degradation and / or isomerization products is observed, either in aseptic filling or during accelerated storage conditions, demonstrating the stability of the aqueous solution of the invention under the tested conditions. Element 2 The oligosaccharides 2'-fucosyl-laotose (2'FL) and lacto-N-neotetraose (LNnT) were mixed in a 10:1 (w / w) ratio and dissolved in water to a final concentration of 10% (w / v). From this solution, three samples were generated with pH 6 and 7 (by adding KOH). These samples were subjected to ultra-high temperature (UHT) treatment followed by aseptic filling of small single-dose bottles. The solutions at different pH levels were analyzed before and after filling the bottles, as well as after different storage times at room temperature (21–26°C). The analysis was performed by HPLC using an amide-SO₄ TSK gel column (150 mm x 4.6 mm, particle size: 3 µm) and detection using a charged aerosol detector. The F or 2'FL (Figure 2a), LNnT (Figure 2d), the fructose isomers of the added 2'FL (indicated as FL iactutose in the graphs, Figure 2d) and of the added LNnT (indicated as LNnT isomer in the graphs, Figure 2e), as well as for their degradation products (lactose, Figure 2c), were also measured. The pH of the solution was also measured. All data are expressed as % of added oligosaccharides. The results indicate that at pH 7, 2FL undergoes a significant transformation, as can be observed from the decreased levels during aseptic filling and over time (Figure 2a). This finding is also confirmed by a considerable amount of FL lactulose at this pH (Figure 2b and Figure 2e, respectively). At pH 6, the situation is considerably different. First, the amounts of 2FL and LNnT appear to be much more stable (Figure 2a and Figure 2d, respectively). Furthermore, the formation of FL lactuose, as well as LNnT isomers, is much lower (Figure 2b and Figure 2e, respectively), indicating the stability of the oligosaccharides in aqueous solution against isomerization. Finally, the 26 levels of lactose remain stable over time, which also indicates stability against hydrolysis of the oligosaccharides. Example 3 The oligosaccharides 2-Tucosyl-laetose (2'FL) and lacto-N-neotetraose (LNnT) were mixed in a 10:1 (w / w) ratio and dissolved in buffered water (phosphate buffer as defined above) to a final concentration of 10% (w / v). The solution was subjected to sterile filtration and filled into a single-dose plastic unit. The resulting pH of the solution before and after sterile filtration was approximately 6. Example 4 0.91 g of LNnT and 9.09 g of 2-FL were dissolved in water (to a final volume of 100 ml), to obtain a final concentration of 1Q g / l (10% w / v). Two aliquots (HMO solutions) were obtained from the resulting solution. In one aliquot, the pH was adjusted to 5 using a citric acid solution (10% w / w). In the other aliquot, the pH was adjusted to 6 using a KOH solution (10% w / w). Four grams of the aforementioned HMO solutions were added to two samples of human breast milk (20 g each). The initial pH of the pure breast milk was measured and recorded as 7.3. The final pH of the samples obtained by dissolving the HMO solutions in human breast milk was measured; the data are shown in Table 1 below. Table 1 pH(aarc) Human breast milk g of human breast milk * 4 g of HMO solution at pH 4.98 g of human breast milk + 4 g of HMO senton at pH 6.00 7.30 694 ?.es It should be understood that several changes and modifications to the preferred embodiments currently described herein will be evident to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its accompanying advantages. Therefore, the aim is to include such changes and modifications in the attached claims.

Claims

1. Aqueous composition comprising an oligosaccharide having a glucose unit at the reducing end and characterized in that the pH of the aqueous composition varies from 5.5 to 6.

5.

2. Aqueous composition according to claim 1 that is a milk fortifier or supplement.

3. Aqueous composition according to claim 1 or 2 characterized in that the pH varies from 5.8 to 6.3, for example from 5.9 to 6.

1.

4. Aqueous composition according to any of claims 1 to 3 comprising a pH modulator.

5. Aqueous composition according to any of claims 1 to 4 further comprising a regulating agent.

6. Aqueous composition according to any of claims 15 ia 5 characterized in that the at least one oligosaccharide is selected from the group consisting of: 2'-FU, 3-SL, 6'-SL, DFL, LNnT, LNT and 3-FL 7. Aqueous composition according to any one of claims 1 to 5 comprising two oligosaccharides having a glucose unit at the reducing end selected from the group consisting of: 2-H-, 3-FL, 3USL, β'-SL, DFL, 20 LNnT and LNT, for example, 2-FL and LNnT being.

8. An aqueous composition according to any one of claims 1 to 5 comprising five oligosaccharides having a glucose unit at the reducing end, selected from the group consisting of: 2-FL, 3-FL, 3'-SL, 6'-SL, DFL, LNnT and LNT, for example, 2-FL, 3-SL, 6'-SL, DFL and LNT being 25 9. Aqueous composition according to any of claims 1 to 8, which does not contain any other nutrients besides at least one hydrochloric acid.

10. An aqueous composition according to any one of claims 1 to 9 comprising oligosaccharides in a concentration ranging from 8 to 35% w / w of the composition. § 11. An aqueous composition according to any one of claims 1 to 10 for use in supporting digestive health, intestinal and / or mucosal maturation and / or immune maturation in infants, in particular infants who were born by cesarean section or who were born prematurely, or who are small for gestational age and / or who had a very low birth weight (LWB or VLBW). 10 12, Use of an aqueous composition according to claim 1 to 10 as a milk fortifier or supplement for infants, in particular infants who were born by cesarean section or who were born prematurely, or who are small for gestational age and / or who had a low or very low birth weight (LWB or VLBW).

13. Method for preventing hydrolysis in aqueous compositions during the heat treatment of oligosaccharides having a glucose unit at the reducing end, the method comprising: a) Providing an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end; b) Adjusting the pH of the aqueous composition to a value ranging from 5.5 to 6.5; c) Optionally subjecting the aqueous composition to a heat treatment.

14. Aqueous composition according to any of claims 25 1 to 11 packaged in an individual dose unit.