Technical Field This invention relates to a synthetic composition comprising proteins, for rehydrating a child who is in state of dehydration. The invention also concerns a non-therapeutic method of rehydrating a child who is in state of dehydration, said method comprising the use of the synthetic composition of the invention.

Background of the Invention

The promotion of physical activities among youth is of great importance in today's society. However, it is important to understand how to benefit from physical exercise during the growing years.

Given the known growth-related differences in thermoregulation and electrolyte losses during exercise, children have different nutritional needs than adults. In this respect, it has been found that children lose around 60% less sodium in their sweat during exercise compared with adults.

One long-recognized risk for children has been exercising in the heat and the associated- sweat-induced dehydration that occurs. Proper hydration is important to maintain normal physiological and psychological functions. On a daily basis, it is not uncommon for active children to have a mild state of dehydration. During exercise, the increased metabolic demand results in an enhanced sweat rate in an effort to thermoregulate. If adequate fluid intake is not provided, the resultant dehydration can have a negative impact on both physiological and psychological factors including increased cardiovascular and thermoregulatory strain, decreased cognitive ability, increased perceived effort and decreased physical performance. Despite the negative side effects of dehydration, children can voluntarily hypohydrate during exercise even if he has access to fluids. Therefore, the combination of inadequate fluid intake both before and during exercise makes the acute rehydration period after exercise critically important for children to replace fluid losses. Thus, there is a need to provide a specific synthetic post-exercise composition for rehydrating children.

There is a need to provide a nutritional composition that enables the convenient, safe and accurate delivery of the most adequate nutrition for children who have lost fluid due to physical exercise, while promoting or at least not inhibiting the children's growth.

The synthetic compositions of the present invention have been designed to promote and/or ensure rehydration of children. It is therefore an object of the invention to provide a synthetic liquid composition for children, particularly well adapted for its use in rehydrating children who are in state of dehydration.

Summary of the Invention

The present inventors have found surprisingly that the administration of a specific dose of proteins, preferably of high quality proteins such as milk-based proteins (whey proteins and casein proteins) and/or soy-based proteins, as a liquid, is particularly effective for rehydrating a child who is in state of dehydration.

Accordingly, in a first aspect of the invention, there is provided a synthetic composition comprising for rehydrating a child who is in state of dehydration, said composition comprising proteins, wherein the composition is administered as a liquid in a dose of about 0.10 to about 0.55, preferably about 0.20 to about 0.35, gram of proteins per kilogram of body mass of the child, and in a volume of 15 to 50 mL of composition per kilogram of body mass of the child, said dose being administered as at least one serving given over a period of time of about 0 min (excluded) duration to about 60 min duration, preferably from 0 (excluded) to 30 minutes.

The lowest duration value corresponds to the duration for one serving.

Thus, in a second aspect of the invention, there is provided a non-therapeutic method of rehydrating a child who is in state of dehydration, said method comprising the use of a synthetic composition comprising proteins, wherein the composition is administered as a liquid in a dose of about 0.10 to about 0.55, preferably about 0.20 to about 0.35, gram of proteins per kilogram of body mass of the child, and in a volume of 15 to 50 mL of composition per kilogram of body mass of the child, said dose being administered as at least one serving given over a period of time of about 0 min (excluded) duration to about 60 min duration, preferably from 0 (excluded) to 30 minutes. The lowest duration value corresponds to the duration for one serving.

Preferably, the composition according to both aspects of the invention when administered as a liquid has a protein content of 0.075 to 10 g/lOOmL, more preferably of 0.75 to 6 g/lOOmL. In this case the composition is preferably administered as a single serve.

In any case the proteins to be ingested by the child do not exceed the recommended amounts according to current guidelines (such as the recommendations of the World Health Organization (WHO)), taking into consideration the age of the child and the overall quantity of proteins ingested during the day.

Detailed description of the invention

For a complete understanding of the present invention and the advantages thereof, reference is made to the following detailed description of the invention. It should be appreciated that various embodiments of the present invention can be combined with other embodiments of the invention and are merely illustrative of the specific ways to make and use the invention, and do not limit the scope of the invention when taken into consideration with the claims and the following detailed description.

In the present description, the following words are given a definition that should be taken into account when reading and interpreting the description, examples and claims. As used herein, the following terms have the following meanings.

The term "child" means a person under the age of 18 years old, preferably aged between 5 and 15 years old. In particular, apart from specific nutritional requirement linked to their growth and development, the diet of a child is similar to that of an adult: it is a post-weaning diet

The term "hypoallergenic composition" means a composition which is unlikely to cause allergic reactions. The term "allergy" means an allergy which has been detected by a medical doctor and which can be treated occasionally or in a more durable manner. The term "food allergy" means an allergy with respect to a nutritional composition.

The term "nutritional" means that it nourishes a subject. The synthetic formula according to the invention is a nutritional composition, usually to be taken orally, or intragastrically, and including a protein source.

The term "dehydration" means a loss in body mass. A mild dehydration usually refers to a loss of 1 to 3 wt % of the body mass, and a severe dehydration usually refers to a loss of more than 3% of the body mass. Even if the child is in good health, dehydration occurs in a child after physical exercise. In that respect, the starting period of rehydration after physical exercise.

The term "rehydration" means the replacement of the losses in body mass, lOOg mass difference being assumed to represent 100 mL fluid loss.

The term "synthetic" means obtained by chemical and/or biological means, contrary to "natural (found in nature)". It encompasses the compositions obtained from natural products (such as cow's milk) transformed by chemical and/or biological means.

All percentages are by weight unless otherwise stated.

As used in this specification, the words "comprises", "comprising", and similar words, are not to be interpreted in an exclusive or exhaustive sense. In other words, they are intended to mean "including, but not limited to".

Any reference to prior art documents in this specification is not to be considered an admission that such prior art is widely known or forms part of the common general knowledge in the field.

The composition of the invention is designed to meet the rehydration needs of children. The composition is aimed to rehydrate children.

According to the invention, the synthetic composition is for rehydrating a child who is in state of dehydration, said composition comprising proteins, wherein the composition is administered as a liquid in a dose of about 0.10 to about 0.55, preferably about 0.20 to about 0.35, gram of proteins per kilogram of body mass of the child, and in a volume of 15 to 50 mL of composition per kilogram of body mass of the child, said dose being administered as at least one serving given over a period of time of about 0 min (excluded) duration to about 60 min duration. The proteins may be milk-based proteins or soy-based proteins. The milk-based proteins generally comprise, preferably consist of, whey proteins and casein proteins. Preferably, the number of servings is at least 2, preferably 3 or 4.

Preferably, the composition further comprises carbohydrate, preferably lactose, in a carbohydrate to protein ratio in the range of from about 3:1 to about 4:1, preferably in a ratio of about 3.5:1.

In a preferred embodiment, the composition further comprises potassium in a range of about 0.5 mmol/L to about 50 mmol/L and sodium in a range of about 20 mmol/L to about 50 mmol/L. Preferably, the composition has an osmolality of about 200 to about 270 mOsm.

In a preferred embodiment, the composition is is especially adapted for children aged 5 to 15, preferably 8 to 15 years old. Preferably, the starting point of the period of time is after physical exercise, and the first serving is given within a period of time of 0 to 30 minutes, preferably of 0 to 15 minutes, from the starting point. In the case where there is only one serving, this first serving is of course the only serving. Usually, this leads the child to ingest an amount of about 50 to about 200%, preferably 100 to 160%, of its fluid loss during physical exercise.

The invention also relates to a non-therapeutic method of rehydrating a child who is in state of dehydration, said method comprising the use of a synthetic composition comprising proteins, wherein the composition is administered as a liquid in a dose of about 0.10 to about 0.55, preferably about 0.20 to about 0.35, gram of proteins per kilogram of body mass of the child, and in a volume of 15 to 50 mL of composition per kilogram of body mass of the child, said dose being administered as at least one serving given over a period of time of about 0 min (excluded) duration to about 60 min duration. This non-therapeutic method comprises the use of the composition of the invention as previously described.

As long as it is administered as a liquid, the synthetic composition of the invention may be in the form of a powder, liquid or concentrated liquid. The composition may be based on a cow's milk, goat's milk or buffalo milk, but also non-dairy proteins such as soy, whey and rice proteins, as well as single or blends of amino acids.

The synthetic nutritional composition is to be consumed by the child as a liquid. For example, the composition may be a powdered composition that is diluted with water, or with milk, to give a final liquid product. The composition according to the invention may also be a concentrated liquid that is diluted with water, or milk, to achieve the final liquid composition to be administered. The composition of the invention may be a liquid product that is directly consumed by the child as it is. When the composition according to the invention may be added to or diluted with milk, the concentration of the proteins already present in the milk (to which the composition is added) is to be taken into consideration as part of the proteins which are to be ingested by the child.

Other standard ingredients known to the skilled person for formulating a nutritional child composition may also be present in the compositions of the invention.

Thus, the composition of the invention may contain other ingredients which may act to enforce the technical effect of the components.

The composition according to the present invention can also contain a carbohydrate source, as mentioned above. Any carbohydrate source conventionally found in nutritional compositions such as lactose, saccharose, maltodextrin, starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose.

The type of protein is not believed to be critical to the present invention provided that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured. Thus, protein sources based on whey, casein and mixtures thereof may be used as well as protein sources based on soy, or even lower quality proteins supplemented with key amino acids. As far as whey proteins are concerned, the protein source may be based on acid whey or sweet whey or mixtures thereof and may include alpha-lactalbumin and beta-lactoglobulin in any desired proportions. The proteins can be at least partially hydrolyzed in order to enhance oral tolerance to allergens, especially food allergens. In that case the composition is a hypoallergenic composition.

In a preferred embodiment, the composition may be cow's milk whey based infant formula. The formula may also be a hypoallergenic (HA) formula in which the cow milk proteins are (partially or extensively) hydrolysed. The formula may also be based on soy milk or a non-allergenic formula, for example one based on free amino acids.

The composition of the invention can also contain all vitamins and minerals, and other micronutrients, understood to be essential in the daily diet. Minimum requirements have been established for certain vitamins and minerals. Examples of minerals, vitamins and other nutrients optionally present in the composition of the invention include vitamin A, vitamin Bl, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. The presence and amounts of specific minerals and other vitamins will vary depending on the intended population. If necessary, the composition of the invention may contain emulsifiers and stabilisers such as soy, lecithin, citric acid esters of mono- and di-glycerides, and the like.

The composition of the invention may also contain other substances which may have a beneficial effect such as lactoferrin, nucleotides, nucleosides, gangliosides, polyamines, and the like.

The preparation of the composition according to the invention will now be described by way of example.

The composition may be prepared in any suitable manner. For example, it may be prepared by blending together a protein source, an optional carbohydrate source, and an optional fat source in appropriate proportions. If used, the emulsifiers may be included at this point. The vitamins and minerals may be added at this point but are usually added later to avoid thermal degradation. Any optional lipophilic vitamins, emulsifiers and the like may be dissolved into the optional fat source prior to blending. Milk or water, preferably water, more preferably water which has been subjected to reverse osmosis, may then be mixed in to form a liquid mixture. The temperature of the water is conveniently in the range between about 50°C and about 80°C to aid dispersal of the ingredients. Commercially available liquefiers may be used to form the liquid mixture. The liquid mixture is then homogenized, for example in two stages.

The liquid mixture may then be thermally treated to reduce bacterial loads, by rapidly heating the liquid mixture to a temperature in the range between about 80°C and about 150°C for a duration between about 5 seconds and about 5 minutes, for example. This may be carried out by means of steam injection, an autoclave or a heat exchanger, for example a plate heat exchanger.

Then, the liquid mixture may be cooled to between about 60°C and about 85°C for example by flash cooling. The liquid mixture may then be again homogenized, for example in two stages between about 10 MPa and about 30 MPa in the first stage and between about 2 MPa and about 10 MPa in the second stage. The homogenized mixture may then be further cooled to add any heat sensitive components, such as vitamins and minerals. The pH and solids content of the homogenized mixture are conveniently adjusted at this point.

The homogenized mixture can be transferred to a suitable drying apparatus such as a spray dryer or freeze dryer and converted to powder. The powder should have a moisture content of less than about 5% by weight. Some of the optional carbohydrate may be added at this stage by dry-mixing along with optional probiotic bacterial strain(s), or by blending them in a syrup form, along with optional probiotic bacterial strain(s), and spray-drying (or freeze -drying).

If a liquid composition is preferred, the homogenized mixture may be sterilized then aseptically filled into suitable containers or may be first filled into the containers and then retorted.

The composition of the invention may be in the form of powder, tablets, capsules, pastilles or a liquid for example, as long as it is a suitable nutritional composition for the child. It may further contain protective hydrocolloids (such as gums, proteins, modified starches), binders, film forming agents, encapsulating agents/materials, wall/shell materials, matrix compounds, coatings, emulsifiers, surface active agents, solubilizing agents (oils, fats, waxes, lecithins etc.), adsorbents, carriers, fillers, co-compounds, dispersing agents, wetting agents, processing aids (solvents), flowing agents, taste masking agents, weighting agents, jellifying agents and gel forming agents. The supplement may also contain conventional pharmaceutical additives and adjuvants, excipients and diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, lignin-sulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavouring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like. The composition can be added to a product acceptable to the child, such as an ingestible carrier or support, respectively. Examples of such carriers or supports are a pharmaceutical or a food composition.

Although the invention has been described by way of example, it should be appreciated that variations and modifications may be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred to in this specification.

The invention is further described with reference to the following example which relates to an experiment. It will be appreciated that the invention as claimed is not intended to be limited in any way by this example.

The advantages, nature, and various additional features of the invention will appear more fully upon consideration of the illustrative experiment now to be described in detail in connection with accompanying drawings. In the drawings: FIG. 1 is a graph plotting the results of the experiment, in terms of body fluid balance (mL) with respect to time (Pre-ex meaning Pre-exercise and Post-ex meaning post- exercise).

FIG. 2 is a graph plotting the results of the experiment, in terms of fraction of beverage retained (%) with respect to time post beverage i.e. post beverage consumption.

Example

This study was designed to provide important information on how different drink matrices rehydrate children after physical exercise. Three milk-based drinks (containing carbohydrate, protein, and fat) were studied for rehydrating children after physical exercise-induced fluid loss (1.5-2% of body weight). Changes in fluid balance (body weight changes) were compared with the ingestion of carbohydrate drinks containing a low (0.75g/100ml; Lo-PRO) and higher (1.5g/100ml; Hi-PRO) protein content versus an energy-matched control (CONT; isoenergetic carbohydrate-containing beverage).

17 children (8 males, 9 females) aged 10-12 years completed the study in which they exercised under a controlled climate (30°C, 50% humidity) for 45mins with periods of running, cycling (variable intensity) and rest designed to simulate normal play. In addition to the drink they received post-exercise, the children had a similar standard diet which included all macro- and micronutrients.

Following exercise they ingested the rehydration beverages in three equal serves over 30 min (i.e. at -30, -15, and Omin) which consisted of a milk protein-based drink (either at a dose of 0.75 or 1.5%) with additional carbohydrates that was provided at an oral dose equivalent to 150% of fluid losses during exercise in the heat.

Details of each beverage are provided in Table 1 below.

Table 1 : composition of experimental beverages

CONT Lo-PRO Hi-PRO

Energy (kcal/100ml) 28 28.4 28.1

Carbohydrate (g/100ml) 7 5.3 5.3

Protein (g/100ml) 0 0.76 1 .50

Fat (g/100ml) 0 0.46 0.10

Na+ (mmol/l) 41 41 41

K+ (mmol/l) 1 1 1

Osmolality (mOsm) 222 249 245 CONT is a comparative drink. Lo-PRO and Hi-PRO are according to the invention, Hi-PRO being particularly preferred.

The change in whole body fluid balance with exercise and after rehydration was determined by the following equation:

Fluid balance (ml) = BW (t) - BW (i)

Where, BW(i) is the pre-exercise body weight in grams, BW(t) is the body weight at a given time in grams. For all fluids, it was assumed that 1ml is equal to lg.

There were no differences between conditions in the volume of beverage consumed (see Table 2 below), as determined by repeated-measures analysis of variance (ANOVA). Independent analysis of the beverages revealed a protein concentration of 7.61 and 14.97 g/l in Lo-PRO and Hi-PRO, respectively. This translated into 7.0±2.1, and 12.5±3.7 g of protein ingested after exercise in the CONT, Lo-PRO, and Hi-PRO conditions, respectively. On a relative basis, this translated into 0.18±0.04, and 0.32±0.08g/kg body weight in the CONT, Lo-PRO, and Hi-PRO conditions, respectively.

Table 2 Volume of beverages consumed.

CONT Lo-PRO Hi-PRO

958 ± 249 971 ± 230 863 ± 222

Values are presented as mean ± SD in ml.

We submitted the fluid balance data to repeated-measures ANOVA, which is a common analytical approach in the field of exercise and hydration and consistent with the approach of previous adult researchers.

Figure 1 provides the graphical representation of the data, which is the Body fluid balance (per protocol analysis) with respect to time. * indicates that value in Hi-PRO is significantly different than in CONT. Error bars are not shown for clarity. ^† indicates that value in Lo-PRO tended to be different than in CONT (p=0.07). Within each condition, there was a difference (p<0.001 for all) between 4h and baseline. In every condition, the difference in fluid balance was < -0.2% indicating that the participants had not returned to a euhydrated state at 4h of recovery. Thus children remain partially dehydrated 4 hours post-activity despite ingestion of fluid replacing 150% of losses. This is in contrast to adults who are typically euhydrated following similar rehydration strategies so children cannot be regarded as "little adults".

At 2h of recovery, fluid balance was less negative in Hi-PRO compared with CONT (p<0.001). At 3h (p=0.005) and 4h (p=0.02) of recovery, fluid balance was significantly less negative in Hi-PRO compared with CONT and tended to be less negative in Lo-PRO compared with CONT (p=0.07) at 3h of recovery only.

Figure 2 provides the graphical representation of the data, which is the fraction of beverage retained after consumption of CONT, Lo-PRO and Hi-PRO (per protocol analysis) with respect to time. Φ indicates that values in Hi-PRO and Lo-PRO are significantly higher than for CONT; # indicates that value in Hi-PRO tended to be higher than for CONT. Error bars are not shown for clarity. Values during the Lo-PRO and Hi-PRO conditions at 2h and 3h of recovery were significantly greater than values at corresponding time points in CONT (all p values <0.02). At 4h of recovery, there was a strong trend (p=0.053) for Hi-PRO values to be greater than CONT. As a conclusion, this experiment shows that protein-containing drinks such as Lo-PRO and Hi-PRO according to the invention, in particular Hi-PRO, favorably affect rehydration in active children.