WO2003039556A1 - Rehydrating formulation - Google Patents

Rehydrating formulation Download PDF

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Publication number
WO2003039556A1
WO2003039556A1 PCT/GB2002/004980 GB0204980W WO03039556A1 WO 2003039556 A1 WO2003039556 A1 WO 2003039556A1 GB 0204980 W GB0204980 W GB 0204980W WO 03039556 A1 WO03039556 A1 WO 03039556A1
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WO
WIPO (PCT)
Prior art keywords
aqueous formulation
concentration
range
galactose
formulation
Prior art date
Application number
PCT/GB2002/004980
Other languages
French (fr)
Inventor
Roderick Frederik Gerardus Joseph King
Simon Edmund George Lester
Original Assignee
Ceretech Limited
Galactogen Products Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ceretech Limited, Galactogen Products Limited filed Critical Ceretech Limited
Priority to APAP/P/2004/003051A priority Critical patent/AP2004003051A0/en
Priority to EA200400636A priority patent/EA200400636A1/en
Priority to BR0213942-1A priority patent/BR0213942A/en
Priority to EP02779653A priority patent/EP1441741A1/en
Priority to JP2003541847A priority patent/JP2005508984A/en
Priority to MXPA04004339A priority patent/MXPA04004339A/en
Priority to CA002466278A priority patent/CA2466278A1/en
Publication of WO2003039556A1 publication Critical patent/WO2003039556A1/en
Priority to NO20041859A priority patent/NO20041859L/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to an aqueous formulation for combatting dehydration comprising a low concentration of galactose and a source of sodium ions ⁇ eg a sodium salt).
  • Galactose is a naturally occurring hexose for which worldwide demand is negligible and reported uses scarce.
  • Prior publications relating to galactose include:
  • WO-A-01/28360 discloses high energy multi-saccharide food products containing galactose and creatine for use in sport or to combat hunger or fatigue;
  • EP-A-0340491 discloses a foodstuff in which the saccharide component is primarily galactose
  • WO-A-96/18313 discloses formulations for increasing creatine uptake comprising creatine, insulin and a simple carbohydrate such as galactose
  • WO-A-98/06418 discloses dietary supplements comprising galactose for nutritional support and treating various disorders
  • US-A-5843921 (Childrens Hospital of Los Angeles) discloses formulations for treatment of diabetes comprising less than 3g per unit of simple sugars including galactose;
  • WO-A-96/08979 discloses sports beverages comprising trehalose and galactose
  • WO-A-90/02494 discloses a sports drink comprising galactose originating from a desalinated and hydrolised whey concentrate
  • EP-A-349712 discloses foodstuffs containing a tooth protecting amount of galactose in the form of lactose hydrosylate.
  • EP-A-184121 discloses anti-caries additives for sucrose foodstuffs comprising galactose I.
  • US-A-5780094 (Marathade Limited) discloses a rehydrating sports drink containing a high concentration of galactose and a proportion of glucose.
  • the abso ⁇ tion of water in the intestine is efficient and effective when driven by sodium co-transport involving a high concentration of galactose and glucose.
  • Galactose advantageously effects more rapid intestinal uptake of water than does glucose.
  • the present invention is based on the recognition that being physiologically adapted to effectively metabolise galactose and glucose (the two constituent sugars of lactose in milk) children are able to exploit sodium co-transport for effective rehydration using a low concentration of galactose.
  • the present invention relates to an improved rehydrating aqueous formulation comprising a low concentration of galactose and a sodium salt to combat dehydration resulting from (for example) diarrhoea.
  • the present invention provides an aqueous formulation for combatting dehydration comprising galactose at a concentration in the range 25 to 135mM, a source of sodium ions and water.
  • the aqueous formulation of the invention is generally more effective than a conventional glucose-containing rehydrating solution in treating extreme dehydration which might otherwise be fatal to a child.
  • galactose unlike glucose does not elicit a primary insulin response.
  • the concentration of galactose in the aqueous formulation is in the range 25 to 130mM, preferably 37 to 120mM, more preferably 40 to 120mM, especially preferably 45 to 90mM.
  • the source of sodium ions in the aqueous formulation of the invention is typically a sodium salt. Any physiologically tolerable sodium salt will suffice. Examples include sodium lactate, sodium chloride, sodium citrate, trisodium citrate, sodium hydrogenphosphate, disodium hydrogen phosphate and sodium bicarbonate.
  • the counter ion ⁇ eg chloride, bicarbonate, phosphate, hydrogenphosphate or citrate) may provide stability and buffering capacity and sodium citrate is advantageous for acidosis associated with diarrhoea of specific aetiology ⁇ eg viral).
  • Sodium chloride is preferred.
  • the concentration of sodium ions may be adapted to facilitate sodium co-transport and replacement of electrolyte loss.
  • the concentration of sodium ions in the aqueous formulation is in the range 25 to lOOmM, preferably 30 to 90mM, particularly preferably 35 to 90mM, more preferably 45 to 90mM, yet more preferably 60 to 90mM.
  • higher sodium concentrations are preferred ⁇ eg 80-90mM such as about 90mM.
  • lower sodium concentrations are preferred.
  • An embodiment of the aqueous formulation further comprises one or more sources of additional ions ⁇ eg potassium, magnesium, calcium or zinc) to advantageously achieve replacement of minerals which have been lost as a symptom of (for example) diarrhoea.
  • the source of an additional ion is typically a salt ⁇ eg a mineral salt) such as a chloride.
  • the aqueous formulation comprises a source of potassium ions ⁇ eg a potassium salt such as potassium chloride).
  • the potassium salt serves to replace electrolyte loss.
  • the concentration of potassium ions in the aqueous formulation is in the range 5 to 35mM, preferably 10 to 30mM, particularly preferably 15 to 25mM, more preferably about 20 to 25mM.
  • an embodiment of the aqueous formulation of the invention further comprises one or more additional carbohydrates.
  • the one or more additional carbohydrates may be a digestible saccharide such as a digestible saccharide selected from one or more of the group consisting of monosaccharides, disaccharides, oligosaccharides and polysaccharides. These may be natural or synthetic saccharides.
  • the one or more additional carbohydrates may be selected from the group consisting of glucose, sucrose, dextrose, fructose, lactose and maltose.
  • the additional carbohydrate is a monosaccharide, particularly preferably glucose.
  • maltodextrin or higher oligosaccharide may be used in place of glucose.
  • the galactose and optionally one or more additional carbohydrates of the aqueous formulation are present in a total amount sufficient to meet the carbohydrate requirements of sodium co-transport for effective rehydration.
  • the total concentration of carbohydrate is in the range 50 to 300mM, preferably 50 to 200mM, particularly preferably 55 to 175mM, more preferably 60 to 135mM, especially preferably 90 to 130mM.
  • galactose and glucose are present in a total amount sufficient to meet the carbohydrate requirements of sodium co-transport in effective rehydration.
  • the ratio of molar concentration of galactose and glucose is in the range 0.6:1 to 1:0.6, preferably 0.8:1 to 1:0.8, particularly preferably 0.9: 1 to 1 :0.9, more preferably the molar concentration ratio is about 1:1.
  • the concentration of glucose in the aqueous formulation is in the range 30 to 135mM, preferably 35 to 130mM, particularly preferably 37 to 120mM, more preferably 40 to lOOmM, especially preferably 45 to 80mM.
  • maltodextrin or higher oligosaccharide is preferably used in place of glucose.
  • the ranges of preferred glucose concentration may be satisfied by a concentration of an oligosaccharide with an appropriate chain length.
  • a maltodextrin of average chain length six could be used at lOmM.
  • a general purpose formulation might typically have a ratio of sodium ion concentration: carbohydrate concentration of about 1:2 eg a concentration of sodium ions of about 60mM and galactose and glucose present at a total concentration of 120mM.
  • Such a formulation would be useful where the circumstance leading to dehydration is diarrhoea as a result of post surgical rest (eg when GI rest is important) or the circumstance leading to dehydration is self-induced (eg through alcohol consumption).
  • the aqueous formulation of the invention may be administered by any convenient route.
  • the aqueous formulation is adapted for oral administration.
  • the aqueous formulation may be palatable and for this purpose may further comprise natural or synthetic flavourings such as fruit flavourings (eg blackcurrant, strawberry, apple, citrus, lemon, lime, orange or cranberry) or caffeine and sweeteners.
  • the aqueous formulation of the invention may further comprise physiologically tolerable stabilisers, anti-oxidants (eg ascorbic acid) and preservatives (eg sodium benzoate or sorbic acid) as desired.
  • physiologically tolerable stabilisers eg ascorbic acid
  • preservatives eg sodium benzoate or sorbic acid
  • the administration dosage generally depends on the level of dehydration and the size and age of the subject. Generally it is advisable for the dose to be equivalent to or slightly greater than the actual or expected loss of bodily water and to be administered at appropriate intervals. Typically a dose of aqueous formulation is in the range 100 to 250ml.
  • Citric acid may be added to the aqueous formulation for partial or total replacement of citrate ion and for buffering purposes (typically to maintain pH in the range 2 to 6).
  • the concentration of citrate ion in the aqueous formulation may be in the range 5 to 30mM, preferably 10 to 25mM, particularly preferably 10 to 15mM.
  • a phosphate salt may be used as an alternative buffering agent.
  • the concentration of chloride ion in the aqueous formulation may be in the range 10 to lOOmM, preferably 30 to 90mM, more preferably 40 to 85mM, especially preferably 45 to 80mM.
  • higher chloride concentrations are preferred ⁇ eg 70-80mM such as about 80mM).
  • the aqueous formulation of the invention may be an aqueous solution, aqueous dispersion or aqueous suspension.
  • the aqueous formulation is an aqueous solution.
  • the aqueous formulation (eg solution) is a reconstituent aqueous formulation (eg solution).
  • a reconstituent aqueous formulation of the invention may be reconstituted by the end user at the point of use from a composition comprising galactose and a source of sodium ions (and optionally one or more sources of additional ions and one or more additional carbohydrates) by addition of a suitable volume of aqueous solvent (eg water).
  • the present invention provides a composition formulable (eg dissolvable) in water to form an aqueous formulation as hereinbefore defined, said composition comprising galactose, a source of sodium ions, optionally an additional carbohydrate and optionally a source of additional ions.
  • the composition comprises galactose in an amount sufficient to form a concentration in the range 25 to 135mM in a specified volume of aqueous solvent (eg water) and a source of sodium ions.
  • the composition of the invention may be provided in any suitable solid or liquid form.
  • the composition may be provided in solid form such as powdered (eg effervescent or non-effervescent powdered) or tablet form or in liquid form such as gel or liquid concentrate form.
  • the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting (eg treating or preventing) dehydration or (B) a medicament formulable (eg dissolvable in water) into an aqueous 25 to 135mM galactose formulation for combatting (eg treating or preventing) dehydration.
  • A an aqueous 25 to 135mM galactose formulation for combatting (eg treating or preventing) dehydration
  • a medicament formulable eg dissolvable in water
  • the aqueous 25 to 135mM galactose formulation is as hereinbefore defined.
  • the medicament is a composition as hereinbefore defined.
  • the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration and associated deficiencies or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration and associated deficiencies.
  • the associated deficiencies may be mineral loss, electrolyte imbalance, etc.
  • the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration in children (eg infants) or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration in children (eg infants).
  • the dehydration and (where present) associated deficiencies are symptoms of diarrhoea .
  • the diarrhoea may be a result of (for example) enterotoxin effects (eg cholera typically in the third world), viral effects (eg rotavirus typically in the developed world) or post surgical rest (eg when GI rest is important).
  • enterotoxin effects eg cholera typically in the third world
  • viral effects eg rotavirus typically in the developed world
  • post surgical rest eg when GI rest is important.
  • the concentration of each component may be tailored to optimise treatment of dehydration and associated deficiencies caused by mild, moderate or severe diarrhoea. For combatting dehydration as a symptom of severe diarrhoea, higher sodium and chloride concentrations are preferred. Alternatively, the circumstances which may lead to dehydration may be self-induced (eg through alcohol consumption).
  • the dehydration or associated deficiencies are life threatening.
  • the present invention provides a method for combatting dehydration in a subject comprising the step of: administering an effective dose of an aqueous formulation as hereinbefore defined to the subject.
  • the present invention provides a method for combatting dehydration and associated deficiencies in a subject comprising the step of: administering an effective dose of an aqueous formulation as hereinbefore defined to the subject.
  • the subject may be any age, preferably the subject is a child (eg an infant).
  • the dehydration and (where present) associated deficiencies are symptoms of diarrhoea (eg severe diarrhoea).
  • the diarrhoea may be a result of (for example) enterotoxin effects (eg cholera typically in the third world), viral effects (eg rotavirus typically in the developed world) or post surgical rest (eg when GI rest is important).
  • enterotoxin effects eg cholera typically in the third world
  • viral effects eg rotavirus typically in the developed world
  • post surgical rest eg when GI rest is important
  • the circumstances which may lead to dehydration may be self- induced (eg through alcohol consumption).
  • Example 1 The present invention will now be described in a non-limitative sense with reference to the following Example.
  • Example 2 The present invention will now be described in a non-limitative sense with reference to the following Example.
  • compositions F, G and H are 60, 40 and 90mM respectively and the chloride concentrations are 45, 45 and 80mM respectively. Higher ⁇ sodium and chloride concentrations are desirable for effective treatment of severe diarrhoea.
  • compositions F, G and H are useful in the treatment of moderate, mild and severe diarrhoea respectively.

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Abstract

The present invention relates to an aqueous formulation for combating dehydration comprising a low concentration of galactose and a source of sodium ions which is particularly effective in children (e.g. infants). The dehydration is typically a symptom of severe diarrhoea.

Description

REHYDRATING FORMULATION
The present invention relates to an aqueous formulation for combatting dehydration comprising a low concentration of galactose and a source of sodium ions {eg a sodium salt).
There are a number of circumstances in which a subject may suffer dehydration and associated deficiencies such as loss of mineral salts. For example, exercise acts to deplete the body of fuel stores and increases the rate of perspiration causing loss of water and mineral salts. These losses can be significant if exercise is prolonged and particularly if ambient temperatures are moderate or high. Other circumstances which may lead to dehydration include excessive temperatures, nutritional deprivation, fever, diarrhoea and vomiting excess as a result of (for example) enterotoxin effects {eg cholera typically in the third world), viral effects {eg rotavirus typically in the developed world) or post surgical rest {eg when GI rest is important). Alternatively, the circumstances which may lead to dehydration may be self-induced (eg through alcohol consumption). In extreme cases, loss of fluid and/or electrolytes may be clinically important or even life threatening, in particular in children and the elderly.
Humans do not function efficiently when dehydrated or when they are suffering an electrolyte imbalance. Rehydrating drinks containing inorganic salts and/or high sugar {eg glucose) content are well established in combatting these disorders. However the administration of glucose may lead to exaggerated insulin responses.
Galactose is a naturally occurring hexose for which worldwide demand is negligible and reported uses scarce. Prior publications relating to galactose include:
(1) WO-A-01/28360 (Marathade Ltd) discloses high energy multi-saccharide food products containing galactose and creatine for use in sport or to combat hunger or fatigue;
(2) EP-A-0340491(Biodyn Ag) discloses a foodstuff in which the saccharide component is primarily galactose; (3) WO-A-96/18313 (University of Nottingham) discloses formulations for increasing creatine uptake comprising creatine, insulin and a simple carbohydrate such as galactose;
(4) WO-A-98/06418 (Mannatech, Inc) discloses dietary supplements comprising galactose for nutritional support and treating various disorders;
(5) US-A-5843921 (Childrens Hospital of Los Angeles) discloses formulations for treatment of diabetes comprising less than 3g per unit of simple sugars including galactose;
(6) WO-A-96/08979 (Quadrant Holdings Cambridge Ltd) discloses sports beverages comprising trehalose and galactose;
(7) WO-A-90/02494 (Svenska Mejeriernas Riksforening Ekonomi AB) discloses a sports drink comprising galactose originating from a desalinated and hydrolised whey concentrate;
(8) EP-A-349712 (Biodyn Ag) discloses foodstuffs containing a tooth protecting amount of galactose in the form of lactose hydrosylate; and
(9) EP-A-184121 (Biodyn Ag) discloses anti-caries additives for sucrose foodstuffs comprising galactose I.
US-A-5780094 (Marathade Limited) discloses a rehydrating sports drink containing a high concentration of galactose and a proportion of glucose. The absoφtion of water in the intestine is efficient and effective when driven by sodium co-transport involving a high concentration of galactose and glucose. Galactose advantageously effects more rapid intestinal uptake of water than does glucose.
The present invention is based on the recognition that being physiologically adapted to effectively metabolise galactose and glucose (the two constituent sugars of lactose in milk) children are able to exploit sodium co-transport for effective rehydration using a low concentration of galactose. In particular, the present invention relates to an improved rehydrating aqueous formulation comprising a low concentration of galactose and a sodium salt to combat dehydration resulting from (for example) diarrhoea.
Thus viewed from one aspect the present invention provides an aqueous formulation for combatting dehydration comprising galactose at a concentration in the range 25 to 135mM, a source of sodium ions and water. The aqueous formulation of the invention is generally more effective than a conventional glucose-containing rehydrating solution in treating extreme dehydration which might otherwise be fatal to a child. Moreover galactose (unlike glucose) does not elicit a primary insulin response.
In a preferred embodiment, the concentration of galactose in the aqueous formulation is in the range 25 to 130mM, preferably 37 to 120mM, more preferably 40 to 120mM, especially preferably 45 to 90mM.
The source of sodium ions in the aqueous formulation of the invention is typically a sodium salt. Any physiologically tolerable sodium salt will suffice. Examples include sodium lactate, sodium chloride, sodium citrate, trisodium citrate, sodium hydrogenphosphate, disodium hydrogen phosphate and sodium bicarbonate. The counter ion {eg chloride, bicarbonate, phosphate, hydrogenphosphate or citrate) may provide stability and buffering capacity and sodium citrate is advantageous for acidosis associated with diarrhoea of specific aetiology {eg viral). Sodium chloride is preferred.
The concentration of sodium ions may be adapted to facilitate sodium co-transport and replacement of electrolyte loss. In a preferred embodiment, the concentration of sodium ions in the aqueous formulation is in the range 25 to lOOmM, preferably 30 to 90mM, particularly preferably 35 to 90mM, more preferably 45 to 90mM, yet more preferably 60 to 90mM. For combatting dehydration as a symptom of severe diarrhoea {eg caused by enterotoxin effects), higher sodium concentrations are preferred {eg 80-90mM such as about 90mM). For combatting dehydration as a symptom of less severe diarrhoea {eg caused by viral effects or when hypernatraemia is a risk), lower sodium concentrations are preferred.
An embodiment of the aqueous formulation further comprises one or more sources of additional ions {eg potassium, magnesium, calcium or zinc) to advantageously achieve replacement of minerals which have been lost as a symptom of (for example) diarrhoea. The source of an additional ion is typically a salt {eg a mineral salt) such as a chloride. Preferably the aqueous formulation comprises a source of potassium ions {eg a potassium salt such as potassium chloride). The potassium salt serves to replace electrolyte loss. In a preferred embodiment, the concentration of potassium ions in the aqueous formulation is in the range 5 to 35mM, preferably 10 to 30mM, particularly preferably 15 to 25mM, more preferably about 20 to 25mM.
An embodiment of the aqueous formulation of the invention further comprises one or more additional carbohydrates. In an embodiment of the invention, the one or more additional carbohydrates may be a digestible saccharide such as a digestible saccharide selected from one or more of the group consisting of monosaccharides, disaccharides, oligosaccharides and polysaccharides. These may be natural or synthetic saccharides. For example, the one or more additional carbohydrates may be selected from the group consisting of glucose, sucrose, dextrose, fructose, lactose and maltose. Preferably the additional carbohydrate is a monosaccharide, particularly preferably glucose. In situations where the osmolality of the aqueous formulation is important (eg where hyperosmolar or isomolar solutions are contra indicated), maltodextrin or higher oligosaccharide may be used in place of glucose.
In a preferred embodiment, the galactose and optionally one or more additional carbohydrates of the aqueous formulation are present in a total amount sufficient to meet the carbohydrate requirements of sodium co-transport for effective rehydration. In a preferred embodiment, the total concentration of carbohydrate is in the range 50 to 300mM, preferably 50 to 200mM, particularly preferably 55 to 175mM, more preferably 60 to 135mM, especially preferably 90 to 130mM.
In a preferred embodiment of the formulation, galactose and glucose are present in a total amount sufficient to meet the carbohydrate requirements of sodium co-transport in effective rehydration. Typically the ratio of molar concentration of galactose and glucose is in the range 0.6:1 to 1:0.6, preferably 0.8:1 to 1:0.8, particularly preferably 0.9: 1 to 1 :0.9, more preferably the molar concentration ratio is about 1:1. In a preferred embodiment, the concentration of glucose in the aqueous formulation is in the range 30 to 135mM, preferably 35 to 130mM, particularly preferably 37 to 120mM, more preferably 40 to lOOmM, especially preferably 45 to 80mM.
In situations where the osmolality of the aqueous formulation is important (eg where hyperosmolar or isomolar solutions are contra indicated), maltodextrin or higher oligosaccharide is preferably used in place of glucose. Thus the ranges of preferred glucose concentration may be satisfied by a concentration of an oligosaccharide with an appropriate chain length. For example, in place of glucose at 60mM, a maltodextrin of average chain length six could be used at lOmM.
A general purpose formulation might typically have a ratio of sodium ion concentration: carbohydrate concentration of about 1:2 eg a concentration of sodium ions of about 60mM and galactose and glucose present at a total concentration of 120mM. Such a formulation would be useful where the circumstance leading to dehydration is diarrhoea as a result of post surgical rest (eg when GI rest is important) or the circumstance leading to dehydration is self-induced (eg through alcohol consumption).
The aqueous formulation of the invention may be administered by any convenient route. Preferably the aqueous formulation is adapted for oral administration. For example, the aqueous formulation may be palatable and for this purpose may further comprise natural or synthetic flavourings such as fruit flavourings (eg blackcurrant, strawberry, apple, citrus, lemon, lime, orange or cranberry) or caffeine and sweeteners.
The aqueous formulation of the invention may further comprise physiologically tolerable stabilisers, anti-oxidants (eg ascorbic acid) and preservatives (eg sodium benzoate or sorbic acid) as desired.
The administration dosage generally depends on the level of dehydration and the size and age of the subject. Generally it is advisable for the dose to be equivalent to or slightly greater than the actual or expected loss of bodily water and to be administered at appropriate intervals. Typically a dose of aqueous formulation is in the range 100 to 250ml.
Citric acid may be added to the aqueous formulation for partial or total replacement of citrate ion and for buffering purposes (typically to maintain pH in the range 2 to 6). Where the source of sodium or other ions is a citrate salt and/or citric acid is added, the concentration of citrate ion in the aqueous formulation may be in the range 5 to 30mM, preferably 10 to 25mM, particularly preferably 10 to 15mM. A phosphate salt may be used as an alternative buffering agent.
Where the source of sodium (and optionally additional ions) is a chloride salt, the concentration of chloride ion in the aqueous formulation may be in the range 10 to lOOmM, preferably 30 to 90mM, more preferably 40 to 85mM, especially preferably 45 to 80mM. For combatting dehydration as a symptom of severe diarrhoea, higher chloride concentrations are preferred {eg 70-80mM such as about 80mM).
The aqueous formulation of the invention may be an aqueous solution, aqueous dispersion or aqueous suspension. Preferably the aqueous formulation is an aqueous solution. Preferably the aqueous formulation (eg solution) is a reconstituent aqueous formulation (eg solution). For example, a reconstituent aqueous formulation of the invention may be reconstituted by the end user at the point of use from a composition comprising galactose and a source of sodium ions (and optionally one or more sources of additional ions and one or more additional carbohydrates) by addition of a suitable volume of aqueous solvent (eg water).
Viewed from a further aspect the present invention provides a composition formulable (eg dissolvable) in water to form an aqueous formulation as hereinbefore defined, said composition comprising galactose, a source of sodium ions, optionally an additional carbohydrate and optionally a source of additional ions. For example, the composition comprises galactose in an amount sufficient to form a concentration in the range 25 to 135mM in a specified volume of aqueous solvent (eg water) and a source of sodium ions. The composition of the invention may be provided in any suitable solid or liquid form. For example, the composition may be provided in solid form such as powdered (eg effervescent or non-effervescent powdered) or tablet form or in liquid form such as gel or liquid concentrate form.
Viewed from a yet further aspect the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting (eg treating or preventing) dehydration or (B) a medicament formulable (eg dissolvable in water) into an aqueous 25 to 135mM galactose formulation for combatting (eg treating or preventing) dehydration.
In a preferred embodiment of the use of the invention, the aqueous 25 to 135mM galactose formulation is as hereinbefore defined.
In a preferred embodiment of the use of the invention, the medicament is a composition as hereinbefore defined.
In a preferred embodiment, the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration and associated deficiencies or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration and associated deficiencies. The associated deficiencies may be mineral loss, electrolyte imbalance, etc.
In a preferred embodiment, the present invention provides the use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration in children (eg infants) or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration in children (eg infants).
Preferably the dehydration and (where present) associated deficiencies are symptoms of diarrhoea . The diarrhoea may be a result of (for example) enterotoxin effects (eg cholera typically in the third world), viral effects (eg rotavirus typically in the developed world) or post surgical rest (eg when GI rest is important). The concentration of each component may be tailored to optimise treatment of dehydration and associated deficiencies caused by mild, moderate or severe diarrhoea. For combatting dehydration as a symptom of severe diarrhoea, higher sodium and chloride concentrations are preferred. Alternatively, the circumstances which may lead to dehydration may be self-induced (eg through alcohol consumption).
In a preferred embodiment of the use of the invention, the dehydration or associated deficiencies are life threatening.
Viewed from a still yet further aspect the present invention provides a method for combatting dehydration in a subject comprising the step of: administering an effective dose of an aqueous formulation as hereinbefore defined to the subject.
Viewed from an even still further aspect the present invention provides a method for combatting dehydration and associated deficiencies in a subject comprising the step of: administering an effective dose of an aqueous formulation as hereinbefore defined to the subject.
Although the subject may be any age, preferably the subject is a child (eg an infant). Preferably the dehydration and (where present) associated deficiencies are symptoms of diarrhoea (eg severe diarrhoea). The diarrhoea may be a result of (for example) enterotoxin effects (eg cholera typically in the third world), viral effects (eg rotavirus typically in the developed world) or post surgical rest (eg when GI rest is important). Alternatively, the circumstances which may lead to dehydration may be self- induced (eg through alcohol consumption).
The present invention will now be described in a non-limitative sense with reference to the following Example. Example
Nine reconstituent aqueous formulations A, Al and B-H were prepared which had the components and concentrations after reconstitution in water shown in Table 1 :
Table 1
Figure imgf000010_0001
A solid mixture of pre- weighed components was prepared such that the specified concentrations were obtained when a certain proportion was dissolved in a specified volume of water. The unit volume of water added to reconstitute the composition may be up to 1000ml. Typically 250ml would be appropriate and a single dose may be made up of one, two or three 250ml unit volumes administered at appropriate intervals. Each aqueous formulation may be flavoured to be palatable as desired using lemon, lime, blackcurrant, orange, citrus or cranberry. The sodium concentration for compositions F, G and H are 60, 40 and 90mM respectively and the chloride concentrations are 45, 45 and 80mM respectively. Higher ■ sodium and chloride concentrations are desirable for effective treatment of severe diarrhoea. Thus compositions F, G and H are useful in the treatment of moderate, mild and severe diarrhoea respectively.
General puφose formulations I, J, K, L, M and N are shown in Table 2.
Table 2
Figure imgf000011_0001

Claims

1. An aqueous formulation for combatting dehydration comprising galactose at a concentration in the range 25 to 135mM, a source of sodium ions and water.
2. An aqueous formulation as claimed in claim 1 wherein the concentration of galactose in the aqueous formulation is in the range 25 to 130mM.
3. An aqueous formulation as claimed in claim 1 or 2 wherein the concentration of galactose in the aqueous formulation is in the range 37 to 120mM,
4. An aqueous formulation as claimed in any preceding claim wherein the concentration of galactose in the aqueous formulation is in the range 40 to 120mM.
5. An aqueous formulation as claimed in any preceding claim wherein the source of sodium ions is sodium chloride optionally together with sodium citrate.
6. An aqueous formulation as claimed in any preceding claim wherein the concentration of sodium ions in the aqueous formulation is in the range 25 to lOOmM.
7. An aqueous formulation as claimed in any preceding claim wherein the concentration of sodium ions in the aqueous formulation is in the range 30 to 90mM.
8. An aqueous formulation as claimed in any preceding claim wherein the concentration of sodium ions in the aqueous formulation is in the range 35 to 90mM.
9. An aqueous formulation as claimed in any preceding claim wherein the concentration of sodium ions in the aqueous formulation is in the range 45 to 90mM.
10. An aqueous formulation as claimed in any preceding claim wherein the concentration of sodium ions in the aqueous formulation is in the range 60 to 90mM.
11. An aqueous formulation as claimed in any preceding claim further comprising a source of potassium ions at a concentration in the aqueous formulation in the range 20 to 25mM.
12. An aqueous formulation as claimed in any preceding claim further comprising one or more additional carbohydrates selected from the group consisting of glucose, sucrose, dextrose, fructose, lactose and maltose.
13. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 50 to 300mM.
14. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 50 to 200mM
15. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 55 to 175mM.
16. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 60 to 135mM
17. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 90 to 130mM.
18. An aqueous formulation as claimed in any of claims 12 to 17 wherein galactose and glucose are present in a total amount sufficient to meet the carbohydrate requirements of sodium co-transport in effective rehydration and the ratio of molar concentration of galactose and glucose is in the range 0.6: 1 to 1 :0.6.
19. An aqueous formulation as claimed in claim 18 wherein the ratio of molar concentration of galactose and glucose is in the range 0.8:1 to 1 :0.8.
20. An aqueous formulation as claimed in claim 18 or 19 wherein the ratio of molar concentration of galactose and glucose is in the range 0.9:1 to 1:0.9.
21. An aqueous formulation as claimed in any of claims 18 to 20 wherein the ratio of molar concentration of galactose and glucose is about 1:1.
22. An aqueous formulation as claimed in any of claims 12 to 21 wherein the concentration of glucose in the aqueous formulation is in the range 30 to 135mM.
23. An aqueous formulation as claimed in any of claims 12 to 22 wherein the concentration of glucose in the aqueous formulation is in the range 35 to 130mM
24. An aqueous formulation as claimed in any of claims 12 to 23 wherein the concentration of glucose in the aqueous formulation is in the range 37 to 120mM
25. An aqueous formulation as claimed in any of claims 12 to 24 wherein the concentration of glucose in the aqueous formulation is in the range 40 to lOOmM
26. An aqueous formulation as claimed as claimed in any of claims 12 to 25 wherein the concentration of glucose in the aqueous formulation is in the range 45 to 80mM.
27. An aqueous formulation as claimed in any preceding claim wherein the concentration of glucose is satisfied at least in part by a glucosidic oligosaccharide.
28. An aqueous formulation as claimed in claim 27 wherein the glucosidic oligosaccharide is maltodextrin.
29. A composition formulable in water to form an aqueous formulation as defined in any preceding claim, said composition comprising galactose, a source of sodium ions, optionally an additional carbohydrate and optionally a source of additional ions.
30. Use of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration.
31. Use as claimed in claim 30 of galactose and a source of sodium ions for the preparation of (A) an aqueous 25 to 135mM galactose formulation for combatting dehydration in children or (B) a medicament formulable into an aqueous 25 to 135mM galactose formulation for combatting dehydration in children.
32. Use as claimed in claim 30 or 31 wherein the dehydration is a symptom of diarrhoea.
33. A method for combatting dehydration in a subject comprising the step of: administering to the subject an effective dose of an aqueous formulation as defined in any of claims 1 to 28.
34. A method as claimed in claim 33 wherein the subject is a child.
PCT/GB2002/004980 2001-11-07 2002-11-04 Rehydrating formulation WO2003039556A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
APAP/P/2004/003051A AP2004003051A0 (en) 2001-11-07 2002-11-04 Rehydrating formulation
EA200400636A EA200400636A1 (en) 2001-11-07 2002-11-04 REGENERATING COMPOSITION
BR0213942-1A BR0213942A (en) 2001-11-07 2002-11-04 Aqueous formulation to combat dehydration, water formulable composition, use of galactose and sodium ion source and method to combat dehydration in a subject
EP02779653A EP1441741A1 (en) 2001-11-07 2002-11-04 Rehydrating formulation
JP2003541847A JP2005508984A (en) 2001-11-07 2002-11-04 Rehydrating preparation
MXPA04004339A MXPA04004339A (en) 2001-11-07 2002-11-04 Rehydrating formulation.
CA002466278A CA2466278A1 (en) 2001-11-07 2002-11-04 Rehydrating formulation
NO20041859A NO20041859L (en) 2001-11-07 2004-05-06 Rehydratiseringsformulering

Applications Claiming Priority (3)

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GB0126746.7 2001-11-07
US34075101P 2001-11-30 2001-11-30
US60/340,751 2001-11-30

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004004740A1 (en) * 2002-07-05 2004-01-15 King Roderick Frederick Gerard Aqueous formulation comprising digestible saccharides to reduce the tendency to cardiovascular disease in a subject
WO2004004741A1 (en) * 2002-07-05 2004-01-15 King Roderick Frederick Gerard Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular disease

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EP0059057A1 (en) * 1981-02-20 1982-09-01 Beecham Group Plc Treatment of diarrhoea
EP0114104A2 (en) * 1983-01-13 1984-07-25 Colorado State University Research Foundation An oral energy-rich composition and solution for combatting diarrhea in mammals
US4652454A (en) * 1983-01-12 1987-03-24 Institut National De La Recherche Agronomique (Inra) Rehydrating composition which can be used especially in the feeding of young animals which can no longer digest milk normally, and a complement for its preparation
US4689319A (en) * 1983-01-13 1987-08-25 Colorado State University Research Foundation Oral energy rich therapy for diarrhea in mammals
WO1996008979A1 (en) * 1994-09-22 1996-03-28 Quadrant Holdings Cambridge Limited Compositions for use in rehydration and nutrition during athletic exercise and methods of making same
US5780094A (en) * 1994-02-16 1998-07-14 Marathade, Ltd. Sports drink

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Publication number Priority date Publication date Assignee Title
GB1158456A (en) * 1967-06-13 1969-07-16 Prodotti Antibiotici Spa Preparations Containing Sugars
EP0059057A1 (en) * 1981-02-20 1982-09-01 Beecham Group Plc Treatment of diarrhoea
US4652454A (en) * 1983-01-12 1987-03-24 Institut National De La Recherche Agronomique (Inra) Rehydrating composition which can be used especially in the feeding of young animals which can no longer digest milk normally, and a complement for its preparation
EP0114104A2 (en) * 1983-01-13 1984-07-25 Colorado State University Research Foundation An oral energy-rich composition and solution for combatting diarrhea in mammals
US4689319A (en) * 1983-01-13 1987-08-25 Colorado State University Research Foundation Oral energy rich therapy for diarrhea in mammals
US5780094A (en) * 1994-02-16 1998-07-14 Marathade, Ltd. Sports drink
WO1996008979A1 (en) * 1994-09-22 1996-03-28 Quadrant Holdings Cambridge Limited Compositions for use in rehydration and nutrition during athletic exercise and methods of making same

Cited By (2)

* Cited by examiner, † Cited by third party
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WO2004004740A1 (en) * 2002-07-05 2004-01-15 King Roderick Frederick Gerard Aqueous formulation comprising digestible saccharides to reduce the tendency to cardiovascular disease in a subject
WO2004004741A1 (en) * 2002-07-05 2004-01-15 King Roderick Frederick Gerard Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular disease

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