WO2004004741A1 - Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular disease - Google Patents
Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular diseaseInfo
- Publication number
- WO2004004741A1 WO2004004741A1 PCT/GB2003/002933 GB0302933W WO2004004741A1 WO 2004004741 A1 WO2004004741 A1 WO 2004004741A1 GB 0302933 W GB0302933 W GB 0302933W WO 2004004741 A1 WO2004004741 A1 WO 2004004741A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- aqueous formulation
- digestible saccharides
- subject
- concentration
- tendency
- Prior art date
Links
- 239000013011 aqueous formulation Substances 0.000 title claims abstract description 64
- 150000001720 carbohydrates Chemical class 0.000 title claims abstract description 61
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 20
- 230000009286 beneficial effect Effects 0.000 title abstract description 4
- 235000014633 carbohydrates Nutrition 0.000 claims abstract description 37
- 229930182830 galactose Natural products 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 150000002500 ions Chemical class 0.000 claims description 13
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 10
- 239000011707 mineral Substances 0.000 claims description 10
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims description 9
- 230000001965 increasing effect Effects 0.000 claims description 9
- 229910001425 magnesium ion Inorganic materials 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
- 229920001542 oligosaccharide Polymers 0.000 claims description 8
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- 239000011734 sodium Substances 0.000 claims description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 7
- 239000011591 potassium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
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- 239000005913 Maltodextrin Substances 0.000 claims description 6
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- 229920002472 Starch Polymers 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
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- 229910001431 copper ion Inorganic materials 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
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- 229960003975 potassium Drugs 0.000 description 4
- 229910001414 potassium ion Inorganic materials 0.000 description 4
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- 239000006046 creatine Substances 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 240000001890 Ribes hudsonianum Species 0.000 description 2
- 235000016954 Ribes hudsonianum Nutrition 0.000 description 2
- 235000001466 Ribes nigrum Nutrition 0.000 description 2
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
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- 159000000000 sodium salts Chemical class 0.000 description 2
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
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- 235000016623 Fragaria vesca Nutrition 0.000 description 1
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- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 241000220225 Malus Species 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
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- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
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- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
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- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
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- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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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
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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 satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising digestible saccharides such as galactose with beneficial effects on a tendency to cardiovascular disease, and to the use of digestible saccharides prophylactically.
- Cardiovascular disease including coronary events and stroke
- cardiovascular disease is a major worldwide concern which effects individuals of any age. It involves significant mortality and has associated widespread economic and clinical implications.
- 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.
- the present invention is based on the recognition that by exercising careful control of carbohydrate nutrition, it may be possible to prevent an increased tendency to cardiovascular disease.
- the present invention relates to an aqueous formulation which essentially satisfies the dietary carbohydrate requirements of a subject in a manner in which oral bacteria will fail to flourish and/or in a manner which lessens the tendency towards a normal insulin response.
- the present invention provides an aqueous formulation for satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising: one or more digestible saccharides at a concentration sufficient to satisfy at least a part of the dietary carbohydrate requirements and water, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject.
- the one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
- the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present at an oral plaque formation inhibiting concentration.
- the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present at a concentration insufficient to provoke a normal insulin response. By lessenening the tendency towards a normal insulin response, there is prevented any increased tendency to arteriosclerosis and to left ventricular hypertrophy.
- cardiovascular eg heart and stroke
- the one or more digestible saccharides may be selected from the group consisting of digestible monosaccharides, disaccharides, oligosaccharides and polysaccharides. These may be natural or synthetic digestible saccharides.
- the one or more digestible saccharides may be selected from the group consisting of galactose, glucose, sucrose, dextrose, fructose, lactose, maltodextrin, starch (soluble) and maltose.
- the one or more digestible saccharides includes a digestible monosaccharide, particularly preferably galactose.
- the one or more digestible saccharides is galactose (ie alone).
- the total concentration of carbohydrate is in the range 50 to 350mM (broadly corresponding to a total carbohydrate concentration of 1-25% w/v depending on the chain length of any carbohydrate higher than a monomer eg 1-15% w/v for maltodextrin or soluble starch), preferably 50 to 310mM, particularly preferably 55 to 250mM, more preferably 60 to 175mM, especially preferably 70 to 160mM.
- the concentration of galactose in the aqueous formulation is in the range 50 to 300mM, preferably 70 to 250mM, more preferably 80 to 200mM.
- the concentration of glucose in the aqueous formulation is in the range 0 to 1 OmM, preferably 0 to 8mM, particularly preferably 0 to 6mM, especially preferably 0 to 2mM, most preferably is zero.
- the concentration of oligosaccharides in the aqueous formulation is in the range 1-15% w/v.
- the oligosaccharide is glucose containing (eg containing a glucose unit).
- Particularly preferred are maltodextrin and soluble starch.
- the presence of oligosaccharides such as maltodextrin and/or soluble starch is advantageous for satisfying carbohydrate requirements whilst not permitting oral bacteria to flourish.
- 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 phosphate and sodium bicarbonate.
- the counter ion eg chloride, bicarbonate, phosphate, hydrogenphosphate or citrate
- the concentration of sodium ions in the aqueous formulation is in the range 1 to lOOmM, preferably 5 to 85mM, particularly preferably 10 to 75mM, more preferably 15 to 45mM, yet more preferably 25 to 40mM.
- the sodium ions advantageously assist co-transport of galactose in the gut.
- a preferred embodiment of the aqueous formulation comprises one or more sources of mineral ions selected from the group consisting of sodium, potassium and magnesium ions.
- the source of a mineral ion is typically a salt such as a chloride, phosphate or citrate.
- the aqueous formulation comprises a source of potassium ions (eg a potassium salt such as potassium chloride or potassium hydrogenphosphate or potassium citrate).
- the concentration of potassium ions in the aqueous formulation is in the range 1 to 35mM, preferably 10 to 25mM, particularly preferably 15 to 20mM.
- the potassium ions are useful in the metabolism of carbohydrates.
- the aqueous formulation comprises a source of magnesium ions (eg a magnesium salt such as magnesium chloride).
- a source of magnesium ions eg a magnesium salt such as magnesium chloride.
- the concentration of magnesium ions in the aqueous formulation is in the range 1 to lOmM, preferably 2 to 8mM, particularly preferably 3 to 7mM, more preferably about 5mM.
- the aqueous formulation is adapted for oral administration to ensure that the one or more digestible saccharides adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject can be most effective.
- the aqueous formulation of the invention may be administered as a consumable (eg a foodstuff, drink or nutritional supplement) or as a prophylactic medicament.
- the aqueous formulation is conveniently 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 for the safety, palatability and acceptability of the aqueous formulation.
- physiologically tolerable stabilisers eg ascorbic acid
- preservatives eg sodium benzoate or sorbic acid
- Citric acid may be added to the aqueous formulation for partial or total replacement of any 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 3 OmM, preferably 10 to 25mM, particularly preferably 10 to 15mM.
- the concentration of chloride ion in the aqueous formulation may be in the range 20 to lOOmM, preferably 30 to 90mM, more preferably 40 to 85mM, especially preferably 50 to 80mM.
- the concentration of phosphate 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.
- the phosphate ions are useful in the metabolism of carbohydrates and may act as a buffer.
- the administration dosage generally depends on the dietary carbohydrate requirements of the subject and reflects the size and age of the subject. Generally it is advisable for the volume dose to be sufficient to substantially fully (eg wholly) satisfy the carbohydrate requirements of the subject and to be administered at appropriate intervals. Typically a dose of aqueous formulation is in the range 100 to 200ml.
- 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 one or more digestible saccharides and optionally one or more sources of mineral ions by addition of a suitable volume of aqueous solvent (eg water).
- the present invention provides a composition formulable (eg dissolvable) in aqueous solvent (eg water) to form an aqueous formulation as hereinbefore defined, said composition comprising one or more digestible saccharides in an amount sufficient to satisfy at least a part of the dietary carbohydrate requirements of a subject, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject.
- 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 is based on the recognition that digestible saccharides may be used in cases of general prevention of an increased risk of cardiovascular disease eg in adult populations (reduction of primary risk) or in prevention of a further increased risk of cardiovascular disease in cases of existing cardiovascular disease (secondary prevention).
- the present invention provides the use of one or more digestible saccharides (and optionally one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions) for the preparation of a medicament for preventing an increased tendency to cardiovascular disease when administered so as to satisfy at least a part of the dietary carbohydrate requirements of the subject.
- the one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
- the medicament may be administered by any route (eg orally or by injection).
- the medicament is administered orally. It may be in a solid or liquid form and may be administered as a foodstuff (eg a bar), nutritional supplement or drink or as a tablet or powder.
- the medicament is or comprises (A) an aqueous formulation or (B) a composition formulable (eg dissolvable in water) into an aqueous formulation as hereinbefore defined.
- a composition formulable eg dissolvable in water
- the one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular disease by being present in the medicament in an oral plaque formation inhibiting amount.
- the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present in the medicament at a concentration insufficient to provoke a primary insulin response.
- cardiovascular eg heart and stroke
- the one or more digestible saccharides include galactose (preferably galactose alone).
- the present invention provides a method for preventing an increased tendency to cardiovascular disease in a subject comprising the step of: administering an aqueous formulation, composition or medicament as hereinbefore defined so as to satisfy at least a part of the dietary carbohydrate requirements of the subject.
- the one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
- 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.
- Examples A, B and D may be particularly useful in satisfying the carbohydrate requirement of a subject whilst not elevating the tendency to cardiovascular (eg heart and stroke) disease.
- cardiovascular eg heart and stroke
- Examples F, G, H, I & J correspond respectively to A, B, C, D & E of the fibre-free formulations specified in Example 1.
- Examples F, G, H, I & J correspond respectively to A, B, C, D & E in terms of their respective use (Examples ABD are equivalent to FGI and Examples CDE are equivalent to HIJ).
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Abstract
The present invention relates to an aqueous formulation for satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising digestible saccharides such as galactose with beneficial effects on a tendency to cardiovascular disease, and to the use of digestible saccharides prophylactically.
Description
AQUEOUS FORMULATION COMPRISING DIGESTIBLE SACCHARIDES WITH BENEFICIAL EFFECTS ON A TENDENCY TO CARDIOVASCULAR DISEASE
The present invention relates to an aqueous formulation for satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising digestible saccharides such as galactose with beneficial effects on a tendency to cardiovascular disease, and to the use of digestible saccharides prophylactically.
Cardiovascular disease (including coronary events and stroke) is a major worldwide concern which effects individuals of any age. It involves significant mortality and has associated widespread economic and clinical implications.
It is known that poor oral hygiene, an imbalanced diet or nutritional deprivation is behind various dental diseases (Nutrition Science News: Oral Health, M Sterling, December 1999). For example, dental cavities arise from the acidic environment created when bacteria feed on food debris in the teeth. These bacteria together with acid, carbohydrates and bacteria form plaque which accumulates further bacteria and holds acid close to the tooth from where it erodes enamel. Bacteria are also responsible for gum disease such as periodontitis and gingivitis. In serious cases of dental disease, bacteria may penetrate into the vascular system leading to an increased tendency to cardiovascular disease.
Conventional foodstuffs for satisfying the dietary carbohydrate requirements of a subject rely heavily on specific sugar content. Oral bacteria are known to thrive on certain sugary foodstuffs.
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.
The present invention is based on the recognition that by exercising careful control of carbohydrate nutrition, it may be possible to prevent an increased tendency to cardiovascular disease. In particular, the present invention relates to an aqueous formulation which essentially satisfies the dietary carbohydrate requirements of a subject in a manner in which oral bacteria will fail to flourish and/or in a manner which lessens the tendency towards a normal insulin response.
Thus viewed from one aspect the present invention provides an aqueous formulation for satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising: one or more digestible saccharides at a concentration sufficient to satisfy at least a part of the dietary carbohydrate requirements and water, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject.
The one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
In a preferred embodiment, the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present at an oral plaque formation inhibiting concentration.
In a preferred embodiment, the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present at a concentration insufficient to provoke a normal insulin response. By lessenening the tendency towards a normal insulin response, there is prevented any increased tendency to arteriosclerosis and to left ventricular hypertrophy.
In an embodiment of the invention, the one or more digestible saccharides may be selected from the group consisting of digestible monosaccharides, disaccharides, oligosaccharides and polysaccharides. These may be natural or synthetic digestible saccharides. For example, the one or more digestible saccharides may be selected from the group consisting of galactose, glucose, sucrose, dextrose, fructose, lactose, maltodextrin, starch (soluble) and maltose. Preferably the one or more digestible saccharides includes a digestible monosaccharide, particularly preferably galactose. Preferably the one or more digestible saccharides is galactose (ie alone).
In a preferred embodiment, the total concentration of carbohydrate is in the range 50 to 350mM (broadly corresponding to a total carbohydrate concentration of 1-25% w/v depending on the chain length of any carbohydrate higher than a monomer eg 1-15% w/v for maltodextrin or soluble starch), preferably 50 to 310mM, particularly preferably 55 to 250mM, more preferably 60 to 175mM, especially preferably 70 to 160mM.
In a preferred embodiment, the concentration of galactose in the aqueous formulation is in the range 50 to 300mM, preferably 70 to 250mM, more preferably 80 to 200mM.
In a preferred embodiment, the concentration of glucose in the aqueous formulation is in the range 0 to 1 OmM, preferably 0 to 8mM, particularly preferably 0 to 6mM, especially preferably 0 to 2mM, most preferably is zero.
In a preferred embodiment, the concentration of oligosaccharides in the aqueous formulation is in the range 1-15% w/v. Preferably the oligosaccharide is glucose containing (eg containing a glucose unit). Particularly preferred are maltodextrin and soluble starch. The presence of oligosaccharides such as maltodextrin and/or soluble starch is advantageous for satisfying carbohydrate requirements whilst not permitting oral bacteria to flourish.
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 phosphate and sodium bicarbonate. The counter ion (eg chloride, bicarbonate, phosphate, hydrogenphosphate or citrate) may provide stability and buffering capacity.
In a preferred embodiment, the concentration of sodium ions in the aqueous formulation is in the range 1 to lOOmM, preferably 5 to 85mM, particularly preferably 10 to 75mM, more preferably 15 to 45mM, yet more preferably 25 to 40mM. The sodium ions advantageously assist co-transport of galactose in the gut.
A preferred embodiment of the aqueous formulation comprises one or more sources of mineral ions selected from the group consisting of sodium, potassium and magnesium ions. The source of a mineral ion is typically a salt such as a chloride, phosphate or citrate.
Preferably the aqueous formulation comprises a source of potassium ions (eg a potassium salt such as potassium chloride or potassium hydrogenphosphate or potassium citrate). In a preferred embodiment, the concentration of potassium ions in the aqueous formulation is in the range 1 to 35mM, preferably 10 to 25mM, particularly preferably 15 to 20mM. The potassium ions are useful in the metabolism of carbohydrates.
Preferably the aqueous formulation comprises a source of magnesium ions (eg a magnesium salt such as magnesium chloride). In a preferred embodiment, the concentration of magnesium ions in the aqueous formulation is in the range 1 to lOmM, preferably 2 to 8mM, particularly preferably 3 to 7mM, more preferably about 5mM.
Preferably the aqueous formulation is adapted for oral administration to ensure that the one or more digestible saccharides adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject can be most effective. The aqueous formulation of the invention may be administered as a consumable (eg a foodstuff, drink or nutritional supplement) or as a prophylactic medicament. The aqueous formulation is conveniently 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 for the safety, palatability and acceptability of the aqueous formulation.
Citric acid may be added to the aqueous formulation for partial or total replacement of any 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 3 OmM, preferably 10 to 25mM, particularly preferably 10 to 15mM.
Where the source of mineral ions is a chloride salt, the concentration of chloride ion in the aqueous formulation may be in the range 20 to lOOmM, preferably 30 to 90mM, more preferably 40 to 85mM, especially preferably 50 to 80mM.
Where the source of ions is a phosphate salt, the concentration of phosphate 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. The phosphate ions are useful in the metabolism of carbohydrates and may act as a buffer.
The administration dosage generally depends on the dietary carbohydrate requirements of the subject and reflects the size and age of the subject. Generally it is advisable for the volume dose to be sufficient to substantially fully (eg wholly) satisfy the carbohydrate requirements of the subject and to be administered at appropriate intervals. Typically a dose of aqueous formulation is in the range 100 to 200ml.
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 one or more digestible saccharides and optionally one or more sources of mineral ions 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 aqueous solvent (eg water) to form an aqueous formulation as hereinbefore defined, said composition comprising one or more digestible saccharides in an amount sufficient to satisfy at least a part of the dietary carbohydrate requirements of a subject, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular (eg heart or stroke) disease in the subject.
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.
From a further patentable viewpoint, the present invention is based on the recognition that digestible saccharides may be used in cases of general prevention of an increased risk of cardiovascular disease eg in adult populations (reduction of primary risk) or in prevention of a further increased risk of cardiovascular disease in cases of existing cardiovascular disease (secondary prevention).
Viewed from a yet further aspect the present invention provides the use of one or more digestible saccharides (and optionally one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions) for the preparation of a medicament for preventing an increased tendency to cardiovascular disease when administered so as to satisfy at least a part of the dietary carbohydrate requirements of the subject.
The one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
The medicament may be administered by any route (eg orally or by injection). Preferably the medicament is administered orally. It may be in a solid or liquid form and may be administered as a foodstuff (eg a bar), nutritional supplement or drink or as a tablet or powder.
Preferably the medicament is or comprises (A) an aqueous formulation or (B) a composition formulable (eg dissolvable in water) into an aqueous formulation as hereinbefore defined.
Preferably the one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular disease by being present in the medicament in an oral plaque formation inhibiting amount.
Preferably the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular (eg heart and stroke) disease in the subject by being present in the medicament at a concentration insufficient to provoke a primary insulin response.
Preferably the one or more digestible saccharides include galactose (preferably galactose alone).
Viewed from an even still further aspect the present invention provides a method for preventing an increased tendency to cardiovascular disease in a subject comprising the step of: administering an aqueous formulation, composition or medicament as hereinbefore defined so as to satisfy at least a part of the dietary carbohydrate requirements of the subject.
The one or more digestible saccharides may be present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements (eg to substantially fully (preferably wholly) satisfy the dietary carbohydrate requirements) of the subject.
The present invention will now be described in a non-limitative sense with reference to the following Examples (by w/v is meant grams per 100ml of water).
Example 1
Five reconstituent aqueous formulations A-E were prepared which had the following components and concentrations after reconstirution in water:
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.
Examples A, B and D may be particularly useful in satisfying the carbohydrate requirement of a subject whilst not elevating the tendency to cardiovascular (eg heart and stroke) disease.
Example 2
Examples F, G, H, I & J correspond respectively to A, B, C, D & E of the fibre-free formulations specified in Example 1. Examples F, G, H, I & J correspond respectively to A, B, C, D & E in terms of their respective use (Examples ABD are equivalent to FGI and Examples CDE are equivalent to HIJ).
Claims
1. An aqueous formulation for satisfying at least a part of the dietary carbohydrate requirements of a subject, said aqueous formulation comprising: one or more digestible saccharides al a concentration sufficient to satisfy at least a part of the dietary carbohydrate requirements and water, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calciu , zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular disease in the subject.
2. An aqueous formulation as claimed in claim 1 wherein the one or more digestible saccharides are present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements .
3. An aqueous formulation as claimed in claim 1 or 2 wherein the one or more digestible saccharides is present at a concentration sufficient to satisfy wholly the dietary carbohydrate requirements of the subject.
4. An aqueous formulation as claimed in any preceding claim wherein the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular disease in the subject by being present at an oral plaque formation inhibiting concentration.
5. An aqueous formulation as claimed in any preceding claim wherein the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular disease in the subject by being present at a concentration insufficient to provoke a normal primary insulin response.
6. An aqueous formulation as claimed in any preceding claim wherein the one or more digestible saccharides are selected from the group consistmg of digestible rnonosaccharides, disaccharides, oligosaccharides and polysaccharides.
7. An aqueous formulation as claimed in claim 6 wherein the one or more digestible saccharides are selected from the group consisting of galactose, glucose, sucrose, dextrose, fructose, lactose, maltodextrin, starch (soluble) and maltose.
8. An aqueous formulation as claimed in claim 6 or 7 wherein the one or more digestible saccharides includes galactose.
9. An aqueous formulation as claimed in claim 8 wherein the one or more digestible saccharides is galactose alone.
10. An aqueous formulation as claimed in claim 6 or 7 wherein the one or more digestible saccharides includes an oligosaccharide.
11. An aqueous formulation as claimed in any preceding claim wherein the total concentration of carbohydrate is in the range 50 to 350m , preferably 50 to 31 OmM, particularly preferably 55 to 250mM, more preferably 60 to 175mM, especially preferably 70 to 160mM.
12. An aqueous formulation as claimed in claim 8 wherein the concentration of galactose in the aqueous formulation is in the range 50 to 300mM, preferably 70 to 250mM, more preferably 80 to 200mM.
13. An aqueous formulation as claimed in any preceding claim wherein the concentration of glucose in the aqueous formulation is zero.
14. An aqueous formulation as claimed in claim 10 wherein the concentration of oligosaccharides in the aqueous formulation is in the range 1-15% w/v.
15. An aqueous formulation as claimed in claim 10 wherein the oligosaccharide is selected from the group consisting of maltodextrin and soluble starch.
16. An aqueous formulation as claimed in any preceding claim adapted for oral administration.
17. An aqueous formulation as claimed in any preceding claim being a reconstituent aqueous formulation.
18. A composition formulable in aqueous solvent to form an aqueous formulation as defined in any preceding claim, said composition comprising one or more digestible saccharides in an amount sufficient to satisfy at least a part of the dietary carbohydrate requirements of a subject, optionally together with one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions, wherein said one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular disease in the subject.
19. Use of one or more digestible saccharides (and optionally one or more sources of mineral ions selected from the group consisting of sodium, potassium, calcium, zinc, copper, manganese and magnesium ions) for the preparation of a medicament for preventing an increased tendency to cardiovascular disease when administered so as to satisfy at least a part of the dietary carbohydrate requirements of the subject.
20. Use as claimed in claim 19 wherein the one or more digestible saccharides are present at a concentration sufficient to satisfy a major proportion of the dietary carbohydrate requirements.
21. Use as claimed in claim 19 or 20 wherein the one or more digestible saccharides are present at a concentration sufficient to substantially fully satisfy the dietaiy carbohydrate requirements of the subject.
22. Use as claimed in any of claims 19 to 21 wherein the one or more digestible saccharides are present at a concentration sufficient to satisfy wholly the dietary carbohydrate requirements of the subject.
23. Use as claimed in any of claims 19 to 22 wherein the medicament is administered orally.
24. Use as claimed in any of claims 19 to 23 wherein the medicament is or comprises an aqueous formulation as defined in any of claims 1 to 16 or a composition as defined in claim 17.
25. Use as claimed in any of claims 19 to 24 wherein the one or more digestible saccharides are adapted not to elevate a tendency to cardiovascular disease by being present in the medicament in an oral plaque formation inhibiting amount.
26. Use as claimed in any of claims 19 to 25 wherein the one or more digestible saccharides are adapted not to elevate the tendency to cardiovascular disease in the subject by being present in the medicament at a concentration insufficient to provoke a normal primary insulin response.
27. Use as claimed in any of claims 19 to 26 wherein the one or more digestible saccharides is galactose alone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003250393A AU2003250393A1 (en) | 2002-07-05 | 2003-07-07 | Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular disease |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39420902P | 2002-07-05 | 2002-07-05 | |
| GB0215589A GB0215589D0 (en) | 2002-07-05 | 2002-07-05 | Formulation |
| US60/394,209 | 2002-07-05 | ||
| GB0215589.3 | 2002-07-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004004741A1 true WO2004004741A1 (en) | 2004-01-15 |
Family
ID=30117098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2003/002933 WO2004004741A1 (en) | 2002-07-05 | 2003-07-07 | Aqueous formulation comprising digestible saccharides with beneficial effects on a tendency to cardiovascular disease |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003250393A1 (en) |
| WO (1) | WO2004004741A1 (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0324720A1 (en) * | 1988-01-14 | 1989-07-19 | Warner-Lambert Company | Saccharide inhibition of dental plaque |
| EP0342369A2 (en) * | 1988-05-14 | 1989-11-23 | Biodyn AG | Caries protection agent |
| WO1990002494A1 (en) * | 1988-09-15 | 1990-03-22 | Svenska Mejeriernas Riksförening Ekonomi Ab | Beverage rich in carbohydrates |
| EP0512599A2 (en) * | 1991-05-09 | 1992-11-11 | Unilever N.V. | Phosphorylated polyhydroxy compounds for tartar control |
| US5780094A (en) * | 1994-02-16 | 1998-07-14 | Marathade, Ltd. | Sports drink |
| EP0922459A1 (en) * | 1997-12-12 | 1999-06-16 | Ernst-Günter Prof. Dr. Dr. Afting | Pharmaceutical compositions comprising D-galactose and the use thereof |
| WO2003039556A1 (en) * | 2001-11-07 | 2003-05-15 | Ceretech Limited | Rehydrating formulation |
-
2003
- 2003-07-07 WO PCT/GB2003/002933 patent/WO2004004741A1/en not_active Application Discontinuation
- 2003-07-07 AU AU2003250393A patent/AU2003250393A1/en not_active Abandoned
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0324720A1 (en) * | 1988-01-14 | 1989-07-19 | Warner-Lambert Company | Saccharide inhibition of dental plaque |
| EP0342369A2 (en) * | 1988-05-14 | 1989-11-23 | Biodyn AG | Caries protection agent |
| WO1990002494A1 (en) * | 1988-09-15 | 1990-03-22 | Svenska Mejeriernas Riksförening Ekonomi Ab | Beverage rich in carbohydrates |
| EP0512599A2 (en) * | 1991-05-09 | 1992-11-11 | Unilever N.V. | Phosphorylated polyhydroxy compounds for tartar control |
| US5780094A (en) * | 1994-02-16 | 1998-07-14 | Marathade, Ltd. | Sports drink |
| EP0922459A1 (en) * | 1997-12-12 | 1999-06-16 | Ernst-Günter Prof. Dr. Dr. Afting | Pharmaceutical compositions comprising D-galactose and the use thereof |
| WO2003039556A1 (en) * | 2001-11-07 | 2003-05-15 | Ceretech Limited | Rehydrating formulation |
Non-Patent Citations (1)
| Title |
|---|
| FRUSTACI ANDREA ET AL: "Improvement in cardiac function in the cardiac variant of Fabry's disease with galactose-infusion therapy", NEW ENGLAND JOURNAL OF MEDICINE, vol. 345, no. 1, 5 July 2001 (2001-07-05), pages 25 - 32, XP009019775, ISSN: 0028-4793 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003250393A1 (en) | 2004-01-23 |
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