WO2016083362A1 - Composition pour améliorer les fonctions cognitives - Google Patents

Composition pour améliorer les fonctions cognitives Download PDF

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Publication number
WO2016083362A1
WO2016083362A1 PCT/EP2015/077480 EP2015077480W WO2016083362A1 WO 2016083362 A1 WO2016083362 A1 WO 2016083362A1 EP 2015077480 W EP2015077480 W EP 2015077480W WO 2016083362 A1 WO2016083362 A1 WO 2016083362A1
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Prior art keywords
composition
dha
composition according
vitamin
blueberry
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PCT/EP2015/077480
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English (en)
Inventor
Peder Esben BILDE
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Fonden For Helene Elsass Centeret
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Publication of WO2016083362A1 publication Critical patent/WO2016083362A1/fr

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or 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
    • 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
    • A23L33/15—Vitamins
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine

Definitions

  • Composition for improving cognitive functions is provided.
  • the present invention is in the field of nutritional (or pharmaceutical) supplements and more particularly relates to a composition for use in improving/enhancing cognitive and motor abilities in humans.
  • Foods containing specific nutrients and vitamins can have a profound effect on the mental and physical fitness of the human mind and body.
  • the relative abundance of specific nutrients could affect cognitive processes due to the fact that influences of dietary factors on neuronal function and synaptic plasticity are responsible for brain health and mental function.
  • Certain foods are therefore frequently consumed as part of a health improving diet. Consuming adequate amount of foods with health promoting effect can be a difficult task, as a result of changing seasons, inadequate supply of the food source, shelf life of the unprocessed food as well as inconvenience in food preparation. There is therefore an increasing demand for industrially prepared compositions that specifically contain the health promoting compounds.
  • Omega-3 fatty acids are polyunsaturated fatty acids having the unsaturated bonds at a particular position, which contributes to the effect on human health.
  • Omega-3 fatty acids preferably have between 18-22 carbons and 3 to 6 double bonds.
  • These omega-3 fatty acids can be in the form of free fatty acids, (alkyl) esters thereof, glycerides thereof, phospholipid esters thereof or mixtures thereof.
  • Such omega-3 fatty acids can be obtained e.g. from marine oils such as fish oils, krill, algae and some specific vegetable oils.
  • omega-3 fatty acids such as DHA in combination with other ingredients have attracted attention as active components with an ability to reduce cognitive deficits in children affected with developmental coordination disorder (Richardson AJ, Montgomery P, Pediatrics 1 15, 1360- 1366 (2005)) and improve coordination, concentration and academic ability in "normal” children (Portwood M, Nutr. Health, 18, 233-247, (2006)).
  • Uridine is another micronutrient, which has been found important in mental fitness.
  • Cells use uridine and fatty acids like DHA in the synthesis of phosphatidylcholine (PC) which is a major component of brain cell membranes.
  • PC also provides the phosphocholine moiety needed to synthesize sphingomyelin (SM), which is the major choline containing brain phospholipid.
  • Vitamin D is able to cross the blood brain barrier and vitamin D receptors are found in the brain suggesting that vitamin D is essential for optimal brain health.
  • Blueberry, green tea and cocoa are rich in a group of phytochemicals called flavonoids. Flavonoids are a class of compounds found to have a neuroprotective effect and potential to promote memory, learning and cognitive function.
  • Flavonoids are strong antioxidants and are able to reduce the damage caused by free radicals. However, it has been suggested that the neuroprotective effect of flavonoids may be mediated by other pathways to protect vulnerable neurons, enhance existing neuronal function, stimulate neuronal regeneration and induce neurogenesis (Spenser EPJ, Genes Nutr, 243-250, (2009)). Hence it is clear from the art that numerous micronutrients independently are reported to have a positive effect on the biochemical and cellular level corresponding to cognitive functions. However, a clear understanding of how these micronutrients can work together and create a synergy corresponding to a greater effect is clearly lacking.
  • WO 2006/127627 relates to a composition of polyunsaturated fatty acids (PFUAs) with or without Uridine.
  • the composition is used as a method of enhancing brain development and increasing intelligence by administering the composition to a subject or a pregnant or nursing mother.
  • the present invention was made in view of the prior art described above, and the object of the present invention is to provide a composition with the ability to improve cognitive functions such as e.g. learning, memory, attention or motorial skills. Another object relates to the provision of a nutritional supplement for improving cognitive functions such as learning, memory, attention and motor skills administration in healthy individuals. A further object relates to the provision of a composition to improve developmental coordination disorder. To solve the problem, the present invention provides a composition comprising:
  • Uridine such as Uridine monophosphate (UMP), or phosphates, acyl derivatives, esters or salts thereof
  • DHA Docosahexaenoic acid
  • the composition formulated for oral administration comprising Uridine, DHA and Vitamin D3 has an ability to improve cognitive and motor abilities in healthy individual.
  • the composition further comprises one or more flavonoid(s) obtainable form blueberry or blueberry extract.
  • the combination of Uridine, DHA, vitamin D3 with flavonoid(s) obtainable form blueberry is able to enhance the effect of Uridine, DHA and vitamin D on cognitive functions and motor skills.
  • the present invention may comprise a pharmaceutical composition for oral administration comprising Uridine, DHA and vitamin D3.
  • the pharmaceutical composition may be used to improve cognitive and motor skills in individuals with Cerebral Palsy.
  • Another aspect of the present invention concerns a method for improving cognitive functions and/or motor skills in a human subject in need thereof, comprising administering to the subject an effective amount of a composition comprising: i) Uridine, such as uridine monophosphate (UMP), or salts, phosphates, acyl derivatives or esters thereof;
  • Uridine such as uridine monophosphate (UMP), or salts, phosphates, acyl derivatives or esters thereof;
  • DHA Docosahexaenoic acid
  • Vitamin D3 such as 25-Hydroxyvitamin D3, or salts thereof.
  • the composition of the present invention when consumed on a daily basis over a prolonged period of time offers the advantage of improved cognitive abilities such learning, memory, attention as well as motor abilities.
  • the combination of the specific micronutrients of the present invention gives the recipient an improved health benefit/effect, compared to the consumption of one or more of the micronutrients separately, as the unique components work in synergy.
  • the combination of the micronutrients in one composition makes it more convenient for individuals to get adequate intake on a daily basis compared to consuming unprocessed foods.
  • the ability to consume this composition which constitutes a cocktail of micronutrients with a clear health benefit is a significant advantage as it would be challenging to get enough of each micronutrient through regular food consumption on a daily and continues basis.
  • composition of the present invention is the ability to preserve micronutrients and prolong shelf life, compared to their natural form.
  • Figure 1 illustrates individual dietary intake of mono- and polyunsaturated fatty acids and vitamin D.
  • 1 -4 represents girls and 5-1 1 represents boys.
  • Bold line represent daily minimum recommended levels of intake
  • E%) Monounsaturated fatty acid intake (E%), recommended level: 10-15 E%.
  • B Polyunsaturated fatty acid intake (E%), recommended level: 5-10 E%.
  • C Vitamin D ( g) intake with (grey bars) and without (black bars) vitamin supplement, recommended level: 7.5 g.
  • Figure 2 illustrates plasma concentrations of vitamin D (A), Docosahexaenoic acid (DHA) (B) and brain-derived neurotrophic factor (BDNF) (C) in boys (black square dots) and girls (grey triangle dots), before and after DDU- and placebo supplement.
  • DHA Docosahexaenoic acid
  • BDNF brain-derived neurotrophic factor
  • Figure 3 illustrates the performance of the subjects in two Mitii training modules; Memory (A) and Mathematics (B) during the intervention periods when children received DDU-supplement (black circles) or placebo (grey circles). The values are given as the decrease in the errors in percentage during each possible training day. The shaded areas mark the standard error for each group. Significant improvement pre compared to post intervention (p ⁇ 0.05, Two-way ANOVA RM).
  • Figure 4 illustrates the performance of the subjects in reading/comprehension test (A) and math test (B) in boys (black square dots) and girls (grey triangle dots) before and after DDU- and placebo supplement.
  • Right upper corner Performance in relation to interventions. Data are mean ⁇ SEM., * p ⁇ 0.05, ** p ⁇ 0.01 compared to pre intervention (Two-way ANOVA RM).
  • Figure 5 illustrates the performance of the subjects before and after DDU- and placebo supplement in CPAL: Speed of performance (A), Percentages correct answers (B). Significant interaction between pre/post and CPAL repetition (Linear mixed mode, p ⁇ 0.05l), GML: Duration (C), Percentages errors (D). Significant interaction between pre/post and GML repetition (Linear mixed model, p ⁇ 0.05).
  • E Error
  • F Speed of performance
  • boys black square dots
  • girls grey triangle dots
  • Right upper corner in E and F Performance in relation to interventions. Data are mean ⁇ SEM., * p ⁇ 0.05 compared to pre intervention (Two-way ANOVA RM).
  • Figure 6 illustrates the average relative success rate for the two different groups of mice. Mice that received a supplement containing blueberry extract had a success rate of about 40%, whereas the group receiving normal supplements without blueberry extracts had a success rate of about 34%.
  • Table 2 Composition of DDU-supplement and Placebo emulsions [wt %].
  • Table 5 Effect of interventions on blood parameters.
  • the invention relates to a composition with the ability to improve cognitive functions such as learning, memory, attention and motor skills.
  • One aspect of the invention is directed to a composition comprising i) Uridine, Uridine monophosphate (UMP) or phosphates, acylderivatives, esters or salts thereof and ii) Docosahexaenoic acid (DHA) in triacylglyceride form, or as free fatty acids, as phospholipids, esters or salts thereof and iii) vitamin D (vitamin D3, 25-Hydroxyvitamin D3) or salt thereof.
  • a preferred embodiment of the invention is a composition comprising i) Uridine monophosphate and ii) Docosahexaenoic acid in triacylglyceride form and iii) vitamin D.
  • Uridine is a nucleoside which has been found important in mental fitness. Uridine can be obtained from a variety of food sources such as sugarcane extract, tomatoes, beer, beetroot and broccoli. Cells use uridine and fatty acids like DHA in the synthesis of phosphatidylcholine (PC) which is a major component of brain cell membranes. PC also provides the phosphocholine moiety needed to synthesize sphingomyelin (SM), which is the major choline containing brain phospholipid.
  • PC phosphatidylcholine
  • SM sphingomyelin
  • the uridine component of the composition may be in the form of uridine, uridine 5'-monophosphate, acylderivatives, esters, salts thereof or any other uridine derivative with properties similar to uridine 5'-monophosphate.
  • Docosahexaenoic acid (DHA; 22:6) is an omega-3 polyunsaturated fatty acid (PUFA), more particular a carboxylic acid with a 22-carbon chain containing six cis double bonds.
  • DHA is the primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. DHA has been linked to several health benefits e.g. anti-inflammatory, cardiovascular, brain development and anti-depressant.
  • DHA is one of the components in the synthesis of phosphatidylcholine (PC).
  • PC phosphatidylcholine
  • DHA can be isolated from a variety of sources.
  • the DHA component of the composition may be in the form of a triacylglyceride, as free fatty acids, as phospholipids, esters, salts thereof or any other DHA derivative with properties similar to docosahexaenoic acid in triacylglyceride form.
  • Vitamin D belongs to a group of fat-soluble secosteroids with multiple functions.
  • the vitamin D receptor (VDR) is present in many cell types including neurons and glial cells and vitamin D may regulate neurotransmission, neuroprotection and brain processes.
  • the VDR have been located in the human cortex and hippocampus, which are key areas for cognitive function.
  • Vitamin D3 also known as cholecalciferol
  • Vitamin D3 can be produced by the human body upon sunlight exposure.
  • Vitamin D needs to be ingested from dietary sources to prevent vitamin D deficiency.
  • Vitamin D deficiency has been associated with numerous diseases such as hyperparathyroidism, osteoporosis, cardiovascular and autoimmune diseases in addition to cognitive impairment.
  • Vitamin D3 is metabolised in the body into its more active metabolites'. Vitamin D3 is hydroxylated in the liver to form 25-hydroxyvitamin D3 (calcidiol) followed by a second hydroxylation in the kidney to form 1 ,25- dihydroxyvitamin D3 (calcitriol). 25-hydroxyvitamin D3 is the major circulating metabolite in serum with a concentration 1000 fold higher than that of 1 ,25- dihydroxyvitamin D3, but 25-hydroxyvitamin D3 has a 500 fold lower affinity for the vitamin D receptor than 1 ,25-dihydroxyvitamin D3.
  • the composition of the invention may in one embodiment comprise vitamin D3. In a further embodiment the composition comprises 25-hydroxyvitamin D3. In another embodiment the composition comprises 1 ,25-dihydroxyvitamin D3.
  • the DHA may be obtainable form fish, krill or alga.
  • Cold water fish have a particularly high content of DHA.
  • DHA can also be isolated form marine microalgae e.g. Crypthecornium cohnii and Schizochytrium.
  • DHA isolated form krill are in the form of phospholipids (mostly phosphatidylcholine).
  • DHA in the form of phospholipids leads to better absorption and delivery of DHA into the brain.
  • Some microalgae produce DHA and may be a suitable source of DHA in the present invention.
  • Microalgae belonging to a genus or class selected from Schizochytrium being the most preferred.
  • Blueberries are a food source rich in micronutrients such as dietary minerals and fibre, vitamins and compounds with high antioxidant capacity.
  • green tea and cocoa are also rich in a group of phytochemicals called flavonoids. Flavonoids are a class of compounds found to have a neuroprotective effect and to promote memory, learning and cognitive function.
  • the composition of the invention may further comprise a flavonoid obtainable from blueberry.
  • the flavonoid is selected from the list consisting of rutin, myricetin, quercetrin, delphinidin, cyaniding, petunidin, peonidin, malvidin anthocynins, procyanidins.
  • the composition may comprise one or more flavonoids that can be isolated from blueberries.
  • the composition of the invention may comprise flavonoid(s) in the form of blueberry or blueberry extract. Blueberries may be formed/converted into a liquid solution which can be added to the composition or from which a blueberry extract containing flavonoids is extracted. The blueberry extract may be further concentrated to increase the concentration of flavonoid(s) added to the composition.
  • Flavonoid(s), blueberry or blueberry extract of the present invention may be isoladed from Vaccinium sp., Vaccinium alaskaense, Vaccinium angustifolium, Vaccinium boreale, Vaccinium caesariense, Vaccinium corymbosum, Vaccinium constablaei, Vaccinium darrowii, Vaccinium elliottii, formosum, Vaccinium fuscatum, Vaccinium hirsutum, Vaccinium myrsinites, Vaccinium myrtilloides, Vaccinium operium, Vaccinium pallidum, Vaccinium simulatum, Vaccinium tenellum, Vaccinium virgatum.
  • the blueberry, blueberry extract or flavonoid(s) is obtained from Vaccinium angustifolium Aiton. In another embodiment the blueberry, blueberry extract or flavonoid(s) is obtained from Vaccinium corymosum L.
  • the seed of Theobroma cacao also known as cacao tree and cocoa tree are used to make cocoa powder which is an ingredient of chocolate.
  • the cocoa seed and cocoa powder is like blueberry a source of antioxidants e.g. flavonoids with neuroprotective effect and the ability to promote memory, learning and cognitive function.
  • one or more flavonoid(s) are isolated form cocoa.
  • the flavonoid is provided in the form of cocoa or cocoa extract. Cocoa may be added to the composition in the form of cocoa powder. All tea plants belong to the species Camellia sinensis. The leaves of Camellia sinensis are harvested and processed into tea.
  • the flavonoid(s) is selected from the list consisting of rutin, catechins, myricetin and quercetin.
  • the flavonoid(s) is provided in the form of white tea or white tea extract.
  • the flavonoid(s) is provided in the form of green tea or green tea extract.
  • composition of the present invention is preferably combined in one dosage form.
  • the components of the composition are present in different concentrations.
  • the composition comprises uridine, phosphate, acyl derivatives, ester or salt thereof at a concentration of 1000 mg per dosage form.
  • the dosage of uridine is within the range of 500- 5000 mg per dosage form.
  • the dosage of uridine is in the range of 200-1200 mg per dosage form.
  • the dosage of uridine is in the range of 500-1000 mg per dosage form.
  • the dosage of uridine is in the range of 1000-2000 mg per dosage form.
  • the dosage uridine is in the range of 2000-3000 mg per dosage form.
  • the dosage of uridine is in the range of 3000-4000 mg per dosage form.
  • the dosage of uridine is in the range of 4000-5000 mg per dosage form.
  • the composition further comprises docosahexaenoic acid (DHA).
  • DHA may be in triacylglyceride form, or as free fatty acids, as phospholipids, esters or salts thereof at a concentration of 500 mg per dose form.
  • the dosage of DHA is within the range of 500-5000 mg per dosage form.
  • the dosage of DHA is within the range of 100-1000 mg per dosage form.
  • the dosage of DHA is within the range of 1000-5000 mg per dosage form.
  • the dosage of DHA is within the range of 2000-5000 mg per dosage form.
  • the dosage of DHA is within the range of 3000-5000 mg per dosage form.
  • the dosage of DHA is within the range of 4000-5000 mg per dosage form.
  • the composition may comprise vitamin D in the form of vitamin D3 , 25- hydroxyvitamin D3, biologically active form or salt thereof at a concentration of 10 g per dosage form.
  • the dosage of vitamin D3 is in the range of 2-20 g per dosage form.
  • the dosage of vitamin D3 is in the range of 10-100 g per dosage form.
  • the dosage of vitamin D3 is in the range of 10-50 g per dosage form.
  • the dosage of vitamin D3 is in the range of 30-80 g per dosage form.
  • the dosage of vitamin D3 is in the range of 50-100 g per dosage form.
  • the composition comprises one or more flavonoid(s) obtainable from blueberry at a concentration within the range of 100-5000 mg per dosage form.
  • the collective concentration of one or more flavonoid(s) is at a concentration within the range of 100-5000 mg per dosage form. In one embodiment the collective concentration of one or more flavonoid(s) is at a concentration within the range of 100-1000 mg per dosage form. In one embodiment the collective concentration of one or more flavonoid(s) is at a concentration within the range of 1000-5000 mg per dosage form. In another embodiment the concentration of one or more flavonoid(s) is within the range of 100-5000 mg per dosage form for each individual flavonoid. In another embodiment the concentration of one or more flavonoid(s) is within the range of 100-1000 mg per dosage form for each individual flavonoid.
  • the concentration of one or more flavonoid(s) is within the range of 1000-5000 mg per dosage form for each individual flavonoid.
  • the composition comprises blueberry extract at a concentration of 500 mg per dosage form.
  • the composition comprises blueberry extract at a concentration within the range of 100-5000 mg per dosage form.
  • the composition comprises blueberry extract at a concentration within the range of 100-1000 mg per dosage form dosage form.
  • the composition comprises blueberry extract at a concentration within the range of 1000-5000 mg per dosage form.
  • the composition comprises per dosage form: 500-5000 mg Uridine, or salts, phosphates, acyl derivatives or esters thereof, 500-5000 mg docosahexaenoic acid (DHA) or esters thereof, 10-100 g vitamine D3 or salts thereof, and/or 100-5000 mg flavonoid obtainable from blueberry;
  • the composition comprises per dosage form: 200-1200 mg Uridine, or salts, phosphates, acyl derivatives or esters thereof, 100-1000 mg docosahexaenoic acid (DHA) or esters thereof, 2-20 g vitamin D3 or salts thereof, and/or 100-5000 mg flavonoid obtainable from blueberry;
  • DHA docosahexaenoic acid
  • the composition comprises per dosage form: about 290 mg Uridine, or salts, phosphates, acyl derivatives or esters thereof, about 500 mg docosahexaenoic acid (DHA) or esters thereof, about 10 g vitamin D3 or salts thereof, and/or about 145 mg flavonoid obtainable from blueberry; and/or 0,1 -10 g blueberry or blueberry extract.
  • the composition is a nutritional supplement.
  • the composition is formulated as a nutritional supplement contained in gelatinous capsules.
  • the capsules may be provided in any shape suitable for oral ingestion, such as capsules having the shape of drops.
  • the composition is formulated for oral administration.
  • the composition is a nutritional supplement for healthy individual.
  • the composition is a nutritional supplement for subjects with congenital or developmental brain disorders.
  • the formulation of the composition is a solid dosage form. Further in some embodiments the composition is a tablet. In another the composition is a liquid dosage form. Further the in some embodiments the liquid composition is a capsule. In another embodiment the composition is a pharmaceutical composition.
  • composition is formulated for oral administration.
  • the pharmaceutical composition is a solid dosage form.
  • the pharmaceutical composition is a liquid dosage form. Further in a preferred embodiment the pharmaceutical composition is a capsule. In other embodiments the pharmaceutical composition is a tablet.
  • the use of the composition is for improving of cognitive functions and/or motor skills in healthy individuals.
  • a composition of the invention is for use in improving cognitive functions and/or motor skills in individuals in need therefore.
  • the composition is for use in improving cognitive functions and/or motor skills in individuals with developmental coordination disorder and congenital brain disorder.
  • the composition is for use in improving the cognitive functions and/or motor skills in healthy individuals.
  • the composition is for use in improving learning in healthy individuals.
  • the composition is for improving learning in individuals with developmental coordination disorder.
  • the composition is for use in improving memory in healthy individuals.
  • the composition is for improving memory in individuals with developmental coordination disorder.
  • composition is for use in improving attention in healthy individuals. In a further embodiment the composition is for use in improving attention in individuals with developmental coordination disorder.
  • composition is for use in improving the cognitive functions and/or motor skills in prepubescent children.
  • composition is for use in improving cognitive functions e.g. attention, learning and/or memory in prepubescent children.
  • Another aspect of the invention is a method for improving cognitive functions and/or motor skills in a human subject in need thereof, comprising administering to the subject an effective amount of a composition comprising: i) Uridine, such as Uridine monophosphate, or salts, phosphates, acyl derivatives or esters thereof; ii) Docosahexaenoic acid (DHA), such as DHA in triacylglyceride form or esters thereof; iii) vitamin D3, such as 25- hydroxyvitamin D3, or salts thereof.
  • Uridine such as Uridine monophosphate, or salts, phosphates, acyl derivatives or esters thereof
  • DHA Docosahexaenoic acid
  • vitamin D3 such as 25- hydroxyvitamin D3, or salts thereof.
  • a preferred embodiment of the invention is a method for improving cognitive functions and/or motor skills in a human subject in need thereof, comprising administering to the subject an effective amount of a composition comprising : i) uridine monophosphate and ii) docosahexaenoic acid in triacylglyceride form and iii) vitamin D3.
  • Another embodiment of the invention is a method for improving cognitive functions and/or motor skills in a human subject in need thereof, comprising administering to the subject an effective amount of a composition which further comprises at least one flavonoid obtainable form blueberry.
  • composition used by the method of improving cognitive functions and/or motor skills comprises at least one flavonoid which is selected from the list consisting of rutin, myricetin, quercetrin delphinidin, cyanidin, petunidin, peonidin, malvidin, anthocynins procyanidins.
  • the at least one flavonoid is provided in the form of blueberry or blueberry extract.
  • the blueberry or blueberry extract is obtained from Vaccinium spp. In another embodiment of the composition the blueberry or blueberry extract is obtained from Vaccinium angustifolium Aiton. In another embodiment of the composition the blueberry or blueberry extract is obtained from Vaccinium corymosum L.
  • An additional embodiment of the invention is a method of activating the transcription factor cAMP response element-binding protein (CREB) by administering a composition according to the invention.
  • CREB transcription factor cAMP response element-binding protein
  • the objective of the present study was to investigate the ability of a composition comprising Uridine, DHA, vitamin D and blueberry extract to affect cognitive and motor functions, according to the present invention.
  • the present study was a randomized double-blinded placebo-controlled cross-over design.
  • the subjects in the study were fourteen prepubescent schoolchildren (6 girls and 8 boys).
  • the average age was 9.6 ⁇ 0.19 yr
  • body weight was 34.5 ⁇ 1 .5 kg
  • body mass index BMI
  • Maximal oxygen uptake (VO2 max) for the group was 1 .85 ⁇ 0.08 l/min with higher levels in boys (2.04 ⁇ 0.07 l/min) compared to girls (1 .60 ⁇ 0.08 l/min, p ⁇ 0.01 , Table 1 ).
  • All subjects were right- handed according to the Edinburgh Handedness Inventory (Neuropsychologia 1971 ;9:97-1 13) and none of them had any history of neurological or psychiatric disorders.
  • a combination of docosahexaenoic acid (DHA), vitamin D, uridine and blueberry extract (DDU-supplement) or a placebo supplement containing medium-chain triacylglycerol was ingested in a 6 week period with a 6 week washout period between trials.
  • the interventions were combined with a cognitive and motor training program consisting of a number of progressively challenging cognitive and motor tasks for 30 minutes a day, 3 days a week. Before the first intervention period four days of diet registration were completed. Before and after each intervention period blood sampling and testing of cognitive parameters such as attention, learning and memory was performed. Furthermore, maximal oxygen uptake (VO 2 inax) was measured on a treadmill before and after the interventions to determine the physical fitness level of the children.
  • DANKOST 3000 was applied providing details about energy intake and macro- and micronutrients.
  • Blood was drawn in the morning following a 12 hours fasting period. Blood was drawn from an antecubital vein with cuff. Plasma or serum was frozen at minus 20 or 80 degrees Celsius for further analysis.
  • the children completed memory and attention tests by using the computer program CogState and the computer exercises were chosen to specifically measure visual attention, learning and executive functions.
  • the program is ideal for pre and post testing design as the tasks are presented in a different way without changing the level.
  • the total time for the test is around 30 minutes and the main outcomes from the test are given by speed and total correct moves/choices.
  • One Back Task subjects had to recall if the card they were presented was similar to the previous card seen.
  • Two Back Task subjects had to recall if the card they were presented to was similar to the second previously seen card.
  • Continuous Paired Associative Learning (CPAL) Task subjects had to memorize the positions of up to seven abstract figures on the computer screen.
  • the children performed an incremental running test to exhaustion on a treadmill.
  • the protocol started with 1 min running at an individual maximal speed (9-1 1 .5 km/h) on slope 0% followed by stepwise 1 % incline every 1 minute until exhaustion. Criteria for reaching maximal oxygen uptake were: RER > 1 .00, a plateau in VO 2 despite increasing slope and unable to continue running despite verbal encouragement.
  • DDU-supplement consisted of a 10 ml o/w emulsion of 500 mg docosahexaenoic acid (DHA) in triacylglyceride form, 10 g vitamin D and 1000 mg uridine (Table 2).
  • DHA docosahexaenoic acid
  • Placebo consisted of a 10 ml o/w emulsion of 2 g MCT oil (medium-chain triglycerides) and artificial colouring (Table 2).
  • Whey protein was used as emulsifier in both types of emulsions.
  • both emulsions contained synthetic blueberry flavour to make the flavour and odour of the two emulsions similar.
  • Table 2 An overview of the different ingredients and their concentrations in the two different emulsions is shown in Table 2.
  • DDU-supplement and placebo emulsions were produced in 2- steps: pre-emulsification and homogenization.
  • whey protein was solubilized in the water and other hydrophilic ingredients were thereafter added to the whey protein-water solution (DDU-supplement: uridine and blue berry extract, artificial flavour; Placebo: artificial colour and flavour).
  • DDU-supplement uridine and blue berry extract, artificial flavour; Placebo: artificial colour and flavour
  • the aqueous solutions were stirred with an Ultra-Turrax (Janke & Kunkel IKA-Labortechnik, Staufen, Germany) and oil mixture (DDU-supplement: DHA 500TG and vitamin D) or oil (Placebo: MCT oil) was added during first min of the 2 minutes total mixing.
  • Pre-emulsions were then homogenized using a two valve table homogenizer at a pressure of 225 bar (GEA Niro Soavi Spa, Parma, Italy).
  • Produced emulsions were bottled (10 ml_), purged with nitrogen to limit lipid oxidation, sealed and pasteurized (72°C). All bottles were cooled at 5°C and thereafter stored at - 20°C until the delivery day.
  • the emulsions were taken daily in the morning together with at least 100 ml yoghurt or orange juice as part of the study subjects breakfast.
  • Oils used for DDU-supplement (Incromega DHA 500TG, 58% DHA) and Placebo (MCT, medium chain length C6-C12 triglycerides, whereof C8 56% and C10 43%, 99.3% triglyceride) were supplied from CRODA (East Yorkshire, England) and Sasol Germany GmbH (Witten, Germany), respectively.
  • Vitamin D, Uridine and blueberry extract were purchased from a local dietary shop, Yamasa Corporation (Chiba, Japan) and DENK Ingerdients GmbH (Munich, Germany), respectively.
  • Artificial flavor and whey protein were donated by A S Einar Willumsen (Broendby, Denmark) and Aria Foods (Viby J, Denmark), respectively.
  • Artificial colours (Dr. Oetker: red, blue and green) were purchased from a local super market.
  • Mitii consists of a number of modules in which the child used visual information, solved a cognitive problem (i.e. mathematical question, memory related task or similar) and responded with a motor act (i.e. bend to pick up needle and blow up balloon with the right answer). Examples of modules are Memory: the children had to memorize a specific order of images and Mathematics: the children had to solve arithmetic tasks as fast as possible. Further details are described earlier (BMC Neurol 201 1 ;1 1 :32).
  • 25(OH)D was used as measurement of plasma vitamin D concentration (J Nutr 2005;235:2739-48), and was measured by a competitive chemiluminescent immunoassay on a immunoDiagnosticSystem (iSYS).
  • DHA C22:6, n-3 in plasma was analyzed as earlier described (Eur J Lipid Sci Technol 2007;109:1993-009). Briefly, plasma lipids were extracted using a modification of the Folch-method, and fatty acid methyl esters (FAME) were produced using a BF 3 -catalyzed method, in which hydroquinone is added as antioxidant (Hamilton, J.R. and Hamilton, S. Extraction of lipids and derivative formation, in Lipid Analysis- A practical Approach. 13-64.1992.
  • BDNF brain- derived neurotrophic factor
  • Blood glucose and haemoglobin concentration were measured on ABL815 (Radiometer Medical A S, Copenhagen, Denmark).
  • Plasma triacylglycerol (TG), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and fatty acids (FA) were measured using enzymatic colorimetric methods (Hitachi 912 automatic analyzer).
  • the present study investigated the effect of cognitive and motor training with and without supplementation of DHA, vitamin, uridine and blueberry extract on motor and cognitive abilities in prepubescent children.
  • the inventors found an overall improvement of cognitive learning after 6 weeks of progressively challenging cognitive and motor tasks, 30 minutes 3 days/week independent of dietary supplementation. This was reflected in a significant progression in the cognitive and motor tasks in the MiTii program (Figure 3), a significant decrease in time to complete reading/comprehension test (Figure 4A), improvement in psychological tests (CPAL and GML tests, Figure 5A-D) and a decrease in percentage of error in the One back Task (Figure 5E). These data show improved attention and working memory after 6 weeks of cognitive training.
  • the participants in present study included 14 healthy, normal weight, prepubescent school children with lipid profile and maximal oxygen uptake comparable to Danish children at similar age (Prev Med 2003;37:363-7). However, the average plasma concentration of vitamin D was 47.7 ⁇ 4.8 nmol/l (19.12 ⁇ 1 .9 ng/ml) before DDU-supplementation, which is considered as vitamin D deficiency (Nimitphong H, Curr Opin Clin Nutr Metab Care 201 1 ;14:7-14). 90-95% of vitamin D formations occur as a result of exposures to sunlight. Our study was initiated in wintertime and stopped during the spring.
  • the length of dietary supplementation is another important factor to consider.
  • the intervention period was 12 month (Osendrap SJ, 2007) while dietary supplementation lasted only 8 weeks in the study by Kennedy et al. (2009) suggesting that cognitive changes take time to occur.
  • cognitive skills were improved after only 6 weeks, even though we did not use higher daily doses of DHA in the present study (500mg) compared to the study by Kennedy et al. (400 mg or 1000 mg).
  • the improvement in the present study could not be attributed to changes in physical fitness level, as this remained unchanged.
  • an internet based training program was applied allowing us to control that each session of practice was completed.
  • the rather fast improvements obtained may be a synergistic effect conferred by the combination of nutrients, which is more effective than DHA alone.
  • the combined intake of vitamin D and DHA resulted in a synergistically protective impact in relation to cerebral ischemia (Neurol Sci 2009;30:207-12) and the administration of DHA and uridine in combination improved memory and cognitive skilled tasks in rodents (Behav Brain Res 2008;191 :1 1 -6).
  • the mixture of important neural substrates in the present study might contribute to improve cognitive learning.
  • it cannot be ruled out that the low initial status in plasma vitamin D concentrations and DHA content in the children in the present study plays a significant role for the rapid improvement in cognitive skills.
  • mice C57BL/6 mice challenged with a motorial precision task challenged.
  • the contents of the supplements are seen in the table below.
  • 30 mice 4 weeks old where mice are regarded as adult by the age of 5 weeks) was divided in 2 groups containing 15 individuals. One group was given ordinary staple food, whereas the other group was given the same staple food supplemented with a blue berry extract rich in flavonoids (ca. 200 mg/kg).
  • the mice were given the respective foods for 2 weeks prior to being challenged and trained with the above mentioned task.
  • the then 6 old mice were trained and challenged with the precision motorial task for 2x20 min every day for a period of 10 days.
  • the task consisted of the mice having to stretch out its paws to grad a treat.
  • the treats were arranged in a steps formation requiring a certain skill to be reachable.
  • 32 treats were arranged in the described manner which also presented the maximum score an individual mouse could attain.
  • mice used in the study were young healthy individuals which have an inherent good capability of learning high precision motorial operations. It is expected to see a larger difference in mice having a neurological defect.
  • the reason for studying healthy mice is that mice with a neurological effect may have a high inter individual variation which may influence the statistical variation of the results.
  • V0 2 max (l/min/kg) 0.55 ⁇ 0.02 0.49 ⁇ 0.02 0.59 ⁇ 0.04*
  • Fibers (g) 26.0 ⁇ 2.09 21.2 ⁇ 1.6 28.8 ⁇ 2.7 ( ⁇ ) >10
  • Vitamin D ( g 4.15 ⁇ 0.84 4.36 ⁇ 1.8 4.02 ⁇ 0.9 7.5
  • Vitamin E (aTE (mg)) 14.1 ⁇ 3.24 12.8 ⁇ 5.3 14.9 ⁇ 4.4 7
  • Vitamin B1 (thiamin) (mg) 9.33 ⁇ 3.35 10.88 ⁇ 6.2 8.44 ⁇ 4.3 1.2
  • Vitamin B2 (riboflavin) (mg) 4.69 ⁇ 1.30 5.14 ⁇ 2.4 4.43 ⁇ 1.7 1.4
  • Vitamin B3 (niacin) (mg) 17.1 ⁇ 1.01 15.6 ⁇ 1.4 17.9 ⁇ 1.2
  • Vitamin B12 ( ⁇ ) 14.2 ⁇ 3.70 15.5 ⁇ 7.0 13.5 ⁇ 4.7 2
  • Vitamin C 250 ⁇ 82 257 ⁇ 162 245 ⁇ 101 50
  • Rl Recommended intake for a child aged 10-1 1 years.
  • a composition comprising:
  • Uridine such as Uridine monophosphate, 5'-uridylic
  • UMP phosphates, acyl derivatives, esters or salts thereof
  • DHA Docosahexaenoic acid
  • DHA such as DHA in triacylglyceride form, or phospholipids, esters or salts thereof;
  • Vitamine D3 such as 25-Hydroxyvitamin D3, or salts thereof.
  • Item 2 The composition according to item 1 , further comprising at least one flavonoid obtainable from blueberrry.
  • Item 3 The composition according to item 2, wherein said at least one flavonoid is selected from the list consisting of rutin, myricetin, quercetrin delphinidin, cyanidin, petunidin, peonidin, malvidin, anthocynins procyanidins and flavonols.
  • said at least one flavonoid is provided in the form of blueberry or blueberry extract,.
  • Item 5 The composition according to item 4, wherein the blueberry or blueberry extract is from Vaccinium spp.
  • Item 6 The composition according to item 4, wherein the blueberry or blueberry extract is from Vaccinium angustifolium Aiton.
  • Item 7 The composition according to item 4, wherein the blueberry or blueberry extract is from Vaccinium corymosum L.
  • Item 8 The composition according to any of the preceding items, wherein said composition comprises uridine, or salts, phosphates, acyl derivatieves or esters thereof at a concentration within the range of 500 - 5000 mg per dose such as 1000 mg per dose.
  • Item 9 The composition according to any of the preceding items, wherein said composition comprises docosahexaenoic acid (DHA) or esters thereof at a concentration within the range of 500 - 5000 mg per dose such as 500 mg per dose.
  • DHA docosahexaenoic acid
  • Item 10 The composition according to any of the preceding items, wherein said composition comprises vitamin D3 or salt thereof at a concentration within the range of 10 - 100 g per does such as 10 g per dose.
  • Item 1 1 The composition according to any of the preceding items, wherein said composition comprises flavonoid obtainable for blueberry at a concentration within the range of 100 - 5000 mg per dose. Item 12. The composition according to any of the preceding items, wherein said composition comprises blueberry extract at a concentration within the range of 100 - 10000 mg per does such as 500 mg per dose. Item 13. The composition according to any of the preceding items, wherein said composition comprises, per dosage form:
  • Uridine or salts, phosphates, acyl derivatives or esters thereof; 500-5000 mg Docosahexaenoic acid (DHA) or esters thereof;
  • Vitamine D3 or salts thereof
  • Item 14 The composition according to any of the preceding items, wherein the composition is formulated as a nutritional supplement, contained in gelatinous capsules.
  • Item 15 The composition according to any of the preceding items, wherein the composition is formulated for oral administration.
  • Item 16 The composition according to any of the preceding items, wherein the composition is a solid dosage form.
  • Item 17 The composition according to any of the preceding items, wherein the composition is a liquid dosage form.
  • Item 18 The composition according to any of the preceding items, wherein the composition is a capsule.
  • Item 19 The composition according to any of the preceding items, wherein the composition is a tablet.
  • Item 20 A pharmaceutical composition comprising the composition according to any of the preceding items.
  • Item 21 The pharmaceutical composition according to any of the preceding items, wherein the composition is formulated for oral administration.
  • Item 22 The pharmaceutical composition according to any of the preceding items, wherein the composition is a solid dosage form.
  • Item 23 The pharmaceutical composition according to any of the preceding items, wherein the composition is a liquid dosage form.
  • Item 24 The pharmaceutical composition according to any of the preceding items, wherein the composition is a capsule.
  • Item 25 The pharmaceutical composition according to any of the preceding items, wherein the composition is a tablet.
  • Item 26 Use of the composition according to any of the preceding items for improving of cognitive functions and/or motor skills.
  • Item 27 A composition according to any of the preceding items for use in improving cognitive functions and/or motor skills.
  • Item 28 The composition according to any of the preceding items for use in improving the cognitive functions and/or motor skills in healthy individuals.
  • Item 29 The composition according to any of the preceding items for use in improving learning in healthy individuals.
  • Item 30 The composition according to any of the preceding items for use in improving memory in healthy individuals.
  • Item 31 The composition according to any of the preceding items for use in improving attention in healthy individuals.
  • Item 32 The composition according to any of the preceding items for use in improving the cognitive functions and/or motor skills in prepubescent children.
  • Item 33 The composition according to any of the preceding items for use in improving cognitive functions e.g. attention, learning and/or memory in prepubescent children.
  • Item 34 A method for improving cognitive functions and/or motor skills in a human subject in need thereof, comprising administering to the subject an effect amount of a composition comprising:
  • Uridine such as Uridine monophosphate (UMP), 5'-uridylic acid or salts, phosphates, acyl derivatives or esters thereof;
  • DHA Docosahexaenoic acid
  • Item 35 The method of item 34, wherein the composition further comprises at least one flavonoid obtainable from blueberry.
  • Item 36 The method according to item 35, wherein said at least one flavonoid is selected from the list consisting of rutin, myricetin, quercetrin delphinidin, cyanidin, petunidin, peonidin, malvidin, anthocynins procyanidins and flavonols.
  • Item 37 The method according to item 35 or 36, wherein said at least one flavonoid is provided in the form of blueberry or blueberry extract.
  • Item 38 The composition according to item 37, wherein the blueberry or blueberry extract is from Vaccinium spp.
  • Item 39 The composition according to item 37, wherein the blueberry or blueberry extract is from Vaccinium angustifolium Aiton.
  • Item 40 The composition according to item 37, wherein the blueberry or blueberry extract is from Vaccinium corymosum L.

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Abstract

L'invention concerne une composition destinée à être utilisée en tant que complément nutritionnel ou médicament. La composition est destinée à être utilisée pour l'améliorer les fonctions cognitives telles que l'apprentissage, la mémoire et l'attention ainsi que la motricité chez des individus qui en ont besoin. Ces individus peuvent être des individus sains ou des individus atteints de troubles du développement congénitaux et/ou du cerveau. La composition peut être sous forme d'une posologie liquide ou solide.
PCT/EP2015/077480 2014-11-25 2015-11-24 Composition pour améliorer les fonctions cognitives WO2016083362A1 (fr)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3263113A1 (fr) * 2016-06-30 2018-01-03 Jürgen Mertin Utilisation et préparation destinés au maintien et à l'amélioration des fonctions cognitives (comprenant colecalciferol, acide gras du omega-3 et ginkgo biloba)
CN109198607A (zh) * 2017-07-03 2019-01-15 北京神飞航天应用技术研究院 一种能提高航天员记忆力的营养餐制剂
US11123306B2 (en) * 2016-03-08 2021-09-21 N.V. Nutricia Method for supporting memory function and/or cognitive function
CN113652304A (zh) * 2021-08-02 2021-11-16 河南中烟工业有限责任公司 一种蓝莓提取物的制备方法及其在加热卷烟中的应用
WO2022258873A1 (fr) 2021-06-09 2022-12-15 Hospital Sant Joan De Deu Combinaison nutraceutique et son utilisation pour le traitement de troubles neurologiques
WO2023144289A1 (fr) * 2022-01-28 2023-08-03 Activ'inside Utilisation d'un mélange de flavanols pour augmenter la concentration de la forme active de la vitamine d, le calcitriol.
WO2024058276A1 (fr) * 2022-09-16 2024-03-21 ヤマサ醤油株式会社 Agent et procédé pour améliorer la mémoire composite d'une personne normale

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006127627A2 (fr) * 2005-05-23 2006-11-30 Massachusetts Institute Of Technology Compositions a base d'acides gras polyinsatures et/ou d'uridine et procedes d'utilisation correspondants
EP2258218A1 (fr) * 2009-06-02 2010-12-08 Nestec S.A. Composition nutritionnelle pour supporter le développement cérébral et fonction des tout-petits
EP2342975A2 (fr) * 2005-12-23 2011-07-13 N.V. Nutricia Composition pour améliorer la composition de la membrane et le fonctionnement de cellules

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006127627A2 (fr) * 2005-05-23 2006-11-30 Massachusetts Institute Of Technology Compositions a base d'acides gras polyinsatures et/ou d'uridine et procedes d'utilisation correspondants
EP2342975A2 (fr) * 2005-12-23 2011-07-13 N.V. Nutricia Composition pour améliorer la composition de la membrane et le fonctionnement de cellules
EP2258218A1 (fr) * 2009-06-02 2010-12-08 Nestec S.A. Composition nutritionnelle pour supporter le développement cérébral et fonction des tout-petits

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
A WINKLER ET AL: "Experten-Statement Souvenaid: Ein diätetisches Lebensmittel in der Behandlung der frühen Alzheimer-Krankheit", JOURNAL FÜR NEUROLOGIE, NEUROCHIRURGIE UND PSYCHIATRIE, vol. 14, no. Suppl 1, 1 January 2013 (2013-01-01), pages 3 - 12, XP055250455 *
A.R. WHYTE ET AL: "The cognitive effects of acute blueberry anthocyanin interventions on 7-9 year old children", APPETITE, vol. 59, no. 2, 1 October 2012 (2012-10-01), pages 637, XP055047614, ISSN: 0195-6663, DOI: 10.1016/j.appet.2012.05.108 *
JEREMY P. E. SPENCER: "Flavonoids and brain health: multiple effects underpinned by common mechanisms", GENES & NUTRITION ; STUDYING THE RELATIONSHIP BETWEEN GENETICS AND NUTRITION IN THE IMPROVEMENT OF HUMAN HEALTH, vol. 4, no. 4, 15 December 2009 (2009-12-15), DE, pages 243 - 250, XP055251986, ISSN: 1555-8932, DOI: 10.1007/s12263-009-0136-3 *
MARK F MCCARTY ET AL: "Practical Strategies for Preserving Good Cognitive Function into Old Age", 31 May 2013 (2013-05-31), XP055250488, Retrieved from the Internet <URL:http://web.archive.org/web/20130531175907/http://www.nutriguard.com/Practical-Strategies-for-Preserving-Good-Cognitive-Function-into-Old-Age.pdf> [retrieved on 20160216] *
MICHAEL HOLICK ET AL: "Vitamin D and neurocognitive function", CLINICAL INTERVENTIONS IN AGING, 2 April 2014 (2014-04-02), pages 559, XP055250558, DOI: 10.2147/CIA.S51785 *
PARLETTA NATALIE ET AL: "Nutritional modulation of cognitive function and mental health", JOURNAL OF NUTRITIONAL BIOCHEMISTRY, BUTTERWORTH PUBLISHERS, STONEHAM, GB, vol. 24, no. 5, 18 March 2013 (2013-03-18), pages 725 - 743, XP028586069, ISSN: 0955-2863, DOI: 10.1016/J.JNUTBIO.2013.01.002 *
WURTMAN ET AL: "Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents", METABOLISM, CLINICAL AND EXPERIMENTAL, W.B. SAUNDERS CO., PHILADELPHIA, PA, US, vol. 57, 1 October 2008 (2008-10-01), pages S6 - S10, XP025412919, ISSN: 0026-0495, [retrieved on 20080916], DOI: 10.1016/J.METABOL.2008.07.007 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11123306B2 (en) * 2016-03-08 2021-09-21 N.V. Nutricia Method for supporting memory function and/or cognitive function
US11918546B2 (en) 2016-03-08 2024-03-05 N.V. Nutricia Method for supporting memory function and/or cognitive function
EP3263113A1 (fr) * 2016-06-30 2018-01-03 Jürgen Mertin Utilisation et préparation destinés au maintien et à l'amélioration des fonctions cognitives (comprenant colecalciferol, acide gras du omega-3 et ginkgo biloba)
CN109198607A (zh) * 2017-07-03 2019-01-15 北京神飞航天应用技术研究院 一种能提高航天员记忆力的营养餐制剂
WO2022258873A1 (fr) 2021-06-09 2022-12-15 Hospital Sant Joan De Deu Combinaison nutraceutique et son utilisation pour le traitement de troubles neurologiques
CN113652304A (zh) * 2021-08-02 2021-11-16 河南中烟工业有限责任公司 一种蓝莓提取物的制备方法及其在加热卷烟中的应用
CN113652304B (zh) * 2021-08-02 2024-02-20 河南中烟工业有限责任公司 一种蓝莓提取物的制备方法及其在加热卷烟中的应用
WO2023144289A1 (fr) * 2022-01-28 2023-08-03 Activ'inside Utilisation d'un mélange de flavanols pour augmenter la concentration de la forme active de la vitamine d, le calcitriol.
FR3132221A1 (fr) * 2022-01-28 2023-08-04 Activ'inside Utilisation d’un mélange de flavanols pour augmenter la concentration de la forme active de la vitamine D, le calcitriol.
WO2024058276A1 (fr) * 2022-09-16 2024-03-21 ヤマサ醤油株式会社 Agent et procédé pour améliorer la mémoire composite d'une personne normale

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