WO2009002165A1 - Lipid composition for improving brain function - Google Patents

Lipid composition for improving brain function Download PDF

Info

Publication number
WO2009002165A1
WO2009002165A1 PCT/NL2008/050410 NL2008050410W WO2009002165A1 WO 2009002165 A1 WO2009002165 A1 WO 2009002165A1 NL 2008050410 W NL2008050410 W NL 2008050410W WO 2009002165 A1 WO2009002165 A1 WO 2009002165A1
Authority
WO
WIPO (PCT)
Prior art keywords
lipid fraction
acid
lipid
fatty acids
product
Prior art date
Application number
PCT/NL2008/050410
Other languages
French (fr)
Inventor
Robert Johan Joseph Hageman
Eline Marleen Van Der Beek
Martine Groenendijk
Patrick Joseph Gerardus Hendrikus Kamphuis
Original Assignee
N.V. Nutricia
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38457798&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2009002165(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by N.V. Nutricia filed Critical N.V. Nutricia
Priority to US12/666,619 priority Critical patent/US8283335B2/en
Priority to PL08766833T priority patent/PL2162019T3/en
Priority to AT08766833T priority patent/ATE538665T1/en
Priority to EP08766833A priority patent/EP2162019B1/en
Priority to BRPI0813320-4A priority patent/BRPI0813320B1/en
Priority to ES08766833T priority patent/ES2378176T3/en
Priority to CN200880024527.0A priority patent/CN101742926B/en
Publication of WO2009002165A1 publication Critical patent/WO2009002165A1/en
Priority to US13/620,382 priority patent/US8759319B2/en

Links

Classifications

    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • 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
    • 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
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • 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
    • 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
    • A61K31/201—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 one or two double bonds, e.g. oleic, linoleic acids
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • 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

  • WO 2003/013276 discloses the use of 30-70 en% of a lipid blend which is rich in oleic acid (50-70 wt%) and spe- cific amounts of ⁇ -6 fatty acids and 1-10 wt% ⁇ -3 fatty acids for increasing intramyo- cellular lipid levels in muscle cells, which is claimed to be beneficial for endurance athletes.
  • the lipid fraction may be used to manufacture a nutritional or pharmaceutical product.
  • a nutritional or pharmaceutical product is suitable for enteral administration to a patient in need of support of his or her brain function.
  • the product comprises some antigens, such as proteins or peptides and the like, which make the product unsuitable for parenteral administration.
  • the invention relates to a nutritional or pharmaceutical product comprising the lipid fraction according to the invention.
  • the product can be used as a supplement and may have a liquid, a semi-liquid or solid form.
  • Good compliance with prescription protocols can be obtained when such products have a dry mass content of more than 32 g per 100 g, preferably 35-96 g per 100 g, more preferably 40- 95 g per 100 g, especially 45-80 g per 100 g ready to use product. Examples are ice cream, puddings and bars, which are known in the art.
  • the lipid fraction comprises preferably more than 15 g DHA, preferably more than 3 g EPA and preferably more than 1 g linolenic acid and preferably more than 3 g, prefer a- bly 4-20 g hexanoic acid and preferably more than 4 g, preferably 5-20 g octanoic acid, per 100 g of all fatty acids.
  • the inclusion of all these fatty acids in these amounts not only improve nutritional status but also may influence the other properties of the brain cells in such a way that a net support of the brain function can be observed.
  • the lipid fraction comprises preferably more than 10 wt% MCT and preferably 0.1-40 wt%, more preferably 1-32 wt%, especially 2-20 wt% of ⁇ -3 LCP ( ⁇ -3 LCP being defined as ⁇ -3 fatty acids having at least two unsaturated carbon-carbon bonds and at least 20 carbon atoms).
  • Best efficacy is obtained and least undesired side effects are obtained when the doses UMP or CMP is per 100 ml ready to use product at least 40 mg, preferably 50-6000, more preferably 60-1000 mg. Most preferably 70-600 mg UMP is included per 100 g of ready to use product.
  • the amount top be used per 100 g pf lipid fraction is preferably at 100 mg, more preferably 200 mg - 20 g, most preferably 400 mg - 1O g per 100 g lipid.
  • the product can be used in an amount of 50-400 ml, especially 75-200 ml, most preferably 100-150 ml per day, based on the ready-to-use liquid.
  • the amount of lipid fraction to be used per day may range from 1 to 100 g, especially 2.5-50 g, most preferably 4-20 g of lipid fraction per day or per daily dosage unit.
  • the liquid comprises per 100 ml 3 g protein (as casein/ whey 80/20), 7 g lipid (MCT/canola/phospholipids/marine oils in a weight ratio of 50/30/6/14) and 8 g di- gestible carbohydrates (as maltodextin 19/ fructose/ lactose in a ratio 60/10/30) and further:
  • the bar for use in a patient suffering from Alzheimer's Disease once or twice per day.
  • the bar comprises per 25 g dry mass:
  • Lipids (40 MCT; milk fat 25, fish oil 15, canola 15, chocolate 5)
  • At least 200 ml per day should be consumed by the person of the product which comprises per 100 ml: Energy 600 kcal

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Endocrinology (AREA)
  • Pediatric Medicine (AREA)
  • Emergency Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention pertains to the use of a lipid fraction for the support of brain function. The lipid fraction comprises the medium-chain fatty acids at least 4 g hexanoic acid and/or at least 5 g octanoic acid, at least 1 g eicosapentaenoic acid, and in addition more than 0.4 g α - linolenic acid per 100 g fatty acids of the lipid fraction.

Description

Lipid composition for improving brain function
Field of the invention
The invention is related to lipid blends which comprise selected fatty acids, and the use thereof in the manufacture of nutritional or pharmaceutical products for improving brain function in a mammal, in particular in the elderly.
Background
The nervous system, in particular the brain, plays an essential role in a mammal's life. For example cognitive, emotional, social, sensory, motoric and regulatory functions are mainly determined by the brain. In the western society more and more diseases, disorders and problems with a proper functioning of the brain are becoming recognised. Young people increasingly experience damage to the brain, for example due to intoxications such as alcohol - or drug abuse, due to traumata such as traumatic brain injury (TBI), for example as a result of sport accidents, work accidents, car accidents and the like, or systematic malnourishment. Also during aging several deleterious changes occur in the nervous system and in particular in the brain. Malfunctioning of the brain is therefore especially a problem in the elderly and more in particular in the frail or malnourished elderly. In this group, several diseases and disorders which are associated with or find their cause in a badly functioning nervous system are therefore relatively frequently observed. Examples are several forms of dementia, such as vascular dementia, Alzheimer's disease, dementia with Lewy bodies; Huntington's disease, Parkinson's disease; mood disorders, such as the various forms of depression, but also other diseases or disorders like abnormal behaviour, for example during daily living, with- drawal from social events and indecisiveness.
Many lipid blends have been used in the manufacture of foods for improving brain function. For example WO 2006/118665 discloses a method of reducing protein aggregation in the brain of a mammal by increasing endogenous ketone levels. The latter can be achieved by administering medium chain fatty acids (MCT) and a low amount of digestible carbohydrates. WO 2007/001883 discloses the use of MCT and carnitine to improve mitochondrial function. US 6,835,750 discloses the use of MCT in a dose of 0.5-10 g/kg body weight per day to treat Alzheimer's disease. However, it is generally known that administration of high doses of MCT may result in gastrointestinal discom- fort. Furthermore, MCT administration results in a satiating effect which may decrease the amount that is consumed of subsequent meals. This is often undesirable in diseased persons or the elderly. Also the ketogenic character of MCT decreases with time, which would mandate the consumption of ever increasing amounts of MCT to obtain the same ketogenic effect. Further, MCT consumption may result in increased plasma levels of for example triglycerides, which is undesirable in persons who are at risk of developing cardiovascular or cerebrovascular disorders, such as the elderly and in obese persons. EP 1282365 discloses the use of a blend which comprises omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUF A's) and phospholipids in conjunction with specific B vitamins to treat vascular diseases and dementia. JP 10136937 discloses a total nutri- tional food comprising docosahexanoic acid, eicosapentaenoic acid and linoleic acid for activating the function of encephalic cells.
Lipid blends have also been proposed for the treatment of disorders, other than for the support of brain function. US 5,886,037 discloses the use of a lipid blend which com- prises 55-95 wt% MCT, 5-25 wt% ω-3 LCP and 0-3 wt% other fatty acids for treatment of dyslipidaemias. EP 1216041 discloses the use of a high amount (35-70 en%) of a lipid blend with 25-70 wt% MCT and ω-6/ω-3 = 2-7: 1 in the manufacture of a food product for the treatment of sepsis or inflammatory shock. WO 2003/013276 discloses the use of 30-70 en% of a lipid blend which is rich in oleic acid (50-70 wt%) and spe- cific amounts of ω-6 fatty acids and 1-10 wt% ω-3 fatty acids for increasing intramyo- cellular lipid levels in muscle cells, which is claimed to be beneficial for endurance athletes. On the other hand, also a blend with 40-65 wt% MCT and MUFA = 0-30 wt% and 20-50 wt% LC saturated fatty acids is disclosed for decreasing the accumulation of intramyocellular lipids in an individual. EP 0175468 discloses the use of a mixture of docosahexanoic acid, eicosapentaenoic acid and gamma-linolenic acid (an ω-6 fatty acid) for the treatment of cancer.
Therefore there is a need for nutritional or pharmaceutical compositions which are suitable for enteral use by a patient in need of a support of brain function, which does not have the disadvantages of prior art compositions, which demonstrates a rapid effect, and which is convenient for use and palatable. The inventors now have found that the use of a lipid fraction, in a specific formulation of the product and optionally in combination with a protein fraction, and/or other components provides these advantages over the prior art solutions for the support of brain function, in particular in the elderly.
Description of the invention
The invention is related to a lipid fraction for the support of brain function, the treatment of neurological disorders or diseases, such as Alzheimer's disease, and the decrease in cognitive function, where the lipid fraction comprises one or more sources of hexanoic acid and/or octanoic acid, a source of eicosapentaenoic acid, and more than 0.4 g α-linolenic acid per 100 g fatty acids of the lipid fraction.
The lipid fraction may be used to manufacture a nutritional or pharmaceutical product. Such product is suitable for enteral administration to a patient in need of support of his or her brain function. Preferably, the product comprises some antigens, such as proteins or peptides and the like, which make the product unsuitable for parenteral administration. Hence, the invention relates to a nutritional or pharmaceutical product comprising the lipid fraction according to the invention. The product can be used as a supplement and may have a liquid, a semi-liquid or solid form.
The liquid forms of the product as claimed can be manufactured with low viscosity, which makes them suitable for administration by tube to a patient. The viscosity of the liquid form is therefore low, preferably less than 40, more preferably 6-30 mPa.s at 20 °C, measured at a shear rate of 100 sec"1. Hence, the invention relates in particular to the use of a composition comprising the lipid fraction according to the invention, wherein the viscosity is less than 40 mPa.s, more preferably between 6 and 30 mPa.s at 20 °C, measured at a shear rate of 100 sec"1.
Preferably, the liquid product comprises a protein fraction, a lipid fraction and a carbo- hydrate fraction, as well as vitamins and minerals or trace elements in order to provide full support of brain function in patients with varying nutritional status. It is important that despite the inclusion of all these ingredients, the osmotic value remains below 500, more preferably 200-470 mOsm per kg product in the product, in order to increase compliance and increase brain support in especially elderly patients. Gastrointestinal discomfort is prevented by this measure. These osmolality values are also applicable in products having a pH between 3.8 and 7 and which are flavoured. The latter properties are important for obtaining superior palatability of the product and an excellent compliance with recommended administration protocols in the longer term. Hence, the invention relates in particular to the use of a composition comprising the lipid fraction ac- cording to the invention, wherein the osmotic value is less than 500 mOsm, more preferably between 200 and 470 mOsm per kg product.
The ready to consume products which have a lipid level above 45 en%, preferably more than 55 en%, most preferably more than 60 en%, up to e.g. 75 en%, will preferably have a higher dry mass content per unit dose than conventional products. Good compliance with prescription protocols can be obtained when such products have a dry mass content of more than 32 g per 100 g, preferably 35-96 g per 100 g, more preferably 40- 95 g per 100 g, especially 45-80 g per 100 g ready to use product. Examples are ice cream, puddings and bars, which are known in the art.
The products, in particular liquid products will have an energy density of more than 0.9 kcal/ml, preferably 1-7 kcal/ml (4.2-29.4 kJ/ml), and most preferably 2.4-6.5 kcal/ml (10.1-27.3 kJ/ml). Hence, the invention further relates to the use of a composition comprising the lipid fraction according to the invention, having an energy density of more than 0.9 kcal/ml, preferably 1-7 kcal/ml (4.2-29.4 kJ/ml), and most preferably 2.4-6.5 kcal/ml (10.1-27.3 kJ/ml).
The lipid fraction as described below in detail has been developed to fully support brain function. Nutritional status of neuronal cells, in particular of neurons, astrocytes and glial cells is improved against prior art lipid blends. Such status can for example be monitored by measuring atrophy of the brain cells, for example by applying MRI (magnetic resonance imaging) methods as known in the art, or determining biochemical or physiological properties of the brain, e.g. by applying PET (positron emission tomography), analysis of cerebrospinal fluid composition or single photon emission tomo- graphy (SPECT).
The lipid fraction comprises at least 0.4, preferably 1-12 weig ht percent (wt%) α- linolenic acid (aLA), and preferably at least 0.4, preferably 1-20 wt% eicosapentaenoic acid (EPA) based on the sum of fatty acids in that fraction. Suitable sources for increas- ing the amount of aLA include canola oil and flax seed oil. The lipid fraction preferably comprises docosahexaenoic acid (DHA) in an amount of at least 0.5, preferably 1-35, more preferably 5-30 wt% of the sum of fatty acids in that fraction and wherein the weight ratio of DHA to EPA is preferably in the range 0.2-7, more preferably 0.8-4. The inclusion of these amounts of DHA in the lipid blend will improve nutritional status of brain cells.
The lipid fraction comprises preferably more than 15 g DHA, preferably more than 3 g EPA and preferably more than 1 g linolenic acid and preferably more than 3 g, prefer a- bly 4-20 g hexanoic acid and preferably more than 4 g, preferably 5-20 g octanoic acid, per 100 g of all fatty acids. The inclusion of all these fatty acids in these amounts not only improve nutritional status but also may influence the other properties of the brain cells in such a way that a net support of the brain function can be observed.
The weight amount of α-linolenic acid is preferably 0.3-1 times the weight amount of linoleic acid in the lipid fraction. It is thought by the inventors that the relatively high amount of α-linolenic acid compared to linoleic acid is not due to a direct effect on the brain cells but instead works indirectly, despite the early nature of the effect that is observed.
The lipid fraction preferably comprises 10-60, more preferably 25-45, most preferably 28-40 g medium chain triglycerides (MCT) per 100 g of the lipid fraction in the product (or the same amounts of the medium-chain fatty acids on 100 g of all fatty acids). Following the dosing regimens for the product, this results in a dose of less than 0.5 g MCT per kg bodyweight per day in order to prevent gastrointestinal discomfort.
The medium-chain fatty acids (MCT) are defined to be linear or branched saturated car- boxylic acids having six, seven, eight, nine or ten carbon atoms. Best results in terms of support of brain function are obtained with linear fatty acids having 6, 7 or 8 carbon atoms and the weight amount of the sum of these fatty acids compared to the sum of the weight amount of 9 and 10 carbon atoms should preferably be more than 2.5.
The best sources of medium chain fatty acids are MCT or selected fractions rich in medium chain fatty acids from coconut oil, lipids or butter from milk, palm kernel oil or palm oil. The sources provide triglycerides with a high content of hexanoic (C6:0) and octanoic acid (C8:0) and may also comprise C10:0 or other fatty acids. It is important that the doses of C6:0 and C8:0 are met, as are the other requirements for the lipid blend. This may result in the use of sources of MCT which have a low level of C 10:0. In particular such MCT comprise less than 20 wt% C 10:0, preferably less than 15 wt% of the fatty acid in that MCT oil. The total amount of ClO fatty acids is preferably less than 10 wt.% of all fatty acids of the composition, more preferably less than 7 wt.%
Also, good results can be obtained when at least one source of hexanoic acid and/or octanoic acid is used which provides 45-100 wt% of hexanoic acid and/or octanoic acid based on the total amount of fatty acids in that source and wherein that source is not medium chain triglyceride oil (MCT). Such sources include di- or monoglycerides comprising one or two saturated fatty acids having a carbon number of 6-10. The use of such ingredients increases palatability and decreases gastrointestinal discomfort after consumption of doses of a bolus of 40 g lipids. Hence, the invention also relates to the use of a lipid fraction comprising a source of di- and monoglycerides, said source providing 45-100 wt% of hexanoic acid and/or octanoic acid, based on the total amount of fatty acids, for improving brain function,
The lipid fraction comprises preferably at least 6 wt% of phospholipids or lyso- phospholipids. This decreases the risk of gastrointestinal discomfort of a product rich in triglycerides comprising hexanoic and octanoic acids. It also facilitates bioavailability of the trace elements and vitamins.
The lipid fraction preferably contributes more than 45 %, more preferably 48-70 % of the energy of the product after administration to a human, using the Atwater factors for digestible carbohydrates (4 kcal/g), proteins (4 kcal/g) and lipids (9 kcal/g) and zero for the organic acids and nutritional fiber, minerals and vitamins in the product. Despite the fact that these products comprise a relatively high amount of lipids, and in particular MCT, administration thereof does not lead to the negative side effects as frequently ob- served by prior art high fat products. These side effects include strong satiating, gastrointestinal discomfort such as sickness and diarrhea, but also include impartment of the availability of other components in the product such as vitamins, trace elements and decreased digestion rates of proteins and carbohydrates. These advantages are thought to be attributed to the selection of the lipid blend alone and in combination with the se- lection of the nature of the other components of the product. The lipid fraction comprises preferably more than 10 wt% MCT and preferably 0.1-40 wt%, more preferably 1-32 wt%, especially 2-20 wt% of ω-3 LCP (ω-3 LCP being defined as ω-3 fatty acids having at least two unsaturated carbon-carbon bonds and at least 20 carbon atoms).
The amount of free fatty acids is preferably less than 2 wt%, more preferably less than 1 wt% in the lipid blend in order to minimise gastrointestinal discomfort.
The lipid fraction is defined to be the part of the ready to use product which is obtained by extraction of that product with a suitable solvent using the accepted method for that particular product as published in the AOAC (American Organisation of Analytical Chemists) Handbook published in 1995. The lipid fraction thus also comprises phospholipids, glycolipids, ceramides, mono-, di- and triglycerides etc.
Preferably the lipid fraction is used in combination with a nucleotide fraction in the product for the support of brain function. Best results in efficacy and low undesired side effects are obtained when the nucleotide fraction comprises a uridine or cytidine source.
The uridine source is preferably selected from the group of uracil, uridine, phosphate forms of uridine like uridine monophosphate, diphosphate, or triphosphate, their salts and the esters of uridine or is phosphates with carboxylic acids in monomeric or in polymeric form. In particular those derivatives of uridine are effective, wherein the uridine has been acylated with acetic acid, n-caproic acid, caprylic acid, or n-capric acid, because these increase the bioavailability of the uridine source. Methods for reacting these medium chain fatty acids to uridines, for example to the 5' position of the uridine are known in the art per se for other fatty acids and comprise conventional acy- lation methods.
The invention also relates to compositions containing 0.05-100 wt.%, especially 0.2-10 wt.% of these uridine C6-C10 acylates, the remainder being food or food-grade component, which especially may comprise 1-75 wt.% of a lipid fraction. The invention also relates to a mixture of the uridine C6-C10 acylates with a lipid composition in a weight ratio between 1:200 and 1:1, especially between 1:60 and 1:3. Doses that must be administered are given as UMP. The amount of other uracil sources can be calculated by taking the molar equivalent to the UMP amount
Similarly the cytidine source is preferably selected from the group of cytidine, its phosphates, its salts and esters of cytidine. Also similar as for uracil doses between various cytidine forms can be compared and calculated into each other.
In order to obtain a better improvement of brain function the sum of the weight amount of uridine, calculated to uracil equivalents, cytidine, calculated to cytosine is at least 2 times, preferably at least 4 times the weight amount of adenine, guanine, thymine, inosine or other nucleobases.
Best efficacy is obtained and least undesired side effects are obtained when the doses UMP or CMP is per 100 ml ready to use product at least 40 mg, preferably 50-6000, more preferably 60-1000 mg. Most preferably 70-600 mg UMP is included per 100 g of ready to use product. The amount top be used per 100 g pf lipid fraction is preferably at 100 mg, more preferably 200 mg - 20 g, most preferably 400 mg - 1O g per 100 g lipid.
Preferably the product comprises a fibre fraction which comprises food grade nutritional fibres. More preferably the fibre comprises more than 10 wt%, especially more than 20 wt.% oligomeric indigestible material having a chain length of 3 to 20 saccharide units. In particular, when the fibre blend comprises (e.g. at least 10 wt.%) oligosaccharides of arabans, mannans, uronic acids (e.g. galacturonans) or galactans or mix- tures thereof, such benefits are observed. In a particular embodiment the fibres co m- prise at least 20 wt%, especially at least 30 wt.% of oligo- and polysaccharides having a molecular weight in the range of 500-10.800 (= DP 3 - 60). Even better results are obtained when the fibre fraction comprises a mixture of oligosaccharides (3-20 units), and polymeric fibres which have a chain length of more than 60 saccharide units, and pos- sibly polymeric fibres of intermediate length (20-60 units). The polymeric fibres include cellulose and hemicellulose-type fibers, like those in pea and soy. Suitable oligo saccharides are synthetic oligosaccharides like galacto-oligosaccharides, or hydrolysed natural fibres, like hydrolysed guar or hydrolysed beet fibre or hydro- lysed pectin or mixtures thereof. In order to obtain best results, the weight amount of fibre in the product should be 0.04-2, preferably 0.07-1, more preferably 0.1-0.8 times the weight amount of lipids in the product. Gastrointestinal discomfort and postprandial lipid profile is significantly improved when the fibre blend is included in the MCT enriched formula.
Other components that beneficially are included are carnitine, vitamins, trace elements, minerals as known in the art. It is preferred to include at least one of folic acid, vitamin B 12 and vitamin B6 in the product and more preferably all three. Folic acid should be included per 100 ml ready to use product in an amount of 50-500 μg, vitamin B6 in an amount of 0.5-5 mg and vitamin B12 0.8-100 μg, or the same amount in a daily dosage unit. With respect to the lipid fraction, the amounts are preferably 0.5-10 mg folic acid, and/or 5-100 mg vitamin B6, and/or 8-2000 μg vitamin B12 per 100 g lipid.
Suitable carnitine sources include L-carnitine or the acyl carnitines known in the art, such as acetyl, butyryl, isobutyryl or propionyl carnitine. Suitable doses are 2-100, preferably 10-80 mg per 100 ml ready to use product or per daily dosage unit.
The product may further comprise proteinaceous material and digestible carbohydrates. The amount of digestible carbohydrates preferably is less than 50 %, more preferably 5-45 %, most preferably 10-40 % of the total energy content.
The product can be used in an amount of 50-400 ml, especially 75-200 ml, most preferably 100-150 ml per day, based on the ready-to-use liquid. The amount of lipid fraction to be used per day may range from 1 to 100 g, especially 2.5-50 g, most preferably 4-20 g of lipid fraction per day or per daily dosage unit.
The product is useful in the improvement or support of brain function, in humans in need of support of brain function, which can be of any age, such as infants, children, adolescents, young adults, adults and elderly. Especially envisioned is the support of brain function in humans at risk for or suffering from injury of the central nervous sys- tern, e.g. brain trauma or spinal cord injury, such as resulting from car accidents, sports accidents, work accidents, combat situations, and the like. In particular is envisionned the elderly, more in particular the frail elderly or non-obese elderly. The product can be effective in humans who are apoE4 positive or negative. The product has the further advantages of decreasing the plasma levels of triglycerides and dicarboxylic acids after consumption of the product compared to the consumption of prior art products that comprise conventional lipid blends. Also the urinary excretion of dicarboxylic acids like adipic acid, suberic and sebacic acid decrease, which is more physiological and support a better use of ketone bodies by the consumer. No side effects are observed such as gastrointestinal discomfort, or a negative influence on brain size or brain growth. The products are highly palatable and appear to create better availability of minerals and vitamins compared to prior art preparations having a similar lipid concentration in the product. These advantages are due to one or more of the differences with prior art formulations.
The inclusion of the hexanoic (C6:0) and/or octanoic acid (C8:0) allows the inclusion of lower amounts of DHA to have the same effect as higher doses of DHA in a product with a lipid blend which does not comprise hexanoic acid and/or octanoic acid. The in- elusion of the medium-chain fatty acids in a lipid blend with DHA also allows the inclusion of lower amounts of medium-chain triglycerides fatty acids while observing the same efficacy as higher doses of medium-chain triglycerides without the lipids blend with DHA.
Support of brain function is meant to be an improvement of skills is related to activities of daily living, cognition, social skills, decision making skills, motoric skills and abilities to live independently from the help of others. Such improvement can be measured by determination of the abilities of the persons to practice them. Activities of daily living include instrumental activities, operational activities, and basal activities. These ac- tivities include the ability to use household appliances, to coordinate one's movements, to make rapid movements, to walk, do the laundry, do the dishes, to apply hygienic practices, to travel, etcetera.
The brain function is also supported in a prodromal patient for a neurological disorder, in a patient suffering from a cognitive decline or in a patient suffering from senile dementia, Alzheimer's disease, diabetes or insulin resistance or in a patient who experienced a physical trauma or toxicological trauma. The product according the invention demonstrates rapid efficacy. If prior art formulations would demonstrate efficacy, they demonstrate this after at least weeks of use. The current formulations demonstrate an efficacy within hours or days after the start of using the formulation.
Standardised protocols are known in the art to measure in a scientifically sound and reliable way the measure of skills as mentioned above.
Examples
Example 1
Liquid for use in a prodromal patient
The liquid comprises per 100 ml 3 g protein (as casein/ whey 80/20), 7 g lipid (MCT/canola/phospholipids/marine oils in a weight ratio of 50/30/6/14) and 8 g di- gestible carbohydrates (as maltodextin 19/ fructose/ lactose in a ratio 60/10/30) and further:
UMP 500 mg [other nucleotides < 10 mg]; cholin 300 mg;
Vitamin B6 1.1 mg; vit B12 2.3 μg; folic acid 300 μg; Other trace elements, minerals and vitamins according to the art for supplements; Galactooligosaccharides 0.6 g; pea fiber 0.6 g Giving an osmolality of 490 mOsm/kg water
The drink is to be administered in an amount of 125 ml per day during one week to a prodromal dementia patient in order to see the effect on brain function and in particular better social skills, more activities and fitness and better cognitive function, and a better alertness and ability to concentrate and pay attention.
Example 2.
Bar for use in a patient suffering from Alzheimer's Disease once or twice per day. The bar comprises per 25 g dry mass:
10.5 g Lipids: (40 MCT; milk fat 25, fish oil 15, canola 15, chocolate 5)
3 g protein (milkprotein)
9 g carbohydrates (glucose syrup)
1 g premix providing 100 ug folic acid, 2 ug vitamin B 12 and 1 mg vitamin B6 and 200 mg UMP
1.5 g fiber (GOS 10, hydrolyzed guar 40, soy fiber 50) Example 3.
Liquid for use in a person suffering from cognitive decline.
At least 200 ml per day should be consumed by the person of the product which comprises per 100 ml: Energy 600 kcal
Protein 3.1 g milk protein
Lipids 14.6 g; 7 g C6:0 + C8:0; 0.2 g α-linolenic acid; 0.6 g eicosapentaenoic acid and
0.9 g docosahexaenoic acid, 5.9 g other fatty acids
Carbohydrates 0.6 g UMP 500 mg
Fiber: 1.5 g of a 1 : 1 mixture of beet fiber and hydro lysed pectin Vitamin A 253 IU; vitamin D 2.2 IU; vitamin C 9 mg; vitamin K 6 μg; thiamin 0.14 mg; riboflavin 0.15 mg; niacin 1.5 mg; vitamin B6 1.1 mg; folic acid 100 μg; vitamin B12 0.9 μg, biotin 4 μg; pantothenic acid 0.6 mg; inositol 4 mg; Na 4.3 mg; K 4.1 mg; Cl 4.3 mg; Ca 86 mg; P 100 mg; Mg 22 mg; Zn 1.2 mg; Fe 1.5 mg; Cu 0.12 mg; Mn 0.13 mg; Iodide 18 μg; Mo 6 μg; Se 4.4 μg; Cr 3 μg
Example 4.
Liquid drink for support of brain function in the elderly, which comprises per 100 ml: Energy 63 O kJ.
Protein 6.O g casein
Lipids 8.7 g comprising a mixture of 50wt% MCT oil, 15% marine oil and 35 wt% vegetable oils
Carbohydrates 12 g (80 maltodextrins, 20 glucose syrup) Dietary fiber 1.2 g of blend of example 3
UMP 400 mg
Other trace elements, minerals and vitamins according the art for supplements
Example 5. Bar suitable for use in a person suffering from physical brain trauma comprising per 50 g:
12 g lipid fraction (7.2 g diglycerides having per 100 g fatty acids therein 80g of the sum of hexaenoic acid and octanoic acid, 2.4 g flaxseed oil, 1.2 g marine oil, 1.2 g soy lecithin ), 21 g digestible carbohydrates (maltodextrins, glycerol) H g skimmed milk powder 1.3 g ash 4.7 g water

Claims

Claims
1. Lipid fraction comprising hexanoic acid and/or octanoic acid, eicosapentaenoic acid, and more than 0.4 g α-linolenic acid per 100 g fatty acids of the lipid fraction for the support of brain function.
2. Lipid fraction according to claim 1, wherein the lipid fraction comprises at least 1 weight percent (wt%) α-linolenic acid and at least 1 wt% eicosapentaenoic acid based on the sum of fatty acids in that fraction.
3. Lipid fraction according to claim 1 or 2, wherein the lipid fraction comprises docosahexaenoic acid (DHA) in an amount of at least 10 wt% of the sum of fatty acids in the lipid fraction and wherein the weight ratio of DHA to EPA is 0.2-7.
4. Lipid fraction according to any one of the preceding claims, wherein the lipid fraction comprises per 100 g fatty acids more than 15 g DHA, more than 3 g EPA, more than 1 g α-linolenic acid, more than 4 g hexanoic acid and more than 5 g octanoic acid.
5. Lipid fraction according to any one of the preceding claims, wherein the weight amount of α-linolenic acid is 0.3-1 times the weight amount of linoleic acid in the lipid fraction
6. Lipid fraction according to any one of the preceding claims, wherein at least one source of hexanoic acid and/or octanoic acid is used which provides 45-100wt% of these fatty acids based on the total amount of fatty acids in that source and wherein that source is not medium chain triglyceride oil.
7. Lipid fraction according to any one of the preceding claims wherein the lipid fraction comprises 10-60 g medium chain triglycerides per 100 g of the lipid fraction.
8. Lipid fraction according to any one of the preceding claims wherein the lipid fraction comprises at least 6 wt% of phospholipids or lysophospho lipids.
9. Lipid fraction according to any one of the preceding claims, wherein the lipid fraction contributes 45-70% of the energy of the product after administration to a human.
10. Lipid fraction according to any one of the preceding claims, wherein the lipid fraction comprises 10-60 wt% MCT and 1-30 wt% ω-3 LCP.
11. Lipid fraction according to any one of the preceding claims, wherein the lipid fraction is combined with of a nucleotide fraction, and wherein the nucleotide fraction comprises a uridine or cytidine source.
12. Lipid fraction according to claim 1 1, wherein the uridine source is selected from the group of uracil, uridine, phosphate forms of uridine, esters of uridine with car- boxylic acids, and the cytidine source is selected from the group of cytidine, its phosphates, esters of cytidine and wherein the sum of the weight amount of uridine, calculated to uracil equivalents, cytidine, calculated to cytosine is at least 2 times, preferably at least 4 times the weight amount of adenine, guanine, thymine, inosine or other nucleobases.
13. Lipid fraction according to any one of the preceding claims, wherein the product comprises a fibre fraction which comprises an oligosaccharide,
14. Lipid fraction according to any one of the preceding claims wherein the product has a dry mass content of more than 32, preferably 35-90, more preferably 40-88 g per 100 g ready to consume product,
15. Lipid fraction according to any one of the preceding claims, wherein the brain function is related to activities of daily living, cognition, social skills, decision making skills, motoric skills and abilities to live independently from the help of others,
16. Lipid fraction according to any one of the preceding claims, wherein the brain function is supported in a prodromal patient for a neurological disorder, or in a patient suffering from senile dementia, from Alzheimer's disease, from diabetes or insulin resistance or from a physical trauma or toxicological trauma.
17. Lipid fraction comprising a source of di- and monoglycerides, said source providing 45-100 wt% of hexanoic acid and/or octanoic acid, for improving brain function,
PCT/NL2008/050410 2007-06-26 2008-06-20 Lipid composition for improving brain function WO2009002165A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
US12/666,619 US8283335B2 (en) 2007-06-26 2008-06-20 Lipid composition for improving brain function
PL08766833T PL2162019T3 (en) 2007-06-26 2008-06-20 Lipid composition for improving brain function
AT08766833T ATE538665T1 (en) 2007-06-26 2008-06-20 LIPID COMPOSITION TO IMPROVE BRAIN FUNCTION
EP08766833A EP2162019B1 (en) 2007-06-26 2008-06-20 Lipid composition for improving brain function
BRPI0813320-4A BRPI0813320B1 (en) 2007-06-26 2008-06-20 LIPID FRACTION, AND PHARMACEUTICAL OR NUTRITIONAL PRODUCT
ES08766833T ES2378176T3 (en) 2007-06-26 2008-06-20 Lipid composition for improvement of brain function
CN200880024527.0A CN101742926B (en) 2007-06-26 2008-06-20 lipid composition for improving brain function
US13/620,382 US8759319B2 (en) 2007-06-26 2012-09-14 Lipid composition for improving brain function

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/NL2007/050306 WO2009002145A1 (en) 2007-06-26 2007-06-26 Lipid composition for improving function of brain functioning
NLPCT/NL2007/050306 2007-06-26

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/666,619 A-371-Of-International US8283335B2 (en) 2007-06-26 2008-06-20 Lipid composition for improving brain function
US13/620,382 Continuation US8759319B2 (en) 2007-06-26 2012-09-14 Lipid composition for improving brain function

Publications (1)

Publication Number Publication Date
WO2009002165A1 true WO2009002165A1 (en) 2008-12-31

Family

ID=38457798

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/NL2007/050306 WO2009002145A1 (en) 2007-06-26 2007-06-26 Lipid composition for improving function of brain functioning
PCT/NL2008/050410 WO2009002165A1 (en) 2007-06-26 2008-06-20 Lipid composition for improving brain function

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/NL2007/050306 WO2009002145A1 (en) 2007-06-26 2007-06-26 Lipid composition for improving function of brain functioning

Country Status (11)

Country Link
US (2) US8283335B2 (en)
EP (2) EP2162019B1 (en)
CN (1) CN101742926B (en)
AT (1) ATE538665T1 (en)
BR (1) BRPI0813320B1 (en)
DK (1) DK2436275T3 (en)
ES (2) ES2432345T3 (en)
PL (2) PL2162019T3 (en)
PT (2) PT2436275E (en)
WO (2) WO2009002145A1 (en)
ZA (1) ZA200909230B (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010088700A1 (en) * 2009-02-02 2010-08-05 Martek Biosciences Corporation Methods for improving cognitive function and decreasing heart rate
WO2012125034A1 (en) 2011-03-14 2012-09-20 N.V. Nutricia Method for treating neurotrauma
US8282965B2 (en) 2007-12-20 2012-10-09 N.V. Nutricia Liquid nucleotides/nucleosides-containing product
US8361989B2 (en) 2007-06-26 2013-01-29 N. V. Nutricia Supporting activities of daily living
WO2013066152A1 (en) 2011-10-31 2013-05-10 N.V. Nutricia Method for improving executive function
US8445458B2 (en) 2007-06-27 2013-05-21 N. V. Nutricia Food composition for prodromal dementia patients
WO2013129914A1 (en) 2012-03-02 2013-09-06 N.V. Nutricia Method for improving functional synaptic connectivity
WO2013129931A1 (en) 2012-03-02 2013-09-06 N.V. Nutricia Method for improving functional synaptic connectivity
US8759319B2 (en) 2007-06-26 2014-06-24 N.V. Nutricia Lipid composition for improving brain function
WO2015084161A1 (en) 2013-12-06 2015-06-11 N.V. Nutricia Composition comprising a uridine source and an omega-3 pufa for improving coordination, balance, grip strength or fine motor skills
WO2015115885A1 (en) 2014-01-31 2015-08-06 N.V. Nutricia Method for reducing white matter lesions, white matter hyperintensities (wmh), leukoaraiosis or periventricular white matter disease in elderly
WO2016148561A1 (en) 2015-03-16 2016-09-22 N.V. Nutricia Method for improving bladder function
US9763971B2 (en) 2011-10-31 2017-09-19 N.V. Nutricia Improving recognition
US10632093B2 (en) 2015-10-23 2020-04-28 N.V. Nutricia Method for improving recognition and/or working memory in hyperphenylalanimenia and phenylketonuria patients
EP2194781B2 (en) † 2007-10-04 2021-03-24 Société des Produits Nestlé S.A. Compositions and methods for enhancing cognitive function
US11123306B2 (en) * 2016-03-08 2021-09-21 N.V. Nutricia Method for supporting memory function and/or cognitive function
US11395810B2 (en) 2007-06-26 2022-07-26 N.V. Nutricia Memory in subjects with mini-mental state examination of 24-26

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG188107A1 (en) * 2008-02-01 2013-03-28 Research In Motion Ltd System and method for uplink timing synchronization in conjunction with discontinuous reception
EP2258216A1 (en) * 2009-06-02 2010-12-08 Nestec S.A. Nutritional Composition for Supporting Brain Development and Function of Toddlers
EP2258218A1 (en) * 2009-06-02 2010-12-08 Nestec S.A. Nutritional Composition for Supporting Brain Development and Function of Toddlers
EP2258217A1 (en) * 2009-06-02 2010-12-08 Nestec S.A. Nutritional Composition for Supporting Brain Development and Function of Children
CN102884201B (en) 2010-01-19 2016-04-13 帝斯曼知识产权资产管理有限公司 Produce microorganism, lipid acid constituent and preparation method thereof and the purposes of timnodonic acid
SG10201707519PA (en) * 2010-12-31 2017-10-30 Abbott Lab Neutral human milk oligosaccharides to promote growth of beneficial bacteria
CN108771240A (en) * 2011-07-21 2018-11-09 帝斯曼知识产权资产管理有限公司 Aliphatic acid composition
US20140256813A1 (en) * 2013-03-08 2014-09-11 Nordic Naturals, Inc. Methods for the treatment of brain injury using omega-3 fatty acids
WO2014171813A1 (en) 2013-04-17 2014-10-23 N.V. Nutricia Nutritional composition for improving brain function in phenylketonuria
CN105517452A (en) * 2013-08-01 2016-04-20 荷兰洛德斯克罗科兰有限公司 Glyceride composition
WO2015034984A1 (en) * 2013-09-05 2015-03-12 Emory University Nutritional formulas comprising medium chain fatty acids or esters thereof and methods related thereto
US9216199B2 (en) 2013-12-05 2015-12-22 Buriva, LLC Nutritional supplement containing phospholipid-DHA derived from eggs
US9549937B2 (en) 2013-12-05 2017-01-24 Burvia, LLC. Composition containing phospholipid-DHA and folate
US9610302B2 (en) 2013-12-05 2017-04-04 Buriva, LLC. Composition containing phospholipid-DHA and B vitamins
US9233114B2 (en) 2013-12-05 2016-01-12 Buriva, LLC Dietary supplement containing phospholipid-DHA derived from eggs
WO2016010102A1 (en) * 2014-07-17 2016-01-21 日清オイリオグループ株式会社 Nutritional composition
TWI722992B (en) * 2014-07-23 2021-04-01 一般財團法人糧食研究會 Brain function improving agent, and preventive or therapeutic agent for cognitive dysfunction
WO2016053085A1 (en) * 2014-09-30 2016-04-07 N.V. Nutricia Composition comprising a uridine source and butyrate producing fibres for preventing gastrointestinal disorders
CN104305192B (en) * 2014-10-23 2016-05-04 贡岳松 Improve functional food of patients of senile dementia memory and preparation method thereof
CA2908184C (en) 2015-10-13 2019-10-22 Roto-gro Inc. Stackable modular rotatable gardening system
WO2017093060A1 (en) * 2015-12-04 2017-06-08 Nestec S.A. Method for improving cognition
JP6256888B2 (en) * 2016-02-29 2018-01-10 高知県公立大学法人 Healthy brain food or healthy beverage and method of administering these
BR112018067926A2 (en) * 2016-03-30 2019-01-02 Nestec Sa nutritional compositions and their uses
WO2017183956A1 (en) * 2016-04-18 2017-10-26 N.V. Nutricia Linoleic acid and alpha-linolenic acid for use for reducing early-life stress induced cognitive decline
EP3445353A1 (en) * 2016-04-18 2019-02-27 N.V. Nutricia Linoleic acid and alpha-li nolenic acid for use for reducing early-life stress induced cognitive decline/reduction in neurogenesis
US20180085331A1 (en) * 2016-09-26 2018-03-29 Garrett E. Wdowin Compositions for mitigating head trauma
US10456368B2 (en) 2016-09-26 2019-10-29 Garrett E. Wdowin Compositions for mitigating brain trauma and methods thereof
PL3600364T3 (en) 2017-06-14 2021-01-11 4D Pharma Research Limited Compositions comprising a bacterial strain of the genus megasphaera and uses thereof
US20210267251A1 (en) * 2018-06-21 2021-09-02 Societe Des Produits Nestle S.A. Compositions and methods using a nicotinamide adenine dinucleotide (nad+) precursor and at least one ketone or ketone precursor
WO2020014051A1 (en) * 2018-07-09 2020-01-16 Wdowin Garrett E Compositions for mitigating brain trauma and methods thereof
AU2022345465A1 (en) 2021-09-17 2024-03-21 N.V. Nutricia Solid composition suitable as a nutritional composition or supplement for animals that suffer from brain related disorders, decline or diseases

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0175468A2 (en) 1984-08-10 1986-03-26 Sentrachem Limited Eicosanoids for use in cancer therapy
JPH06237734A (en) * 1991-11-06 1994-08-30 Sanwa Kagaku Kenkyusho Co Ltd Food composition for hypofunctional disease
JPH10136937A (en) 1996-11-08 1998-05-26 Takashi Morita Nutritive composite food for improving brain cell function, potentiating vascular cell and improving systemic cell function
US5886037A (en) 1996-11-20 1999-03-23 N.V. Nutricia Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia
EP1216041A2 (en) 1999-09-13 2002-06-26 Societe Des Produits Nestle S.A. High lipid diet
EP1282365A2 (en) 2000-05-08 2003-02-12 N.V. Nutricia Preparation for the prevention and/or treatment of vascular disorders
WO2003013276A1 (en) 2001-08-08 2003-02-20 Societe Des Produits Nestle S.A. Lipid blends and food products containing oleic fatty acid and omega-6 fatty acids, designed to increase the intramyocellular lipid level
US20040001817A1 (en) * 2002-05-14 2004-01-01 Giampapa Vincent C. Anti-aging nutritional supplement
US6835750B1 (en) 2000-05-01 2004-12-28 Accera, Inc. Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II
WO2006118665A2 (en) 2005-05-03 2006-11-09 Accera, Inc. Method for reducing levels of disease associated proteins
WO2007001883A2 (en) 2005-06-20 2007-01-04 Accera, Inc. Method to reduce oxidative damage and improve mitochondrial efficiency

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3600197A (en) 1968-08-27 1971-08-17 Merck & Co Inc Flavor enhancing compositions for foods and beverages
JP2525624B2 (en) * 1987-09-21 1996-08-21 雪印乳業株式会社 Baby milk powder containing polyunsaturated fatty acids
US5378488A (en) 1993-06-10 1995-01-03 Abbott Laboratories Aseptic processing of infant formula
JP3576318B2 (en) 1996-06-19 2004-10-13 明治乳業株式会社 Nutrient composition containing nucleic acid-related substance
EP0891719A1 (en) 1997-07-14 1999-01-20 N.V. Nutricia Nutritional composition containing methionine
JP3731983B2 (en) * 1997-08-27 2006-01-05 明治製菓株式会社 Drugs for improving night noise in dementia dogs
US8518882B2 (en) 1998-07-31 2013-08-27 Massachusetts Institute Of Technology Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same
US20070004670A1 (en) 1998-07-31 2007-01-04 Richard Wurtman Compositions containing citicoline, and methods of use thereof
FR2787799B1 (en) 1998-12-23 2001-03-09 Rhodia Chimie Sa COMPOSITION COMPRISING AN INORGANIC BARK AND A CORE COMPRISING AT LEAST ONE POLYHYDROXYL COMPOUND
GB9925709D0 (en) 1999-10-30 1999-12-29 Smithkline Beecham Plc Composition
DE60138019D1 (en) 2000-05-01 2009-04-30 Accera Inc USE OF TRIGLYCERIDES WITH MEDIUM-WIDE CHAINS FOR THE TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE
HUP0400732A3 (en) 2001-04-30 2007-05-29 Trommsdorff Arzneimittel Pharmaceutically active uridine esters
US6942874B2 (en) 2001-05-25 2005-09-13 Linguagen Corp. Nucleotide compounds that block the bitter taste of oral compositions
NL1019368C2 (en) 2001-11-14 2003-05-20 Nutricia Nv Preparation for improving receptor performance.
US20030114415A1 (en) 2001-12-14 2003-06-19 Wurtman Richard J. Compositions and methods for treating and preventing memory impairment using citicoline
EP2123282A3 (en) 2003-10-24 2010-01-20 N.V. Nutricia Immunemodulating oligosaccharides
US7090879B2 (en) 2004-03-18 2006-08-15 Abbott Laboratories Nutritional formula containing select carotenoid combinations
US9572830B2 (en) 2004-05-13 2017-02-21 Massachusetts Institute Of Technology Uridine effects on dopamine release
CA2579851C (en) 2004-09-15 2018-09-04 Massachusetts Institute Of Technology Use of uridine for improving cognitive and neurological functions
EP1656839A1 (en) 2004-11-11 2006-05-17 N.V. Nutricia Nutrition containing lipid blend
FR2885491B1 (en) * 2005-05-16 2020-03-06 Nutricos Technologies TREATMENT OF KERATINIC DROUGHT WITH GLYCERIDES
PL1888081T3 (en) 2005-05-23 2017-07-31 Massachusetts Institute Of Technology Compositions containing pufa and methods of use thereof
JP5967855B2 (en) 2005-06-30 2016-08-10 サントリーホールディングス株式会社 Composition having an activity of reducing daytime activity and / or depressive symptoms
JP5697293B2 (en) 2005-06-30 2015-04-08 サントリーホールディングス株式会社 Composition having an improving effect on lowering of higher brain function due to organic brain injury
KR20130101596A (en) 2005-07-08 2013-09-13 마텍 바이오싸이언스스 코포레이션 Polyunsaturated fatty acids for treatment of dementia and pre-dementia-related conditions
WO2007058523A1 (en) 2005-11-17 2007-05-24 N.V. Nutricia Composition with docosapentaenoic acid
US20070140992A1 (en) 2005-12-21 2007-06-21 Lynn Schick Taste masking of essential oils using a hydrocolloid
ATE509624T1 (en) 2005-12-23 2011-06-15 Nutricia Nv COMPOSITION CONTAINING POLYUNSATURATED FATTY ACIDS, PROTEINS, MANGANEOUS AND/OR MOLYBDENES AND NUCLEOTIDES/NUCLEOSIDES, FOR THE TREATMENT OF DEMENTIA
WO2009002166A1 (en) 2007-06-26 2008-12-31 N.V. Nutricia Improving memory in subjects with mini-mental state examination of 24-26
WO2009002148A1 (en) 2007-06-27 2008-12-31 N.V. Nutricia Food composition for prodromal dementia patients
WO2009002146A1 (en) 2007-06-26 2008-12-31 N.V. Nutricia Supporting activities of daily living
WO2009002145A1 (en) 2007-06-26 2008-12-31 N.V. Nutricia Lipid composition for improving function of brain functioning
PL2222311T3 (en) 2007-12-20 2013-08-30 Nutricia Nv Liquid nucleotides/nucleosides-containing product
JP5397321B2 (en) 2009-06-09 2014-01-22 株式会社デンソー Parking assistance system

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0175468A2 (en) 1984-08-10 1986-03-26 Sentrachem Limited Eicosanoids for use in cancer therapy
JPH06237734A (en) * 1991-11-06 1994-08-30 Sanwa Kagaku Kenkyusho Co Ltd Food composition for hypofunctional disease
JPH10136937A (en) 1996-11-08 1998-05-26 Takashi Morita Nutritive composite food for improving brain cell function, potentiating vascular cell and improving systemic cell function
US5886037A (en) 1996-11-20 1999-03-23 N.V. Nutricia Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia
EP1216041A2 (en) 1999-09-13 2002-06-26 Societe Des Produits Nestle S.A. High lipid diet
US6835750B1 (en) 2000-05-01 2004-12-28 Accera, Inc. Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II
EP1282365A2 (en) 2000-05-08 2003-02-12 N.V. Nutricia Preparation for the prevention and/or treatment of vascular disorders
WO2003013276A1 (en) 2001-08-08 2003-02-20 Societe Des Produits Nestle S.A. Lipid blends and food products containing oleic fatty acid and omega-6 fatty acids, designed to increase the intramyocellular lipid level
US20040001817A1 (en) * 2002-05-14 2004-01-01 Giampapa Vincent C. Anti-aging nutritional supplement
WO2006118665A2 (en) 2005-05-03 2006-11-09 Accera, Inc. Method for reducing levels of disease associated proteins
WO2007001883A2 (en) 2005-06-20 2007-01-04 Accera, Inc. Method to reduce oxidative damage and improve mitochondrial efficiency

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"American Organisation of Analytical Chemists", 1995
DATABASE WPI Week 199439, Derwent World Patents Index; AN 1994-312783, XP002494932 *

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8759319B2 (en) 2007-06-26 2014-06-24 N.V. Nutricia Lipid composition for improving brain function
US11395810B2 (en) 2007-06-26 2022-07-26 N.V. Nutricia Memory in subjects with mini-mental state examination of 24-26
US8361989B2 (en) 2007-06-26 2013-01-29 N. V. Nutricia Supporting activities of daily living
US8791089B2 (en) 2007-06-26 2014-07-29 N.V. Nutricia Supporting activities of daily living
EP2412250B1 (en) 2007-06-27 2015-08-05 N.V. Nutricia Food composition for prodromal dementia patients
US8445458B2 (en) 2007-06-27 2013-05-21 N. V. Nutricia Food composition for prodromal dementia patients
EP2194781B2 (en) † 2007-10-04 2021-03-24 Société des Produits Nestlé S.A. Compositions and methods for enhancing cognitive function
US8282965B2 (en) 2007-12-20 2012-10-09 N.V. Nutricia Liquid nucleotides/nucleosides-containing product
US9687555B2 (en) 2007-12-20 2017-06-27 N.V. Nutricia Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent
US8604000B2 (en) 2007-12-20 2013-12-10 N.V. Nutricia Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent
EP2244591B1 (en) 2007-12-20 2017-08-16 N.V. Nutricia A palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent
EP2609812B1 (en) 2007-12-20 2018-08-29 N.V. Nutricia Liquid nucleotides/nucleosides-containing product
US9132196B2 (en) 2007-12-20 2015-09-15 N. V. Nutricia Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent
CN108324706A (en) * 2009-02-02 2018-07-27 帝斯曼知识产权资产有限公司 The method for improving cognitive function and reducing heart rate
WO2010088700A1 (en) * 2009-02-02 2010-08-05 Martek Biosciences Corporation Methods for improving cognitive function and decreasing heart rate
US9579336B2 (en) 2011-03-14 2017-02-28 N.V. Nutricia Method for treating neurotrauma
WO2012125034A1 (en) 2011-03-14 2012-09-20 N.V. Nutricia Method for treating neurotrauma
WO2012125020A1 (en) 2011-03-14 2012-09-20 N.V. Nutricia Method for treating neurotrauma
US10071072B2 (en) 2011-03-14 2018-09-11 N.V. Nutricia Method for treating neurotrauma
US9763971B2 (en) 2011-10-31 2017-09-19 N.V. Nutricia Improving recognition
RU2637089C2 (en) * 2011-10-31 2017-11-29 Н.В. Нютрисиа Method for control functions improvement
WO2013066152A1 (en) 2011-10-31 2013-05-10 N.V. Nutricia Method for improving executive function
EP2773361B1 (en) 2011-10-31 2019-02-27 N.V. Nutricia Method for improving executive function
WO2013129931A1 (en) 2012-03-02 2013-09-06 N.V. Nutricia Method for improving functional synaptic connectivity
WO2013129914A1 (en) 2012-03-02 2013-09-06 N.V. Nutricia Method for improving functional synaptic connectivity
EP3919053A1 (en) 2013-12-06 2021-12-08 N.V. Nutricia Composition comprising a uridine source, an omega-3 pufa for improving coordination, balance, grip strength or fine motor skills
WO2015084161A1 (en) 2013-12-06 2015-06-11 N.V. Nutricia Composition comprising a uridine source and an omega-3 pufa for improving coordination, balance, grip strength or fine motor skills
US10675292B2 (en) 2014-01-31 2020-06-09 N.V. Nutricia Method for reducing white matter lesions, white matter hyperintensities (WMH), leukoaraiosis or periventricular white matter disease in elderly
WO2015115885A1 (en) 2014-01-31 2015-08-06 N.V. Nutricia Method for reducing white matter lesions, white matter hyperintensities (wmh), leukoaraiosis or periventricular white matter disease in elderly
WO2015115899A1 (en) 2014-01-31 2015-08-06 N.V. Nutricia Method for reducing white matter lesions, white matter hyperintensities (wmh), leukoaraiosis or periventricular white matter disease in elderly
WO2016148568A1 (en) 2015-03-16 2016-09-22 N.V. Nutricia Method for improving bladder function
WO2016148561A1 (en) 2015-03-16 2016-09-22 N.V. Nutricia Method for improving bladder function
US10632093B2 (en) 2015-10-23 2020-04-28 N.V. Nutricia Method for improving recognition and/or working memory in hyperphenylalanimenia and phenylketonuria patients
US11918546B2 (en) 2016-03-08 2024-03-05 N.V. Nutricia Method for supporting memory function and/or cognitive function
US11123306B2 (en) * 2016-03-08 2021-09-21 N.V. Nutricia Method for supporting memory function and/or cognitive function

Also Published As

Publication number Publication date
BRPI0813320B1 (en) 2018-08-07
US20110009357A1 (en) 2011-01-13
ES2378176T3 (en) 2012-04-09
ES2432345T3 (en) 2013-12-02
BRPI0813320A2 (en) 2015-01-06
PT2436275E (en) 2013-10-31
US8759319B2 (en) 2014-06-24
CN101742926A (en) 2010-06-16
CN101742926B (en) 2017-06-09
PL2162019T3 (en) 2012-05-31
EP2436275A1 (en) 2012-04-04
US8283335B2 (en) 2012-10-09
DK2436275T3 (en) 2013-10-28
ATE538665T1 (en) 2012-01-15
US20130018012A1 (en) 2013-01-17
WO2009002145A1 (en) 2008-12-31
PL2436275T3 (en) 2013-12-31
ZA200909230B (en) 2010-09-29
EP2436275B1 (en) 2013-07-24
EP2162019B1 (en) 2011-12-28
EP2162019A1 (en) 2010-03-17
PT2162019E (en) 2012-03-20

Similar Documents

Publication Publication Date Title
EP2162019B1 (en) Lipid composition for improving brain function
EP2170104B1 (en) Food composition for prodromal dementia patients
EP2861087B1 (en) Metabolic imprinting effects of nutrition with large lipid globules comprising milk fat and vegetable fat
US20010022980A1 (en) Dietary supplement for individuals under stress
Decsi et al. Growth, fatty acid composition of plasma lipid classes, and plasma retinol and a‐tocopherol concentrations in full‐term infants fed formula enriched with Zω‐6 and u‐3 long‐chain polyunsaturated fatty acids
EP3077005B1 (en) Composition comprising a uridine source and an omega-3 pufa for improving coordination, balance, grip strength or fine motor skills
TW201438719A (en) Human milk oligosaccharides to ameliorate symptoms of stress
EP2554058A1 (en) Functional food supplement intended, in particular, for nutrition and for prevention and improvement in cases of neurological alterations, neurodegenerative alterations or cognitive disorders
Kiso Pharmacology in health foods: effects of arachidonic acid and docosahexaenoic acid on the age-related decline in brain and cardiovascular system function
EP3179868B1 (en) Lipid composition for improving behaviour
EP2554057A1 (en) Enteral or oral food product intended, in particular, for nutrition and for the prevention and improvement of neurological alterations, neurodegenerative alterations or cognitive disorders
NZ719159B2 (en) Lipid composition for improving body composition during catch-up growth
MX2008007189A (en) Nutritional supplement containing long-chain polyunsaturated fatty acids

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880024527.0

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08766833

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2008766833

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 12666619

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0813320

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20091223