WO2010104375A1 - Stigmastérol pour le traitement de la maladie d'alzheimer - Google Patents

Stigmastérol pour le traitement de la maladie d'alzheimer Download PDF

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Publication number
WO2010104375A1
WO2010104375A1 PCT/NL2009/050315 NL2009050315W WO2010104375A1 WO 2010104375 A1 WO2010104375 A1 WO 2010104375A1 NL 2009050315 W NL2009050315 W NL 2009050315W WO 2010104375 A1 WO2010104375 A1 WO 2010104375A1
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WO
WIPO (PCT)
Prior art keywords
composition
stigmasterol
weight
beta
use according
Prior art date
Application number
PCT/NL2009/050315
Other languages
English (en)
Inventor
Marcus Otto Walter Grimm
Tobias Hartmann
Petra FRIEß-JAVORKOVÅ
Ulrich Laufs
Oliver WEINGÄRTNER
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
Application filed by N.V. Nutricia filed Critical N.V. Nutricia
Priority to EP10708409A priority Critical patent/EP2405773A1/fr
Priority to BRPI1009814-3A priority patent/BRPI1009814A2/pt
Priority to PCT/NL2010/050133 priority patent/WO2010104394A1/fr
Priority to CN2010800202802A priority patent/CN102421304A/zh
Publication of WO2010104375A1 publication Critical patent/WO2010104375A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention is directed to the use of stigmasterol for the treatment of a disorder of the nervous system, in particular an amyloidosis of the nervous system, e.g. Alzheimer's disease.
  • amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues.
  • a protein or peptide is described as being amyloid if, due to an alteration in its secondary structure, it takes on a particular aggregated insoluble form similar to the beta-pleated sheet. Symptoms vary widely depending upon the site of amyloid deposition.
  • Cerebral amyloidosis is a significant aspect of Alzheimer's disease, for which there is currently no cure and that affects a considerable part of the human population, in particular of elderly people.
  • Several publications have reported in general terms that subjects suffering from various age-related disorders may benefit from specific classes of compounds, e.g., originating from plants.
  • compositions comprising one or more free (unesterified) phytosterols and/or phytostanols which are substantially completely dissolved in one or more es- terified phytosterols and/or phytostanols.
  • free (unesterified) phytosterols and/or phytostanols which are substantially completely dissolved in one or more es- terified phytosterols and/or phytostanols.
  • the compositions may be used for treatment of dementia.
  • no experimental results are given, nor any possible explanation of how such treatment would be effective.
  • WO 06/121558 describes a composition allegedly suitable for treatment of a variety of age-related disorders, e.g. Alzheimer's disease.
  • the composition comprises one or more of a variety of active components, including statins, bisphonoates, polyphenolic compounds and omega-3 fatty acids. It is men- tioned that the composition may also comprise phytosterols for inhibiting cholesterol absorption. The use of stigmasterol (or another specific phytosterol) specifically for treatment of amyloidosis of the nervous system is not shown.
  • WO 00/30666 relates to a composition
  • a composition comprising plant matter from a plant of the genus Uncaria.
  • the composition may amongst others be used for a variety of brain stimulating uses, such as improving mental alertness, for reducing or preventing amyloid protein deposits or for promoting or supporting pancreatic function in a patient.
  • the composition may contain a mixture of the plant sterols beta- sitosterol, stigmasterol and campesterol. The effectiveness of a specific phytosterol, in particular stigmasterol for treatment of amyloidosis of the nervous system is not shown.
  • phytosterols have different effects on a specific pathology, namely on pathologic aggregation of a peptide (A ⁇ ), cleaved from Amyloid Precursor Protein (APP) via a cascade of beta-secretase activity and gamma- secretase activity.
  • a ⁇ pathologic aggregation of a peptide
  • APP Amyloid Precursor Protein
  • phytosterols may in fact have an adverse effect on at least some forms of amyloidosis, in particular on amyloidosis of beta-amyloid peptide (A ⁇ ) in the nervous system of a mammal. It is an object of the invention to provide a use of a specific compound, which may be present in a pharmaceutical composition, a nutraceutical composition or a food composition, in the manufacture of a composition for prophylactic or therapeutic treatment of pathologic aggregation of beta- amyloid peptide in the nervous system, in particular the cerebral system of a mammal.
  • the present invention relates to the use of stigmasterol in the manufacture of a food composition, a nutraceutical composition, or a pharmaceutical composition for prophylactic or therapeutic treatment of amyloidosis of beta-amyloid peptide (A ⁇ ) in the nervous system of a mammal, in particular the central nervous system of a mammal, more in particular in the cerebral part of the nervous system of a mammal.
  • a ⁇ beta-amyloid peptide
  • the invention further relates to the use of stigmasterol in the manufacture of a food composition, a nutraceutical composition, or a pharmaceutical composition for prophylactic or therapeutic treatment of Alzheimer's disease.
  • the invention further relates to stigmasterol for use as a gamma- secretase inhibitor and/or for use as a beta-secretase inhibitor.
  • stigmasterol for use as a gamma- secretase inhibitor and/or for use as a beta-secretase inhibitor.
  • Such use may be non-medical (in an in vitro application) or medical, in which case the stigmasterol may in particular be for use as a gamma secretase inhibitor in the brain or another part of the nervous system of a mammal.
  • Phytosterols are a group of steroid alcohols, phytochemicals naturally occurring in plants. Common phytosterols are stigmasterol, ergosterol, beta- sitosterol, campesterol and brassicasterol.
  • Amyloidosis is a group of diseases characterised by deposition of amyloids in the nervous system of a mammal.
  • Amyloid is a generic term referring to a group of diverse, but specific extracellular protein deposits which all have common properties, staining characteristics, and x-ray diffraction spectra. Regardless of the nature of the amyloid protein deposited all amyloids have the following characteristics: 1) an amorphous appearance at the light microscopic level and appear eosinophilic using hematoxylin and eosin stains; 2) typically stain with Congo red and demonstrate a red/green birefringence as viewed under polarized light. 3) typically contain a predominant beta-pleated sheet secondary structure, and 4) ultrastructurally amyloid usually consist of non-branching fibrils of indefinite length and with a diameter of 7-10 nm.
  • amyloidosis forms include the amyloid associated with Alzheimer's disease, Down's syndrome and Hereditary cerebral hemorrhage with amyloidosis of the Dutch type (wherein the specific amyloid is referred to as beta-amyloid protein or AB), the amyloid associated with chronic inflammation, various forms of malignancy and Familial Mediterranean Fever (wherein the specific amyloid is referred to as AA amyloid or inflammation-associated amyloidosis), the amyloid associated with multiple myeloma and other B-cell dyscrasias (wherein the specific amyloid is referred to as AL amyloid), the amyloid associated with type 11 diabetes (wherein the specific amyloid is referred to as amylin or islet amyloid), the amyloid associated with the prion diseases including Creutzfeldt- Jakob disease, Gerstmann-Straussler syndrome, kuru and animal scrapie (wherein the specific amyloid is referred to as PrP amyloid),
  • the amount of such other phytos- terols and optionally cholesterol is relatively low, or even that these other compounds are absent from any food composition, nutraceutical composition, or pharmaceutical composition for prophylactic or therapeutic treatment of amyloidosis of beta-amyloid peptide (A ⁇ ) in the nervous system of a mammal.
  • the concentration of stigmasterol in a composition of the invention as a weight percentage of the sum of phytosterols, in particular stigmasterol, ergosterol, beta- sitosterol, brassicasterol, and campesterol, and optionally also including cholesterol is 25-100 weight%, in particular 50 to 100 weight%, preferably 75 to 100 weight%, more preferably 90 to 100 weight%, in particular 95 to 100 weight%, more in particular 98 to 100 weight%.
  • the concentration of stigmasterol in a composition of the invention as a weight percentage of the sum of phytosterols, in particular stigmasterol, ergosterol, beta- sitosterol, brassicasterol and campesterol, and optionally also including cholesterol is 25-100 weigh t%, in particular 50 to 100 weight%, more in particular 75 to 100 weight%, 90 to 100 weight%, 95 to 100 weight%, or 98 to 100 weight%.
  • the stigmasterol is for treatment of a human, in particular an elderly person.
  • an elderly person is a person of the age of 50 or more, in particular of the age of 55 or more, more in particular of the age of 60 or more, more in particular of the age of 65 or more.
  • This rather broad definition takes into account the fact that the average age varies between different populations, on different continents, etc.
  • Most developed world countries have accepted the chronological age of 65 years as a definition of 'elderly' or older person (associated with the age at which one may begin to receive pension benefits), but like many westernized concepts, this does not adapt well to e.g. the situation in Africa.
  • a composition of the present invention usually contains stigmasterol in an amount sufficient to administer to a subject (in particular a human adult (average weight about 70 kg)) a daily dosage of at least 0.5 mg/day , at least 5 mg/day, at least 25 mg/day, at least 50 mg/day, at least 100 mg/day, at least 200 mg/day, at least 400 mg/day, or at least 800 mg/day.
  • the daily dosage may be 4000 mg/day or less, 2000 mg/day or less, 1000 mg/day or less, 500 mg/day or less, or 250 mg/day or less.
  • nutraceutical composition which may be a food or beverage
  • the amount of stigmasterol contained therein is suitably present in the composition in a quantity to provide the daily dosage in a single serving.
  • serving denotes an amount of food or beverage normally ingested by a human adult with a meal at a time and may range, e.g., from about 1 g (such as a nutritional shot) to about 500 g.
  • the present invention (a composition comprising) stigmasterol may be used as a nutritional supplement, e.g., as an additive to a multi- vitamin preparations comprising vitamins and minerals which are essential for the maintenance of normal metabolic function but are not synthesized in the body, especially for the treatment or prevention of age-related decline in brain neuronal function and/or cognitive functioning in a mammal.
  • the pharmaceutical composition may be solid or liquid galenical formulation.
  • solid galenical formulations are tablets, capsules (e.g. hard or soft shell gelatine capsules), pills, sachets, powders, granules and the like which contain the active ingredient together with conventional galenical carriers.
  • Any conventional carrier material can be utilized.
  • the carrier material can be organic or inorganic inert carrier material suitable for oral administration. Suitable carriers include water, gelatine, gum Arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like. Additionally, additives such as flavouring agents, preservatives, stabilizers, emulsifying agents, buffers and the like may be added in accordance with accepted practices of pharmaceutical compounding. While the individual active ingredients are suitably administered in a single composition they may also be administered in individual dosage units.
  • composition may contain the daily dosage in one or more dosage units.
  • the dosage unit may be in a liquid form or in a solid form, wherein in the latter case the daily dosage may be provided by one or more solid dosage units, e.g. in one or more capsules or tablets.
  • a composition according to the invention in particular a nutritional composition, such as a food or beverage or a supplement composition for a food or beverage, may comprise one or more further ingredients, such as, protein, fat, digestible carbohydrates, dietary fibres, such as indigestible carbohydrates, minerals, vitamins, organic acids, and flavouring agents.
  • additional ingredients are, e.g. described in WO2003/041701 (N.V. Nutricia) and WO2007/073178 (N.V. Nutricia).
  • a nutritional composition according to the invention may comprise protein, preferably intact protein. Proteins enable the manufacturing of palatable products. Especially elderly and AD patients benefit from the protein as it strengthens their motor skills.
  • the nutritional composition according to the invention comprises milk protein.
  • the nutritional composition according to the invention comprises a protein selected from the group consisting of whey protein, casein or casemate.
  • the nutritional composition according to the invention comprises ca- strigate, more preferably the nutritional composition according to the invention comprises at least 70 weight%, more preferably at least 90 weight% casein and/or caseinate, based on total protein.
  • the proteins are included in intact (unhydrolyzed) form, in order to have a palatable product.
  • Such high molecular weight proteins increase the viscosity of the heat-treated liquid product, compared to the hydrolyzed forms.
  • the present inventors were able to make an acceptable product, with good palatability and limited viscosity, by applying the measures according the invention, still avoiding precipitation.
  • the nutritional composition according to the invention comprises between 0.2 and 16 gram protein per 100 ml, preferably between 0.2 and 10 gram protein per 100 ml, more preferably between 1 and 6 grams protein per 100 ml, more preferably between 2 and 5 grams protein per 100 ml.
  • the nutritional composition according to the invention may comprise fat.
  • fat may be a solid, a semi-solid or a liquid (oil) at room temperature (25 °C).
  • the fat may include medium chain triglycerides (MCT, mainly 8 to 10 carbon atoms long), long chain triglycerides (LCT, typically at least 12 carbon atoms long) or any combination of the two types.
  • MCT medium chain triglycerides
  • LCT long chain triglycerides
  • MCTs are beneficial because they are easily absorbed and metabolized. Moreover, the use of MCTs will reduce the risk of nutrient malabsorption.
  • LCT sources such as rapeseed oil, more in particular rapeseed oil low in erucic acid, sunflower oil, corn oil, palm kernel fat, coconut fat, palm oil, or mixtures thereof are preferred because they provide more energy per unit of fat.
  • the composition comprises one or more polyunsaturated fatty acids (PUFA' s) , in particular one or more PUFA's selected from docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and ei- cosapentaenoic acid (EPA).
  • PUFA' s polyunsaturated fatty acids
  • the fat comprises 30 to 60 weight% of animal or algal fat, 40 to 70 weight% of vegetable fat and optionally 0 to 20 weight% of MCTs based on total fat of the nutritional composition according to the invention.
  • the animal fat preferably comprises none or a low amount of milk fat, i.e. lower than 6 weight%, especially lower than 3 weight%.
  • a mixture comprising one or more oils selected from the group of corn oil, egg oil, canola oil and marine oil may be present.
  • Egg oils, fish oils and algal oils are a preferred source of non- vegetable fats.
  • Marine oils containing DHA and/or EPA are preferably present in the nutritional composition according to the invention for obtaining a positive health effect, such as, for instance, the prevention of cardiovascular risks.
  • the concentration preferably is 25 weight% or less, more preferably 15 weight% or less of the fat.
  • the amount of EPA ranges preferably between 4 weigh t% and 15 weight%, more preferably between 8 weight% and 13 weight% of the fat.
  • the nutritional composition according to the invention comprises a phospholipid, preferably 0.1 to 50 weigh t% phospholipids, based on total weight of lipids, more preferably 0.5 to 20 weight%, more preferably between 1 and 5 weight%, based on total weight of lipids.
  • the nutritional composition according to the invention contains at least one selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol.
  • the total amount of lipids is preferably between 10 and 30 weight% on dry matter, and/or between 2 and 6 g lipid per 100 ml for a liquid composition. Inclusion of phospholipids improve the stability of the nutritional composition according to the invention.
  • the nutritional composition according to the invention comprises one or more digestible carbohydrates.
  • the digestible carbohydrates positively influence the operational skills of a subject, and add to the advantageous effect of the nutritional composition according to the invention.
  • the total amount of digestible carbohydrates is preferably between 25 and 80 weight% on dry matter basis, preferably 40 to 80 weight.
  • the composition preferably contains between 1 and 50 gram digestible carbohydrates per 100 ml of a liquid product, more preferably between 5 and 30 grams per 100 ml, more preferably 10 to 30 grams of digestible carbohydrates per 100 ml.
  • digestible carbohydrates are digestible pentoses, digestible hexoses and digestible oligosaccharides, e.g. digestible disaccharides and digestible trisaccharides. More specifically one or more digestible carbohydrates may be chosen selected from the group of galactose, mannose, ribose sucrose, trehalose, palatinose, lactose, maltodextrose, maltose and glucose.
  • a nutritional composition according to the invention comprises one or more non- digestible carbohydrates (dietary fibres) such as oligosaccharides.
  • oligosaccharides in particular refers to saccharides comprising 3 to 25 monosaccharide units per molecule.
  • the oligosaccharide ⁇ ) may in particular be selected from the group of fructo- oligosaccharides (FOS), galacto-oligo ⁇ saccharides (GOS), trans-galacto- oligosaccharides (TOS), xylo-oligosaccharides (XOS), soy oligosaccharides, and the like.
  • composition according to the invention comprises a mixture of neutral and acid oligosaccharides, such as disclosed in WO 2005/039597 (N.V. Nutricia); compositions disclosed therein are incorporated herein by reference.
  • taurine taurine
  • cystein manganese
  • molybdenum zinc
  • selenium magnesium
  • chromium iron
  • copper vitamin A
  • vitamin Bl vitamin B2
  • vitamin B3 vitamin B5
  • vitamin B6 folic acid
  • vitamin B12 vitamin C
  • vitamin D vitamin D
  • vitamin E biotin
  • a liquid nutritional composition of the invention (food/nutraceutical) has an energy density of 80 to 450 kcal per 100 ml of the composition, more preferably between 90 and 250 kcal per ml of the liquid nu- tritional composition.
  • This is in particular considered advantageous because persons suffering from neuropathies or neurological problems often experience problems with eating. Their sensory capabilities and/or control of muscles generally have become imparted, as well as in some instances their ambition to apply proper eating habits. Part of these patients may experience a general loss in appetite and a relatively large part of this patient group became malnourished.
  • a liquid nutritional composition is relatively easy to administer, and by having an energetic value in the specified range, such people can relatively easily obtain sufficient caloric intake.
  • Liquid nutritional products preferably have a long shelf life.
  • increasing shelf life by heat treatments often results in destabilisation of the products and/or palatability, leading to a product which is undesirable.
  • a nutritional composition according to the invention can be subjected to a heat treatment without major adverse effects on the palatability.
  • the nutritional composition according to the invention is preferably heat-treated, more preferably the composition is subjected to a sterilization treatment.
  • the nutritional composition according to the invention is subjected to an ultra-high temperature treatment (UHT-treatment).
  • UHT-treatment ultra-high temperature treatment
  • Such UHT-treatment is preferably applied in line, i.e. before the liquid final product is filled in the package of the unit.
  • a food composition (for use) in a accordance with the invention may in particular be selected from the group of spreads ; yoghurts, custards, ice-creams, butter, and other dairy products ; dairy- substitute products ; fruit drinks ; candy bars, and cookies.
  • the invention is further directed to a specific composition comprising stigmasterol, namely a food composition, a nutraceutical composition, or a pharmaceutical composition, comprising stigmasterol, wherein the stigmasterol concentration in the composition as a weight percentage of the sum of phytosterols, in particular stigmasterol, ergosterol, beta- sitosterol, brassi- casterol, and campesterol, and optionally also including cholesterol is 25-100 weight%, in particular 50 to 100 weight%, preferably 75 to 100 weight%, more preferably 90 to 100 weight%, in particular 95 to 100 weight%, more in particular 98 to 100 weight%.
  • the stigmasterol concentration as percentage of the total dry weight can be chosen within wide limits.
  • the concentration may be at least 0.05 weight%, at least 0.1 weight%, at least 0.25 weight%, at least 0.5 weight%, at least 1 weight% or at least 2.5 weigh t% based on the total dry weight of the composition.
  • the concentration may be 90 weight% or less, 75 weight% or less, 50 weight% or less , 25 weight% or less, 10 weight% or less or 5 weight% or less, based on the total dry weight of the composition.
  • the composition is in a dosage unit form, e.g. in a packaging such as a bottle, a carton, a cup, in a strip (in case of a pharmaceutical or nutritional supplement), or the like.
  • the dosage unit form may provide 0.5 to 2000 mg, in particular 5 to 1000 mg, more in particular 25 to 500 mg stigmasterol.
  • the invention is further directed to prophylactic or therapeutically treating amyloidosis of beta-amyloid peptide (A ⁇ ) in the nervous system of a mammal, the method comprising administering an effective dose of stigmasterol to the mammal.
  • a ⁇ beta-amyloid peptide
  • the invention is further directed to prophylactic or therapeutically treating Alzheimer's disease, the method comprising administering an effective dose of stigmasterol to a mammal suffering from Alzheimer's disease or having a risk of developing Alzheimer's disease.
  • a mammal suffering from Alzheimer's disease or having a risk of developing Alzheimer's disease is considered to have a risk.
  • mammals are considered to have a risk of developing Alzheimer's disease in case they have an increased genetic risk or in case they are elderly.
  • the administration may in particular be an enteral administration, although in principle any other form of administration may be used, depending upon the form in which the stigmasterol is to be administered.
  • Alternative forms of administration are known in the art and include injection, administration as a suppository, etc.
  • Campesterol, ergosterol, beta- sitosterol, stigmasterol and cholesterol were obtained from SIGMA ALDRICH.
  • stock solutions of 10 niM in ethanol were prepared and stored at -20°C under non oxidizing conditions.
  • D EMEM Dulbecco's Modified Eagle's Medium
  • FCS foetal calf serum
  • MEM Ix Non-essential Amino Acid Solution
  • SH-SY5Y-wt cells were scraped and cracked in a buffer, containing 10 mM Tris- HCl pH 7.4. After separation of total membranes via ultracentrifugation, re- suspended membranes were incubated with 100 ⁇ M of sterol and gamma- secretase activity was measured by detecting the fluorescence- generating cleavage product of a specific gamma-secretase-substrate. Experiments were reproduced three times.
  • Table 1 Effect of various (plant)- sterols on gamma-secretase-activity in vitro.

Abstract

L'invention porte sur l'utilisation du stigmastérol dans la fabrication d'une composition alimentaire, d'une composition nutraceutique ou d'une composition pharmaceutique pour le traitement prophylactique ou thérapeutique de l'amyloïdose d'un peptide bêta-amyloïde (Aβ) dans le système nerveux d'un mammifère. L'invention porte en outre sur l'utilisation du stigmastérol dans la fabrication d'une composition alimentaire, d'une composition nutraceutique ou d'une composition pharmaceutique pour le traitement prophylactique ou thérapeutique de la maladie d'Alzheimer.
PCT/NL2009/050315 2009-03-12 2009-06-08 Stigmastérol pour le traitement de la maladie d'alzheimer WO2010104375A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP10708409A EP2405773A1 (fr) 2009-03-12 2010-03-12 Stigmastérol pour le traitement de la maladie d'alzheimer
BRPI1009814-3A BRPI1009814A2 (pt) 2009-03-12 2010-03-12 Uso de estigmasterol, e, composição.
PCT/NL2010/050133 WO2010104394A1 (fr) 2009-03-12 2010-03-12 Stigmastérol pour le traitement de la maladie d'alzheimer
CN2010800202802A CN102421304A (zh) 2009-03-12 2010-03-12 用于治疗阿尔茨海默病的豆甾醇

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL2009050121 2009-03-12
NLPCT/NL2009/050121 2009-03-12

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Publication Number Publication Date
WO2010104375A1 true WO2010104375A1 (fr) 2010-09-16

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PCT/NL2010/050133 WO2010104394A1 (fr) 2009-03-12 2010-03-12 Stigmastérol pour le traitement de la maladie d'alzheimer

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CN (1) CN102421304A (fr)
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WO (2) WO2010104375A1 (fr)

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CN104398523B (zh) * 2014-11-03 2017-01-25 南昌大学 (22反式)‑3β‑羟基‑胆甾‑5,22‑二烯‑24‑酮在神经保护药物中的应用
CN109793783A (zh) * 2017-11-16 2019-05-24 西双版纳华坤生物科技有限责任公司 一种用于阿尔兹海默症预防与治疗物质的应用及制备方法
AU2019308873A1 (en) * 2018-07-26 2021-02-04 Wista Laboratories Ltd. Optimised dosage of diaminophenothiazines in populations

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999032097A2 (fr) * 1997-12-18 1999-07-01 Forbes Medi-Tech Inc. Procede pour prevenir et retarder l'apparition de la maladie d'alzheimer, et composition utilisee a cet effet
WO2000030666A1 (fr) * 1998-11-24 2000-06-02 University Of Washington Composition et procedes pour inhiber la formation de depots de substances amyloides dans le cerveau
WO2000041491A2 (fr) * 1999-01-15 2000-07-20 Nutrahealth Ltd (Uk) Aliments ou boissons modifies ou additifs pour aliments et boissons
WO2001003712A1 (fr) * 1999-07-09 2001-01-18 Astion Development Aps Composition contenant des extraits de butyrospermum parkii et utilisation en tant que medicament ou supplement alimentaire
WO2005049037A1 (fr) * 2003-10-24 2005-06-02 The Coca-Cola Company Procede de preparation de dispersions de phytorosterol pour utilisation dans des boissons
WO2005094610A1 (fr) * 2004-03-26 2005-10-13 The Procter & Gamble Company Agent de revetement stable comprenant du sterol
WO2007124597A1 (fr) * 2006-05-01 2007-11-08 Forbes Medi-Tech Inc. Composition comprenant un ou plusieurs phytostérols et/ou phytostanols estérifiés dans lesquels sont solubilisés un ou plusieurs phytostérols et/ou phytostanols non estérifiés afin d'améliorer les bienfaits thérapeutiques et la formulation
EP2036444A1 (fr) * 2007-09-05 2009-03-18 Dietetics Pharma S.r.l. Préparation nutraceutique liquide contenant des stérols d'origine végétale

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060078533A1 (en) 2004-10-12 2006-04-13 Omoigui Osemwota S Method of prevention and treatment of aging and age-related disorders including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, arthritis, type 2 diabetes, dementia, alzheimer's disease and cancer
WO2005039597A2 (fr) 2003-10-24 2005-05-06 N.V. Nutricia Oligosaccharides immunomodulatrices

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999032097A2 (fr) * 1997-12-18 1999-07-01 Forbes Medi-Tech Inc. Procede pour prevenir et retarder l'apparition de la maladie d'alzheimer, et composition utilisee a cet effet
WO2000030666A1 (fr) * 1998-11-24 2000-06-02 University Of Washington Composition et procedes pour inhiber la formation de depots de substances amyloides dans le cerveau
WO2000041491A2 (fr) * 1999-01-15 2000-07-20 Nutrahealth Ltd (Uk) Aliments ou boissons modifies ou additifs pour aliments et boissons
WO2001003712A1 (fr) * 1999-07-09 2001-01-18 Astion Development Aps Composition contenant des extraits de butyrospermum parkii et utilisation en tant que medicament ou supplement alimentaire
WO2005049037A1 (fr) * 2003-10-24 2005-06-02 The Coca-Cola Company Procede de preparation de dispersions de phytorosterol pour utilisation dans des boissons
WO2005094610A1 (fr) * 2004-03-26 2005-10-13 The Procter & Gamble Company Agent de revetement stable comprenant du sterol
WO2007124597A1 (fr) * 2006-05-01 2007-11-08 Forbes Medi-Tech Inc. Composition comprenant un ou plusieurs phytostérols et/ou phytostanols estérifiés dans lesquels sont solubilisés un ou plusieurs phytostérols et/ou phytostanols non estérifiés afin d'améliorer les bienfaits thérapeutiques et la formulation
EP2036444A1 (fr) * 2007-09-05 2009-03-18 Dietetics Pharma S.r.l. Préparation nutraceutique liquide contenant des stérols d'origine végétale

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VOLPE ET AL.: "Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia", BRITISH JOURNAL OF NUTRITION, vol. 86, 2001, pages 233 - 239, XP002551880 *

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