WO2011034532A1 - Compositions à base de stilbène et méthodes d'utilisation - Google Patents

Compositions à base de stilbène et méthodes d'utilisation Download PDF

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Publication number
WO2011034532A1
WO2011034532A1 PCT/US2009/057310 US2009057310W WO2011034532A1 WO 2011034532 A1 WO2011034532 A1 WO 2011034532A1 US 2009057310 W US2009057310 W US 2009057310W WO 2011034532 A1 WO2011034532 A1 WO 2011034532A1
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Prior art keywords
pterostilbene
human
administered
effective amount
carbohydrate
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PCT/US2009/057310
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English (en)
Inventor
Bruce W. Kneller
Daniel C. Pierce
Joseph Babick, Jr.
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Gaspari Nutrition, Inc.
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Priority to CA002677950A priority Critical patent/CA2677950A1/fr
Priority to PCT/US2009/057310 priority patent/WO2011034532A1/fr
Priority to US12/687,962 priority patent/US20100119499A1/en
Publication of WO2011034532A1 publication Critical patent/WO2011034532A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • 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

Definitions

  • Additional dietary supplements that can increase the rate or quantity of absorption, rate or quantity of nutrient partitioning, or rate or quantity of use of various athletic performance-enhancing nutrients (including, but not limited to, carbohydrates, proteins, vitamins, minerals, amino acids, creatine by skeletal muscle cells and tissues) are desirable for improving weight loss, increasing lean muscle mass, and/or improving athletic performance.
  • Stilbenes are small (molecular weight of 210-278 g/mol) , naturally-occurring compounds found in a wide range of plant sources, aromatherapy products, and dietary compositions. Stilbenes exist as stereoisomers in E and Z forms, depending on where functional groups are attached in relation to one another on either side of the double bond. Naturally-occurring stilbenes
  • stilbenoid compounds include, but are not limited to, piceatannol, pinosylvin, rhapontigenin, tamoxifen, and pterostilbene .
  • Pterostilbene is thought to be a key compound found predominantly in blueberries (as well as grapes) that exhibits anti-fungal, anti- cancer, anti-hypercholesterolemia, and anti- hypertriglyceridemia properties, as well as the ability to delay and reverse cognitive decline.
  • compositions, formulations and methods relating to one or more stilbene-based compounds for use in humans can improve
  • the stilbene-based compound is pterostilbene .
  • the invention relates to a method of increasing athletic performance, lowering blood sugar level and/or increasing lean muscle mass in a human comprising administering an effective amount of a
  • stilbene-based compound to said human.
  • the stilbene-based compound is pterostilbene.
  • the pterostilbene is administered orally.
  • the effective amount of pterostilbene is from about 3 mg to about 25 mg per dose, from about 3 mg to about 10 mg per dose, or from about 5 mg to about 10 mg per dose.
  • the effective amount of pterostilbene is from about 0.03 mg/kg bodyweight of the human to about 0.165 mg/kg bodyweight of the human per dose .
  • more than one dose comprising an effective amount of pterostilbene is administered to the human (e.g., two or more doses spaced over time, each dose comprising an effective amount of pterostilbene) .
  • the pterostilbene is co ⁇ administered with one or more non-carbohydrate nutrients.
  • the non-carbohydrate nutrient may be
  • creatine and its salts, esters, amides and chelates selected from the group consisting of creatine and its salts, esters, amides and chelates; creatinol-O- phosphate; the amino acids leucine, isoleucine, valine, taurine, beta-alanine, arginine, ornithine, aspartic acid, glutamine, glutaric acid, agmatine, citrulline, norvaline, glycine, and cysteine and salts, esters, amides and chelates of said amino acids; ketoisocaproate and sodium, potassium, calcium and magnesium salts thereof; the dipeptides carnitine, anserine and carnosine and salts and esters thereof; and dipeptide-containing proteins .
  • the pterostilbene is co ⁇ administered with one or more carbohydrate nutrients.
  • the carbohydrate nutrient may be selected from the group consisting of: rice oligodextrin; amylose; amylopectin; glucose; maltodextrin; maltose;
  • the pterostilbene is co ⁇ administered with one or more non-carbohydrate nutrients and one or more carbohydrate nutrients.
  • an effective amount of pterostilbene can be co-administered with both a carbohydrate nutrient and creatine or a salt, ester, amide or chelate thereof.
  • the pterostilbene is co ⁇ administered with one or more compounds not found in a pterostilbene natural source.
  • the pterostilbene is co- administered with one or more compounds selected from the group consisting of methylxanthines (e.g., caffeine, theobromine, theophylline) , glucuronolactone, animal digestive enzymes (e.g., lipase, bromelain, pancreatin, amylase, lactase) , and carbohydrates not found in a pterostilbene natural source (e.g., isomaltulose,
  • the invention further relates to a formulation or composition comprising an amount of pterostilbene
  • the formulation or composition comprises creatine or a salt, ester, amide or chelate thereof; in some embodiments the formulation comprises from about 250 mg to about 10,000 mg of creatine or a salt, ester, amide or chelate thereof per dose.
  • the formulation comprises from about 3 mg to about 25 mg of pterostilbene per dose. In some embodiments the formulation comprises greater than about 0.002 percent pterostilbene by weight, for example from about 0.002 to about 100 percent pterostilbene by weight. In some embodiments the formulation comprises one or more carbohydrate nutrients in addition to pterostilbene. In some embodiments the formulation comprises one or more non-carbohydrate nutrients in addition to pterostilbene.
  • the formulation comprises, in addition to pterostilbene, one or more compounds selected from the group consisting of methylxanthines (e.g., caffeine, theobromine, theophylline) , glucuronolactone, animal digestive enzymes (e.g., lipase, bromelain, pancreatin, amylase, lactase) , and carbohydrates not found in pterostilbene natural sources (e.g.,
  • FIG. 1 shows pterostilbene (trans-3, 5-dimethoxy-4 ' - hydroxystilbene) , molecular formula C16H16O3 , having a molecular weight of about 256.3 g/mol (CAS#537-42-8 ) .
  • FIG. 2 shows resveratrol (3, 4 ',5-
  • Trihydroxystilbene molecular formula C14H12O3 , having a molecular weight of about 228.246 g/mol (CAS# 501-36-0).
  • Insulin is a polypeptide hormone that has extensive effects on metabolism and other body functions, such as vascular compliance. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose and other nutrients from the blood. Insulin causes glucose to be stored as glycogen in the liver and muscle. Insulin also inhibits the body's use of fat as an energy source. When insulin is absent (or present at low levels) , glucose is not taken up by the cells of the body; the body begins to use fat as an energy source (for example, by transfer of lipids from adipose tissue to the liver for mobilization as an energy source) . As its level is a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells) . It has several other anabolic effects throughout the body. When control of insulin levels fails, diabetes mellitus results.
  • Insulin is produced in the pancreas and released when any of several stimuli is detected.
  • the stimuli include ingested protein and glucose in the blood
  • carbohydrates produced from digested food. Certain carbohydrates produce glucose and thereby increase blood glucose levels. In target cells, carbohydrates initiate a signal transduction, which has the effect of increasing glucose uptake and storage. Ultimately insulin is degraded, terminating the response.
  • the beta cells in the islets of Langerhans in the pancreas release insulin in two phases.
  • insulin release is rapidly triggered in response to increased blood glucose levels.
  • the second phase is a sustained, slow release of newly formed vesicles that are triggered independent of sugar levels.
  • the description of first phase release is as follows:
  • Glucose goes into the glycolysis and the respiratory cycle where multiple high-energy ATP molecules are produced by oxidation
  • Inositol 1 , 4 , 5-triphosphate (IP3) binds to receptor proteins in the membrane of endoplasmic reticulum (ER) . This allows the release of Ca2+ from the ER via IP3 gated channels, and further raises the cell concentration of calcium; 7. Significantly increased amounts of calcium in the cells causes release of previously synthesized insulin, which has been stored in secretory vesicles. This is the main mechanism for release of insulin.
  • insulin release takes place generally upon food or other nutrient intake (not limited to glucose or carbohydrate intake) , and the beta cells are also somewhat influenced by the autonomic nervous system.
  • acetylcholine released from vagus nerve endings (parasympathetic nervous system)
  • glucose-dependent insulinotropic peptide GIP
  • Three amino acids alanine, glycine and arginine
  • the sympathetic nervous system (via Alpha2- adrenergic stimulation as demonstrated by the agonists clonidine or methyldopa) inhibits the release of insulin.
  • circulating adrenaline will activate Beta2-Receptors on the beta cells in the pancreatic islets to promote insulin release. This is important, as muscle cannot benefit from the raised blood sugar resulting from adrenergic stimulation (increased gluconeogenesis and glycogenolysis from the low blood insulin: glucagon state) unless insulin is present to allow for GLUT-4 translocation in the tissue. Therefore, beginning with direct innervation, norepinephrine
  • adrenaline from the adrenal medulla will stimulate beta2-receptors thereby promoting insulin release.
  • muscle cells myocytes
  • adipocytes fat cells
  • the actions of insulin on human metabolism include control of cellular intake of certain substances
  • the actions of insulin at the cellular level include:
  • Increased glycogen synthesis - insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is directly useful in reducing high blood glucose levels as in diabetes;
  • Arterial muscle tone forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract; and
  • Insulin is usually administered via subcutaneous injection by single-use syringes with needles, an insulin pump, or by repeated-use insulin pens with needles.
  • Pterostilbene is a stilbene found, for example, in deerberry and rabbiteye blueberries, unripe Pinot noir and Botrytis vinifera infected Chardonnay grapes, and immature berries of Pinot and Gamay varieties (J Agric Food Chem 52:4713-9 (2004); J Agric Food Chem 48:6103- 6105 (2000); Plant Physiol Biochem 26:603-1 (1988)).
  • Pterostilbene has been shown to elicit significant anti-oxidant activity in vitro that is comparable to the activity of resveratrol. Research has demonstrated that pterostilbene inhibits cintronellal thermo-oxidation by an EQ value of 335 mM (-90.9 mg/ml) , and that
  • pterostilbene scavenges for 2 , 2-diphenyl-l-picrylhydrazyl (DPPH) radicals with an EC 50 value of about 30 mM (-7.68 mg/ml) (J Nat Prod 60:609-10 (1997)). Additionally, pterostilbene inhibits 2 , 2 ' -azo-bis (2-amidinopropane) (ABAP) -derived peroxyl radicals with a total reactive antioxidant potential of 237 +/- 58 mM (-60.7 mg/ml) as compared to resveratrol at 253 +/- 53 mM (-57.7 mM/ml) (J Agric Food Chem 50:3453-7 (2002)). Further, 2-diphenyl-l-picrylhydrazyl (DPPH) radicals with an EC 50 value of about 30 mM (-7.68 mg/ml) (J Nat Prod 60:609-10 (1997)). Additionally, pterostilbene inhibits 2 , 2
  • TBARS thiobarbituric acid reactive substances
  • Pterostilbene and Pterocarpus marsupium extracts that have been shown to contain pterostilbene have reported anti-diabetic properties. Research demonstrated that pterostilbene can lower the blood glucose level in streptozotocin-induced hyperglycemic rats by 42% (J Nat Prod 60: 609-10 (1997)). Pterocarpus marsupium, which contains pterostilbene in its heartwood, has also been shown to have anti-hyperglycemic properties and provide significant protection against hypertriglyceridemia and hyperinsulinemia (Diabetes Obes Metab 7:414-20 (2005)). In the development of new drugs and dietary
  • MSRD maximum recommended starting dose
  • NOAELs no adverse effects levels
  • FDA/CDER guiding document provides tables and algorithmic processes for determining the HED.
  • page 7 of this document provides a table based on several species of test animals and appropriate formulae to convert these animal doses to HED based on body surface area.
  • the test animal is a rat, the following formulae are provided:
  • HED animal dose in mg/kg x (animal weight in kg/human weight in kg) 0.33
  • the range for pterostilbene would be expected to be between 1.357 mg/kg of bodyweight (based on pterostilbene dose of lOmg/kg bodyweight in the rat) and 6.542 mg/kg of bodyweight (based on pterostilbene dose of 40 mg/kg bodyweight in the rat) .
  • a human with a bodyweight of -100kg would be able to safely use a dose of pterostilbene of about 135 mg to about 654 mg.
  • test subject Within fifteen minutes of oral administration at this dose, the human test subject began to experience symptoms of profound hypoglycemia, including shakiness, dysphoria, and diaphoresis. Testing of the subject's whole blood glucose level by "finger prick" methodology using a commercial glucometer revealed that the test subject's whole blood glucose level had dropped about 50 mg/dL during this time period. The test subject was immediately treated with oral glucose and other
  • pterostilbene is effective in significantly reducing whole blood glucose levels in healthy, adult humans in doses as low as 0.03 mg/kg of bodyweight (actual dose given 3 mg orally) to about 0.165 mg/kg of bodyweight (actual dose given 20 mg orally) without inducing clinically significant side effects including, but not limited to, nausea, dysphoria,
  • pterostilbene At oral dosing above 0.165 mg/kg (actual dose tested 20 mg) pterostilbene is capable of inducing profound hypoglycemia (e.g., whole blood glucose at or below 55 mg/dL) and the side effects associated with this condition. Accordingly, at the doses predicted by the FDA/CDER formula, oral administration of pterostilbene to humans would likely be fatal.
  • hypoglycemia .
  • Such dietary nutrients include, but are not limited to, creatine and its salts esters, amides and chelates, creatinol-O-phosphate, branched chain amino acids (leucine, isoleucine, valine) and their salts, esters, amides and chelates, branched chain keto-acids including, but not limited to ketoisocaproate and its salts, other ergogenic, performance-enhancing amino acids including, but not limited to, taurine, beta-alanine, arginine, ornithine, aspartic acid, glutamine, glutaric acid, agmatine, citrulline, norvaline, glycine, cysteine and their salts, ester, amides and chelates, performance enhancing dipeptides including, but not limited to, carnitine, anserine and carnosine and their salts and esters and proteins that are known to contain dipeptides such as whey or soy or egg protein isolates or
  • exogenous dietary carbohydrates including but not limited to rice oligodextrin, amylose, amylopectin, glucose, maltodextrin, maltose, isolmaltulose, leucrose, trehalulose, ribose, trehalose, and/or fructose in conjunction with pterostilbene and a non-carbohydrate based dietary nutrient or nutrients simultaneously further increases the athletic performance-enhancing effects of pterostilbene and the non-carbohydrate dietary nutrient (s) by up to 50% and also increases the
  • compositions and methods of the present invention are provided.
  • athletic performance e.g., muscle size, and/or muscle strength, and/or muscle endurance in individuals.
  • athletic performance e.g., muscle size, and/or muscle strength, and/or muscle endurance in individuals.
  • athlete performance and/or “athletic
  • athletic performance and/or athletic functions include, but are not limited to, maximal muscle power, muscular endurance, running speed and endurance, swimming speed and endurance, throwing power, lifting and pulling power.
  • compositions of the invention can function as insulinogenic agents or insulin mimetics.
  • compositions and methods of the present invention will be of particular importance to bodybuilders and other athletes, the usefulness of compositions and methods of the invention is not limited to those groups. Rather, any individual (i.e., human) may beneficially use the compositions and methods of the invention.
  • compositions according to the present invention may be employed in methods for supplementing the diet of an individual, e.g., an athlete, and/or for enhancing an individual's muscle mass and/or muscle size and/or strength, and/or endurance.
  • the present invention provides methods of supplementing the dietary intake of an individual comprising administering to the individual an effective amount of a composition (e.g., pterostilbene or a nutritional supplement comprising pterostilbene) according to the present invention to increase athletic performance or athletic function is said individual.
  • a composition e.g., pterostilbene or a nutritional supplement comprising pterostilbene
  • the invention also relates to methods of improving athletic performance and/or athletic function in an individual comprising administering an effective amount of a pterostilbene (alone or in combination with other agents, e.g., in a dietary supplements or
  • compositions, formulations and methods relating to one or more stilbene-based compounds for use in humans.
  • compositions and formulations comprising, consisting of or consisting essentially of an effective amount of the stilbene-based insulinogenic compound can improve athletic performance, lower blood glucose levels, and increase lean muscle mass when administered (e.g., orally) to a human.
  • the stilbene-based compound is pterostilbene.
  • compositions and forumations of the invention can preferably be dietary supplements, dietary formulations, or nutraceuticals .
  • dietary supplements preferably be dietary supplements, dietary formulations, or nutraceuticals .
  • nutraceuticals preferably be dietary supplements, dietary formulations, or nutraceuticals .
  • the terms "nutrient” and “dietary supplement” and “nutraceutical” are used interchangeably to refer to any substance that is a food or part of a food and provides medical or health
  • compositions falling under the label "nutrient” and “dietary supplement” may range from isolated nutrients, nutritional or dietary supplements, and specific diets, to genetically engineered designer foods, herbal products, and processed foods such as cereals, soups, and beverages.
  • the term has been used to refer to a product isolated or purified from foods, and generally sold in medicinal forms not usually associated with foods and demonstrated to have a physiological benefit or provide protection against chronic disease.
  • compositions and formulations of the invention will comprise an effective amount of pterostilbene; in some embodiments compositions and formulations of the
  • inventions will further comprise at least one (i.e., one or more) compounds or compositions which are not found in a natural source of pterostilbene.
  • at least one i.e., one or more compounds or compositions which are not found in a natural source of pterostilbene.
  • composition or compound which is not found in a natural source of pterostilbene is an active agent (i.e., is an agent which has a physiological effect either alone or in combination with pterostilbene) .
  • Pterostilbene can be obtained as known in the art by chemical synthesis methods (see, for example, US Patent
  • the pterostilbene of the invention is
  • compositions or formulation separated from one or more (e.g., from all) compounds with which it exists in a natural source.
  • compositions of the present invention is defined as an amount effective, at dosages and for periods of time necessary, to achieve the desired result.
  • the amount of pterostilbene may be effective to increase athletic performance, lower blood sugar levels and/or increase lean muscle mass in a human to whom the
  • compositions of the invention are administered.
  • the effective amount of compositions of the invention may vary according to factors such as age, sex, and weight of the individual.
  • Dosage regime may be adjusted to provide the optimum response. Several divided doses may be administered daily, or the dose may be proportionally reduced as indicated by the exigencies of an individual's situation. As will be readily appreciated, a composition in
  • servings need not be limited to daily administration, and may be on an every second or third day or other convenient effective basis.
  • administration on a given day may be in a single serving or in multiple servings spaced throughout the day
  • each dose will comprise an effective amount of
  • the invention relates, for example, to a formulation comprising an amount of pterostilbene effective to increase athletic performance in a human to whom the formulation is administered, and creatine or a salt, ester, amide or chelate thereof.
  • the invention also relates to a formulation comprising an amount of
  • pterostilbene effective to reduce blood sugar levels or to increase lean muscle mass in a human to whom it is administered.
  • the effective amount is from about 3 mg to about 25 mg of pterostilbene per dose, more particularly from about 5 mg to about 10 mg of pterostilbene per dose.
  • the effective amount is from about 3 mg to about 25 mg of pterostilbene per dose, more particularly from about 5 mg to about 10 mg of pterostilbene per dose.
  • formulation comprises from about 250 mg to about 10,000 mg of creatine or a salt, ester, amide or chelate thereof per dose.
  • the formulations and compositions of the invention may, for example, comprise from about 0.002 to about 100 percent pterostilbene by weight.
  • compositions and formulations of the invention will comprise at least about 0.002 percent pterostilbene by weight .
  • the formulation comprises one or more carbohydrate nutrients in addition to comprising pterostilbene.
  • the carbohydrate nutrient can be one or more of rice oligodextrin; amylose;
  • amylopectin glucose; maltodextrin; maltose;
  • the non- carbohydrate nutrient may be one or more of creatine and its salts, esters, amides and chelates; creatinol-O- phosphate; the amino acids leucine, isoleucine, valine, taurine, beta-alanine, arginine, ornithine, aspartic acid, glutamine, glutaric acid, agmatine, citrulline, norvaline, glycine, and cysteine and salts, esters, amides and chelates of said amino acids; ketoisocaproate and sodium, potassium, calcium and magnesium salts thereof; the dipeptides carnitine, anserine and carnosine and salts and esters thereof; and dipeptide-containing proteins .
  • the formulation or compositions of the invention comprise one or more compounds or compositions which are not found in a natural source of pterostilbene, and in a preferred embodiment the one or more compounds or compositions are active agents.
  • the composition is formulated as a tablet, capsule, caplet, powder, suspension, gel preparation, aqueous solution, solid food form (e.g., chewable bar or wafer), or liquid dosage form such as elixirs, syrups, dispersed powders, granules or emulsions.
  • the composition is formulated as a tablet, capsule, caplet, powder, suspension, gel preparation, aqueous solution, solid food form (e.g., chewable bar or wafer), or liquid dosage form such as elixirs, syrups, dispersed powders, granules or emulsions.
  • the composition is formulated as a tablet, capsule, caplet, powder, suspension, gel preparation, aqueous solution, solid food form (e.g., chewable bar or
  • compositions and formulations of the invention may be administered effectively by other routes
  • the route of administration is oral, and suitable means are especially tablets, caplets, capsules, pulls, suspensions, solutions (e.g., drinks), elixirs that can be produced in ways that are commonly used and familiar to one skilled in the art, with the additives and vehicles that are commonly used.
  • suitable means are especially tablets, caplets, capsules, pulls, suspensions, solutions (e.g., drinks), elixirs that can be produced in ways that are commonly used and familiar to one skilled in the art, with the additives and vehicles that are commonly used.
  • extended release or time release formulations are among technologies known to the skilled artisan and suitable for use with the invention.
  • compositions can be administered or formulated alone or can be formulated with or
  • composition or formulation is administered before, concurrent with or after other optional components such as other active ingredients.
  • other optional components such as other active ingredients.
  • the composition or formulation is administered before, concurrent with or after other optional components such as other active ingredients.
  • pterostilbene contains one or more of the following ingredients, preferably as an active
  • Carbohydrates including, but not limited to, isomaltulose, trehalose, maltodextrin, glucose, sucrose, fructose, lactose, amylose, and/or ribose; • Water soluble vitamins including, but not limited to, Vitamin C, Vitamin Bl, Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B12, and/or Vitamin K (and derivatives) ;
  • ⁇ Minerals including, but not limited to,
  • magnesium, and/or iron (and derivatives) (preferably in amounts less than the RDA) ;
  • Amino acids including, but not limited to, L- arginine, L-ornithine, L-glutamine, L-tyrosine, L- taurine, L-leucine, L-isoleucine, and/or L-valine (and derivatives) ;
  • methylxanthines e.g. - caffeine
  • glucuronolactone and derivatives
  • Nutraceutically acceptable hypoglycemic agents including, but not limited to, alpha-lipoic acid and its derivatives, cinnamon bark, bitter melon extracts,
  • Gymnema Sylvestre extracts 4-hydroxy-isoleucine
  • Creatine and its salts e.g., creatine
  • esters e.g., creatine ethyl ester
  • chelates amides, ethers (and derivatives) ;
  • compositions may contain pharmaceutically, e.g., nutraceutically, acceptable excipients, according to methods and procedures well known in the art.
  • excipient refers to substances that are typically of little or no therapeutic value, but are useful in the manufacture and compounding of various pharmaceutical preparations and which generally form the medium of the composition. These substances include, but are not limited to, coloring, flavoring, and diluting agents; emulsifying, dispersing and suspending agents, ointments, bases, pharmaceutical solvents; antioxidants and preservatives; and miscellaneous agents. Suitable excipients are described, for example, in Remington's Pharmaceutical Sciences.
  • compositions and formulations according to the present invention can further comprise one or more acceptable carriers.
  • acceptable carriers are known in the nutritional supplement arts, and the carrier can be any suitable carrier.
  • the carrier need only be suitable for administration to animals, including humans, and be able to act as a carrier without
  • the carrier (s) may be selected based upon the desired administration route and dosage form of the composition.
  • the nutritional supplement compositions according to the present invention are suitable for use in a variety of dosage forms, such as liquid form and solid form (e.g., a chewable bar or wafer) .
  • the compositions and formulations comprise a solid dosage form, such as a tablet or capsule.
  • suitable carriers for use in tablet and capsule compositions include, but are not limited to, organic and inorganic inert carrier materials such as gelatin, starch, magnesium stearate, talc, gums, silicon dioxide, stearic acid, cellulose, and the like.
  • the carrier is substantially inert, but it should be noted that the nutritional supplement compositions of the present invention may contain further active ingredients in addition to pterostilbene .
  • the invention also relates to a method of increasing athletic performance, lowering blood sugar level and/or increasing lean muscle mass in a human comprising
  • stilbene-based compound is pterostilbene. In one embodiment the pterostilbene is administered orally.
  • athletic functions refers to the sum of physical attributes which can be dependent to any degree on skeletal muscle contraction.
  • athletic functions include, but are not limited to, maximal muscular strength, muscular endurance, running speed and endurance, swimming speed and endurance, throwing power, lifting and pulling power.
  • improving or increasing athletic performance or function includes enhancing an individual's muscle mass and/or muscle size and/or strength, and/or endurance.
  • the effective amount of pterostilbene is from about 3 mg to about 25 mg per dose, from about 3 mg to about 10 mg per dose, or from about 5 mg to about 10 mg per dose. In certain embodiments the effective amount of pterostilbene is from about 0.03 mg/kg bodyweight of the human to about 0.165 mg/kg bodyweight of the human per dose.
  • more than one dose comprising an effective amount of pterostilbene is administered to the human (e.g., two or more doses spaced over time, each dose comprising an effective amount of pterostilbene) .
  • the pterostilbene can be co-administered with one or more non-carbohydrate nutrients.
  • the non- carbohydrate nutrient may be selected from the group consisting of creatine and its salts, esters, amides and chelates; creatinol-O-phosphate ; the amino acids leucine, isoleucine, valine, taurine, beta-alanine, arginine, ornithine, aspartic acid, glutamine, glutaric acid, agmatine, citrulline, norvaline, glycine, and cysteine and salts, esters, amides and chelates of said amino acids; ketoisocaproate and sodium, potassium, calcium and magnesium salts thereof; the dipeptides carnitine, anserine and carnosine and salts and esters thereof; and dipeptide-containing proteins.
  • the pterostilbene is co ⁇ administered with one or more carbohydrate nutrients.
  • the carbohydrate nutrient may be selected from the group consisting of: rice oligodextrin; amylose; amylopectin; glucose; maltodextrin; maltose;
  • the pterostilbene is co ⁇ administered with both one or more non-carbohydrate nutrients and one or more carbohydrate nutrients.
  • an effective amount of pterostilbene can be co ⁇ administered with both a carbohydrate nutrient and creatine or a salt, ester, amide or chelate thereof.
  • the pterostilbene is co- administered with one or more compounds not found in a pterostilbene natural source. In some embodiments the pterostilbene is co-administered with one or more
  • methylxanthines e.g., caffeine, theobromine,
  • pterostilbene natural source e.g., isomaltulose, trehalose, leucrose, amylose, trehalulose, rice oligodextrin.
  • co-administration includes, but is not limited to, concurrent administration of multiple compositions, either as separate compositions or in admixture. Co-administration also includes
  • compositions proximal in time as long as the co-administered compositions exhibit the synergistic or enhanced functional effect observed when the compositions are administered concurrently.
  • the synergistic effect or enhanced effect need not be of the same scope or magnitude as observed upon concurrent administration .
  • co-administration of an effective amount of pterostilbene and a non-carbohydrate nutrient exhibits an improved effect on athletic performance as compared with either nutrient alone.
  • this co ⁇ administration exhibits an enhanced or synergistic effect on athletic performance which is greater than the
  • carbohydrate nutrient further enhances this effect.
  • ADP to ATP regeneration increases, and/or glycogen synthesis in muscle increase.
  • the invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process.
  • the invention also includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.
  • the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the listed claims is introduced into another claim dependent on the same base claim (or, as relevant, any other claim) unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise.
  • Non-limiting examples of pterostilbene used with non-carbohydrate dietary nutrients and pterostilbene used with non-carbohydrate dietary nutrients plus exogenous carbohydrates are provided in the examples below.
  • the servings set forth in these examples are designed for an athlete with a body mass of about 70 kilograms. Daily values can be increased or decreased, depending on the body mass of the individual athlete and individual needs and requirements.
  • an athlete consumes one serving of the food supplement described herein daily; typically the athlete will consume a serving of the food supplement about 30-60 minutes before exercise.
  • Each serving is about 85.855 grams and contains the following:
  • Each 85.855 gram serving is administered as a powder dissolved into about 500-750 milliliters of water or fruit juice to provide a liquid drink.
  • an athlete consumes two servings of the food supplement as described herein daily; typically the athlete will consume one serving of the food
  • Each serving is about 99.005 grams and contains the following:
  • Each approximately 99.010 gram serving is mixed in about 500-1000 milliliters of water or fruit juice to provide a liquid drink.
  • an athlete consumes three servings of the food supplement as described herein daily;
  • the athlete will consume one serving of the food supplement about 30-60 minutes before exercise or athletic activity, the second serving of the food
  • Each serving is about 19.8021 grams and contains the following:
  • Each approximately 19.8021 gram serving is mixed in about 300-500 milliliters of water or fruit juice to provide a liquid drink.

Abstract

Cette invention concerne des compositions, des préparations et des méthodes concernant un ou plusieurs composés à base de stilbène à utiliser chez l'être humain. En particulier, l'administration à l'être humain (par ex. par voie orale) de compositions et de préparations contenant une dose efficace d'un composé insulinogène à base de stilbène permet d'accroître les performances athlétiques, d'abaisser les taux de glycémie et d'augmenter la masse musculaire maigre.
PCT/US2009/057310 2009-09-17 2009-09-17 Compositions à base de stilbène et méthodes d'utilisation WO2011034532A1 (fr)

Priority Applications (3)

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CA002677950A CA2677950A1 (fr) 2009-09-17 2009-09-17 Compositions a base de stilbene et methodes d'utilisation connexes
PCT/US2009/057310 WO2011034532A1 (fr) 2009-09-17 2009-09-17 Compositions à base de stilbène et méthodes d'utilisation
US12/687,962 US20100119499A1 (en) 2009-09-17 2010-01-15 Stilbene-based compositions and methods of use therefor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2009/057310 WO2011034532A1 (fr) 2009-09-17 2009-09-17 Compositions à base de stilbène et méthodes d'utilisation

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009082459A2 (fr) * 2007-12-24 2009-07-02 Natrol, Inc. Composition anti-vieillissement contenant du resvératrol et méthode d'administration

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009082459A2 (fr) * 2007-12-24 2009-07-02 Natrol, Inc. Composition anti-vieillissement contenant du resvératrol et méthode d'administration

Non-Patent Citations (4)

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Title
"New Life Extension Mix with Standardized Blueberry Extract", LIFE EXTENSION MAGAZINE, 2005, Retrieved from the Internet <URL:http://www.lef.org> *
MANICKAM, M. ET AL.: "Antihyperglycemic Activity of Phenolics from Pterocarpus marsupium", JOURNAL OF NATURAL PRODUCT, vol. 60, no. 6, 1997, pages 609 - 610 *
PARI, L. ET AL.: "Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide-induced diabetic rats", LIFE SCIENCE., vol. 79, 2006, pages 641 - 645, XP028050877, DOI: doi:10.1016/j.lfs.2006.02.036 *
RIMANDO, A.M. ET AL.: "Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY., vol. 53, no. 9, 2005, pages 3403 - 3407, XP002418072, DOI: doi:10.1021/jf0580364 *

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