WO2013173719A1 - Compositions de phytonutriments et procédés d'utilisation - Google Patents

Compositions de phytonutriments et procédés d'utilisation Download PDF

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Publication number
WO2013173719A1
WO2013173719A1 PCT/US2013/041600 US2013041600W WO2013173719A1 WO 2013173719 A1 WO2013173719 A1 WO 2013173719A1 US 2013041600 W US2013041600 W US 2013041600W WO 2013173719 A1 WO2013173719 A1 WO 2013173719A1
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WIPO (PCT)
Prior art keywords
extract
compounds
momodica
hesperidin
catechins
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PCT/US2013/041600
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English (en)
Inventor
Veera R. KONDA
Andrea Lyra HELLER
Anu Desai
Brian J. CARROLL
Matthew L. Tripp
Jeffrey S. Bland
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Metaproteomics, Llc
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Publication of WO2013173719A1 publication Critical patent/WO2013173719A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine

Definitions

  • the present invention relates to phytonutrient compositions and methods of using the same for preventing, reducing, or treating genetic damage induced by
  • compositions and methods may be used to reduce oxidized low density lipoproteins (OxLDL), myeloperoxidase (MPO), and plasminogen activator inhibitor- 1 (PAI-1).
  • OxLDL oxidized low density lipoproteins
  • MPO myeloperoxidase
  • PAI-1 plasminogen activator inhibitor- 1
  • DNA damage can occur naturally and is usually repaired via natural repair processes in the body. It is when the rate of damage exceeds the body's ability to keep up with repairs that health problems ensue.
  • liver and kidney damage chloroform
  • mesotheilioma asbestos
  • reproductive damage dioxins
  • nerve damage pesticides
  • cerebral palsy ADHD, epilepsy, and Tourette syndrome have been ascribed to fetal exposure to various chemicals.
  • Atherosclerosis otherwise known as hardening and narrowing of the arteries is a progressive process which silently and slowly blocks arteries, thereby placing blood flow at risk. Is is also the usual cause of heart attacks, strokes, and peripheral vascular disease, also known as cardiovascular disease.” Cardiovascular disease is the No. 1 killer in America, with more than 800,000 deaths in 2005.
  • LDL low density lipoproteins
  • HDL High density lipoproteins
  • the loss of the protective effect of HDL is poorly understood but has been attributed to oxidative damage of the HDL by
  • MPO myeloperoxidase
  • OxLDL LDL
  • PAI-1 plasminogen activator inhibitor 1
  • MPO and OxLDL plasminogen activator inhibitor 1
  • the present invention relates to phytonutrient compositions and methods of using the same for preventing, reducing, or treating genetic damage induced by
  • compositions and methods are used to reduce oxidized low density lipoproteins (OxLDL), myeloperoxidase (MPO), and plasminogen activator inhibitor-1 (PAI-1).
  • OxLDL oxidized low density lipoproteins
  • MPO myeloperoxidase
  • PAI-1 plasminogen activator inhibitor-1
  • a first embodiment of the invention describes phytonutrient compositions for preventing, reducing, or treating genetic damage induced by environmental agents, where the compositions comprise therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • a second embodiment of the invention describes methods for preventing, reducing, or treating genetic damage induced by environmental agents, where the methods comprise administering a composition comprising therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • a third embodiment of the invention describes phytonutrient compositions for reducing OxLDL, MPO, and PAI-1, where the compositions comprise therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • a fourth embodiment of the invention describes the use of a composition for simultaneously reducing serum OxLDL, MPO, and PAI-1 levels in a subject in need thereof, wherein said use comprises administering a composition comprising therapeutically effective amounts of two or more compounds or extracts selected from the group consisting of Acacia niiotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and said composition is in a dosage form suitable for oral administration wherein said dosage form provides: a. from 0.5 m ⁇ I to 10 mg ; of Acacia niiotica extract;
  • Figure 1 Panel A: A graphic representation of the Tail Moment for cells treated with OG5459 as measured in the Trevigen, Inc., CometAssay ® .
  • Panel B Table of date used for generation of Panel A graphic representation.
  • Figure 2 Panel A: A graphic representation of the % DNA in the tail for cells treated with OG5459 as measured in the Trevigen, Inc., CometAssay ® .
  • Panel B Table of date used for generation of Panel A graphic representation.
  • Figure 3 Panel A: A graphic representation of the Tail Moment for cells treated with OG5507 as measured in the Trevigen, Inc., CometAssay ® .
  • Panel B Table of date used for generation of Panel A graphic representation.
  • Figure 4 Panel A: A graphic representation of the % DNA in the tail for cells treated with OG5507 as measured in the Trevigen, Inc., CometAssay ® .
  • Panel B Table of date used for generation of Panel A graphic representation.
  • Figure 5 Panels A & B: Representative images for cells treated with
  • FIG. 6 Panels A & B: Representative images for cells treated with
  • Figure 7 Representative effects of four week supplementation with phytonutrient composition of the invention on reduced serum AxLDL, PAI-1 and MPO levels in humans. (* p ⁇ 0.05 compared with V2 vs. V3
  • the present invention relates to phytonutrient compositions and methods of using the same for preventing, reducing, or treating genetic damage induced by
  • compositions and methods may be used to reduce oxidized low density lipoproteins (OxLDL), myeloperoxidase (MPO), and plasminogen activator inhibitor-1 (PAI-1).
  • OxLDL oxidized low density lipoproteins
  • MPO myeloperoxidase
  • PAI-1 plasminogen activator inhibitor-1
  • variable can be equal to any integer value of the numerical range, including the end-points of the range.
  • variable can be equal to any real value of the numerical range, including the end-points of the range.
  • a variable that is described as having values between 0 and 2 can be 0, 1 or 2 for variables that are inherently discrete, and can be 0.0, 0.1, 0.01, 0.001 , or any other real value for variables that are inherently continuous.
  • a first embodiment of the invention describes phytonutrient compositions for preventing, reducing, or treating genetic damage induced by environmental agents, where the compositions comprise therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • the composition provides per dosage form: a. from 0.5 mg to 10 mg of Acacia nilotica extract;
  • a "phytonutrient” refers to nutrients derived from plant materials shown to be necessary for sustaining human life. Encompassed within
  • phytonutrients are "phytochemicals", that is, plant derived compounds not yet classified as substances needed for sustaining life yet known to have properties useful for aiding in the prevention of disease.
  • genetic damage refers to damage to the cell's DNA (either physical or in the sense of its information capacity) when it mutates (or deviates) from its original form.
  • substances which can damage DNA such as, for example, oxidizing agents, alkylating agents and electromagnetic radiation. Damage by these agents includes cross linking between the pyrimidine bases, base modifications and double strand breaks.
  • extract refers to the solid material resulting from
  • solvent refers to a liquid of aqueous or organic nature possessing the necessary characteristics to extract solid material from plant material.
  • solvents would include water, steam, superheated water, methanol, ethanol, hexane, chloroform, liquid C0 2 , liquid N 2 or any combinations of such materials.
  • acacia refers to any member of leguminous trees and shrubs of the genus Acacia.
  • the botanical compound derived from acacia is derived from Acacia catechu or Acacia nilotica.
  • the Acacia catechu or Acacia nilotica compound is selected from the group consisting of gum resin, bark powder, heartwood powder, and an Acacia catechu or Acacia nilotica extract.
  • the extract is selected from acidic, alkaline, polar solvent, nonpolar solvent, and gastric fluid extracts.
  • treating is meant reducing, preventing, and/or reversing the symptoms in the individual to which a compound of the invention has been administered, as compared to the symptoms of an individual not being treated according to the invention.
  • a practitioner will appreciate that the compounds, compositions, and methods described herein are to be used in concomitance with continuous clinical evaluations by a skilled practitioner (physician or veterinarian) to determine subsequent therapy. Hence, following treatment the practitioners will evaluate any improvement in the treatment of the pulmonary inflammation according to standard methodologies. Such evaluation will aid and inform in evaluating whether to increase, reduce or continue a particular treatment dose, mode of administration, etc.
  • a compound of the invention may be administered prophylactically, prior to any development of symptoms.
  • the term "therapeutic,” “therapeutically,” and permutations of these terms are used to encompass therapeutic, palliative as well as prophylactic uses.
  • by “treating or alleviating the symptoms” is meant reducing, preventing, and/or reversing the symptoms of the individual to which a compound of the invention has been administered, as compared to the symptoms of an individual receiving no such administration.
  • therapeutically effective amount is used to denote treatments at dosages effective to achieve the therapeutic result sought.
  • therapeutically effective amount of the compound of the invention may be lowered or increased by fine tuning and/or by administering more than one compound of the invention, or by administering a compound of the invention with another compound. See, for example, Meiner, C.L., “Clinical Trials: Design, Conduct, and Analysis,” Monographs in Epidemiology and Biostatistics, Vol. 8 Oxford University Press, USA (1986).
  • the invention therefore provides a method to tailor the administration/treatment to the particular exigencies specific to a given mammal.
  • therapeutically effective amounts may be easily determined for example empirically by starting at relatively low amounts and by step-wise increments with concurrent evaluation of beneficial effect.
  • compounds may be identified either by their chemical structure, chemical name, or common name. When the chemical structure and chemical or common name conflict, the chemical structure is determinative of the identity of the compound.
  • the compounds described herein may contain one or more chiral centers and/or double bonds and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), enantiomers or diastereomers.
  • the chemical structures depicted herein encompass all possible enantiomers and stereoisomers of the illustrated or identified compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure or diastereomerically pure) and enantiomeric and stereoisomeric mixtures.
  • Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to the skilled artisan.
  • the compounds may also exist in several tautomeric forms including the enol form, the keto form and mixtures thereof. Accordingly, the chemical structures depicted herein encompass all possible tautomeric forms of the illustrated or identified compounds.
  • the compounds described also encompass isotopically labeled compounds where one or more atoms have an atomic mass different from the atomic mass conventionally found in nature.
  • isotopes that may be incorporated into the compounds of the invention include, but are not limited to, 2 H, 3 H, 13 C, 14 C, 15 N, , 8 0, 17 0, etc.
  • Compounds may exist in unsolvated forms as well as solvated forms, including hydrated forms and as N-oxides. In general, compounds may be hydrated, solvated or N-oxides. Certain compounds may exist in multiple crystalline or amorphous forms. Also contemplated within the scope of the invention are congeners, analogs, hydrolysis products, metabolites and precursor or prodrugs of the compound. In general, unless otherwise indicated, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present invention.
  • Compounds according to the invention may be present as salts.
  • pharmaceutically acceptable salts of the compounds are contemplated.
  • a “pharmaceutically acceptable salt” of the invention is a combination of a compound of the invention and either an acid or a base that forms a salt (such as, for example, the magnesium salt, denoted herein as "Mg or "Mag”) with the compound and is tolerated by a subject under therapeutic conditions.
  • a pharmaceutically acceptable salt of a compound of the invention will have a therapeutic index (the ratio of the lowest toxic dose to the lowest therapeutically effective dose) of 1 or greater. The person skilled in the art will recognize that the lowest therapeutically effective dose will vary from subject to subject and from indication to indication, and will thus adjust accordingly.
  • compositions according to the invention are optionally formulated in a pharmaceutically acceptable vehicle with any of the well known pharmaceutically acceptable carriers, including diluents and excipients [see Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, Mack Publishing Co., Easton, PA 1990 and Remington: The Science and Practice of Pharmacy, Lippincott, Williams & Wilkins, 1995]. While the type of pharmaceutically acceptable carrier/vehicle employed in generating the compositions of the invention will vary depending upon the mode of administration of the composition to a mammal, generally pharmaceutically acceptable carriers are physiologically inert and nontoxic. Formulations of compositions according to the invention may contain more than one type of compound of the invention), as well as any other pharmacologically active ingredient useful for the treatment of the symptom/condition being treated.
  • compositions of the invention may be provided in a pharmaceutically acceptable vehicle using formulation methods known to those of ordinary skill in the art.
  • the compositions of the invention can be administered by standard routes, though preferably administration is by inhalation routes.
  • the compositions of the invention include those suitable for oral, inhalation, rectal, ophthalmic (including intravitreal or intracameral), nasal, topical (including buccal and sublingual), vaginal, or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, and intratracheal).
  • polymers may be added according to standard methodologies in the art for sustained release of a given compound.
  • Formulations suitable for administration by inhalation include formulations that can be dispensed by inhalation devices known to those in the art. Such formulations may include carriers such as powders and aerosols.
  • the present invention encompasses liquid and powdered compositions suitable for nebulization and intrabronchial use, or aerosol compositions administered via an aerosol unit dispensing metered doses ("MDI").
  • MDI aerosol unit dispensing metered doses
  • the active ingredient may be formulated in an aqueous pharmaceutically acceptable inhalant vehicle, such as, for example, isotonic saline or bacteriostatic water and other types of vehicles that are well known in the art.
  • Powder compositions containing the anti-inflammatory compounds of the present invention include, by way of illustration, pharmaceutically acceptable powdered preparations of the active ingredient thoroughly intermixed with lactose or other inert powders acceptable for intrabronchial administration.
  • the powder compositions can be administered via a dispenser, including, but not limited to, an aerosol dispenser or encased in a breakable capsule which may be inserted by the patient into a device that punctures the capsule and blows the powder out in a steady stream.
  • Aerosol formulations for use in the subject method typically include propellants, surfactants, and co-solvents and may be filled into conventional aerosol containers that are closed by a suitable metering valve.
  • Formulations of compositions of the present invention suitable for nasal administration include a coarse powder having a particle size, for example, in the range of 20 to 500 microns which is administered in the manner in which snuff is administered, i.e., by rapid inhalation through the nasal passage from a container of the powder held close up to the nose.
  • Suitable formulations, wherein the carrier is a liquid, for administration, for example via a nasal spray, aerosol, or as nasal drops include aqueous or oily solutions of the compound of the invention.
  • compositions of the invention may be presented as discrete units such as capsules, caplets, gelcaps, cachets, pills, or tablets each containing a predetermined amount of the active ingredient as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil emulsion and as a bolus, etc.
  • administration of a composition of all of the aspects of the present invention may be effected by liquid solutions, suspensions or elixirs, powders, lozenges, micronized particles and osmotic delivery systems.
  • Formulations of compositions according to the aspects of the present invention suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, stabilizers, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
  • the formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) conditions requiring only the addition of the sterile liquid carrier, for example, water for injections, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
  • a tablet may be made by compression or molding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent.
  • Molded tablets may be made by molding, in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent.
  • the tablets may be optionally coated or scored and may be formulated to provide a slow or controlled release of the active ingredient therein.
  • compositions of the present invention for rectal administration may be prepared as a suppository with a suitable base comprising, such as, for example, cocoa butter.
  • Formulations of compositions of the present invention suitable for topical administration in the mouth include lozenges comprising the ingredients in a flavored basis, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the ingredient to be administered in a suitable liquid carrier.
  • Formulations of compositions of the present invention suitable for topical administration to the skin may be presented as ointments, creams, gels, lotions and pastes comprising the ingredient to be administered in a pharmaceutical acceptable carrier.
  • a topical delivery system contemplated is a transdermal patch containing the ingredient to be administered.
  • compositions according to the aspects of the present invention suitable for vaginal administration may be presented as pessaries, suppositories, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the compound of the invention such pharmaceutically acceptable carriers as are known in the art to be appropriate.
  • compositions of the present invention are intended for use with any mammal that may experience the benefits of the methods of the invention.
  • mammals Foremost among such mammals are humans, although the invention is not intended to be so limited, and is applicable to veterinary uses.
  • "mammals” or “mammal in need” include humans as well as non-human mammals, particularly domesticated animals including, without limitation, cats, dogs, and horses.
  • a second embodiment of the invention describes methods for preventing, reducing, or treating genetic damage induced by environmental agents, where the methods comprise administering a composition comprising therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • the composition of the method provides per dosage form: a. from 0.5 ni£ I to 10 mg ; of Acacia nilotica extract;
  • a third embodiment of the invention describes phytonutrient compositions for reducing OxLDL, MPO, and PAI-1 , where the compositions comprise therapeutically effective amounts of two or more compounds selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and the composition is in a dosage form suitable for oral administration.
  • the composition provides per dosage form: a. from 0.5 mg to 10 mg of Acacia nilotica extract;
  • a fourth embodiment of the invention describes the use of a composition for simultaneously reducing serum OxLDL, MPO, and PAI-1 levels in a subject in need thereof, wherein said use comprises administering a composition comprising therapeutically effective amounts of two or more compounds or extracts selected from the group consisting of Acacia nilotica extract, artichoke extract, blueberry extract, catechins, chlorogenic acid, cinnamon, ellagic acid, grape seed extract, hesperidin, Momodica extract, prune extract, rosemary extract, and watercress extract and said composition is in a dosage form suitable for oral administration wherein said dosage form provides: a. from 0.5 m ⁇ I to 10 mg of Acacia nilotica extract;
  • f. from 0.5 mg to 10 mg of cinnamon; g- from 10 mg to 100 mg of ellagic acid;
  • the number of compounds or extracts of the composition used preferably three or more compounds or extracts; more preferably four, five or six compounds or extracts; and most preferably seven compounds or extracts of the composition of the invention.
  • compositions OG5495 and OG5507 To evaluate effects of test compositions OG5495 and OG5507 on healthy and hydrogen peroxide treated Jurkat cells by CometAssay.
  • the formulations for compositions OG5495 and OG5507 are presented in Table 1 below.
  • test compositions OG5495 and OG5507 were evaluated for the effects of test compositions OG5495 and OG5507 on healthy and hydrogen peroxide treated Jurkat cells. The test procedures are summarized below
  • OG5495 79 mg of OG5495 or 50 mg of OG5507 was suspended in DMSO. The compound solution was allowed to sit for 20 minutes at room temperature and vortex for 30 seconds every 5 minutes a. OG5495 was clarified (5000x g, 10 minutes) and transferred to a new tube.
  • a 20 mg/ml solution was prepared by combining 10 ⁇ 100 mg/ml stock and
  • OG5495 At 100 ⁇ g/ml compound OG5495 appeared to induce DNA damage in Jurkat cells. This was demonstrated by an increase in tail moment and %DNA in the tail comparing DMSO and 100 ⁇ g/ml compound controls. Cells pretreated with 100 ⁇ g/ml OG5495 and exposed to 20 ⁇ H2O2 showed a decrease in tail moment and %DNA in the tail relative to H 2 0 2 alone.
  • OG5507 At 100 ⁇ g/ml, compound OG5507 induced minimal damage; however, the %DNA in the tail is in the range where cells are considered healthy (less than 10% for %DNA in the tail). Unlike OG5495, OG5507 had a protective affect on Jurkat cells pretreated with 100 ⁇ g/ml of the compound before exposure to 20 ⁇ H 2 0 2 . A dramatic decrease in both tail moment and %DNA in the tail was observed in cells pretreated with OG5507 compared to the untreated cells when exposed to 20 ⁇ H 2 0 2 . A protective effect, although at a much lower level, was also seen in cells pretreated with 20 ⁇ g/ml of OG5507 compared to the untreated cells when exposed to 20 ⁇ H 2 0 2 .
  • the clinical protocol used was IRB approved and the subjects were consented prior to both screening and the study visits (V where N is the visit number (i.e., first visit, second visit, etc.)).
  • Food Restrictions Subject participant intake of food antioxidants was limited to only two servings total of fruits plus vegetables each day and not more than the amounts specified in Table 4 below.
  • the numbers in Table 4 describe the frequencies of consumption of allowed foods during study participation (i.e., maximum number of times food could be consumed as part of 14 serving limit for each week). Serving sizes were limited to 2 ounces of salad, 8 ounces of other kinds of vegetables on list, 8 ounces of apple, 8 ounces of pear, 5 ounces of banana, and 9 ounces of citrus fruit.
  • Serum PAI-1 levels were measured using a solid phase ELISA kit
  • the PAI- 1 levels were measured according to the protocols provided by manufacturer. The monoclonal antibody specific for human PAI-1 had been coated onto the wells. The serum was diluted with sample buffer (2 fold) and triplicates were used for each sample in a 96 well microtiter plate. The plates were read at 450nM using a plate reader and the PAI-1 levels were measured using the standard supplied along with the kit. The data represent mean +SEM of 15 subjects. The significance difference was measured based on p values calculated using paired t test. *p ⁇ 0.05 compared with V2 vs. V3.
  • MPO myeloperoxidase
  • Myeloperoxidase was measured using a solid phase two-site ELISA kit (#10-
  • MPO levels were measured according to the protocols provided by manufacturer. This immune assay is based on the sandwich technique in which two monoclonal antibodies are directed against separate antigenic determinants on the MPO-molecule.
  • the serum was diluted for 5 times with sample buffer and triplicates were used for each sample in 96 well microtiter plate.
  • the plates were read at 450nM using a plate reader and the MPO levels were measured using the standards supplied along with the kit.
  • the data represent mean +SEM of 15 subjects. The significance difference was measured based on p values calculated using paired t test. *p ⁇ 0.05 compared with V2 vs. V3.
  • Oxidized LDL levels were measured using a solid phase two-site ELISA kit
  • OxLDL levels were measured according to the protocols provided by manufacturer. This immuno assay is based on the sandwich technique in which two monoclonal antibodies are directed against separate antigenic determinants on the oxidized apolipoprotein B molecule.
  • the serum was diluted for with sample buffer (1 :6561) and triplicates were used for each sample in 96 well microtiter plate. The plates were read at 450nM using plate reader and the MPO levels were measured using the standard supplied along with the kit. The data represent mean +SEM of 15 subjects. The significance difference was measured based on p values calculated using paired t test.

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Abstract

La présente invention concerne des compositions à base de phytonutriments et des procédés d'utilisation de celles-ci pour prévenir, réduire ou traiter un endommagement génétique induit par des toxines environnementales. En outre, lesdites compositions et lesdits procédés sont utilisés pour réduire les lipoprotéines basses densités oxydées (OxLDL), la myéloperoxydase (MPO) et l'inhibiteur 1 des activateurs du plasminogène (PAI-1).
PCT/US2013/041600 2012-05-18 2013-05-17 Compositions de phytonutriments et procédés d'utilisation WO2013173719A1 (fr)

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US20080089941A1 (en) * 2006-06-01 2008-04-17 Mower Thomas E Fucoidan compositions and methods
US20080286254A1 (en) * 2007-05-17 2008-11-20 Kaneka Corporation Composition comprising licorice polyphenol
US20090087501A1 (en) * 2007-10-01 2009-04-02 Colgate-Palmolive Company Oral Compositions Containing Botanical Extracts
US20100092583A1 (en) * 2003-03-13 2010-04-15 Chantal Matar Antioxidant-Enriched Fruit Extracts and Uses Thereof in the Treatment and Prevention of Diabetes and Obesity
US20100112099A1 (en) * 2008-11-04 2010-05-06 Metaproteomics, Llc Phytochemical compositions and methods for activating amp-kinase
US20100150895A1 (en) * 2005-11-23 2010-06-17 Elizabeth Mazzio Nutraceutical agent for attenuating the Neurodegenerative process associated with Parkinson's disease
US20110159121A1 (en) * 2009-12-24 2011-06-30 LifeSpan Extension, LLC Methods and compositions for identifying, producing and using plant-derived products for modulating cell function and aging
US20110305791A1 (en) * 2005-04-06 2011-12-15 Nestec S.A. Method and composition for nutritionally improving glucose control and insulin action
WO2013090715A1 (fr) * 2011-12-15 2013-06-20 Metaproteomics, Llc Compositions de phytonutriments et procédés de protection contre les dommages cellulaires et de l'adn médiés par les radicaux libres

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US20100092583A1 (en) * 2003-03-13 2010-04-15 Chantal Matar Antioxidant-Enriched Fruit Extracts and Uses Thereof in the Treatment and Prevention of Diabetes and Obesity
US20110305791A1 (en) * 2005-04-06 2011-12-15 Nestec S.A. Method and composition for nutritionally improving glucose control and insulin action
US20100150895A1 (en) * 2005-11-23 2010-06-17 Elizabeth Mazzio Nutraceutical agent for attenuating the Neurodegenerative process associated with Parkinson's disease
US20080089941A1 (en) * 2006-06-01 2008-04-17 Mower Thomas E Fucoidan compositions and methods
US20080286254A1 (en) * 2007-05-17 2008-11-20 Kaneka Corporation Composition comprising licorice polyphenol
US20090087501A1 (en) * 2007-10-01 2009-04-02 Colgate-Palmolive Company Oral Compositions Containing Botanical Extracts
US20100112099A1 (en) * 2008-11-04 2010-05-06 Metaproteomics, Llc Phytochemical compositions and methods for activating amp-kinase
US20110159121A1 (en) * 2009-12-24 2011-06-30 LifeSpan Extension, LLC Methods and compositions for identifying, producing and using plant-derived products for modulating cell function and aging
WO2013090715A1 (fr) * 2011-12-15 2013-06-20 Metaproteomics, Llc Compositions de phytonutriments et procédés de protection contre les dommages cellulaires et de l'adn médiés par les radicaux libres
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