US20190269166A1 - Nutritional supplement - Google Patents

Nutritional supplement Download PDF

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US20190269166A1
US20190269166A1 US16/419,513 US201916419513A US2019269166A1 US 20190269166 A1 US20190269166 A1 US 20190269166A1 US 201916419513 A US201916419513 A US 201916419513A US 2019269166 A1 US2019269166 A1 US 2019269166A1
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supplement
person
weight
turmeric
peganum harmala
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US16/419,513
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Gene H. Zaid
Beth Ann Wolf
Larry D. Crow
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Ankh Life Sciences Ltd
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Ankh Life Sciences Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/11Aldehydes
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15Vitamins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/888Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962Allium, e.g. garden onion, leek, garlic or chives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9066Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger

Definitions

  • the present invention is broadly concerned with high-quality nutritional supplements which have beneficial effects including support for normal blood glucose and cholesterol levels, prostate health, and normal cellular division. More particularly, the invention is concerned with such supplements including respective quantities of turmeric, Peganum harmala , and Arum palaestinum.
  • Peganum harmala is a perennial, glabrous plant which grows spontaneously in the Eastern Mediterranean region. The plant is well known in Iran and is widely distributed and used in the support and maintenance of human health. Studies carried out on the chemical compositions of Peganum harmala extracts confirm that beta-carboline and quinazoline alkaloids are important compounds of this plant. The plant is one of the most frequently used plants to aide in hypertension and cardiac health worldwide. See, Moloudizargari et al, Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids , Pharmacogn Rev. 7(14): pp. 199-212, 2013.
  • Curcuma longa has been used for thousands of years as a spice and medicinal herb. Turmeric includes minor amounts of curcumin, which has shown to provide anti-inflammatory effects and is a strong anti-oxidant.
  • ⁇ -sitosterol is a plant sterol which offers a number of health benefits, whether it naturally occurs in foods or as a part of supplements. See, Cooper, Health Benefits of ⁇ - sitosterol , Livestrong.com, Aug. 14, 2017. Vitamin C and garlic also have well-known health benefits.
  • the present invention provides new nutritional supplements comprising individual quantities of turmeric, Peganum harmala , and Arum palaestinum , and especially combinations of these which produce synergistic results.
  • synergy or synergism means that the three-component compositions of the invention exhibit a joint action where the compositions produce an effect greater than that which may be obtained by use of individual components in equivalent quantities.
  • the turmeric is present in an amount greater than either of the remaining two extracts, and indeed greater than any of the other ingredients of the compositions, e.g., ⁇ -sitosterol, vanillin compound(s), garlic, and Vitamin C.
  • the compositions are advantageously in powdered form and may be provided as individual capsules for daily oral administration.
  • the invention also provides methods of supporting human health by appropriately administering to a person the nutritional supplements hereof.
  • the supplements may be used in support of the promotion of normal blood glucose and cholesterol levels, for the promotion of prostate health, and for supporting normal cellular division.
  • FIG. 1 is a graph illustrating the effect of a three-component plant extract composition (MIR001) made up of Arum palaestinum, Peganum harmala , and Curcuma longa versus Arum palaestinum alone on cellular division, as set forth in the Example;
  • MIR001 three-component plant extract composition
  • FIG. 2 is a graph illustrating the effect of MIR001 versus Arum palaestinum alone, as set forth in the Example;
  • FIG. 3 is a graph illustrating the effect of MIR001 versus Curcuma longa alone, as set forth in the Example;
  • FIG. 4 is another graph illustrating the effect of MIR001 versus Curcuma longa alone, as set forth in the Example;
  • FIG. 5 is a graph illustrating the effect of MIR001 versus Peganum harmala alone, as set forth in the Example;
  • FIG. 6 is another graph illustrating the effect of MIR001 versus Peganum harmala alone, as set forth in the Example;
  • FIG. 7 is a graph illustrating the effect of MIR001 versus the RPMI/FBS test vehicle alone, as set forth in the Example.
  • FIG. 8 is another graph illustrating the effect of MIR001 versus the RPMI/FBS test vehicle alone, as set forth in the Example.
  • nutritional supplements in accordance with the invention comprise (or consist essentially of, or consist of) individual quantities of turmeric, Peganum harmala , and Arum palaestinum , as the principal ingredients serving to provide health benefits.
  • the amount of turmeric is greater than either of Peganum harmala and Arum palaestinum , e.g., such three-component compositions would typically include from about 40-70% turmeric, and from about 15-35% each of Peganum harmala and Arum palaestinum , based upon the total weight of the three-component supplements taken as 100% by weight.
  • More preferred supplements include these three ingredients together with ⁇ -sitosterol, garlic, and Vitamin C, and again the amount of turmeric is preferably greater than any of these other ingredients.
  • such six-component compositions would typically include from about 15-25% turmeric, from about 5-15% each of Peganum harmala, Arum palaestinum , ⁇ -sitosterol, and garlic, and from about 8-20% Vitamin C. All of the foregoing percentages are by weight, based upon the total weight of the supplements taken as 100% by weight.
  • the supplements may also include significant amounts of vanillin compound(s), such as one or more of vanillin, vanilla, isovanillin, orthovanillin, and ethyl vanillin, which would correspondingly reduce the amounts of the other ingredients therein.
  • the supplements may improve other active agents, preservatives, buffering agents, salts, carriers, excipients, diluents, or other ingredients.
  • ingredients can be in the form of acceptable esters or salts.
  • the esters and salts should be generally safe, non-toxic, and neither biologically nor otherwise undesirable and are acceptable for human use, and which possess the desired degree of activity. Accordingly, the recitation herein of the ingredients of the supplements of the invention is intended to embrace not only the named ingredients, but also any acceptable esters or salts thereof.
  • Exemplary acceptable salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-phenylpropionic acid, 4,4′-methylenebis(3-hydroxy-2-ene-1-carboxylic acid), 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, acetic acid, aliphatic mono- and dicarboxylic acids, aliphatic sulfuric acids, aromatic sulfuric acids, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, cinnamic acid, citric acid, cyclopentanepropionic acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic
  • the acceptable salts also include base addition salts which may be formed when acidic protons present are capable of reacting with inorganic or organic bases.
  • Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide and calcium hydroxide.
  • Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine and the like. It should be recognized that the particular anion or cation forming a part of any salt of this invention is not critical, so long as the salt, as a whole, is acceptable. Additional examples of acceptable salts and their methods of preparation and use are presented in Handbook of Pharmaceutical Salts Properties, and Use , P. H. Stahl & C. G. Wermuth eds., ISBN 978-3-90639-058-1 (2008).
  • the supplements should contain from about 8-15% (more preferably from about 9-11%) Vitamin C, from about 5-11% (more preferably from about 7-9%) garlic, from about 35-45% (more preferably from about 38-42%) vanillin compound(s), from about 5-11% (more preferably from about 7-9%) ⁇ -sitosterol, from about 12-20% (more preferably from about 14-17) turmeric, from about 5-11% (more preferably from about 7-9%) Peganum harmala , and from about 5-11% (more preferably from about 7-9%) Arum palaestinum , where all percentages are by weight, based upon the total weight of the supplements taken as 100% by weight.
  • all of the ingredients are at least food grade and are blended together as powders.
  • the Peganum harmala and Arum palaestinum powders may be obtained by drying and pulverizing the complete plants, including leaves, stems, and bulbs; it is not essential that all of the plant parts be used, i.e., use may be made of the leaves, and/or stems, and/or bulbs.
  • the blended powders should be of a size to pass through a 50-mesh screen while being retained by a 100-mesh screen. Still further, the blended powders are placed in capsules for ease of dosage.
  • the capsules should each contain from about 500-1500 mg of the blended powders, most preferably 1000 mg.
  • the blended ingredients may be prepared as liquid dispersions or solutions using appropriate, non-interfering dispersants or solvents; other possible dosage forms include gels, suspensions, or solids such as tablets or pills.
  • the supplements of the invention are designed for administration to humans, in particularly those seeking to promote or support normal blood glucose levels, normal cholesterol levels, prostate health, and normal cellular division.
  • the supplements may be administered in any convenient manner, such as by oral, rectal, nasal, ophthalmic, parenteral (including intraperitoneal, gastrointestinal, intrathecal, intravenous, cutaneous (e.g., dermal patch), subcutaneous (e.g., injection or implant), or intramuscular) routes.
  • parenteral including intraperitoneal, gastrointestinal, intrathecal, intravenous, cutaneous (e.g., dermal patch), subcutaneous (e.g., injection or implant), or intramuscular) routes.
  • the administration would be oral, and the recommended dosage level would be four such capsules per day, taken twice daily, two capsules per serving.
  • the present description also uses numerical ranges to quantify certain parameters relating to various embodiments of the invention. It should be understood that when numerical ranges are provided, such ranges are to be construed as providing literal support for claim limitations that only recite the lower value of the range as well as claim limitations that only recite the upper value of the range. For example, a disclosed numerical range of about 10 to about 100 provides literal support for a claim reciting “greater than about 10” (with no upper bounds) and a claim reciting “less than about 100” (with no lower bounds).
  • Afaya Plus a product referred to as “Afaya Plus” was administered to several individuals.
  • Afaya Plus was in the form of capsules, with each capsule containing the preferred ingredients prepared in the ratios outlined above.
  • Arum palaestinum Boiss were identified morphologically during field collection from growing habitats in the Vietnamese region, and seeds from the plants were then planted in a growth chamber for germination (samples are on file at the Missouri Botanical Garden (MBG) for verification, voucher #Croat 95,466 (MO)).
  • the plant extract was analyzed using gas chromatography-mass spectrometry (GC-MS) to verify identification of A. palaestinum .
  • GC-MS gas chromatography-mass spectrometry
  • Portions of the plants were cut into wedges and boiled in water for 4 hours, whereupon the wedges were dried to completion in an 80° C. oven.
  • Peganum harmala seeds and powdered Curcuma longa (turmeric) root were purchased from commercial sources.
  • a combined product made up of all three of the plant sources were prepared by mixing the powdered extracts at a ratio of 50% by weight turmeric, and 25% by weight each of the A. palaestinum and P. harmala , followed by boiling for 3 hours. Aliquots were stored at ⁇ 20° C., and thawed 30 minutes prior to testing in a 37° C. water bath. The thawed aliquots were then vortexed thoroughly and diluted to 6% and 3% concentrations in RPMI with 10% FBS growth media. The individual components of MIR001 were similarly prepared by boiling, freezing, thawing, diluting, and with the addition of RPMI and FBS to create comparative samples.
  • 3D models were removed from the micromolds with gentle pipetting and rinsing followed by media change in RPMI with reduced FBS (0.5%). Approximately 25-50 spheroids were distributed per well of a 96 well plate for experimentation.
  • 3D spheroids were seeded and immediately checked microscopically for consistency of cluster distribution between wells. Both cell lines were exposed to multiple replicates of increasing doses of MIR001. Each assay was conducted on a 96 well plate, including 4-6 replicates. In like manner, the individual extracts of MIR001 were tested, along with the RPMI/FBS vehicle.
  • the MIR001 and extract stock solutions were diluted in RPMI with 10% FBS to reach final desired concentrations.
  • spheroids were exposed to the test article for 24 hours, followed by exposure to 10% PrestoBlue cell viability reagent (Invitrogen) before being loaded into the Enspire microplate reader (Perkin Elmer), with excitation at 490 nm and emission at 560 nm. Background values, obtained from media plus supplement only, were subtracted from each well. For comparisons, changes in PrestoBlue values were normalized to the 0 supplement condition.
  • FIGS. 1-6 The effects of the individual plant extracts on ovarian spheroids was first tested. The results demonstrated that while each plant extract had some in vitro effect, the combination MIR001 was significantly more effective than each extract alone. These results are set forth in FIGS. 1-6 .
  • the A. palaestinum plant extract alone was the least effective ( FIG. 1 ), while C. longa (turmeric; FIG. 3 ) and P. Harmala ( FIG. 5 ) were more effective, at the highest concentrations tested.
  • the same effect was noted when lung spheroids were exposed to MIR001; however, the differences were even greater.
  • A. palaestinum alone failed to have even 20% effect in the lung spheroids, while MIR001 caused 80% effect at the same concentration ( FIG. 2 ). Turmeric had greater variability between trials, but failed to reach more than 60% effect ( FIG. 4 ).
  • P. harmala induced little effect alone ( FIG. 6 ).

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Abstract

Nutritional supplements comprising individual quantities of turmeric, Peganum harmala, and Arum palaestinum are provided, which promote several aspects of human health. Advantageously, the turmeric is present in an amount greater than that of Peganum harmala or Arum palaestinum, and the supplements may contain additional beneficial ingredients, such as β-sitosterol, vanillin, garlic, and Vitamin C.

Description

    CROSS-REFERENCE TO RELATED APPLICATION
  • This application is a division of application Ser. No. 16/115,284 filed Aug. 28, 2018, which claims the benefit of U.S. Provisional Application Ser. 62/634,406 filed Feb. 23, 2018, incorporated by reference herein in its entirety.
  • BACKGROUND OF THE INVENTION Field of the Invention
  • The present invention is broadly concerned with high-quality nutritional supplements which have beneficial effects including support for normal blood glucose and cholesterol levels, prostate health, and normal cellular division. More particularly, the invention is concerned with such supplements including respective quantities of turmeric, Peganum harmala, and Arum palaestinum.
  • Description of the Prior Art
  • A variety of plants have been employed in the support and maintenance of human health. For example, plants from the hills and mountains of Israel, Palestine, and the Golan Heights have been used for many years for supporting and maintaining human health. Among these are extracts of Arum palaestinum Boiss. See, for example, Said et al. Ethnopharmacological Survey of Medicinal Herbs in Israel, the Golan Heights and the West Bank Region. J. Ethnopharmacology. 83 (2002): 251-265.
  • Peganum harmala is a perennial, glabrous plant which grows spontaneously in the Eastern Mediterranean region. The plant is well known in Iran and is widely distributed and used in the support and maintenance of human health. Studies carried out on the chemical compositions of Peganum harmala extracts confirm that beta-carboline and quinazoline alkaloids are important compounds of this plant. The plant is one of the most frequently used plants to aide in hypertension and cardiac health worldwide. See, Moloudizargari et al, Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids, Pharmacogn Rev. 7(14): pp. 199-212, 2013.
  • Curcuma longa (turmeric) has been used for thousands of years as a spice and medicinal herb. Turmeric includes minor amounts of curcumin, which has shown to provide anti-inflammatory effects and is a strong anti-oxidant. β-sitosterol is a plant sterol which offers a number of health benefits, whether it naturally occurs in foods or as a part of supplements. See, Cooper, Health Benefits of β-sitosterol, Livestrong.com, Aug. 14, 2017. Vitamin C and garlic also have well-known health benefits.
  • Other references include U.S. Pat. Nos. 6,596,313, 8,039,025, and 9,402,834; US Patent Publications Nos. 2015/0374624 and 2017/0042867; Foreign references CN102886014, EP1902631, JP2007174910, and KR101478253; and the following non-patent references: Ali-Shtayeh et al. “National List of Medicinal Plants in Palestine—West Bank and Gaza Strip” BERC, 2014, pp 1-27; Ben-Arye et al. “Integrative oncology in the Middle East: from traditional herbal knowledge to contemporary cancer care” Annals of Oncology, 2011, Vol. 23, pp 211-221; and Qneibi et al. “Evaluation of taste, total phenols and antioxidant for fresh, roasted, shade dried and boiled leaves of edible Arum palaestinum Bioss” Marmara Pharmaceutical Journal, 2017, Vol. 22, pp 52-58.
  • While the aforementioned naturally occurring products have individually shown promise for various aspects of human health, there have heretofore been no attempts to combine these ingredients for the preparation of beneficial nutritional supplements exhibiting synergistic effects.
  • SUMMARY OF THE INVENTION
  • The present invention provides new nutritional supplements comprising individual quantities of turmeric, Peganum harmala, and Arum palaestinum, and especially combinations of these which produce synergistic results. As used herein, synergy or synergism means that the three-component compositions of the invention exhibit a joint action where the compositions produce an effect greater than that which may be obtained by use of individual components in equivalent quantities.
  • In preferred practice, the turmeric is present in an amount greater than either of the remaining two extracts, and indeed greater than any of the other ingredients of the compositions, e.g., β-sitosterol, vanillin compound(s), garlic, and Vitamin C. For ease of production and administration, the compositions are advantageously in powdered form and may be provided as individual capsules for daily oral administration.
  • The invention also provides methods of supporting human health by appropriately administering to a person the nutritional supplements hereof. The supplements may be used in support of the promotion of normal blood glucose and cholesterol levels, for the promotion of prostate health, and for supporting normal cellular division.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a graph illustrating the effect of a three-component plant extract composition (MIR001) made up of Arum palaestinum, Peganum harmala, and Curcuma longa versus Arum palaestinum alone on cellular division, as set forth in the Example;
  • FIG. 2 is a graph illustrating the effect of MIR001 versus Arum palaestinum alone, as set forth in the Example;
  • FIG. 3 is a graph illustrating the effect of MIR001 versus Curcuma longa alone, as set forth in the Example;
  • FIG. 4 is another graph illustrating the effect of MIR001 versus Curcuma longa alone, as set forth in the Example;
  • FIG. 5 is a graph illustrating the effect of MIR001 versus Peganum harmala alone, as set forth in the Example;
  • FIG. 6 is another graph illustrating the effect of MIR001 versus Peganum harmala alone, as set forth in the Example;
  • FIG. 7 is a graph illustrating the effect of MIR001 versus the RPMI/FBS test vehicle alone, as set forth in the Example; and
  • FIG. 8 is another graph illustrating the effect of MIR001 versus the RPMI/FBS test vehicle alone, as set forth in the Example.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • In their broadest aspects, nutritional supplements in accordance with the invention comprise (or consist essentially of, or consist of) individual quantities of turmeric, Peganum harmala, and Arum palaestinum, as the principal ingredients serving to provide health benefits. In such three-component supplements, the amount of turmeric is greater than either of Peganum harmala and Arum palaestinum, e.g., such three-component compositions would typically include from about 40-70% turmeric, and from about 15-35% each of Peganum harmala and Arum palaestinum, based upon the total weight of the three-component supplements taken as 100% by weight. More preferred supplements include these three ingredients together with β-sitosterol, garlic, and Vitamin C, and again the amount of turmeric is preferably greater than any of these other ingredients. For example, such six-component compositions would typically include from about 15-25% turmeric, from about 5-15% each of Peganum harmala, Arum palaestinum, β-sitosterol, and garlic, and from about 8-20% Vitamin C. All of the foregoing percentages are by weight, based upon the total weight of the supplements taken as 100% by weight. The supplements may also include significant amounts of vanillin compound(s), such as one or more of vanillin, vanilla, isovanillin, orthovanillin, and ethyl vanillin, which would correspondingly reduce the amounts of the other ingredients therein.
  • Additional ingredients may be included in the production of complete nutritional supplements. Thus, the supplements may improve other active agents, preservatives, buffering agents, salts, carriers, excipients, diluents, or other ingredients.
  • Some or all of the ingredients can be in the form of acceptable esters or salts. The esters and salts should be generally safe, non-toxic, and neither biologically nor otherwise undesirable and are acceptable for human use, and which possess the desired degree of activity. Accordingly, the recitation herein of the ingredients of the supplements of the invention is intended to embrace not only the named ingredients, but also any acceptable esters or salts thereof.
  • Exemplary acceptable salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-phenylpropionic acid, 4,4′-methylenebis(3-hydroxy-2-ene-1-carboxylic acid), 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, acetic acid, aliphatic mono- and dicarboxylic acids, aliphatic sulfuric acids, aromatic sulfuric acids, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, cinnamic acid, citric acid, cyclopentanepropionic acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, heptanoic acid, hexanoic acid, hydroxynaphthoic acid, lactic acid, laurylsulfuric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, o-(4-hydroxybenzoyl)benzoic acid, oxalic acid, p-chlorobenzenesulfonic acid, phenyl-substituted alkanoic acids, propionic acid, p-toluenesulfonic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tartaric acid, tertiarybutylacetic acid, trimethylacetic acid, and the like. The acceptable salts also include base addition salts which may be formed when acidic protons present are capable of reacting with inorganic or organic bases. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine and the like. It should be recognized that the particular anion or cation forming a part of any salt of this invention is not critical, so long as the salt, as a whole, is acceptable. Additional examples of acceptable salts and their methods of preparation and use are presented in Handbook of Pharmaceutical Salts Properties, and Use, P. H. Stahl & C. G. Wermuth eds., ISBN 978-3-90639-058-1 (2008).
  • In terms of amounts, the supplements should contain from about 8-15% (more preferably from about 9-11%) Vitamin C, from about 5-11% (more preferably from about 7-9%) garlic, from about 35-45% (more preferably from about 38-42%) vanillin compound(s), from about 5-11% (more preferably from about 7-9%) β-sitosterol, from about 12-20% (more preferably from about 14-17) turmeric, from about 5-11% (more preferably from about 7-9%) Peganum harmala, and from about 5-11% (more preferably from about 7-9%) Arum palaestinum, where all percentages are by weight, based upon the total weight of the supplements taken as 100% by weight.
  • Advantageously, all of the ingredients are at least food grade and are blended together as powders. The Peganum harmala and Arum palaestinum powders may be obtained by drying and pulverizing the complete plants, including leaves, stems, and bulbs; it is not essential that all of the plant parts be used, i.e., use may be made of the leaves, and/or stems, and/or bulbs. The blended powders should be of a size to pass through a 50-mesh screen while being retained by a 100-mesh screen. Still further, the blended powders are placed in capsules for ease of dosage. The capsules should each contain from about 500-1500 mg of the blended powders, most preferably 1000 mg. While such powdered formulations are preferred for ease of manufacture and administration, it should be understood that the invention is not so limited. For example, the blended ingredients may be prepared as liquid dispersions or solutions using appropriate, non-interfering dispersants or solvents; other possible dosage forms include gels, suspensions, or solids such as tablets or pills.
  • The supplements of the invention, in whatever physical form, are designed for administration to humans, in particularly those seeking to promote or support normal blood glucose levels, normal cholesterol levels, prostate health, and normal cellular division. The supplements may be administered in any convenient manner, such as by oral, rectal, nasal, ophthalmic, parenteral (including intraperitoneal, gastrointestinal, intrathecal, intravenous, cutaneous (e.g., dermal patch), subcutaneous (e.g., injection or implant), or intramuscular) routes. Where the aforementioned capsules are used, the administration would be oral, and the recommended dosage level would be four such capsules per day, taken twice daily, two capsules per serving.
  • Additional advantages of the various embodiments of the invention will be apparent to those skilled in the art upon review of the disclosure herein. It will be appreciated that the various embodiments described herein are not necessarily mutually exclusive unless otherwise indicated herein. For example, a feature described or depicted in one embodiment may also be included in other embodiments, but is not necessarily included. Thus, the present invention encompasses a variety of combinations and/or integrations of the specific embodiments described herein.
  • The present description also uses numerical ranges to quantify certain parameters relating to various embodiments of the invention. It should be understood that when numerical ranges are provided, such ranges are to be construed as providing literal support for claim limitations that only recite the lower value of the range as well as claim limitations that only recite the upper value of the range. For example, a disclosed numerical range of about 10 to about 100 provides literal support for a claim reciting “greater than about 10” (with no upper bounds) and a claim reciting “less than about 100” (with no lower bounds).
  • In the following examples, a product referred to as “Afaya Plus” was administered to several individuals. Afaya Plus was in the form of capsules, with each capsule containing the preferred ingredients prepared in the ratios outlined above.
  • Person 1
      • Person 1 began taking Afaya Plus, 4 capsules daily (2 in the am and 2 in the pm). Baseline blood work was drawn before starting Afaya Plus. After 1 month of administration, Person 1's total cholesterol dropped 11 mg/dL (210 to 199) and the LDL dropped 7 mg/dL (135-128). This occurred while the person did not report any change in lifestyle, diet, or exercise regimen.
  • Person 2
      • Person 2 began taking Afaya Plus, 2 capsules daily (1 in the am and 1 in the pm). Baseline blood work was drawn before starting Afaya Plus. After 1 month of administration, Person 2's total cholesterol dropped 34 mg/dL (247 to 213) and the LDL dropped 31 mg/dL (167 to 136). This occurred while the person did not report any change in lifestyle, diet, or exercise regimen.
  • Person 3
      • Person 3 began taking Afaya Plus, 2 capsules daily (1 in the am and 1 in the pm). Baseline blood work was drawn before starting Afaya Plus. After 5 months of administration Person 3's PSA dropped 0.7 ng/mL (1.2 to 0.5), A1C dropped 0.3% (6.1 to 5.8), total cholesterol dropped 19 mg/dL (141 to 122), LDL dropped 4 mg/dL (79 to 75; this occurred after the person was already on high dose statin therapy) and Triglycerides dropped 41 mg/dL (123 to 82). This occurred while the person did not report any change in lifestyle, diet, or exercise regimen.
  • Person 4
      • Person 4 began taking Afaya Plus, 2 capsules daily (1 in the am and 1 in the pm). Baseline blood work was drawn before starting Afaya Plus. After 1 month of administration Person 4's A1C dropped 0.2% (5.5 to 5.3) and triglycerides dropped 87 mg/dL (251 to 164). This occurred while the person did not report any change in lifestyle, diet, or exercise regimen.
  • Person 5
      • Person 5 began taking Afaya Plus, 2 capsules daily (1 in the am and 1 in the pm). Baseline blood work was drawn before starting Afaya Plus. After 1 year of administration Person 5's PSA dropped 0.28 ng/mL or (0.63 to 0.35). Fasting glucose measurements have trended down over a 1-year period pulled every 3 months (114, 119, 101, 95 mg/dL respectively).
  • Person 6
      • Person 6 began taking Afaya Plus, 2 capsules daily (administration times unknown). Person 6's PSA dropped 2.87 ng/mL (3.37 to 0.500) over a period of 15 months of administration (3.37, 1.87, 0.95, 0.72, 0.500 ng/mL respectively).
  • Person 7
      • Person 7 began taking Afaya Plus, 2 capsules daily (administration times unknown). Person 7's A1C dropped 0.2% (6.1 to 5.9) over a 6-month period. Person 7 has also reported a downward trend in his 2 hour post prandial sugar levels.
  • Person 8
      • Person 8 began taking Afaya Plus, 2 capsules daily (administration times unknown). Person 8's A1C dropped 0.6% (5.8 to 5.2) over a 4-month period. Person 8 has since discontinued taking metformin.
  • Person 9
      • Person 9 began taking Afaya Plus (dosage level unknown). Person 9's PSA dropped 1.41 ng/mL (7.1 to 5.69) after 3 months of administration. Person 9's A1C dropped 0.4% (6.5 to 6.1) after 6 months of administration.
  • Person 10
      • Person 10 began taking 6 capsules per day—lowered Total Cholesterol from 188 to 151; LDL from 115 to 87; fasting glucose from 106 to 98 in 1 month.
  • Person 11
      • Person 11 began taking 2 capsules per day—Lowered Total Cholesterol from 157 to 134 in 1 month; LDL from 86 to 70 in 1 month; A1C from 5.7 to 5.3 over 1 year (TM began taking steroids during this time); PSA lowered from 0.63 to 0.35 over 9 months.
  • Person 12
      • Person 12 began taking 4 capsules per day—Lowered Total Cholesterol from 223 to 203 in 1 month; LDL from 140 to 117 in 2 months.
  • Person 13
      • Person 13 began taking 4 capsules per day—lowered Total Cholesterol from 214 to 207 in 1 month; LDL from 137 to 124 in 1 month; lowered fasting glucose from 95 to 85 in 1 month
  • Person 14
      • Person 14 began taking 4 capsules per day—lowered Total Cholesterol from 218 to 197 in 2 months; lowered A1C from 5.5 to 4.9 in 4 months; PSA lowered 7.2 to 1.9 in 3 months
  • Person 15
      • Person 15 began taking 4 capsules per day—lowered Total Cholesterol from 152 to 134 in 2 months; LDL from 95 to 80 in 2 months
  • Person 16
      • Person 16 began taking 4 capsules per day—lowered A1C from 8.0 to 6.6 in 5 months
  • Person 17
      • Person 17 began taking 4 capsules per day—lowered Total Cholesterol from 217 to 169 in 1 month; LDL from 147 to 94 in 1 month;
  • Person 18
      • Person 18 began taking 2 capsules per day—lowered Total Cholesterol from 151 to 134 in 2 months; LDL from 97 to 71 in 2 months; fasting glucose from 80 to 66 in 2 months
  • Person 19
      • Person 19 began taking 2 capsules per day—lowered A1C from 6.0 to 5.3 in 7 months
  • Person 20
      • Person 20 began taking 2 capsules per day—Lowered fasting glucose from 112 to 87 in 2 months
  • Person 21
      • Person 21 began taking 2 capsules per day—lowered Total Cholesterol from 173 to 162 in 2 months; LDL from 107 to 92 in 2 months; lowered fasting glucose from 92 to 78 in 1 month
  • Person 22
      • Person 22 began taking 2 capsules per day—lowered Total Cholesterol from 200 to 182 in 2 months; lowered LDL from 143 to 123 in 2 months; lowered fasting glucose from 128 to 96 in 2 months
  • Person 23
      • Person 23 began taking 2 capsules per day—lowered fasting glucose from 98 to 84 in 2 months
  • Person 24
      • Person 24 began taking 2 capsules per day—Lowered Total Cholesterol from 191 to 183 in 1 month; LDL from 98 to 83 in 1 month
  • Person 25
      • Person 25 began taking 2 capsules per day—lowered Total Cholesterol from 291 to 257 in 1 month; LDL from 180 to 165 in 1 month;
  • Person 26
      • Person 26 began taking 2 capsules per day—Lowered Total Cholesterol from 232 to 213 in 1 month; LDL from 160 to 146 in 1 month
  • Person 27
      • Person 27 began taking 1 capsule per day—lowered Total Cholesterol from 208 to 190 in 1 month; LDL from 102 to 87 in 1 month; fasting glucose from 93 to 82 in 2 months
  • Person 28
      • Person 29 began taking 1 capsule per day—lowered fasting glucose from 184 to 99 in 2 months
  • Person 29
      • Person 29 began taking 4 capsules per day lowered PSA from 2.9 to 2.0 in 3 months; lowered fasting glucose from 111 to 93 in 3 months
  • Person 30
      • Person 30 began taking 2 capsules per day—lowered Total Cholesterol from 257 to 233 in 1 month
  • Person 31
      • Person 31 began taking 4 capsules per day—lowered LDL from 131 to 107 in 1 month
  • Person 32
      • Person 32 began taking 2 capsules per day—Lowered Total Cholesterol from 146 to 129 in 3 months; LDL from 84 to 65 in 3 months
  • Person 33
      • Person 33 began taking 4 capsules per day lowered PSA from 433.8 to 5.5 in 7 months; lowered A1C from 7.6 to 6.4 in 7 months
  • Person 34
      • Person 34 began taking 2 capsules per day. Blood glucose levels were taken, and illustrated a trend toward lowering of such levels over a period of 210 days, at both morning and two-hour post-prandial (PM) times.
  • Person 35
      • Person 35 began taking 4 capsules per day, had to decrease to 3 capsules per day because of glucose levels getting to low. Blood glucose levels were taken, and illustrated a trend toward lowering of such levels over a period of 210 days, at both morning and two-hour post-prandial (PM) times. This Person also had to lower the amount of supplement taken to prevent glucose levels from getting too low. This occurred around day 180.
    Example
  • In this example, a set of tests were carried out to compare the effects of the three principal plant extracts used in the invention, alone and in combination, on 3D spheroids from two cancers, namely ovarian and lung cancer.
  • Materials and Methods.
  • Arum palaestinum Boiss were identified morphologically during field collection from growing habitats in the Palestinian region, and seeds from the plants were then planted in a growth chamber for germination (samples are on file at the Missouri Botanical Garden (MBG) for verification, voucher #Croat 95,466 (MO)). The plant extract was analyzed using gas chromatography-mass spectrometry (GC-MS) to verify identification of A. palaestinum. Portions of the plants were cut into wedges and boiled in water for 4 hours, whereupon the wedges were dried to completion in an 80° C. oven. Peganum harmala seeds and powdered Curcuma longa (turmeric) root were purchased from commercial sources.
  • A combined product made up of all three of the plant sources (MIR001) were prepared by mixing the powdered extracts at a ratio of 50% by weight turmeric, and 25% by weight each of the A. palaestinum and P. harmala, followed by boiling for 3 hours. Aliquots were stored at −20° C., and thawed 30 minutes prior to testing in a 37° C. water bath. The thawed aliquots were then vortexed thoroughly and diluted to 6% and 3% concentrations in RPMI with 10% FBS growth media. The individual components of MIR001 were similarly prepared by boiling, freezing, thawing, diluting, and with the addition of RPMI and FBS to create comparative samples.
  • Human lung cells and human ovarian cells were grown in RPMI 1640 and supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. In order to form 3D cell clusters, cells were seeded into micromolds at the time of passage. The micromold process has been described previously, Ramachandran K, et al. Engineering Islets for Improved Performance by Optimized Reaggregation in a Micromold. Tissue Eng Part A. 2013; 19(5-6):604-12. The process enhances cell aggregation but restricts the aggregates to less than 100 μm in diameter. Cells were grown in the micromolds for 48 hours at 37° C. and 5% CO2, resulting in the formation of uniform 3D spheroids. The 3D models were removed from the micromolds with gentle pipetting and rinsing followed by media change in RPMI with reduced FBS (0.5%). Approximately 25-50 spheroids were distributed per well of a 96 well plate for experimentation.
  • 3D spheroids were seeded and immediately checked microscopically for consistency of cluster distribution between wells. Both cell lines were exposed to multiple replicates of increasing doses of MIR001. Each assay was conducted on a 96 well plate, including 4-6 replicates. In like manner, the individual extracts of MIR001 were tested, along with the RPMI/FBS vehicle.
  • The MIR001 and extract stock solutions were diluted in RPMI with 10% FBS to reach final desired concentrations. In each experiment, spheroids were exposed to the test article for 24 hours, followed by exposure to 10% PrestoBlue cell viability reagent (Invitrogen) before being loaded into the Enspire microplate reader (Perkin Elmer), with excitation at 490 nm and emission at 560 nm. Background values, obtained from media plus supplement only, were subtracted from each well. For comparisons, changes in PrestoBlue values were normalized to the 0 supplement condition.
  • Results
  • The effects of the individual plant extracts on ovarian spheroids was first tested. The results demonstrated that while each plant extract had some in vitro effect, the combination MIR001 was significantly more effective than each extract alone. These results are set forth in FIGS. 1-6. The A. palaestinum plant extract alone was the least effective (FIG. 1), while C. longa (turmeric; FIG. 3) and P. Harmala (FIG. 5) were more effective, at the highest concentrations tested. The same effect was noted when lung spheroids were exposed to MIR001; however, the differences were even greater. A. palaestinum alone failed to have even 20% effect in the lung spheroids, while MIR001 caused 80% effect at the same concentration (FIG. 2). Turmeric had greater variability between trials, but failed to reach more than 60% effect (FIG. 4). Likewise, P. harmala induced little effect alone (FIG. 6).
  • The effects were specific to MIR001, because subsequent studies exposing the 3D spheroids to MIR001 versus the vehicle showed that the latter had no effect on ovarian spheroids (FIG. 7) or lung spheroids (FIG. 8).
  • These results demonstrate that the three-component composition MIR001 gave significant results as compared with the individual extracts, thus confirming a synergistic effect.

Claims (19)

We claim:
1. A method of supporting human health by administering to a person a nutritional supplement comprising individual quantities of turmeric, Peganum harmala, and Arum palaestinum, said turmeric present in an amount greater than either of the amounts of said Peganum harmala, and said Arum palaestinum, said supplement in the form of a capsule, gel, blended powder, liquid, suspension, tablet or pill, said supplement exhibiting an anti-cancer effect against human lung cancer cells, or human ovarian cancer cells, which is greater than the individual anti-cancer effect of turmeric, Peganum harmala, or Arum palaestinum.
2. The method of claim 1, said supplement including β-sitosterol.
3. The method of claim 1, said supplement including a vanillin compound.
4. The method of claim 1, said supplement including garlic.
5. The method of claim 1, said supplement including Vitamin C.
6. The method of claim 1, said supplement also including garlic, β-sitosterol, and Vitamin C, said turmeric being present in an amount greater than any of Peganum harmala, Arum palaestinum, garlic, β-sitosterol, and Vitamin C.
7. The method of claim 1, said supplement having from about 8-15% by weight Vitamin C, from about 5-11% by weight garlic, from about 35-45% by weight vanillin, from about 5-11% by weight β-sitosterol, from about 12-20% by weight turmeric, from about 5-11% by weight Peganum harmala, and from about 5-11% Arum palaestinum.
8. The method of claim 1, said supplement being in powdered form in a capsule.
9. The method of claim 1, said supplement having from about 9-11% by weight Vitamin C, from about 7-9% by weight garlic, from about 38-42% by weight vanillin, from about 7-9% by weight β-sitosterol, from about 14-17% by weight turmeric, from about 7-9% by weight Peganum harmala, and from about 7-9% Arum palaestinum.
10. The method of claim 1, said turmeric, Peganum harmala, and Arum palaestinum are food grade ingredients.
11. The method of claim 1, including the step of orally administering the nutritional supplement to the person.
12. The method of claim 1, said person seeking to support or promote normal blood glucose levels.
13. The method of claim 1, said person seeking to support or promote prostate health.
14. The method of claim 1, said person seeking to support or promote normal cholesterol levels.
15. The method of claim 1, said person seeking to promote normal cellular division.
16. A supplement in accordance with claim 1, for use in the support or promotion of normal blood glucose levels.
17. A supplement in accordance with claim 1, for use in the support or promotion of prostate health.
18. A supplement in accordance with claim 1, for use in the support or promotion of normal cholesterol levels.
19. A supplement in in accordance with claim 1, for use in the support or promotion of normal cellular division.
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US20220175868A1 (en) * 2020-12-04 2022-06-09 Ankh Life Sciences Limited INHIBITION OF SARS-CoV-2 VIRUS BY ARUM PALAESTINUM

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US6596313B2 (en) 2001-08-06 2003-07-22 The Quigley Corporation Nutritional supplement and methods of using it
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US20220175868A1 (en) * 2020-12-04 2022-06-09 Ankh Life Sciences Limited INHIBITION OF SARS-CoV-2 VIRUS BY ARUM PALAESTINUM

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