WO2014159677A1 - Method of preparing a muscadine pomace extract - Google Patents
Method of preparing a muscadine pomace extract Download PDFInfo
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- WO2014159677A1 WO2014159677A1 PCT/US2014/024717 US2014024717W WO2014159677A1 WO 2014159677 A1 WO2014159677 A1 WO 2014159677A1 US 2014024717 W US2014024717 W US 2014024717W WO 2014159677 A1 WO2014159677 A1 WO 2014159677A1
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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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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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)
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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)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
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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)
- A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
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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)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
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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)
- A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- This invention relates to methods for making an antioxidant composition that contains muscadine grape extract, and in particular extracts obtained from bronze and purple muscadine grapes.
- ROS Reactive oxygen species
- Oxidative stress is considered to be associated with the pathogenesis of chronic inflammatory diseases such as diabetes, cancer, atherosclerosis and other cardiovascular diseases, as well as with degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease. Moreover, multiple lines of evidence support the view that oxidative stress is a central mechanism underlying normal aging. Accordingly, a need exists to develop compositions and methods to inhibit oxidative stress.
- Grapes contain several bioactive polyphenolic compounds, including flavonoids (such as flavan-3-ols and oligomers thereof known as proanthocyanidins; flavonols, anthocyanins, and flavanones) and non- flavonoids (such as phenolic acids, tannins and stilbene derivatives, for example resveratrol).
- flavonoids such as flavan-3-ols and oligomers thereof known as proanthocyanidins; flavonols, anthocyanins, and flavanones
- non- flavonoids such as phenolic acids, tannins and stilbene derivatives, for example resveratrol
- the non-flavonoid resveratrol has been considered to mediate many of the beneficial effects of grape products on the human cardiovascular system.
- the protective and anti -inflammatory effects of the flavonoids are believed to be due to free radical scavenging, various effects on cellular signaling pathways and gene expression, and selective interference with a multitude of factors that affect the cell division cycle of rapidly and abnormally proliferating mammalian cells.
- compositions are disclosed herein for producing a muscadine pomace solvent extract composition that contains a combination of bronze muscadine pomace extract and purple muscadine pomace extract. It has unexpectedly been found that the combination of the extracts from the different colored grapes desirably increases the ellagic acid solubility in the composition. It has also been found that the solubility of the ellagic acid can be further increased by including in the composition and/or extraction method an anthocyanin that is not obtained from an extract of the pomace-only. The anthocyanin can be obtained, for example, from the whole purple muscadine grapes or another colored fruit such as blueberry, blackberry, or raspberry, or a fruit processing waste stream.
- the anthocyanin is obtained from the juice or skins or both of such a colored fruit.
- bronze muscadine grape pomace-only and whole purple muscadine grapes are solvent extracted either separately or together, for example with water, such that the combined extracts contain anthocyanins from the whole purple muscadine grape.
- the combined extract may then be combined with an extract of a purple muscadine pomace-only to produce the composition having unexpectedly increased ellagic acid solubility.
- the purple muscadine pomace includes pomace contained in whole purple muscadine grapes, and the purple muscadine pomace extract comprises at least in part an extract from whole purple muscadine grapes.
- the purple muscadine pomace extract can therefore include a mixture of extract from (a) whole purple muscadine grapes; and (b) extract from the pomace-only portion of the purple muscadine grapes from which juice has previously been extracted.
- the muscadine grape extract can be solely from bronze and purple muscadine pomace-only wherein the pomace-only consists essentially of the pomace without the juice.
- the bronze muscadine pomace extract can be combined with the purple muscadine pomace extract (such as purple muscadine pomace- only extract) to produce muscadine pomace extract in which the bronze muscadine pomace extract and purple muscadine pomace extract are present in a ratio that ranges from 0.1 to 10 (weight to weight) and the muscadine pomace extract has a polyphenol content of at least 2%, for example about 4% or more.
- the bronze muscadine pomace extract and purple muscadine pomace extract are present in a ratio that ranges from 0.3 to 3.
- the "pomace extract” includes extract from pomace-only and/or the pomace component of a whole grape.
- the bronze and purple extracts can be produced either simultaneously or sequentially.
- simultaneous extraction bronze muscadine pomace-only (without whole grapes) and whole purple muscadine grapes are combined and simultaneously solvent extracted to provide a mixed extract from (a) the bronze pomace-only and (b) an extract of the whole purple grape (which includes an extract of juice contained within whole purple grape and an extract of the pomace-only portion of the whole purple grape).
- bronze and purple muscadine pomace-only (without any bronze or purple whole grapes) are combined and simultaneously extracted.
- the bronze pomace-only, purple pomace-only and whole purple grapes are combined and all three are simultaneously extracted.
- purple muscadine pomace from other than the whole grapes (for example pomace-only) and bronze muscadine pomace from other than the whole grapes (for example pomace-only) are separately extracted, and then those extracts are combined.
- the combined purple/bronze extracts are then in turn combined with an extract from purple muscadine pomace (not whole grapes) or an extract from whole purple muscadine grapes, or a combination of an extract from whole purple grapes and an extract from bronze pomace (not whole grapes).
- the bronze muscadine pomace extract and the purple muscadine pomace extract are prepared prior to combining the bronze muscadine pomace extract with the purple muscadine pomace extract to produce a muscadine pomace extract having a polyphenol content of at least 2%.
- the bronze muscadine pomace and purple muscadine pomace are extracted with water to produce the bronze muscadine pomace extract and the purple muscadine pomace extract prior to combining the bronze muscadine pomace extract with the purple muscadine pomace extract to produce the muscadine pomace extract having a polyphenol content of at least 2%.
- Preparing the bronze muscadine pomace extract and the purple muscadine pomace extract can further include filtering the bronze muscadine extract and purple muscadine extract either (a) separately prior to combining them or (b) together after combining them, to produce the muscadine extract having a polyphenol content of at least 2%.
- the bronze and purple pomace extracts may also be fermented either separately or in combination to help remove extracted sugars. Such fermentation may occur either before or after filtering the muscadine pomace extract.
- the bronze and purple muscadine extracts may further be concentrated so that each extract comprises 20% to 50% solids in a liquid, for example about 40% solids in a liquid.
- the muscadine pomace extract is concentrated after filtering the muscadine pomace extract.
- An excipient or additional ingredient can be added to the extract after extraction, for example to make an antioxidant composition.
- the additional ingredients may include resveratrol or anthocyanins.
- anthocyanins are added during extraction by extracting whole purple muscadine grapes to simultaneously extract the pomace of the grape and the anthocyanins that are present in the grape juice.
- compositions are also disclosed that are made by the foregoing or other methods.
- the ratio of bronze muscadine pomace extract to purple muscadine pomace extract in the composition is present in a ratio that ranges from 0.1 to 10 (weight to weight) and the muscadine pomace extract has a polyphenol content of at least 2%.
- These compositions can be administered to a subject in need of them to inhibit cellular aging by preventing or inhibiting one or more processes associated with cellular aging, such as free radical formation or activity.
- the purple muscadine pomace extract includes (a) an extract of whole purple muscadine grapes; (b) an extract of purple muscadine pomace from other than whole grapes; or (c) a mixture of (a) and (b).
- the composition may be included in a non-beverage food, a beverage, a dietary supplement, a cosmetic composition, or an anti-aging supplement
- the compositions may be used in a method of inhibiting oxidative stress by administering to a subject in need thereof a dose of the composition sufficient to reduce or inhibit oxidative stress. In some embodiments, the dose is administered 10 to 30 minutes before or after meal consumption.
- the muscadine composition can include resveratrol or an anthocyanin from a source other than muscadine pomace or muscadine grape in an antioxidant composition.
- the composition can contain resveratrol from Japanese knotweed extract in an antioxidant composition or anthocyanin from a source other than muscadine pomace, such as the juice in whole purple muscadine grapes, or anthocyanins from another colored fruit such as black currant, blueberry, blackberry or raspberry added during the extraction process.
- the anthocyanins can be from a fruit processing waste stream.
- the waste stream anthocyanins can be from the skins of colored fruit after they have been processed to purees, jellies, jams, and fruit juice concentrates.
- the waste stream would be added during the extraction process and not subsequently added to the composition after the extraction process is complete.
- the end product antioxidant composition can also have additional anthocyanins (for example from elderberry extract) added to it.
- the extract is prepared from a mixture of starting materials (such as the muscadine pomace plus added anthocyanin source) that contains a ratio in the starting materials of anthocyanins to ellagic acid that ranges from 0.5: 1 to 5: 1 (weight:weight) such as 1: 1 (weight:weight) or 1.3: 1 (weight:weight) .
- the muscadine pomace material combined with the additional fruit material such as black currant, blueberry, blackberry or raspberry would have a ratio of anthocyanins to ellagic acid of at least 0.5: 1, for example as great at 5: 1.
- the ratio is at least 1: 1, 2: 1, or 3: 1, and/or is no more than 5: 1 or 4: 1.
- the weight ratio of anthocyanins to ellagic acid in the combined starting materials is more than 0.5: 1, 1: 1, 10: 1, or 20: 1.
- the weight ratio of anthocyanins to ellagic acid in the combined starting materials is no more than 30: 1, 40: 1 or 50: 1.
- the extract is prepared from a mixture of extracts (such as muscadine pomace extract plus added anthocyanin from an extract of a colored fruit such as elderberry fruit) wherein the weight ratio of anthocyanins to ellagic acid in the combined extract materials is more than 0.5: 1, 1: 1, 10: 1, or 20: 1, for example it could be 24: 1. In other examples the weight ratio of anthocyanins to ellagic acid in the combined starting materials is no more than 30: 1, 40: 1 or 50: 1.
- the muscadine pomace extract contains or is prepared by
- the muscadine pomace extract contains or is obtained by extracting (a) whole purple muscadine grapes and (b) a mixture of bronze and purple muscadine pomace in a ratio of (a) to (b) that ranges from 1:7 to 1: 16 (weight:weight) such as 1:9
- the muscadine pomace extract is prepared from whole purple muscadine grapes, purple muscadine pomace, and bronze muscadine pomace wherein the ratio in them of anthocyanins to ellagic acid of at least 0.5: 1, for example the ratio ranges from 0.5: 1 to 5: 1 (weight: weight) such as 1: 1 (weight:weight) or 1.3: 1 (weight:weight) .
- ROS Reactive oxygen species
- Exemplary routes of administration include, but are not limited to, oral, injection (such as subcutaneous, intramuscular, intradermal, intraperitoneal, intravenous, and intratumoral), sublingual, transdermal, intranasal, topical and inhalation routes.
- injection such as subcutaneous, intramuscular, intradermal, intraperitoneal, intravenous, and intratumoral
- sublingual transdermal
- intranasal topical and inhalation routes.
- Anthocyanin A water-soluble vacuolar pigment found in many plants that may appear red, purple or blue depending on the pH. Anthocyanins belong to a parent class of molecules called flavonoids that are synthesized via a phenylpropanoid pathway. Anthocyanins have the general chemical structure shown below:
- Anthocyanins from a source other than muscadine refers to anthocyanins obtained from a source other than a muscadine grape.
- non-muscadine sources include elderberry , black currant fruit, blueberry, black raspberry, red raspberry, bilberry, grape or purple carrot.
- Antioxidant activity Activity that reduces oxidative stress, for example by scavenging and neutralizing oxidative free radicals. Antioxidant activity can be measured using the methods disclosed herein as well as those known in the art, including the Oxygen Radical Absorbance Capacity (ORAC) assay, the Ferric Reducing Ability of Plasma (FRAP) assay, and the Trolox Equivalent Antioxidant Capacity (TEAC) assay.
- ORAC Oxygen Radical Absorbance Capacity
- FRAP Ferric Reducing Ability of Plasma
- TEAC Trolox Equivalent Antioxidant Capacity
- a composition has antioxidant activity and can be used as an antioxidant if it has a total ORAC of at least 24 ⁇ Trolox Equivalents per mg polyphenol ⁇ moleTE/mg polyphenol).
- Antioxidant composition A composition that has antioxidant activity.
- Antioxidative effective amount An amount sufficient to induce an antioxidant effect in a subject to whom the amount of a composition is administered.
- the composition induces a selectively synergistic increase in ORACupophiiic antioxidant activity by increasing ORACupophiiic to a greater extent than what would be predicted from the addition of the ORACupophiiic values of the individual components of the composition.
- Blackberry Perennial plant from the Rubus genus in the Rosaceae family that produces an edible blackberry fruit.
- Black currant A woody shrub in the family Grossulariaceae that produces piquant black currant berries .
- Blueberry Perennial flowering plants with indigo-colored berries from the section Cyanococcus within the genus Vaccinium.
- the blueberry fruit of these plants is a berry that is reddish-purple and eventually dark purple when ripe.
- Elderberry (Sambucus nigra): A plant belonging to the Adoxaceae family found in Europe and North America with several regional varieties or subspecies. The flowers are in flat corymbs. The berries are black to glaucous blue and contain anthocyanins and other
- polyphenolics for example, proanthocyanidins and flavonols such as quercetin
- amount and type of anthocyanins and other polyphenolics vary depending upon the variety.
- an “elderberry extract” is a material obtained by extracting an elderberry according to any extraction method known to one of skill in the art, so long as it has the desired activity (e.g., color stabilizing activity, antioxidant activity or a combination thereof).
- the elderberry extract can include a fruit juice obtained by compressing elderberry fruit, or an extract obtained by extracting whole fruit of elderberry or a suitable portion of skin or seed of the fruit according to known extraction methods, such as solvent (for example water) extraction.
- an elderberry extract a crushed product of an elderberry fruit or a dried elderberry fruit concentrate can be used as "an elderberry extract.”
- the elderberry fruit (or an extract of it) can be used as a source of additional anthocyanins to be added to a muscadine grape extract to improve the solubility of ellagic acid in the muscadine grape extract.
- Excipient An inactive substance used as a carrier for the active ingredients of a composition.
- Excipients can include substances that are used as bulk in formulations with very potent active ingredients, allow for convenient and accurate dosage, stabilize the active ingredients, and make the delivery system optically and/or organoleptically acceptable.
- examples of pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol, and the like.
- the disclosed anti-aging supplement includes the following excipients: glycerin, sorbitol, colloidal silicon dioxide, and a natural flavoring additive.
- Extract To separate a substance from a matrix.
- An extract is also the substance made by extracting a part of a raw material, for example by using pressure or a solvent such as ethanol and/or water. Extracts may be in liquid or powder form. Particular examples of extracts disclosed herein are in liquid form.
- a "solvent extract”" refers to an extract obtained by exposing a target to a liquid solvent that solubilizes the desired substance contained in a product.
- a “water extract” is an extract obtained by water extraction of a product. Solvent extracts remove target substances from the product according to the solubility of the target substance in the solvent. Certain of the extracts disclosed herein are solvent extract, such as water extracts.
- Inhibiting including preventing) cellular aging: Inhibiting (for example preventing) one or more processes associated with cellular aging, such as inhibiting free radical formation or activity in a subject who ingests the composition.
- Preventing cellular aging refers to an intervention that ameliorates a sign or symptom of cellular aging. Preventing includes prophylaxis to delay the onset of one or more processes associated with cellular aging.
- a disclosed composition decreases or delays a process associated with cellular aging by at least 10%, at least 20%, at least 50%, or even at least 90%. Such decreases can be measured using the methods disclosed herein as well as those known in the art.
- Japanese Knotweed (Fallopia japonica, Polygonum cuspidatum): a large herbaceous perennial plant which is native to Eastern Asia in Japan, China and Korea. It is a concentrated source of resveratrol and its glucoside piceid (up to 0.05 to 0.2 % of fresh weight).
- Muscadine Grape (Vitus rotundifolia) Grapes native to the southeastern United States, and found in the wild from Delaware to the Gulf of Mexico and westward to Missouri, Kansas, Oklahoma, and Texas. Muscadines are well adapted to the warm, humid conditions of the southeastern United States. The fruit is borne in small, loose clusters of 3-40 grapes, quite unlike the large, tight bunches characteristic of European and American grapes. The round, 1 to 1-1/2 inch fruits have a thick, tough skin and contain up to 5 hard, oblong seeds. In color the fruits range from greenish bronze through bronze, pinkish red, purple and almost black. Many different varieties of muscadine grapes are available, including female (pistillate) varieties such as Black Beauty, Black Fry, Darlene, Fry, Higgins, Jumbo, Scuppernong,
- bronze colored varieties of muscadine grapes are identified by those skilled in the art as including Carlos, Chowan, Doreen, Higgins, Magnolia, Nonemiss, Pamlico, Roanoke, Scuppernong, Sterling, and Summit cultivars. Purple varieties are darker skinned then the bronze colored varieties and include Albermarle, Bountiful, Cowart, GA-1, Hunt, NC-1, Noble, Regale, Tarheel, and Jumbo. Some of the purple varieties are also referred to as Black colored.
- the phytochemical constituents of the whole muscadine grape differ from Vitis vinifera. Muscadines have a higher total phenolic content distinguished by high ellagic, gallic, and flavonoid glycoside concentrations. The presence of ellagic acid in muscadine grapes is unique and is found in the form of free ellagic acid, ellagic acid glycosides, methoxylated derivatives and ellagitannins. Another unique feature is the anthocyanin chemistries observed in
- muscadines Present as 3,5-diglucosides (as opposed to 3-glucosides) of delphinidin, cyanidin, petunidin, peonidin, and malvidin in non-acylated forms, these compounds and the natural color influence from other anthocyanins present within the grape impart a dark purple color to juice and pomace obtained from the purple varieties. Purple pomace extracts contain anthocyanins while bronze pomace extracts do not.
- the red and purple colored anthocyanins found in purple muscadine grapes are polyphenolic compounds that have antioxidant properties.
- Purple and bronze muscadine grapes contain several other flavonoid classes of polyphenols with flavan-3-ols and their oligomers being the most abundant class and flavonols being the second most abundant flavonoids present in whole muscadines.
- the major phenolics reported for the muscadine skin fraction are ellagic acid, myricetin, quercetin, and kaempferol while those reported for seeds are epicatechin, catechin and gallic acid (Pastrana-Bonilla et al. J. Agric. Food Chem. 51:5497-5503, 2003).
- a muscadine grape contains pomace and juice. "Other than the whole grape” includes a muscadine grape from which at least some of the juice has been extracted, and in some examples includes less than 95% or 90% of the original juice in the grape.
- Pharmaceutically Acceptable Vehicles The pharmaceutically acceptable vehicles (carriers) useful in this disclosure are conventional. Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, PA, 19th Edition (1995), describes compositions and formulations suitable for pharmaceutical delivery of one or more compositions, such as one or more muscadine compositions, and additional pharmaceutical agents.
- parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.
- pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.
- physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like
- solid compositions for example, powder, pill, tablet, or capsule forms
- conventional non-toxic solid vehicles can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate.
- compositions can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.
- non-toxic auxiliary substances such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.
- Polyphenols also known as polyhydroxyphenols, phenolics and polyphenolics: A class of organic compounds characterized by the presence of multiple phenol structural units. Many of them are derived from plants, and can generally be divided into flavonoids, phenolic acids and stilbenes although there are multiple subclasses of flavonoids and phenolic acids.
- Polyphenols found in plants are usually complex mixtures of different polyphenol classes and moreover may be conjugated to sugar groups (polyphenol glycosides) or may occur in the aglycone form (without sugar group attachments).
- Polyphenols from a source other than muscadine refers to polyphenols that are present in or obtained from a product other than a muscadine grape and includes multiple classes of polyphenols such as flavonoids, tannins and phenolic acids. Examples of such non-muscadine sources include elderberry, black currant, blueberry, black raspberry, red raspberry, blackberry, bilberry, cloudberry, chokeberry, gooseberry, pomegranate, grape or purple carrot.
- a pomace extract is a bronze muscadine pomace extract, a purple muscadine pomace extract or a combination thereof.
- Many different varieties of muscadine grape pomaces are available as starting materials, and they include female (pistillate) varieties such as Black Beauty, Black Fry, Darlene, Fry, Higgins, Jumbo, Scuppernong, Sugargate, Summit, Supreme, and Sweet Jenny, and self-fertile varieties such as Carlos, Cowart, Dixieland, Dixie Red, Fry Seedless, Magnolia, Nesbitt, Noble, Redgate, Regale and Sterling.
- Muscadine pomace contains phenolic compounds, including gallic acid and ellagic acid, having antioxidant properties.
- the pomace can be present in a whole grape wherein the whole grape contains at least 90 or 95% of the juice of the grape, or the pomace can be substantially isolated and consist essentially only of the pomace once the grape has been compressed to remove the juice.
- Pomace-only The pomace portion of a grape from which juice has been removed, for example by compression of the grape.
- pomace-only refers to a pomace that contains no more than 1% juice as a percentage of its weight. In some embodiments the pomace- only contains no more than 0.5% juice as a percentage of its weight.
- a purified substance is one in which the substance is more enriched than the substance in its natural environment, for example in a fruit (e.g., grape).
- a preparation is purified such that the substance represents at least about 5% (such as, but not limited to, at least 10%, 20%, 30%, 40%, 50%, 70%, 80%, 90%, 95%, 98% or 99%) of the total content of the preparation.
- a disclosed composition with antioxidant activity includes trans-resveratrol with a minimum purity of at least 50%, 70%, 80%, 90%, 95%, 98% or 99% of the total resveratrol preparation (by weight).
- a "purified pomace" is a pomace in a grape from which some or substantially all of the juice has been removed.
- Purple carrot (Daucus carota): a cultivar of carrot containing anthocyanin pigments.
- a "purple carrot extract” can be obtained by extracting a purple carrot according to any extraction method known in the art, such as pressing or solvent extractions, so long as the extract has the desired activity (e.g., color stabilizing activity, antioxidant activity or a combination thereof).
- a purple carrot extract has the property of stabilizing muscadine color pigment and can therefore be subsequently utilized as color-stabilizing additive.
- Raspberry Plant species in the genus Rubus, such as Rubus idaeus (red raspberry) or Rubus occidentalis (black raspberry) that produces an edible raspberry fruit.
- Resveratrol A phytoalexin that is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase.
- Resveratrol exists as two structural isomers: cis- and trans-resveratrol.
- Trans-resveratrol can undergo isomerisation to the cis-form when heated or exposed to ultraviolet irradiation.
- Resveratrol is found in widely varying trace amounts, on average it is less than 0.0001 (of fresh weight) when measured in grapes, raspberries, mulberries, plums, peanuts, berries of Vaccinium species, including blueberries, bilberries, and cranberries, and some pines, such as Scots pine and eastern white pine; the richest natural sources of resveratrol aglycone (up to 0.05 % of fresh weight) are the roots and stalks of giant knotweed and Japanese knotweed.
- any resveratrol present is found primarily in the skin and seeds. The amount of resveratrol found in grape skins varies with the grape cultivar, its geographic origin, and exposure to fungal infection. However, as noted above, it is typically present in only trace amounts.
- resveratrol can include natural trans-resveratrol extracted from a plant, such as grapes, or synthetic trans-resveratrol.
- resveratrol can include modified formulations of trans-resveratrol such as microencapsulated or water dispersible forms.
- Resveratrol from a source other than muscadine refers to resveratrol that is present in or obtained from a product other than a muscadine grape (or any subcomponent of the muscadine grape, such as its seeds). Resveratrol is substantially absent from solvent-extracted (such as water-extracted) muscadine pomace, and in some disclosed examples the muscadine pomace solvent extract is substantially free from resveratrol until the resveratrol from another source is added to the extract.
- Subject Living multi-cellular vertebrate organisms, a category that includes both human and veterinary subjects, such as a companion animal, including a cat, dog or horse.
- a "subject in need of an increase in mitochondrial biogenesis and/or antioxidant activity" is a subject who may benefit from such an increase, such as a subject who desires to decrease signs of age, offset tissue damage caused by oxidation, and/or improve cardiovascular, neurological, tumor-related, skin- appearance or other conditions that are associated with oxidative stress.
- Therapeutically Effective Amount An amount of a composition that alone, or together with an additional agent(s) (for example additional antioxidants), induces the desired response (e.g., prevents or inhibits cellular aging).
- additional agent(s) for example additional antioxidants
- the preparations disclosed herein can be administered in therapeutically effective amounts.
- Waste stream Material from a particular production process that is discarded or otherwise considered unproductive in the production of a desired end product.
- the skins of the fruits may be removed and not used in the product produced by the process. In that case the fruit skins would be considered part of a waste stream in the production process.
- Whole-grape A grape as it is found in nature, or which has been slightly compressed for example by a shipping process.
- a "whole grape” contains the pomace and at least 90% (for example 95%) of the original juice content.
- Red grapes are among the many foods that have been the subject of intense research.
- the antioxidant effects of red grapes have been widely attributed to the polyphenolic compounds, such as resveratrol and procyanidins, the latter which appear in substantial quantities in the grapes.
- the inventors developed a method to promote the solubility of ellagic acid in a muscadine pomace extract by combining a bronze and purple muscadine pomace extract.
- the combination of bronze and purple muscadine pomace extract was found to surprisingly increase the solubility of ellagic acid in the combined extract.
- compositions that contained increased levels of ellagic acid in combination with supplemental resveratrol were found to have surprisingly synergistic lipophilic antioxidant activity, particularly as measured by ORAC.
- the synergistic antioxidant activity in the lipophilic ORAC (ORACu pop hiiic) suggested that the antioxidant activity would be particularly effective in lipophilic environments, such as that found in low density lipoprotein (LDL).
- LDL low density lipoprotein
- the exogenous source of resveratrol was Japanese knotweed extract.
- muscadine extracts with improved ellagic acid solubility can be administered either alone or in combination with other compounds in a non-beverage food, a beverage, dietary supplement or a topical ointment.
- a bronze muscadine pomace extract with a purple muscadine pomace extract to produce a muscadine pomace extract
- the ratio of bronze muscadine pomace extract to purple muscadine pomace extract ranges from 0.1 to 10 (weight to weight), such as 0.3 to 3 (weight to weight).
- the combined extract could be extracted by separate extraction of bronze and purple muscadine grapes with subsequent combination of the extracts, or by simultaneous extraction of bronze and purple muscadine grapes combined in desired ratios.
- WO 2010/014870 and WO 2010/014873 the inventors determined the antioxidant capacity of the disclosed muscadine pomace extract and a Japanese knotweed extract, standardized to 98% trans-resveratrol, separately and in combination (in either a mixture or dietary supplement) as measured by an ORAC assay. Both hydrophilic antioxidant capacity and lipophilic antioxidant capacity of the samples were measured. These studies demonstrated a strong synergistic lipophilic antioxidant effect of a mixture of the muscadine pomace extract and Japanese knotweed root extract, standardized to 98% trans-resveratrol. The selective synergy exhibited in the lipophilic conditions was unexpected.
- the muscadine extract utilized in the composition can be a natural extract and can vary by species and extraction process while retaining synergistic lipophilic antioxidant activity. In particular examples specifically disclosed ratios of muscadine polyphenols to resveratrol are present in the composition.
- a composition containing Japanese knotweed extract, standardized to 98% trans- resveratrol, in combination with a muscadine pomace extract has improved lipophilic antioxidant capacity when compared to the sum of the lipophilic antioxidant capacities contributed by the individual extracts contained in the composition.
- Oxidative processes occurring in lipophilic environments are thought to initiate the pathogenesis of many disease states, such as low density lipoprotein (LDL) oxidation in atherosclerosis and obesity-induced insulin resistance in Type II diabetes.
- LDL low density lipoprotein
- oxidation of dietary lipids within the gastrointestinal tract leads to absorption of cytotoxic and genotoxic lipid peroxidation products such as malondialdehyde (MDA).
- MDA malondialdehyde
- Lipophilic antioxidants have been found to be effective in reducing various types of skin damage by inhibiting lipid peroxidation and the products produced by lipid peroxidation, such as cross-linking agents. Since oxidative stress is a central mechanism underlying normal aging, the disclosed antioxidant compositions are useful for inhibiting free radical production or activity, thereby slowing processes associated with cellular aging.
- muscadine pomace extract compositions having improved antioxidant activity.
- the muscadine pomace extract compositions were disclosed as components of a non-beverage food, a beverage, a liquid or solid dietary supplement or a topical ointment. Methods of producing the disclosed
- compositions include combining a muscadine (Vitis rotundifolia) pomace extract having a polyphenol content of at least 2% and trans-resveratrol from a source other than muscadine with a minimum purity of at least 5%, wherein a ratio of muscadine polyphenols to trans-resveratrol is in the range of 0.1/1 to 10/1 (weight to weight).
- a muscadine Vitis rotundifolia
- trans-resveratrol from a source other than muscadine with a minimum purity of at least 5%
- Methods of producing the disclosed compositions include combining a muscadine (Vitis rotundifolia) pomace extract having a polyphenol content of at least 2% and trans-resveratrol from a source other than muscadine with a minimum purity of at least 5%, wherein a ratio of muscadine pomace extract to trans- resveratrol is in the range of 0.2/1 to 50/1 (weight to weight), such as 5/1 to 50/1 (weight to weight) including 20/1 to 50/1 (weight to weight), such as 18 to 1 (weight to weight), thereby producing a muscadine pomace extract and trans-resveratrol mixture with antioxidant activity.
- the ratio of bronze to purple muscadine pomace extract ranges from 0.1 to 10, such as 0.3 to 3, as described in further detail below.
- Muscadine pomace extracts disclosed in WO 2010/014870 and WO 2010/014873 are derived from bronze muscadine pomace and purple muscadine pomace.
- the ratio of bronze muscadine pomace extract to purple muscadine pomace extract in the muscadine pomace extract range from 0.1 to 10 (weight to weight), such as 0.3 to 3 (weight to weight).
- the ratio of bronze muscadine pomace extract to purple muscadine pomace extract is about 2.75 to about 1 (weight to weight), 2.5 to about 1 (weight to weight), about 2.25 to about 1 (weight to weight), about 2 to about 1 (weight to weight), about 1.5 to about 1 (weight to weight), or about 1 to about 1 (weight to weight).
- the ratio is about 10 to about 1, about 7.5 to about 1, or about 5 to about 1.
- the ratio of bronze muscadine pomace extract to purple muscadine pomace extract is about 2.25 to about 1 (weight to weight).
- the muscadine (Vitis rotundifolia) pomace extract has a polyphenol content of at least 2%.
- the polyphenol content is at least 3%, at least 3.5%, at least 4%, at least 4.5%, at least 5%, at least 6%, at least 8%, at least 10%, at least 12%, or at least 14%.
- the muscadine (Vitis rotundifolia) pomace extract has a polyphenol content of about 4%.
- the disclosed muscadine pomace extracts include 20% to 50% solids, such as at least 25%, at least 30%, at least 35%, at least 37%, at least 40%, at least 42%, at least 44%, at least 46% or at least 48%, in a liquid.
- the extract includes about 40% solids in a liquid.
- the muscadine pomace can be extracted while either present in a whole grape or from purified pomace that is substantially free of grape juice.
- the purified pomace is the skin seeds and pulp remaining after at least 50% of juice in the grape has been removed.
- the purified pomace is the skin, seeds and pulp remaining after at least 60%, 70%, 80% or 90% of the juice has been removed from the grape, such that the pomace consists essentially of only the skin, seeds and pulp.
- Extracts prepared from grape pomace contained in the whole grape have the advantage of containing extracted components from both the grape pomace and the grape juice.
- Purple muscadine grapes contain anthocyanins in their juice such that solvent extraction of the purple grape provides an extract that contains additional amounts of anthocyanins that contribute to the ability of the purple muscadine extract to solubilize ellagic acid in the combined bronze and purple muscadine grape extracts.
- WO 2010/014870 and WO 2010/014873 also disclose methods of making muscadine pomace extracts wherein the ratio of bronze muscadine pomace extract to purple muscadine pomace extract ranges from 0.1 to 10 (weight to weight), such as 0.3 to 3 (weight to weight).
- the extracts can be obtained by any extraction method, such as pressing under pressure or extracting with a solvent, particular examples are solvent extracted, for example with alcohol, water (such as heated water), or a combination of alcohol and water.
- muscadine pomace extracts are prepared by simultaneously extracting bronze muscadine pomace and purple muscadine pomace that are present in proportions that yield desired ratios of bronze and purple extract.
- bronze muscadine pomace extracts and purple muscadine pomace extracts are prepared separately.
- bronze muscadine pomace and purple muscadine pomace are separately extracted with water, preferably heated water.
- the extract can further be fermented to remove extracted sugars.
- fermentation is performed following extracting the bronze muscadine pomace and purple muscadine pomace but prior to combining the bronze muscadine pomace extract with the purple muscadine pomace extract to produce a disclosed muscadine pomace extract.
- fermentation is performed after combining the bronze muscadine pomace extract with purple muscadine pomace extract in the desired post extraction ratio (such as at about a 2:25 to 1 bronze to purple ratio).
- Fermentation may be performed by any method known to one of skill in art, including those described herein.
- yeast and yeast nutrients can be added to the pomace and fermentation continued until the residual sugar content is converted to ethanol.
- two pounds of yeast are added per 1000 gallons of IX (unconcentrated) extract; fermentation is typically complete after three days.
- the amount and/or strain of yeast and duration and temperature of fermentation may vary according to individual methods known to one of skill in art.
- enzymes are used to clarify and/or settle residues or to improve extraction yield in the pomace extracts. Examples of such enzymes include pectinase or a blend of enzymes from Aspergillus niger that are commercially available from sources such as Scott Laboratories. These enzymes may be added to the pomace extract before or during fermentation.
- the bronze muscadine pomace extracts and purple muscadine pomace extracts are filtered prior to and/or following fermentation. Filtration can be performed according to general methods known to those of skill in the art. In a particular example, extracts are filtered through sieves of appropriate mesh size, such as USP mesh (typically 120 mesh) or a similar cloth filter (for example filters commercially available from Millipore Corporation).
- appropriate mesh size such as USP mesh (typically 120 mesh) or a similar cloth filter (for example filters commercially available from Millipore Corporation).
- methods of making muscadine pomace extracts further include concentrating the bronze muscadine pomace extract and the purple muscadine pomace extract so that each extract includes 20% to 50% solids, such as at least 25%, at least 30%, at least 35%, at least 37%, at least 40%, at least 42%, at least 44%, at least 46% or at least 48%, in a liquid.
- the extracts are concentrated so that each extract includes about 40% solids in a liquid.
- Generally known methods for concentrating samples including methods for concentrating samples disclosed herein, can be used to concentrate the bronze and purple extracts.
- the muscadine pomace extract is dried down into a powder form and re-constituted in water at 40% solids level.
- concentration by removal of the extraction solvent through evaporation under vacuum using a batch or continuous process involves placing the extract in a vessel under a vacuum of 20 -29" of mercury while heating the vessel jacket to provide energy to increase the vapor pressure of the solvent. Solvent vapors are condensed external to the vessel and the rate of condensation controls the temperature of the condensate. The same principles apply to a continuous evaporation process but with the advantage that the condensate is exposed to elevated
- bronze and purple pomace are extracted separately and each of the extracts is filtered prior to combining the bronze and purple pomace extract at the desired ratio.
- this method can further include fermenting the combined muscadine pomace extract to remove extracted sugars.
- more than one filtering step is used, for example by filtering the extract prior to and following fermentation.
- the method can further include concentrating the extract, as described herein. For example, the extract is concentrated by removal of the extraction solvent through evaporation under vacuum.
- the purple muscadine pomace extract can include (a) an extract of whole purple muscadine grapes; (b) an extract of purple muscadine pomace from other than whole grapes; or (c) a mixture of (a) and (b).
- the whole purple grapes contain grape juice that is a source of anthocyanins from other than the grape pomace, and when solvent extracted from the whole grape these anthocyanins have now been found to surprisingly enhance solubility of ellagic acid in the mixture of bronze and purple muscadine grape extracts.
- additional sources of anthocyanins can also be provided by a colored fruit or a byproduct of a colored fruit other than purple muscadine grapes, such as a blueberry, blackberry or raspberry fruit.
- the anthocyanin is from a product of a fruit processing stream such as a juice concentrate or a by-product of a fruit processing stream such as fruit skins that are separated from a fruit puree processing stream.
- the additional anthocyanins from the whole purple muscadine grapes or other colored fruit substantially increases the solubility of ellagic acid, which is a desirable antioxidant in the muscadine grapes.
- the muscadine pomace extract is produced by simultaneously extracting whole purple muscadine grapes and bronze muscadine pomace in a ratio that ranges from 1:5 to 1: 12 (weight:weight).
- an extract is produced that contains an extract of (a) whole purple muscadine grapes and (b) a mixture of bronze and purple muscadine pomace in a ratio of (a) to (b) that ranges from 1:7 to 1: 16
- the muscadine pomace extract is derived from whole purple muscadine grapes, bronze muscadine pomace and purple muscadine pomace in any combination wherein the ratio of anthocyanin to ellagic acid in the starting materials (whole grapes and pomace) ranges from 0.5: 1 to 5: 1 (weight:weight).
- the muscadine pomace extract is derived from bronze muscadine pomace and purple muscadine pomace in combination with an additional source of anthocyanin (such as whole purple muscadine grapes or other colored fruit such as blackberry, raspberry, black currant or blueberry fruit, or a waste stream of any of these fruits) wherein the ratio of anthocyanin to ellagic acid ranges from 0.5: 1 to 5: 1 (weight:weight).
- anthocyanin such as whole purple muscadine grapes or other colored fruit such as blackberry, raspberry, black currant or blueberry fruit, or a waste stream of any of these fruits
- compositions with improved antioxidant activity include a muscadine (Vitis rotundifolia) pomace extract having a polyphenol content of at least 2% and trans-resveratrol from a source other than muscadine grapes (such as a Japanese knotweed root extract) with a minimum purity of at least 5%, wherein a ratio of muscadine polyphenols to trans-resveratrol is in the range of 0.1/1 to 10/1 (weight to weight), thereby providing a composition with antioxidant activity.
- a muscadine (Vitis rotundifolia) pomace extract having a polyphenol content of at least 2% and trans-resveratrol from a source other than muscadine grapes (such as a Japanese knotweed root extract) with a minimum purity of at least 5%
- a ratio of muscadine polyphenols to trans-resveratrol is in the range of 0.1/1 to 10/1 (weight to weight), thereby providing a composition with antioxidant
- the composition includes a muscadine (Vitis rotundifolia) pomace extract having a total polyphenol content of at least 3%, at least 3.5%, at least 4%, at least 4.5%, at least 5%, at least 6%, at least 8%, at least 10%, at least 12% or at least 14% and trans- resveratrol from a source other than muscadine grapes with a minimum purity of at least 5%, at least 10%, at least 25%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 98%.
- a muscadine (Vitis rotundifolia) pomace extract having a total polyphenol content of at least 3%, at least 3.5%, at least 4%, at least 4.5%, at least 5%, at least 6%, at least 8%, at least 10%, at least 12% or at least 14% and trans- re
- the composition includes a muscadine (Vitis rotundifolia) pomace extract with a polyphenol content of about 4% and trans-resveratrol from a source other than muscadine grapes with a minimum purity of at least 98%.
- a muscadine Viis rotundifolia
- trans-resveratrol from a source other than muscadine grapes with a minimum purity of at least 98%.
- the composition includes a muscadine pomace extract with 20% to 50% solids, such as at least 23%, at least 25%, at least 30%, at least 35%, at least 37%, at least 40%, at least 42%, at least 44%, at least 46% or at least 48%, in a liquid.
- the extract includes about 40% solids in a liquid.
- the resveratrol includes at least 5% trans-resveratrol, such as at least 10% trans-resveratrol, at least 20% trans-resveratrol, at least 30% trans-resveratrol, at least 40% trans-resveratrol, at least 50% trans-resveratrol, at least 55%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 98% trans-resveratrol.
- trans-resveratrol such as at least 10% trans-resveratrol, at least 20% trans-resveratrol, at least 30% trans-resveratrol, at least 40% trans-resveratrol, at least 50% trans-resveratrol, at least 55%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 98% trans-resveratrol.
- resveratrol includes at least 50% trans-resveratrol, such as at least 55%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 98% trans-resveratrol extracted from Japanese Knotweed (Polygonum cuspidatum) root. It is contemplated that other trans-resveratrol sources can be used in the disclosed composition including synthetic trans-resveratrol.
- the disclosed antioxidant composition has a ratio of muscadine polyphenols to trans-resveratrol of at least 0.1 to 1 (weight to weight), such as, 0.25 to 1, 0.5 to 1, 0.6 to 1, 0.65 to 1, 0.7 to 1, 0.75 to 1, 0.8 to 1, 0.9 to 1 or 1 to 1 (weight to weight).
- the ratio of muscadine polyphenols to trans-resveratrol may be as high as 10 to 1 (weight to weight), such as 2 to 1, 3 to 1, 4 to 1, 5 to 1, 7.5 to 1 or 9 to 1 (weight to weight).
- the disclosed antioxidant composition has a ratio of muscadine polyphenols to trans-resveratrol of 0.75 to 1 (weight to weight).
- the disclosed antioxidant composition has a ratio of muscadine pomace extract to trans-resveratrol ranging from 0.2/1 to 50/1 (weight to weight), such as 0.5 to 1, 1 to 1, 5 to 1, 10 to 1, 15 to 1, 20 to 1, 22 to 1, 25 to 1, 30 to 1, 35 to 1, 40 to 1, or 45 to 1 (weight to weight).
- compositions with antioxidant activity have a total
- a disclosed composition has a total ORAC of 24 ⁇ / ⁇ polyphenol.
- compositions further include an elderberry extract, a purple carrot extract, an excipient (such as glycerin, sorbitol, colloidal silicon dioxide, or a natural flavoring additive) or a combination thereof.
- an elderberry extract and purple carrot extract can be included to provide color to the composition or for additional antioxidant activity.
- the antioxidant composition is further combined with polyphenols (such as anthocyanins) from a source other than muscadine.
- polyphenols such as anthocyanins
- the components are combined so that the antioxidant composition includes at least 10% polyphenols, for example up to 35% polyphenols, such as 12-32%.
- the elderberry extract provides at least one-fourth of the total polyphenols in the muscadine/elderberry mixture, for example one-third to two-thirds of the total polyphenols and at least one fifth, for example 25% to 90% of the anthocyanins in the muscadine/elderberry mixture.
- the extract includes bronze muscadine pomace extract and an additional anthocyanin not obtained from the bronze muscadine pomace, wherein the additional anthocyanin is obtained from a purple whole muscadine grape extract, wherein the bronze muscadine pomace extract and purple whole muscadine grape extract are solvent extracts; and/or an anthocyanin-containing extract from fruit of black currant, blueberry, black raspberry, red raspberry, or blueberry.
- compositions can be provided in a non-beverage food, a beverage, or a liquid or solid dietary supplement.
- the disclosed compositions are provided as a beverage.
- the compositions herein can be fortified with one or more nutrients, especially one or more vitamins and/or minerals.
- vitamins and minerals include iron, zinc, copper, calcium, phosphorous, niacin, thiamin, folic acid, pantothenic acid, iodine, vitamin A, vitamin C, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin D, vitamin E, and vitamin K.
- Commercially available sources of the vitamins and minerals may also be included in the present compositions.
- food and beverage compositions can also include one or more dietary fibers.
- dietary fiber is meant complex carbohydrates resistant to digestion by mammalian enzymes, such as the carbohydrates found in plant cell walls and seaweed or produced by microbial fermentation. Examples of these complex carbohydrates are brans, celluloses, hemicelluloses, pectins, gums and mucilages, seaweed extract, and biosynthetic gums.
- Sources of the cellulosic fiber include vegetables, fruits, seeds, cereals, and man-made fibers (for example, by bacterial synthesis).
- Commercial fibers such as purified plant cellulose or cellulose flour can also be used.
- Naturally occurring fibers include fiber from whole citrus peel, citrus albedo, sugar beets, citrus pulp and vesicle solids, apples, apricots, and watermelon rinds.
- Beverage acidity can be adjusted to and maintained within a desired range by conventional methods such as the use of food grade acid buffers.
- beverage acidity within the above recited ranges is a balance between maximum acidity for microbial inhibition and optimum acidity for the desired beverage flavor.
- the beverage compositions has a pH from about 2 to about 8, such as from about 2 to about 4.5 or about 2.7 to about 4.2.
- Organic as well as inorganic edible acids may be used to adjust the pH of the beverage composition.
- the acids can be present in their undissociated form or as their respective salts, including potassium or sodium hydrogen phosphate, potassium or sodium dihydrogen phosphate salts.
- the acids include citric acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, pyruvic acid or mixtures thereof.
- the acidulant can also serve as an antioxidant to stabilize beverage components. Examples of commonly used antioxidant include but are not limited to ascorbic acid, EDTA (ethylenediaminetetraacetic acid), and salts thereof. E. Methods of making muscadine compositions with antioxidant activity
- Muscadine pomace extract compositions with antioxidant activity can be made by a variety of methods.
- the compositions can be prepared by dissolving, dispersing, or otherwise mixing all components singularly or in suitable combinations together and in water where appropriate, and agitating the mixture with a mechanical stirrer until all of the ingredients have been solubilized or adequately dispersed. Separate solutions or mixtures may be combined. The final mixture can optionally be pasteurized or filled aseptically under appropriate process conditions to promote shelf- stability.
- a muscadine (Vitis rotundifolia) pomace extract having a polyphenol content of at least 2% is combined with resveratrol from a source other than muscadine wherein the resveratrol has a minimum purity of at least 5% (such as at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99%) wherein a ratio of muscadine polyphenols to trans-resveratrol is in the range of 0.1/1 to 10/1 (weight to weight), for example 0.75 to 1, thereby producing a muscadine pomace extract and trans-resveratrol mixture with antioxidant activity.
- the disclosed methods can further include preparing the muscadine pomace extract prior to combining the muscadine pomace extract with trans-resveratrol.
- the muscadine pomace extract is prepared by combining a bronze muscadine pomace extract with a purple muscadine pomace extract.
- the muscadine pomace extract is prepared by extracting a mixture of bronze muscadine pomace and purple muscadine pomace simultaneously; in some instances the pomace is contained in whole purple muscadine grapes such that the extraction can be performed on a mixture of bronze pomace and purple muscadine grapes.
- the muscadine pomace extract can be prepared according to known methods such as crushing, pressing, extraction, filtering (several times), and concentration of the extract by vacuum evaporation followed by freezing.
- the extraction process can further include the use of enzymes for clarifying or facilitating extraction.
- enzymes for clarifying or facilitating extraction.
- a blend of enzymes from Aspergillus niger or pectinase can be used for these purposes.
- Commercial examples include Scottzyme KS and ScottzymePEC5L from Scott Laboratories.
- compositions are prepared by utilizing muscadine pomace extracts with a total phenol concentration of at least 2%.
- muscadine pomace extracts with a total phenol concentration of at least 2%.
- commercially available muscadine extracts with a total phenol concentration of at least 2% can be used to prepare the disclosed compositions with antioxidant activity.
- the composition with antioxidant activity is prepared by combining a muscadine pomace extract and resveratrol with a fruit extract wherein the fruit extract is present in sufficient amounts to substantially increase the solubility of ellagic acid in the muscadine pomace extract.
- Another disclosed embodiment is a method of making an antioxidant composition by combining a muscadine (Vitis rotundifolia) pomace extract with resveratrol from a source other than muscadine, wherein a ratio of muscadine pomace extract polyphenols to trans-resveratrol is in the range of 0.1/1 to 10/1 (weight to weight), and the resulting composition has a polyphenol content of at least 2%.
- the muscadine pomace extract may optionally be concentrated prior to combining it with the resveratrol from a source other than muscadine.
- the muscadine pomace extract and resveratrol are combined with polyphenols from a source other than muscadine (such as a source of anthocyanins), for example from one or more of an extract of elderberry, black currant, blueberry, black raspberry, red raspberry, blackberry, bilberry, cloudberry, chokeberry, gooseberry, grape or purple carrot.
- a source other than muscadine such as a source of anthocyanins
- the method includes combining a mixture of bronze and purple muscadine pomace extract and elderberry fruit extract having a polyphenol content of at least 5% with a Japanese Knotweed root extract.
- the Japanese Knotweed root extract is at least 98% resveratrol
- the muscadine pomace extract is a mixture of bronze and purple muscadine pomace extract.
- the bronze and purple muscadine pomace extracts are combined or otherwise present in a ratio that ranges from 0.1 to 10.
- bronze and purple muscadine pomace extract are solvent extracted, either separately or together, to obtain a mixture of bronze and purple muscadine pomace extract containing solubilized ellagic acid, then the mixture of bronze and purple muscadine pomace extract are concentrated, for example to a solids content of at least 40%.
- the concentrated bronze and purple muscadine pomace extract mixture is combined with resveratrol from a source other than the muscadine pomace extract to obtain an antioxidant mixture, such that the ratio of muscadine pomace extract polyphenols to trans-resveratrol in the antioxidant mixture is in a range of 0.1/1 to 10/1 (weight to weight), and the resulting antioxidant composition has a polyphenol content of at least 2%.
- the antioxidant composition is further combined with polyphenols (such as anthocyanins) from a source other than muscadine, for example by adding a colored fruit extract to the antioxidant composition.
- polyphenols such as anthocyanins
- the anthocyanins are from a source other than the pomace of the muscadine grape, for example anthocyanins from the juice of the muscadine grape introduced during the extraction process.
- the components are combined so that the antioxidant composition includes at least 10% polyphenols, for example up to 35% polyphenols, such as 12-32%.
- compositions have surprisingly synergistic lipophilic antioxidant activity. It is known that oxidative stress is a central mechanism underlying normal aging. It is also known that lipophilic antioxidants are capable of inhibiting various types of skin damage. Based on these observations, methods are disclosed for inhibiting cellular aging, for example by inhibiting or reducing free radical production or activity. In one example, a dose of the composition is administered to a subject in need of antioxidant activity and the dose is sufficient to inhibit or reduce one or more processes associated with cellular aging, such as free radical formation or activity in the subject.
- composition is also useful to treat any disorder associated with oxidative stress.
- the present extracts and combined compositions can be used to reduce, prevent or treat oxidative stress associated with the pathogenesis of chronic inflammatory diseases such as diabetes, cancer, atherosclerosis and other cardiovascular disease as well as with degenerative diseases of the central nervous system or brain, such as Alzheimer's disease and Parkinson's disease.
- Some embodiments of the methods improve skin quality by inhibiting or reducing free radical formation or activity in a skin cell by applying a solution or topical ointment containing a muscadine pomace extract either alone or in combination with additional active ingredients, including without being limited to resveratrol.
- the solution or topical ointment includes a disclosed muscadine pomace extract without resveratrol.
- the solution or topical ointment includes both a disclosed muscadine pomace extract and resveratrol, such as a muscadine pomace extract with a ratio of muscadine polyphenols to resveratrol of about 0.75 to 1 (weight to weight).
- the composition includes polyphenols (such as anthocyanins) from a source other than muscadine, for example from elderberry fruit extract.
- polyphenols such as anthocyanins
- the method can be performed by a clinician or other healthcare provider, or can be designed for home use. The method can reduce the appearance of skin changes associated with aging, visibly reduce human skin wrinkles, and improve the textural quality of skin.
- compositions and kits for improving skin quality can include a disclosed composition (including oral or topical) with antioxidant activity or muscadine extract and one or more additional anti-aging compositions, such as one or more additional antioxidants.
- Muscadine pomace extract compositions may be included in skin quality improvement kits for use in the home or by a clinician such as a physician or aesthetician.
- the kit can include applicators to apply the composition to skin, and instructions for use.
- the instructions can be written or in a digital formal (such as a videotape, DVD or CD) for use with electronic devices such as computers, CD players, mp3 players or DVD players and the like.
- the kit is suitable for use in the home.
- the kit includes the muscadine composition and one or more additional anti-aging compounds, such as another antioxidant (e.g., vitamin C, vitamin E, selenium and/or beta-carotene), either in two separate containers or as a single composition in a single container.
- another antioxidant e.g., vitamin C, vitamin E, selenium and/or beta-carotene
- the disclosed muscadine pomace extracts and compositions can be useful for inhibiting one or more oxidative processes, such as free radical formation associated with cellular events such as cellular aging.
- the compositions can include a pharmaceutical carrier and at least one disclosed muscadine pomace extract either alone or in combination with resveratrol from a source other than muscadine.
- the composition also contains a pharmaceutical carrier and at least one disclosed muscadine pomace extract either alone or in combination with resveratrol from a source other than muscadine.
- the composition also contains a
- the pharmaceutical carrier can be for pharmaceutical or non-pharmaceutical uses, for example a use that may or may not require regulatory approval prior to sale for a particular purpose, such as a drug.
- a "pharmaceutical composition” as used herein refers to a composition that contains a
- a composition is administered orally to a mammalian subject, such as a human, in the form of a non-beverage food, a beverage or a dietary supplement.
- a composition is administered topically to a skin surface of a mammalian subject, such as a human.
- the method includes daily administration of at least 1 mg of the composition to the subject (such as a human subject).
- a human can be administered at least 1 g or at least 10 g of the composition daily, such as 1 g to 5 g daily, 5 g to 10 g daily, for example 7 g daily.
- the subject is administered at least 5 g of the composition including muscadine pomace extract and
- the subject is administered at least 6.3 g orally of such composition.
- the dosage can be administered in divided doses (such as 2, 3, or 4 divided doses per day), or in a single dosage daily.
- the subject is administered the therapeutic composition on a multiple daily dosing schedule, for example on at least two consecutive days, 10 consecutive days, and so forth, and may continue for a period of weeks, months, or years.
- the composition is administered daily for a period of at least 30 days, such as at least 2 months, at least 4 months, at least 6 months, at least 12 months, at least 24 months, or at least 36 months.
- This example illustrates the effects of various specific ratios of bronze to purple pomace extracts on ellagic acid solubility, in both a non-concentrated and a concentrated extract.
- the mixture of bronze and purple extract increases the ellagic acid solubility.
- the resulting extract mixtures were at a IX concentration since no concentration of the separate bronze and purple pomace extracts had taken place.
- a IX concentration typically contained about a 2% solids solution (100 grams of solution equal to 2 grams of dry extract). Approximately 20 milliliters of each ratio was transferred into a respective glass test tube and capped with foil. Samples were heated for 30 minutes at 85 °C, then removed from the heat source and allowed to come to room temperature. Samples were then filtered through 0.45 ⁇ PTFE filter w/GMF and analyzed via HPLC/MS to determine their content of ellagic acid.
- Dietary supplements that can be consumed to prevent or inhibit one or more processes associated with cellular aging are disclosed in WO 2010/014870 and WO 2010/014873, which are incorporated by reference.
- the dietary supplement includes instructions regarding dosages.
- the instructions can indicate that 5 milliliters of a liquid supplement (approximately one teaspoon) can be taken daily before a meal and used as an anti-aging supplement for inhibiting one or more processes associated with cellular aging.
- Example 3
- This example demonstrates the improved antioxidant capacity of a mixture of Japanese knotweed extract and muscadine pomace extract as measured by an Oxygen Radical Absorbance Capacity (ORAC) assay.
- the antioxidant capacity of two botanical extracts separately or in combination was evaluated using the ORAC assay. This assay has been used to measure the antioxidant capacity of a wide range of foods and beverages and is the basis for the data contained in the USDA
- the measured hydrophilic ORAC value of the mixture is similar to the predicted value based on the additive effects of the two extracts. However, the measured lipophilic ORAC value of the mixture is five times greater than the predicted additive value resulting in a 20% increase in the total ORAC value.
- Table 4 shows the results expressed as ORAC value per gram of material (versus per mg polyphenol as shown in Table 3). As displayed in Table 4, the synergistic effects of the muscadine pomace extract and Japanese knotweed root extract mixture in producing lipophilic antioxidant capacity are maintained when values are expressed as ORAC per gram of material: Table 4
- the improved antioxidant activity of the muscadine/resveratrol mixture is not limited to the particular ratios of muscadine and resveratrol tested in this Example 3.
- Elderberry fruit extract contains significant amounts of anthocyanins (but no ellagic acid) and thus experiments were performed to determine whether the soluble ellagic acid content within a muscadine pomace extract (bronze and purple pomace mixture) is influenced by the addition of anthocyanins from elderberry fruit extract.
- This example shows that soluble ellagic acid content within a muscadine pomace extract is significantly increased by the addition of elderberry fruit extract presumably owing to its anthocyanin content.
- Particular amounts tested in this Example are not limitations on the invention itself, but are only included as specific examples of working embodiments within the scope of the claims.
- elderberry fruit extract powder can be at least 20%, 30%, 40%, 50%, 60% or 65% of the combined weight of the elderberry fruit extract powder and the muscadine grape extract powder.
- the weight ratio of anthocyanins to ellagic acid in the combined powders is more than 0.5: 1, 1: 1, 10: 1, or 20: 1, for example in the example provided in Example 4 the ratio weight ratio of anthocyanins to ellagic acid in the combined powders is 24: 1.
- This example also illustrates that the added anthocyanins need not be present in the originally extracted materials, but can also be present in extracts (or even powdered forms of the extracts) that are mixed together after initial extraction.
- ellagic acid concentrations were measured in (1) dried powdered muscadine pomace extract (2: 1 ratio of bronze to purple pomace) and (2) a mixture of the above muscadine pomace extract and dried powdered elderberry fruit extract (containing
- Table 6 shows that the endogenous anthocyanins in the muscadine pomace extract (from the purple pomace) enhanced the percentage of total ellagic acid that becomes solubilized.
- the increasing levels of solids content are attended by increasing content of endogenous
- elderberry fruit extract anthocyanins
- Table 7 shows that the inclusion of additional and exogenous anthocyanins from elderberry fruit extract greatly and unexpectedly enhanced the solubility of the ellagic acid contained within the muscadine pomace extract, such that greater than 50%, 60% or even 70% of the soluble ellagic acid was solubilized. As the levels of solids were increased, the content of total anthocyanins (endogenous and exogenous) also increased and the percentage of soluble ellagic acid rose from 51% to 75% of the total ellagic acid content of the muscadine pomace extract.
- exogenous anthocyanins from elderberry fruit extract enhanced the solubility of ellagic acid at all levels of solids content when compared to the muscadine pomace extract alone.
- the addition of exogenous anthocyanins from elderberry extract enabled the solubilization of 75% of the total ellagic acid content whereas the endogenous anthocyanins from the purple pomace solubilized only 50% of the total ellagic acid content.
- anthocyanins do not need to be present in the original raw materials that are extracted, but this example does not limit the invention to the particular ratios tested in this Example 4.
- muscadine pomace such as pomace-only wherein the juice comprises less than 1% of the weight of the pomace-only.
- the muscadine pomace extracts are derived from combining bronze muscadine pomace extract and purple muscadine pomace extract in various ratios.
- the bronze muscadine pomace extract and purple muscadine pomace extract may be prepared separately before combining them at particular ratios or the bronze muscadine pomace and purple muscadine pomace may be combined at various ratios and then extracted simultaneously.
- the process disclosed in the present example is similar, except the purple muscadine pomace can be contained in a whole muscadine grape that either has all its original juice, or from which no more than 5% or 10% of the juice content has been extracted.
- the whole purple muscadine grape containing a purple muscadine pomace component is therefore used instead of purple muscadine pomace-only.
- the whole bronze muscadine grape may also be substituted for bronze muscadine pomace, in the present example the whole bronze muscadine grape is not used, but only the bronze pomace is used.
- the starting materials in this example are bronze muscadine pomace-only, purple muscadine pomace-only and whole purple muscadine grapes.
- the whole purple muscadine grapes (which include the partially crushed or compressed whole purple muscadine grapes) can be added to bronze muscadine pomace-only or to a mixture of bronze and purple muscadine pomaces-only.
- the mixture of bronze and purple muscadine pomaces-only can be extracted simultaneously with the whole purple grapes.
- anthocyanins found in the whole purple muscadine grape (but not the whole bronze muscadine grape) contribute additional anthocyanins to the extract that unexpectedly solubilize the ellagic acid in the extract to help retain the full polyphenol content of the starting materials.
- a colored (containing anthocyanins) fruit processing waste stream such as blueberry skins can be mixed with bronze muscadine pomace or to a mixture of bronze and purple muscadine pomaces-only in addition to or as a substitute for the whole purple muscadine grapes.
- the blueberry skins are part of a "waste- stream" in this example if they are a by-product of the production of blueberry juice or blueberry puree.
- the blueberry skins would typically be discarded as waste from the blueberry juice and/or puree production process but they can instead be used as an additional source of anthocyanins for the solubilization of ellagic acid in the muscadine pomace extract.
- any source of anthocyanins other than purple muscadine grapes and/or purple muscadine pomace can be used (such as anthocyanin-enriched fruit juice concentrates or extracts).
- Fruit juice concentrate from colored fruits is a particularly rich source of anthocyanins that can be extracted along with the bronze and purple muscadine pomace extract to desirably enhance ellagic acid solubility in the extract.
- the ratios of bronze muscadine pomace to purple muscadine pomace range from 10: 1 (weight to weight) to 1 : 10
- the combined solvent extracts contain extracts comprising, or are prepared from a ratio of whole purple muscadine grapes to bronze muscadine pomace that ranges from 1 :5 to 1 : 12 (weight:weight).
- the solvent extracts are comprised of or are prepared from a ratio of whole purple muscadine grapes to a mixture of bronze and purple muscadine pomaces that ranges from 1 :7 to 1 : 16 (weight:weight).
- the ratio of anthocyanins to ellagic acid in the starting materials ranges from 0.5: 1 to 5: 1 (weight: weight). In other examples the ratio is at least 1 : 1, 2: 1, or 3: 1, and/or is no more than 5: 1 or 4: 1. In other examples, the weight ratio of anthocyanins to ellagic acid in the combined starting materials is more than 0.5: 1, 1 : 1, 10: 1, or 20: 1. In other examples the weight ratio of anthocyanins to ellagic acid in the combined starting materials is no more than 30: 1, 40: 1 or 50: 1.
- ellagic acid in muscadine grapes is unique among grapes ⁇ Vitus species).
- Example 1 As described in Example 1, the addition of purple muscadine pomace-only extract to bronze muscadine pomace-only extract enhanced the solubility of ellagic acid. It has been found that anthocyanins (found in purple, but not bronze, muscadine grapes/pomace) mediated part or all of this effect. As shown in Example 1, a ratio of 2: 1 bronze:purple muscadine pomace-only extracts was sufficient to produce the maximum increase in solubility of ellagic acid in extracts at IX concentration (2% solids), although the method is not limited to the production of only the maximum increase in solubility.
- pomace-only refers to grape pomace of a grape from which at least 95% of the juice content has been removed, while a "whole grape” refers to a grape that contains at least 90% (in some examples at least 95%) of its original juice content.
- Two muscadine pomace extracts were prepared in a pilot-scale trial.
- extract A bronze muscadine pomace-only and purple muscadine pomace-only were extracted separately in hot water and then mixed into a 2: 1 (weight:weight) ratio (bronze muscadine pomace-only extract:purple muscadine pomace-only extract).
- the combined extract was then filtered, fermented, refiltered and concentrated to 40% solids as described previously.
- Extract B was prepared by extracting bronze muscadine pomace-only plus whole purple grapes in a 8.7: 1 (weight:weight) ratio (bronze pomace-only:whole purple grapes) and separately extracting purple muscadine pomace-only and then mixing the resulting extracts in a 15: 1 (weight: weight) ratio such that the ratio of bronze muscadine pomace-only extract, purple muscadine pomace- only extract, and whole purple muscadine grape extract was 13.8: 1: 1.6.
- extract B can also be described as being a mixture of bronze muscadine pomace-only and purple muscadine pomace-only extracts in a 10: 1 ratio (bronze:purple, weight to weight). Extract B was filtered, fermented, refiltered and concentrated to 40% solids as described for extract A.
- Example 1 As shown in Example 1, a mixture of pomace-only extracts at the IX concentration (2% solids) at a ratio of bronze pomace-only extract to purple pomace-only extract greater than 2: 1 (such as 3: 1 or as shown in the example 25:75 Purple/Bronze Ratio), produced negligible increases (4.4%) in ellagic acid solubility. Similar increases (about 10%) in ellagic acid solubility were observed at bronze:purple ratios of 2: 1, 1: 1, and 1:2 suggesting that maximal increases in ellagic acid solubility required at least a 2: 1 ratio of bronze to purple pomace-only extracts (or at least 1 part purple to 2 parts bronze).
- the invention is not limited to addition of a particular amount of whole grape, although particular examples are those in which the mixture of starting materials (pomace and whole grapes) contains a weight ratio of anthocyanins to ellagic acid of at 0.5 to 1, and in other examples that weight ratio is no more than 5: 1.
Abstract
Description
Claims
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MX2015012676A MX366664B (en) | 2013-03-14 | 2014-03-12 | Method of preparing a muscadine pomace extract. |
KR1020157029287A KR20150131270A (en) | 2013-03-14 | 2014-03-12 | Method of preparing a muscadine pomace extract |
CA2904636A CA2904636C (en) | 2013-03-14 | 2014-03-12 | Method of preparing a muscadine pomace extract |
JP2016501617A JP6445518B2 (en) | 2013-03-14 | 2014-03-12 | Method for preparing muscadine impomas extract |
CN201480015151.2A CN105188419B (en) | 2013-03-14 | 2014-03-12 | The method for preparing muscat pomace extract |
PH12015501949A PH12015501949A1 (en) | 2013-03-14 | 2015-09-03 | Method for preparing a muscadine pomace extract |
HK16107264.6A HK1219209A1 (en) | 2013-03-14 | 2016-06-22 | Method of preparing a muscadine pomace extract |
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US13/828,707 US9173916B2 (en) | 2008-07-31 | 2013-03-14 | Method of preparing a muscadine pomace extract |
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US6190716B1 (en) * | 1999-02-17 | 2001-02-20 | Scott O. Galbreath, Jr. | Method for preparing a grape derived product |
WO2005110404A2 (en) * | 2004-04-20 | 2005-11-24 | University Of Maryland | Compositions and methods for enhancing the effectiveness of a chemotherapeutic agent |
US20100004344A1 (en) * | 2007-01-17 | 2010-01-07 | Nbc Nutraceutic Business Consulting | Anti-oxidant dietary composition containing fruits and vegetables, method for preparing the same and use of the composition |
US20110177183A1 (en) * | 2008-07-31 | 2011-07-21 | Ianiro Teodoro T | Method of preparing a muscadine pomace extract |
US20130202725A1 (en) * | 2008-07-31 | 2013-08-08 | Shaklee Corporation | Method of preparing a muscadine pomace extract |
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JP3283553B2 (en) * | 1991-12-10 | 2002-05-20 | 株式会社創研 | Cosmetics |
JP5010077B2 (en) * | 2001-09-05 | 2012-08-29 | ライオン株式会社 | Ellagic acid dispersion and composition for external use |
US20040234671A1 (en) * | 2003-05-20 | 2004-11-25 | Ector Betty J. Houston | Method and system for processing muscadine grape pomace |
SG10201700743PA (en) * | 2006-02-10 | 2017-03-30 | Mannatech Inc | All natural multivitamin and multimineral dietary supplement formulations for enhanced absorption and biological utilization |
EP2033526A1 (en) * | 2007-09-07 | 2009-03-11 | Probelte Pharma, S.A. | Nutritional products comprising pomegranate extracts containing ellagitannins and their use |
WO2010014870A2 (en) * | 2008-07-31 | 2010-02-04 | Shaklee Corporation | Muscadine compositions with improved anti-oxidant activity |
TWI484918B (en) * | 2008-07-31 | 2015-05-21 | Shaklee Corp | Method of preparing a muscadine pomace extract |
WO2011155505A1 (en) * | 2010-06-09 | 2011-12-15 | 花王株式会社 | Manufacturing method for polyphenol composition |
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US6190716B1 (en) * | 1999-02-17 | 2001-02-20 | Scott O. Galbreath, Jr. | Method for preparing a grape derived product |
WO2005110404A2 (en) * | 2004-04-20 | 2005-11-24 | University Of Maryland | Compositions and methods for enhancing the effectiveness of a chemotherapeutic agent |
US20100004344A1 (en) * | 2007-01-17 | 2010-01-07 | Nbc Nutraceutic Business Consulting | Anti-oxidant dietary composition containing fruits and vegetables, method for preparing the same and use of the composition |
US20110177183A1 (en) * | 2008-07-31 | 2011-07-21 | Ianiro Teodoro T | Method of preparing a muscadine pomace extract |
US20130202725A1 (en) * | 2008-07-31 | 2013-08-08 | Shaklee Corporation | Method of preparing a muscadine pomace extract |
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CA2904636A1 (en) | 2014-10-02 |
KR20150131270A (en) | 2015-11-24 |
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CN105188419A (en) | 2015-12-23 |
JP2016518110A (en) | 2016-06-23 |
MY171947A (en) | 2019-11-08 |
TWI621444B (en) | 2018-04-21 |
TW201501721A (en) | 2015-01-16 |
MX2015012676A (en) | 2016-02-16 |
CA2904636C (en) | 2021-05-04 |
PH12015501949A1 (en) | 2016-01-11 |
CN105188419B (en) | 2018-06-19 |
HK1219209A1 (en) | 2017-03-31 |
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