EP1735004A1 - Dietary supplement and method of processing same - Google Patents
Dietary supplement and method of processing sameInfo
- Publication number
- EP1735004A1 EP1735004A1 EP05731006A EP05731006A EP1735004A1 EP 1735004 A1 EP1735004 A1 EP 1735004A1 EP 05731006 A EP05731006 A EP 05731006A EP 05731006 A EP05731006 A EP 05731006A EP 1735004 A1 EP1735004 A1 EP 1735004A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- resveratrol
- small molecules
- biologically active
- composition
- encapsulated composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
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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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
Definitions
- the present invention relates to an encapsulated composition including biologically active small molecules and a method of processing the composition to maintain biological activity and, in particular, to maintain its ability to activate (express) or deactivate (silence) the Sirtuin 1 gene.
- BACKGROUND Resveratrol is a naturally occurring phenolic fungicide produced by some plants in response to injury or fungal infection. It is one of a group of compounds (called phytoalexins) produced in plants during times of environmental stress such as adverse weather or attacks by insects, animals, or pathogenic microorganisms (e.g., fungi). Resveratrol is the parent molecule of a family of polymers called viniferins.
- resveratrol content of a wine depends not only on the type of grape, but also on the length of time the grape skins/seeds are present during the fermentation process (i.e., the amount of time the skins/seeds are left in contact with the juice).
- the resveratrol concentration is significantly (approximately ten times) higher in red wine than in white wine because during red wine production, the skins/seeds are left in contact with the juice for a longer period of time, increasing the a-mount of resveratrol from the skins/seeds.
- the total resveratrol concentration may range from 0.6 to 15 mg/1.
- resveratrol is biologically active, providing several health benefits including cancer prevention, anti-inflammatory properties, and cardiovascular effects.
- Resveratrol functions as a moderate antioxidant, quenching free radical damage linked to several cancers.
- Resveratrol also inhibits the transcription factor NF- ⁇ B, which stimulates genes responsible for cell survival, inflammation, and proliferation of cancer.
- NF- ⁇ B transcription factor
- resveratrol sensitizes them to tumor necrosis factor- ⁇ , which initiates apoptosis (cell death).
- Epidemiological, in vitro, and animal studies also suggest that a high resveratrol intake is associated with a reduced incidence of cardiovascular disease (producing antiplatelet and hypolipidemic effects).
- resveratrol increases the life span of yeast, worms, and mice by slowing cellular degeneration. It has been suggested that 3 to 15 milligrams of resveratrol (the amount present in 3-5 glasses of red wine) is believed to be sufficient to produce the above effects. In order to provide the aforementioned benefits, however, the resveratrol, once produced, must remain biologically active. Maintaining the biological activity of resveratrol is difficult. Resveratrol has a half-life of about one day; consequently, upon exposure to the ambient environment, it completely oxidizes within two days. Once oxidized, its ability to affect biological systems diminishes.
- raw resveratrol When used in dietary supplements, raw resveratrol is genexally produced as an alcohol extract from plant sources (e.g., Giant Knotweed), which is then dried into a powder, encapsulated or put into pill form, which, in turn, are sealed in airtight packaging.
- plant sources e.g., Giant Knotweed
- resveratrol as a raw material generally exhibits effective biological activity, when the resveratrol powder is mixed and blended in the process of encapsulation, it is exposed to oxygen, eventually losing some if not all of its biological activity " before it can reach the consumer.
- HPLC high performance liquid chromatography
- resveratrol may lack significant biological activity.
- resveratrol may exhibit certain antioxidant, estrogen-like, cholesterol-controlling effect s, it loses its genomic biological activity.
- Enzymatic biological activity e.g., the ability to activate and deactivate human enzymes
- has been demonstrated only in preserved resv ⁇ eratrol molecules e.g., as the molecules exist is in wine or in research-grade resveratrol.
- a dietary supplement including stabilized resveratrol that retains its biological activity and, in particular, its enzymatic biological activity.
- an object of the present invention is to provide an encapsulated composition including a biologically active resveratrol, and to a method of encapsulating the composition such that the resveratrol remains biologically active when ingested by a consumer. It is another object of the invention to provide a method of encapsulating small molecule plant polyphenols capable of stimulating enzymatic activity such that the enzymatic activity is preserved. It is a further object of the invention to provide an encapsulated composition having a genomic effect, including activation and/or deactivation of human enzymes.
- a dietary supplement including an encapsulated resveratrol composition in which the efficacy of the resveratrol is maintained by preventing its exposure to oxygen during the encapsulation process.
- a still further object of the present invention is to prevent metal-induced oxidation of dietary supplement ingredients during the processing and packaging of the supplement .
- the embodiments of the present invention provide an encapsulated composition including (1) small molecules of a plant or synthetic source in their biologically active form and (2) optionally at least one of (a) an emulsifier, (b) an antioxidant, and (c) a chelating agent.
- the embodiments further provide a method of encapsulating a compo sition including the steps of (1) deriving material including biologically active small molecules derived from a plant source or formed synthetically and (2) encapsulating the material dn a substantially oxygen-free environment.
- deriving material including biologically active small molecules derived from a plant source or formed synthetically
- encapsulating the material dn a substantially oxygen-free environment.
- the biologically active small molecules of plant or synthetic source may include small molecule plant polyphenols such as resveratrol, quercetin, fisetin, butein, piceatonol, isoliquiritigenin, which, by virtue of their small size and molecular weight, are able to pass through cell walls, enter the cell nucleus, and alter certain gene-controlled mechanisms.
- a preferred small molecule plant polyphenol is resveratrol (molecular weight 228.25), which has been shown to activate Sirtuin-1 controlled enzyme activity better than other polyphenols.
- Resveratrol may be formed synthetically or derived naturally from sources such as plant material, including grapes and knotweed.
- the resveratrol includes the trans stereoisomer of the molecule, namely, trans-3,4' -,5 trihydoxystilbene, which possesses the following chemical structure:
- the small molecules of plant or synthetic source preferably remain biologically active for time periods after which the molecules would naturally become biologically inactive due to degradative processes such as oxidation.
- resveratrol possesses a half-life of approximately one day; consequently, it typically loses significant biological activity within two days of exposure to ambient conditions and during processing of dietary supplements.
- Another embodiment of the invention relates to a method of encapsulating small molecules of plant or synthetic source including the steps of (1) deriving mate_rial including small molecules of plant or synthetic source; (2) encapsulating the material in a substantially oxygen-free environment; and (3) optionally adding (a) a chelating agent, (b) an.
- the material including small molecules may be derived naturally or synthetically formed.
- the material moreover, should be biologically active.
- Biological activity is intended to include the ability of the small molecules to pass through -a cell wall, enter the cell nucleus, and beneficially alter gene-controlled enzymes, in particular, the Sirtuin 1 enzyme.
- the biologically active material is naturally derived, i.e., derived from at least one natural source such as plants (or parts thereof, such as tubers or fruit (including pulp and skins) from the plant).
- One preferred source is the seeds and/or skins of grapes, such as Nitis vinifera, Nitis labrusca, and Nitis rotundifolia.
- Another preferred source is Polygonum (Giant Knotweed) and, in particular, 1 -polygonum cuspidatum (a species of giant knotweed).
- the natural derivation process includes those processes generally known in the art, including an extraction process in which a solvent is used to extract the small molecules from a natural source.
- the solvent includes aqueous solvents, organic solvents, and mixtures thereof.
- the solvent may include, but is not limited to, alcohols sixch as ethanol.
- the extracted small molecule material may include aqueous or organic solvent extracts of plants (or parts thereof), fruit juices (e.g., grape juice), and fermented liquors (e.g. wine) produced from plants or fruit juice, or mixtures of any of the foregoing.
- the extracted material may further include inert plant material naturally removed during the extraction process.
- the extracted material may be processed (physically and/or chemically) to remove the solvent and increase the concentration of the small molecules.
- the solvent may be removed from the extract (e.g., by drying), leaving a dried powder.
- the derived material including small molecules is then encapsulated in a substantially oxygen-free environment.
- the phrase "substantially oxygen-free" is intended to include environments having less than less than about 100 parts per million oxygen.
- the encapsulation process would take place immediately after the extraction or formation of the small molecules and be shielded from exposure to light, heat, and oxygen.
- the material including small molecules may be stored in a substantially oxygen-free environment until encapsulated.
- the encapsulation process includes the steps of (1) providing a capsule including a head portion and a body portion; (2) at least partially filling the body portion with the material including biologically active small molecules; (3) axially positioning th-e head portion over the body portion such that the portions at least partially overlap; and (4) forming a fluid tight (air and liquid impermeable) seal along the overlapping portions.
- the material comprising the capsule portions is not particularly limited.
- the capsule portions comprise material possessing a low oxygen transmission rate.
- the capsule portions comprise a material having an oxygen transmission rate (as measured by ASTM D3985) of less than about 165 cm 3 /rrx 2 /day for 100 ⁇ m, more preferably less than about 4 cm 3 /m 2 /day for 100 ⁇ m, and most preferably less than about 1 cm /m /day for 100 ⁇ m.
- Exemplary materials comprising the capsule portions include, but are not limited to, an ingestible material such as gelatin, hydroxypropyl methylcellulose, or starch.
- the material may include- e gelatin having an oxygen transmission rate of about 3.5 cm 3 /m 2 /day for 100 ⁇ m.
- the resulting capsules may include hard gelatin capsules or soft gelatin capsules having an oxygen transmission rate of up to about 0.04 cm 3 /capsule/day (ASTM D3985 at 27°C and rel. humidity of 50%).
- opaque capsules are highly preferred. This can be achieved- by adding pigment such as titanium dioxide to the capsule material formulation. Titanium- dioxide is inert and possesses a high molecular weight, which prevents it from being absorbed into blood circulation when ingested.
- Opaque capsules function to prevent the degradation of the resveratrol-containing composition by light degenerative processes such as pho-tooxidation.
- a commercially available, opaque capsule having low oxygen permeability is available from Capsugel (Greenwood, SC— www.capsugel.com), sold under the trade name Licaps®.
- the system used to encapsulate the composition including biologically active small molecules material must create a fluid-tight (air and liquid impermeable) seal a-round capsule portions.
- a particularly preferred encapsulation system and process is disclosed in WO 01/08631 Al , incorporated herein by reference in its entirety. In this system and associated process, a capsule head portion and a capsule body portion are placed in a filliixg chamber. The capsule body portion is filled with the desired dosage material, and the cap sule portions are then telescopically joined such that the head portion partially overlaps the body portion.
- a sealing liquid including a solvent is applied in the gap formed between the overlapping sections, and the capsule is dried to remove the solvent and form a fluid-tight seal.
- the encapsulation process occurs in a substantially oxygen-free environment, hi addition, it is preferred the encapsulation process take place in a darkened (substantially light free) environment.
- small molecules such as resveratrol lose their biological activity upon exposure to light and/or oxygen (due, e.g., to oxidation processes). Consequently, the composition containing small molecules should be mixed and/or encapsulated in a system including airtight and darkened mbcing and filling chambers having a substantially oxygen-free environment.
- Oxygen may be removed using a vacuum, replacing the oxygen within the system with an inert gas flush, or a combination thereof.
- the system can be purged of oxygen using a controlled nitrogen blanket.
- the system is kept substantially oxygen free through the use of a nitrogen flush during the encapsulation process.
- a nitrogen purge may also be used to remove oxygen from each individual capsule. Specifically, prior to sealing, a positive pressure can be applied to each capsule to replace any oxygen present within the capsule with nitrogen. Upon sealing, a nitrogen bubble remains within the capsule.
- a commercially available enc apsulation system capable of filling capsules in a substantially oxygen-free and light-free environment is available from Capsugel (Greenwood, SC— www.capsugel.com), sold under the trade name CPS 1000 Capsule Filling Machine.
- the above process produces an encapsulated composition suitable as an orally ingestible dosage of biologically active small molecules (e.g., resveratrol).
- the composition including the biologically active small molecules may include up to 100% " by weight small molecule material.
- the composition may contain additives to stabilize the biological activity of the small molecules, to improve their biological availability upon ingestion, and/or to improve their absorption and passage through biological barriers.
- the composition may include one or more of (1) a chelating agent, (2) an antioxidant, and (3) an emulsifier.
- a chelating agent (chelator) may be added to further preserve the biological activity of the small molecule material by preventing metal-induced oxidation.
- Oxygen in the presence of metals such as iron, may be reduced to hydrogen peroxide by phenols.
- Hydrogen peroxide in turn, may oxidize small molecules such as resveratrol and quercetin.
- Metals such as iron have special oxygen transfer properties, which, when combined with hydrogen peroxide, produce a more reactive and destructive form of iron, namely, Fe 3+ .
- an iron II (Fe 2+ ) salt reacts with hydrogen peroxide to form an iron III (Fe 3+ ) salt and a highly reactive hydroxyl radical. Consequently, it is believed obstructing the Fenton reaction can bio ck the oxidation of small molecules derived from a plant or synthetic source (e.g., resveratrol and quercetin).
- a chelating agent e.g., a metal chelator such as NDGA (nordihydroguaiaretic acid: l,4-bis[3,4-dihydroxyphenyl]2.,3dimethylbutane) functions to counter the oxidation of resveratrol by hydrogen peroxide.
- NDGA functions, in part, by converting the more reactive form of iron (Fe 3+ ) to its less reactive form (Te 2+ ).
- Fe 3+ more reactive form of iron
- Te 2+ less reactive form
- Phytic acid also called inositol hexaphosphate
- Phytic acid is an iron-binding molecule typically used as a food preservative due to its ability to block iron-driven oxidation, similar to the action of NDGA.
- phytic acid functions as a metal chelator that minimizes, if not prevents, the occurrence of the Fenton reaction.
- Phytic Acid is a naturally derived material that conies from whole grains and seeds of plant sources, including corn, wheat, rice, soybean, sesame, and oat.
- the amount of chelating agent is not particularly limited, so long as it is sufficient to bind metals within the composition.
- the chelating agent may be present in a range of about 0 - 25% by weight, more preferably in a range of about 5 - 15% by weight, and most preferably in a range of about 7-10% by weight.
- an antioxidant may be added to the composition not only to provide additional biological activity to the composition, but also to prevent the degradation of the composition caused by oxidation.
- the normal processes o oxidation (plus a minor contribution from ionizing radiation) produce highly reactive free radicals. These can readily react with and damage other molecules. In some cases, the body uses this to fight infection, i other cases, the damage may continue to the body's own cells.
- the composition may include a phenolic antioxidant such as a flavonoid.
- the composition may include a flavanol compound such as quercetin.
- Quercetin in addition to having antioxidant properties, is a small molecule plant polyphenol that exhibits enzymatic biological activity (incli ⁇ ding sirtuin enzyme activation) similar to that of resveratrol. Quercetin also functions to prohibit the sulfation of resveratrol once ingested.
- the amount of antioxidant in the composition is not particularly limited.
- the antioxidant may be present in a range of about 0 - 50%) by weight, more preferably in a range of about 15 - 35% by weight, and most preferably in a range of about 20 - 30 % by weight.
- An emulsifier may be added to the composition to enhance the bioavailability of the composition (i.e., to enhance the ability of the body to absorb and use the small molecules once ingested).
- the emulsifier may comprise a phospholipid- such as lecithin (phosphatidylcholine).
- the amount of emulsifier present in the composition is preferably in the range of about 0 - 50% by weight, more preferably in an amount of 15 - 45% by weight, and most preferably in a range of about 25% > - 40% by weight.
- the amount of nxaterial including small molecules is preferably in a range of about 1 - 70%> by weight, m-ore preferably in a range of about 5 - 30%) by weight, and most preferably in an amount of about 10 - 20%o by weight.
- the amount of resveratrol available for oral consumption is preferably in the range of about 3 to 70 mg.
- the additives may be combined with the material including small molecules at any tim-e before the capsule is sealed.
- the material including small molecules resveratrol material may be extracted, dried, mixed with an additive, and then encapsulated.
- the additives may be placed in the capsule before or after the material includin-g small molecules is placed in a capsule.
- the resulting capsules may be packaged to prevent degradation of the small molecules in the event a capsule ruptures.
- the capsules may be individually enclosed in a blister pack including an airtight compartment.
- a substantially oxygen-free environment can be maintained within the container by adding an oxygen absorbing packet capable of maintaining the amount of free oxygen within the bottle to less than about 100 parts per million or less.
- any packaging used is flushed with nitrogen before sealed.
- the present invention comprises a practical, economic method of maintaining the biological activity of components present in a composition containing small molecule plant polyphenols such as resveratrol by preventing the degradation of the components.
- inventive compositions and processes are believed to maintain the biological activity of the composition by preventing oxidation caused by oxidizing metals (i.e., metals naturally found in dietary supplement formulas, or metals provided in trace amounts as part of herbal extracts, or metals on surfaces of formulation, mixing and encapsulation machinery), which can trigger or accelerate the oxidation (spoilage) of the composition and destroy the biological activity of the components.
- oxidizing metals i.e., metals naturally found in dietary supplement formulas, or metals provided in trace amounts as part of herbal extracts, or metals on surfaces of formulation, mixing and encapsulation machinery
- This is further achieved by stabilizing the ingredient(s) in question against metal-induced oxidation through the addition of a chelating agent, and, as noted above, performing the handling and encapsulation of the dietary supplement in a substantially oxygen-free environment.
- the small molecules present in the inventive encapsulated compositions maintain biological activity for substantial time periods after the normal life of the small molecules. For example, under ambient conditions, the half-life of resveratrol is approximately one day. In the manufacture and distribution of dietary supplements, however, it typically takes several weeks after encapsulation before the composition reaches a consumer.
- the embodiments of the instant invention form dietary supplements including small molecules that remain biological active upon reaching the consumer. In particular, it forms dietary supplements including resveratrol capable of enzymatic biological activity.
- the small molecules remain biologically active for at least about four months after encapsulation, more preferably at least about eight months after encapsulation, and most preferably at least about one year or indefinitely.
- biologically active small molecules derived from a plant source or formed synthetically, as well as compositions containing biologically active small molecules, provide various health benefits.
- biologically active small molecules are capable of enzymatic activity, activating human "longevity genes".
- longevity genes a class of regulatory genes that are shared by almost all living organisms. These genes function as a feedback system to enhance survival during times of stress, such as during drought or famine. Once activated, these longevity genes induce defensive changes at the cellular level, such as slowing metabolism and enhancing cellular respiration, to help the body adapt to an adverse environment.
- One particular stress the restriction of calories provided to an organism, extends lifespan in numerous species by activating enzymes (or proteins) called sirtuins (a family of deacetylases).
- sirtuins (Silent Information Regulator enzymes) act as longevity genes due to their ability to control the rate of aging in organisms such as such as yeast, roundworms, and fruit flies.
- SIR2 Silicon Information Regulator gene 2
- SIR2 Small Information Regulator gene 2
- yeast cells which is homolgous to Sirtuin 1 in humans, becomes activated when under biological stress.
- aging is directly linked to SIR2 activity.
- Overexpression of SIR2 increases DNA stability, increases silencing and suppression of rDNA recombination, speeds cellular repairs, and enhances mother-daughter cell replicative lifespan.
- Sirtuin 1 which is located in the nucleus, is a human sirtuin- having the greatest homology to SIR2. Human sirtuins appear to act as guardian enzymes that protect cells and enhance cellular survival. SIRTl, for example, has been shown to suppxess the p53 enzyme system normally involved in suppressing tumor growth and instigating cell death (apoptosis). Inhibiting the activity of a tumor suppressor gene may not be readily deemed to be beneficial until it is recognized that SIRTl inhibition prevents the cycle of premature aging and apoptosis normally.
- SIRTl By suppressing p53 activity, SIRTl prevents the cycle of premature aging and apoptosis normally induced when cellular DNA is dam-aged or stressed, thus giving cells enough time to repair any damage and prevent unnecessary cell death.
- small molecules such as resveratrol are capable of activating SIR2.
- resveratrol decreases rDNA recombination and extends lifespan, similar to that which occurs during calorie restriction.
- Small molecules such as resveratrol moreover, have been shown to activate SIRTl in human cells, enhancing the survival rate of cells stressed by irradiation.
- a dietary supplement including a composition formed and encapsulated using the above-described process, to activate longevity genes, namely the sirtuin enzymes SIR2 and SIRTl.
- the activation of the SIRTl enzyme increases the survival rates of human cells, suppressing apoptosis.
- the encapsulated compositions including small molecules are suitable for use in making dietary supplements, as well as prescription medications.
- Example Small molecules in the form of resveratrol were obtained "via ethanol extraction from vitis vinifera and polygonum cuspidatum. The ethanol was remo ed, and the resulting extract comprised approximately 25%o vinis vinifera skin resveratrol and 25% polygonum cuspidatum resveratrol, with the remainder comprising non-resvexatrol, inert plant material.
- the biological activity of the resveratrol in the extract was confirmed using a SIRTl Fluorescent Activity Assay/Drug Discovery Kit AK-555 (available from Biomol® Research Laboratories, hie; Plymouth Meeting, PA; www.biomol.com).
- the extract was kept in a nitrogen environment and added to a mixture including approximately 25 %> by weight quercetin; 33%o by weight lecithin; and 9% phytic acid (in the form of rice bran extract). The remainder of the composition included approximately 33%> by weight resveratrol extract.
- the resulting slurry was placed into a capsule-filling machine. Individual dosages were encapsulated in gelatin capsules tinted with titanium oxide (Licaps® capsules available from Capsugel; Greenwood, SC; www.capsugel.com).
- the dosages were encapsulated in a substantially oxygen- free environment using a capsule-filling machine continually flushed with nitrogen (the Capsugel CFS 1000 Capsule Filling and Sealing Machine, available from Capsugel; Greenwood, SC; www.capsugel.com).
- Each resulting capsule included at least 15 mg resveratrol, 100 mg lecithin, 75 mg quercetin, and 25 mg pb-ytic acid.
- These capsule samples were stored under ambient conditions for approximately eight months.
- the samples were tested for biological activity by determining whether each sample could activate sirtuin enzymes and, in particular, whether the samples stimulated SIRTl catalytic activity. The samples were tested four months and eight months after encapsulation.
- Tests were performed using a SIRTl Fluorescent Activity Assay/Drug Discovery Kit -A-K-555 (available from Biomol® Research Laboratories, Inc.; Madison Meeting, PA; xyww.biomol.com). Upon testing, it was determined that the resveratrol contained within the samples was biologically active, stimulating SIRTl activity, producing up to about an eight-fold stimulation in enzymatic activity compared to when no resveratrol is present. Similarly, the biological activity of the quercetin was tested, and it was determined that the encapsulated quercetin maintained biological activity (i.e., the ability to stimulate SIRTT activity compared to when no quercetin is present).
- the invention is comprised of multiple methods of manufacturing and preserving maximum biological activity (including having the ability to activate sirtuin enzymes) and the structural form of plant polyphenols and other dietary supplement ingredients against degradation (via, e.g., oxidation), including but not limited to tlxe manufacture of raw material and its placement into capsules.
- the above-described method economically produces an encapsulated composition including concentrated resveratrol having properties similar to that made available in research-grade resveratrol or resveratrol as it exists in a sealed wine bottle.
- the present invention is useful in manufacturing encapsulated formulations that can be ingested as a dietary supplement.
- the capsule may be of any shape and size, and may be made breakable to enable the removal of the composition from the capsule.
- the capsule material moreover, may comprise any material having a low oxygen transmission rate.
- the comp ositions including small molecules may exist as a dried powder, a liquid suspension, a gel, or a slurry.
- the formulations may include other additives, fillers, etc. suitable for dietary supplement formulations, so long as the additives do not degrade the biological activity or the bioavailabilty of the material including small molecules.
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- Animal Behavior & Ethology (AREA)
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- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
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- Nutrition Science (AREA)
- Botany (AREA)
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- Biotechnology (AREA)
- Medical Informatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Microbiology (AREA)
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- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Biochemistry (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
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- Medicines Containing Plant Substances (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US55995504P | 2004-04-07 | 2004-04-07 | |
PCT/US2005/010466 WO2005099761A1 (en) | 2004-04-07 | 2005-03-28 | Dietary supplement and method of processing same |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1735004A1 true EP1735004A1 (en) | 2006-12-27 |
EP1735004A4 EP1735004A4 (en) | 2011-11-09 |
Family
ID=35149781
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05731006A Withdrawn EP1735004A4 (en) | 2004-04-07 | 2005-03-28 | Dietary supplement and method of processing same |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1735004A4 (en) |
JP (1) | JP4963670B2 (en) |
KR (1) | KR101213141B1 (en) |
CN (1) | CN1956733B (en) |
WO (1) | WO2005099761A1 (en) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007008548A2 (en) * | 2005-07-07 | 2007-01-18 | Sirtris Pharmaceuticals, Inc. | Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders |
WO2007096078A1 (en) * | 2006-02-24 | 2007-08-30 | Dsm Ip Assets B.V. | Use of resveratrol and derivatives thereof for promoting the wellness state in mammals |
DE202007019029U1 (en) * | 2007-03-09 | 2010-04-15 | Wilhelm, Hermann-Josef | Basic material from a plant |
WO2009039195A1 (en) * | 2007-09-20 | 2009-03-26 | Resveratrol Partners, Llc | Resveratrol-containing compositions for modulating gene product concentration or activity |
WO2009082459A2 (en) * | 2007-12-24 | 2009-07-02 | Natrol, Inc. | Anti-aging composition containing resveratrol and method of administration |
DE102008035285A1 (en) * | 2008-07-02 | 2010-01-07 | Hermann-Josef Wilhelm | Extraction of active substances from group of anthraquinone and phenols and/or polyphenols from a plant, where new plant variety Igniscum (CPVO 2007/0149) or Candy (CPVO 2007/1958) registered to variety protection is requisitioned as plant |
US9173916B2 (en) | 2008-07-31 | 2015-11-03 | Shaklee Corporation | Method of preparing a muscadine pomace extract |
TWI448250B (en) * | 2008-07-31 | 2014-08-11 | Shaklee Corp | Muscadine composition with improved anti-oxidant activity |
US9132162B2 (en) | 2008-07-31 | 2015-09-15 | Shaklee Corporation | Muscadine compositions with anti-oxidant activity |
CN103623135B (en) | 2008-07-31 | 2015-12-09 | 嘉康利公司 | The preparation method of Vitis rotundifolia pomace extract |
MY155394A (en) * | 2008-07-31 | 2015-10-15 | Shaklee Corp | Muscadine composition with improved anti-oxidant activity |
DE102008037337A1 (en) * | 2008-08-11 | 2010-02-25 | Hermann-Josef Wilhelm | Process for the preparation of active substances, in particular phenols from a plant |
JP5916321B2 (en) * | 2011-09-05 | 2016-05-11 | 株式会社山田養蜂場本社 | Transresveratrol-containing composition |
US8916528B2 (en) | 2011-11-16 | 2014-12-23 | Resveratrol Partners, Llc | Compositions containing resveratrol and nucleotides |
US10335433B2 (en) * | 2013-04-10 | 2019-07-02 | Mimedx Group, Inc. | NDGA polymers and metal complexes thereof |
JP6343126B2 (en) * | 2013-05-14 | 2018-06-13 | 森永製菓株式会社 | Method for stabilizing stilbenes contained in plant extract or solution thereof, and plant extract containing stilbenes or solution thereof |
JP6209360B2 (en) * | 2013-05-14 | 2017-10-04 | 森永製菓株式会社 | Piceatannol solution and method for stabilizing piceatannol solution |
US9446142B2 (en) * | 2013-05-28 | 2016-09-20 | Mimedx Group, Inc. | Polymer chelator conjugates |
JP2019529348A (en) | 2016-07-19 | 2019-10-17 | シャクリー コーポレイション | Muscadine topical composition with low content of condensed tannin molecules |
KR101990060B1 (en) | 2017-07-21 | 2019-09-30 | 주식회사 송이산업 | Method for preparation of resveratrol nano-capsue and the nano-capsule therefrom |
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US4963385A (en) * | 1989-06-02 | 1990-10-16 | Nabisco Brands, Inc. | Stabilized emulsions containing highly unsaturated oils |
US6190716B1 (en) * | 1999-02-17 | 2001-02-20 | Scott O. Galbreath, Jr. | Method for preparing a grape derived product |
WO2003013566A1 (en) * | 2001-08-03 | 2003-02-20 | Shaklee Corporation | High molecular weight, lipophilic, orally ingestible bioactive agents in formulations having improved bioavailability |
US20030133945A1 (en) * | 2002-01-11 | 2003-07-17 | Farley Michael Donald | Natural food supplement |
WO2003086267A2 (en) * | 2002-04-10 | 2003-10-23 | Miller Fred H | Multi-phase, multi-compartment capsular system |
WO2004022220A1 (en) * | 2002-09-04 | 2004-03-18 | Southwest Research Institute | Microencapsulation of oxygen or water sensitive materials |
WO2004105517A1 (en) * | 2003-05-27 | 2004-12-09 | Dsm Ip Assets B.V. | Novel nutraceutical compositions and use thereof |
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JP2560051B2 (en) * | 1987-12-11 | 1996-12-04 | 扶桑薬品工業株式会社 | Light-shielding capsule formulation |
US6184248B1 (en) * | 1996-09-05 | 2001-02-06 | Robert K. K. Lee | Compositions and methods for treatment of neurological disorders and neurodegenerative diseases |
EA002760B1 (en) * | 1996-09-20 | 2002-08-29 | Дзе Ховард Фаундейшн | Plant-derived flavonol-containing food supplements and methods of use |
DE19714450A1 (en) * | 1997-04-08 | 1998-10-15 | Schwabe Willmar Gmbh & Co | Stable extract of Hypericum perforatum L., process for its preparation and pharmaceutical preparation |
PT948965E (en) * | 1997-07-11 | 2004-08-31 | Toray Industries | STABILIZABLE MEDICINAL COMPOSITIONS CONTAINING A 4,5-EPOXYMORPHINAN DERIVATIVE |
US6251478B1 (en) * | 1999-12-22 | 2001-06-26 | Balchem Corporation | Sensitive substance encapsulation |
JP2003119127A (en) * | 2001-10-10 | 2003-04-23 | Kanegafuchi Chem Ind Co Ltd | Stable preparation of reduced coenzyme q |
-
2005
- 2005-03-28 JP JP2007507358A patent/JP4963670B2/en not_active Expired - Fee Related
- 2005-03-28 EP EP05731006A patent/EP1735004A4/en not_active Withdrawn
- 2005-03-28 WO PCT/US2005/010466 patent/WO2005099761A1/en not_active Application Discontinuation
- 2005-03-28 CN CN2005800107544A patent/CN1956733B/en not_active Expired - Fee Related
-
2006
- 2006-10-02 KR KR1020067020587A patent/KR101213141B1/en not_active IP Right Cessation
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US4963385A (en) * | 1989-06-02 | 1990-10-16 | Nabisco Brands, Inc. | Stabilized emulsions containing highly unsaturated oils |
US6190716B1 (en) * | 1999-02-17 | 2001-02-20 | Scott O. Galbreath, Jr. | Method for preparing a grape derived product |
WO2003013566A1 (en) * | 2001-08-03 | 2003-02-20 | Shaklee Corporation | High molecular weight, lipophilic, orally ingestible bioactive agents in formulations having improved bioavailability |
US20030133945A1 (en) * | 2002-01-11 | 2003-07-17 | Farley Michael Donald | Natural food supplement |
WO2003086267A2 (en) * | 2002-04-10 | 2003-10-23 | Miller Fred H | Multi-phase, multi-compartment capsular system |
WO2004022220A1 (en) * | 2002-09-04 | 2004-03-18 | Southwest Research Institute | Microencapsulation of oxygen or water sensitive materials |
WO2004105517A1 (en) * | 2003-05-27 | 2004-12-09 | Dsm Ip Assets B.V. | Novel nutraceutical compositions and use thereof |
Non-Patent Citations (1)
Title |
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See also references of WO2005099761A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP2007532543A (en) | 2007-11-15 |
KR101213141B1 (en) | 2012-12-17 |
JP4963670B2 (en) | 2012-06-27 |
KR20070041427A (en) | 2007-04-18 |
WO2005099761A1 (en) | 2005-10-27 |
EP1735004A4 (en) | 2011-11-09 |
CN1956733A (en) | 2007-05-02 |
CN1956733B (en) | 2012-10-10 |
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