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WO2009120217A1 - Compositions cosmétiques destinées à l’inhibition d’espèces d’oxygène réactif - Google Patents

Compositions cosmétiques destinées à l’inhibition d’espèces d’oxygène réactif Download PDF

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Publication number
WO2009120217A1
WO2009120217A1 PCT/US2008/058697 US2008058697W WO2009120217A1 WO 2009120217 A1 WO2009120217 A1 WO 2009120217A1 US 2008058697 W US2008058697 W US 2008058697W WO 2009120217 A1 WO2009120217 A1 WO 2009120217A1
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Prior art keywords
arnox
cosmetic
composition
skin
aging
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Ceased
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PCT/US2008/058697
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English (en)
Inventor
Dale Kern
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Nu Skin International Inc
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Nu Skin International Inc
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Priority to PCT/US2008/058697 priority Critical patent/WO2009120217A1/fr
Publication of WO2009120217A1 publication Critical patent/WO2009120217A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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)
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • 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
    • 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)
    • A61K36/79—Schisandraceae (Schisandra family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/522—Antioxidants; Radical scavengers

Definitions

  • the invention relates to extracts of natural products useful in sequestering serum aging factors that may be administered internally or topically. More particularly, the invention relates to agents and compositions thereof for use cosmetically to inhibit or ameliorate aging-related oxidation and methods for their use as skin care products.
  • NOX The plasma membrane NADH oxidase
  • NADH hydroquinone
  • CLOX hydroquinone
  • tNOX A hormone-insensitive and drug-responsive form of the NOX designated tNOX has been described that is specific for cancer cells. For example, see U.S. Patent No. 5,605,810, which is incorporated herein by reference in its entirety.
  • arNOX NADH oxidase
  • the aging-related isoform of NADH oxidase (arNOX) is a member of this family of proteins.
  • the circulating form of arNOX increases markedly in human sera and in lymphocytes of individuals, especially until the age of 65.
  • the arNOX protein is uniquely characterized by an ability to generate superoxide radicals, which may contribute significantly to aging-related changes including atherogenesis and other action-at-a-distance aging phenomena.
  • Activity of arNOX in aging cells and in sera has been described previously. See, for example, PCT Pub. App. No. WO 00/57871, which is incorporated by reference in its entirety herein.
  • ROS reactive oxygen species
  • co-enzyme Q ubiquinone
  • PCT Pub. App. Nos. WO 00/57871, WO 01/72318, and WO 01/72319 the disclosures of which are incorporated herein by reference in their entirety.
  • co-enzyme Q is not completely satisfactory for several reasons: it is costly, it oxidizes easily losing its efficacy, and preparations containing coenzyme Q must be specially packaged to prevent loss of function.
  • agents and methods currently exist which may inhibit arNOX activity, challenges still exist. Accordingly, it would be an improvement in the art to augment or even replace previously disclosed agents and techniques with the agents and techniques that inhibit arNOX but that are also non-toxic and naturally occurring.
  • the skin in particular is vulnerable to damage by reactive oxygen species.
  • the skin is composed of two major layers.
  • the stratum corneum, or epidermis is the top layer and forms a protective covering for the skin and controls the flow of water and substances in and out of the skin.
  • the dermis is the lower level of the skin and provides the strength, elasticity and the thickness to the skin.
  • the main cell type of the dermis is fibroblasts, which are responsible for synthesis and secretion of all the dermal matrix components such as collagen, elastin and glycosaminoglycans. Collagen provides the strength, elastin the elasticity, and glycosamino- gl yeans the moistness and plumpness of the skin.
  • the skin In addition to being damaged by reactive oxygen species the skin is subject to various damaging stressors.
  • the skin may be damaged or abused by many factors in the environment. Some are naturally occurring such as UV radiation from the sun, wind and even mechanical insults such as cuts, scrapes and the like. Other, man-made insults also occur daily. These include the use of soaps, emulsifier-based cosmetics, hot water, organic solvents, air conditioning and central heating. Further, other insults to the skin may result from or be part of dermatological disorders or the normal aging process (chronoaging), which may be accelerated by exposure of skin various external stressors (e.g. photoaging).
  • Symptoms of aging skin include dryness, itchiness, thinning or thickening of the skin, wrinkles and fine lines, areas of hyperpigmentation commonly referred to as liver spots and areas underneath the skin where blood vessels have ruptured (telangietasias).
  • Anti-aging cosmetic and medical products treat or delay the visible signs of actual aging and weathered skin such as wrinkles, lines, sagging, hyperpigmentation and age spots are desirable.
  • most cosmetic or medicinal products do not address causes of such symptoms e.g., the production and build up of arNOX related radicals derived from ROS. Accordingly, there is a demand for effective natural skin treatments and preventative compositions and methods for using the same.
  • the present invention is directed to naturally occurring agents which may be administered either internally or topically which specifically inhibit arNOX and ameliorate some of its aging related effects.
  • agents can take the form of isolated agents or plant extracts.
  • arNOX inhibitory agents can be used alone, they may also be used as compositions comprising multiple arNOX inhibitory agents and/or formulations including compounds having other beneficial effects on the body.
  • the inventors have found that by adding arNOX inhibitors to cosmetics, the inhibitors can have beneficial effects that augment the normal skin care regimen.
  • the invention comprises a composition useful for ameliorating the effects of aging comprising an effective amount of at least one arNOX inhibitory agent.
  • the arNOX inhibitory agent is effective in decreasing the effects of aging.
  • the invention further includes a cosmetically or pharmaceutically acceptable carrier.
  • the arNOX inhibitory agent is present in a plant extract.
  • the arNOX inhibitory agent is purified from a plant extract.
  • the plant is selected from broccoli, shiitake, coleus, rosemary, lotus, artichoke, sea rose, tangerine, Oenothera biennis, astaxanthin, red orange, Schisandra chinensis, Lonicera, Fagopyrum, carrot, Narcissus tazetta or olive.
  • the invention can be administered in any suitable way.
  • the invention can be administered topically, orally, parenterally, transdermally or rectally.
  • effects of aging include lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratoses and actinic keratoses.
  • the invention comprises a cosmetic composition for ameliorating the effects of aging comprising a cosmetically effective amount of at least one arNOX inhibitory agent wherein the arNOX inhibitory agent is effective in decreasing the effects of aging upon the skin.
  • the invention includes a cosmetically acceptable carrier.
  • the carrier may include powders, emollients, lotions and liquids.
  • the arNOX inhibitory agent is derived from a plant.
  • the plant is selected from broccoli, shitake, coleus rosemary, lotus, artichoke, sea rose tangerine, Oenothera biennis, astaxanthin, red orange, Schisandra chinensis, Lonicera, Fagopyrum, carrot, Narcissus tazetta or olive.
  • the cosmetic composition according to this exemplary embodiment can be administered in any effective manner.
  • the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally or rectally.
  • the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap or a shampoo.
  • the invention includes a cosmetic method for ameliorating the effects of aging comprising applying to the skin a cosmetic composition comprising an effective amount of an arNOX inhibitor, wherein at least one arNOX mediated effect of aging is inhibited.
  • the arNOX inhibitor is a plant extract.
  • the arNOX inhibitor is purified from a plant extract.
  • the arNOX inhibitory agent is present in a concentration of between about 5 ⁇ g/ml to about 500 ⁇ g/ml. In other exemplary embodiments, the inhibitory agent is present in a concentration of between about 15 - 100 ⁇ g/ml.
  • the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally or rectally or in any other effective manner. In some exemplary embodiments, the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap or a shampoo.
  • the invention comprises a kit.
  • the kit may include a volume of an arNOX inhibitory agent and instruction for use.
  • the kit may further include a cosmetic preparation so that the arNOX inhibitory agent can be added to the cosmetic preparation prior to use.
  • the one or various arNOX inhibitory agents may be applied or administered in various ways. Such as, for example, topical administration, formulated, for example as a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap, a shampoo or a sunscreen and in the form of a tea or capsule or any other effective manner.
  • the invention relates to agents for sequestering serum aging factors, and methods for using the same. More particularly, the invention relates to agents and methods for using such factors, to prevent or treat disorders and complications of disorders resulting from cell damage
  • the agents of the invention comprise at least one naturally occurring arNOX inhibitor.
  • One embodiment of the invention comprises agents that bind arNOX and inhibit the ability of arNOX to generate reactive oxygen species as well as methods of using such agents to inhibit the ability of arNOX to generate reactive oxygen species.
  • the invention provides pharmaceutical and/or cosmetic compositions, methods of use, and kits comprising inhibitory agents for the treatment or amelioration of disorders or effects resulting from oxidative changes in cells that result in aging by targeting an aging-related isoform of NADH oxidase (arNOX), shed into the sera by aging cells.
  • the compositions may contain inhibitory agents extracted from plants.
  • the compositions of the invention may comprise at least one broccoli product, whether alone or with other inhibition agents and inhibit the activity of an aging-related isoform of NADH oxidase shed into the sera by aging cells, wherein the other inhibitory agent may comprise extracts, for example, of shitake, lotus, artichoke, astaxanthin and the like.
  • active agents or extracts can be used in combination with other arNOX inhibitors, such as, ubiquinones, extracts of Schisandra chinensis, or Lonicera japonica, or extracts of Fagopyrum cymosum, Narcissus tazetta and the like or in combination with lotions, emollients and preservatives as necessary.
  • arNOX inhibitors such as, ubiquinones, extracts of Schisandra chinensis, or Lonicera japonica, or extracts of Fagopyrum cymosum, Narcissus tazetta and the like or in combination with lotions, emollients and preservatives as necessary.
  • the term "cosmetic” refers to a substances intended to be applied to the body for cleansing, beautifying, promoting attractiveness, or altering the appearance.
  • extract refers to a solution obtained by steeping or soaking a substance in a solvent and removing the active ingredient.
  • the solvent can be any suitable solvent including but not limited to alcohol, water or the like. In some instances the extract is concentrated or the solvent can be evaporated and the active ingredient resuspended or solubilized in a different solvent.
  • disorder refers to any condition of a living animal or plant body or of one of its parts that impairs normal functioning comprising any ailment, disease, illness, clinical condition, pathological condition, weakened condition, unsound condition, and any abnormal or undesirable physical condition.
  • reactive oxygen species refers to oxygen derivatives from oxygen metabolism or the transfer of free electrons, resulting in the formation of free radicals (e.g., superoxides or hydroxyl radicals).
  • antioxidant refers to compounds that neutralize the activity of reactive oxygen species or inhibit the cellular damage done by said reactive species.
  • the term "pharmaceutically acceptable carrier” refers to a carrier medium that does not interfere with the effectiveness of the biological activity of the active ingredient, is chemically inert, and is not toxic to the patient to whom it is administered.
  • the term “pharmaceutically acceptable derivative” refers to any homolog, analog, or fragment corresponding to the formulations described in this application, which exhibit antioxidant activity, and is relatively non-toxic to the subject.
  • therapeutic agent refers to any molecule, compound, or treatment, preferably an antioxidant, which assists in the prevention or treatment of the disorders, or complications of disorders caused by reactive oxygen species.
  • agent that sequesters arNOX refers to any molecule, compound, or treatment that interacts with arNOX, thus decreasing the reaction of arNOX with other substrates and inhibits the ability of arNOX to generate reactive oxygen species.
  • antioxidants cellular components, and target proteins defined herein are abbreviated as follows: mitochondrial DNA mtDNA nicotinamide adenine dinucleotide NADH cell surface hydroquinone (NADH) oxidase with protein disulfide-thiol isomerase activity NOX
  • NOX specific to cancer cells tNOX low density lipoprotein LDL plasma membrane oxido-reductase chain PMOR ubiquinone or coenzyme Q CoQ coenzyme Qi 0 CoQi 0 reactive oxygen species ROS
  • the present invention is directed to naturally occurring agents which may be administered either internally or topically which specifically inhibit arNOX and ameliorate some of its aging related effects.
  • agents can take the form of isolated agents or plant extracts.
  • arNOX inhibitory agents can be used alone, they may also be used as compositions comprising multiple arNOX inhibitory agents and/or formulations including compounds having other beneficial effects on the body.
  • the inventor has found that by adding arNOX inhibitors to cosmetics, the inhibitors can have beneficial effects that augment the normal skin care regimen.
  • the invention comprises a composition useful for ameliorating the effects of aging comprising an effective amount of at least one arNOX inhibitory agent.
  • the arNOX inhibitory agent is effective in decreasing the effects of aging.
  • the invention further includes a cosmetically or pharmaceutically acceptable carrier.
  • the arNOX inhibitory agent is present in a plant extract.
  • the arNOX inhibitory agent is purified from a plant extract.
  • the plant is selected from broccoli, shitake, coleus rosemary, lotus, artichoke, sea rose tangerine, Oenothera biennis, astaxanthin, red orange, Schisandra chinensis, Lonicera, Fagopyrum, carrot, Narcissus tazetta or olive.
  • the invention can be administered in any suitable way.
  • the invention can be administered topically, orally, parenterally, transdermally, rectally or any other effective method.
  • effects of aging include lines, wrinkles, hyperpigmentation, loss of hydration, loss of elasticity, decrease in collagen, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratoses and actinic keratoses.
  • the invention comprises a cosmetic composition for ameliorating the effects of aging comprising a cosmetically effective amount of at least one arNOX inhibitory agent wherein the arNOX inhibitory agent is effective in decreasing the effects of aging upon the skin.
  • the invention includes a cosmetically acceptable carrier.
  • the carrier may include powders, emollients, lotions, creams, liquids and the like.
  • the arNOX inhibitory agent is derived from a plant.
  • the plant is selected from broccoli, shitake, coleus, rosemary, lotus, artichoke, sea rose, tangerine, Oenothera biennis, astaxanthin, red orange, Schisandra chinensis, Lonicera, Fagopyrum, carrot, Narcissus tazetta or olive.
  • the cosmetic composition according to this exemplary embodiment can be administered in any exemplary manner.
  • the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally or rectally.
  • the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap or a shampoo.
  • the invention includes a cosmetic method for ameliorating the effects of aging comprising applying to the skin a cosmetic composition comprising an effective amount of an arNOX inhibitor, wherein at least one arNOX mediated effect of aging is inhibited.
  • the arNOX inhibitor is a plant extract
  • the arNOX inhibitor is purified from a plant extract.
  • the arNOX inhibitory agent is present in a concentration of between about 5 ⁇ g/ml to about 500 ⁇ g/ml.
  • the concentration of the active agent is present in a concentration of between about 15 to 100 ⁇ g/ml.
  • the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally, rectally or by any other effect method.
  • the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap or a shampoo.
  • the invention comprises a kit.
  • the kit may include a volume of an arNOX inhibitory agent and instruction for use.
  • the kit may further include a cosmetic preparation such that the arNOX inhibitory agent can be added to the cosmetic preparation prior to use.
  • the one or various arNOX inhibitory agents may be applied or administered in various ways. Such as, for example, topical administration in any effective manner, such as, for example, a cream, a milk, a lotion, a gel, a suspension of lipid or polymeric microspheres or nanospheres or vesicles, a soap, a shampoo or a sunscreen and in the form of a tea or capsule or any other effective manner.
  • NADH oxidase is a unique cell surface protein with hydroquinone (NADH) oxidase and protein disulfide-thiol interchange activities that normally responds to hormone- and growth factors.
  • a hormone insensitive and drug-responsive form of the activity designated tNOX also has been described, which is specific for cancer cells.
  • the invention encompasses research related to arNOX, an aging-related isoform of the cell surface NADH oxidase, which is capable of oxidizing reduced quinones.
  • the NOX protein is anchored in the outer leaflet of the plasma membrane (Morre, 1995, Biochem. Biophys. Acta. 1240:201-208; and DeHahn et al., 1997, Biochem. Biophys. Acta. 1328:99-108).
  • NOX activity was shown to be shed in soluble form from the cell surface (Morre et al., 1996, Biochim. Biophys. Acta 1280:197-206). The presence of the shed form in the circulation provides an opportunity to use patient sera as a source of the NOX protein for isolation and characterization
  • the invention is based on the identification of arNOX, which is a constitutive cell surface NADH oxidase protein (cNOX) capable of oxidizing reduced quinones.
  • cNOX constitutive cell surface NADH oxidase protein
  • the NOX proteins have been postulated to link the accumulation of lesions in mitochondrial DNA to cell surface accumulations of reactive oxygen species as one consequence of its role as a terminal oxidase in a plasma membrane electron transport chain (Morre, D. M. et al., 2000, J. Expl Biol 203:1513-1521).
  • Cells with functionally deficient mitochondria become characterized by an anaerobic metabolism.
  • NADH accumulated from the glycolytic production of ATP and an elevated plasma membrane electron transport activity become necessary to maintain the NAD+/NADH homeostasis essential for survival.
  • the characteristics of aged cells includes those that express and/or shed arNOX, and include, but are not limited to, those exhibiting one or more of the following characteristics: an age-related PMOR system, the ability to generate reactive oxygen species, and have functionally defective mitochondria.
  • One embodiment of the invention is the utilization of agents to reduce the negative effects of aging cells.
  • the invention encompasses methods for detecting cell-membrane associated arNOX and soluble arNOX in sera. See, e.g., PCT Pub. App. No. WO 00/57871, which is incorporated herein by reference in its entirety.
  • the invention further contemplates using arNOX as a diagnostic tool when oxidative damage to cells and/or tissue is suspected. As such, arNOX in tissue, cells, or circulation may be detected.
  • Embodiments include: detection by employing antibodies specific to arNOX, which may be conjugated to a wide variety of labels, wherein the label provides a detectable signal. For example radioisotopes, enzymes, fluorescence and the like may be utilized as labels. Examples of detection techniques comprise: detection based upon
  • the present invention has utilized in vitro and in vivo methods for screening for agents which target arNOX.
  • in vitro selection methods several types of methods are likely to be particularly convenient and/or useful for screening test agents comprising: methods which measure a binding interaction between two or more components; and methods which measure the activity of an enzyme which is one of the interacting components, i.e., arNOX. See, for example, the description in Pub. App. No. WO 00/57871, the disclosure of which is incorporated herein by reference.
  • Binding interactions between two or more components can be measured in a variety of ways known in the art.
  • One approach is to label one of the components with an easily detectable label, place it together with the other component(s) in conditions under which they would normally interact (e.g., ubiquinone), perform a separation step which separates bound labeled component from unbound labeled component, and then measure the amount of bound component.
  • the test agent may be labeled with a various detectable markers, and the separation step in this type of approach can be accomplished in various ways. See, for example, Pub. App. No. WO 00/57871.
  • the invention encompasses the use of topical administration of natural plant extracts, alone or in the form of a cream emollient, lotion or the like, to maintain skin vitality.
  • a preferred embodiment of the invention comprises the topical administration of a cream, lotion, emollient or the like, which comprises an arNOX inhibiting extract, to the skin of patients to maintain and improve skin vitality.
  • the present invention provides compositions comprising active agent(s), which prevent and/or ameliorate skin damage and associated conditions, particularly those resulting from aging and associated with arNOX. Further, the invention encompasses methods for utilizing said compositions.
  • the stratum corneum is the layer of the skin that forms the top surface layer and serves to protect the skin while controlling moisture and the flow of substances in and out of the skin. As this barrier function is broken down, the skin suffers damaging effects, thus further contributing to premature aging. These damaging effects causing premature aging of the skin are a concern for many individuals wishing to maintain healthy, youthful looking and feeling skin. Reactive oxygen species participate in a number of destructive reactions potentially lethal to
  • Reactive oxygen species are responsible in part for deleterious cellular interactions including impairing fibroblast cells ability to produce healthy collagen and elastin.
  • the skin is subject to deterioration through dermatological disorders, environmental abuse (wind, air conditioning, central heating) or through the normal aging process (chronoaging), which may be accelerated by exposure of skin to sun (photoaging).
  • a preferred embodiment of the invention provides naturally occurring active agents from plants for the treatment of skin.
  • the active agents prevent and/or ameliorate skin damage and associated conditions.
  • the processed plant products sequester arNOX activity.
  • the processed plant products inhibit reactive oxygen species.
  • agents and methods of the invention prevent and/or improve the health of the skin.
  • the agents may improve skin tone, e.g., tautness of skin, color and appearance of pores, elasticity, hydration and/or help diminish the appearance of fine lines and visible signs of aging.
  • the agents positively affect the body's natural production of collagen and elastin.
  • the agents of the invention minimize the effects of environmental agitators such as pollution, sun, free radicals and stress.
  • One embodiment of the invention provides composition for preventing and reducing the effects of the production of reactive oxygen species and methods for using the same.
  • the invention encompasses the use of active agents derived from plants to at least partially sequester or inhibit arNOX activity. Further, the invention contemplates the use of other synthetic and natural compounds to sequester arNOX activity.
  • the present invention discloses compositions, which treat the skin and delay the visible signs of actual aging and weathered skin such as wrinkles, lines, sagging, hyperpigmentation and age spots.
  • the present invention also decreases the appearance and condition of sensitive, dry and/or flaky skin, serves to soothe red, and/or irritated skin, and treats spots, pimples, blemishes, and other skin irregularities.
  • the present invention advances prior art compositions by providing compositions and methods for using the same not previously disclosed.
  • the invention provides pharmaceutical or cosmetic compositions, methods of use, and pharmaceutical or cosmetic kits for the treatment of disorders resulting from oxidative changes in cells that result in aging by targeting an aging- related isoform of NADH oxidase (arNOX), shed into the sera by aging cells.
  • the compositions may contain agents extracted from plants.
  • the compositions of the invention may comprise at least one extract shown to inhibit arNOX activity, whether alone or with other inhibition agents and, at least partially, inhibit or block the activity of an aging-related isoform of NADH oxidase shed into the sera by aging cells.
  • the composition may comprise ubiquinones, natural extracts or agents derived therefrom known to comprise active agents useful in inhibiting arNOX, together with other compounds known in the art to make creams, lotions, emollients and the like.
  • Such other compounds may comprise gums, fillers, preservatives and the like.
  • Vehicles other than, or in addition to water can include liquid or solid emollients, solvents, humectants, thickeners and powders.
  • the vehicle may be from 0.1% to 99.9%, preferably from 25% to 80% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.
  • the vehicle is at least 80% water, by weight of the vehicle.
  • water comprises at between about 50% to 85% of the composition by weight.
  • water is present between about 0.1% to 55%, by weight of the composition.
  • other vehicles are used in the above recited concentrations.
  • An oil or oily material may be present, together with an emulsif ⁇ er to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending largely on the average hydrophilic- lipophilic balance (HLB) of the emulsifier employed.
  • HLB hydrophilic- lipophilic balance
  • compositions may also include sunscreens.
  • Sunscreens include those materials commonly employed to block ultraviolet light.
  • Illustrative compounds are the derivatives of PABA, cinnamate and salicylate.
  • octyl methoxycinnamate and 2- hydroxy-4-methoxy benzophenone also known as oxybenzone
  • methoxycinnamate and 2-hydroxy-4-methoxy benzophenone are commercially available under the trademarks, Parsol MCX and Benzophenone-3, respectively.
  • the exact amount of sunscreen employed in the emulsions can vary depending upon the degree of protection desired from the sun's UV radiation.
  • Emollients may further be incorporated into cosmetic compositions of the present invention. Levels of such emollients may range from 0.5% to 50%, preferably between 5% and 30% by weight of the total composition. Emollients may be classified under such general chemical categories as esters, fatty acids and alcohols, polyols and hydrocarbons.
  • Esters may be mono- or di-esters.
  • Acceptable examples of fatty di-esters include dibutyl adipate, diethyl sebacate, diisopropyl dimerate, and dioctyl succinate.
  • Acceptable branched chain fatty esters include 2-ethyl-hexyl myristate, isopropyl stearate and isostearyl palmitate.
  • Acceptable tribasic acid esters include triisopropyl trilinoleate and trilauryl citrate.
  • Acceptable straight chain fatty esters include lauryl palmitate, myristyl lactate, and stearyl oleate.
  • Preferred esters include coco-caprylate/caprate (a blend of coco-caprylate and coco-caprate), propylene glycol myristyl ether acetate, diisopropyl adipate and cetyl octanoate.
  • Suitable fatty alcohols and acids include those compounds having from 10 to 20 carbon atoms. Especially preferred are such compounds such as cetyl, myristyl, palmitic and stearyl alcohols and acids.
  • polyols which may serve as emollients are linear and branched chain alkyl polyhydroxyl compounds.
  • propylene glycol, sorbitol and glycerin are preferred.
  • polymeric polyols such as poly-propylene glycol and polyethylene glycol.
  • Butylene and propylene glycol are also especially preferred as penetration enhancers.
  • Exemplary hydrocarbons which may serve as emollients are those having hydrocarbon chains anywhere from 12 to 30 carton atoms. Specific examples include mineral oil, petroleum jelly, squalene and isoparaffins.
  • compositions of the present invention comprise thickeners.
  • a thickener will usually be present in amounts anywhere from 0.1 to 20% by weight, preferably from about 0.5% to 10% by weight of the composition.
  • Exemplary thickeners are cross-linked
  • polyacrylate materials available under the trademark CARBOPOL® from the B.F. Goodrich Co. Gums may be employed such as xanthan, carrageenan, gelatin, karaya, pectin and locust beans gum. Under certain circumstances the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance; silicone gums in excess of 10 centistokes and esters such as glycerol stearate have dual functionality.
  • Powders may be incorporated into the cosmetic composition of the invention.
  • These powders include chalk, talc, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof.
  • adjunct minor components may also be incorporated into the cosmetic compositions. These ingredients may include coloring agents, opacifiers and perfumes. Amounts of these other adjunct minor components may range anywhere from 0.001% up to 20% by weight of the composition.
  • composition of the invention may be used for topical application to human skin, as an agent for conditioning, moisturizing and smoothing the skin, increasing the flexibility and elasticity and preventing or reducing the appearance of wrinkled, lined or aged skin.
  • Formulations of the present invention offer a response to the loss of skin tone and promotes benefits to effectively boost hydration and firmness of the surface layer of the skin, all while working to repair the underlying layers of the skin with antioxidants and other beneficial ingredients to help diminish the appearance of fine lines and wrinkles and to restore visible tone and elasticity.
  • such anti-oxidants are specifically directed to inhibit arNOX.
  • a small quantity of the composition comprised of from about 1 to 1000 ml of active agent, is applied to the skin.
  • a quantity of composition comprising from about 1 to 100 ml of active agent is applied to the skin. This process may be repeated several times daily for any period of time.
  • the composition is applied to the skin once in the morning and once in the evening.
  • the topical skin care composition of the invention can be formulated as a lotion, a cream, a gel or the like.
  • the composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer.
  • a lotion or a cream can be packaged in a bottle or a roll-ball applicator, or a propellant-driven aerosol device or a container fitted with a pump suitable for finger operation.
  • the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar.
  • the invention accordingly also provides a closed container containing a cosmetically acceptable composition as herein defined.
  • Buffy coats a mixture of lymphocytes and platelets. Such buffy coats are commercially available from, for example Rockland Immunochemicals (Gilbertsville, PA). The blood samples were maintained at 4 °C prior to collection and assay. Ca. 10 7 cells were added to each assay. Cell numbers were determined using a hemocytometer.
  • the assay consists of 150 ⁇ l serum or 40 ⁇ l buffy coats in PBSG buffer (8.06 g NaCl, 0.2 g KCl, 0.18 g Na 2 HPO 4 , 0.26 g KH 2 PO 4 , 0.13 g CaCl 2 , 0.1 g MgCl 2 1.35 g glucose dissolved in 1000 ml deionized water, adjusted to pH 7.4, filtered and stored at 4 °C) Rates were determined using an SLM Aminco DW-2000 spectrophotometer (Milton Roy, Rochester, NY, USA) in the dual wave length mode of operation with continuous measurements over 1 min every 1.5 min. After 45 min, test compounds were added and the reaction was continued for 45 min. After 45 min.. A millimolar extinction coefficient of 19.1 cm "1 was used
  • Table I provides the results of some arNOX inhibition experiments.
  • Group 1 Product - Blue Label ⁇ Narcissus, Schizandra, Honeysuckle, Rhizoma Fagopy ⁇ , 6 subjects
  • Group 5 Product - Yellow with Black Line Label (Fagopyrum Rhizoma Extract, 7 subjects)
  • Group 6 Product - Red with Black Line Label (Narcissus + Schizandra Extract, 6 subjects)
  • Subjects were instructed to apply the assigned Group # product to the right or left side of the face and to apply Control Product - No Color Label to the opposite side of the face twice daily (in the morning and evening) after cleansing their faces.
  • Subjects were clinically graded on the right and left sides of the face for the following parameters: fine wrinkles (periocular), coarse wrinkles (periocular), skin texture (cheeks), overall discoloration, brightness (cheeks), clarity of skin, pore size (forehead and nose area), pore distribution/structure, and overall skin radiance.
  • Subjects were clinically graded on the right and left sides of the face for objective irritation parameters (erythema, edema, scaling) and subjective irritation parameters (burning, stinging, itching, tightness, tingling).
  • Skin luminance measurements were made in triplicate using a Chroma Meter CR400 (Konica-Minolta, Japan) skin luminance analyzer and were taken on pigmented lesions (selected by the investigator) on the right and left sides of the face to instrumentally assess changes in skin color/tone.
  • Chroma Meter CR400 Konica-Minolta, Japan
  • the Fitzpatrick Skin Classification is based on the skin's unprotected response to the first 30-45 minutes of sun exposure after a winter season without sun exposure.
  • the categories of the skin types are as follows:
  • the Chroma Meter has a detachable head for easy and independent analysis of selected areas. The following values were recorded:
  • L* Describes the relative brightness on a gray scale from black to white; values increase as the skin becomes brighter and lighter
  • a* Describes the color hue ranging from red to green; values increase with improvements in skin vascularization, increased blood flow, and improved skin tone
  • b* Describes the color hue ranging from blue to yellow; values typically decrease with skin lightening
  • Chroma Meter measurement was taken on a non-pigmented (normal) area on one side of the face for each subject.
  • a single visco-elasticity measurement was taken using the Cutometer ® SEM 575 (Courage + Khazaka, Germany) viscoelasticity meter. Measurements were taken on the center of each subject's right and left cheeks in order to assess the viscoelastic properties of the skin.
  • the measuring principle is based on suction. Negative pressure is created in the device and the skin is drawn into the aperture of the probe. Inside the probe, the penetration depth is determined by a non-contact optical measuring system. The light intensity varies due to the penetration depth of the skin. The resistance of the skin to be sucked up by the negative pressure (firmness and its ability to return into its original position (elasticity) are displayed on the instrument as curves at the end of each measurement.
  • Three-hundred (300) mbar of negative pressure was applied and released through an 8-millimeter (mm) probe.
  • the movement of the skin into and out of the probe was recorded during the application and release of suction, and resiliency and extensibility were calculated.
  • Subjects were provided with written usage instructions, a calendar of future visits, and a daily diary to record test material application times and comments.
  • Subjects also completed a Subject Skin Change Evaluation Questionnaire and a Subject Evaluation Questionnaire regarding test material attributes, tolerance, and improvements in skin condition parameters on the right and left sides of the face.
  • Table 4 presents the results of the clinical grading and instrumentation for each test material. Mean values at Week 4 and Week 8 are statistically compared to mean Baseline values for significant differences. The average percent change from Baseline is listed in parentheses (-- indicates this value could not be calculated).
  • ⁇ 0- Indicates a statistically significant (p ⁇ 0 05) decrease compared to Baseline O" Indicates a statistically significant (p ⁇ 0 05) increase compared to Baseline
  • Pore Size - nose area 4.58 3.75 -0- (-18.1%) 3.25 (-29.0%)
  • ⁇ 0- Indicates a statistically significant (p ⁇ 0.05) decrease compared to Baseline
  • ft Indicates a statistically significant (p ⁇ 0.05) increase compared to Baseline
  • ⁇ 0- Indicates a statistically significant (p ⁇ 0 05) decrease compared to Baseline ft Indicates a statistically significant (p ⁇ 0 05) increase compared to Baseline
  • Fine Wrinkles - periocular area 4.40 4.10 (-6.8%) 3.60 ⁇ (-18.1%)
  • Pore Size - nose area 5.10 4.90 (-3.9%) 4.70 (-7.8%)
  • ⁇ 0- Indicates a statistically significant (p ⁇ 0, 05) decrease compared to Baseline
  • ft Indicates a statistically significant (p ⁇ 0.05) increase compared to Baseline
  • Fine Wrinkles - periocular area 4.50 3.83 (-14.8%) 3.67 ⁇ 0 (-18.5%)
  • Pore Size - nose area 5.00 4.50 (-10.0%) 3.83 ⁇ (-23.3%)

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Abstract

La présente invention concerne une composition et un procédé qui présentent des propriétés anti-vieillissement. Ladite composition comprend un agent inhibiteur d’arNOX présent dans un extrait végétal naturel et qui est utile topiquement en tant que cosmétique. Les symptômes du vieillissement incluent les lignes, les rides, l’hyperpigmentation, la déshydratation, la perte d’élasticité, l’angiome, la sécheresse, le prurit, la télangiectasie, le purpura actinique, les kératoses séborrhéiques et les kératoses actiniques. L’invention peut être utilisée plusieurs fois par jours sans effets délétères.
PCT/US2008/058697 2008-03-28 2008-03-28 Compositions cosmétiques destinées à l’inhibition d’espèces d’oxygène réactif Ceased WO2009120217A1 (fr)

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FR2975298A1 (fr) * 2011-05-16 2012-11-23 Silab Sa Utilisation cosmetique de peptides de cynara scolymus
US10251832B2 (en) 2017-05-26 2019-04-09 Mary Kay Inc. Cosmetic compositions and methods
CN116209426A (zh) * 2020-08-07 2023-06-02 胞外体干细胞株式会社 包含青花菜外排体作为活性成分的抗老化和抗氧化化妆品组合物和包含其的功能性化妆品

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2975298A1 (fr) * 2011-05-16 2012-11-23 Silab Sa Utilisation cosmetique de peptides de cynara scolymus
US10251832B2 (en) 2017-05-26 2019-04-09 Mary Kay Inc. Cosmetic compositions and methods
US10881603B2 (en) 2017-05-26 2021-01-05 Mary Kay Inc. Cosmetic compositions and methods
US11534391B2 (en) 2017-05-26 2022-12-27 Mary Kay Inc. Cosmetic compositions and methods
US12233151B2 (en) 2017-05-26 2025-02-25 Mary Kay Inc. Cosmetic compositions and methods
CN116209426A (zh) * 2020-08-07 2023-06-02 胞外体干细胞株式会社 包含青花菜外排体作为活性成分的抗老化和抗氧化化妆品组合物和包含其的功能性化妆品

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