WO2012006107A2 - Compositions de soins de la peau - Google Patents

Compositions de soins de la peau Download PDF

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Publication number
WO2012006107A2
WO2012006107A2 PCT/US2011/042224 US2011042224W WO2012006107A2 WO 2012006107 A2 WO2012006107 A2 WO 2012006107A2 US 2011042224 W US2011042224 W US 2011042224W WO 2012006107 A2 WO2012006107 A2 WO 2012006107A2
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Prior art keywords
skin
panax
compositions
acid
composition
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PCT/US2011/042224
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English (en)
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WO2012006107A3 (fr
Inventor
Dana F. Flavin
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Stemtide, Inc.
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Publication of WO2012006107A2 publication Critical patent/WO2012006107A2/fr
Publication of WO2012006107A3 publication Critical patent/WO2012006107A3/fr

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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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the inventions disclosed and taught herein relate generally to topically-applied compositions for personal care and to the rejuvenation, renewal, repair and maintenance of healthy skin on a mammal. More specifically, the inventions disclosed herein are related to topically-applied skin care compositions and formulations for maintaining skin health and imparting rejuvenated skin exhibiting reduced wrinkles and an anti-aging effect to mammals, particularly human beings.
  • vitamin A As a therapeutic agent. Many of these early treatment methodologies involved the administration of vitamin A internally in the form of the ester of vitamin A, vitamin A palmitate. This approach changed over time to focus on the topical application of vitamin A in its acid form (retinoic acid), which in early reports suggested that vitamin A could potentially retard the effects of aging on the skin.
  • vitamin A in its acid form retinoic acid
  • the use of vitamin A in its various forms has limited applicability from a long-term treatment standpoint. Therefore, interest in a number of other natural products with potential skin rejuvenating effects has been the focus of much recent research for topical application.
  • U.S. Patent No. 6,146,650 describes the use of liposomes to deliver a combination of collagen, avocado oil, aloe and vital nutrients such as vitamins A, C, D and E to the skin.
  • U.S. Patent No. 6,281 ,236 describes cosmetic compositions containing allantoin and an emulsifier such as natural beeswax for the treatment of skin.
  • Vitamins have also been used, alone or in combinations, to prevent or reverse skin damage and/or improve the quality of skin tone in individuals, and in particular, skin damage associated with inflammation due to UV radiation.
  • U.S. Pat. Nos. 5,574,063, 5,545,398, 5,409,693, and 5,376,361 describe the use of fatty acid esters of ascorbic acid (e.g., vitamin C palmitate) or tocotrienol (vitamin E) for the treatment and prevention of skin damage from sun exposure.
  • 5,817,621 describes a skin cream comprising a lipid ointment, vitamin A, a salicylic acid, D-camphor, a biogenic GABAergic substance, a dopaminergic substance, M-cholionolyics, pancreatin, ascorbic acid, pantothenic acid calcium salt, and vitamin D 2 as a means to cause a high trophoprotective effect followed by a restoration of skin physiological functions.
  • U.S. Patent No. 7,608,642 describes pharmaceutical compositions and methods for managing wound and skin care, in particular methods and compositions that employ compounds that can promote skin cell renewal, wound healing, proliferation of fibroblasts and/or keratinocytes, and the production of collagen.
  • These compositions include as active ingredients giberellic acid compounds, a jasmonic acid compound, and a zeatin compound, in combination.
  • inventions disclosed and taught herein are directed to skin rejuvenation, minor wound repair, and wrinkle reduction compositions and formulations in the form of cosmetic creams, as well as methods for treating the skin of a mammal such as a human to facilitate the management, prevention, and treatment of one or more such skin conditions.
  • Cream or lotion compositions and formulations are described herein, for use in the therapeutic renewal and rejuvenation of the skin of a patient, by activating through the use of specific target components which act, alone or in synergistic combination, to increase the generation of stem, epidermal, or other cells in the skin; to activate or increase collagen synthesis in the skin; to activate or increase endogenous hyaluronic acid synthesis in the epidermis; to activate or increase the hydration of the skin, and to activate or increase the stem cell and fibroblast migration within the epidermis to sites of needed repair on the skin.
  • the use of the skin care composition cream, lotion, or other dermal application compositions of the present invention yield progress towards dramatically younger looking skin, rehydration and a decrease in signs of aging such as dryness, thin skin, deep wrinkles and dull appearances.
  • a skin cream composition comprising a therapeutically effective amount of L-arginine, and one or more extracts of a Panax, Cimicifuga, and/or a Trifolium species in a cosmetic vehicle.
  • a skin rejuvenating composition comprising a therapeutically effective amount of L-arginine, and one or more extracts of a Panax, Cimicifuga, and/or a Trifolium species in a cosmetic vehicle.
  • a cosmetic, pharmaceutical, or dermatological therapeutically effective skin rejuvenating or minor wound-healing composition comprising, as an active ingredient, an effective quantity of at least L-arginine, and one or more extracts of a Panax, Cimicifuga, and/or a Trifolium species in a cosmetic vehicle.
  • a method for conditioning the skin of a mammal comprising applying topically to the skin of a patient a composition comprising L-arginine and one or more extracts of a Panax, Cimicifuga, and/or a Trifolium species in a cosmetic vehicle.
  • the species is a Panax species selected from the group consisting of Panax Araliaceae, Panax bipinnatifidus, Panax ginseng, Panax japonicus, Panax quinquefolius, Panax trifolius, Panax vietnamensis, Panax wangianus, and Panax zingiberensis.
  • the Cimicifuga species is selected from the group consisting of C. racemosa, C. dahurica, C. foetida, and C. acerina.
  • the extract is from the root of the plant.
  • the vehicle further comprises one or more additional ingredients selected from the group consisting of an emulsifier, a thickener, a skin emollient, and a inorganic particulate material.
  • a gel, paste, cream, lotion, emulsion, or ointment is described, wherein the composition includes at least one anti-oxidant, L-arginine, one or more extracts of a Panax species, one or more extracts from a Cimicifuga species, one or more extracts from a Trifolium species, all of which are contained in a cosmetic vehicle.
  • a skin rejuvenation composition which comprises at least one anti-oxidant; L- arginine; one or more extracts of a Panax species; one or more extracts of a Cimicifuga species; one or more extracts of a Trifolium species; and vitamin B 5 or a derivative thereof, all of which are contained in a cosmetic vehicle.
  • This skin rejuvenation compositions may further comprise an epidermal skin cell activator, an epidermal stem-cell activator (a compound or combination of compounds that activate stem-cells within the subject to replenish elastin and collagen in the skin), a collagen synthesis activator (a compound or combination of compounds that enhance collagen synthesis within the dermis or skin of a subject, such as by activating growth factors for such a purpose), a hyaluronic acid synthesis activator (a compound or combination of compounds working in synergy with each other that accelerate the hyaluronic acid synthesis activity in a subject, bringing about the activation of dermal cells in the patient), a skin hydration activator (a compound or series of compounds that affects the Skin Hydration Index of a subject's skin (which reflects the skin's moisture level), as measured according to the calculation of individual Skin Hydration values of specific areas, as described by Farage, M.A., et a ⁇ .
  • an epidermal skin cell activator a compound or combination of compounds that
  • fibroblast migration activator a compound or series of compounds that increases the trajectories of individual fibroblasts as they migrate towards a wound region in a subject, singly or in combination.
  • a skin cream comprising at least one anti-oxidant; one or more extracts of a Panax species; one or more extracts of a Cimicifuga species; one or more extracts of a Trifolium species; L- arginine or an analog, oligomer, or derivative thereof, and a vehicle or moisturizer base
  • the vehicle or moisturizer base comprises octyl stearate and xanthan gum.
  • the vehicle or moisturizer base comprises water and at least one natural fat or oil.
  • the skin cream comprises a humectant, a thickener, and at least one preservative.
  • FIG. 1 illustrates a general illustration of the anatomy of the skin epidermis.
  • the term "dermatologically-acceptable,” as used herein, means that the described or referenced compositions or components thereof are suitable for use in contact with mammalian skin tissue without undue toxicity, incompatability, instability, allergic response, and the like.
  • the term "dermis” refers to the layer of skin that forms the foundation upon which the epidermis lies. The primary cellular components of the dermis are the dermal fibroblasts that exist in a sea of extracellular matrix within the dermis.
  • epidermis refers to the layer of skin over the dermis.
  • the epidermis is a stratified squamous epithelium, composed primarily of keratinocytes. Keratinocytes within the epidermis are organized into four layers including the basal, spinous, granular, and cornified layers.
  • hexoses refers to any six-membered D or L saccharide. Such hexoses include allose, altrose, glucose, mannose, galose, idose, galactose and talose. The hexose utilized may also be a deoxy hexose.
  • keratinous tissue refers to keratin-containing layers disposed as the outermost protective covering of mammals (e.g., humans, dogs, cats, etc.) that includes, but is not limited to, skin, lips, hair, toenails, fingernails, cuticles, hooves, etc.
  • pentose refers to any five-membered D or L saccharide or sugar. Such pentoses include ribose, arabinose, xylose and lyxose. The pentose utilized may also be a deoxy pentose.
  • safe and effective amount means an amount of a compound or composition sufficient to significantly induce a positive benefit, such as a positive appearance of the skin or a positive feel to the skin, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan.
  • GRAS compound refers to those compounds which are classified as Generally Recognized As Safe compounds as certified by the U.S. FDA.
  • sagging means the laxity, slackness, or the like condition of skin that occurs as a result of loss of, damage to, alterations to, and/or abnormalities in dermal elastin.
  • skin refers to the outer covering of an animal body; the outermost layer of skin is called the epidermis, the layer beneath the epidermis is called the dermis.
  • skin stem cells refers to those stem cells that reside in the basal layer of the epidermis and/or at the base of hair follicles.
  • the terms “smoothing” and “softening” as used herein mean altering the surface of the skin and/or keratinous tissue such that its tactile feel is improved. “Signs of skin aging” include, but are not limited to, all outwardly visible or tactilely perceptible manifestations as well as any other macro or micro effects due to skin aging. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g., chronological aging and/or environmental damage.
  • sugar residue means any sugar available to one of skill in the art.
  • a sugar residue can be a hexose or a pentose.
  • topical application means to apply or spread the compositions of the present invention onto the surface of the skin tissue or within a wound.
  • compositions for promoting skin renewal and rejuvenation, increasing cell proliferation, for stimulating collagen, stem-cell and fibronectin production in the skin, and for wound repair/tissue healing in the case of minor wounds to the dermal tissue can also be used to reverse the effects of aging in all types and layers of skin tissues including the dermis, epidermis, keratinous tissues, mucosal tissues and the like. Such compositions are also useful for treating minor wounds, stimulating tissue growth, enhancing skin thickness, and for reversing the effects of aging on skin, as well as activating stem cells in the skin and dermal area of an individual to which the composition is applied.
  • compositions and methods of manufacturing such compositions that employ GRAS compounds which can act to promote the generation of stem, epidermal or other skin cells in the epidermis, activation of collagen synthesis, activation of hyaluronic acid synthesis, enhanced skin hydration, and dermal healing by stimulating stem cell and fibroblast migration to sites of needed repair.
  • GRAS compounds which can act to promote the generation of stem, epidermal or other skin cells in the epidermis, activation of collagen synthesis, activation of hyaluronic acid synthesis, enhanced skin hydration, and dermal healing by stimulating stem cell and fibroblast migration to sites of needed repair.
  • compositions of the present invention contain an effective amount of a compound from a Panax species of ginseng plant, a compound from a Cimicifuga species of plant (black cohosh), a genistein compound, a compound from a Trifolium species of plant, and optioinally, L-arginine, as well as combinations thereof as well as acceptable carriers and other ingredients.
  • These compositions may also further include one or more of an epidermal skin cell activator, a collagen synthesis activator, a hyaluronic acid synthesis activator, a skin hydration activator, and a fibroblast migration activator, singly or in combination, as appropriate, in therapeutically effective amounts.
  • FIG. 1 is an illustration of the general anatomy of a region of skin 10, shown in a perspective view illustrating the various subcutaneous layers 20 of the skin.
  • the skin is divided into the epidermis 22 (sometimes referred to as the intrafolicular epidermis), the dermis 24, and the hypodermis 26 (also known as the subcutaneous tissue, or pauniculus adiposus).
  • the epidermis extends from about 0.05 mm to about 1 .5 mm below the surface of the skin, and comprises the lamina lucinda and the lamina densa.
  • the dermis 24 is below the epidermis, is separated from the epidermis by the dermoepidermal junction 25, and has a thickness from about 1 .4 mm to about 4 mm, depending upon the location.
  • the dermis comprises the upper, papillary dermis and the lower, reticular dermis (known as the "deep layer").
  • Below the dermis is the subcutaneous tissue 26, which has an average thickness of from about 1 cm to about 4 cm, although this thickness increases on obese individuals.
  • a hair follicle 12 extends into the dermis layer 24. Surrounding the hair follicle 12 are typically located sebaceous glands 14, and bulge regions, 16, the latter of which has been associated with stem cell production in the skin of mammals.
  • compositions of the present disclosure are skin rejuvenating, renewal, and/or wound treating compositions comprising an effective amount of a compound from a Panax species of gensing plant, a compound from a Cimicifuga species of plant (black cohosh), a genistein compound, a compound from a Trifolium species of plant, and optionally L-arginine, as well as combinations thereof, and acceptable carriers and other ingredients suitable for use in preparing a therapeutic cosmetic cream for topical application.
  • compositions described herein provide their therapeutic effect in combating skin wrinkles, in skin rejuvenation, and in minor wound repair, at least in part due to causing epidermal stem cell activation and stem cell motivated repair.
  • compositions of the instantly described compositions benefit by the synergistic effect of the inclusion of L-arginine, which acts to increase N0 2 processing and in turn increases the increased activity of epidermal stem cells.
  • compositions having the same therapeutic effects can be prepared, containing as additional or replacement active ingredients therapeutically effective amounts of extracts from chaste tree berry ( Vitex agnus-castus), dong quai ⁇ Angelica sinensis), evening primrose oil ⁇ Oenethera biennis), motherwort ⁇ Leonurus cardiaca), and licorice ⁇ Glycyrrhiza glabra), separately or in combination with the ingredients described herein.
  • chaste tree berry Vitex agnus-castus
  • dong quai ⁇ Angelica sinensis dong quai ⁇ Angelica sinensis
  • evening primrose oil ⁇ Oenethera biennis evening primrose oil
  • motherwort ⁇ Leonurus cardiaca motherwort ⁇ Leonurus cardiaca
  • licorice ⁇ Glycyrrhiza glabra separately or in combination with the ingredients described herein.
  • the topical cream compositions of the present invention preferably include one or more compounds ("Panax compounds”) contained within the extracts of the genus Panax , also known commonly as ginseng, such as extracts from the root of a Panax ginseng species, including Panax Araliaceae, Panax bipinnatifidus, Panax ginseng, Panax japonicus, Panax quinquefolius, Panax trifolius, Panax vietnamensis, Panax wangianus, and Panax zingiberensis, as well as pseudoginseng species (e.g., Panax pseudoginseng).
  • ginseng such as extracts from the root of a Panax ginseng species, including Panax Araliaceae, Panax bipinnatifidus, Panax ginseng, Panax japonicus, Panax quinquefolius, Panax trifolius, Panax vietnamensis, Panax wangianus,
  • Specific compounds for use in the present formulations include extracts containing ginsenoside Rb-i , Rb 2 , Rc, Rd, Re, Rf, Rg-i , Ro, and combinations thereof, as well as any of these ginsenosides in their substantially pure form.
  • the Panax compounds present in the compositions of the instant invention are in an amount ranging from about 0.01 % to about 50%, or from about 0.1 % to about 10%, or from about 0.5% to about 10%, or from about 1 % to about 5%, or from about 2% to about 5%, by weight of the composition, of the Panax compound.
  • the Panax compounds useful in the compositions of the present invention include compounds of general formula (I), below: I.
  • R 1 is H or Glc- 2 Glc-, ;
  • R 2 is H, Rha- 2 Glc-0-, Glc- 2 Glc-0-, Glc-O, O— Glc 2 — Rha, O— Glc 2 — Xyl, O— Glc 2 (Ac)— Xyl, or O— Glc 2 (Ac)— Rha;
  • Panax compounds may be included as the substantially pure material, e.g. pure Rb-i , a metabolite thereof, a salt thereof, or as a mixture, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • compositions of the present invention may preferably include natural hormone extracts of clover and clover flowers, especially those of the genus Trifolium (e.g., Trifolium pratense or Trifolium subterraneum), such as flavonins, glycosides, isoflavones, saponins, soyasaponinsins, and extracts of the genus Trifolium containing combinations of such compounds, in amounts ranging from about 0.05 to about 20.0 wt. %, inclusive.
  • natural hormone extracts of clover and clover flowers especially those of the genus Trifolium (e.g., Trifolium pratense or Trifolium subterraneum), such as flavonins, glycosides, isoflavones, saponins, soyasaponinsins, and extracts of the genus Trifolium containing combinations of such compounds, in amounts ranging from about 0.05 to about 20.0 wt. %, inclusive.
  • Exemplary extracts of the Trifolium species suitable for use with the compositions of the present invention will include one or more isoflavones of the following general structure (II), in an amount ranging from about 0.05 to about 20.0 wt. %, inclusive,
  • Ri is H or CH 3 ;
  • R 2 is H, OH, CH 3 or OCH 3 ; and
  • R 3 is H or CH 3 , as well as derivatives, hydrates, prodrugs, and pharmaceutically acceptable salts thereof.
  • the Trifolium compounds may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • compositions of the present invention also preferably include one or more constituents of the Cimicifuga species of plants, including Cimicifuga racemosa, C. simplex, C. rhizoma, C. dahurica, C. foetida, C. acerina, and C. heracleifolia, herein referred to generally as "cimicifuga compounds", including the extracts of such Cimicifuga spp., particularly C. racemosa.
  • the Cimicifuga compounds present in the compositions of the instant invention are in an amount ranging from about 0.01 % to about 50%, or from about 0.1 % to about 10%, or from about 0.5% to about 10%, or from about 1 % to about 5%, or from about 2% to about 5%, by weight of the composition, of the Cimicifuga compound.
  • the Cimicifuga compounds useful in the compositions of the present invention include compounds of formula (III), below,
  • R 1 is H, OH, or OCH 3 ;
  • R 2 is H, OH, or OCH 3 ;
  • R 3 is H, CH 3 , or C n H n+ i ;
  • R 4 is H, Ac, CH 3 , C 2 H 5 , Gal, or Glc;
  • R 5 is H, Ac, CH 3 , C 2 H 5 , Gal, or Glc;
  • R 6 is H, OH, OCH 3 , O— Gal, or O— Glc;
  • R 7 is H, OH, OCH 3 , O— Gal, or O— Glc;
  • R 8 is H, OH, OCH 3 , O— Gal, or O— Glc, as well as derivatives thereof, metabolites thereof, hydrates thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof.
  • the Cimicifuga compounds may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • compositions and formulations of the present disclosure may further contain a safe and effective amount of one or more chemical agents generally referred to herein as "anti-wrinkle compounds.”
  • anti-wrinkle compounds suitable for use in the compositions of the present invention include, but are not limited to, D- and L-amino acids, including the sulfur-containing D- and L-amino acids (both natural and un-natural, such as a- and ⁇ -amino acids) and their derivatives (e.g., alkyl derivatives or amino acid analogs) and salts, particularly the N-acetyl derivatives, a preferred example of which is N-acetyl-L-cysteine; thiols (e.g.
  • ethane thiol phytic acid, lipoic acid, and similar acids containing phosphorus, sulfur, nitrogen, and the like; lysophosphatidic acid; skin peel agents (e.g., phenol and the like), vitamin B 3 compounds and retinoids that enhance the health and/or appearance of skin tissues.
  • compositions of the present invention may contain a safe and effective amount of one or more vitamin B 3 compounds.
  • the compositions can contain from about 0.01 % to about 50%, or from about 0.1 % to about 10%, or from about 0.5% to about 1 0%, or from about 1 % to about 5%, or from about 2% to about 5%, by weight of the composition, of the vitamin B 3 compound.
  • vitamin B 3 compound means a compound having the general formula IV, below:
  • R is -CONH 2 (e.g., niacinamide), --COOH (e.g., nicotinic acid) or -CH 2 OH (e.g., nicotinyl alcohol), derivatives thereof, and salts of any of the foregoing.
  • exemplary derivatives of the foregoing vitamin B 3 compounds include nicotinic acid esters, including non-vasodilating esters of nicotinic acid (e.g., tocopheryl nicotinate), nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.
  • the vitamin compounds may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • vitamin B 3 compounds for use with the compositions and formulations of the present disclosure are well known in the art and are commercially available from a number of commercial sources, including but not limited to, the Sigma Chemical Company (St. Louis, Mo.); ICN Biomedicals, Inc. (Irvin, Calif.) and Aldrich Chemical Company (Milwaukee, Wis.).
  • compositions of the present invention may contain a safe and effective amount of a vitamin B 5 compound.
  • the compositions can contain from about 0.01 % to about 50%, or from about 0.1 % to about 10%, or from about 0.5% to about 10%, or from about 1 % to about 5%, or from about 2% to about 5%, by weight of the composition, of the vitamin B 5 compound.
  • vitamin B 5 compound means a compound having the general formula V, below:
  • R is OH, CO 2 H, or S— S— (CH 2 )2NHC(O)CH 2 (2)— NHC(O)C(OH)CH(CH 3 ) 2 CH 2 OH (pantethine).
  • compositions of the present invention may contain a safe and effective amount of a vitamin C compound, or analog or derivative thereof, including vitamin C a vitamin C complex, or a mineral ascorbate.
  • a vitamin C compound is present in the composition of the present disclosure, it is preferred that it is present is an amount ranging from about 10 mg to about 500 mg per 55 kg of body weight of the animal, more preferably in an amount ranging from about 25 mg to about 400 mg per 55 kg of body weight of the animal, and more preferably in an amount ranging from about 25 mg to about 250 mg per 55 kg of body weight of the animal.
  • compositions of the present invention may also contain vitamin E (tocopherol) and/or one or more Vitamin E compounds or derivatives of tocopherol.
  • the tocopherols employed in the present invention include cc-tocopheraol, ⁇ - tocopherol, ⁇ -tocopherol, and ⁇ -tocopherol, as well as any of the known tocotrienols and combinations thereof, as well as derivatives of tocopherol of the structure VI, below:
  • n is an integer from 6 to 13, including 7, 8, 9, 10, 1 1 , and 12;
  • R is hydrogen, alkyl, alkenyl, an ether, a silyl ether, or acetate; and
  • R 2 is an optionally substituted nitrogen-containing heterocycle or a polycyclic nitrogen-containing heterocycleand pharmaceutically acceptable salts thereof.
  • Exemplary tocopherol derivatives suitable for use in the compositions described herein include, but are not limited to, selected from the group consisting of (R)-2-(9-(1 H-imidazol-1 -yl)nonyl)-2, 5,7,8- tetramethylchroman-6-ol ; (R)-1 -(9-(6-(tert-butyldimethylsilyloxy)-2, 5,7,8 tetramethylchroman-2-yl)nonyl)-1 H-1 ,2,3-triazole; ( R)-1 -(9-(6-(tert- butyldimethylsilyloxy)-2,5,7,8-tetramethylchroman-2-yl)- nonyl)-1 H-1 ,2,4-triazole; ( R)- 2-(9-(1 H-1 ,2,4-triazol-1 -yl)nonyl)-2,5,7,8-tetramethyl-chroman-6-ol
  • the vitamin E compounds present in the compositions of the instant invention are in an amount ranging from about 0.01 % to about 20%, or from about 0.1 % to about 10%, or from about 0.5% to about 1 0%, or from about 1 % to about 5%, or from about 2% to about 5%, by weight of the composition, of the tocopherol, vitamin E compound.
  • compositions of the present invention may also contain a retinoid.
  • retinoid includes all natural and/or synthetic analogs of Vitamin A or retinol- like compounds that possess the biological activity of Vitamin A in the skin as well as the geometric isomers and stereoisomers of these compounds.
  • the retinoid can, for example, be retinol, retinol esters (e.g., C 2 -C 2 2 alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinal, and/or retinoic acid (including all- trans retinoic acid and/or 1 3-c/s-retinoic acid).
  • retinoids other than retinoic acid are used. These compounds are available in the art and are commercially available from a number of sources, e.g., Sigma Chemical Company (St. Louis, Mo.), and Boerhinger Mannheim (Indianapolis, Ind.). Other retinoids that are useful in the therapeutic compositions described herein include those described in U.S. Pat. No. 4,677,120; U.S. Pat. No. 4,885,31 1 ; U.S. Pat. No. 5,049,584; U.S. Pat. No. 5,124,356; and U.S. patent Reissue No. 34,075.
  • Suitable retinoids for use with the compositions and formulations of the present disclosure include tocopheryl- retinoate, tocopherol ester of cis- or frans-retinoic acid, adapalene (6-[3-(1 -adamantyl)- 4-methoxyphenyl]-2-naphthoic acid), and tazarotene (ethyl 6-[2-(4,4- dimethylthiochroman-6-yl)-ethynyl]nicotinate).
  • Desirable retinoids include but are not limited to retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retinal and combinations thereof.
  • the retinoid may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • the retinoid is substantially pure (>95% pure), or essentially pure (>98% pure).
  • compositions of this invention may contain a safe and effective amount of the retinoid, such that the resultant composition is safe and effective for regulating or improving the condition of skin tissues.
  • the compositions and methods of the invention can improve visible and/or tactile discontinuities in skin, or improve signs of skin aging.
  • the compositions preferably contain from about 0.005% to about 2% by weight, or from about 0.01 % to about 2% by weight, retinoid.
  • Retinol can also be used in an amount of from about 0.01 % to about 1 .5% weight.
  • Retinol esters can be used in an amount of from or about 0.01 % by weight to or about 2.5% by weight (e.g., about 1 %).
  • Retinoic acids can be used in an amount of from or about 0.01 % by weight to or about 2.5% weight.
  • Tocopheryl-retinoate, adapalene, and tazarotene can be used in an amount of from or about 0.01 % to or about 2% weight.
  • Amino acids including but not limited to alpha-amino acids, beta-amino acids, and derivatives and analogs thereof, in both the L- and D- form (as appropriate) may be included in the compositions of the present invention in safe and effective amounts.
  • amino acid refers to both naturally-occurring and synthetic amino acids, including both alpha- and beta-amino acids.
  • Exemplary amino acids suitable for use in the compositions described herein include but are not limited to L- arginine, L-aspartamine, aspartic acid, L-proline, L-serine, L-tyrosine, L-tryptophan, L- lysine, L-glycine, L-leucine, L- alanine, L-phenylalanine, L-valine, L-cysteine, L- methionine, and L-glutamine.
  • the compositions of the present invention include at least the amino acid L-arginine or a similar sulfur-containing amino acid such as an oligomer of L-arginine (e.g., from 2 to 20 residues of L-arginine or an L-arginine analog, or from 2 to 20 residues of L-arginine or an L-arginine analog, or from 2 to 10 residues of L-arginine or an L-arginine analog), an L-arginine analog, or an L-arginine analog oligomer linked through a labile bond to a polymeric matrix, in a therapeutically effective amount ranging from about 0.1 to about 15.0 wt. %, by weight of the total composition.
  • an oligomer of L-arginine e.g., from 2 to 20 residues of L-arginine or an L-arginine analog, or from 2 to 20 residues of L-arginine or an L-arginine analog, or from 2 to 10 residues of L-arginine or an
  • Peptides including but not limited to, di-, tri-, tetra-, and pentapeptides and derivatives thereof, may be included in the compositions and formulations of the present invention in amounts that are safe and effective.
  • peptides refers to both the naturally occurring peptides and synthesized peptides, as well as peptidomimetics. Also useful herein are naturally occurring and commercially available compositions that contain peptides.
  • Suitable dipeptides for use herein include Camosine (beta-ala-his).
  • Suitable tripeptides for use herein include, gly-his-lys, arg-lys-arg, and his-gly-gly.
  • Preferred tripeptides and derivatives thereof include palmitoyl-gly-his-lys, which may be purchased as Biopeptide CLTM (100 ppm of palmitoyl-gly-his-lys commercially available from Sedenna, France); Peptide CK (arg-lys-arg); Peptide CK+ (ac-arg-lys- arg-NH 2 ); and a copper derivative of his-gly-gly sold commercially as lamin, from Sigma (St. Louis, Mo.).
  • peptides can be present in amounts ranging from about 1 x10 "6 % to about 10% by total weight of the composition, or from about 1 x10 "6 % to about 0.1 % by total weight of the composition, or from about 1 x10 "5 % to about 0.01 % by total weight of the composition, by weight of the composition.
  • the compositions can contain from about 0.1 % to about 5%, by weight of the composition, of such peptides.
  • compositions can contain from about 0.1 % to about 10%, by weight compositions, of MATRIXYLTM and/or Biopeptide CLTM peptide- containing compositions.
  • compositions of the present invention may also include a safe and effective amount of an anti-oxidant/radical scavenger.
  • the anti-oxidant/radical scavenger is especially useful for providing protection against ultraviolet radiation that can cause increased scaling or texture changes in the stratum corneum and against other environmental agents that can cause skin damage.
  • a safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject invention, for example, ranging from about 0.1 % to about 10%, or from about 1 % to about 5%, by weight of the composition.
  • Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the trade name TroloxTM), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., ⁇ , ⁇ -diethylhydroxylamine, amino-gianidine), sulfitydryl compounds (e.g., gluta
  • anti-oxidants/radical scavengers are selected from tocopherol sorbate and other esters of tocopherol.
  • tocopherol sorbate for example, the use of tocopherol sorbate in topical compositions and applicable to the present invention is described in U.S. Pat. No. 4,847,071 .
  • compositions and formulations of the present invention may also contain a safe and effective amount of one or more chelators or chelating agents.
  • chelator or “chelating agent” means an active agent capable of removing one or more metal ions from a system by forming a complex so that the metal ion cannot readily participate in or catalyze chemical reactions.
  • the inclusion of a chelator or chelating agent in the compositions of the present disclosure is useful for providing protection against ultraviolet radiation that can contribute to excessive scaling or skin texture changes and against other environmental agents that can cause skin damage to a subject.
  • a safe and effective amount of a chelating agent that may be added to the compositions of the subject invention ranges, for example, from about 0.1 % to about 10%, or from about 1 % to about 5%, or from about 0.1 % to about 1 %, of the weight of the total composition.
  • Exemplary chelators that are useful with the compositions described herein are disclosed in U.S. Patent No. 5,487,884, as well as .
  • the chelators useful in compositions of the subject disclosure include but are not limited to ethylenediamine tetraacetic acid (EDTA); furildioxime, furilnonoxime and derivatives thereof; 2,2'-dipyridylamine; 1 ,10-phenanthroline; di-2- pyridylketone; 2-furildioxime; 2,3-bis(2-pyridyl)pyrazine; 1 -hydroxy-4-methyl-6-(2,4,4- trimethylpentyl)-2(1 H)-pyridone; 2,3-dihydroxybenzoic acid; ethylenediamine-N,N- bis(2-hydroxyphenylacetic acid), dimethyl ester; 1 , 1 '-carbonyldiimidazole; 1 ,2-dimethyl- 3-hydroxypyrid-4-one; 2,4,6-tri(2-pyridyl)-1 ,3,5-triazine; 1 -pyrrolidinecarbodithioic acid;
  • compositions of the present disclosure may optionally contain a flavonoid compound.
  • Flavonoids are broadly disclosed in U.S. Pat. Nos. 5,686,082 and 5,686,367, both of which are herein incorporated by reference.
  • Flavonoids suitable for use in the present invention are flavanones selected from unsubstituted flavanones, mono-substituted flavanones, and mixtures thereof; chalcones selected from unsubstituted chalcones, mono-substituted chalcones, di-substituted chalcones, tri- substituted chalcones, and mixtures thereof; flavones selected from unsubstituted flavones, mono-substituted flavones, di-substituted flavones, and mixtures thereof; one or more isoflavones; coumarins selected from unsubstituted coumarins, mono- substituted coumarins, di-substitute
  • substituted as used herein with reference to flavonoids means flavonoids wherein one or more hydrogen atom of the flavonoid has been independently replaced with hydroxyl, Ci-C 8 alkyl, C 1 -C4 alkoxyl, O-glycoside, and the like or a mixture of these substituents.
  • mono-hydroxy flavanones e.g., 2'- hydroxy flavanone, 6-hydroxy flavanone, 7-hydroxy flavanone, etc.
  • mono-alkoxy flavanones e.g., 5-methoxy flavanone, 6-methoxy flavanone, 7-methoxy flavanone, 4'- methoxy flavanone, etc.
  • unsubstituted chalcone e.g.
  • unsubstituted trans-chalcone mono-hydroxy chalcones (e.g., 2'-hydroxy chalcone, 4'-hydroxy chalcone, etc.), di- hydroxy chalcones (e.g., 2',4-dihydroxy chalcone, 2',4'-dihydroxy chalcone, 2,2'- dihydroxy chalcone, 2',3-dihydroxy chalcone, 2',5'-dihydroxy chalcone, etc.), and tri- hydroxy chalcones (e.g., 2',3',4'-trihydroxy chalcone, 4,2',4'-trihydroxy chalcone, 2,2',4'-trihydroxy chalcone, etc.), unsubstituted flavone, 7,2'-dihydroxy flavone, 3',4'- dihydroxy naphthoflavone, 4'-hydroxy flavone, 5,6-benzoflavone, and 7,8- benzofla
  • unsubstituted flavanone, methoxy flavanones, unsubstituted chalcone, 2',4-dihydroxy chalcone, and mixtures thereof are used in the compositions of the invention.
  • unsubstituted flavanone, unsubstituted chalcone (especially the trans isomer), and mixtures thereof are used in the compositions of the invention.
  • Flavonoids can be synthesized or obtained as extracts from natural sources (e.g., plants). The naturally sourced material can also further be derivatized (e.g., an ester or ether derivative prepared following extraction from a natural source).
  • Flavonoid compounds useful herein are also commercially available from a number of sources, e.g., Indofine Chemical Company, Inc. (Somerville, N.J.), Steraloids, Inc. (Wilton, N.H.), and Aldrich Chemical Company, Inc. (Milwaukee, Wis.). Mixtures of such flavonoid compounds may also be used.
  • the flavonoid compounds can be present in the invention, for example, at concentrations of from about 0.01 % to about 20%, more preferably from about 0.1 % to about 10%, and still more preferably from about 0.5% to about 5%.
  • a safe and effective amount of an anti-inflammatory agent may be added to the compositions of the present invention, for example, from about 0.1 % to about 10%, or from about 0.5% to about 5%, of the composition may include an anti-inflammatory agent, including non-steroidal anti-inflammatory agents (NSAIDS).
  • NSAIDS non-steroidal anti-inflammatory agents
  • the antiinflammatory agent can enhance the appearance of the skin, for example, by contributing to a more uniform and acceptable skin tone or color.
  • the exact amount of anti-inflammatory agent to be used in the compositions will depend on the particular anti-inflammatory agent utilized since such agents vary widely in potency.
  • Steroidal anti-inflammatory agents suitable for use with the compositions of the present disclosure include but are not limited to, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone
  • a second class of anti-inflammatory agents that is useful in the compositions includes the nonsteroidal anti-inflammatory agents (NSAIDs).
  • NSAIDs nonsteroidal anti-inflammatory agents
  • a variety of compounds are encompassed by this group.
  • Anti-inflammatory and Anti-Rheumatic Drugs K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985)
  • Anti-inflammatory Agents Chemistry and Pharmacology, 1 , R. A. Scherrer, et al., Academic Press, New York.
  • NSAIDs non-steroidal anti-inflammatory agents
  • the oxicams such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP-14,304
  • benorylate trilisate, safapryn, solprin, diflunisal, and fendosal
  • the acetic acid derivatives such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac
  • the fenamates such as mefenamic, meclofenamic, flufenamic, niflum
  • non-steroidal anti-inflammatory agents may also be employed, as well as the dermatologically acceptable salts and esters of these agents.
  • etofenamate a flufenamic acid derivative
  • ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbinac are often used.
  • Ibuprofen, naproxen, ketoprofen, etofenamate, aspirin and flufenamic acid are frequently used.
  • agents are useful in methods of the present invention.
  • Such agents may suitably be obtained as an extract by suitable physical and/or chemical isolation from natural sources (e.g., plants, fungi, byproducts of microorganisms) or can be synthetically prepared.
  • candelilla wax bisabolol (e.g., alpha bisabolol), aloe vera, plant sterols (e.g., phytosterol), Manjistha (extracted from plants in the genus Rubia, particularly Rubia Cordifolia), and Guggal (extracted from plants in the genus Commiphora, particularly Commiphora Mukul), kola extract, chamomile, red clover extract, and sea whip extract, may be used.
  • bisabolol e.g., alpha bisabolol
  • aloe vera e.g., plant sterols (e.g., phytosterol)
  • Manjistha extracted from plants in the genus Rubia, particularly Rubia Cordifolia
  • Guggal extracted from plants in the genus Commiphora, particularly Commiphora Mukul
  • kola extract chamomile
  • red clover extract and sea whip extract
  • Additional anti-inflammatory agents useful herein include compounds of the Licorice (the plant genus/species Glycyrrhiza glabra) family, including glycyrrhetic acid, glycyrrhizic acid, and derivatives thereof (e.g., salts and esters).
  • Suitable salts of the foregoing compounds include metal and ammonium salts.
  • Suitable esters include C 2 - C 24 saturated or unsaturated esters of the acids, or Ci 0 -C 24 , or Ci 6 -C 24 .
  • oil soluble licorice extract examples include oil soluble licorice extract, the glycyrrhizic and glycyrrhetic acids themselves, monoammonium glycyrrhizinate, monopotassium glycyrrhizinate, dipotassium glycyrrhizinate, 1 -beta-glycyrrhetic acid, stearyl glycyrrhetinate, and 3-stearyloxy-glycyrrhetinic acid, and disodium 3-succinyloxy-beta- glycyrrhetinate.
  • Stearyl glycyrrhetinate is preferred in accordance with select aspects of the present disclosure.
  • compositions of the present invention may also contain a safe and effective amount of an anti-cellulite agent.
  • anti-cellulite agents are substances which i) exhibit beta-stimulation (adrenergic beta- agonists) to further enhance lipolysis into the dermal adipocytes; ii) act as collagen synthesis stimulators; iii) improve poor vascularity conditions associated to the cellulitic areas by a vasokinetic activity; or iv) exert adenylate cyclase agonist and/or anti- phosphodiesterase activities so as to accelerate the reduction of fatty deposits located in the cellulite-affected area.
  • Suitable anti-cellulite agents suitable for use with the compositions described herein may include, but are not limited to, xanthine compounds (e.g., caffeine, theophylline, theobromine, and aminophylline), ascorbates, triterpenoids such as Asiatic acid, inositol phosphate and phytic acid, nicotinates, salicylates including methyl salicylate, and natural-product extracts such as alkaloids and plant extracts containing flavones.
  • xanthine compounds e.g., caffeine, theophylline, theobromine, and aminophylline
  • ascorbates triterpenoids such as Asiatic acid, inositol phosphate and phytic acid, nicotinates, salicylates including methyl salicylate, and natural-product extracts such as alkaloids and plant extracts containing flavones.
  • Anti-cellulite agents are preferably employed in a proportion of at least 0.05 %, generally in a proportion of from about 0.05% to about 20%, preferably from about 0.10 % to about 10 % by weight of the composition in order to maximize efficacy at optimum cost.
  • compositions of the present invention may also contain a safe and effective amount of a topical anesthetic.
  • topical anesthetic drugs suitable for inclusion in the compositions of the present invention include but are not limited to benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof.
  • the amount of topical anesthetic in the compositions ranges from about 0.001 % to about 10%, such as from about 0.01 % to about 5% such as from about 0.05% to about 2% by weight, based on the total weight of the composition.
  • compositions of the present invention may contain a tanning compound.
  • the compositions can contain from about 0.1 % to about 20%, or from about 2% to about 7%, or from about 3% to about 6%, by weight of the composition, of dihydroxyacetone as an artificial tanning compound.
  • Exemplary tanning compounds suitable for use with the instant compositions include dihydroxyacetone (and derivatives and analogs thereof), which is also known as DHA or 1 ,3-dihydroxy-2- propanone, as well as other self-tanning compounds.
  • This material is represented by the chemical formula C 3 H 6 0 3 , and can exist as a mixture of monomers and dimers, with the dimers predominating in the solid crystalline state. Upon heating or melting, the dimers break down to yield the monomers. This conversion of the dimeric form to the monomeric form also occurs in aqueous solution.
  • Dihydroxyacetone is also known to be more stable at acidic pH values.
  • compositions of the present invention may optionally contain one or more skin-lightening agents.
  • the compositions can contain from about 0.1 % to about 10%, or from about 0.2% to about 5%, or from about 0.5% to about 2%, by weight of the composition, of a skin lightening agent.
  • Suitable skin lightening agents include but are not limited to kojic acid, arbutin, ascorbic acid and derivatives thereof (e.g., magnesium ascorbyl phosphate or sodium ascorbyl phosphate), and extracts (e.g., mulberry extract, placental extract).
  • Skin lightening agents suitable for use herein also include those described by Rendon, M.I., et al. [Dermatol.
  • compositions of the present invention may comprise a skin soothing or skin-healing compound.
  • Skin soothing or skin healing compounds suitable for use herein include panthenoic acid derivatives (including panthenol, dexpanthenol, ethyl panthenol), aloe vera, allantoin, bisabolol, and dipotassium glycyrrhizinate.
  • a safe and effective amount of a skin soothing or skin healing compound may be added to the present composition, foe example, from about 0.1 % to about 30%, or from about 0.5% to about 20%, or from about 0.5% to about 10%, by weight of the composition formed.
  • compositions of the present invention may contain one or more antimicrobial and/or anti-fungal compounds. Such compounds are capable of destroying microbes, preventing the development of microbes or preventing the pathogenic action of microbes.
  • a safe and effective amount of an anti-microbial or anti-fungal compound may be added to the present compositions, for example, from about 0.001 % to about 10%, or from about 0.01 % to about 5%, or from about 0.05% to about 2%, by weight of the composition formulated.
  • antimicrobial and antifungal compounds suitable for use with the presently described compositions include but are not limited to ⁇ -lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, 2,4,4'- trichloro-2'-hydroxy diphenyl ether, 3,4,4'-trichlorobanilide, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, neomycin, netihnicin, paromomycin, streptomycin, tobramycin
  • Examples of particular compounds useful herein include those selected from benzoyl peroxide, 3-hydroxy benzoic acid, glycolic acid, lactic acid, 4-hydroxy benzoic acid, 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, cis- retinoic acid, trans-retinoic acid, retinol, phytic acid, N-acetyl-L-cysteine, lipoic acid, azelaic acid, arachidonic acid, benzoylperoxide, tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen, resorcinol, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, 2,4,4'-trichloro-2'-hydroxy diphenyl ether, 3,4,4'- trichlorocarbanilide, octopirox, lidocaine hydrochloride, clotrimaz
  • compositions of the subject invention may optionally contain a sunscreen compound.
  • sunscreen compound includes both sunscreen agents and physical sun blocks. Suitable sunscreen compounds may be either organic or inorganic, and preferably are GRAS compounds.
  • Inorganic sunscreens useful herein include the following metallic oxides; titanium dioxide having an average primary particle size of from about 15 nm to about 100 nm, zinc oxide having an average primary particle size of from about 15 nm to about 150 nm, zirconium oxide having an average primary particle size of from about 15 nm to about 150 nm, iron oxide having an average primary particle size of from about 15 nm to about 500 nm, and mixtures thereof.
  • the inorganic sunscreens can be present in the amount of from about 0.1 % to about 20%, or from about 0.5% to about 10%, or from about 1 % to about 5%, by weight of the composition.
  • Desirable compounds suitable for use in the compositions of the present disclosure include but are not limited to 2-ethylhexyl-p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-t-butyl methoxydibenzoyl-methane (commercially available as PARSOL 1789), 2-hydroxy-4-methoxybenzophenone, octyldimethyl-p-aminobenzoic acid, digalloyltrioleate, 2,2-dihydroxy-4- methoxybenzophenone, ethyl-4-(bis(hydroxy-propyl))aminobenzoate, 2-ethylhexyl-2- cyano-3,3-diphenylacrylate, 2-ethylhexyl-salicylate, glyceryl-p-aminobenzoate, 3,3,5- tri-methylcyclohexylsalicylate, methylanthranilate, p-d
  • the organic sunscreen compounds used in the compositions of the invention are 2-ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoyl-methane, 2-hydroxy-4-methoxybenzo-phenone, 2- phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene and mixtures thereof.
  • the sun-screening agents which are particularly desirable in accordance with at least one aspect of the present disclosure include those which have, in a single molecule, two distinct chromophore moieties that exhibit different ultra-violet radiation absorption spectra. One of the chromophore moieties absorbs predominantly in the UVB radiation range and the other absorbs strongly in the UVA radiation range.
  • Desirable members of this class of sun-screening agents are 4-N,N-(2- ethylhexyl)methyl-aminobenzoic acid ester of 2,4-dihydroxybenzophenone; N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N,N-(2- ethylhexyl)methyl-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N,N- (2-ethylhexyl)methyl-aminobenzoic acid ester of 2-hydroxy-4-(2-hydroxyethoxy) benzophenone; 4-N,N-(2-ethylhexyl)-methylaminobenzoic acid ester of 4-(2- hydroxyethoxy)dibenzoylmethane; N,N-di-(2-ethylhexyl)-4-aminobenzo
  • sunscreen compounds include 4,4'-t-butylmethoxydibenzoyl- methane, 2-ethylhexyl-p-methoxycinnamate, phenyl benzimidazole sulfonic acid, and octocrylene.
  • a safe and effective amount of the organic sunscreen compound is used, typically from about 1 % to about 20%, more typically from about 2% to about 10% by weight of the composition. Exact amounts will vary depending upon the sunscreen or sunscreens chosen and the desired Sun Protection Factor (SPF).
  • SPF Sun Protection Factor
  • compositions of the invention may contain a particulate material, for example, a inorganic, metallic oxide. These particulates can be coated or uncoated, charged or uncharged. Charged particulate materials are disclosed, for example, in U.S. Patent No. 5,997,887, to Ha, et al..
  • Particulate materials suitable for use with the compositions described herein include but are not limited to bismuth oxychloride, iron oxide, mica, mica treated with barium sulfate and TiO 2 , silica, nylon, polyethylene, talc, styrene, polypropylene, ethylene/acrylic acid copolymer, sericite, titanium dioxide, bismuth oxychloride, iron oxide, aluminum oxide, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, polymethyl methacrylate, and mixtures thereof.
  • Inorganic particulate materials suitable for use herein also include metal oxides wherein the metals are from the transition metal series of the Periodic Table of Elements, including but not limited to Ti0 2 , ZnO, or Zr0 2 , all of which are commercially available from a number of sources.
  • a suitable particulate material contains the material available from U.S. Cosmetics (e.g., the TRONOX® TiO 2 series, such as TRONOX® CR-837, a rutile TiO 2 ).
  • Particulate materials can be present in the compositions disclosed herein in levels ranging from about 0.01 % to about 2%, or from about 0.05% to about 1 .5%, or from about 0.1 % to about 1 %, by weight of the composition.
  • compositions of the present invention may contain a conditioning agent selected from humectants, moisturizers, or skin conditioners.
  • a conditioning agent selected from humectants, moisturizers, or skin conditioners.
  • humectants selected from humectants, moisturizers, or skin conditioners.
  • a variety of these materials can be employed and each can be present at a level of from about 0.01 % to about 20%, more preferably from about 0.1 % to about 10%, and still more preferably from about 0.5% to about 7% by weight of the composition.
  • These materials include, but are not limited to, guanidine; urea; glycolic acid and glycolate salts (e.g.
  • aloe vera in any of its variety of forms (e.g., aloe vera gel); polyhydroxy alcohols such as sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanetriol, propylene glycol, butylene glycol, hexylene glycol and the like; polyethylene glycols; sugars (e.g., melibiose) and starches; sugar and starch derivatives (e.g., alkoxylated glucose, fucose, glucosamine); hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; panthenol; allantoin; and mixtures thereof. Also useful herein are propoxylated glycerols.
  • conditioning agents are various C-1 -C30 monoesters and polyesters of sugars and related materials. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties.
  • Desirable conditioning agents for use with the instant composition are selected from urea, guanidine, sucrose polyester, panthenol, dexpanthenol, allantoin, and combinations thereof.
  • compositions of the present invention can contain one or more thickening agents, in an amount ranging from about 0.1 % to about 5%, or from about 0.1 % to about 4%, or from about 0.25% to about 3%, by weight of the composition.
  • thickening agents suitable for use with the present compositions include, but are not limited to, those selected from the group consisting of carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, and gums, as well as combinations thereof.
  • These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and esters of these acrylic acids and the substituted acrylic acids, wherein the crosslinking agent contains two or more carbon-carbon double bonds and is derived from a polyhydric alcohol.
  • Polymers useful in the present invention are more fully described in U.S. Pat. No. 5,087,445, to Haffey, et al., and in the CTFA International Cosmetic Ingredient Dictionary and Handbook, Eleventh Edition, 2006 (vols. 1 -4).
  • carboxylic acid polymers useful herein include the carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerytritol.
  • the carbomers are available as the CARBOPOLTM 900 series from B.F. Goodrich (e.g., CARBOPOLTM).
  • other suitable carboxylic acid polymeric agents include copolymers of C-io-30 alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., d. 4 alcohol) esters, wherein the crosslinking agent is an allyl ether of sucrose or pentaerytritol.
  • copolymers are known as acrylates/ C-m-30 alkyl acrylate crosspolymers and are commercially available as CarbopolTM 1342, CarbopolTM 1382, Pemulen TR-1 , and Pemulen TR-2, available from B.F. Goodrich.
  • carboxylic acid polymer thickeners useful herein are those selected from carbomers, acrylates/Ci 0 -C 3 o alkyl acrylate crosspolymers, and mixtures thereof.
  • compositions of the present invention can optionally contain crosslinked polyacrylate polymers useful as thickeners or gelling agents including both cationic and nonionic polymers, with the cationics being generally preferred.
  • crosslinked nonionic polyacrylate polymers and crosslinked cationic polyacrylate polymers include those described in U.S. Pat. No. 5,100,660, to Hawe et al.
  • compositions of the present invention can optionally contain polyacrylamide polymers, especially nonionic polyacrylamide polymers including substituted branched or unbranched polymers. More preferred among these polyacrylamide polymers is the nonionic polymer given the CTFA designation polyacrylamide and isoparaffin and laureth-7, available under the Trade name SEPIGELTM 305, available from the Seppic Corporation (Fairfield, N.J.).
  • polyacrylamide polymers useful herein include multi-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids.
  • Commercially available examples of these multi-block copolymers include Hypan SR150H, SS500V, SS500W, SSSA100H, and Hypan SS201 available from Lipo Chemicals, Inc., (Patterson, N.J.).
  • Polysaccharides refer to gelling agents that contain a backbone of repeating sugar (i.e., carbohydrate) units.
  • Nonlimiting examples of polysaccharide gelling agents include those selected from cellulose, carboxymethyl hydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof.
  • alkyl-substituted celluloses are also useful herein.
  • the hydroxy groups of the cellulose polymer is hydroxyalkylated (preferably hydroxyethylated or hydroxypropylated) to form a hydroxyalkylated cellulose that is then further modified with a C-10-C30 straight chain or branched chain alkyl group through an ether linkage.
  • these polymers are ethers of C-10-C30 straight or branched chain alcohols with hydroxyalkylcelluloses.
  • alkyl groups useful herein include those selected from stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyi (i.e.
  • alkyl groups derived from the alcohols of coconut oil palmityl, oleyl, linoleyl, linolenyl, ricinoleyl, behenyl, and mixtures thereof.
  • Preferred among the alkyl hydroxyalkyl cellulose ethers is the material given the CTFA designation cetyl hydroxyethylcellulose, which is the ether of cetyl alcohol and hydroxyethylcellulose. This material is available under the trade name NATROSOLTM CS Plus from Aqualon Corporation (Wilmington, Del.).
  • polysaccharides include scleroglucans that are a linear chain of (1 ->3) linked glucose units with a (1 ->6) linked glucose every three units, a commercially available example of which is CLEAROGELTM CS1 1 from Michel Mercier Products Inc. (Mountainside, N.J.).
  • Other thickening and gelling agents useful herein include materials that are primarily derived from natural sources.
  • Nonlimiting examples of these gelling agent gums include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluroinic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboyxmethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.
  • compositions of the invention can therefore include desirable thickening agents such as carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof, more preferably selected from carboxylic acid polymers, polyacrylamide polymers, and mixtures thereof.
  • compositions further include water sufficient to provide the remaining weight of the composition.
  • Deionized or distilled water may be employed.
  • Inorganic agents with or without organic modifications may form a part of the compositions disclosed herein.
  • the total amount of these agents in the composition is in the range from about 0.5 to about 5% by weight of the composition.
  • the inorganic agent preferably comprises at least one smectite clay.
  • at least 20% by weight of the inorganic agent is a smectite clay, more preferably at least 30%, even more preferably at least 40% and optimally at least 50% by weight of the inorganic agent is a smectite clay.
  • the smectite clay is chosen from the group consisting of: aluminum silicates, such as the montmorillonites (bentonites, hectorites and derivatives thereof); purified magnesium aluminum silicates (commercially available as VEEGUMTM in various grades); purified sodium magnesium silicates (commercially available as LAPONITETM in various grades); organically modified smectites including tetra alkyl and/or trialkyi ammonium smectites (organically modified montmorillonite clays) such as quaternium-18 bentonite, quaternium-18 hectorite, stearalkonium bentonite and stearalkonium hectorite; and mixtures thereof.
  • aluminum silicates such as the montmorillonites (bentonites, hectorites and derivatives thereof
  • purified magnesium aluminum silicates commercially available as VEEGUMTM in various grades
  • purified sodium magnesium silicates commercially available as LAPONITETM in various grades
  • Montmorillonites represent clay minerals, which belong to the dioctahedral smectites, and are materials which swell in water but do not become plastic.
  • the layer packets in the 3-layer structure of the montmorillonites can swell as the result of reversible incorporation of water (in a 2-7 fold amount) and other substances, such as, for examples, alcohols, glycols, pyridine, cc-picoline, ammonium compounds, hydroxyaluminosilicate ions, etc.
  • montmorillonite Since montmorillonite has a large capacity for ion exchange, aluminum can be replaced by Mg, Fe(ll), Fe(lll), Zn, Pb, Cr, Cu and others.
  • the resulting negative charge of the octahedral layers is balanced by cations, in particular Na + (sodium montmorillonite) and Ca 2+ (calcium montmorillonite) in interlayer positions.
  • the balance of the inorganic agent may be selected individually or as mixtures from the following: silicas, silicates, colloidal silicas, silicate pigments in which the free -OH (hydroxyl) groups on the surface of the particles have been (completely or partially) organically modified, chalk, talc, kaolin, Fullers earth, sodium polyacrylate, chemically modified magnesium aluminum silicate, hydrated aluminum silicate, zinc oxide, titanium oxide, and mixtures thereof.
  • compositions useful for the methods of the present invention are generally prepared by conventional methods such as are known in the art of making topical compositions. Such methods typically involve mixing of the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like.
  • sunscreens, UV filters and other solids in the composition have to be dispersed in suitable solvents (in some instances, pre-dispersions of selected components, such as in a mineral oil or the like, are available to facilitate the procedure). Then, emollients, emulsifiers, lipophilic components (consistency factors) are combined and melted at an elevated temperature (e.g., from about 75 °C to about 95 °C). Stabilizers (thickeners) may then be dispersed separately under stirring in the water phase until homogeneous gel is formed and heated to 80 °C. The two mixtures are combined progressively to form the emulsion, via mixing under intensive stirring until emulsion is formed.
  • suitable solvents in some instances, pre-dispersions of selected components, such as in a mineral oil or the like, are available to facilitate the procedure.
  • emollients, emulsifiers, lipophilic components consististency factors
  • Stabilizers may then be dispersed separately under stirring in the water
  • Sensitive components like the actives described herein (e.g., Cimicifuga extracts and ginsenosides), special additives, and preservatives should preferably be added after the mixture has been cooled (e.g., to a temperature ranging from about 20-40 °C), in order to keep their properties intact.
  • Sensitive components like the actives described herein (e.g., Cimicifuga extracts and ginsenosides), special additives, and preservatives should preferably be added after the mixture has been cooled (e.g., to a temperature ranging from about 20-40 °C), in order to keep their properties intact.
  • compositions of the present invention are useful for stimulating cellular growth, stimulating stem-cell activation and growth in skin tissues, stimulating collagen production and/or stimulating fibronectin production in skin tissues, and/or promoting wound closure in skin tissues of a mammal, such as a human. Such increased cell growth and/or increased collagen, stem-cell or fibronectin production can help regulate or rejuvenate mammalian skin tissues.
  • the compositions of the invention can be used for both prophylactic and therapeutic treatment of skin conditions.
  • compositions of the invention can be used for wound healing, thickening skin tissue (i.e., building the epidermis and/or dermis layers of the skin and where applicable the keratinous layers of the nail and hair shaft), preventing and/or retarding atrophy of mammalian skin, preventing and/or retarding the appearance of spider vessels and/or red blotchiness on mammalian skin, preventing and/or retarding the appearance of dark circles under the eye of a mammal, preventing and/or retarding sallow-colored mammalian skin, preventing and/or retarding sagging of mammalian skin, softening and/or smoothing lips, hair and nails of a mammal, preventing and/or relieving itch of mammalian skin, regulating skin texture (e.g.
  • Treating skin tissues involves topically applying to the skin tissue a safe and effective amount of a composition of the present invention.
  • the amount of the composition that is applied, the frequency of application and the period of use will vary widely depending upon the level of the genestein antioxidant, ginseng extract, arginine, and/or Cimicifuga spp. extract in a given composition and the level of regulation desired, for example, in light of the level of skin tissue damage present or expected to occur.
  • the composition is chronically applied to the skin.
  • chronic topical application refers to the continued topical application of the composition over an extended period during the subject's lifetime, for example, for a period of at least about one week, or for a period of at least about one month, or for at least about three months, or for at least about six months, or for at least about one year. While benefits are obtainable after various periods of use (e.g., two, five, ten or twenty days), chronic application can continue throughout the subject's lifetime. Typically applications would be on the order of about once per day over such extended periods, however application rates can vary from about once per week up to about three times per day or more.
  • a wide range of quantities of the compositions of the present invention can be employed to provide a skin appearance and/or feel benefit.
  • Quantities of the present compositions that are typically applied per application are, in mg composition/cm 2 skin, from about 0.01 mg/cm 2 to about 10 mg/cm 2 .
  • a desirable and useful application amount is about 1 mg/cm 2 to about 2 mg/cm 2 .
  • Regulating skin tissue condition can be practiced by applying a composition in the form of a skin lotion, cream, gel, foam, ointment, paste, emulsion, spray, conditioner, tonic, cosmetic, lipstick, foundation, nail polish, after-shave, or the like that is preferably intended to be left on the skin or other keratin structure for some esthetic, prophylactic, therapeutic or other benefit (i.e., a "leave-on" composition).
  • a composition in the form of a skin lotion, cream, gel, foam, ointment, paste, emulsion, spray, conditioner, tonic, cosmetic, lipstick, foundation, nail polish, after-shave, or the like that is preferably intended to be left on the skin or other keratin structure for some esthetic, prophylactic, therapeutic or other benefit (i.e., a "leave-on" composition).
  • the composition After applying the composition to the skin, it can be left on the skin for a period of at least about 15 minutes,
  • any part of the external portion of the face, hair, and/or nails can be treated, e.g., face, lips, gums, under-eye area, eyelids, scalp, neck, torso, arms, hands, legs, feet, fingernails, toenails, scalp hair, eyelashes, eyebrows, etc.
  • the composition can be applied with the fingers or with an implement or device (e.g., pad, cotton ball, applicator pen, spray applicator, dental applicator and the like).
  • Another approach to ensure a continuous exposure of the skin to at least a minimum level of the beneficial compositions of the invention is to apply the composition in a patch, for example, to selected tissues such as the face.
  • a patch for example, to selected tissues such as the face.
  • the patch can be occlusive, semi-occlusive or non-occlusive and can be adhesive or non-adhesive.
  • the composition can be contained within the patch or be applied to the skin prior to application of the patch. In a typical application the patch is preferably left on the skin for a period of at least about 5 minutes, or at least about 15 minutes, or at least about 30 minutes, or at least about 1 hour, or at night as a form of night therapy.
  • Example 1 Preparation of Exemplary Anti-Aging Cream.
  • a typical anti-aging cream of the present disclosure is formed by mixing and heating, as appropriate, the components recited in Table 1 (below), until the mixture is homogenous.
  • the mixture is cooled to a temperature ranging from about 10 °C to about 30 °C, preferably from about 10 °C to about 20 °C, prior to the addition of the natural product actives, such as the ginsenosides, Trifolium extract(s), Cimicifuga extract(s), and the like, so as to ensure that the natural product actives are not damaged prior to complete admixing of the composition.
  • the mixture may then be applied directly to the dermal surface of patients to reduce wrinkles, such as wrinkles on the face and hands

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
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  • Microbiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)

Abstract

Cette invention porte sur des compositions et des procédés de fabrication de telles compositions qui emploient des composés GRAS qui peuvent servir à favoriser la production de cellules souches, de cellules épidermiques ou d'autres cellules de la peau dans l'épiderme, l'activation de la synthèse de collagène, l'activation de la synthèse d'acide hyaluronique, une hydratation accrue de la peau et une cicatrisation cutanée accrue par stimulation de la migration de cellules souches et de fibroblastes vers des sites ayant besoin d'une réparation. Ces compositions et procédés sont utiles pour le rajeunissement de la peau et pour le traitement de certaines affections de vieillissement se rapportant à la peau ou d'autres affections d'endommagement cutané, dont la réduction des rides et le traitement de lésions cutanées mineures.
PCT/US2011/042224 2010-06-28 2011-06-28 Compositions de soins de la peau WO2012006107A2 (fr)

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CN110664699A (zh) * 2019-11-23 2020-01-10 吉林省丽芙泉生物科技有限公司 一种人参护肤原液制备工艺
WO2021191811A1 (fr) * 2020-03-24 2021-09-30 Acupharm Investments (Pty) Limited Nouvelle composition de gel pour plaie
WO2024146868A1 (fr) * 2023-01-05 2024-07-11 The Boots Company Plc Compositions pour peau affectée par les hormones

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Publication number Priority date Publication date Assignee Title
CN110664699A (zh) * 2019-11-23 2020-01-10 吉林省丽芙泉生物科技有限公司 一种人参护肤原液制备工艺
WO2021191811A1 (fr) * 2020-03-24 2021-09-30 Acupharm Investments (Pty) Limited Nouvelle composition de gel pour plaie
WO2024146868A1 (fr) * 2023-01-05 2024-07-11 The Boots Company Plc Compositions pour peau affectée par les hormones

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