WO2016105332A1 - Peptides et leur utilisation dans le traitement de la peau - Google Patents

Peptides et leur utilisation dans le traitement de la peau Download PDF

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Publication number
WO2016105332A1
WO2016105332A1 PCT/US2014/071803 US2014071803W WO2016105332A1 WO 2016105332 A1 WO2016105332 A1 WO 2016105332A1 US 2014071803 W US2014071803 W US 2014071803W WO 2016105332 A1 WO2016105332 A1 WO 2016105332A1
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WIPO (PCT)
Prior art keywords
skin
improvement
composition
acid
appearance
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PCT/US2014/071803
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English (en)
Inventor
Jolanta Idkowiak Baldys
Uma Santhanam
Original Assignee
Avon Products, Inc.
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Publication date
Application filed by Avon Products, Inc. filed Critical Avon Products, Inc.
Priority to PCT/US2014/071803 priority Critical patent/WO2016105332A1/fr
Publication of WO2016105332A1 publication Critical patent/WO2016105332A1/fr

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Classifications

    • 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
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • 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

Definitions

  • the present invention relates generally to topical formulations comprising peptides and associated methods of diminishing the dermatological signs of aging and/or improving health or appearance of human skin.
  • the invention relates to the use of a peptide comprising the sequence AECK (SEQ ID NO: 1), AEC (SEQ ID NO: 2), or ECK (SEQ ID NO: 3) in a topical formulation.
  • the formulations may promote the production of hyaluronic acid when topically applied to human skin and improve the appearance or health of the skin.
  • Hyaluronic acid is one of the chief components of the skin's extracellular matrix and it contributes significantly to cell proliferation, tissue repair, and plays an important role in the overall health of the epidermis.
  • HA is associated with tissue "hydration" in the skin, and increased amounts of HA correlate with reduced skin damage, increased skin elasticity, and anti-aging benefits, such as reduced appearance of wrinkles and fine lines.
  • the present invention provides peptides and cosmetic formulations containing them useful for improving the health and/or appearance of human integuments (skin, lips, nails, hair, etc.), particularly skin, affected by dermatological signs of photo- and intrinsic aging.
  • the peptides of the invention are believed to be capable of increasing hyaluronic acid (HA) production in skin and therefore are expected to have a beneficial effect on improving the appearance of signs of skin aging (e.g., diminishing the appearance of wrinkles and/or fine lines, tightening sagging skin, thickening thinning skin, evening skin tone, etc.).
  • HA hyaluronic acid
  • peptides are provided comprising the sequence
  • AECK Al-Glu-Cys-Lys
  • SEQ ID NO: 1 AECK (Ala-Glu-Cys-Lys) (SEQ ID NO: 1) or a derivative or fragment thereof, including, without limitation, the peptide having the structure of formula (I):
  • each of the amino acids in the sequence AECK (SEQ ID NO: 1) is in the L optical configuration, although all stereoconfigurations are included within the scope of the invention.
  • fragments of the peptide of formula (I) are provided.
  • compositions for topical use comprising a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof, the peptide being dispersed or dissolved in a physiologically acceptable carrier or vehicle.
  • the peptide will typically comprise from about 0.0001% to about 5% by weight of the composition, more typically, from about 0.001% to about 2.5% by weight, or from about 0.01% to about 1% by weight.
  • the carrier or vehicle may comprise, for example an aqueous serum, or a water-in-oil or oil-in-water emulsion, which may further include various adjuvants such as thickeners, emulsifiers, gellants, emollients, humectants, UV absorbers, antioxidants, pH adjusters, chelators, film formers, preservatives, colorants, fragrances, and the like.
  • the adjuvants may comprise, individually or collectively, from about 0.00001% to about 98% by weight of the composition.
  • the topical preparations of the invention may further include one or more additional skincare active agents, such as a retinoid (e.g., retinol, retinyl palmitate, retinyl acetate, retinaldehyde, retinoic acid, etc.), an antioxidant (e.g., ascorbic acid, thiodipropionic acid or esters thereof, including dilauryl thiodipropionate), a-hydroxy acids (e.g., glycolic acid), collagenase inhibitor, antiinflammatories, anti-acne agents, salicylic acid and derivatives, depigmenting agent, N-acetyl tyrosinamide, phytol, and botanicals, to name a few.
  • additional skincare active agents such as a retinoid (e.g., retinol, retinyl palmitate, retinyl acetate, retinaldehyde, retinoic acid, etc.), an antioxidant (e.g
  • methods for improving the appearance of human skin affected by dermatological signs of photo- and intrinsic aging and/or improving the health of human skin comprising topically applying to an area of skin in need thereof a composition comprising, in a topically acceptable vehicle, an effective amount of a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof.
  • the treatment of wrinkles and/or fine lines on human skin comprising topically applying to an area of the skin in need thereof (e.g., applying to a wrinkle or fine line) a composition comprising a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof, for a time sufficient to improve the aesthetic appearance of said human skin (e.g., to reduce the number or severity of wrinkles and/or fine lines).
  • a composition comprising a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof, for a time sufficient to improve the aesthetic appearance of said human skin (e.g., to reduce the number or severity of wrinkles and/or fine lines).
  • the treatment of sagging skin comprising topically applying to an area of the skin in need thereof (e.g., applying to an area of sagging skin such as the cheeks or jowls) a composition comprising a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof, for a time sufficient to improve the aesthetic appearance of said human skin (e.g., to tighten the sagging skin including prematurely thinned skin).
  • the treatment of thin skin comprising topically applying to an area of the skin in need thereof (e.g., applying to an area of thin skin) a composition comprising a peptide comprising the sequence AECK (SEQ ID NO: 1) or a derivative or fragment thereof, for a time sufficient to improve the aesthetic appearance of said human skin (e.g., to thicken the skin).
  • the treatment may be a least once or twice daily and may be continued for a period of at least four weeks, typically at least eight weeks or longer until a visible improvement is seen.
  • skin includes, without limitation, the lips, skin of the face, hands, arms, neck, scalp, and chest.
  • skin includes skin that is prematurely thinned, and may be diagnosed as such by a dermatologist.
  • the thin skin is skin of a female under the age of 40 or skin of a premenopausal female.
  • the term “consisting essentially of is intended to limit the invention to the specified materials or steps and those that do not materially affect the basic and novel characteristics of the claimed invention, as understood from a reading of this specification.
  • amino acid is intended to include naturally occurring amino acids as well as non-naturally occurring amino acids and includes any small molecule (MW ⁇ 1,000 Daltons) having at least one carboxyl group and at least one primary or secondary amine group capable of forming peptide bonds.
  • peptide is intended to include any molecule comprising at least two amino acids joined by a peptide bond and therefore includes di-peptides, tri-peptides, oligopeptides, and polypeptides having up to about 20 amino acid residues.
  • peptide also embraces structures having one or more linkers, spacers, or terminal groups which are not amino acids.
  • the peptides of the invention comprise, consist essentially of, or consist of the sequence AECK (Ala-Glu-Cys-Lys) (SEQ ID NO: 1), the sequence AEC (Ala-Glu-Cys) (SEQ ID NO: 2), or the sequence ECK (SEQ ID NO: 3).
  • a peptide comprising the sequence AECK (SEQ ID NO: 1) may have one or more additional amino acids joined to the amino and/or carboxy terminus via peptide bonds.
  • the peptide comprising the sequence AECK (SEQ ID NO: 1), AEC (SEQ ID NO: 2), or ECK (SEQ ID NO: 3) will have from 4 to 10 or from 4-9 or from 4-8 or from 4-7 or from 4-6 amino acids.
  • the peptide will comprise a hydrocarbon chain on the amino and/or carboxyl terminus, including, without limitation, C 1-24 or C6-i 8 or C 12-18 aliphatic hydrocarbons, which may be straight chained or branched or cyclic.
  • the peptide includes the reaction product of a peptide with a fatty acid or fatty alcohol.
  • the N-terminus may be reacted with a C IA fatty acid (e.g., palmitic acid) to form an amide bond.
  • the carboxyl terminus may be reacted with a C6-24 fatty alcohol (e.g., cetyl alcohol) to form an ester.
  • C6-24 fatty alcohol e.g., cetyl alcohol
  • These fatty derivatives may improve the lipophilicity of the peptide.
  • the phrase "consisting essentially of,” as used herein, is intended to mean that additional amino acids or other residues may be present at either terminus of the peptide and/or on a side chain provided they do not substantially impair the activity of the peptide to stimulate HA production.
  • the peptide has the structure of formula (I):
  • Tripeptide fragments of AECK are also contemplated to be useful including AEC (SEQ ID NO: 2) and ECK (SEQ ID NO: 3), having formulas (II) and (III), respectively:
  • the peptide comprises only natural amino acids and includes the sequence (L)-Ala-(L)-Glu-(L)-Cys-(L)-Lys (SEQ ID NO: 1).
  • the peptide comprises non-natural amino acids, and may, for example, include the sequence (D)-Ala-(D)-Glu-(D)-Cys-(D)-Lys (SEQ ID NO: 4).
  • the peptide comprises a combination of natural (L-) and non-natural (D-) aminoacids.
  • one or more D-amino acids may be added at the amino and/or carboxyl terminus to alter the functionality, selectivity, or hydrolytic stability of the peptide.
  • the peptides referenced in the present disclosure comprise only natural (L-) amino acids.
  • Topically acceptable salts, esters, and prodrugs (collectively “derivatives”) of the peptides of the invention are also suitable.
  • the esters may include C 1-24 aliphatic hydrocarbon esters of the carboxyl terminus and/or the carboxyl side chain, including C 1-24 or Ci-18 or Ci-16 or C 1-12 or C e alkyl esters.
  • Salts will typically be acid addition salts formed by the reaction of the peptide with an inorganic or an organic acid.
  • Inorganic acids include mineral acids such as HC1 and H 2 S0 4 , and the like.
  • Organic acids include citric, benzoic, tartaric, malic, maleic, succinic, acetic, and propionic acid.
  • Prodrugs include any esters or amides that hydrolyze in vivo to yield the peptide of formula (I). Examples of suitable prodrugs can be found in the book entitled “Prodrugs and Targeted Delivery: Towards Better ADME Properties," Volume 47 (201 1), published by WILEY-VCH Verlag & Co, which is herein incorporated by reference in its entirety.
  • the prodrug is formed by reacting the peptide with glyoxylic acid to produce peptidyl-a-hydroxylglycine derivatives having improved stability.
  • the prodrugs may include terminal N-acetyl derivatives, side chain N-acetyl derivatives, N-hydroxy methylation or N-phthalidation of its N-terminus and/or side chain.
  • either terminus may be functionalized with an amino acid of the form H 2 N-(CH 2 ) consult-C0 2 H where "n" is an integer from 1-10, including amino valeric acid.
  • a lysine-amino valeric acid group is added at either terminus through a peptide bond.
  • Suitable amine protecting groups include, without limitation, benzoyloxycarbonyl (Cbz), tert- butoxycarbonyl (t-Boc), and 9-flourenylmethloxycarbonyl (FMOC).
  • the carboxyl group may be protected by forming an acid or base labile ester such as a methyl, ethyl, benzyl, or trimethylsilyl esters.
  • the first and second amino acids are reacted in a suitable solvent such as water or DMF in the presence of an in situ activating agent such as ⁇ , ⁇ '-dicyclohexylcarbodiimide (DCCI), diisopropylcarbodiimide (DIPCDI), or l-ethyl-3-(3'- dimethylaminopropyl)carbodiimide (EDCI) to effect peptide bond formation.
  • DCCI ⁇ , ⁇ '-dicyclohexylcarbodiimide
  • DIPCDI diisopropylcarbodiimide
  • EDCI l-ethyl-3-(3'- dimethylaminopropyl)carbodiimide
  • selective deprotection of the amino group of the first amino acid is accomplished by acid hydrolysis under conditions that do not remove the carboxyl protecting group of the second amino acid. The procedure is repeated with additional amino protected amino acids.
  • Solid phase synthesis such as the well-
  • compositions according to the invention may be formulated in a variety of forms for topical application and will typically comprise from about 0.0001% by weight to about 20% by weight of the peptide. More typically, the peptide will comprise from about 0.001% by weight to about 10% by weight, and more preferably from about 0.01% by weight to about 5% by weight of the composition. In one embodiment, the active peptide will comprise from about 0.1% by weight to about 0.25% by weight or to about 0.5% by weight or to about 1% by weight of the composition.
  • the compositions may comprise an effective amount of the peptide, by which is meant an amount sufficient to stimulate production of HA in the skin. In other embodiments, the amount of peptide will be sufficient to diminish the appearance of dermatological signs of aging in a given area of skin when topically applied thereto daily for a period of at least eight weeks.
  • the peptides of the invention are provided in physiologically acceptable vehicles or carriers.
  • vehicle may be either hydrophobic or hydrophilic.
  • Suitable, hydrophobic carriers include, for example, waxy non-ionic substances commonly used in cosmetics, such as esters and ethers of fatty alcohols and of fatty acids, with carbon chain length from C 4 to C22, preferably from Cs to C 18 , or from C 12 to C 18 .
  • Examples of a fatty hydrophobic carriers include isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, the benzoate of C 12 -C 15 alcohols, cetearyl octanoate, cetyl palmitate, myristyl myristate, myristyl lactate, cetyl acetate, propylene glycol dicaprylate/caprate, decyl oleate, acetylated lanolin, stearyl heptanoate, diisostearyl malate, octyl hydroxystearate, octyl hydroxystearate, isopropyl isostearate, and the like.
  • Suitable hydrophilic carriers may comprise, for example, water, lower alcohols
  • glycols and alkoxylated glycols commonly used in cosmetics including ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, and the like.
  • the topically acceptable vehicle may be in the form of an emulsion.
  • suitable emulsions include water-in-oil emulsions, oil-in-water emulsions, silicone-in-water emulsions, water-in-silicone emulsions, wax-in-water emulsions, water-oil-water triple emulsions or the like having the appearance of a cream, gel or microemulsions.
  • the term "oil” includes silicone oils unless otherwise indicated.
  • the emulsion may include an emulsifier, such as a nonionic, anionic or amphoteric surfactant, or a gellant, typically in an amount from about 0.001% to about 5% by weight.
  • the topically acceptable vehicle may include water; vegetable oils; mineral oils; ester oils such as octal palmitate, isopropyl myristate and isopropyl palmitate; ethers such as dicapryl ether and dimethyl isosorbide; alcohols such as ethanol and isopropanol; fatty alcohols such as cetyl alcohol, cetearyl alcohol, stearyl alcohol and behenyl alcohol; isoparaffins such as isooctane, isododecane (IDD) and isohexadecane; silicone oils such as cyclomethicone, dimethicone, dimethicone cross-polymer, polysiloxanes and their derivatives, preferably organomodified derivatives including PDMS, dimethicone copolyol, dimethiconols, and amodimethiconols; hydrocarbon oils such as mineral oil, petrolatum, isoeicosane and polyolefins,
  • Aqueous vehicles may include one or more solvents miscible with water, including lower alcohols, such as ethanol, isopropanol, and the like.
  • the vehicle may comprise from about 50% to about 99% by weight of the composition.
  • the compositions may include one or more additional skin actives, including but not limited to, retinoids, botanicals, keratolytic agents, desquamating agents, keratinocyte proliferation enhancers, collagenase inhibitors, elastase inhibitors, depigmenting agents, anti-inflammatory agents, steroids, anti-acne agents, antioxidants, and advanced glycation end-product (AGE) inhibitors, to name but a few.
  • skin actives including but not limited to, retinoids, botanicals, keratolytic agents, desquamating agents, keratinocyte proliferation enhancers, collagenase inhibitors, elastase inhibitors, depigmenting agents, anti-inflammatory agents, steroids, anti-acne agents, antioxidants, and advanced glycation end-product (AGE) inhibitors, to name but a few.
  • the amounts of these various ingredients are those conventionally used in the cosmetic field to achieve their intended purpose, and range individually or collectively typically from about 0.001
  • Exemplary anti-aging components include, without limitation, botanicals (e.g.,
  • exfoliating agents e.g., glycolic acid, 3,6,
  • retinoids include, without limitation, retinoic acid (e.g., all-trans, or
  • retinoids will typically be included in amounts from about 0.0001% to about 5% by weight, more typically from about 0.01% to about 2.5% by weight, or from about 0.1% to about 1.0% by weight.
  • compositions according to this embodiment will typically include an antioxidant such as ascorbic acid and/or BHT and/or a chelating agent such as EDTA or a salt thereof (e.g., disodium EDTA) in amounts effective to stabilize the retinoid (e.g., 0.0001% - 5%).
  • an antioxidant such as ascorbic acid and/or BHT
  • a chelating agent such as EDTA or a salt thereof (e.g., disodium EDTA) in amounts effective to stabilize the retinoid (e.g., 0.0001% - 5%).
  • the topical compositions of the present invention may also include one or more of the following: a skin penetration enhancer; an emollient, such as isopropyl myristate, petrolatum, volatile or non-volatile silicones oils (e.g., methicone, dimethicone), ester oils, mineral oils, and fatty acid esters; a humectant, such as glycerin, hexylene glycol or caprylyl glycol; a skin plumper, such as palmitoyl oligopeptide, collagen, collagen and/or glycosaminoglycan (GAG) enhancing agents; a sunscreen, such as avobenzone or octyl methoxycinnamate; an exfoliating agent; and an antioxidant.
  • a skin penetration enhancer such as isopropyl myristate, petrolatum, volatile or non-volatile silicones oils (e.g., methicone, dimethicone), ester oils,
  • Suitable exfoliating agents include, for example, alpha-hydroxy acids, beta- hydroxy acids, oxa-acids, oxadiacids, and their derivatives such as esters, anhydrides and salts thereof.
  • Suitable hydroxy acids include, for example, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, 2-hydroxyalkanoic acid, mandelic acid, salicylic acid and derivatives thereof.
  • One exemplary exfoliating agent is glycolic acid.
  • the exfoliating agent may comprise from about 0.001% to about 20% by weight of the composition.
  • antioxidants examples include compounds having phenolic hydroxy functions, such as ascorbic acid and its derivatives/esters; beta-carotene; catechins; curcumin; ferulic acid derivatives (e.g., ethyl ferulate, sodium ferulate); gallic acid derivatives (e.g., propyl gallate); lycopene; reductic acid; rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherol and its derivatives, including tocopheryl acetate; uric acid; or any mixtures thereof.
  • ferulic acid derivatives e.g., ethyl ferulate, sodium ferulate
  • gallic acid derivatives e.g., propyl gallate
  • lycopene reductic acid
  • rosmarinic acid tannic acid
  • tetrahydrocurcumin tocopherol and its derivatives, including tocopheryl acetate; uric acid; or any mixtures thereof
  • antioxidants are those that have one or more thiol functions (-SH), in either reduced or non-reduced form, such as glutathione, lipoic acid, thioglycolic acid, and other sulfhydryl compounds.
  • the antioxidant may be inorganic, such as bisulfites, metabisulfites, sulfites, or other inorganic salts and acids containing sulfur.
  • Antioxidants may comprise, individually or collectively, from about 0.001% to about 10 % (w/w), or from about 0.01% to about 5% (w/w) of the total weight of the composition.
  • vitamins such as tocopherol and ascorbic acid
  • vitamin derivatives such as ascorbyl monopalmitate, tocopheryl acetate, and Vitamin E palmitate
  • thickeners such as hydroxyalkyl cellulose, carboxymethylcellulose, carbombers, and vegetable gums such as xanthan gum
  • gelling agents such as ester-terminated polyester amides
  • structuring agents such as metal chelating agents such as EDTA or salts thereof
  • pigments such as ethanolamine, sodium hydroxide, etc.
  • pH adjusters citric acid, ethanolamine, sodium hydroxide, etc.
  • composition may optionally comprise other components known to those skilled in the art including, but not limited to, film formers, moisturizers, minerals, viscosity and/or rheology modifiers, anti-acne agents, insect repellents, skin cooling compounds, skin protectants, lubricants, fragrances, preservatives, stabilizers, and mixtures thereof.
  • film formers moisturizers, minerals, viscosity and/or rheology modifiers
  • anti-acne agents anti-acne agents
  • insect repellents insect repellents
  • skin cooling compounds skin protectants, lubricants, fragrances, preservatives, stabilizers, and mixtures thereof.
  • fragrances preservatives, stabilizers, and mixtures thereof.
  • preservatives preservatives, stabilizers, and mixtures thereof.
  • stabilizers and mixtures thereof.
  • the foregoing may individually or collectively comprise from about 0.0001% to about 20% by weight of the composition.
  • compositions contemplated by this disclosure can include one or more compatible cosmetically acceptable adjuvants commonly used and known by the skilled practitioner, such as colorants, pearls, chromalites, micas, pigments, dyes, fragrances, emollients, humectants, preservatives, vitamins, chelators, thickeners, anesthetics, anti- allergenics, antifungals, antimicrobials, other anti-inflammatory agents, antioxidants, antiseptics, depigmenting agents, film formers, insect repellents, pharmaceutical agents, photostabilizing agents, sunscreens, stabilizers, surfactants, thickeners, viscosity modifiers, and botanicals.
  • compatible cosmetically acceptable adjuvants commonly used and known by the skilled practitioner, such as colorants, pearls, chromalites, micas, pigments, dyes, fragrances, emollients, humectants, preservatives, vitamins, chelators, thickeners, anesthetics, anti- allergenics, anti
  • the topical compositions of the present disclosure may also include a skin penetration enhancer, a surface smoother, a skin plumper, an optical diffuser, an exfoliation promoter, and an antioxidant. Details with respect to these and other suitable cosmetic ingredients can be found in the "International Cosmetic Ingredient Dictionary and Handbook," 10th Edition (2004), published by the Cosmetic, Toiletry, and Fragrance Association (CTFA), at pp. 2177-2299, which is herein incorporated by reference in its entirety.
  • CTFA Cosmetic, Toiletry, and Fragrance Association
  • the amounts of these various substances are those that are conventionally used in the cosmetic or pharmaceutical fields, for example, they can constitute from about 0.01% to about 20% of the total weight of the composition.
  • a sunscreen may be included to protect the skin from damaging ultraviolet rays.
  • the sunscreen provides both UVA and UVB protection, by using either a single sunscreen or a combination of sunscreens.
  • the sunscreens that can be employed in the present compositions are avobenzone, cinnamic acid derivatives (such as octylmethoxy cinnamate), octyl salicylate, oxybenzone, octocrylene, titanium dioxide, zinc oxide, or any mixtures thereof.
  • the sunscreen may be present from about 1 wt % to about 30 wt % of the total weight of the composition.
  • the topical composition will have a pH range from 1 to
  • the composition will have a pH in the range of from 3.5 to 7 or from 7-10.5. In some embodiments, the pH will be in the range of 3-4, or 4-5, or 5-6, or 6-7, or 7-8, or 8-9, or 9-10, or 10-1 1, or 1 1-12.
  • Suitable pH adjusters such as sodium hydroxide, citric acid and triethanolamine may be added to bring the pH within the desired range.
  • Another embodiment of the present disclosure is directed to the delivery of the described compositions by the use of targeted delivery systems, for example, liposomes, microspheres (see, e.g., U.S. Pat. No. 5,770,222 to Unger et al), and the like, so that the components and/or active constituents can more readily reach and affect the subcutaneous layer of the area of application, e.g., face or neck, or the other area of the skin.
  • targeted delivery systems for example, liposomes, microspheres (see, e.g., U.S. Pat. No. 5,770,222 to Unger et al), and the like, so that the components and/or active constituents can more readily reach and affect the subcutaneous layer of the area of application, e.g., face or neck, or the other area of the skin.
  • compositions may be formulated in a variety of product forms, such as, for example, a lotion, cream, serum, spray, aerosol, cake, ointment, essence, gel, paste, patch, pencil, towelette, mask, stick, foam, elixir, concentrate, and the like, particularly for topical administration.
  • a lotion, cream, serum, spray, aerosol, cake, ointment, essence, gel, paste, patch, pencil, towelette, mask, stick, foam, elixir, concentrate, and the like particularly for topical administration.
  • the composition is formulated as a lotion, cream, ointment, or gel.
  • the invention also provides a method for ameliorating and/or preventing signs of human skin photo- and intrinsic aging comprising topically applying the compositions of the invention.
  • the compositions of the invention are preferably applied to affected skin areas once or twice daily for as long as is necessary to achieve desired anti-aging results.
  • Methods for enhancing the production of HA in human skin comprising topically applying to an area of the skin in need thereof (e.g., sagging skin, thinning skin, skin suffering from wrinkles and fine lines, etc.) a topical composition comprising a topically acceptable vehicle, and an effective amount of a peptide of the invention (e.g., SEQ ID NOs: 1-3), for a time sufficient to improve the appearance thereof.
  • the treatment may be a least once or twice daily and may last for a period of at least four weeks, typically at least eight weeks or longer.
  • composition may optionally further comprise a retinoid and/or an alpha-hydroxy acid (e.g., glycolic acid) and/or a beta-hydroxy acid (e.g., salicylic acid or a derivative) in amounts effective to improve the appearance of skin.
  • a retinoid and/or an alpha-hydroxy acid e.g., glycolic acid
  • a beta-hydroxy acid e.g., salicylic acid or a derivative
  • the compositions are applied topically to improve the aesthetic appearance of human skin.
  • the method comprises topically applying to an area of the skin in need thereof a composition comprising an effective amount of a peptide of the invention (e.g., SEQ ID NOs: 1-3) for a time sufficient to improve the aesthetic appearance of said human skin.
  • a composition comprising an effective amount of a peptide of the invention (e.g., SEQ ID NOs: 1-3) for a time sufficient to improve the aesthetic appearance of said human skin.
  • the compositions are topically applied to the skin in effective amounts, by which is meant an amount sufficient to achieve a measurable improvement in skin health or reduction in one or more dermatological signs of aging with daily (once, twice, etc.) administration, typically for a period of at least one week or more.
  • the aesthetic improvement of human skin may be an improvement of any attribute or characteristic of skin, including without limitation: treatment, reduction, and/or prevention of fine lines or wrinkles;
  • a method for the treatment of wrinkles and/or fine lines on the skin human skin comprising topically applying to an area of the skin in need thereof (e.g., applying to a wrinkle or fine line) a composition comprising a peptide of the invention (e.g., SEQ ID NOs: 1-3), for a time sufficient to improve the aesthetic appearance of said human skin.
  • the treatment may be a least once or twice daily and may last for a period of at least four weeks, typically at least eight weeks or longer.
  • composition may optionally further comprise a retinoid (e.g., retinol or retinyl palmitate) and/or an alpha-hydroxy acid (e.g., glycolic acid) and/or a beta- hydroxy acid (e.g., salicylic acid or derivative) in amounts effective to improve the appearance of skin.
  • a retinoid e.g., retinol or retinyl palmitate
  • an alpha-hydroxy acid e.g., glycolic acid
  • beta- hydroxy acid e.g., salicylic acid or derivative
  • methods for reducing the severity of, reducing the number of, or preventing or forestalling the onset of, wrinkles or fine lines on human skin comprising topically applying to an area of the skin in need thereof (e.g., wrinkled skin), an effective amount (e.g., 0.001% - 1% by weight, w/w) of a peptide of the invention (e.g., SEQ ID NOs: 1-3) in combination with an effective amount (e.g., 0.01% - 5% by weight, w/w) of retinol and/or an effective amount (e.g., 0.001% - 5% by weight, w/w) of an alpha-hydroxy acid (e.g., glycolic acid) and/or a beta-hydroxy acid (e.g., salicylic acid).
  • an effective amount e.g., 0.001% - 1% by weight, w/w
  • an alpha-hydroxy acid e.g., glycolic acid
  • a beta-hydroxy acid
  • the invention provides a method for treating aging skin by topically applying a composition comprising a HA-stimulating peptide (e.g., SEQ ID NOs: 1-3), typically in a physiologically acceptable vehicle, over the affected area for a period of time sufficient to remediate, reverse, reduce, ameliorate, or prevent dermatological signs of aging.
  • a composition comprising a HA-stimulating peptide (e.g., SEQ ID NOs: 1-3), typically in a physiologically acceptable vehicle, over the affected area for a period of time sufficient to remediate, reverse, reduce, ameliorate, or prevent dermatological signs of aging.
  • the improvement in the condition and/or aesthetic appearance is selected from the group consisting of: reducing dermatological signs of chronological aging, photo-aging, hormonal aging, and/or actinic aging; preventing and/or reducing the appearance of lines and/or wrinkles; reducing the noticeability of facial lines and wrinkles, facial wrinkles on the cheeks, forehead, perpendicular wrinkles between the eyes, horizontal wrinkles above the eyes, and around the mouth, marionette lines, and particularly deep wrinkles or creases; improving the appearance of suborbital lines and/or periorbital lines; reducing the appearance of crow's feet; rejuvenating and/or revitalizing skin, particularly aging skin; reducing skin fragility; preventing and/or reversing of loss of glycosaminoglycans and/or collagen; ameliorating the effects of estrogen imbalance; preventing skin atrophy; preventing, reducing, and/or treating hyperpigmentation or hypopigmentation; minimizing skin discoloration; improving skin tone, radiance, clarity and/or
  • the peptides of the invention will be used to reduce the severity of fine lines or wrinkles, often in combination with retinol.
  • the composition will typically be applied to the skin one, two, or three times daily for as long as is necessary to achieve desired results.
  • the treatment regimen may comprise daily application for at least one week, at least two weeks, at least four weeks, at least eight weeks, or at least twelve weeks or more. Chronic treatment regimens are also contemplated.
  • compositions of the invention will be applied to the skin in an amount from about 0.001 to about 100 mg/cm 2 , more typically from about 0.01 to about 20 mg/cm 2 , or from about 0.1 to about 10 mg/cm 2 .
  • compositions of the invention will be useful for treating thin skin by topically applying the composition comprising the active peptides (e.g., SEQ ID NOs: 1-3) to thin skin of an individual in need thereof.
  • Thin skin is intended to include skin that is thinned due to chronological aging, menopause, or photo-damage and skin that is thinning prematurely.
  • the treatment is for thin skin in men, whereas other embodiments treat thin skin in women, pre-menopausal or postmenopausal, as it is believed that skin thins differently with age in men and women, and in particular in women at different stages of life.
  • the method of the invention may be employed prophylactically to forestall aging including in individuals that have not manifested signs of skin aging, most commonly in individuals under 25 years of age.
  • the method may also reverse or treat signs of aging once manifested as is common in individuals over 25 years of age, or to slow the progression of dermatological aging in such individuals.
  • the compositions of the invention comprising active peptides (e.g., SEQ ID NOs: 1-3) are applied to human skin to reduce sebum production or improve the appearance of skin affected by cellulite, and/or reduce unwanted lipogenesis or increase lipolysis.
  • the peptides of the invention can be formulated in topically acceptable vehicles (as described herein) and may include one or more additional agents such as anti-acne ingredients (e.g., salicylic acid, benzoyl peroxide and other peroxides, sulfur, retinoids, etc.) in the case of a facial composition, or, in the case of a cellulite treatment, the formulation may comprise any ingredients suitable for treatment of cellulite, including without limitation, perilla oil and other unsaturated fatty oils and omega-3 fatty acids such as alpha-linolenic acid; caffeine; theophylline; xanthines; retinoids (e.g., retinol); and the like.
  • anti-acne ingredients e.g., salicylic acid, benzoyl peroxide and other peroxides, sulfur, retinoids, etc.
  • the formulation may comprise any ingredients suitable for treatment of cellulite, including without limitation, perilla oil and other unsaturated fatty oils and
  • a cellulite treatment according to the invention will typically be applied topically to skin suffering from cellulite, including skin of the buttocks and thighs for a period of time sufficient to improve the appearance thereof, including for example, daily treatment for at least four weeks, at least eight weeks, at least twelve weeks, or longer.
  • the compositions are topically applied to treat acne.
  • compositions described herein comprising active peptides can be used to treat and/or prevent hyper-pigmentation of skin and/or of the hair, for example, to lighten skin or hair.
  • the compositions are topically applied to the skin or hair, for example to an area of hyper- pigmented skin or hair.
  • Hyper-pigmentation includes any coloration of an individual's skin or hair that is darker than desired by the individual and that is caused by melanocytes. Such unwanted pigmentation may also be called discoloration.
  • Hyper-pigmented areas of the skin include areas of discrete or mottled hyper-pigmentation.
  • Areas of discrete hyper- pigmentation can be distinct, uniform areas of darker color and may appear as brown spots or freckles on the skin, including marks commonly called pigment spots or "age spots.” Areas of mottled hyper-pigmentation of the skin can be dark blotches that are larger and more irregular in size and shape than areas of discrete pigmentation. Areas of hyper-pigmentation also include areas of tanned skin, for example, skin tanned due to UV exposure. Hyper-pigmented hair includes any shade of hair that is darker than desired.
  • Treating hyper-pigmentation or hyper-pigmented skin/hair refers to eradicating, reducing, ameliorating, or reversing one or more of the unwanted features associated with hyper-pigmentation, such as producing a perceptible lightening of the skin or hair in the affected area.
  • Lightening hyper-pigmented areas of the skin may be desirable, in one embodiment, in diminishing age spots; lightening a suntan; evening or optimizing skin tones, e.g., in areas of mottled hyper-pigmentation; in treating melasmic and chloasmic patches, freckles, after-burn scars, and post-injury hyper-pigmentation.
  • Preventing hyper- pigmentation or hyper-pigmented skin refers to affording skin, not yet affected by hyper- pigmentation, a benefit that serves to avoid, delay, forestall, or minimize one or more unwanted features associated with skin hyper-pigmentation, such as reducing the darkness or size of hyper-pigmented areas that eventually develop.
  • the peptides of the invention are intended for oral use, including for pharmaceutical use.
  • Pharmaceutical formulations will include pharmaceutically acceptable carriers (i.e., diluents and excipients).
  • the pharmaceutical compositions may be included in solid dosage forms, including compressed tablets and capsules, or in liquid or powder forms (including lyophilized powders of the peptide suitable for reconstitution with water).
  • Pharmaceutical dosage forms will typically include from about 0.1 mg to about 200 mg, or from about 1 mg to about 100 mg of the peptides of the invention.
  • the dosage forms may be immediate release, in which case they will typically comprise a water-soluble or dispersible carrier such as microcrystalline cellulose, mannitol, hydroxypropyl methyl cellulose, PVP or the like, or may be delayed, sustained, or modified release, in which case they may comprise water-insoluble polymers such as cellulose ethers (e.g., ethylcellulose), alone or in combination with water soluble or dispersible polymers, to regulate the rate of dissolution of the dosage form in the stomach.
  • a water-soluble or dispersible carrier such as microcrystalline cellulose, mannitol, hydroxypropyl methyl cellulose, PVP or the like
  • water-insoluble polymers such as cellulose ethers (e.g., ethylcellulose)
  • the composition is intended for use as a non-therapeutic treatment.
  • the composition is an article intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance, in accordance with the US FD&C Act, ⁇ 201(i).
  • Human dermal fibroblast cells were grown in a 96 well plate in DMEM media
  • HA Hyaluronic Acid
  • Results are summarized in Table 1 below as percent change of HA production relative to vehicle control:
  • a peptide of Formula I effectively increases hyaluronic acid production in human dermal fibroblast cells by 90-150% at 0.001% concentration.

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Abstract

L'invention concerne des procédés permettant de diminuer les signes du vieillissement et/ou d'améliorer l'état de santé des téguments humains, tels que la peau, et des compositions utiles à cet effet. Les compositions selon l'invention comprennent un peptide ayant la séquence AECK (SEQ ID NO : 1) ou un dérivé de celui-ci, dans un véhicule acceptable par voie topique.
PCT/US2014/071803 2014-12-22 2014-12-22 Peptides et leur utilisation dans le traitement de la peau WO2016105332A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11318077B2 (en) 2017-09-29 2022-05-03 Rodan & Fields, Llc Retinaldehyde containing compositions and methods of use

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US6589540B1 (en) * 1999-12-23 2003-07-08 Coreana Cosmetics Co., Ltd. Cosmetic composition for skin care containing retinol and epidermal growth factor
US20030129687A1 (en) * 1995-02-14 2003-07-10 Ruben Steven M. Keratinocyte growth factor-2
WO2004069871A1 (fr) * 2003-02-05 2004-08-19 Queensland University Of Technology Complexes a facteurs de croissance et modulation de la migration et de la croissance cellulaires
WO2008157483A2 (fr) * 2007-06-14 2008-12-24 The Research Foundation Of State University Of New York Polypeptides et procédés d'utilisation

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Publication number Priority date Publication date Assignee Title
US20030129687A1 (en) * 1995-02-14 2003-07-10 Ruben Steven M. Keratinocyte growth factor-2
US6589540B1 (en) * 1999-12-23 2003-07-08 Coreana Cosmetics Co., Ltd. Cosmetic composition for skin care containing retinol and epidermal growth factor
WO2004069871A1 (fr) * 2003-02-05 2004-08-19 Queensland University Of Technology Complexes a facteurs de croissance et modulation de la migration et de la croissance cellulaires
WO2008157483A2 (fr) * 2007-06-14 2008-12-24 The Research Foundation Of State University Of New York Polypeptides et procédés d'utilisation

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11318077B2 (en) 2017-09-29 2022-05-03 Rodan & Fields, Llc Retinaldehyde containing compositions and methods of use

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