WO2009085236A2 - Compositions et procédés d'utilisation d'analogues de la substance p. - Google Patents

Compositions et procédés d'utilisation d'analogues de la substance p. Download PDF

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Publication number
WO2009085236A2
WO2009085236A2 PCT/US2008/013947 US2008013947W WO2009085236A2 WO 2009085236 A2 WO2009085236 A2 WO 2009085236A2 US 2008013947 W US2008013947 W US 2008013947W WO 2009085236 A2 WO2009085236 A2 WO 2009085236A2
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Prior art keywords
xaa
composition
seq
skin
met
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WO2009085236A3 (fr
Inventor
Hal Siegel
Michael K. Wilhelm
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Immuneregen Biosciences Inc
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Immuneregen Biosciences Inc
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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
    • A61Q19/007—Preparations for dry skin
    • 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
    • A61Q19/005—Preparations for sensitive skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • 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
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners

Definitions

  • compositions and methods for use of Substance P analogs to enhance the appearance of human skin can be administered as creams, ointments, liquids, lotions and the like.
  • compositions comprising substance P analogs useful for improving the texture or appearance of human skin.
  • the compositions can be, for example, cosmetic or cosmeceutical compositions.
  • the substance P analog is of Formula (I):
  • Xaa 1 is Arg, Lys, 6-N methyllysine, or (6-N, 6-N) dimethyllysine;
  • Xaa 2 is Pro or Ala
  • Xaa 3 is Lys, Arg, 6-N-methyllysine, or (6-N, 6-N) dimethyllysine;
  • Xaa 4 is Pro or Ala
  • Xaa 5 is GIn or Asn
  • Xaa 6 is GIn or Asn
  • Xaa 7 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
  • Xaa 8 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
  • Xaa 9 is GIy, Pro, Ala, or sarcosine (N-methylglycine);
  • Xaa 10 is Leu, VaI, He, Norleucine, Met, Met sulfoxide, Met sulfone, N- methylleucine, or N-methylvaline;
  • Xaa 1 ' is Met, Met sulfoxide, Met sulfone, or Norleucine;
  • Z 1 is R 2 N- or RC(O)NR-;
  • Z 2 is -C(O)NR 2 or -C(O)OR or a salt thereof; wherein each R is independently -H, (Ci -C 6 ) alkyl, (Ci -C 6 ) alkenyl, (Ci -C 6 ) alkynyl, (C 5 -C 20 ) aryl, (C 6 -C 26 ) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl; and each "— " between residues Xaa 1 through Xaa 1 ' independently designates an amide linkage, a substitute amide linkage or an isostere of an amide.
  • the substance P analog can be of Formula (I) as described herein, wherein Xaa 1 is Arg; Xaa 2 is Pro; Xaa 3 is Lys; Xaa 4 is Pro; Xaa 5 is GIn; Xaa 6 is GIn; Xaa 7 is Phe or Phe substituted with chlorine at position 4; Xaa 8 is Phe, or Phe substituted with chlorine at position 4; Xaa 9 is GIy, Pro or N- methylglycine; Xaa 10 is Leu; and Xaa" is Met, Met sulfoxide, Met sulfone, or Norleucine.
  • Formula (I) as described herein, wherein Xaa 1 is Arg; Xaa 2 is Pro; Xaa 3 is Lys; Xaa 4 is Pro; Xaa 5 is GIn; Xaa 6 is GIn; Xaa 7 is Phe or Phe substituted with chlorine at position 4; Xa
  • the substance P analog can be of Formula (I) as described herein wherein the "— " between residues Xaa 1 through Xaa 1 ' designates -C(O)NH-; Z 1 is H 2 N-; and Z 2 is -C(O)NH 2 .
  • the substance P analog can be selected from the group consisting of:
  • RPKPQQFFGLM (SEQ ID NO. : 1 );
  • RPKPQQFFMeGIyLM(O 2 ) (SEQ ID NO. : 2);
  • RPKPQQFFGLM(O 2 ) (SEQ ID NO. : 3);
  • RPKPQQFFMeGIyLM(O) (SEQ ID NO. : 4);
  • RPKPQQFFGLNIe SEQ ID NO.: 5
  • RPKPQQFFPLM (SEQ ID NO. : 6)
  • RPKPQQFFMeGIyLM (SEQ ID NO. : 7);
  • RPKPQQFTGLM (SEQ ID NO. : 8);
  • RPKPQQFFGLM(O) (SEQ ID NO. : 10);
  • the substance P analog can be Z,-RPKPQQFFMeGlyLM(O 2 )-Z 2 ; wherein Z, is NH 2 and Z 2 is C(O)NH 2 .
  • substance P (SEQ ID NO. 1) refers to peptide sequence: Arg Pro Lys Pro GIn GIn Phe Phe GIy Leu Met, or the single letter representation RPKPQQFFGLM (SEQ ID NO 1).
  • the peptide can be amidated at the carboxy terminus represented as RPKPQQFFGLM-NH 2 .
  • the methods and compositions provide a cosmetically effective amount of compounds of Formula I to improve the texture or appearance of human skin.
  • the compositions are those which, when administered to the skin, render a benefit or an effect of ameliorating or improving the texture or appearance of the skin.
  • the amelioration or improvement of the skin can be either short-term or long-term.
  • the improvement or amelioration of the skin can be an amelioration of an abnormal skin condition.
  • the abnormal skin condition to be ameliorated by administering a composition can be dry skin, severe dry skin, skin flakiness, wrinkles (both course and fine, caused by either intrinsic or extrinsic damage), blemished skin, inflammatory dermatoses, age-related skin changes, and/or the effects of skin atrophy.
  • the compositions and methods provide for use of the substance P analogs as a rubefacient.
  • the cosmetic compositions are those which, when administered to the skin can be cosmetically effective, i.e., the compositions can improve the texture or appearance thereof, without necessarily rendering a benefit, or mask the appearance of abnormal skin.
  • improving the texture or appearance of the skin is meant to encompass enhancing the skin's natural look or feel so as to increase the beauty or smoothness of the skin from its pre-treated state, or to mask abnormal skin. This can include providing a temporary moisturizing effect to the epidermis of the skin or creating a rosy or red effect to the skin.
  • Such abnormal skin conditions or diseases include, but are not limited to dry skin, severe dry skin, skin flakiness, wrinkles (both coarse and fine, caused by either intrinsic or extrinsic damage), blemished skin, inflammatory dermatoses, age-related changes, and/or the effects of skin atrophy.
  • the methods provide for reducing the appearance of skin atrophy by administering to a subject an effective amount of a composition comprising one or more compounds of Formula I.
  • the methods provide for ameliorating disorders including but not limited to dry skin, severe dry skin, skin flakiness, wrinkles (both coarse and fine, caused by intrinsic as well as extrinsic damage), blemished skin, inflammatory dermatoses, age-related skin changes and/or skin atrophy.
  • the administration of the compositions can be to the skin, hair or nails of a human as a cosmetic composition.
  • the administration of the composition can be by a personal care composition such as bathing compositions including, for example, bath beads, shower gel and the like.
  • the compositions can be a substance P analog associated with a fat soluble compound.
  • the substance P analog and the fat soluble compound can be covalently bound, made into a complex (e.g. co-lyophilized without covalent bonds), or linked or adjoined in some fashion.
  • the fat soluble compound can enhance skin penetration. 4. DEFINITIONS
  • skin atrophy refers to the thinning or general degradation of the dermis layer of human skin often characterized by a decrease in collagen or elastin as well as decreased number, size and doubling potential of fibroblast cells.
  • cosmetically effective amount refers to an amount of compound or composition sufficient to improve the texture or appearance of skin, without necessarily rendering a benefit thereto, or to mask the appearance of abnormal skin.
  • improving the texture or appearance of the skin is meant to encompass enhancing the skin's natural look or feel so as to increase the beauty or smoothness of the skin from its pre-treated state, or to mask abnormal skin conditions. This can include providing a temporary moisturizing effect to the epidermis of the skin or creating a rosy or red effect to the skin.
  • compositions to be administered to the skin which improves the texture or appearance thereof, without necessarily rendering a benefit, or mask the appearance of abnormal skin. Such improvement includes providing a temporary moisturizing effect to the epidermis of mammalian skin.
  • cosmetic refers to a composition to be administered to the skin which improves the texture or appearance thereof and has biologically active ingredients that purportedly render a benefit to the user.
  • alkyl refers to a saturated branched, straight chain or cyclic hydrocarbon radical. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, hexyl, and the like. In preferred embodiments, the alkyl groups are (Cj -C 6 ) alkyl.
  • alkenyl refers to an unsaturated branched, straight chain or cyclic hydrocarbon radical having at least one carbon-carbon double bond. The radical may be in either the cis or trans conformation about the double bond(s).
  • Typical alkenyl groups include, but are not limited to, ethenyl, propenyl, isopropenyl, butenyl, isobutenyl, tert-butenyl, pentenyl, hexenyl and the like.
  • the alkenyl group is (Cj -C 6 ) alkenyl.
  • alkynyl refers to an unsaturated branched, straight chain or cyclic hydrocarbon radical having at least one carbon-carbon triple bond.
  • Typical alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, isobutynyl, pentynyl, hexynyl and the like.
  • the alkynyl group is (Ci -C 6 ) alkynyl.
  • aryl refers to an unsaturated cyclic hydrocarbon radical having a conjugated ⁇ electron system.
  • Typical aryl groups include, but are not limited to, penta- 2,4-diene, phenyl, naphthyl, anthracyl, azulenyl, chrysenyl, coronenyl, fluoranthenyl, indacenyl, idenyl, ovalenyl, perylenyl, phenalenyl, phenanthrenyl, picenyl, pleiadenyl, pyrenyl, pyranthrenyl, rubicenyl, and the like.
  • the aryl group is (C 5 -C 20 ) aryl, with (C 5 -C 10 ) being particularly preferred.
  • alkaryl refers to a straight-chain alkyl, alkenyl or alkynyl group wherein one of the hydrogen atoms bonded to a terminal carbon is replaced with an aryl moiety.
  • Typical alkaryl groups include, but are not limited to, benzyl, benzylidene, benzylidyne, benzenobenzyl, naphthenobenzyl and the like.
  • the alkaryl group is (C 6 -C 26 ) alkaryl, i.e., the alkyl, alkenyl or alkynyl moiety of the alkaryl group is (Ci -C 6 ) and the aryl moiety is (C 5 -C 20 ).
  • the alkaryl group is (C 6 -C 13 ) alkaryl, i.e., the alkyl, alkenyl or alkynyl moiety of the alkaryl group is (Ci -C 3 ) and the aryl moiety is (C 5 -C 10 ).
  • alkheteroaryl refers to a straight-chain alkyl, alkenyl or alkynyl group where one of the hydrogen atoms bonded to a terminal carbon atom is replaced with a heteroaryl moiety.
  • the alkheteroaryl group is 6-26 membered alkheteroaryl, i.e., the alkyl, alkenyl or alkynyl moiety of the alkheteroaryl is (Ci -C 6 ) and the heteroaryl is a 5-20-membered heteroaryl.
  • the alkheteroaryl is 6-13 membered alkheteroaryl, i.e., the alkyl, alkenyl or alkynyl moiety is a 5-10 membered heteroaryl.
  • heteroaryl refers to an aryl moiety wherein one or more carbon atoms is replaced with another atom, such as N, P, O, S, As, Se, Si, Te, etc.
  • Typical heteroaryl groups include, but are not limited to, acridarsine, acridine, arsanthridine, arsindole, arsindoline, carbazole, ⁇ -carboline, chromene, cinnoline, furan, imidazole, indazole, indole, indolizine, isoarsindole, isoarsinoline, isobenzofuran, isochromene, isoindole, isophosphoindole, isophosphinoline, isoquinoline, isothiazole, isoxazole, naphthyridine, perimidine, phenanthridine, phenanthroline, phenazine, phosphoin
  • substituted alkyl, alkenyl, alkynyl, aryl alkaryl, heteroaryl or alkheteroaryl refers to an alkyl, alkenyl, alkynyl, aryl, alkaryl, heteroaryl or alkheteroaryl group in which one or more hydrogen atoms is replaced with another substituent.
  • Preferred substituents include —OR, -SR, -NRR, -NO 2 , -CN, halogen, -C(O)R, -C(O)OR and -C(O)NR, wherein each R is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, alkaryl, heteroaryl or alkheteroaryl. 5. THE METHODS
  • the methods provided herein generally comprise administering a composition to the skin which renders a benefit or an effect of ameliorating or improving the texture or appearance of the skin.
  • the amelioration or improvement of the skin can be either short-term or long-term.
  • the improvement or amelioration of the skin can be an amelioration of an abnormal skin condition.
  • the abnormal skin condition to be ameliorated by administering a composition include, but are not limited to, dry skin, severe dry skin, skin flakiness, wrinkles (both course and fine, caused by either intrinsic or extrinsic damage), blemished skin, inflammatory dermatoses, age- related skin changes, and/or the effects of skin atrophy.
  • the compositions and methods provide for use of the substance P analogs as a rubefacient.
  • compositions can be used in the compositions.
  • excipients including excipients, vehicles, emollients, suspending agents, wetting agents and the like.
  • topical Drug Delivery Formulations 1989, Informa Healthcare, 1 st edition, Barel, Payne and Maibach, eds., Handbook of Cosmetic, Science and Technology, 2001, Informa Healthcare, 1 st edition, Draelos and Thaman, eds. Cosmetic Formulation of Skin Care Products (Cosmetic Science and Technology Series Vol.
  • the methods and compositions can be used in conjunction with dermatological procedures such as dermabrasion (e.g. microderm abrasion), dermaplaning, chemical or acid peels, dermal fillers, (e.g. Restylane®, Medicis, Scottsdale, AZ), fibroblast injections (e.g. autologous fibroblasts, Isolagen Inc., Exton, PA), silicone injections, laser surgery and the like.
  • the procedures are surgical.
  • the procedures are cosmetic.
  • the compositions can be applied as a liquid spritz following dermabrasion or acid peel.
  • the compositions can be in a lotion or cream formulation for application following silicone or fibroblast injections.
  • the number of wrinkles on the skin of a subject administered a composition as described herein is reduced. In one embodiment, the depth of a wrinkle on the skin of a subject administered a composition as described herein is reduced
  • the compositions can be a substance P analog associated with a fat soluble compound.
  • the substance P analog and the fat soluble compound can be covalently bound, made into a complex (e.g. co-lyophilized without covalent bonds), linked or adjoined in some fashion.
  • the fat soluble compound can enhance skin penetration.
  • the substance P analog can be associated with a fat soluble compound, wherein the fat soluble compound is a lipid.
  • the fat soluble compound can be saturated, unsaturated, natural or synthetic lipid or combinations thereof.
  • the lipid can be any of the eight categories of lipids: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides, as set forth by the Lipid Metabolites and Pathways Strategy established by the American Society of Biochemistry and Molecular Biology. These categories are based on the functional backbone of the lipid molecule from a chemical standpoint. The categories are further subdivided into classes and subclasses to handle the existing and emerging arrays of lipid structures which are within the scope of the present invention. Fahy et al., 2005, J. Lipid Res. 46: 839-62.
  • the lipid can be a fatty acid or conjugate, octadecaoid, eicosanoid, docosanoid, fatty alcohol, fatty aldehyde, fatty ester, fatty amide, fatty nitrile, fatty ether, hydrocarbon, oxygenated hydrocarbon or combination thereof.
  • the lipid can be a glycerolipids, including, but not limited to, monoradylglycerol, diradylflycerol, triradylglycerol, glycosylmonoradylglycerol, glycosyldiradylglycerol or combinations thereof.
  • the glycerophospholipids can be glycerophosphocholines, glycerophosphoethanolamine, glycerophosphoserine, glycerophosphoglycerol, glycerophosphoglycerophosphate, glycerophosphoinositol, glycerophosphoinositol monophosphate, glycerophosphoinositol bisphosphate, glycerophosphoinositol trisphosphate, glycerophosphate, glyceropyrophosphate, glycerophosphoglycerophosphoglycerol, cytidine-5' -diphosphate (CDP) glycerol, glycerophosphoglucose lipid, glycerophosphoinositolglycan, glycerophosphonocholine, glycerophosphonoethanolamine, di-glycerol tetraether phospholipid (caldarchaeols),
  • the sphingolipids can be sphingoid bases, ceramides, phosphophingolipids, phosphonosphingolipids, neutral glycosphingolipids, acidic glycosphingolipids, basic glycosphingolipids, amphoteric glycosphingolipids, arsenosphingolipids or combinations thereof.
  • the sterols can be steroids, secosteroids, bile acids and derivatives thereof, steroid conjugates or combinations thereof.
  • the prenol lipids can be isoprenoids, quinones, hydroquinones, polyprenols, hopanoids or combinations thereof.
  • the saccharolipids can be acylaminosugars, acylaminosugar glycans, acyltrehaloses, acyltrehalose glycans or combinations thereof.
  • the polyketides can be macrolide polyketides, aromatic polyketides, non-ribosomal peptide/polyketide hybrids or combinations thereof.
  • compositions can be formulated for topical application to keratin materials such as the skin, the hair, or the nails.
  • the substance P analogs as described herein can be administered to human skin.
  • the compositions can be applied topically.
  • the topical compositions can be a solution (including collodions, liniments, aqueous and oleaginous solutions), suspension, gel, emulsion, lotion, ointment, cream, salve, lip balm, liquid, transdermal patch, tape, strip or gauze.
  • the skin care composition can be a skin protectant treatment, body lotion, facial cream, moisturizing cream, facial cleansing emulsion, surfactant-based facial cleanser, facial exfoliating gel, facial toner, exfoliating cream, facial mask, or the like.
  • the hair care composition can be a shampoo, conditioner, anti-dandruff treatment, styling aid, styling conditioner, hair repair or treatment serum, lotion, cream, pomade, and chemical treatments.
  • the styling aids can be a spray, mousse, rinse, gel, foam or the like.
  • the chemical treatments are selected from the group consisting of permanent waves, relaxers, and permanent, semi-permanent, and temporary color treatments and combinations thereof.
  • the composition can be a sunscreen, skin protectant, anti-dandruff product, body wash, or bath composition.
  • the composition may be in the form of an emulsified vehicle, such as a nutrient cream or lotion, a stabilized gel or dispersioning system, such as skin softener, a nutrient emulsion, a nutrient cream, a massage cream, a treatment serum, a liposomal delivery system, a topical facial pack or mask, a surfactant-based cleansing system such as a shampoo or body wash, an aerosolized or sprayed dispersion or emulsion, a hair or skin conditioner or a styling aid.
  • an emulsified vehicle such as a nutrient cream or lotion, a stabilized gel or dispersioning system, such as skin softener, a nutrient emulsion, a nutrient cream, a massage cream, a treatment serum, a liposomal delivery system, a topical facial pack or mask, a sur
  • the substance P analogs can be formulated into various compositions as described herein using generally recognized dermatological and cosmetic ingredients including excipients, carriers, vehicles, emollients, suspending agents, wetting agents and the like.
  • the composition provides a means whereby the substance P analog can be diluted, dispersed, conveyed to and distributed on the skin surface, hair or nails at an appropriate concentration.
  • the compositions can be a form used for this type of application including, oil-in-water emulsion, water-in-oil emulsion, silicone emulsion, microemulsion, nanoemulsion, or an aqueous or oily gel or liquid.
  • the composition is an aqueous emulsion that can be a water-in-oil emulsion, or an oil-in-water emulsion.
  • the composition is an aqueous fat emulsion in which the aqueous phase of the emulsion acts as a carrier.
  • Surfactants can be used in the compositions.
  • Preferred surfactants are those which make it possible to obtain an oil-in-water or wax-in-water emulsion.
  • the surfactants are nonionic surfactants: fatty acids, fatty alcohols, polyethoxylated or polyglycerolated fatty alcohols such as polyethoxylated stearyl or cetylstearyl alcohol, fatty acid esters of sucrose, alkyl glucose esters, in particular polyoxyethylenated fatty esters Of Ci-C 6 alkyl glucose and mixtures thereof; anionic surfactants: C 16 -C 30 fatty acids neutralized with amines, aqueous ammonia or alkaline salts, and mixtures thereof.
  • the proportion of the fatty phase ranges from about 2% to about 80% by weights and preferably from about 5% to about 50% by weight relative to the total weight of the composition.
  • the fatty substances, emulsifiers and co-emulsifiers included in the composition in emulsion form are those conventionally formulated in the art.
  • the emulsifier and co-emulsifier are preferably present in the composition in a proportion ranging from about 0.3% to about 30% by weight and preferably from about 0.5% to about 20% by weight relative to the total weight of the composition.
  • Emulsifiers and co-emulsifiers include fatty acid esters of polyethylene glycol, such as PEG-100 stearate, PEG-50 stearate and PEG-40 stearate, fatty acid esters of polyols, such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates commercially available under the trademark Tween®20 (Uniqema, Chicago, IL), or Tween®60 (Uniqema, Chicago, IL), for example, or mixtures thereof.
  • Tween®20 Uniqema, Chicago, IL
  • Tween®60 Uniqema, Chicago, IL
  • Fatty substances that can be used in the compositions include, but are not limited to, oils and mineral oils (liquid petroleum jelly), oils of plant origin, oils of animal origin (lanolin), synthetic oils (perhydrosqualene), silicone oils (cyclomethicone) and fluoro oil (perfluoro polyethers).
  • Fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums (including silicone gums) can be fatty substances in the compositions described herein.
  • compositions comprise one or more aqueous gel or hydrogel or hydrophilic gelling agents.
  • thickening agents include, but are not limited to, carbomers, cellulose base materials, gums, algin, agar, pectins, clays, carrageenan, gelatin, mineral or modified mineral thickeners, polyethylene glycol and polyalcohols, polyacrylamide and iother polymeric thickeners.
  • the thickening agents that give the stability and optimal flow characteristics of the composition are preferably used.
  • Lipophilic gelling agents include, for example, modified clays uschy as bentones, metal salts of fatty acids and hydrophobic silica.
  • compositions can further comprise an effective amount of a physiologically acceptable antioxidant selected from the group consisting of butylated p-cresol, butylated hydroxyquinone monomethyl ether, or a tocopherol.
  • a physiologically acceptable antioxidant selected from the group consisting of butylated p-cresol, butylated hydroxyquinone monomethyl ether, or a tocopherol.
  • the compositions can further comprise one or more natural or modified sterol compounds such as cholesterol and plant sterol (phytosterol), including stigmasterol, campesterol, ⁇ -sitosterol, chalinosterol, clionasterol, brassicasterol, ⁇ -spinasterol, dancosterol, desmosterol or poriferasterol.
  • the compositions can be comprised of one or more moisturizers or emollients (e.g. a compound that has occlusive, humectants or lubricating properties) wherein the emollient can be glycerin, aminobenzoic acid, octinoxate, betacarotine, stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane- 1,2-diol, butane- 1, 3 -diol, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, dimethylpolysiloxane, di-n
  • moistures include, but are not limited to, ceramides, sphingoid-based compounds, lecithins, glycosphingolipids, phospholipids, cholesterol and derivatives thereof, phytosterols (stigmaterol, ⁇ -sitosterol, or campersterol), essentially fatty acids, 1, 2-diaculglycerol, 4-chromanone, pentacyclic trite ⁇ enes, petroleum jelly and lanolin, threalose and derivatives thereof, hyaluronic acid and derivatives thereof, glycerol, pentanediol pidolates, amino acids (for examples) serine, proline, flutamates, arginine), xylitol, urea, creatine, flucosamines, lactic acid, lactates, polyglyceryl acrylate, ectoin and derivatives thereof, pyrrolidone-carboxylic acid and derivatives thereof, N-lauroyl-pyrrlidone
  • the composition can be comprised of one or more herbal or botanical extracts or oils.
  • exemplary botanicals can be algae, aloe vera, menthol, glucosamine, chondroitin, a capsaicinoid, arnica, coriander oil, chamomile, Roman chamomile, Epilobium angustifolium (willowherb), feverfew, St.
  • Preferred embodiments include the arnica plant or oils or extracts thereof.
  • the arnica plant has a bright yellow, daisy-like flower, and preparations made from the flowering heads have been used in homeopathic medicine for hundreds of years.
  • the active components in arnica are sesquiterpene lactones, which reduce inflammation and decrease pain.
  • Arnica extract also stimulates the activity of white blood cells that perform much of the digestion of congested blood and disperse trapped, disorganized fluids from bumped and bruised tissue, joints and muscles.
  • Arnica extract is known to stimulate blood circulation. Furthermore, it has antibacterial and antiinflammatory qualities that can reduce swelling or edema.
  • Arnica extract can comprise from about 1% to about 10% of the composition. Preferably, Arnica extract comprises from about 3% to about 5% of the composition. An particularly preferred concentration of arnica extract is about 4% of the composition.
  • the compositions can be formulated with emu oil.
  • Emu oil is generally comprised of myristic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, elaidic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidic acid and eicosenoic acid.
  • the preparation of emu oil from an emu has been described in U.S. Patent No. 6,103,246. Also disclosed therein are preparations comprising emu oil and at least one medically active component, such as lactic acid or some other alpha-hydroxy acid.
  • Emu oil can comprise from about 1% to about 10% of the composition.
  • emu oil comprises from about 4% to about 6% of the composition.
  • a particularly preferred concentration of emu oil is about 5% of the composition.
  • the compositions can be comprised of one or more vitamins wherein the vitamins can be tocopheryl acetate (vitamin E), retinyl palmitate (vitamin A), ascorbyl palmitate (vitamin C) or ergocalciferol (vitamine D).
  • the vitamin can be from the vitamin B family including thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folic acid (B9) or cobalamin (B 12) or combinations thereof.
  • Cobalamin can be any form of a cobalt containing vitamer compound including, cyanocobalamin, hydroxocobalamin, methylcobalamin or 5-deoxyadenosylcobalamin (adenosylcobalamin).
  • the compositions can be comprised of one or more skin protectants or therapeutic agents wherein the skin protectants or therapeutic agents can be octinoxate, urea, niacinamide, salicylic acid, farnesol, alpha-hydroxy acids, sulfur containing compounds, retinoids, peptides, amino acids, zinc oxide, iron oxide or lanolin.
  • the peptides can be pentapeptides. See, U.S. Patent No. 6,493,326.
  • the therapeutic agents can be antimicrobial or antifungal agents.
  • the compositions can comprise a substance P analog and one or more sunscreen ingredients.
  • the compositions can further comprise one or more ultra-violet (UV) screening agents capable of screening out UVA or UVB radiation, or both UVA and UVB radiation.
  • UV ultra-violet
  • UV screening agents can be: (a) Benzophenone derivatives: 2,4-dihydroxybenzophenone (benzophenone-1); 2,2'4,4'-tetrahydroxybenzophenone (benzophenone-2); (b) 2- hydroxy-4-methoxybenzophenone (benzophenone-3), (Uvinul M40®, BASF, Florham Park, NJ) 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (benzopheonone-6), 5-chloro-2- hydroxybenzophenone (benzophenone-7); 2,2'-dihydroxy-4-methoxybenzophenone (benzophenone-8); the disodium salt of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone- 5,5'-disulfonic acid (benzophenone-9); 2-hydroxy-4-methoxy-4'-methylbenzophenone (benzophenone- 10); benzophenone-11; 2-hydroxy-4-(octyloxy)benzophen
  • Exemplary compounds for screening out UVB radiation include: (a) salicylic acid derivatives, in particular homomenthyl salicylate and octyl salicylate; (b) cinnamic acid derivatives, in particular 2-ethylhexyl p-methoxycinnamate, (Parsol MCX®, Givaudan, Vernier, Switzerland); (c) liquid ⁇ , ⁇ '-diphenylacrylate derivatives, in particular 2-ethylhexyl ⁇ -cyano- ⁇ , ⁇ '-diphenylacrylate, or octocrylene (Uvinul N539®, BASF, Florham Park, NJ); (d) p-aminobenzoic acid derivatives; (e) 4- methylbenzylidenecamphor (Eusolex 6300®, Merck, Whitehouse Station, NJ); (f) 2- phenylbenzimidazole-5 -sulfonic acid (Eusolex 232®, Merck, Whitehouse
  • Other compounds for screening out UVA and UVB radiation can be plant extracts, such as rosemary (rosmarinic acid) and extracts of the genus Leontopodium, in particular Leontopodium alpinum or Leontopodium stracheyi; and benzotriazole silicone, as described in FR-A-2,642,968.
  • the sunscreen can be homomenthyl salicylate (homosalate), 2-ethylhexyl salicylate (octyl salicylate), p-aminobenzoic acid (PABA), octyl dimethyl p-aminobenzoate (octyl dimethyl PABA or padimate O), 2-hydroxy-4- methoxy benzophenone (benzophenone-3, oxybenzone), 2-hydroxy-4-methoxy benzophenone-5-sulfonic acid (benzophenone-4-sulisobenzone), 2-ethylhexyl-p- methoxycinnamate (octyl methoxycinnamate) or butyl methoxydibenzoylmethane (avobenzone).
  • homomenthyl salicylate homosalate
  • 2-ethylhexyl salicylate octyl salicylate
  • PABA p-aminobenzoic acid
  • PABA
  • the composition can also comprise a vehicle to enable the active ingredient to be conveyed to the skin in an appropriate dilution.
  • the composition can be in a form of liquid, suspension, emulsion, lotion or cream.
  • compositions of the invention presents a wide range of possibilities depending on the required product from of the composition. Suitable vehicles can be classified as described hereinafter.
  • Cosmetic vehicles are substances which can act as diluents, dispersants, or solvents for the substance P analogs that can promote the application and distribution of the composition on the skin at an appropriate concentration; the vehicle is preferably one which can aid penetration of the active ingredient into the skin, thus ensuring that the effectiveness of the active ingredient is prolonged because of improved properties.
  • Compositions can include water is a vehicle, and/or at least one cosmetically acceptable vehicle other than water.
  • Vehicles other than water that can be used in the compositions can include solids or liquids such as propellants, solvents, humectants, thickeners and powders.
  • Examples of each of these types of vehicles, which can be used singly or as mixtures of one or more carriers, are as follows: (a) Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluorethane, monochlorodigluoromethane, trichlorotrifluorethane, propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide; (b) Solvents, such as ethyl alcohol, methylene chloride, isopropanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, tetrahydrofuran; (c
  • the amount of vehicle in the composition should preferably be sufficient to carry at least a portion of the active ingredient to the skin in an amount which is sufficient effectively to provide skin benefit.
  • the amount of the vehicle can comprise the major portion of the composition, particularly where little or no other ingredients are present in the composition.
  • the composition will accordingly comprise from 15% to 99.989% and preferably from 50% to 99.5% by weight of the vehicle or vehicles.
  • the compositions can further comprise additives and excipients that are common in cosmetics such as preservatives, solvents, fragrances, fillers, pigments, odor absorbers and dyestuffs.
  • the amounts of these additives and excipients are those conventionally employed in the field under consideration and range for example, from about 0.01% to about 20% of the total weight of the composition. Depending on their nature, these additives and excipients can be introduced into the fatty phase or into the aqueous phase.
  • excipients are, steric acid, caprylic/capric triglyceride, glyceryl stearate, PEG-100, PEG-400, PEG-600, dimethicone, distarch phosphate, cetearyl alcohol, ceteareth-20, phenoxyethanol, squalane, EDTA, methylparaben, triethanolamine, propylparaben, allantoin, benzyl alcohol, cetyl alcohol, distearyldimonium chloride, isopropyl palmitate, petrolatum, sodium chloride, water, mineral oil, stearic acid, carbomer, sodium lauryl sulfate, propylene glycol, polysorbate 20, panthenol, xanthan gum or fragrance.
  • the composition can also be in a formulation as a mask for the face or the body.
  • the mask can comprise a backing sheet impregnated with the substance P analogs to exert a cosmetic effect on the skin.
  • the backing sheet can be in a dry or web state, preferably stretchable at least in the wet state, in order to enable the mask to be adapted to fit the shape of the face or of the portion of the body to be covered.
  • the backing sheet can be made of paper, fabric, cloth, or a polymeric material.
  • a process for the preparation of a cosmetic composition for topical application to skin which comprises mixing a substance P analog of Formula (I) with a suitable vehicle to provide a concentration of from 0.001% to about 40%.
  • the substance P analog can be at a concentration of about 0.1% to about 0.5%.
  • the substance be analog can be at a concentration of about 0.1% to about 5%.
  • compositions can be formulated as liquids, for example as a lotion or milk for use in conjunction with an applicator such as a roll-ball applicator, or a spray device such as an aerosol can containing propellant, or a container fitted with a pump to dispense the liquid product.
  • an applicator such as a roll-ball applicator
  • a spray device such as an aerosol can containing propellant
  • a container fitted with a pump to dispense the liquid product.
  • the compositions can be solid or semi-solid, for example sticks, creams or gels, for use in conjunction with a suitable applicator or simply a tube, bottle or lidded jar, or as a liquid-impregnated fabric, such as a tissue wipe.
  • the compositions can be a bathing composition such as bath beads comprising substance P analogs.
  • the compositions can be used in the shower.
  • the compositions can be bath beads comprising a cosmetically effective amount of the substance P analogs.
  • the bath beads are also perfumed.
  • the bath beads can be made by techniques known in the art. Compositions in which an active ingredient is tumbled with a mixture of about 0.2% to about 2.0% of an oily perfume and about 0.3% to about 2.0% of a water soluble polyalkylene ether emollient to cause the perfume and the emollient to be distributed over the beads.
  • a non-limiting object of the bath beads is to help create an aura of body comfort with a scented, premeasured, moisturizing and muscle soothing bath product which also improves the texture of the skin.
  • the emollient or moisturizing oils which can be utilized in or to form moisturizing beads and generally known and referred to in the art as bath oils.
  • Suitable bath or emollient oils include, for example, mink oil, lanolin, liquid lanolin esters and other lanolin derivaties, cocoa butter, lower alkanol esters of saturated fatty acids such as isopropyl palmitate, ispropyl myristate, isopropyl stearate, isopropyl linoleate, methyl laurate, ethyl stearate, and the like.
  • glycerol esters of saturated fatty acids e.g., glyceryl monostearate, glyceryl monolaurate, glyceryl tripalmitate, the cholesterol esters of saturated fatty acids, polyethers such as polymers of propylene oxide, Ci 2 -CiS alcohols, e.g., oleyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, and adducts of C 1 2-C 18 alcohols with 1 to 4 moles of ethylene oxide, e.g., ethoxylated lauryl alcohol containing about 1 mole of ethylene oxide per mole of lauryl alcohol, glycols such as dipropylene glycol, oily liquids, e.g., the vegetable oils such as olive oil, cottonseed oil, corn oil, almond oil, peanut oil, and the like, hydrocarbons such as mineral oils, light liquid petrolatum and the like, and similar absorbable substances which soften, moisturize or give the effect of
  • the compositions can further include a coloring agent.
  • Coloring agents are included in preferred embodiments of the personal care bath products.
  • the coloring agents provide a pleasing color to the bath water, and can be suggestive of the fragrant agent used.
  • a coloring agent which imparts a pink color to the water can be used in conjunction with a rose fragrant agent.
  • a blue agent can be used to suggest hyacinth, and a green agent for mimosa. See, U.S. Patent Number 4,659,495.
  • Lotions can be either suspensions or emulsions but generally are fluid liquids that are typically used for their lubricating effect. Creams are emulsions and are typically opaque, thick liquids or soft solids. Creams also have the added feature that they tend to "vanish” or disappear with rubbing.
  • the topical compositions can be an aerosol or powder.
  • the topical compositions can be impregnated in an apparatus such as a transdermal patch, tape, strip or gauze.
  • the compositions can be a spritz, i.e. a liquid composition for spraying or atomization.
  • the compositions can be sprayed onto the skin or scalp.
  • Apparatuses for atomizing a liquid composition are known in the art including U.S. Patent Numbers 6,569,458, 3,584,792 and WO 2007/002048.
  • the particle size of the liquid composition will be larger with a spraying apparatus than with an atomizer. The method of application and other characteristics and qualities of the composition and use thereof is to be considered when using a liquid composition.
  • compositions can be a cosmetic cloths, tape or bandage comprising the substance P analog.
  • examples known in the art are Biore®
  • kits for administering a cosmetically effective amount of a substance P analog can comprise more than one composition for improving the appearance of human skin.
  • the substance P analogs can have a modified methionine residue.
  • the methionine residue side chain S can be oxidated.
  • the methionine is methionine sulfoxide (-NH-
  • the methionine is methionine sulfone or methionine S, S, dioxide, (-NH-CHa (CO)-CH 2 -CHa 2 -S(O 2 )CH 3 ) , also referred to herein as Met(O) 2 .
  • the substance P analog can be of Formula (I):
  • Xaa 1 is Arg, Lys, 6-N methyllysine, or (6-N, 6-N) dimethyllysine;
  • Xaa 2 is Pro or Ala
  • Xaa 3 is Lys, Arg, 6-N-methyllysine, or (6-N, 6-N) dimethyllysine;
  • Xaa 4 is Pro or Ala
  • Xaa 5 is GIn or Asn
  • Xaa 6 is GIn or Asn
  • Xaa 7 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
  • Xaa 8 is Tyr, Phe, or Phe substituted with chlorine at position 2, 3 or 4;
  • Xaa 9 is GIy, Pro, Ala, or N-methylglycine
  • Xaa 10 is Leu, VaI, lie, Norleucine, Met, Met sulfoxide, Met sulfone, N-
  • Xaa 1 ' is Met, Met sulfoxide, Met sulfone, or Norleucine;
  • Z is R 2 N- or RC(O)NR-;
  • Z 2 is -C(O)NR 2 or -C(O)OR or a salt thereof; each R is independently H, (Ci -C 6 ) alkyl, (Ci -C 6 ) alkenyl, (Ci -C 6 ) alkynyl, (C 5 -C 20 ) aryl, (C 6 -C 26 ) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl; and each "— " between residues Xaa 1 through Xaa 1 ' independently designates an amide linkage, a substitute amide linkage or an isostere of an amide.
  • substance P analogs can be of Formula (I) wherein
  • Xaa is Phe or Phe substituted with chlorine at position 4; Xaa is Phe, or Phe substituted with chlorine at position 4; Xaa 9 is GIy, Pro or N-methylglycine; Xaa 10 is Leu; and Xaa 11 is Met, Met sulfoxide, Met sulfone, or Norleucine.
  • the "— " between residues Xaa 1 through Xaa 11 of the substance P analogs can be -C(O)NH-; and Zi is H 2 N-; and Z 2 is -C(O)NH 2 .
  • the substance P analogs can be selected from the group consisting of:
  • RPKPQQFFGLM (SEQ ID NO.: 1);
  • RPKPQQFFMeGIyLM(O 2 ) (SEQ ID NO.: 2);
  • RPKPQQFFGLM(O 2 ) (SEQ ID NO. : 3);
  • RPKPQQFFMeGIyLM(O) (SEQ ID NO. : 4);
  • RPKPQQFFGLNIe SEQ ID NO.: 5
  • RPKPQQFFPLM (SEQ ID NO. : 6)
  • RPKPQQFFMeGIyLM SEQ ID NO.: 7
  • RPKPQQFTGLM (SEQ ID NO. : 8);
  • RPKPQQF(4-C1)F(4-C1)GLM (SEQ ID NO.: 9); or
  • the substance P analog can be Zi-RPKPQQFFMeGlyLM(O 2 )-Z 2 ; wherein Zi is NH 2 and Z 2 is C(O)NH 2 .
  • the amino (designated herein as Zi) or carboxy terminus (designated herein as Z 2 ) of the substance P analogs can be modified.
  • the N- and/or C-terminal charges of the substance P analogs can be an N-acylated peptide amide, ester, hydrazide, alcohol and substitutions thereof.
  • either the N- and/or C-terminus (preferably both termini) of the substance P analogs are blocked.
  • Typical N-terminal blocking groups include RC(O)-, where R is -H, (Cj -C 6 ) alkyl, (Ci -C 6 ) alkenyl, (Ci -C 6 ) alkynyl, (C 5 -C 20 ) aryl, (C 6 - C 26 ) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl.
  • Preferred N- terminal blocking groups include acetyl, formyl and dansyl.
  • Typical C-terminal blocking groups include -C(O)NRR and -C(O)OR, where each R is independently defined as above.
  • Preferred C-terminal blocking groups include those where each R is independently methyl. In another preferred embodiment the C-terminal group is amidated.
  • Substituted amides generally include, but are not limited to, groups of the formula -C(O)NR-, where R is (Ci -C 6 ) alkyl, substituted (Ci -C 6 ) alkyl, (Ci -C 6 ) alkenyl, substituted (Ci -C 6 ) alkenyl, (Ci -C 6 ) alkynyl, substituted (Ci -C 6 ) alkynyl, (C 5 -C 20 ) aryl, substituted (C 5 -C 20 ) aryl, (C 6 -C 26 ) alkaryl, substituted (C 6 -C 26 ) alkaryl, 5- 20 membered heteroaryl, substituted 5-20 membered heteroaryl, 6-26 membered alkheteroaryl and substituted 6-26 membered alkheteroaryl.
  • R is (Ci -C 6 ) alkyl, substituted (Ci -C 6
  • Compounds having such non-amide linkages and methods for preparing such compounds are well-known in the art (see, e.g., Spatola, March 1983, Vega Data Vol. 1, Issue 3; Spatola, 1983, "Peptide Backbone Modifications" In: Chemistry and Biochemistry of Amino Acids Peptides and Proteins, Weinstein, ed., Marcel Dekker, New York, p.
  • amide linkages can be replaced with peptidomimetic or amide mimetic moieties which do not significantly interfere with the structure or activity of the peptides. Suitable amide mimetic moieties are described, for example, in Olson et al, 1993, J. Med. Chem. 36:3039-3049.
  • the kit can further comprise tapes, bandages or gauzes for use with the substance P analog and can be in separate, or divided or undivided containers.
  • the components of the kit can be in liquid, dried, lyophilized, or frozen form, as is convenient for the end user and good for shelf life. 7. EXAMPLES
  • Example 2 Light Lotion [0095] The following presents an exemplary light lotion formulation that can be used in accordance with the methods and compositions described herein.
  • Example 10 Leave on Hair Conditioner [0101] The following presents an exemplary leave-in hair conditioner formulation that can be used in accordance with the methods and compositions described herein.
  • the sum of the erythema and edema scores for the test article and control sites were calculated for only the 24, 48 and 72 hour observation periods for each rabbit. The total scores were divided by 6 (2 observation sites x 3 observation periods) to determine the Primary Irritation Score observation average.
  • the response of the test article is categorized based on the Primary Irritation Index shown in Table 2.
  • the Primary Irritation Index (PII) is determined by adding the Primary Irritation Score for each animal and dividing the total score by the number of animals. See, Handbook of Toxicology, 2 nd ed. Derelanko and Hollinger eds., CRC Press, Dermatotoxicology, 4 th ed. Marzuli and Maibach eds. Hemisphere Publishing Corp., New York, NY 1991, United States Environmental Protection Administration, Office of Prevention, Pesticides and Toxic Substances (OPPTS), Health Effects Test Guidelines, OPPTS 870. 1200 Acute Dermal Toxicity.
  • a test sample was prepared by mixing 16 mg of Homspera® with 1 14.3 ml of saline. An induction procedure was initiated using a 0.4 ml sample of test article applied to the left flank site of the test group animals. Prepared control patches were applied to the negative control animals. The animals were wrapped with an elastic bandage and secured with hypoallergenic tape. The bandaging and patches were removed after 6 to 8 hours of exposure. At 24 hours ( ⁇ 2 hours) after topical application, the sites were assessed for erythema and edema using the grading scale provided in Table 1. This procedure was repeated once per week for three weeks for a total of three inductions.
  • a challenge procedure was initiated, following a two week rest period.
  • the animals were topically patched on the opposite flank with the appropriate test article on the test animals and the control on the control animals.
  • the patches were removed after 6 to 8 hours of exposure.
  • the dermal patch sites were observed for erythema and edema at 24, 48 and 72 ( ⁇ 2) hours after patch removal.
  • Each animal was assessed for a sensitization response based upon the dermal scores.
  • the negative control material had a 0% incidence and a grade of 0 for severity. None of the animals tested demonstrated signs of edema or erythema in response to a secondary challenge with following a 14-day recovery period. Homspera® does not cause dermal sensitization.
  • a topical test composition is formulated into a commercially available base such as a PEG base such as polyethylene glycol 400 (60% by weight) and polyethylene glycol 3350 (40% by weight).
  • the control composition containing no Homspera®, the second composition containing 100 nM Homspera®.
  • the test compositions are mixed thoroughly, placed in small jars and stored at 4 0 C until ready for use.
  • Each jar is labeled with a blinded ID indicator and area to be applied. The trial optimally includes at least 20 or as many as 100 subjects. Each subject receives 2 jars of composition, one test composition and one control. Each subject is instructed to apply the composition on either their right or left inner elbow as indicated by the label on the jar.
  • Test subject exclusion criteria could include recent (within 6 months) microdermabrasion, chemical peels, skin resurfacing, facial plastic surgery, facial skin cancer, acne outbreak within the facial area to be studied; electrolysis or depilatory used to remove facial hair in the region around the mouth, chin, and philltrum (area between the nose and upper lip); renal dysfunction; allergies to products containing polyethylene glycol; recent history (last 6 months) of atopic dermatitis or other skin condition that results in redness, rash, in area to be tested; recent (within one month) history of facial sunburn; recent (within one month) use of Retin-A® or other prescription strength anti-acne medication or topical bleaches used in area to be treated or other medications that induce facial skin irritation or the presence of scars within the test area.
  • Subjects are instructed to apply a dime sized amount of cream each to the periorbital, nasoliabia, cheek and forehead region each night for 30 nights. Measurements are taken weekly.
  • Example 18 The effect of an exemplary substance P analog, Homspera® on fibroblast proliferation 7.18.1. Material and Methods
  • Homspera® (as the acetate salt) was obtained by ImmuneRegen from CS Bio. The peptide was shipped under refrigerated conditions and stored at -20°C until reconstitution. Reconstitution of Homspera® was performed by dissolving compound to 1 mg/ml final concentration in sterile phosphate buffer saline (PBS) pH 7.4, then storing reconstituted Homspera® at 4°C in polypropylene enclosure. Appropriate dilutions were made from this 1 mg/ml working stock by diluting with sterile PBS. Spantide I (CAS 91224-37-2) was obtained from Sigma Aldrich and was added at a concentration of 10 ⁇ M.
  • PBS sterile phosphate buffer saline
  • Normal human fibroblasts were obtained from ATCC (passage 2-3) and grown in IMDM-Glutamax media (Invitrogen #31980-030) containing 10% Fetal Bovine Serum (FBS) (Invitrogen #10437-028) and penicillin- streptomycin-amphotericin B (Invitrogen #15240-104). These cells were cultivated up to passage 40. Cells were trypsinized using 0.05% Trypsin (Invitrogen #15400-054) in calcium and magnesium-free Hanks solution (Invitrogen #14170), followed by neutralization in Iscoves medium containing 10% FBS. Cells were maintained in a cell incubator at 37 0 C and 5% CO 2 .
  • MTT assay Invitrogen Molecular Probes M6494 was performed. See, Mosman, 1983, J. Immunol. Methods 65: 55. Briefly, cells were plated into 96-well tissue culture plates at 2,000 cells per well. Cultures were then treated with Homspera®; total well volume was kept to 0.ImL. MTT was weighed (5mg) and dissolved in distilled water, filtered using a 200 micron syringe filter and stored in the dark at 4°C. Ten ⁇ L MTT was added to each well and mixed. Cultures were incubated for 4 hours with MTT. Then medium was removed and 200 ⁇ L DMSO was added to each well and the absorbance was measured on an ELISA plate reader with a test wavelength of 570 nm and a reference wavelength of 630 nm to obtain sample signal.
  • Homspera® was tested at various concentrations (within the range of 0.01-10 ⁇ M) under varying growth conditions (serum-free or serum containing) for defined periods of time (24, 48 or 72 hrs) under serum-starved (0.5% FBS) or serum containing conditions (2.5% vs. 5% vs. 10% FBS), respectively.
  • serum-starved 0.5% FBS
  • serum containing conditions 2.5% vs. 5% vs. 10% FBS
  • Homspera® normal foreskin fibroblasts were seeded in a 96 well plate using IMDM (media) containing 0.5% FBS. The following day, these serum-starved cells were treated with various amounts of Homspera® or Homspera® + antagonist-(Spantide I) for a period of 1 or 3 days. Cells were pretreated with Homspera® in serum free media (0.5% FBS) for 3 hours. Spantide I was added 1 -hour prior to the addition of Homspera® in the 1 O ⁇ M- Homspera®- treated group treated with Spantide I.
  • Homspera® concentration increased proliferation at 1-day post-treatment in a dose-dependent manner when cultures were exposed to 5% FBS.
  • Homspera® could have a short-term (about 1-day) effect on the proliferation of human dermal fibroblasts cultured in 5% FBS and a longer-term (about 3 day) effect on the proliferation of human dermal fibroblasts cultured in 0.5% FBS as determined by MTT assay.

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Abstract

La présente invention concerne des compositions et des procédés permettant l'utilisation d'analogues de la Substance P pour améliorer l'aspect de la peau humaine. Ces compositions peuvent s'administrer sous forme de crèmes, d'onguents, de liquides, de lotions, et analogues.
PCT/US2008/013947 2007-12-21 2008-12-19 Compositions et procédés d'utilisation d'analogues de la substance p. Ceased WO2009085236A2 (fr)

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JP2014520797A (ja) * 2011-06-27 2014-08-25 株式会社アモーレパシフィック 化粧料組成物を含む皮膚美容キットおよび塗布方法
WO2018230751A1 (fr) * 2017-06-14 2018-12-20 주식회사 바이오솔루션 Composition cosmétique pour diminuer les rides ou l'inflammation, contenant de la substance p
CN113081882A (zh) * 2021-04-13 2021-07-09 福建卫生职业技术学院 一种免洗护肤擦浴液及其制备方法

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AU2003293582A1 (en) * 2002-12-18 2004-07-22 Mark L. Witten Stimulation of hair regrowth
US20080167248A1 (en) * 2004-04-26 2008-07-10 Immuneregen Biosciences, Inc. Anti-Aging Effects Of Substance P
US7776827B2 (en) * 2007-07-27 2010-08-17 Immuneregen Biosciences, Inc. Method of using substance P analogs for treatment amelioration of myelodysplastic syndrome

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Publication number Priority date Publication date Assignee Title
JP2014520797A (ja) * 2011-06-27 2014-08-25 株式会社アモーレパシフィック 化粧料組成物を含む皮膚美容キットおよび塗布方法
WO2018230751A1 (fr) * 2017-06-14 2018-12-20 주식회사 바이오솔루션 Composition cosmétique pour diminuer les rides ou l'inflammation, contenant de la substance p
JP2020510005A (ja) * 2017-06-14 2020-04-02 バイオソリューション カンパニー・リミテッドＢｉｏ Ｓｏｌｕｔｉｏｎ Ｃｏ Ｌｔｄ 物質ｐを含むしわの改善または抗炎症化粧料組成物
CN111182887A (zh) * 2017-06-14 2020-05-19 株式会社生物解决方案有限公司 用于改善皮肤皱纹或抗炎活性的包括物质p的化妆品组合物
EP3574892A4 (fr) * 2017-06-14 2020-08-12 Bio Solution Co., Ltd. Composition cosmétique pour diminuer les rides ou l'inflammation, contenant de la substance p
CN113081882A (zh) * 2021-04-13 2021-07-09 福建卫生职业技术学院 一种免洗护肤擦浴液及其制备方法

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