WO2025194297A1

WO2025194297A1 - A cosmetic composition and a method for inhibiting carbamylation

Info

Publication number: WO2025194297A1
Application number: PCT/CN2024/082114
Authority: WO
Inventors: Xi Yang; Yan Wu
Original assignee: Estee Lauder Cos Innovation R & D China Co Ltd; ELC Management LLC
Current assignee: Estee Lauder Cos Innovation R & D China Co Ltd; ELC Management LLC
Priority date: 2024-03-18
Filing date: 2024-03-18
Publication date: 2025-09-25
Anticipated expiration: 2026-09-18
Also published as: TW202537618A

Abstract

It relates to a cosmetic composition, and a method for inhibiting carbamylation. The cosmetic composition comprises at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus.

Description

A COSMETIC COMPOSITION AND A METHOD FOR INHIBITING CARBAMYLATION

Technical Field of the Disclosure

The present disclosure relates to the field of cosmetic or dermatologic composition. Particularly, the present disclosure is directed to a new cosmetic and/or dermatological composition for inhibiting carbamylation of protein.

Background of the Disclosure

Carbamylation is the adding of cyanate group to the protein amino groups. Protein carbamylation is a hallmark in aging. Carbamylation accumulates in skin and collagen with aging, especially in reticular layer of dermis. Carbamylation of collagen is known to inhibit collagen cross-link formation, which further alters the collagen bundle quality and the mechanical properties of connective tissues. Inhibiting carbamylation could be a new approach to address skin aging.

Since carbamylation on skin is a newly reported phenomenon (since 2016) , there had been little report on cosmetic ingredients that have carbamylation inhibition properties.

There is a need for a cosmetic and/or dermatological composition for inhibiting carbamylation of protein, particularly on skin.

Summary

The present disclosure relates to a cosmetic composition comprising at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus. The present disclosure also relates to a method for inhibiting carbamylation of protein, particularly on skin, comprising applying a cosmetic composition comprising at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus.

The cosmetic composition can achieve technical effect of inhibiting protein carbamylation of skin cells, thereby achieving anti-aging and brightening effect for skin. In addition, compared to the decarboxylated oligopeptide or a salt thereof or the extract of Rosa sp. genus (such as Rosa Chinensis Flower extract) alone, the combination of decarboxylated oligopeptide or a salt thereof and the extract of Rosa sp. genus (such as Rosa Chinensis Flower extract) can obtain an unexpected synergistic effect of inhibiting protein carbamylation.

Detailed Description

Definitions and Conventions

All percentages mentioned herein are percentages by weight unless otherwise indicated.

As used herein, “carbamylation” means the adding of cyanate group to the protein amino groups.

As used herein, "comprising" means that a list of elements is not necessarily limited to those explicitly recited.

As used herein, "cosmetically acceptable" means that compositions or components are suitable for use in contact with human keratinous tissue.

As used herein, "molecular weight" refers to the weight average molecular weight, unless otherwise stated.

Unless otherwise stated: all numerical amounts are understood to be modified by the word "about, " all percentages are by weight of the total composition, and all ratios are weight ratios.

It should be understood that every numerical range expressly recited herein will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly recited herein.

A. Methods

In some embodiments, the disclosure is related to a method for inhibiting carbamylation of protein, particularly on skin, comprising applying a cosmetic composition comprising at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus.

Preferably, the cosmetic composition is applied topically.

Preferably, the method is useful for preventing or slowing carbamylation.

B. Cosmetic Compositions

In some embodiments, the cosmetic compositions of the disclosure may be topical compositions. In one aspect, the topical compositions may be in the form of solids, liquids, or gels. In one aspect, the topical compositions may be aqueous based or anhydrous. Aqueous based compositions may be in the form of emulsions, solutions, or dispersions.

This disclosure is directed to a cosmetic composition comprising at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus.

Decarboxylated oligopeptide

In some embodiments, the at least one decarboxylated oligopeptide is selected from the group consisting of compounds of the formula (I) :

R1-X1- (AA) n-X2 (I)

where:

X1 represents an N-terminal amino acid;

X2 represents a decarboxylated amino acid;

AA represents any amino acid or derivative thereof, and n is 0 or 1;

R1 represents the primary amine function of X1, either free or substituted by a protective grouping that may be chosen from either an acetyl group, a benzoyl group, a tosyl group, or a benzyloxycarbonyl group.

In some embodiments, X1 is selected from the group consisting of alanine, glycine, isoleucine, leucine, and valine, preferably alanine.

In some embodiments, X2 is selected from the group consisting of tryptamine, histamine, cadaverine, agmatine, and pyrrolidine, preferably histamine.

In some embodiments, the at least one decarboxylated oligopeptide or a salt thereof is decarboxy carnosine, decarboxy carnosine HCl or decarboxy carnosine 2HCl.

In some embodiments, based on the total weight of the cosmetic composition, the at least one decarboxylated oligopeptide has a content from about 0.00001%to about 0.5%by weight; preferably from about 0.00005%to about 0.1 %by weight; more preferably, from about 0.0005%to about 0.05%by weight, calculated on the basis of the free base of decarboxylated oligopeptide.

In some embodiments, the at least one decarboxylated oligopeptide or a salt thereof is Decarboxy carnosine 2HCL (purchased from Exsymol under the tradename Alistin) .

Extract of Rosa sp. genus

In some embodiments, the at least one extract of Rosa sp. genus is selected from the group consisting of plant extract of Rosa sp. genus, fruit extract of Rosa sp. genus, flower extract of Rosa sp. genus, leaf extract of Rosa sp. genus, stem extract of Rosa sp. genus, root extract of Rosa sp. genus and mixtures thereof;

preferably, the at least one extract of Rosa sp. genus is a flower extract of Rosa sp. genus.

In some embodiments, the at least one extract of Rosa sp. genus is selected from the group consisting of Rosa Chinensis extract, Rosa Centifolia extract, Rosa Roxburghii extract, Rosa Grandiflorus extract, Rosa Odorata extract, Rosa Gallica extract, Rosa Canina extract, Rosa Laevigata extract, Rosa Rugosa extract, Rosa Multiflora extract, Rosa Moschata extract, Rosa Damascena extract, Rosa Rubiginosa extract; preferably, the at least one extract of Rosa sp. genus is Rosa Chinensis extract, more preferably, the at least one extract of Rosa sp. genus is Rosa Chinensis flower extract.

In some embodiments, the extract comprises total flavonoids in a content from 20%-50%, preferably 25%-45%, more preferably 30%-40%, and total polyphenols in a content from 50%-80%, preferably 55%-75%, more preferably 60%-70%, by weight. In some embodiments, the extract is obtained by extraction with a solvent selected from the group consisting of polyols (e.g. butanediol, propanediol, glycerin) , ethanol, water, and a mixture of ethanol and water, preferably, the ratio of ethanol to water in the mixture ranges from1: 2 -10: 1, preferably from 1: 1 -5: 1, more preferably from 3: 2 -3: 1. For example, the extract can be obtained by a process comprising ethanol/water extraction, filtration, column chromatograph, concentration, and freeze drying. In some embodiments, based on the total weight of the cosmetic composition, the at least one extract of Rosa sp. genus has a content from about 0.00002%to about 1%by weight, preferably from about 0.00005%to about 0.1%by weight, more preferably from about 0.00007%to about 0.07%by weight, even more preferably from about 0.0007%to about 0.07 %by weight.

In some embodiments, the cosmetic composition has a weight ratio between the extract of Rosa sp. genus and the decarboxylated oligopeptide from about 1: 25000 -2000: 1, preferably 1: 4000 -100: 1, more preferably 0.7: 1000 -70: 1, more preferably 0.7: 700 –0.7: 0.7, calculated on the basis of the free base of decarboxylated oligopeptide. A non-limiting example of the extract of Rosa sp. genus is Rosa Chinensis Flower extract (purchased from Ingredi Biotech Co., LTD. under the tradename Rogina, composition: 70%Rosa Chinensis Flower extract/30%Maltodextrin) .

Other ingredients:

The topical composition may further contain the following ingredients:

Oils

Suitable oils include silicones, esters, vegetable oils, synthetic oils, including but not limited to those set forth herein. The oils may be volatile or nonvolatile, and are preferably in the form of a pourable liquid at room temperature. If present, the oils may range from about 0.5 to about 85%, preferably from about 1 to about 75%, more preferably from about 5 to about 65%by weight of the total composition. Cyclic and linear volatile silicones are available from various commercial sources including Dow Chemical Corporation and Momentive (formerly General Electric Silicones) . The Dow Chemical linear volatile silicones are sold under the trade names Dowsil and Xiameter 244, 245, 344, and 200 fluids. These fluids include hexamethyldisiloxane (viscosity 0.65 centistokes (abbreviated cst) ) , octamethyltrisiloxane (1.0 cst) , decamethyltetrasiloxane (1.5 cst) , dodecamethylpentasiloxane (2 cst) and mixtures thereof, with all viscosity measurements being at 25℃.

Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone, a branched volatile silicone having the general formula:

Methyl trimethicone may be purchased from Shin-Etsu Silicones under the trade name TMF-1.5, having a viscosity of 1.5 centistokes at 25℃.

Also suitable are various straight or branched chain paraffinic hydrocarbons having 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 8 to 16 carbon atoms. Suitable hydrocarbons include pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane, and C_8-20 isoparaffins. Suitable C₁₂ isoparaffins are manufactured by Permethyl Corporation under the tradename Permethyl 99A. Various C₁₆ isoparaffins commercially available, such as isohexadecane (having the tradename Permethyl R) , are also suitable.

Also suitable are esters formed by the reaction of a carboxylic acid and an alcohol.

The alcohol and the carboxylic acids may both have fatty (C6-30) chains. Examples include hexyl laurate, butyl isostearate, hexadecyl isostearate, cetyl palmitate, isostearyl neopentanoate, stearyl heptanoate, isostearyl isononanoate, stearyl lactate, stearyl octanoate, stearyl stearate, isononyl isononanoate, and so on.

The ester may also be in the dimer or trimer form. Examples of such esters include diisotearyl malate, neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, dioctyl malate, and so on. Examples of other types of esters include those from arachidonic, citric, or behenic acids, such as triarachidin, tributyl citrate, triisostearyl citrate, tri C_12-13 alkyl citrate, tricaprylin, tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl behenate; or tridecyl cocoate, tridecyl isononanoate, and so on.

Synthetic or naturally occurring glyceryl esters of fatty acids, or triglycerides, are also suitable for use in the compositions. Both vegetable and animal sources may be used. Examples of such oils include castor oil, lanolin oil, C_10-18 triglycerides, caprylic/capric/triglycerides, sweet almond oil, apricot kernel oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, ink oil, olive oil, palm oil, illipe butter, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil, walnut oil, and the like.

Also suitable are synthetic or semi-synthetic glyceryl esters, such as fatty acid mono-, di-, and triglycerides which are natural fats or oils that have been modified, for example, mono-, di-or triesters of polyols such as glycerin. In an example, a fatty (C_12-22) carboxylic acid is reacted with one or more repeating glyceryl groups. glyceryl stearate, diglyceryl diiosostearate, polyglyceryl-3 isostearate, polyglyceryl-4 isostearate, polyglyceryl-6 ricinoleate, glyceryl dioleate, glyceryl diisotearate, glyceryl tetraisostearate, glyceryl trioctanoate, diglyceryl distearate, glyceryl linoleate, glyceryl myristate, glyceryl isostearate, PEG castor oils, PEG glyceryl oleates, PEG glyceryl stearates, PEG glyceryl tallowates, and so on.

Nonvolatile silicone oils, both water soluble and water insoluble, are also suitable for use in the composition. Such silicones preferably have a viscosity ranging from about greater than 5 to 800,000 cst, preferably 20 to 200,000 cst at 25℃. Suitable water insoluble silicones include amine functional silicones such as amodimethicone. Examples include dimethicone, phenyl dimethicone, diphenyl dimethicone, phenyl trimethicone, or trimethylsiloxyphenyl dimethicone. Other examples include alkyl dimethicones such as cetyl dimethicone, stearyl dimethcone, behenyl dimethicone, and the like.

Surfactants

The composition may contain one or more surfactants, especially if in the emulsion form. However, such surfactants may be used if the compositions are anhydrous also, and will assist in dispersing ingredients that have polarity, for example pigments. Such surfactants may be silicone or organic based. The surfactants will aid in the formation of stable emulsions of either the water-in-oil or oil-in-water form. If present, the surfactant may range from about 0.001 to 30%, preferably from about 0.005 to 25%, more preferably from about 0.1 to 20%by weight of the total composition.

Silicone surfactants may be generically referred to as dimethicone copolyol or alkyl dimethicone copolyol. In some cases the number of repeating ethylene oxide or propylene oxide units in the polymer are also specified, such as a dimethicone copolyol that is also referred to as PEG-15/PPG-10 dimethicone, which refers to a dimethicone having substituents containing 15 ethylene glycol units and 10 propylene glycol units on the siloxane backbone. It is also possible for one or more of the methyl groups in the above general structure to be substituted with a longer chain alkyl (e.g. ethyl, propyl, butyl, etc. ) or an ether such as methyl ether, ethyl ether, propyl ether, butyl ether, and the like.

Examples of silicone surfactants are those sold by Dow Silicones under the tradename Dowsil 3225C Formulation Aid having the CTFA name cyclotetrasiloxane (and) cyclopentasiloxane (and) PEG/PPG-18 dimethicone; or 5225C Formulation Aid, having the CTFA name cyclopentasiloxane (and) PEG/PPG-18/18 dimethicone; or Dowsil 190 Surfactant having the CTFA name PEG/PPG-18/18 dimethicone; or Dowsil 193 Fluid, Dowsil 5200 having the CTFA name lauryl PEG/PPG-18/18 methicone; or Abil EM 90 having the CTFA name cetyl PEG/PPG-14/14 dimethicone sold by Goldschmidt; or Abil EM 97 having the CTFA name bis-cetyl PEG/PPG-14/14 dimethicone sold by Goldschmidt; or Abil WE 09 having the CTFA name cetyl PEG/PPG-10/1 dimethicone in a mixture also containing polyglyceryl-4 isostearate and hexyl laurate; or KF-6011 sold by Shin-Etsu Silicones having the CTFA name PEG-11 methyl ether dimethicone; KF-6012 sold by Shin-Etsu Silicones having the CTFA name PEG/PPG-20/22 butyl ether dimethicone; or KF-6013 sold by Shin-Etsu Silicones having the CTFA name PEG-9 dimethicone; or KF-6015 sold by Shin-Etsu Silicones having the CTFA name PEG-3 dimethicone; or KF-6016 sold by Shin-Etsu Silicones having the CTFA name PEG-9 methyl ether dimethicone; or KF-6017 sold by Shin-Etsu Silicones having the CTFA name PEG-10 dimethicone; or KF-6038 sold by Shin-Etsu Silicones having the CTFA name lauryl PEG-9 polydimethylsiloxyethyl dimethicone.

Also suitable are various types of crosslinked silicone surfactants that are often referred to as emulsifying elastomers that contain at least one hydrophilic moiety such as polyoxyalkylenated groups. Polyoxyalkylenated silicone elastomers that may be used in at least one embodiment of the disclosure include those sold by Shin-Etsu Silicones under the names KSG-21 , KSG-20, KSG-30, KSG-31, KSG-32, KSG-33; KSG-210 which is dimethicone/PEG-10/15 crosspolymer dispersed in dimethicone; KSG-310 which is PEG-15 lauryl dimethicone crosspolymer; KSG-320 which is PEG-15 lauryl dimethicone crosspolymer dispersed in isododecane; KSG-330 (the former dispersed in triethylhexanoin) , KSG-340 which is a mixture of PEG-10 lauryl dimethicone crosspolymer and PEG-15 lauryl dimethicone crosspolymer. Also suitable are polyglycerolated silicone elastomers like those disclosed in PCT/WO 2004/024798, which is hereby incorporated by reference in its entirety.

Such elastomers include Shin-Etsu’s KSG series, such as KSG-710 which is dimethicone/polyglycerin-3 crosspolymer dispersed in dimethicone; or lauryl dimethicone/polyglycerin-3 crosspolymer dispersed in a variety of solvent such as isododecane, dimethicone, triethylhexanoin, sold under the Shin-Etsu tradenames KSG-810, KSG-820, KSG-830, or KSG-840. Also suitable are silicones sold by Dow Silicones under the tradenames 9010 and DC9011.

The composition may comprise one or more nonionic organic surfactants. Suitable nonionic surfactants include alkoxylated alcohols, or ethers, formed by the reaction of an alcohol with an alkylene oxide, usually ethylene or propylene oxide. Preferably the alcohol is either a fatty alcohol having 6 to 30 carbon atoms. Examples of such ingredients include Steareth 2-100, which is formed by the reaction of stearyl alcohol and ethylene oxide and the number of ethylene oxide units ranges from 2 to 100; Beheneth 5-30 which is formed by the reaction of behenyl alcohol and ethylene oxide where the number of repeating ethylene oxide units is 5 to 30; Ceteareth 2-100, formed by the reaction of a mixture of cetyl and stearyl alcohol with ethylene oxide, where the number of repeating ethylene oxide units in the molecule is 2 to 100; Ceteth 1-45 which is formed by the reaction of cetyl alcohol and ethylene oxide, and the number of repeating ethylene oxide units is 1 to 45, and so on. All recitations of units include all whole integers between the range.

Other alkoxylated alcohols are formed by the reaction of fatty acids and mono-, di-or polyhydric alcohols with an alkylene oxide. For example, the reaction products of C_6- ₃₀ fatty carboxylic acids and polyhydric alcohols which are monosaccharides such as glucose, galactose, methyl glucose, and the like, with an alkoxylated alcohol. Examples include polymeric alkylene glycols reacted with glyceryl fatty acid esters such as PEG glyceryl oleates, PEG glyceryl stearate; or PEG polyhydroxyalkanotes such as PEG dipolyhydroxystearate wherein the number of repeating ethylene glycol units ranges from 3 to 1000.

Other suitable nonionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation, in particular ethoxylation of sorbitan provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters such as the polysorbates. For example, the polyalkyoxylated sorbitan can be esterified with C6-30, preferably C12-22 fatty acids. Examples of such ingredients include Polysorbates 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquiisostearate, sorbitan stearate, and so on.

Humectants

It may also be desirable to include one or more humectants in the composition. If present, such humectants may range from about 0.001 to 25%, preferably from about 0.005 to 20%, more preferably from about 0.1 to 15%by weight of the total composition. Examples of suitable humectants include glycols, sugars, and the like. Suitable glycols are in monomeric or polymeric form and include polyethylene and polypropylene glycols such as PEG 4-200, which are polyethylene glycols having from 4 to 200 repeating ethylene oxide units; as well as C_1-6 alkylene glycols such as propylene glycol, butylene glycol, pentylene glycol, and the like. Suitable sugars, some of which are also polyhydric alcohols, are also suitable humectants. Examples of such sugars include glucose, fructose, honey, hydrogenated honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, and so on. Also suitable is urea. Preferably, the humectants used in the composition of the disclosure are C_1-6, preferably C_2-4 alkylene glycols, most particularly butylene glycol.

Botanical Extracts

It may be desirable to include one or more botanical extracts in the compositions. If so, suggested ranges are from about 0.0001 to 10%, preferably about 0.0005 to 8%, more preferably about 0.001 to 5%by weight of the total composition. Suitable botanical extracts include extracts from plants (herbs, roots, flowers, fruits, seeds) such as flowers, fruits, vegetables, and so on, including yeast ferment extract, Padina Pavonica extract, thermus thermophilis ferment extract, camelina sativa seed oil, boswellia serrata extract, olive extract, Aribodopsis Thaliana extract, Acacia Dealbata extract, Acer Saccharinum (sugar maple) , acidopholus, acorus, aesculus, agaricus, agave, agrimonia, algae, aloe, citrus, brassica, cinnamon, orange, apple, blueberry, cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea, chamomile, willowbark, mulberry, poppy, and those set forth on pages 1646 through 1660 of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, Volume 2. Further specific examples include, but are not limited to, Glycyrrhiza Glabra, Salix Nigra, Macrocycstis Pyrifera, Pyrus Malus, Saxifraga Sarmentosa, Vitis Vinifera, Morus Nigra, Scutellaria Baicalensis, Anthemis Nobilis, Salvia Sclarea, Rosmarinus Officianalis, Citrus Medica Limonum, Panax Ginseng, Siegesbeckia Orientalis, Fructus Mume, Ascophyllum Nodosum, Bifida Ferment lysate, Glycine Soja extract, Beta Vulgaris, Haberlea Rhodopensis, Polygonum Cuspidatum, Citrus Aurantium Dulcis, Vitis Vinifera, Selaginella Tamariscina, Humulus Lupulus, Citrus Reticulata Peel, Punica Granatum, Asparagopsis, Curcuma Longa, Menyanthes Trifoliata, Helianthus Annuus, Hordeum Vulgare, Cucumis Sativus, Evernia Prunastri, Evernia Furfuracea, and mixtures thereof.

Particulate Materials

The compositions of the disclosure may contain particulate materials in the form of pigments, inert particulates, or mixtures thereof. If present, suggested ranges are from about 0.01-75%, preferably about 0.5-70%, more preferably about 0.1-65%by weight of the total composition. In the case where the composition may comprise mixtures of pigments and powders, suitable ranges include about 0.01-75%pigment and 0.1-75%powder, such weights by weight of the total composition.

The particulate matter may be colored or non-colored powders. Suitable non-pigmented powders include bismuth oxychloride, titanated mica, fumed silica, spherical silica, polymethylmethacrylate, micronized teflon, boron nitride, acrylate copolymers, aluminum silicate, aluminum starch octenylsuccinate, bentonite, calcium silicate, cellulose, chalk, corn starch, diatomaceous earth, fuller's earth, glyceryl starch, hectorite, hydrated silica, kaolin, magnesium aluminum silicate, magnesium trisilicate, maltodextrin, montmorillonite, microcrystalline cellulose, rice starch, silica, talc, mica, titanium dioxide, zinc laurate, zinc myristate, zinc rosinate, alumina, attapulgite, calcium carbonate, calcium silicate, dextran, kaolin, nylon, silica silylate, silk powder, sericite, soy flour, tin oxide, titanium hydroxide, trimagnesium phosphate, walnut shell powder, or mixtures thereof. The above mentioned powders may be surface treated with lecithin, amino acids, mineral oil, silicone, or various other agents either alone or in combination, which coat the powder surface and render the particles more lipophilic in nature.

Suitable pigments are organic or inorganic. Organic pigments are generally various aromatic types including azo, indigoid, triphenylmethane, anthroquinone, and xanthine dyes which are designated as D&C and FD&C blues, browns, greens, oranges, reds, yellows, etc. Organic pigments generally consist of insoluble metallic salts of certified color additives, referred to as the Lakes. Inorganic pigments include iron oxides, ultramarines, chromium, chromium hydroxide colors, and mixtures thereof. Iron oxides of red, blue, yellow, brown, black, and mixtures thereof are suitable.

Vitamins and Antioxidants

The compositions of the disclosure may contain vitamins and/or coenzymes, as well as antioxidants. If so, 0.001-10%, preferably 0.01-8%, more preferably 0.05-5%by weight of the total composition is suggested. Suitable vitamins include ascorbic acid and derivatives thereof such as ascorbyl palmitate, tetrahexydecyl ascorbate, and so on; the B vitamins such as thiamine, riboflavin, pyridoxin, and so on, as well as coenzymes such as thiamine pyrophoshate, flavin adenin dinucleotide, folic acid, pyridoxal phosphate, tetrahydrofolic acid, and so on. Also suitable is Vitamin E and derivatives thereof such as Vitamin E acetate, nicotinate, or other esters thereof. In addition, Vitamins D and K are suitable.

The disclosure will be further described in connection with the following examples which are set forth for the purposes of illustration only.

EXPERIMENTAL EXAMPLES

Biological experiment

Reagents used in this experiment:

Decarboxy carnosine 2HCL (purchased from Exsymol under the tradename Alistin; molecular weight: 255.14) ;

Rosa Chinensis Flower extract (purchased from Ingredi Biotech Co., LTD. under the tradename Rogina, composition: 70%Rosa Chinensis Flower extract/30%Maltodextrin) ; The extract is obtained by a process comprising ethanol/water (3: 2 -3: 1) extraction, filtration, column chromatograph, concentration, and freeze drying. The extract comprises total flavonoids in a content from 30%-40%, and total polyphenols in a content from 60%-70%, by weight.

TrypLE Express (purchased from Life Technologies) ;

Asian primary fibroblasts (purchased from Biocell) ;

Dulbecco's Modification of Eagle's Medium (DMEM) 4.5 g/L glucose, L-glutamine, and sodium pyruvate (purchased from Corning) ;

Fetal Bovine Serum (purchased from Corning) ;

Anti-homocitrulline antibody (pab01012-P, Covalab)

Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor^TM 488 (A-11008, Invitrogen)

Sodium cyanate (S107362, purchased from Aladdin)

Instruments used in this experiment:

Operetta CLS High content imaging System purchased from PerkinElmer.

Stock solutions:

Decarboxy carnosine 2HCL was dissolved in H₂O at a concentration of 5%as stock solution.

Rosa Chinensis Flower extract was solubilized in filter sterile DMSO at a concentration of 5%as stock solution.

Experimental procedure:

Human dermal fibroblasts (HDFs) were maintained in the cultures established in Dulbecco’s Modified Eagle’s Medium (DMEM) with 10%Fetal Bovine Serum in 5%CO₂, 95%humidified incubator at 37℃ and passaged using TrypLE Express.

1. 2x10⁴ HDFs were seeded in 24-well plates for 24h before changing medium.

2. Sodium cyanate was prepared in culture media at 1.5mM, with or without Alistin and/or Rogina diluted to the final concentration.

3. HDFs were further treated for 48h, before fixed by 4%PFAand immunostained with anti-homocitrulline antibody and Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa FluorTM 488.

4. The green fluorescence were captured by Operetta CLS High content imaging System purchased from PerkinElmer. For each group, at least three fields were captured, and the fluorescent intensity was calculated by Image J as mean grey value.

5. Protection rate is calculated according to the following equation:
Protection Rate (％) ＝100％x (Induced-Sample) / (Induced-Control)

"Control" inthe equation is the data of background without Sodium cyanate, Alistin and Rogina.

"Induced" in the equation is the data of thetest group with Sodium cyanate and without Alistin and Rogina.

"Sample" in the equation is the data of the test group with Sodium cyanate and with Alistin and/or Rogina.

"% Rogina" in the following table refers to the sample with Sodium cyanate and Rogina but without Alistin.

"%Alistin" in the following table refers to the sample with Sodium cyanate and Alistin but without Rogina.

"%Rogina + %Alistin" inthe following table refers to the sample with Sodium cyanate, Rogina, and Alistin.

Results:

The experimental results were evaluated by the isobole method for synergistic effects, as described in the article titled “Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective, ” Medicina 2019, 55 (4) , 110, which is herein incorporated in its entirety. According to the isobole method, when OE means the observed effects, and da and db represent the doses of ingredient a and ingredient b, respectively (thus OE (da, db) means the observed effects of the combination of Ingredients a at da and b at db; and OE (da) means the observed effects of Ingredient a at da and OE (da) means the observed effects of Ingredient b at db) , three mathematic equations may be derived:
OE (da, db) = OE (da) +OE (db) (1)
OE (da, db) > OE (da) +OE (db) (2)
OE (da, db) < OE (da) +OE (db) (3)

If the observed effects satisfy equation (1) , the effects of two ingredients are the simple sum of the single effects, and two ingredients do not interact and thus there is no synergy. If the observed effects satisfy equation (2) , the result represents the real synergism (or potentiation) , where the effects of two ingredients are more than the simple sum of the single effects.

If the observed effects satisfy equation (3) , the result represents the opposite effects of synergism, as the effects of two ingredients are less than the simple sum of the single effects.

Method to test formulation efficacy of anti-carbamylation:

1. Fullthickness skin equivalent models (Biocell) were equilibrated for 24 hours in culture media at air liquid interface in 5%CO₂, 95%humidified incubator at 370C.

2. The assay media was replaced with fresh and the models were treated topically with formulation. For induction of carbamylation, sodium cyanate was added to the assay medium in bottom well at a concentration of 1M.

3. The treatment was repeated 3 times every 24 hours, after which the tissue was imbedded in OCT and cryosectioned, and carbamylation was detected by anti-homocitrulline antibody.

The combination of Alistin with at least one extract of Rosa sp. genus, particularly Rosa Chinensis flower extract, can be made into a formulation with common carriers, auxiliaries, or excipients in a conventional preparation process. Exemplary formulations and preparation processes thereof are provided below. All the ingredients used in the formulations are well known in the art and commercially available.

Formulation example 1: A serum formulation according to the present invention was prepared as follows:

1) add 1 first, then with homo, slowly add 2 at RT;

2) Homo the material of 1) for 15-30 min until uniform;

3) add 3, 4, 5, 6 at RT and homo 5 min until uniform;

4) add 7&8 and homo 5 min until uniform; and

5) discharge.

Formulation example 2: A serum formulation according to the present invention was prepared as follows:

1) add 1 in;

2) pre-mix 2&3 well, add into 1) , mix well;

3) pre-mix 4&5 well, add into 1) , emulsify for 15min;

4) add 6&7&8 at RT and homo 5 min until uniform;

5) add 9&10 and homo 5 min until uniform;

6) with homo, slowly add 11, homo 10 min until uniform; and

7) discharge.

Other Embodiments

While the invention has been described in connection with the preferred embodiment, it is not intended to limit the scope of the invention to the particular form set forth but, on the contrary, it is intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims. Therefore, other embodiments, including those can be easily modified by a person skilled in the art from the present disclosure, are also within the claims.

Claims

A cosmetic composition comprising at least one decarboxylated oligopeptide or a salt thereof and at least one extract of Rosa sp. genus.
The cosmetic composition of Claim 1, wherein the at least one decarboxylated oligopeptide is selected from the group consisting of compounds of the formula (I) :
R1-X1- (AA) n-X2 (I)

where:

X1 represents an N-terminal amino acid;

X2 represents a decarboxylated amino acid;

AA represents any amino acid or derivative thereof, and n is 0 or 1;

R1 represents the primary amine function of X1, either free or substituted by a protective grouping that may be chosen from either an acetyl group, a benzoyl group, a tosyl group, or a benzyloxycarbonyl group.
The cosmetic composition of Claim 2, wherein

X1 is selected from the group consisting of alanine, glycine, isoleucine, leucine, and valine, preferably alanine.
The cosmetic composition of claim 2 or 3, wherein

X2 is selected from the group consisting of tryptamine, histamine, cadaverine, agmatine, and pyrrolidine, preferably histamine.
The cosmetic composition of any one of claims 1-4, wherein

the at least one decarboxylated oligopeptide or a salt thereof is decarboxy carnosine, decarboxy carnosine HCl or decarboxy carnosine 2HCl.
The cosmetic composition of any one of claims 1-5, wherein

based on the total weight of the cosmetic composition,

the at least one decarboxylated oligopeptide has a content from about 0.00001%to about 0.5%by weight; preferably from about 0.00005%to about 0.1 %by weight; more preferably, from about 0.0005%to about 0.05%by weight, calculated on the basis of the free base of decarboxylated oligopeptide.
The cosmetic composition of any one of claims 1-6, wherein

the at least one extract of Rosa sp. genus is selected from the group consisting of Rosa Chinensis extract, Rosa Centifolia extract, Rosa Roxburghii extract, Rosa Grandiflorus extract, Rosa Odorata extract, Rosa Gallica extract, Rosa Canina extract, Rosa Laevigata extract, Rosa Rugosa extract, Rosa Multiflora extract, Rosa Moschata extract, Rosa Damascena extract, Rosa Rubiginosa extract;

preferably, the at least one extract of Rosa sp. genus is Rosa Chinensis extract, more preferably, the at least one extract of Rosa sp. genus is Rosa Chinensis flower extract.
The cosmetic composition of any one of claims 1-7, wherein

the at least one extract of Rosa sp. genus is selected from the group consisting of plant extract of Rosa sp. genus, fruit extract of Rosa sp. genus, flower extract of Rosa sp. genus, leaf extract of Rosa sp. genus, stem extract of Rosa sp. genus, root extract of Rosa sp. genus and mixtures thereof;

preferably, the at least one extract of Rosa sp. genus is a flower extract of Rosa sp. genus.
The cosmetic composition of any one of claims 1-8, wherein

the extract comprises total flavonoids in a content from 20%-50%, preferably 25%-45%, more preferably 30%-40%, and total polyphenols in a content from 50%-80%, preferably 55%-75%, more preferably 60%-70%, by weight.
The cosmetic composition of any one of claims 1-9, wherein

the extract is obtained by extraction with a solvent selected from the group consisting of polyols (e.g. butanediol, propanediol, glycerin) , ethanol, water, and a mixture of ethanol and water, preferably, the ratio of ethanol to water in the mixture ranges from 1: 2 -10: 1, preferably from 1: 1 -5: 1, more preferably from 3: 2 -3: 1.
The cosmetic composition of any one of claims 1-10, wherein

based on the total weight of the cosmetic composition,

the at least one extract of Rosa sp. genus has a content from about 0.00002%to about 1%by weight, preferably from about 0.00005%to about 0.1%by weight, more preferably from about 0.00007%to about 0.07%by weight,

even more preferably from about 0.0007%to about 0.07 %by weight.
The cosmetic composition of any one of claims 1-11, wherein

the cosmetic composition has a weight ratio between the extract of Rosa sp. genus and the decarboxylated oligopeptide from about 1: 25000 -2000: 1, preferably 1: 4000 -100: 1, more preferably 0.7: 1000 -70: 1, more preferably 0.7: 700 –0.7: 0.7, calculated on the basis of the free base of decarboxylated oligopeptide.
A cosmetic product comprising the cosmetic composition according to any one of claims 1-12.
Use of the cosmetic composition according to any one of claims 1-12 in the manufacture of a cosmetic product for inhibiting carbamylation of protein, particularly on skin.
A method for inhibiting carbamylation of protein, particularly on skin, comprising applying the cosmetic composition according to any one of claims 1-12 or the cosmetic product according to claim 13, preferably, wherein the cosmetic composition or the cosmetic product is applied topically.