Cosmetic composition containing decarboxylated oligopeptide and pyracantha extract and method for treating lipofuscin

Abstract

The cosmetic composition comprises at least one decarboxylated oligopeptide and at least one pyracantha extract. The decarboxylated oligopeptide may be a decarboxylated dipeptide or a decarboxylated tripeptide. The decarboxylated oligopeptide may be in free form or in salt form. The cosmetic composition may exhibit the ability to prevent or slow lipofuscin production and / or accumulation. The method for treating lipofuscin comprises topical application of a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one pyracantha extract.

Description

BACKGROUND OF THE INVENTION

[0001] Due to the role of pigments in the perception of skin flawlessness and skin aging, the cosmetic industry has made great efforts in skin pigment treatment. For example, many products have been developed for the treatment of "age spots", which are pigment-rich skin blemishes and have been considered related to aging.

[0002] Cosmetic products generally adopt the following approaches to treat skin pigments: 1) removing existing pigments from the skin wholly or partly; and / or 2) preventing or slowing down the production and / or accumulation of pigments in the skin. Since approaches 1) and 2) usually achieve the pigment reduction effect through different mechanisms, a method or product effective for one approach is not expected to be effective for the other. In addition, when the second approach is adopted, a method or product capable of preventing or slowing down the production and / or accumulation of one pigment is generally not expected to have a similar effect on other pigments, because different pigments have different chemical properties and are usually produced and accumulated in the skin through different pathways.

[0003] Lipofuscin, often referred to as "aging pigment", is a complex mixture of protein and lipid derivatives, which appears yellowish-brown under an optical microscope and has the property of autofluorescence. Lipofuscin is related to aging because its abundance in human tissues is closely related to the age of the subject. For example, in the field of skin care, lipofuscin is considered to be one of the two key pigments contributing to "age spots" (the other being melanin). Due to the link between lipofuscin and aging, the cosmetic industry highly desires active ingredients, compositions and methods capable of reducing lipofuscin in the skin. However, the treatment of lipofuscin is very difficult to obtain because 1) lipofuscin is known as a pigment that is difficult to remove once it is produced in the skin; and 2) the scientific community still lacks a good understanding of the mechanism / pathway of lipofuscin generation and / or accumulation, so targeted research cannot be carried out.

[0004] The present disclosure relates to a cosmetic composition comprising a decarboxylated oligopeptide and an extract of Pyracantha, and a method for treating lipofuscin in the skin by topically applying a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one extract of Pyracantha.

[0005] Detailed description

[0006] Definitions and conventions

[0007] Unless otherwise specified, all percentages mentioned herein are percentages by weight.

[0008] As used herein, "decarboxylation" means a chemical reaction that removes a carboxyl group and releases carbon dioxide.

[0009] As used herein, "decarboxylated amino acid" means an amino acid derivative that is the decarboxylation product of the corresponding amino acid. For example, decarboxylated tryptophan is tryptamine; decarboxylated phenylalanine is phenethylamine; decarboxylated tyrosine is tyramine; decarboxylated histidine is histamine; decarboxylated serine is ethanolamine; decarboxylated glutamate is γ-aminobutyric acid; decarboxylated lysine is cadaverine; decarboxylated arginine is agmatine; decarboxylated proline is pyrrolidine; decarboxylated ornithine is putrescine; decarboxylated 5-hydroxytryptophan is serotonin; and decarboxylated levodopa is dopamine.

[0010] As used herein, "peptide" means a chain of amino acids linked by peptide bonds.

[0011] As used herein, "oligopeptide" means a short-chain peptide composed of 2 to 20 amino acids, which includes dipeptides, tripeptides, tetrapeptides, and pentapeptides.

[0012] As used herein, "decarboxylated peptide" means a peptide derivative in which its C-terminal amino acid is replaced by the corresponding decarboxylated amino acid.

[0013] As used herein, "comprising" means that the list of elements is not necessarily limited to those expressly recited.

[0014] As used herein, "cosmetically acceptable" means that the composition or component is suitable for contact with human keratinous tissue.

[0015] As used herein, "molecular weight" refers to the weight-average molecular weight, unless otherwise specified.

[0016] As used herein, "QS" means a sufficient amount of 100%.

[0017] Unless otherwise specified: all 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.

[0018] It should be understood that each numerical range expressly recited herein will include each narrower numerical range falling within such broader numerical range, as if such narrower numerical ranges were all expressly recited herein.

[0019] As used herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to "an element" is a reference to one or more elements and includes equivalents thereof known to those skilled in the art. Similarly, for another example, a reference to "a step" or "a means" is a reference to one or more steps or means and may include sub-steps and subordinate means.

[0020] As used herein, a sentence that describes a series of alternates will be interpreted as if a series of sentences were provided such that each given alternative is provided as a sentence by itself. For example, the sentence "In some embodiments, the composition comprises A, B, or C" should be interpreted as if written as the following three separate sentences: "In some specific embodiments, the composition comprises A. In some embodiments, the composition comprises B. In some embodiments, the composition comprises C." As another example, the sentence "In some embodiments, the composition comprises at least A, B, or C" should be interpreted as if written as the following three separate sentences: "In some embodiments, the composition comprises at least A. In some embodiments, the composition comprises at least B. In some embodiments, the composition comprises at least C."

[0021] As used herein, "and / or" means "and" or "or". For example, "A and / or B" means "A, B, or both A and B", and "A, B, C, and / or D" means "A, B, C, D, or a combination thereof", and the "A, B, C, D, or a combination thereof" means any subset of A, B, C, and D, e.g., a single-member subset (e.g., A or B or C or D), a two-member subset (e.g., A and B; A and C; etc.), or a three-member subset (e.g., A, B, and C; or A, B, and D; etc.), or all four members (e.g., A, B, C, and D).

[0022] A. Method

[0023] In some embodiments, the present disclosure relates to a method for treating lipofuscin, the method comprising topically applying a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract.

[0024] In some preferred embodiments, the method for treating lipofuscin comprises topically applying a cosmetic composition having an effect of preventing or slowing down the generation and / or accumulation of lipofuscin.

[0025] B. Cosmetic composition

[0026] In some embodiments, the cosmetic composition of the present disclosure may be a topical composition. In one aspect, the topical composition may be in the form of a solid, liquid, or gel. In one aspect, the topical composition may be water-based or anhydrous-based. The water-based composition may be in the form of an emulsion, solution, or dispersion.

[0027] The present disclosure relates to a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract.

[0028] Decarboxylated oligopeptide

[0029] As decarboxylation products of the corresponding peptides, some decarboxylated peptides occur naturally. In living organisms, the decarboxylation reaction of peptides requires specific enzymes and strict conditions, which are very unlikely to be met in the case of topical application. It should also be understood in the art that decarboxylated peptides generally play very different roles / functions in biological pathways from those played by their corresponding peptides.

[0030] The cosmetic compositions of the present disclosure may contain at least one decarboxylated oligopeptide. The total weight of the at least one decarboxylated oligopeptide may be from about 0.0001% to about 5%, preferably from about 0.001% to about 1%, more preferably from about 0.005% to about 0.1%, and most preferably from about 0.01% to about 0.05% based on the total weight of the cosmetic composition. In some preferred embodiments, the cosmetic compositions of the present disclosure contain one decarboxylated oligopeptide.

[0031] The decarboxylated oligopeptides of the present disclosure may comprise a compound of formula (1):

[0032] R1-X1-(AA)n-X2-R2

[0033] Wherein:

[0034] X1 represents an N-terminal amino acid;

[0035] X2 represents a decarboxylated amino acid;

[0036] AA represents any amino acid or its derivative, and n is 0 or 1;

[0037] R1 represents the primary amine functionality of X1, which is free or substituted by a protective group, which may be selected from an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group;

[0038] When X2 does not contain a carboxyl group, R2 does not exist; when X2 contains a carboxyl group, R2 represents the hydroxyl group of the carboxyl functionality of X2, which is free or substituted by a protective group, which may be selected from a C1 to C20 alkyl chain or an NH2, NHY or NYY group, where Y represents a C1 to C4 alkyl chain.

[0039] In some preferred embodiments, the amino acids are selected from alanine (A), arginine (R), asparagine (N), aspartic acid (D), cysteine (C), glutamic acid (E), glutamine (Q), glycine (G), histidine (H), isoleucine (I), leucine (L), lysine (K), methionine (M), phenylalanine (F), proline (P), serine (S), threonine (T), tryptophan (W), tyrosine (Y), valine (V), and mixtures thereof.

[0040] The decarboxylated oligopeptides of the present disclosure can be in free form or in salt form. When in salt form, the decarboxylated oligopeptides can be in the form of trifluoroacetate, acetate, or chloride salt. The preferred salt form of the decarboxylated oligopeptides is the chloride salt form.

[0041] In some embodiments, n is 1 and the decarboxylated oligopeptide is a decarboxylated tripeptide.

[0042] In some embodiments, n is 0 and the decarboxylated oligopeptide is a decarboxylated dipeptide.

[0043] In some preferred embodiments, X1 is selected from alanine, glycine, isoleucine, leucine, and valine.

[0044] In some alternative preferred embodiments, X2 is selected from tryptamine, histamine, cadaverine, agmatine, and pyrrolidine.

[0045] In some more preferred embodiments, X1 is selected from alanine, glycine, isoleucine, leucine, and valine; and X2 is selected from tryptamine, histamine, cadaverine, agmatine, and pyrrolidine.

[0046] In some alternative more preferred embodiments, X1 is alanine.

[0047] In some alternative more preferred embodiments, X2 is histamine.

[0048] In some particularly preferred embodiments, X1 is alanine and X2 is histamine.

[0049] In some preferred embodiments, R1 is free.

[0050] In some preferred embodiments, n is 0.

[0051] In the most preferred embodiments, X1 is alanine, X2 is histamine, R1 is free, and n is 0. When this most preferred embodiment is in free form, the decarboxylated oligopeptide is carcinine (alternatively referred to as decarboxylated carnosine). When this most preferred embodiment is in chloride salt form, the decarboxylated oligopeptide has the INCI name Decarboxy Carnosine HCL, which is commercially available from Exsymol under the trade name Alistin.

[0052] Pyracantha extract

[0053] Pyracantha is a genus of thorny evergreen shrubs in the Rosaceae family, which includes seven species: Pyracantha angustifolia, Pyracantha atalantioides, Pyracantha coccinea, Pyracantha crenulate, Pyracantha fortuneana, Pyracantha koidzumii, and Pyracantha rogersiana. All Pyracantha species have small white flowers. The fruits of the Pyracantha genus are red, orange, or yellow pome fruits.

[0054] The cosmetic composition of the present disclosure may contain at least one Pyracantha extract. The total weight of the at least one Pyracantha extract may be from about 0.00001% to about 1%, preferably from about 0.00005% to about 0.1%, more preferably from about 0.0001% to about 0.05%, and most preferably from about 0.0005% to about 0.01% based on the total weight of the cosmetic composition. In some preferred embodiments, the cosmetic composition of the present disclosure contains one Pyracantha extract.

[0055] In some embodiments, the Pyracantha extract of the present disclosure may be selected from Pyracantha angustifolia extract, Pyracantha atalantioides extract, Pyracantha coccinea extract, Pyracantha crenulate extract, Pyracantha fortuneana extract, Pyracantha koidzumii extract, Pyracantha rogersiana extract, and mixtures thereof. The preferred Pyracantha extract is Pyracantha fortuneana extract.

[0056] In some embodiments, the Pyracantha extract of the present disclosure may be selected from Pyracantha plant extract, Pyracantha fruit extract, Pyracantha flower extract, Pyracantha leaf extract, Pyracantha stem extract, Pyracantha root extract, and mixtures thereof. The preferred Pyracantha extract is Pyracantha fruit extract.

[0057] In some embodiments, the Pyracantha extract of the present disclosure may be selected from Pyracantha angustifolia extract, Pyracantha atalantioides extract, Pyracantha coccinea extract, Pyracantha crenulate extract, Pyracantha fortuneana extract, Pyracantha koidzumii extract, Pyracantha rogersiana extract, and mixtures thereof; wherein the Pyracantha extract is prepared from a Pyracantha plant, a Pyracantha fruit, a Pyracantha flower, a Pyracantha leaf, a Pyracantha stem, a Pyracantha root, or a mixture thereof.

[0058] In some preferred embodiments, the Pyracantha extract of the present disclosure is Pyracantha fruit extract.

[0059] In some more preferred embodiments, the Pyracantha fruit extract is prepared by enzymatic hydrolysis. Preferably, the enzymatic hydrolysis is carried out with an enzyme mixture comprising polygalacturonase, cellulase, and pectinase. More preferably, the weight ratio of polygalacturonase, cellulase, and pectinase in the enzyme mixture is 1:1:1.

[0060] A non-limiting example of the Pyracantha fruit extract is commercially available from Ingredi Biotech under the trade name WonderFlame.

[0061] Preferably, the Pyracantha fruit extract can be prepared according to the method described in WO2022227286A1, which is incorporated herein by reference in its entirety. The preparation method includes the following steps: 1) Enzymatic hydrolysis: Take fruits of the Pyracantha genus, add a complex enzyme for enzymatic hydrolysis, and obtain an enzymatic hydrolysis mixture; 2) Ethanol extraction: Add ethanol to the enzymatic hydrolysis mixture for extraction, filtration, and concentration to obtain an ethanol extract; 3) Macroporous adsorption resin purification: Load the ethanol extract onto a macroporous adsorption resin for purification and collect the analytical solution; and 4) Drying: Concentrate and dry the analytical solution to obtain a solution. Preferably, in step 1), the complex enzyme used for enzymatic hydrolysis comprises polygalacturonase, cellulase, and pectinase; the temperature of enzymatic hydrolysis is about 37°C to about 42°C; the enzymatic hydrolysis time period is about 1 to about 3 hours; and the pH value of the enzymatic hydrolysis mixture is about 4.5 to about 6.5. More preferably, in step 1), the weight ratio of polygalacturonase, cellulase, and pectinase in the complex enzyme is 1:1:1. Preferably, in step 3), the macroporous adsorption resin is selected from ADS-7, LS-300B, NKA-9, HPD300, HPD600, HPD100, LS46, LS32, LS308, AB-8, LS305, and D101.

[0062] In some preferred embodiments, the weight ratio of at least one decarboxylated oligopeptide to at least one Pyracantha genus extract can be about 1:20 to about 500:1, preferably about 1:10 to about 300:1, more preferably about 1:5 to about 200:1, and most preferably about 1:1 to about 100:1.

[0063] In some more preferred embodiments, the cosmetic composition of the present disclosure comprises a decarboxylated oligopeptide and a Pyracantha genus extract.

[0064] In some most preferred embodiments, the cosmetic composition of the present disclosure comprises carcinine and Pyracantha fruit extract.

[0065] In some most preferred embodiments, the cosmetic composition of the present disclosure comprises Decarboxy Carnosine HCL and Pyracantha fruit extract.

[0066] In some particularly preferred embodiments, the cosmetic composition of the present disclosure comprises DecarboxyCarnosine HCL and Pyracantha fruit extract, wherein the weight ratio of Decarboxy Carnosine HCL to Pyracantha fruit extract is from about 1:20 to about 500:1, preferably from about 1:10 to about 300:1, more preferably from about 1:5 to about 200:1, and most preferably from about 1:1 to about 100:1.

[0067] Other ingredients:

[0068] The topical composition may further contain the following ingredients:

[0069] Oil

[0070] Suitable oils include silicones, esters, vegetable oils, synthetic oils, including but not limited to those described herein. The oil may be volatile or non-volatile and is preferably in the form of a pourable liquid at room temperature. If present, the oil may be from about 0.5% to about 85% by weight of the total composition, preferably from about 1% to about 75%, more preferably from about 5% to about 65%.

[0071] Cyclic and linear volatile silicones are available from various commercial sources, including Dow Chemical Corporation and Momentive (formerly General Electric Silicones). Dow Chemical's 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 as cst)), octamethyltrisiloxane (1.0 cst), decamethyltetrasiloxane (1.5 cst), dodecamethylpentasiloxane (2 cst), and mixtures thereof, all viscosity measurements being made at 25°C.

[0072] Suitable branched volatile silicones include alkyl polytrimethylsiloxanes such as methyl polytrimethylsiloxane, branched volatile silicones having the following general formula:

[0073]

[0074] Methyl polytrimethylsiloxane is available from Shin-Etsu Silicones under the trade name TMF-1.5 and has a viscosity of 1.5 centistokes at 25°C.

[0075] Also suitable are various straight-chain or branched-chain alkanes 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 isoparaffin. Suitable C 12 isoparaffins are produced by Permethyl Corporation under the trade name Permethyl 99A. Various commercially available C 16 isoparaffins, such as isocetane (having the trade name Permethyl R), are also suitable.

[0076] Also suitable are esters formed by the reaction of carboxylic acids and alcohols. Both the alcohol and the carboxylic acid can have a fatty (C6-30) chain. Examples include hexyl laurate, butyl isostearate, cetyl isostearate, cetyl palmitate, isostearyl neopentanoate, stearyl heptanoate, isostearyl isononanoate, stearyl lactate, stearyl octanoate, stearyl stearate, isononyl isononanoate, and the like.

[0077] The esters can also be in the form of dimers or trimers. Examples of such esters include diisostearyl malate, neopentyl glycol dicaprylate, dibutyl sebacate, dicetyl stearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, dioctyl malate, and the like.

[0078] Examples of other types of esters include those from arachidonic acid, citric acid or behenic acid, such as triarachidin, tributyl citrate, triisostearyl citrate, tri-C 12-13 alkyl citrate, tributyl citrate, trioctyl citrate, tridecyl behenate, tris(octyldodecyl) citrate, tridecyl behenate; or tridecyl cocoate, tridecyl isononanoate, and the like.

[0079] Synthetic or naturally occurring fatty acid glycerides or triglycerides are also suitable for use in the composition. Both plant and animal sources can be used. Examples of such oils include castor oil, lanolin oil, C 10-18Triglycerides, caprylic / capric triglyceride, sweet almond oil, almond oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, inkoil, olive oil, palm oil, illipe butter, rapeseed oil, soybean oil, grape seed oil, sunflower seed oil, walnut oil, etc.

[0080] Also suitable are synthetic or semi-synthetic glycerides, such as fatty acid monoglycerides, diglycerides and triglycerides, which are modified natural fats or oils, such as monoesters, diesters or triesters of polyols (such as glycerol). In one example, a fatty acid (C 12-22 ) carboxylic acid is reacted with one or more repeating glycerol groups. Stearyl glyceride, diisostearyl diglyceride, polyglyceryl-3 isostearate, polyglyceryl-4 isostearate, polyglyceryl-6 ricinoleate, dioleyl glyceride, diisostearyl glyceride, tetraisostearyl glyceride, trioctanoin, distearyl diglyceride, linoleyl glyceride, myristyl glyceride, isostearyl glyceride, PEG castor oils, PEG glyceryl oleates, PEG glyceryl stearates, PEG glyceryl tallowates, etc.

[0081] Non-volatile silicone oils (both water-soluble and water-insoluble) are also suitable for the composition. Such silicones preferably have a viscosity of about greater than 5 to 800,000 cst, preferably 20 to 200,000 cst at 25 °C. Suitable water-insoluble silicones include amine-functional silicones, such as amodimethicone. Examples include polydimethylsiloxane, phenylpolydimethylsiloxane, diphenylpolydimethylsiloxane, phenyltrimethylsiloxane or trimethylsilyloxy phenyl polydimethylsiloxane. Other examples include alkyl polydimethylsiloxanes, such as cetyl polydimethylsiloxane, stearyl polydimethylsiloxane, behenyl polydimethylsiloxane, etc.

[0082] Surfactant

[0083] The composition may contain one or more surfactants, especially if in emulsion form. However, if the composition is also anhydrous, such surfactants can be used and will help to disperse polar components, such as pigments. Such surfactants can be silicone-based or organic-based. The surfactant will help to form a stable emulsion in the form of oil-in-water or water-in-oil. If present, the surfactant can be about 0.001% to 30% by weight of the total composition, preferably about 0.005% to 25%, more preferably about 0.1% to 20%.

[0084] Silicone surfactants can generally be referred to as polydimethylsiloxane copolyols or alkyl polydimethylsiloxane copolyols. In some cases, the number of repeating ethylene oxide or propylene oxide units in the polymer is also specified. For example, polydimethylsiloxane copolyol, also known as PEG-15 / PPG-10 polydimethylsiloxane, refers to polydimethylsiloxane having a substituent containing 15 ethylene glycol units and 10 propylene glycol units on the siloxane backbone. One or more of the methyl groups in the above general structure can also be replaced by longer-chain alkyl groups (such as ethyl, propyl, butyl, etc.) or ethers such as methyl ether, ethyl ether, propyl ether, butyl ether, etc.

[0085] Examples of silicone surfactants are those with CTFA names of cyclotetrasiloxane (and) cyclopentasiloxane (and) PEG / PPG-18 dimethicone sold by Dow Silicones under the trade name Dowsil 3225C Formulation Aid; or 5225C Formulation Aid with CTFA name of cyclopentasiloxane (and) PEG / PPG-18 / 18 dimethicone; or Dowsil 190 Surfactant with CTFA name of PEG / PPG-18 / 18 dimethicone; or Dowsil 193 Fluid, Dowsil 5200 with CTFA name of lauryl PEG / PPG-18 / 18 polymethylsiloxane; or Abil EM 90 sold by Goldschmidt with CTFA name of cetyl PEG / PPG-14 / 14 dimethicone; or Abil EM 97 sold by Goldschmidt with CTFA name of bis-cetyl PEG / PPG-14 / 14 dimethicone; or Abil WE09 with CTFA name of cetyl PEG / PPG-10 / 1 dimethicone and also containing polyglyceryl-4 isostearate and hexyl laurate in the mixture; or KF-6011 sold by Shin-Etsu Silicones with CTFA name of PEG-11 methyl ether dimethicone; KF-6012 sold by Shin-Etsu Silicones with CTFA name of PEG / PPG-20 / 22 butyl ether dimethicone; or KF-6013 sold by Shin-Etsu Silicones with CTFA name of PEG-9 dimethicone; or KF-6015 sold by Shin-Etsu Silicones with CTFA name of PEG-3 dimethicone; or KF-6016 sold by Shin-Etsu Silicones with CTFA name of PEG-9 methyl ether dimethicone; or KF-6017 sold by Shin-Etsu Silicones with CTFA name of PEG-10 dimethicone; or KF-6038 sold by Shin-Etsu Silicones with CTFA name of lauryl PEG-9 dimethicone methoxysilylethyl dimethicone.

[0086] Also suitable are various types of crosslinked silicone surfactants commonly referred to as emulsifying elastomers, which contain at least one hydrophilic moiety such as a polyoxyalkylenated group. Polyoxyalkylenated silicone elastomers that can be used in at least one embodiment of the present disclosure include those sold by Shin-Etsu Silicones under the following names: KSG-21, KSG-20, KSG-30, KSG-31, KSG-32, KSG-33; KSG-210, which is a polydimethylsiloxane / PEG-10 / 15 crosslinked polymer dispersed in polydimethylsiloxane; KSG-310, which is a PEG-15 lauryl polydimethylsiloxane crosslinked polymer; KSG-320, which is a PEG-15 lauryl polydimethylsiloxane crosslinked polymer dispersed in isododecane; KSG-330 (precursor dispersed in triethylhexanoin), KSG-340, which is a mixture of a PEG-10 lauryl polydimethylsiloxane crosslinked polymer and a PEG-15 lauryl polydimethylsiloxane crosslinked polymer.

[0087] Also suitable are polyglycerolated silicone elastomers, such as those disclosed in PCT / WO2004 / 024798, which is hereby incorporated by reference in its entirety. Such elastomers include the KSG series from Shin-Etsu, for example KSG-710, which is a polydimethylsiloxane / polyglycerol-3 crosslinked polymer dispersed in polydimethylsiloxane; or lauryl polydimethylsiloxane / polyglycerol-3 crosslinked polymers sold under the Shin-Etsu trade names KSG-810, KSG-820, KSG-830 or KSG-840 and dispersed in various solvents (such as isododecane, polydimethylsiloxane, triethylhexanoin). Also suitable are silicones sold by Dow Silicones under the trade names 9010 and DC9011.

[0088] The composition may comprise one or more non-ionic organic surfactants. Suitable non-ionic surfactants include alkoxylated alcohols or ethers formed by the reaction of an alcohol with an alkylene oxide, typically ethylene oxide or propylene oxide. Preferably, the alcohol is a fatty alcohol having 6 to 30 carbon atoms. Examples of such components include Steareth 2-100, which is formed by the reaction of stearyl alcohol and ethylene oxide and the number of ethylene oxide units is 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 from 5 to 30; Ceteareth 2-100, which is formed by the reaction of a mixture of cetyl alcohol and stearyl alcohol with ethylene oxide, where the number of repeating ethylene oxide units in the molecule is from 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 1-45 and so on. All listings of units include all integers between the ranges.

[0089] Other alkoxylated alcohols are formed by the reaction of fatty acids and unit alcohols, diols or polyols with alkylene oxides. For example, C 6-30 Reaction products of fatty carboxylic acids and polyols (which are monosaccharides such as glucose, galactose, methylglucose, etc.) with alkoxylated alcohols. Examples include polymeric alkylene glycols reacted with fatty acid glycerides, such as PEG glycerol oleate, PEG glycerol stearate; or PEG polyhydroxyalkanoates, such as PEG dimer hydroxy stearate, where the number of repeating ethylene glycol units is from 3 to 1000.

[0090] Other suitable non-ionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation of sorbitan, especially ethoxylation provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters, such as polysorbates. For example, polyalkoxylated sorbitan can be esterified with C 6-30 fatty acids, preferably C 12-22 fatty acids. Examples of such components include polysorbate 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquiisostearate, sorbitan stearate and so on.

[0091] Humectant

[0092] It may also be desirable to include one or more humectants in the composition. If present, such humectants may be 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 diols, sugars, etc. Suitable diols are in monomeric or polymeric form and include polyethylene glycol and polypropylene glycol, such as PEG4-200, which is polyethylene glycol having from 4 to 200 repeating ethylene oxide units; and C 1-6 alkylene diols, such as propylene glycol, butylene glycol, pentylene glycol, etc. Suitable sugars (some of which are also polyols) are also suitable humectants. Examples of such sugars include glucose, fructose, honey, oxidized honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, etc. Urea is also suitable. Preferably, the humectant for the composition of the present disclosure is C 1-6 alkylene diol, preferably C 2-4 alkylene diol, most particularly butylene glycol.

[0093] Plant extract

[0094] It may be desirable to include one or more plant extracts in the composition. If so, the recommended ranges are from about 0.0001% to 10%, preferably from about 0.0005% to 8%, more preferably from about 0.001% to 5% by weight of the total composition. Suitable plant extracts include those from plants (herbs, rhizomes, flowers, fruits, seeds), such as flowers, fruits, vegetables, etc., which include yeast fermentation extracts, Padina pavonica extracts, Thermus thermophilis fermentation extracts, Camelina sativa seed oil, Boswellia serrata extracts, olive extracts, Arabidopsis Thaliana extracts, Acacia Dealbata extracts, Acer (sugar maple) extracts, Lactobacillus acidopholus, Acorus, Aesculus, Agaricus, Agave, Agrimonia, algae, aloe vera, Citrus, Brassica, cinnamon, orange, apple, blueberry, cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea, chamomile, willow bark, mulberry, and those described on pages 1646 to 1660 of Volume 2 of the CTFA Cosmetic Ingredient Handbook, 8th Edition.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.

[0095] Granular material

[0096] The compositions of the present disclosure may contain particulate materials in the form of pigments, inert particles, or mixtures thereof. If present, the recommended ranges are from about 0.01% to 75%, preferably from about 0.5% to 70%, more preferably from about 0.1% to 65% by weight of the total composition. In cases where the composition may contain a mixture of pigment and powder, suitable ranges include from about 0.01% to 75% pigment and from 0.1% to 75% powder, these weights being based on the weight of the total composition.

[0097] The particulate matter may be colored or colorless powders. Suitable non-pigment powders include bismuth oxychloride, titanated mica, fumed silica, spherical silica, polymethyl methacrylate, micronized polytetrafluoroethylene, boron nitride, acrylate copolymer, aluminum silicate, starch aluminum octenyl succinate, bentonite, calcium silicate, cellulose, chalk, corn starch, diatomaceous earth, fuller's earth, glycerol starch, lithium montmorillonite, 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, silylated silica, silk powder, sericite, soy flour, tin oxide, titanium hydroxide, trimagnesium phosphate, walnut shell powder, or mixtures thereof. The powders mentioned above may be surface-treated individually or in combination with lecithin, amino acids, mineral oil, silicone, or various other reagents, which coat the powder surface and make the particles more lipophilic in nature.

[0098] Suitable pigments are organic or inorganic. Organic pigments are generally of various aromatic types, including azo, indigoid, triphenylmethane, anthraquinone, and xanthine dyes, which are named D&C and FD&C blues, browns, greens, oranges, reds, yellows, etc. Organic pigments generally consist of insoluble metal salts of certified coloring additives, called Lakes. Inorganic pigments include iron oxides, ultramarines, chromium, chromium hydroxide pigments, and mixtures thereof. Iron oxides of red, blue, yellow, brown, black, and mixtures thereof are suitable.

[0099] Vitamins and antioxidants

[0100] The compositions of the present disclosure may contain vitamins and / or coenzymes and antioxidants. If so, it is recommended in an amount of 0.001% to 10%, preferably 0.01% to 8%, more preferably 0.05% to 5% by weight of the total composition. Suitable vitamins include ascorbic acid and its derivatives such as ascorbyl palmitate, ascorbyl tetrakis(hexyldecanoate), etc.; B vitamins such as thiamine, riboflavin, pyridoxine, etc., and coenzymes such as thiamine pyrophosphate, flavin adenine dinucleotide, folic acid, pyridoxal phosphate, tetrahydrofolic acid, etc. Also suitable are vitamin E and its derivatives such as vitamin E acetate, vitamin E nicotinate or other esters thereof. Additionally, vitamin D and K are suitable.

[0101] The present disclosure will be further described in conjunction with the following examples, which are set forth for illustrative purposes only.

[0102] Experimental Examples

[0103] Reagents used in this experiment: 5 mg Leupeptin hemisulfate (MCE); iron(III) chloride (purchased from Sigma); 30% hydrogen peroxide solution; TrypLE Express (purchased from Life Technologies); primary Asian keratinocytes (purchased from Lifeline); DermaLife K keratinocyte complete medium set (purchased from Lifeline); Decarboxy Carnosine HCL (purchased from Exsymol under the trade name Alistin); Pyracantha fruit extract (purchased from Ingredi Biotech Co., LTD. under the trade name Wonder Flame).

[0104] Instruments used in this experiment: Operetta CLS high-content imaging system purchased from PerkinEImer.

[0105] Stock solutions prepared for this experiment: Leupeptin and cell culture medium should be stored at 4 °C and can be used throughout the experiment. Iron(III) chloride and hydrogen peroxide solutions should be freshly prepared each time either solution is needed.

[0106] A Leupeptin stock solution was prepared by dissolving 5 mg of Leupeptin hemisulfate in 10.13 mL of molecular grade water to prepare a 1 mM stock solution.

[0107] An iron(III) chloride solution was prepared by dissolving 30.41 mg of FeCl3 in 25 mL of molecular grade water to prepare a 7.5 mM stock solution.

[0108] The hydrogen peroxide solution was prepared by dissolving 2.84 μL of 30% H2O2 in 25 mL of molecular grade water to prepare a 1 mM stock solution.

[0109] Experimental procedure:

[0110] Table 1. Formulation of lipofuscinogenic medium

[0111] Added reagent Volume added per mL (μL) Final concentration (μM) 1 mM Leupeptin 40 40 7.5 mM Iron(III) chloride 6 45 1 mM Hydrogen peroxide 10 10 Cell culture medium (Step 4) 944 N / A

[0112] 1. Seed 5×10^4 keratinocytes or fibroblasts in a 12-well plate for 24 h, then change the medium.

[0113] 2. Prepare the lipofuscinogenic medium by thoroughly mixing the stock solutions according to Table 1.

[0114] 3. Add 1 mL of the lipofuscinogenic medium to each well in the plate.

[0115] 4. Change the medium every 48 h. Prepare a new lipofuscinogenic medium solution according to Table 1 using the stock solution generated as described above each time. At each medium change, wash the cells with phosphate buffered saline (with calcium and magnesium) to remove any residual waste.

[0116] 5. At the start of day 6, add the active ingredient of interest at the desired concentration.

[0117] 6. Continuously change the medium with the medium containing the active ingredient of interest in a 48-hour schedule.

[0118] 7. At the end of day 10, prepare the cells for confocal detection to measure the spontaneous fluorescence intensity.

[0119] Results:

[0120] Collect the original autofluorescence intensity data in relative fluorescence units (RFU). Control data is collected on control samples, where cells are prepared only with cell culture medium. Induction data is collected on induction samples, where cells are prepared only with lipofuscin-generating medium without any active ingredients. Component data is collected on the corresponding component samples, where cells are prepared with lipofuscin-generating medium with the corresponding active ingredient or combination of active ingredients. For each data point, samples are prepared and measured at least three times, and the average intensity and standard deviation (SD) are shown in Examples 1-4, where Component a is DecarboxyCarnosine HCL and Component b is Pyracantha fortuneana fruit extract. The inhibition rate is calculated based on the following formula: Inhibition rate = 1 - ((Average of component sample - Average of control sample) / (Average of induction sample - Average of control sample)), where the average of the component sample is the average autofluorescence intensity of the corresponding component sample; the average of the control is the average autofluorescence intensity of the control sample; and the average of the induction is the average autofluorescence intensity of the induction sample.

[0121] Example 1: The weight ratio of Component a and Component b is 100:1

[0122]

[0123] Example 2: The weight ratio of Component a and Component b is 20:1

[0124]

[0125] Example 3: The weight ratio of Component a and Component b is 4:1

[0126]

[0127] Example 4: The weight ratio of Component a and Component b is 1:1

[0128]

[0129] Result analysis

[0130] The experimental results were evaluated by the isobolographic method for synergy, 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 incorporated herein by reference in its entirety. According to the isobolographic method, when OE represents the observed effect, and da and db represent the doses of component a and component b, respectively (thus, OE(da,db) represents the effect observed for the combination of component a at da and component b at db; and OE(da) represents the effect observed for component a at da, and OE(db) represents the effect observed for component b at db), three mathematical equations can be derived:

[0131] OE(da, db) = OE(da) + OE(db) (1)

[0132] OE(da, db) > OE(da) + OE(db) (2)

[0133] OE(da, db) < OE(da) + OE(db) (3)

[0134] If the observed effect satisfies equation (1), the effects of the two components are a simple addition of the individual effects, and the two components do not interact, so there is no synergy.

[0135] If the observed effect satisfies equation (2), the result represents true synergy (or potentiation), where the effects of the two components are greater than the simple sum of the individual effects.

[0136] If the observed effect satisfies equation (3), the result represents the opposite of synergy, as the effects of the two components are less than the simple addition of the individual effects.

[0137] In this specific experiment, OE (the observed effect) means the inhibition rate. The evaluation based on the isobolographic method is shown in Table 2.

[0138] Table 2: Effects of Decarboxy Carnosine HCL (Component a) and Pyracantha Fruit Extract (Component b) on Preventing or Slowing Down the Formation and / or Accumulation of Lipofuscin

[0139]

[0140] As the data shows, for all Examples 1-4, each OE(da,db) is greater than the corresponding OE(da)+OE(db), which satisfies formula (2). Thus, the results exhibit a true synergy (or enhancement), where the effects of the two components (a and b) are greater than the simple sum of the individual effects. In summary, the combination of Decarboxy Carnosine HCL and Pyracantha fruit extract exhibits an unexpected synergistic effect in preventing or slowing down the formation and / or accumulation of lipofuscin.

[0141] Other embodiments

[0142] Although the present invention has been described in connection with the preferred embodiments, it is not intended to limit the scope of the invention to the specific forms described. 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. Accordingly, other embodiments (including those that can be readily modified by those skilled in the art from the present disclosure) are also covered by the scope of the claims.

Claims

1. A cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract.

2. The cosmetic composition according to claim 1, wherein the at least one decarboxylated oligopeptide is selected from compounds of formula (I): R1-X1-(AA)n-X2-R2 Wherein: X1 represents an N-terminal amino acid; X2 represents a decarboxylated amino acid; AA represents any amino acid or its derivative, and n is 0 or 1; R1 represents the primary amine function of X1, which is free or substituted by a protective group, and the protective group may be selected from an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group; and When X2 does not contain a carboxyl group, R2 does not exist; or when X2 contains a carboxyl group, R2 represents the hydroxyl group of the carboxyl function of X2, which is free or substituted by a protective group, and the protective group may be selected from a C1 to C20 alkyl chain or an NH2, NHY or NYY group, where Y represents a C1 to C4 alkyl chain; And mixtures thereof.

3. The cosmetic composition according to claim 2, wherein X1 is selected from alanine, glycine, isoleucine, leucine and valine.

4. The cosmetic composition according to claim 2, wherein X2 is selected from tryptamine, histamine, cadaverine, agmatine and pyrrolidine.

5. The cosmetic composition according to claim 1, wherein the at least one decarboxylated oligopeptide is present in an amount of about 0.0001% to about 5% by weight of the total weight of the cosmetic composition.

6. The cosmetic composition according to claim 1, wherein the at least one Pyracantha extract is selected from: Pyracantha angustifolia extract, Pyracantha atalantioides extract, Pyracantha coccinea extract, Pyracantha crenulata extract, Pyracantha fortuneana extract, Pyracantha koidzumii extract, Pyracantha lanceolata extract, and mixtures thereof.

7. The cosmetic composition according to claim 6, wherein the at least one Pyracantha extract is selected from Pyracantha plant extract, Pyracantha fruit extract, Pyracantha flower extract, Pyracantha leaf extract, Pyracantha stem extract, Pyracantha root extract, and mixtures thereof.

8. The cosmetic composition according to claim 1, wherein the at least one Pyracantha extract is present in an amount of about 0.00001% to about 1% by weight of the total weight of the cosmetic composition.

9. A method for treating lipofuscin, which comprises topically applying a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract.

10. The method for treating lipofuscin according to claim 9, wherein the cosmetic composition has the effect of preventing or slowing down the generation and / or accumulation of lipofuscin.

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