Cosmetic composition containing decarboxylated oligopeptides 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 salt form. The cosmetic composition may exhibit the ability to prevent or delay the formation and / or accumulation of lipofuscin. A method of treating lipofuscin involves topical application of a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract.

Description

[Technical Field]

[0001] The cosmetics industry has been keen to treat skin pigmentation due to the role of pigments in the perception of skin perfection and skin aging. For example, many products have been developed to treat "age spots," which are pigmented skin blemishes that are perceived as being associated with aging. [Background technology]

[0002] Cosmetics generally employ the following approaches to treat skin pigmentation: 1) completely or partially removing existing pigment from the skin, and / or 2) preventing or delaying the production and / or accumulation of pigment in the skin. Approaches 1) and 2) generally achieve their pigment-reducing effects through different mechanisms, so methods or products effective for one approach are not expected to be effective for the other. Furthermore, when employing the second approach, methods or products that can prevent or delay the production and / or accumulation of one pigment are generally not expected to have the same effect on other pigments. This is because different types of pigments have different chemical properties and are generally produced and accumulated in the skin through different pathways.

[0003] Lipofuscin, also known as the "aging pigment," is a complex mixture of protein and lipid derivatives that appears yellowish-brown under a light microscope and possesses autofluorescence properties. Lipofuscin is associated with aging because its abundance in human tissues closely correlates with the subject's age. For example, in the skincare field, lipofuscin is recognized as one of the two main pigments (the other being melanin) that cause "age spots." Due to the association between lipofuscin and aging, the cosmetics industry has a strong demand for active ingredients, compositions, and methods to reduce lipofuscin in the skin. However, treating lipofuscin is extremely difficult for two reasons: 1) lipofuscin is known to be a difficult pigment to remove once it is produced in the skin, and 2) the scientific community does not yet fully understand the mechanisms / pathways of lipofuscin production and / or accumulation, making targeted research impossible. [Overview of the project]

[0004] This disclosure relates to a cosmetic composition comprising a decarboxylated oligopeptide and a Pyracantha extract, and to a method for treating lipofuscin in the skin by topical application of a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one Pyracantha extract. [Modes for carrying out the invention]

[0005] Definitions and Terms

[0006] All percentages mentioned herein are weight percentages unless otherwise specified.

[0007] In this specification, "decarboxylation" refers to a chemical reaction that removes carboxyl groups and releases carbon dioxide.

[0008] As used herein, “decarboxylated amino acid” means an amino acid derivative which is the decarboxylation product of the corresponding amino acid. For example, decarboxylated tryptophan is tryptamine, decarboxylated phenylalanine is phenylethylamine, decarboxylated tyrosine is tyramine, decarboxylated histidine is histamine, decarboxylated serine is ethanolamine, decarboxylated glutamic acid is gamma-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.

[0009] As used herein, "peptide" means a chain of amino acids linked by peptide bonds.

[0010] As used herein, "oligopeptide" means a short-chain peptide consisting of 2 to 20 amino acids, including dipeptides, tripeptides, tetrapeptides, and pentapeptides.

[0011] As used herein, "decarboxylated peptide" means a peptide derivative in which the C-terminal amino acid is substituted with the corresponding decarboxylated amino acid.

[0012] As used herein, “contains” means that the list of elements is not necessarily limited to those explicitly enumerated.

[0013] As used herein, “cosmetic-grade” means that the composition or component is suitable for use in contact with human stratum corneum.

[0014] As used herein, "molecular weight" refers to the weight-average molecular weight unless otherwise specified.

[0015] As used herein, "QS" means a quantity sufficient to make 100%.

[0016] Unless otherwise specified, all figures are understood to be modified by the word "approximately," all percentages are relative to the total weight of the composition, and all ratios are weight ratios.

[0017] All numerical ranges expressly described herein include any narrower numerical ranges that fall within such broader ranges, and all such narrower numerical ranges should be understood as if they were expressly described herein.

[0018] As used herein, the singular forms "a," "an," and "the" include plural references unless the context explicitly indicates otherwise. Therefore, for example, a reference to "an element" refers to one or more elements, including their equivalents known to those skilled in the art. Similarly, as another example, a reference to "a step" or "a means" refers to one or more steps or means, which may include substeps or subordinate means.

[0019] Where used herein, a statement listing a set of alternatives shall be interpreted as a set of statements, such that each of the alternatives is defined by itself in a separate statement. For example, the statement "In some embodiments, the composition comprises A, B, or C" shall be interpreted as being written as three separate statements: "In some embodiments, the composition comprises A. In some embodiments, the composition comprises B. In some embodiments, the composition comprises C." As another example, the statement "In some embodiments, the composition comprises at least A, B, or C" shall be interpreted as being written as three separate statements: "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."

[0020] As used herein, “and / or” means “and” or “or.” For example, “A and / or B” means “A, B, or both A and B,” “A, B, C, and / or D” means “A, B, C, D, or any combination thereof,” and “A, B, C, D, or any combination thereof” means any subset of A, B, C, and D, for example, one member subset (e.g., A or B or C or D), two member subsets (e.g., A and B, A and C, etc.), three member subsets (e.g., A, B and C, or A, B and D, etc.), or all four members (e.g., A, B, C and D).

[0021] A. Method In some embodiments, the present disclosure relates to a method for treating lipofuscin, the method comprising topical application of a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one pyracantha extract.

[0022] In some preferred embodiments, the method of treating lipofuscin includes the topical application of a cosmetic composition having an effect of preventing or delaying the generation and / or accumulation of lipofuscin.

[0023] B. Cosmetic Composition 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. The water-based composition may be in the form of an emulsion, solution, or dispersion.

[0024] The present disclosure relates to a cosmetic composition comprising at least one decarboxylated oligopeptide and at least one extract of the genus Pyracantha.

[0025] Decarboxylated Oligopeptide Some decarboxylated peptides occur naturally as decarboxylation products of the corresponding peptides. In vivo, the decarboxylation reaction of peptides requires specific enzymes and strict conditions, which are almost impossible to meet in the context of topical application. It is also understood in this field that decarboxylated peptides usually play very different roles / functions from those of the corresponding peptides in biological pathways.

[0026] The cosmetic composition of the present disclosure may contain at least one decarboxylated oligopeptide. The total weight of the at least one decarboxylated oligopeptide may range 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 composition of the present disclosure contains one decarboxylated oligopeptide.

[0027] The decarboxylated oligopeptide of the present disclosure may include a compound of formula (I).

[0028] R1-X1-(AA)n-X2-R2

[0029] (In the formula,

[0030] X1 represents the N-terminal amino acid,

[0031] X2 represents a decarboxylated amino acid.

[0032] AA represents any amino acid or its derivative, and n is 0 or 1.

[0033] R1 represents the primary amine functional group of X1, which is either free or substituted with a protecting group which can be selected from an acetyl group, a benzoyl group, a tosyl group, or a benzyloxycarbonyl group.

[0034] If X2 does not contain a carboxyl group, R2 is absent; or, if X2 contains a carboxyl group, R2 represents the hydroxyl group of the carboxyl functional group of X2, which is either free or substituted by a protecting group that can be selected from a C1-C20 alkyl chain, or from an NH2, NHY, or NYY group (where Y represents a C1-C4 alkyl chain).

[0035] In some preferred embodiments, the amino acids are selected from the group consisting of 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.

[0036] The decarboxylated oligopeptides of this disclosure may be in free form or in salt form. In the case of salt form, the decarboxylated oligopeptides may be in the form of trifluoroacetate, acetate, or chloride salt. The preferred salt form of the decarboxylated oligopeptide is the chloride salt form.

[0037] In some embodiments, n is 1, and the decarboxylated oligopeptide is a decarboxylated tripeptide.

[0038] In some embodiments, n is 0, and the decarboxylated oligopeptide is a decarboxylated dipeptide.

[0039] In some preferred embodiments, X1 is selected from the group consisting of alanine, glycine, isoleucine, leucine, and valine.

[0040] In some alternative preferred embodiments, X2 is selected from the group consisting of tryptamine, histamine, cadaverine, agmatine, and pyrrolidine.

[0041] In some more preferred embodiments, X1 is selected from the group consisting of alanine, glycine, isoleucine, leucine, and valine, and X2 is selected from the group consisting of tryptamine, histamine, cadaverine, agmatine, and pyrrolidine.

[0042] In some alternative and more preferred embodiments, X1 is alanine.

[0043] In some alternative, more preferred embodiments, X2 is histamine.

[0044] In some particularly preferred embodiments, X1 is alanine and X2 is histamine.

[0045] In some preferred embodiments, R1 is free.

[0046] In some preferred embodiments, n is 0.

[0047] In the most preferred embodiment, 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 calcinin (also called decarboxycarnosine). When this most preferred embodiment is in chloride salt form, the decarboxylated oligopeptide has the INCI name decarboxycarnosine HCl and is commercially available from Exsymol under the trade name Alistin.

[0048] Pyracantha extract The genus Pyracantha is a genus of thorny evergreen shrubs in the rose family, and includes the following seven species: Pyracantha angustifolia, Pyracantha atalantioides, Pyracantha coccinea, Pyracantha crenulate, Pyracantha fortuneana, Pyracantha koidzumii, and Pyracantha rogersiana. All species of the genus Pyracantha produce small white flowers. The fruits of the genus Pyracantha are red, orange, or yellow pome-shaped fruits.

[0049] The cosmetic compositions of this disclosure may contain at least one pyracantha extract. The total weight of the at least one pyracantha extract may be in the range of about 0.00001 to about 1%, preferably about 0.00005 to about 0.1%, more preferably about 0.0001 to about 0.05%, and most preferably about 0.0005 to about 0.01%, based on the total weight of the cosmetic composition. In some preferred embodiments, the cosmetic compositions of this disclosure contain one pyracantha extract.

[0050] In some embodiments, the Pyracantha extracts of the present disclosure may be selected from the group consisting of Pyracantha angustifolia extract, Pyracantha atalantioides extract, Pyracantha coccinea extract, Pyracantha crenulate extract, Pyracantha fortuneana extract, Pyracantha koidzumii extract, Pyracantha rogersiana extract, and mixtures thereof. A preferred Pyracantha extract is Pyracantha fortuneana extract.

[0051] In some embodiments, the pyracantha extracts of the present disclosure may be selected from the group consisting of pyracantha plant extracts, pyracantha fruit extracts, pyracantha flower extracts, pyracantha leaf extracts, pyracantha stem extracts, pyracantha root extracts, and mixtures thereof. A preferred pyracantha extract is pyracantha fruit extract.

[0052] In some embodiments, the Pyracantha extracts of the present disclosure may be selected from the group consisting of 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 extracts are prepared from Pyracantha plant extracts, Pyracantha fruit extracts, Pyracantha flower extracts, Pyracantha leaf extracts, Pyracantha stem extracts, Pyracantha root extracts, or mixtures thereof.

[0053] In some preferred embodiments, the pyracantha extract of this disclosure is pyracantha fortunaneana fruit extract.

[0054] In a more preferred embodiment, the pyracantha fortunaneana fruit extract is prepared by enzymatic hydrolysis. Preferably, the enzymatic hydrolysis is carried out using 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.

[0055] A non-exclusive example of Pyracantha fortunaneana fruit extract is commercially available from Ingredi Biotech under the brand name Wonder Flame.

[0056] Preferably, pyracantha fortuneana fruit extract can be prepared according to the method described in WO2022227286A1 (which is incorporated in whole herein). The preparation method includes the following steps: 1) Enzymatic hydrolysis: Collect pyracantha fruit and perform enzymatic hydrolysis with compound enzymes to obtain an enzymatic hydrolysis mixture; 2) Alcohol extraction: Extract the enzymatic hydrolysis mixture with ethanol, filter, and concentrate to obtain an ethanol extract; 3) Purification with macroporous adsorption resin: Purify the ethanol extract by filling it into a macroporous adsorption resin and collect the analytical solution; and 4) Drying: Concentrate the analytical solution and dry it to obtain a solution. Preferably, in step 1), the compound enzyme for enzymatic hydrolysis includes polygalacturonase, cellulase, and pectinase, the temperature of enzymatic hydrolysis is about 37°C to about 42°C, the time of enzymatic hydrolysis is about 1 hour 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 adsorbent resin is selected from the group consisting of ADS-7, LS-300B, NKA-9, HPD300, HPD600, HPD100, LS46, LS32, LS308, AB-8, LS305, and D101.

[0057] In some preferred embodiments, the weight ratio of at least one decarboxylated oligopeptide to at least one Pyracantha extract may be in the range of 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.

[0058] In some more preferred embodiments, the cosmetic composition of the present disclosure comprises a decarboxylated oligopeptide and a pyracantha extract.

[0059] In some of the most preferred embodiments, the cosmetic composition of the present disclosure comprises calcinin and pyracantha fortunaneana fruit extract.

[0060] In some of the most preferred embodiments, the cosmetic composition of the present disclosure comprises decarboxycarnosine HCl and pyracantha fortunaneana fruit extract.

[0061] In some particularly preferred embodiments, the cosmetic composition of the present disclosure comprises decarboxycarnosine HCl and pyracantha fortuneana fruit extract, wherein the weight ratio of decarboxycarnosine HCl to pyracantha fortuneana fruit extract is in the range of 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.

[0062] Other ingredients: The topical composition may further contain the following ingredients:

[0063] oil Suitable oils include, but are not limited to, silicones, esters, vegetable oils, and synthetic oils, as described herein. The oil may be volatile or non-volatile and is preferably in the form of a liquid that can be injected at room temperature. If present, the oil may be in the range of about 0.5 to about 85% by weight, preferably about 1 to about 75% by weight, and more preferably about 5 to about 65% by weight of the total composition.

[0064] Cyclic and linear volatile silicones are available from a variety of commercial sources, including Dow Chemical Corporation and Momentive (formerly General Electric Silicones). Dow Chemical's linear volatile silicones are marketed under the trade names Dowsil and Xiameter 244, 245, 344, and 200 fluid. 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 taken at 25°C.

[0065] Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone, and branched volatile silicones having the following general formula. [ka]

[0066] Methyltrimethicone, with a viscosity of 1.5 centistokes at 25°C, can be purchased from Shin-Etsu Silicones under the trade name TMF-1.5.

[0067] Various linear or branched 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, are also suitable. Suitable hydrocarbons include pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane, and C 8~20 Isoparaffins are an example. Appropriate C 12 Isoparaffin is manufactured by Permethyl Corporation under the trade name Permethyl 99A. Various types of C are available on the market. 16 Isoparaffins, such as isohexadecane (which has the trade name Permethyl R), are also preferred.

[0068] Esters formed by the reaction of carboxylic acids and alcohols are also preferred. Both the alcohol and the carboxylic acid may 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, and isononyl isononanoate.

[0069] Esters may also exist in the form of dimers or trimers. Examples of such esters include diisostearyl malate, neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, and dioctyl malate.

[0070] Other examples of ester types include trialacidine, tributyl citrate, triisostearyl citrate, and tri-C citrate. 12~13 Examples include alkyl groups, tricaprylin, tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl behenate, and other compounds derived from arachidonic acid, citric acid, or behenate, or tridecyl cocoate and tridecyl isononanoate.

[0071] Synthetic or naturally occurring fatty acid glyceryl esters or triglycerides are also suitable for use in this composition. Both plant and animal sources may be used. Examples of such oils include castor oil, lanolin oil, and C. 10~18Examples include triglycerides, caprylic / capric triglycerides, sweet peach oil, apricot kernel oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, ink oil, olive oil, coconut oil, illipe oil, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil, and walnut oil.

[0072] Furthermore, synthetic or semi-synthetic glyceryl esters of fatty acid monoglycerides, diglycerides, and triglycerides, which are modified natural fats or oils, as well as monoesters, diesters, or triesters of polyols such as glycerin, are also suitable. In one example, fat (C 12~22 Carboxylic acids react with one or more repeating glyceryl groups, glyceryl stearate, diglyceryl diisostearate, 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 oil, PEG glyceryl oleate, PEG glyceryl stearate, PEG glyceryl tauroate, etc.

[0073] Non-volatile silicone oils (both water-soluble and water-insoluble) are also suitable for use in this composition. Such silicones preferably have a viscosity in the range of about 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 dimethicone, phenyl dimethicone, diphenyl dimethicone, phenyl trimethicone, or trimethylsiloxyphenyl dimethicone. Other examples include alkyl dimethicones such as cetyl dimethicone, stearyl dimethicone, and behenyl dimethicone.

[0074] surfactants The composition may contain one or more surfactants, especially when in emulsion form. However, such surfactants can also be used when the composition is anhydrous and help disperse polar components, such as pigments. Such surfactants may be silicone-based or organic. The surfactants assist in the formation of stable emulsions, either water-in-oil or oil-in-water. If present, the surfactant may be in the range of about 0.001 to 30% by weight, preferably about 0.005 to 25% by weight, and more preferably about 0.1 to 20% by weight of the total composition.

[0075] Silicone surfactants can generally be referred to as dimethicone copolyols or alkyldimethicone copolyols. In some cases, the number of repeating ethylene oxide or propylene oxide units in the polymer is also specified; for example, a dimethicone copolyol, also called PEG-15 / PPG-10 dimethicone, refers to a dimethicone having substituents containing 15 ethylene glycol units and 10 propylene glycol units on a siloxane skeleton. It is also possible for one or more of the methyl groups in the above general structure to be substituted with longer-chain alkyl groups (e.g., ethyl, propyl, butyl, etc.) or ether groups (e.g., methyl ether, ethyl ether, propyl ether, butyl ether, etc.).

[0076] Examples of silicone surfactants include those sold by Dow Silicones under the trade names Dowsil 3225C Formulation Aid (containing CTFA names cyclotetrasiloxane and cyclopentasiloxane and PEG / PPG-18 dimethicone), or 5225C Formulation Aid (containing CTFA names cyclopentasiloxane and PEG / PPG-18 / 18 dimethicone), or Dowsil 190 Surfactant (containing CTFA names PEG / PPG-18 / 18 dimethicone), or Dowsil 193 Fluid, Dowsil 5200 (containing CTFA names lauryl PEG / PPG-18 / 18 methicone), or Abil EM 90 (containing CTFA names cetyl PEG / PPG-14 / 14 dimethicone), or Abil EM 90, sold by Goldschmidt. 97 (CTFA name: bis-cetyl PEG / PPG-14 / 14 dimethicone), or Abil WE 09 (CTFA name: cetyl PEG / PPG-10 / 1 dimethicone) in a mixture also containing polyglyceryl-4 isostearate and hexyl laurate, or KF-6011 (CTFA name: PEG-11 methyl ether dimethicone) sold by Shin-Etsu Silicones, KF-6012 (CTFA name: PEG / PPG-20 / 22 butyl ether dimethicone) sold by Shin-Etsu Silicones, or KF-6013 (CTFA name: PEG-9 dimethicone) sold by Shin-Etsu Silicones, or KF-6015 (CTFA name: PEG-3 dimethicone) sold by Shin-Etsu Silicones, or Shin-Etsu KF-6016 (containing PEG-9 methyl ether dimethicone as the CTFA) sold by Silicones, or KF-6017 (containing PEG-10 dimethicone as the CTFA) sold by Shin-Etsu Silicones, or Shin-EtsuThis is KF-6038 (containing the CTFA name lauryl PEG-9 polydimethylsiloxyethyl dimethicone), sold by Silicones.

[0077] Various types of cross-linked silicone surfactants, often called emulsifying elastomers, containing at least one hydrophilic moiety such as a polyoxyalkylene group, are also suitable. Polyoxyalkylene silicone elastomers that may be used in at least one embodiment of this 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 (a dimethicone / PEG-10 / 15 crosspolymer dispersed in dimethicone); KSG-310 (a PEG-15 lauryl dimethicone crosspolymer); KSG-320 (a PEG-15 lauryl dimethicone crosspolymer dispersed in isododecane); KSG-330 (the former dispersed in triethylhexanoin); and KSG-340 (a mixture of PEG-10 lauryl dimethicone crosspolymer and PEG-15 lauryl dimethicone crosspolymer).

[0078] Polyglycerol-modified silicone elastomers, such as those disclosed in International Publication No. 2004 / 024798 (which is incorporated herein by reference in its entirety), are also preferred. Examples of such elastomers include KSG-710, a dimethicone / polyglycerin-3 crosspolymer dispersed in dimethicone, or Shin-Etsu's KSG series, such as lauryl dimethicone / polyglycerin-3 crosspolymers dispersed in various solvents such as isododecane, dimethicone, and triethylhexanoin, sold under Shin-Etsu's trade names KSG-810, KSG-820, KSG-830, or KSG-840. Silicones sold by Dow Silicones under trade names 9010 and DC9011 are also preferred.

[0079] This composition may contain 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 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, formed by the reaction of stearyl alcohol with ethylene oxide and having 2 to 100 ethylene oxide units; beheneth 5-30, formed by the reaction of behenyl alcohol with ethylene oxide and having 5 to 30 repeating ethylene oxide units; ceteareth 2-100, formed by the reaction of a mixture of cetyl alcohol and stearyl alcohol with ethylene oxide and having 2 to 100 repeating ethylene oxide units in the molecule; and ceteth 1-45, formed by the reaction of cetyl alcohol with ethylene oxide and having 1 to 45 repeating ethylene oxide units. All enumeration of units includes all integers within the range.

[0080] Other alkoxylated alcohols are formed by the reaction of fatty acids and monohydric, dihydric, or polyhydric alcohols with alkylene oxides. For example, C 6~30 These are reaction products of polyhydric alcohols, which are fatty carboxylic acids and monosaccharides such as glucose, galactose, and methylglucose, with alkoxylated alcohols. Examples include glyceryl fatty acid esters such as PEG-glyceryl oleate and PEG-glyceryl stearate; or polymer alkylene glycols obtained by reacting with PEG polyhydroxyalkanoates such as PEG-dipolyhydroxystearate, which has a repeating ethylene glycol unit count ranging from 3 to 1000.

[0081] Other suitable nonionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation of sorbitan, particularly ethoxylation, provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters such as polysorbate. For example, polyalkoxylated sorbitan can be esterified with C6-30, preferably C12-22 fatty acids. Examples of such components include polysorbates 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquisoisostearate, sorbitan stearate, and the like.

[0082] Humectant It may also be desirable to include one or more humectants in the composition. When present, such humectants can be in the range of about 0.001-25% by weight, preferably about 0.005-20% by weight, more preferably about 0.1-15% 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 glycols such as PEG4-200 having 4-200 repeating ethylene oxide units, polypropylene glycol, and C 1~6 alkylene glycols such as propylene glycol, butylene glycol, pentylene glycol, and the like. Suitable sugars are also suitable humectants, and some of these sugars are also polyhydric alcohols. Examples of such sugars include glucose, fructose, honey, hydrogenated honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, and the like. Also, urea is suitable. Preferably, the humectant used in the composition of the present disclosure is C 1~6 , preferably C 2~4 alkylene glycol, most specifically butylene glycol.

[0083] Plant extract It may be desirable to include one or more plant extracts in this composition. In that case, the recommended range is about 0.0001 to 10% by weight of the total composition, preferably about 0.0005 to 8% by weight, and more preferably about 0.001 to 5% by weight. Suitable plant extracts include yeast fermentation extract, Padina Pavonica extract, Thermus Thermophilis fermentation extract, Camelina Sativa seed oil, Boswellia Serrata extract, olive extract, Arabidopsis Thaliana extract, Acacia Dealbata extract, and Acer palmatum extract. Examples include extracts from plants (herbs, roots, flowers, fruits, seeds), such as Saccharinum (sugar maple), Acidopholus, Acorus, Aesculus, Agaricus, Agave, Agrimonia, algae, aloe, citrus fruits, Brassica, cinnamon, orange, apple, blueberry, cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea, chamomile, willowbark, mulberry, poppy, and extracts from plants (herbs, roots, flowers, fruits, seeds), including those listed on pages 1646-1660 of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, Volume 2.Further examples, though not limited to them, include licorice (Glycyrrhiza Glabra), black willow (Salix Nigra), giant bladderwort (Macrocycstis Pyrifera), Pyrus Malus, saxifrage (Saxifraga Sarmentosa), European grape (Vitis Vinifera), black mulberry (Morus Nigra), golden flower (Scutellaria Baicalensis), Roman chamomile (Anthemis Nobilis), clary sage (Salvia Sclarea), rosemary (Rosmarinus Officianalis), lemon (Citrus Medica Limonum), ginseng (Panax Ginseng), Japanese fir (Siegesbeckia Orientalis), plum (Fructus Mume), and Ascophyllum nodosum. Nodosum, Bifida Ferment Lysate, Glycine Soja Extract, Sugar Beet (Beta Vulgaris), Haberlea Rhodopensis, Polygonum Cuspidatum, Orange (Citrus Aurantium Dulcis), European Grape (Vitis Vinifera), Selaginella Tamariscina, Hops (Humulus Lupulus), Ponkan Peel (Citrus Reticulata), Pomegranate (Punica Granatum), Asparagopsis, Turmeric (Curcuma Longa), Menyanthes Trifoliata, Sunflower (Helianthus Annuus), Barley (Hordeum Vulgare), Cucumis Examples include Sativus, Evernia Prunastri, Evernia Furfuracea, and mixtures thereof.

[0084] particulate material The compositions of this disclosure may contain particulate materials in the form of pigments, inert particles, or mixtures thereof. If present, the recommended range may be about 0.01 to 75% by weight, preferably about 0.5 to 70% by weight, and more preferably about 0.1 to 65% by weight of the total composition. If the composition may contain a mixture of pigments and powders, a preferred range is about 0.01 to 75% by weight of pigments and 0.1 to 75% by weight of the total composition.

[0085] The particulate matter may be a colored powder or an uncolored powder. Suitable non-colored powders include bismuth oxychloride, titanate mica, fumed silica, spherical silica, polymethyl methacrylate, micronized Teflon (registered trademark), boron nitride, acrylate copolymer, aluminum silicate, aluminum starch octenyl succinate, 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, silylated silica, silk powder, sericite, soy flour, tin oxide, titanium hydroxide, trimagnesium phosphate, walnut shell powder, or mixtures thereof. The above powder may be surface-treated with lecithin, amino acids, mineral oil, silicone, or various other agents, either alone or in combination, thereby coating the powder surface and making the particles more lipophilic.

[0086] Suitable pigments are organic or inorganic. Organic pigments are a variety of aromatic types, including azo, indigoid, triphenylmethane, antroquinone, and xanthine dyes, generally referred to as D&C and FD&C blue, brown, green, orange, red, yellow, etc. Organic pigments generally consist of insoluble metal salts of certified color additives called Lakes. Inorganic pigments include iron oxide, ultramarine, chromium, chromium hydroxide pigments, and mixtures thereof. Iron oxides of red, blue, yellow, brown, black, and mixtures thereof are preferred.

[0087] Vitamins and antioxidants The compositions of this disclosure may contain vitamins and / or coenzymes, as well as antioxidants. In this case, 0.001 to 10% by weight, preferably 0.01 to 8% by weight, and more preferably 0.05 to 5% by weight of the total composition is recommended. Suitable vitamins include ascorbic acid and its derivatives such as ascorbyl palmitate and tetrahexyldecyl ascorbate, B vitamins such as thiamine, riboflavin, and pyridoxine, and coenzymes such as thiamine pyrophosphate, flavin adenine dinucleotide, folic acid, pyridoxal phosphate, and tetrahydrofolic acid. Vitamin E and its derivatives, such as vitamin E acetate, nicotinate, or other esters thereof, are also preferred. In addition, vitamins D and K are preferred.

[0088] This disclosure is further described in relation to the embodiments set out below for illustrative purposes only. [Examples]

[0089] 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); Asian primary keratinocytes (purchased from Lifeline); DermaLife K keratinocyte medium complete kit (purchased from Lifeline); decarboxycarnosine HCl (purchased from Exsymol under the brand name Alistin); pyracantha fortuneana fruit extract (purchased from Ingredi Biotech Co., LTD. under the brand name Wonder Flame).

[0090] Equipment used in this experiment: Operetta CLS High Content Imaging System purchased from PerkinElmer.

[0091] The stock solutions prepared for this experiment—leupeptin and cell culture medium—should be stored at 4°C and used throughout the experiment. Iron(III) chloride solution and hydrogen peroxide solution should be prepared fresh each time they are needed.

[0092] Leupeptin stock solution was prepared by dissolving 5 mg of leupeptin hemisulfate in 10.13 mL of molecular-grade water to create a 1 mM stock solution.

[0093] The iron(III) chloride solution was prepared by dissolving 30.41 mg of FeCl3 in 25 mL of molecular-grade water to make a 7.5 mM stock solution.

[0094] The hydrogen peroxide solution was prepared by dissolving 2.84 μL of 30% H2O2 in 25 mL of molecular-grade water to make a 1 mM stock solution.

[0095] Experimental Procedure [Table 1]

[0096] 1.5x10 4 Individual keratinocytes or fibroblasts were seeded in 12-well plates and left for 24 hours before the culture medium was changed.

[0097] 2. Lipofuscin-producing media were prepared by thoroughly mixing the stock solutions according to Table 1.

[0098] 3. Add 1 mL of lipofuscin-producing medium to each well of the plate.

[0099] 4. The culture medium was changed every 48 hours. Each time, a new lipofuscin-producing medium solution was prepared using the stock solution prepared as described above, according to Table 1. After each medium change, the cells were washed with phosphate-buffered saline (containing calcium and magnesium) to remove residual waste.

[0100] 5. At the beginning of day 6, the target active ingredient was added at the desired concentration.

[0101] 6. The culture medium was continuously replaced every 48 hours with a medium containing the target active ingredient.

[0102] 7. At the end of day 10, the cells were prepared for confocal imaging and their autofluorescence intensity was measured.

[0103] result Raw autofluorescence intensity data were collected in relative fluorescence units (RFU). Control data were collected from control samples prepared with cells in cell culture medium only. Inducement data were collected from induction samples prepared with cells in lipofuscin-producing medium containing no active ingredients. Component data were collected from corresponding component samples prepared with cells in lipofuscin-producing medium containing the corresponding active ingredient or combination of active ingredients. For each data point, the sample was prepared and measured at least three times, and the mean intensity and standard deviation (SD) are shown in Examples 1-4. Here, component a is decarboxycarnosine HCl, and component b is pyracantha fortunaneana fruit extract. The inhibition rate was calculated based on the formula "Inhibition rate = 1 - ((Mean of component sample - Mean of control sample) / (Mean of induction sample - Mean of control sample))". Here, the mean of component sample is the mean autofluorescence intensity of the corresponding component sample, the mean of control sample is the mean autofluorescence intensity of the control sample, and the mean of induction sample is the mean autofluorescence intensity of the induction sample.

[0104] Example 1: Weight ratio of components a and b is 100:1 TIFF2026509594000003.tif58148

[0105] Example 2: Weight ratio of components a and b: 20:1 TIFF2026509594000004.tif58148

[0106] Example 3: Weight ratio of components a and b: 4:1 TIFF2026509594000005.tif58148

[0107] Example 4: Weight ratio of components a and b: 1:1 TIFF2026509594000006.tif58148

[0108] Results analysis The experimental results were evaluated using the isobole method for synergistic effects, as described in the paper titled "Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective" (the full text of which is incorporated herein by reference), published in Medicina 2019, 55(4), 110. According to the isobole method, OE represents the observed effect, and da and db represent the doses of component a and component b, respectively (therefore, OE(da,db) represents the observed effect of the combination of component a at da and component b at db, OE(da) represents the observed effect of component a at da, and OE(db) represents the observed effect of component b at db), and three mathematical equations can be derived.

[0109] OE(da,db) = OE(da) + OE(db) (1) OE(da,db)>OE(da)+OE(db) (2) OE(da,db) <OE(da)+OE(db) (3)

[0110] If the observed effect satisfies equation (1), then the effect of the two components is a simple sum of single effects, the two components do not interact, and therefore there is no synergistic effect.

[0111] If the observed effect satisfies equation (2), the result represents a true synergistic (or enhancing) effect, where the effect of the two components is greater than the simple sum of the effects of the single components.

[0112] If the observed effect satisfies equation (3), the effect of the two components is smaller than the simple sum of the individual effects, and therefore the result represents the opposite effect of the synergistic effect.

[0113] In this particular experiment, OE (Observed Effect) refers to the inhibition rate. The evaluation based on the isobole method is shown in Table 2.

[0114] [Table 2]

[0115] From the data presented, in all examples 1-4, each OE(da,db) is greater than the corresponding OE(da)+OE(db), satisfying equation (2). Therefore, this result indicates a true synergistic (or enhancing) effect, showing that the effect of the two components (a and b) is greater than the simple sum of their individual effects. In summary, the combination of decarboxycarnosine HCl and Pyracantha fortunaneana fruit extract showed an unexpected synergistic effect of preventing or delaying the production and / or accumulation of lipofuscin.

[0116] Other Embodiments While the present invention has been described in relation to preferred embodiments, it is not intended to limit the scope of the invention to the specific forms described herein. Rather, it is intended to encompass alternatives, modifications, and equivalents that may fall within the spirit and scope of the invention as defined in the appended claims. Accordingly, other embodiments, including those readily modifiable by those skilled in the art from this disclosure, are also within the scope of the claims.

Claims

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

2. At least one decarboxylated oligopeptide is given by formula (I): R1-X1-(AA)n-X2-R2 (In the formula, X1 represents the N-terminal amino acid, X2 represents a decarboxylated oligopeptide, AA represents an amino acid or its derivative, and n is 0 or 1. R1 represents the primary amine functional group of X1, which is either free or substituted with a protecting group which can be selected from an acetyl group, a benzoyl group, a tosyl group, or a benzyloxycarbonyl group. If X2 does not contain a carboxyl group, R2 is absent; or if X2 contains a carboxyl group, R2 represents the hydroxyl group of the carboxyl functional group of X2, which is free, or a C1-C20 alkyl chain, or NH ２ It is substituted with a protecting group that can be selected from NHY or NYY groups (where Y represents a C1-C4 alkyl chain). A cosmetic composition according to claim 1, selected from the group consisting of compounds and mixtures thereof.

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

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

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

6. The cosmetic composition according to claim 1, wherein at least one Pyracantha extract is selected from the group consisting of Pyracantha angustifolia extract, Pyracantha atalantioides extract, Pyracantha coccinea extract, Pyracantha crenulate extract, Pyracantha fortuneana extract, Pyracantha koidzumii extract, Pyracantha rogersiana extract, and mixtures thereof.

7. The cosmetic composition according to claim 6, wherein at least one pyracantha extract is selected from the group consisting of 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 at least one Pyracantha extract is present in an amount of about 0.00001% to about 1% of the total weight of the cosmetic composition.

9. A method for treating lipofuscin, comprising topical application of a cosmetic composition containing at least one decarboxylated oligopeptide and at least one pyracantha extract.

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

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