Topical composition for skin containing ergothioneine and dipeptide-1 or derivative thereof and use thereof

Abstract

A composition comprising ergothioneine and dipeptide-1 or a derivative thereof, wherein the composition can effectively reduce the discomforts of redness, swelling, heat, itching, and pain in the skin, inhibit inflammatory responses, and promote barrier repair. Use of said composition as a proopiomelanocortin expression promoter or a β-endorphin generation promoter, and use of ergothioneine as a proopiomelanocortin expression promoter or a β-endorphin promoter. A method for inflammation resisting, soothing, skin barrier repair, wound healing, hair growth promotion, aging resisting, and pain alleviation, and a method for promoting proopiomelanocortin (POMC) expression or β-endorphin generation.

Description

Skin external use composition containing ergothioneine and dipeptide-1 or its derivatives and use thereof Technical Field

[0001] The present application relates to the field of cosmetics, and in particular to a skin external-use composition containing ergothioneine and dipeptide-1 or its derivatives, a use thereof, and the use of ergothioneine. Background Art

[0002] The skin, the largest organ in the human body, covers the entire body and performs multiple functions, including protection, temperature regulation, and sensory perception. Through its abundant sensory nerve endings, it perceives stimuli such as pain, touch, pressure, and temperature, influencing the skin's neuroendocrine system, including the production and transmission of various neurotransmitters and hormones. This influences the function of skin cells, regulates cellular activity, and responds to environmental changes. It participates in skin health and disease processes, ultimately impacting overall homeostasis.

[0003] Proopiomelanocortin (POMC) is a precursor protein that can be cleaved to generate a variety of active peptides and regulate a variety of metabolic processes. Therefore, POMC plays a key regulatory role in skin barrier repair and soothing skin inflammation. Promoting its expression is beneficial to the barrier recovery and health of inflamed skin, sensitive skin, and people with symptoms such as redness, swelling, and itching.

[0004] Beta-endorphin (BETA) is an endogenous peptide produced by POMC cleavage and belongs to the endorphin family. It plays multiple physiological roles in the human body: 1) BETA is a potent analgesic that, by binding to μ-opioid receptors in the skin, induces fibroblast proliferation and capillary growth, thereby promoting skin tissue regeneration and barrier repair; 2) BETA may affect blood flow to the skin, thereby affecting temperature regulation and other functions; 3) After binding to receptors, BETA inhibits the binding of α-MSH and MC1-R, thereby promoting the expression of the anti-inflammatory cytokine IL-10 and inhibiting the expression of TNF-α, achieving anti-inflammatory effects.

[0005] Summary of the Invention

[0006] After in-depth research, the inventors of the present application unexpectedly discovered that ergothioneine or dipeptide-1 or its derivatives all have the effect of promoting POMC expression and promoting β-endorphin synthesis. By using ergothioneine and dipeptide-1 or its derivatives in combination, the effect of promoting POMC and β-endorphin expression can be significantly improved, thereby completing the present invention.

[0007] The specific technical solutions of this application are as follows:

[0008] 1. A composition for external use on skin, comprising: ergothioneine, and dipeptide-1 or a derivative thereof.

[0009] 2. The composition according to claim 1, wherein the mass ratio of ergothioneine to dipeptide-1 or its derivative is (1 to 30):1.

[0010] 3. The composition according to claim 1, wherein the mass ratio of ergothioneine to dipeptide-1 or its derivative is (5 to 25):1.

[0011] 4. The composition according to any one of items 1 to 3, wherein the dipeptide-1 derivative is acetyl dipeptide-1 cetyl ester.

[0012] 5. Use of the composition according to any one of items 1 to 4 as a proopiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

[0013] 6. The use according to item 5, wherein the composition is used for anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0014] 7. Use of ergothioneine as a pro-opiomelanocortin (POMC) expression promoter or β-endorphin production promoter.

[0015] 8. The method according to claim 7, wherein the ergothioneine is used for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0016] 9. A method for anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief, comprising administering an effective amount of the composition of any one of items 1 to 4 to a subject in need thereof.

[0017] 10. A method for promoting proopiomelanocortin (POMC) expression or β-endorphin production, comprising administering an effective amount of the composition according to any one of items 1 to 4 to a subject in need thereof.

[0018] 11. A method for promoting pro-opiomelanocortin (POMC) expression or β-endorphin production, comprising administering an effective amount of ergothioneine to a subject in need thereof.

[0019] Effects of the Invention

[0020] Ergothioneine or dipeptide-1 or their derivatives all have the effect of promoting POMC expression and promoting β-endorphin synthesis, which expands the application scope of the above substances.

[0021] Further combining the two in a certain proportion can significantly promote the expression of POMC and the synthesis of β-endorphin, which not only reduces production costs but also enables the ingredients to fully exert their efficacy. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG1 is a histogram of POMC gene expression of the test samples of various examples and comparative examples of the present application.

[0023] FIG2 is a bar graph showing the β-endorphin content of the test samples of various examples and comparative examples of the present application. DETAILED DESCRIPTION

[0024] The present application is described in detail below in conjunction with specific embodiments. It should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided in order to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art. It should be noted that "including" or "comprising" as mentioned throughout the specification and claims are open-ended terms and should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present invention, but the description is for the purpose of illustrating the general principles of the present application and is not intended to limit the scope of the present application. The scope of protection of the present application shall be as defined by the appended claims.

[0025] In one aspect, the present application provides a composition comprising: ergothioneine, and dipeptide-1 or a derivative thereof.

[0026] The above-mentioned "composition" of the present application is sufficient as long as it can achieve the effects described in the present application. The "composition" includes but is not limited to the simultaneous or sequential use of the components. The "simultaneous use" includes use together in the same preparation or separately in different preparations. The "sequential use" includes use in sequence in different preparations, and there is no limitation on the order of sequential use.

[0027] Ergothioneine is a naturally occurring amino acid derivative with a structure shown in Formula 1. It has diverse physiological effects in the human body and is gaining increasing attention in dermatology. It is considered a powerful antioxidant.

[0028] Dipeptides are the simplest peptides, protein fragments or substances composed of an amide bond (i.e., -CO-NH-) formed by the dehydration condensation of the α-carboxyl group of one amino acid and the α-amino group of another amino acid. Their molecules contain only one peptide bond. They are a general term for a large class of substances.

[0029] In some embodiments, the mass ratio of the ergothioneine to the dipeptide-1 or its derivative is (1-30):1, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, etc., preferably (5-25):1. By controlling the mass ratio of ergothioneine to the dipeptide-1 or its derivatives within the above range, the efficacy in promoting the expression of proopiomelanocortin (POMC) or the production of β-endorphin can be further enhanced, thereby further enhancing the efficacy in anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, pain relief, etc.

[0030] In some embodiments, the dipeptide-1 is a dipeptide formed by dehydration condensation of tyrosine and arginine.

[0031] In some embodiments, the dipeptide-1 is a dipeptide formed by dehydration condensation of L-tyrosine and L-arginine.

[0032] In some embodiments, the dipeptide-1 is L-tyrosyl-L-arginine.

[0033] Dipeptide-1 (D-1), also known as Kyotomorphin, is a bioactive peptide that is often used in the formulation of skin care products. Its structure is shown in Formula 2.

[0034] In some embodiments, the dipeptide-1 derivative is acetyl dipeptide-1 cetyl ester (AD-1), having the molecular formula C 33 H 57 N5O5, molecular weight 603.84. Acetyl Dipeptide-1 Cetyl Ester is a laboratory-engineered synthetic peptide that combines acetic acid and cetyl alcohol with dipeptide-1, composed of arginine and tyrosine. It can promote skin firming and has the same biological efficacy as natural peptides, which helps to enhance skin elasticity.

[0035] On the other hand, the present application also provides use of the composition as a pro-opiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

[0036] In some embodiments, the composition is used in anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, pain relief, etc.

[0037] In yet another aspect, the present application also provides the use of ergothioneine as a pro-opiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

[0038] In some embodiments, the ergothioneine is used for anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0039] The present application also provides the use of ergothioneine in preparing medicines for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0040] The present application also provides the use of ergothioneine in preparing cosmetics for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, and anti-aging effects.

[0041] In another aspect, the present application also provides the use of dipeptide-1 or its derivatives as a pro-opiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

[0042] In some embodiments, the dipeptide-1 or its derivatives are used in anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0043] The present application also provides the use of dipeptide-1 or its derivatives in the preparation of drugs for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief.

[0044] The present application also provides the use of dipeptide-1 or its derivatives in the preparation of cosmetics for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, and anti-aging effects.

[0045] In some embodiments, the dipeptide-1 is a dipeptide formed by dehydration condensation of tyrosine and arginine.

[0046] In some embodiments, the dipeptide-1 is a dipeptide formed by dehydration condensation of L-tyrosine and L-arginine.

[0047] In some embodiments, the dipeptide-1 is L-tyrosyl-L-arginine.

[0048] In some embodiments, the dipeptide-1 derivative is acetyl dipeptide-1 cetyl ester.

[0049] Ergothioneine, dipeptide-1 or its derivatives can all promote POMC expression and β-endorphin synthesis. The combination of ergothioneine and dipeptide-1 or its derivatives can further promote POMC expression and β-endorphin synthesis, achieving anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief effects. The combination of the two has a synergistic effect.

[0050] The present application also provides a method for anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief, which comprises administering an effective amount of any of the aforementioned compositions comprising ergothioneine and dipeptide-1 or its derivatives to a subject in need.

[0051] The present application also provides a method for promoting proopiomelanocortin (POMC) expression or β-endorphin production, comprising administering an effective amount of any of the aforementioned compositions comprising ergothioneine and dipeptide-1 or a derivative thereof to a subject in need thereof.

[0052] The present application also provides a method for promoting pro-opiomelanocortin (POMC) expression or β-endorphin production, comprising administering an effective amount of ergothioneine to a subject in need thereof.

[0053] In some embodiments, the administering comprises topical administration.

[0054] In some embodiments, the administering comprises administering to a subject's skin, scalp, hair, eyelashes, nails, or the like.

[0055] As used herein, the term "subject in need thereof" refers to an individual in need of achieving a desired (eg, beneficial) effect, and the individual can be treated or improved by the composition described herein.

[0056] The term "effective amount" or "effective dose" as used herein refers to an amount of the composition sufficient to achieve a desired (e.g., beneficial) effect in a subject receiving the composition, such as an amount sufficient to improve one or more symptoms of the subject in a statistically significant manner, to delay the worsening of progressive symptoms in a statistically significant manner, or to prevent the onset of other related symptoms in a statistically significant manner, or any combination thereof. An effective amount or dose can be administered once or multiple times within a given time period. The effective amount or dose can depend on the purpose of administration, and can be determined by one skilled in the art based on the needs of the subject. When referring to a single active ingredient administered alone, the effective amount or dose refers to that single ingredient. When referring to a combination, the effective amount or dose refers to the combined amount of the active ingredients that produce the desired effect, whether administered continuously or simultaneously.

[0057] Example

[0058] This application provides a general and / or specific description of the materials and experimental methods used in the experiments. In the following examples, the sources of some materials and reagents are shown in Table 1 below. The reagents or instruments used without indicating the manufacturer are all conventional reagents or instruments that can be purchased commercially.

[0059] Table 1

[0060] Example 1

[0061] Prepare complete culture medium solution: mix DMEM basal culture medium, FBS fetal bovine serum, and PS double antibody solution in a mass ratio of 89:10:1;

[0062] Prepare the test sample solution: weigh 0.036 g of EGT and dissolve it in the complete culture medium solution to prepare an EGT working solution, wherein the EGT content is 60 μg / mL.

[0063] Example 2

[0064] The difference between this embodiment and embodiment 1 is that, in preparing the test sample solution, 0.036 g of D-1 was weighed and prepared into a D-1 working solution with a complete culture medium solution, wherein the content of D-1 was 60 μg / mL.

[0065] Example 3

[0066] The difference between this embodiment and embodiment 1 is that, in preparing the test sample solution, 0.036 g of AD-1 was weighed and prepared into an AD-1 working solution with a complete culture medium solution, wherein the content of AD-1 was 60 μg / mL.

[0067] Example 4

[0068] The difference between this embodiment and Example 1 is that in the preparation of the test sample solution, EGT and D-1 at a mass ratio of 20:1 are dissolved in a complete culture medium solution to prepare a working solution of EGT and D-1, wherein the content of EGT is 57.14 μg / mL and the content of D-1 is 2.86 μg / mL.

[0069] Example 5

[0070] The difference between this embodiment and Example 1 is that in the preparation of the test sample solution, EGT and D-1 at a mass ratio of 9:1 are dissolved in a complete culture medium solution to prepare a working solution of EGT and D-1, wherein the content of EGT is 54 μg / mL and the content of D-1 is 6 μg / mL.

[0071] Example 6

[0072] The difference between this embodiment and Example 1 is that in the preparation of the test sample solution, EGT and D-1 at a mass ratio of 1:1 are dissolved in a complete culture medium solution to prepare a working solution of EGT and D-1, wherein the content of EGT is 30 μg / mL and the content of D-1 is 30 μg / mL.

[0073] Example 7

[0074] The difference between this embodiment and embodiment 4 is that in the preparation of the test sample solution, D-1 is replaced by AD-1.

[0075] Example 8

[0076] The difference between this embodiment and embodiment 5 is that in the preparation of the test sample solution, D-1 is replaced by AD-1.

[0077] Example 9

[0078] The difference between this example and Example 5 is that EGT, D-1, and trehalose at a mass ratio of 9:1:1 are dissolved in a complete culture medium solution to prepare a working solution of EGT, D-1, and trehalose, wherein the content of EGT is 54 μg / mL, the content of D-1 is 6 μg / mL, and the content of trehalose is 6 μg / mL.

[0079] Comparative Example 1

[0080] The difference between this comparative example and Example 1 is that in the preparation of the test sample solution, EGT and D-1 at a mass ratio of 40:1 were dissolved in a complete culture medium solution to prepare a working solution of EGT and D-1, wherein the content of EGT was 58.54 μg / mL and the content of D-1 was 1.46 μg / mL.

[0081] Comparative Example 2

[0082] The difference between this comparative example and Example 1 is that in the preparation of the test sample solution, EGT and D-1 at a mass ratio of 1:9 were dissolved in a complete culture medium solution to prepare a working solution of EGT and D-1, wherein the content of EGT was 6 μg / mL and the content of D-1 was 54 μg / mL.

[0083] Comparative Example 3

[0084] The difference between this comparative example and Example 1 is that in the preparation of the test sample solution, 0.036 g of carnosine was weighed and prepared into a carnosine working solution with a complete culture medium solution, wherein the content of carnosine was 60 μg / mL.

[0085] Comparative Example 4

[0086] The difference between this comparative example and Example 1 is that in the preparation of the test sample solution, EGT and carnosine at a mass ratio of 9:1 were dissolved in a complete culture medium solution to prepare a working solution of EGT and carnosine, wherein the content of EGT was 54 μg / mL and the content of carnosine was 6 μg / mL.

[0087] Test Case

[0088] The test sample solutions of the above-mentioned embodiments and comparative examples were subjected to cytological tests according to the following method.

[0089] Test Example 1. Cell-based test method for relative expression of POMC gene

[0090] 1) Cell seeding: 6×10 5 Keratinocytes were seeded into 6-well plates at a seeding density of 100 cells / well and incubated in an incubator (37°C, 5% CO2) (Thermo, 3111) for 24 h;

[0091] 2) Solution preparation: Prepare the working solution of the test substance according to the test plan (Table 2);

[0092] 3) Dosing: Dosing was performed according to the test protocol in Table 2. Complete medium containing the test substance working solution was added to the sample group wells, and complete medium was added to the blank control group (BC). 1 mL of sample was added to each well, and three replicates were set up for each group. After dosing, the 6-well plates were placed in an incubator (37°C, 5% CO2) and incubated for 24 hours.

[0093] 4) Cell collection: After 24 h of culture, collect the cell supernatant, wash twice with 1 mL / well D'Hanks buffer, lyse the cells by pipetting, and collect the sample;

[0094] 5) Gene expression detection: After the cells were treated with RNA-Quick Purification Kit, samples were collected and RNA extraction, reverse transcription and fluorescence quantitative PCR were performed using a fluorescence quantitative PCR instrument (BioRad, CFX Connect) according to the kit instructions. Methods are used to calculate the results and obtain the test results;

[0095] 6) Statistical analysis of results: t-test statistical analysis was used for comparison between groups with a confidence level of 95%.

[0096] Use letters to indicate the difference between the results. There is no significant difference between two groups of results with the same letters, such as a vs a, or a vs ab; there is a significant difference between two groups of results with completely different letters, such as a vs b.

[0097] Test Example 2. β-Endorphin-Expressing Cell Test Method

[0098] 1) Cell seeding: 3×10 5 Keratinocytes were seeded into 12-well plates at a seeding density of 100 cells / well and incubated in an incubator (37°C, 5% CO2) for 24 h;

[0099] 2) Solution preparation: Prepare the working solution of the test substance according to the test plan (Table 2);

[0100] 3) Dosing: Dosing was performed according to the test protocol in Table 2. Complete medium containing the test substance working solution was added to the sample group wells, and complete medium was added to the blank control group (BC). 1 mL of sample was added to each well, and three replicates were set up for each group. After dosing, the 6-well plates were placed in an incubator (37°C, 5% CO2) and incubated for 24 hours.

[0101] 4) Cell collection: After 24 h of culture, the cell supernatant was collected and gently washed twice with 1 mL / well PBS buffer. The cells were then trypsinized and centrifuged at 1000 × g for 5 minutes. The cells were then disrupted by repeated freeze-thaw cycles and centrifuged at 1500 × g for 10 minutes. The supernatant was collected for analysis.

[0102] 5) Protein expression detection: According to the kit instructions, the optical density (OD value) of each well was measured at a wavelength of 450 nm using a microplate reader, and the precise concentration of endorphin in each group was calculated;

[0103] 6) Statistical analysis of results: t-test statistical analysis was used for comparison among groups with a confidence level of 95%.

[0104] Use letters to indicate the difference between the results. There is no significant difference between two groups of results with the same letters, such as a vs a, or a vs ab; there is a significant difference between two groups of results with completely different letters, such as a vs b.

[0105] The experimental parameters and test results of each embodiment and comparative example are listed in Table 2 below.

[0106] Table 2

[0107] As can be seen from Table 2 above, ergothioneine, dipeptide-1 or its derivatives can promote POMC expression and promote β-endorphin synthesis when used separately. The combination of ergothioneine and dipeptide-1 or its derivatives in a certain mass ratio can further promote POMC expression and β-endorphin synthesis, achieving anti-inflammatory, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging, and pain relief effects.

[0108] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application in any other manner. Any person skilled in the art may utilize the above disclosed technical content to modify or modify the present application into equivalent embodiments with equivalent variations. However, any simple modifications, equivalent variations, and modifications to the above embodiments that do not depart from the technical content of the present application and are based on the technical essence of the present application shall still fall within the scope of protection of the present application.

Claims

1. A composition for external use on skin, wherein: It includes: Ergothioneine, and dipeptide-1 or its derivatives.

2. The composition according to claim 1, wherein The mass ratio of the ergothioneine to the dipeptide-1 or its derivative is (1-30):

1.

3. The composition according to claim 1, wherein The mass ratio of the ergothioneine to the dipeptide-1 or its derivative is (5-25):

1.

4. The composition according to any one of claims 1 to 3, wherein The dipeptide-1 derivative is acetyl dipeptide-1 cetyl ester.

5. Use of the composition according to any one of claims 1 to 4 as a pro-opiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

6. The use according to claim 5, wherein The composition is used in anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging and pain relief.

7. Use of ergothioneine as a pro-opiomelanocortin (POMC) expression promoter or a β-endorphin production promoter.

8. The use according to claim 7, wherein The ergothioneine is used in anti-inflammation, soothing, skin barrier repair, wound healing, hair growth promotion, anti-aging and pain relief.

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