Composition, preparation method and application thereof

Abstract

The present invention provides a composition, including one of carnosine or caffeine and a compound of formula (I); the mass ratio of one of carnosine or caffeine and the compound of formula (I) is 1:5 to 2:1. The present inventors can reduce the content of inflammatory factors IL-6 and TNF-ɑ by selecting the above-mentioned specific components in combination with a specific ratio, have a soothing effect, and can solve the problem of facial inflammation in sensitive people. The above-mentioned composition of the present invention also has an antioxidant effect, can protect the skin, and alleviate the damage caused by the external environment.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a composition, a preparation method and application thereof. Background Art

[0002] In recent years, the demand for multifunctional skin care ingredients in the cosmetics field has grown significantly. As lifestyles and environmental conditions change, factors such as air pollution, ultraviolet radiation and psychological stress have an increasingly significant impact on skin health. These external stresses often lead to impaired skin barrier function, increased inflammation, increased sensitivity and premature aging. Therefore, the development of active compounds with both soothing and antioxidant effects has become an important topic in skin care research.

[0003] The inflammatory response of the skin is usually closely related to the damage of the barrier function and the abnormal expression of inflammatory factors caused by external stimuli, which manifests as sensitive symptoms such as redness, tingling, and itching. At the same time, oxidative stress is one of the important mechanisms of skin aging. Excessive free radicals produced by the environment and endogenous metabolism can damage cell membranes, proteins, and DNA, thereby accelerating skin aging. For this reason, exploring molecules that can simultaneously relieve inflammatory responses and scavenge free radicals has important theoretical significance and practical value.

[0004] Current studies have shown that plant extracts (such as chamomile, licorice and green tea extracts) and classic antioxidants (such as vitamin C, coenzyme Q10) can relieve skin inflammation and anti-oxidation to a certain extent. However, these active substances have certain limitations in application. For example, the content of active ingredients in plant extracts may fluctuate due to the source of raw materials and extraction process, and vitamin antioxidants may degrade under certain environmental conditions. Therefore, finding compounds with a clear mechanism of action and suitable for actual cosmetic formulations has become a key goal of current research. Summary of the invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide a composition, which has the technical effects of soothing, anti-oxidation and anti-inflammatory.

[0006] This patent involves a new type of compound with dual functions of soothing and anti-oxidation. It shows the potential to reduce skin sensitivity and inhibit oxidative damage by regulating skin inflammatory pathways and effectively scavenging free radicals.

[0007] The invention provides a composition, comprising one of carnosine or caffeine and a compound of formula (I); the mass ratio of the one of carnosine or caffeine to the compound of formula (I) is 1:5-2:1.

[0008]

[0009] Wherein, R1 is selected from H, CH3, or -CH2CH3; preferably, R1 is selected from H or CH3;

[0010] R2 is selected from H, CH3, or -CH2CH3; preferably, R2 is selected from H or CH3;

[0011] R3 is selected from H, CH3, or -CH2CH3; preferably, R2 is selected from H or CH3;

[0012] In some preferred embodiments of the present invention, the compound of formula (I) specifically includes the following structure:

[0013]

[0014] According to the present invention, the mass ratio of one of the carnosine or caffeine to the compound of formula (I) is 1:5 to 2:1.

[0015] According to the present invention, the mass ratio of one of the carnosine or caffeine to the compound of formula (I) is 1:2 to 2:1.

[0016] In some specific embodiments, the mass ratio of one of carnosine or caffeine to the compound of formula (I) is 1:5, 1:1, 1:2 or 2:1; or a ratio range between any two of the above.

[0017] In some specific embodiments, the mass ratio of one of the carnosine or caffeine to the compound of formula (I) is 1:1.

[0018] In some specific embodiments, the amount of carnosine or caffeine added is 1000 μg / mL; and the amount of the compound of formula (I) added is 1000 μg / mL.

[0019] The compound of the above-mentioned formula (I) structure can be specifically one or more of formula I-1-1, formula I-2-1, formula I-2-2, formula I-2-3 or formula I-2-4.

[0020] The present invention creatively discovered that the series of compounds have antioxidant and soothing effects and can be used in the field of cosmetics. In addition, the series of compounds can be used in combination with carnosine to have a synergistic effect; the series of compounds can be used in combination with caffeine to have a synergistic effect.

[0021] The present invention also provides the use of any one of the above-mentioned compositions in the preparation of soothing, anti-oxidation and anti-inflammatory products.

[0022] The present invention provides the use of any one of the above-mentioned compositions in the preparation of a soothing product. The soothing includes relieving pain, relieving redness and / or brightening.

[0023] The present inventors have found that the compound of formula (I) and carnosine have a soothing effect; the compound of formula (I) and caffeine have a soothing effect.

[0024] The present invention provides the use of any one of the above-mentioned compositions in the preparation of antioxidant products. The antioxidant includes scavenging PTIO free radicals and DPPH free radicals.

[0025] The inventors have found that the compound of formula (I) and carnosine have a synergistic antioxidant effect; the compound of formula (I) and caffeine have a synergistic antioxidant effect.

[0026] The present invention provides the use of any one of the above-mentioned compositions in the preparation of anti-inflammatory products. The anti-inflammatory effect includes reducing the levels of inflammatory factors IL-6 and TNF-ɑ.

[0027] The inventors have found that the compound of formula (I) and carnosine have a synergistic anti-inflammatory effect; the compound of formula (I) and caffeine have a synergistic anti-inflammatory effect.

[0028] The present invention provides a soothing, anti-oxidation and anti-inflammatory product, the raw materials of which include the composition described in any one of the above technical solutions.

[0029] The specific components or proportions of the above-mentioned composition have been clearly described in the present invention and will not be repeated here.

[0030] In some preferred embodiments of the present invention, the product is a cosmetic. The present invention also includes conventional auxiliary materials in the cosmetic field, which are not limited thereto.

[0031] The dosage form of the cosmetic is liquid, lotion, emulsion, powder or cream.

[0032] The skin-friendly cleansing cosmetics of the present invention include, but are not limited to, facial cleansers, makeup remover water (milk), cleansing cream (honey), facial masks, floral water, itching powder, talcum powder or bath lotion; the skin-friendly care cosmetics include skin care creams, lotions or toners.

[0033] The present invention provides a soothing, anti-oxidation and anti-inflammatory emulsion, comprising the following raw materials in parts by weight:

[0034]

[0035]

[0036] When the total amount is 100 parts, the above parts by weight are equivalent to mass percentage.

[0037] The compound of the structure of formula (I) described in the present invention can specifically be one or more of formula I-1-1, formula I-2-1, formula I-2-2, formula I-2-3 or formula I-2-4; the mass ratio of formula I-1-1, formula I-2-1, formula I-2-2, formula I-2-3 or formula I-2-4 is 1:1:1:1:1.

[0038] The compound of the formula (I) of the present invention has been clearly described above and will not be repeated here.

[0039] In a preferred embodiment of the present invention, the following raw materials are included in parts by weight:

[0040]

[0041] In the above emulsion of the present invention, sodium hyaluronate has a moisturizing effect and can enhance the skin barrier function; panthenol can repair damaged skin and enhance the soothing effect. Glycerin is a moisturizer that can prevent water loss; β-glucan is an antioxidant that can reduce irritation. Betaine is a moisturizer that can improve skin softness. Caprylyl glycol is a preservative that can increase the stability of the formula.

[0042] The present invention also provides a method for preparing the soothing, anti-oxidation and anti-inflammatory product according to any one of the above technical solutions, comprising the following steps:

[0043] Water, glycerin, panthenol, betaine and sodium hyaluronate are mixed and heated to dissolve, and then β-glucan is added. After cooling to room temperature, a compound having a structure of formula (I), carnosine or caffeine is added. After stirring, caprylyl glycol is added, and the pH value is adjusted to 5.5-6.0.

[0044] In some preferred embodiments of the present invention,

[0045] Add the water in the formula and begin stirring. Add glycerin, panthenol, betaine and sodium hyaluronate in order, ensuring complete dissolution. Heat the solution to 45°C to promote dissolution and homogeneity. Slowly add beta-glucan and maintain low speed stirring. When the solution temperature drops to room temperature (about 25°C), slowly add the above compounds and stir evenly. Add caprylyl glycol as a preservative and ensure that the formula is evenly distributed. Adjust the final pH value to between 5.5 and 6.0 to meet the skin's suitable range.

[0046] The method of using the emulsion of the present invention is: after cleansing the face in the morning and evening, use the soothing, anti-sugar and brightening emulsion of the present invention on the entire face; the frequency of use can be selected as 2 times / d.

[0047] The present invention provides a composition, comprising one of carnosine or caffeine and a compound of formula (I); the mass ratio of one of carnosine or caffeine to the compound of formula (I) is 1:5 to 2:1. The present inventors can reduce the content of inflammatory factors IL-6 and TNF-ɑ by selecting the above-mentioned specific components in combination with a specific ratio, have a soothing effect, and can solve the problem of facial inflammation in sensitive people. The above-mentioned composition of the present invention also has an antioxidant effect, can protect the skin, and alleviate the damage caused by the external environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 Effects of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 on the inflammatory factor IL-6;

[0049] Figure 2 Effects of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 on the inflammatory factor TNF-ɑ;

[0050] Figure 3 The ability of formula I-1-1, formula I-2-1, formula I-2-2, formula I-2-3, and formula I-2-4 to scavenge PTIO free radicals;

[0051] Figure 4 Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 have the ability to scavenge DPPH free radicals. DETAILED DESCRIPTION

[0052] The present invention provides a composition and a preparation method and application thereof. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and they all fall within the scope of protection of the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0053] It should be understood that the expression "one or more of..." includes each of the items recited after the expression individually and in various different combinations of two or more of the recited items, unless otherwise understood from the context and usage. The expression "and / or" in combination with three or more recited items should be understood to have the same meaning, unless otherwise understood from the context.

[0054] The use of the terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, for example not excluding other unrecited elements or steps, unless otherwise specifically stated or otherwise understood from the context.

[0055] In this application, the term "and / or" describes the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural.

[0056] In this application, "at least one" means one or more, "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0057] It should be understood that the order of steps or the order in which certain actions are performed is not important as long as the present invention remains operable. In addition, two or more steps or actions may be performed simultaneously.

[0058] The use of any and all examples or exemplary language, such as "for example" or "including", herein is intended only to better illustrate the invention and does not limit the scope of the invention unless otherwise claimed. No language in this specification should be construed as indicating that any non-claimed element is essential to the practice of the invention.

[0059] In addition, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all ranges, quantities, values ​​and percentages used in this disclosure are modified by "about". Here, "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range.

[0060] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0061] Some cases are recorded in the embodiments and comparative examples of the present invention, wherein the embodiments show certain implementation modes of the present invention. However, this does not mean that the effects of the present invention can only be achieved in these cases.

[0062] In order to further illustrate the present invention, a composition provided by the present invention and its preparation method and application are described in detail below in conjunction with embodiments.

[0063] The structures involved in the embodiments of the present invention are shown in Table 1:

[0064] Table 1: Basic information of Thiohistidine

[0065]

[0066]

[0067] Among them, mouse macrophages (RAW264.7) were from Wuhan Pronocell Life Science Co., Ltd.; lipopolysaccharide (LPS) was from Beijing Solebow Technology Co., Ltd.; RAW264.7 special culture medium was from Wuhan Pronocell Life Science Co., Ltd.; mouse tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit was from Wuhan Elerite Biotechnology Co., Ltd.; mouse interleukin 6 (IL-6) enzyme-linked immunosorbent assay kit was from Wuhan Elerite Biotechnology Co., Ltd.; DPPH reagent was from Beijing Solebow Technology Co., Ltd.; PTIO reagent was from Merck KGaA, Darmstadt, Germany.

[0068] Example 1

[0069] This compound has anti-inflammatory effects and can reduce the levels of inflammatory factors IL-6 and TNF-ɑ.

[0070] Experimental process: 2 million RAW264.7 cells (P7) were plated in each well of a 6-well plate. After 24 hours, 2 mL of dexamethasone (DEX, 100 μg / mL), Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 were added, with three replicates in each group. After 1.5 hours, 2 μL of 1000 μg / mL LPS was added except for the Control group. Continue to culture for 24 hours, collect the supernatant, centrifuge, take the supernatant, dilute 200 times for TNF-α experiment and 50 times for IL-6 experiment, and then use the mouse tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit and mouse interleukin 6 (IL-6) enzyme-linked immunosorbent assay kit to detect the concentrations of inflammatory factors TNF-α and IL-6, respectively. Within 15 minutes after adding the stop solution, detect its absorbance at 450 nm. The specific groups are shown in Table 2 below:

[0071] Table 2: Anti-inflammatory experimental groups

[0072]

[0073]

[0074] Experimental results:

[0075] Lipopolysaccharide (LPS) can promote inflammation, produce a large number of inflammatory factors and promote the expression of related inflammatory proteins. LPS is often used to activate mouse leukemia macrophages (RAW264.7) as a cell inflammation model. Figure 1 As shown: Compared with the negative control group, the IL-6 contents of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 groups were reduced by 27.70%, 28.05%, 28.74%, 19.58%, and 16.48%, respectively, and all were significant and statistically significant (P<0.05 was considered statistically significant, "*," P<0.05; "**," P<0.01; "****," P<0.0001).

[0076] Table 3: Effects of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 on IL-6

[0077]

[0078] As shown in Table 4 and Figure 2 As shown: the TNF-ɑ content of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 groups decreased by 41.29%, 38.01%, 33.23%, 26%, and 15.09%, respectively, and all were significant and statistically significant (P<0.05 was considered statistically significant, "**," P<0.01; "****," P<0.0001)

[0079] Table 4: Effects of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, and Formula I-2-4 on TNF-ɑ

[0080]

[0081] Embodiment 2:

[0082] This compound has antioxidant effects and can scavenge PTIO and DPPH free radicals.

[0083] Experimental process:

[0084] Take 140 μL of PTIO aqueous solution (22.5 mg / mL) and 140 μL of sample solution (ergothioneine, 10000 ppm, compound formula I-1-1, 10000 ppm, formula I-2-1, 10000 ppm, formula I-2-2, 10000 ppm, formula I-2-3, 10000 ppm, formula I-2-4, 10000 ppm) in a 96-well plate, react in the dark for 30 minutes, and detect its absorbance at 557 nm. Ergothioneine is the positive control group, and each group has 5 replicates.

[0085] Experimental results:

[0086] As shown in Table 5 and Figure 3 As shown: Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, Formula I-2-4 can remove 66.05%, 73.76%, 62.94%, 25.15%, and 52.59% of PTIO free radicals, and all are significant and statistically significant. (P<0.05 is considered statistically significant, "***," P<0.001; "****," P<0.0001).

[0087] Table 5: Ability of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, Formula I-2-4 to scavenge PTIO free radicals

[0088]

[0089] Experimental process:

[0090] 140 μL of DPPH ethanol solution (0.12 mg / mL) and 140 μL of sample solution (ergothioneine, 10000 ppm; Formula I-1-1, 10000 ppm, Formula I-2-1, 10000 ppm, Formula I-2-2, 10000 ppm, Formula I-2-3, 10000 ppm, Formula I-2-4, 10000 ppm) were placed in a 96-well plate, reacted in the dark for 30 minutes, and the absorbance was detected at 517 nm. Ergothioneine was used as the positive control group.

[0091] Experimental results:

[0092] like Figure 4 As shown: Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, Formula I-2-4 can remove 62.27%, 72.86%, 60.32%, 29.25%, 41.98% of DPPH free radicals, and all are significant and statistically significant. (P<0.05 is considered statistically significant, "****," P<0.0001).

[0093] Table 6: Ability of Formula I-1-1, Formula I-2-1, Formula I-2-2, Formula I-2-3, Formula I-2-4 to scavenge DPPH free radicals

[0094]

[0095]

[0096] Example 3: Formula I-1-1 and carnosine have a synergistic effect; Formula I-1-1 and caffeine have a synergistic effect.

[0097] Experimental steps: 2 million RAW264.7 cells (P7) were plated in each well of a 6-well plate. After 24 hours, 2 mL of the positive control sample (100 μg / mL dexamethasone) or the experimental group 1 sample (1000 μg / mL of Formula I-1-1) or the experimental group 2 sample (1000 μg / mL carnosine) or the experimental group 3 sample (1000 μg / mL caffeine) or the experimental group 4 sample (1000 μg / mL of Formula I-1-1 + 1000 μg / mL carnosine) or the experimental group 5 sample (1000 μg / mL of Formula I-1-1 + 1000 μg / mL caffeine) or the experimental group 6 sample (1000 μg / mL carnosine + 1000 μg / mL caffeine) was added. After 1.5 hours, 2 μL of 1000 μg / mL LPS was added except for the Control group. Continue to culture for 24 hours, collect the supernatant, centrifuge, take the supernatant, dilute 200 times for TNF-α experiment and 50 times for IL-6 experiment, then use mouse tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit and mouse interleukin 6 (IL-6) enzyme-linked immunosorbent assay kit to detect the concentrations of inflammatory factors TNF-α and IL-6, respectively, add the stop solution within 15 minutes, and detect the absorbance at 450 nm (three replicate wells for each group).

[0098] Experimental results: As shown in Tables 7 and 8: Formula I-1-1 can significantly inhibit the protein levels of IL-6 and TNF-ɑ. In the experiment of inhibiting IL-6 inflammatory factor and TNF-ɑ inflammatory factor, Formula I-1-1 has a synergistic effect with carnosine (CI value>1.15). Formula I-1-1 has a synergistic effect with caffeine (CI value>1.15). Carnosine and caffeine do not have a synergistic effect (CI value<1.15).

[0099] Lipopolysaccharide (LPS) can promote inflammation, produce a large number of inflammatory factors and promote the expression of related inflammatory proteins. LPS is often used to activate mouse leukemia macrophages (RAW264.7) as a cell inflammation model. As shown in Table 7: Formula I-1-1 can significantly inhibit the protein level of IL-6. Formula I-1-1 has a synergistic effect with carnosine, with a CI value of 1.19 (CI value>1.15). Formula I-1-1 has a synergistic effect with caffeine, with a CI value of 1.46 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.99 (CI value<1.15). The synergistic effect was calculated according to King's method (CI values ​​between 0.85 and 1.15 are simple addition; between 1.15 and 20 are enhancement, >20 are significant enhancement; CI values ​​between 0.85 and 0.55 are antagonistic, <0.55 are obvious antagonistic).

[0100] The inhibitory effect of Formula I-1-1 combined with carnosine on IL-6 is significantly better than that of Formula I-1-1 or carnosine alone. The inhibitory effect of "Formula I-1-1 + carnosine" on IL-6 is significantly higher than that of Formula I-1-1 (P<0.05); the inhibitory effect of "Formula I-1-1 + carnosine" on IL-6 is significantly higher than that of carnosine (P<0.01) (P<0.05 is considered significant and statistically significant).

[0101] The inhibitory effect of Formula I-1-1 combined with caffeine on IL-6 is significantly better than that of Formula I-1-1 or caffeine alone. The inhibitory effect of "Formula I-1-1 + caffeine" on IL-6 is significantly higher than that of Formula I-1-1 (P<0.05); the inhibitory effect of "Formula I-1-1 + caffeine" on IL-6 is significantly higher than that of caffeine (P<0.001) (P<0.05 is considered significant and statistically significant).

[0102] As shown in Table 8: Formula I-1-1 can significantly inhibit the protein level of TNF-ɑ. Formula I-1-1 has a synergistic effect with carnosine, with a CI value of 1.17 (CI value>1.15). Formula I-1-1 has a synergistic effect with caffeine, with a CI value of 1.22 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.97 (CI value<1.15). The synergistic effect was calculated according to King's method (CI values ​​between 0.85 and 1.15 are simple addition; between 1.15 and 20 are enhancement, >20 are significant enhancement; CI values ​​between 0.85 and 0.55 are antagonism, <0.55 are obvious antagonism).

[0103] The inhibitory effect of Formula I-1-1 combined with carnosine on TNF-ɑ is significantly better than that of Formula I-1-1 or carnosine alone. The inhibitory effect of "Formula I-1-1 + carnosine" on TNF-ɑ is significantly higher than that of Formula I-1-1 (P<0.0001); the inhibitory effect of "Formula I-1-1 + carnosine" on TNF-ɑ is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0104] The inhibitory effect of Formula I-1-1 combined with caffeine on TNF-ɑ is significantly better than that of Formula I-1-1 or caffeine alone. The inhibitory effect of "Formula I-1-1 + caffeine" on TNF-ɑ is significantly higher than that of Formula I-1-1 (P<0.0001); the inhibitory effect of "Formula I-1-1 + caffeine" on TNF-ɑ is significantly higher than that of caffeine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0105] Table 7: Synergistic effect of formula I-1-1 with carnosine or caffeine

[0106]

[0107]

[0108] Table 8: Synergistic effect of formula I-1-1 with carnosine or caffeine

[0109]

[0110]

[0111] Experimental steps: 140 μL of PTIO (22.5 mg / mL) solution was added to a 96-well plate. Then 140 μL of positive control sample (10000 μg / mL ergothioneine) or experimental group 1 sample (10000 μg / mL Ⅰ-1-1) or experimental group 2 sample (10000 μg / mL carnosine) or experimental group 3 sample (10000 μg / mL caffeine) or experimental group 4 sample (10000 μg / mL Ⅰ-1-1 + 10000 μg / mL carnosine) or experimental group 5 sample (10000 μg / mL Ⅰ-1-1 + 10000 μg / mL caffeine) or experimental group 6 sample (10000 μg / mL carnosine + 10000 μg / mL caffeine) was added, and the reaction was protected from light for 5 minutes, and the absorbance was detected at 557 nm (three replicate wells were set for each group).

[0112] Experimental steps: 140 μL of DPPH (0.12 mg / mL) solution was added to a 96-well plate. Then 140 μL of positive control sample (10000 μg / mL ergothioneine) or experimental group 1 sample (10000 μg / mL Ⅰ-1-1) or experimental group 2 sample (10000 μg / mL carnosine) or experimental group 3 sample (10000 μg / mL caffeine) or experimental group 4 sample (10000 μg / mL Ⅰ-1-1 + 10000 μg / mL carnosine) or experimental group 5 sample (10000 μg / mL Ⅰ-1-1 + 10000 μg / mL caffeine) or experimental group 6 sample (10000 μg / mL carnosine + 10000 μg / mL caffeine) was added, and the reaction was protected from light for 5 minutes, and the absorbance was detected at 517 nm (three replicate wells were set for each group).

[0113] Experimental results: As shown in Tables 9 and 10, Formula I-1-1 can significantly scavenge DPPH free radicals and PTIO free radicals. In the experiment of scavenging DPPH free radicals and PTIO free radicals, Formula I-1-1 has a synergistic effect with carnosine.

[0114] As shown in Table 9: In scavenging DPPH free radicals, the CI value of Formula I-1-1 combined with carnosine is 1.18 (CI value>1.15). Formula I-1-1 has a synergistic effect with caffeine, with a CI value of 1.20 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.91 (CI value<1.15).

[0115] The effect of formula I-1-1 combined with carnosine in scavenging PTIO free radicals is significantly better than that of formula I-1-1 or carnosine alone. The effect of "formula I-1-1 + carnosine" in scavenging PTIO free radicals is significantly higher than that of formula I-1-1 (P<0.0001); the effect of "formula I-1-1 + carnosine" in scavenging PTIO free radicals is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0116] The effect of formula I-1-1 combined with caffeine in scavenging PTIO free radicals was significantly better than that of formula I-1-1 or caffeine alone. The effect of "formula I-1-1 + caffeine" in scavenging PTIO free radicals was significantly higher than that of formula I-1-1 (P<0.0001); the effect of "formula I-1-1 + caffeine" in scavenging PTIO free radicals was significantly higher than that of caffeine (P<0.0001) (P<0.05 was considered significant and statistically significant).

[0117] As shown in Table 10: In scavenging DPPH free radicals, the CI value of Formula I-1-1 combined with carnosine is 1.16 (CI value>1.15). Formula I-1-1 has a synergistic effect with caffeine, with a CI value of 1.22 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 1.06 (CI value<1.15).

[0118] The effect of formula I-1-1 combined with carnosine in scavenging DPPH free radicals is significantly better than that of formula I-1-1 or carnosine alone. The effect of "formula I-1-1 + carnosine" in scavenging DPPH free radicals is significantly higher than that of formula I-1-1 (P<0.001); the effect of "formula I-1-1 + carnosine" in scavenging DPPH free radicals is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant). The effect of formula I-1-1 combined with caffeine in scavenging DPPH free radicals is significantly better than that of formula I-1-1 or caffeine alone. The effect of "formula I-1-1 + caffeine" in scavenging DPPH free radicals is significantly higher than that of formula I-1-1 (P<0.01); the effect of "formula I-1-1 + caffeine" in scavenging DPPH free radicals is significantly higher than that of caffeine (P<0.001) (P<0.05 is considered significant and statistically significant).

[0119] Table 9: Antioxidant synergistic effect of formula I-1-1 and carnosine or caffeine

[0120]

[0121]

[0122] Table 10: Antioxidant synergistic effect of formula I-1-1 and carnosine or caffeine

[0123]

[0124] Example 4: Formula I-2-1 and carnosine have a synergistic effect; Formula I-2-1 and caffeine have a synergistic effect.

[0125] Experimental steps: 2 million RAW264.7 cells (P7) were plated in each well of a 6-well plate. After 24 hours, 2 mL of the positive control sample (100 μg / mL dexamethasone) or the experimental group 1 sample (1000 μg / mL of Formula I-2-1) or the experimental group 2 sample (1000 μg / mL carnosine) or the experimental group 3 sample (1000 μg / mL caffeine) or the experimental group 4 sample (1000 μg / mL of Formula I-2-1 + 1000 μg / mL carnosine) or the experimental group 5 sample (1000 μg / mL of Formula I-2-1 + 1000 μg / mL caffeine) or the experimental group 6 sample (1000 μg / mL carnosine + 1000 μg / mL caffeine) was added. After 1.5 hours, 2 μL of 1000 μg / mL LPS was added except for the Control group. Continue to culture for 24 hours, collect the supernatant, centrifuge, take the supernatant, dilute 200 times for TNF-α experiment and 50 times for IL-6 experiment, then use mouse tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit and mouse interleukin 6 (IL-6) enzyme-linked immunosorbent assay kit to detect the concentrations of inflammatory factors TNF-α and IL-6, respectively, add the stop solution within 15 minutes, and detect the absorbance at 450 nm (three replicate wells for each group).

[0126] Experimental results: Lipopolysaccharide (LPS) can promote inflammation, produce a large number of inflammatory factors and promote the expression of related inflammatory proteins. LPS is often used to activate mouse leukemia macrophages (RAW264.7) as a cell inflammation model. As shown in Table 11: Formula I-2-1 can significantly inhibit the protein level of IL-6. Formula I-2-1 has a synergistic effect with carnosine, with a CI value of 1.30 (CI value>1.15). Formula I-2-1 has a synergistic effect with caffeine, with a CI value of 1.42 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.99 (CI value<1.15). The synergistic effect was calculated according to King's method (CI values ​​between 0.85 and 1.15 are simple addition; between 1.15 and 20 are enhancement, >20 are significant enhancement; CI values ​​between 0.85 and 0.55 are antagonistic, <0.55 are obvious antagonistic).

[0127] The inhibitory effect of Formula I-2-1 combined with carnosine on IL-6 is significantly better than that of Formula I-2-1 or carnosine alone. The inhibitory effect of "Formula I-2-1 + carnosine" on IL-6 is significantly higher than that of Formula I-2-1 (P<0.001); the inhibitory effect of "Formula I-2-1 + carnosine" on IL-6 is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0128] The inhibitory effect of Formula I-2-1 combined with caffeine on IL-6 is significantly better than that of Formula I-2-1 or caffeine alone. The inhibitory effect of "Formula I-2-1 + caffeine" on IL-6 is significantly higher than that of Formula I-2-1 (P<0.001); the inhibitory effect of "Formula I-2-1 + caffeine" on IL-6 is significantly higher than that of caffeine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0129] As shown in Table 12: Formula I-2-1 can significantly inhibit the protein level of TNF-ɑ. Formula I-2-1 has a synergistic effect with carnosine, with a CI value of 1.17 (CI value>1.15). Formula I-2-1 has a synergistic effect with caffeine, with a CI value of 1.21 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.93 (CI value<1.15). The synergistic effect was calculated according to King's method (CI values ​​between 0.85 and 1.15 are simple addition; between 1.15 and 20 are enhancement, >20 are significant enhancement; CI values ​​between 0.85 and 0.55 are antagonism, <0.55 are obvious antagonism).

[0130] The inhibitory effect of Formula I-2-1 combined with carnosine on TNF-ɑ is significantly better than that of Formula I-2-1 or carnosine alone. The inhibitory effect of "Formula I-2-1 + carnosine" on TNF-ɑ is significantly higher than that of Formula I-2-1 (P<0.0001); the inhibitory effect of "Formula I-2-1 + carnosine" on TNF-ɑ is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0131] The inhibitory effect of Formula I-2-1 combined with caffeine on TNF-ɑ is significantly better than that of Formula I-2-1 or caffeine alone. The inhibitory effect of "Formula I-2-1 + caffeine" on TNF-ɑ is significantly higher than that of Formula I-2-1 (P<0.0001); the inhibitory effect of "Formula I-2-1 + caffeine" on TNF-ɑ is significantly higher than that of caffeine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0132] Table 11: Synergistic effect of formula I-2-1 with carnosine or caffeine

[0133]

[0134] Table 12: Synergistic effect of formula I-2-1 with carnosine or caffeine

[0135]

[0136]

[0137] Experimental steps: 140 μL of PTIO (22.5 mg / mL) solution was added to a 96-well plate. Then 140 μL of positive control sample (10000 μg / mL ergothioneine) or experimental group 1 sample (10000 μg / mL Ⅰ-2-1) or experimental group 2 sample (10000 μg / mL carnosine) or experimental group 3 sample (10000 μg / mL caffeine) or experimental group 4 sample (10000 μg / mL Ⅰ-2-1 + 10000 μg / mL carnosine) or experimental group 5 sample (10000 μg / mL Ⅰ-2-1 + 10000 μg / mL caffeine) or experimental group 6 sample (10000 μg / mL carnosine + 10000 μg / mL caffeine) was added, and the reaction was protected from light for 5 minutes, and the absorbance was detected at 557 nm (three replicate wells were set for each group).

[0138] Experimental steps: Add 140 μL of DPPH (0.12 mg / mL) solution to a 96-well plate. Then add 140 μL of positive control sample (10000 μg / mL ergothioneine) or experimental group 1 sample (10000 μg / mL Ⅰ-2-1) or experimental group 2 sample (10000 μg / mL carnosine) or experimental group 3 sample (10000 μg / mL caffeine) or experimental group 4 sample (10000 μg / mL Ⅰ-2-1 + 10000 μg / mL carnosine) or experimental group 5 sample (10000 μg / mL Ⅰ-2-1 + 10000 μg / mL caffeine) or experimental group 6 sample (10000 μg / mL carnosine + 10000 μg / mL caffeine), react in the dark for 5 minutes, and detect the absorbance at 517 nm (three replicate wells for each group).

[0139] Experimental results: As shown in Tables 13 and 14: Formula I-2-1 can significantly scavenge DPPH free radicals and PTIO free radicals. In the experiment of scavenging DPPH free radicals and PTIO free radicals, Formula I-2-1 has a synergistic effect with carnosine (CI value>1.15). Formula I-2-1 has a synergistic effect with caffeine (CI value>1.15). Carnosine and caffeine do not have a synergistic effect (CI value<1.15).

[0140] As shown in Table 13: In scavenging DPPH free radicals, the CI value of Formula I-2-1 combined with carnosine is 1.24 (CI value>1.15). Formula I-2-1 has a synergistic effect with caffeine, with a CI value of 1.21 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 0.91 (CI value<1.15).

[0141] The effect of formula I-2-1 combined with carnosine in scavenging PTIO free radicals is significantly better than that of formula I-2-1 or carnosine alone. The effect of "formula I-2-1 + carnosine" in scavenging PTIO free radicals is significantly higher than that of formula I-2-1 (P<0.0001); the effect of "formula I-2-1 + carnosine" in scavenging PTIO free radicals is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0142] The effect of formula I-2-1 combined with caffeine in scavenging PTIO free radicals is significantly better than that of formula I-2-1 or caffeine alone. The effect of "formula I-2-1 + caffeine" in scavenging PTIO free radicals is significantly higher than that of formula I-2-1 (P<0.0001); the effect of "formula I-2-1 + caffeine" in scavenging PTIO free radicals is significantly higher than that of caffeine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0143] As shown in Table 14: In scavenging DPPH free radicals, the CI value of Formula I-2-1 combined with carnosine is 1.17 (CI value>1.15). Formula I-2-1 has a synergistic effect with caffeine, with a CI value of 1.17 (CI value>1.15). Carnosine and caffeine do not have a synergistic effect, with a CI value of 1.06 (CI value<1.15).

[0144] The effect of formula I-2-1 combined with carnosine in scavenging DPPH free radicals is significantly better than that of formula I-2-1 or carnosine alone. The effect of "formula I-2-1 + carnosine" in scavenging DPPH free radicals is significantly higher than that of formula I-2-1 (P<0.01); the effect of "formula I-2-1 + carnosine" in scavenging DPPH free radicals is significantly higher than that of carnosine (P<0.0001) (P<0.05 is considered significant and statistically significant). The effect of formula I-2-1 combined with caffeine in scavenging DPPH free radicals is significantly better than that of formula I-2-1 or caffeine alone. The effect of "formula I-2-1 + caffeine" in scavenging DPPH free radicals is significantly higher than that of formula I-2-1 (P<0.001); the effect of "formula I-2-1 + caffeine" in scavenging DPPH free radicals is significantly higher than that of caffeine (P<0.0001) (P<0.05 is considered significant and statistically significant).

[0145] Table 13: Antioxidant synergistic effect of formula I-2-1 and carnosine or caffeine

[0146]

[0147] Table 14: Antioxidant synergistic effect of formula I-2-1 and carnosine or caffeine

[0148]

[0149] Example 5: Formulation

[0150] Table 15: Soothing Antioxidant Lotion Formula

[0151]

[0152]

[0153] Preparation process: Prepare the components according to Table 15. Add the water in the formula to the main mixer and start stirring. Add glycerin, betaine and sodium hyaluronate in sequence to ensure complete dissolution. Heat the solution to 45°C to promote dissolution and uniformity. Slowly add dipotassium glycyrrhizinate and β-glucan, maintaining low speed stirring. When the solution temperature drops to room temperature (about 25°C), slowly add compound 1-1, compound 2-1, compound 2-3, compound 2-4, and stir evenly. Add caprylyl glycol as a preservative and ensure that the formula is evenly distributed. Adjust the final pH value to between 5.5-6.0 to meet the skin's suitable range. After stirring, pour the solution into a storage container.

[0154] Experimental process: 10 volunteers with sensitive skin were selected. After facial cleansing in the morning and evening, the soothing anti-sugar brightening lotion in Example 3 was applied to the entire face twice a day for 28 consecutive days.

[0155] Subjective evaluation of subjects: After 28 days of use, the subjective evaluation of the subjects was conducted, including the improvement of skin feel, pain relief, redness, and brightening. The evaluation standards are divided into three levels: good, general, and poor. In addition, during the follow-up visit for product safety evaluation, the subjects were evaluated for adverse reactions and asked whether they had symptoms such as erythema and tingling on their faces. If the above symptoms occurred, a patch test was performed to evaluate the correlation with the test product.

[0156] Subjective evaluation of the subjects After 28 days of use, the subjects conducted a subjective evaluation, which included improvements in four aspects: skin feel, pain relief, redness, and brightening. See Table 16 for details.

[0157] Table 16 Subjective evaluation of subjects

[0158]

[0159] Product Safety Evaluation During the entire research process, no adverse reactions occurred in the subjects, which confirmed that the soothing antioxidant lotion has a high safety profile.

[0160] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A composition, characterized in that The invention comprises a compound of the structure of formula (I) and one of carnosine or caffeine; the mass ratio of the compound of the structure of formula (I) to one of carnosine or caffeine is 1:5 to 2:1; Wherein, R1, R2 or R3 are independently selected from H, CH3, or -CH2CH3.

2. The composition according to claim 1, characterized in that The compound of formula (I) specifically includes the following structure:

3. The composition according to claim 1, characterized in that The mass ratio of one of the carnosine or caffeine to the compound of formula (I) is 1:

1.

4. Use of the composition according to any one of claims 1 to 3 in the preparation of soothing, anti-oxidation and anti-inflammatory products.

5. The use according to claim 4, characterized in that: The anti-oxidation includes scavenging PTIO free radicals and DPPH free radicals; The anti-inflammatory treatment includes reducing the levels of inflammatory factors IL-6 and TNF-ɑ; The soothing includes pain relief, redness relief and / or brightening.

6. A soothing, anti-oxidant and anti-inflammatory product, characterized in that: The raw material comprises the composition according to any one of claims 1 to 3.

7. The product according to claim 5, characterized in that The product is a cosmetic, and the dosage form of the cosmetic is a liquid, lotion, emulsion, powder or cream.

8. A soothing, anti-oxidant and anti-inflammatory lotion, characterized in that: The invention comprises the following raw materials in parts by weight:

9. A method for preparing the soothing, anti-oxidation and anti-inflammatory drug according to claim 8, characterized in that: The steps include: Water, glycerin, panthenol, betaine and sodium hyaluronate are mixed and heated to dissolve, and then β-glucan is added. After cooling to room temperature, a compound of formula (I), carnosine or caffeine is added. After stirring, caprylyl glycol is added, and the pH value is adjusted to 5.5-6.

0.

10. The preparation method according to claim 9, characterized in that: The heating temperature is 40-50°C.

Images