Application of creatinine in cosmetics and related products

Abstract

The invention relates to application of creatinine in cosmetics and related products, and belongs to the technical field of cosmetics. According to the scheme, the creatinine with relieving, anti-inflammatory and whitening effects is added and matched with the nicotinamide to be used in the cosmetic composition, the adding amount of the nicotinamide is 1.0-4.0 wt%, the adding amount of the creatinine is 0.0001-2.0 wt%, the creatinine and the nicotinamide are matched, the equivalent and even slightly good whitening effect can be achieved, meanwhile, the using amount of the nicotinamide is effectively reduced, and the skin whitening effect is improved. Therefore, the problems of skin allergy, redness, swelling, acnes and other side effects caused by addition of high-concentration nicotinamide in the prior art are solved, in addition, the essence lotion product provided by the invention also has the effects of moisturizing, repairing and maintaining a weak acid skin environment, can meet the requirements of consumers for moisturizing, whitening and maintaining skin health, and has a good market prospect. And the method has important market economic value.

Description

Technical Field

[0001] The present application relates to an application of creatinine in cosmetics and related products, belonging to the technical field of cosmetics. Background Art

[0002] The structural formula of creatinine is Figure 1 As shown, the CAS number is 60-27-5, the molecular formula is C4H7N3O, and the molecular weight is 113.12. Creatinine is a natural amino acid derivative, which is widely present in mammalian cells. It is a mild whitening and freckle-removing raw material with no cytotoxicity and no side effects after long-term use. It has the dual functions of inhibiting tyrosinase activity and inhibiting melanosome transfer. Its inhibition of tyrosinase activity is a competitive inhibitor rather than a reductive inhibitor. The inhibitory effect is stable and not easy to change color. It is an amino acid derivative with mild skin-lightening properties and serves as a supplement to other skin-lightening and whitening activities. It achieves anti-inflammatory effects by antagonizing the effects of serotonin and prostaglandins or interfering with the synthesis of prostaglandins. It has analgesic effects similar to phenylbutazone.

[0003] For example, niacinamide is a recognized whitening ingredient with good whitening and freckle-removing effects. However, the amount of niacinamide added in most whitening products is relatively high. High concentrations of niacinamide may cause safety issues to the skin. The niacin in niacinamide may cause skin allergies and side effects such as redness, swelling, and acne. The side effects of niacinamide-containing skin care products mainly come from niacin, a by-product contained in niacinamide. Niacin is irritating. People who are intolerant may experience mild burning or itching after using niacinamide-containing products. People with sensitive skin should pay special attention.

[0004] Based on multiple test results, the expert panel of the Cosmetic Ingredient Review Committee of the United States determined that the use of 3% concentration of niacinamide in cosmetics has no significant irritation, sensitization and photosensitivity to the skin, and niacinamide itself has no carcinogenic effect, and is generally considered to be safe for long-term use. However, some studies have suggested that if the concentration of niacinamide in cosmetics exceeds 4%, it may cause intolerance reactions in 20% of people, so people with sensitive skin and dermatitis patients should be cautious when using products containing high concentrations of niacinamide.

[0005] Niacinamide is a widely used and cost-effective whitening additive. If the dosage of niacinamide is reduced, the whitening effect of the cosmetics will be reduced. Therefore, how to ensure the whitening effect while reducing the dosage of niacinamide, or even achieve better whitening effect to reduce the dosage and thus reduce costs, is a very important and worthy issue to study. If the above problems can be solved, it will inevitably play a very good role in promoting the application of niacinamide in cosmetics, and as a safe product with low production cost and good whitening effect, it will also have a very good market effect. Summary of the invention

[0006] In order to solve the above problems, the application of creatinine in cosmetics and related products are provided, wherein the combination of creatinine and niacinamide can effectively reduce the dosage of niacinamide while achieving equivalent or even slightly better whitening effect, and can solve the problem of side effects such as skin allergies, redness, swelling, acne, etc. caused by adding high concentration of niacinamide in the prior art.

[0007] The present application provides an application of creatinine and niacinamide in cosmetics with antioxidant and / or anti-inflammatory and / or whitening effects, wherein the content of niacinamide is 1.0 to 4.0 wt %, and the content of creatinine is 0.0001 to 2.0 wt %.

[0008] Optionally, the content of nicotinamide is 2.0-4.0 wt %, and the content of creatinine is 0.1-1.0 wt %.

[0009] Optionally, the content of nicotinamide is 2.5-3.5wt%, and the content of creatinine is 0.2-0.5wt%.

[0010] Optionally, the content of nicotinamide is selected from 1.0wt%, 1.1wt%, 1.2wt%, 1.3wt%, 1.4wt%, 1.5wt%, 1.6wt%, 1.7wt%, 1.8wt%, 1.9wt%, 2.0wt%, 2.1wt%, 2.3wt%, 2.4wt%, 2.5wt%, 2.6wt%, 2.7wt%, 2.8wt%, 2.9wt%, 3.0wt%, 3.1wt%, 3.2wt%, 3.3wt%, 3.4wt%, 3.5wt%, 3.6wt%, 3.7wt%, 3.8wt%, 3.9wt% and 4.0wt% and any value in the range therebetween.

[0011] Optionally, the content of creatinine is selected from 0.0001wt%, 0.001wt%, 0.01wt%, 0.1wt%, 0.20wt%, 0.21wt%, 0.22wt%, 0.23wt%, 0.24wt%, 0.25wt%, 0.26wt%, 0.27wt%, 0.28wt%, 0.29wt%, 0.30wt%, 0.31wt%, 0.32wt%, 0.33wt%, 0.34wt%, 0.35wt%, 0.36wt%, 0.37wt%, 0.38wt%, 0.39wt%, 0.40wt%, 0.41wt%, 0.42wt%, 0.43wt%, 0.44wt%, 0.45wt%, 0.46wt%, 0.47wt%, 0.48wt%, 0.49wt%, 0.50wt%, 0.51wt%, 0.52wt%, 0.53wt%, 0.54wt%, 0.55wt%, 0.56wt%, 0.57wt%, 0.58wt%, 0.59wt%, 0.60wt%, 0.61wt%, 0.62wt%, 0.63wt%, 0.64wt%, 0.65wt%, 0.66wt%, 0.67wt%, 0.68wt%, 0.69wt%, 0.70wt%, 0.71wt%, 0.72wt%, 0.73wt%, 0.74wt%, 0.75wt%, 0.76wt%, 0.77wt%, 0.78 .33wt%, 0.34wt%, 0.35wt%, 0.36wt%, 0.37wt%, 0.38wt%, 0.38wt%, 0.40wt%, 0.41wt%, 0.42wt%, 0.43wt%, 0.44wt%, 0.45wt%, 0.46wt%, 0.47wt%, 0.48wt%, 0.49wt% and 0.50wt% and any value in the range therebetween.

[0012] The present application provides a cosmetic composition, which comprises creatinine and niacinamide, wherein the content of the niacinamide is 1.0 to 4.0 wt %, and the content of the creatinine is 0.0001 to 2.0 wt %.

[0013] Optionally, the content of nicotinamide is 2.0-4.0 wt %, and the content of creatinine is 0.1-1.0 wt %.

[0014] Optionally, the content of nicotinamide is 2.5-3.5wt%, and the content of creatinine is 0.2-0.5wt%.

[0015] Optionally, the content of nicotinamide is selected from 1.0wt%, 1.1wt%, 1.2wt%, 1.3wt%, 1.4wt%, 1.5wt%, 1.6wt%, 1.7wt%, 1.8wt%, 1.9wt%, 2.0wt%, 2.1wt%, 2.3wt%, 2.4wt%, 2.5wt%, 2.6wt%, 2.7wt%, 2.8wt%, 2.9wt%, 3.0wt%, 3.1wt%, 3.2wt%, 3.3wt%, 3.4wt%, 3.5wt%, 3.6wt%, 3.7wt%, 3.8wt%, 3.9wt% and 4.0wt% and any value in the range therebetween.

[0016] Optionally, the content of creatinine is selected from 0.0001wt%, 0.001wt%, 0.01wt%, 0.1wt%, 0.20wt%, 0.21wt%, 0.22wt%, 0.23wt%, 0.24wt%, 0.25wt%, 0.26wt%, 0.27wt%, 0.28wt%, 0.29wt%, 0.30wt%, 0.31wt%, 0.32wt%, 0.33wt%, 0.34wt%, 0.35wt%, 0.36wt%, 0.37wt%, 0.38wt%, 0.39wt%, 0.40wt%, 0.41wt%, 0.42wt%, 0.43wt%, 0.44wt%, 0.45wt%, 0.46wt%, 0.47wt%, 0.48wt%, 0.49wt%, 0.50wt%, 0.51wt%, 0.52wt%, 0.53wt%, 0.54wt%, 0.55wt%, 0.56wt%, 0.57wt%, 0.58wt%, 0.59wt%, 0.60wt%, 0.61wt%, 0.62wt%, 0.63wt%, 0.64wt%, 0.65wt%, 0.66wt%, 0.67wt%, 0.68wt%, 0.69wt%, 0.70wt%, 0.71wt%, 0.72wt%, 0.73wt%, 0.74wt%, 0.75wt%, 0.76wt%, 0.77wt%, 0.78 .33wt%, 0.34wt%, 0.35wt%, 0.36wt%, 0.37wt%, 0.38wt%, 0.38wt%, 0.40wt%, 0.41wt%, 0.42wt%, 0.43wt%, 0.44wt%, 0.45wt%, 0.46wt%, 0.47wt%, 0.48wt%, 0.49wt% and 0.50wt% and any value in the range therebetween.

[0017] The present application provides a cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects, which comprises, by weight: 0.1-0.5 parts of thickener, 3-7 parts of polyol, 0.1-5 parts of moisturizer, 2-5 parts of emulsifier, 1-20 parts of emollient oil, 0.5-4 parts of silicone oil, 1-4 parts of pH adjuster, 0.1-1 parts of preservative, 1.0-4.0 parts of niacinamide and 0.0001-2.0 parts of creatinine;

[0018] Optionally, the thickener is selected from one or more of carbomer, sodium carbomer, ammonium polyacryloyldimethyltaurate, xanthan gum, acrylic acid (ester) / C10-30 alkyl acrylate cross-linked polymer, ammonium acryloyldimethyltaurate / VP copolymer; the polyol is selected from one or more of glycerol, butylene glycol, and propylene glycol; the moisturizer is selected from one or more of betaine, panthenol, allantoin, sodium hyaluronate, trehalose, and glyceryl glucoside; the emulsifier is selected from cetearyl alcohol, C14-22 alcohol and C12-20 alkyl glucoside and glucose mixture, behenyl alcohol, cetearyl alcohol and cetearyl glucoside and glucose mixture, polyol One or more of a mixture of glycerol-3, lecithin and phytosterols, stearic acid, cetearyl olive oil ester, sodium stearoyl lactylate and cetearyl alcohol; the emollient oil is selected from one or more of shea butter, ethylhexyl palmitate, jojoba oil, meadowfoam seed oil, caprylic capric triglyceride; the silicone oil is selected from one or more of dimethicone, dimethiconol, dimethicone / vinyl dimethicone crosspolymer; the pH adjuster is selected from one or more of sodium hydroxide and arginine; the preservative is selected from one or more of p-hydroxyacetophenone, phenoxyethanol, ethylhexylglycerin and hexylene glycol.

[0019] Among them, the mixture of cetearyl alcohol, cetearyl glucoside and glucose is a mixture of cetearyl alcohol, cetearyl glucoside and glucose, the mixture of cetearyl olivate, sodium stearoyl lactylate and cetearyl alcohol is a mixture of cetearyl olivate, sodium stearoyl lactylate and cetearyl alcohol, the mixture of C14-22 alcohol, C12-20 alkyl glucoside and glucose is a mixture of C14-22 alcohol, C12-20 alkyl glucoside and glucose, and the mixture of polyglycerol-3, lecithin and phytosterols is a mixture of polyglycerol-3, lecithin and phytosterols.

[0020] Optionally, the content of nicotinamide is 2.0 to 4.0 parts, and the content of creatinine is 0.1 to 1.0 parts;

[0021] Optionally, the content of niacinamide is 2.5 to 3.5 parts, and the content of creatinine is 0.2 to 0.5 parts.

[0022] The present application provides a cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects, which comprises, by weight: 0.1-0.3 parts of carbomer, 0.1-0.3 parts of allantoin, 3-7 parts of glycerol, 0.3-0.7 parts of betaine, 2-6 parts of butylene glycol, 1.0-2.0 parts of cetearyl alcohol, 0.2-0.8 parts of a mixture of C14-22 alcohol and C12-20 alkyl glucoside and glucose, cetearyl alcohol and 0.5-1.5 parts of a mixture of cetearyl glucoside and glucose, 3-7 parts of shea butter, 1-5 parts of ethylhexyl palmitate, 0.2-0.8 parts of jojoba oil, 1-3 parts of polydimethylsiloxane, 0.01-0.07 parts of sodium hydroxide, 1.0-5.0 parts of niacinamide, 0.0001-2.0 parts of creatinine, 0.1-0.5 parts of p-hydroxyacetophenone, 0.2-0.6 parts of phenoxyethanol, and 0.01-0.2 parts of ethylhexylglycerin.

[0023] Optionally, the content of niacinamide is 2.0-4.0 parts, and the content of creatinine is 0.1-1.0 parts.

[0024] Optionally, the content of niacinamide is 2.5 to 3.5 parts, and the content of creatinine is 0.2 to 0.5 parts.

[0025] Optionally, the cosmetic composition further comprises essence, and the amount of essence added can be selected by those skilled in the art as needed.

[0026] The present application provides a method for preparing any one of the above-mentioned cosmetic compositions with antioxidant and / or anti-inflammatory and / or whitening effects, the preparation method comprising the following steps:

[0027] 1) Stir butylene glycol, glycerin and carbomer evenly for use; add allantoin and betaine to the mixture of butylene glycol, glycerin and carbomer, stir evenly, and then add them to the mixture of butylene glycol, glycerin and carbomer, heat at 80-85° C. and mix well to prepare phase A;

[0028] 2) mixing cetearyl alcohol, C14-22 alcohol and C12-20 alkyl glucoside and glucose mixture, cetearyl alcohol and cetearyl glucoside and glucose mixture, shea butter, ethylhexyl palmitate, jojoba oil, and polydimethylsiloxane, heating to 80-85° C. and mixing well to prepare phase B;

[0029] 3) adding water to sodium hydroxide as phase C, adding water to niacinamide and creatinine and mixing well as phase D, and mixing hydroxyacetophenone, phenoxyethanol, and ethylhexylglycerin as phase E;

[0030] 4) Mix phases A and B and emulsify and homogenize for 5 to 8 minutes, then stir and cool to 48 to 50° C., add phase C and stir evenly, continue to add phase D and stir evenly, then stir and cool to 43 to 45° C., add phase E and stir evenly to obtain the cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects.

[0031] Optionally, the cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects further comprises essence, and the step 4) further comprises the step of adding the essence and stirring evenly.

[0032] The beneficial effects of this application include but are not limited to:

[0033] 1. According to the application of creatinine in cosmetics and related products of the present application, the addition of creatinine and niacinamide in combination can reduce the amount of niacinamide used in whitening products, thereby reducing irritation and side effects while ensuring better or even better whitening effects.

[0034] 2. According to the application of creatinine in cosmetics and related products of the present application, the addition amount of niacinamide is 1.0-4.0wt%, and the addition amount of creatinine is 0.0001-2.0wt%. The above-mentioned addition amounts of niacinamide and creatinine are used in combination to ensure a good whitening effect while reducing the amount of niacinamide used, thereby reducing the irritation of cosmetics and reducing side effects.

[0035] 3. According to the application of creatinine in cosmetics and related products of the present application, the application of niacinamide and creatinine in cosmetics has the effects of whitening, anti-inflammatory and soothing, and antioxidant, and the amount of niacinamide used in cosmetic products is reduced compared to the cosmetics in the prior art, and has lower irritation. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0037] Figure 1 is the molecular structural formula of creatinine involved in this application;

[0038] Figure 2 This is a graph of the antioxidant test results involved in Example 3 of the present application;

[0039] Figure 3 This is a Masson-Fontana staining result diagram of melanin inhibition involved in Example 4 of the present application;

[0040] Figure 4 This is a skin chromaticity value result diagram involved in Example 6 of the present application;

[0041] Figure 5 This is a skin gloss result diagram involved in Example 6 of the present application;

[0042] Figure 6 This is the skin chromaticity value ITA° result diagram involved in Example 6 of the present application;

[0043] Figure 7 is a diagram of stratum corneum moisture content involved in Example 7 of the present application;

[0044] Figure 8 This is a graph showing the transepidermal water loss results involved in Example 7 of the present application;

[0045] Fig. 9 This is a graph showing the results of maintaining skin pH in Example 7 of the present application. DETAILED DESCRIPTION

[0046] The present application is described in detail below in conjunction with examples, but the present application is not limited to these examples. Unless otherwise specified, the raw materials and catalysts in the examples of the present application are purchased through commercial channels. For example, C14-22 alcohol is a well-known nonionic surfactant, and C12-20 alkyl glucoside is another well-known nonionic surfactant.

[0047] The present application scheme is described below through specific embodiments.

[0048] Example 1 Creatinine Anti-Inflammation Relief Test

[0049] The specific experimental grouping design in this embodiment is shown in Table 1 below.

[0050] Table 1 Experimental group design

[0051]

[0052] In this embodiment, the detection index is the content of PEG-2. In the concentration detection, the concentration of the standard is used as the ordinate and the OD value is used as the abscissa to draw a standard curve. 450 The value is obtained, and the corresponding concentration is found to calculate the content of the sample. Finally, the average value of the three replicate wells in each group is taken as the final content result. The standard curve is: y = 111.75 x 2 +95.659ⅹ+18.9(R 2 =0.9968).

[0053] In the cell seeding step, cells in the logarithmic growth phase were collected and the cell density was 1×10 5Each well was inoculated into a 24-well plate and cultured in a 37°C, 5% CO2 incubator for 24 hours. In the sampling step, the sample was added when the cell plating rate in the 24-well plate reached 90%, and UVB irradiation (40mJ / cm2) was performed after the sample was added. The blank control group was cell culture medium, 1mL per well, the negative control group was cell culture medium (UVB irradiation), 1mL per well, the positive control group was culture medium containing positive drugs (kojic acid) (UVB irradiation), 1mL per well, and the sample group was culture medium containing the test substance (UVB irradiation), 1mL per well. After the sampling is completed, the 24-well plate is placed in an incubator (37°C, 5% CO2) and cultured for 24 hours.

[0054] The ELISA detection method includes: after the culture is completed, the cell culture fluid is collected in a 1.5 mL Eppendorf tube, centrifuged at 4°C and 1000×g to obtain the supernatant for detection. Inhibition rate (%) = (1-T / C)×100%, where T is the average content of the test substance and C is the average content of the negative control.

[0055] The cytotoxicity test results are shown in Table 2 below, and the experimental test results are shown in Table 3 below.

[0056] Table 2 Cytotoxicity results

[0057]

[0058]

[0059] Table 3 PEG-2 test results

[0060] Group PEG-2 content mean ± standard deviation (SD) Inhibition rate (5) P-value Negative control 222.19±4.35 -- -- 0.6 186.33±2.73 16.14％ ** 0.3 194.14±3.46 12.63％ ** 0.15 197.30±2.84 11.20％ ** Positive Control 164.31±2.79 26.05％ **

[0061] Note: Compared with the negative control group, there is a significant difference, *P<0.05, **P<0.01. There is no significant difference, P>0.05, indicated by "ns".

[0062] According to the test results in Table 3, compared with the negative control, the PGE-2 content in the test sample group decreased at concentrations of 0.6%, 0.3%, and 0.15%, and there were significant differences (P<0.05), indicating that the test sample creatinine has the effect of inhibiting PGE-2, that is, it has anti-inflammatory effect.

[0063] Example 2 Creatinine Anti-Glycation Test

[0064] Glycosylated proteins (Advanced Glyeation End Products, AGEs) are products of Maillard reaction, fat oxidation and other reactions. In this example, a Maillard simulation reaction system of bovine serum albumin and glucose was established, and the fluorescence intensity was measured at a specific wavelength. The fluorescence intensity was used to represent the AGEs content, and the inhibitory effect of the sample on the formation of glycosylated proteins was calculated.

[0065] AGEs inhibition rate (%) = [1-(AB) / (CD)] × 100, wherein A is the fluorescence intensity of the AGEs solution added with the test substance or the positive substance, B is the fluorescence intensity of the PB solution added with the test substance or the positive substance, C is the fluorescence intensity of the AGEs solution without the test substance or the positive substance, D is the fluorescence intensity of the PB solution without the test substance or the positive substance, the positive substance is the aminoguanidine sulfate group, and the experimental group is the creatinine group. The test results are shown in Table 4 below.

[0066] Table 4 Anti-glycation test results

[0067]

[0068]

[0069] According to the results in Table 4, the IC of the positive control group was calculated. 50 :0.8874mg / mL(95%Cl:0.5782mg / mL-1.362mg / mL); Sample group IC 50 :0.2697%(95%C1:0.1973%-0.3686%). Under the conditions of this experiment, the smaller the concentration of the test substance required to achieve half inhibition rate, i.e. IC 50 The smaller the value, the stronger the ability of the test substance to inhibit the formation of glycosylated proteins. When the concentration was 1.5625% (w / w), the inhibition rate of the sample on the formation of glycosylated proteins was 53.42%, indicating that creatinine has an inhibitory effect on the formation of glycosylated proteins.

[0070] Example 3 Creatinine Antioxidant Efficacy Test

[0071] The reagent is a DNA dye with weak fluorescence itself. It can be oxidized by oxygen free radicals (ROS) in the cell. The oxidation products combine with DNA to produce bright green fluorescence. It is soluble in organic solvents (such as dimethyl sulfoxide), and the main component of zebrafish yolk sac is fat. The permeability of the yolk sac is strong, and the staining is obvious. Menadione can produce active oxygen free radicals. When the amount of free radicals produced is greater than the body's clearance capacity, oxidative stress occurs. The fluorescence intensity of the zebrafish yolk sac is used to evaluate whether the sample has an antioxidant effect.

[0072] The zebrafish were stained with a specific ROS fluorescent reagent. After staining, 10 zebrafish were randomly selected from each experimental group and photographed under a fluorescence microscope. Advanced image processing software was used to analyze and collect data, and the fluorescence intensity (S) of the zebrafish yolk sac was analyzed. The antioxidant effect of the sample was calculated according to the formula to determine whether it had antioxidant effect. The antioxidant effect was calculated according to the following formula.

[0073] Antioxidant effect (%) = (S model control group - S sample group) / (S model control group - S normal control group) × 100%. The test results are shown in Table 5 below.

[0074] Table 5 Antioxidant test results

[0075] Test items Detection concentration (%) effect(%) P-value Test results Antioxidant Effect 0.2 34 ＜0.001 Significant

[0076] Combination Figure 2 As shown in the results of Table 5, the fluorescence intensity of zebrafish yolk sac in the sample creatinine group was significantly lower than that in the model control group, which revealed that creatinine has an antioxidant effect.

[0077] Example 4 Creatinine + Nicotinamide Whitening Efficacy Test

[0078] In this example, based on the co-culture system of primary keratinocytes (KCs) and melanocytes (MCs), the whitening efficacy of each group of samples in Table 6 was evaluated from the perspective of melanin transport. First, the cell viability of creatinine and nicotinamide was detected respectively. Specifically, creatinine and nicotinamide samples were prepared in serum-free medium at 1%, 0.5%, 0.2%, 0.05%, 0.02%, 0.01%, and 0.001% concentrations (w / v) under sterile conditions. KCs were cultured at 5×10 4 The cells / mL were inoculated in a 96-well plate and cultured under saturated humidity, 5% CO2, and 37°C. Samples were added the next day. 24 hours after adding samples, the cell metabolic activity was detected by CCK-8 method, and the cell survival rate was calculated according to the following formula: Cell survival rate = (OD value of sample group - OD value of apoptosis group) / (OD value of blank control group - OD value of apoptosis group) × 100%, and the results are shown in Tables 7 and 8 below.

[0079] Then the whitening effect was determined. The specific composition of the test sample is shown in Table 6. Specifically, KCs cells were cultured at 5×10 5The density of cells / well was inoculated in a 6-well plate and cultured overnight at saturated humidity, 5% CO2, and 37°C. The next day, MCs were inoculated in a Transwell with a pore size of 8 pm, and the Transwell was placed in a 6-well plate for co-culture with KCs. On the second day of co-culture, samples were added according to Table 6, and the medium was changed every day thereafter. After 7 days of culture, half of the cells in each group were fixed for Masson-Fontana staining; the other half of the cells were not added and replaced with ordinary culture medium for continued culture for 2 days, and then fixed for Masson-Fontana staining. After Masson-Fontana staining, each group was photographed under a 20× objective lens, and 3 fields of view were randomly selected to count 100 keratinocytes, and the melanin transfer rate was calculated: Melanin transfer rate % = number of KCs containing melanin granules / total number of KCs × 100%.

[0080] Table 6 Melanin content experimental grouping table

[0081]

[0082]

[0083] The cell viability results are shown in Tables 7 and 8 below: the cell viability was close to 100% at a creatinine concentration of 0.5%, and the cell viability was close to 100% at a nicotinamide concentration of 0.2%, creatinine CV90 = 0.507% (95% CI: 0.157% to 0.778%), and nicotinamide CV90 = 0.247% (95% CI: 0.152% to 0.889%).

[0084] Table 7 Creatinine cell viability test results

[0085] W / V OD450 Cell viability 1％ 0.252±0.010 26.9％±1.1％ 0.5％ 1.012±0.044 108.1％±4.7％ 0.2％ 1.086±0.013 116.0％±1.4％ 0.05％ 1.152±0.036 123.1％±3.8％ 0.02％ 1.212±0.023 129.5％±2.4％ 0.01％ 1.160±0.037 123.9％±3.9％ 0.001％ 1.024±0.023 109.4％±2.5％ Blank control group 0.936±0.011 100％±1.2％

[0086] Table 8 Nicotinamide cell viability test results

[0087] W / V OD450 Cell viability 1％ 0.008±0.004 0.9％±0.4％ 0.5％ 0.315±0.014 34.8％±1.5％ 0.2％ 0.972±0.029 107.3％±3.3％ 0.05％ 1.211±0.072 133.8％±11.2％ 0.02％ 1.112±0.101 122.8％±2.4％ 0.01％ 1.112±0.145 122.8％±16.0％ 0.001％ 1.111±0.047 122.7％±5.2％ Blank control group 0.905±0.058 100％±6.4％

[0088] Whitening test results Figure 3As shown in Table 9 below: Compared with the negative control group, after 7 days of treatment with 0.5% creatinine and 0.3% creatinine + 0.2% nicotinamide in the co-culture system of KCs and MCs, the proportion of melanin particles transferred to keratinocytes was extremely significantly reduced (P<0.01), with a decrease rate of 72.3%±4.6% and 95.2%±3.9%, respectively. After 7 days of treatment with the sample, the sample was removed and cultured for 2 days. Compared with the negative control group, the proportion of melanin particles transferred to keratinocytes in the 0.5% creatinine group and the 0.3% creatinine + 0.2% nicotinamide group was significantly reduced (P<0.01), with a decrease rate of 66.7%±5.7% and 96.7%±2.2%, respectively. Compared with the samples treated for 7 days, the melanin transfer rate in keratinocytes did not change significantly after removing 0.5% creatinine or 0.3% creatinine + 0.2% nicotinamide for 2 days (P>0.05), and no obvious melanin reversion was observed after the samples were removed and cultured for another 2 days.

[0089] Table 9 Melanin transfer rate

[0090] Melanin transfer rate Drop rate Negative control group (7D) 20.75％±4.91％ / Positive control group (7D) 1.75％±0.50％ 91.6％±2.4％ Creatinine group (7D) 5.75％±0.96％ 72.3％±4.6％ Creatinine + niacinamide group (7D) 1.00％±0.82％ 95.2％±3.9％ Negative control group (9D) 22.50％±2.08％ / Positive control group (9D) 2.00％±0.82％ 91.1％±3.6％ Creatinine group (9D) 7.50％±1.29％ 66.7％±5.7％ Creatinine + niacinamide group (9D) 0.75％±0.50％ 96.7％±2.2％

[0091] According to the data results in Table 9, compared with the groups using niacinamide alone or creatinine alone, the combination of niacinamide and creatinine significantly reduced the proportion of melanin particles transferred to keratinocytes and had a better transfer effect, indicating that the combination of creatinine and niacinamide can synergistically enhance the effect and better inhibit the transfer of melanin particles to keratinocytes, and no obvious darkening was observed after discontinuation of use.

[0092] Example 5 Essence milk product

[0093] Based on the results of laboratory cell experiments, the experimenters used niacinamide and creatinine in a specific cosmetic product to further verify their synergistic whitening effect. It should be noted that there are still differences between the production of actual products and laboratory cell experiments. For example, the amount of niacinamide used in the laboratory cell experiment in Example 4 is 0.5%, while the amount of niacinamide used in the essence milk product in this embodiment is higher than the amount used in the laboratory cell experiment. In the field of cosmetics, it is common for laboratory tests to be different from actual product tests. For example, most of the existing whitening products have a niacinamide addition of 5%, and some whitening products have a niacinamide addition of up to 8%, such as Sesderma's brightening body milk niacinamide and AlphaHydrox niacinamide fruit acid body milk, which have an addition of 6%, and the initial niacinamide diamond light whitening hand cream niacinamide addition of 8%. According to the test results of cell survival rate in Example 4, it can also be known that niacinamide is irritating to cells, which can also explain the importance of using creatinine in combination with niacinamide in this application to reduce the amount of niacinamide.

[0094] A serum milk, the specific composition ratio of the sample is shown in Table 10 below, and the preparation method comprises the following steps:

[0095] (1) Phase A: Mix butylene glycol, glycerol and carbomer evenly for later use. Weigh the remaining raw materials of phase A according to the ratio requirements, mix evenly, add the mixture of butylene glycol, glycerol and carbomer, heat to 80-85°C, 83°C is selected here, and then mix evenly.

[0096] (2) Mix the raw materials of phase B and heat them to 80-85°C, 83°C is selected here, and they are completely dissolved and set aside; the raw materials of phase C, phase D, and phase E are dispersed separately and set aside, and the raw materials of phase E can be heated appropriately, and the heating temperature does not exceed 50°C;

[0097] (3) After the raw materials of phase A and phase B are evenly dispersed, the raw materials of phase B are added to phase A and emulsified and homogenized for 5 to 8 minutes, and 6 minutes is selected here. After the emulsification is completed, the temperature is stirred and cooled. After the temperature drops to 48 to 50°C, the raw materials of phase C are added and stirred evenly. After stirring evenly, the raw materials of phase D are added and stirred evenly. After stirring evenly, the temperature is continued to be lowered. After the temperature drops to 43 to 45°C, the raw materials of phase E are added and stirred evenly. After stirring evenly, the essence milk sample A is obtained. The specific composition ratio is shown in Table 10.

[0098] It should be noted that those skilled in the art can also add an appropriate amount of flavor to adjust the smell of the essence milk according to needs.

[0099] Table 10 Mass content of each component of essence milk

[0100]

[0101]

[0102] Example 6 Human body whitening efficacy detection

[0103] The experimenters conducted a whitening efficacy test on the essence milk product prepared in Example 5, wherein sample A is the product in Example 5, i.e., an essence milk emulsion containing 3g niacinamide and 0.3g creatinine, sample B contains 2g niacinamide and 1g creatinine, and sample C contains 4g niacinamide and 0.1g creatinine. In addition, a comparative sample 1 having the same main ingredients and preparation method as those in Example 5 was used for control, wherein comparative sample 1 contains 5g niacinamide but does not add creatinine. The difference between sample A and sample B, sample C, and comparative sample 1 is only in the addition of niacinamide and creatinine. Apart from this, the same basic system as shown in Table 10 is used for preparation.

[0104] 35 volunteers who met the criteria (Chinese healthy subjects aged 18 to 60, both male and female) were selected to participate in the test, excluding: 1) pregnant or breastfeeding women, or those who have plans to get pregnant in the near future; 2) highly sensitive constitution, allergic diseases, and a history of cosmetic allergies; 3) suffering from skin diseases such as psoriasis, eczema, atopic dermatitis, severe acne, or other chronic systemic diseases; 4) birthmarks, pigmentation, inflammation, scars, pigmented moles, hirsutism, etc. on the skin of the test site; 5) oral or topical anti-inflammatory drugs such as corticosteroids in the past month; 6) cosmetics with such efficacy or other products with similar efficacy have been used in the past 2 weeks; 7) participated in human clinical trials of cosmetics in the past month; 8) other clinical evaluations deemed unsuitable for participation in the test. Product use methods include: subjects use the test product in the test area according to the design of the test plan. Subjects use it after bathing and drying the water. Frequency of use: once every 1 to 2 days. During the entire test period, long-term sun exposure, outdoor sports, travel, etc. are not allowed. Cosmetics or medicines with similar efficacy to the product shall not be used, and subjects shall not change their daily care habits. SPSS analysis software was used to compare the measured values ​​at different time points with the baseline values, and the Shapiro-Wilk Test was used to perform a significance test for the normal distribution of the data difference. If p (bilateral)>0.05, it was normally distributed, and a paired sample t test was performed, with a significant difference level α of 0.05. If p (bilateral)<0.05, it was non-normally distributed, and a Wilcoxon signed rank test was performed, with a significant difference level α of 0.05. The amount of change after using the product (△ difference) = data after use - data before use, the rate of change after using the product = (data after use - data before use) / data before use, measurement requirements: test 3 times and take the average value.

[0105] Among them, the skin chromaticity L* value is the whiteness of the skin. The higher the value, the "brighter" the skin. Unit: dimensionless. Measuring instrument: skin color test probe Colorimeter CL400 (Courage&Khazaka, Germany). The skin chromaticity ITA° value is the brightness of the skin. The higher the value, the "brighter" the skin. Unit: °. Measuring instrument: skin color test probe ColorimeterCL400 (Courage&Khazaka, Germany). The higher the skin glossiness value, the glossier the skin. Unit: dimensionless. Measuring instrument: skin glossiness probe Glossymeter GL200 (Courage&Khazaka, Germany). The results are as follows: Figure 4 , Figure 5 , Figure 6 shown.

[0106] Compared with before using the test product, sample A: after using the test product for 2 weeks, the L* value of the calf skin color increased significantly by 2.91% (p<0.001), and after using the test product for 4 weeks, the L* value of the calf skin color increased significantly by 5.37% (p<0.001); sample B: after using the test product for 2 weeks, the L* value of the calf skin color increased significantly by 2.35% (p<0.001), and after using the test product for 4 weeks, the L* value of the calf skin color increased significantly by 4.65% (p<0.001); sample C: compared with before using the test product: after using the test product for 2 weeks, the L* value of the calf skin color increased significantly by 2.91% (p<0.001), and after using the test product for 4 weeks, the L* value of the calf skin color increased significantly by 5.29% (p<0.001).

[0107] Comparison of sample 1 with that before using the test product: After using the test product for 2 weeks, the L* value of the calf skin color increased significantly by 2.55% (p<0.001); After using the test product for 4 weeks, the L* value of the calf skin color increased significantly by 3.97% (p<0.001).

[0108] After using the test product for 2 weeks, the ITA° value of the calf skin color of sample A increased significantly by 11.52% (p<0.001); after using the test product for 4 weeks, the ITA° value of the calf skin color increased significantly by 26.65% (p<0.001); after using the test product for 2 weeks, the ITA° value of the calf skin color of sample B increased significantly by 8.97% (p<0.001), and after using the test product for 4 weeks, the ITA° value of the calf skin color increased significantly by 23.06% (p<0.001); after using the test product for 2 weeks, the ITA° value of the calf skin color of sample C increased significantly by 9.78% (p<0.001); after using the test product for 4 weeks, the ITA° value of the calf skin color increased significantly by 23.96% (p<0.001).

[0109] Compared with Sample 1, after using the test product for 2 weeks, the ITA° value of the calf skin chromaticity significantly increased by 9.53% (p<0.001); after using the test product for 4 weeks, the ITA° value of the calf skin chromaticity significantly increased by 23.00% (p<0.001).

[0110] After using the test product for 2 weeks, the glossiness of the calf skin of sample A increased significantly by 8.80% (p<0.001); after using the test product for 4 weeks, the glossiness of the calf skin increased significantly by 15.54% (p<0.001); after using the test product for 2 weeks, the glossiness of the calf skin of sample B increased significantly by 7.50% (p<0.001), and after using the test product for 4 weeks, the glossiness of the calf skin increased significantly by 13.16% (p<0.001); after using the test product for 2 weeks, the glossiness of the calf skin of sample C increased significantly by 7.95% (p<0.001); after using the test product for 4 weeks, the glossiness of the calf skin increased significantly by 13.68% (p<0.001).

[0111] Compared with Sample 1, after using the test product for 2 weeks, the glossiness of the calf skin increased significantly by 7.53% (p<0.001); after using the test product for 4 weeks, the glossiness of the calf skin increased significantly by 12.24% (p<0.001).

[0112] The above human test results show that the essence milk lotion with niacinamide + creatinine added in the embodiment of the present application has a comparable whitening effect compared with the essence milk lotion with 5% high-concentration niacinamide added in the comparative sample 1, and even has a better whitening effect in some test results. It can be reasonably expected that the solution provided by the present application can reduce the amount of niacinamide used in whitening products, alleviate the side effects of skin redness, swelling, acne, etc. caused by nicotinic acid in high-concentration niacinamide, and at the same time achieve a comparable whitening effect. In addition, the in vitro test results show that the solution of the present application has a good soothing and anti-inflammatory effect, and the prepared skin care products have the advantages of low irritation and higher safety.

[0113] Example 7 Moisturizing, repairing, and maintaining the weakly acidic environment of the skin

[0114] 35 volunteers who met the criteria (Chinese healthy subjects aged 18 to 60, both male and female) were selected to participate in the test, and the exclusion criteria were consistent with the whitening effect. Measuring instruments: Corneometer CM825 (Courage & Khazaka, Germany), measurement requirements: 6 tests to get the average value; Tewameter TM 300 (Courage & Khazaka, Germany), measurement requirements: 3 tests to get the average value; Skin pH tester and test probe Skin-pH-Meter PH 905 (Courage aRhazaka, Germany), measurement requirements: 3 tests to get the average value.

[0115] In the test indicators: the higher the moisture value, the higher the moisture content of the stratum corneum of the skin. Unit: Corneometer Unit, abbreviated as CU. The lower the transepidermal loss value, the less transepidermal water loss. Unit: g / (hm 2 ). The pH value of the weakly acidic environment of the skin ranges from 4.5 to 6.5. Unit: dimensionless. Test results are as follows Figure 7 , Figure 8 , Fig. 9 shown.

[0116] Compared with before using the test product of Example 4: after using the test product for 2 weeks, the moisture content of the calf stratum corneum was significantly increased by 39.30% (p<0.001); after using the test product for 4 weeks, the moisture content of the calf stratum corneum was significantly increased by 70.86% (p<0.001); after using the test product for 2 weeks, the transepidermal water loss of the calf was significantly reduced by 21.60% (p<0.001); after using the test product for 4 weeks, the transepidermal water loss of the calf was significantly reduced by 31.88% (p<0.001); after using the test product for 2 weeks, the mean pH value of the calf skin pH was 5.08, which could maintain the weak acid environment of the skin (p<0.01) (the pH value of the weak acid environment of the skin ranged from 4.5 to 6.5); after using the test product for 4 weeks, the mean pH value of the calf skin pH was 4.97, which could maintain the weak acid environment of the skin (p<0.001) (the pH value of the weak acid environment of the skin ranged from 4.5 to 6.5).

[0117] The above is only the embodiment of the present application, and the protection scope of the present application is not limited by these specific embodiments, but is determined by the claims of the present application. For those skilled in the art, the present application can have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the technical ideas and principles of the present application should be included in the protection scope of the present application.

Claims

1. Application of creatinine and nicotinamide in cosmetics with antioxidant and / or anti-inflammatory and / or whitening effects, characterized in that: The content of the nicotinamide is 1.0-4.0 wt %, and the content of the creatinine is 0.0001-2.0 wt %.

2. The use according to claim 1, characterized in that: The content of the nicotinamide is 2.0-4.0 wt %, and the content of the creatinine is 0.1-1.0 wt %.

3. The use according to claim 2, characterized in that: The content of the nicotinamide is 2.5-3.5wt%, and the content of the creatinine is 0.2-0.5wt%.

4. A cosmetic composition, characterized in that The cosmetic composition comprises creatinine and niacinamide, wherein the content of the niacinamide is 1.0-4.0 wt %, and the content of the creatinine is 0.0001-2.0 wt %.

5. The cosmetic composition according to claim 4, characterized in that The content of the nicotinamide is 2.0-4.0 wt %, and the content of the creatinine is 0.1-1.0 wt %.

6. The cosmetic composition according to claim 5, characterized in that The content of the nicotinamide is 2.5-3.5wt%, and the content of the creatinine is 0.2-0.5wt%.

7. A cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects, characterized in that: The cosmetic composition comprises, by weight: 0.1 to 0.5 parts of thickener, 3 to 7 parts of polyol, 0.1 to 5 parts of moisturizer, 2 to 5 parts of emulsifier, 1 to 20 parts of emollient oil, 0.5 to 4 parts of silicone oil, 1 to 4 parts of pH adjuster, 0.1 to 1 parts of preservative, 1.0 to 4.0 parts of niacinamide and 0.0001 to 2.0 parts of creatinine; Optionally, the thickener is selected from one or more of carbomer, sodium carbomer, ammonium polyacryloyldimethyltaurate, xanthan gum, acrylic acid (ester) / C10-30 alkyl acrylate cross-linked polymer, ammonium acryloyldimethyltaurate / VP copolymer; the polyol is selected from one or more of glycerol, butylene glycol, and propylene glycol; the moisturizer is selected from one or more of betaine, panthenol, allantoin, sodium hyaluronate, trehalose, and glyceryl glucoside; the emulsifier is selected from cetearyl alcohol, C14-22 alcohol and C12-20 alkyl glucoside and glucose mixture, behenyl alcohol, cetearyl alcohol and cetearyl glucoside and glucose mixture, polyol One or more of a mixture of glycerol-3, lecithin and phytosterols, stearic acid, cetearyl olive oil ester, sodium stearoyl lactylate and cetearyl alcohol; the emollient oil is selected from one or more of shea butter, ethylhexyl palmitate, jojoba oil, meadowfoam seed oil, caprylic capric triglyceride; the silicone oil is selected from one or more of dimethicone, dimethiconol, dimethicone / vinyl dimethicone crosspolymer; the pH adjuster is selected from one or more of sodium hydroxide and arginine; the preservative is selected from one or more of p-hydroxyacetophenone, phenoxyethanol, ethylhexylglycerin and hexylene glycol.

8. The cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects according to claim 7, characterized in that: The content of nicotinamide is 2.0 to 4.0 parts, and the content of creatinine is 0.1 to 1.0 parts; Optionally, the content of niacinamide is 2.5 to 3.5 parts, and the content of creatinine is 0.2 to 0.5 parts.

9. The cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects according to claim 7, characterized in that: 0.1-0.3 parts of carbomer, 0.1-0.3 parts of allantoin, 3-7 parts of glycerin, 0.3-0.7 parts of betaine, 2-6 parts of butylene glycol, 1.0-2.0 parts of cetearyl alcohol, 0.2-0.8 parts of a mixture of C14-22 alcohol and C12-20 alkyl glucoside and glucose, 0.5-1.5 parts of a mixture of cetearyl alcohol and cetearyl glucoside and glucose, 3-7 parts of shea butter, 1-5 parts of ethylhexyl palmitate, 0.2-0.8 parts of jojoba oil, 1-3 parts of polydimethylsiloxane, 0.01-0.07 parts of sodium hydroxide, 1.0-5.0 parts of niacinamide, 0.0001-2.0 parts of creatinine, 0.1-0.5 parts of p-hydroxyacetophenone, 0.2-0.6 parts of phenoxyethanol, and 0.01-0.2 parts of ethylhexylglycerin.

10. The method for preparing the cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects according to claim 9, characterized in that: The preparation method comprises the following steps: 1) Stir butylene glycol, glycerin and carbomer evenly for use; add allantoin and betaine to the mixture of butylene glycol, glycerin and carbomer, stir evenly, and then add them to the mixture of butylene glycol, glycerin and carbomer, heat at 80-85° C. and mix well to prepare phase A; 2) mixing cetearyl alcohol, C14-22 alcohol and C12-20 alkyl glucoside and glucose mixture, cetearyl alcohol and cetearyl glucoside and glucose mixture, shea butter, ethylhexyl palmitate, jojoba oil, and polydimethylsiloxane, heating to 80-85° C. and mixing well to prepare phase B; 3) adding water to sodium hydroxide as phase C, adding water to niacinamide and creatinine and mixing well as phase D, and mixing hydroxyacetophenone, phenoxyethanol, and ethylhexylglycerin as phase E; 4) Mix phases A and B and emulsify and homogenize for 5 to 8 minutes, then stir and cool to 48 to 50° C., add phase C and stir evenly, continue to add phase D and stir evenly, then stir and cool to 43 to 45° C., add phase E and stir evenly to obtain the cosmetic composition with antioxidant and / or anti-inflammatory and / or whitening effects.

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