Screening method of organic acid efficiently acting on skin target spot

Abstract

The invention focuses on the field of cosmetic material screening, and particularly relates to an organic acid screening technology efficiently acting on skin targets. The method is characterized by comprising the following steps: firstly, locking a key skin target receptor according to a target skin care effect; then, pre-selecting potential small molecular organic acids based on the use frequency; then, precise docking of a receptor and organic acid ligands is realized by using an advanced molecular docking technology, and binding energy of all ligands and the receptor is calculated; finally, according to the binding energy, the most adaptive organic acid is efficiently screened out. According to the technology, through computer simulation, the binding mode and affinity of micromolecule and macromolecular targets are deeply predicted, and an efficient organic acid ligand screening method is successfully constructed. The method can quickly and accurately predict the interaction between the organic acid and the skin target spot, assists in accurately customizing the optimal organic acid formula according to different skin care requirements, and realizes the maximization of the skin care effect.

Description

Technical Field

[0001] The invention relates to the field of cosmetic material screening, and in particular to a method for screening organic acids that effectively act on skin targets. Background Art

[0002] As the core functional ingredients in cosmetics, organic acids not only have the function of regulating pH balance, but also exhibit multiple significant effects such as acne removal, oil control, exfoliation, and skin brightening. However, the current selection and optimization of organic acids in cosmetic formulas mainly rely on empirical rules and repeated experimental processes. This method is not only costly and time-consuming, but also often fails to fully tap the potential effectiveness of organic acids.

[0003] Currently, the application of organic acids in the cosmetics field faces the following challenges:

[0004] There are many types of organic acids, and the interaction mechanism between them and skin tissue and other active ingredients has not been fully explained. This situation leads to a lack of scientific theoretical guidance in the formulation optimization process, making it difficult to quickly screen out the optimal combination through traditional empirical matching methods.

[0005] Existing methods for selecting organic acids are difficult to meet the personalized needs of precision skin care. When faced with customized needs for different skin care effects, these methods seem to be powerless and cannot quickly customize the most suitable organic acid formula.

[0006] The lack of a systematic organic acid efficacy evaluation system makes it difficult to objectively compare the performance of different organic acid combinations, thus affecting the optimization and upgrading of the formula.

[0007] In recent years, molecular docking technology has achieved remarkable achievements in the field of drug design. It can accurately predict the binding mode and affinity between small molecules and macromolecular targets through computer simulation of fine interactions between molecules. Although the application of this technology in the field of cosmetics is still in the initial exploration stage, especially in the practice of organic acid optimization, it is still relatively rare. However, with the rapid development of artificial intelligence and machine learning technology, the use of these cutting-edge technologies to optimize cosmetic formulas has shown great potential.

[0008] Therefore, it is urgent to develop a cosmetic organic acid optimization model based on molecular docking technology to achieve the following core objectives:

[0009] (1) Rapidly predict the interaction between organic acids and key skin targets (such as 5α-reductase, tyrosinase, etc.) to provide a scientific basis for formula design.

[0010] (2) Based on specific skin care efficacy targets, the optimal organic acid combination formula is intelligently recommended to meet the personalized needs of precise skin care.

[0011] (3) Through comparative analysis and efficacy verification with empirical formulas, the accuracy and reliability of predictions are continuously improved, providing the cosmetics industry with a more objective, scientific and efficient method for the preparation of organic acids.

[0012] In view of this, the present invention comes into being, aims to solve the above-mentioned problems and promote the innovation and development of the application of organic acids in the field of cosmetics. Summary of the invention

[0013] In view of the deficiencies in the prior art, the present invention innovatively proposes a method for efficiently screening organic acids that specifically bind to skin targets. This method cleverly integrates molecular docking technology, and with the help of advanced computer simulation methods, accurately simulates the intricate interaction process between macromolecular receptors and small molecule organic acid ligands, and then accurately predicts the binding mode and affinity strength between small molecules and skin target macromolecules. Based on this, we have successfully constructed a set of efficient and accurate organic acid screening methods. This method has significant advantages and can quickly and accurately predict the interaction between organic acids and various skin targets, providing strong scientific support for formula design. More importantly, it can also intelligently screen out the optimal organic acid combination and its precise concentration ratio according to different skin care efficacy target requirements, thereby meeting the diversified needs of personalized and precise skin care.

[0014] In order to achieve the above object, the technical solution adopted by the present invention is:

[0015] A method for screening organic acids that efficiently interact with skin targets comprises the following steps:

[0016] Step 1: Screen the corresponding skin target receptors by target efficacy; pre-select small molecule organic acids according to the frequency of use;

[0017] Step 2, molecular docking the receptor screened in step 1 with the small molecule organic acid ligand, and calculating the binding energy of all organic acid ligands and the receptor;

[0018] Step 3: According to the binding energy calculated in step 2, suitable organic acids are screened out.

[0019] The present invention provides a method for screening organic acids that efficiently interact with skin targets. First, the corresponding macromolecular receptors of the skin targets are screened out according to the target efficacy. For example, when pursuing whitening efficacy or acne scar removal efficacy, tyrosinase becomes the corresponding macromolecular receptor of the skin target. Next, ligands are pre-selected from organic acids commonly used on the market, such as lactobionic acid, tartaric acid, azelaic acid, salicylic acid, etc.; then, the macromolecular receptors are molecularly docked with small molecule organic acid ligands, and all the binding energies of the ligands and receptors are calculated; finally, the matching organic acids are screened out according to the size of the binding energy. The present invention uses molecular docking technology to simulate the interaction between macromolecular receptors and small molecule organic acid ligands by computer, predict the binding mode and affinity between small molecules and macromolecular targets, thereby constructing an efficient method for screening organic acid ligands, which can quickly predict the interaction between organic acids and skin targets.

[0020] Furthermore, in step 2, the specific operation of molecular docking is as follows:

[0021] Download the three-dimensional structure data of the organic acid ligand from PubChem database and convert it into mol2 format;

[0022] Obtaining structural data of the receptor from the UniProt database;

[0023] The molecules were docked with organic acid molecules using AutoDock Tools.

[0024] Furthermore, in step 3, the screening method is as follows: the organic acid ligand corresponding to a negative binding energy can bind to the receptor, and the larger the absolute value of the negative binding energy, the stronger the binding ability, and based on this, the suitable organic acid is screened out.

[0025] Furthermore, the method also includes:

[0026] Orthogonal tests are conducted on the adapted organic acids, combined with human efficacy verification, to determine the organic acids and organic acid usage concentrations that effectively act on skin targets.

[0027] Using orthogonal factor experiments, we can efficiently and labor-savingly determine the optimal concentration of organic acids. Then, through human efficacy verification, we can more accurately verify whether the selected organic acids and their concentrations are correct.

[0028] Preferably, the method further comprises: comparing the human efficacy verification results of the organic acids and the organic acid concentrations that act efficiently on the skin targets with the human efficacy verification results of the empirical formula, and the effect merit is the final organic acid and the organic acid concentration. The method of the present invention not only saves time and effort to determine the optimal concentration of the organic acid through the orthogonal factor test, but also further ensures the accuracy of the screening results through human efficacy verification. More importantly, by comparing the human efficacy verification results of the organic acids and the organic acid concentrations that act efficiently on the skin targets with the human efficacy verification results of the empirical formula, it is possible to scientifically and intuitively evaluate which scheme is more effective, thereby selecting the final organic acid and its optimal concentration. This comparative verification method not only improves the reliability of the screening results, but also provides strong data support for the research and development of new products, which helps to promote the innovative development of the cosmetics and pharmaceutical fields.

[0029] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0030] 1. Compared with traditional empirical formulas, the present invention uses molecular docking technology to more directly, clearly, scientifically, quickly and effectively screen out organic acids that match skin targets. Furthermore, combined with human efficacy verification, we can obtain more accurate types and concentrations of organic acids.

[0031] 2. By comparing with empirical formulas and verifying their efficacy, the present invention can continuously optimize the screening method, improve the accuracy of prediction, and provide a more objective, scientific and effective configuration method for organic acid formulas in the cosmetics field.

[0032] 3. The present invention can not only greatly improve the efficiency of cosmetic formula development, but also provide a scientific basis for the formulation of precise skin care plans, thereby promoting the cosmetics industry to move in a more precise and efficient direction. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Visualization results of 5α-reductase and organic acid ligands.

[0034] Figure 2 This is the visualization result of another group of 5α-reductase and organic acid ligands. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be elaborated in detail below. It is worth noting that the examples listed are only part of the many implementation methods of the present invention, and do not cover all of them. All other implementation forms that can be derived by ordinary technicians in this field without creative work on the basis of the embodiments of the present invention should be included in the protection scope covered by the present invention.

[0036] Example 1

[0037] The present invention provides a method for screening an organic acid with high efficiency on skin targets, comprising the following steps:

[0038] Step 1: Screen the corresponding skin target receptors by target efficacy; pre-select small molecule organic acids according to the frequency of use;

[0039] Step 2, molecular docking the receptor screened in step 1 with the small molecule organic acid ligand, and calculating the binding energy of all organic acid ligands and the receptor;

[0040] Step 3: According to the binding energy calculated in step 2, suitable organic acids are screened out.

[0041] For example, if you want to screen out organic acids with exfoliating effects, you can select the most important desmosome skin target for exfoliation. Commonly used acids on the market include lactic acid, azelaic acid, salicylic acid, glycolic acid, tartaric acid, malic acid, gluconolactone, and lactobionic acid. Pre-screen out suitable organic acids. The specific steps are:

[0042] 1. Molecular docking methods and results

[0043] 1. Methods

[0044] The three-dimensional structure of organic acids was downloaded from the PubChem database in SDF format and modified to mol2 format by OpenBabel 2.4.1 software. At the same time, the structure file of the target desmosome enzyme (UniProt ID: Q08188) was obtained from the UniProt database. Next, molecular docking was performed using AutoDockTools 1.5.6. The binding energy between the skin target receptor and the organic acid ligand is negative, indicating that docking can occur naturally, and the binding energy is positive, indicating that docking is unsuccessful. Finally, the docking results were visualized using PyMol software. (Docking box (Grid Box) condition parameters: x-dim, y-dim, z-dim) = (116, 86, 126) Spacing: 0.525 (x-center, y-center, z-center) = (0, 0, -0.111), the structure is shown in Table 1.

[0045] Table 1

[0046]

[0047]

[0048] 2. Binding energy of different organic acids to desmosome enzymes

[0049] According to the molecular docking results, the smaller the negative value of the binding energy between the skin target receptor and the small molecule organic acid ligand, the tighter the binding, and the more likely it is to achieve a therapeutic effect through the target. Table 2 shows the calculation results of the binding energy between desmosomes and various small molecule organic acid ligands.

[0050] Table 2

[0051] NO. Skin target receptors Small molecule organic acid ligand Binding energy (kCal / mol) 1 Desmosome lactic acid -4.47 2 Desmosome Azelaic acid -5.08 3 Desmosome Salicylic acid -4.67 4 Desmosome Glycolic acid -3.05 5 Desmosome tartaric acid -2.41 6 Desmosome Malic Acid -2.94 7 Desmosome Gluconolactone -4.19 8 Desmosome Lactobionic acid 43.15

[0052] After analyzing the binding energy of lactobionic acid with desmosomes, we found that its binding energy was positive. This result shows that lactobionic acid has no effect on skin target desmosomes. On the contrary, the binding energy of azelaic acid with desmosomes is negative, and the absolute value is the largest among all negative values, which shows that azelaic acid has a significant effect on skin target desmosomes and is the most effective ingredient.

[0053] In addition, salicylic acid, lactic acid and gluconolactone also showed certain effects on desmosomes, but the absolute values ​​of the negative binding energies of the three acids with desmosomes were smaller than the absolute values ​​of the binding energies of azelaic acid with desmosomes. Therefore, these three acids can be used as suboptimal choices.

[0054] 2. Human efficacy verification

[0055] In order to further obtain the appropriate concentration of organic acids and further verify the effectiveness of the organic acids screened by the above method, the present invention can also perform a three-factor three-level orthogonal test on the above screened organic acids, as well as human efficacy verification, the method and results are as follows:

[0056] According to the principle of orthogonal experimental design, the formula factors and level design of salicylic acid, azelaic acid and lactic acid combination were designed, as shown in Table 3.

[0057] Table 3

[0058]

[0059]

[0060] The details of the three-factor three-level orthogonal experiment are shown in Table 4.

[0061] Table 4

[0062] Experiment No. Azelaic acid Salicylic acid lactic acid 1 Level 1 Level 1 Level 1 2 Level 1 Level 2 Level 3 3 Level 1 Level 3 Level 2 4 Level 2 Level 1 Level 3 5 Level 2 Level 2 Level 2 6 Level 2 Level 3 Level 1 7 Level 3 Level 1 Level 2 8 Level 3 Level 2 Level 1 9 Level 3 Level 3 Level 3

[0063] According to the orthogonal experimental design, the experimental group is a gel product prepared by configuring organic acid with the existing formula auxiliary agent for subsequent human efficacy verification, as shown in Table 5.

[0064] Table 5

[0065]

[0066]

[0067] Carry out corresponding exfoliation efficacy test: the test method is shown in Table 6.

[0068] Table 6

[0069]

[0070] The results of orthogonal experimental analysis are shown in Table 7. It should be noted that the following test data adopts the average value.

[0071] Table 7

[0072]

[0073]

[0074] The data analysis results show that the best exfoliating composition for the early stages of acne is a combination of 2.0% azelaic acid, 0.5% salicylic acid, and 2.0% lactic acid in a specific ratio.

[0075] Furthermore, in order to ensure that the types and concentrations of organic acids selected are more accurate, we can also compare the human efficacy with empirical formulas. The specific method is as follows:

[0076] The gel product obtained by screening the organic acid combination of Example 1 through the above molecular docking-orthogonal test is set as screening group 1, and the mass percentage of each component of screening group 1 is: 2.0% azelaic acid, 0.5% salicylic acid, 2.0% lactic acid, 0.12% xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The organic acid gel product designed according to the empirical formula is set as empirical group 1, and the specific mass percentage of each component of empirical group 1 is: 0.15% azelaic acid, 0.2% salicylic acid, 5.5% lactic acid, 0.12 xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The human efficacy verification method of empirical group 1 is consistent with the human efficacy verification method of screening group 1, and the effect index test results are shown in Table 8.

[0077] Table 8

[0078]

[0079] It can be seen that the effect of screening group 1 is better, which can illustrate that the screening method of the present invention is faster and more accurate.

[0080] Example 2

[0081] The present invention provides a method for screening an organic acid with high efficiency on skin targets, comprising the following steps:

[0082] Step 1: Screen the corresponding skin target receptors by target efficacy; pre-select small molecule organic acids according to the frequency of use;

[0083] Step 2, molecular docking the receptor screened in step 1 with the small molecule organic acid ligand, and calculating the binding energy of all organic acid ligands and the receptor;

[0084] Step 3: According to the binding energy calculated in step 2, suitable organic acids are screened out.

[0085] For example, if you want to screen out organic acids with acne-removing effects, you can select the most important acne-removing 5α-reductase skin target. Commonly used acids on the market include lactic acid, azelaic acid, salicylic acid, glycolic acid, tartaric acid, malic acid, gluconolactone, and lactobionic acid. Pre-screen out suitable organic acids. The specific steps are:

[0086] 1. Molecular docking methods and results

[0087] 1. Methods

[0088] The three-dimensional structure of organic acid was downloaded from PubChem database in SDF format and modified into mol2 format by OpenBabel 2.4.1 software. At the same time, the structural file of target 5α-reductase (UniProt ID: P18405) was obtained from UniProt database. Next, molecular docking was performed using AutoDockTools 1.5.6. The binding energy of skin target receptor and organic acid ligand was negative, indicating that docking can occur naturally, and the binding energy was positive, indicating that docking was unsuccessful. Finally, the docking results were visualized using PyMol software. (Conditional parameters of docking box (Grid Box): x-dim, y-dim, z-dim) = (116, 86, 126) Spacing: 0.525 (x-center, y-center, z-center) = (0, 0, -0.111), the structure of organic acid is shown in Table 1 in Example 1.

[0089] 2. Results

[0090] According to the molecular docking results, the smaller the negative value of the binding energy between the skin target receptor and the small molecule organic acid ligand, the tighter the binding, and the more likely it is to achieve a therapeutic effect through the target. Table 9 shows the calculation results of the binding energy between 5α-reductase and various small molecule organic acid ligands.

[0091] Table 9

[0092]

[0093]

[0094] It is also possible to visualize the binding of skin target receptors to organic acid ligands, e.g. Figure 1 and Figure 2 As shown, Figure 1 The a in is the combination of 5α-reductase and lactic acid. Figure 1 The b in the formula is the combination of 5α-reductase and azelaic acid. Figure 1 The c in is the combination of 5α-reductase and salicylic acid. Figure 1 The d in is the combination of 5α-reductase and glycolic acid. Figure 2 The a in is the combination of 5α-reductase and tartaric acid. Figure 2 The b in the formula is the combination of 5α-reductase and malic acid. Figure 2 The c in is the combination of 5α-reductase and gluconolactone. Figure 2 The d in is the combination of 5α-reductase and lactobionic acid. It can be seen from Table 9 and the attached figure that after studying the effects of different organic acids on the skin target 5α-reductase, we came to the following conclusions: Studies have shown that lactobionic acid has no effect on 5α-reductase. This means that lactobionic acid may not be an effective ingredient in skin treatments targeting this target. Salicylic acid shows the best effect on the skin target 5α-reductase. As a commonly used topical dermatological drug, salicylic acid has the properties of reducing skin lipids and anti-inflammatory properties. Others are lactic acid, azelaic acid, glycolic acid, etc. Based on the above analysis, it is recommended to use an organic acid combination formula with salicylic acid as the main ingredient, supplemented by azelaic acid and lactic acid.

[0095] 2. Human efficacy verification

[0096] In order to further obtain the appropriate concentration of organic acids and further verify the effectiveness of the organic acids screened by the above method, the present invention can also perform a three-factor three-level orthogonal test on the above screened organic acids, as well as human efficacy verification, the method and results are as follows:

[0097] According to the principle of orthogonal experimental design, the formula factors and level design of the salicylic acid, azelaic acid and lactic acid combination were designed, as shown in Table 10.

[0098] Table 10

[0099] level Azelaic acid Salicylic acid lactic acid 1 1％ 0.2％ 0.5％ 2 2％ 0.5％ 1.0％ 3 5％ 1.0％ 2.0％

[0100] The three-factor three-level orthogonal experiment is shown in Table 11.

[0101] Table 11

[0102]

[0103]

[0104] According to the orthogonal experimental design, the experimental group is a gel product prepared by configuring organic acid with the existing formula auxiliary agent for subsequent human efficacy verification, as shown in Table 12.

[0105] Table 12

[0106]

[0107] Conduct corresponding acne removal efficacy test: the test method is shown in Table 13.

[0108] Table 13

[0109]

[0110] The results of the orthogonal experiment are shown in Table 14. It should be noted that the following test data are average values.

[0111] Table 14

[0112]

[0113]

[0114] According to the data analysis results, the best combination for mid-stage acne is a product containing 1.0% azelaic acid, 0.5% salicylic acid, and 1.0% lactic acid.

[0115] Furthermore, in order to ensure that the types and concentrations of organic acids selected are more accurate, we can also compare the human efficacy with empirical formulas. The specific method is as follows:

[0116] The gel product obtained by screening the organic acid combination of Example 2 through the above molecular docking-orthogonal test is set as screening group 2, and the mass percentage of each component of screening group 2 is: 1.0% azelaic acid, 0.5% salicylic acid, 1.0% lactic acid, 0.12% xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The organic acid gel product designed according to the empirical formula is set as empirical group 2, and the specific mass percentage of each component of empirical group 2 is: 0.15% azelaic acid, 0.2% salicylic acid, 5.5% lactic acid, 0.12 xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The human efficacy verification method of empirical group 2 is consistent with the human efficacy verification method of screening group 2, and the effect index test results are shown in Table 15. It should be noted that the following test data adopts the average value.

[0117] Table 15

[0118]

[0119] It can be seen that the effect of screening group 2 is better, which can illustrate that the screening method of the present invention is faster and more accurate.

[0120] Example 3

[0121] The present invention provides a method for screening an organic acid with high efficiency on skin targets, comprising the following steps:

[0122] Step 1: Screen the corresponding skin target receptors by target efficacy; pre-select small molecule organic q acids according to the frequency of use;

[0123] Step 2, molecular docking the receptor screened in step 1 with the small molecule organic acid ligand, and calculating the binding energy of all organic acid ligands and the receptor;

[0124] Step 3: According to the binding energy calculated in step 2, suitable organic acids are screened out.

[0125] For example, if you want to screen out organic acids that can remove acne scars, you can select the most important tyrosinase skin target for removing acne scars. Commonly used acids on the market include lactic acid, azelaic acid, salicylic acid, glycolic acid, tartaric acid, malic acid, gluconolactone, and lactobionic acid. Pre-screen out suitable organic acids. The specific steps are:

[0126] 1. Molecular docking methods and results

[0127] 1. Methods

[0128] The three-dimensional structure of organic acid was downloaded from PubChem database as SDF format and modified into mol2 format by OpenBabel 2.4.1 software. At the same time, the structure file of target tyrosinase (UniProt ID: P14679) was obtained from UniProt database. Next, molecular docking was performed using AutoDockTools 1.5.6. The binding energy of skin target receptor and organic acid ligand was negative, indicating that docking can occur naturally, and the binding energy was positive, indicating that docking was unsuccessful. Finally, the docking results were visualized using PyMol software. (Conditional parameters of docking box (Grid Box): x-dim, y-dim, z-dim) = (116, 86, 126) Spacing: 0.525 (x-center, y-center, z-center) = (0, 0, -0.111), the structure of organic acid is shown in Table 1 in Example 1.

[0129] 2. Results

[0130] According to the molecular docking results, the smaller the negative value of the binding energy between the skin target receptor and the small molecule organic acid ligand, the tighter the binding, and the more likely it is to achieve a therapeutic effect through the target. Table 16 shows the calculation results of the binding energy between tyrosinase and various small molecule organic acid ligands.

[0131] Table 16

[0132] NO. Skin target receptors Small molecule ligands Binding energy (kCal / mol) 1 Tyrosinase lactic acid -4.3 2 Tyrosinase Azelaic acid .3.29 3 Tyrosinase Salicylic acid .3.08 4 Tyrosinase Glycolic acid .2.29 5 Tyrosinase tartaric acid .2.87 6 Tyrosinase Malic Acid .2.66 7 Tyrosinase Gluconolactone .2.55 8 Tyrosinase Lactobionic acid 1.64

[0133] After analyzing the binding energy of lactobionic acid and tyrosinase, we found that its binding energy is positive. This result shows that lactobionic acid has no effect on skin target tyrosinase. On the contrary, the binding energy of lactic acid and tyrosinase is negative, and the absolute value is the largest among all negative values, which shows that lactic acid has a significant effect on skin target tyrosinase and is the most effective ingredient.

[0134] In addition, azelaic acid, salicylic acid, and tartaric acid also show a certain effect on tyrosinase, but the absolute values ​​of the negative binding energy of these three acids are smaller than the absolute value of the binding energy of lactobionic acid with tyrosinase. Therefore, these three acids can be used as suboptimal choices.

[0135] 2. Human efficacy verification

[0136] In order to further obtain the appropriate concentration of organic acids and further verify the effectiveness of the organic acids screened by the above method, the present invention can also perform a three-factor three-level orthogonal test on the above screened organic acids, as well as human efficacy verification, the method and results are as follows:

[0137] According to the principle of orthogonal experimental design, the formula factors and level design of the salicylic acid, azelaic acid and lactic acid combination were designed, as shown in Table 17.

[0138] Table 17

[0139] level Azelaic acid Salicylic acid lactic acid 1 1％ 0.2％ 0.5％ 2 2％ 0.5％ 1.0％ 3 5％ 1.0％ 2.0％

[0140] The three-factor three-level orthogonal experiment is shown in Table 18.

[0141] Table 18

[0142] Experiment No. Azelaic acid Salicylic acid lactic acid 1 Level 1 Level 1 Level 1 2 Level 1 Level 2 Level 3 3 Level 1 Level 3 Level 2 4 Level 2 Level 1 Level 3 5 Level 2 Level 2 Level 2 6 Level 2 Level 3 Level 1 7 Level 3 Level 1 Level 2 8 Level 3 Level 2 Level 1 9 Level 3 Level 3 Level 3

[0143] According to the orthogonal experimental design, the experimental group is a gel product prepared by configuring organic acid with the existing formula auxiliary agent for subsequent human efficacy verification, as shown in Table 19.

[0144] Table 19

[0145]

[0146] Conduct corresponding acne scar removal efficacy test: the test method is shown in Table 20.

[0147] Table 20

[0148]

[0149]

[0150] The results of orthogonal experimental analysis are shown in Table 21.

[0151] Table 21

[0152]

[0153] Therefore, according to the data analysis results, the best composition for fading acne marks after acne is a product containing 1.0% azelaic acid, 0.2% salicylic acid, and 5.0% lactic acid.

[0154] Furthermore, in order to ensure that the types and concentrations of organic acids selected are more accurate, we can also compare the human efficacy with empirical formulas. The specific method is as follows:

[0155] The gel product obtained by screening the organic acid combination of Example 3 through the above molecular docking-orthogonal test is set as screening group 3. The mass percentage of each component of screening group 3 is: 1.0% azelaic acid, 0.2% salicylic acid, 5.0% lactic acid, 0.12% xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The organic acid gel product designed according to the empirical formula is set as empirical group 3. The specific mass percentage of each component of empirical group 3 is: 0.15% azelaic acid, 0.2% salicylic acid, 5.5% lactic acid, 0.12 xanthan gum (CG-T), 4% butylene glycol, 2% glycerol polyether-26 (G26), 1% betaine, 1.1% PHL preservative, and the balance is water. The human efficacy verification method of empirical group 3 is consistent with the human efficacy verification method of screening group 3, and the effect index test results are shown in Table 22. It should be noted that the following test data adopts the average value.

[0156] Table 22

[0157]

[0158] It can be seen that the effect of screening group 3 is better, which can illustrate that the screening method of the present invention is faster and more accurate.

[0159] This invention uses advanced molecular docking technology and precise computer simulation to deeply explore the interaction mechanism between macromolecular receptors and small molecule organic acid ligands, and successfully predicts the binding mode and affinity of small molecules to skin target macromolecules. Based on this, we have constructed an efficient and accurate organic acid ligand screening system, which can quickly and accurately evaluate the interaction effect of organic acids with various skin targets.

[0160] This innovative technology is not only applicable to the specific targets in the above-mentioned embodiments, but also has a wide range of applicability, and can accurately screen targets for different skin care effects. For example, in terms of anti-wrinkle and firming effects, we screen organic acids for metalloproteinase (MMPs) targets; in terms of soothing effects, we focus on nuclear transcription factor-κB (NF-κB) targets; at the same time, for barrier repair effects, we can select epidermal growth factor receptor (EGFR) targets for screening; in addition, in terms of antioxidant effects, we can select peroxisome proliferator-activated receptor γ (PPARγ) targets.

[0161] Through the method of the present invention, we can quickly lock in the best organic acid combination, providing a more objective, scientific and effective configuration strategy for the organic acid formula design in the cosmetics field.

[0162] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for screening organic acids that efficiently interact with skin targets, characterized in that: The following steps are involved: Step 1: Screen the corresponding skin target receptors by target efficacy; pre-select small molecule organic acids according to the frequency of use; Step 2, molecular docking the receptor screened in step 1 with the small molecule organic acid ligand, and calculating the binding energy of all organic acid ligands and the receptor; Step 3: According to the binding energy calculated in step 2, suitable organic acids are screened out.

2. The screening method according to claim 1, characterized in that In step 2, the specific operation of molecular docking is as follows: Download the three-dimensional structure data of the organic acid ligand from PubChem database and convert it into mol2 format; Obtaining structural data of the receptor from the UniProt database; Molecular docking of the receptor with organic acids was performed using AutoDock Tools.

3. The screening method according to claim 1, characterized in that The screening method in step 3 is: The organic acid ligand corresponding to a negative binding energy can bind to the receptor. The larger the absolute value of the negative binding energy, the stronger the binding ability. Based on this, suitable organic acids are screened out.

4. The screening method according to claim 3, characterized in that The following steps are also included: The organic acids screened out in step 3 are subjected to orthogonal test methods and combined with human efficacy verification to ultimately determine the organic acids and their usage concentrations that are highly effective with skin targets.

5. The screening method according to claim 4, characterized in that The following steps are also included: The human efficacy verification results of organic acids and organic acid usage concentrations that effectively act on skin targets are compared with the human efficacy verification results of empirical formulas, and the effect merit is the final organic acid and organic acid usage concentration.

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