Method for evaluating tenderness of water aqua product

Abstract

The method comprises the following steps: washing, unloading and molding, setting a blank control group and a sample group, collecting subjective feeling data, collecting objective measurement data, processing and calculating the data, and outputting an evaluation result, data processing and calculation are carried out according to acquired subjective feeling data and objective measurement data of a blank control group and a sample group; respectively calculating comprehensive evaluation indexes of the blank control group and the sample group according to the following formula; and finally, comparing the calculated comprehensive evaluation index of the sample group with the comprehensive evaluation index of the blank control group to obtain an evaluation result, and outputting the evaluation result.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetic product quality evaluation, and in particular to a method for evaluating the mildness of an aqueous product. Background Art

[0002] Currently, there are many methods to evaluate the mildness of water-based cosmetics. In vitro biological tests cover cytotoxicity experiments, chicken embryo chorioallantoic membrane tests, zebrafish embryo tail fin incision neutrophil tests, etc.; in vitro model reconstruction tests include reconstructed epidermal model tissue vitality method and keratinocyte interleukin-8 production inhibition method; human tests include subjective evaluation method, semi-subjective evaluation method and objective evaluation method; these methods evaluate the irritation of water-based cosmetics to cells, tissues and human skin from different angles to determine their mildness.

[0003] Among them, the in vitro biological test method has the following disadvantages:

[0004] Cytotoxicity testing: Due to differences between cell culture environments and the complex physiological environment of human skin, in vitro cell responses cannot fully represent actual human exposure. Furthermore, using a single cell type (e.g., using only one type of keratinocyte) makes it difficult to fully reflect the combined effects of cosmetics on multiple skin cells (e.g., fibroblasts, melanocytes, etc.).

[0005] The chick chorioallantoic membrane (CAM) test: The chick embryo's skin tissue structure and physiological mechanisms differ from those of humans, and its response pattern to cosmetic ingredients may differ from that of humans. Furthermore, this test is highly subjective in its scoring, requiring high technical skills and chick embryo conditions. The results are easily affected by the experimental process, resulting in poor reproducibility.

[0006] Neutrophil granulocyte assay using zebrafish embryo tail fin incision: Although zebrafish embryos share some similarities with humans in their early developmental stages, their growth environment and physiological systems differ significantly from those of humans. Furthermore, when working with cosmetics containing complex ingredients, the limited metabolic capacity of zebrafish embryos may not accurately reflect the human body's actual metabolism and response to these ingredients.

[0007] The in vitro reconstruction model testing method has the following disadvantages:

[0008] Reconstructing the tissue vitality of the epidermal model: The structure of this model is relatively simple and lacks the complete structure and function of human skin. For example, it does not have accessory structures such as sebaceous glands and sweat glands. Therefore, it cannot fully simulate the complex physiology and barrier function of real skin, resulting in possible deviations in its evaluation of the mildness of cosmetics and is not comprehensive.

[0009] Keratinocyte interleukin-8 production inhibition assay: This method primarily focuses on the inflammatory factor interleukin-8, assessing mildness from the perspective of a single inflammatory marker, while ignoring other potential stimulatory mechanisms and inflammation-related indicators. Furthermore, variations in cell culture conditions and the heterogeneity of individual cells can easily lead to poor reproducibility of experimental results.

[0010] The human testing method has the following disadvantages:

[0011] Semi-subjective and objective evaluation methods: When testing on a specific population, long-term follow-up is required, and recruiting suitable subjects can be challenging, increasing R&D costs and reducing efficiency. Furthermore, significant differences between individual subjects, such as skin type, lifestyle, and allergy history, can increase variability in results, impacting the accuracy of the assessment.

[0012] Subjective evaluation: Consumers' subjective assessments of the mildness of cosmetics are easily influenced by factors such as personal preferences, expectations, and usage habits. This makes it difficult to standardize evaluation criteria, resulting in highly subjective results and relatively low scientific validity. Furthermore, the complex and diverse environments in which consumers actually use cosmetics make it difficult to eliminate the influence of other factors (such as environmental changes and the use of other products) on test results.

[0013] In summary, existing methods for evaluating the mildness and non-irritation efficacy of aqueous products generally have the following limitations: insufficient safety, such as lactic acid sting / capsaicin sting causing persistent erythema and stinging in sensitive skin subjects; long test cycles and high costs; highly subjective results; inability to fully simulate the complex physiology and barrier function of real skin; differences in human skin tissue structure and physiological mechanisms; significant differences in growth environment and physiological system from the human body; and a lack of applicability to actual usage scenarios. Summary of the Invention

[0014] The object of the present invention is to provide a method for evaluating the mildness of aqueous products, which can effectively solve the above-mentioned technical problems existing in the prior art.

[0015] The present application discloses a method for evaluating the mildness of an aqueous solution product, which comprises the following steps:

[0016] Washing and Unloading Modeling: The left and right sides of the faces of multiple subjects were washed and unloaded six times using a soap-based cleanser. Each wash lasted for 1 minute, and after the last wash, the subjects waited 10 minutes to make the left and right sides of their faces resemble those of sensitive skin with mildly damaged skin barriers. The left and right sides of the faces of the subjects had healthy, non-sensitive, medium-dry skin.

[0017] Set up a blank control group and a sample group: randomly apply the membrane cloths fully soaked in deionized water and the test solution sample to the left and right sides of the face of the subjects who have completed the washing and modeling for 10 minutes;

[0018] Subjective feeling data collection: After washing and removing the model, 30 seconds after applying the mask, 5 minutes after applying the mask, and 10 minutes after applying the mask, sensory feedback including but not limited to tingling, itching, burning, and dryness was collected on the left and right sides of each subject's face before and after applying the blank control group and the sample group. The levels of sensory feedback in the four aspects were quantified from no feeling to severe feeling as [w 下限 , w 上限 】The greater the feeling, the greater the score;

[0019] Objective measurement data collection: After modeling and removal, and after removing the patch, use a measuring instrument to measure the transepidermal water loss (TEWL) and skin color a* value on the left and right sides of each subject's face before and after applying the blank control group and the sample group.

[0020] Data processing and calculation: Based on the subjective perception data and objective measurement data collected from the blank control group and sample group, the comprehensive evaluation index of the blank control group and sample group was calculated according to the following formula (1):

[0021]

[0022] Among them, Q is the comprehensive evaluation index, w 1ij 、w 2ij 、w 3ij 、w 4ij The scores of each sensory feedback of each subject collected at four time points, x 1i 、x 2i The TEWL value of each subject collected at two time points, y 1i 、y 2i is the a* value of each subject collected at two time points, m is the number of subjects, A and B are the weights of subjective indicators and objective indicators, respectively;

[0023] Evaluation result output: Compare the comprehensive evaluation index of the sample group and the comprehensive evaluation index of the blank control group calculated by formula (1). If:

[0024] If the comprehensive evaluation index of the sample group is less than that of the blank control group, the evaluation result is output that the water-based product has a repairing and soothing effect;

[0025] If the comprehensive evaluation index of the sample group equals the comprehensive evaluation index of the blank control group, the evaluation result of the aqueous solution product is mild and non-irritating.

[0026] If the comprehensive evaluation index of the sample group is greater than that of the blank control group, the evaluation result that the aqueous product has skin irritation is output.

[0027] Preferably, the steps of data processing and calculation further include:

[0028] The change in TEWL value of each subject x 2i -x 1i and the change in a* value y 2i -y 1i The first correlation analysis was performed to obtain the threshold interval of the relationship between TEWL value and a* value. The subjective feeling data and objective measurement data of the subjects outside the threshold interval of the relationship between TEWL value and a* value were eliminated and the valid data were retained. Then the calculation was performed according to formula (1). In formula (1), m is the number of valid subjects corresponding to the retained valid data, and the TEWL value change x is 2i -x 1i Represents the objective change in the subject's barrier function, the change in a* value y 2i -y 1i Represents changes in the subjects' inflammatory response.

[0029] Preferably, the steps of data processing and calculation further include:

[0030] The total value of TEWL value and a* value of each subject after washing and modeling is x 1i +y 1i The total value of the four sensory feedbacks after applying the film for 10 minutes is w 4i1 +w 4i2 +w 4i3 +w 4i4 The second correlation analysis is performed to obtain the objective-subjective first relationship threshold interval. The subjective feeling data and objective measurement data of the subjects outside the objective-subjective first relationship threshold interval are eliminated and the valid data are retained and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0031] Preferably, the steps of data processing and calculation further include:

[0032] The total value of TEWL value and a* value of each subject after removing the patch cloth is x 1i +y 1i The total value of the four sensory feedback after washing and modeling is w 1i1 +w 1i2 +w 1i3 +w 1i4Perform a second correlation analysis to obtain an objective-subjective second relationship threshold interval. Exclude the subjective perception data and objective measurement data of the subjects outside the objective-subjective second relationship threshold interval, retain the valid data, and then calculate according to formula (1). Here, m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0033] Preferably, the step of data processing and calculation further includes:

[0034] Sum the scores of the four sensory feedbacks collected for each subject at each time point Sort them in ascending order, and exclude the m1 data at the front and end of the sequence to obtain an optimized subjective index interval, where 1%*m < m1 < 5%*m; exclude the subjective perception data and objective measurement data of the subjects outside the optimized subjective index interval, retain the valid data, and then calculate according to formula (1). Here, m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0035] Preferably, the step of data processing and calculation further includes:

[0036] For each subject, respectively, the change amount x of the TEWL value 2i -x 1i and the change amount y of the a* value 2i -y 1i Sort them in ascending order, and exclude the m2 data at the front and end of the sequence to obtain an optimized objective index interval, where 1%*m < m2 < 5%*m; exclude the subjective perception data and objective measurement data of the subjects outside the optimized objective index interval, retain the valid data, and then calculate according to formula (1). Here, m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0037] Preferably, the left and right faces of the subject are intact skin without open wounds, damage, or ulceration, and the water content of the stratum corneum is lower than 65 C.U.

[0038] Preferably, use a TEWAMeter TM300 to measure the trans-epidermal water loss rate TEWL value and a Colorimeter CL400 to measure the skin color a* value.

[0039] Preferably, A = 50%, B = 50%.

[0040] Preferably, the grades of the sensory feedback in four aspects include 5 grades: no feeling, slight, moderate, obvious, and severe, and each grade corresponds to a quantified score of [0, 4].

[0041] Compared with the prior art, the mildness evaluation method of an aqueous product provided by the embodiment of the present invention has the following advantages:

[0042] 1. Innovation in barrier simulation technology: Through soap-based cleansing combined with real-time TEWL detection, the degree of barrier damage is precisely controlled through standardized cleaning times (6 times) and time (60 seconds / time), so that the skin condition (transepidermal water loss rate, stratum corneum permeability) in the test area is highly consistent with mildly sensitive skin, solving the core problem of the disconnect between in vitro models and human body reactions.

[0043] 2. Use the saturated patch test method: Use the membrane cloth saturation immersion method to increase the contact area and penetration rate between the sample and the skin, closely fitting the high permeability characteristics of the aqueous sample, thereby improving the correlation between the evaluation results and the actual consumer experience.

[0044] 3. Improved safety: The modeling process only temporarily affects the superficial layers of the stratum corneum, and the skin barrier naturally repairs itself within 24 hours. Furthermore, the non-invasive nature of the mask patch improves test subject acceptance compared to traditional sensitive skin testing, without the risk of long-term irritation.

[0045] 4. It greatly improves the test willingness of subjects, does not need to rely on specific populations, and is easier to recruit subjects, solving the problem of difficulty in recruiting subjects with naturally sensitive skin.

[0046] 5. This method has low experimental cost, does not require additional instruments and equipment, is simple and easy to operate, does not require high operator requirements, and the experimental results are more intuitive and can quantify the response to stimulation.

[0047] 6. This method can be effectively applied to the mild and non-irritating evaluation of aqueous samples, plays an important role in sample safety, has good practical significance and application value, and can be used for high-throughput sample screening. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In order to more clearly illustrate the technical solution of the present invention, the following is a brief introduction to the drawings required for use in the implementation. Obviously, the drawings described below are only some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0049] Figure 1 This is a flow chart of a method for evaluating the mildness of an aqueous product provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0050] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0051] refer to Figure 1 The embodiment of the present invention provides a method for evaluating the mildness of an aqueous product, which includes steps S1 to S6:

[0052] S1. Washing and Unloading Modeling: The left and right sides of the faces of multiple subjects were washed and unloaded six times using a soap-based facial cleanser, with each wash lasting 1 minute. After the final wash, the subjects waited 10 minutes until the left and right sides of their faces were in a state close to that of mildly damaged sensitive skin barriers. The left and right sides of the faces of the subjects had healthy, non-sensitive, medium-dry skin.

[0053] Specifically, the left and right sides of the face of the subject have intact skin without open wounds, damage, or ulcers, and the moisture content of the stratum corneum is less than 65 C.U.

[0054] S2. Set up a blank control group and a sample group: randomly apply the membrane cloths fully soaked in deionized water and the test solution sample to the left and right sides of the face of the subjects who have completed the washing and modeling for 10 minutes;

[0055] S3. Subjective feeling data collection: After washing and removing the model, 30 seconds after applying the mask, 5 minutes after applying the mask, and 10 minutes after applying the mask, sensory feedback including stinging, itching, burning, and dryness was collected from the left and right sides of each subject's face before and after applying the blank control group and the sample group. The levels of sensory feedback in the four aspects were quantified from no feeling to severe feeling as [w 下限 , w 上限 】The greater the feeling, the greater the score;

[0056] In specific implementation, the levels of sensory feedback in four aspects can be set to include no feeling, slight, moderate, obvious, and severe, and each level corresponds to a quantitative score of [0, 4].

[0057] S4. Objective measurement data collection: After modeling is completed and after the application of the patch is removed (preferably, 10 minutes after the sample is removed), use a measuring instrument to measure the transepidermal water loss (TEWL) value and skin color a* value of each subject's left and right sides of the face before and after the blank control group and the sample group are applied;

[0058] For example, the TEWAMeter TM300 is used to measure the transepidermal water loss rate TEWL value and the ColorimeterCL400 is used to measure the skin color a* value to evaluate the effect of the sample on the skin barrier repair ability and soothing ability.

[0059] S5. Data processing and calculation: Based on the subjective perception data and objective measurement data collected from the blank control group and the sample group, the comprehensive evaluation index of the blank control group and the sample group is calculated according to the following formula (1):

[0060]

[0061] Among them, Q is the comprehensive evaluation index, w 1ij 、w 2ij 、w 3ij 、w 4ij The scores of each sensory feedback of each subject collected at four time points, x 1i 、x 2i The TEWL value of each subject collected at two time points, y 1i 、y 2i is the a* value of each subject collected at two time points, m is the number of subjects, A and B are the weights of subjective indicators and objective indicators, respectively;

[0062] Understandable, w 1ij 、w 2ij 、w 3ij 、w 4ij The value of [w 下限 , w 上限 】within the scope of.

[0063] Preferably, A=50%, B=50%.

[0064] S6. Evaluation result output: Compare the comprehensive evaluation index of the sample group and the comprehensive evaluation index of the blank control group calculated by formula (1). If:

[0065] If the comprehensive evaluation index of the sample group is less than that of the blank control group, the evaluation result is output that the water-based product has a repairing and soothing effect;

[0066] If the comprehensive evaluation index of the sample group equals the comprehensive evaluation index of the blank control group, the evaluation result of the aqueous solution product is mild and non-irritating.

[0067] If the comprehensive evaluation index of the sample group is greater than that of the blank control group, the evaluation result that the aqueous product has skin irritation is output.

[0068] It can be understood that the present invention has shown through a large number of experimental studies that whether the aqueous solution sample is mild and non-irritating has a corresponding relationship with subjective scores and objective indicators; based on this research result, the present invention evaluates the mildness and non-irritation of the aqueous solution sample by combining the subjective scores and objective indicators of the blank control group and the test sample group.

[0069] Subjective indicators are weighted 50% and objective indicators are weighted 50%. Objective and subjective indicators are equally important. This model is used to evaluate the mildness of aqueous products. Mildness is assessed using a comprehensive index that includes both subjective scores and objective measurements.

[0070] That is: mildness and non-irritation comprehensive index = 50% × average subjective total score + 50% × average objective total score.

[0071] Average total objective score = 1 / 2 * 50% * (average change in TEWL value + average change in a* value)

[0072] Furthermore, the average of the subjective total score is obtained from at least one of the subject's self-assessment questionnaire or intelligent instrument (e.g., EVALWISE AI).

[0073] Preferably, the average of the subjective total score is obtained from the subject's self-assessment questionnaire.

[0074] in:

[0075] 1) Average total subjective score = (sum of stinging + itching + burning + dryness scores at each collection time point) / total number of participants; lower scores indicate less irritating samples; higher scores indicate more irritating samples.

[0076] 2) The average change in TEWL value represents the objective change in the barrier function of the subjects

[0077] average value Where x = the value of the individual parameter measurement, m = the number of valid subjects

[0078]

[0079] in Average TEWL value (e.g. 10 minutes after removing the patch)

[0080] in

[0081] It can be understood that the smaller the average change in TEWL value, the better the barrier repair.

[0082] 3) The average change in a* value represents the change in the subject's inflammatory response

[0083] average value Where y = individual parameter measurement, m = number of valid subjects

[0084]

[0085] in

[0086] in

[0087] It can be understood that the smaller the average change in the a* value, the better the redness reduction effect.

[0088] It is understood that in order to make the evaluation results of the mildness evaluation method of an aqueous product provided by the present invention more accurate, the collected data can be cleaned (to eliminate abnormal data) before calculation. The data cleaning (to eliminate abnormal data) process includes at least one of the following methods:

[0089] Data cleaning method 1:

[0090] The change in TEWL value of each subject x 2i -x 1i and a* value change y 2i -y 1i The first correlation analysis was performed to obtain the threshold interval of the relationship between TEWL value and a* value. The subjective feeling data and objective measurement data of the subjects outside the threshold interval of the relationship between TEWL value and a* value were eliminated and the valid data were retained. Then the calculation was performed according to formula (1). In formula (1), m is the number of valid subjects corresponding to the retained valid data, and the TEWL value change x is 2i -x 1i Represents the objective change in the subject's barrier function, the change in a* value y 2i -y 1i Represents changes in the subjects' inflammatory response.

[0091] It can be understood that under normal data conditions, the change in TEWL value of each subject x 2i -x 1i and a* value change y 2i -y 1iThe correlation between them (for example, the difference or ratio) is often within a reasonable threshold range. When the data is abnormal (due to equipment failure, operational errors, individual abnormal reactions of subjects or environmental interference, the data deviates significantly from the expected or group rules), resulting in the data being too large or too small, the correlation between the two will often exceed this reasonable threshold range. At this time, the credibility of the subjective feeling data and objective measurement data collected for the subject is low, and they are not calculated as evaluation indicators and need to be deleted. It is understandable that the above threshold range can be pre-set to a range, for example, it can be set to [30%*p, 70%*p], where p is the calculated change in TEWL value of each subject x 2i -x 1i and the change in a* value y 2i -y 1i The mean or median of the association (e.g., difference or ratio) between the two groups.

[0092] Data cleaning method 2:

[0093] The total value of TEWL value and a* value of each subject after washing and modeling is x 1i +y 1i The total value of the four sensory feedbacks after applying the film for 10 minutes is w 4i1 +w 4i2 +w 4i3 +w 4i4 The second correlation analysis is performed to obtain the objective-subjective first relationship threshold interval. The subjective feeling data and objective measurement data of the subjects outside the objective-subjective first relationship threshold interval are eliminated and the valid data are retained and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0094] Similarly, under normal data conditions, the total value of TEWL and a* value of each subject after washing and modeling is x 1i +y 1i And the total value of the four sensory feedback after applying the film for 10 minutes 4i1 +w 4i2 +w 4i3 +w 4i4The correlation between them (for example, the difference or ratio) is often within a reasonable threshold range. When the data is abnormal (due to equipment failure, operational errors, individual abnormal reactions of subjects or environmental interference, the data deviates significantly from the expected or group rules), resulting in the data being too large or too small, the correlation between the two will often exceed this reasonable threshold range. At this time, the credibility of the subjective feeling data and objective measurement data collected for the subject is low, and they are not calculated as evaluation indicators and need to be deleted. It can be understood that the above threshold range can be pre-set to a range, for example, it can be set to [30%*p, 70%*p], where p is the total value x of the TEWL value and a* value calculated for each subject after the washing and modeling is completed. 1i +y 1i And the total value of the four sensory feedback after applying the film for 10 minutes 4i1 +w 4i2 +w 4i3 +w 4i4 The mean or median of the association (e.g., difference or ratio) between the two groups.

[0095] Data cleaning method three:

[0096] The total value of TEWL value and a* value of each subject after removing the patch cloth is x 1i +y 1i The total value of the four sensory feedback after washing and modeling is w 1i1 +w 1i2 +w 1i3 +w 1i4 The second correlation analysis is performed to obtain the objective-subjective second relationship threshold interval. The subjective feeling data and objective measurement data of the subjects outside the objective-subjective second relationship threshold interval are eliminated and the valid data are retained and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0097] Similarly, under normal data conditions, the total value of TEWL value and a* value of each subject after removing the patch is x 1i +y 1i The total value of the four sensory feedback after washing and modeling is w 1i1 +w 1i2 +w 1i3 +w 1i4The association (such as difference or ratio) between them often lies within a reasonable threshold range. When the data is abnormal (when the data deviates significantly from the expected or group pattern due to equipment failure, operation error, individual abnormal reaction of the subject, or environmental interference, etc.), resulting in the data being too large or too small, it often makes the association between the two exceed this reasonable threshold range. At this time, the credibility of the subjective perception data and objective measurement data collected for this subject is relatively low and is not used as an evaluation index for calculation, and it needs to be deleted. It can be understood that the above-mentioned threshold range can be set in advance within a certain range, for example, it can be set as [30%*p, 70%*p], where p is the total value x of the TEWL value and a* value of each subject after removing the application film 1i +y 1i and the total value w of its four sensory feedbacks after completing the washing, unloading, and modeling 1i1 +w 1i2 +w 1i3 +w 1i4 the average or median of the association (such as difference or ratio) between them

[0098] It can be understood that in order to make the evaluation result of a mildness evaluation method for an aqueous product provided by the present invention more accurate, in addition to performing data cleaning (to exclude abnormal data) on the collected data, data optimization can also be performed before calculation. Among them, the data optimization process includes at least one of the following methods:

[0099] Data optimization method one:

[0100] Sum the scores of the four sensory feedbacks collected for each subject at each time point Sort them from small to large in sequence, and剔除 the m1 data ranked at the front and end of the sequence to obtain an optimized subjective index range, 1%*m < m1 < 5%*m;剔除 the subjective perception data and objective measurement data of the subjects outside the optimized subjective index range, retain the valid data, and then calculate according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data

[0101] Data optimization method two:

[0102] The change amount x of the TEWL value collected for each subject respectively 2i -x 1i and the change amount y of the a* value 2i -y 1iSort them in ascending order, and obtain the optimized objective index interval by excluding the first m2 and the last m2 data in the sequence, where 1%*m < m2 < 5%*m; exclude the subjective feeling data and objective measurement data of the subjects outside the optimized objective index interval, retain the valid data, and then calculate according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

[0103] Compared with the existing methods for evaluating the mildness and non-irritation of aqueous products, the core technical problems solved by the present invention are: insufficient simulation authenticity (systematic deviation between existing in vitro models / animal experiments and actual human reactions), efficiency and cost defects (long test cycle, reliance on high-cost equipment and scarce sensitive skin populations), and safety risks (traditional methods (such as lactic acid stinging test) may cause persistent skin damage); this method ensures that it only temporarily affects the superficial layer of the stratum corneum, the film cloth application is non-invasive, and the skin barrier can naturally repair within 24 hours, without long-term stimulation risks, conforms to the actual use scenario, and the evaluation results are objective and reliable.

[0104] To make the purposes, technical solutions and advantages of the embodiments and comparative examples of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. Where specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. The components of the formulations in the embodiments, unless otherwise specified, are all conventional commercially available samples. The soap-based facial cleanser was provided by the company (INCI:); the positive sample known to be non-irritating and having soothing and repairing effects was provided by the company (INCI:); the negative sample known to be irritating was provided by the company (INCI:); deionized water was provided as a blank control.

[0105] Specific Example 1 Optimization and Verification of Model Establishment Parameters

[0106] 1. Determine the subjects: Recruit healthy subjects with dry and normal skin, with the water content of the stratum corneum lower than 65 C.U., non-sensitive skin, and no skin integrity damage such as open wounds, breaks, ulcers, etc. in the test area.

[0107] 2. Control group setting: Arrange a blank control group (deionized water), a positive control group (a sample known to be non-irritating and having soothing and repairing effects), and a negative control group (a sample known to be irritating). Necessity of negative / positive control: Only used in the model verification stage (not necessary for daily tests).

[0108] 3. By verifying the effects of the number of cleaning times, cleaning time and waiting time on the skin barrier damage model, determine the optimal parameter combination as (cleaning 6 times, 1 minute each time, waiting for 10 minutes) to ensure the repeatability and safety of the model.

[0109] 4. This experiment will test different combinations of the following three factors:

[0110] Washing times: 3 to 7 times, 6 times under optimal conditions

[0111] Cleaning time: 0.5-1.5 minutes, 1 minute under optimal conditions

[0112] Waiting time: 5 minutes to 30 minutes, 10 minutes under optimal conditions.

[0113] 5. Scope and Process of Examples

[0114] Example 1: Maximum test condition combination verification

[0115] Example 2: Minimum condition combination verification

[0116] Example 3: Verification of the optimal condition combination

[0117] Comparative Example 1: Cleaned with water only once, the rest was the same as Example 3

[0118] Comparative Example 2: Clean once, cleaning time 10s, waiting time 2 minutes, the rest is the same as Example 3

[0119] Comparative Example 3: 10 cleanings, 2 minutes of cleaning time, 60 minutes of waiting time, and the rest are the same as Example 3. The following is a detailed description of Examples 1, 2, 3 and the comparative example:

[0120] Example 1-3, Comparative Example 2-3:

[0121] Identify several healthy subjects with dry skin (subjects) and ensure that they meet the screening criteria, that is, the skin has no abnormal symptoms such as inflammation, damage, sensitivity, etc., the stratum corneum moisture content is less than 65 C.U., and it is non-sensitive skin (TEWL < 20g / m 2 The test environment was maintained at a temperature of 20°C to 22°C and a relative humidity of 40% to 60%. The subjects were asked to sit quietly in this environment for at least 20 minutes. The subjects were required not to use cosmetics or skincare products in the test area within 24 hours before the test.

[0122] The test area was cleaned for each subject, with the specific number of washes, wash duration, and waiting time specified in Examples 1-3 and Comparative Examples 2-3. A soap-based cleansing and modeling process was performed, with gentle circular massage movements to remove some lipids and corneocytes from the stratum corneum, thereby simulating a mildly damaged sensitive skin barrier. After the final cleansing, the TEWL and a* values ​​were measured using a TEWAMeter™ 300 and a Colorimeter CL400, respectively, following the waiting times specified in Examples 1-3 and Comparative Examples 2-3.

[0123] Soak the membrane cloth fully with the aqueous solution sample to be tested, ensure that the membrane cloth is completely wet, and apply a sufficient amount of sample to the test area.

[0124] After the modeling is completed, and at four time points, namely, 30 seconds, 5 minutes, and 10 minutes after the sample is applied, subjective data of the subjects are collected to record their sensory feedback in terms of tingling, itching, burning, dryness, etc., and scored using a 0-4 point grading scale (0 points for no feeling, 1 point for mild, 2 points for moderate, 3 points for obvious, and 4 points for severe). At the same time, a willingness survey of the subjects can be conducted after the modeling is completed. In addition, at four time points, namely, before the modeling is completed, after the modeling is completed, and 10 minutes and 24 hours after the sample is removed, the subjects are subjected to instrumental testing. The test content includes measurement using a transepidermal water loss meter (TEWAMeter TM300) and a skin color tester (Colorimeter CL400) to evaluate the effect of the sample on the skin barrier repair ability and soothing ability, and to observe the recovery of the skin condition within 24 hours after the modeling.

[0125] Collect data and conduct analysis to determine the effect of model establishment under the optimal combination of conditions, observe its performance in subjective scores and objective indicators, compare it with Examples 1 and 2, and verify the superiority of the optimal combination of conditions.

[0126] Comparative Example 1: Control Group (Clean with Water Only) Combination Verification

[0127] Subjects were prepared according to the subject screening criteria and test environment requirements described in Example 3. Control subjects cleansed their faces with water only to remove surface dirt without disrupting the skin's natural barrier. After cleansing, subjects sat quietly in a constant temperature and humidity environment for at least 15 minutes to ensure skin stability. All other conditions were the same as in Example 3.

[0128] 6. Result judgment: Combine subjective feelings, barrier function, and inflammatory response to verify the mildness and non-irritation of the sample.

[0129] 1) If the comprehensive index of the positive control group is less than that of the deionized water group and the comprehensive index of the negative control group is greater than that of the deionized water group, the model is established; Necessity of negative / positive controls: Only used in the model validation stage (not required for routine testing).

[0130] 2) If the comprehensive index of the sample is less than that of the deionized water group, it means that the sample has a repairing and soothing effect;

[0131] If the comprehensive index of the sample = the comprehensive index of the deionized water group, it means that the sample is mild and non-irritating;

[0132] If the comprehensive index of the sample is greater than that of the deionized water group, it means that the sample is skin irritating;

[0133] 7. Experimental results

[0134] This method was proven to be harmless to the subjects' skin and that the skin could return to normal within 24 hours (there was no significant difference between the TEWL value 24 hours after modeling and the TEWL value before modeling (p>0.05), indicating that the skin could recover within 24 hours and no permanent damage was caused). For details, please refer to Table 1.

[0135] Table 1

[0136]

[0137]

[0138] Specific Example 2 Verification method and consistency with sensitive skin

[0139] Specific steps of the experiment:

[0140] N subjects with sensitive skin (referring to the Sensitive Skin Group Standard T / GDCA 029-2023: Evaluation of the Efficacy of Cosmetics for Sensitive Skin, with a skin sensitivity score of 21 or higher) were randomly selected. After washing their faces once with water, the subjects were asked to sit quietly in a constant temperature and humidity chamber for at least 15 minutes and then randomly divided into two groups. TEWL and a* values ​​were measured. A negative control and a positive control (a known mild baseline sample for the positive control and a known irritant sample for the negative control) were assigned using a randomization table. Both the positive and negative control samples were applied, and subjective evaluations were recorded at four time points: after modeling with a rinsing and removal procedure, and after applying the mask for 30 seconds, 5 minutes, and 10 minutes. A willingness survey was also conducted after modeling with a rinsing and removal procedure. Instrumental testing, covering TEWL and a* values, was performed after modeling with a rinsing and removal procedure and 10 minutes after removing the patch.

[0141] Experimental results: After washing and removing the model, the reaction of the model to the sample is consistent with that of sensitive skin, and it can replace sensitive skin, and the subjects are more willing to do so. For details, please refer to Table 2:

[0142] Table 2

[0143]

[0144]

[0145] Experimental conclusion:

[0146] Example 1 (maximal test condition combination): The subjects' willingness was relatively low (<80%) due to excessive cleaning.

[0147] Example 2 (suboptimal combination): However, due to insufficient cleansing, the TEWL value failed to reach the threshold of sensitive skin (<20g / m 2 / h), which shows that the irritation to the skin and the degree of barrier damage under this condition are at a moderate level and do not meet the test conditions.

[0148] Example 3 (optimal condition combination): The comprehensive index of the positive control group is less than that of the deionized water group, and the comprehensive index of the negative control group is greater than that of the deionized water group, indicating that the model is established. Under the optimal condition combination, the TEWL value can be stabilized at 20-35g / m after washing and modeling. 2 / h, which is consistent with sensitive skin status. TEWL values ​​after 24 hours were not significantly different from those before modeling (P>0.05), indicating that the model does not cause permanent damage to the skin and has good safety and reusability. Subjects' willingness was high, >90%. This shows that this condition is less irritating to the skin and causes minimal damage to the skin barrier, confirming the model's validation.

[0149] Comparative Example 1 (control group): The total subjective score of the negative control was not much different from the blank control score, and the TEWL value was no different from the baseline (p>0.05), which shows that the skin condition without cleaning intervention is the best and the skin barrier function remains intact. This result further verifies the necessity of soap-based cleaning as a model for constructing a damaged barrier; simply using clean water for cleaning cannot simulate the state of sensitive skin. The change in skin barrier function is caused by the specific cleaning treatment of the experimental group (multiple cleanings with soap-based cleansers), rather than environmental conditions, instrument errors or other uncontrolled factors.

[0150] Through the comparative analysis of the above data, it is clear that the optimal combination of conditions (Example 3) is the most suitable for evaluating the mildness of aqueous solution samples. This combination minimizes skin irritation and damage while ensuring that it can simulate mild damage to the skin barrier to a certain extent. Other parameter combinations failed to meet the model validity requirements due to either excessive cleaning intensity or insufficient cleaning. The data from the control group further confirmed the rationale of the experimental design and provided a reliable reference for evaluating the mildness of aqueous solution samples.

[0151] From the experimental data, it is strongly proved that the model established by the present invention has a high correlation and consistency with sensitive skin in evaluating the mildness of aqueous samples, which fully verifies that the model can effectively replace sensitive skin for sample mildness evaluation. The transepidermal water loss rate after modeling obtained by the washing and unloading modeling method is highly consistent with the transepidermal water loss rate of sensitive skin. This shows that the skin condition of healthy subjects with dry skin treated by the cleaning method of the present invention is very close to that of sensitive skin in terms of the degree of mild damage to the barrier function, successfully simulating the key physiological characteristics of sensitive skin, and providing a reliable simulation basis for the subsequent mildness evaluation of sensitive skin.

[0152] The scoring results of the negative control patch samples also showed consistency between the model presented in this paper and the sensitive skin negative control. This demonstrates that the model can accurately reflect the degree of irritation of aqueous samples of varying mildness levels on similarly sensitive skin conditions. This indicates that the model's sensitivity and ability to discern sample irritation are comparable to those of real sensitive skin, effectively distinguishing between mild samples.

[0153] Furthermore, the scoring results of the model presented here are consistent with those of sensitive skin samples when applying different samples. This further confirms that the model's ability to assess the comprehensive effects of aqueous solutions on similarly sensitive skin, both in terms of subjective perception and objective physiological indicators, is consistent with the actual responses of sensitive skin. This ensures that the results of sample screening and evaluation using this model have good extrapolation and practical reference value.

[0154] Furthermore, the results showed that the subjects had a high acceptance of the six cleansing sessions, and combined with the analysis of the transepidermal water loss rate after 24 hours, it was found that the skin condition could be significantly restored, indicating that the model does not cause permanent damage to the skin and has good safety and reusability. Compared with directly testing subjects with naturally sensitive skin, the model of the present invention not only solves the problem of recruiting subjects with naturally sensitive skin, but also reduces the dependence on a specific population, while improving the safety of the test and the acceptance of the subjects.

[0155] In summary, the verification method of the present invention has good consistency with sensitive skin, and there is a significant correlation between the mildness evaluation results of the aqueous sample and the actual reaction of sensitive skin. This fully proves that this model can be used as an effective alternative tool for evaluating the mildness of aqueous samples, providing a more convenient, economical, reliable and practical evaluation method for sample development and screening. It has important practical significance and broad application prospects. The TEWL value after 24 hours was not significantly different from the TEWL value before modeling (P>0.05), indicating that the model will not cause permanent damage to the skin and has good safety and reusability.

[0156] The above disclosures are merely some preferred embodiments of the present invention, and certainly cannot be used to limit the scope of the present invention. A person skilled in the art will understand that all or part of the processes of the above embodiments and equivalent changes made in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. A method for evaluating the mildness of an aqueous product, characterized in that: Including steps: Washing and Unloading Modeling: The left and right sides of the faces of multiple subjects were washed and unloaded six times using a soap-based cleanser. Each wash lasted for 1 minute, and after the last wash, the subjects waited 10 minutes to make the left and right sides of their faces resemble those of sensitive skin with mildly damaged skin barriers. The left and right sides of the faces of the subjects had healthy, non-sensitive, medium-dry skin. Set up a blank control group and a sample group: randomly apply the membrane cloths fully soaked in deionized water and the test solution sample to the left and right sides of the face of the subjects who have completed the washing and modeling for 10 minutes; Subjective feeling data collection: After washing and removing the model, 30 seconds after applying the mask, 5 minutes after applying the mask, and 10 minutes after applying the mask, sensory feedback including stinging, itching, burning, and dryness was collected from the left and right sides of each subject's face before and after applying the blank control group and the sample group. The levels of sensory feedback in the four aspects were quantified from no feeling to severe feeling. 下限 , w 上限 】The greater the feeling, the greater the score; Objective measurement data collection: After modeling and removal, and after removing the patch, use a measuring instrument to measure the transepidermal water loss (TEWL) and skin color a* value on the left and right sides of each subject's face before and after applying the blank control group and the sample group. Data processing and calculation: Based on the subjective perception data and objective measurement data collected from the blank control group and sample group, the comprehensive evaluation index of the blank control group and sample group was calculated according to the following formula (1): Among them, Q is the comprehensive evaluation index, w 1ij 、w 2ij 、w 3ij 、w 4ij The scores of each sensory feedback of each subject collected at four time points, x 1i 、x 2i The TEWL value of each subject collected at two time points, y 1i 、y 2i is the a* value of each subject collected at two time points, m is the number of subjects, A and B are the weights of subjective indicators and objective indicators, respectively; Evaluation result output: Compare the comprehensive evaluation index of the sample group and the comprehensive evaluation index of the blank control group calculated by formula (1). If: If the comprehensive evaluation index of the sample group is less than that of the blank control group, the evaluation result is output that the water-based product has a repairing and soothing effect; If the comprehensive evaluation index of the sample group equals the comprehensive evaluation index of the blank control group, the evaluation result of the aqueous solution product is mild and non-irritating. If the comprehensive evaluation index of the sample group is greater than that of the blank control group, the evaluation result that the aqueous product has skin irritation is output.

2. The method for evaluating the mildness of an aqueous product according to claim 1, characterized in that: The steps of data processing and calculation also include: The change in TEWL value of each subject x 2i -x 1i and a* value change y 2i -y 1i The first correlation analysis was performed to obtain the threshold interval of the relationship between TEWL value and a* value. The subjective feeling data and objective measurement data of the subjects outside the threshold interval of the relationship between TEWL value and a* value were eliminated and the valid data were retained. Then the calculation was performed according to formula (1). In formula (1), m is the number of valid subjects corresponding to the retained valid data, and the TEWL value change x is 2i -x 1i Represents the objective change in the subject's barrier function, the change in a* value y 2i -y 1i Represents changes in the subjects' inflammatory response.

3. The method for evaluating the mildness of an aqueous product according to claim 2, characterized in that: The steps of data processing and calculation also include: The total value of TEWL value and a* value of each subject after washing and modeling is x 1i +y 1i The total value of the four sensory feedbacks after applying the film for 10 minutes is w 4i1 +w 4i2 +w 4i3 +w 4i4 The second correlation analysis is performed to obtain the objective-subjective first relationship threshold interval. The subjective feeling data and objective measurement data of the subjects outside the objective-subjective first relationship threshold interval are eliminated and the valid data are retained and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

4. The method for evaluating the mildness of an aqueous product according to claim 3, characterized in that: The steps of data processing and calculation also include: The total value of TEWL value and a* value of each subject after removing the patch cloth is x 1i +y 1i The total value of the four sensory feedback after washing and modeling is w 1i1 +w 1i2 +w 1i3 +w 1i4 The second correlation analysis is performed to obtain the objective-subjective second relationship threshold interval. The subjective feeling data and objective measurement data of the subjects outside the objective-subjective second relationship threshold interval are eliminated and the valid data are retained and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

5. The method for evaluating the mildness of an aqueous product according to claim 4, characterized in that: The steps of data processing and calculation also include: The sum of the scores of the four sensory feedbacks collected from each subject at each time point Sort them in ascending order from small to large, and剔除 the first m1 and the last m_{1} data in the sequence, and an optimized subjective index interval is obtained, where 1%*m < m_{1} < 5%*m;剔除 the subjective feeling data and objective measurement data of the subjects outside the optimized subjective index interval,保留 the valid data, and then calculate according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

6. The method for evaluating the mildness of an aqueous product according to claim 4, characterized in that: The steps of data processing and calculation also include: The change amount x of the TEWL value collected from each subject 2i -x 1i and the change amount y of the a* value 2i -y 1i are sorted from small to large in sequence, and the m2 data ranked at the forefront and the end of the sequence are excluded to obtain an optimized objective index interval, where 1%*m < m2 < 5%*m; the subjective feeling data and objective measurement data of the subjects outside the optimized objective index interval are excluded to retain the valid data and then calculated according to formula (1), where m in formula (1) is the number of valid subjects corresponding to the retained valid data.

7. The method for evaluating the mildness of an aqueous product according to claim 1, wherein: The left and right sides of the face of the test subject had intact skin without open wounds, damage, or ulcers, and the moisture content of the stratum corneum was less than 65 C.U. as measured by Corneometer CM825.

8. The method for evaluating the mildness of an aqueous product according to claim 1, characterized in that: The transepidermal water loss (TEWL) value was measured using TEWAMeter TM300 and the skin color (a* value) was measured using Colorimeter CL400.

9. The method for evaluating the mildness of an aqueous product according to claim 1, characterized in that: A=50%, B=50%.

10. The method for evaluating the mildness of an aqueous product according to claim 1, wherein: The levels of sensory feedback in the four aspects include no feeling, mild, moderate, obvious, and severe, and each level corresponds to a quantitative score of [0, 4].

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