CN109116009B - Method for evaluating compound mildness - Google Patents
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- CN109116009B CN109116009B CN201810833969.5A CN201810833969A CN109116009B CN 109116009 B CN109116009 B CN 109116009B CN 201810833969 A CN201810833969 A CN 201810833969A CN 109116009 B CN109116009 B CN 109116009B
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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Abstract
The present invention relates to a method for evaluating the mildness of a compound, and a method for screening mild compounds comprising using the method. In particular to a method for evaluating the mildness of a compound, which comprises the following steps: testing the skin condition of the subject before and after the compound is applied on the skin by using a skin detection instrument to obtain physiological index parameters representing the skin state before and after the compound is applied on the skin; and substituting the difference value of the physiological index parameters into a skin damage factor function obtained by a discriminant analysis method to obtain a skin damage factor value, and judging the mildness of the compound based on the skin damage factor value. The invention can effectively carry out quantitative description on the mildness of the compound.
Description
Technical Field
The invention relates to a method for evaluating the mildness (or skin injury) of a compound. The assessment method of the present invention is effective in quantitatively describing the mildness (skin lesion) of the compound.
Background
With the development of modern society and the improvement of living standard of people, various daily chemical products increasingly enter the lives of people. A part of daily chemical products (such as skin cleaning products and the like) directly act on the skin of people; other daily chemical products (such as liquid detergent, washing powder and the like) inevitably contact with the skin of people when in use.
For example, skin cleansing products have long become essential products for daily life. The main function of the skin cleaning product is to remove grease, dirt and the like attached to the skin through a surfactant. The surfactant in the skin cleaning product is used for dissolving dirt and grease, so that the cleaning is facilitated. However, repeated cleansing procedures can cause discomfort symptoms of skin tightness, dryness, disruption of stratum corneum barrier function, redness, irritation, itching, and the like.
These symptoms of discomfort characterize whether the product is mild to the skin, i.e. whether it is irritating to the skin, and whether it is likely to damage the skin. Therefore, the mildness of the product plays an increasingly important role in daily chemical products.
When developing and producing daily chemical products, it is necessary to evaluate whether the daily chemical products will damage the skin, which is also called mildness evaluation. Currently, methods for evaluating the mildness of daily chemicals are classified into in vitro methods and in vivo methods, and the in vivo methods are classified into animal methods and human methods.
The in vitro experiment method comprises zein dissolution experiment, lipid dissolution/extraction experiment, liposome dissolution experiment, chick embryo allantoic membrane experiment, erythrocyte hemolysis experiment, neutral red uptake experiment, etc. The in vitro experiment method is simple and easy to operate, can be carried out in large batch, but the obtained result has a certain difference with the actual use reaction condition of a human body, and the condition in actual use cannot be well represented. In addition, there is a problem that the resulting mildness trends may not be consistent as evaluated by different in vitro experimental methods for the same two cleansing products or surfactants.
The animal experiment method comprises an animal skin irritation evaluation method and a rabbit eye irritation evaluation method, the operability is strong, and the experiment result is generally judged by visual observation. Although the experimental result can be observed intuitively, the problems of strong subjectivity of the scoring standard and poor repeatability of the detection result among laboratories exist. Moreover, there is still a certain gap between animal and human in biological species, and animal experiments cannot fully characterize the actual use condition in human. In addition, with the increasing ethical requirements of society, animal experiments are facing increasing criticism and reprimand and are restricted in some countries.
The human body experiment method can be divided into an expert evaluation method, an instrument test method and a consumer self-perception method according to a final evaluation mode; according to the cleaning intensity, the method can be divided into a spot-sticking experimental method, an intensified cleaning method and a common use method; according to the test site, there are elbow cleansing, forearm cleansing, half-face cleansing and hand cleansing. The human body experimental method is closer to the feeling and cognition of the consumers after actual use, but the experimental results are different due to the influence of test parts and recruitment of subjects, and the evaluation on a large scale is difficult. At present, the problem that a plurality of evaluation parameters are obtained by a human body experiment method, and each parameter can only reflect the mildness of the parameter from one side surface is solved, so that the mildness of a skin cleaning product or a surfactant cannot be comprehensively represented. Safety and mildness of surfactants "by suzuan et al (daily chemical industry, 1998, 6 th) outlines safety and mildness of surfactants, corresponding evaluation methods, and the relationship between the structure of surfactants and safety and mildness.
The terrestrial light Chong "Mild surfactant" ("daily chemical industry" 1997, 6 th) discusses the irritancy of surfactants and their evaluation methods. The authors believe that "the same chemical structure, because of the obvious differences in the irritation tests between manufacturers, routes and raw materials, is used as reference and must be carefully and carefully evaluated when selected". The accompanying table shows the degree of irritation of some surfactants:
TABLE 1 irritation Strength of some surfactants
CN101257847A discloses a method for evaluating the degree of skin damage caused by ultraviolet light and the degree of physiological skin aging, wherein a statistical method of Principal Component Analysis (PCA), SIMCA or KNN is used. However, this method cannot be used to evaluate the mild irritancy of the compounds.
CN108074644A discloses a peace and fitness evaluation method based on skin measurement, in which a skin detection instrument is used to test the skin condition of a user to obtain multiple physiological indexes representing the skin state, and then a principal component analysis model is generated by using a principal component analysis method according to the physiological indexes. The physiological indicators used include one or more of cheek moisture content average, cheek moisture loss, cheek oil, cheek MI average, cheek EI average, cheek L value, cheek a value, cheek B value, cheek ITA value, average value of cheek gloss, cheek elasticity R2, cheek elasticity R5, cheek elasticity R7, cheek PH value, cheek average Ra, cheek average Rz, cheek average Rp, amount of facial skin blood perfusion, pO2 average, pCO2 average, infrared cheek average. Although this method can judge whether the user has mild constitution by the above physiological indexes, the above method is not suitable for the assessment of the mildness of the compound.
Therefore, it is necessary to develop a method for evaluating the mildness of a compound, which eliminates the interference of human factors and can reflect the mildness of the compound more accurately.
Disclosure of Invention
The invention provides a method for evaluating the mildness of a compound, which comprises the following steps:
testing the skin condition of the subject before and after the compound is applied on the skin by using a skin detection instrument to obtain physiological index parameters representing the skin state before and after the compound is applied on the skin;
substituting the difference value of the physiological index parameter into a skin damage factor function obtained by a discriminant analysis method to obtain a skin damage factor value, wherein the difference value of the physiological index parameter is the physiological index parameter after the compound is used on the skin, namely the physiological index parameter before the compound is used on the skin;
compound mildness was judged based on skin injury factor values.
The invention aims to provide a method for evaluating the mildness of a compound, which eliminates the interference of human factors and can more accurately reflect the mildness of the compound.
Another object of the invention is the use of the method of the invention for evaluating the mildness of a compound.
The invention provides a concept of Skin Damage factors (SDI, Skin Damage Index), and finds that the Skin Damage factors can sensitively distinguish the mildness of various compounds, thereby providing a new method for screening compounds with different mildness according to the application field.
The inventor researches the physiological mechanism of skin affected by the compound, selects a plurality of skin physiological parameters, determines the difference value of the skin physiological parameters before and after using the compound through the test of an instrument, and tests the discrimination effect of the skin physiological parameters by adopting a statistical method of discrimination analysis to obtain the skin physiological parameters with good detection significance level and the weight thereof, thereby obtaining the skin injury factor function. Compound mildness can be quantitatively assessed by the skin injury factor function.
The present invention has been made based on the above-described principle, and therefore, one aspect of the present invention relates to a method for evaluating the mildness of a compound.
Another aspect of the invention relates to the use of the method of the invention for assessing the mildness of a compound in screening for compounds.
Detailed Description
The evaluation method of the present invention will be explained below.
Whether a surfactant-containing compound is mild to the skin depends primarily on the surfactant and cleansing conditions used therein. The mechanism of skin damage caused by surfactant-containing compounds is divided into three areas:
(1) reactivity: it is meant that the surfactant-containing compound adsorbs proteins in the stratum corneum, resulting in protein denaturation. If skin barrier-associated proteins are adsorbed, denaturation of these proteins leads to a decrease in skin barrier function.
(2) Permeability: refers to the ability of surfactant-containing compounds to penetrate transdermally, which is believed to be one of the causes of various inflammatory conditions of the skin. The surfactant-containing compound after transdermal penetration is combined with proteins in the stratum corneum to cause temporary curling of the proteins, the curling of the proteins promotes the surfactant in the compound to penetrate deeper into the skin, and the surfactant penetrating into the skin changes the original structural state of the skin and the compatibility between adjacent molecules, so that contact dermatitis and dermal dermatitis are caused, skin irritation is caused, even allergic reaction is caused, and the phenomena of irritation and itching appear on the skin.
(3) Dissolution property: refers to the degree of dissolution of the surfactant-containing compound into the skin's own moisturizing ingredients (such as NMF), intercellular lipids, and free amino acids and fats in the stratum corneum. Excessive dissolution of these moisturizing components can destroy skin oil and surface layers, reduce skin water retention capacity, and cause desquamation of skin, thereby causing skin tightness, prickling and dry feeling. Even more so, it will have a lytic effect on the cells in the stratum corneum.
Starting from the above mechanism, the inventors adopted the following skin physiological indicators as parameters for evaluation:
(1) skin hydration (simply "hydration") represents how much water is present in the skin, and the higher the hydration, the more water is present in the skin. In one example of the present invention, Corneometer CM825 was selected to determine skin hydration.
(2) The degree of scaling (abbreviated as "SEsc") represents the degree of dryness of the skin, the greater the SEsc, the drier the skin. In one example of the invention, Visioscan VC98 was chosen to determine the degree of scaling.
(3) The skin pH (abbreviated as "pH") represents the skin surface pH. In one embodiment of the invention, Skin pH is determined by selecting Skin-pH-Meter pH 905.
(4) The skin barrier function is also known as Transepidermal water loss (TEWL), which refers to the loss of water from the interior of the body through the epidermis into the surrounding atmosphere through diffusion and evaporation processes. TEWL in humans is also referred to as imperceptible water loss, as it is a process where organisms have little physiological control. In the present invention, TEWL values were measured using aquaFlux, a bio x company.
(5) Skin tightness (abbreviated as "R0") represents the maximum height of the skin pulled up under negative pressure, and the smaller the R0, the tighter the skin. In one embodiment of the invention, the skin tightness is characterized by the R0 parameter measured by the instrument Cutomer MPA 580.
In the present invention, the term "compound" means a single compound or a combination of two or more compounds.
The compounds evaluated in the present invention may be any compound that may come into contact with human skin during use. The compound can be directly acted on the skin of people, and can also be contacted with the skin of people when in use.
Examples of the compound directly acting on human skin include one or more components of skin cleansing products for cleansing the skin, such as cleansing milk, cleansing foam, cleansing soap, body wash, shampoo, cleansing gel, makeup remover oil, and makeup remover water (including sheet-like articles obtained by impregnating a base material such as nonwoven fabric with a compound to wipe off makeup or sebum dirt).
The compound which comes into contact with the skin of a person at the time of use may be one or more components selected from washing powder, laundry detergent, liquid detergent, dish washing powder, dish washing salt, household detergent, and oil stain remover.
In one embodiment of the invention, the compound is a surfactant.
The present invention is further illustrated by the following examples.
Examples
Example 1 establishment of skin Damage factor function
(1) Volunteer selection: 40 healthy 22-50-year-old women with no obvious scars, no obvious dry desquamation and pigmentation on the forearm parts are selected as subjects.
(2) Selecting a test object: as test substances, 3 representative surfactants were selected: potassium myristate (soap-based surfactant), sodium lauryl sulfate (K12, anionic surfactant) and sodium lauroyl glutamate (amino acid-based surfactant) were prepared at a solution concentration of 12 wt%, and clear water was used as a control.
(3) Dotting and grouping: the forearm parts of the hands are dotted and grouped, and the dotted area of each volunteer is 2 multiplied by 4cm2The experiment was divided into 4 groups: a clear water group, a potassium myristate group, a sodium lauryl sulfate group and a sodium lauroyl glutamate group.
(4) Measuring basic values of skin physiological parameters: the forearm of the subject was cleaned with clear water, and the subject was allowed to sit still in a constant temperature and humidity room for 30 minutes, and then the forearm of the subject was tested with the following instruments.
[ Table 1]
(5) Cleaning the skin with the test article: cleaning skin for 10 times, divided into three days, 4 times every day for the first two days, 2 times every day for the last 2 times, and 1.5h for each time; the cleaning time was 2 minutes each and the post-cleaning rinsing time was 30 s.
(6) Measurement of the value of the physiological parameter of the skin after the use of the test article: after equilibration for 30 minutes in a constant temperature and humidity chamber at 1h after the last cleaning, the forearm site was again tested for skin hydration, scaling SEsc, skin pH, skin barrier function (TEWL) and skin tightness (R0) using the instrument in table 1.
Then, the differences Δ hydration, Δ SEsc, Δ pH, Δ TEWL, Δ R0 for each skin physiological parameter are calculated, where Δ hydration, Δ SEsc, Δ TEWL, Δ pH, and Δ R0 represent the differences of skin hydration, scaling, skin barrier function, skin pH, skin tightness minus the skin hydration, scaling, skin barrier function, skin pH, skin tightness in the base of the skin physiological parameter after the test object is applied to the skin.
(7) Establishing a skin injury factor (SDI) function: establishing a skin injury factor function by a discriminant analysis method by taking different classes of tested substances as dependent variables and taking the delta hydration degree, the delta SEsc, the delta pH, the delta TEWL and the delta R0 as independent variables; the established skin injury factor formula is as follows:
SDI-2.841-0.119 × Δ hydration +1.231 × Δ SEsc +0.037 × Δ TEWL +0.603 × Δ pH-6.621 × Δ R0
The difference between the parameters before and after washing is shown in Table 2.
[ Table 2]
Example 2 evaluation of two different test substances using the skin injury factor function
(1) Volunteer selection: 30 healthy 22-50-year-old women with no obvious scars, no obvious dry desquamation and pigmentation on the forearm parts are selected as subjects.
(2) Selecting a test object: alkyl glucoside and sodium lauryl alcohol ether sulfate which are proved to have difference in mildness by an in vitro experiment method are selected as test substances to be prepared into a solution with the concentration of 12 weight percent, and clear water is used as a control.
(3) Dotting and grouping: the forearm parts of the hands are dotted and grouped, and the dotted area of each volunteer is 2 multiplied by 4cm2The experiment is divided into 3 groups: a clear water group, an alkyl glucoside group and a sodium lauryl alcohol ether sulfate group.
(4) Measuring basic values of skin physiological parameters: the forearm of the subject was cleaned with clean water and allowed to sit in a constant temperature and humidity room for 30 minutes before being tested using the instruments described in Table 1, respectively.
(5) Cleaning the skin with the test article: cleaning skin for 10 times, divided into three days, 4 times every day for the first two days, 2 times every day for the last 2 times, and 1.5h for each time; the cleaning time was 2 minutes each and the post-cleaning rinsing time was 30 s.
(6) Measurement of the value of the physiological parameter of the skin after the use of the test article: after equilibration for 30 minutes in a constant temperature and humidity chamber at 1h after the last cleaning, the forearm site was again tested for skin hydration, scaling SEsc, skin pH, skin barrier function (TEWL) and skin tightness (R0) using the instrument in table 1.
Then, the differences Δ hydration, Δ SEsc, Δ pH, Δ TEWL, Δ R0 for each skin physiological parameter were calculated.
(7) The differences in the physiological parameters of the skin were substituted into the skin injury factor function obtained in example 1 to calculate the SDI values of the two test subjects, and the results are shown in table 3.
Table 3 alkyl glucoside and sodium lauryl ether sulfate skin injury factor (SDI) values (X ± SD) (n ═ 20)
As can be seen from Table 3, there is a significant difference in SDI values between the alkyl glucoside and sodium lauryl ether sulfate.
In addition, the test substance used was previously measured by the in vitro test method known in the art, zein dissolution test and chick embryo chorioallantoic membrane test, and it was found that alkyl glucoside (nonionic surfactant) is superior in mildness to sodium lauryl alcohol ether sulfate (anionic surfactant).
In example 2, the skin damage factor function obtained in example 1 was used to evaluate the mildness of alkyl glucosides and sodium lauryl ether sulfate, confirming that the method is able to distinguish between surfactants with different mildness, and that alkyl glucosides have a mildness superior to sodium lauryl ether sulfate, consistent with the conclusions obtained from the in vitro method.
Example 3 sensitivity of skin injury factor values in differentiating mildness of Compounds
In example 3, a compound generally considered to be very mild (harobur baby mild shampoo shower gel) was selected, and its SDI value was compared with the SDI value of clear water, which demonstrates that the skin damage factor function can distinguish the very mild compound from the clear water with higher sensitivity.
(1) Volunteer selection: 20 healthy 22-50-year-old women with no obvious scars, no obvious dry desquamation and pigmentation on the forearm parts are selected as subjects.
(2) Selecting a test object: a mild shampoo shower cream for heroin infants was selected as the test substance and clear water was used as the control.
(3) Dotting and grouping: the forearm parts of the hands are dotted and grouped, and the dotted area of each volunteer is 2 multiplied by 4cm2The experiment is divided into 2 groups: clear water group, Haro flash group.
(4) Measuring basic values of skin physiological parameters: the forearm of the subject was cleaned with clean water and allowed to sit in a constant temperature and humidity room for 30 minutes before being tested using the instruments described in Table 1, respectively.
(5) Cleaning the skin with the test article: cleaning skin for 10 times, divided into three days, 4 times every day for the first two days, 2 times every day for the last 2 times, and 1.5h for each time; the cleaning time was 2 minutes each and the post-cleaning rinsing time was 30 s.
(6) Measurement of the value of the physiological parameter of the skin after the use of the test article: after equilibration for 30 minutes in a constant temperature and humidity chamber at 1h after the last cleaning, the forearm site was again tested for skin hydration, scaling SEsc, skin pH, skin barrier function (TEWL) and skin tightness (R0) using the instrument in table 1.
Then, the differences Δ hydration, Δ SEsc, Δ pH, Δ TEWL, Δ R0 for each skin physiological parameter were calculated.
(7) The differences in the physiological parameters of the skin were substituted into the skin lesion factor function obtained in example 1 to calculate SDI values of the test substance and the clear water, and the results are shown in table 4.
[ Table 4]
As can be seen from table 4, if the changes in a single skin physiological parameter (Δ hydration, Δ SEsc, Δ TEWL, Δ pH and Δ R0) are used to compare the heroflash baby mild shampoo and the plain water, it is difficult to distinguish between the two. In particular, if Δ SEsc, Δ pH, Δ R0 were compared separately for harobur mild shampoo shower cream and plain water, respectively, it would be found difficult to distinguish the harobur mild shampoo shower cream from the plain water; if the delta hydration levels and delta TEWL of the harovirus infant mild shampoo bath and the plain water, respectively, are compared separately, it will be found that the delta hydration levels and delta TEWL means differ by more than SDI, but the standard deviation of these two parameters is greater relative to their mean, which is difficult to use separately to distinguish between the harovirus infant mild shampoo bath and the plain water.
However, after substituting Δ hydration degree, Δ SEsc, Δ TEWL, Δ pH and Δ R0 into the skin damage factor function obtained in example 1 to obtain SDI values, two SDI values with distinct differentiation can be obtained, and the SDI value of the harobur baby mild shampoo body lotion is greater than the SDI value of the clear water, indicating that the harobur baby mild shampoo body lotion is less mild than the clear water.
From table 4, it was found that for compounds with relatively close mildness, in the case where differences between them cannot be distinguished using a single skin physiological parameter, they can be distinguished if a skin damage factor function is employed, and thus the skin damage factor function of the present study is more sensitive in evaluating the mildness of the product, and is suitable for the development of mild compounds, especially mild skin cleansing products.
According to the above examples, it is confirmed that the present invention effectively quantitatively describes the mildness of a surfactant-containing compound by a discriminant analysis function to evaluate the mildness of the compound, and the used physiological index parameters are obtained by an instrumental objective test, so that a final evaluation index can be quantitatively obtained, and the evaluation index is more objective, more comprehensive and more sensitive than that of the conventional human body evaluation method.
Claims (5)
1. A method for assessing the mildness of a compound, comprising:
testing the skin condition of the subject before and after the compound is applied on the skin by using a skin detection instrument to obtain physiological index parameters representing the skin state before and after the compound is applied on the skin;
substituting the difference value of the physiological index parameter into a skin damage factor function obtained by a discriminant analysis method to obtain a skin damage factor value, wherein the difference value of the physiological index parameter is the physiological index parameter after the compound is used on the skin, namely the physiological index parameter before the compound is used on the skin;
determining compound mildness based on the skin injury factor value;
wherein the skin damage factor function is:
skin injury factor-2.841-0.119 × Δ hydration +1.231 × Δ SEsc +0.037 × Δ TEWL +0.603 × Δ pH-6.621 × Δ R0
Wherein Δ hydration, Δ SEsc, Δ TEWL, Δ pH, and Δ R0 represent the difference between the skin hydration, scaling, skin barrier function, skin pH, and skin tightness after application of the compound to the skin, minus the skin hydration, scaling, skin barrier function, skin pH, and skin tightness before application of the compound to the skin, respectively.
2. The method of assessing the mildness of a compound according to claim 1, wherein the compound is a surfactant-containing compound.
3. The method of assessing the mildness of a compound according to claim 1, wherein the compound is a skin cleansing compound.
4. The method of assessing the mildness of a compound according to claim 1, wherein the compound is a mild skin cleansing compound.
5. Use of the method of claim 1 for assessing the mildness of a compound in screening for a compound.
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