Synergistic repair composition for sensitive skin multi-barrier damage and application thereof

Abstract

The invention belongs to the field of cosmetics, and particularly relates to a synergistic repair composition for sensitive skin multi-barrier damage and application of the synergistic repair composition. The invention relates to a synergistic repair composition aiming at damaged multiple barriers of sensitive skin. The synergistic repair composition comprises the following components in parts by weight: 10-25 parts of a physical barrier functional component, 3-10 parts of an immune barrier functional component, 3-10 parts of a microbial barrier functional component and 56-84 parts of a solvent. According to the technology, starting from a skin barrier damage mechanism, through screening and scientific matching of the functional components, the synergistic interaction effect of repairing the damaged skin barrier is generated among the components while the self effects of the functional components are fully exerted.

Description

Technical Field

[0001] This invention relates to a synergistic repair composition for sensitive skin with multiple damaged barriers, belonging to the field of cosmetic technology. Background Technology

[0002] Sensitive skin is a common skin condition in clinical practice, also known as sensitive skin syndrome. Its occurrence is mainly related to impaired skin barrier function.

[0003] The skin barrier, broadly speaking, includes the physical barrier, microbial barrier, and immune barrier; narrowly defined, it usually refers to the physical barrier. Studies have shown that people with sensitive skin typically experience dryness, moisture loss, and increased transepidermal water loss (TEWL) compared to those with non-sensitive skin. Furthermore, research has found that while the microbiome in normal skin is in dynamic equilibrium, the Staphylococcus spp. population in sensitive skin exhibits abnormalities, with a significant decrease in Staphylococcus epidermidis.

[0004] Damaged skin barrier primarily occurs on the face, but can also occur on the hands, feet, and scalp. Its main characteristics include dry, tight, and red skin; even slight irritation can cause itching, peeling, and even burning and stinging, and in severe cases, can lead to negative emotions or psychological symptoms. Due to the complexity of sensitive skin and other skin damage causes, there is currently no specific treatment; therefore, using targeted cosmetics and engaging in conscious daily skincare is particularly important.

[0005] A search revealed Chinese invention patent application number CN 202110136624.6, which discloses a composition for repairing the skin barrier of sensitive skin, including swertiamarin, purslane extract, Panax notoginseng extract, Artemisia argyi extract, and Pulsatilla chinensis extract. This patent demonstrates through efficacy testing in reducing redness and spider veins that the composition can effectively address sensitization issues in sensitive skin, such as redness, swelling, and itching. Chinese invention patent application number CN 110897906 A discloses a skin barrier repair composition that can be used in cosmetics, including fresh milk, rice bran extract, flaxseed extract, and hydrolyzed corn protein. Experiments have shown that this composition can significantly increase the moisture content of the stratum corneum and reduce transepidermal water loss. Analysis of the composition's components reveals that this invention primarily repairs damaged physical barriers. Chinese invention patent application CN 111265468 A combines bifida ferment lysate, oat ferment lysate, and a skin-like lipid complex. Through human hydration and microbiome quantity comparison experiments, it was demonstrated that this composition can repair both the physical and microbial barriers of the skin. As previously mentioned, human skin contains multiple barriers, and its damage has various causes. Damage to the physical barrier is mainly related to factors such as the loss of lipid components in the stratum corneum; skin flora imbalance easily leads to damage to the microbial barrier; and damage to the immune barrier is mainly related to the increased secretion of inflammatory factors and substances in the skin. Therefore, repairing only part of the barrier is insufficient to achieve optimal results for damaged skin.

[0006] Furthermore, different barrier components may have synergistic or antagonistic effects, requiring scientific research and rational combination to achieve ideal results. Some literature reports that certain ceramides not only repair the skin's physical barrier but also reduce skin sensitivity, exhibiting strong anti-allergic effects and demonstrating a certain immune barrier repair function. Other studies have found that some microbial metabolites with microbial barrier repair functions, such as *Saccharomyces cerevisiae* fermentation filtrate, also inhibit the expression of inflammatory factors, exerting anti-inflammatory and immune barrier repair effects. However, these inferences have not yet been experimentally confirmed, and the rationality of their multi-component combinations needs further screening and verification. Our previous experiments found that components with immune barrier repair functions, such as stearyl glycyrrhizic acid ester, can also effectively relieve skin redness and reduce sensitivity; however, they have a killing effect on beneficial skin bacteria such as *Staphylococcus epidermidis*, which is detrimental to the balance of the skin's microecology.

[0007] Existing invention patents mainly focus on repairing one or two skin barriers in cases of skin barrier damage, with less attention paid to multiple barriers. Furthermore, most focus on the efficacy of different barrier repair ingredients themselves, with little research on the synergistic or antagonistic effects of a particular barrier repair ingredient on other barriers. Summary of the Invention

[0008] The purpose of this invention is to address the underlying mechanisms of skin barrier damage by providing a synergistic repair composition for multiple barriers in sensitive skin. Through the screening and rational formulation of active ingredients, this composition achieves multiple repair objectives against damage to the skin's physical, microbial, and immune barriers. This composition not only specifically repairs the corresponding damaged barriers but also promotes synergistic effects, enhancing the repair efficacy against different barriers. Furthermore, this composition can be applied to various dosage forms such as skincare creams, lotions, and serums.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] A synergistic repair composition for sensitive skin with multiple barrier defects comprises the following components in parts by weight: 10-25 parts of physical barrier function ingredient, 3-10 parts of immune barrier function ingredient, 3-10 parts of microbial barrier function ingredient, and 56-84 parts of solvent. The selected physical barrier repair ingredient effectively replenishes lipids between skin cells, relieving symptoms such as dryness and tightness; the immune barrier repair ingredient reduces skin inflammation, relieving symptoms such as itching and stinging; and the microbial barrier repair ingredient promotes the growth of beneficial bacteria in the skin, maintaining the skin's microecological balance.

[0011] Furthermore, the physical barrier active ingredient includes one or more of ceramide NP, cholesterol, and stearic acid.

[0012] Furthermore, the aforementioned synergistic repair composition for multiple barrier damage in sensitive skin includes one or more of the following immune barrier active ingredients: ammonium glycyrrhizate, kava extract, and stearyl glycyrrhetinic acid ester.

[0013] Furthermore, in the aforementioned synergistic repair composition for multiple barrier damage in sensitive skin, the microbial barrier active ingredient includes one or more of Lactobacillus / soy milk fermentation filtrate, inulin, and lactic acid bacteria fermentation lysate.

[0014] Furthermore, in the aforementioned synergistic repair composition for sensitive skin with multiple barrier damage, the solvent comprises one or more of propylene glycol, butylene glycol, and PEG-40 hydrogenated castor oil.

[0015] Further, the composition comprises the following components in parts by weight: 10-18 parts of physical barrier efficacy component, 3-8 parts of immune barrier efficacy component, 3-8 parts of microbial barrier efficacy component, and 64-84 parts of solvent.

[0016] Furthermore, the composition comprises the following components in parts by weight: 18 parts of physical barrier efficacy component, 8 parts of immune barrier efficacy component, 8 parts of microbial barrier efficacy component, and 64 parts of solvent.

[0017] Another object of the present invention is to provide the use of the composition in the preparation of skin care products.

[0018] Furthermore, the skincare products mentioned are selected from skincare creams, lotions, and serums.

[0019] Another objective of this invention is to provide a skincare product that provides synergistic repair of multiple skin barriers for sensitive skin and / or other damaged skin, characterized by containing the aforementioned composition.

[0020] Beneficial effects:

[0021] This invention patent provides a synergistic repair composition for multiple barrier damage in sensitive skin. It can effectively strengthen the skin barrier, regulate the skin microecological balance, and relieve symptoms such as dryness, itching, stinging, and redness. The components are rationally proportioned and synergistically enhance each other, thereby producing a good repair effect on the damaged skin barrier. Attached Figure Description

[0022] Figure 1 It represents the number of Staphylococcus epidermidis bacteria that grow after adding different test samples. Detailed Implementation

[0023] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0024] In the following examples and comparative examples, the Lactobacillus / soybean milk fermentation filtrate was purchased from Sentia, France; and the Lactobacillus fermentation lysate was purchased from CLR, Germany.

[0025] Example 1

[0026] A synergistic repair composition for sensitive skin with multiple barrier damage, comprising the following components in parts by weight: 7 parts ceramide NP, 4 parts cholesterol, 9 parts stearic acid, 8 parts lactobacillus / soy milk fermentation filtrate, 8 parts kava pepper extract, and 64 parts PEG-40 hydrogenated castor oil.

[0027] Example 2

[0028] A synergistic repair composition for sensitive skin with multiple barrier damage, comprising the following components in parts by weight: 3 parts ceramide NP, 2 parts cholesterol, 5 parts stearic acid, 3 parts inulin, 3 parts ammonium glycyrrhizate, and 84 parts propylene glycol.

[0029] Example 3

[0030] A synergistic repair composition for sensitive skin with multiple barrier damage, comprising the following components in parts by weight: 5 parts ceramide NP, 3 parts cholesterol, 7 parts stearic acid, 5 parts lactic acid bacteria fermentation lysate, 5 parts stearyl glycyrrhetinic acid ester, and 75 parts butylene glycol.

[0031] Comparative Example 1

[0032] The only difference between this comparative example and Example 1 is that the composition contains only the same amount of physical barrier components, excluding other barrier components in the composition.

[0033] Comparative Example 2

[0034] The only difference between this comparative example and Example 1 is that the composition contains only the same amount of the microbial barrier component, excluding other barrier components in the composition.

[0035] Comparative Example 3

[0036] The only difference between this comparative example and Example 1 is that the composition contains only the same amount of immune barrier components, excluding other barrier components in the composition.

[0037] Comparative Example 4

[0038] The only difference between this comparative example and Example 1 is that the composition contains physical barrier components and microbial barrier components, but does not include immune barrier components in the composition.

[0039] Comparative Example 5

[0040] The only difference between this comparative example and Example 1 is that the composition contains physical barrier components and immune barrier components, but does not include microbial barrier components in the composition.

[0041] Comparative Example 6

[0042] The only difference between this comparative example and Example 1 is that the composition contains immune barrier components and microbial barrier components, but does not include physical barrier components in the composition.

[0043] In the comparative examples, one or two barrier components were reduced, while the other components were prepared according to the preferred embodiment 1. The above composition was then dissolved to form a composition solution. Ten parts of the composition solution were added to 90 parts of deionized water and mixed thoroughly for use in evaluating the performance of the skincare product.

[0044] Performance Evaluation

[0045] 1. Evaluation of physical barrier function

[0046] 1.1 Experimental Principle

[0047] The principle behind the stratum corneum moisture content test is that water has a very high dielectric constant (approximately 81), far exceeding that of other substances (approximately 7). When a test probe comes into contact with the skin, the change in capacitance reflects the moisture content of the stratum corneum; the higher the moisture content, the higher the capacitance, and vice versa. The test data is a relative value. By measuring the change in the capacitance of the stratum corneum before and after product use, the change in stratum corneum moisture content can be measured, thereby evaluating the repair effect on the physical barrier function.

[0048] 1.2 Experimental Procedure

[0049] (1) Four volunteers were selected for this experiment. Before the experiment, the subjects were required to clean the inside of their forearms and then wipe them clean with a dry tissue.

[0050] (2) After cleaning, mark the measurement area on the inside of the subject's forearms. Before the formal test, the subject should sit quietly in a compliant room for at least 20 minutes without drinking water or beverages. The forearms should be exposed, placed in the testing position, and kept relaxed. Mark 3x3cm on the inside of the volunteer's left and right arms. 2 In the test area, multiple areas can be marked simultaneously on the same arm, with a 1cm interval between areas.

[0051] (3) The test product and blank control were randomly distributed on the left and right arms. After adjusting the instrument according to the instruction manual of the capacitance method skin moisture meter, the initial values ​​of the test area and control area were measured, and each area was measured in parallel 3 times.

[0052] (4) The amount of product applied to the test area was (2.0±0.1 mg) / cm². 2 The control area is not coated with the product.

[0053] (5) The moisture content was measured 1h, 2h and 6h after the sample was applied. During the experiment, the test areas of the four volunteers were equilibrated in a constant temperature and humidity environment (temperature 20±2℃; relative humidity 50%±2%) for 30min.

[0054] The specific results are shown in Table 1:

[0055] Table 1. Changes in water content of the stratum corneum over 6 hours (n=4)

[0056]

[0057] Note: * This indicates that P < 0.05; ** This indicates that P < 0.01

[0058] As can be seen from the results in Table 1, the changes in stratum corneum moisture content of Examples 1, 2, and 3 containing the complete composition within 1 to 6 hours were higher than those of the blank group, Comparative Examples 1, 2, and 3 containing only one barrier function ingredient, and Comparative Examples 4, 5, and 6 containing two barrier function ingredients. At the same time, the changes in stratum corneum moisture content of Example 1 containing the complete composition within 1 hour and 2 hours were significantly different from those of the blank group.

[0059] 2. Evaluation of microbial barrier function and its synergistic effects

[0060] 2.1 Experimental Principle

[0061] Studies have shown that the main change in skin microbiota in sensitive skin compared to normal skin is the reduction of Staphylococcus epidermidis. Therefore, Staphylococcus epidermidis was chosen as the primary focus of this study. The effect of the product on the growth of Staphylococcus epidermidis was measured to examine the product's repair effect on the microbial barrier function.

[0062] 2.2 Experimental Procedure

[0063] (1) Prepare nutrient broth culture medium and nutrient agar culture medium, and autoclave them.

[0064] (2) Reviving frozen Staphylococcus epidermidis: Take frozen Staphylococcus epidermidis and add it to 10 mL of nutrient broth. Shake at 37°C for 24 h until the medium becomes turbid. Heat the inoculation loop in the outer flame of an alcohol lamp and let it cool to room temperature. Then, use the inoculation loop to streak the liquid medium in a "Z" pattern on the nutrient agar medium and incubate upside down at 37°C for 24 h. Afterward, store in a 4°C refrigerator for later use.

[0065] (3) Take the nutrient agar medium (stored at 4℃) of the above-mentioned inoculated test strain. Pick 3-5 colonies from the plate and transfer them to 10mL of nutrient broth medium. Shake at 37℃ for 24h to obtain a fresh bacterial suspension.

[0066] (4) Prepare nutrient broth liquid culture medium without the test product and nutrient broth culture medium containing the test product respectively, and inoculate 100 μL of Staphylococcus epidermidis into each medium and shake at 37°C for 24 h.

[0067] (5) After the cultured bacterial suspension is serially diluted, colony counting is performed.

[0068] Specific results are as follows Figure 1 As shown in Table 2:

[0069] Table 2. Number of Staphylococcus epidermidis bacteria

[0070]

[0071] from Figure 1It can be seen that Example 1, containing the complete composition, exhibited the strongest growth-promoting effect on Staphylococcus epidermidis and the highest growth rate. Meanwhile, Examples 1, 2, and 3, which added the complete composition, all showed significant differences compared to the control group.

[0072] Using the data in Table 2, the number of Staphylococcus epidermidis bacteria and the matrix value were calculated after removing the influence of the matrix (other components in the composition besides the active ingredient under investigation). The specific calculation method is as follows:

[0073] The number of Staphylococcus epidermidis bacteria growing in physical barrier active ingredient A = the number of Staphylococcus epidermidis bacteria growing in Example 1 - the number of Staphylococcus epidermidis bacteria growing in Comparative Example 6;

[0074] The number of Staphylococcus epidermidis bacteria growing in microbial barrier active ingredient B = the number of Staphylococcus epidermidis bacteria growing in Example 1 - the number of Staphylococcus epidermidis bacteria growing in Comparative Example 5;

[0075] The number of Staphylococcus epidermidis bacteria growing in immune barrier functional ingredient C = the number of Staphylococcus epidermidis bacteria growing in Example 1 - the number of Staphylococcus epidermidis bacteria growing in Comparative Example 4;

[0076] The number of Staphylococcus epidermidis growths in the combination of physical barrier active ingredient A and microbial barrier active ingredient B = the number of Staphylococcus epidermidis growths in Example 1 - the number of Staphylococcus epidermidis growths in Comparative Example 3;

[0077] The number of Staphylococcus epidermidis bacteria growing in the combination of physical barrier active ingredient A and immune barrier active ingredient C = the number of Staphylococcus epidermidis bacteria growing in Example 1 - the number of Staphylococcus epidermidis bacteria growing in Comparative Example 2;

[0078] The number of Staphylococcus epidermidis growths in the microbial barrier functional ingredient B + immune barrier functional ingredient C = the number of Staphylococcus epidermidis growths in Example 1 - the number of Staphylococcus epidermidis growths in Comparative Example 1;

[0079] The composition excluding the active ingredient matrix = (number of *Staphylococcus epidermidis* growths in Comparative Example 1 - number of *Staphylococcus epidermidis* growths in Comparative Example A + number of *Staphylococcus epidermidis* growths in Comparative Example 2 - number of *Staphylococcus epidermidis* growths in Comparative Example B + number of *Staphylococcus epidermidis* growths in Comparative Example 3 - number of *Staphylococcus epidermidis* growths in Comparative Example C) ÷ 3

[0080] Based on the above calculation results, the number of Staphylococcus epidermidis bacteria growing in the three active ingredients and the three active ingredients containing the matrix can be further calculated. The specific calculation results are shown in Table 3.

[0081] Table 3. Synergistic Effect Analysis

[0082]

[0083] Note: A represents physical barrier function components; B represents microbial function components; C represents immune barrier function components.

[0084] As shown in Table 3, after removing the influence of the matrix, the combination of the three barrier function components effectively promoted the growth of Staphylococcus epidermidis, with a higher number of growths than those containing only one barrier function component or two barrier function components. Even after considering the matrix influence, the number of Staphylococcus epidermidis grown in Example 1 containing the same components was greater than in Example 1, indicating a synergistic effect among the three function components.

[0085] The above results indicate that Example 1, containing the complete composition, effectively promotes the growth of Staphylococcus epidermidis, and its effect on repairing the microbial barrier is significantly better than that of the blank group, the control group containing only one barrier-active ingredient, and the control group containing two barrier-active ingredients. Only through reasonable screening and combination of the three barrier-active ingredients can their full efficacy be achieved.

[0086] 3. Evaluation of immune barrier function and its synergistic effects

[0087] 3.1 Experimental Principle

[0088] Histamine is a key mediator of type I hypersensitivity reactions. It can directly irritate the skin, leading to allergic reactions. When the body is exposed to physical or chemical stimuli or an allergic reaction occurs, intracellular histamine is released, triggering a triple reaction: itching, caused by the stimulation of unmyelinated C-fibers; wheals, caused by increased permeability of capillary and venule walls, manifesting as localized redness and swelling; and flare, caused by the release of vasoactive neuropeptides from afferent nerve fibers. Topical application to the skin may elicit a sensitive reaction, but the body absorbs histamine over time, so the sensitive reaction is temporary and does not cause tissue damage. Therefore, we established a histamine stimulation experimental model as a method for evaluating the effectiveness of histamine in relieving redness.

[0089] 3.2 Experimental Procedure

[0090] (1) Preparation of irritant: An aqueous solution containing 1% histamine. Take 20 mg of histamine and add it to 2 ml of distilled water. Shake well to dissolve.

[0091] (2) Four healthy volunteers were selected. Before participating in the test, no skin care products were used on the test site. The subjects should sit quietly in a standard room for at least 20 minutes before the formal test. The test site was exposed, placed in the test position, and kept relaxed.

[0092] (3) Rest for 20 minutes in a laboratory at a temperature of 21±1℃ and a relative humidity of 50±5%. Draw a 3×3cm line on the inner side of both front arms of the subject. 2The experimental area was marked with a specific size for the experiment. 40 μL of the stimulant was transferred using a pipette and applied to the marked areas on both arms of the subject. The stimulant was then gently dabbed two or three times with a finger wearing a cot, forming a circular area with a diameter of 4 mm. Once the experimental area turned red, 0.036 g of the test substance was applied to the stimulated area on each forearm.

[0093] (4) Record the time of erythema fading after the test substance is applied to the subjects.

[0094] The specific results are shown in Table 4:

[0095] Table 4. Erythema resolution time in subjects (n=4)

[0096]

[0097]

[0098] As can be seen from Table 4, after using Example 1 containing the complete composition, the erythema faded in the shortest time compared with the blank group, Comparative Examples 1, 2, and 3 containing only one barrier function ingredient, and Comparative Examples 4, 5, and 6 containing two barrier function ingredients.

[0099] Using the data in Table 4, the reduction time for erythema fading for each and two active ingredients after removing the influence of the matrix was calculated. To ensure that the results are positive, the specific calculation method is as follows:

[0100] The time for erythema to fade was shortened by physical barrier active ingredient A = erythema time in Comparative Example 6 - erythema time in Example 1;

[0101] The time for erythema to fade was shortened by the microbial barrier active ingredient B = the time for erythema to fade in Comparative Example 5 - the time for erythema to fade in Example 1;

[0102] The time for erythema to fade was shortened by the immune barrier active ingredient C = the time for erythema to fade in Comparative Example 4 - the time for erythema to fade in Example 1;

[0103] The shortened erythema regression time of physical barrier active ingredient A + microbial barrier active ingredient B = erythema regression time of Comparative Example 3 - erythema regression time of Example 1;

[0104] The time for erythema regression shortened by physical barrier active ingredient A + immune barrier active ingredient C = erythema regression time of Comparative Example 2 - erythema regression time of Example 1;

[0105] The time for erythema regression shortened by microbial barrier active ingredient B + immune barrier active ingredient C = erythema regression time of Comparative Example 1 - erythema regression time of Example 1;

[0106] Based on the above calculation results, the reduction time of erythema fading by the three active ingredients can be further calculated. Specific calculation results are shown in Table 5.

[0107] Table 5. Synergistic Effect Analysis

[0108]

[0109]

[0110] Note: A represents physical barrier function components; B represents microbial function components; C represents immune barrier function components.

[0111] As can be seen from Table 5, the combination of the three barrier function ingredients can effectively reduce erythema, and the erythema reduction time is longer than that of ingredients containing only one barrier function ingredient or ingredients containing two barrier function ingredients.

[0112] The above results indicate that the three barrier-functional components, when properly combined, have a better effect on repairing the immune barrier than the control group containing one barrier-functional component and the control group containing two barrier-functional components.

Claims

1. A synergistic repair composition for multiple barrier damage in sensitive skin, comprising the following components in parts by weight: 10-25 parts of physical barrier efficacy component, 3-10 parts of immune barrier efficacy component, 3-10 parts of microbial barrier efficacy component, and 56-84 parts of solvent.

2. The composition according to claim 1, characterized in that: The physical barrier active ingredient is a mixture of ceramide NP, cholesterol, and stearic acid.

3. The composition according to claim 1, characterized in that: The immune barrier active ingredient is selected from one of the following: ammonium glycyrrhizate, kava extract, 4-tert-butylcyclohexanol, and stearyl glycyrrhetinic acid ester.

4. The composition according to claim 1, characterized in that: The active ingredient for the microbial barrier is selected from one of the following: Lactobacillus / soy milk fermentation filtrate, inulin, and lactic acid bacteria fermentation lysate.

5. The composition according to claim 1, characterized in that: The solvent is selected from propylene glycol, butylene glycol, and PEG-40 hydrogenated castor oil.

6. The composition according to any one of claims 1 to 5, comprising the following components in parts by weight: 10 to 18 parts of physical barrier efficacy component, 3 to 8 parts of immune barrier efficacy component, 3 to 8 parts of microbial barrier efficacy component, and 64 to 84 parts of solvent.

7. The composition according to claim 6, comprising the following components in parts by weight: 18 parts of physical barrier efficacy component, 8 parts of immune barrier efficacy component, 8 parts of microbial barrier efficacy component, and 64 parts of solvent.

8. The use of the composition according to any one of claims 1 to 5 in the preparation of skin care products.

9. The application as described in claim 8, characterized in that: The skincare products mentioned are selected from skincare creams, lotions, and serums.

10. A skincare product with a synergistic repair effect on multiple skin barriers for sensitive skin and / or other damaged skin, characterized in that... The composition comprising any one of claims 1 to 7.

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