Composition, use and cosmetics

By combining hydrolyzed corn starch and sodium heparin in cosmetics, and adding citrus fruit extract and 4-tert-butylcyclohexanol, the anti-allergic effect is significantly improved, the problem of limited anti-allergic function of sodium heparin is solved, and better is achieved soothing and redness-fading effects.

CN118750412BActive Publication Date: 2024-12-27HUAANTANG BIOTECH GRP CO LTD
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Patent Information

Application Number
CN202411215991.5
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-09-02
Publication Date
2024-12-27
Estimated Expiration
2044-09-02

AI Technical Summary

Technical Problem

In the prior art, the anti-allergic function of heparin sodium is limited, making it difficult to achieve better results in cosmetics.

Method used

Hydrolyzed corn starch and sodium heparin were combined, and citrus fruit extract and/or 4-tert-butylcyclohexanol were added as synergistic ingredients. The significant soothing and redness effects were verified through AI screening and in vitro cell experiments.

Benefits of technology

It significantly improves the anti-allergic effect, is better than the activity of a single or missing combination component, and can synergistically cover the five core targets related to redness, itching and pain, significantly reduces the sting and redness caused by histamine pricking and capsaicin stimulation. degree.

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Abstract

The invention belongs to the field of daily chemicals, and discloses a composition, use, and cosmetics. The composition consists of sodium heparin, hydrolyzed corn starch, and a synergistic component; the synergistic component is citrus fruit extract and / or 4-tert-butyl cyclohexanol; the weight ratio of sodium heparin to hydrolyzed corn starch is 0.005-0.5:0.1-5. The composition can achieve a more excellent soothing effect by compounding hydrolyzed corn starch and sodium heparin.
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Description

Technical Field

[0001] The invention belongs to the field of daily chemicals, and in particular relates to a composition, use and cosmetics. Background Art

[0002] The anti-allergic function of heparin sodium can be found in the following literature:

[0003] Prior art 1: A Chinese invention patent application with publication number CN102379838B discloses a method for preparing and applying a soothing and calming cosmetic, which discloses that low molecular weight heparin is a polysaccharide component inherent in the human body, is non-irritating to the skin, has stable chemical properties, and also has anti-inflammatory and anti-allergic effects.

[0004] Prior art 2: A Chinese invention patent application with publication number CN109512760A discloses a method for preparing a compound plant soothing and repairing essence, which discloses that the soothing and anti-inflammatory agents are bisabolol, paeonol, rohanol, glycyrrhetinic acid, and heparin sodium, and the mass ratio of bisabolol, paeonol, rohanol, glycyrrhetinic acid, and heparin sodium is 2-3:2-3:1-2:2-3:1-2.

[0005] During the screening of anti-allergic formulas, it was indeed discovered that sodium heparin alone has certain anti-allergic functions.

[0006] The technical problem to be solved in this case is: how to further improve the anti-allergic ability of heparin sodium. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention aims to provide a composition, which is compounded with hydrolyzed corn starch and sodium heparin, and uses citrus fruit extract and / or 4-tert-butyl cyclohexanol as synergistic ingredients, which can achieve a more excellent anti-allergic effect. The composition is screened by AI and is effective against multiple targets, and can show significant soothing and redness-removing effects at both the in vitro cell experiment level and the clinical experiment level, and its effect is better than the single active ingredient or the lack of one active ingredient in the combination.

[0008] Meanwhile, the invention also provides application and cosmetics of the composition.

[0009] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0010] A composition consists of sodium heparin, hydrolyzed corn starch and a synergistic component; the synergistic component is citrus fruit extract and / or 4-tert-butyl cyclohexanol; the weight ratio of the sodium heparin to the hydrolyzed corn starch is 0.005-0.5:0.1-5.

[0011] In the preliminary experiments of the present invention, it was found that a composition containing sodium heparin and hydrolyzed corn starch and the weight ratio of sodium heparin and hydrolyzed corn starch in the composition was 0.005-0.5:0.1-5, preferably when the weight ratio of sodium heparin and hydrolyzed corn starch was 0.01-0.5:0.1-5, showed a relatively excellent anti-allergic effect, and after the stinging test of human histamine prick, the redness test, and the capsaicin stimulation modeling test, it was found that the above two can have a relatively excellent synergistic effect. At the beginning of the development of the present invention, by querying relevant information, the five core targets associated with redness, itching, and pain were found-TRPV1, TRPA1, NK1R, HR1, and ETAR. Then, the AI ​​molecular simulation docking platform was used to screen the compounds in the "Catalogue of Used Cosmetic Raw Materials (2021 Edition)" to find active substances targeting the docking of the five major receptors-sodium heparin and hydrolyzed corn starch (maltotetraose).

[0012] Among them, hydrolyzed corn starch is a polysaccharide obtained by hydrolyzing natural corn starch. It appears as a white crystalline powder and has a high content of maltotetraose. Maltotetraose is a member of the maltooligosaccharide family. In addition to having good film-forming properties, this substance can also promote the expression of moisturizing-related proteins, inhibit the release of inflammatory factors, hinder the activation of nerve receptors, and exert long-lasting moisturizing, antipruritic and anti-allergic effects. Maltotetraose has a unique molecular structure and has a good shielding effect on itch nerves.

[0013] After analysis, it is believed that the principle of the synergy between the above two substances lies in the fact that the combination of these two substances can cover the five core receptors associated with redness, itching and pain, so they have a good synergistic effect in soothing.

[0014] In the ongoing experiments, it was found that when citrus fruit extract and / or 4-tert-butyl cyclohexanol were used as synergistic ingredients, the anti-allergic effect could be further significantly improved and showed obvious synergy.

[0015] Citrus fruit extract is rich in flavonoids, alkaloids and other ingredients, which can inhibit the activation of TRPV1, an important receptor in the skin that causes nerve stimulation. It can effectively relieve the burning, redness and tingling sensation caused by sensitive skin when it is stimulated, making the skin feel comfortable.

[0016] 4-tert-Butylcyclohexanol is a specific TRPV1 antagonist, and has been proven in human tests to be effective in blocking the burning or stinging sensation caused by capsaicin, thereby effectively relieving skin discomfort.

[0017] It can be seen that further antagonism of TRPV1 can improve the anti-allergic effect of sodium heparin and hydrolyzed corn starch under the condition of simultaneous presence of sodium heparin and hydrolyzed corn starch.

[0018] The specific synergistic mechanism is:

[0019] The AI ​​screening covers the component that inhibits TRPV 1 receptors, which is heparin sodium, but it ranks slightly behind. In order to further make up for the efficacy in TRPV1 inhibition, the raw materials on the market for TRPV1 inhibition were screened, and it was found that 4-tert-butyl cyclohexanol and citrus fruit extract can effectively enhance the soothing effect of the composition. The synergistic effect is analyzed because 4-tert-butyl cyclohexanol can regulate the activity of TRPV1 itself, thereby inhibiting the influx of calcium ions and alleviating nerve perception. Citrus fruit extract inhibits TRPV1 receptors from four aspects. It can inhibit the expression of TRPV1 receptors in keratinocytes, inhibit the activation of TRPV1 receptors in keratinocytes, inhibit the expression of TRPV1 receptors in nerve cells, and also inhibit the activation of TRPV1 receptors in nerve cells. By adding two substances separately, or by synergizing the two substances, the expression and activation of TRPV1 receptors can be inhibited throughout the chain, and the influx of calcium ions can be reduced, thereby enhancing the effects of heparin sodium and hydrolyzed corn starch (maltotetraose) in relieving burning and pain.

[0020] The heparin sodium of the present invention may further include heparinoid sodium; heparinoid sodium is a sulfonic mucopolysaccharide formed by sulfonation of natural glycosaminoglycan, and is similar to heparin sodium in terms of activity and function.

[0021] In the above composition, the weight ratio of heparin sodium to hydrolyzed corn starch is 0.01-0.5:0.1-5.

[0022] In the above composition, the weight ratio of heparin sodium to the synergistic component is 0.005-0.5:0.01-5.

[0023] In the above composition, when the synergistic component is citrus fruit extract, the weight ratio of heparin sodium to the synergistic component is 0.005-0.5:0.05-3;

[0024] When the synergistic component is 4-tert-butyl cyclohexanol, the weight ratio of heparin sodium to the synergistic component is 0.005-0.5:0.01-2.

[0025] At the same time, the present invention also discloses the use of the above-mentioned composition in preparing cosmetics and agents for soothing effects.

[0026] In addition, the present invention also discloses the use of the above composition in preparing cosmetics with soothing effect.

[0027] Finally, the present invention also discloses a cosmetic comprising any one of the above compositions.

[0028] In the above-mentioned cosmetic, the concentration of the composition is 0.105wt% to 13.5wt%.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] The present invention uses sodium heparin and hydrolyzed corn starch to effectively reduce the irritation of cosmetics, and the excellent soothing performance exhibited by the composition can improve the application prospects of many cosmetics on the skin. The mechanism of the soothing performance exhibited by the present invention is that the combination of sodium heparin and hydrolyzed corn starch can cover the five core receptors associated with redness, itching and pain, and has a good synergistic effect in soothing.

[0031] The AI ​​screening covers the component that inhibits TRPV 1 receptors, which is heparin sodium, but it ranks slightly behind. In order to further make up for the efficacy in TRPV1 inhibition, the raw materials on the market for TRPV1 inhibition were screened, and it was found that 4-tert-butyl cyclohexanol and citrus fruit extract can effectively enhance the soothing effect of the composition. The synergistic effect is analyzed because 4-tert-butyl cyclohexanol can regulate the activity of TRPV1 itself, thereby inhibiting the influx of calcium ions and alleviating nerve perception. Citrus fruit extract inhibits TRPV1 receptors from four aspects. It can inhibit the expression of TRPV1 receptors in keratinocytes, inhibit the activation of TRPV1 receptors in keratinocytes, inhibit the expression of TRPV1 receptors in nerve cells, and also inhibit the activation of TRPV1 receptors in nerve cells. By adding two substances separately, or by synergizing the two substances, the expression and activation of TRPV1 receptors can be inhibited throughout the chain, and the influx of calcium ions can be reduced, thereby enhancing the effects of heparin sodium and hydrolyzed corn starch (maltotetraose) in relieving burning and pain. DETAILED DESCRIPTION

[0032] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0033] Source of reagents:

[0034] Heparin sodium: purchased from Synsil Organic Inc., product model: Arboris ® SDH;

[0035] Hydrolyzed corn starch: purchased from Shanghai Zibang Biopharmaceutical Co., Ltd., product model: BINMOIS MAT;

[0036] Citrus fruit extract: purchased from Shanghai Jiakai Biological Co., Ltd., product model: Calmner vCR;

[0037] 4-tert-Butyl cyclohexanol; purchased from SymSitive (Shanghai) Co., Ltd., product model: SymSitive® 1609.

[0038] Part I Study on the soothing properties of sodium heparin and hydrolyzed corn starch

[0039] The test formula of this part is an emulsion, which has good spreadability and can accurately demonstrate the soothing effect of the combination of the present invention in the subsequent testing process.

[0040] After testing, there is no difference in irritation between the emulsion of the present invention (without sodium heparin and hydrolyzed corn starch) and the blank group, which proves that the emulsion system of the present invention can more scientifically and accurately reflect the soothing performance of the present invention.

[0041] Table 1 below is the formula of the composition of the present invention; the base material in Table 1 refers to the formula in Table 2;

[0042] Table 1 Composition formula

[0043] Heparin sodium content / wt% Hydrolyzed corn starch content / wt% Base material content / wt% Example 1 0.01 5 Up to 100 Example 2 0.5 0.1 Up to 100 Example 3 0.2 2 Up to 100 Example 4 0.01 0.1 Up to 100 Example 5 0.3 3 Up to 100 Example 6 0.005 5 Up to 100 Example 7 0.005 0.1 Up to 100 Example 8 0.1 2 Up to 100 Example 9 0.005 2 Up to 100 Example 10 0.2 0.1 Up to 100 Embodiment 11 0.2 0.5 Up to 100 Comparative Example 1 0.2 0 Up to 100 Comparative Example 2 0 2 Up to 100 Comparative Example 3 0.01 0 Up to 100 Comparative Example 4 0 0.1 Up to 100 Control group (base material) 0 0 Up to 100 blank 0 0 0

[0044] Table 2 Base material formula

[0045]

[0046] The preparation process of Table 2 is as follows:

[0047] 1. Heat the raw materials of phase A to 70-90°C until completely dissolved;

[0048] 2. Add the ingredients of phase B into the main pot and heat to 70-90℃ until completely dissolved;

[0049] 3. Add phase A into the main pot of phase B and emulsify and homogenize at 70-90°C for 1-6 minutes;

[0050] 4. Add phase C to the main pot, continue homogenizing for 0.5-3 minutes, and start cooling;

[0051] 5. Cool down to below 60℃ and add dissolved phase D into the main pot;

[0052] 6. Add dissolved phase E into the main pot and stir;

[0053] 7. Add phase F to the main pot and stir to dissolve;

[0054] 8. Cool down to below 45℃ and filter out the material.

[0055] Performance Testing

[0056] The performance test is divided into three parts: human histamine prick test-stinging test; human histamine prick test-redness test; capsaicin stimulation modeling test;

[0057] The test project was fully notified to the subjects before it was carried out, and with the subjects' consent, the subjects' rights and interests were fully protected, which complied with ethical requirements.

[0058] The specific test method is:

[0059] Human Histamine Prick Test - Sting and Redness Test:

[0060] Histamine stimulation is a classic model for inducing inflammation. Skin inflammation caused by histamine mainly includes: itching, redness, pimples, blisters, etc. Using the performance of the histamine model, the anti-inflammatory and redness-removing ability test is fast and intuitive.

[0061] Number of testers: 10; Gender: Both men and women; Age: 18-55 years old;

[0062] Environmental conditions: Each subject was allowed to relax and achieve equilibrium at a constant temperature of 21±1°C and a relative humidity of 50±10%RH;

[0063] Test site: inner side of arm;

[0064] Reagent materials and instruments: histamine phosphate, medical pricking needles, soothing samples;

[0065] Test method (puncture method): Use a puncture needle to puncture the test area on the inside of the arm, and the standard is no bleeding; use 1% histamine phosphate solution, drip 0.02ml on the inside of the arm, absorb the histamine solution after 5 minutes, and wait for about 10 minutes. Apply 0.02g of sample to the 2*2cm area of ​​the sample area and the control area, record the redness and itching of the arm at each time point, and score and record.

[0066] The test parts were evaluated at the corresponding time nodes (0min, 15min, 30min).

[0067] Histamine pain improvement rate (%) = (pain score at 0 minute after histamine prick modeling - pain score at n minutes after histamine prick modeling) × 100% / pain score at 0 minute after histamine prick modeling;

[0068] Histamine redness improvement rate (%) = (redness score at 0 minutes after histamine pricking modeling - redness score at n minutes after histamine pricking modeling) × 100% / redness score at 0 minutes after histamine pricking modeling;

[0069] Itch / pain scoring criteria:

[0070] 5 points: obvious severe itching / pain, can't help scratching / unbearable;

[0071] 4 points: obvious itching / pain, want to scratch from time to time / can tolerate it;

[0072] 3 points: slight itching / pain, no treatment is required;

[0073] 2 points: vague itching / pain, which cannot be accurately described;

[0074] 1 point: No itching / pain.

[0075] Redness rating scale:

[0076] 5 points: obvious and severe redness;

[0077] 4 points: obvious redness;

[0078] 3 points: moderate redness;

[0079] 2 points: very slight redness;

[0080] 1 point: No redness, same skin color as untreated area.

[0081] Capsaicin stimulation model test

[0082] TRPV1, also known as the capsaicin receptor, plays a key role in pain and nociception. Once activated, it causes an influx of calcium ions, generates an action potential, and the electrical signal is transmitted along the nerves through the thalamus and then generates heat and pain in the cerebral cortex. For example, capsaicin, UV, over-acid environment, retinol, phenoxyethanol, etc. can all cause its activation. The activation of TRPV1 can trigger an inflammatory response in the skin, interfere with barrier repair, and accelerate skin aging.

[0083] Number of testers: 10; Gender: Both men and women; Age: 18-55 years old;

[0084] Environmental conditions: Each subject was allowed to relax and achieve equilibrium at a constant temperature of 21±1°C and a relative humidity of 50±10%RH;

[0085] Test site: inner side of arm;

[0086] Reagent materials and instruments: 3% capsaicin ethanol solution, spot tester, skin color test probe (ColorimeterCL400), soothing sample;

[0087] Test method: Asian adult subjects were selected, 170μL of 3% capsaicin ethanol solution was added to the patch tester, and the patch was applied to the designated inner forearm area for 15 minutes. Stimulate the skin on the inner forearm area to produce stable erythema, use the sample once on the test area, and test the redness a* value with the skin color test probe (Colorimeter CL400) to evaluate the product's efficacy in soothing reddened skin.

[0088] Redness fading rate at n minutes (%) = (redness a* value at 0 minutes after capsaicin modeling - redness a* value at n minutes after capsaicin modeling) × 100% / redness a* value at 0 minutes after capsaicin modeling;

[0089] The test results can be seen in Tables 3 and 4;

[0090] Table 3 Histamine prick test results

[0091]

[0092] Result analysis:

[0093] 1. At different time points, the improvement rates of stinging and redness in the blank group and the control group (base material) were similar. Therefore, the base material did not affect the stinging and redness, and the influence of the base material on the stinging and redness was excluded;

[0094] It can be seen from Comparative Examples 1, 2, 3 and 4 that when the dosage of heparin sodium reaches 0.2wt% or more, it can show a certain soothing performance, which is slightly better than hydrolyzed corn starch (without considering the dosage); the performance of heparin sodium used alone is equivalent to that of Example 7;

[0095] It can be seen from the above comparative examples that when the dosage of heparin sodium and hydrolyzed corn starch is controlled to a certain level, a certain soothing effect can be achieved.

[0096] 2. At different time points, Example 3 is significantly better than Comparative Examples 1 and 2 in reducing the degree of stinging and redness, indicating that heparin sodium and hydrolyzed corn starch can synergistically and significantly reduce the degree of stinging and redness after histamine prick.

[0097] 3. At different time points, the improvement rate of reducing the pain and the redness in Example 4 were significantly better than those in Comparative Examples 3 and 4, indicating that sodium heparin and hydrolyzed corn starch can synergistically significantly reduce the pain and redness after histamine prick.

[0098] 4. If the improvement rate of 30 min greater than 50% is used as an evaluation index of excellent performance, from Examples 6, 7, and 9, if the amount of heparin sodium is 0.005wt%, the amount of hydrolyzed corn starch reaches 2.0wt% or more to achieve the excellent standard; from the results of Examples 2, 4, 7, and 10, if the amount of hydrolyzed corn starch is 0.1wt%, the amount of heparin sodium reaches 0.1wt% or more to achieve the excellent standard.

[0099] At the same time, according to the results of Comparative Example 1, Comparative Example 2 and Example 7, even if the amount of heparin sodium and hydrolyzed corn starch is very small, there is still a strong internal synergy between the two.

[0100] The fundamental reason for the synergy in soothing performance between sodium heparin and hydrolyzed corn starch is that the combination of the two can cover the five core targets of TRPV1, TRPA1, NK1R, HR1, and ETAR, so that the performance can be comprehensively exerted to achieve the best soothing effect.

[0101] Table 4 Capsaicin stimulation model test results

[0102]

[0103] Result analysis:

[0104] 1. At different time points, the red fading rates of the blank group and the control group (base material) were similar. Therefore, the base material did not affect the degree of red fading, and the influence of the base material on the degree of red fading was excluded;

[0105] 2. At different time points, the redness fading rate of Example 3 was significantly better than that of Comparative Example 1 and Comparative Example 2, indicating that heparin sodium and hydrolyzed corn starch can synergistically improve the redness fading degree after capsaicin modeling;

[0106] 3. At different time points, the redness fading rate of Example 4 was significantly better than that of Comparative Examples 3 and 4, indicating that sodium heparin and hydrolyzed corn starch can synergistically improve the redness fading degree after capsaicin modeling.

[0107] Part II Study on the anti-allergic properties of sodium heparin, hydrolyzed corn starch, citrus fruit extract, and 4-tert-butyl cyclohexanol

[0108] Table 5 below is the formula of the composition of the present invention; the base material in Table 5 refers to the formula in Table 6;

[0109] Table 5 Composition formula

[0110] Scope of protection Heparin sodium content / wt% Hydrolyzed corn starch content / wt% Citrus fruit extract / wt% 4-tert-Butyl cyclohexanol / wt% Base material content / wt% Example 4 0.01 0.1 0 0 Up to 100 Comparative Example 3 0.01 0 0 0 Up to 100 Comparative Example 4 0 0.1 0 0 Up to 100 Example 12 0.01 0.1 0.05 0 Up to 100 Embodiment 13 0.01 0.1 1.5 0 Up to 100 Embodiment 14 0.01 0.1 3 0 Up to 100 Embodiment 15 0.01 0.1 0 0.01 Up to 100 Example 16 0.01 0.1 0 1 Up to 100 Embodiment 17 0.01 0.1 0 2 Up to 100 Embodiment 18 0.01 0.1 0.05 0.01 Up to 100 Comparative Example 5 0.01 0 0.05 0 Up to 100 Comparative Example 6 0 0.1 0.05 0 Up to 100 Comparative Example 7 0.01 0 0 0.01 Up to 100 Comparative Example 8 0 0.1 0 0.01 Up to 100 Control group (base material) 0 0 0 0 Up to 100 blank 0 0 0 0 0

[0111] Table 6 Formula of base material

[0112]

[0113] The preparation process of Table 6 is as follows:

[0114] 1. Heat the raw materials of phase A to 70-90°C until completely dissolved;

[0115] 2. Add the ingredients of phase B into the main pot and heat to 70-90℃ until completely dissolved;

[0116] 3. Add phase A into the main pot of phase B and emulsify and homogenize at 70-90°C for 1-6 minutes;

[0117] 4. Add phase C to the main pot and continue homogenizing for 0.5-3 minutes;

[0118] 5. Add D to the main pot, stir evenly, and start cooling;

[0119] 6. Cool down to below 60℃ and add dissolved phase D into the main pot;

[0120] 7. Add dissolved phase E into the main pot and stir;

[0121] 8. Add phase F to the main pot and stir to dissolve;

[0122] 9. Cool down to below 45℃ and filter out the material.

[0123] Performance Testing

[0124] Human Histamine Prick Test - Redness Test

[0125] The test method refers to the human histamine prick test-redness test in Part 1.

[0126] The test results can be seen in Table 7;

[0127] Table 7 Histamine prick test results

[0128]

[0129] Result analysis:

[0130] 1. At different time points, the improvement rates of redness in the blank group and the control group (base material) were similar. Therefore, the control group with base material did not affect the redness, excluding the influence of base material on the redness;

[0131] 2. 15 minutes and 30 minutes after histamine prick application, the improvement rate of redness in Examples 12-14 was higher than that in Example 4, indicating that the addition of citrus fruit extract on the basis of heparin sodium and hydrolyzed corn starch has a synergistic effect of reducing the redness, and the synergistic effect of reducing the redness is better with the increase of citrus fruit extract;

[0132] 3. 15min and 30min after histamine prick application, the improvement rate of redness in Examples 15-17 was improved compared with that in Example 4, indicating that the addition of 4-tert-butyl cyclohexanol to heparin sodium and hydrolyzed corn starch has a synergistic effect of reducing the redness, and the effect of synergistically reducing the redness is better with the increase of 4-tert-butyl cyclohexanol;

[0133] 4. 15min and 30min after histamine pricked the sample, the improvement rate of redness in Example 12 was significantly improved compared with Comparative Examples 5-6. This shows that the addition of citrus fruit extract on the basis of sodium heparin and hydrolyzed corn starch has a significant effect in reducing redness. However, in the absence of sodium heparin or hydrolyzed corn starch, the addition of citrus fruit extract did not significantly reduce the redness;

[0134] 5. 15min and 30min after histamine pricked the sample, the improvement rate of redness in Example 15 was significantly improved compared with Comparative Examples 7-8. This shows that adding 4-tert-butyl cyclohexanol to sodium heparin and hydrolyzed corn starch has a significant effect in reducing redness. However, in the absence of sodium heparin or hydrolyzed corn starch, adding 4-tert-butyl cyclohexanol did not significantly reduce the redness;

[0135] 6. 15min and 30min after histamine prick application, the improvement rate of redness in Example 18 was further improved compared with Examples 12 and 15. This indicates that the synergistic effect of adding citrus fruit extract and 4-tert-butyl cyclohexanol to sodium heparin and hydrolyzed corn starch is more obvious, and the four raw materials of sodium heparin, hydrolyzed corn starch, citrus fruit extract and 4-tert-butyl cyclohexanol have a synergistic effect.

[0136] Part III In vitro experiments

[0137] Histamine calcium flux assay

[0138] 1. Materials and Methods

[0139] 1.1 Main reagents and consumables: NHEK (normal human primary keratinocytes) cells, EMEM culture medium, PBS Tablets, 0.25% Trypsin-EDTA (1X), double antibody (Pen Strep, PS), 96-well black-walled transparent bottom plate, Fluo-4 calcium ion detection kit, histamine, loratadine, etc.

[0140] 1.2 Instruments and equipment: constant temperature water bath, cell imaging multifunctional microplate detector, fully automatic cell analyzer, carbon dioxide incubator, biological safety cabinet, etc.

[0141] 2. Principle of the method

[0142] The itch-related HR1 receptor can be activated by the specific itch-inducing agent histamine, thereby promoting the release of downstream signaling molecules such as phospholipase A2 (PLA2), lipoxygenase (LOX), and protein kinase C (PKC), further activating itch-related ion channels such as transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and other calcium ion channels, promoting the opening of Ca 2+ channels. 2+ Influx of calcium in the cells completes the conduction of itch signals. NHEK cells are normal human epidermal keratinocytes that express a large number of HR1 receptors and calcium ion channels. Therefore, NHEK cells can be used to detect the relative level of intracellular calcium before and after histamine stimulation with the help of the Fluo-4 calcium ion detection kit to evaluate the efficacy of the raw materials to relieve itch.

[0143] 3. Experimental Procedure

[0144] 3.1 Prepare NHEK cells: Prepare a cell suspension with a density of 2.0×10^5 / mL, take 100 μL into a 96-well black-walled transparent bottom plate, and culture in a carbon dioxide incubator for 24 h.

[0145] 3.2 Sample preincubation: Preincubate for about 4 hours.

[0146] Positive group: 1 μM loratadine;

[0147] The sample group preparation is shown in Table 8 below, and the dosing details of each group are shown in Table 9 below:

[0148] Table 8 Sample set preparation details

[0149] Sample name Heparin sodium content / wt% Hydrolyzed corn starch content / wt% Water content / wt% Embodiment 19 0.2 2 Up to 100 Embodiment 20 0.005 2 Up to 100 Embodiment 21 0.2 0.1 Up to 100 Comparative Example 9 0.2 0 Up to 100 Comparative Example 10 0 2 Up to 100

[0150] Table 9 Experimental groups and drug administration details

[0151] Group Sample pre-incubation Stimulants Blank group Culture medium / Model Group Culture medium 10 μM histamine Positive group Culture medium + loratadine 10 μM histamine Sample set Culture medium + sample 10 μM histamine

[0152] 3.3 Incubate the dye: Incubate the dye according to the Fluo-4 Calcium Assay Kit procedure.

[0153] 3.4 Secondary incubation of samples: Secondary incubation of samples was performed for approximately 30 min.

[0154] 3.5 Detection: After adding histamine stimulation, the fluorescence intensity data was detected using the kinetic mode of the cell imaging multi-function microplate reader.

[0155] 3.6 Data processing: The maximum fluorescence intensity data after the addition of histamine stimulation was selected and divided by the fluorescence intensity data before stimulation to obtain the relative fluorescence intensity.

[0156] 3.7 Data analysis: Each group has ≥3 valid data, and the average value of the relative fluorescence intensity of each group is calculated. Compared with the relative fluorescence intensity value of the model group, the smaller the relative fluorescence intensity value of the sample group is, the better the sample is in relieving histamine-induced itching;

[0157] The calculation formula is: inhibition rate (%) = (relative fluorescence intensity of the model group - relative fluorescence intensity of the sample group) / relative fluorescence intensity of the model group × 100%.

[0158] 3.8 Histamine calcium flux test results refer to Table 10;

[0159] Table 10 Histamine calcium flux test results

[0160] Group Relative fluorescence intensity Inhibition rate Blank group 0.547 / Model Group 1.000 / Positive group 0.608 39.2% Embodiment 19 0.664 33.6% Embodiment 20 0.707 29.3% Embodiment 21 0.960 20.5% Comparative Example 9 0.942 5.8% Comparative Example 10 0.894 10.6%

[0161] Results Analysis

[0162] 1. Compared with Comparative Examples 9-10, the histamine calcium flow inhibition rate of Example 19 is significantly better than that of Comparative Examples 9-10, indicating that heparin sodium and hydrolyzed corn starch can synergistically significantly reduce histamine-induced itching;

[0163] 2. Compared with Comparative Example 10, the histamine calcium flow inhibition rate of Example 20 is significantly better than that of Comparative Example 10, indicating that a small amount of heparin sodium added to hydrolyzed corn starch can synergistically and significantly reduce histamine-induced itching;

[0164] 3. Compared with Comparative Example 9, the histamine calcium flow inhibition rate of Example 21 is significantly better than that of Comparative Example 9, indicating that adding a small amount of hydrolyzed corn starch on the basis of heparin sodium can synergistically and significantly reduce histamine-induced itching.

[0165] Part 4 Application Formulation

[0166] Application Formula 1 - Soothing Essence

[0167] The application formula 1 can refer to the following table 11, which is as follows:

[0168] Table 11 Soothing Essence Formula

[0169]

[0170] The preparation process of Table 11 is as follows:

[0171] 1. Heat the raw materials of phase A to 70-90°C and dissolve completely;

[0172] 2. Add the dissolved phase B ingredients into the main pot, stir evenly, and start cooling;

[0173] 3. Cool down to below 60℃, add dissolved phase C into the main pot and stir evenly;

[0174] 4. Add phase D to the main pot and stir to dissolve;

[0175] 5. Cool down to below 45℃ and filter out the material.

[0176] Application Formula 2 - Redness Relief Lotion

[0177] Application formula 2 can refer to Table 12 below, as follows:

[0178] Table 12 Redness-Repairing Soothing Lotion Formula

[0179]

[0180] The preparation process of Table 12 is as follows:

[0181] 1. Heat the raw materials of phase A to 70-90°C and dissolve completely;

[0182] 2. Add the ingredients of phase B into the main pot and heat to 70-90°C until completely dissolved;

[0183] 3. Add the dissolved phase A ingredients into the main pot, stir evenly, and start cooling;

[0184] 4. Cool down to below 60℃, add dissolved phase C into the main pot and stir evenly;

[0185] 5. Add phase D and phase E to the main pot and stir to dissolve;

[0186] 6. Cool down to below 45℃ and filter out the material.

[0187] Application Formula 3 - Redness Relief Cream

[0188] The application formula 3 can refer to the following table 13, which is as follows:

[0189] Table 13 Redness-Relief Cream Formula

[0190]

[0191] The preparation process of Table 13 is as follows:

[0192] 1. Heat the raw materials of phase A to 70-90°C and dissolve completely;

[0193] 2. Add the ingredients of phase B into the main pot and heat to 70-90°C until completely dissolved;

[0194] 3. Add the dissolved phase A ingredients into the main pot, stir evenly, and start cooling;

[0195] 4. Cool down to below 60℃, add dissolved phase C into the main pot and stir evenly;

[0196] 5. Add dissolved phase D and phase E into the main pot and stir to dissolve;

[0197] 6. Cool down to below 45℃ and filter out the material.

[0198] The present invention illustrates the process method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned process steps, and it does not mean that the present invention must rely on the above-mentioned process steps to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A composition, characterized in that It is composed of sodium heparin, hydrolyzed corn starch and a synergistic component; the synergistic component is citrus fruit extract or 4-tert-butyl cyclohexanol; the weight ratio of sodium heparin to hydrolyzed corn starch is 0.005-0.5:0.1-5; when the synergistic component is citrus fruit extract, the weight ratio of sodium heparin to the synergistic component is 0.005-0.5:0.05-3; When the synergistic component is 4-tert-butyl cyclohexanol, the weight ratio of heparin sodium to the synergistic component is 0.005-0.5:0.01-2.

2. The composition according to claim 1, characterized in that The weight ratio of the heparin sodium to the hydrolyzed corn starch is 0.01-0.5:0.1-5.

3. Use of the composition as claimed in claim 1 or 2 in preparing cosmetics with soothing effect.

4. A cosmetic, characterized in that: Containing the composition as claimed in claim 1 or 2.

5. The cosmetic according to claim 4, characterized in that: The concentration of the composition is 0.105 wt % to 13.5 wt %.