A skin external composition and use thereof

Abstract

The application discloses a composition for repairing skin barrier and application thereof, and the composition comprises sialic acid, hyaluronic acid or a salt thereof, and acetylated hyaluronic acid or a salt thereof. The composition of the application combines sialic acid (SA) with specific hyaluronic acid substances (HA) in a reasonable matching relationship, does not significantly weaken the antioxidant and anti-inflammatory effects of SA and HA, and can even produce a synergistic effect on the antioxidant and / or anti-inflammatory effects.

Description

Technical Field

[0001] This application relates to the field of cosmetic technology, specifically to a topical skin composition and its use. Background Technology

[0002] With the increasing number of people with "sensitive skin", skin barrier damage is not only caused by damage to the stratum corneum structure, but also by inflammatory responses and oxidative stress, which can lead to further damage to the skin.

[0003] While inflammation is a natural defense mechanism that initiates the skin's repair process, excessive inflammation can cause additional damage. During inflammation, the immune system releases a series of inflammatory factors (such as cytokines and chemokines), which attract immune cells, including white blood cells, to the site of injury. An excess of inflammatory factors can lead to an overgrowth of immune cells, causing them to attack surrounding healthy tissues and triggering or worsening skin damage.

[0004] Oxidative stress can lead to further skin damage: for example, free radicals can damage intercellular lipids, proteins, and DNA, leading to loss of cell function; they can also stimulate further inflammation and slow down the rate of barrier repair; at the same time, they can disrupt the connections between cells, making the skin barrier loose.

[0005] Therefore, when repairing the skin barrier, it is essential not only to promote the recovery of the stratum corneum structure but also to help the skin regulate inflammatory factors and inhibit oxidative stress. Skincare formulations typically employ ingredients that inhibit inflammatory factors and provide antioxidants to aid barrier repair. However, the combined use of these two methods does not yield ideal results in repairing skin barrier damage. Achieving a more satisfactory effect in repairing skin barrier damage is a pressing technical problem that needs to be solved in this field. Summary of the Invention

[0006] To address the problems existing in the prior art, this application aims to find a composition that can achieve both good antioxidant and anti-inflammatory effects, thereby obtaining a more ideal effect in repairing skin barrier damage. However, the inventors of this application discovered through experiments that when substances with antioxidant and / or anti-inflammatory effects are used in combination, one aspect of the antioxidant and anti-inflammatory effects may be significantly weakened, thus hindering skin barrier repair. To solve this problem, the inventors further discovered that combining sialic acid (SA) with specific hyaluronic acid (HA) substances in a reasonable combination relationship does not significantly weaken the antioxidant and anti-inflammatory effects of SA and HA, and may even produce a synergistic effect in antioxidant and / or anti-inflammatory effects, thus completing this invention.

[0007] Specifically, this application adopts the following scheme:

[0008] 1. A topical skin composition comprising sialic acid, hyaluronic acid or a salt thereof, and acetylated hyaluronic acid or a salt thereof;

[0009] The mass ratio of the total amount of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is greater than 1.5:1;

[0010] The mass ratio of the hyaluronic acid or its salt to acetylated hyaluronic acid or its salt is less than 1:1.

[0011] 2. The composition according to claim 1, wherein the mass ratio of the total amount of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is 2:1 to 8:1.

[0012] 3. The composition according to item 1 or 2, wherein the mass ratio of the hyaluronic acid or its salt to acetylated hyaluronic acid or its salt is 1:40 to 1:3.

[0013] 4. The composition according to any one of items 1-3, wherein the molecular weight of the hyaluronic acid or a salt thereof is less than 10,000 Da.

[0014] 5. The composition according to any one of items 1-4, wherein the molecular weight of the acetylated hyaluronic acid or its salt is 1 to 10 wDa.

[0015] 6. Use of the composition of any one of items 1-5 as an antioxidant and anti-inflammatory agent.

[0016] 7. Use of the composition of any one of items 1-5 as a skin barrier repair agent.

[0017] 8. The use of the composition of any one of items 1-5 as a skin care product.

[0018] Invention Effects

[0019] The composition of this application does not significantly weaken the inhibitory effects of SA and HA on oxidative stress and anti-inflammatory effects, and can achieve good antioxidant and anti-inflammatory effects at the same time.

[0020] Furthermore, the composition of this application can achieve both antioxidant and anti-inflammatory effects, and further produce a synergistic effect.

[0021] Based on the findings of this application, a reasonable approach is provided for using SA and HA to effectively enhance the skin barrier repair function of products. Detailed Implementation

[0022] The following description provides exemplary embodiments of this application, including various details to aid understanding, and should be considered merely exemplary. Therefore, those skilled in the art will recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. Similarly, for clarity and brevity, descriptions of well-known functions and structures are omitted in the following description.

[0023] This application provides a composition for repairing the skin barrier, comprising sialic acid, hyaluronic acid or a salt thereof, and acetylated hyaluronic acid or a salt thereof.

[0024] The above-described "composition" in this application is sufficient to achieve the effects described in this application. The "composition" includes, but is not limited to, the simultaneous or sequential use of the components. "Simultaneous use" includes using them together in the same formulation or using them separately in different formulations. "Sequential use" includes using them sequentially in different formulations, and there are no restrictions on the order of sequential use.

[0025] Sialic acid (SA) is an acidic carbohydrate compound, a naturally occurring carbohydrate found in many tissues and secretions of living organisms. It was initially isolated from submandibular gland mucin, hence its name. Sialic acid is a polysaccharide molecule composed of nine carbohydrate units.

[0026] The hyaluronic acid refers to a biopolymer material composed of linearly linked repeating units N-acetyl-D-glucosamine and D-glucuronic acid. The hyaluronic acid or its salts are used to include hyaluronic acid itself, its salts, or combinations thereof.

[0027] The hyaluronic acid or its salts described in this application, for example, are water-soluble salts of hyaluronic acid, including any one or more of sodium hyaluronate, potassium hyaluronate, zinc hyaluronate, calcium hyaluronate, silver hyaluronate, gold hyaluronate, magnesium hyaluronate, cobalt hyaluronate, and tetrabutylammonium hyaluronate. Preferably, the hyaluronic acid salt is selected from one or more of sodium hyaluronate, zinc hyaluronate, potassium hyaluronate, and bismuth hyaluronate.

[0028] The acetylated hyaluronic acid or its salt is a derivative of hyaluronic acid or its salt, prepared by acetylation of hyaluronic acid or its salt. The molecular weight range of sodium acetylated hyaluronic acid can be obtained by measuring the relative viscosity using an Ubbelohde viscometer and calculating it according to a formula.

[0029] The acetylated hyaluronic acid or its salts described in this application, for example, are water-soluble salts of acetylated hyaluronic acid, including any one or more of: sodium acetylated hyaluronic acid, potassium acetylated hyaluronic acid, zinc acetylated hyaluronic acid, calcium acetylated hyaluronic acid, silver acetylated hyaluronic acid, gold acetylated hyaluronic acid, magnesium acetylated hyaluronic acid, cobalt acetylated hyaluronic acid, and tetrabutylammonium acetylated hyaluronic acid. Preferably, the acetylated hyaluronic acid salt is selected from one or more of sodium acetylated hyaluronic acid salt, zinc acetylated hyaluronic acid salt, potassium acetylated hyaluronic acid salt, and bismuth acetylated hyaluronic acid salt.

[0030] In the composition of this application, the mass ratio of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is greater than 1.5:1; for example, it can be 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, 15:1, 20:1, 30:1, 50:1, 100:1. In some embodiments, the mass ratio of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is 2:1 to 8:1.

[0031] In the composition of this application, the mass ratio of hyaluronic acid or its salt to acetylated hyaluronic acid or its salt is less than 1:1, for example, it can be 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:25, 1:30, 1:40, 1:50, or 1:100. In some embodiments, the mass ratio of hyaluronic acid or its salt to acetylated hyaluronic acid or its salt is 1:40 to 1:3.

[0032] In the compositions of this application, the molecular weight of the hyaluronic acid or its salt may be less than 10,000 Da, for example, 9,900 Da, 9,800 Da, 9,500 Da, 9,300 Da, 9,000 Da, 8,500 Da, 8,000 Da, 7,500 Da, 7,000 Da, 6,500 Da, 6,000 Da, 5,500 Da, 5,000 Da, 4,800 Da, 4,500 Da, 4,300 Da, 4,000 Da, 3,500 Da, 3,000 Da, 2,500 Da, 2,000 Da, 1,500 Da, 1,000 Da, 500 Da, or 100 Da. In some embodiments, the molecular weight of the hyaluronic acid or its salt is less than 5,000 Da.

[0033] The molecular weight of the acetylated hyaluronic acid or its salt can be 1 to 10 wDa, for example, 1 wDa, 1.5 wDa, 2 wDa, 2.3 wDa, 3 wDa, 3.1 wDa, 3.2 wDa, 3.3 wDa, 3.4 wDa, 3.5 wDa, 3.6 wDa, 3.7 wDa, 3.8 wDa, 3.9 wDa, 4 wDa, 4.1 wDa, 4.2 wDa, 4.3 wDa, 4.4 wDa, 4.5 wDa, 4.6 wDa, 4.7 wDa, 4.8 wDa, 4.9 wDa, 5 wDa, 5.5 wDa, 6 wDa, 6.5 wDa, 7 wDa, 7.5 wDa, 8 wDa, 8.5 wDa, 9 wDa, 9.5 wDa. In some embodiments, the molecular weight of the acetylated hyaluronic acid or its salt is 3 to 5 wDa.

[0034] The degree of substitution of the acetylated hyaluronic acid or its salt can be 55-85%, for example, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, or 85%.

[0035] The intrinsic viscosity of the acetylated hyaluronic acid or its salt can be 0.1-10.0 dl / g, for example, 0.1 dl / g, 0.2 dl / g, 0.3 dl / g, 0.4 dl / g, 0.5 dl / g, 0.6 dl / g, 0.7 dl / g, 0.8 dl / g, 0.9 dl / g, 1.0 dl / g, 2.0 dl / g, 3.0 dl / g, 4.0 dl / g, 5.0 dl / g, 6.0 dl / g, 7.0 dl / g, 8.0 dl / g, 9.0 dl / g, 10.0 dl / g, etc.

[0036] The compositions of this application may further include components such as antioxidants, preservatives and mildew inhibitors, humectants, surfactants, pH adjusters, fragrances, pigments, and functional additives.

[0037] This application further provides the use of the compositions described in any of the preceding claims as antioxidants and anti-inflammatory agents.

[0038] This application further provides the use of the compositions described in any of the preceding claims as skin barrier repair agents.

[0039] The compositions described in any of the preceding claims are suitable for people with sensitive skin or for preventing the development of sensitive skin.

[0040] This application also provides the use of the compositions described in any of the preceding claims as skin care products.

[0041] The skin care products can be in liquid, semi-solid, or solid form, including but not limited to serums, sunscreens, oils, body lotions, bath products, eye care products, face masks, facial cleansers, makeup removers, foundations, pressed powders, blushes, body makeup products, eyebrow pencils, eyeshadows, eyelid products, eyelash products, eye makeup removers, lip balms, lip glosses, regular lipsticks, lip liners, etc.

[0042] Example

[0043] Reagents and Instruments

[0044] The main reagent sources and instrument information are shown in Tables 1 and 2.

[0045] Table 1

[0046]

[0047] Table 2

[0048]

[0049] Experiment Example 1 Antioxidant Experiment

[0050] 1. Sample preparation

[0051] Prepare sample solutions according to the composition and concentration of each component in Table 4, using water as the solvent.

[0052] 2. T / SHRH 006-2018 Cosmetics - Free Radical (DPPH) Scavenging Test

[0053] 2.1 Grouping

[0054] Set up sample wells (T), sample background wells (T0), positive control wells (P), positive control background wells (P0), DPPH wells (C), and solvent background wells (C0) on the ELISA plate. For each sample, three parallel wells should be set up for each test concentration of the sample wells (T), and three parallel wells should also be set up for each DPPH well (C).

[0055] 2.2 Test substance treatment

[0056] Add 50 μL of sample solution of the same concentration to the sample well (T) and sample background well (T0), and add 50 μL of positive control solution (vitamin E) of the same concentration to the positive control well (P) and positive control background well (P0). Add 95% ethanol to all wells to a total of 150 μL and mix well. Add 50 μL of DPPH ethanol solution to the sample well (T), DPPH well (C), and positive control well (P), and replace the sample background well (T0), solvent background well (C0), and positive control background well (P0) with 95% ethanol. See Table 3 for the specific sample values ​​for each well. Gently shake and let stand at room temperature for 5 minutes.

[0057] 2.3 Detection

[0058] Transfer the ELISA plate into the microplate reader and measure the absorbance at 517 nm. The half-maximal inhibitory concentration (IC50) of vitamin E in the positive control ranged from 0.02 mg / mL to 0.06 mg / mL, indicating that the experimental system was effective.

[0059] 2.4 Result Calculation

[0060] The clearance rate is calculated as follows:

[0061] Clearance rate (%) = [1 - (T - T0) / (C - C0)] * 100%

[0062] in:

[0063] T represents the absorbance of the sample tube, which is the absorbance of the solution after the sample reacts with DPPH.

[0064] T0 is the background absorbance of the sample.

[0065] C is the average of three absorbance values ​​of the DPPH tube, which is the absorbance value of the DPPH solution without the sample added.

[0066] C0 is the solvent background absorbance.

[0067] Table 3

[0068] / T <![CDATA[T0]]> C <![CDATA[C0]]> P <![CDATA[P0]]> Sample solution (μL) 50 50 / / / / Positive control solution (μL) / / / / 50 50 95% ethanol solvent (μL) 100 150 150 200 100 150 DPPH ethanol solution (μL) 50 / 50 / 50 /

[0069] 3. Experimental Results

[0070] The clearance rates of each embodiment and comparative example are shown in Table 4.

[0071] Among them, the clearance rate data is compared with the control group -1:

[0072] A positively significant difference is marked with (+*), indicating "enhanced effect".

[0073] A negatively significant difference is marked as (-*), which means "weakened effect".

[0074] Table 4

[0075] serial number Composition concentration Clearance rate (%) Comparative Example-1 20mg / ml SA 35.02 Comparative Example-2 20mg / ml LMWHA-1 6.44(-*) Comparative Example-3 20mg / ml AcHA 11.60(-*) Comparative Example-4 16mg / ml SA, 4mg / ml LMWHA-1 20.89(-*) Comparative Example -5 10mg / ml SA, 10mg / ml LMWHA-1 9.97(-*) Comparative Example-6 4 mg / ml SA, 16 mg / ml LMWHA-1 7.38(-*) Comparative Example - 7 16 mg / ml SA, 4 mg / ml AcHA 46.33(+*) Comparative Example -8 10 mg / ml SA, 10 mg / ml AcHA 30.26(-*) Comparative Example -9 4 mg / ml SA, 16 mg / ml AcHA 14.17(-*) Comparative Example -10 16mg / ml SA, 2mg / ml LMWHA-1, 2mg / ml AcHA 28.61(-*) Comparative Example-11 16mg / ml SA, 3mg / ml LMWHA-1, 1mg / ml AcHA 29.76(-*) Comparative Example-12 16mg / ml SA, 3.6mg / ml LMWHA-1, 0.4mg / ml AcHA 23.88(-*) Comparative Example-13 12mg / ml SA, 2mg / ml LMWHA-1, 6mg / ml AcHA 29.43(-*) Example A 16mg / ml SA, 0.2mg / ml LMWHA-1, 3.8mg / ml AcHA 40.53(+*) Example B 16mg / ml SA, 1mg / ml LMWHA-1, 3mg / ml AcHA 36.21(+) Example C 16mg / ml SA, 1mg / ml LMWHA-2, 3mg / ml AcHA 38.33(+) Example D 14mg / ml SA, 1.5mg / ml LMWHA-1, 4.5mg / ml AcHA 37.42(+)

[0076] Experiment Example 2: Anti-inflammatory Experiment

[0077] 1. Sample preparation

[0078] Prepare sample solutions according to the composition and concentration of each component in Table 5, using high-glucose DMEM culture medium (10% fetal bovine serum) as the solvent.

[0079] 2. Cell seeding: Collect cells in the logarithmic growth phase and seed them at a density of 1×10⁶ cells / year. 4 Inoculate 1 cell per well into a 96-well plate and incubate at 37°C in a 5% CO2 incubator for 24 hours.

[0080] 3. Sample Distribution: Samples were distributed when the cell deposition rate in the 96-well plates reached 40%-60%. The blank control group consisted of 200 μL of high-glucose DMEM medium (10% fetal bovine serum) per well; the negative control group consisted of 200 μL of cell culture medium containing LPS per well; the positive control group consisted of 200 μL of culture medium containing the positive control drug (dexamethasone) and LPS per well; and the sample group consisted of 200 μL of culture medium containing the sample solution and LPS per well. After sample distribution, the 96-well plates were incubated in an incubator (37℃, 5% CO2) for 24 h. Specific parameters are shown in Table 6.

[0081] 4. ELISA detection: After the culture is completed, collect the cell culture medium into a 1.5mL Eppendorf tube, centrifuge at 4℃ and 1000×g to collect the supernatant, and perform ELISA detection.

[0082] 5. Result Calculation

[0083] IL-6 expression levels were calculated as follows:

[0084] IL-6 expression level = T / C

[0085] in:

[0086] T-experimental group IL-6 content value;

[0087] C-negative control group IL-6 content value.

[0088] 6. Experimental Results

[0089] Considering that comparative examples 4, 5, 6, and 8-13 in Table 4 have already shown (-*) results, these protocols are not within the scope of this application. Therefore, the anti-inflammatory experiments will not test these protocols. The expression levels of inflammatory factors (IL-6) in other examples and comparative examples are shown in Table 5.

[0090] In the IL-6 expression data, a comparison was made with Comparative Example-3:

[0091] A positively significant difference is marked with (+*), indicating a "weakened effect".

[0092] A negatively significant difference is marked as (-*), indicating "increased effect".

[0093] Table 5

[0094] serial number Composition concentration IL-6 expression level Comparative Example-1 5mg / ml SA 0.413(+*) Comparative Example-2 5mg / ml LMWHA-1 0.518(+*) Comparative Example-3 5mg / ml AcHA 0.394 Comparative Example-4 4 mg / ml SA, 1 mg / ml LMWHA-1 NA Comparative Example -5 2.5mg / ml SA, 2.5mg / ml LMWHA-1 NA Comparative Example-6 1 mg / ml SA, 4 mg / ml LMWHA-1 NA Comparative Example - 7 4 mg / ml SA, 1 mg / ml AcHA 0.448(+*) Comparative Example -8 2.5 mg / ml SA, 2.5 mg / ml AcHA NA Comparative Example -9 1 mg / ml SA, 4 mg / ml AcHA NA Comparative Example -10 4mg / ml SA, 0.5mg / ml LMWHA-1, 0.5mg / ml AcHA NA Comparative Example-11 4mg / ml SA, 0.75mg / ml LMWHA-1, 0.25mg / ml AcHA NA Comparative Example-12 4mg / ml SA, 0.9mg / ml LMWHA-1, 0.1mg / ml AcHA NA Comparative Example-13 3mg / ml SA, 0.5mg / ml LMWHA-1, 1.5mg / ml AcHA NA Example A 4mg / ml SA, 0.05mg / ml LMWHA-1, 0.95mg / ml AcHA 0.393 Example B 4mg / ml SA, 0.25mg / ml LMWHA-1, 0.75mg / ml AcHA 0.392 Example C 4mg / ml SA, 0.25mg / ml LMWHA-2, 0.75mg / ml AcHA 0.351(-*) Example D 3.5mg / ml SA, 0.375mg / ml LMWHA-2, 1.125mg / ml AcHA 0.330(-*)

[0095] Table 6

[0096]

[0097] As can be seen from the data in Tables 4 and 5, the compositions in the examples do not significantly weaken the inhibitory effects of SA and HA on oxidative stress and anti-inflammatory effects, and may even produce a synergistic effect on the inhibitory effects of oxidative stress or anti-inflammatory effects. This provides a reasonable application path for SA and HA to effectively enhance the skin barrier repair function of products.

[0098] Although the embodiments of this application have been described above in conjunction with the specific embodiments described, this application is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the teachings of this specification and without departing from the scope of protection of the claims of this application, and these are all within the scope of protection of this application.

Claims

1. A topical skin composition, wherein, Including sialic acid, hyaluronic acid or its salts with a molecular weight of less than 10,000 Da, and acetylated hyaluronic acid or its salts with a molecular weight of 1 to 10 wDa; The mass ratio of the total amount of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is greater than 1.5:1; The mass ratio of the hyaluronic acid or its salt to acetylated hyaluronic acid or its salt is 1:40 to 1:

3.

2. The composition according to claim 1, wherein, The mass ratio of sialic acid to hyaluronic acid or its salt and acetylated hyaluronic acid or its salt is 2:1 to 8:

1.

3. Use of the composition according to claim 1 or 2 in the preparation of antioxidants and anti-inflammatory agents.

4. Use of the composition according to claim 1 or 2 in the preparation of a skin barrier repair agent.

5. The use of the composition according to claim 1 or 2 in the preparation of skin care products.

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