A composition for lifting skin firmness and uses thereof

Abstract

The application provides a composition for improving skin firmness and its use. The composition comprises: (a) at least one hyaluronic acid disaccharide, (b) one or both of palmitoyl pentapeptide-4 and recombinant collagen peptide, wherein (a) comprises: (a-1) saturated hyaluronic acid disaccharide, (a-2) unsaturated hyaluronic acid disaccharide. The application finds that the mixed hyaluronic acid disaccharide comprising saturated and unsaturated hyaluronic acid disaccharides can improve the arrangement state of collagen, providing a new solution strategy for maintaining or improving skin elasticity and firmness. When the hyaluronic acid disaccharide is used together with palmitoyl pentapeptide-4 or recombinant collagen peptide, the two can further improve the arrangement state of collagen within a certain proportion range, more significantly maintaining or restoring skin elasticity and firmness, improving the extracellular matrix, and thus improving aging at the root.

Description

Technical Field

[0001] This application belongs to the field of biotechnology, and specifically relates to a composition for improving skin firmness and its use. Background Technology

[0002] The decline of the skin's extracellular matrix (ECM) leads to skin aging, resulting in wrinkles, roughness, and sagging. As a crucial component supporting the ECM structure, collagen levels decline with age. After age 20, skin collagen levels decrease by approximately 1% annually; by age 50, collagen levels in areas frequently exposed to sunlight, such as the face and forearms, can drop to 50% of their original levels. Furthermore, factors such as chronic inflammation can further accelerate collagen loss. Therefore, active ingredients that promote collagen production are frequently used in anti-aging skincare formulations.

[0003] However, increasing collagen content is only one aspect of improving the ECM; the arrangement of collagen is a more important factor affecting ECM function. Studies have shown that in ECM matrices with identical composition but different collagen arrangement orientations, cell differentiation and expression exhibit drastically different characteristics. Improving the orderly arrangement of collagen can further maintain skin elasticity and firmness. Summary of the Invention

[0004] In view of the problems existing in the prior art, this application provides a composition for improving skin firmness and its use.

[0005] Specifically, this application relates to the following aspects: 1. A composition comprising: (a) At least one hyaluronic acid disaccharide, (b) One or both of palmitoyl pentapeptide-4 and recombinant collagen peptides. Among them, (a) includes: (a-1) Saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

[0006] 2. The composition according to item 1, wherein the mass ratio of (a-1) to (a-2) is 1:(0.1-5).

[0007] 3. The composition according to item 1 or 2, wherein the mass ratio of (a) and (b) is 1:(0.001-8).

[0008] 4. The composition according to any one of items 1-3, wherein the recombinant collagen peptide is a type III recombinant collagen peptide.

[0009] 5. Use of the composition of any one of items 1-4 in improving the arrangement of collagen in the skin; Preferably, improving the arrangement of collagen in the skin includes causing collagen fibers to form robust, three-dimensional fiber clusters; Preferably, the use of the composition in improving the extracellular matrix.

[0010] 6. Use of the composition of any one of items 1-4 in anti-aging.

[0011] 7. Use of the composition of any one of items 1-4 in improving skin firmness and / or elasticity.

[0012] 8. The use of hyaluronic acid disaccharide in improving the arrangement of collagen in the skin. The hyaluronic acid disaccharide comprises: (a-1) Saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

[0013] 9. The use of the hyaluronic acid disaccharide in improving skin firmness and / or elasticity, according to the use described in item 8; Preferably, improving the arrangement of collagen in the skin includes causing collagen fibers to form robust, three-dimensional fiber clusters; Preferably, its use in improving the extracellular matrix.

[0014] 10. The use according to item 8 or 9, wherein the mass ratio of (a-1) and (a-2) is 1:(0.1-5).

[0015] Technical effects of this application This application is the first to discover that a specific hyaluronic acid disaccharide can improve the arrangement of collagen, providing a new solution for maintaining or improving skin elasticity and firmness; Furthermore, this application is the first to combine specific hyaluronic acid disaccharide with palmitoyl pentapeptide-4 or recombinant collagen peptides, and found that the two can further improve the arrangement of collagen within a specific ratio range, thereby achieving a synergistic effect in maintaining or improving skin elasticity and firmness, and more significantly maintaining or restoring skin elasticity and firmness. Furthermore, this application improves the extracellular matrix through the combined application of specific hyaluronic acid disaccharides with palmitoyl pentapeptide-4 or recombinant collagen peptides, thereby fundamentally improving aging. Attached Figure Description

[0016] Figure 1 This is an image of the collagen arrangement in human skin explants, captured using a scanning electron microscope. Figure 1 (a) is healthy skin. Figure 1 (b) is photoaged skin. Figure 1 (c) is skin treated with PP4 alone after photoaging. Figure 1 (d) is skin treated with C3P alone after photoaging. Figure 1 (e) is skin treated with O-HA alone after photoaging. Figure 1 (f) is skin treated with a composition containing O-HA and PP4 after photoaging. Figure 1 (g) is skin treated with a composition containing HA and C3P after photoaging. Detailed Implementation

[0017] The present application is further illustrated below with reference to embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0018] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. While similar or identical methods and materials may be applied in experimental or practical applications, materials and methods are described herein. In case of conflict, the definitions included herein shall prevail. Furthermore, materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific embodiments, but is not intended to limit the scope of the application.

[0019] While increasing the collagen content of the skin can slow down the deepening of wrinkles, if the collagen fibers cannot form a good arrangement, the skin's elasticity and firmness will still be difficult to improve.

[0020] To address the problems existing in the prior art, this application provides a composition comprising: (a) At least one hyaluronic acid disaccharide, (b) One or both of palmitoyl pentapeptide-4 and recombinant collagen peptides. Among them, (a) includes: (a-1) Saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

[0021] In some implementations, the mass ratio of (a-1) to (a-2) is 1:(0.1-5), for example, it can be 1:0.1, 1:0.2, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, and any value between these values. In some implementations, the mass ratio of (a-1) to (a-2) is 1:(0.5-2.5). In some implementations, the mass ratio of (a-1) to (a-2) is 1:(1-2).

[0022] In some implementations, the mass ratio of (a) to (b) is 1:(0.001-8), for example, it can be 1:0.001, 1:0.01, 1:0.05, 1:0.1, 1:0.5, 1:1, 1:1.5, 1:2, 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, and any value between these values. In some implementations, the mass ratio of (a) to (b) is 1:(0.01-5).

[0023] The type of recombinant collagen peptide is not limited and can be any type of recombinant collagen peptide known in the art. In some embodiments, the recombinant collagen peptide is a type III recombinant collagen peptide.

[0024] In some implementations, the recombinant collagen peptides include type III recombinant collagen.

[0025] In some embodiments, the sequence of the type III recombinant collagen peptide includes SEQ ID NO. 1, SEQ ID NO. 2 or SEQ ID NO. 3 as shown in patent CN114805551B.

[0026] In some implementations, the type III recombinant collagen peptide is the recombinant type III collagen disclosed in patent CN114805551B.

[0027] The type III recombinant collagen peptides described in this application are recombinant type III humanized collagen purchased from Bloomage Biotechnology Co., Ltd.

[0028] In some implementations, the reducing ends of (a-1) and (a-2) can be N-acetylglucosamine or uronic acid. That is, the reducing ends of (a-1) and (a-2) can both be N-acetylglucosamine, or (a-1) can be uronic acid and (a-2) can be N-acetylglucosamine.

[0029] In some implementations, the reducing ends of (a-1) and (a-2) can be N-acetylglucosamine.

[0030] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, (b) palmitoyl pentapeptide-4, and (a) comprises: (a-1) a saturated hyaluronic acid disaccharide, and (a-2) an unsaturated hyaluronic acid disaccharide.

[0031] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, (b) palmitoyl pentapeptide-4, wherein (a) comprises: (a-1) a saturated hyaluronic acid disaccharide, and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(0.1-5), and the mass ratio of (a) to (b) is 1:(0.001-8).

[0032] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, (b) palmitoyl pentapeptide-4, wherein (a) comprises: (a-1) a saturated hyaluronic acid disaccharide, and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(0.5-2.5), and the mass ratio of (a) to (b) is 1:(0.01-5).

[0033] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, and (b) palmitoyl pentapeptide-4. (a) comprises: (a-1) a saturated hyaluronic acid disaccharide and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(1-2), and the mass ratio of (a) to (b) is 1:(0.01-5).

[0034] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, (b) a type III recombinant collagen peptide, (a) comprising: (a-1) a saturated hyaluronic acid disaccharide, and (a-2) an unsaturated hyaluronic acid disaccharide.

[0035] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, and (b) a type III recombinant collagen peptide, wherein (a) comprises: (a-1) a saturated hyaluronic acid disaccharide and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(0.1-5), and the mass ratio of (a) to (b) is 1:(0.001-8).

[0036] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, and (b) a type III recombinant collagen peptide, wherein (a) comprises: (a-1) a saturated hyaluronic acid disaccharide and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(0.5-2.5), and the mass ratio of (a) to (b) is 1:(0.01-5).

[0037] In some embodiments, the composition comprises: (a) at least one hyaluronic acid disaccharide, and (b) a type III recombinant collagen peptide, wherein (a) comprises: (a-1) a saturated hyaluronic acid disaccharide and (a-2) an unsaturated hyaluronic acid disaccharide. The mass ratio of (a-1) to (a-2) is 1:(1-2), and the mass ratio of (a) to (b) is 1:(0.01-5).

[0038] This application also provides the use of the above composition in anti-aging.

[0039] This application also provides the use of the above composition in improving the arrangement of collagen in the skin.

[0040] In some implementations, improving the arrangement of collagen in the skin may include causing collagen fibers to form robust, three-dimensional clusters of fibers.

[0041] In some implementations, improving the arrangement of collagen in the skin includes improving the extracellular matrix.

[0042] This application also provides the use of the above composition in improving skin firmness and / or elasticity.

[0043] This application also provides the use of hyaluronic acid disaccharide in improving the collagen arrangement in the skin, wherein the hyaluronic acid disaccharide comprises: (a-1) saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

[0044] The mass ratio of (a-1) and (a-2) is as described above.

[0045] In some implementations, improving the arrangement of collagen in the skin improves skin firmness and / or elasticity.

[0046] In some implementations, improving the arrangement of collagen in the skin may include causing collagen fibers to form robust, three-dimensional clusters of fibers.

[0047] In some implementations, improving the arrangement of collagen in the skin includes improving the extracellular matrix.

[0048] This application discovers that hyaluronic acid disaccharides containing both saturated and unsaturated hyaluronic acid disaccharides can improve the arrangement of collagen, providing a new solution for maintaining or improving skin elasticity and firmness. When this hyaluronic acid disaccharide is used in combination with palmitoyl pentapeptide-4 or recombinant collagen peptides, the two can further improve the arrangement of collagen within a specific ratio range, thereby achieving a synergistic effect in maintaining or improving skin elasticity and firmness, more significantly maintaining or restoring skin elasticity and firmness, improving the extracellular matrix, and thus fundamentally improving aging.

[0049] Example The main raw materials used in this application are as follows: Palmitoyl pentapeptide-4 (denoted as PP4) is from Zhejiang Paipai Biotechnology Co., Ltd.

[0050] Type III recombinant collagen peptide (C3P) is from Bloomage Biotechnology Co., Ltd.

[0051] Hydrolyzed sodium hyaluronate (abbreviated as O-HA112, O-HA120, S1-HA, S2-HA) is supplied by Bloomage Biotechnology Co., Ltd., wherein: O-HA112: Hydrolyzed sodium hyaluronate with a molecular weight of 400 Da, containing two types of disaccharide molecules: saturated hyaluronate disaccharide (HA2) with N-acetylglucosamine at the reducing end and unsaturated hyaluronate disaccharide (ΔHA2) with N-acetylglucosamine at the reducing end, with a mass ratio of HA2:ΔHA2 of 1:1.2.

[0052] O-HA120: Hydrolyzed sodium hyaluronate with a molecular weight of 400 Da, containing two types of disaccharide molecules: saturated hyaluronate disaccharide (HA2) with N-acetylglucosamine at the reducing end and unsaturated hyaluronate disaccharide (ΔHA2) with N-acetylglucosamine at the reducing end, with a mass ratio of HA2:ΔHA2 of 1:2.

[0053] S1-HA: Hydrolyzed sodium hyaluronate with a molecular weight of 400 Da, containing only saturated hyaluronic acid disaccharide (HA2) with N-acetylglucosamine at the reducing end.

[0054] S2-HA: Hydrolyzed sodium hyaluronate with a molecular weight of 400 Da, containing only unsaturated hyaluronic acid disaccharide (ΔHA2) with N-acetylglucosamine at the reducing end.

[0055] Example Prepare the essence of groups A1 to D4 according to Table 1.

[0056] Taking group A1 as an example, PP4, O-HA112, ethylene glycol, and pentanediol were dissolved in water to obtain an essence. The essence contained 0.01% PP4, 0.01% O-HA112, 5% butylene glycol, and 2% pentanediol.

[0057] Table 1

[0058] Test case Experimental Example 1: Skin Explant Experiment (1) Preparation of skin explant samples Human skin tissue was pretreated to prepare skin explant samples. The preparation steps were as follows: First, subcutaneous fat was removed, and the skin was cut into 1cm × 1cm sample pieces. Then, the samples were rinsed three times with phosphate-buffered saline (PBS) containing penicillin (100 U / mL) and streptomycin (100 μg / mL). Finally, the skin was placed in DMEM and incubated at 37°C and 5% CO2 for 24 hours.

[0059] (2) Grouping The experiment was divided into seven groups: a, b, c, d, e, f, and g. Group a served as the blank control group, consisting of normal, healthy skin that received no treatment. Group b served as the negative control group, where the skin explant samples were irradiated with ultraviolet light (10 J / cm²). 2 UVA + 80 J / cm 2 UVB was used to create a photoaging skin model; groups c to g were the experimental groups. After photoaging modeling, the skin explants were placed in culture media containing different active ingredients. The active ingredients and their concentrations in the culture media are shown in Table 2. All skin explants were placed on gelatin sponges for aero-liquid culture, and the drug-containing culture medium was changed daily. The culture was carried out at 37°C and 5% CO2 for 2 days.

[0060] Table 2

[0061] (3) Test To observe the collagen arrangement in the above samples, a sample of approximately 1 mm was taken. 3The skin explant samples were placed in 1.5 mL centrifuge tubes, 2.5% glutaraldehyde was added, and the samples were fixed overnight at 4 °C. Subsequently, they were post-fixed with 1% osmium tetroxide, dehydrated stepwise with a gradient of ethanol solutions, dried, fixed on the sample stage, sputtered with gold, and then observed.

[0062] Test results are as follows Figure 1 As shown in the figure, the collagen in groups e, f, and g is arranged in an orderly manner, especially groups f and g, which even reach the collagen arrangement state of normal healthy skin. This indicates that specific hyaluronic acid disaccharides can improve the collagen arrangement state. Furthermore, combining specific hyaluronic acid disaccharides with PP4 or C3P can further improve the collagen arrangement in photoaged skin, making it more orderly and forming strong, three-dimensional fiber clusters, thereby more significantly maintaining or restoring skin elasticity and firmness.

[0063] Trial Example 2: Clinical Trial To further verify the effect of collagen arrangement on skin elasticity and firmness, the following clinical trial was conducted.

[0064] Each test group (A1-D4) had 8 participants. All participants were healthy Chinese women aged 40-60 years. Furthermore, to ensure data comparability between groups, participants were screened before testing: their initial periocular skin firmness F4 score was between 9 and 12, and their crow's feet wrinkle level was between 2 and 4.

[0065] Each participant applied the designated test formula (the serums from groups A1 to D4 prepared in the previous examples) to the area around their eyes, 1 ml each morning and evening, for 4 weeks. Other cosmetic products were discontinued during the testing period.

[0066] At two time points, Week-0 and Week-4, the skin elasticity index F4 of the periorbital area was tested using a multifunctional skin analyzer, the Cutometer MPA 580. F4 was determined using a cyclic negative pressure traction mode; the lower the value, the stronger the skin's firmness and support.

[0067] Groups A1-A9, B1-B3, C1-C11, and D1-D4 were used as one comparative study group. Within each group, a two-tailed t-test (α = 0.05) was used for pairwise comparisons, with statistical differences between groups distinguished by labeled letters. If the labeled letters of the two groups were completely different (e.g., a and b), the difference was statistically significant; if the two groups shared some letters (e.g., a and ab), the difference was not statistically significant.

[0068] The test results are shown in Table 3.

[0069] Table 3

[0070] The comparisons of A1, A4-A9 with A2, A3, and B1 with B2, B3 in Table 3 show that the combined application of specific hyaluronic acid disaccharides and palmitoyl pentapeptide-4, within a specific ratio range, can further improve the arrangement of collagen, thereby achieving a synergistic effect in maintaining or improving skin elasticity and firmness, and more significantly maintaining or restoring skin elasticity and firmness.

[0071] The comparison of C1, C4-C8 with C2, C3, and C9 with C10, C11 in Table 3 shows that the combined application of specific hyaluronic acid disaccharides and recombinant collagen peptides can further improve the arrangement of collagen within a specific ratio range, thereby achieving a synergistic effect in maintaining or improving skin elasticity and firmness, and more significantly maintaining or restoring skin elasticity and firmness.

Claims

1. A composition comprising: (a) At least one hyaluronic acid disaccharide, (b) One or both of palmitoyl pentapeptide-4 and recombinant collagen peptides. in, (a) includes: (a-1) Saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

2. The composition according to claim 1, wherein the mass ratio of (a-1) to (a-2) is 1:(0.1-5).

3. The composition according to claim 1 or 2, wherein the mass ratio of (a) and (b) is 1:(0.001-8).

4. The composition according to any one of claims 1-3, wherein the recombinant collagen peptide is a type III recombinant collagen peptide.

5. Use of the composition according to any one of claims 1-4 in improving the arrangement of collagen in the skin; Preferably, improving the arrangement of collagen in the skin includes causing collagen fibers to form robust, three-dimensional fiber clusters; Preferably, the use of the composition in improving the extracellular matrix.

6. Use of the composition according to any one of claims 1-4 in anti-aging.

7. Use of the composition of any one of claims 1-4 in improving skin firmness and / or elasticity.

8. The use of hyaluronic acid disaccharide in improving the arrangement of collagen in the skin. in, The hyaluronic acid disaccharide comprises: (a-1) Saturated hyaluronic acid disaccharide, (a-2) Unsaturated hyaluronic acid disaccharide.

9. The use of the hyaluronic acid disaccharide in improving skin firmness and / or elasticity, according to claim 8; Preferably, improving the arrangement of collagen in the skin includes causing collagen fibers to form robust, three-dimensional fiber clusters; Preferably, its use in improving the extracellular matrix.

10. The use according to claim 8 or 9, wherein the mass ratio of (a-1) and (a-2) is 1:(0.1-5).

Images