Hyaluronic acid modified nonapeptide as well as preparation method and application thereof

Abstract

The invention discloses a hyaluronic acid modified nonapeptide, a preparation method and application thereof, and relates to the field of cosmetic peptides. The hyaluronic acid modified cosmetic peptide has a structural formula as shown in a formula (I): M-C (I), wherein M represents sodium hyaluronate, the structure of the sodium hyaluronate is shown in the formula (II), and in the formula (II), y is a natural number larger than or equal to 1; c represents a cosmetic peptide, the cosmetic peptide comprises a polypeptide with cosmetic and / or skin care efficacy or a derivative thereof, and the polypeptide comprises a dipeptide, a tripeptide, a tetrapeptide, a pentapeptide, a hexapeptide, a heptapeptide, an octapeptide or a nonapeptide; wherein M-terminal glucuronic acid is in open-loop linkage with amino in the C structure. The hyaluronic acid modified cosmetic peptide provided by the invention not only can maintain the property of sodium hyaluronate, but also can have the functionality of polypeptide, and the stability of the prepared novel compound is obviously improved, so that the hyaluronic acid modified cosmetic peptide has a wide application prospect in the field of cosmetics / skin care products.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic peptides, specifically relating to a nonapeptide modified with hyaluronic acid, its preparation method, and its uses. Background Technology

[0002] Hyaluronic acid, a large-molecule polysaccharide, was first isolated from the vitreous humor of bovine eyes by Meyer and Palmer, professors of ophthalmology at Columbia University in 1934. Its aqueous solution is transparent and glassy, ​​hence its other name, hyaluronic acid. Hyaluronic acid is a naturally occurring biological substance widely found in tissues such as the vitreous humor of the eye, skin, umbilical cord, and synovial fluid of joints. Early hyaluronic acid was primarily extracted from rooster combs. However, due to cost and raw material limitations, its use was not further expanded. Currently, cosmetic and pharmaceutical hyaluronic acid is mainly produced through microbial fermentation. Fermentation is not limited by animal raw materials, has lower costs, is easy to scale up, and produces products with higher purity and easier control of relative molecular mass. Research in this field began in China in the 1980s and has now achieved significant results. Hyaluronic acid produced in my country using fermentation methods is now at an internationally advanced level in both quality and quantity. Hyaluronic acid is a major component of the extracellular matrix and intercellular matrix, acting as a filler between cells and playing a crucial role in the morphology, structure, and function of the skin. Hyaluronic acid is increasingly used in cosmetics due to its moisturizing, repairing, and nourishing properties, good skin affinity, and safety. Furthermore, its biodegradability, biocompatibility, chemical modification capabilities, and in vivo targeting properties have made it a focus of attention in the field of protein and peptide modification. This invention utilizes hyaluronic acid-modified cosmetic peptides and further investigates their synthesis methods and applications. Summary of the Invention

[0003] The purpose of this invention is to provide hyaluronic acid-modified cosmetic peptides, their preparation methods, and their uses. These hyaluronic acid-modified cosmetic peptides retain the properties of sodium hyaluronate while also containing the functionality of polypeptides. Furthermore, the stability of the novel compounds prepared is significantly improved, and they have broad application prospects in the field of cosmetics / skincare products.

[0004] The technical solution adopted by the present invention to achieve the above objectives is as follows: A hyaluronic acid-modified cosmetic peptide, the structural formula of which is shown in formula (I): MC (I); Wherein, M represents sodium hyaluronate, whose structure is shown in formula (II): (II), where y is a natural number ≥ 1; C represents beauty peptides, which include polypeptides or their derivatives that have beauty and / or skin care effects. These polypeptides include dipeptides, tripeptides, tetrapeptides, pentapeptides, hexapeptides, heptapeptides, octapeptides, nonapeptides, or other polypeptides. In this invention, the M-terminal glucuronic acid is linked to the amino group in the C-structure. Hyaluronic acid is modified with cosmetic peptides using a substitution reaction. Sodium hyaluronate and the peptides are covalently linked to form a new chemical substance that retains the properties of sodium hyaluronate while also possessing the functionality of the peptides. This compound exhibits multiple effects, with significantly enhanced stability compared to the original. For example, the compound demonstrates superior moisturizing properties; some compounds show significant improvements in anti-wrinkle and firming properties, whitening properties, antioxidant capacity, and anti-glycation properties, while also effectively improving soothing abilities. This invention covalently couples hyaluronic acid and cosmetic peptides to generate hyaluronic acid-modified cosmetic peptides. Direct chemical modification creates a novel chemical structure, fundamentally endowing the compound with superior properties. The preparation method is simple. Furthermore, this invention provides applications in cosmetics and beauty products, significantly enhancing the effects of functional cosmetics, such as moisturizing, anti-aging and firming, whitening, soothing, antioxidant, and anti-glycation effects, thereby improving user satisfaction.

[0005] Preferably, y is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12; more preferably, y = 1, 2, or 3.

[0006] Specifically, the compound represented by formula (I) includes the structure shown in formula (III): (III); in, The above n is a natural number; The R mentioned above represents the remaining portion of the cosmetic peptide structure after removing the reactive amino group; The aforementioned beauty peptides include polypeptides or their derivatives that have beauty and / or skincare effects, including dipeptides, tripeptides, tetrapeptides, pentapeptides, hexapeptides, heptapeptides, octapeptides, nonapeptides, or other polypeptides.

[0007] Preferably, n = 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24. More preferably, n = 0 or 1 or 2 or 3.

[0008] Specifically, the dipeptide or its derivatives include one of dipeptide-2 and carnosine; preferably carnosine.

[0009] Specifically, the tripeptide or its derivatives include one of snake venom-like peptides, tripeptide-1, tripeptide-5, tripeptide-8, tripeptide-38, and palmitoyl tripeptide-38; preferably tripeptide-1 or tripeptide-8.

[0010] Specifically, the tetrapeptide or its derivatives include one of tetrapeptide-5, tetrapeptide-7, tetrapeptide-9, tetrapeptide-11, tetrapeptide-30 and tetrapeptide-15, or include a tetrapeptide with the amino acid sequence H-Asp-Val-Lys-Tyr-OH; tetrapeptide-7 and tetrapeptide-15 are preferred.

[0011] Specifically, the pentapeptide or its derivatives include one of pentapeptide-4 and myristopentipeptide-4; pentapeptide-4 is preferred.

[0012] Specifically, hexapeptides or their derivatives include one of hexapeptide-1, hexapeptide-8, hexapeptide-9, hexapeptide-11, and hexapeptide-38, or one of the hexapeptides with the amino acid sequences H-Arg-Arg-Gln-Met-Glu-Glu-NH2, H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, H-Trp-Phe-Arg-Leu-Ala-His-NH2, and H-Trp-Phe-Arg-D-Leu-Ala-His-NH2.

[0013] Preferably, the hexapeptide or its derivatives include hexapeptide-1, hexapeptide-8, hexapeptide-9, and hexapeptide-11; more preferably, the amino acid sequence is one of the hexapeptides with the sequence H-Arg-Arg-Gln-Met-Glu-Glu-NH2, H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, H-Trp-Phe-Arg-Leu-Ala-His-NH2, and H-Trp-Phe-Arg-D-Leu-Ala-His-NH2.

[0014] Specifically, heptapeptides or their derivatives include heptapeptides with the amino acid sequences H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH or H-Glu-Glu-Met-Gln-Arg-Arg-Ala-NH2.

[0015] Specifically, the octapeptide or its derivatives include an octapeptide with the amino acid sequence H-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH2.

[0016] Specifically, nonapeptides or their derivatives include nonapeptide-1.

[0017] Specifically, the compound shown in (Ⅰ) above includes one or more of H-Glu-Glu-Met-Gln-Arg-Arg-NH-sodium hyaluronate, sodium hyaluronate-NH-Phe-Val-Ala-Pro-Phe-Pro-OH, H-His-D-Phe-Arg-NH-sodium hyaluronate, H-His-Ala-Leu-Arg-Phe-Trp-NH-sodium hyaluronate, H-Trp-Phe-Arg-D-Leu-Ala-His-NH-sodium hyaluronate, H-Trp-Phe-Arg-Leu-Ala-His-NH-sodium hyaluronate, H-Arg-Arg-Gln-D-Met-Glu-Glu-NH-sodium hyaluronate, or H-Arg-Arg-Gln-Met-Glu-Glu-NH-sodium hyaluronate.

[0018] Furthermore, the compound shown in (Ⅰ) above may also include one or more of the following: sodium hyaluronate-HN-Gly-Gln-Pro-Arg-OH, sodium hyaluronate-HN-Lys-Thr-Thr-Lys-Ser-OH, H-Lys-Leu-Ala-Lys-Lys-NH-sodium hyaluronate, H-Gly-Pro-Gln-Gly-Pro-Gln-NH-sodium hyaluronate, H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH-sodium hyaluronate, H-Tyr-Pro-Phe-Phe-NH-sodium hyaluronate, sodium hyaluronate-NH-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH, or sodium hyaluronate-NH-Asp-Val-Lys-Tyr-OH.

[0019] It should be noted that the hyaluronic acid-modified beauty peptides described above can represent a case where the bonding between hyaluronic acid (sodium) and the beauty peptide has only one reactive site, or a case where multiple reactive sites exist. Furthermore, the bonding portion includes the reaction between the active amino group in the beauty peptide structure and the active hydroxyl group in the terminal ring of the hyaluronic acid (sodium) structure, which can further polymerize.

[0020] More preferably, the compound represented by formula (I) above includes one or more of the following: A2; A4; A6; B2; B4; B6; D2; D4; D6; E2; E4; E6; F2; F4; F6; G2; G4; G6. The present invention also discloses a method for preparing hyaluronic acid modified beauty peptides, comprising: using sodium hyaluronate to undergo a condensation reaction with the beauty peptides to obtain hyaluronic acid modified beauty peptides.

[0021] Furthermore, the synthetic route for the hyaluronic acid-modified cosmetic peptides described above is as follows: ; Where n is a natural number; Y is Na or H; Peptide = R; R is the remaining part of the cosmetic peptide structure after removing the reactive amino group; X includes H, sodium, or potassium; The aforementioned beauty peptides include polypeptides or their derivatives that have beauty and / or skincare effects, and the polypeptides include dipeptides, tripeptides, tetrapeptides, pentapeptides, hexapeptides, heptapeptides, octapeptides, nonapeptides or other polypeptides.

[0022] It should be noted that the final form of the hyaluronic acid-modified cosmetic peptide provided by the present invention can be a hyaluronic acid-modified cosmetic peptide, or it can be a hydrochloride, sulfate, phosphate, acetate, sodium salt, potassium salt, trifluoroacetate, maleate or fumarate, etc.

[0023] The preparation method of the above-mentioned hyaluronic acid modified beauty peptide includes: using sodium hyaluronate to react with the beauty peptide in a ring-opening reaction to obtain the hyaluronic acid modified beauty peptide.

[0024] Specifically, the preparation method of the above-mentioned hyaluronic acid-modified beauty peptides includes the following steps: The beauty peptide was added to an organic solvent and stirred to dissolve. Then, TFA was added and stirred for 0.5-1 h. DIEA was then added, followed by the weighing and addition of sodium hyaluronate. The reaction was carried out overnight at 40-50℃ with stirring. LC-MS analysis showed that the reaction was basically complete. Acetic acid was then added, and the reaction was carried out in a water bath at 30-45℃ for 2-4 h for rearrangement. LC-MS analysis showed that the reaction was basically complete. Finally, reverse chromatography was performed to purify the hyaluronic acid-modified beauty peptide.

[0025] Specifically, the organic solvents mentioned above are selected from single or mixed solvents such as DMF, N,N-diethylacetamide, DMSO, acetonitrile, N-methylpyrrolidone (NMP), methanol, ethanol, acetone, THF, dichloromethane, ethyl acetate, dioxane, and water; DMSO is preferred.

[0026] Specifically, the mass-to-volume ratio of the above-mentioned beauty peptides to DMSO is 1g:8-25mL; preferably 1g:10mL.

[0027] Specifically, the mass-to-volume ratio of the aforementioned beauty peptides to TFA is 1g:0-1.2mL.

[0028] Specifically, the mass ratio of the aforementioned beauty peptide to DIEA is 1:0.5-5.5; preferably 1:0.8-2.5.

[0029] Specifically, the molar ratio of the aforementioned beauty peptide to hyaluronic acid is 1:2-8; preferably 1:3-5; more preferably 1:4.

[0030] Specifically, the mass-to-volume ratio of the aforementioned beauty peptide to acetic acid is 1g:4-10mL; preferably 1g:5-9mL; more preferably 1g:8mL.

[0031] Another object of the present invention is to disclose the use of the above-mentioned hyaluronic acid modified beauty peptides in the preparation of cosmetics and / or skin care products.

[0032] This invention further discloses the use of the above-mentioned hyaluronic acid-modified cosmetic peptides in enhancing the moisturizing properties of cosmetics and / or skin care products.

[0033] The present invention also discloses the use of the above-mentioned hyaluronic acid-modified beauty peptides in enhancing the soothing properties of cosmetics and / or skin care products.

[0034] The present invention also discloses the use of the above-mentioned hyaluronic acid modified cosmetic peptides in enhancing the anti-wrinkle and firming properties of cosmetics and / or skin care products.

[0035] This invention also discloses the use of the above-mentioned hyaluronic acid-modified beauty peptides in enhancing the whitening properties of cosmetics and / or skin care products.

[0036] The present invention also discloses the use of the above-mentioned hyaluronic acid-modified cosmetic peptides in enhancing the anti-glycation properties of cosmetics and / or skin care products.

[0037] The present invention also discloses the use of the above-mentioned hyaluronic acid-modified cosmetic peptides in enhancing the antioxidant properties of cosmetics and / or skin care products.

[0038] A cosmetic product comprising the aforementioned hyaluronic acid-modified beauty peptides.

[0039] A skincare product containing the aforementioned hyaluronic acid-modified beauty peptides.

[0040] The beneficial effects of this invention include: This invention modifies hyaluronic acid with cosmetic peptides, forming new compounds through the Maillard reaction. These compounds retain the properties of sodium hyaluronate while incorporating the functionality of peptides, and their stability and efficacy are significantly enhanced compared to the original compounds. For example, the compounds exhibit superior moisturizing properties; some compounds show significant improvements in anti-wrinkle and firming properties, whitening properties, antioxidant capacity, and anti-glycation properties, while their soothing ability is also effectively improved. The hyaluronic acid-modified cosmetic peptides provided by this invention are directly chemically modified to form novel chemical structures, fundamentally endowing the compounds with superior properties. The preparation method is simple. Furthermore, this invention provides applications in cosmetics and beauty products, significantly enhancing the effects of functional cosmetics, such as moisturizing, anti-aging and firming, whitening, soothing, antioxidant, and anti-glycation effects, thereby improving user satisfaction.

[0041] Therefore, this invention provides hyaluronic acid-modified cosmetic peptides, their preparation methods, and their uses. These hyaluronic acid-modified cosmetic peptides retain the properties of sodium hyaluronate while also containing the functionality of polypeptides. Furthermore, the stability of the novel compounds prepared is significantly improved, making them promising for applications in the cosmetics / skincare industry. Attached Figure Description

[0042] Figure 1 The mass spectrum test results are for H-Gly-Gln-Pro-Arg-OH prepared in Example 1; Figure 2 The liquid chromatogram test results of H-Gly-Gln-Pro-Arg-OH prepared in Example 1; Figure 3 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 1. Figure 4 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptides prepared in Example 1; Figure 5The mass spectrum test results are for H-Lys-Thr-Thr-Lys-Ser-OH prepared in Example 2; Figure 6 The liquid chromatogram test results of H-Lys-Thr-Thr-Lys-Ser-OH prepared in Example 2; Figure 7 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptides prepared in Example 2; Figure 8 The mass spectrum of the hyaluronic acid-modified cosmetic peptide prepared in Example 2 at 5.801 min is obtained by liquid chromatography. Figure 9 The mass spectrum of the hyaluronic acid-modified cosmetic peptide prepared in Example 2 at 6.102 min is obtained by liquid chromatography. Figure 10 The mass spectrum of the hyaluronic acid-modified cosmetic peptide prepared in Example 2 is obtained from the liquid chromatography test at 6.558 min. Figure 11 The mass spectrum test results are for H-Lys-Leu-Ala-Lys-Lys-NH2 prepared in Example 3; Figure 12 The LC-MS test results for H-Lys-Leu-Ala-Lys-Lys-NH2 prepared in Example 3; Figure 13 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 3. Figure 14 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 3. Figure 15 The mass spectrum test results of H-Glu-Glu-Met-Gln-Arg-Arg-NH2 prepared in Example 4; Figure 16 The LC-MS test results for H-Glu-Glu-Met-Gln-Arg-Arg-NH2 prepared in Example 4 are shown below. Figure 17 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide D2 prepared in Example 4. Figure 18 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide D2 prepared in Example 4. Figure 19 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide D4 prepared in Example 4. Figure 20 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide D4 prepared in Example 4; Figure 21 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide D6 prepared in Example 4. Figure 22 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide D6 prepared in Example 4. Figure 23 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 5. Figure 24 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide prepared in Example 5; Figure 25 The mass spectrum test results of H-Gly-Pro-Gln-Gly-Pro-Gln-NH2 prepared in Example 6; Figure 26 The liquid chromatogram test results of H-Gly-Pro-Gln-Gly-Pro-Gln-NH2 prepared in Example 6; Figure 27 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 6. Figure 28 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide prepared in Example 6; Figure 29 The mass spectrum test results of H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH2 prepared in Example 7; Figure 30 The liquid chromatography results of H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH2 prepared in Example 7; Figure 31 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 7. Figure 32 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptides prepared in Example 7; Figure 33 The mass spectrum test results are for H-Phe-Val-Ala-Pro-Phe-Pro-OH prepared in Example 8; Figure 34 The LC-MS test results for H-Phe-Val-Ala-Pro-Phe-Pro-OH prepared in Example 8; Figure 35 The mass spectrum test results are for the hyaluronic acid-modified cosmetic peptide H2 prepared in Example 8; Figure 36The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide H2 prepared in Example 8. Figure 37 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide H4 prepared in Example 8. Figure 38 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide H4 prepared in Example 8. Figure 39 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide H6 prepared in Example 8. Figure 40 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide H6 prepared in Example 8. Figure 41 The mass spectrum test results of H-His-D-Phe-Arg-NH2 prepared in Example 9; Figure 42 LC-MS test results for H-His-D-Phe-Arg-NH2 prepared in Example 9; Figure 43 The mass spectrum test results are for the hyaluronic acid-modified cosmetic peptide L2 prepared in Example 9; Figure 44 The liquid chromatography results are for the hyaluronic acid-modified cosmetic peptide L2 prepared in Example 9. Figure 45 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide L4 prepared in Example 9. Figure 46 The liquid chromatography results of the hyaluronic acid-modified beauty peptide L4 prepared in Example 9; Figure 47 The mass spectrometry results of the hyaluronic acid-modified cosmetic peptide L6 prepared in Example 9; Figure 48 The liquid chromatography results of the hyaluronic acid-modified beauty peptide L6 prepared in Example 9; Figure 49 The mass spectrum test results of H-Tyr-Pro-Phe-Phe-NH2 prepared in Example 10; Figure 50 The liquid chromatogram test results of H-Tyr-Pro-Phe-Phe-NH2 prepared in Example 10; Figure 51 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptides prepared in Example 10. Figure 52 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide prepared in Example 10; Figure 53The mass spectrometry results are for some products (reaction products of sodium hyaluronate and beauty peptides with y=1, y=2 and y=3) prepared in Example 11. Figure 54 High performance liquid chromatography test results of some products (reaction products of sodium hyaluronate and beauty peptides with y=1, y=2 and y=3) in the hyaluronic acid modified beauty peptide prepared in Example 11. Figure 55 The mass spectrometry results are for some products (reaction products of sodium hyaluronate and beauty peptide with y=2 and y=3) prepared in Example 11. Figure 56 The liquid chromatography results are shown for partial products (reaction products of sodium hyaluronate and beauty peptide with y=2 and y=3) prepared in Example 11. Figure 57 The mass spectrum test results for H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH prepared in Example 12; Figure 58 The liquid chromatography results of H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH prepared in Example 12; Figure 59 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide prepared in Example 12; Figure 60 The mass spectrum test results of the sample at 11.577 min in the liquid chromatogram of the hyaluronic acid modified beauty peptide prepared in Example 12; Figure 61 The mass spectrum test results of the sample at 12.223 min in the liquid chromatogram of the hyaluronic acid modified beauty peptide prepared in Example 12; Figure 62 The mass spectrum test results are for H-Asp-Val-Lys-Tyr-OH prepared in Example 13; Figure 63 The liquid chromatography results are for H-Asp-Val-Lys-Tyr-OH prepared in Example 13; Figure 64 The liquid chromatography results of the hyaluronic acid-modified cosmetic peptide prepared in Example 13; Figure 65 The mass spectrum test result of the sample at 8.226 min in the liquid chromatogram of the hyaluronic acid modified beauty peptide prepared in Example 13; Figure 66The mass spectrum test results of the sample at 12.711 min in the liquid chromatogram of the hyaluronic acid modified beauty peptide prepared in Example 13; Figure 67 The mass spectrum test results of H-His-Ala-Leu-Arg-Phe-Trp-NH2 prepared in Example 14; Figure 68 The liquid chromatography results for H-His-Ala-Leu-Arg-Phe-Trp-NH2 prepared in Example 14; Figure 69 The mass spectrum test results are for the hyaluronic acid-modified cosmetic peptide A2 prepared in Example 14; Figure 70 The liquid chromatography results are for the hyaluronic acid-modified beauty peptide A2 prepared in Example 14. Figure 71 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide A4 prepared in Example 14. Figure 72 The liquid chromatography results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 73-1 Partial 1H NMR spectrum test results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 73-2 Partial 1H NMR spectrum test results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 73-3 Partial 1H NMR spectrum test results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 73-4 Partial 1H NMR spectrum test results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 73-5 Partial 1H NMR spectrum test results of the hyaluronic acid-modified beauty peptide A4 prepared in Example 14; Figure 74-1 The partial carbon NMR spectrum results are for the hyaluronic acid-modified beauty peptide A4 prepared in Example 14. Figure 74-2 The partial carbon NMR spectrum results are for the hyaluronic acid-modified beauty peptide A4 prepared in Example 14. Figure 74-3 The partial carbon NMR spectrum results are for the hyaluronic acid-modified beauty peptide A4 prepared in Example 14. Figure 74-4 The partial carbon NMR spectrum results are for the hyaluronic acid-modified beauty peptide A4 prepared in Example 14. Figure 74-5The partial carbon NMR spectrum results are for the hyaluronic acid-modified beauty peptide A4 prepared in Example 14. Figure 75 Two-dimensional Cosy plot test results of hyaluronic acid modified beauty peptide A4 prepared in Example 14; Figure 76 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide A6 prepared in Example 14. Figure 77 The liquid chromatography results are for the hyaluronic acid-modified beauty peptide A6 prepared in Example 14. Figure 78 The mass spectrum test results for H-Trp-Phe-Arg-D-Leu-Ala-His-NH2 prepared in Example 27; Figure 79 The liquid chromatography results of H-Trp-Phe-Arg-D-Leu-Ala-His-NH2 prepared in Example 27; Figure 80 The liquid chromatography results are for the hyaluronic acid-modified beauty peptide E2 prepared in Example 27. Figure 81 The mass spectrum test results are for the hyaluronic acid-modified cosmetic peptide E2 prepared in Example 27; Figure 82 The mass spectrum test results are for the hyaluronic acid-modified cosmetic peptide E4 prepared in Example 27; Figure 83 The liquid chromatography results are for the hyaluronic acid-modified beauty peptide E4 prepared in Example 27. Figure 84 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide E6 prepared in Example 27. Figure 85 The liquid chromatography results of the hyaluronic acid-modified beauty peptide E6 prepared in Example 27; Figure 86 The mass spectrum test results of H-Trp-Phe-Arg-Leu-Ala-His-NH2 prepared in Example 28; Figure 87 The liquid chromatography results of H-Trp-Phe-Arg-Leu-Ala-His-NH2 prepared in Example 28; Figure 88 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide B2 prepared in Example 28. Figure 89 The liquid chromatography results of the hyaluronic acid-modified beauty peptide B2 prepared in Example 28; Figure 90The liquid chromatography results of the hyaluronic acid-modified beauty peptide B4 prepared in Example 28; Figure 91 The liquid chromatography results of the hyaluronic acid-modified beauty peptide B4 prepared in Example 28; Figure 92 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide B6 prepared in Example 28. Figure 93 The liquid chromatography results of the hyaluronic acid-modified beauty peptide B6 prepared in Example 28; Figure 94 The mass spectrum test results of H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2 prepared in Example 29; Figure 95 The liquid chromatography results of H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2 prepared in Example 29; Figure 96 The liquid chromatography results of the hyaluronic acid-modified beauty peptide G2 prepared in Example 29; Figure 97 The liquid chromatography results of the hyaluronic acid-modified beauty peptide G2 prepared in Example 29; Figure 98 The liquid chromatography results of the hyaluronic acid-modified beauty peptide G4 prepared in Example 29; Figure 99 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide G4 prepared in Example 29. Figure 100 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide G6 prepared in Example 29. Figure 101 The liquid chromatography results of the hyaluronic acid-modified beauty peptide G6 prepared in Example 29; Figure 102 Mass spectrum test results of H-Arg-Arg-Gln-Met-Glu-Glu-NH2 prepared in Example 30; Figure 103 The liquid chromatography test results of H-Arg-Arg-Gln-Met-Glu-Glu-NH2 prepared in Example 30; Figure 104 The liquid chromatography results of the hyaluronic acid-modified beauty peptide F2 prepared in Example 30; Figure 105 The liquid chromatography results of the hyaluronic acid-modified beauty peptide F2 prepared in Example 30; Figure 106The liquid chromatography results of the hyaluronic acid-modified beauty peptide F4 prepared in Example 30; Figure 107 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide F4 prepared in Example 30. Figure 108 The mass spectrometry results are for the hyaluronic acid-modified cosmetic peptide F6 prepared in Example 30. Figure 109 The liquid chromatography results of the hyaluronic acid-modified beauty peptide F6 prepared in Example 30. Detailed Implementation

[0043] To make the objectives, technical solutions, and advantages of the present invention clearer, the technical solutions of the present invention will be further described in detail below with reference to specific embodiments: It should be noted that the hyaluronic acid used in Examples 1-30 of this invention is hydrolyzed sodium hyaluronate, purchased from Shandong Baolijia Biotechnology Co., Ltd. It is a mixture, and its main components include disaccharide sodium hyaluronate, tetrasaccharide sodium hyaluronate, and hexasaccharide sodium hyaluronate, with a mass ratio of 1:5:3.

[0044] Example 1: A method for synthesizing H-Gly-Gln-Pro-Arg-OH, comprising: 3.13 mmol of Wang resin was placed in a 125 mL solid-phase synthesis reactor. 7.5 mmol of amino acid Fmoc-Arg(Pbf)-OH was added, followed by 15 mL of dichloromethane (DCM), 2.01 mL of pyridine, and 1.78 mL of DBU. The mixture was reacted at 25 °C for 3 h. After filtration, the resin was washed three times with 15 mL of DMF solution each time. 15 mL of end-capping solution (containing Ac2O, DMF, and DIEA, with a mass ratio of Ac2O:DMF:DIEA of 10:84:6) was added, and the mixture was reacted for 15 min. After filtration, the resin was washed twice with 15 mL of dichloromethane, twice with 15 mL of methanol, and twice with 15 mL of DMF. 15 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. After filtration, the deprotection solution was removed, and the resin was washed six times with 15 mL of DMF each time. The mixture was then dried and set aside for use.

[0045] Take 5 mmol Fmoc-Pro-OH.H2O and 5 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 5 mL DMF and 0.8 mL DIC, let stand for 15 min, and then add the solution from the 50 mL beaker to the above 125 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 15 mL each time. After washing, proceed to the next step of the reaction. Add 15 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 15 mL each time. Dry and set aside for later use.

[0046] Take 7.5 mmol Fmoc-Gln(Trt)-OH and 7.5 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 5 mL DMF and 1.2 mL DIC, let stand for 15 min, and then add the solution from the 50 mL beaker to the above 125 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 15 mL of DMF solution each time. After washing, proceed to the next step of the reaction. Add 15 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 15 mL of DMF solution. Dry and set aside for later use.

[0047] 7.5 mmol Fmoc-Gly-OH and 7.5 mmol HOBt were placed in a 50 mL beaker, cooled to 5 °C, and 5 mL DMF and 1.2 mL DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 50 mL beaker was added to the 125 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 15 mL of DMF solution each time. After washing, the next reaction was carried out. 15 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 15 mL of DMF solution each time, twice with 15 mL of methanol, twice with 15 mL of DCM solution, and twice with 15 mL of methanol. The mixture was dried under vacuum to obtain the peptide resin of H-AA1-AA2-AA3-AA4-Wang- resin, where AA1 is Gly, AA2 is Gln (Trt), AA3 is Pro, and AA4 is Arg (Pbf). The above peptide resin was cleaved using TFA / Tis / H2O (TFA, Tis, and H2O volume ratio 90:5:5) at a volume of 30 mL for 2.5 h. The cleavage solution was then added to 300 mL of diethyl ether (5 °C), precipitating a white solid. After centrifugation, H-Gly-Gln-Pro-Arg-OH was obtained, and its mass spectrometry (MS / MS) was analyzed. Figure 1 ) and high performance liquid chromatography (HPLC) Figure 2)like Figure 1-2 As shown.

[0048] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.46g of H-Gly-Gln-Pro-Arg-OH.2TFA, add 5mL of DMSO and stir to dissolve. Add 0.785g of DIEA, and a tetrapeptide precipitates. Then weigh 2.1g of hyaluronic acid, heat in a water bath at 45℃ for 15 minutes, stir until the reaction solution is clear, and continue to react at 45℃ overnight. LC-MS analysis shows the reaction is essentially complete. Add 4mL of acetic acid, heat in a water bath at 35℃, and allow the rearrangement reaction to proceed for 3 hours. LC-MS analysis shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-10% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 3 and Figure 4 As shown.

[0049] Example 2: A method for synthesizing H-Lys-Thr-Thr-Lys-Ser-OH, comprising: 8.75 mmol CTC resin was placed in a 250 mL solid-phase synthesis reactor, 17.5 mmol amino acid Fmoc-Ser(tBu)-OH was added, 75 mL dichloromethane was added, and 7.0 mL DIEA was added. The reaction was carried out at 25 °C for 3 h, 10 mL methanol was added, and the reaction was carried out for 5 min. The mixture was filtered, and the resin was washed twice with dichloromethane (75 mL each time), twice with methanol (75 mL each time), and twice with DMF (75 mL each time). 75 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed 6 times with DMF solution (75 mL each time). The mixture was then dried and set aside for use.

[0050] Take 21 mmol Fmoc-Lys(Boc)-OH and 21 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 50 mL DMF solution and 3.2 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 75 mL each time. After washing, proceed to the next step of the reaction. Add 75 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 65 mL each time. Dry and set aside for later use.

[0051] Take 21 mmol Fmoc-Thr(tBu)-OH and 21 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 50 mL DMF solution and 3.2 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 75 mL each time. After washing, proceed to the next step of the reaction. Add 75 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 65 mL each time. Dry and set aside for later use.

[0052] Take 21 mmol Fmoc-Thr(tBu)-OH and 21 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 50 mL DMF solution and 3.2 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 75 mL each time. After washing, proceed to the next step of the reaction. Add 75 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 65 mL each time. Dry and set aside for later use.

[0053] Take 21 mmol Fmoc-Lys(Boc)-OH and 21 mmol HOBt in a 100 mL beaker, cool to 2-8 °C, add 50 mL DMF solution and 3.2 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 75 mL each time. After washing, proceed to the next step of the reaction. Add 75 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with DMF solution, 65 mL each time, then wash twice with methanol, 75 mL each time, wash twice with DCM solution, 75 mL each time, wash twice with methanol, 75 mL each time, and dry under vacuum to obtain H-Lys(Boc)-Thr(tBu)-Thr(tBu)-Lys(Boc)-Ser(tBu)-CTC- resin. Take 4.14 g of the above peptide resin, add 40 mL of cleavage buffer TFA / Tis / H2O (TFA, Tis and H2O volume ratio is 90:5:5), stir and react at 30℃ for 2.5 h, filter to remove resin, and obtain filtrate; dry the filtrate to obtain H-Lys-Thr-Thr-Lys-Ser-OH, and its mass spectrometry and high performance liquid chromatography characterization results are as follows. Figure 5 and Figure 6 As shown.

[0054] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Lys-Thr-Thr-Lys-Ser-OH.3TFA, add 5 mL of DMSO and stir to dissolve. Add 82 μL of TFA and stir for 0.5 h. Then add 0.641 g of DIEA, followed by 1.71 g of hyaluronic acid. The mixture was stirred overnight in a water bath at 45°C. LC-MS analysis showed the reaction was essentially complete. Then, 4 mL of acetic acid was added, and the mixture was subjected to a rearrangement reaction in a water bath at 35°C for 3 h. LC-MS analysis showed the reaction was essentially complete. Finally, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-10% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to prepare hyaluronic acid-modified cosmetic peptides, and their high-performance liquid chromatography characterization was as follows: Figure 7 As shown in the figure; samples were collected at 5.801 min, 6.102 min, and 6.558 min for mass spectrometry characterization, and the results are as follows. Figure 8 , Figure 9 , Figure 10 As shown.

[0055] Example 3: A method for synthesizing H-Lys-Leu-Ala-Lys-Lys-NH2, comprising: Place 10 mmol AM resin in a 250 mL solid-phase synthesis reactor, add 70 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 70 mL of DMF solution each time, and dry for later use.

[0056] Take 20 mmol Fmoc-Linker and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 70 mL DMF solution each time. Dry and set aside for later use.

[0057] Take 20 mmol Fmoc-Lys(Boc)-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 70 mL DMF solution each time. Dry and set aside for later use.

[0058] Take 20 mmol Fmoc-Lys(Boc)-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 70 mL DMF solution each time. Dry and set aside for later use.

[0059] Take 20 mmol Fmoc-Ala-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 70 mL each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 70 mL each time. Dry and set aside for later use.

[0060] Take 20 mmol Fmoc-Leu-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete; wash the resin three times with DMF solution, 70 mL each time; after washing, proceed to the next step of the reaction; add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with DMF solution, 40 mL each time, and dry for later use.

[0061] 20 mmol Fmoc-Lys(Boc)-OH and 20 mmol HOBt were placed in a 100 mL beaker, cooled to 5 °C, and 35 mL DMF solution and 3.1 mL DIC were added. The mixture was allowed to stand for 15 min. The solution in the 100 mL beaker was then added to the 250 mL solid-phase synthesis reactor, and the mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 70 mL DMF solution each time. After washing, the next reaction was carried out. 70 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL DMF solution each time. The resin was dried under vacuum to obtain the peptide resin of H-Lys(Boc)-Leu-Ala-Lys(Boc)-Lys(Boc)-Linker-AM resin. In the above peptide resin, 100 mL of cleavage buffer TFA / Tis / H2O (TFA, Tis, and H2O volume ratio 90:5:5) was added, and cleavage was performed for 2.5 hours. The cleavage buffer was then added to 1000 mL of diethyl ether (5℃) solution, precipitating a white solid. This solid was centrifuged and vacuum dried to obtain H-Lys-Leu-Ala-Lys-Lys-NH2. Its mass spectrometry and LC-MS characterization results are as follows: Figure 11 and Figure 12 As shown.

[0062] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Lys-Leu-Ala-Lys-Lys-NH2.4TFA, add 10 mL of DMSO and stir to dissolve. Add 107 μL of TFA, stir at room temperature for 0.5 h, then add 0.557 g of DIEA, followed by 1.49 g of hyaluronic acid. The mixture is stirred overnight in a water bath at 45 °C. LC-MS analysis shows the reaction is essentially complete. Add 4 mL of acetic acid, and the mixture is subjected to a rearrangement reaction in a water bath at 35 °C for 3 h. LC-MS analysis shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-10% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 13 and Figure 14 As shown.

[0063] Example 4: A method for synthesizing H-Glu-Glu-Met-Gln-Arg-Arg-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter, remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use. Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0064] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete; wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction; add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0065] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0066] Take 10 mmol Fmoc-Gln(Trt)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0067] Take 10 mmol Fmoc-Met-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0068] Take 10 mmol Fmoc-Glu(otBu)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0069] Take 15 mmol Fmoc-Glu(otBu)-OH, 1 mmol HOBt was placed in a 100 mL beaker, cooled to 5 °C, and 15 mL of DMF solution was added. The mixture was allowed to stand for 15 min, and the solution in the 100 mL beaker was then added to the 100 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 30 mL of DMF solution each time. After washing, the next reaction was carried out. 40 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL of DMF solution each time. The resin was dried under vacuum. Then, it was washed twice with 40 mL of methanol each time, twice with 40 mL of DCM solution, and twice with 40 mL of methanol each time. The mixture was dried under vacuum to obtain the peptide resin of H-Glu(otBu)-Glu(otBu)-Met-Gln(Trt)-Arg(Pbf)-Arg(Pbf)-Linker-AM resin. The above peptide resin was cut with 100 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 1000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-Glu-Glu-Met-Gln-Arg-Arg-NH2 was obtained. Its mass spectrometry and high-performance liquid chromatography characterization results are as follows. Figure 15 and Figure 16 As shown.

[0070] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-Glu-Glu-Met-Gln-Arg-Arg-NH2.3TFA, add 10mL of DMSO and stir to dissolve. Add 889mg of DIEA, then add 3.67g of hyaluronic acid. The mixture is stirred and reacted overnight at 45℃ in a water bath. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35℃ in a water bath for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 1g of crude product and dilute with 200mL of H2O; Packing material: 50DAC, C18; Flow rate: 60 mL / min; Wavelength: 220 nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 60 mL / min; Sample loading: Flow rate: 60 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: D2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 17 and Figure 18 As shown; D4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 19 and Figure 20 As shown; D6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 21 and Figure 22 As shown.

[0071] Example 5: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Gly-His-Lys-OH.2AcOH, add 10 mL of DMSO and stir for 5 min to dissolve. Add 286 μL of TFA, stir for 1 min until the solution becomes clear, stir for another 0.5 h, add 3 g of hyaluronic acid, stir to dissolve, add 1.11 g of DIEA, stir for 1 min, and then react overnight at 45℃ in a water bath. LC-MS analysis showed the reaction was essentially complete. Add 4 mL of acetic acid, and then react in a water bath at 35℃ for 3 h for rearrangement. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography results are as follows: Figure 23 and Figure 24 As shown.

[0072] Example 6: A method for synthesizing H-Gly-Pro-Gln-Gly-Pro-Gln-OH, comprising: Place 10 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0073] Take 20 mmol Fmoc-Linker and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0074] Take 20 mmol Fmoc-Glu-OtBu and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to a 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 30 mL DMF solution each time. Dry and set aside for later use.

[0075] Take 20 mmol Fmoc-Pro-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0076] Take 20 mmol Fmoc-Gly-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 30 mL DMF solution each time. Dry and set aside for later use.

[0077] Take 20 mmol Fmoc-Gln(Trt)-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0078] Take 20 mmol Fmoc-Pro-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0079] Take 20 mmol Fmoc-Gly-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 4.6 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete; wash the resin three times with DMF solution, 30 mL each time; after washing, proceed to the next step of the reaction; add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with DMF solution, 40 mL each time, and dry for later use. Then wash twice with methanol, 40 mL each time, twice with DCM solution, 40 mL each time, and twice with methanol, 40 mL each time. Vacuum drying yielded H-BB1-BB2-BB3-BB4-BB5-BB6-Linker-AM resin, wherein AA1 is Gly; AA2 is Pro; AA3 is Gln; AA4 is Gly; AA5 is Pro; and AA6 is Gln.

[0080] 8.3 g of the above peptide resin was cleaved for 2.5 h with 50 mL of cleavage buffer (TFA, Tis, and H2O in a volume ratio of 90:5:5). The cleavage buffer was then added to 500 mL of diethyl ether (5 °C), precipitating a white solid. The solid was centrifuged and dried under vacuum to obtain H-Gly-Pro-Gln-Gly-Pro-Gln-OH. Its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 25 and Figure 26 As shown.

[0081] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g of H-Gly-Pro-Gln-Gly-Pro-Gln-OH.TFA, add 5mL of DMSO and stir to dissolve. Add 0.834g of DIEA, then add 2.23g of hyaluronic acid. The mixture is stirred overnight in a water bath at 45℃. LC-MS analysis shows the reaction is essentially complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction in a water bath at 35℃ for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 27 and Figure 28 As shown.

[0082] Example 7: A method for synthesizing H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0083] Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h, the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time; after washing, proceed to the next step of the reaction; add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with DMF solution, 30 mL each time, and dry for later use.

[0084] Take 15 mmol Fmoc-Val-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0085] Take 15 mmol Fmoc-Pro-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0086] Take 15 mmol Fmoc-Lys(Boc)-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 30 mL each time. Dry and set aside for later use.

[0087] Take 15 mmol Fmoc-Phe-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0088] Take 10 mmol Fmoc-D-Trp(Boc)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0089] Take 15 mmol Fmoc-Arg(Pbf)-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete; wash the resin three times with 30 mL DMF solution each time. After washing, proceed to the next step of the reaction; add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use.

[0090] Take 10 mmol Fmoc-D-Phe-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 30 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0091] Take 15 mmol Fmoc-Pro-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 100 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 30 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 40 mL each time. Dry and set aside for later use.

[0092] 15 mmol Fmoc-Met-OH and 15 mmol HOBt were placed in a 100 mL beaker, cooled to 5 °C, and 15 mL DMF solution and 2.3 mL DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 100 mL beaker was added to the 100 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 30 mL DMF solution each time. After washing, the next reaction was carried out. 40 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL DMF solution each time. The resin was dried under vacuum. Then, it was washed twice with 40 mL methanol each time, twice with 40 mL DCM solution each time, and twice with 40 mL methanol each time. The resin was dried under vacuum to obtain the peptide resin of H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-Linker-AM resin.

[0093] 5.7 g of the above peptide resin was cleaved for 2.5 h with 50 mL of cleaving buffer TFA / anisole / EDT / phenol / H2O (TFA:anisole:EDT:phenol:H2O mass ratio of 87.5:5:2.5:2.5:2.5). The cleaving buffer was then added to 500 mL of diethyl ether (5℃) solution, precipitating a white solid. The solid was centrifuged and vacuum dried to obtain H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH2. Its mass spectrometry and high-performance liquid chromatography are shown below. Figure 29 and Figure 30 As shown.

[0094] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g of H-Met-Pro-{D-Phe}-Arg-{D-Trp}-Phe-Lys-Pro-Val-NH2.3TFA, add 5mL of DMSO and stir to dissolve. Add 0.375g of DIEA, then add 1g of hyaluronic acid. The mixture is stirred overnight in a water bath at 45℃. LC-MS analysis shows the reaction is essentially complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction in a water bath at 35℃ for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 15-35% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 31 and Figure 32 As shown.

[0095] Example 8: A method for synthesizing H-Phe-Val-Ala-Pro-Phe-Pro-OH, comprising: 12.5 mmol CTC resin was placed in a 125 mL solid-phase synthesis reactor, 25 mmol amino acid Fmoc-Pro-OH was added, 100 mL dichloromethane was added, and then 10.9 mL DIEA was added. The reaction was carried out at 25 °C for 3 h, then 15 mL methanol was added and the reaction was carried out for 5 min. The mixture was filtered, and the resin was washed twice with 100 mL of dichloromethane, twice with 100 mL of methanol, and twice with 100 mL of DMF. 100 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was then filtered to remove the deprotection solution, and then washed 6 times with 20 mL of DMF solution each time. The mixture was then dried and set aside for use.

[0096] Take 20 mmol Fmoc-Phe-OH and 20 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 30 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution in the 100 mL beaker to the above 250 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete; wash the resin three times with 100 mL DMF solution each time; after washing, proceed to the next step of the reaction; add 100 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 20 mL DMF solution each time, and dry for later use.

[0097] Take 20 mmol Fmoc-Pro-OH and 20 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 30 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution in the 100 mL beaker to the above 250 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete; wash the resin three times with DMF solution, 100 mL each time; after washing, proceed to the next step of the reaction; add 100 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 20 mL each time, and dry for later use.

[0098] Take 20 mmol Fmoc-Ala-OH and 20 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 8 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution in the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 100 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 20 mL DMF solution each time. Dry and set aside for later use.

[0099] Take 20 mmol Fmoc-Val-OH and 20 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 8 mL DMF solution and 20 mmol DIC, let stand for 5 min, and then add the solution in the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 100 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 20 mL DMF solution each time. Dry and set aside for later use.

[0100] 20 mmol Fmoc-Phe-OH and 20 mmol HOBt were placed in a 50 mL beaker, cooled to 5 °C, and 30 mL DMF solution and 3.1 mL DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 100 mL beaker was added to the 250 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 100 mL DMF solution each time. After washing, the next reaction was carried out. 100 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution. The resin was then washed six times with 20 mL DMF solution each time, followed by two washes with 100 mL methanol each time, two washes with 100 mL DCM solution each time, and two washes with 100 mL methanol each time. The resin was then dried under vacuum to obtain H-Phe-Val-Ala-Pro-Phe-Pro-CTC- resin. 2g of the above peptide resin was cleaved with 20mL of TFA / DCM cleavage buffer (TFA to DCM volume ratio 2:98) at 30℃ for 1 hour. The cleavage buffer was then dried to obtain H-Phe-Val-Ala-Pro-Phe-Pro-OH. Its mass spectrometry and LC-MS characterization results are as follows: Figure 33 and Figure 34 As shown. The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.56 g of H-Phe-Val-Ala-Pro-Phe-Pro-OH.TFA, add 6 mL of DMSO and stir to dissolve. Add 0.75 g of DIEA, then add 2.2 g of hyaluronic acid. The mixture is stirred and reacted overnight at 45°C in a water bath. LC-MS analysis shows the reaction is essentially complete. Add 4 mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35°C in a water bath for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified cosmetic peptides with different structures were obtained from the collected qualified products: The hyaluronic acid-modified beauty peptide H2, with n=0 in its structure (i.e., y=1 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 35 and Figure 36 As shown; The hyaluronic acid-modified beauty peptide H4, with n=1 in its structure (i.e., y=2 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 37 and Figure 38 As shown; The hyaluronic acid-modified beauty peptide H6, with n=2 in its structure (i.e., y=3 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 39 and Figure 40 As shown.

[0101] Example 9: A method for synthesizing H-His-D-Phe-Arg-NH2, comprising: Place 10 mmol AM resin in a 250 mL solid-phase synthesis reactor, add 70 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with DMF solution, 70 mL each time, and dry for later use.

[0102] Take 20 mmol Fmoc-Linker and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 70 mL each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 70 mL each time. Dry and set aside for later use.

[0103] Take 20 mmol Fmoc-Arg(Pbf)-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 70 mL each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 70 mL each time. Dry and set aside for later use.

[0104] Take 20 mmol Fmoc-D-Phe-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete; wash the resin three times with DMF solution, 70 mL each time; after washing, proceed to the next step of the reaction; add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with DMF solution, 70 mL each time, and dry for later use.

[0105] 20 mmol Fmoc-His(Trt)-OH and 20 mmol HOBt were placed in a 100 mL beaker, cooled to 5 °C, and 35 mL DMF solution and 20 mmol DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 100 mL beaker was added to the 250 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 70 mL DMF solution each time. After washing, the next reaction was carried out. 70 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL DMF solution each time. The resin was dried under vacuum and then washed twice with methanol each time, twice with DCM solution each time, and twice with methanol each time. The resin was dried under vacuum to obtain the peptide resin of H-His(Trt)-D-Phe-Arg(Pbf)-Linker-AM. The above peptide resin was cleaved using TFA / Tis / H2O (TFA, Tis, and H2O volume ratio 90:5:5) at a volume of 100 mL for 2.5 h. The cleavage solution was then added to 1000 mL of diethyl ether (5°C), precipitating a white solid. This solid was centrifuged and vacuum dried to obtain H-His-D-Phe-Arg-NH2. Its mass spectrometry and LC-MS characterization results are as follows: Figure 41 and Figure 42 As shown. The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Where n=2, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-His-D-Phe-Arg-NH2.3TFA, add 5 mL of DMSO and stir to dissolve. Add 661 mg of DIEA, then add 1.94 g of hyaluronic acid. The mixture is stirred and reacted overnight at 45°C in a water bath. LC-MS analysis shows the reaction is essentially complete. Add 4 mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35°C in a water bath for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified cosmetic peptides with different structures were obtained from the collected qualified products: The hyaluronic acid-modified beauty peptide L2, with n=0 in its structure (i.e., y=1 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 43 and Figure 44 As shown; The hyaluronic acid-modified beauty peptide L4, with n=1 in its structure (i.e., y=2 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 45 and Figure 46 As shown; The hyaluronic acid-modified beauty peptide L6, with n=2 in its structure (i.e., y=3 in the structure of the raw hyaluronic acid), and the product prepared from the beauty peptide, were characterized by mass spectrometry and high-performance liquid chromatography as follows: Figure 47 and Figure 48 As shown.

[0106] Example 10: A method for synthesizing H-Tyr-Pro-Phe-Phe-NH2, comprising: Place 10 mmol of AM resin in a 250 mL solid-phase synthesis reactor, add 70 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 70 mL of DMF solution each time, and dry for later use.

[0107] Take 20 mmol Fmoc-Linker and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor. Stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 70 mL DMF solution each time. Dry and set aside for later use.

[0108] Take 20 mmol Fmoc-Phe-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, and then add the solution from the 100 mL beaker to the above 250 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete; wash the resin three times with 70 mL DMF solution each time; after washing, proceed to the next step of the reaction; add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, and then wash six times with 70 mL DMF solution each time, and dry for later use.

[0109] Take 20 mmol Fmoc-Phe-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 250 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 70 mL DMF solution each time, and dry for later use.

[0110] Take 20 mmol Fmoc-Pro-OH and 20 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 35 mL DMF solution and 3.1 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 250 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 70 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 70 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 70 mL DMF solution each time, and dry for later use.

[0111] 20 mmol Fmoc-Tyr(tBu)-OH and 20 mmol HOBt were placed in a 100 mL beaker, cooled to 5 °C, and 35 mL DMF solution and 3.1 mL DIC were added. The mixture was allowed to stand for 15 min, and then the solution in the 100 mL beaker was added to the 250 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 70 mL DMF solution each time. After washing, the next reaction was carried out. 70 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL DMF solution each time. The resin was dried under vacuum to obtain the peptide resin of H-Tyr(tBu)-Pro-Phe-Phe-Linker-AM resin. The above peptide resin was cleaved using TFA / Tis / H2O (TFA, Tis, and H2O volume ratio 90:5:5) at a volume of 100 mL for 2.5 h. The cleavage solution was then added to 1000 mL of diethyl ether (5°C), precipitating a white solid. This solid was centrifuged and vacuum dried to obtain H-Tyr-Pro-Phe-Phe-NH2. Its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 49 and Figure 50 As shown.

[0112] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g of H-Tyr-Pro-Phe-Phe-NH2.TFA, add 5mL of DMSO and stir to dissolve. Add 0.771g of DIEA, then add 2.27g of hyaluronic acid. The mixture is stirred overnight in a water bath at 45℃. LC-MS analysis shows the reaction is essentially complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction in a water bath at 35℃ for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified cosmetic peptides were prepared. The mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 51 and Figure 52 As shown.

[0113] Example 11: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g H-β-Ala-His-OH.TFA, add 10mL DMSO and stir to dissolve. Add 0.5g TFA and stir for 10min. Then add 2.5g DIEA and 6.85g hyaluronic acid. React overnight in a water bath at 45℃ with stirring. LC-MS analysis shows the reaction is essentially complete. Add 4mL acetic acid and allow the reaction to rearrange for 3h in a water bath at 35℃. LC-MS analysis shows the reaction is essentially complete. Then perform reverse chromatography purification under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-10% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to prepare hyaluronic acid-modified beauty peptides. The mass spectrometry and high-performance liquid chromatography characterization results of the products containing the beauty peptides combined with two tetrasaccharide sodium hyaluronates or the beauty peptides combined with one hexasaccharide sodium hyaluronate and one disaccharide sodium hyaluronate are as follows: Figure 53 and Figure 54As shown, the peak position of the high-performance liquid chromatography (HPLC) was 6.460 min, and the molecular weight of the product was 872.3 / 582.0. The mass spectrometry and HPLC characterization results of the products of the beauty peptide with one hexasaccharide sodium hyaluronate and one tetrasaccharide sodium hyaluronate are shown below. Figure 55 and Figure 56 As shown, the peak position in the high performance liquid chromatography is 7.202 min, and the molecular weight of the product is 708.4 / 1061.8 / 1415.8.

[0114] Example 12: A method for synthesizing H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH, comprising: 7.5 mmol of Wang resin was placed in a 125 mL solid-phase synthesis reactor. 15 mmol of amino acid Fmoc-Ala-OH was added, followed by 50 mL of dichloromethane, 4.8 mL of pyridine, and 4.2 mL of DBU. The mixture was reacted at 25 °C for 3 h. After filtration, the resin was washed three times with 50 mL of DMF solution each time. 50 mL of end-capping solution Ac2O / DMF / DIEA (Ac2O, DMF, and DIEA in a volume ratio of 10:84:6) was added, and the mixture was reacted for 15 min. After filtration, the resin was washed twice with 50 mL of dichloromethane, twice with 50 mL of methanol, and twice with 50 mL of DMF. 50 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. After filtration, the deprotection solution was removed, and the resin was washed six times with 50 mL of DMF solution each time. The mixture was then dried and ready for use.

[0115] Take 15 mmol Fmoc-Arg(Pbf)-OH and 15 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 20 mL DMF solution and 2.32 mL DIC, let stand for 15 min, then add the solution from the 50 mL beaker to the 125 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 15 mL of DMF solution each time. After washing, proceed to the next step of the reaction. Add 50 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 50 mL of DMF solution each time, and dry for later use.

[0116] Take 15 mmol Fmoc-Arg(Pbf)-OH and 15 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 20 mL DMF solution and 2.32 mL DIC, let stand for 15 min, then add the solution from the 50 mL beaker to the 125 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 15 mL of DMF solution each time. After washing, proceed to the next step of the reaction. Add 50 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 50 mL of DMF solution each time, and dry for later use.

[0117] Take 15 mmol Fmoc-Gln(Trt)-OH and 15 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 20 mL DMF solution and 2.32 mL DIC, let stand for 15 min, then add the solution from the 50 mL beaker to the 125 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 15 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 50 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 50 mL DMF solution each time, and dry for later use.

[0118] Take 15 mmol Fmoc-Met-OH and 15 mmol HOBt in a 50 mL beaker, cool to 5 °C, add 20 mL DMF solution and 2.32 mL DIC, let stand for 15 min, then add the solution from the 50 mL beaker to the 125 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 15 mL of DMF solution each time. After washing, proceed to the next step of the reaction. Add 50 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 50 mL of DMF solution each time, and dry for later use.

[0119] 15 mmol Fmoc-Glu(OtBu)-OH and 15 mmol HOBt were placed in a 50 mL beaker, cooled to 5 °C, and 20 mL DMF solution and 2.32 mL DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 50 mL beaker was then added to the 125 mL solid-phase synthesis reactor described above. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 15 mL of DMF solution each time. After washing, the next step of the reaction was carried out: 50 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was then filtered to remove the deprotection solution, and then washed six times with 50 mL of DMF solution each time. The resin was then dried and set aside for later use.

[0120] 15 mmol Fmoc-Glu(OtBu)-OH and 15 mmol HOBt were placed in a 50 mL beaker, cooled to 5 °C, and 20 mL DMF solution and 2.32 mL DIC were added. The mixture was allowed to stand for 15 min, and the solution in the 50 mL beaker was then added to the 125 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 15 mL of DMF solution each time. After washing, the next step of the reaction was carried out: 50 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 50 mL of DMF solution each time, twice with 50 mL of methanol solution each time, twice with 50 mL of DCM solution each time, and twice with 50 mL of methanol solution each time. Vacuum drying yielded H-AA1-AA2-AA3-AA4-AA5-AA6-AA7-Wang- resin, wherein AA1 is Glu (OtBu); AA2 is Glu (OtBu); AA3 is Met; AA4 is Gln (Trt); AA5 is Arg (Pbf); AA6 is Arg (Pbf); and AA7 is Ala.

[0121] 4.22 g of the above peptide resin was cut with 40 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 400 mL of diethyl ether (5℃) solution, and a white solid precipitated. The solid was centrifuged and vacuum dried to obtain H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH. The mass spectrometry and high performance liquid chromatography characterization results are as follows. Figure 57 and Figure 58 As shown.

[0122] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g of H-Glu-Glu-Met-Gln-Arg-Arg-Ala-OH.3TFA, add 5mL of DMSO and stir to dissolve. Then add 0.46g of DIEA and 1.24g of hyaluronic acid. The mixture is stirred and reacted overnight at 45℃ in a water bath. LC-MS analysis shows the reaction is essentially complete. Then add 4mL of acetic acid and allow the mixture to undergo a rearrangement reaction at 35℃ in a water bath for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Finally, reverse chromatography purification is performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-10% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified beauty peptides were obtained. The high-performance liquid chromatography (HPLC) test results are as follows: Figure 59 As shown in the figure. The sample at 11.577 min is a product of a cosmetic peptide bound to a tetrasaccharide sodium hyaluronate, and its mass spectrometry characterization results are as follows. Figure 60 As shown; the sample at 12.223 min is a product of the combination of a beauty peptide and a hexasaccharide sodium hyaluronate, and its mass spectrometry characterization results are as follows. Figure 61 As shown.

[0123] Example 13: A method for synthesizing H-Asp-Val-Lys-Tyr-OH, comprising: 6.25 mmol of CTC resin was placed in a 250 mL solid-phase synthesis reactor. 12.5 mmol of amino acid Fmoc-Tyr(tBu)-OH was added, followed by 120 mL of dichloromethane and 8.7 mL of DIEA. The reaction was carried out at 25 °C for 3 h. Then, 12.5 mL of methanol was added, and the reaction was continued for 5 min. The mixture was filtered, and the resin was washed twice with 150 mL of dichloromethane, twice with 150 mL of methanol, and twice with 390 mL of DMF. 65 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was then filtered to remove the deprotection solution, and then washed six times with 120 mL of DMF solution each time. The mixture was then dried and stored for later use.

[0124] Take 15 mmol Fmoc-Lys(Boc)-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 14 mL DMF solution and 1.89 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 250 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 120 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 65 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 120 mL DMF solution each time, and dry for later use.

[0125] Take 15 mmol Fmoc-Val-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 10 mL DMF solution and 2.32 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 250 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 120 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 65 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 120 mL DMF solution each time, and dry for later use.

[0126] 15 mmol Fmoc-Asp(OtBu)-OH and 15 mmol HOBt were placed in a 100 mL beaker, cooled to 5 °C, and 13 mL DMF solution and 2.32 mL DIC were added. The mixture was allowed to stand for 15 min, and then the solution in the 100 mL beaker was added to the 250 mL solid-phase synthesis reactor. The mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 120 mL DMF solution each time. After washing, the next reaction was carried out. 65 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 120 mL DMF solution each time. Then, it was washed twice with 125 mL methanol each time, twice with 125 mL DCM solution each time, and twice with 125 mL methanol each time. The resin was dried under vacuum to obtain H-Asp(OtBu)-Val-Lys(Boc)-Tyr(tBu)-CTC-resin. 4.89 g of the above peptide resin was cleaved using TFA / Tis / H2O (TFA, Tis, and H2O volume ratio 90:5:5) at a volume of 40 mL. The mixture was stirred at 30 °C for 2.5 h, filtered to remove the resin, and the filtrate was obtained. The filtrate was dried to obtain the crude peptide H-Asp-Val-Lys-Tyr-OH. Its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 62 and Figure 63 As shown.

[0127] A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Asp-Val-Lys-Tyr-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 0.773 g of DIEA and 2.1 g of hyaluronic acid. Maintain a water bath temperature of 45°C and stir for 15 min to dissolve. Continue stirring and reacting overnight. LC-MS analysis shows the reaction is essentially complete. Add 4 mL of acetic acid and maintain a water bath temperature of 35°C for a rearrangement reaction for 3 h. LC-MS analysis again shows the reaction is essentially complete. Then perform reverse chromatography purification under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected, and hyaluronic acid-modified beauty peptides were obtained. The high-performance liquid chromatography (HPLC) test results are as follows: Figure 64 As shown in the figure. The sample at 8.226 min is a product of the combination of a beauty peptide and two hexasaccharides of sodium hyaluronate; its mass spectrometry characterization results are shown below. Figure 65 As shown; the sample at 12.711 min is a product of a cosmetic peptide combined with one hexasaccharide sodium hyaluronate, one disaccharide sodium hyaluronate, or a cosmetic polypeptide combined with two tetrasaccharide sodium hyaluronates. Its mass spectrometry characterization results are as follows. Figure 66 As shown.

[0128] Example 14: A method for synthesizing H-His-Ala-Leu-Arg-Phe-Trp-NH2, comprising: Place 30 mmol AM resin in a 500 mL solid-phase synthesis reactor, add 200 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 200 mL of DMF solution each time, and dry for later use.

[0129] Take 10 mmol Fmoc-Linker and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step: add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0130] Take 60 mmol Fmoc-Trp(Boc)-OH and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0131] Take 60 mmol Fmoc-Phe-OH and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0132] Take 60 mmol Fmoc-Arg(Pbf)-OH and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0133] Take 60 mmol Fmoc-Leu-OH and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0134] Take 60 mmol Fmoc-Ala-OH and 60 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 60 mL DMF solution and 9.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 500 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 100 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry for later use.

[0135] Take 90 mmol Fmoc-His(Trt)-OH and 90 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 100 mL DMF solution and 13.9 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to a 500 mL solid-phase synthesis reactor, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 150 mL DMF solution each time. After washing, proceed to the next step. Add 200 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 200 mL DMF solution each time, and dry. Then wash twice with 200 mL methanol each time, twice with 200 mL DCM solution each time, and twice with 200 mL methanol each time. Vacuum drying yielded a peptide resin of H-AA1-AA2-AA3-AA4-AA5-AA6-Linker-AM, wherein AA1 is His (Trt); AA2 is Ala; AA3 is Leu; AA4 is Arg (Pbf); AA5 is Phe; and AA6 is Trp.

[0136] The above peptide resin was cut with 690 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 7000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-His-Ala-Leu-Arg-Phe-Trp-NH2 was obtained. Its mass spectrometry and high performance liquid chromatography characterization results are as follows: Figure 67 and Figure 68 As shown.

[0137] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-His-Ala-Leu-Arg-Phe-Trp-NH2.TFA, add 10mL of DMSO and stir to dissolve. Add 1.28g of DIEA, stir for 5 minutes, then add 3.75g of hyaluronic acid. Maintain the reaction in a water bath at 45℃ overnight. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid, maintain the reaction in a water bath at 35℃, and allow the rearrangement reaction to proceed for 3 hours. LC-MS analysis again shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: A2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 69 and Figure 70 As shown; A4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 71 and Figure 72 As shown, its hydrogen NMR spectrum is as follows: Figures 73-1 to 73-5As shown, and the carbon spectrum is as follows Figures 74-1 to 74-5 As shown, its two-dimensional cosy map is as follows: Figure 75 As shown; A6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 76 and Figure 77 As shown.

[0138] Example 15: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-β-Ala-Pro-Dab-NH-Bzl.TFA, add 5 mL of DMSO and stir to dissolve. Add 704.32 mg of DIEA, stir for 5 min, then add 2064.08 mg of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 3 mL of acetic acid, maintain a water bath temperature of 35℃, and proceed with the rearrangement reaction for 3 h. LC-MS analysis shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0139] Example 16: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Dab-Val-Dab-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 833.2 mg of DIEA and stir for 5 min. Next, add 2441.79 mg of hyaluronic acid, maintain the temperature in a water bath at 45°C, and stir to react overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature in a water bath at 35°C, and proceed with the rearrangement reaction for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0140] Example 17: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Lys-Val-Lys-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 708.03 mg of DIEA and stir for 5 min. Next, add 2074.97 mg of hyaluronic acid, maintain the temperature in a water bath at 45°C, and stir to react overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature in a water bath at 35°C, and allow the rearrangement reaction to proceed for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0141] Example 18: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Gln-Asp-Val-His-OH.TFA, add 5 mL of DMSO and stir to dissolve. Add 531.55 mg of DIEA, stir for 5 min, then add 1557.76 mg of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 3 mL of acetic acid, maintain a water bath temperature of 35℃, and proceed with the rearrangement reaction for 3 h. LC-MS analysis shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0142] Example 19: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Pro-Pro-Tyr-Leu-OH.TFA, add 5 mL of DMSO and stir to dissolve. Add 541.25 mg of DIEA, stir for 5 min, then add 1586.20 mg of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 3 mL of acetic acid, maintain a water bath temperature of 35℃, and proceed with the rearrangement reaction for 3 h. LC-MS analysis shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0143] Example 20: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Pro-Lys-Glu-Lys-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 528.27 mg of DIEA and stir for 5 min. Next, add 1548.14 mg of hyaluronic acid, maintain the temperature in a water bath at 45°C, and stir to react overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature in a water bath at 35°C, and proceed with the rearrangement reaction for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0144] Example 21: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Val-Trp-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 871.74 mg of DIEA and stir for 5 min. Next, add 2554.72 mg of hyaluronic acid, maintain the temperature in a water bath at 45°C, and stir to react overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature in a water bath at 35°C, and proceed with the rearrangement reaction for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0145] Example 22: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Ser-Val-Val-Val-Arg-Thr-NH2.TFA, add 5 mL of DMSO and stir to dissolve. Add 404.41 mg of DIEA, stir for 5 min, then add 1176.38 mg of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 3 mL of acetic acid, maintain a water bath temperature of 35℃, and proceed with the rearrangement reaction for 3 h. LC-MS analysis shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0146] Example 23: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g Pal-Lys-Met(O)2-Lys-OH.2TFA, add 7mL DMSO and stir to dissolve. Then add 391.22mg DIEA, stir for 5min, then add 1146.50mg hyaluronic acid. Maintain the reaction temperature at 45℃ in a water bath and stir overnight. LC-MS analysis showed the reaction was essentially complete. Add 3mL acetic acid, maintain the temperature at 35℃ in a water bath, and allow the rearrangement reaction to proceed for 3h. LC-MS analysis showed the reaction was essentially complete. Then perform reverse chromatography purification under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0147] Example 24: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-Lys-Met(O)2-Lys-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 604.37 mg of DIEA and stir for 5 min. Next, add 1771.19 mg of hyaluronic acid, maintain the temperature in a water bath at 45°C, and stir to react overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature in a water bath at 35°C, and proceed with the rearrangement reaction for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0148] Example 25: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5g of H-Val-Gly-Val-Ala-Pro-Gly-OH.2TFA, add 7mL of DMSO and stir to dissolve. Then add 530.41mg of DIEA, stir for 5min, and then add 1554.41mg of hyaluronic acid. Maintain the reaction temperature at 45℃ in a water bath and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 3mL of acetic acid, maintain the temperature at 35℃ in a water bath, and allow the rearrangement reaction to proceed for 3h. LC-MS analysis again shows the reaction is essentially complete. Then perform reverse chromatography purification under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0149] Example 26: A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 0.5 g of H-bataAla-His-Ser-His-OH.2TFA, add 7 mL of DMSO and stir to dissolve. Then add 587.07 mg of DIEA, stir for 5 min, and then add 1720.46 mg of hyaluronic acid. Maintain the reaction temperature at 45℃ in a water bath and stir overnight. LC-MS analysis showed the reaction was essentially complete. Add 3 mL of acetic acid, maintain the temperature at 35℃ in a water bath, and allow the rearrangement reaction to proceed for 3 h. LC-MS analysis showed the reaction was essentially complete. Then, reverse chromatography purification was performed under the following conditions: Dissolution: Take 0.5g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B=100:0, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 0-20% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Qualified products were collected to produce hyaluronic acid-modified beauty peptides.

[0150] Example 27: A method for synthesizing H-Trp-Phe-Arg-D-Leu-Ala-His-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0151] Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step: add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0152] Take 10 mmol Fmoc-His(Trt)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0153] Take 10 mmol Fmoc-Ala-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0154] Take 10 mmol Fmoc-D-Leu-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0155] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use.

[0156] Take 10 mmol Fmoc-Phe-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 15 mmol Fmoc-Trp(Boc)-OH and 1 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 30 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Then wash twice with 40 mL methanol each time, twice with 40 mL DCM solution each time, and twice with 40 mL methanol each time. Vacuum drying yielded a peptide resin of H-AA1-AA2-AA3-AA4-AA5-AA6-Linker-AM, wherein AA1 is Trp(Boc); AA2 is Phe; AA3 is Arg; AA4 is D-Leu; AA5 is Ala; and AA6 is His(Trt).

[0157] The above peptide resin was cut with 110 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 1000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-Trp-Phe-Arg-D-Leu-Ala-His-NH2 was obtained. Its mass spectrometry and high performance liquid chromatography characterization results are as follows: Figure 78 and Figure 79 As shown.

[0158] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-Trp-Phe-Arg-D-Leu-Ala-His-NH2.TFA, add 10mL of DMSO and stir to dissolve. Add 1.28g of DIEA, stir for 5 minutes, then add 3.75g of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid and allow the mixture to rearrange at a constant temperature for 2 hours. LC-MS analysis again shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: E2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 80 and Figure 81 As shown; E4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 82 and Figure 83 As shown; E6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 84 and Figure 85 As shown.

[0159] Example 28: A method for synthesizing H-Trp-Phe-Arg-Leu-Ala-His-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0160] Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step: add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0161] Take 10 mmol Fmoc-His(Trt)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0162] Take 10 mmol Fmoc-Ala-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0163] Take 10 mmol Fmoc-Leu-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0164] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use.

[0165] Take 10 mmol Fmoc-Phe-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 15 mmol Fmoc-Trp(Boc)-OH and 1 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 2.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 30 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Then wash twice with 40 mL methanol each time, twice with 40 mL DCM solution each time, and twice with 40 mL methanol each time. Vacuum drying yielded a peptide resin of H-AA1-AA2-AA3-AA4-AA5-AA6-Linker-AM, wherein AA1 is Trp(Boc); AA2 is Phe; AA3 is Arg; AA4 is D-Leu; AA5 is Ala; and AA6 is His(Trt).

[0166] The above peptide resin was cut with 110 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 1000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-Trp-Phe-Arg-Leu-Ala-His-NH2 was obtained. Its mass spectrometry and high performance liquid chromatography characterization results are as follows. Figure 86 and Figure 87 As shown.

[0167] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-Trp-Phe-Arg-Leu-Ala-His-NH2.TFA, add 10mL of DMSO and stir to dissolve. Add 1.28g of DIEA, stir for 5 minutes, then add 3.75g of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid and allow the reaction to rearrange for 2 hours at a constant temperature. LC-MS analysis again shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: B2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 88 and Figure 89 As shown; B4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 90 and Figure 91 As shown; B6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 92 and Figure 93 As shown.

[0168] Example 29: A method for synthesizing H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0169] Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step: add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0170] Take 10 mmol Fmoc-Glu(otBu)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 10 mmol Fmoc-Glu(otBu)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 10 mmol Fmoc-D-Met-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use.

[0171] Take 10 mmol Fmoc-Gln(Trt)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0172] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0173] Take 15 mmol Fmoc-Arg(Pbf)-OH and 15 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 20 mL DMF solution and 2.3 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with DMF solution, 20 mL each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with DMF solution, 40 mL each time, and dry. Then wash twice with methanol, 40 mL each time, twice with DCM solution, 40 mL each time, and twice with methanol, 40 mL each time. Vacuum drying yields H-AA1-AA2-AA3-AA4-AA5-AA6-Linker-AM peptide resin, wherein AA1 is Arg(Pbf); AA2 is Arg(Pbf); AA3 is Gln(Trt); AA4 is D-Met; AA5 is Glu(otBu); and AA6 is Glu(otBu).

[0174] The above peptide resin was cut with 110 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 1000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2 was obtained. Its mass spectrometry and high performance liquid chromatography characterization results are as follows. Figure 94 and Figure 95 As shown.

[0175] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-Arg-Arg-Gln-D-Met-Glu-Glu-NH2.TFA, add 10mL of DMSO and stir to dissolve. Add 1.25g of DIEA, stir for 5 minutes, then add 3.67g of hyaluronic acid. Maintain the temperature in a water bath at 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid and allow the reaction to rearrange for 2 hours at a constant temperature. LC-MS analysis again shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: G2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 96 and Figure 97 As shown; G4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 98 and Figure 99 As shown; G6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 100 and Figure 101 As shown.

[0176] Example 30: A method for synthesizing H-Arg-Arg-Gln-Met-Glu-Glu-NH2, comprising: Place 5 mmol AM resin in a 100 mL solid-phase synthesis reactor, add 30 mL of 20% Pip / DMF (v / v) solution, stir for 30 min, filter to remove the deprotection solution, then wash 6 times with 30 mL of DMF solution each time, and dry for later use.

[0177] Take 10 mmol Fmoc-Linker and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step: add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0178] Take 10 mmol Fmoc-Glu(otBu)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 10 mmol Fmoc-Glu(otBu)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use. Take 10 mmol Fmoc-Met-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 40 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 40 mL DMF solution each time, and dry for later use.

[0179] Take 10 mmol Fmoc-Gln(Trt)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 1.5 mL DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0180] Take 10 mmol Fmoc-Arg(Pbf)-OH and 10 mmol HOBt in a 100 mL beaker, cool to 5 °C, add 15 mL DMF solution and 10 mmol DIC, let stand for 15 min, then add the solution from the 100 mL beaker to the 100 mL solid-phase synthesis reactor mentioned above, stir and react for 1.5 h until the reaction is complete. Wash the resin three times with 20 mL DMF solution each time. After washing, proceed to the next step of the reaction. Add 30 mL of 20% Pip / DMF (v / v) solution, stir and react for 30 min, filter to remove the deprotection solution, then wash six times with 30 mL DMF solution each time, and dry for later use.

[0181] 15 mmol Fmoc-Arg(Pbf)-OH and 15 mmol HOBt were placed in a 100 mL beaker and cooled to 5 °C. 20 mL of DMF solution and 2.3 mL of DIC were added, and the mixture was allowed to stand for 15 min. The solution from the 100 mL beaker was then added to the 100 mL solid-phase synthesis reactor described above, and the mixture was stirred for 1.5 h until the reaction was complete. The resin was washed three times with 20 mL of DMF solution each time. After washing, the next step of the reaction was carried out. 40 mL of 20% Pip / DMF (v / v) solution was added, and the mixture was stirred for 30 min. The mixture was filtered to remove the deprotection solution, and then washed six times with 40 mL of DMF solution and dried. The resin was then washed twice with 40 mL of methanol, twice with 40 mL of DCM solution, and twice with 40 mL of methanol. Vacuum drying yields H-AA1-AA2-AA3-AA4-AA5-AA6-Linker-AM peptide resin, wherein AA1 is Arg(Pbf); AA2 is Arg(Pbf); AA3 is Gln(Trt); AA4 is Met; AA5 is Glu(otBu); and AA6 is Glu(otBu).

[0182] The above peptide resin was cut with 110 mL of TFA / anisole / phenol / H2O / EDT (the mass ratio of TFA, anisole, phenol, H2O and EDT was 87.5:5:2.5:2.5:2.5) for 2.5 h. The cutting solution was added to 1000 mL of diethyl ether (5℃) solution, and a white solid precipitated. After centrifugation and vacuum drying, H-Arg-Arg-Gln-Met-Glu-Glu-NH2 was obtained. Its mass spectrometry and high performance liquid chromatography characterization results are as follows. Figure 102 and Figure 103 As shown.

[0183] The synthetic route for a hyaluronic acid-modified cosmetic peptide is as follows: ; Wherein, -COOX is -COONa; A method for preparing hyaluronic acid-modified cosmetic peptides includes the following steps: Weigh 1g of H-Arg-Arg-Gln-Met-Glu-Glu-NH2.TFA, add 10mL of DMSO and stir to dissolve. Add 1.25g of DIEA, stir for 5 minutes, then add 3.67g of hyaluronic acid. Maintain a water bath temperature of 45℃ and stir overnight. LC-MS analysis shows the reaction is essentially complete. Add 8mL of acetic acid and allow the reaction to rearrange for 2 hours at a constant temperature. LC-MS analysis again shows the reaction is essentially complete. Then, perform reverse chromatography purification under the following conditions: Dissolution: Take 0.2g of crude product and dilute with 100mL of H2O; Packing material: 21.2*250mm, 10-120, C18; Flow rate: 10mL / min; Wavelength: 220nm; Mobile phase: A: 1% HAc; B: ACN; Equilibration: A:B = 95:5, equilibration for 10 min, flow rate: 10 mL / min; Sample loading: Flow rate: 10 mL / min; Elution: 12-32% B for 60 min; Column cleaning: Clean with 80% ACN until baseline equilibrium is reached; Three types of hyaluronic acid-modified beauty peptides with different structures were obtained from the collected qualified products, as shown below: F2, its mass spectrometry and high-performance liquid chromatography characterization results are as follows Figure 104 and Figure 105 As shown; F4, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 106 and Figure 107 As shown; F6, its mass spectrometry and high-performance liquid chromatography characterization results are as follows: Figure 108 and Figure 109 As shown.

[0184] Example 31: A method for preparing a hyaluronic acid-modified cosmetic peptide includes the following steps: Weigh 0.56g of H-Phe-Val-Ala-Pro-Phe-Pro-OH.TFA (prepared in Example 8), add 6mL of DMSO and stir to dissolve. Add 0.75g of DIEA, then add 2.2g of hyaluronic acid (y=1). The mixture is stirred overnight at 45℃ in a water bath. The reaction is detected by LC-MS and is basically complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35℃ in a water bath for 3 hours. The reaction is detected by LC-MS and is basically complete. Then, reverse chromatography is performed to purify the hyaluronic acid-modified beauty peptide.

[0185] Example 32: A method for preparing a hyaluronic acid-modified cosmetic peptide includes the following steps: Weigh 0.56g of H-Phe-Val-Ala-Pro-Phe-Pro-OH.TFA (prepared in Example 8), add 6mL of DMSO and stir to dissolve. Add 0.75g of DIEA, then add 2.2g of hyaluronic acid (y=2). The mixture is stirred overnight in a water bath at 45℃. The reaction is then analyzed by LC-MS, and the reaction is basically complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35℃ in a water bath for 3 hours. The reaction is then analyzed by LC-MS, and the reaction is basically complete. Finally, reverse chromatography is performed to purify the hyaluronic acid-modified beauty peptide.

[0186] Example 33: A method for preparing a hyaluronic acid-modified cosmetic peptide includes the following steps: Weigh 0.56g of H-Phe-Val-Ala-Pro-Phe-Pro-OH.TFA (prepared in Example 8), add 6mL of DMSO and stir to dissolve. Add 0.75g of DIEA, then add 2.2g of hyaluronic acid (y=3). The mixture is stirred overnight in a water bath at 45℃. The reaction is then analyzed by LC-MS, and the reaction is basically complete. Add 4mL of acetic acid, and the mixture is subjected to a rearrangement reaction at 35℃ in a water bath for 3 hours. The reaction is then analyzed by LC-MS, and the reaction is basically complete. Finally, reverse chromatography is performed to purify the hyaluronic acid-modified beauty peptide.

[0187] Experimental Example 1: 1. Moisturizing performance test The AQP3 content test results are as follows: (1) Cell seeding: Seed cells into 24-well plates and incubate overnight in an incubator (37°C, 5% CO2); (2) Solution preparation: Prepare the working solution of the test substance according to the experimental design (as shown in Table 1); Table 1. AQP3 Experimental Design Table

[0188] (3) Add test substance: After culturing in an incubator (37℃, 5% CO2) for 24 h, add test substance according to the table and continue culturing for 24 h; (4) Sample collection: Discard the supernatant and rinse the cells with PBS 3 times; (5) Immunofluorescence staining: a. Fix cells with methanol, wash three times with PBS, and then block each well with 1 mL of BSA for 1 hour. b. Discard the blocking solution, add primary antibody to each well, and incubate overnight at 4°C. Discard the primary antibody and wash three times with PBS; c. Add secondary antibody to each well and incubate for 2 hours; discard the secondary antibody and wash 3 times with PBS; d. Add DAPI to each well for nuclear staining, incubate for 10 min, discard the DAPI, rinse 3 times with PBS, and then take pictures using a fluorescence microscope; (6) Results analysis: The fluorescence intensity of AQP3 was quantitatively analyzed using Image Pro Plus software.

[0189] The HA content was tested as follows: (1) Cell seeding: Seed cells into 24-well plates and incubate overnight in an incubator (37°C, 5% CO2); (2) Solution preparation: Prepare the working solution of the test substance according to the experimental design (Table 2); Table 2 HA Experimental Design Table

[0190] (3) Add test substance: After culturing in an incubator (37℃, 5% CO2) for 24h, add test substance according to the table and continue culturing for 24h; (4) Sample collection: Collect the supernatant and determine the HA content using an ELISA kit.

[0191] Results analysis: Table 3-1 AQP3 Test Results

[0192] Analysis of the data in Table 3-1 shows that the hyaluronic acid-modified beauty peptides prepared in the embodiments of the present invention have excellent moisturizing properties and can effectively increase the AQP3 content. Specifically, the hyaluronic acid-modified beauty peptides D4 and D6 prepared in Example 4 of the present invention have excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, when the three structures (D2, D4, and D6) of hyaluronic acid-modified beauty peptides are mixed in a certain mass ratio, they also exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The three hyaluronic acid-modified beauty peptides with structures (E2, E4, E6) prepared in Example 27 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Similarly, the three hyaluronic acid-modified beauty peptides with structures (B2, B4, B6) prepared in Example 28 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides with structures (G2, G4, G6) prepared in Example 29 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The three hyaluronic acid-modified beauty peptides (F2, F4, F6) with specific structures prepared in Example 30 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The hyaluronic acid-modified beauty peptides A4 and A6 prepared in Example 14 of this invention also exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides (A2, A4, A6) with specific structures, when mixed in a certain mass ratio, also exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL.

[0193] Table 3-2 AQP3 Test Results

[0194] Analysis of the data in Table 3-2 shows that the hyaluronic acid-modified beauty peptides prepared in the embodiments of the present invention exhibit excellent promoting effects on AQP3, with even better effects on increasing its content. Specifically, the hyaluronic acid-modified beauty peptides prepared in Examples 1-2, 5-7, and 10-13 of the present invention have excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides with structures (D2, D4, D6) prepared in Example 4 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; the three hyaluronic acid-modified beauty peptides with structures (H2, H4, H6) prepared in Example 8 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; and the three hyaluronic acid-modified beauty peptides with structures (L2, L4, L6) prepared in Example 9 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL.

[0195] Table 4 HA Test Results

[0196] Analysis of the data in Table 4 shows that the hyaluronic acid-modified beauty peptides prepared in Examples 2 and 8 of this invention exhibit excellent promoting effects on HA, with a particularly good effect on increasing its content. Specifically, the hyaluronic acid-modified beauty peptides prepared in Example 2 of this invention have excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides with structures (H2, H4, H6) prepared in Example 8 of this invention, when mixed in a certain mass ratio, exhibit excellent moisturizing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL.

[0197] 2. Anti-wrinkle and firming performance test The content of type I collagen and MMP-1 was tested as follows: (1) Cell seeding: Seed cells into 24-well plates and incubate overnight in an incubator (37°C, 5% CO2); (2) Solution preparation: Prepare the working solution of the test substance according to the experimental design (Table 5); Table 5 Experimental Design Table

[0198] (3) UVA radiation: After 24 hours of incubation, the total dose received by the negative control group, positive control group, and sample group was 9 J / cm². 2 The control group was placed under UVA radiation, while the blank control group was placed in the same environment (UVA radiation dose of 0 J / cm²). 2 ); (4) Adding test substances: According to the experimental design, after irradiation, test substances were added to each well in groups. 1 mL of cell culture medium was added to each well of the blank control group and negative control group; 1 mL of cell culture medium containing vitamin C and vitamin E was added to each well of the positive control group; 1 mL of culture medium containing the corresponding concentration of test substances was added to each well of the sample group; after adding the test substances, the 24-well plate was placed in an incubator (37℃, 5% CO2) and incubated for 24 h. (5) Collect the supernatant for determination of type I collagen and MMP-1 content; (6) Results analysis: The comparison between groups was performed using t-test statistical analysis, and all statistical analyses were two-tailed.

[0199] Table 6 MMP-1 Test Results

[0200] Table 7-1 Results of Type I Collagen Test

[0201] Analysis of the data in Tables 6 and 7-1 shows that the hyaluronic acid-modified cosmetic peptides prepared in the embodiments of the present invention exhibit excellent inhibitory effects on MMP-1 and excellent promoting effects on Collagen I. Specifically, the hyaluronic acid-modified cosmetic peptides D4 and D6 prepared in Example 4 of the present invention have excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, when the three structures (D2, D4, and D6) of the hyaluronic acid-modified cosmetic peptides are mixed in a certain mass ratio, they also exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The three hyaluronic acid-modified beauty peptides with structures (E2, E4, E6) prepared in Example 27 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Similarly, the three hyaluronic acid-modified beauty peptides with structures (B2, B4, B6) prepared in Example 28 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides with structures (G2, G4, G6) prepared in Example 29 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The three hyaluronic acid-modified cosmetic peptides (F2, F4, F6) with specific structures prepared in Example 30 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The hyaluronic acid-modified cosmetic peptides A4 and A6 prepared in Example 14 of this invention also exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified cosmetic peptides (A2, A4, A6) with specific structures, when mixed in a certain mass ratio, also exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL.

[0202] Table 7-2 Results of Type I Collagen Test

[0203] Analysis of the data in Table 7-2 shows that the hyaluronic acid-modified cosmetic peptides prepared in Examples 1-2, 5-7 and 10-13 of this invention have excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL and 0.25 mg / mL. Furthermore, the three hyaluronic acid-modified beauty peptides with structures (D2, D4, D6) prepared in Example 4 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; the three hyaluronic acid-modified beauty peptides with structures (H2, H4, H6) prepared in Example 8 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; and the three hyaluronic acid-modified beauty peptides with structures (L2, L4, L6) prepared in Example 9 of this invention, when mixed in a certain mass ratio, exhibit excellent anti-wrinkle and firming effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL.

[0204] 3. Soothing performance test IL-6 content test (1) Cell seeding: Seed cells into 24-well plates and incubate overnight in an incubator (37°C, 5% CO2); (2) Solution preparation: Prepare the working solution of the test substance according to the experimental design (as shown in Table 8); Table 8 Experimental Design for IL-6 Synthesis

[0205] (3) Add test substance: According to the experimental group, when the cell plating rate in the 24-well plate reaches 40%~60%, add test substance to the group. Each group has 3 replicates. Place the 24-well plate in an incubator (37℃, 5% CO2) for 24 h. (4) Detection: After 24 hours of incubation, the supernatant was collected and the IL-6 content was determined using an ELISA kit.

[0206] Table 9. Results of Soothing Performance Tests

[0207] Analysis of the data in Table 9 shows that the hyaluronic acid-modified beauty peptide prepared in Example 2 of this invention has a soothing effect at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; the hyaluronic acid-modified beauty peptide prepared in Example 5 of this invention has a soothing effect at a concentration of 0.063 mg / mL; the hyaluronic acid-modified beauty peptide prepared in Example 6 of this invention has a soothing effect at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; the hyaluronic acid-modified beauty peptide prepared in Example 7 of this invention has a soothing effect at a concentration of 0.125 mg / mL; and the three structures of hyaluronic acid-modified beauty peptides prepared in Example 9 of this invention... Hyaluronic acid-modified beauty peptides, mixed in a certain mass ratio, exhibit soothing effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL. The hyaluronic acid-modified beauty peptides prepared in Example 10 of this invention exhibit soothing effects at a concentration of 0.063 mg / mL. The hyaluronic acid-modified beauty peptides prepared in Example 13 of this invention exhibit soothing effects at a concentration of 0.125 mg / mL. The hyaluronic acid-modified beauty peptides prepared in Example 11 of this invention exhibit soothing effects at concentrations of 0.063 mg / mL and 0.125 mg / mL. The hyaluronic acid-modified beauty peptides prepared in Example 12 of this invention exhibit soothing effects at concentrations of 0.063 mg / mL and 0.25 mg / mL.

[0208] 4. Whitening performance test The melanin content was tested as follows: Table 10 Experimental Design for Melanin Content

[0209] Logarithmic growth phase cells were collected and seeded into 24-well plates. After culturing in an incubator (37℃, 5% CO2) for 24 h, the test substance was added according to the table based on the cytotoxicity results. Untreated cells were used as blank controls. Three replicates were set up for each group.

[0210] After adding the drug, the cells were cultured in an incubator (37℃, 5% CO2) for 24 hours. The supernatant was discarded, and 0.5 mL of 1M NaOH containing 10% DMSO was added. The cells were incubated at 80℃ for 1 hour. The 1M NaOH containing 10% DMSO was used as a solvent control. The absorbance value was read under an ELISA reader and the relative inhibition rate of melanin in the cells was calculated.

[0211]

[0212] Table 11 Whitening Performance Test Results

[0213] Analysis of the data in Table 11 shows that the hyaluronic acid-modified beauty peptides prepared in Example 7 of this invention have excellent whitening effects at concentrations of 0.063 mg / mL, 0.125 mg / mL, and 0.25 mg / mL; and the whitening effects at concentrations of 0.125 mg / mL and 0.25 mg / mL are comparable to or higher than those of the positive control group.

[0214] 5. Anti-glycation performance test A mixed solution containing bovine serum albumin and glucose was prepared using PBS and filtered through a 0.22 μm filter membrane to serve as the 2× glycation reaction solution. The reaction systems for each group were prepared according to the table.

[0215] Table 12 AGEs Removal Test Reaction System

[0216] After thorough mixing, the mixture was incubated at 55°C for 4 days. PBS was used as a negative control instead of the sample, aminoguanidine hydrochloride (100 mg / mL) as a positive control, and PBS was used instead of the glycosylation reaction solution as a control system. After the reaction, the incubated solution was cooled to room temperature, centrifuged at 2000 rpm for 5 min, and the supernatant was filtered through a 0.22 μm filter. 200 μL of the reaction solution was then added to each well of a 96-well plate, and the AGEs inhibition rate was calculated using a fluorescence microplate reader at an excitation wavelength of 320 nm and an emission wavelength of 460 nm, according to the following formula.

[0217]

[0218] In the formula: A - Fluorescence intensity of the saccharification system with added test substance; B - Fluorescence intensity of the PBS solution containing the test substance; C - Fluorescence intensity of the saccharified system without the addition of the test substance; D - Fluorescence intensity of PBS solution without added test substance.

[0219] Table 13 Results of Anti-glycation Performance Tests

[0220] Analysis of the data in Table 13 shows that the hyaluronic acid-modified cosmetic peptide prepared in Example 11 of this invention has a scavenging effect on advanced glycation end products at concentrations of 0.0625 mg / mL and 0.25 mg / mL.

[0221] 6. Antioxidant performance test The ROS content test results are as follows: (1) Cell seeding: Seed cells into 24-well plates and incubate overnight in an incubator (37°C, 5% CO2); (2) Solution preparation: Prepare the working solution of the test substance according to the experimental design (Table 13).

[0222] Table 14 ROS Experimental Design Table

[0223] (3) Add test substance: After culturing in an incubator (37℃, 5% CO2) for 24h, add test substance according to the table and continue culturing for 24h; (4) Modeling: Wash twice with PBS, use untreated cells as blank control, and the remaining groups are stimulated with UVB according to the conditions in the table, with the VC+VE group as positive control. (5) ROS content detection: The DCFH-DA probe stock solution was diluted with serum-free culture medium. 500 μL of the diluted DCFH-DA probe was added to each well and incubated in a cell culture incubator at 37℃. After 30 min, the cells were washed three times with serum-free DMEM culture medium to thoroughly remove probes that had not entered the cells. The cells were observed and photographed using a fluorescence microscope at an excitation wavelength of 488 nm.

[0224] (6) Results analysis: The ROS fluorescence intensity was quantitatively analyzed using Image Pro Plus software.

[0225] Table 15 Antioxidant Performance Test Results

[0226] Analysis of the data in Table 15 shows that the hyaluronic acid-modified beauty peptide prepared in Example 11 of this invention has better antioxidant capacity at concentrations of 0.125 mg / mL and 0.25 mg / mL, and its antioxidant capacity at a concentration of 0.25 mg / mL is comparable to that of the positive control.

[0227] The conventional techniques described in the above embodiments are existing technologies known to those skilled in the art, and therefore will not be described in detail here.

[0228] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A hyaluronic acid-modified cosmetic peptide, wherein the structural formula of the hyaluronic acid-modified cosmetic peptide is shown in Formula (I): MC (I); in, M represents sodium hyaluronate, whose structure is shown in formula (II): (II), where y is a natural number ≥ 1; C represents beauty peptides, which include polypeptides or their derivatives that have beauty and / or skin care effects, and the polypeptides include nonapeptides; In this structure, the M-terminal glucuronic acid linkes the amino group in the X structure.

2. The hyaluronic acid-modified cosmetic peptide according to claim 1, characterized in that: The compound represented by formula (I) includes the structure shown in formula (III): (III); in, n is a natural number; R is the remaining part of the cosmetic peptide structure after removing the reactive amino group; The beauty peptides include polypeptides or their derivatives that have beauty and / or skincare effects, and the polypeptides include dipeptides and nonapeptides.

3. The hyaluronic acid-modified cosmetic peptide according to claim 1 or 2, characterized in that: The nonapeptide or its derivatives include nonapeptide-1.

4. A method for preparing the hyaluronic acid-modified cosmetic peptide according to claim 1 or 2, comprising: Hyaluronic acid-modified beauty peptides were prepared by reacting sodium hyaluronate with beauty peptides via a ring-opening reaction.

5. The method for preparing hyaluronic acid-modified cosmetic peptides according to claim 4, characterized in that: The molar ratio of the beauty peptide to sodium hyaluronate is 1:2-8.

6. Use of the hyaluronic acid-modified cosmetic peptide obtained by the preparation method of claim 4 in the preparation of cosmetics and / or skin care products.

7. The use of the hyaluronic acid-modified cosmetic peptides obtained by the preparation method of claim 4 in enhancing the moisturizing, firming, anti-wrinkle, or anti-aging properties of cosmetics and / or skincare products.

8. The use of the hyaluronic acid-modified cosmetic peptides obtained by the preparation method of claim 4 in enhancing the soothing, antioxidant, or whitening properties of cosmetics and / or skincare products.

9. A cosmetic product comprising the hyaluronic acid-modified beauty peptide of claim 1.

Images