A short peptide compound and its preparation method, cosmetic composition and application

Abstract

The present invention relates to a short peptide compound and a preparation method thereof, a cosmetic composition and an application thereof. The amino acid sequence of the short peptide compound of the present invention is X-RSPMWKYS-OH, wherein X is CH3CO or CF3CO. The short peptide compound provided by the present invention is prepared into a short peptide chain by using a peptide segment containing amino acids with anti-aging and repair effects such as serine, tyrosine, proline, arginine and lysine, and then the N-terminus of the short peptide chain is functionalized with acetyl or trifluoroacetyl, thereby changing the chemical spatial structure of the short peptide chain and the fat solubility when passing through a biological membrane, and preparing a short peptide compound one and a short peptide compound two, and the obtained short peptide compound one and short peptide compound two respectively have significant anti-inflammatory and repair effects. At the same time, a mild Fmoc route is adopted in the preparation method, and the condensation reaction time of each step is short, which shortens the production cycle, and the raw material source is convenient, the process is stable, the quality is controllable, the product yield and purity are high, and large-scale production can be achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of skin care product raw materials, in particular to a group of short peptide compounds and a preparation method, a cosmetic composition and application thereof. Background Art

[0002] Short peptides are compounds formed by the condensation reaction of two to ten amino acids through intermolecular carboxyl and amino groups, in which the group linking two amino acids is called a "peptide bond". The biological activity of short peptide compounds is mainly affected by their amino acid sequence, amino acid residue active groups and their spatial structure, and they show great prospects in the fields of bioengineering, medicine and materials.

[0003] Short peptide compounds have the characteristics of low sensitization, high biological activity and easy absorption. Because they are widely used in the cosmetics industry, they can effectively improve and repair skin problems, such as anti-aging, promoting skin repair and enhancing skin elasticity, soothing problematic skin and whitening anti-oxidation, etc. According to the interaction mode between peptides and protein receptors widely present in the skin, they can be roughly divided into several types such as signal peptides, neurotransmitter inhibitory peptides, carrier peptides, enzyme inhibitory peptides, etc. In addition, some specific types of peptide compounds, such as antibacterial peptides and hydrolyzed protein peptides, are also widely concerned for the development of acne, anti-dandruff and oral products.

[0004] The core work of functional peptide raw material research and development is to screen and optimize the amino acid sequence through reasonable structural design. With the development of scientific research and technology, peptide active ingredients have gradually replaced many traditional ingredients and even some medical beauty methods. For example, through scientific formula and complementary effects, some innovative peptide products have performed well in improving the moisture content of the stratum corneum, anti-inflammatory and anti-acne, and surface skin barrier repair. This also provides more options for the development and application of functional skin care products. Summary of the invention

[0005] In view of the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a short peptide compound and a preparation method thereof, a cosmetic composition and application thereof, aiming to provide a short peptide compound that can be used in cosmetic products, wherein the short peptide compound contains a peptide segment of amino acids with anti-aging and repair effects, and the N-terminus of the short peptide chain is functionalized with acetylation or trifluoroacetyl, thereby changing the chemical spatial structure of the peptide chain and the fat solubility when passing through the biological membrane, so that the obtained short peptide compound has significant anti-inflammatory and repair effects, thereby solving the problem in the prior art that there is a lack of ideal functional peptide raw materials for the development and application of cosmetic products.

[0006] The technical solution of the present invention is as follows:

[0007] In the first aspect of the present invention, the amino acid sequence of the short peptide compound is X-RSPMWKYS-OH, wherein X is CH3CO or CF3CO;

[0008] When X is CH3CO, the short peptide compound is a short peptide compound 1 having the structural formula (I):

[0009]

[0010] When X is CF3CO, the short peptide compound has the structural formula (II) of the short peptide compound 2:

[0011]

[0012]

[0013] The second aspect of the present invention provides a method for preparing the short peptide compound, comprising the steps of:

[0014] (1) The first solid phase resin L-Ser(tBu)-CTC Resin is prepared mainly using 2-chlorotrityl chloride resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine;

[0015] (2) mainly using the first solid phase resin L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine to prepare the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin;

[0016] (3) The third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly by using the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl;

[0017] (4) mainly using the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan to prepare the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin;

[0018] (5) preparing the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTCResin and N-(9-fluorenylmethoxycarbonyl)-L-methionine;

[0019] (6) preparing the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-proline;

[0020] (7) The seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly using the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine;

[0021] (8) The eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly using the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl);

[0022] (9) adding 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and acetic acid to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and reacting for 2-3 hours, washing and drying the reaction product to obtain a ninth solid phase resin, and then cleaving the ninth solid phase resin with a cleavage solution, rotary evaporating to obtain a reaction residue, then precipitating the reaction residue with isopropyl ether, and finally separating and purifying to obtain the short peptide compound one;

[0023] Alternatively, 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and trifluoroacetic acid are added to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin to react for 2-3 hours, the reaction product is washed and dried to obtain a ninth solid phase resin, and then the ninth solid phase resin is cracked with a cracking solution and rotary evaporated to obtain a reaction residue, and then the reaction residue is precipitated with isopropyl ether, and finally separated and purified to obtain the short peptide compound two.

[0024] The third aspect of the present invention provides a cosmetic composition, comprising the short peptide compound and a carrier acceptable to cosmetic products, wherein the carrier acceptable to cosmetic products comprises one or more of water, glycerin, alcohols, vegetable oils, and vaseline.

[0025] The fourth aspect of the present invention provides a use of the cosmetic composition in cosmetic products.

[0026] It should be noted that the beauty products include skin care products and cosmetics.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The short peptide compound provided by the present invention is prepared by using a peptide segment containing amino acids such as serine (Ser), tyrosine (Tyr), proline (Pro), arginine (Arg) and lysine (Lys) with anti-aging and repair effects to form a short peptide chain, and then the N-terminus of the short peptide chain is functionalized with acetylation or trifluoroacetyl, thereby changing the chemical spatial structure of the short peptide chain and the fat solubility when passing through the biological membrane, and preparing a short peptide compound one and a short peptide compound two, and the obtained short peptide compound one and short peptide compound two have significant anti-inflammatory and repair effects respectively. At the same time, the preparation method adopts a mild Fmoc route, the condensation reaction time of each step is short, the production cycle is shortened, and the raw material source is convenient, the process is stable, the quality is controllable, the product yield and purity are high, and large-scale production can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the mass spectrum of the short peptide compound 1 prepared in Example 1 of the present invention.

[0030] Figure 2 This is the mass spectrum of the short peptide compound 2 prepared in Example 2 of the present invention.

[0031] Figure 3 This is a high performance liquid chromatography (HPLC) detection spectrum of the short peptide compound 1 prepared in Example 1 of the present invention.

[0032] Figure 4 This is a high performance liquid chromatography (HPLC) detection spectrum of the short peptide compound 2 prepared in Example 2 of the present invention.

[0033] Figure 5 This is a graph showing the effect of the short peptide compound 1 prepared in Example 1 of the present invention on cell proliferation in a RAW264.7 cell toxicity test.

[0034] Figure 6 This is a graph showing the effect of the short peptide compound 2 prepared in Example 2 of the present invention on cell proliferation in a HaCaT cell toxicity test.

[0035] Figure 7 The gene expression of interleukin 6 (IL-6) in the RAW264.7 cell anti-inflammatory test of the short peptide compound 1 prepared in Example 1 of the present invention.

[0036] Figure 8 The gene expression of tumor necrosis factor α (TNF-α) in the RAW264.7 cell anti-inflammatory test of the short peptide compound 1 prepared in Example 1 of the present invention.

[0037] Fig. 9The gene expression of interleukin 1β (IL-1β) in the RAW264.7 cell anti-inflammatory test of the short peptide compound 1 prepared in Example 1 of the present invention.

[0038] Fig.10 The gene expression of aquaporin 3 (AQP3) in the HaCaT cell repair test of the short peptide compound 2 prepared in Example 2 of the present invention.

[0039] Fig.11 This is the gene expression of hyaluronan synthase 3 (HAS3) in the HaCaT cell repair experiment of the short peptide compound 2 prepared in Example 2 of the present invention.

[0040] Fig.12 The gene expression of keratin 1 (KRT-1) in the cell repair experiment of HaCaT cells by the short peptide compound 2 prepared in Example 2 of the present invention.

[0041] Fig.13 The gene expression of keratin 14 (KRT-14) in the cell repair experiment of HaCaT cells by the short peptide compound 2 prepared in Example 2 of the present invention. DETAILED DESCRIPTION

[0042] The present invention provides a short peptide compound and a preparation method thereof, a cosmetic composition and application. To make the purpose, technical solution and effect of the present invention clearer and more specific, the present invention is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0043] Unless otherwise defined, all technical terms and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0044] The following describes it in detail through specific embodiments.

[0045] The embodiment of the present invention provides a short peptide compound, wherein the amino acid sequence is X-RSPMWKYS-OH, wherein X is CH3CO or CF3CO;

[0046] When X is CH3CO, the short peptide compound is a short peptide compound 1 having the structural formula (I):

[0047]

[0048] When X is CF3CO, the short peptide compound has the structural formula (II) of the short peptide compound 2:

[0049] .

[0051] The short peptide compound provided by the present invention is prepared into a short peptide chain by using a peptide segment containing amino acids such as serine (Ser), tyrosine (Tyr), proline (Pro), arginine (Arg) and lysine (Lys) with anti-aging and repair effects, and then the N-terminus of the short peptide chain is functionalized with acetylation or trifluoroacetyl, thereby changing the chemical spatial structure of the short peptide chain and the fat solubility when passing through the biological membrane, to prepare a short peptide compound one and a short peptide compound two, and the obtained short peptide compound one and short peptide compound two have significant anti-inflammatory and repair effects, respectively.

[0052] The present invention also provides a method for preparing a short peptide compound, comprising the steps of:

[0053] (1) The first solid phase resin L-Ser(tBu)-CTC Resin is prepared mainly using 2-chlorotrityl chloride resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine;

[0054] (2) mainly using the first solid phase resin L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine to prepare the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin;

[0055] (3) The third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly by using the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl;

[0056] (4) mainly using the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan to prepare the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin;

[0057] (5) preparing the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTCResin and N-(9-fluorenylmethoxycarbonyl)-L-methionine;

[0058] (6) preparing the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-proline;

[0059] (7) The seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly using the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine;

[0060] (8) The eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly using the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl);

[0061] (9) adding 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and acetic acid to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and reacting for 2-3 hours, washing and drying the reaction product to obtain a ninth solid phase resin, and then cleaving the ninth solid phase resin with a cleavage solution, rotary evaporating to obtain a reaction residue, then precipitating the reaction residue with isopropyl ether, and finally separating and purifying to obtain the short peptide compound one;

[0062] Alternatively, 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and trifluoroacetic acid are added to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin to react for 2-3 hours, the reaction product is washed and dried to obtain a ninth solid phase resin, and then the ninth solid phase resin is cracked with a cracking solution and rotary evaporated to obtain a reaction residue, and then the reaction residue is precipitated with isopropyl ether, and finally separated and purified to obtain the short peptide compound two.

[0063] In a specific embodiment, step (1) specifically comprises: adding 2-chlorotrityl chloride resin (CTC resin) into a reactor, and then adding N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine (English name Fmoc-L-Ser(tBu)-OH) and N-methylmorpholine in dimethylformamide to react; then adding methanol, and after the reaction is complete, removing Fmoc, and then solid-liquid separation to obtain the first solid phase resin L-Ser(tBu)-CTC Resin.

[0064] It should be noted here that before N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine is added to the reactor, the CTC Resin needs to be swollen. Specifically, the reaction liquid DCM can be added for swelling, and the reaction liquid is drained after swelling.

[0065] It should be noted that before removing Fmoc with a piperidine-dimethylformamide solution, the solid phase resin was first swollen with DCM, and the reaction solution was drained after 30 minutes.

[0066] In a specific embodiment, step (2) specifically includes: adding N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine (English name Fmoc-L-Tyr(tBu)-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide in dimethylformamide solution to a reactor containing the first solid phase resin L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0067] In a specific embodiment, step (3) specifically comprises: adding a dimethylformamide solution of 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl (English name Fmoc-L-Lys(Boc)-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide into a reactor containing the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0068] In a specific embodiment, step (4) specifically comprises: adding a dimethylformamide solution of N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan (English name Fmoc-L-Trp(Boc)-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing a third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, reacting, removing Fmoc, and then performing solid-liquid separation to obtain a fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0069] In a specific embodiment, step (5) specifically comprises: adding a dimethylformamide solution of N-(9-fluorenylmethoxycarbonyl)-L-methionine (English name: Fmoc-L-Met-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing a fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain a fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0070] In a specific embodiment, step (6) specifically comprises: adding a dimethylformamide solution of 9-fluorenylmethoxycarbonyl-L-proline (English name: Fmoc-L-Pro-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0071] In a specific embodiment, step (7) specifically comprises: adding a dimethylformamide solution of N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine (English name: Fmoc-L-Ser(tBu)-OH), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0072] In a specific embodiment, step (8) specifically comprises: adding a seventh solid phase resin containing L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin reactor was added with 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) (English name Fmoc-L-Arg(Pbf)-OH), 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide in dimethylformamide solution. After the reaction was completed, Fmoc removal was performed, followed by solid-liquid separation to obtain the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin.

[0073] In a specific embodiment, in steps (1)-(8), Fmoc removal is carried out using a dimethylformamide solution of piperidine, wherein the mass concentration of piperidine in the dimethylformamide solution is 10-20 wt %, and the Fmoc protecting group can be completely removed.

[0074] In a specific embodiment, in steps (1) to (8), the solid-liquid separation step comprises: separating the solid phase material by suction filtration, and then washing the solid phase resin obtained in each step with dimethylformamide, methanol and dichloromethane one or more times, preferably 2-3 times.

[0075] In a specific embodiment, the molar ratio of N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine, N-methylmorpholine and 2-chlorotrityl chloride resin in step (1) is 2:5:1; the molar ratio of the amino acid with a protective group, 1-hydroxybenzotriazole, N,N'-diisopropylcarbodiimide and the solid phase resin used in each step in steps (2) to (8) is 2:2:2:1; the amino acid with a protective group in each step in steps (2) to (8) is N -(9-Fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine, 9-Fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl, N-(9-Fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan, N-(9-Fluorenylmethoxycarbonyl)-L-methionine, 9-Fluorenylmethoxycarbonyl-L-proline, N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine and 9-Fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl).

[0076] In a specific embodiment, in step (9), the molar ratio of acetic acid or trifluoroacetic acid, 1-hydroxybenzotriazole, N,N'-diisopropylcarbodiimide and the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin is (1.8-2.5):(1.8-2.5):(1.8-2.5):1, and the reaction can be completed.

[0077] In a specific embodiment, in step (9), the lysis solution is trifluoroacetic acid lysis solution, the mass volume ratio of the ninth solid phase resin to the lysis solution is 1 g:20 mL, and the lysis time is 2-3 h.

[0078] An embodiment of the present invention further provides a cosmetic composition, comprising the short peptide compound and a carrier acceptable for cosmetic products, wherein the carrier acceptable for cosmetic products comprises one or more of water, glycerin, alcohols, vegetable oils, and vaseline.

[0079] In a specific embodiment, it is experimentally determined that the anti-inflammatory concentration of the short peptide compound 1 in the cosmetic composition is 50-2000 ppm.

[0080] In a specific embodiment, it is experimentally determined that the moisturizing (barrier repair) effective concentration of the short peptide compound II in the cosmetic composition is 50-200 ppm.

[0081] The reagent materials used in the following examples include:

[0082] 2-Chlorotrityl chloride resin (English name: CTC resin), N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine (English name: Fmoc-L-Ser(tBu)-OH), N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine (English name: Fmoc-L-Tyr(tBu)-OH), 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl (English name: Fmoc-L-Lys(Boc)-OH), N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan (English name: Fmoc-L-Trp(Boc)-OH), N-(9-fluorenylmethoxycarbonyl)- L-methionine (English name: Fmoc-L-Met-OH), 9-fluorenylmethoxycarbonyl-L-proline (English name: Fmoc-L-Pro-OH), 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) (English name: Fmoc-L-Arg(Pbf)-OH), 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl, N-methylmorpholine, methanol, acetic acid (abbreviated as AcOH), trifluoroacetic acid (abbreviated as TFA), 1-hydroxybenzotriazole (abbreviated as HOBT), N,N'-diisopropylcarbodiimide (abbreviated as DIC) and piperidine.

[0083] Also included are solvents: N,N-dimethylformamide (DMF), dichloromethane (DCM), trifluoroacetic acid (TFA), methanol (MeOH), acetonitrile (ACN), and glacial isopropyl ether.

[0084] The above materials are all commercially available.

[0085] Example 1

[0086] The specific operation process for the preparation of short peptide compounds is as follows:

[0087] (1) Weigh CTC Resin (12 g, 20.16 mmol, 1.0 equivalent) with a loading of 1.68 mmol / g and add it to the reactor, then add DCM (150 mL) for swelling, and drain the reaction solution after 30 minutes. Dissolve Fmoc-L-Ser(tBu)-OH (15.46 g, 40.32 mmol, 2.0 equivalent) and N-methylmorpholine (10.20 g, 100.80 mmol, 5.0 equivalent) in DMF (150 mL) and add them to the reactor, and react for about 4 hours. Add anhydrous MeOH (10 mL) to block the unreacted CTC Resin, and react for about 1 hour. Take a small amount of resin for ninhydrin test, the result is negative, indicating that the reaction is complete. After stopping the reaction, the obtained resin was washed once with DMF (150 mL), each time for 2 min; washed once with DCM (150 mL), each time for 2 min; washed once with MeOH (150 mL), each time for 2 min; the obtained solid resin was transferred to a vacuum constant temperature drying oven at 40°C and dried overnight. The newly generated Fmoc-L-Ser(tBu)-CTC Resin was calculated to have a loading degree of 1 mmol / g (12 mmol, resin loading rate 60%). DCM (150 mL) was added to the reactor for swelling, and the reaction liquid was drained after 30 min. The Fmoc protecting group was removed with 20% piperidine-DMF solution (150 mL), and the reaction was carried out for about 30 min. A small amount of resin was taken for ninhydrin detection, and the result was positive, indicating that the reaction was complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 min, and the solid-liquid separation was performed to obtain the first solid phase resin L-Ser(tBu)-CTC Resin (12 mmol).

[0088] (2) Add Fmoc-L-Tyr(tBu)-OH (11.02 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Ser(tBu)-CTC Resin (12 mmol). React for 2–3 h. Take a small amount of resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL of DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. Take a small amount of resin for ninhydrin test. The result is positive, indicating that the reaction is complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes, and the solid-liquid separation was performed to obtain the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol).

[0089] (3) Add Fmoc-L-Lys(Boc)-OH (11.24 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol) and react for 2–3 h. Take a small amount of the resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL of DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. Take a small amount of the resin for ninhydrin test. The result is positive, indicating that the reaction is complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes, and the solid-liquid separation was performed to obtain the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol);

[0090] (4) Add Fmoc-L-Trp(Boc)-OH (12.64 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol) and react for 2–3 h. Take a small amount of the resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL of DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. Take a small amount of the resin for ninhydrin test. The result is positive, indicating that the reaction is complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes, and the solid-liquid separation was performed to obtain the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol);

[0091] (5) Add Fmoc-L-Met-OH (8.91 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol) and react for 2–3 h. Take a small amount of the resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL of DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. Take a small amount of the resin for ninhydrin test. The result is positive, indicating that the reaction is complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes, and the solid-liquid separation was performed to obtain the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol);

[0092] (6) Add Fmoc-L-Pro-OH (8.10 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol) and react for 2–3 h. Take a small amount of the resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL of DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. Take a small amount of the resin for ninhydrin test. The result is positive, indicating that the reaction is complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes, and the solid-liquid separation was performed to obtain the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol);

[0093] (7) Add Fmoc-L-Ser(tBu)-OH (9.20 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTCResin (12 mmol) and react for 2–3 h. Take a small amount of resin for ninhydrin test. The result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin with 200 mL DMF twice, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. A small amount of resin was taken for ninhydrin test, and the result was positive, indicating that the reaction was complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200mL DMF, each time for 2 minutes, and solid-liquid separation was performed to obtain the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12mmol);

[0094] (8) Add Fmoc-L-Arg(Pbf)-OH (15.57 g, 24 mmol, 2.0 equivalent), HOBT (3.24 g, 24 mmol, 2.0 equivalent), DIC (3.02 g, 24 mmol, 2.0 equivalent), and DMF (150 mL) to a reactor containing L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12 mmol) and react for 2–3 h. Take a small amount of the resin for ninhydrin test, and the result is negative, indicating that the reaction is complete. After stopping the reaction, drain the reaction solution and wash the obtained resin twice with 200 mL of DMF, each time for 2 minutes. Remove the Fmoc protecting group with 20% piperidine in DMF solution (150 mL) and react for about 30 min. A small amount of resin was taken for ninhydrin test, and the result was positive, indicating that the reaction was complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200mL DMF, each time for 2 minutes; 200mL DCM and 200mL MeOH were alternately washed twice, each time for 2 minutes, and solid-liquid separation was performed to obtain the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (12mmol). The solid resin was placed in a constant temperature vacuum drying oven at 40℃ and dried overnight, and then divided into two equal parts, each of which was 6mmol for the synthesis of short peptide compound 1 and short peptide compound 2.

[0095] (9) Acetic acid (0.72 g, 12 mmol, 2.0 equiv), HOBT (1.62 g, 12 mmol, 2.0 equiv), DIC (1.51 g, 12 mmol, 2.0 equiv), and DMF (100 mL) were added to a reactor containing L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin (6 mmol). The reaction was allowed to proceed for 2–3 h. A small amount of the resin was taken for ninhydrin detection, and the result was negative, indicating that the reaction was complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes; 200 mL DCM and 200 mL MeOH were alternately washed twice, each time for 2 minutes, and the solid-liquid separation was performed to obtain Ac-L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin. The solid resin was placed in a constant temperature vacuum drying oven at 40°C and dried.

[0096] Example 2

[0097] The difference from Example 1 is that step (9) is different, specifically:

[0098] To a reactor containing L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin(6mmol), trifluoroacetic acid (1.37g, 12mmol, 2.0 equivalent), HOBT (1.62g, 12mmol, 2.0 equivalent), DIC (1.51g, 12mmol, 2.0 equivalent), and DMF (100mL) were added and the reaction was carried out for 2-3h. A small amount of resin was taken for ninhydrin test, and the result was negative, indicating that the reaction was complete. After stopping the reaction, the reaction solution was drained, and the obtained resin was washed twice with 200 mL DMF, each time for 2 minutes; 200 mL DCM and 200 mL MeOH were alternately washed twice, each time for 2 minutes, and solid-liquid separation was performed to obtain Tfa-L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin. The solid resin was placed in a constant temperature vacuum drying oven at 40°C and dried.

[0099] The resins obtained in the above-mentioned Examples 1 and 2 were cleaved using a 94% trifluoroacetic acid solution at 0°C as a classical cleavage solution, and the reaction was carried out for about 3 hours. After the reaction was completed, the solid and liquid were separated. The filtrate obtained in the vacuum rotary evaporation step (9) was concentrated to remove most of the trifluoroacetic acid. The obtained reaction residues were precipitated with frozen isopropyl ether, and the crude peptide products of the short peptide compound 1 and the short peptide compound 2 were precipitated by centrifugation, vacuum dried, and finally separated and purified to obtain the short peptide compound 1 and the short peptide compound 2 respectively.

[0100] The purification steps specifically include

[0101] (1) First, the crude peptide products of the short peptide compound 1 and the short peptide compound 2 obtained above were subjected to sample purity analysis. After the retention time of the main peak was determined, the samples were analyzed by linear gradient analysis.

[0102] (2) Weigh 50 mg of crude peptides of short peptide compound 1 and short peptide compound 2, dissolve and dilute to 3 mL with mobile phase. After filtering with a 0.45 μm organic filter membrane, perform gradient separation with a high performance liquid chromatograph, collect the corresponding mobile phase at the retention time of the target absorption peak, and freeze-dry to obtain the target peptide, that is, obtain the short peptide compound, which is recorded as short peptide compound 1 and short peptide compound 2.

[0103] Chromatographic column: C18 column (4.6×250mm, 5μl)

[0104] Mobile phase A: 0.1% trifluoroacetic acid / water solution

[0105] Mobile B: Acetonitrile

[0106] Flow rate: 1ml / min

[0107] Column temperature: 30°C

[0108] Detection wavelength: 250nm, 210nm

[0109] Injection volume: 5 μl

[0110] Time-mobile phase gradient table for separation of short peptide compound 1 and short peptide compound dipeptide by high performance liquid chromatography:

[0111]

[0112]

[0113] (3) 200 mg of the short peptide compound 1 and the short peptide compound 2 were placed in a 10 mL dissolution bottle, deionized water was added, and after ultrasonic dissolution, the samples were filtered with a 0.45 μm organic phase filter to obtain the supernatant. This step was used to mass produce the short peptide compound 1 or the short peptide compound 2.

[0114] (4) Put it into HPLC, prepare the peak by linear gradient, and confirm whether the MS is correct;

[0115] (5) In order to meet the required purity of the liquid volume, the purity of the collected liquid should be tracked and fed back;

[0116] (6) Concentrate the collected qualified solution to 40-50 mL at 40°C;

[0117] (7) The concentrated solution was placed in a 100 mL beaker and frozen in a freezer;

[0118] (8) After HPLC purification, freeze-drying was performed to obtain the short peptide compound 1 and the short peptide compound 2 of the present invention.

[0119] Test 1

[0120] Mass spectrometry test of short peptide compound 1 and short peptide compound 2

[0121] The two short peptide compounds obtained in Example 1 and Example 2 were subjected to mass spectrometry test. The two short peptide compounds included short peptide compound 1 (Ac-RS octapeptide) and short peptide compound 2 (Tfa-RS octapeptide). The test results are shown in Figure 1 and Figure 2 , proving that the examples of the present invention successfully synthesized short peptide compound 1 (Ac-RS octapeptide) and short peptide compound 2 (Tfa-RS octapeptide).

[0122] Test 2

[0123] Purity test of short peptide compound 1 and short peptide compound 2

[0124] The two short peptide compounds obtained in Example 1 and Example 2 were subjected to high performance liquid chromatography (HPLC) detection under 254 nm fluorescence conditions. The detection results are as follows: Figure 3 , Figure 4 As shown, according to the peak area in the figure, the purity of the short peptide compound 1 (Ac-RS octapeptide) was determined to be 95.11%, and the purity of the short peptide compound 2 (Tfa-RS octapeptide) was determined to be 96.86%.

[0125] Test 3

[0126] Cytotoxicity test of short peptide compound 1 and short peptide compound 2

[0127] The effect on cell proliferation was detected using a CCK8 detection kit. The specific operation is as follows: human immortalized epidermal cells (HaCaT cells) and mouse mononuclear macrophage leukemia cells (RAW 264.7 cells) were cultured in a complete medium of DMEM high glucose medium + 10% fetal bovine serum + 1% penicillin & streptomycin (hereinafter referred to as complete medium) at 37°C in a cell culture incubator with 5% CO2.

[0128] HaCaT cells and RAW 264.7 cells were plated in 96-well plates at 10,000 cells per well for 24 hours, and 100 μl of complete culture medium containing the short peptide compound 1 (Ac-RS octapeptide) and compound 2 (Tfa-RS octapeptide) was added. Each group had 6 replicate wells. After incubation for 24 hours, the old culture medium was removed, and 110 μl of culture medium containing CCK8 solution (complete culture medium: CCK8 = 10:1) was added. After incubation for 2 hours in a cell culture incubator at 37°C and 5% CO2, the absorbance of each well was measured at 450 nm by a microplate reader to calculate the cell survival rate.

[0129] The experimental results are as follows Figure 5 As shown, the results showed that within the range of less than or equal to 2000 ppm, the short peptide compound 1 (Ac-RS octapeptide) had no effect on the proliferation of RAW 264.7 cells.

[0130] The experimental results are as follows Figure 6 As shown, the results showed that within the range of less than 200 ppm, the short peptide compound di(Tfa-RS octapeptide) had no effect on the proliferation of HaCaT cells.

[0131] Test 4

[0132] Test of the effect of short peptide compounds on cell anti-inflammatory effects

[0133] Mouse mononuclear macrophage leukemia cells (RAW 264.7 cells) were cultured in a complete medium (hereinafter referred to as complete medium) of DMEM high glucose medium + 10% fetal bovine serum + 1% penicillin & streptomycin at 37°C in a cell culture incubator with 5% CO2. RAW264.7 cells were plated in 6-well plates with 400,000 cells per well for 24 hours, and different concentrations of compound 1 (Ac-RS octapeptide) and 2ug / ml LPS (normal control group was not treated with LPS) were co-treated for 24 hours. The cells were collected, RNA was extracted, reverse transcribed into cDNA, and then the fluorescence quantitative PCR method was used to detect the gene expression of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). The results are shown in Figure 2. Figure 7-Figure 9 As shown, compared with the modeling group to which LPS was added alone, the short peptide compound 1 (Ac-RS octapeptide) significantly reduced the expression of related genes, indicating that the short peptide compound prepared in the embodiment of the present invention has a certain anti-inflammatory effect.

[0134] Test 5

[0135] Test of the repair effect of short peptide compound 2

[0136] Human immortalized epidermal cells (HaCaT cells) were cultured in a complete medium (hereinafter referred to as complete medium) of DMEM high glucose medium + 10% fetal bovine serum + 1% penicillin & streptomycin at 37°C in a cell culture incubator with 5% CO2. HaCaT cells were plated in 6-well plates with 200,000 cells per well for 24 hours. HaCaT cells were treated with different concentrations of short peptide compound II (Tfa-RS octapeptide) for 48 hours, cells were collected, RNA was extracted, reverse transcribed into cDNA, and then fluorescent quantitative PCR method was used to detect the gene expression of aquaporin 3 (AQP3), hyaluronan synthase 3 (HAS3), keratin 1 (KRT-1) and keratin 14 (KRT-14). The results are as follows Figure 10-13 As shown, compared with the normal control group, the short peptide compound II (Tfa-RS octapeptide) significantly promoted the expression of related genes, indicating that the short peptide compound II prepared in the embodiment of the present invention has a certain repair effect.

[0137] It should be understood that the application of the present invention is not limited to the above examples. For ordinary technicians in this field, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A short peptide compound, characterized in that: The amino acid sequence of the short peptide compound is X-RSPMWKYS-OH, wherein X is CH3CO or CF3CO; When X is CH3CO, the short peptide compound is a short peptide compound 1 having the structural formula (I): When X is CF3CO, the short peptide compound has the structural formula (II) of the short peptide compound 2:

2. A method for preparing the short peptide compound according to claim 1, characterized in that: Includes steps: (1) The first solid phase resin L-Ser(tBu)-CTC Resin is prepared mainly using 2-chlorotrityl chloride resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine; (2) mainly using the first solid phase resin L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine to prepare the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; (3) The third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared mainly by using the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl; (4) mainly using the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan to prepare the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; (5) preparing the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTCResin and N-(9-fluorenylmethoxycarbonyl)-L-methionine; (6) preparing the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-proline; (7) preparing the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin mainly using the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine; (8) The seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)- The eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin was prepared from L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl); (9) adding 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and acetic acid to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin and reacting for 2-3 hours, washing and drying the reaction product to obtain a ninth solid phase resin, and then cleaving the ninth solid phase resin with a cleavage solution, rotary evaporating to obtain a reaction residue, then precipitating the reaction residue with isopropyl ether, and finally separating and purifying to obtain the short peptide compound one; Alternatively, 1-hydroxybenzotriazole, a dimethylformamide solution of N,N'-diisopropylcarbodiimide and trifluoroacetic acid are added to the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin to react for 2-3 hours, the reaction product is washed and dried to obtain a ninth solid phase resin, and then the ninth solid phase resin is cracked with a cracking solution and rotary evaporated to obtain a reaction residue, and then the reaction residue is precipitated with isopropyl ether, and finally separated and purified to obtain the short peptide compound two.

3. The method for preparing a short peptide compound according to claim 2, characterized in that: Step (1) specifically comprises: adding 2-chlorotrityl chloride resin into a reactor, and then adding N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine and N-methylmorpholine in dimethylformamide to react; then adding methanol, and after the reaction is complete, removing Fmoc, and then solid-liquid separation to obtain the first solid phase resin L-Ser(tBu)-CTC Resin; Step (2) specifically comprises: adding a dimethylformamide solution of N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-tyrosine, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the first solid phase resin L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then performing solid-liquid separation to obtain a second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (3) specifically comprises: adding a dimethylformamide solution of 9-fluorenylmethoxycarbonyl-L-lysine-ε-tert-butyloxycarbonyl, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the second solid phase resin L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then performing solid-liquid separation to obtain a third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (4) specifically comprises: adding a dimethylformamide solution of N-(9-fluorenylmethoxycarbonyl)-N1-tert-butyloxycarbonyl-L-tryptophan, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the third solid phase resin L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, reacting, removing Fmoc, and then performing solid-liquid separation to obtain a fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (5) specifically comprises: adding a dimethylformamide solution of N-(9-fluorenylmethoxycarbonyl)-L-methionine, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing a fourth solid phase resin L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then performing solid-liquid separation to obtain a fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (6) specifically comprises: adding a dimethylformamide solution of 9-fluorenylmethoxycarbonyl-L-proline, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the fifth solid phase resin L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (7) specifically comprises: adding a dimethylformamide solution of N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine, 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the sixth solid phase resin L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)- L-Tyr(tBu)-L-Ser(tBu)-CTC Resin; Step (8) specifically comprises: adding a dimethylformamide solution of 9-fluorenylmethoxycarbonyl-L-arginine (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl), 1-hydroxybenzotriazole and N,N'-diisopropylcarbodiimide to a reactor containing the seventh solid phase resin L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin, removing Fmoc after the reaction is complete, and then separating the solid and liquid to obtain the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTCResin.

4. The method for preparing a short peptide compound according to claim 3, characterized in that: In steps (1) to (8), Fmoc removal is carried out using a dimethylformamide solution of piperidine, wherein the mass concentration of piperidine in the dimethylformamide solution is 10-20 wt %; In steps (1) to (8), the solid-liquid separation step comprises: separating the solid phase material by suction filtration, and then washing the solid phase resin obtained in each step with dimethylformamide, methanol and dichloromethane one or more times in sequence.

5. The method for preparing a short peptide compound according to claim 3, characterized in that: In step (1), the molar ratio of N-[(9H-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine, N-methylmorpholine and 2-chlorotrityl chloride resin is 2:5:1; in each step from step (2) to step (8), the molar ratio of the amino acid with a protective group, 1-hydroxybenzotriazole, N,N'-diisopropylcarbodiimide and the solid phase resin used in each step is 2:2:2:1; in each step from step (2) to step (8), the amino acid with a protective group is N-(9-fluorene-9-ylmethoxy)carbonyl]-O-tert-butyl-L-serine, N-methylmorpholine and 2-chlorotrityl chloride resin are respectively The following are the amino acids 1, 2, 3, 4, 5-dihydrobenzofuran-5-yl and 1, 2, 3, 4-dihydrobenzofuran-5-yl.

6. The method for preparing a short peptide compound according to claim 2, characterized in that: In step (9), the molar ratio of the acetic acid or trifluoroacetic acid, 1-hydroxybenzotriazole, N,N'-diisopropylcarbodiimide and the eighth solid phase resin L-Arg(Pbf)-L-Ser(tBu)-L-Pro-L-Met-L-Trp(Boc)-L-Lys(Boc)-L-Tyr(tBu)-L-Ser(tBu)-CTC Resin is (1.8-2.5):(1.8-2.5):(1.8-2.5):

1.

7. The method for preparing a short peptide compound according to claim 2, characterized in that: In step (9), the lysis solution is trifluoroacetic acid lysis solution, the mass volume ratio of the ninth solid phase resin to the lysis solution is 1 g:20 mL, and the lysis time is 2-3 h.

8. A cosmetic composition, characterized in that The invention comprises the short peptide compound according to claim 1 and a carrier acceptable for cosmetic products.

9. The cosmetic composition according to claim 8, characterized in that The anti-inflammatory effective concentration of the short peptide compound 1 in the cosmetic composition is 50-2000 ppm, and the moisturizing effective concentration of the short peptide compound 2 in the cosmetic composition is 50-200 ppm.

10. Use of the cosmetic composition according to claim 8 or 9 in cosmetic products.

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