Cosmetic and medical material solubilization and synergistic effect method

Abstract

The application discloses a cosmetical and medical material solubilization and synergistic effect method, belongs to the solubilization technical field of peptides and derivatives, and particularly relates to adding liposoluble polypeptide derivatives and / or collagen peptides, which are taken as typical palmitoyl blue copper peptides, and N-acetylneuraminic acid and / or N derivative glucosamine into a dissolving system, so that the solubility of target polypeptide derivatives is improved, the N derivative glucosamine is prepared by reacting nicotinoyl chloride and D-glucosamine hydrochloride, the dissolving system includes any one of 'water', 'a mixed solution of water, glycerol and caprylyl glycol' and 'a mixed solution of water, glycerol, 1,2-hexanediol and ethylhexylglycerin', and the palmitoyl blue copper peptide can be dissolved into the solvent system under different proportions of the polypeptide derivatives and the N-acetylneuraminic acid and / or N derivative glucosamine. The solubilization mixture obtained by the application can effectively improve the solubility of the polypeptide derivatives in water.

Description

Technical Field

[0001] This invention belongs to the field of peptide solubilization technology, specifically relating to a method for enhancing the solubility and efficacy of cosmetic and medical aesthetic ingredients. Background Technology

[0002] Peptides are structural components of proteins, linked by amino groups through a specific sequence of amidation. Peptides play a vital role in the growth, development, and metabolism of organisms, and also exert a crucial regulatory influence on the natural aging and skin care processes. Certain short peptides with specific sequences offer benefits to the skin by: helping to eliminate excess free radicals, restoring normal skin cell behavior, slowing down cell aging, inhibiting tyrosinase activity, promoting skin whitening, and facilitating skin repair and regeneration. These beneficial short peptides are often referred to as beauty peptides.

[0003] Blue copper peptide is the most typical example, with its basic amino acid sequence being glycine-histidine-lysine (GHK). As an active tripeptide, it is a normal component of human plasma, saliva, and urine, with its content declining with age. GHK is present in the α2 chain of type I collagen. When damage activates proteolytic enzymes (early signals for skin repair), GHK is released to the site of injury, playing a local healing role. In recent years, GHK's ability to promote tissue regeneration, as well as its anti-inflammatory and antioxidant properties, have been confirmed in tissues such as bone, skin, and liver. In vivo, GHK readily forms a copper-containing tripeptide complex (GHK-Cu) with Cu, enhancing its bioavailability. GHK-Cu, along with signaling pathway molecules related to dermal repair and skin regeneration, forms a sophisticated regulatory network, restoring cellular signaling pathways in the dermis to their optimal state and restoring genes to a healthier state.

[0004] Unlike other cosmetic active ingredients that only act on the stratum corneum, most cosmetic peptides target the epidermis or even the dermis. However, the hydrophilic nature of these peptides makes them extremely difficult to penetrate the stratum corneum lipid layer, requiring them to overcome various obstacles to reach deeper layers of the skin and exert their effects. Palmitic acid, as a major component of the stratum corneum lipids, has minimal impact on skin irritation. Once incorporated into the skin, it can disrupt the accumulation of intercellular lipids and reduce the skin's resistance to the diffusion of hydrophilic active ingredients. Its 16-carbon chain, covalently modified into the amino acid residues of cosmetic peptides via thioester bonds, can significantly improve the transdermal properties and stability of these peptides.

[0005] The introduction of palmitoyl groups further increases the penetration of peptides into human skin and improves their stability, delaying the hydrolysis of peptides by skin enzymes during diffusion. After the introduction of palmitic acid groups, transdermal absorption is more than 17 times that of the original peptide. However, this improved transdermal absorption comes at the cost of hydrophilic properties; it is only soluble in non-polar solvents such as ether and carbon tetrachloride, or slightly soluble in some extreme polar solvents such as 80% isopropanol and 60% acetonitrile, exhibiting strong cytotoxicity. The addition of these solvents can cause severe skin irritation, which is detrimental to the design and construction of cosmetics.

[0006] In addition, collagen peptides, mainly composed of long-chain collagen, often play a role in moisturizing and hydrating in medical aesthetics and cosmetics. These polymer materials usually require a lot of effort to dissolve during the preparation process. Summary of the Invention

[0007] The purpose of this invention is to provide a method for improving the solubility of peptide derivatives in aqueous solvents and enhancing the solubility of cosmetic and medical aesthetic ingredients.

[0008] This invention introduces an organic acid system that is less irritating to the skin or even has positive benefits, and combines it with palmitoylated polypeptides and high molecular weight collagen peptides to improve their insolubility in pure aqueous solutions and fully expand their application range.

[0009] The technical solution adopted by the present invention to achieve the above objectives is as follows: A solubilizing mixture comprises a polypeptide derivative and a solubilizing agent, wherein the molar ratio of the polypeptide derivative to the solubilizing agent is 1:0.17-15. This invention, by compounding the polypeptide derivative and the solubilizing agent in a certain proportion, enables the polypeptide derivative to successfully dissolve in an aqueous reagent under the action of the solubilizing agent. The principle is likely that the solubilizing agent interacts with the palmitoyl group in the polypeptide derivative, and simultaneously, under the action of the hydrophilic groups or structures in the solubilizing agent, the polypeptide derivative successfully dissolves in the aqueous reagent.

[0010] Preferably, the solubilizing agent includes at least one of N-acetylneuraminic acid and N-derived glucosamine, wherein the N-derived glucosamine has a nicotinic acid group; or, the solubilizing agent is N-acetylneuraminic acid, and the molar ratio of the polypeptide derivative to N-acetylneuraminic acid is 1:0.17-10; or, the solubilizing agent is N-derived glucosamine, wherein the N-derived glucosamine has a nicotinic acid group, and the molar ratio of the polypeptide derivative to N-derived glucosamine is 1:0.2-5. This invention prepares N-derived glucosamine by reacting nicotinic acid chloride with D-glucosamine hydrochloride. The N-derived glucosamine contains both nicotinic acid and glucose groups, and the glucose groups contain a large number of polar groups, exhibiting strong hydrophilicity. Under the influence of the nicotinic acid groups, glucose groups, and their binding structure, the solubility of the polypeptide derivative in aqueous reagents is improved.

[0011] Preferably, the solubilizing agent is N-acetylneuraminic acid and N-derived glucosamine, and the molar ratio of the polypeptide derivative, N-acetylneuraminic acid and N-derived glucosamine is 1:0.125-10:0.05-5.

[0012] Preferably, the polypeptide derivative is at least one of palmitoyl copper peptide, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, palmitoyl tetrapeptide-7, and collagen. The polypeptide derivative is a poorly soluble polypeptide.

[0013] This invention discloses a polypeptide derivative solution, comprising: the above-mentioned solubilizing mixture, and a solvent system.

[0014] Preferably, the polypeptide derivatives are typically lipid-soluble palmitoyl copper peptides, including palmitoyl tripeptides, tetrapeptides, pentapeptides, as well as long-chain collagen and corresponding polypeptide derivatives. Preferably, the amount of polypeptide derivative is 200ppm-6000ppm.

[0015] Preferably, the solvent system is water; or, the solvent system is a mixture of water, glycerol and octyl glycol; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol and ethylhexylglycerol.

[0016] More preferably, the mass ratio of water, glycerol and octylglycol in the solvent system is 79-97.8:2-10:0.2-1; or, the mass ratio of water, glycerol, 1,2-hexanediol and ethylhexylglycerol in the solvent system is 71.8-83.95:15-25:1-3:0.05-0.2.

[0017] This invention discloses a method for preparing a polypeptide derivative solution, comprising: mixing the above-mentioned solubilizing mixture with a solvent system to prepare a polypeptide derivative solution.

[0018] Preferably, the solvent system is water, and the solubilizing mixture is directly added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, and octyl glycol, and the solubilizing mixture is added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, and octyl glycol, the solubilizing mixture is added to water to dissolve, and then mixed with glycerol and octyl glycol; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, and the solubilizing mixture is added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, the solubilizing mixture is added to water to dissolve, and then mixed with glycerol, 1,2-hexanediol, and ethylhexylglycerol.

[0019] Preferably, the solubilizing mixture contains N-derived glucosamine, which is prepared by reacting nicotinic acid chloride with D-glucosamine hydrochloride.

[0020] Preferably, in the preparation of nicotinic acid chloride, nicotinic acid is added to dichloromethane and stirred and mixed, and then oxalyl chloride solution is added at 0-10°C. After the addition is completed, the mixture is stirred and mixed, and the reaction is carried out at 20-40°C for 2-12 hours. The reaction is monitored by TLC. After the reaction is completed, dichloromethane and oxalyl chloride are removed by vacuum distillation to obtain nicotinic acid chloride.

[0021] More preferably, in the preparation of nicotinic acid chloride, the amount of nicotinic acid used is 20-40 wt% of dichloromethane.

[0022] More preferably, in the preparation of nicotinic acid chloride, the oxaloyl chloride solution is prepared by mixing oxaloyl chloride and dichloromethane, the oxaloyl chloride solution contains 40-60 wt% oxaloyl chloride, the amount of oxaloyl chloride used in the oxaloyl chloride solution is based on the oxaloyl chloride content, and the amount of oxaloyl chloride used is 80-120 wt% of nicotinic acid.

[0023] Preferably, in the preparation of N-derived glucosamine, D-glucosamine hydrochloride is added to methanol, then sodium methoxide is added, and the mixture is stirred at 20-40°C for 0.5-2 hours. After stirring, an acyl chloride solution is added and reacted for 2-8 hours. The reaction is monitored by TLC. After the reaction is complete, the mixture is filtered, washed with diethyl ether, and dried to obtain N-derived glucosamine.

[0024] More preferably, in the preparation of N-derived glucosamine, the amount of D-glucosamine hydrochloride used is 1-3 wt% of methanol.

[0025] More preferably, in the preparation of N-derived glucosamine, the amount of sodium methoxide used is 80-120 wt% of D-glucosamine hydrochloride.

[0026] More preferably, in the preparation of N-derived glucosamine, the acyl chloride solution is composed of an acyl chloride reagent and 1,4-dioxane, the acyl chloride reagent being nicotinic acid chloride, the content of the acyl chloride reagent in the acyl chloride solution being 20-40 wt%, and the amount of acyl chloride used being based on the nicotinic acid chloride, the amount of nicotinic acid chloride being 80-120 wt% of D-glucosamine hydrochloride.

[0027] Preferably, in the preparation of the polypeptide derivative sample solution, the polypeptide derivative and N-acetylneuraminic acid are added to the solvent system and stirred and shaken at 20-40℃ for 1-12 hours to obtain the polypeptide derivative sample solution.

[0028] More preferably, in the preparation of the polypeptide derivative sample solution, the solvent system is purified water.

[0029] More preferably, in the preparation of the polypeptide derivative sample solution, the amount of polypeptide derivative used is 200ppm-6000ppm.

[0030] More preferably, in the preparation of the polypeptide derivative sample solution, the polypeptide derivative (pal-GHK-Cu) and N-acetylneuraminic acid are mixed in a molar ratio of 1:0.17-10.

[0031] More preferably, in the preparation of the polypeptide derivative sample solution, the polypeptide derivative (pal-GHK-Cu) and N-acetylneuraminic acid are mixed in a molar ratio of 1:0.2-10.

[0032] More preferably, in the preparation of the polypeptide derivative sample solution, the polypeptide derivative (pal-GHK-Cu) and N-acetylneuraminic acid are mixed in a molar ratio of 1:0.25-10.

[0033] Preferably, N-derived glucosamine can be added during the preparation of the polypeptide derivative sample solution. When the solvent system is purified water, the polypeptide derivative, N-acetylneuraminic acid and N-derived glucosamine are mixed in a molar ratio of 1:0.125-10:0.05-5.

[0034] Preferably, in the preparation of the polypeptide derivative sample solution, after adding N-derived glucosamine, the solvent system is a mixture of purified water, glycerol and octyl glycol. The purified water, glycerol and octyl glycol are mixed in a mass ratio of 79-97.8:2-10:0.2-1, and the polypeptide derivative, N-acetylneuraminic acid and N-derived glucosamine are mixed in a molar ratio of 1:0.125-10:0.05-5.

[0035] Preferably, in the preparation of the polypeptide derivative sample solution, after adding N-derived glucosamine, the solvent system is a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol. The purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol in the solvent system are mixed in a mass ratio of 71.8-83.95:15-25:1-3:0.05-0.2, and the polypeptide derivative, N-acetylneuraminic acid and N-derived glucosamine are mixed in a molar ratio of 1:0.125-10:0.05-5.

[0036] This invention improves the solubility of peptide derivatives by incorporating peptide derivatives and N-acetylneuraminic acid and / or N-derived glucosamine into the dissolving system. The N-derived glucosamine is prepared by reacting nicotinyl chloride with D-glucosamine hydrochloride. The dissolving system includes any one of "water," "a mixture of water, glycerol, and caprylyl glycol," and "a mixture of water, glycerol, 1,2-hexanediol, and ethylhexylglycerol." Different ratios of peptide derivatives and N-acetylneuraminic acid and / or N-derived glucosamine allow the peptide derivatives to dissolve in the solvent system, thus providing the following beneficial effect: improved solubility of peptide derivatives in aqueous solvents. Therefore, this invention is a method for enhancing the solubility of peptide derivatives in aqueous solvents for cosmetic and medical aesthetic raw materials. Attached Figure Description

[0037] Figure 1 This is an infrared spectrum. Detailed Implementation

[0038] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings: The palmitoyl blue copper peptide used in this invention is from Zhejiang Paipai Biotechnology Co., Ltd.

[0039] Example 1: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:10.

[0040] Example 2: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.5.

[0041] Example 3: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.25.

[0042] Example 4: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.17.

[0043] Example 5: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of nicotinic acid chloride: Nicotinic acid was added to dichloromethane and stirred. Then, oxaloyl chloride solution was added at 0°C. After the addition was complete, the mixture was stirred and stirred. The reaction was carried out at 30°C for 6 hours, monitored by TLC. After the reaction was completed, dichloromethane and oxaloyl chloride were removed by vacuum distillation to obtain nicotinic acid chloride. The amount of dichloromethane used was 100g, and the amount of nicotinic acid used was 30g. The oxaloyl chloride solution was prepared by mixing oxaloyl chloride and dichloromethane, and contained 50wt% oxaloyl chloride. The amount of oxaloyl chloride used was based on the oxaloyl chloride content, and the amount of oxaloyl chloride used was 30g.

[0044] Preparation of N-derived glucosamine: D-glucosamine hydrochloride was added to methanol, followed by sodium methoxide. The mixture was stirred at 30°C for 1 hour. After stirring, an acyl chloride solution was added and reacted for 5 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was filtered, washed with diethyl ether, and dried to obtain N-derived glucosamine. The amount of methanol used was 100 g, the amount of D-glucosamine hydrochloride was 2 g, and the amount of sodium methoxide was 2 g. The acyl chloride solution was prepared by mixing an acyl chloride reagent with 1,4-dioxane. The acyl chloride reagent was nicotinic acid chloride, and the content of the acyl chloride reagent in the acyl chloride solution was 30 wt%. The amount of nicotinic acid chloride used in the acyl chloride solution was based on the amount of nicotinic acid chloride, which was 2 g.

[0045] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, and the amount of palmitoyl copper blue peptide used was 2000 ppm. The palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.125:0.05.

[0046] Example 6: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this embodiment and Example 5 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0047] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, and the amount of palmitoyl copper blue peptide used was 4000 ppm. The palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.125:0.05.

[0048] Example 7: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this embodiment and Example 5 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0049] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-derived glucosamine were mixed at a molar ratio of 1:0.2.

[0050] Example 8: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed in a molar ratio of 1:1.

[0051] Example 9: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.5.

[0052] Example 10: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.25.

[0053] Example 11: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of nicotinic acid chloride: Nicotinic acid was added to dichloromethane and stirred. Then, oxaloyl chloride solution was added at 0°C. After the addition was complete, the mixture was stirred and stirred. The reaction was carried out at 30°C for 6 hours, monitored by TLC. After the reaction was completed, dichloromethane and oxaloyl chloride were removed by vacuum distillation to obtain nicotinic acid chloride. The amount of dichloromethane used was 100g, and the amount of nicotinic acid used was 30g. The oxaloyl chloride solution was prepared by mixing oxaloyl chloride and dichloromethane, and contained 50wt% oxaloyl chloride. The amount of oxaloyl chloride used was based on the oxaloyl chloride content, and the amount of oxaloyl chloride used was 30g.

[0054] Preparation of N-derived glucosamine: D-glucosamine hydrochloride was added to methanol, followed by sodium methoxide. The mixture was stirred at 30°C for 1 hour. After stirring, an acyl chloride solution was added and reacted for 5 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was filtered, washed with diethyl ether, and dried to obtain N-derived glucosamine. The amount of methanol used was 100 g, the amount of D-glucosamine hydrochloride was 2 g, and the amount of sodium methoxide was 2 g. The acyl chloride solution was prepared by mixing an acyl chloride reagent with 1,4-dioxane. The acyl chloride reagent was nicotinic acid chloride, and the content of the acyl chloride reagent in the acyl chloride solution was 30 wt%. The amount of nicotinic acid chloride used in the acyl chloride solution was based on the amount of nicotinic acid chloride, which was 2 g.

[0055] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.25:0.05.

[0056] Example 12: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.17.

[0057] Example 13: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this embodiment and Example 11 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0058] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.17:0.05.

[0059] Example 14: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this embodiment and Example 11 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0060] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.125:0.05.

[0061] Example 15: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed in a molar ratio of 1:1.

[0062] Example 16: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed in a molar ratio of 1:0.5.

[0063] Example 17: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the molar ratio of palmitoyl copper blue peptide and N-acetylneuraminic acid was 1:0.25.

[0064] Example 18: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed in a molar ratio of 1:0.17.

[0065] Example 19: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of nicotinic acid chloride: Nicotinic acid was added to dichloromethane and stirred. Then, oxaloyl chloride solution was added at 0°C. After the addition was complete, the mixture was stirred and stirred. The reaction was carried out at 30°C for 6 hours, monitored by TLC. After the reaction was completed, dichloromethane and oxaloyl chloride were removed by vacuum distillation to obtain nicotinic acid chloride. The amount of dichloromethane used was 100g, and the amount of nicotinic acid used was 30g. The oxaloyl chloride solution was prepared by mixing oxaloyl chloride and dichloromethane, and contained 50wt% oxaloyl chloride. The amount of oxaloyl chloride used was based on the oxaloyl chloride content, and the amount of oxaloyl chloride used was 30g.

[0066] Preparation of N-derived glucosamine: D-glucosamine hydrochloride was added to methanol, followed by sodium methoxide. The mixture was stirred at 30°C for 1 hour. After stirring, an acyl chloride solution was added and reacted for 5 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was filtered, washed with diethyl ether, and dried to obtain N-derived glucosamine. The amount of methanol used was 100 g, the amount of D-glucosamine hydrochloride was 2 g, and the amount of sodium methoxide was 2 g. The acyl chloride solution was prepared by mixing an acyl chloride reagent with 1,4-dioxane. The acyl chloride reagent was nicotinic acid chloride, and the content of the acyl chloride reagent in the acyl chloride solution was 30 wt%. The amount of nicotinic acid chloride used in the acyl chloride solution was based on the amount of nicotinic acid chloride, which was 2 g.

[0067] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.17:0.05.

[0068] Example 20: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this embodiment and Example 19 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0069] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide, N-acetylneuraminic acid, and N-derived glucosamine were mixed in a molar ratio of 1:0.125:0.05.

[0070] Example 21: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl pentapeptide-4 sample solution: Palmitoyl pentapeptide-4 and N-acetylneuraminic acid were added to the solvent system and stirred and shaken at 30°C for 3 hours to obtain the palmitoyl pentapeptide-4 sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl pentapeptide-4 used was 2000 ppm, and the molar ratio of palmitoyl pentapeptide-4 and N-acetylneuraminic acid was 1:0.125.

[0071] Example 22: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl pentapeptide-4 sample solution: Palmitoyl pentapeptide-4 and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 3 hours to obtain a palmitoyl pentapeptide-4 sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl pentapeptide-4 used was 2000 ppm, and the molar ratio of palmitoyl pentapeptide-4 and N-acetylneuraminic acid was 1:0.125.

[0072] Example 23: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl tripeptide-8 sample solution: Palmitoyl tripeptide-8 and N-acetylneuraminic acid were added to the solvent system and stirred and shaken at 30°C for 3 hours to obtain palmitoyl tripeptide-8 sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl pentapeptide-4 used was 2000 ppm, and the palmitoyl tripeptide-8 and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.125.

[0073] Example 24: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl tripeptide-8 sample solution: Palmitoyl tripeptide-8 and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 3 hours to obtain palmitoyl tripeptide-8 sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl tripeptide-8 used was 2000 ppm, and palmitoyl tripeptide-8 and N-acetylneuraminic acid were mixed in a molar ratio of 1:0.125.

[0074] Example 25: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl tetrapeptide-7 sample solution: Palmitoyl tetrapeptide-7 and N-acetylneuraminic acid were added to the solvent system and stirred and shaken at 30℃ for 3 h to obtain palmitoyl tetrapeptide-7 sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol. The purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol were mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl tetrapeptide-7 used was 600 ppm, and palmitoyl tetrapeptide-7 and N-acetylneuraminic acid were mixed in a molar ratio of 1:1.

[0075] Example 26: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl tetrapeptide-7 sample solution: Palmitoyl tetrapeptide-7 and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 3 hours to obtain a palmitoyl tetrapeptide-7 sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl tetrapeptide-7 used was 600 ppm, and palmitoyl tetrapeptide-7 and N-acetylneuraminic acid were mixed in a molar ratio of 1:2.

[0076] Example 27: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of animal-derived collagen peptide sample solution: Collagen and N-acetylneuraminic acid were added to a solvent system and stirred at 30°C for 5 hours to obtain a collagen sample solution. The solvent system was purified water, and the amount of collagen used was 5000 ppm. Collagen and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.2.

[0077] Comparative Example 1: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 2 hours to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.125.

[0078] Comparative Example 2: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 7 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0079] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-derived glucosamine were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was purified water, the amount of palmitoyl copper blue peptide used was 4000 ppm, and the palmitoyl copper blue peptide and N-derived glucosamine were mixed at a molar ratio of 1:0.15.

[0080] Comparative Example 3: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 10 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0081] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, and octyl glycol, with a mass ratio of 94.5:5:0.5. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the palmitoyl copper blue peptide and N-acetylneuraminic acid were mixed at a molar ratio of 1:0.125.

[0082] Comparative Example 4: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 18 lies in the preparation of the palmitoyl copper blue peptide-like solution.

[0083] Preparation of palmitoyl copper blue peptide sample solution: Palmitoyl copper blue peptide and N-acetylneuraminic acid were added to a solvent system and stirred and shaken at 30°C for 12 h to obtain a palmitoyl copper blue peptide sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl copper blue peptide used was 2000 ppm, and the molar ratio of palmitoyl copper blue peptide and N-acetylneuraminic acid was 1:0.125.

[0084] Comparative Example 5: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 21 lies in the preparation of the palmitoyl pentapeptide-4 sample solution.

[0085] Preparation of palmitoyl pentapeptide-4 sample solution: Palmitoyl pentapeptide-4 was added to the solvent system and stirred and shaken at 30℃ for 12 h to obtain the sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl pentapeptide-4 used was 2000 ppm.

[0086] Comparative Example 6: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 24 lies in the preparation of the palmitoyl tripeptide-8 sample solution.

[0087] Preparation of palmitoyl tripeptide-8 sample solution: Palmitoyl tripeptide-8 was added to the solvent system and stirred and shaken at 30℃ for 12 h to obtain the sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, with a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl pentapeptide-4 used was 2000 ppm.

[0088] Comparative Example 7: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 25 lies in the preparation of the palmitoyl tetrapeptide-7 sample solution.

[0089] Preparation of palmitoyl tetrapeptide-7 sample solution: Palmitoyl tetrapeptide-7 was added to the solvent system and stirred and shaken at 30℃ for 12 h to obtain the sample solution. The solvent system was a mixture of purified water, glycerol, 1,2-hexanediol and ethylhexylglycerol, mixed in a mass ratio of 77.9:20:2:0.1. The amount of palmitoyl tetrapeptide-7 used was 2000 ppm.

[0090] Comparative Example 8: A method for promoting the solubility and enhancing the efficacy of cosmetic and medical aesthetic ingredients The difference between this comparative example and Example 27 lies in the preparation of the collagen peptide-like solution.

[0091] Preparation of collagen peptide sample solution: Collagen peptides were added to a solvent system and stirred at 30°C for 12 hours to obtain the sample solution. The solvent system was purified water, and the amount of collagen peptides used was 5000 ppm.

[0092] Experimental example: The N-derived glucosamine prepared in Example 5 was characterized by infrared spectroscopy, and the results are as follows: Figure 1 As shown, at 3342cm -1 The infrared absorption peak for hydroxyl groups is at 1647 cm⁻¹. -1 The infrared absorption peak for the carbonyl group is at 1542 cm⁻¹. -1 The infrared absorption peak at 1052 cm⁻¹ represents the carbon-nitrogen double bond in nicotinic acid. -1 The infrared absorption peaks for carbon, oxygen, and hydrogen are located at this point.

[0093] This invention tested the methods of the above embodiments and comparative examples. The palmitoyl copper blue peptide sample solution in this invention includes not only cases where palmitoyl copper blue peptide is completely dissolved, but also cases where it is partially dissolved or completely insoluble. This distinction is not made for the sake of consistency. Which specific case the palmitoyl copper blue peptide sample solution refers to needs to be determined based on the technical effect. The dissolution of palmitoyl copper blue peptide in the palmitoyl copper blue peptide sample solution in this invention is shown in Table 1. Specifically, when palmitoyl copper blue peptide is directly mixed with purified water, within the usable range of palmitoyl copper blue peptide, the molar ratio of palmitoyl copper blue peptide to N-acetylneuraminic acid is in the range of 1:0.25-10, and it can be completely dissolved after 2 hours of shaking. However, when the molar ratio of palmitoyl copper blue peptide to N-acetylneuraminic acid is... When the molar ratio of the acids was 1:0.17, complete dissolution required 12 hours of shaking. When the molar ratio of palmitoyl copper peptide to N-acetylneuraminic acid was 1:0.125, it could not dissolve even after 12 hours of shaking. However, after reacting nicotinic acid chloride with D-glucosamine hydrochloride to prepare N-derived glucosamine, a molar ratio of palmitoyl copper peptide, N-acetylneuraminic acid, and N-derived glucosamine of 1:0.125:0.05 resulted in complete dissolution with only 2 hours of shaking. Conversely, without N-acetylneuraminic acid, a molar ratio of palmitoyl copper peptide to N-derived glucosamine of 1:0.2 required 12 hours of shaking for complete dissolution. Furthermore, a molar ratio of palmitoyl copper peptide to N-derived glucosamine of 1:0.2 resulted in complete dissolution with only 2 hours of shaking. When the molar ratio of palmitoyl copper blue peptide to N-acetylneuraminic acid is 1:0.15, it cannot be dissolved even after 12 hours of shaking. The solvent system in this invention also includes a mixture of purified water, glycerol, and caprylyl glycol, or a mixture of purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol. In the solvent system of the mixture of purified water, glycerol, and caprylyl glycol, when the molar ratio of palmitoyl copper blue peptide to N-acetylneuraminic acid is 1:0.25 or 1:0.17, it can only partially dissolve even after 12 hours of shaking. Dissolving palmitoyl copper blue peptide and N-acetylneuraminic acid in purified water at a ratio of 1:0.25 or 1:0.17 before adding glycerol and caprylyl glycol does not cause precipitation of palmitoyl copper blue peptide. Therefore, the solvent system... The method of preparation also affects the solubility of palmitoyl copper peptide, and may cause some palmitoyl copper peptide to remain insoluble. However, after adding N-derived glucosamine, even when palmitoyl copper peptide, N-acetylneuraminic acid, and N-derived glucosamine are mixed in a molar ratio of 1:0.125:0.05, they can still be completely dissolved after shaking. Furthermore, when the molar ratio of palmitoyl copper peptide to N-acetylneuraminic acid is 1:0.125, it cannot be dissolved in this solvent system. In a solvent system of "purified water, glycerol, 1,2-hexanediol, and ethylhexylglycerol", when the molar ratio of palmitoyl copper peptide to N-acetylneuraminic acid is 1:0.17, it can only partially dissolve even after 12 hours of shaking.Palmitoyl copper blue peptide (PCP) and N-acetylneuraminic acid (NNA) were first dissolved in purified water, and then glycerol, 1,2-hexanediol, and ethylhexylglycerol were added. This did not cause PCP to precipitate. Therefore, the solvent system used can affect the solubility of PCP and may result in some PCP remaining insoluble. However, after adding N-derived glucosamine, even when PCP, NNA, and N-derived glucosamine were mixed in a molar ratio of 1:0.125:0.05, they could still be completely dissolved after shaking. Furthermore, when the molar ratio of PCP to NNA was 1:0.125, it was insoluble in this solvent system.

[0094] Table 1. Solubility of palmitoyl copper blue peptide in different solvent systems In addition, Examples 21-27 and Comparative Examples 5-8 compared other polypeptide derivatives besides palmitoyl copper peptide. The difference between the examples and the comparative examples lies in the addition or absence of N-acetylneuraminic acid. Palmitoyl pentapeptide-4 and tripeptide-8 could not be completely dissolved in the solvent system without N-acetylneuraminic acid; the introduction of N-acetylneuraminic acid effectively promoted dissolution. Palmitoyl tetrapeptide-7 was difficult to dissolve, and increasing the proportion of N-acetylneuraminic acid helped with dissolution. Furthermore, N-acetylneuraminic acid accelerated the dissolution of collagen peptides.

[0095] Table 2. Solubility of polypeptide derivatives in different systems The above embodiments are for illustrative purposes only and are not intended to limit the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all equivalent technical solutions also fall within the scope of this invention, and the patent protection scope of this invention should be defined by the claims.

Claims

1. A polypeptide derivative solution, comprising: Solubilizing mixtures and solvent systems; The solubilizing mixture comprises: a polypeptide derivative and a solubilizing agent, wherein the molar ratio of the polypeptide derivative to the solubilizing agent is 1:0.17-15; The polypeptide derivative is at least one of palmitoyl copper peptide, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, palmitoyl tetrapeptide-7, and collagen. The solubilizing agent is N-acetylneuraminic acid and N-derived glucosamine, the N-derived glucosamine having a nicotinic acid group, and the molar ratio of the polypeptide derivative, N-acetylneuraminic acid and N-derived glucosamine is 1:0.125-10:0.05-5. The preparation steps of the N-derived glucosamine are as follows: D-glucosamine hydrochloride is added to methanol, then sodium methoxide is added, and the mixture is stirred and mixed at 20-40℃ for 0.5-2 hours. After stirring, an acyl chloride solution is added and reacted for 2-8 hours, monitored by TLC. After the reaction is complete, the mixture is filtered, washed with diethyl ether, and dried to obtain N-derived glucosamine. The acyl chloride solution is composed of nicotinic acid and 1,4-dioxane, with the content of nicotinic acid in the solution being 20-40 wt%. The amount of nicotinic acid used is based on the amount of nicotinic acid in the solution, and the amount of nicotinic acid used is 80-120 wt% of D-glucosamine hydrochloride. The preparation steps of the nicotinic acid chloride are as follows: Nicotinic acid is added to dichloromethane and stirred and mixed, then oxalyl chloride solution is added at 0-10℃. After the addition is complete, the mixture is stirred and mixed, and the reaction is carried out at 20-40℃ for 2-12 hours, monitored by TLC. After the reaction is complete, dichloromethane and oxalyl chloride are removed by vacuum distillation to obtain nicotinic acid chloride. The solvent system is water; or, the solvent system is a mixture of water, glycerol and octyl glycol; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol and ethylhexylglycerol.

2. The polypeptide derivative solution according to claim 1, characterized in that: The amount of the polypeptide derivative is 200ppm-6000ppm.

3. The polypeptide derivative solution according to claim 1, characterized in that: The mass ratio of water, glycerol and octylglycol in the solvent system is 79-97.8:2-10:0.2-1; or the mass ratio of water, glycerol, 1,2-hexanediol and ethylhexylglycerol in the solvent system is 71.8-83.95:15-25:1-3:0.05-0.

2.

4. A method for preparing a polypeptide derivative solution, comprising: The solubilizing mixture is mixed with a solvent system to prepare the polypeptide derivative solution according to claim 1.

5. The method for preparing a polypeptide derivative solution according to claim 4, characterized in that: The solvent system is water, and the solubilizing mixture is directly added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, and octyl glycol, and the solubilizing mixture is added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, and octyl glycol, and the solubilizing mixture is dissolved in water and then mixed with glycerol and octyl glycol; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, and the solubilizing mixture is added to the solvent system and mixed to dissolve; or, the solvent system is a mixture of water, glycerol, 1,2-hexanediol, and ethylhexylglycerol, and the solubilizing mixture is dissolved in water and then mixed with glycerol, 1,2-hexanediol, and ethylhexylglycerol.

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