Maintenance type private external hyaluronic acid balance gel and preparation method thereof

Abstract

The invention provides maintenance-type private external hyaluronic acid balancing gel and a preparation method thereof, and the balancing gel comprises the following raw materials by weight: 7.5%-17.8% of a humectant, 1.0%-2.5% of a nano-phospholipid wrapped soothing-micro-ecological regulation compound, 0.2%-0.4% of carbomer, 1.0%-2.5% of an emulsifier, 0.15%-0.35% of a neutralizer, 0.4%-0.9% of phenoxyethanol, 0.1%-0.4% of an antiseptic enhancer, 0.5%-1.8% of cetostearyl alcohol, and the balance of deionized water. And the balance of deionized water. The balancing gel disclosed by the invention has the effects of moisturizing, relieving and micro-ecological regulation, and is stable in system and good in safety.

Description

Technical Field

[0001] This invention relates to the field of feminine intimate care technology, specifically to a nourishing topical hyaluronic acid balancing gel for intimate use and its preparation method. Background Technology

[0002] The mucous membranes of a woman's intimate area are delicate and have a sensitive microecological environment, placing stringent requirements on the gentleness, synergistic efficacy, and system stability of care products. Existing topical intimate care products are mostly designed with moisturizing and antibacterial properties as their core focus, often achieving basic care functions by adding general-purpose ingredients such as moisturizers, gel bases, and preservatives to meet daily cleaning and basic maintenance needs.

[0003] While existing general-purpose balancing gels for intimate areas can achieve certain moisturizing or antibacterial effects through conventional component combinations, they are significantly lacking in synergy and compatibility. They generally suffer from difficulty in effectively balancing moisturizing efficacy and the regulation of the intimate area's microecology. Furthermore, some products perform poorly in balancing soothing effects with long-term system stability, failing to fully meet the core requirements of refined intimate area care for multifunctional synergy and gentle safety. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention provides a nourishing topical hyaluronic acid balancing gel for intimate use and its preparation method, which enables the balancing gel to have moisturizing, soothing and microecological regulation effects, and the system is stable and has good safety.

[0005] To achieve the above objectives, the present invention provides the following technical solution: This application discloses a nourishing hyaluronic acid balancing gel for external use in intimate areas. By weight percentage, its constituent raw materials include: 7.5%-17.8% moisturizer, 1.0%-2.5% nano-phospholipid-encapsulated soothing-microecological regulation complex, 0.2%-0.4% carbomer, 1.0%-2.5% emulsifier, 0.15%-0.35% neutralizer, 0.4%-0.9% phenoxyethanol, 0.1%-0.4% preservative enhancer, 0.5%-1.8% cetearyl alcohol, and the balance being deionized water.

[0006] By implementing the above technical solutions, the moisturizer can exert its moisturizing effect, the nano-phospholipids encapsulating the soothing-microecological regulation complex can achieve a soothing effect and regulate the microecology of the intimate area, the carbomer can build a stable gel structure, the emulsifier can promote the fusion of various raw materials to improve the stability of the system, the neutralizer can adjust the pH value of the system to ensure product stability, phenoxyethanol and preservative enhancers work synergistically to exert a broad-spectrum antibacterial effect to ensure product safety, cetearyl alcohol can optimize the skin feel and system stability, and deionized water as a solvent can fully dissolve and disperse the components. The synergistic effect of the components makes the balanced gel have the effects of moisturizing, soothing and microecological regulation, and the system is stable and safe.

[0007] Preferably, the emulsifier is stearyl alcohol polyether-20 or cetyl alcohol polyether-12, the neutralizer is triethanolamine or 2-amino-2-methyl-1-propanol, and the preservative enhancer is ethylhexylglycerin or octyl glycol.

[0008] By setting up the above technical solution, stearyl alcohol polyether-20 or cetyl alcohol polyether-12, as emulsifiers, can promote the full fusion of the oil phase and the aqueous phase in the gel system, improving the system stability and skin feel; triethanolamine or 2-amino-2-methyl-1-propanol, as neutralizers, can adjust the pH value of the system and help the gel matrix form a stable network structure, giving the product good thixotropic properties; ethylhexylglycerin or octyl glycol, as preservative enhancers, can work synergistically with preservatives to exert a broad-spectrum antibacterial effect, enhancing the product's preservative efficacy. The three work together to ensure the system stability, user experience, and safety of the gel product.

[0009] Preferably, the humectant is composed of the following raw materials by weight percentage of the total components: 0.5%-1.5% chitosan-arginine-grafted sodium hyaluronate crosspolymer, 0.2%-0.5% acetylated sodium hyaluronate, 0.3%-0.8% hydrolyzed sodium hyaluronate, 3.0%-7.0% glycerin, 2.0%-5.0% butylene glycol, and 1.5%-3.0% panthenol.

[0010] By setting up the above technical solution, glycerin and butylene glycol can quickly replenish and retain moisture, hydrolyzed sodium hyaluronate can penetrate deep into the mucous membrane to replenish moisture, acetylated sodium hyaluronate can improve skin permeability and long-lasting water-locking ability, chitosan-arginine-grafted sodium hyaluronate crosspolymer can enhance mucous membrane adhesion to prolong moisturizing time, and panthenol can be converted into pantothenic acid to participate in lipid metabolism and strengthen the skin barrier. The components work synergistically to achieve a comprehensive moisturizing effect of deep hydration, long-lasting moisturization and skin barrier strengthening.

[0011] Preferably, the weight-average molecular weight of the chitosan-arginine-grafted sodium hyaluronate crosspolymer is 800-1200 kDa, the weight-average molecular weight of the acetylated sodium hyaluronate is 50-80 kDa, and the number-average molecular weight of the hydrolyzed sodium hyaluronate is 8-9 kDa; the carbomer used is Carbomer 980, which has a weight-average molecular weight of 1500-2500 kDa.

[0012] By setting up the above technical solution, the high molecular weight of chitosan-arginine-grafted sodium hyaluronate cross-linked polymer can form a stable cationic three-dimensional network structure, enhancing mucosal adhesion for long-lasting water retention and assisting in repair; the medium molecular weight of acetylated sodium hyaluronate balances skin permeability and long-lasting water retention, while the small molecular characteristics of hydrolyzed sodium hyaluronate can penetrate deep into the mucosa for hydration and repair. The three form a synergistic effect of molecular weight gradient, comprehensively covering the needs of surface water retention and deep repair; Carbomer 980, with its high molecular weight, constructs a stable gel network, giving the product good thixotropy, providing a stable carrier for the above ingredients to exert their effects, and jointly ensuring the product's moisturizing, repairing efficacy and usage stability.

[0013] Preferably, the raw materials of the chitosan-arginine-grafted sodium hyaluronate crosspolymer, by weight, are as follows: 2.5-4.0 parts sodium hyaluronate, 1.2-2.0 parts chitosan, 0.8-1.5 parts L-arginine, 0.6-1.2 parts 1,4-butanediol diglycidyl ether, and 120-180 parts acetic acid solution with a molar concentration of 0.10-0.15 mol / L; the weight-average molecular weight of sodium hyaluronate is 1000-1500 kDa, and the degree of deacetylation of chitosan is 92%-95%.

[0014] By setting up the above technical solution, chitosan with a high degree of deacetylation and sodium hyaluronate with a weight-average molecular weight of 1000-1500 kDa can be fully dissolved in 0.10-0.15 mol / L acetic acid solution and uniformly mixed with L-arginine. Through the cross-linking effect of 1,4-butanediol diglycidyl ether, a structurally stable chitosan-arginine-grafted sodium hyaluronate cross-linked polymer is formed. This polymer retains the moisturizing properties of sodium hyaluronate and the mucosal adhesion advantages of chitosan, and also endows the mucosal repair activity with the modification of L-arginine, thus achieving synergistic effects of moisturizing, adhesion and repair functions.

[0015] Preferably, the preparation method of the chitosan-arginine-grafted sodium hyaluronate crosslinked polymer includes the following steps: 1) Add chitosan and L-arginine to an acetic acid solution and stir at 250-350 r / min at 35-40℃ for 1.5-2.5 h to form a homogeneous and transparent solution. Then add sodium hyaluronate, heat to 45-50℃ and continue stirring for 2.5-3.5 h. 2) Slowly add 1,4-butanediol diglycidyl ether dropwise to the mixture obtained in 1) at a rate of 1.5-2.5 mL / h, stirring at a speed of 250-350 r / min during the dropwise addition. After the dropwise addition is completed, keep the mixture at 55-60℃ for 5-7 h. After the reaction is completed, adjust the pH of the system to 6.8-7.2 with sodium hydroxide solution with a molar concentration of 0.10-0.15 mol / L, and let it stand for 1.5-2.5 h. 3) Centrifuge the mixture obtained in 2) at a speed of 3500-4500 r / min for 20-25 min, collect the precipitate, wash the precipitate with deionized water 4-6 times, and then dry it under vacuum at 65-75℃ for 9-12 h. After cooling to room temperature, pulverize it and pass it through a 100-120 mesh sieve to obtain the chitosan-arginine-grafted sodium hyaluronate cross-linked polymer.

[0016] By setting up the above technical solution, this preparation method controls the appropriate temperature and stirring speed to fully disperse and fuse chitosan, L-arginine, and sodium hyaluronate. Then, 1,4-butanediol diglycidyl ether is slowly added and kept at a constant temperature for cross-linking reaction, ensuring that the three are effectively grafted and form a stable cross-linked structure. Subsequently, after centrifugation and washing to remove impurities, vacuum drying, and sieving, a high-purity and well-dispersed powdered chitosan-arginine-grafted sodium hyaluronate cross-linked polymer is obtained, ensuring that it can form a cationic three-dimensional network moisturizing film, which has the core functions of mucosal adhesion and repair activity.

[0017] Preferably, the raw materials of the nano-phospholipid-encapsulated soothing-microecological regulation complex are as follows, by weight: 2.0-3.5 parts soybean phospholipids, 2-3 parts anhydrous ethanol, 0.6-1.2 parts bisabolol, 0.5-1.0 parts dipotassium glycyrrhizate, 1.5-2.5 parts probiotic fermentation metabolites, 0.8-1.5 parts polyethylene glycol-400, and 150-200 parts phosphate buffer with a pH of 6.5-7.0. The probiotic fermentation metabolites are a concentrate prepared by fermenting a mixture of Lactobacillus plantarum and Lactobacillus rhamnosus at a mass ratio of 1:1, and then concentrating the resulting fermentation broth. The molar concentration of the phosphate buffer is 0.05-0.10 mol / L.

[0018] By setting up the above technical solution, soybean lecithin, as a carrier raw material, can be dissolved and dispersed in a suitable environment provided by phosphate buffer solution with a pH of 6.5-7.0 and a molar concentration of 0.05-0.10 mol / L, with the help of anhydrous ethanol. Combined with the stabilizing effect of polyethylene glycol-400, it can effectively encapsulate bisabolol, dipotassium glycyrrhizate, and probiotic fermentation metabolites in the form of a concentrate made by fermenting Lactobacillus plantarum and Lactobacillus rhamnosus in a 1:1 mass ratio. This allows the soothing and anti-inflammatory components and the microecological regulating components to be synergistically loaded, ensuring the stability of each functional component and promoting their synergistic effect.

[0019] Preferably, the preparation method of the nano-phospholipid-encapsulated soothing-microecological regulation complex includes the following steps: a. First, add soybean lecithin to anhydrous ethanol and stir at 150-200 r / min for 5-10 min at 40-45℃. Then, slowly inject the mixture into phosphate buffer preheated to 60-65℃, add polyethylene glycol-400 at the same time, and stir at 500-800 r / min for 15-20 min to obtain lecithin dispersion. b. Add bisabolol, dipotassium glycyrrhizate and probiotic fermentation metabolites to the phospholipid dispersion, emulsify under ultrasonic conditions of 40-45℃ and 250-350W for 20-30 minutes, then place the emulsion in a high-pressure homogenizer and homogenize it 4-8 times under a pressure of 60-80MPa to make the emulsion particle size 150-250nm, thus obtaining a homogenized emulsion; c. The homogenized emulsion was filtered through a 0.20-0.22 μm microporous membrane for sterilization, and then freeze-dried at -45℃ to -35℃ and a vacuum of 10-15 Pa for 18-24 h to obtain a nano-phospholipid-encapsulated soothing-microecological regulation complex.

[0020] By setting up the above technical solution, ultrasonic emulsification fully disperses bisabolol, dipotassium glycyrrhizate, and probiotic fermentation metabolites in a system formed by soybean lecithin, anhydrous ethanol, phosphate buffer, and polyethylene glycol-400. High-pressure homogenization process makes the emulsion particle size 150-250nm. After filtration sterilization and freeze-drying, a soothing-microecological regulation complex encapsulated in nano-phospholipids with uniform particle size, high safety, and good stability is finally obtained. This achieves synergistic loading of soothing and microecological regulation components, improves the transdermal penetration efficiency of active ingredients, and ensures their synergistic efficacy.

[0021] This application also discloses a method for preparing a nourishing topical hyaluronic acid balancing gel for intimate areas, comprising the following steps: S1. Preparation of aqueous phase: First, add deionized water to the aqueous phase pot, then slowly add and disperse carbomer 980. Stir at 400-450 r / min for 15-20 min at 25-30℃. Then, raise the temperature to 72-78℃ and stir at 600-800 r / min for 20-25 min. Next, cool the temperature to 50-55℃, add glycerol, butylene glycol and hydrolyzed sodium hyaluronate, and finally stir at 350-450 r / min for 15-20 min to obtain the aqueous phase. S2, Oil phase preparation: Add the emulsifier and cetearyl alcohol to the oil phase pot, heat to 78-82℃, stir at 250-350 r / min for 15-20 min, and then keep warm to 75-78℃ to obtain the oil phase; S3, Emulsion Mixing: Slowly inject the oil phase into the aqueous phase while stirring at a speed of 450-550 r / min for 20-25 min. First, mix the chitosan-arginine-grafted sodium hyaluronate cross-linked polymer with a pH of 6.5-7.0 and a molar concentration of 0.05-0.10 mol / L at a mass-volume ratio of 1 g: 1 mL. Then, inject the mixture into the oil and aqueous phase mixture and continue stirring for 25-35 min. S4. Homogenization process: Place the mixture obtained in S3 in a high-shear homogenizer and homogenize it 2-3 times at a speed of 2500-3500 r / min, each time for 5-8 min; S5, pH adjustment Cool the system obtained from S4 to 52-58℃, slowly add the neutralizing agent dropwise, adjust the pH of the system to 3.8-4.5, then reduce the stirring speed to 250-350 r / min and stir for 15-20 min; S6. Material mixing: The soothing-microecological regulation complex encapsulated in nano-phospholipids was mixed with phosphate buffer solution with a pH of 6.5-7.0 and a molar concentration of 0.05-0.10 mol / L at a mass-to-volume ratio of 1 g: 1.5 mL. The mixture was stirred at 150-200 r / min for 10-15 min to obtain a suspension. The system obtained in S5 was cooled to 38-42℃, and then acetylated sodium hyaluronate and panthenol were added. The mixture was stirred at 250-350 r / min for 15-20 min. The suspension was then added, and the mixture was stirred for another 20-25 min. Finally, the mixture was cooled to 25-30℃, and phenoxyethanol and a preservative enhancer were added. The mixture was stirred for another 10-15 min to obtain a gel. S7, Degassing and Filling The gel was degassed for 10-15 minutes under vacuum conditions of 25-30℃ and -0.09MPa to -0.07MPa, then filled and sealed in a sterile environment to obtain a maintenance-type intimate external hyaluronic acid balancing gel.

[0022] By setting up the above technical solution, the aqueous and oil phases are prepared stepwise and then emulsified, mixed, and homogenized under high shear to ensure that Carbomer 980 is fully integrated with each component, thus constructing a stable gel system. The pH value of the system is adjusted to 3.8-4.5, which is suitable for the weakly acidic environment of the intimate area and is conducive to maintaining the balance of the microecology. The chitosan-arginine-grafted sodium hyaluronate cross-linked polymer is pretreated with phosphate buffer and the soothing-microecological regulation complex is encapsulated with nano-phospholipids to ensure its uniform dispersion and synergistic effect with functional ingredients such as acetylated sodium hyaluronate and panthenol. Vacuum degassing and aseptic filling further ensure the purity and safety of the product, and finally, a stable, synergistic, and suitable-for-intimate care hyaluronic acid balancing gel for external use is obtained.

[0023] Preferably, the system temperature needs to be controlled at 68-72℃ during the homogenization process in step S4.

[0024] By setting up the above technical solution, it is possible to ensure that the emulsifier can play its full role and promote the efficient fusion of the oil phase and the water phase, while maintaining the stability of the gel network structure of Carbomer 980 and avoiding uneven emulsification and damage to gel performance caused by excessively high or low temperatures, thereby ensuring the uniformity and stability of the subsequent product system.

[0025] The beneficial effects of this invention are as follows: Moisturizers provide hydration, nano-phospholipids encapsulate a soothing-microecological regulation complex to achieve a soothing effect and regulate the microecology of the intimate area, carbomer builds a stable gel structure, emulsifiers promote the fusion of various ingredients to enhance system stability, neutralizers adjust the pH value of the system to ensure product stability, phenoxyethanol and preservative enhancers work synergistically to exert a broad-spectrum antibacterial effect to ensure product safety, cetearyl alcohol optimizes the product's feel and system stability, and deionized water serves as a solvent to fully dissolve and disperse the components. The synergistic effect of these components gives the balanced gel moisturizing, soothing, and microecological regulation effects, and the system is stable and has good safety.

[0026] Glycerin and butylene glycol can quickly replenish and lock in moisture, hydrolyzed sodium hyaluronate can penetrate deep into the mucous membrane to replenish moisture, acetylated sodium hyaluronate can improve skin permeability and long-lasting water-locking ability, chitosan-arginine-grafted sodium hyaluronate crosspolymer can enhance mucous membrane adhesion to prolong moisturizing time, and panthenol can be converted into pantothenic acid to participate in lipid metabolism and strengthen the skin barrier. The components work synergistically to achieve a comprehensive moisturizing effect of deep hydration, long-lasting moisturization and skin barrier strengthening.

[0027] Highly deacetylated chitosan and sodium hyaluronate with a weight-average molecular weight of 1000-1500 kDa can be fully dissolved in 0.10-0.15 mol / L acetic acid solution and uniformly mixed with L-arginine. Through cross-linking with 1,4-butanediol diglycidyl ether, a structurally stable chitosan-arginine-grafted sodium hyaluronate cross-linked polymer is formed. This polymer retains the moisturizing properties of sodium hyaluronate and the mucosal adhesion advantages of chitosan, and also endows the mucosal repair activity with the modification of L-arginine, thus achieving synergistic effects of moisturizing, adhesion and repair. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Example 1: This embodiment discloses a maintenance-type intimate topical hyaluronic acid balancing gel, the raw materials of which include: 0.5% chitosan-arginine-grafted sodium hyaluronate crosspolymer with a weight average molecular weight of 800kDa, 0.2% acetylated sodium hyaluronate with a weight average molecular weight of 50kDa, 0.3% hydrolyzed sodium hyaluronate with a number average molecular weight of 8kDa, 3.0% glycerin, 2.0% butylene glycol, 1.5% panthenol, 1.0% nano-phospholipid-encapsulated soothing-microecological regulation complex, 0.2% carbomer 980 with a weight average molecular weight of 1500kDa, 1.0% stearyl alcohol polyether-20, 0.15% triethanolamine, 0.4% phenoxyethanol, 0.1% ethylhexylglycerin, 0.5% cetearyl alcohol, and the balance being deionized water.

[0030] The raw materials of the chitosan-arginine grafted sodium hyaluronate crosspolymer are as follows, by weight: 2.5 parts of sodium hyaluronate with a weight average molecular weight of 1000 kDa, 1.2 parts of chitosan with a degree of deacetylation of 92%, 0.8 parts of L-arginine, 0.6 parts of 1,4-butanediol diglycidyl ether, and 120 parts of acetic acid solution with a molar concentration of 0.10 mol / L.

[0031] The preparation method of chitosan-arginine-grafted sodium hyaluronate crosslinked polymer includes the following steps: 1) Add chitosan and L-arginine to an acetic acid solution and stir at 250 r / min for 1.5 h at 35 °C to form a homogeneous and transparent solution. Then add sodium hyaluronate, heat to 45 °C and continue stirring at 250 r / min for 2.5 h. 2) Add 1,4-butanediol diglycidyl ether slowly dropwise to the mixture obtained in 1) at a rate of 1.5 mL / h, stirring at a speed of 250 r / min during the dropwise addition. After the dropwise addition is completed, keep the mixture at 55℃ for 5 h. After the reaction is completed, adjust the pH of the system to 6.8 with a sodium hydroxide solution with a molar concentration of 0.10 mol / L, and let it stand for 1.5 h. 3) The mixture obtained in 2) was centrifuged at 3500 r / min for 20 min, the precipitate was collected, and the precipitate was washed 4 times with deionized water. Then it was dried under vacuum at 65℃ for 9 h, cooled to room temperature, pulverized and passed through a 100-mesh sieve to obtain chitosan-arginine-grafted sodium hyaluronate cross-linked polymer.

[0032] The components of the nano-phospholipid-encapsulated soothing-microecological regulation complex, by weight, are as follows: 2.0 parts soybean phospholipids, 2 parts anhydrous ethanol, 0.6 parts bisabolol, 0.5 parts dipotassium glycyrrhizate, 1.5 parts probiotic fermentation metabolites, 0.8 parts polyethylene glycol-400, and 150 parts phosphate buffer solution with a pH of 6.5. The probiotic fermentation metabolites are a concentrate prepared by fermenting a mixture of Lactobacillus plantarum and Lactobacillus rhamnosus at a mass ratio of 1:1, and then concentrating the resulting fermentation broth. The phosphate buffer solution has a molar concentration of 0.05 mol / L.

[0033] The preparation method of the soothing-microecological regulation complex encapsulated in nano-phospholipids includes the following steps: a. First, add soybean lecithin to anhydrous ethanol and stir at 150 r / min for 5 min at 40℃. Then, slowly inject the mixed solution into phosphate buffer preheated to 60℃, add polyethylene glycol-400 at the same time, and stir at 500 r / min for 15 min to obtain lecithin dispersion. b. Add bisabolol, dipotassium glycyrrhizate and probiotic fermentation metabolites to the phospholipid dispersion, emulsify for 20 min under ultrasonic conditions at 40℃ and 250W, then place the emulsion in a high-pressure homogenizer and homogenize it 4 times under a pressure of 60MPa to make the emulsion particle size 150-250nm, thus obtaining a homogenized emulsion. c. The homogenized emulsion was filtered through a 0.20 μm microporous membrane for sterilization, and then freeze-dried at -45 °C and 10 Pa for 18 h to obtain a nano-phospholipid-encapsulated soothing-microecological regulation complex.

[0034] This embodiment also discloses a method for preparing a nourishing topical hyaluronic acid balancing gel for intimate areas, comprising the following steps: S1. Preparation of aqueous phase: First, deionized water was added to the aqueous phase pot, and carbomer 980 was slowly added and dispersed. The mixture was stirred at 400 r / min for 15 min at 25 °C, then heated to 72 °C and stirred at 600 r / min for 20 min. The mixture was then cooled to 50 °C, and glycerol, butylene glycol and hydrolyzed sodium hyaluronate were added. Finally, the mixture was stirred at 350 r / min for 15 min to obtain the aqueous phase. S2, Oil phase preparation: Stearyl alcohol polyether-20 and cetearyl alcohol were added to the oil phase pot, heated to 78°C, stirred at 250 r / min for 15 min, and then kept at 75°C to obtain the oil phase. S3, Emulsion Mixing: Slowly inject the oil phase into the aqueous phase while stirring at 450 r / min for 20 min. First, mix the chitosan-arginine-grafted sodium hyaluronate cross-linked polymer with a pH of 6.5 and a molar concentration of 0.05 mol / L phosphate buffer at a mass-volume ratio of 1 g: 1 mL. Then, inject the mixture into the oil and aqueous phase mixture and continue stirring for 25 min. S4. Homogenization process: The mixture obtained from S3 was placed in a high-shear homogenizer and homogenized twice at a speed of 2500 r / min, each time for 5 min, and the system temperature was controlled at 68℃ during the process. S5, pH adjustment The system obtained from S4 was cooled to 52°C, and triethanolamine was slowly added dropwise to adjust the pH of the system to 3.8. Then the stirring speed was reduced to 250 r / min and stirred for 15 min. S6. Material mixing: The soothing-microecological regulation complex encapsulated in nano-phospholipids was mixed with phosphate buffer (pH 6.5, 0.05 mol / L) at a mass-to-volume ratio of 1 g: 1.5 mL and stirred at 150 rpm for 10 min to obtain a suspension. The system obtained in S5 was cooled to 38 °C, and then acetylated sodium hyaluronate and panthenol were added. The mixture was stirred at 250 rpm for 15 min, followed by the addition of the suspension. The mixture was stirred for another 20 min. Finally, the mixture was cooled to 25 °C, and phenoxyethanol and ethylhexylglycerin were added. The mixture was stirred for another 10 min to obtain a gel. S7, Degassing and Filling The gel was degassed for 10 minutes under vacuum conditions of 25℃ and -0.09MPa, then filled and sealed in a sterile environment to obtain a maintenance-type intimate external hyaluronic acid balancing gel.

[0035] Example 2: This embodiment discloses a maintenance-type intimate topical hyaluronic acid balancing gel, the raw materials of which include: 1.5% chitosan-arginine-grafted sodium hyaluronate crosspolymer with a weight average molecular weight of 1200kDa, 0.5% acetylated sodium hyaluronate with a weight average molecular weight of 80kDa, 0.8% hydrolyzed sodium hyaluronate with a number average molecular weight of 9kDa, 7.0% glycerin, 5.0% butylene glycol, 3.0% panthenol, 2.5% nano-phospholipid-encapsulated soothing-microecological regulation complex, 0.4% carbomer 980 with a weight average molecular weight of 2500kDa, 2.5% cetyl alcohol polyether-12, 0.35% triethanolamine, 0.9% phenoxyethanol, 0.4% octyl glycol, 1.8% cetearyl alcohol, and the balance being deionized water.

[0036] The raw materials of the chitosan-arginine grafted sodium hyaluronate crosspolymer are as follows, by weight: 4.0 parts of sodium hyaluronate with a weight average molecular weight of 1500 kDa, 2.0 parts of chitosan with a degree of deacetylation of 95%, 1.5 parts of L-arginine, 1.2 parts of 1,4-butanediol diglycidyl ether, and 180 parts of acetic acid solution with a molar concentration of 0.15 mol / L.

[0037] The preparation method of chitosan-arginine-grafted sodium hyaluronate crosslinked polymer includes the following steps: 1) Add chitosan and L-arginine to an acetic acid solution and stir at 350 r / min for 2.5 h at 40 °C to form a homogeneous and transparent solution. Then add sodium hyaluronate, heat to 50 °C and continue stirring at 350 r / min for 3.5 h. 2) Add 1,4-butanediol diglycidyl ether slowly dropwise to the mixture obtained in 1) at a rate of 2.5 mL / h, stirring at a speed of 350 r / min during the dropwise addition. After the dropwise addition is completed, keep the mixture at 60℃ for 7 h. After the reaction is completed, adjust the pH of the system to 7.2 with a sodium hydroxide solution with a molar concentration of 0.15 mol / L, and let it stand for 2.5 h. 3) The mixture obtained in 2) was centrifuged at 4500 r / min for 25 min, the precipitate was collected, and the precipitate was washed 6 times with deionized water. Then it was dried under vacuum at 75℃ for 12 h, cooled to room temperature, pulverized and passed through a 120 mesh sieve to obtain chitosan-arginine-grafted sodium hyaluronate cross-linked polymer.

[0038] The components of the nano-phospholipid-encapsulated soothing-microecological regulation complex, by weight, are as follows: 3.5 parts soybean phospholipids, 3 parts anhydrous ethanol, 1.2 parts bisabolol, 1.0 part dipotassium glycyrrhizate, 2.5 parts probiotic fermentation metabolites, 1.5 parts polyethylene glycol-400, and 200 parts phosphate buffer solution with a pH of 7.0. The probiotic fermentation metabolites are a concentrate prepared by fermenting a mixture of Lactobacillus plantarum and Lactobacillus rhamnosus at a mass ratio of 1:1, and then concentrating the resulting fermentation broth. The phosphate buffer solution has a molar concentration of 0.10 mol / L.

[0039] The preparation method of the soothing-microecological regulation complex encapsulated in nano-phospholipids includes the following steps: a. First, add soybean lecithin to anhydrous ethanol and stir at 200 r / min for 10 min at 45℃. Then, slowly inject the mixed solution into phosphate buffer preheated to 65℃, add polyethylene glycol-400 at the same time, and stir at 800 r / min for 20 min to obtain lecithin dispersion. b. Add bisabolol, dipotassium glycyrrhizate and probiotic fermentation metabolites to the phospholipid dispersion, emulsify for 30 min under ultrasonic conditions at 45℃ and 350W, then place the emulsion in a high-pressure homogenizer and homogenize it 8 times under a pressure of 80MPa to make the emulsion particle size 150-250nm, thus obtaining a homogenized emulsion. c. The homogenized emulsion was filtered through a 0.22 μm microporous membrane for sterilization, and then freeze-dried at -35 °C and 15 Pa for 24 h to obtain a nano-phospholipid-encapsulated soothing-microecological regulation complex.

[0040] This embodiment also discloses a method for preparing a nourishing topical hyaluronic acid balancing gel for intimate areas, comprising the following steps: S1. Preparation of aqueous phase: First, deionized water was added to the aqueous phase pot, and carbomer 980 was slowly added and dispersed. After stirring at 450 r / min for 20 min at 30 °C, the temperature was raised to 78 °C and then kept at 800 r / min for 25 min. After cooling to 55 °C, glycerol, butylene glycol and hydrolyzed sodium hyaluronate were added. Finally, the mixture was stirred at 450 r / min for 20 min to obtain the aqueous phase. S2, Oil phase preparation: Cetyl alcohol polyether-12 and cetearyl alcohol were added to the oil phase pot, heated to 82°C, stirred at 350 r / min for 20 min, and then kept at 78°C to obtain the oil phase. S3, Emulsion Mixing: Slowly inject the oil phase into the aqueous phase while stirring at 550 r / min for 25 min. First, mix the chitosan-arginine-grafted sodium hyaluronate cross-linked polymer with a pH of 7.0 and a molar concentration of 0.10 mol / L phosphate buffer at a mass-volume ratio of 1 g: 1 mL. Then, inject the mixture into the oil and aqueous phase mixture and continue stirring for 35 min. S4. Homogenization process: The mixture obtained from S3 was placed in a high-shear homogenizer and homogenized three times at a speed of 3500 r / min, each time for 8 min, during which the system temperature was controlled at 72℃. S5, pH adjustment The system obtained from S4 was cooled to 58℃, and triethanolamine was slowly added dropwise to adjust the pH of the system to 4.5. Then the stirring speed was reduced to 350 r / min and stirred for 20 min. S6. Material mixing: The soothing-microecological regulation complex encapsulated in nano-phospholipids was mixed with phosphate buffer (pH 7.0, 0.10 mol / L) at a mass-to-volume ratio of 1 g: 1.5 mL and stirred at 200 rpm for 15 min to obtain a suspension. The system obtained in S5 was cooled to 42 °C, and then acetylated sodium hyaluronate and panthenol were added. The mixture was stirred at 350 rpm for 20 min, followed by the addition of the suspension. The mixture was stirred for another 25 min. Finally, the mixture was cooled to 30 °C, and phenoxyethanol and octyl glycol were added. The mixture was stirred for another 15 min to obtain a gel. S7, Degassing and Filling The gel was degassed for 15 minutes under vacuum conditions of 30℃ and -0.07MPa, then filled and sealed in a sterile environment to obtain a maintenance-type intimate external hyaluronic acid balancing gel.

[0041] Example 3: This embodiment discloses a maintenance-type intimate topical hyaluronic acid balancing gel, the raw materials of which include: 1.0% of chitosan-arginine-grafted sodium hyaluronate crosspolymer with a weight average molecular weight of 1000kDa, 0.35% of acetylated sodium hyaluronate with a weight average molecular weight of 65kDa, 0.5% of hydrolyzed sodium hyaluronate with a number average molecular weight of 8.5kDa, 5.5% of glycerin, 3.5% of butylene glycol, 2.2% of panthenol, 1.8% of nano-phospholipid-encapsulated soothing-microecological regulation complex, 0.3% of carbomer 980 with a weight average molecular weight of 2000kDa, 1.8% of stearyl alcohol polyether-20, 0.25% of 2-amino-2-methyl-1-propanol, 0.65% of phenoxyethanol, 0.3% of ethylhexylglycerin, 1.1% of cetearyl alcohol, and the balance being deionized water.

[0042] The raw materials of the chitosan-arginine grafted sodium hyaluronate crosspolymer are as follows, by weight: 3.2 parts of sodium hyaluronate with a weight average molecular weight of 1300 kDa, 1.6 parts of chitosan with a degree of deacetylation of 93.5%, 1.1 parts of L-arginine, 0.9 parts of 1,4-butanediol diglycidyl ether, and 150 parts of acetic acid solution with a molar concentration of 0.12 mol / L.

[0043] The preparation method of chitosan-arginine-grafted sodium hyaluronate crosslinked polymer includes the following steps: 1) Add chitosan and L-arginine to an acetic acid solution and stir at 300 r / min for 2 h at 37 °C to form a homogeneous and transparent solution. Then add sodium hyaluronate, raise the temperature to 47 °C and continue stirring at 300 r / min for 3 h. 2) Add 1,4-butanediol diglycidyl ether slowly dropwise to the mixture obtained in 1) at a rate of 2 mL / h, stirring at a speed of 300 r / min during the dropwise addition. After the dropwise addition is completed, keep the mixture at 57℃ for 6 h. After the reaction is completed, adjust the pH of the system to 7.0 with sodium hydroxide solution with a molar concentration of 0.12 mol / L, and let it stand for 2 h. 3) The mixture obtained in 2) was centrifuged at 4000 r / min for 22 min, the precipitate was collected, and the precipitate was washed 5 times with deionized water. Then it was dried under vacuum at 70℃ for 11 h, cooled to room temperature, pulverized and passed through a 110 mesh sieve to obtain chitosan-arginine-grafted sodium hyaluronate cross-linked polymer.

[0044] The components of the nano-phospholipid-encapsulated soothing-microecological regulation complex, by weight, are as follows: 2.5 parts soybean phospholipid, 2.5 parts anhydrous ethanol, 0.9 parts bisabolol, 0.7 parts dipotassium glycyrrhizate, 2.0 parts probiotic fermentation metabolites, 1.1 parts polyethylene glycol-400, and 175 parts phosphate buffer solution with a pH of 7.0. The probiotic fermentation metabolites are a concentrate prepared by fermenting a mixture of Lactobacillus plantarum and Lactobacillus rhamnosus at a mass ratio of 1:1, and then concentrating the resulting fermentation broth. The phosphate buffer solution has a molar concentration of 0.07 mol / L.

[0045] The preparation method of the soothing-microecological regulation complex encapsulated in nano-phospholipids includes the following steps: a. First, add soybean lecithin to anhydrous ethanol and stir at 175 r / min for 7 min at 42℃. Then, slowly inject the mixed solution into phosphate buffer preheated to 62℃, add polyethylene glycol-400 at the same time, and stir at 650 r / min for 17 min to obtain lecithin dispersion. b. Add bisabolol, dipotassium glycyrrhizate and probiotic fermentation metabolites to the phospholipid dispersion, emulsify for 25 min under ultrasonic conditions at 42℃ and 300W, then place the emulsion in a high-pressure homogenizer and homogenize it 6 times under a pressure of 70MPa to make the emulsion particle size 150-250nm, thus obtaining a homogenized emulsion. c. The homogenized emulsion was filtered through a 0.21 μm microporous membrane for sterilization, and then freeze-dried at -40 °C and 12 Pa for 21 h to obtain a nano-phospholipid-encapsulated soothing-microecological regulation complex.

[0046] This embodiment also discloses a method for preparing a nourishing topical hyaluronic acid balancing gel for intimate areas, comprising the following steps: S1. Preparation of aqueous phase: First, deionized water was added to the aqueous phase pot, and carbomer 980 was slowly added and dispersed. The mixture was stirred at 425 r / min for 17 min at 27 °C, then heated to 75 °C and stirred at 700 r / min for 22 min. The mixture was then cooled to 52 °C, and glycerol, butylene glycol and hydrolyzed sodium hyaluronate were added. Finally, the mixture was stirred at 400 r / min for 17 min to obtain the aqueous phase. S2, Oil phase preparation: Stearyl alcohol polyether-20 and cetearyl alcohol were added to the oil phase pot, heated to 80°C, stirred at 300 r / min for 17 min, and then kept at 77°C to obtain the oil phase. S3, Emulsion Mixing: Slowly inject the oil phase into the aqueous phase while stirring at 500 r / min for 22 min. First, mix the chitosan-arginine-grafted sodium hyaluronate cross-linked polymer with a pH of 7.0 and a molar concentration of 0.07 mol / L phosphate buffer at a mass-volume ratio of 1 g: 1 mL. Then, inject the mixture into the oil and aqueous phase mixture and continue stirring for 30 min. S4. Homogenization process: The mixture obtained from S3 was placed in a high-shear homogenizer and homogenized three times at a speed of 3000 r / min, each time for 6 min, during which the system temperature was controlled at 70℃. S5, pH adjustment The system obtained in S4 was cooled to 55℃, and 2-amino-2-methyl-1-propanol was slowly added dropwise to adjust the pH of the system to 4.0. Then the stirring speed was reduced to 300 r / min and stirred for 17 min. S6. Material mixing: The soothing-microecological regulation complex encapsulated in nano-phospholipids was mixed with phosphate buffer (pH 7.0, molar concentration 0.07 mol / L) at a mass-to-volume ratio of 1 g: 1.5 mL and stirred at 175 r / min for 12 min to obtain a suspension. The system obtained in S5 was cooled to 40 °C, and then acetylated sodium hyaluronate and panthenol were added. The mixture was stirred at 300 r / min for 17 min, followed by the addition of the suspension. The mixture was stirred for another 22 min. Finally, the mixture was cooled to 27 °C, and phenoxyethanol and ethylhexylglycerin were added. The mixture was stirred for another 12 min to obtain a gel. S7, Degassing and Filling The gel was degassed for 12 minutes under vacuum conditions of 27℃ and -0.08MPa, then filled and sealed in a sterile environment to obtain a maintenance-type intimate external hyaluronic acid balancing gel.

[0047] Comparative Example 1: A maintenance-type intimate external hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that chitosan-arginine grafted sodium hyaluronate cross-linked polymer is not added.

[0048] Comparative Example 2: A maintenance-type intimate external hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that the soothing-microecological regulation complex encapsulated with nano-phospholipids is not added.

[0049] Comparative Example 3: A maintenance-type intimate topical hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that ordinary sodium hyaluronate cross-linked polymer (without arginine grafting) is used instead of chitosan-arginine grafted sodium hyaluronate cross-linked polymer.

[0050] Comparative Example 4: A maintenance-type intimate external hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that a single probiotic ferment replaces the nano-phospholipids to encapsulate the soothing-microecological regulation complex (which does not contain bisabolol or dipotassium glycyrrhizate).

[0051] Comparative Example 5: A maintenance-type hyaluronic acid balancing gel for intimate use and its preparation method are disclosed. The only difference between this gel and Example 3 is that panthenol is not added.

[0052] Comparative Example 6: A maintenance-type intimate external hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that no acetylated sodium hyaluronate is added.

[0053] Comparative Example 7: A maintenance-type intimate topical hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that stearyl alcohol polyether-10 is used instead of stearyl alcohol polyether-20.

[0054] Comparative Example 8: A maintenance-type intimate external hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that L-arginine was not added during the preparation of the chitosan-arginine grafted sodium hyaluronate crosslinked polymer.

[0055] Comparative Example 9: A maintenance-type intimate topical hyaluronic acid balancing gel and its preparation method are disclosed. The only difference between this gel and Example 3 is that high-pressure homogenization was not performed during the preparation of the nano-phospholipid-encapsulated soothing-microecological regulation complex.

[0056] Comparative Example 10: A maintenance-type hyaluronic acid balancing gel for intimate use and its preparation method are disclosed. The only difference between this gel and Example 3 is that no preservative enhancer (ethylhexylglycerin) is added.

[0057] The balancing gels obtained in Examples 1-3 and Comparative Examples 1-10 were tested for 12-hour moisturizing rate, mucosal repair rate (7 days), erythema reduction rate (4 hours), inhibition zone diameter, TEWL reduction rate, mucosal irritation index, pH stability time, and sensory score. The test methods and reference standards are as follows: 1. 12-hour moisturizing rate test Following the national standard GB / T 35914-2018 "Guideline for Evaluation of Moisturizing Efficacy of Cosmetics", a skin moisture content meter (Corneometer CM825) was used for testing. Twenty healthy volunteers (aged 25-45, half male and half female) were selected. A 5cm × 5cm test area was selected on the inner arm. After cleansing, the area was acclimatized for 30 minutes in a constant temperature and humidity chamber (25℃, 50% relative humidity) to determine the initial skin moisture content (C0). A sample was applied (at a dosage of 2 mg / cm²). 2 After that, the moisture content (C) was measured 12 hours later. 12 According to the formula "12h moisturizing rate (%) = (C)", the 12h moisturizing rate (%) is calculated as follows: 12 The result is calculated as "-C0) / C0×100%", and the average of the 20 volunteers is taken as the final result.

[0058] 2. Mucosal repair rate (7 days) test Referring to the industry standard "QB / T 5482-2020 Evaluation Method for Skin Repair Efficacy of Cosmetics", tissue sectioning combined with ImageJ software analysis was used. An in vitro rabbit vaginal mucosal epithelial cell injury model was constructed, divided into an experimental group and a control group (treated with physiological saline); the experimental group received daily application of samples (at a dose of 2 mg / cm³). 2The control group was coated with an equal amount of physiological saline and cultured for 7 days. Cell samples were collected, paraffin sections were prepared, stained with hematoxylin and eosin (HE), and observed under a microscope. The ratio of the repaired area to the total damaged area was analyzed using ImageJ software to calculate the mucosal repair rate.

[0059] 3. Erythema fading rate (4h) detection Referring to the industry standard "QB / T 4964-2016 Evaluation Method for Soothing Efficacy of Cosmetics", a capsaicin-induced erythema test was used. Fifteen healthy volunteers were selected, and a 3cm × 3cm test area was selected on the back. A 1% capsaicin solution was applied to induce erythema. After 30 minutes, the initial erythema value was measured (a0 value measured using a colorimeter). The sample was then applied (at a dosage of 2 mg / cm²). 2 Four hours later, the a4 value was measured again and calculated according to the formula "Erythema fading rate (%) = (a0-a4) / a0×100%".

[0060] 4. Detection of inhibition zone diameter Referring to the national standard "QB / T 4348-2012 Evaluation Method for Antibacterial Effect in Cosmetics", the agar diffusion method was used. *Escherichia coli* and *Staphylococcus aureus* were separately inoculated onto nutrient agar medium to prepare bacterial suspensions (10... 6 CFU / mL); 0.1 mL of sample was added to a sterile Oxford cup, placed on the surface of the culture medium, and incubated at 37°C for 24 h. The diameter of the inhibition zone was measured (mm, the result is the average diameter of the inhibition zone for the two strains).

[0061] 5. Other testing items Transdermal water loss (TEWL) reduction rate: Measured using a Tewameter TM300 transdermal water loss meter, in accordance with international standard ISO 15196:2003, "Guideline for calibration and use of skin moisture loss measuring instruments". TEWL reduction rate (%) = (TEWL0 - TEWL1) / TEWL0 × 100%, where TEWL0 is the transdermal water loss before application, and TEWL1 is the water loss 12 hours after application.

[0062] Mucosal irritation index: Calculated by applying patch test scores from 30 healthy volunteers, in accordance with the national standard GB / T 35919-2018 "Test Method for Mucosal Irritation of Cosmetics".

[0063] pH stabilization time: Mix the product with artificial vaginal solution at a volume ratio of 1:1, place in a constant temperature environment of 37℃, and measure the pH value every 2 hours using a precision pH meter (accuracy ±0.01). Record the total time for the pH to remain in the range of 4.0-4.5.

[0064] Sensory evaluation: A panel of 10 experts rated the product's spreadability, stickiness, and absorption speed on a scale of 1 to 5, and the average score was taken. 1 point represents poor spreadability / strong stickiness / slow absorption, and 5 points represents excellent spreadability / no stickiness / fast absorption.

[0065] The results are shown in Table 1.

[0066] Table 1 Performance parameters of the equilibrium gels obtained in Examples 1-3 and Comparative Examples 1-10 Group 12-hour moisturizing rate Mucosal repair rate (7 days) Erythema regression rate (4h) Diameter of the inhibition zone (mm) TEWL reduction rate Mucosal irritation index pH stabilization time (h) Sensory rating (points) Example 1 75.8 82.3 78.5 24.6 58.2 0.07 60 4.3 Example 2 83.5 87.6 83.2 26.8 65.4 0.06 68 4.6 Example 3 91.2 93.5 88.7 29.5 72.8 0.04 72 4.9 Comparative Example 1 42.6 65.8 62.3 20.1 35.6 0.08 52 3.5 Comparative Example 2 56.3 70.2 58.7 15.3 42.8 0.09 36 3.7 Comparative Example 3 63.5 75.4 70.1 22.4 48.5 0.07 55 3.9 Comparative Example 4 68.7 78.6 65.4 18.7 51.2 0.08 42 4.0 Comparative Example 5 85.6 76.3 82.5 27.3 56.4 0.05 66 4.2 Comparative Example 6 72.4 80.5 81.3 26.9 53.7 0.06 63 4.1 Comparative Example 7 70.2 82.1 79.6 25.8 50.3 0.07 61 3.6 Comparative Example 8 65.8 72.4 73.2 23.5 45.2 0.07 54 3.7 Comparative Example 9 71.3 79.2 74.6 21.8 52.6 0.06 48 4.0 Comparative Example 10 88.7 90.3 85.4 22.6 68.5 0.12 69 4.5 Using Example 3 as the control group, the performance differences and causes of Comparative Examples 1-10 are analyzed as follows: Comparative Example 1 (without chitosan-arginine-grafted sodium hyaluronate crosspolymer): 12-hour moisturizing rate decreased from 91.2% to 42.6%, a change of 53.3%; mucosal repair rate decreased from 93.5% to 65.8%, a change of 29.6%; TEWL reduction rate decreased from 72.8% to 35.6%, a change of 51.1%. The reason is that without this cationic core component (chitosan-arginine-grafted sodium hyaluronate crosspolymer), the system cannot form a three-dimensional network moisturizing film, resulting in a significant decrease in mucosal adhesion. This prevents both long-term moisture retention and the initiation of mucosal repair signal transduction through the arginine-mediated nitric oxide synthesis pathway, leading to a significant weakening of both moisturizing and repair functions.

[0067] Comparative Example 2 (without nano-phospholipid-encapsulated soothing-microecological regulation complex): Erythema reduction rate decreased from 88.7% to 58.7%, a change of 33.8%; inhibition zone diameter decreased from 29.5 mm to 15.3 mm, a change of 48.1%; pH stabilization time shortened from 72 h to 36 h, a change of 50.0%. This was mainly due to the lack of nano-phospholipid carriers, which reduced the transdermal penetration efficiency of bisabolol and dipotassium glycyrrhizate, preventing the anti-inflammatory components from effectively reaching the deep mucosa; at the same time, the absence of the complex fermentation metabolites of Lactobacillus plantarum and Lactobacillus rhamnosus made it impossible to inhibit the proliferation of harmful bacteria and maintain the weakly acidic environment of the intimate area, resulting in the loss of the synergistic effect of microecological regulation and soothing.

[0068] Comparative Example 3 (using ordinary sodium hyaluronate cross-linked polymer instead of chitosan-arginine-grafted sodium hyaluronate cross-linked polymer): 12-hour moisturizing rate decreased from 91.2% to 63.5%, a change of 30.4%; TEWL reduction rate decreased from 72.8% to 48.5%, a change of 33.4%; mucosal repair rate decreased from 93.5% to 75.4%, a change of 19.4%. Ordinary sodium hyaluronate cross-linked polymer lacks L-arginine grafting modification, thus losing both the mucosal adhesion advantage brought by its cationic properties and the activating effect of arginine on repair pathways. It cannot form a synergistic "adhesion-slow release-repair" system with other moisturizing and repairing ingredients in the system, resulting in a simultaneous decrease in both moisturizing durability and repair efficiency.

[0069] Comparative Example 4 (using a single probiotic ferment to replace nano-phospholipids to encapsulate the soothing-microecological regulation complex (excluding bisabolol and dipotassium glycyrrhizate)): The diameter of the inhibition zone decreased from 29.5 mm to 18.7 mm, a change of 36.6%; the erythema reduction rate decreased from 88.7% to 65.4%, a change of 26.3%; and the pH stabilization time shortened from 72 h to 42 h, a change of 41.7%. The antibacterial spectrum of the single probiotic ferment was narrower than that of the two-probiotic complex system, and it could not form a "antibacterial-anti-inflammatory" synergy with the soothing ingredients, resulting in a double weakening of the microecological regulation and soothing effects.

[0070] Comparative Example 5 (without panthenol): Mucosal repair rate decreased from 93.5% to 76.3%, a change of 18.3%; TEWL reduction rate decreased from 72.8% to 56.4%, a change of 22.5%. Panthenol, as a key precursor of lipid metabolism, can be converted into pantothenic acid to participate in skin barrier lipid synthesis. Its absence leads to an insufficient microenvironment for mucosal barrier repair, preventing the formation of a "structural support-lipid replenishment" repair synergy with chitosan-arginine-grafted sodium hyaluronate crosspolymer. Although the moisturizing function is less affected, the barrier repair efficiency is significantly reduced.

[0071] Comparative Example 6 (without acetylated sodium hyaluronate): 12-hour hydration rate decreased from 91.2% to 72.4%, a change of 20.6%; TEWL reduction rate decreased from 72.8% to 53.7%, a change of 26.2%; mucosal repair rate decreased from 93.5% to 80.5%, a change of 13.9%. Acetylated sodium hyaluronate has excellent skin permeability and long-lasting water-locking ability. Its absence leads to insufficient deep moisturizing ability of the system and also prevents other repair ingredients from penetrating to damaged mucosal areas, thus affecting the overall repair efficacy.

[0072] Comparative Example 7 (using stearyl alcohol polyether-10 instead of stearyl alcohol polyether-20): Sensory score decreased from 4.9 to 3.6, a change of 26.5%; TEWL reduction rate decreased from 72.8% to 50.3%, a change of 31.7%; 12-hour moisturizing rate decreased from 91.2% to 70.2%, a change of 23.0%. Steearyl alcohol polyether-20 has good compatibility with carbomer 980 and can form a stable emulsion-gel complex system, while stearyl alcohol polyether-10 has poor compatibility, resulting in decreased system stability and reduced stability of the gel system and mucosal adhesion time. The hydrophilic-lipophilic balance (HLB) value of stearyl alcohol polyether-10 is about 13-14, and the difference in compatibility with carbomer 980 (HLB≈24) prevents the formation of liquid crystal structure, resulting in a worse gel feel, a shorter residence time of active ingredients on the mucosal surface, and a simultaneous decrease in moisturizing and barrier repair effects.

[0073] Comparative Example 8 (prepared without L-arginine in the chitosan-arginine-grafted sodium hyaluronate crosslinked polymer): The mucosal repair rate decreased from 93.5% to 72.4%, a change of 22.6%; the 12-hour moisturizing rate decreased from 91.2% to 65.8%, a change of 27.8%; and the TEWL reduction rate decreased from 72.8% to 45.2%, a change of 37.9%. The absence of L-arginine reduced the number of polymer cationic sites, significantly decreased mucosal adhesion, and prevented the activation of the repair signaling pathway by promoting nitric oxide synthesis. This resulted in the breakdown of the synergistic effect of "moisturizing film formation - repair signal initiation," significantly reducing both moisturizing durability and repair efficiency.

[0074] Comparative Example 9 (Preparation of the soothing-microecological regulation complex encapsulated in nano-phospholipids without high-pressure homogenization): The diameter of the inhibition zone decreased from 29.5 mm to 21.8 mm, a change of 26.1%; the erythema reduction rate decreased from 88.7% to 74.6%, a change of 15.9%; and the pH stabilization time shortened from 72 h to 48 h, a change of 33.3%. High-pressure homogenization is a key process to ensure the uniformity of the nano-phospholipid carrier particle size. The absence of this step leads to uneven carrier particle size distribution, decreased transdermal penetration efficiency, and inconsistent release rates of functional components, failing to form the synergistic effect of "anti-inflammatory components-probiotic metabolites," thus weakening the soothing and microecological regulation effects.

[0075] Comparative Example 10 (without added preservative enhancer (ethylhexylglycerin)): The diameter of the inhibition zone decreased from 29.5 mm to 22.6 mm, a change of 23.4%; the mucosal irritation index increased from 0.04 to 0.12, a change of 200%. Ethylhexylglycerin and phenoxyethanol have a synergistic preservative effect. Its absence leads to a narrowing of the antibacterial spectrum and a decrease in antibacterial strength. To ensure the preservative effect of the product, ethylhexylglycerin can reduce the mucosal irritation of phenoxyethanol. Its absence directly manifests the irritant effect of phenoxyethanol, thus leading to an increase in the mucosal irritation index. At the same time, due to insufficient antibacterial ability, the auxiliary stabilizing effect on the intimate microecology is weakened, but the core functional components are not affected, so the decrease in indicators such as moisturizing and repair is relatively small.

[0076] In summary, the chitosan-arginine-grafted sodium hyaluronate crosspolymer enhances long-lasting moisturizing and mucosal repair capabilities, while the nano-phospholipid-encapsulated soothing-microecological regulation complex improves its soothing and anti-inflammatory effects and microecological stability. Acetylated sodium hyaluronate and panthenol synergistically enhance repair efficacy, and the emulsifier and gel matrix optimize product stability and skin feel. The synergistic effect of these components significantly improves the moisturizing, repairing, soothing, and microecological regulation properties of the balanced gel.

[0077] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A leave-on intimate topical hyaluronic acid balancing gel, characterized in that, The composition raw materials include, in percentage by weight: moisturizing agent 7.5%-17.8%, nano-phospholipid-coated soothing-microecological regulating complex 1.0%-2.5%, carbomer 0.2%-0.4%, emulsifier 1.0%-2.5%, neutralizing agent 0.15%-0.35%, phenoxyethanol 0.4%-0.9%, preservative enhancer 0.1%-0.4%, cetyl stearyl alcohol 0.5%-1.8%, and the balance being deionized water.

2. The emollient intimate external use hyaluronan balancing gel of claim 1, wherein, The emulsifier is stearyl alcohol polyether-20 or cetyl alcohol polyether-12, the neutralizing agent is triethanolamine or 2-amino-2-methyl-1-propanol, and the preservative enhancer is ethylhexylglycerin or caprylyl glycol.

3. The emollient intimate external use hyaluronan balancing gel of claim 1, wherein, The moisturizing agent is composed of the following raw materials in percentage by weight of the total components: chitosan-arginine grafted sodium hyaluronate cross-linked polymer 0.5%-1.5%, acetylated sodium hyaluronate 0.2%-0.5%, hydrolyzed sodium hyaluronate 0.3%-0.8%, glycerol 3.0%-7.0%, butanediol 2.0%-5.0%, and panthenol 1.5%-3.0%.

4. The emollient intimate external use hyaluronan balancing gel of claim 3, wherein, The weight average molecular weight of the chitosan-arginine grafted sodium hyaluronate cross-linked polymer is 800-1200 kDa, the weight average molecular weight of the acetylated sodium hyaluronate is 50-80 kDa, and the number average molecular weight of the hydrolyzed sodium hyaluronate is 8-9 kDa; the carbomer is carbomer 980, and the weight average molecular weight thereof is 1500-2500 kDa.

5. The emollient intimate external use hyaluronic acid balancing gel according to claim 3, characterized in that, The composition raw materials of the chitosan-arginine grafted sodium hyaluronate cross-linked polymer are as follows in parts by weight: sodium hyaluronate 2.5-4.0 parts, chitosan 1.2-2.0 parts, L-arginine 0.8-1.5 parts, 1,4-butanediol diglycidyl ether 0.6-1.2 parts, and acetic acid solution with a molar concentration of 0.10-0.15 mol / L 120-180 parts; the weight average molecular weight of the sodium hyaluronate is 1000-1500 kDa, and the degree of deacetylation of the chitosan is 92%-95%.

6. The emollient intimate external use hyaluronic acid balancing gel according to claim 5, characterized in that, The preparation method of the chitosan-arginine grafted sodium hyaluronate cross-linked polymer comprises the following steps: 1) chitosan and L-arginine are added into an acetic acid solution, stirred at a speed of 250-350 r / min at 35-40 ℃ for 1.5-2.5 h to form a uniform transparent solution, and then sodium hyaluronate is added, the temperature is raised to 45-50 ℃, and stirring is continued for 2.5-3.5 h; 2) 1,4-butanediol diglycidyl ether is slowly added to the mixture obtained in 1) at a speed of 1.5-2.5 mL / h, stirring is carried out at a speed of 250-350 r / min during the adding process, after the adding is completed, the reaction is carried out at 55-60 ℃ for 5-7 h, after the reaction is completed, the pH value of the system is adjusted to 6.8-7.2 by using a sodium hydroxide solution with a molar concentration of 0.10-0.15 mol / L, and the system is left to stand for 1.5-2.5 h; 3) centrifugal separation of the mixture obtained in 2) at a speed of 3500-4500 r / min for 20-25 min, collection of the precipitate, washing of the precipitate with deionized water for 4-6 times, and then drying under vacuum at 65-75℃ for 9-12 h, crushing after cooling to room temperature and passing through a 100-120 mesh sieve to obtain the chitosan-arginine grafted sodium hyaluronate cross-linked polymer.

7. The emollient intimate external use hyaluronic acid balancing gel of claim 3, wherein, The composition of the nano-phospholipid-coated soothing-microecological regulation complex is as follows in terms of weight parts: soybean phospholipid 2.0-3.5 parts, anhydrous ethanol 2-3 parts, farnesol 0.6-1.2 parts, disodium glycyrrhizinate 0.5-1.0 parts, probiotic fermentation metabolite 1.5-2.5 parts, polyethylene glycol-400 0.8-1.5 parts, phosphate buffer solution with a pH value of 6.5-7.0 150-200 parts, and the probiotic fermentation metabolite is a concentrate prepared from a fermentation broth obtained by fermenting a mixture of Lactobacillus plantarum and Lactobacillus rhamnosus at a mass ratio of 1:1, and the molar concentration of the phosphate buffer solution is 0.05-0.10 mol / L.

8. The emollient intimate external use hyaluronic acid balancing gel according to claim 7, characterized in that, The preparation method of the nano-phospholipid-coated soothing-microecological regulation complex comprises the following steps: a. First, the soybean phospholipid is added to anhydrous ethanol, and stirred at a speed of 150-200 r / min at 40-45℃ for 5-10 min, and then the mixed solution is slowly injected into the preheated phosphate buffer solution at 60-65℃, and polyethylene glycol-400 is added, and stirred at a speed of 500-800 r / min for 15-20 min to obtain a phospholipid dispersion; b. Farnesol, disodium glycyrrhizinate and probiotic fermentation metabolite are added to the phospholipid dispersion, and emulsified under ultrasonic conditions at a temperature of 40-45℃ and a power of 250-350W for 20-30 min, and then the emulsion is placed in a high-pressure homogenizer and homogenized at a pressure of 60-80 MPa for 4-8 cycles to obtain an emulsion with a particle size of 150-250 nm; c. The homogenized emulsion is filtered through a 0.20-0.22 μm microporous filter to remove bacteria, and then freeze-dried under the conditions of -45℃ to -35℃ and a vacuum degree of 10-15 Pa for 18-24 h to obtain the nano-phospholipid-coated soothing-microecological regulation complex.

9. A method of preparing the maintenance type private use hyaluronic acid balancing gel according to any one of claims 3-8, characterized by, Comprising the following steps: S1, water phase preparation: First, deionized water is added to the water phase kettle, and carbomer 980 is slowly added and dispersed, and stirred at a speed of 400-450 r / min at 25-30℃ for 15-20 min, and then heated to 72-78℃, and stirred at a speed of 600-800 r / min for 20-25 min, and then cooled to 50-55℃, and glycerol, butanediol and sodium hyaluronate are added, and finally stirred at a speed of 350-450 r / min for 15-20 min to obtain the water phase; S2, oil phase preparation: The emulsifier and cetylstearyl alcohol are added to the oil phase kettle, heated to 78-82℃, and stirred at a speed of 250-350 r / min for 15-20 min, and then kept at 75-78℃ to obtain the oil phase; S3, emulsion mixing: Slowly inject the oil phase into the water phase, stirring at a speed of 450-550 r / min, and continue stirring for 20-25 min; first mix the chitosan-arginine grafted sodium hyaluronate cross-linked polymer with the phosphate buffer solution with a pH value of 6.5-7.0 and a molar concentration of 0.05-0.10 mol / L at a mass-volume ratio of 1 g:1 mL, and then inject the mixed solution into the mixed system of the oil phase and the water phase, and continue stirring for 25-35 min; S4, homogenization treatment: Put the mixed solution obtained in S3 into a high-shear homogenizer, and homogenize at a speed of 2500-3500 r / min for 2-3 times, each time for 5-8 min; S5, pH adjustment Cool the system obtained in S4 to 52-58℃, slowly add the neutralizing agent, adjust the pH value of the system to 3.8-4.5, then reduce the stirring speed to 250-350 r / min, and stir for 15-20 min; S6, material mixing: Mix the nano-phospholipid-wrapped soothing-microecological regulation complex with the phosphate buffer solution with a pH value of 6.5-7.0 and a molar concentration of 0.05-0.10 mol / L at a mass-volume ratio of 1 g:1.5 mL, stir at a speed of 150-200 r / min for 10-15 min, and obtain a suspension; cool the system obtained in S5 to 38-42℃, then add acetylated sodium hyaluronate and panthenol, stir at a speed of 250-350 r / min for 15-20 min, then add the suspension, continue stirring for 20-25 min, finally, cool to 25-30℃, add phenoxyethanol and preservative enhancer, continue stirring for 10-15 min, and obtain a gel; S7, defoaming and filling Defoam the gel at 25-30℃ under vacuum conditions of-0.09 MPa to-0.07 MPa for 10-15 min, fill in a sterile environment, and seal and package to obtain the maintenance type private use hyaluronic acid balance gel.

10. The method of making the emollient intimate external use hyaluronan balancing gel of claim 9, wherein, The temperature of the system needs to be controlled at 68-72℃ during the homogenization process of step S4.