A multi-stage release cooling composition and a method of making the same

Abstract

This invention discloses a multi-stage cooling composition and its preparation method, belonging to the technical field of daily chemical and cosmetic compositions. The composition comprises an immediate-release cooling agent, encapsulated sustained-release cooling particles, microencapsulated delayed-release cooling particles, a polyol, a humectant, an emulsifying dispersant, a film-forming regulator, a thickening and stabilizing agent, a pH adjuster, a preservative, and deionized water. The microencapsulated delayed-release cooling particles have an encapsulation adsorption composite core, a calcium alginate ion gel inner shell, a chitosan-phytate polyelectrolyte intermediate shell, and an ethyl cellulose-silica hydrophobic outer shell. This composition can achieve rapid cooling, mid-stage sustained release, and sustained cooling in the later stages, reducing the sudden release, volatilization loss, and irritation of the cooling agent, and improving storage stability and dispersion stability.

Description

Technical Field

[0001] This invention relates to the field of daily chemical products and cosmetic compositions, specifically to a multi-stage cooling composition and its preparation method. Background Technology

[0002] Cooling compositions are widely used in cosmetics, personal care products, cooling gels, body lotions, oral care products, and other topical daily chemical products. Existing cooling systems typically use cooling agents such as menthol, menthyl lactate, WS-3, WS-23, and menthone glycerol acetal as the main functional ingredients. These cooling agents can act on cold receptors on the skin or mucous membrane surface, giving users a cooling, soothing, and cooling sensation.

[0003] However, existing cooling compositions still have the following shortcomings: First, low-molecular-weight cooling agents are highly volatile and tend to release rapidly in the initial stage of use after being added directly to the system, resulting in an excessively strong initial cooling sensation and obvious irritation, while the cooling sensation decays quickly and it is difficult to maintain a long-lasting cooling experience; Second, although single encapsulation or single microencapsulation technology can delay the release of cooling agents to a certain extent, the release is usually at a single level, resulting in slow onset, discontinuous release, insufficient cooling sensation in the later stages, or unstable encapsulation rate; Third, the shell structure of some microencapsulation systems is not strong enough and is prone to rupture under conditions of formulation stirring, storage, application friction, or temperature and humidity changes, leading to premature leakage of cooling agents; Fourth, oil-containing cooling agents have poor dispersion stability in aqueous or semi-aqueous systems, and are prone to precipitation, layering, aroma loss, or fluctuations in cooling intensity; Fifth, existing cooling products usually cannot simultaneously achieve "rapid cooling, sustained release, prolonged cooling, low irritation, and storage stability".

[0004] Therefore, it is necessary to provide a new multi-stage cooling composition that uses cooling carriers with different release rates to release the cooling agent in the early, middle and late stages of use, thereby achieving continuous, stable and lasting cooling sensation, while improving the stability, dispersibility and user comfort of the cooling agent. Summary of the Invention

[0005] The purpose of this invention is to address the problems of existing technologies, such as excessively rapid release of cooling agents, short duration of cooling sensation, strong initial irritation, significant subsequent attenuation of cooling sensation, and insufficient storage stability of cooling particles. This invention provides a multi-stage release cooling composition and its preparation method. This composition achieves staged release of the cooling component through the synergistic effect of an immediate-release cooling agent, encapsulated sustained-release cooling particles, and microencapsulated delayed-release cooling particles. This results in a composition that exhibits rapid onset of action, sustained release in the middle stage, and prolonged cooling sensation in the later stages of use.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is: a multi-stage cooling-releasing composition, which, by mass, is prepared from the following raw materials: 0.05-2.00 parts of cooling agent, 0.20-6.00 parts of encapsulated slow-release cooling particles, 0.20-8.00 parts of microencapsulated slow-release cooling particles, 3.00-18.00 parts of polyol, 0.50-8.00 parts of humectant, 0.10-3.00 parts of emulsifying dispersant, 0.05-2.00 parts of film-forming regulator, 0.05-1.50 parts of thickening stabilizer, 0.02-0.80 parts of pH adjuster, 0.05-1.00 parts of preservative, and 50.00-90.00 parts of deionized water.

[0007] Furthermore, the instant cooling agent includes one or more of menthol, menthone glycerol acetal, WS-23, WS-3, and menthyl lactate.

[0008] Furthermore, the inclusion-release cooling particles are cyclodextrin inclusion-type cooling particles, which are prepared by mass fractions of 100 parts of cyclodextrin, 5-35 parts of menthyl lactate, 1-15 parts of WS-3, 80-350 parts of ethanol and 70-300 parts of deionized water.

[0009] Furthermore, the microcapsule delayed-release cooling particles are multi-layered core-shell structured particles composed of an inclusion adsorption composite core, an alginate calcium ion gel inner shell, a chitosan-phytate polyelectrolyte intermediate shell, and an ethyl cellulose-silica hydrophobic outer shell.

[0010] Furthermore, the microcapsule delayed-release cooling particles are prepared from the following raw materials by weight: 100 parts of cooling composite core material, 10-35 parts of β-cyclodextrin, 20-70 parts of porous corn starch, 8-30 parts of medium-chain triglycerides, 2-12 parts of glyceryl monostearate, 6-22 parts of sodium alginate, 1-8 parts of sodium carboxymethyl cellulose, 2-10 parts of calcium chloride, 4-18 parts of chitosan, 0.5-5 parts of lactic acid, 0.5-6 parts of sodium phytate, 5-20 parts of ethyl cellulose, 0.5-5 parts of lecithin, 0.5-5 parts of hydrophilic fumed silica, 80-300 parts of ethanol, and 300-1200 parts of deionized water.

[0011] Furthermore, the cooling composite core material is composed of menthol, menthyl lactate, WS-23, and menthone glycerol acetal in a mass ratio of 20-55:15-45:5-25:5-25.

[0012] Furthermore, the instant cooling agent is composed of 0.02-0.80 parts of menthol, 0.01-0.60 parts of WS-23, and 0.02-0.60 parts of menthone glycerol acetal.

[0013] Furthermore, the cyclodextrin group is primarily β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or methyl-β-cyclodextrin.

[0014] Further, the preparation method of the encapsulated sustained-release cooling particles is as follows: β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or methyl-β-cyclodextrin is added to deionized water at a temperature of 45-65℃ and stirred at 500-1000 r / min for 20-60 min to obtain a cyclodextrin solution; menthyl lactate and WS-3 are dissolved in an ethanol aqueous solution with a volume fraction of 40-75% prepared from ethanol and deionized water to obtain a cooling agent solution; the cooling agent... The agent solution was added to the cyclodextrin solution at a dropping rate of 0.5-3.0 mL / min, and the inclusion reaction was carried out at 45-60℃ and 600-1200 r / min for 2-6 h. Then, the temperature was lowered to 0-10℃ and allowed to stand for crystallization for 4-12 h. After filtration, the mixture was washed with deionized water and dried at 35-50℃ and a vacuum of 0.06-0.09 MPa for 6-16 h. The mixture was then sieved through a 100-500 mesh sieve to obtain the inclusion slow-release cooling particles.

[0015] Furthermore, the preparation method of the microcapsule delayed-release cooling particles is as follows: S1. Add β-cyclodextrin to a deionized water-ethanol mixture with a volume ratio of 65-85:15-35, controlling the solid-liquid ratio of β-cyclodextrin to the mixture to be 1g:8-20mL. Stir for 20-50min at 45-60℃ and 500-900r / min, and adjust the pH to 6.0-7.0 to obtain a β-cyclodextrin dispersion. Mix the cooling composite core material, medium-chain triglycerides, and glyceryl monostearate at 40-55℃ for 15-35min to obtain a cooling... Oil phase: The cooling oil phase is added to the β-cyclodextrin dispersion at a dropping rate of 0.5-3.0 mL / min, and sheared and emulsified at 6000-12000 r / min for 10-30 min, then ultrasonically dispersed at 20-28 kHz for 5-20 min. Porous corn starch is then added, and the mixture is stirred at 35-45℃ and 600-1000 r / min for 1-3 h. Ethanol is removed under a vacuum of 0.06-0.09 MPa to obtain the inclusion adsorption composite core.

[0016] S2. Add sodium alginate and sodium carboxymethyl cellulose to deionized water, controlling the total solid content to be 1.0-4.5 wt%. Stir at 25-35℃ and 500-900 r / min for 40-90 min to obtain an anion film-forming solution. Add the inclusion adsorption composite core to the anion film-forming solution, controlling the solid-liquid ratio of the inclusion adsorption composite core to the anion film-forming solution to be 1 g: 8-18 mL. Disperse at 500-1000 r / min for 20-5 minutes. After 0 min, a core material suspension is obtained; the core material suspension is sprayed into a calcium chloride aqueous solution with a concentration of 1.0-4.0 wt% through a dual-fluid atomizing nozzle at a feed rate of 1.0-8.0 mL / min, the atomization pressure is 0.15-0.35 MPa, the temperature of the calcium chloride aqueous solution is 20-30℃, the stirring speed is 200-500 r / min, and the gel solidification is carried out for 30-90 min to obtain a primary microcapsule with a calcium alginate ion gel inner shell.

[0017] S3. Add chitosan to deionized water, add lactic acid to dissolve and adjust the pH to 4.8-5.6 to prepare a chitosan film-forming solution with a chitosan concentration of 0.3-2.0 wt%. Add the primary microcapsules to the chitosan film-forming solution, controlling the solid-liquid ratio of the primary microcapsules to the chitosan film-forming solution to 1 g: 10-25 mL. Stir at 25-35℃ and 300-700 r / min for 30-90 min to allow chitosan to be deposited on the inner shell surface of the calcium alginate ion gel through electrostatic interaction. Then, add a sodium phytate aqueous solution with a concentration of 0.2-2.0 wt% to the system at a dropping rate of 0.3-2.0 mL / min, adjust the pH to 5.2-5.8, and continue the reaction for 20-60 min to obtain secondary microcapsules with a chitosan-phytate polyelectrolyte intermediate shell.

[0018] S4. Ethyl cellulose, lecithin, and glyceryl monostearate are added to an ethanol aqueous solution with a volume concentration of 80-95%, and stirred at 35-50℃ and 400-800 r / min for 30-80 min to obtain a hydrophobic coating solution. The hydrophobic coating solution is added to the secondary microcapsule suspension at a dropping rate of 0.5-3.0 mL / min, and hydrophilic fumed silica is added. The mixture is then coated at 30-45℃ and 400-800 r / min for 40-120 min, and then cooled to 20-25℃ at a cooling rate of 0.5-1.5℃ / min to allow ethyl cellulose and silica to deposit and form a hydrophobic shell.

[0019] S5. Filter the obtained product, wash it with deionized water until the conductivity of the washing solution is ≤80μS / cm, and dry it at 35-45℃ and vacuum degree 0.06-0.09MPa for 6-14h. After sieving through a 100-400 mesh sieve, microcapsule delayed-release cooling particles are obtained.

[0020] Furthermore, the polyol includes one or more of glycerol, propylene glycol, butylene glycol, 1,3-propanediol, and dipropylene glycol.

[0021] Furthermore, the moisturizer includes one or more of sodium hyaluronate, betaine, trehalose, panthenol, and allantoin.

[0022] Furthermore, the emulsifying dispersant includes one or more of PEG-40 hydrogenated castor oil, polysorbate-20, polyglycerol fatty acid ester, and hydrogenated lecithin.

[0023] Furthermore, the thickening stabilizer includes one or more of carbomer, xanthan gum, hydroxyethyl cellulose, and acrylate crosslinking polymers.

[0024] Furthermore, the film-forming regulator includes one or more of polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl methylcellulose, pullulan, and acrylate copolymers.

[0025] Furthermore, the pH adjuster is selected from one or more of citric acid, sodium citrate, lactic acid, sodium lactate, arginine, triethanolamine, and sodium hydroxide.

[0026] Furthermore, the preservative is selected from one or more of phenoxyethanol, ethylhexylglycerin, caprylyl glycol, sodium benzoate, and potassium sorbate.

[0027] A multi-stage cooling-releasing composition can also be used in medical polymer materials, medical consumables, and dental biomaterials.

[0028] A method for preparing a multi-stage cooling composition includes the following steps: A1. Add deionized water to the mixing container and stir at 25-45℃ and 400-900r / min. Add thickening and stabilizer, disperse for 20-60min, then add polyol and humectant, and continue stirring for 10-40min to obtain aqueous matrix. A2. Add the instant cooling agent to the emulsifying dispersant and stir for 10-40 minutes at 30-50℃ and 300-800r / min to dissolve or uniformly disperse the instant cooling agent and obtain the instant cooling premix. A3. Add the instant cooling premix to the aqueous matrix and homogenize at 1000-5000 r / min for 3-15 min. Then add the encapsulated slow-release cooling particles and stir at 600-1500 r / min for 10-30 min to obtain the initial mixed system. A4. Cool or keep the initial mixed system to 20-35℃, add film-forming regulator, preservative and pH adjuster to adjust the pH of the system to 5.0-7.0, then add microcapsule delayed-release cooling particles, and stir under low shear at 200-800r / min for 10-40min to obtain the compound system. A5. Degas the compound system under a vacuum of 0.04-0.08 MPa for 5-20 minutes, and filter it through an 80-200 mesh sieve to obtain the multi-stage cooling composition.

[0029] Furthermore, before being added to the initial mixing system, the encapsulated slow-release cooling particles are first wetted with a wetting solution prepared by polyol and deionized water at a mass ratio of 1:1-5 to form an encapsulated slow-release cooling particle slurry with a solid content of 20-60 wt%.

[0030] Furthermore, before being added to the compound system, the microcapsule delayed-release cooling particles are pre-dispersed in a dispersion prepared by deionized water, polyol and emulsifying dispersant at a mass ratio of 10-40:1-10:0.1-1.0 to form a microcapsule delayed-release cooling particle slurry with a solid content of 5-40wt%.

[0031] Furthermore, both the encapsulated slow-release cooling particle slurry and the microencapsulated delayed-release cooling particle slurry are used at 20-35℃, and the stirring linear velocity after the addition of the microencapsulated delayed-release cooling particles is controlled at 0.2-1.5m / s.

[0032] Compared with the prior art, the beneficial effects of the present invention are: 1. This multi-stage cooling composition constructs a three-stage cooling release system through an immediate-release cooling agent, encapsulated slow-release cooling particles, and microencapsulated delayed-release cooling particles, so that the cooling agent is released sequentially in the initial, middle and late stages of use. This not only provides a rapid cooling effect, but also prolongs the duration of the cooling sensation, avoiding the problem of traditional cooling products being "too strong in the early stage and insufficient in the later stage".

[0033] 2. The encapsulated slow-release cooling particles in this composition can reduce the volatilization loss and burst release of the cooling agent, making the cooling release more stable. The microencapsulated slow-release cooling particles adopt a multi-layer core-shell structure with an encapsulated adsorption composite core, a calcium alginate ion gel inner shell, a chitosan-phytate polyelectrolyte intermediate shell, and an ethyl cellulose-silica hydrophobic outer shell. This structure can improve the encapsulation efficiency, shell density, and storage stability of the cooling agent, and reduce the migration, precipitation, and premature release of the cooling agent during the formulation storage process.

[0034] 3. This composition, through the combination of polyols, humectants, emulsifying dispersants, film-forming regulators, and thickening stabilizers, enables the cooling particles to have good suspension and dispersion and coating uniformity in the system, which can improve the skin feel and reduce the irritation and burning sensation caused by directly adding high concentrations of cooling agents, making the cooling experience more gentle, continuous, and long-lasting.

[0035] 4. The preparation method uses mild process conditions and does not employ high-temperature destructive treatment, which can reduce the loss of cooling agent volatilization. At the same time, by adding microcapsule delayed-release cooling particles with low shear, the risk of damage to the multi-layer core-shell structure during the preparation process is reduced. The resulting composition has good centrifugal stability, storage stability and application compatibility, and is suitable for use in cooling gels, body care lotions, sprays, facial care products, after-sun repair products and other topical daily chemical products. Attached Figure Description

[0036] Figure 1 Fourier transform infrared spectrum of the microcapsule delayed-release cooling particles obtained in Example 1 of this invention. Detailed Implementation

[0037] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of the present invention, and 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.

[0038] Preparation Example 1 Preparation of microencapsulated delayed-release cooling granules: 1. Raw material components by weight: The microcapsule delayed-release cooling particles of this preparation example were prepared from the following raw materials in parts by weight: 100 parts cooling composite core material, 24 parts β-cyclodextrin, 50 parts porous corn starch, 18 parts medium-chain triglycerides, 6 parts glyceryl monostearate, 10 parts sodium alginate, 3 parts sodium carboxymethyl cellulose, 5 parts calcium chloride, 5 parts chitosan, 1.5 parts lactic acid, 1.5 parts sodium phytate, 12 parts ethyl cellulose, 2.5 parts lecithin, 2.5 parts hydrophilic fumed silica, 180 parts ethanol, and 1050 parts deionized water.

[0039] The cooling composite core material is composed of menthol, menthyl lactate, WS-23, and menthone glycerol acetal in a mass ratio of 40:30:15:15.

[0040] Three parts of the glyceryl monostearate are used to prepare the cooling oil phase, and the other three parts are used to prepare the hydrophobic coating liquid.

[0041] The porous starch (porous corn starch) was purchased from Liaoning Lida Biotechnology Co., Ltd.

[0042] The amount of deionized water added to the system during the preparation process is used as the basis, and the amount of deionized water used for washing is not included in the above-mentioned mass fraction.

[0043] 2. Preparation method: S1. Add 24 parts of β-cyclodextrin to a deionized water-ethanol mixture consisting of 188 parts of deionized water and 62 parts of ethanol. Stir at 50℃ and 700 r / min for 35 min, controlling the pH of the system to 6.4-6.6 to obtain a β-cyclodextrin dispersion. Add 100 parts of cooling composite core material, 18 parts of medium-chain triglycerides, and 3 parts of glyceryl monostearate to a mixing container. Stir and mix at 48℃ for 25 min to obtain a cooling oil phase. Add the cooling oil phase to the β-cyclodextrin dispersion at a dropping rate of 1.5 mL / min and shear emulsify at 9000 r / min for 20 min, then ultrasonically disperse at 24 kHz for 12 min. Subsequently, add 50 parts of porous corn starch and stir at 40℃ and 800 r / min for 2 h. Remove ethanol under a vacuum of 0.08 MPa until the ethanol content in the system is ≤1.0 wt%, to obtain an inclusion adsorption composite core.

[0044] S2. Add 10 parts sodium alginate and 3 parts sodium carboxymethyl cellulose to 312 parts deionized water and stir for 60 min at 30℃ and 700 r / min to prepare an anionic film-forming solution with a total solid content of 4.0 wt%. Add the inclusion adsorption composite core obtained in S1 to the anionic film-forming solution and disperse for 35 min at 700 r / min to obtain a core material suspension. Add 5 parts calcium chloride to 120 parts deionized water to prepare a calcium chloride aqueous solution with a mass concentration of 4.0 wt% and control the temperature of the calcium chloride aqueous solution at 25℃. Spray the core material suspension into the calcium chloride aqueous solution through a dual-fluid atomizing nozzle at a feed rate of 4.0 mL / min, with an atomization pressure of 0.25 MPa and a stirring speed of 350 r / min. Allow the gel to solidify for 60 min, filter, and obtain primary microcapsules with a calcium alginate ion gel inner shell.

[0045] S3. Add 5 parts chitosan to 244 parts deionized water and 1.5 parts lactic acid. Stir at 30℃ and 600 r / min until the chitosan is completely dissolved to prepare a chitosan film-forming solution with a chitosan concentration of 2.0 wt% and a pH of 5.1-5.3. Add the primary microcapsules to the chitosan film-forming solution and stir at 30℃ and 500 r / min for 60 min to allow chitosan to deposit on the inner shell surface of the calcium alginate ion gel. Add 1.5 parts sodium phytate to 73.5 parts deionized water to prepare a sodium phytate aqueous solution with a mass concentration of 2.0 wt%. Add the sodium phytate aqueous solution to the system at a dropping rate of 0.8 mL / min, control the pH of the system to 5.4-5.6, and continue the reaction for 40 min to obtain secondary microcapsules with a chitosan-phytate polyelectrolyte intermediate shell.

[0046] S4. Add 12 parts ethyl cellulose, 2.5 parts lecithin and 3 parts glyceryl monostearate to an ethanol aqueous solution with a volume concentration of approximately 90% consisting of 118 parts ethanol and 16 parts deionized water. Stir at 42°C and 600 r / min for 60 min to obtain a hydrophobic coating solution. Add the hydrophobic coating solution to the secondary microcapsule suspension at a dropping rate of 1.2 mL / min, and add 2.5 parts hydrophilic fumed silica. Co-coat at 38°C and 600 r / min for 90 min, and then cool down to 22°C at a cooling rate of 1.0°C / min to deposit ethyl cellulose and hydrophilic fumed silica to form a hydrophobic shell.

[0047] S5. Filter the product obtained in S4, wash it with deionized water until the conductivity of the washing solution is ≤80μS / cm, and dry it at 40℃ and vacuum degree 0.08MPa for 10h. After sieving through a 200-mesh sieve, microcapsule delayed-release cooling particles are obtained.

[0048] like Figure 1 As shown. Approximately 3400 cm⁻¹ in the spectrum. -1 The broad and strong absorption peak can be attributed to the OH stretching vibration in β-cyclodextrin, porous starch, sodium alginate, sodium carboxymethyl cellulose, chitosan, and Si-OH; approximately 2920-2850 cm⁻¹. -1 The absorption peak at approximately 1730-1740 cm⁻¹ corresponds to the CH stretching vibration in the cooling core material, medium-chain triglycerides, glyceryl monostearate, and ethyl cellulose; -1 The nearby peaks can be attributed to the C=O stretching vibrations of the ester groups in menthyl lactate, medium-chain triglycerides, and glyceryl monostearate; approximately 1600-1550 cm⁻¹. -1 Nearby absorption is associated with carboxylates of alginate / sodium carboxymethyl cellulose, chitosan amino groups, and bound water; approximately 1450-1370 cm⁻¹ -1 It consists of CH bending vibration and carboxylate symmetric vibration; approximately 1240-1050 cm.-1 Strong absorption bands correspond to the COC / CO stretching vibration of polysaccharides, the PO / P=O vibration of phytates, and the Si-O-Si stretching vibration of silica, at 1000 cm⁻¹. -1 The following weak peaks are related to glycosidic bond, Si-O and phosphate structure vibrations.

[0049] Preparation Example 2 Preparation of encapsulated sustained-release cooling granules: 1. Raw material components by weight: The encapsulated sustained-release cooling granules of this preparation example were prepared from the following raw materials by weight: 100 parts hydroxypropyl-β-cyclodextrin, 22 parts menthyl lactate, 6 parts WS-3, 120 parts ethanol, and 260 parts deionized water.

[0050] The ethanol and a portion of the deionized water are used to prepare an ethanol aqueous solution with a volume fraction of 60%, which serves as a solvent for menthyl lactate and WS-3. The remaining deionized water is used to dissolve hydroxypropyl-β-cyclodextrin.

[0051] 2. Preparation method: 100 parts of hydroxypropyl-β-cyclodextrin were added to 200 parts of deionized water and stirred at 55°C and 800 r / min for 40 min to obtain a cyclodextrin solution. 22 parts of menthyl lactate and 6 parts of WS-3 were added to a 60% (v / v) ethanol aqueous solution composed of 120 parts of ethanol and 60 parts of deionized water and stirred at 35°C and 500 r / min for 20 min to obtain a cooling agent solution. The cooling agent solution was added to the cyclodextrin solution at a dropping rate of 1.2 mL / min. In a dextrin solution, the inclusion reaction was carried out at 52℃ and 900 r / min for 4 h. After the reaction, the temperature was lowered to 6℃ at a rate of 0.8℃ / min, and the mixture was allowed to stand at 6℃ for 8 h to crystallize. The mixture was then filtered, and the filter cake was washed twice with deionized water. The amount of deionized water used for each wash was twice the mass of the filter cake. Washing was stopped when there was no obvious ethanol odor in the washing liquid. The resulting filter cake was dried at 42℃ and 0.08 MPa under vacuum for 10 h, and then sieved through a 300-mesh sieve to obtain the inclusion slow-release cooling particles.

[0052] Comparative Preparation Example 1 The microcapsule delayed-release cooling granules were prepared according to the preparation method in Preparation Example 1, except that 24 parts of β-cyclodextrin were replaced with 24 parts of commercially available maltodextrin, and the rest remained the same as in Preparation Example 1.

[0053] Comparative Preparation Example 2 The microencapsulated delayed-release cooling granules were prepared according to the preparation method in Preparation Example 1, except that 50 parts of porous corn starch were replaced with 50 parts of commercially available ordinary corn starch, and the rest remained the same as in Preparation Example 1.

[0054] Comparative preparation example 3 The microcapsule delayed-release cooling particles were prepared according to the preparation method in Preparation Example 1, except that 10 parts of sodium alginate were replaced with 10 parts of sodium carboxymethyl cellulose, and the total amount of sodium carboxymethyl cellulose used in the preparation of the anionic film-forming solution was 13 parts, while the rest remained the same as in Preparation Example 1.

[0055] Comparative preparation example 4 The microcapsule delayed-release cooling particles were prepared according to the preparation method in Preparation Example 1, except that the 5 parts of calcium chloride used for gel solidification in S2 were replaced with 5 parts of anhydrous magnesium chloride, and a magnesium chloride aqueous solution with a mass concentration of 4.0 wt% was prepared. Everything else was the same as in Preparation Example 1.

[0056] Comparative preparation example 5 The microcapsule delayed-release cooling particles were prepared according to the preparation method in Preparation Example 1, except that 5 parts of chitosan were replaced with 5 parts of hydroxyethyl cellulose, and the rest remained the same as in Preparation Example 1.

[0057] Comparative preparation example 6 The microcapsule delayed-release cooling particles were prepared according to the preparation method in Preparation Example 1, except that 1.5 parts of sodium phytate were replaced with 1.5 parts of sodium tripolyphosphate, and the sodium phytate aqueous solution was added to the system with the same mass concentration and dropping method as in Preparation Example 1. Everything else was the same as in Preparation Example 1.

[0058] Comparative preparation example 7 The microcapsule delayed-release cooling particles were prepared according to the preparation method in Preparation Example 1, except that 12 parts of ethyl cellulose were replaced with 12 parts of polyvinylpyrrolidone K30, and the rest remained the same as in Preparation Example 1.

[0059] Comparative Preparation Example 8 The preparation of the encapsulated sustained-release cooling particles was carried out according to the preparation method in Preparation Example 2, except that 100 parts of hydroxypropyl-β-cyclodextrin were replaced with 100 parts of commercially available maltodextrin, and the rest remained the same as in Preparation Example 2.

[0060] Comparative preparation example 9 The preparation of the encapsulated sustained-release cooling granules was carried out according to the preparation method in Preparation Example 2, except that 100 parts of hydroxypropyl-β-cyclodextrin were replaced with 100 parts of commercially available ordinary corn starch, and the rest remained the same as in Preparation Example 2.

[0061] Comparative Preparation Example 10 The preparation of the encapsulated sustained-release cooling granules was carried out by referring to the preparation method in Preparation Example 2, except that 6 parts of WS-3 were replaced with 6 parts of menthol, and the rest remained the same as in Preparation Example 2.

[0062] Example 1 Preparation of a multi-stage cooling-releasing composition: 1. Raw material components by weight: The multi-stage cooling composition of this embodiment is prepared from the following raw materials in parts by weight: 0.65 parts cooling agent, 3.00 parts encapsulated slow-release cooling particles obtained in Preparation Example 2, 4.50 parts microencapsulated slow-release cooling particles obtained in Preparation Example 1, 10.00 parts glycerin, 3.00 parts betaine, 1.20 parts PEG-40 hydrogenated castor oil, 0.60 parts polyvinylpyrrolidone, 0.45 parts hydroxyethyl cellulose, 0.08 parts citric acid, 0.18 parts sodium citrate, 0.45 parts phenoxyethanol, 0.15 parts ethylhexylglycerin, and 75.74 parts deionized water.

[0063] The instant cooling agent is composed of 0.25 parts menthol, 0.15 parts WS-23 and 0.25 parts menthone glycerol acetal.

[0064] Of the 10.00 parts of glycerol, 6.66 parts were used to prepare the aqueous matrix, 1.13 parts were used to prepare the encapsulated slow-release cooling particle slurry, and 2.21 parts were used to prepare the microencapsulated delayed-release cooling particle slurry.

[0065] Of the 1.20 parts of PEG-40 hydrogenated castor oil, 0.98 parts were used to prepare an immediate cooling premix and 0.22 parts were used to prepare a microcapsule delayed-release cooling granule slurry.

[0066] Of the 75.74 parts of deionized water, 61.30 parts were used to prepare the aqueous matrix, 3.38 parts were used to prepare the encapsulated slow-release cooling particle slurry, and 11.06 parts were used to prepare the microencapsulated slow-release cooling particle slurry.

[0067] 2. Preparation method: A1. Add 61.30 parts of deionized water to the mixing container and stir at 35℃ and 600 r / min. Slowly add 0.45 parts of hydroxyethyl cellulose and continue stirring for 45 min to fully wet and evenly disperse the hydroxyethyl cellulose. Then add 6.66 parts of glycerol and 3.00 parts of betaine and continue stirring at 35℃ and 600 r / min for 25 min to obtain the aqueous matrix.

[0068] A2. Add the instant cooling agent composed of 0.25 parts menthol, 0.15 parts WS-23 and 0.25 parts menthone glycerol acetal to 0.98 parts PEG-40 hydrogenated castor oil, and stir for 25 minutes at 40℃ and 500 r / min to dissolve or uniformly disperse the instant cooling agent, thus obtaining an instant cooling premix.

[0069] A3. Add the instant cooling premix to the aqueous matrix and homogenize at 3000 r / min for 8 min; separately, mix 1.13 parts of glycerol and 3.38 parts of deionized water to obtain a wetting solution with a glycerol to deionized water mass ratio of 1:3. Add 3.00 parts of the encapsulated slow-release cooling particles obtained in Preparation Example 2 to the wetting solution and stir at 25°C and 600 r / min for 10 min to form an encapsulated slow-release cooling particle slurry with a solid content of 39.94 wt%; add the encapsulated slow-release cooling particle slurry to the system and stir at 900 r / min for 20 min to obtain the initial mixed system.

[0070] A4. Cool the initial mixture to 28°C, add 0.60 parts of polyvinylpyrrolidone, 0.45 parts of phenoxyethanol and 0.15 parts of ethylhexylglycerin, and stir for 15 min at 28°C and 600 r / min; then add 0.08 parts of citric acid and 0.18 parts of sodium citrate, and control the pH of the system to 5.8-6.2. Separately, 11.06 parts of deionized water, 2.21 parts of glycerol, and 0.22 parts of PEG-40 hydrogenated castor oil were mixed to obtain a dispersion with a mass ratio of deionized water, glycerol, and PEG-40 hydrogenated castor oil of 25:5:0.5. 4.50 parts of the microcapsule delayed-release cooling particles obtained in Preparation Example 1 were added to the dispersion, and the mixture was stirred at 25°C and 300 r / min for 12 min to form a microcapsule delayed-release cooling particle slurry with a solid content of 25.01 wt%. The microcapsule delayed-release cooling particle slurry was added to the system, and the mixture was stirred under low shear at 350 r / min for 25 min. The stirring linear velocity after the addition of the microcapsule delayed-release cooling particles was controlled to be 0.8 m / s to obtain the compound system.

[0071] A5. The compound system was defoamed for 12 minutes under a vacuum of 0.06 MPa and then filtered through a 120-mesh sieve to obtain the multi-stage cooling composition.

[0072] Example 2 The preparation of a multi-stage cooling composition was carried out according to the preparation method of Example 1, except that 0.65 parts of the immediate-release cooling agent, 3.00 parts of the encapsulated slow-release cooling particles obtained in Preparation Example 2, 4.50 parts of the microencapsulated delayed-release cooling particles obtained in Preparation Example 1, and 75.74 parts of deionized water were adjusted to 0.45 parts of the immediate-release cooling agent, 2.40 parts of the encapsulated slow-release cooling particles obtained in Preparation Example 2, 5.20 parts of the microencapsulated delayed-release cooling particles obtained in Preparation Example 1, and 76.29 parts of deionized water, respectively, while the rest remained the same as in Example 1.

[0073] The instant cooling agent is composed of 0.18 parts of menthol, 0.10 parts of WS-23, and 0.17 parts of menthone glycerol acetal.

[0074] Example 3 The preparation of a multi-stage cooling composition was carried out according to the preparation method of Example 1, except that the following components were adjusted: 0.65 parts of immediate-release cooling agent, 3.00 parts of encapsulated sustained-release cooling particles obtained in Preparation Example 2, 4.50 parts of microencapsulated delayed-release cooling particles obtained in Preparation Example 1, 10.00 parts of glycerol, 3.00 parts of betaine, and 75.74 parts of deionized water were respectively adjusted to: 0.85 parts of immediate-release cooling agent, 4.20 parts of encapsulated sustained-release cooling particles obtained in Preparation Example 2, 3.60 parts of microencapsulated delayed-release cooling particles obtained in Preparation Example 1, 9.00 parts of glycerol, 2.50 parts of betaine, and 76.39 parts of deionized water. The remaining components were the same as in Example 1.

[0075] The instant cooling agent is composed of 0.35 parts menthol, 0.20 parts WS-23 and 0.30 parts menthone glycerol acetal.

[0076] Example 4 The preparation of a multi-stage cooling composition was carried out according to the preparation method of Example 1, except that 0.65 parts of the immediate-release cooling agent, 3.00 parts of the encapsulated sustained-release cooling particles obtained in Preparation Example 2, 4.50 parts of the microencapsulated delayed-release cooling particles obtained in Preparation Example 1, 1.20 parts of PEG-40 hydrogenated castor oil, 0.60 parts of polyvinylpyrrolidone, 0.45 parts of hydroxyethyl cellulose, and 75.74 parts of deionized water were adjusted to 0.55 parts of the immediate-release cooling agent, 3.60 parts of the encapsulated sustained-release cooling particles obtained in Preparation Example 2, 5.00 parts of the microencapsulated delayed-release cooling particles obtained in Preparation Example 1, 1.40 parts of PEG-40 hydrogenated castor oil, 0.80 parts of polyvinylpyrrolidone, 0.55 parts of hydroxyethyl cellulose, and 74.34 parts of deionized water, respectively, while the rest remained the same as in Example 1.

[0077] The instant cooling agent is composed of 0.20 parts of menthol, 0.15 parts of WS-23 and 0.20 parts of menthone glycerol acetal.

[0078] Comparative Examples 1-7 The preparation of a multi-stage cooling composition was carried out by referring to the preparation method of Example 1, except that the microcapsule delayed-release cooling particles were replaced with the microcapsule delayed-release cooling particles prepared in Comparative Preparation Examples 1-7, and the rest remained the same as in Example 1.

[0079] Comparative Example 8 The preparation of a multi-stage cooling composition was carried out by referring to the preparation method of Example 1, except that 4.50 parts of the microcapsule delayed-release cooling particles obtained in Preparation Example 1 were replaced with 4.50 parts of uncoated cooling composite core material, and the rest remained the same as in Example 1.

[0080] The uncoated cooling composite core material is composed of menthol, menthyl lactate, WS-23 and menthone glycerol acetal in a mass ratio of 40:30:15:15, and the mixing conditions are 48°C and 500r / min for 25min.

[0081] Comparative Example 9 The preparation of a multi-stage cooling composition was carried out by referring to the preparation method of Example 1, except that 4.50 parts of the microcapsule delayed-release cooling particles obtained in Preparation Example 1 were replaced with 4.50 parts of monolayer calcium alginate microcapsules, and the rest remained the same as in Example 1.

[0082] The preparation method of the monolayer calcium alginate microcapsules is as follows: After obtaining primary microcapsules with calcium alginate ion gel inner shells according to steps S1 and S2 of Preparation Example 1, without performing the S3 chitosan-phytate polyelectrolyte intermediate shell coating and the S4 ethyl cellulose-silica hydrophobic outer shell coating, the obtained primary microcapsules are directly filtered, washed with deionized water until the conductivity of the washing solution is ≤80μS / cm, and dried at 40℃ and 0.08MPa vacuum for 10h. After sieving through a 200-mesh sieve, monolayer calcium alginate microcapsules are obtained.

[0083] Comparative Examples 10-12 The preparation of a multi-stage cooling composition was carried out by referring to the preparation method of Example 1, except that the encapsulated sustained-release cooling particles were replaced with the encapsulated sustained-release cooling particles prepared in Comparative Preparation Examples 8-10, and the rest remained the same as in Example 1.

[0084] Comparative Example 13 The preparation of a multi-stage cooling composition was carried out according to the preparation method of Example 1, except that 3.00 parts of the encapsulated sustained-release cooling particles obtained in Preparation Example 2 were replaced with 3.00 parts of the unencapsulated cooling agent mixture, and the rest remained the same as in Example 1.

[0085] The unencapsulated cooling agent mixture was prepared by mixing menthyl lactate and WS-3 at a mass ratio of 22:6, under the following conditions: 35°C, 500 r / min, and stirring for 20 min.

[0086] Comparative Example 14 The preparation of a multi-stage cooling composition was carried out according to the preparation method of Example 1, except that 3.00 parts of the encapsulated sustained-release cooling particles obtained in Preparation Example 2 were replaced with 3.00 parts of blank hydroxypropyl-β-cyclodextrin particles, and the rest remained the same as in Example 1.

[0087] The method for preparing the blank hydroxypropyl-β-cyclodextrin particles is as follows: 100 parts of hydroxypropyl-β-cyclodextrin are added to 200 parts of deionized water and stirred at 55℃ and 800 r / min for 40 min; then the temperature is lowered to 6℃ at a cooling rate of 0.8℃ / min and allowed to stand at 6℃ for 8 h; after filtration, the filter cake is washed twice with deionized water, and the amount of deionized water used each time is twice the mass of the filter cake; the obtained filter cake is dried at 42℃ and 0.08 MPa vacuum for 10 h, and then sieved through a 300-mesh sieve to obtain blank hydroxypropyl-β-cyclodextrin particles.

[0088] Performance testing: 1. In vitro cumulative release rate test of cooling agent Weigh 1.00 g of the multi-stage cooling composition obtained in each example and comparative example, and evenly coat it on the surface of a dialysis membrane, with a coating area of ​​9.00 cm². 2 The dialysis membrane was pre-soaked in a 50% ethanol aqueous solution for 12 hours. The sample-coated dialysis membrane was fixed between the donor and receiver chambers of a Franz diffusion cell. 20.00 mL of a 50% ethanol aqueous solution was added to the receiver chamber as the receiving medium, and the temperature of the receiving medium was controlled at 32 ± 0.5 °C. The magnetic stirring speed was 300 r / min. 1.00 mL of the receiving solution was collected at 5 min and 3 h, and an equal volume and temperature of fresh receiving medium were added simultaneously. After filtration through a 0.22 μm organic filter membrane, the contents of menthol and menthyl lactate were determined by gas chromatography, and the cumulative release rate of the cooling agent at each time point was calculated using the following formula: Cumulative release rate / % = M t / M0×100%.

[0089] In the formula, M t Mt represents the total mass of cooling agent released cumulatively into the receiving medium at time point t, in mg; M0 represents the theoretical total mass of cooling agent in the test sample, in mg. The immediate-release cooling effect was evaluated by the 5-minute release rate, and the mid-range sustained-release effect was evaluated by the 3-hour release rate. Data are shown in Table 1.

[0090] 2. Cooling Agent Volatilization Loss Test: Weigh 2.00 g of the samples obtained from each example and comparative example, and spread them evenly in a 60 mm diameter glass petri dish, controlling the sample layer thickness to be 1.0-1.5 mm. Place the petri dish in a constant temperature and humidity chamber at 32±1℃ and 50±5% relative humidity, and take samples at 0 h and 6 h respectively. Add 20.00 mL of anhydrous ethanol to the sample, extract by ultrasonication for 20 min, and then filter through a 0.22 μm organic filter membrane. Determine the total content of residual cooling agent in the sample by gas chromatography. Calculate the volatile loss rate using the following formula: Volatilization Loss Rate / % = (M0 - M t ) / M0×100%. Where M0 is the total mass of the cooling agent in the 0h sample, in mg; Mt The value represents the total residual cooling agent in the sample at time point t, expressed in mg. A lower evaporation loss rate indicates a stronger ability of the composition to retain the cooling agent, and less loss of the cooling agent during storage and use. The data are shown in Table 1.

[0091] 3. Centrifugal Stability Test: Take 10.00g of the samples obtained from each example and comparative example, place them in a 15mL centrifuge tube, and centrifuge at 3000r / min for 30min at 25±2℃. After centrifugation, observe whether the samples show stratification, oil separation, sedimentation, flocculation, or obvious particle aggregation. Simultaneously, determine the content of the cooling agent in the upper and lower layers of the samples before and after centrifugation. The specific method is as follows: Take 0.50g of the upper and lower layer samples respectively, add 10.00mL of anhydrous ethanol, extract ultrasonically for 20min, filter, and determine the cooling agent content using gas chromatography. Calculate the difference rate of content between the upper and lower layers using the following formula: Difference rate of content between upper and lower layers / % = |C u -C d | / C0×100%.

[0092] In the formula, C u The content of cooling agent in the upper sample is expressed in mg / g; C d C represents the content of cooling agent in the lower layer sample, in mg / g; C0 represents the average content of cooling agent in the sample before centrifugation, in mg / g. A smaller difference in content between the upper and lower layers indicates a more uniform dispersion of cooling particles in the system and better centrifugal stability. The data are shown in Table 1.

[0093] Table 1 Performance test results of the multi-stage release cooling compositions obtained in each embodiment and comparative example Table 1 shows that the overall trend in the examples indicates that the immediate-release cooling agent, the encapsulated slow-release cooling particles, and the microencapsulated delayed-release cooling particles form a relatively complete three-stage release structure. The immediate-release component is responsible for early cooling, the cyclodextrin encapsulation particles reduce the burst release and volatilization of the mid-stage cooling agent, and the multilayer microcapsules gradually increase diffusion resistance through the "encapsulation and adsorption composite core - calcium alginate gel inner shell - chitosan - phytate intermediate shell - ethyl cellulose / silica hydrophobic outer shell". Therefore, the examples generally show that the early release is not too fast, the mid-stage release is relatively continuous, the volatilization loss is low, and the dispersion stability after centrifugation is good. In the comparative examples, if any key structure is damaged, the release regulation ability will decrease. Replacing β-cyclodextrin or porous starch will weaken the core material's encapsulation / adsorption capacity, increasing the early release and volatilization loss. The gel layer, chitosan-phytate layer, or hydrophobic shell of ethyl cellulose reduce the density and mechanical stability of the shell, making the particles more prone to aggregation, sedimentation, or oil separation, and exacerbating the premature migration of the cooling agent. The uncoated cooling composite core material, lacking any barrier, exhibits the most significant burst release, volatilization, and system inhomogeneity. While single-layer calcium alginate microcapsules provide some barrier effect, the lack of an intermediate reinforcing layer and hydrophobic shell results in significantly insufficient stability and delayed release. When the encapsulated sustained-release particles are replaced by maltodextrin, ordinary starch, or other components, the continuity of mid-release decreases, indicating the necessity of cyclodextrin encapsulation and the WS-3 / menthol lactate combination for sustained-release cooling. Blank cyclodextrin particles, lacking effective cooling agent loading, appear to have lower release and volatilization, but they cannot actually provide sufficient mid-release cooling and should not be interpreted as having superior performance. Therefore, the data trends in Table 1 mechanistically demonstrate that the multi-stage release structure of this invention has a synergistic effect on reducing burst release, minimizing volatilization loss, improving dispersion stability, and prolonging cooling release.

[0094] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A multi-stage release cooling composition characterized in that, By weight, it is prepared from the following raw materials: 0.05-2.00 parts of cooling agent, 0.20-6.00 parts of encapsulated slow-release cooling particles, 0.20-8.00 parts of microencapsulated slow-release cooling particles, 3.00-18.00 parts of polyol, 0.50-8.00 parts of humectant, 0.10-3.00 parts of emulsifying dispersant, 0.05-2.00 parts of film-forming regulator, 0.05-1.50 parts of thickening stabilizer, 0.02-0.80 parts of pH adjuster, 0.05-1.00 parts of preservative, and 50.00-90.00 parts of deionized water; The instant cooling agent includes one or more of menthol, menthone glycerol acetal, WS-23, WS-3, and menthyl lactate; The inclusion-encapsulated sustained-release cooling particles are cyclodextrin inclusion-encapsulated cooling particles, which are prepared by mass fractions of 100 parts of cyclodextrin, 5-35 parts of menthyl lactate, 1-15 parts of WS-3, 80-350 parts of ethanol and 70-300 parts of deionized water. The microcapsule delayed-release cooling particles are multi-layered core-shell structured particles composed of an inclusion adsorption composite core, an alginate calcium ion gel inner shell, a chitosan-phytate polyelectrolyte intermediate shell, and an ethyl cellulose-silica hydrophobic outer shell. The microcapsule delayed-release cooling granules are prepared from the following raw materials by weight: 100 parts cooling composite core material, 10-35 parts β-cyclodextrin, 20-70 parts porous corn starch, 8-30 parts medium-chain triglycerides, 2-12 parts glyceryl monostearate, 6-22 parts sodium alginate, 1-8 parts sodium carboxymethyl cellulose, 2-10 parts calcium chloride, 4-18 parts chitosan, 0.5-5 parts lactic acid, 0.5-6 parts sodium phytate, 5-20 parts ethyl cellulose, 0.5-5 parts lecithin, 0.5-5 parts hydrophilic fumed silica, 80-300 parts ethanol, and 300-1200 parts deionized water. The cooling composite core material is composed of menthol, menthyl lactate, WS-23 and menthone glycerol acetal in a mass ratio of 20-55:15-45:5-25:5-25.

2. A multi-stage release cooling composition according to Claim 1 wherein, The instant cooling agent is composed of 0.02-0.80 parts of menthol, 0.01-0.60 parts of WS-23, and 0.02-0.60 parts of menthone glycerol acetal.

3. The multi-stage cooling composition according to claim 1, characterized in that, The main cyclodextrins are β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or methyl-β-cyclodextrin; The preparation method of the encapsulated sustained-release cooling particles is as follows: β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or methyl-β-cyclodextrin is added to deionized water at a temperature of 45-65℃ and stirred at 500-1000 r / min for 20-60 min to obtain a cyclodextrin solution; menthyl lactate and WS-3 are dissolved in an ethanol aqueous solution with a volume fraction of 40-75% prepared from ethanol and deionized water to obtain a cooling agent solution; the cooling agent solution is then... The liquid was added to the cyclodextrin solution at a dropping rate of 0.5-3.0 mL / min, and the inclusion reaction was carried out at 45-60℃ and 600-1200 r / min for 2-6 h. Then, the temperature was lowered to 0-10℃ and allowed to stand for crystallization for 4-12 h. The mixture was filtered, washed with deionized water, and dried at 35-50℃ and a vacuum of 0.06-0.09 MPa for 6-16 h. The mixture was then sieved through a 100-500 mesh sieve to obtain the inclusion slow-release cooling particles.

4. The multi-stage cooling composition according to claim 1, characterized in that, The preparation method of the microcapsule delayed-release cooling particles: S1. Add β-cyclodextrin to a deionized water-ethanol mixture with a volume ratio of 65-85:15-35, controlling the solid-liquid ratio of β-cyclodextrin to the mixture to be 1g:8-20mL. Stir for 20-50min at 45-60℃ and 500-900r / min, and adjust the pH to 6.0-7.0 to obtain a β-cyclodextrin dispersion. Mix the cooling composite core material, medium-chain triglycerides, and glyceryl monostearate at 40-55℃ for 15-35min to obtain a cooling... Oil phase: The cooling oil phase is added to the β-cyclodextrin dispersion at a dropping rate of 0.5-3.0 mL / min, and sheared and emulsified at 6000-12000 r / min for 10-30 min, then ultrasonically dispersed at 20-28 kHz for 5-20 min, followed by the addition of porous corn starch, and stirred at 35-45℃ and 600-1000 r / min for 1-3 h, and ethanol is removed under vacuum of 0.06-0.09 MPa to obtain the inclusion adsorption composite core; S2. Add sodium alginate and sodium carboxymethyl cellulose to deionized water, controlling the total solid content to be 1.0-4.5 wt%. Stir at 25-35℃ and 500-900 r / min for 40-90 min to obtain an anion film-forming solution. Add the inclusion adsorption composite core to the anion film-forming solution, controlling the solid-liquid ratio of the inclusion adsorption composite core to the anion film-forming solution to be 1 g: 8-18 mL. Disperse at 500-1000 r / min for 20-5 minutes. 0 min, to obtain a core material suspension; the core material suspension is sprayed into a calcium chloride aqueous solution with a concentration of 1.0-4.0 wt% through a dual-fluid atomizing nozzle at a feed rate of 1.0-8.0 mL / min, the atomization pressure is 0.15-0.35 MPa, the temperature of the calcium chloride aqueous solution is 20-30℃, the stirring speed is 200-500 r / min, and the gel solidification is 30-90 min, to obtain a primary microcapsule with a calcium alginate ion gel inner shell; S3. Add chitosan to deionized water, add lactic acid to dissolve and adjust the pH to 4.8-5.6 to prepare a chitosan film-forming solution with a chitosan concentration of 0.3-2.0 wt%. Add the primary microcapsules to the chitosan film-forming solution, controlling the solid-liquid ratio of the primary microcapsules to the chitosan film-forming solution to 1 g: 10-25 mL. Stir at 25-35℃ and 300-700 r / min for 30-90 min to allow chitosan to be deposited on the inner shell surface of the calcium alginate ion gel through electrostatic interaction. Then, add a sodium phytate aqueous solution with a concentration of 0.2-2.0 wt% to the system at a dropping rate of 0.3-2.0 mL / min, adjust the pH to 5.2-5.8, and continue the reaction for 20-60 min to obtain secondary microcapsules with a chitosan-phytate polyelectrolyte intermediate shell. S4. Add ethyl cellulose, lecithin and glyceryl monostearate to an ethanol aqueous solution with a volume concentration of 80-95%, and stir at 35-50℃ and 400-800r / min for 30-80min to obtain a hydrophobic coating solution. The hydrophobic coating solution was added to the secondary microcapsule suspension at a dropping rate of 0.5-3.0 mL / min, and hydrophilic fumed silica was added. The mixture was coated at 30-45℃ and 400-800 r / min for 40-120 min, and then cooled to 20-25℃ at a cooling rate of 0.5-1.5℃ / min to deposit ethyl cellulose and silica to form a hydrophobic shell. S5. Filter the obtained product, wash it with deionized water until the conductivity of the washing solution is ≤80μS / cm, and dry it at 35-45℃ and vacuum degree 0.06-0.09MPa for 6-14h. After sieving through a 100-400 mesh sieve, microcapsule delayed-release cooling particles are obtained.

5. The multi-stage cooling composition according to claim 1, characterized in that, The polyols include one or more of glycerol, propylene glycol, butylene glycol, 1,3-propanediol, and dipropylene glycol; The moisturizing agent includes one or more of sodium hyaluronate, betaine, trehalose, panthenol, and allantoin.

6. The multi-stage cooling composition according to claim 1, characterized in that, The emulsifying dispersant includes one or more of PEG-40 hydrogenated castor oil, polysorbate-20, polyglycerol fatty acid ester, and hydrogenated lecithin; The thickening stabilizer includes one or more of carbomer, xanthan gum, hydroxyethyl cellulose, and acrylate crosslinking polymers; The film-forming regulator includes one or more of polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl methylcellulose, pullulan, and acrylate copolymers.

7. The multi-stage cooling composition according to claim 1, characterized in that, The pH adjuster is selected from one or more of citric acid, sodium citrate, lactic acid, sodium lactate, arginine, triethanolamine, and sodium hydroxide. The preservative is selected from one or more of phenoxyethanol, ethylhexylglycerin, caprylyl glycol, sodium benzoate, and potassium sorbate.

8. A method for preparing a multi-stage cooling composition as described in any one of claims 1-7, characterized in that, Includes the following steps: A1. Add deionized water to the mixing container and stir at 25-45℃ and 400-900r / min. Add thickening and stabilizer, disperse for 20-60min, then add polyol and humectant, and continue stirring for 10-40min to obtain aqueous matrix. A2. Add the instant cooling agent to the emulsifying dispersant and stir for 10-40 minutes at 30-50℃ and 300-800r / min to dissolve or uniformly disperse the instant cooling agent and obtain the instant cooling premix. A3. Add the instant cooling premix to the aqueous matrix and homogenize at 1000-5000 r / min for 3-15 min. Then add the encapsulated slow-release cooling particles and stir at 600-1500 r / min for 10-30 min to obtain the initial mixed system. A4. Cool or keep the initial mixed system to 20-35℃, add film-forming regulator, preservative and pH adjuster to adjust the pH of the system to 5.0-7.0, then add microcapsule delayed-release cooling particles, and stir under low shear at 200-800r / min for 10-40min to obtain the compound system. A5. Degas the compound system under a vacuum of 0.04-0.08 MPa for 5-20 minutes, and filter it through an 80-200 mesh sieve to obtain the multi-stage cooling composition.

9. The method for preparing a multi-stage cooling composition according to claim 8, characterized in that, Before being added to the initial mixing system, the encapsulated slow-release cooling particles are first wetted with a wetting solution prepared by polyol and deionized water at a mass ratio of 1:1-5 to form an encapsulated slow-release cooling particle slurry with a solid content of 20-60wt%. Before being added to the compounding system, the microcapsule delayed-release cooling particles are first pre-dispersed in a dispersion prepared by deionized water, polyol and emulsifying dispersant at a mass ratio of 10-40:1-10:0.1-1.0 to form a microcapsule delayed-release cooling particle slurry with a solid content of 5-40wt%.

10. A method for preparing a multi-stage cooling composition according to claim 8, characterized in that, Both the encapsulated slow-release cooling particle slurry and the microencapsulated delayed-release cooling particle slurry are used at 20-35℃, and the stirring linear velocity after the addition of the microencapsulated delayed-release cooling particles is controlled at 0.2-1.5m / s.

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