A ternary supramolecular eutectic composition containing mandelic acid, its preparation method and application

Abstract

This invention belongs to the field of cosmetic technology, specifically relating to a ternary supramolecular cocrystal composition containing mandelic acid, its preparation method, and its application. The ternary supramolecular cocrystal composition containing mandelic acid is composed of mandelic acid, succinic acid, and dimethyl sulfone in a mass ratio of 1-4:1:1. The preparation method is as follows: mandelic acid, succinic acid, and dimethyl sulfone are vacuum dried to remove moisture and impurities, yielding pretreated raw materials. These pretreated raw materials are then added to a ball mill, and 10-20% (by mass) of anhydrous ethanol is added as a grinding aid solvent for grinding to obtain a mixture. Finally, the ethanol solvent is removed by drying to obtain the ternary supramolecular cocrystal composition containing mandelic acid. This invention uses specific raw material ratios and a specific process to prepare the ternary supramolecular cocrystal, which forms a stable crystal structure through a hydrogen bond network. This significantly improves its stability, exfoliating efficacy, and acne-reducing efficacy in cosmetic applications, while also reducing irritation to inflamed skin.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology, specifically relating to a ternary supramolecular eutectic composition containing mandelic acid, its preparation method, and its application. Background Technology

[0002] Mandelic acid, also known as mandelic acid or bitter mandelic acid, is an α-hydroxy acid with lipid-soluble properties. It can penetrate deep into the stratum corneum of the skin, gently exfoliating dead skin cells, improving enlarged pores, and brightening the complexion. It also has an inhibitory effect on inflammatory acne and is widely used in skin-renewing cosmetics. Currently, most commercially available mandelic acid products are added in a free form, which has the following technical drawbacks: First, it has poor water solubility, leading to unstable formulation systems and frequent crystallization; second, it is highly irritating, as direct contact with free mandelic acid can lower the skin's surface pH, causing discomfort such as erythema and stinging on sensitive skin.

[0003] Supramolecular cocrystallization technology assembles active ingredients and excipient molecules into stable crystal structures through intermolecular non-covalent bonds (such as hydrogen bonds and van der Waals forces), significantly improving the stability, solubility, and bioavailability of active ingredients while reducing irritation. Existing technologies include binary supramolecular acid systems; for example, the invention patent with publication number CN 116217379 A describes the reaction of tranexamic acid and mandelic acid to form a supramolecular salt. This supramolecular tranexamic acid-mandelic acid ion salt can better retain the efficacy of mandelic acid, such as its antioxidant properties, inhibition of melanocyte activity, and inhibition of tyrosinase activity. Simultaneously, it effectively improves the skin permeability of mandelic acid, enhancing its bioavailability; moreover, it has lower skin irritation, thus enhancing its application effect. However, research on ternary supramolecular cocrystallization of mandelic acid is currently limited, and there is a lack of corresponding theoretical and technical support regarding the mechanism of action and process conditions for the formation of ternary supramolecular cocrystallization of mandelic acid. Summary of the Invention

[0004] In view of the shortcomings and deficiencies of the existing technology, the primary objective of the present invention is to provide a ternary supramolecular eutectic composition containing mandelic acid.

[0005] Another object of the present invention is to provide a method for preparing the above-mentioned ternary supramolecular eutectic composition containing mandelic acid.

[0006] Another object of the present invention is to provide the application of the above-mentioned ternary supramolecular eutectic composition containing mandelic acid in cosmetics.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] A ternary supramolecular eutectic composition containing mandelic acid is composed of mandelic acid, succinic acid, and dimethyl sulfone in a mass ratio of 1 to 4:1:1.

[0009] The above-mentioned compositional conditions are necessary for the formation of specific ternary supramolecular eutectic compositions.

[0010] Preferably, the ternary supramolecular eutectic composition is composed of mandelic acid, succinic acid, and dimethyl sulfone in a mass ratio of 2~3:1:1.

[0011] The ternary supramolecular eutectic composition obtained under the above-mentioned preferred ratio conditions has better application formulation stability and application effect.

[0012] Mandelic acid (CAS: 90-64-2) has the following general physicochemical properties: molecular weight 152.15, melting point 119-121℃, water solubility 150g / L (20℃), pKa 3.85 (25℃). It is a white crystal or crystalline powder with skin-renewing and acne-removing effects.

[0013] It serves as the core active ingredient in the eutectic composition of this invention, and its mechanism of action is as follows: It contains a carboxyl (-COOH) and hydroxyl (-OH) double hydrogen bond donor. Under a specific ratio, it forms a carboxylic acid dimer (-COOH···HOOC-) through the carboxyl group and succinic acid, and at the same time forms a -OH···O=S hydrogen bond with the sulfone oxygen (O=S=O) of dimethyl sulfone through the hydroxyl group.

[0014] Succinic acid (CAS: 110-15-6) has the following general physicochemical properties: molecular weight 118.09, melting point 185-187℃, water solubility 56.2 g / L (20℃), pKa 4.21 / 5.64.

[0015] In the eutectic composition of this invention, it acts as a structural stabilizer, with the following mechanism of action: containing dicarboxyl groups, it acts as a "molecular bridge" and can simultaneously bind to mandelic acid molecules, solving the dispersion problem of mandelic acid and enhancing the stability of the eutectic structure. In the application of this invention, succinic acid, as a dicarboxylic acid, can enhance the exfoliating effect of mandelic acid.

[0016] Dimethyl sulfone (CAS: 67-71-0) has the following general physicochemical properties: molecular weight 78.13, melting point 109℃, good water solubility, and is a white needle-like crystal.

[0017] In the cocrystal composition of the present invention, it acts as a hydrogen bond acceptor and a penetration enhancer, and its mechanism of action is as follows: It contains a sulfone group (-SO2-) double strong hydrogen bond acceptor, which can anchor mandelic acid molecules to enhance the stability of the cocrystal, and at the same time has its own transdermal absorption enhancement effect, synergistically enhancing the skin penetration efficiency of mandelic acid.

[0018] By precisely controlling the intermolecular forces through specific ratios, a structurally stable supramolecular cocrystal is formed: under the condition that the mass ratio of mandelic acid, succinic acid and dimethyl sulfone is 1~4:1:1, a multi-level mixed hydrogen bond network is constructed through "carboxylic acid dimer hydrogen bonds + hydroxyl-sulfone hydrogen bonds" to form a stable ternary supramolecular cocrystal. Different properties are presented by the difference in mandelic acid content, which can be adapted to different cosmetic efficacy needs, and all meet the core conditions for the formation of supramolecular cocrystal (functional group complementarity and non-covalent bond synergistic effect).

[0019] The preparation method of the above-mentioned ternary supramolecular eutectic composition containing mandelic acid includes the following preparation steps:

[0020] (1) Raw material pretreatment: Take mandelic acid, succinic acid and dimethyl sulfone according to the mass ratio, place them in a vacuum drying oven and vacuum dry to remove moisture and impurities, and obtain the pretreated raw materials;

[0021] This step involves pre-drying the raw materials to remove moisture, in order to prevent the strong hydrogen bonding of water molecules from affecting the formation of the eutectic.

[0022] (2) Mixing and grinding: Add the pretreated raw materials from step (1) into a planetary ball mill, add 10-20% of the total mass of the raw materials with anhydrous ethanol as a grinding aid solvent and grind to obtain a mixture;

[0023] This step uses anhydrous ethanol, which has weak hydrogen bonding and good dispersibility, as a grinding aid to ensure thorough mixing of the raw materials and the initial formation of intermolecular interactions. The amount of grinding aid solvent must be strictly controlled at 10-20% of the total mass of the raw materials. Too much solvent will result in excessively slow crystallization, while too little will fail to effectively promote intermolecular interactions.

[0024] (3) Solvent removal: The mixture from step (2) is dried to remove the ethanol solvent, resulting in a ternary supramolecular eutectic composition containing mandelic acid.

[0025] Furthermore, the vacuum drying mentioned in step (1) refers to drying at 55~65℃ and -0.08~-0.1MPa for 12~36h.

[0026] Furthermore, the grinding mentioned in step (2) refers to grinding for 1 to 2 hours at room temperature and a rotation speed of 200 to 300 r / min.

[0027] The above grinding conditions ensure that the raw material particles are sufficiently refined, promoting the formation of eutectic.

[0028] Furthermore, the preferred method for drying and removing the ethanol solvent in step (3) is as follows:

[0029] The mixture after grinding in step (2) was placed in a fume hood and the ethanol was allowed to evaporate naturally at room temperature until constant weight was obtained, resulting in a loose solid. Then it was placed in a vacuum drying oven and vacuum dried for 6 to 24 hours at 45 to 55°C and -0.08 to -0.1 MPa to remove residual ethanol solvent, resulting in a high-purity ternary supramolecular eutectic composition powder.

[0030] By pre-drying through natural evaporation at room temperature and subsequent vacuum drying, the ethanol solvent can be effectively removed while maintaining the good crystal form and eutectic morphology of the eutectic composition.

[0031] Application of the above-mentioned ternary supramolecular eutectic composition containing mandelic acid in cosmetics.

[0032] Furthermore, the cosmetic is an essence, and the amount of the ternary supramolecular eutectic composition containing mandelic acid added to the essence is 6~12wt% (about 2~8wt% based on mandelic acid), and the pH of the essence is controlled at 3.0~5.0.

[0033] The above-mentioned serum can achieve highly effective skin rejuvenation and acne removal, while taking into account both gentleness and activity stability.

[0034] Cosmetic formulations can also be combined with conventional excipients, such as moisturizers, soothing agents, preservatives, thickeners, and citrate-sodium citrate buffer pairs (0.1~0.3%). Buffer pairs can precisely adjust the product's pH to a set range (3.0~5.0 for serums, 3.0~6.0 for toners), while ensuring the product's stability, safety, and user experience.

[0035] More preferably, the serum formulation comprises the following ingredients in weight percentages:

[0036] Ternary supramolecular eutectic: 6-12%

[0037] 1,3-Propanediol 4~6%,

[0038] Sodium hyaluronate 0.1~0.3%,

[0039] Panthenol 0.5-2%,

[0040] Dipotassium glycyrrhizate 0.05~0.15%,

[0041] Preservative 0.1~0.6%,

[0042] pH adjuster 0.1~0.3%,

[0043] Deionized water balance.

[0044] Furthermore, the cosmetic is a toner, and the amount of the ternary supramolecular eutectic composition containing mandelic acid added to the toner is 1-5 wt% (approximately 0.3-3.3% based on mandelic acid), and the pH of the toner is controlled at 3.0-6.0.

[0045] More preferably, the formula of the lotion includes the following ingredients in weight percentage:

[0046] Ternary supramolecular eutectic 1~5%

[0047] Glycerin 3-6%,

[0048] 1-3% polyethylene glycol

[0049] Plant extracts 0.1-1%,

[0050] Disodium EDTA 0.01~0.1%,

[0051] Preservative 0.1~0.6%,

[0052] pH adjuster 0.1~0.3%,

[0053] Deionized water balance.

[0054] Compared with the prior art, the beneficial effects of the present invention are:

[0055] (1) Significantly improved stability: The ternary supramolecular eutectic forms a stable crystal structure through a hydrogen bond network, which can effectively resist the degradation of mandelic acid by light and temperature, extending the product shelf life to more than 24 months, and improving the stability of free mandelic acid products by more than 30%.

[0056] (2) Significantly reduced irritation: Succinic acid adjusts the pH of the system to 4.5~5.5 (close to the physiological pH of the skin), while the eutectic structure reduces the content of free mandelic acid. According to Draize skin irritation test, the irritation score is reduced by more than 50% compared with the traditional 6% mandelic acid essence, making it suitable for sensitive skin.

[0057] (3) Optimized bioavailability: Dimethyl sulfone promotes the penetration of eutectic components through the stratum corneum of the skin. According to the Franz diffusion cell transdermal absorption test, the cumulative transdermal amount in 24 hours is more than 40% higher than that of free mandelic acid, and the skin-renewing effect is more significant.

[0058] (4) The preparation process is environmentally friendly and efficient: the grinding-solvent evaporation method is adopted, which does not require high temperature and high pressure conditions. The ethanol solvent can be recycled and reused, resulting in low production costs and making it suitable for large-scale industrial production. Attached Figure Description

[0059] Figure 1The images show the XRD characterization results of free mandelic acid, succinic acid, and dimethyl sulfone crystalline powders, as well as the ternary supramolecular eutectic products obtained in Examples 1-2 and Examples 4-5.

[0060] Figure 2 The image shows the XRD characterization results of the binary composition of mandelic acid: succinic acid = 2:1.

[0061] Figure 3 The image shows the XRD characterization results of the binary composition of mandelic acid: dimethyl sulfone = 2:1.

[0062] Figure 4 The image shows the XRD characterization results of the succinic acid: dimethyl sulfone (DMSF) binary composition in a 1:1 ratio. Detailed Implementation

[0063] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto.

[0064] Example 1

[0065] (1) Raw material pretreatment: Weigh 20g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.09MPa for 24h.

[0066] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 6g of anhydrous ethanol (15% of the total mass of the raw materials), grind at 250r / min at room temperature for 1.5h.

[0067] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0068] (4) Refining and drying: Vacuum drying at 50℃ and -0.09MPa for 12h yielded 38.2g of ternary supramolecular eutectic powder with a yield of 95.5%.

[0069] Example 2

[0070] (1) Raw material pretreatment: Weigh 30g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.1MPa for 24h.

[0071] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 8g of anhydrous ethanol (20% of the total mass of the raw materials), grind at 300r / min at room temperature for 2h.

[0072] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and evaporate it to constant weight at room temperature in a fume hood to obtain a loose solid.

[0073] (4) Refining and drying: Vacuum drying at 50℃ and -0.1MPa for 12h yielded 47.8g of ternary supramolecular eutectic powder with a yield of 95.6%.

[0074] Example 3

[0075] (1) Raw material pretreatment: Weigh 25g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 65℃ and -0.1MPa for 12h.

[0076] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 4.5g of anhydrous ethanol (10% of the total mass of the raw materials), grind at 300r / min at room temperature for 1h.

[0077] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0078] (4) Refining and drying: Vacuum drying at 55℃ and -0.1MPa for 6h yielded 43.4g of ternary supramolecular eutectic powder with a yield of 96.4%.

[0079] Example 4

[0080] Compared with Example 1, the ratio of mandelic acid, succinic acid, and dimethyl sulfone in this embodiment is adjusted to 1:1:1. The specific steps are as follows:

[0081] (1) Raw material pretreatment: Weigh 10g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.09MPa for 24h.

[0082] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 4.5g of anhydrous ethanol (15% of the total mass of the raw materials), grind at 250r / min at room temperature for 1.5h.

[0083] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0084] (4) Refining and drying: Vacuum drying at 50℃ and -0.09MPa for 12h yielded 28.6g of ternary supramolecular eutectic powder with a yield of 95.3%.

[0085] Example 5

[0086] Compared with Example 1, the ratio of mandelic acid, succinic acid, and dimethyl sulfone in this comparative example was adjusted to 4:1:1. The specific steps are as follows:

[0087] (1) Raw material pretreatment: Weigh 40g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.09MPa for 24h.

[0088] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 9g of anhydrous ethanol (15% of the total mass of the raw materials), grind at 250r / min at room temperature for 1.5h.

[0089] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0090] (4) Refining and drying: Vacuum drying at 50℃ and -0.09MPa for 12h yielded 57.1g of ternary supramolecular eutectic powder with a yield of 95.2%.

[0091] The ternary supramolecular eutectic products obtained in Examples 1-2 and 4-5 above were characterized by XRD, and the results are as follows: Figure 1 As shown ( Figure 1 From top to bottom, the components are: mandelic acid, succinic acid, dimethyl sulfone, mandelic acid:succinic acid:dimethyl sulfone = 1:1:1 (ternary supramolecular cocrystal composition of Example 4), mandelic acid:succinic acid:dimethyl sulfone = 2:1:1 (ternary supramolecular cocrystal composition of Example 1), mandelic acid:succinic acid:dimethyl sulfone = 3:1:1 (ternary supramolecular cocrystal composition of Example 2), and mandelic acid:succinic acid:dimethyl sulfone = 4:1:1 (ternary supramolecular cocrystal composition of Example 5). Figure 1 The results show that, compared with the characteristic peaks of pure mandelic acid, succinic acid, and dimethyl sulfone, a series of novel characteristic diffraction peaks were observed in the ternary supramolecular cocrystal product. This indicates that during the formation of the cocrystal product, the strong interaction between hydrogen bond donors and hydrogen bond acceptors (such as hydrogen bond network reconstruction) disrupted the original lattice energy of the two raw materials, thereby breaking their respective long-range lattice order and indicating that the sample formed an independent crystal structure.

[0092] To further demonstrate the necessary conditions for the formation of the ternary supramolecular eutectic composition of the present invention, binary compositions of mandelic acid: succinic acid = 2:1, mandelic acid: dimethyl sulfone = 2:1, and succinic acid: dimethyl sulfone = 1:1 (preparation process is the same as in Example 1) were characterized by XRD, and the results are as follows: Figure 2 ( Figure 2 From top to bottom, they correspond to: mandelic acid, succinic acid, and a binary composition of mandelic acid:succinic acid = 2:1. Figure 3 ( Figure 3 From top to bottom, they correspond to: mandelic acid, dimethyl sulfone, and a binary composition of mandelic acid:dimethyl sulfone = 2:1. Figure 4 ( Figure 4The components from top to bottom are: succinic acid, dimethyl sulfone, and a binary composition of succinic acid:dimethyl sulfone = 1:1 (as shown in the image). Figure 2 The results show that in the binary composition of mandelic acid and succinic acid, the strong characteristic peaks of the pure substances disappear and weaken in the composition, indicating that the crystal packing mode has been disrupted and the long-range order has been significantly reduced. Furthermore, no new crystallization diffraction peaks were observed, indicating that no new eutectic compound has formed in the system, but rather lattice disruption has occurred. Figure 3 The results showed that no new characteristic diffraction peaks were observed in the spectra of the mandelic acid + dimethyl sulfone binary composition, ruling out the possibility of the formation of a new eutectic compound. However, the spectra were not a simple linear superposition of the signals from the two components, indicating that the original crystal lattice was severely perturbed during the mixing process. A broadened diffuse diffraction peak was also observed, indicating the presence of a hydrogen-bonded network (short-range order) within the system, but a lack of long-range order characteristic of crystals—a typical feature of amorphous or liquid structures. Figure 4 The results showed that no new characteristic peaks were observed in the succinic acid + dimethyl sulfone binary composition, indicating that a eutectic compound with an independent crystal lattice structure was not formed. However, compared with the theoretical physical mixing pattern, the diffraction peak intensities of the mixture exhibited a nonlinear change. This selective attenuation of characteristic peaks suggests that intermolecular interactions occurred between the two components during the mixing process, leading to a disturbance of the long-range order of some crystal planes and a reduction in crystallinity.

[0093] The above results indicate that using a mass ratio of mandelic acid, succinic acid, and dimethyl sulfone of 1 to 4:1:1 is a necessary condition for forming specific ternary supramolecular eutectic compositions.

[0094] Example 6

[0095] Compared with Example 1, the amount of anhydrous ethanol added in this embodiment is 7.5% of the total mass of the raw materials. The specific steps are as follows:

[0096] (1) Raw material pretreatment: Weigh 20g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.09MPa for 24h.

[0097] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 3g of anhydrous ethanol (7.5% of the total mass of the raw materials), grind at 250r / min at room temperature for 1.5h.

[0098] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0099] (4) Refining and drying: Vacuum drying at 50℃ and -0.09MPa for 12h yielded 38.4g of ternary supramolecular eutectic powder with a yield of 96.0%.

[0100] Example 7

[0101] Compared with Example 1, the amount of anhydrous ethanol added in this embodiment is 25% of the total mass of the raw materials. The specific steps are as follows:

[0102] (1) Raw material pretreatment: Weigh 20g of mandelic acid, 10g of succinic acid and 10g of dimethyl sulfone, place them in a vacuum drying oven and dry at 60℃ and -0.09MPa for 24h.

[0103] (2) Mixing and grinding: Add the dried raw materials to a planetary ball mill, add 10g of anhydrous ethanol (25% of the total mass of the raw materials), grind at 250r / min at room temperature for 1.5h.

[0104] (3) Solvent evaporation: Transfer the ground mixture to a petri dish and place it in a fume hood to evaporate to constant weight at room temperature to obtain a loose solid.

[0105] (4) Refining and drying: Vacuum drying at 50℃ and -0.09MPa for 12h yielded 38.1g of ternary supramolecular eutectic powder with a yield of 95.3%.

[0106] Example 8

[0107] An essence containing a ternary supramolecular eutectic composition of mandelic acid has the following formulation composition as shown in Table 1.

[0108] Table 1. Composition of the serum formula

[0109]

[0110] The preparation method of the essence is as follows: Deionized water is heated to 70°C, sodium hyaluronate is added and stirred to dissolve, the temperature is lowered to 45°C, and ternary supramolecular eutectic, 1,3-propanediol, panthenol, and dipotassium glycyrrhizate are added in sequence and stirred until completely dissolved; the pH of the system is adjusted to 3.7~4.0 with a citrate-sodium citrate buffer, the temperature is lowered to room temperature, phenoxyethanol is added and stirred evenly, and then filtered to obtain the essence.

[0111] Example 9

[0112] A toner containing a ternary supramolecular eutectic composition of mandelic acid has the following formulation composition as shown in Table 2.

[0113] Table 2. Composition of Toner Formula

[0114]

[0115] The preparation method of the toner is as follows: Deionized water is added to a mixing tank, followed by glycerin, polyethylene glycol-400, and disodium EDTA in sequence. The mixture is stirred until dissolved, and then a ternary supramolecular eutectic is added and stirred until completely dissolved. The pH of the system is adjusted to 4.0-4.5 using a citric acid-sodium citrate buffer, and then calendula extract and chlorphenesin are added. The mixture is stirred evenly, allowed to stand, and then filtered to obtain the toner.

[0116] Comparative Example 1

[0117] An essence containing mandelic acid, compared with Example 8, uses free mandelic acid, succinic acid, and dimethyl sulfone instead of the ternary supramolecular eutectic, and its formulation composition is shown in Table 3 below.

[0118] Table 3. Composition of a standard free mandelic acid serum formula

[0119]

[0120] The preparation method of the essence is as follows: Deionized water is heated to 70°C, sodium hyaluronate is added and stirred to dissolve, the temperature is lowered to 45°C, and mandelic acid, succinic acid, dimethyl sulfone, 1,3-propanediol, panthenol, and dipotassium glycyrrhizate are added in sequence and stirred until completely dissolved; the pH of the system is adjusted to 3.7~4.0 with a citrate-sodium citrate buffer, the temperature is lowered to room temperature, phenoxyethanol is added and stirred evenly, and then filtered to obtain the essence.

[0121] Performance testing and effect verification: The ternary supramolecular eutectic obtained in Examples 1-7 was used to prepare serum products according to the formula and preparation method of Example 8, and the serum product obtained in Comparative Example 1 was used as a control group to test the corresponding performance.

[0122] (1) Stability test

[0123] The serum samples to be tested (three replicates per group) were stored for three months in a 45℃ constant temperature incubator, a -15℃ freezer, and a simulated natural light environment, respectively. The retention rate of mandelic acid or the layering and crystallization were tested. The test results are shown in Table 4 below.

[0124] Table 4 Stability Test Results

[0125]

[0126] The results in Table 4 show that the ternary supramolecular eutectic of this invention significantly improves the stability of mandelic acid. Furthermore, excessively high or low mandelic acid ratios, as well as excessively high or low amounts of anhydrous ethanol as the grinding solvent during mixing and grinding, will affect eutectic formation and lead to decreased stability.

[0127] (2) Skin irritation test

[0128] Following the guidelines of the "Cosmetic Safety Technical Specifications," the Draize method was used to conduct human skin patch tests on 30 volunteers. The tested serum sample was applied to each volunteer, and skin reactions were observed after 24 hours (skin reaction grading criteria: Grade 0 - negative reaction; Grade 1 - suspicious reaction, only slight erythema; Grade 2 - weak positive reaction (erythema reaction); erythema, infiltration, edema, and possible papules; Grade 3 - strong positive reaction (vesicular reaction); erythema, infiltration, edema, papules, and vesicles; reaction may extend beyond the tested area; Grade 4 - very strong positive reaction (confluent vesicular reaction); obvious erythema, severe infiltration, edema, and confluent vesicles; reaction extends beyond the tested area). The test results are shown in Table 5 below.

[0129] Table 5 Results of Skin Irritation Test

[0130]

[0131] The results in Table 5 show that the ternary supramolecular eutectic of the present invention significantly reduces the irritation of mandelic acid and stabilizes the pH at 3.7-4.0, which can maintain the activity of mandelic acid and avoid excessive skin irritation.

[0132] (3) Exfoliating efficacy test

[0133] Eighty volunteers with significant facial keratin buildup (stratum corneum thickness ≥20μm) were randomly divided into eight groups of 10 each. Each group used the serum sample to be tested once every evening for 28 consecutive days. The thickness of the stratum corneum was measured before use, after 14 days and 28 days of use using a skin stratum corneum analyzer. The reduction rate was calculated and the skin sensations during use were recorded. The test results are shown in Table 6 below.

[0134] Table 6 Exfoliation Efficacy Test Results

[0135]

[0136] The results in Table 6 show that the ternary supramolecular eutectic of the present invention has significantly improved exfoliation efficiency and is gentler, making it less likely to cause skin barrier damage.

[0137] (4) Acne-removing efficacy test

[0138] Referring to the "Guidelines for Evaluating the Efficacy of Cosmetic Acne Treatment", 80 volunteers with facial inflammatory acne (papules and pustules) (each with 10-20 pimples on their face) were selected and randomly divided into eight groups of 10 people each. They used the serum sample to be tested once in the morning and once in the evening for 28 consecutive days. The number of pimples and the average time for redness and swelling to subside were recorded. The test results are shown in Table 7 below.

[0139] Table 7 Results of Acne Treatment Efficacy Test

[0140]

[0141] The results in Table 7 show that the essence of this invention has a more significant acne-removing effect and faster redness and swelling reduction through the synergistic effect of ternary supramolecular eutectic.

[0142] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A ternary supramolecular eutectic composition containing mandelic acid, characterized in that: The ternary supramolecular co-crystal composition comprises mandelic acid, succinic acid, and dimethyl sulfone in a mass ratio of 1~4:1:

1. The preparation method of the ternary supramolecular co-crystal composition includes the following preparation steps: (1) Raw material pretreatment: Take mandelic acid, succinic acid and dimethyl sulfone according to the mass ratio, place them in a vacuum drying oven and vacuum dry to remove moisture and impurities, and obtain the pretreated raw materials; (2) Mixing and grinding: Add the pretreated raw materials from step (1) into a planetary ball mill, add 10-20% of the total mass of the raw materials with anhydrous ethanol as a grinding aid solvent and grind to obtain a mixture; (3) Solvent removal: The mixture from step (2) is dried to remove the ethanol solvent, resulting in a ternary supramolecular eutectic composition containing mandelic acid.

2. The ternary supramolecular eutectic composition containing mandelic acid according to claim 1, characterized in that: The ternary supramolecular eutectic composition is composed of mandelic acid, succinic acid, and dimethyl sulfone in a mass ratio of 2~3:1:

1.

3. A method for preparing a ternary supramolecular eutectic composition containing mandelic acid as described in claim 1 or 2, characterized in that: The preparation steps include the following: (1) Raw material pretreatment: Take mandelic acid, succinic acid and dimethyl sulfone according to the mass ratio, place them in a vacuum drying oven and vacuum dry to remove moisture and impurities, and obtain the pretreated raw materials; (2) Mixing and grinding: Add the pretreated raw materials from step (1) into a planetary ball mill, add 10-20% of the total mass of the raw materials with anhydrous ethanol as a grinding aid solvent and grind to obtain a mixture; (3) Solvent removal: The mixture from step (2) is dried to remove the ethanol solvent, resulting in a ternary supramolecular eutectic composition containing mandelic acid.

4. The method for preparing a ternary supramolecular eutectic composition containing mandelic acid according to claim 3, characterized in that: The vacuum drying mentioned in step (1) refers to drying at 55~65℃ and -0.08~-0.1MPa for 12~36h; the grinding mentioned in step (2) refers to grinding at room temperature and 200~300r / min for 1~2h.

5. The method for preparing a ternary supramolecular eutectic composition containing mandelic acid according to claim 3, characterized in that: The method for drying and removing the ethanol solvent in step (3) is as follows: The mixture after grinding in step (2) was placed in a fume hood and the ethanol was allowed to evaporate naturally at room temperature until constant weight was obtained, resulting in a loose solid. Then it was placed in a vacuum drying oven and vacuum dried for 6 to 24 hours at 45 to 55°C and -0.08 to -0.1 MPa to remove residual ethanol solvent, resulting in a high-purity ternary supramolecular eutectic composition powder.

6. The application of the ternary supramolecular eutectic composition containing mandelic acid as described in claim 1 or 2 in cosmetics.

7. The application according to claim 6, characterized in that: The cosmetic product is an essence, and the amount of the ternary supramolecular eutectic composition containing mandelic acid added to the essence is 6~12wt%, and the pH of the essence is controlled at 3.0~5.

0.

8. The application according to claim 7, characterized in that: The serum formula comprises the following ingredients in percentage by weight: Ternary supramolecular eutectic: 6-12% 1,3-Propanediol 4~6%, Sodium hyaluronate 0.1~0.3%, Panthenol 0.5-2%, Dipotassium glycyrrhizate 0.05~0.15%, Preservative 0.1~0.6%, pH adjuster 0.1~0.3%, Deionized water balance.

9. The application according to claim 6, characterized in that: The cosmetic is a toner, and the amount of the ternary supramolecular eutectic composition containing mandelic acid added to the toner is 1-5 wt%, and the pH of the toner is controlled at 3.0-6.

0.

10. The application according to claim 9, characterized in that: The formula of the toner includes the following ingredients in percentage by weight: Ternary supramolecular eutectic 1~5% Glycerin 3-6%, 1-3% polyethylene glycol Plant extracts 0.1-1%, Disodium EDTA 0.01~0.1%, Preservative 0.1~0.6%, pH adjuster 0.1~0.3%, Deionized water balance.

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