Ellagic acid-pca sodium co-crystal and preparation method and application thereof

Abstract

The application provides a kind of ellagic acid-PCA sodium co-crystal and its preparation method and application, belong to the field of cosmetics technology.The X-ray powder diffraction pattern of the ellagic acid-PCA sodium co-crystal described in the application has characteristic peaks at 2θ angles of 7.9±0.2°, 13.5±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2° and 38.9±0.2°.The ellagic acid-PCA sodium co-crystal prepared by the co-crystal technology of the application improves the water dispersibility and stability of ellagic acid, so that it can be easily applied in water-dispersible cosmetics, such as cosmetic water, milk, cream products, etc.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, specifically to an ellagic acid-PCA sodium eutectic, its preparation method, and its application. Background Technology

[0002] Ellagic acid, also known as ellagic acid or oleuropeinic acid, possesses anti-inflammatory, antibacterial, antioxidant, and anti-allergic properties. It also enhances immunity, lowers blood pressure, calms the nerves, and promotes blood clotting. In cosmetics, it offers anti-aging, whitening, astringent, and moisturizing effects. Ellagic acid is a polyphenolic dilactone. Its lipophilic portion has four rings, while its hydrophilic portion has four phenolic groups and two lactone rings. These structural characteristics result in poor water and lipophilic solubility, leading to low solubility, poor dispersibility, instability, and difficulty in absorption, significantly limiting its application in cosmetics.

[0003] The chemical structural formula of ellagic acid is as follows: .

[0004] Existing literature also reports various delivery systems for ellagic acid, including organic solvent solubilization, nano-suspensions, nanostructured lipid carriers, and cyclodextrin inclusion complexes. However, the preparation processes of nano-formulations and lipid carriers are complex and costly, and the problem of residual organic solvents is difficult to solve effectively, limiting their application in cosmetics and other fields. While the above methods can solve the problem of the instantaneous dispersion ability of ellagic acid, during storage, ellagic acid is prone to redeposition due to many factors such as solvent evaporation and temperature changes, forming sediment at the bottom, which makes it difficult to meet the requirements of long-term product stability in practical applications.

[0005] Chinese patent application CN114010532A discloses a two-component, one-way sustained-release skin repair film. Ellagic acid and sodium PCA are added directly to a mixed solution of sodium alginate and carboxymethyl chitosan as active ingredients to obtain a mixture. Sodium alginate and carboxymethyl chitosan act as the film-forming framework for shaping, but do not change the solubility or dispersion properties of the loaded components. However, the film-forming framework material also limits its application to a peel-off hydrogel film, making it unsuitable for use in ordinary water, lotion, or cream products.

[0006] Cocrystals can be divided into inorganic cocrystals and organic cocrystals. Generally, organic cocrystals are crystals formed by the association of two or more compounds through non-covalent bonds in a certain chemical ratio. Non-covalent bonds include hydrogen bonds, π-π stacking interactions, and ionic interactions. Currently, there is no known application of ellagic acid-sodium PCA cocrystal technology in the cosmetics field. Summary of the Invention

[0007] In view of this, the present invention provides an ellagic acid-PCA sodium cocrystal, its preparation method and application. By utilizing cocrystal technology, the water dispersibility and stability of ellagic acid are improved, making it easier to use in water-dispersible cosmetics, such as toners, lotions, creams and other products.

[0008] To achieve the above objectives, the present invention provides an ellagic acid-sodium PCA eutectic, wherein the X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.2°, 13.5±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2°, and 38.9±0.2°.

[0009] XRD characterization results showed that the ellagic acid-sodium PCA eutectic exhibited unique diffraction peaks at 2θ = 7.9±0.2°, 13.5±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2°, and 38.9±0.2°, confirming the formation of the new crystal form. By forming a eutectic with ellagic acid and sodium pyrrolidone-5-carboxylate (sodium PCA), a stable eutectic structure was constructed using the hydrogen bonding between the two. This also improved the dispersibility of ellagic acid in polyhydroxy solvent systems such as water, effectively solving the problems of poor dispersion and poor formulation stability of ellagic acid in existing technologies.

[0010] Furthermore, the X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.1°, 13.5±0.1°, 19.1±0.1°, 19.8±0.1°, 23.9±0.1°, 27.5±0.1°, and 38.9±0.1°.

[0011] Furthermore, the X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.2°, 13.5±0.2°, 16.3±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2°, 28.3±0.2°, 36.2±0.2°, and 38.9±0.2°.

[0012] Furthermore, the X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.1°, 13.5±0.1°, 16.3±0.1°, 19.1±0.1°, 19.8±0.1°, 23.9±0.1°, 27.5±0.1°, 28.3±0.1°, 36.2±0.1°, and 38.9±0.1°.

[0013] A method for preparing ellagic acid-sodium PCA eutectic includes the following steps: (1) Mix ellagic acid with an organic solvent to obtain an ellagic acid solution; under ultrasonic conditions, add sodium PCA aqueous solution dropwise to the ellagic acid solution. After the addition is complete, continue ultrasonic treatment and then filter to obtain a clear solution. (2) In a sealed environment, the antisolvent is diffused into the clear solution to precipitate crystals. The crystals are then filtered, washed, and dried to obtain ellagic acid-sodium PCA eutectic.

[0014] To address the technical challenges of low solubility and poor dispersibility of ellagic acid in aqueous media, this invention employs a eutectic modification strategy, using sodium PCA as the eutectic ligand, to prepare ellagic acid-sodium PCA eutectic via solution co-crystallization. Ultrasonic cavitation promotes hydrogen bonding between ellagic acid and sodium PCA molecules, leading to the formation of a stable crystal structure through intermolecular forces and hydrogen bonding, ultimately resulting in the ellagic acid-sodium PCA eutectic.

[0015] Furthermore, the molar ratio of ellagic acid to sodium PCA is 1:(0.5-2).

[0016] Furthermore, the organic solvent is at least one selected from N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO); Furthermore, the antisolvent is ether or acetone.

[0017] Furthermore, the ultrasound parameters include: ultrasound power of 130-195W, working frequency of 20-25kHz; ultrasound duration of 2-6s per session, interval of 2-6s, total ultrasound time of 2-6min; and temperature of 28-35℃.

[0018] The total ultrasound time is the sum of the cumulative ultrasound time and the cumulative interval time.

[0019] Furthermore, the dropping rate of the sodium PCA aqueous solution is 1-10 mL / min.

[0020] Furthermore, the cell disruptor probe has a diameter of 6 mm.

[0021] An ellagic acid-sodium PCA eutectic complex, comprising the ellagic acid-sodium PCA eutectic or the ellagic acid-sodium PCA eutectic prepared by the preparation method.

[0022] Furthermore, it also includes a supramolecular ionic liquid, which comprises D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride (CAS: 58-56-0), with the mass ratio of D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride being 1:(1-10):(0.05-0.2).

[0023] Furthermore, the cyclodextrin derivative is hydroxypropyl betacyclodextrin.

[0024] A supramolecular ionic liquid is formed by D-panthenol, cyclodextrin derivatives, and pyridoxine hydrochloride, and then loaded with ellagic acid-sodium PCA eutectic. Through intermolecular forces and hydrogen bonds, a stable complex is formed, which can significantly improve the dispersibility of ellagic acid without changing its molecular structure, thus expanding its application in cosmetic formulations.

[0025] The preparation method of the ellagic acid-sodium PCA co-crystal complex includes the following steps: 1) D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride were mixed and ground to obtain a supramolecular ionic liquid; 2) After mixing the ellagic acid-sodium PCA eutectic with the supramolecular ionic liquid, the mixture was ground to obtain the ellagic acid-sodium PCA eutectic complex.

[0026] This invention prepares an ellagic acid-sodium PCA eutectic complex via a two-step grinding method. First, a supramolecular ionic liquid is prepared by co-grinding D-panthenol, a cyclodextrin derivative, and pyridoxine hydrochloride. Then, this ionic liquid is mixed and ground with the ellagic acid-sodium PCA eutectic to obtain the final product. This method is simple to operate, operates under mild conditions, and is low in cost, making it suitable for industrial production.

[0027] Furthermore, the mass ratio of ellagic acid-sodium PCA eutectic to supramolecular ionic liquid is 1:(10-50).

[0028] Further, in step 1), the grinding rate is 100-700 rpm and the grinding time is 0.5-1 h.

[0029] Furthermore, in step 2), the grinding rate is 300-700 rpm and the grinding time is 0.5-2 h.

[0030] The application of the ellagic acid-sodium PCA eutectic, the ellagic acid-sodium PCA eutectic or the ellagic acid-sodium PCA eutectic complex prepared by the preparation method in cosmetics.

[0031] The above-described technical solution of the present invention has at least the following beneficial effects: The ellagic acid-sodium PCA cocrystal of this invention utilizes the hydrogen bonding between ellagic acid and sodium PCA to construct a stable cocrystal structure, breaking the strong π-π packing between ellagic acid molecules. The ellagic acid-sodium PCA cocrystal complex further utilizes a supramolecular ionic liquid to carry the ellagic acid-sodium PCA cocrystal, forming a dual solubilization system that gradually improves the dispersibility and stability of ellagic acid. This allows for its application in cosmetics, enhancing the stability, skin penetration, and synergistic sun protection effects of ellagic acid.

[0032] The ellagic acid-sodium PCA eutectic complex formed by the ellagic acid-sodium PCA eutectic and supramolecular ionic liquid of this invention is completely dispersed in water, with no precipitation observed after 10 minutes, exhibiting good stability and dispersibility. However, if the ellagic acid-sodium PCA eutectic is replaced with ellagic acid, or a simple blend of ellagic acid and sodium PCA, partial precipitation or precipitation after standing occurs, resulting in poor dispersibility and stability. Furthermore, the components in the supramolecular ionic liquid are synergistic and indispensable; the absence of any one component will reduce the dispersibility and stability of the ellagic acid-sodium PCA eutectic complex in water.

[0033] The ellagic acid-sodium PCA cocrystal complex of the present invention can be used in cosmetics, improving the stability, skin permeability, and synergistic effect of ellagic acid in sun protection; moreover, its preparation method is simple, the cost is low, and it is suitable for large-scale production. Attached Figure Description

[0034] Figure 1 X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic prepared in Example 1; Figure 2 X-ray powder diffraction pattern of sodium PCA; Figure 3 The X-ray powder diffraction pattern of ellagic acid; Figure 4 The images show the samples prepared in Example 2 and Comparative Examples 1-6 after being mixed with water for 0 minutes. Figure 5 The images show the samples prepared in Example 2 and Comparative Examples 1-6 after being mixed with water for 10 minutes. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0036] The cyclodextrin derivative used in the specific embodiments of the present invention is hydroxypropyl beta-cyclodextrin, which was purchased from Shandong Binzhou Zhiyuan Biotechnology Co., Ltd.; ellagic acid was purchased from Guangzhou Jahwa Chemical Co., Ltd.; and sodium PCA was purchased from Cosfa International Trading (Guangzhou) Co., Ltd.

[0037] Example 1 A method for preparing ellagic acid-sodium PCA eutectic includes the following steps: (1) Weigh 0.0046 mol of ellagic acid into a glass reaction vessel, add 125 g of DMAc, and stir until completely dissolved to obtain an ellagic acid solution; 0.0046 mol of sodium PCA was dissolved in 24.82 g of deionized water to obtain an aqueous solution of sodium PCA; The cell disruptor probe has a diameter of 6 mm and an operating frequency of 20-25 kHz. The probe is immersed below the surface of the ellagic acid solution, and ultrasonic oscillation is applied. The ultrasonic parameters are: ultrasonic power 195 W, ultrasonic time 2 s per session, interval time 2 s, and temperature 28-35℃. During the probe operation, sodium PCA aqueous solution is added to the ellagic acid solution at a rate of 10 ml / min. After the addition is complete, ultrasonication continues for 5 min until the mixture becomes relatively clear. After filtration, a clear solution is obtained. (2) Transfer the clear solution to a clean beaker and place the beaker in a sealed desiccator. Add the antisolvent diethyl ether to the bottom of the desiccator beforehand, seal the desiccator, and use the solvent diffusion method to diffuse the antisolvent into the ellagic acid-PCA sodium solution to precipitate crystals. After filtration, washing and drying, obtain the ellagic acid-PCA sodium eutectic.

[0038] X-ray powder diffraction patterns of sodium PCA, ellagic acid, and the ellagic acid-sodium PCA eutectic prepared in Example 1 were measured using a Bruker D8 ADVANCE X-ray diffractometer with Cu-Kα irradiation at a wavelength of λ=1.54Å. The tests were performed at room temperature in step scan mode with the following parameters: scanning range from 3° to 40° in the 2θ interval, step size (Δ2θ): 0.02°, and peak position accuracy of approximately ±0.02°.

[0039] The X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic prepared in Example 1 is as follows: Figure 1 As shown in Table 1, the 2θ angles of the main characteristic diffraction peaks and their corresponding relative diffraction intensities (arranged in ascending order of 2θ) are shown in Table 1.

[0040] Table 1. Main characteristic diffraction peaks of ellagic acid-sodium PCA eutectic

[0041] The X-ray powder diffraction pattern of sodium PCA is as follows: Figure 2 As shown in Table 2, the 2θ angles of the main characteristic diffraction peaks and their corresponding relative diffraction intensities (arranged in ascending order of 2θ) are shown in Table 2.

[0042] Table 2 Main characteristic diffraction peaks of sodium PCA

[0043] The X-ray powder diffraction pattern of ellagic acid is as follows: Figure 3 As shown in Table 3, the 2θ angles of the main characteristic diffraction peaks and their corresponding relative diffraction intensities (arranged in ascending order of 2θ) are shown in Table 3.

[0044] Table 3. Main characteristic diffraction peaks of ellagic acid

[0045] From Tables 1-3 and Figures 1-3 It is evident that the ellagic acid-sodium PCA eutectic, sodium PCA, and ellagic acid exhibit completely different X-ray powder diffraction patterns, indicating that the ellagic acid-sodium PCA eutectic is not a simple superposition of the diffraction peaks of the raw materials. Compared to ellagic acid and sodium PCA, the eutectic pattern shows significant changes: the characteristic main peaks of the raw materials (such as 9.61° for ellagic acid, 17.71° for sodium PCA, and the strong peaks at 12.23° / 12.07° for both) completely disappear, while entirely new diffraction peaks appear at 7.89°, 13.54°, 19.78°, and 38.93°. Furthermore, the strongest reference peak of the eutectic shifts to 13.54°, and the relative intensity (65.6%) of its second strongest peak (27.53°) far exceeds the peak intensity of the raw materials at adjacent angles. This evidence strongly suggests that the prepared samples are not physically mixed, but rather form an ellagic acid-sodium PCA eutectic with a novel lattice arrangement.

[0046] Example 2 A method for preparing an ellagic acid-sodium PCA eutectic complex includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride in a mass ratio of 1:1:0.05 and mix them together. Then, grind them using a planetary ball mill at a grinding speed of 500 rpm for 1 h to obtain the supramolecular ionic liquid for later use. 2) Add 5g of the ellagic acid-sodium PCA cocrystal prepared in Example 1 to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the ellagic acid-sodium PCA cocrystal complex.

[0047] Example 3 This embodiment is basically the same as that of embodiment 1, except that the preparation of ellagic acid-sodium PCA eutectic is as follows: in step (1), the ultrasonic power is 130W, the ultrasonic time is 6s each time, the interval time is 6s, and the total ultrasonic time is 6min.

[0048] Example 4 This embodiment is basically the same as that of embodiment 1, except that the preparation of ellagic acid-sodium PCA eutectic is as follows: in step (1), the ultrasonic power is 150W, the ultrasonic time is 3s each time, the interval time is 3s, and the total ultrasonic time is 2min.

[0049] Example 5 This embodiment is basically the same as that of embodiment 1, except that in the preparation of ellagic acid-sodium PCA eutectic: in step (2), acetone is used as the antisolvent.

[0050] Example 6 This embodiment is basically the same as that of embodiment 1, except that the preparation of ellagic acid-sodium PCA eutectic is as follows: in step (1), the molar ratio of ellagic acid to sodium PCA is 1:0.5.

[0051] Example 7 This embodiment is basically the same as that of embodiment 1, except that the preparation of ellagic acid-sodium PCA eutectic is as follows: in step (1), the molar ratio of ellagic acid to sodium PCA is 1:2.

[0052] Example 8 This embodiment is basically the same as embodiment 2, except that in step 2), the mass ratio of ellagic acid-sodium PCA eutectic to supramolecular ionic liquid is 1:20.

[0053] Example 9 This embodiment is basically the same as embodiment 2, except that in step 2), the mass ratio of ellagic acid-sodium PCA eutectic to supramolecular ionic liquid is 1:50.

[0054] Example 10 This embodiment is basically the same as embodiment 2, except that in step 1), the mass ratio of D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride is 1:10:0.2.

[0055] Example 11 This embodiment is basically the same as embodiment 2, except that in step 1), the mass ratio of D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride is 1:5:0.1.

[0056] Comparative Example 1 This embodiment is basically the same as Embodiment 2, except that in step 2), pure ellagic acid is added to a supramolecular ionic liquid for mixing. Specifically, it includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride in a mass ratio of 1:1:0.05 and mix them together. Then, grind them using a planetary ball mill at a grinding speed of 500 rpm for 1 h to obtain the supramolecular ionic liquid for later use. 2) Add 5g of pure ellagic acid to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the ellagic acid complex.

[0057] Comparative Example 2 This embodiment is basically the same as Embodiment 2, except that in step 2), sodium PCA is added to the supramolecular ionic liquid for mixing. Specifically, it includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride in a mass ratio of 1:1:0.05 and mix them together. Then, grind them using a planetary ball mill at a grinding speed of 500 rpm for 1 h to obtain the supramolecular ionic liquid for later use. 2) Add 5g of sodium PCA to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the sodium PCA complex.

[0058] Comparative Example 3 This embodiment is basically the same as Embodiment 2, except that in step 2), ellagic acid and sodium PCA are physically mixed before being added to the supramolecular ionic liquid. Specifically, it includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol, cyclodextrin derivative and pyridoxine hydrochloride in a mass ratio of 1:1:0.05 and mix them together. Then, grind them using a planetary ball mill at a grinding speed of 500 rpm for 1 h to obtain the supramolecular ionic liquid for later use. 2) After physically mixing ellagic acid and sodium PCA (5g total, with a molar ratio of 1:1), add 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind using a planetary ball mill at a grinding rate of 500rpm for 2h to obtain an ellagic acid-sodium PCA mixture.

[0059] Comparative Example 4 This embodiment is basically the same as Example 2, except that the supramolecular ionic liquid does not contain cyclodextrin derivatives. It includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol and pyridoxine hydrochloride in a mass ratio of 1:0.05, mix them together, and then grind them using a planetary ball mill at a grinding rate of 500 rpm for 1 h to obtain the supramolecular ionic liquid for later use. 2) Add 5g of the ellagic acid-sodium PCA cocrystal prepared in Example 1 to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the ellagic acid-sodium PCA cocrystal complex.

[0060] Comparative Example 5 This embodiment is basically the same as Example 2, except that the supramolecular ionic liquid does not contain D-panthenol. It includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh out cyclodextrin derivative and pyridoxine hydrochloride in a mass ratio of 1:0.05, mix them together, and grind them using a planetary ball mill at a grinding rate of 500 rpm for 1 hour to obtain supramolecular ionic liquid for later use. 2) Add 5g of the ellagic acid-sodium PCA cocrystal prepared in Example 1 to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the ellagic acid-sodium PCA cocrystal complex.

[0061] Comparative Example 6 This embodiment is basically the same as Example 2, except that the supramolecular ionic liquid does not contain pyridoxine hydrochloride. It includes the following steps: 1) Preparation of supramolecular ionic liquid: Weigh D-panthenol and cyclodextrin derivative in a mass ratio of 1:1, mix them together, and grind them using a planetary ball mill at a grinding rate of 500 rpm for 1 hour to obtain supramolecular ionic liquid for later use. 2) Add 5g of the ellagic acid-sodium PCA cocrystal prepared in Example 1 to 50g of the supramolecular ionic liquid prepared in step 1) and mix. After mixing, grind the mixture using a planetary ball mill at a grinding rate of 500 rpm for 2 hours to obtain the ellagic acid-sodium PCA cocrystal complex.

[0062] The samples prepared in Example 2 and Comparative Examples 1-6 were dispersed in water to obtain an aqueous dispersion with a mass concentration of 5%. Their appearance was observed and compared, and their dispersibility and stability in water were investigated. The results are shown in Table 4. Figure 4 and Figure 5 As shown.

[0063] Table 4. Dispersibility and stability in water of Examples 2 and Comparative Examples 1-6

[0064] like Figure 4 As shown, after the samples prepared in Example 2 and Comparative Examples 1-6 were mixed with water for 0 min, from left to right, they are Example 2, Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5, and Comparative Example 6.

[0065] like Figure 5 As shown, after the samples prepared in Example 2 and Comparative Examples 1-6 were mixed with water for 10 minutes, from left to right, they are Example 2, Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5, and Comparative Example 6.

[0066] Combined with Table 4, Figure 4 and Figure 5 As shown in Example 2 and Comparative Examples 1-3, the ellagic acid-sodium PCA eutectic complex is completely dispersed in water, appearing milky white, and does not settle even after standing for 10 minutes. However, ellagic acid + supramolecular ionic liquid and ellagic acid + sodium PCA (physical mixture) + supramolecular ionic liquid both show precipitation after standing for 10 minutes. Therefore, it can be concluded that, when both contain supramolecular ionic liquids, the ellagic acid-sodium PCA eutectic prepared according to this invention is beneficial for improving the dispersibility of ellagic acid in water.

[0067] Combined with Table 4, Figure 4 and Figure 5 As can be seen from Example 2 and Comparative Examples 4-6, if the supramolecular ionic liquid lacks cyclodextrin derivatives, D-panthenol or pyridoxine hydrochloride, the dispersibility of the ellagic acid-sodium PCA eutectic complex in water will be reduced.

[0068] Therefore, it can be seen that the ellagic acid-sodium PCA cocrystal complex prepared by combining ellagic acid-sodium PCA cocrystal with supramolecular ionic liquid is beneficial to improving the dispersibility and stability of ellagic acid in water.

Claims

1. A eutectic mixture of ellagic acid and sodium PCA, characterized in that: The X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.2°, 13.5±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2°, and 38.9±0.2°.

2. The ellagic acid-sodium PCA eutectic according to claim 1, characterized in that: The X-ray powder diffraction pattern of the ellagic acid-sodium PCA eutectic exhibits characteristic peaks at 2θ angles of 7.9±0.2°, 13.5±0.2°, 16.3±0.2°, 19.1±0.2°, 19.8±0.2°, 23.9±0.2°, 27.5±0.2°, 28.3±0.2°, 36.2±0.2°, and 38.9±0.2°.

3. A method for preparing the ellagic acid-PCA sodium eutectic according to claim 1 or 2, characterized in that, Includes the following steps: (1) Mix ellagic acid with an organic solvent to obtain an ellagic acid solution; under ultrasonic conditions, add sodium PCA aqueous solution dropwise to the ellagic acid solution. After the addition is complete, continue ultrasonic treatment and then filter to obtain a clear solution. (2) In a sealed environment, the antisolvent is diffused into the clear solution to precipitate crystals. The crystals are then filtered, washed, and dried to obtain ellagic acid-sodium PCA eutectic.

4. The preparation method according to claim 3, characterized in that, The molar ratio of ellagic acid to sodium PCA is 1:(0.5-2).

5. The preparation method according to claim 3, characterized in that, The organic solvent is at least one of DMAc, DMF, and DMSO.

6. The preparation method according to claim 3, characterized in that, The antisolvent is ether or acetone.

7. The preparation method according to any one of claims 3-6, characterized in that, In step (1), the ultrasonic parameters include: ultrasonic power of 130-195W, working frequency of 20-25kHz; ultrasonic time of each session of 2-6s, interval time of 2-6s, total ultrasonic time of 2-6min; and temperature of 28-35℃.

8. An ellagic acid-sodium PCA eutectic complex, characterized in that: Includes the ellagic acid-sodium PCA eutectic as described in claim 1 or 2, or the ellagic acid-sodium PCA eutectic prepared by the preparation method described in any one of claims 3-7.

9. The ellagic acid-sodium PCA eutectic complex according to claim 8, characterized in that: It also includes supramolecular ionic liquids, which include D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride, wherein the mass ratio of D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride is 1:(1-10):(0.05-0.2). The preparation method of the ellagic acid-sodium PCA co-crystal complex includes the following steps: 1) D-panthenol, cyclodextrin derivatives and pyridoxine hydrochloride were mixed and ground to obtain a supramolecular ionic liquid; 2) After mixing the ellagic acid-sodium PCA eutectic with the supramolecular ionic liquid, the mixture was ground to obtain the ellagic acid-sodium PCA eutectic complex.

10. The application of the ellagic acid-sodium PCA eutectic according to claim 1 or 2, the ellagic acid-sodium PCA eutectic prepared by the preparation method according to any one of claims 3-7, or the ellagic acid-sodium PCA eutectic complex according to claim 8 or 9 in cosmetics.

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