Supramolecular ellagic acid ionic salt composition, preparation method thereof and application of supramolecular ellagic acid ionic salt composition for preparing cosmetics

Abstract

The invention discloses a supramolecular ellagic acid ionic salt composition, a preparation method thereof and application of the supramolecular ellagic acid ionic salt composition in preparing cosmetics. The supramolecular ellagic acid ionic salt composition is prepared from raw materials including ellagic acid, and the concentration of the ellagic acid accounting for the total volume of the supramolecular ellagic acid ionic salt composition is 0.1% w / v-2% w / v; the concentration of PEG accounting for the total volume of the supramolecular ellagic acid ionic salt composition is 15% w / v-85% w / v, and the average molecular weight of PEG is 200-400; the concentration of the antioxidant accounting for the total volume of the supramolecular ellagic acid ionic salt composition is 0.1% w / v-0. 5% w / v; and the molar weight of the basic ion ligand is 1-6 times that of the ellagic acid. According to the supramolecular ellagic acid ionic salt composition and the preparation method thereof disclosed by the embodiment of the invention, the solubility, permeability and formula stability of ellagic acid can be improved on the basis that the ellagic acid has oxidation resistance.

Description

Technical Field

[0001] The present application belongs to the technical field of cosmetics, and in particular relates to a supramolecular ellagic acid ion salt composition, a preparation method thereof, and use thereof in preparing cosmetics. Background Art

[0002] Ellagic acid belongs to Class IV of the biopharmaceutics classification system (BSC), which means that it has low solubility (solubility in PBS solution with a pH of 7.4 is <10 mg / ml) and low osmotic pressure (0.13x10 -6 The solubility of ellagic acid in pure water at 37°C is about 7.9μg / ml, which is related to the special planar structure of ellagic acid. The benzene ring in ellagic acid easily forms hydrophobic crystals with the benzene rings of other ellagic acid molecules. Although the hydroxyl groups in the molecule have certain water solubility, the hydrogen bonding between molecules is more inclined to form a more stable regular layered crystal structure. The low solubility and the very low bioavailability make it difficult for ellagic acid to play its due role in practical applications.

[0003] In order to make ellagic acid play its effect in vivo, improve bioavailability, and make ellagic acid fully dissolved is the key. The prior art provides a partial scheme for improving the solubility of ellagic acid, including nano / micron-sized microemulsions of different particle sizes composed of ellagic acid and different media and different production methods. This kind of "shell-core" structure is mostly used for drug sustained release, such as anti-solvent co-precipitation method. The ellagic acid loading capacity of 326mg per gram of zein can be achieved, which can be sustained release in about a week. For example, ellagic acid wrapped with cyclodextrin can reach a solubility of about 50μg / ml. Or ellagic acid can reach a solubility of 2.5mg / ml~4mg / ml in ellagic acid nano-microemulsions mixed with oils, surfactants, and PEG400. Higher ellagic acid solubility is wrapped by amino acid-modified dendritic macromolecules loaded with ellagic acid, with a loading capacity of 53%, and the solubility of ellagic acid after solubilization can reach 9mg / ml. Alternatively, various organic solvents are used to solubilize ellagic acid, especially alkaline organic solvents such as N-methylpyrrolidone and pyridine. The mechanism is that the alkaline group forms an ionic salt with the weakly acidic phenolic hydroxyl group of ellagic acid, but the use of such organic solvents in cosmetics is strictly limited. Therefore, ellagic acid is generally used in cosmetic formulas through a compromise method, such as using triethanolamine, tromethamine, sodium carbonate, sodium bicarbonate, sodium hydroxide and other organic and inorganic alkaline substances as pH regulators to solubilize the undissolved ellagic acid in the formula.

[0004] As mentioned above, the solubility of ellagic acid in alkaline organic solvents is higher than that in water, but the use of alkaline organic solvents that solubilize ellagic acid in cosmetics is strictly limited. Although other alkaline substances such as basic carbonates and alkalis can significantly solubilize ellagic acid. But its biggest problem is that the pH of cosmetic formulas is generally acidic to neutral, and the process for providing ellagic acid uses alkali-soluble acid precipitation purification. Therefore, when ellagic acid is used in cosmetics, it will face the technical problem of ellagic acid precipitation. After ellagic acid is precipitated, it is still low in solubility, which will cause cosmetic precipitation or turbidity. In addition, the antioxidant capacity of ellagic acid is also reduced after the phenolic hydroxyl group and the alkaline group form ionic salts. Moreover, although the solubility of ellagic acid ionic salts is significantly improved, the stability is not high, and it is sensitive to temperature, pH light, resulting in precipitation, blackening and other deterioration, and poor stability. At present, it is urgent to solve the problem that the solubility of ellagic acid is high, the antioxidant property is reduced, and the poor stability is difficult to take into account. Summary of the invention

[0005] The embodiments of the present application provide a supramolecular ellagic acid ion salt composition and a preparation method thereof, which can improve the solubility and stability of ellagic acid while maintaining the antioxidant capacity, and take into account the antioxidant capacity of ellagic acid and have high solubility and stability.

[0006] In the first aspect, the present application provides a supramolecular ellagic acid ion salt composition, the raw materials of which include: ellagic acid, whose concentration is 0.1% w / v to 2% w / v of the total volume of the supramolecular ellagic acid ion salt composition; PEG, whose concentration is 15% w / v to 85% w / v of the total volume of the supramolecular ellagic acid ion salt composition, and the average molecular weight of PEG is 200 to 400; antioxidant, whose concentration is 0.1% w / v to 0.5% w / v of the total volume of the supramolecular ellagic acid ion salt composition; alkaline ionic ligand, which is 1 to 6 times the molar amount of ellagic acid; ultrapure water, which is prepared with PEG into a solvent for the supramolecular ellagic acid ion salt composition.

[0007] According to the embodiments of the present application, the mass ratio of ellagic acid, antioxidant, PEG, ultrapure water, and alkaline ion ligand is (0.02-0.15): (0.01-0.03): (5.6-16.8): (5-15): (0.1-0.3).

[0008] According to an embodiment of the present application, the antioxidant is selected from gallic acid, propyl gallate, ascorbic acid, tocopherol, sodium sulfite or a combination thereof.

[0009] According to an embodiment of the present application, the alkaline ion ligand is selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, tromethamine, triethanolamine, lysine, arginine or a combination thereof.

[0010] According to the embodiments of the present application, the molecular weight of PEG is 300, and the concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 15% w / v to 85% w / v.

[0011] According to the embodiments of the present application, the molecular weight of PEG is 300, and the concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 25% w / v to 75% w / v.

[0012] According to an embodiment of the present application, the concentration of ellagic acid in the total volume of the supramolecular ellagic acid ion salt composition is 0.5% w / v to 1.5% w / v.

[0013] According to an embodiment of the present application, the concentration of ellagic acid in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.75% w / v.

[0014] According to an embodiment of the present application, the concentration of propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.3% w / v.

[0015] According to an embodiment of the present application, the concentration of propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.05% w / v to 0.15% w / v.

[0016] According to an embodiment of the present application, the molar ratio of ellagic acid to the basic ionic ligand satisfies: 1:(1-4).

[0017] According to an embodiment of the present application, the molar ratio of ellagic acid to lysine satisfies: 1:(1-6). Optionally, the molar ratio of ellagic acid to lysine satisfies: 1:(1-4).

[0018] According to an embodiment of the present application, the concentration of lysine in the total volume of the supramolecular ellagic acid ion salt composition is 0.5% w / v to 1.5% w / v.

[0019] According to an embodiment of the present application, the solubility of ellagic acid in the supramolecular ellagic acid ion salt composition is 1.5 mg / ml to 7.5 mg / ml.

[0020] In a second aspect, the present application provides a method for preparing an ellagic acid supramolecular ionic salt composition, comprising:

[0021] Providing ellagic acid, antioxidant, PEG, ultrapure water, and alkaline ion ligand; wherein the average molecular weight of PEG is 200 to 400;

[0022] Dispersing ellagic acid, an antioxidant, and PEG according to the ratio of the supramolecular ellagic acid ion salt composition to obtain a first dispersion;

[0023] Ultrapure water and alkaline ion ligands are added to the first dispersion liquid for dispersion to prepare an ellagic acid supramolecular ion salt composition.

[0024] In a third aspect, the present application provides a use of a supramolecular ellagic acid ion salt composition for preparing cosmetics.

[0025] The supramolecular ellagic acid ion salt composition and the preparation method thereof of the embodiments of the present application can combine the characteristics of ellagic acid forming a stable supramolecular structure in PEG and the characteristics of ellagic acid forming an ion salt with high solubility under alkaline conditions to prepare a supramolecular ellagic acid ion salt composition with antioxidant ability, good stability and high solubility, thereby facilitating practical application in the formulation system of cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solution of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0027] Figure 1 They are the PXRD test patterns of ellagic acid and lysine respectively.

[0028] Figure 2 These are the PXRD test patterns of the physical mixture of ellagic acid and lysine and the supramolecular ellagic acid ion salt.

[0029] Figure 3 This is a graph showing the toxicity test results of the supramolecular ellagic acid ion salt composition prepared in Example 2 on immortalized human keratinocytes.

[0030] Figure 4 It is the dose-depth curve of Raman spectrum of 0.5wt.% ellagic acid aqueous solution.

[0031] Figure 5 The weighted depth dose map of the Raman spectrum of a 0.5 wt. % ellagic acid aqueous solution at different time points.

[0032] Figure 6 It is the Raman spectrum dose-depth curve of the supramolecular ellagic acid ion salt composition with a concentration of 0.5 wt.%.

[0033] Figure 7 1 is a weighted depth dose map of the Raman spectrum of the supramolecular ellagic acid ion salt composition of 0.5 wt.% at different time points.

[0034] Figure 8 This is a physical picture of the stability test of the supramolecular ellagic acid composition prepared in Example 1 under different conditions. DETAILED DESCRIPTION

[0035] The features and exemplary embodiments of various aspects of the present application will be described in detail below. In order to make the purpose, technical solutions and advantages of the present application clearer, the present application will be further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are only intended to explain the present application, rather than to limit the present application. For those skilled in the art, the present application can be implemented without the need for some of these specific details. The following description of the embodiments is only to provide a better understanding of the present application by illustrating the examples of the present application.

[0036] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the statement "include..." do not exclude the presence of other identical elements in the process, method, article or device including the elements.

[0037] The inventors of the present application found in the process of improving the solubility of existing ellagic acid that amino acids are amphiphilic molecules, with both alkaline amino groups and acidic carboxylic acid groups. Ellagic acid can be solubilized using alkaline amino acids, such as lysine, arginine, and serine, and the principle is also to form ionic salts. Among them, histidine and ellagic acid can form gels, and arginine is more unstable and easy to precipitate than lysine, and arginine is compared with ellagic acid. There is also evidence that the ionic salt formed by ellagic acid-lysine can reach a solubility of 12.99mg / ml. Although the formation of ionic salts can greatly improve the solubility of ellagic acid, its stability is poor. The inventors of the present application verified that the ionic salt formed by ellagic acid-lysine can dissolve in the short term, but after being placed for a period of time, there will be precipitation, which is difficult to pass the cosmetic stability test. And the inventors of the present application further found in the process of improvement that the solubility of ellagic acid in PEG solvents is higher, because the phenolic hydroxyl group of ellagic acid and the PEO block in PEG form a hydrogen bond connection, and the two form a supramolecular structure. The form of PEG with an average molecular weight of 700 to 900 is semi-solid, and the PEG with an average molecular weight further increased becomes a state of light white waxy solid or flake paraffin or fluid powder, which is not suitable as a component of cosmetics. The PEG with an average molecular weight of 200 to 600 is in liquid form. Among the PEGs of various molecular weights, the most commonly used in cosmetics is PEG-400 (PEG-8), PEG-300 (PEG-6) is also used to a certain extent, and PEG-200 (PEG-4) is used relatively less. And the inventors further found that the solubility of ellagic acid in PEG-200 is higher than that in PEG-300, and the solubility of ellagic acid in PEG-300 is higher than that in PEG-400.

[0038] To solve the problems of the prior art, based on the above findings, the present application provides a supramolecular ellagic acid ion salt composition and a preparation method thereof and use thereof in preparing cosmetics. The preparation method of the supramolecular ellagic acid ion salt composition provided in the examples of the present application is first introduced below.

[0039] In a first aspect, a method for preparing a supramolecular ellagic acid ion salt composition comprises:

[0040] S1. providing ellagic acid, antioxidant, PEG, ultrapure water, and alkaline ion ligand; wherein the average molecular weight of PEG is 200 to 400;

[0041] S2, dispersing ellagic acid, antioxidant, and PEG according to the ratio of the supramolecular ellagic acid ion salt composition to obtain a first dispersion;

[0042] S3. Add ultrapure water and alkaline ion ligands to the first dispersion to disperse the mixture, thereby obtaining an ellagic acid supramolecular ion salt composition.

[0043] The preparation method of the supramolecular ellagic acid ion salt composition of the embodiment of the present application is to compound ellagic acid with PEG and alkaline ion ligands, combine the characteristics of ellagic acid in PEG to form a stable supramolecular structure, and the characteristics of ellagic acid in alkaline conditions to form an ionic salt with high solubility, while maintaining antioxidant capacity, to obtain a supramolecular ellagic acid ion salt composition with stable structure and high ellagic acid solubility, so that it is easy to enter into the formulation system of cosmetics for practical application.

[0044] In the embodiment of the present application, ellagic acid is first dispersed and mixed with an antioxidant and PEG to prevent ellagic acid from being oxidized, and the phenolic hydroxyl groups contained in ellagic acid and the PEO blocks in PEG first form a supramolecular structure connected by hydrogen bonds, so that ellagic acid maintains effective antioxidant capacity. Then, the phenolic hydroxyl groups that do not form intermolecular hydrogen bonds in the supramolecular structure are dispersed with basic ionic ligands to obtain a supramolecular ellagic acid ion salt composition containing a partial ion salt.

[0045] In the embodiments of the present application, ultrasonic equipment can be used to disperse the raw materials in each step. Optionally, the ultrasonic power is 50W to 180W, preferably 120W; the ultrasonic treatment time is 5 minutes to 45 minutes, preferably 15 minutes.

[0046] In a second aspect, an embodiment of the present application provides a supramolecular ellagic acid ion salt composition, wherein ellagic acid has a concentration of 0.1% w / v to 2% w / v of the total volume of the supramolecular ellagic acid ion salt composition; PEG has a concentration of 15% w / v to 85% w / v of the total volume of the supramolecular ellagic acid ion salt composition, and the average molecular weight of PEG is 200 to 400; an antioxidant has a concentration of 0.1% w / v to 0.5% w / v of the total volume of the supramolecular ellagic acid ion salt composition; an alkaline ionic ligand has a molar amount of 1 to 6 times that of ellagic acid; and ultrapure water is prepared with PEG to form a solvent for the supramolecular ellagic acid ion salt composition.

[0047] The supramolecular ellagic acid ion salt composition of the embodiment of the present application can improve the solubility, permeability and formulation stability of ellagic acid while maintaining the effective antioxidant capacity of ellagic acid, thereby enabling the supramolecular ellagic acid ion salt composition to be incorporated into a cosmetic formulation system and put into practical use.

[0048] In the embodiments of the present application, the mass ratio of ellagic acid, antioxidant, PEG, ultrapure water, and alkaline ion ligand is (0.02-0.15): (0.01-0.03): (5.6-16.8): (5-15): (0.1-0.3). The supramolecular ellagic acid ion salt meeting this ratio has good solubility, permeability, and stability.

[0049] In the embodiments of the present application, PEG and ultrapure water are used as the solvent of the supramolecular ellagic acid ion salt composition, which can not only improve the solubility and permeability of the supramolecular ellagic acid ion salt composition by using PEG as the main solvent, but also ionize the alkaline ion ligand in the ultrapure water as the auxiliary solvent to provide an alkaline environment, and make part of the phenolic hydroxyl groups in the ellagic acid molecules react with the cations to form ionic salts, thereby improving the solubility of the supramolecular ellagic acid ion salt composition. Since the supramolecular ellagic acid is dispersed in PEG and ultrapure water, it can be incompletely saturated and dissolved in the mixed system, and most of the phenolic hydroxyl groups are retained in PEG, so that the ellagic acid can improve the solubility stability and permeability of the supramolecular ellagic acid ion salt on the basis of having antioxidant ability.

[0050] In the embodiments of the present application, the concentration of ellagic acid in the total volume of the supramolecular ellagic acid ionic salt composition is 0.5% w / v to 1.5% w / v. Exemplarily, the concentration of ellagic acid in the total volume of the supramolecular ellagic acid ionic salt composition is 0.6% w / v, 0.75% w / v, 0.8% w / v, 1.0% w / v, 1.2% w / v, 1.4% w / v.

[0051] In an embodiment of the present application, the molecular weight of PEG is 300, and the concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 15% w / v to 85% w / v. Exemplarily, the concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 16% w / v, 18% w / v, 20% w / v, 24% w / v, 28% w / v, 30% w / v, 32% w / v, 35% w / v, 38% w / v, 40% w / v, 45% w / v, 48% w / v, 50% w / v, 55% w / v, 60% w / v, 63% w / v, 68% w / v, 70% w / v, 72% w / v, 75% w / v, 78% w / v, 80% w / v, 81% w / v, 83% w / v, 85% w / v.

[0052] In the embodiment of the present application, the molecular weight of PEG is 300, and the concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 25% w / v to 75% w / v. Alternatively, the concentration of PEG with a molecular weight of 300 in the total volume of the supramolecular ellagic acid ion salt composition is 28% w / v to 84% w / v.

[0053] In some embodiments of the present application, PEG can be selected from PEG-200, PEG-300, PEG-400 or a combination thereof. For example, PEG can be selected from PEG-200 alone to react with ellagic acid to form hydrogen bonds, or PEG-200 and PEG-300 can be selected to form hydrogen bonds with ellagic acid, or a combination of PEG-200 and PEG-400 can be selected to form hydrogen bonds with ellagic acid. Alternatively, a combination of PEG-300 and PEG-400 can be selected to form hydrogen bonds with ellagic acid.

[0054] In the embodiments of the present application, PEG with an average molecular weight of 200 to 300 is selected, so that the phenolic hydroxyl group of ellagic acid and the PEO segment of PEG can form supramolecular hydrogen bonds, so as to improve the solubility of ellagic acid and enable ellagic acid to penetrate into the skin with a smaller molecular structure, rather than staying on the skin surface in the form of undissolved aggregated solid particles, thereby improving the bioavailability of ellagic acid. And maintain a relatively flexible molecular structure, when the supramolecular hydrogen bonds between some ellagic acid and PEG are destroyed, new supramolecular hydrogen bonds can be quickly formed with adjacent PEG molecules, so that the solubility of ellagic acid remains stable. Or form ionic salts with basic ion ligands, so that the solubility of ellagic acid remains stable.

[0055] In the embodiments of the present application, the molar ratio of ellagic acid to the basic ion ligand satisfies: 1:(1-6). The basic ion ligand is selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, tromethamine, triethanolamine, lysine, arginine or a combination thereof.

[0056] The inventors of the present application have found that the antioxidant property of ellagic acid originates from its phenolic hydroxyl groups, and therefore, the antioxidant capacity is reduced after the weakly acidic phenolic hydroxyl groups of ellagic acid are occupied by alkaline ion ligands to form ionic salts. Therefore, ellagic acid must retain some phenolic hydroxyl groups to have antioxidant capacity.

[0057] In the embodiment of the present application, the ellagic acid molecular structure comprises four phenolic hydroxyl groups. When ellagic acid is first dissolved in PEG to form a solution, part of the phenolic hydroxyl groups in the ellagic acid molecule first form hydrogen bonds with the PEO segments in the PEG, and the two form a supramolecular structure. Since the PEG in the supramolecular ellagic acid ion salt composition is obviously excessive relative to the amount of ellagic acid, ellagic acid and PEG mainly form supramolecular hydrogen bonds. This structure allows the phenolic hydroxyl groups in the ellagic acid to exist in large quantities, which can keep the supramolecular ellagic acid ion salt composition effective antioxidant capacity, avoid being oxidized, and improve the stability of the supramolecular ellagic acid ion salt composition in the form of a solution. While ellagic acid and PEG form a hydrogen-bonded, stable supramolecular structure, ellagic acid can also be coated in PEG in large quantities, improving the solubility of ellagic acid to a certain extent. The remaining phenolic hydroxyl groups in the ellagic acid molecule react with the basic groups in the basic ion ligand to form ionic salts, further increasing the solubility of ellagic acid.

[0058] In an embodiment of the present application, lysine is preferably used as the alkaline ion ligand. The alkaline ion ligand is preferably lysine, and the molar ratio of ellagic acid to lysine satisfies: 1: (1 to 6). Exemplarily, the molar ratio of ellagic acid to lysine satisfies: 1: 1.5, 1: 1.8, 1: 2.0, 1: 2.2, 1: 2.5, 1: 2.8, 1: 3, 1: 3.3, 1: 3.5, 1: 4.0, 1: 4.2, 1: 4.5, 1: 4.8, 1: 5.0, 1: 5.4, 1: 5.6, 1: 5.9. In some embodiments, the molar ratio of ellagic acid to lysine satisfies: 1: (1 to 4).

[0059] Taking lysine as an example, lysine itself is a basic amino acid, and the amino group it contains is alkaline after ionization in water, and the phenolic hydroxyl group contained in ellagic acid is weakly acidic, and the acid and base groups combine to form ionic bonds to form salts. In addition, lysine is an amphoteric compound containing an acidic carboxyl group, and the degree of ionization in an aqueous solution is affected by pH, so there will be a part of the phenolic hydroxyl group of ellagic acid and the PEO block hydrogen bond connection in PEG to form a supramolecular compound, and part of it forms an ionic bond with lysine. Therefore, lysine is mainly used in the supramolecular ellagic acid ion salt composition to provide an alkaline environment. At the position where hydrogen bonds cannot be completely covered, the weakly acidic phenolic hydroxyl group contained in ellagic acid can react with the alkaline ions hydrolyzed by lysine to form a stronger ionic bond, preventing ellagic acid from precipitating. It should be noted that lysine will only form an ionic bond with the phenolic hydroxyl group of ellagic acid after ionization in water, and the solubility of a single lysine in PEG is relatively poor. Arginine or a combination of lysine and arginine can also play the same role. Optionally, water is deionized water.

[0060] In an embodiment of the present application, the antioxidant is selected from gallic acid, propyl gallate, ascorbic acid, tocopherol, sodium sulfite or a combination thereof, preferably propyl gallate.

[0061] In the examples of the present application, the concentration of propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.5% w / v.

[0062] In the examples of the present application, the concentration of propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.3% w / v.

[0063] In the embodiments of the present application, the solubility of ellagic acid in the supramolecular ellagic acid ion salt composition reaches 1 mg / ml to 7.5 mg / ml. Within this solubility range, ellagic acid can be stably present in the supramolecular ellagic acid ion salt composition, and ellagic acid can also have an antioxidant function, so that the ellagic acid in the cosmetics containing the supramolecular ellagic acid ion salt composition can remain stable after a period of time without precipitation of ellagic acid, thereby being able to pass the stability test requirements of cosmetics.

[0064] Illustratively, the solubility of ellagic acid in the supramolecular ellagic acid ionic salt composition is 1.5 mg / ml, 2.2 mg / ml, 2.4 mg / ml, 2.7 mg / ml, 2.8 mg / ml, 3 mg / ml, 3.2 mg / ml, 3.5 mg / ml, 3.8 mg / ml, 4.0 mg / ml, 4.2 mg / ml, 4.5 mg / ml, 4.9 mg / ml, 5.0 mg / ml, 5.4 mg / ml, 5.6 mg / ml, 6.0 mg / ml, 6.3 mg / ml, 6.5 mg / ml, 6.8 mg / ml, 7.0 mg / ml, 7.2 mg / ml, 7.3 mg / ml, and 7.5 mg / ml.

[0065] In a third aspect, the embodiments of the present application provide a use of a supramolecular ellagic acid ion salt composition for preparing cosmetics. Optionally, the cosmetics can be water, milk, cream, essence, or facial mask of an emulsified system.

[0066] In the embodiments of the present application, the supramolecular ellagic acid ion salt composition can be added as an additive to cosmetics with a pH value of 6.1 to 7.5. The supramolecular ellagic acid ion salt composition can solve the problem of ellagic acid precipitation when ellagic acid is used in cosmetics.

[0067] According to the cytotoxicity test, the supramolecular ellagic acid ion salt composition can be added to cosmetics in an amount greater than zero and ≤2.5wt.%. Exemplarily, the amount of the supramolecular ellagic acid ion salt composition added to cosmetics is preferably 0.2wt.%, 0.4wt.%, 0.5wt.%, 0.7wt.%, 0.8wt.%, 0.9wt.%, 1.0wt.%, 1.1wt.%, 1.2wt.%, 1.25wt.%, 1.3wt.%, 1.4wt.%, 1.5wt.%, 1.6wt.%, 1.75wt.%, 1.8wt.%, 1.9wt.%, 1.95wt.%, 2.0wt.%, 2.2wt.%, 2.4wt.%. Preferably, the amount of the supramolecular ellagic acid ion salt composition added to cosmetics is 0.3wt.% to 1.5wt.%.

[0068] The technical solution of the present application is further illustrated below through specific embodiments and comparative examples. The following are the sources of some of the materials used in the embodiments or comparative examples. The raw materials or reagents not mentioned in the present application can be obtained through commercial channels: ellagic acid, purity: 99%+, Shanghai Lijing Industrial Co., Ltd.; PEG-300, whose volume is calculated or converted to mass at a density of 1.12 g / ml; alkaline ion ligands: lysine and arginine; antioxidant: propyl gallate (hereinafter referred to as PG), reagent grade; ultrapure water, also known as UP water.

[0069] Example 1

[0070] A supramolecular ellagic acid ion salt composition comprises raw materials: ellagic acid with masses of 0.02g, 0.01g, 5.6g and 0.1g, an antioxidant, PEG, lysine and an appropriate amount of ultrapure water; wherein the average molecular weight of PEG is 300, namely PEG-300; and the antioxidant is propyl gallate.

[0071] The preparation method of a supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 5 mL (i.e., 5.6 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0072] Example 2

[0073] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with a mass of 0.05g, 0.02g, 5.6g and 0.1g, an antioxidant, PEG, lysine and an appropriate amount of ultrapure water; wherein the average molecular weight of PEG is 300, namely PEG-300, and the antioxidant is propyl gallate.

[0074] The preparation method of a supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 5 mL (i.e., 5.6 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0075] Example 3

[0076] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with a mass of 0.05g, 0.02g, 10g and 0.1g, an antioxidant, PEG, lysine and an appropriate amount of ultrapure water; wherein the average molecular weight of PEG is 300, namely PEG-300, and the antioxidant is propyl gallate.

[0077] The preparation method of a supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0078] Example 4

[0079] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with masses of 0.05g, 0.02g, 10g and 0.1g, an antioxidant, PEG, lysine, and 10g of ultrapure water; wherein the average molecular weight of PEG is 300, namely PEG-300, and the antioxidant is propyl gallate.

[0080] The preparation method of the supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0081] Example 5

[0082] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with masses of 0.08g, 0.02g, 10g, 10g and 0.1g, an antioxidant, PEG, ultrapure water and lysine; wherein the average molecular weight of PEG is 300, i.e. PEG-300, and the antioxidant is propyl gallate.

[0083] The preparation method of a supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0084] Example 6

[0085] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with masses of 0.08g, 0.02g, 10g, 10g and 0.24g, an antioxidant, PEG, ultrapure water and lysine; wherein the average molecular weight of PEG is 300, i.e. PEG-300, and the antioxidant is propyl gallate.

[0086] The preparation method of a supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0087] Example 7

[0088] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with masses of 0.08g, 0.02g, 10g, 10g and 0.24g, an antioxidant, PEG, ultrapure water, lysine and arginine; wherein the average molecular weight of PEG is 300, i.e. PEG-300, and the antioxidant is propyl gallate; wherein the mass ratio of lysine to arginine is 1:1.

[0089] The preparation method of the supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding lysine and arginine to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0090] Example 8

[0091] A supramolecular ellagic acid ion salt composition comprises: ellagic acid with masses of 0.08g, 0.02g, 10g, 10g and 0.24g, an antioxidant, PEG, ultrapure water and sodium hydroxide; wherein the average molecular weight of PEG is 300, i.e. PEG-300, and the antioxidant is propyl gallate.

[0092] The preparation method of the supramolecular ellagic acid ion salt composition comprises: weighing ellagic acid and an antioxidant according to the above ratio, adding them to 8.93 mL (i.e., 10 g) of PEG-300, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a first dispersion; adding ultrapure water to the first dispersion until the total volume of the supramolecular ellagic acid ion salt composition is 20 ml, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a second dispersion; adding sodium hydroxide to the second dispersion, dispersing them by ultrasonic treatment for 8 minutes, and obtaining a supramolecular ellagic acid ion salt composition.

[0093] Comparative Example 1

[0094] Weigh 0.5 g of ellagic acid and 0.03 g of propyl gallate, add 5.6 g (5 ml) of PEG-300, sonicate for 5 min, add 15 ml of ultrapure water, sonicate for 5 min, then add 0.1 g of lysine, sonicate for 15 min to precipitate the ellagic acid.

[0095] Comparative Example 2

[0096] Weigh 0.02 g of ellagic acid and 0.01 g of propyl gallate, add 3.5 g (3.125 ml) of PEG-300, sonicate for 5 min, add 15 ml of ultrapure water, sonicate for 5 min, then add 0.1 g of lysine, sonicate for 15 min to precipitate the ellagic acid.

[0097] Comparative Example 1

[0098] An ellagic acid composition comprises ellagic acid and lysine in a mass ratio of 1:1 and 0.01 g of an antioxidant, and ultrapure water is added to make the total volume of the composition 20 ml, and the mixture is physically mixed to precipitate ellagic acid.

[0099] Comparative Example 2

[0100] A supramolecular ellagic acid ion salt composition comprises lysine and ellagic acid in a mass ratio of 1:1, 0.04 g of an antioxidant, and 5.6 g of PEG-300. Ultrapure water is added to make the total volume of the composition 20 ml, and the composition is prepared by physical mixing, and ellagic acid is precipitated.

[0101] Comparative Example 3

[0102] A supramolecular ellagic acid composition comprises lysine and ellagic acid in a mass ratio of 1:4, 0.01 g of an antioxidant, and 5.6 g of PEG-300. Ultrapure water is added to make the total volume of the composition 20 ml, and the composition is physically mixed to precipitate ellagic acid.

[0103] The compositions and contents of Examples 1-8, Comparative Examples 1-2 and Reference Examples 1-3 are summarized in Table 1 below:

[0104] Table 1

[0105]

[0106]

[0107] From the above comparison, it can be concluded that the concentration of ellagic acid in the supramolecular ionic salt composition exceeds 2% w / v, PEG-300 is lower than 20% w / v, and propyl gallate exceeds 0.15% w / v; when the molar ratio of lysine to ellagic acid is 1:1, the solubility of ellagic acid is insufficient and ellagic acid precipitates.

[0108] By comparing the components of the supramolecular ellagic acid ion salt composition of Examples 1-8 and Comparative Examples 1-2, it can be concluded that when the content of ellagic acid is high, the content of PEG is low, and the content of propyl gallate is high, when lysine is insufficient, the solubility of ellagic acid will be insufficient, resulting in the precipitation of ellagic acid to form a suspension / precipitate.

[0109] Test Section

[0110] 1. Characterization of supramolecular ellagic acid ion salt compositions

[0111] Powder X-ray crystal diffraction (PXRD) test

[0112] The PXRD test parameters are: Cu-Ka radiation, tube voltage: 40KV, wavelength: 1.5406A, tube current: 40mA, step size: 0.02°, scanning speed: 8° / min, and the main spectral lines are expressed in terms of crystal plane spacing d, Bragg angle 2θ (expressed as ±0.2) and relative intensity (expressed as a percentage of the strongest spectral line).

[0113] Since PXRD can only test solid samples, the supramolecular ellagic acid ion salt containing PEG cannot be sent for sample, so only the component of the supramolecular ellagic acid ion salt that removes moisture is tested here. Figure 1 As shown, they are the PXRD test patterns of ellagic acid and lysine, respectively. Figure 2 These are the PXRD test patterns of the physical mixture of ellagic acid and lysine and the supramolecular ellagic acid ion salt.

[0114] contrast Figure 1 and Figure 2It can be concluded that the characteristic peaks of the supramolecular ellagic acid ion salt are significantly different from those of individual ellagic acid and lysine and their physical mixture. The peak on the left side of the PXRD spectrum of lysine alone is missing, but the characteristic peak on the right side of ellagic acid is still retained, indicating that an amorphous ellagic acid ion salt is formed in Example 1.

[0115] 2. Cytotoxicity test of supramolecular ellagic acid ion salt composition

[0116] The supramolecular ellagic acid ion salt composition prepared in Example 2 was prepared with PBS into dilutions of 0.3125wt.%, 0.625wt.%, 1.25wt.%, 2.5wt.%, 5wt.%, and 10wt.%, respectively, and the cytotoxicity test was performed using HaCaT cells (i.e., human immortalized keratinocytes). The specific content of the test process is as follows: immortalized human keratinocytes were cultured in a medium containing 10% (v / v) fetal bovine serum and 1% double antibody (1×10 5 Immortalized human keratinocytes were grown in a DMEM medium containing 100 mg / L penicillin and 100 mg / L streptomycin at 37°C and 5% CO2 until the cell confluence reached 85%-95%. Immortalized human keratinocytes in the logarithmic growth phase were digested with 0.05% (v / v) trypsin, and the digestion reaction was terminated with DMEM medium containing 10% (v / v) fetal bovine serum. The number of cells per unit volume of the cell suspension was adjusted to 2×10 using a cell counting plate. 5 / ml, inoculated into 96-well plates at a ratio of 200 μL per well, and incubated at 37°C, 5% CO2 for a certain period of time until the cell confluence reached 45%-60%.

[0117] Sample group: Then remove the old culture medium, add 200 μL of serum-free culture medium containing 0.3125wt.%, 0.625wt.%, 1.25wt.%, 2.5wt.%, 5wt.%, 10wt.% of the supramolecular ellagic acid ion salt composition to the corresponding test wells, and incubate at 37°C, 5% CO2 for 24 hours. Make 4 replicate wells for each mass concentration of the test solution.

[0118] Control group (CTR group): 200 μL of serum-free culture medium without supramolecular ellagic acid ion salt composition was added to the corresponding test wells containing cells, and incubated at 37° C. and 5% CO 2 for 24 h;

[0119] Blank group: No supramolecular ellagic acid ion salt composition and serum-free culture medium were added to the corresponding test wells, and the cells were incubated at 37° C. and 5% CO 2 for 24 h;

[0120] Then, 20 μL of CCK8 solution was added to each well of the sample group, blank group, and control group, and then incubated for 3 h. The absorbance value was measured at 450 nm, and the cell survival rate of each group was calculated;

[0121] Cell survival rate (%) = (sample group - blank group) / (control group - blank group) * 100%.

[0122] PBS is a phosphate buffer for cell culture, and the preparation method is as follows: potassium dihydrogen phosphate (KH2PO4): 0.27g; disodium hydrogen phosphate (Na2HPO4): 1.42g; sodium chloride (NaCl): 8g; potassium chloride (KCl) 0.2g; add about 800mL of deionized water and stir thoroughly to dissolve, then add concentrated hydrochloric acid to adjust the pH to 7.4, and finally make up to 1L.

[0123] In the cytotoxicity test, the higher the cell survival rate, the lower the cytotoxicity of the supramolecular ellagic acid ion salt composition. The results of the toxicity test of the supramolecular ellagic acid ion salt composition on immortalized human keratinocytes are shown in FIG. Figure 3 As shown in the figure: when the mass concentration of the supramolecular ellagic acid ion salt composition is 1.25wt.%, the immortalized human keratinocytes have normal morphology and the relative cell viability value is about 100%; when the mass concentration of the supramolecular ellagic acid ion salt composition is 2.5wt.%, the immortalized human keratinocytes have normal morphology and the relative cell viability value is about 80%; when the mass concentration of the supramolecular ellagic acid ion salt composition is higher than 2.5wt.% and reaches 5wt.%, the immortalized human keratinocytes have normal morphology and the relative cell viability value is about 75%; as the mass concentration of the supramolecular ellagic acid ion salt composition is further increased to 10wt%, the immortalized human keratinocytes have normal morphology, but the relative cell viability value is about 50%, indicating that when the mass concentration of the supramolecular ellagic acid ion salt composition is above 2.5%, the cell viability value of the immortalized human keratinocytes will decrease significantly. Therefore, according to the CCK8 test results, the supramolecular ellagic acid ion salt composition has no cytotoxicity to immortalized human keratinocytes within a mass concentration range of 2.5 wt.% and below.

[0124] 3. Permeability, solubility and stability of supramolecular ellagic acid ion salt compositions

[0125] 1. Permeability test of supramolecular ellagic acid ion salt composition

[0126] Firstly, ellagic acid was prepared into an aqueous solution with a concentration of 0.5wt.% for Raman spectroscopy dose test. The Raman spectroscopy dose-depth curves at 5min, 30min and 60min were tested respectively, and the weighted depth dose of the ellagic acid aqueous solution at 5min, 30min and 60min time points was calculated.

[0127] like Figure 4 As shown in the figure, the content curve T1 of 0.5wt.% ellagic acid aqueous solution on the skin surface changes from 1.6mg / cm 3 Rapidly reduced to 0.3 mg / cm 3 Even to zero, and distributed in the skin surface; 0.5wt.% ellagic acid aqueous solution in 30min skin surface content curve T2 from 1.9mg / cm 3 Rapidly reduced to 0.1 mg / cm 3 Even to zero, and penetrated from the skin surface into the skin 0.3μm; 0.5wt.% ellagic acid aqueous solution in 60min skin surface content curve T3 from 0.2mg / cm 3 Reduced to zero, and from the skin surface to 0.2μm inside the skin. Figure 5 As shown, it is the weighted depth dose of the Raman spectrum of 0.5wt.% ellagic acid aqueous solution at T1 (5min), T2 (30min), and T3 (60min). The weighted depth dose of the Raman spectrum at T1 and T2 is 1.1μg / cm 2 , 1.08μg / cm 2 , which is significantly greater than the weighted depth dose of 0.2 μg / cm at T3 2 , indicating that ellagic acid can penetrate into the skin in a short period of time, but the amount of penetration is small.

[0128] Next, the supramolecular ellagic acid was formulated into a supramolecular ellagic acid ion salt composition with a concentration of 0.5wt.%, which is a mixed solution. Raman spectroscopy dose test was performed on it. The Raman spectroscopy dose-depth curves at 5min, 30min and 60min were tested respectively, and the weighted depth doses of the supramolecular ellagic acid ion salt composition at 5min, 30min and 60min time points were calculated.

[0129] like Figure 6 As shown in FIG. 1 , the supramolecular ellagic acid ion salt composition penetrates from the skin surface to 25 μm inside the skin at T1 (5 min), and has basically completely penetrated into the skin at T2 (30 min) and T3 (60 min); this can also be seen from Figure 7 The weighted depth dose of the 0.5 wt.% supramolecular ellagic acid ion salt composition under T1 (5 min), T2 (30 min), and T3 (60 min) Raman spectra weighting is obtained as shown in FIG. Figure 7 As shown, the weighted depth dose of 0.5 wt.% supramolecular ellagic acid ion salt composition at T1 (5 min) is 26 μg / cm 2 , which is significantly higher than the weighted depth dose of T2 (30min) and T3 (60min). Figure 5and 7 A blank group was set as a comparison benchmark.

[0130] from Figure 4 and Figure 6 as well as Figure 5 and Figure 7 It can be concluded from the comparison that, compared with the penetration effect of 0.5wt.% ellagic acid aqueous solution, the 0.5wt.% supramolecular ellagic acid ion salt composition of the embodiment of the present application can obviously make a large amount of supramolecular ellagic acid penetrate into the skin in a short period of time, which is about 23 times the penetration amount of ellagic acid aqueous solution, indicating that the supramolecular ellagic acid ion salt composition has good permeability. Figure 5 Compared with the weighted depth dose within 30 minutes Figure 7 The weighted depth dose within 30 minutes was low, indicating that the retention of supramolecular ellagic acid in the supramolecular ellagic acid ion salt composition in the skin was also significantly better.

[0131] 2. Solubility of supramolecular ellagic acid ion salt

[0132] The results of multiple experiments conducted in this application show that the ellagic acid content of about 1% w / v is the limit of the supramolecular loading of PEG-300, which corresponds to an ellagic acid content of 10 mg / ml, but the instant solubility is not equal to the equilibrium solubility. There is a risk of precipitation of ellagic acid at this content. Although adding alkaline ion ligands to the dispersion of PEG-300 and ellagic acid cannot further improve the solubility of ellagic acid, the supramolecular ellagic acid ion salt formed after the dissociation of the alkaline ion ligand can delay and weaken the precipitation of ellagic acid while maintaining the high solubility of ellagic acid. Therefore, in actual use, considering the solubility and stability of ellagic acid, the solubility of ellagic acid in the supramolecular ellagic acid ion salt composition is set to 1.5 mg / ml to 7.5 mg / ml, so that the solubility and stability of ellagic acid reach a more reasonable balance. It should be noted that: the instant concentration refers to the solubility of the supramolecular ellagic acid ion salt composition when it is just prepared, and the equilibrium concentration refers to the solubility of the ellagic acid ion salt composition after being stored for a period of time.

[0133] The present application tests the equilibrium solubility of the supramolecular ellagic acid ion salt composition at 25°C by the saturation solubility method. The testing steps of the saturation solubility method include: adding an excess of the supramolecular ellagic acid ion salt composition to water, dissolving it by stirring or heating until it can no longer be dissolved, and measuring the amount of the remaining undissolved solute to obtain the saturated solubility. The results show that the supramolecular ellagic acid ion salt composition of the present invention has an equilibrium solubility of 3.3 mg / ml at 25°C based on ellagic acid, and no precipitation is generated when placed for a long time.

[0134] 3. Stability test of supramolecular ellagic acid ion salt

[0135] The supramolecular ellagic acid ion salt compositions prepared in Examples 1-8 and the ellagic acid compositions of Comparative Examples 1-2 were subjected to stability tests on their own, and some of the examples were subjected to stability tests in cosmetic samples. The test contents included:

[0136] (1) The supramolecular ellagic acid ion salt composition of Example 1 was sequentially observed at room temperature (25°C), room temperature (25°C) light, high temperature (48°C), low temperature (-16°C), high and low temperature cycle for 1 week, 4 weeks, and 12 weeks respectively to obtain the stability of each supramolecular ellagic acid ion salt composition, and the test results are recorded in Table 2. The supramolecular ellagic acid ion salt compositions of Examples 2-8 and Comparative Examples 1-2 were sequentially observed at room temperature (25°C), room temperature (25°C) light, high temperature (48°C), low temperature (-16°C), high and low temperature cycle for 1 week, 4 weeks, and 12 weeks respectively to obtain the dissolution stability of each supramolecular ellagic acid ion salt composition, and the test results are recorded in Table 3.

[0137] The ellagic acid supramolecular ionic salt composition prepared in Example 1 was subjected to stability tests under various conditions according to item (1), and the test results are recorded in the following Table 2:

[0138] Table 2 Stability of the supramolecular ellagic acid ion salt composition prepared in Example 1

[0139]

[0140] According to Table 2 and Figure 8 The test results show that the supramolecular ellagic acid ion salt composition prepared in Example 1 has no change in odor under various stability accelerated test conditions; the color does not change under low temperature conditions, and a trace amount of precipitation begins to occur in the fourth week, but it does not affect the overall effect; when stored at room temperature, the color begins to gradually deepen from the fourth week, and a trace amount of precipitation begins to occur in the second week, which does not affect the overall effect; under room temperature and light conditions, the color begins to deepen slightly from the second week, and a trace amount of precipitation begins to occur, but it does not affect the overall effect; under high temperature experiments, the color begins to deepen slightly from the second week, and a trace amount of precipitation begins to occur, which has the effect of accelerating oxidation. It is a physical and chemical property of polyphenols and is difficult to change. If the phenolic hydroxyl groups are blocked, oxidation discoloration can be partially prevented, but it also loses its core antioxidant activity.

[0141] The dissolution stability test results of the supramolecular ellagic acid ion salt compositions of Examples 1-8 and Comparative Examples 1-2 are recorded in the following Table 3, and only the precipitation of ellagic acid is compared. Insufficient solubility or destruction of the supramolecular ion salt structure will lead to the precipitation of ellagic acid, so as to facilitate the comparison of the stability of the supramolecular ellagic acid ion salt compositions of Examples 1-8 and the ellagic acid compositions and supramolecular ion salt compositions prepared in Comparative Examples 1-2:

[0142] Table 3 Stability of ellagic acid ion salt composition and ellagic acid composition

[0143]

[0144] It can be concluded from the stability test data in Table 3 that the ellagic acid composition of Comparative Example 1 and the ellagic acid ion salt composition of Comparative Example 2 cannot be fully dissolved, and obvious precipitation occurs under various test conditions, while the supramolecular ellagic acid ion salt compositions of Examples 1-8 of the present application exhibit good solubility and stability, with only slight precipitation under non-low temperature, non-high temperature, and non-high temperature and low temperature cycles, and have relatively high overall stability.

[0145] (2) Referring to the stability test method of item (1), the stability of the supramolecular ellagic acid ion salt composition of Example 1 in the cosmetic samples was tested respectively, and the test results were recorded in Table 5. The ingredients of the cosmetic sample (pH = 6.44) are shown in Table 4. The amount of the supramolecular ellagic acid composition of Example 1 added as the test raw material is 10wt.% of the total mass of the sample. The sample emulsification system formula is:

[0146] Table 4

[0147]

[0148]

[0149] Formula preparation method: Add the raw materials of phase A to the oil phase pot, heat to 85°C, stir evenly and set aside. Add the raw materials of phase B in sequence, add to 85°C, and stir evenly. Add phase A to phase B, homogenize at 3000rpm for 5 minutes, stir and cool to 45°C, add phase C, stir evenly until the pH value of the material is neutral to acidic, add phase D and stir evenly, add appropriate amount of phase E to adjust the pH value to 6.44. Cool to 37°C, discharge, and obtain a cosmetic containing a supramolecular ellagic acid ion salt composition.

[0150] Table 5 Stability of ellagic acid ion salt composition and ellagic acid composition in cosmetics at pH = 6.44

[0151]

[0152] From the stability test data in Table 5, it can be concluded that the clear and transparent supramolecular ellagic acid ion composition after dilution in Example 1 can be used in cosmetic formulations. The addition amount of 10wt.% is relatively high. At such a high concentration, under normal room temperature and low temperature conditions, the stability is excellent, and the smell and color do not change and no precipitation occurs; under accelerated experimental conditions such as high temperature, there is only a slight discoloration. The supramolecular ellagic acid ion salt with a lower addition amount has better stability because of the lower phenolic hydroxyl content; on the contrary, the ellagic acid composition of Comparative Example 1 has insufficient solubility and cannot be added to the formulation, and is directly precipitated in the form of a precipitate visible to the naked eye, indicating the advantages of the supramolecular ellagic acid ion salt composition in the application of cosmetic formulations.

[0153] The above is only a specific implementation method of the present application. Those skilled in the art can clearly understand that for the convenience and simplicity of description, the specific working process described above can refer to the corresponding process in the aforementioned method embodiment, and will not be repeated here. It should be understood that the protection scope of the present application is not limited to this. Any technician familiar with the technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed in the present application, and these modifications or replacements should be included in the protection scope of the present application.

Claims

1. A supramolecular ellagic acid ion salt composition, characterized in that: Ingredients include: Ellagic acid, with a concentration of 0.1% w / v to 2% w / v of the total volume of the supramolecular ellagic acid ion salt composition; PEG, the concentration of which accounts for 15% w / v to 85% w / v of the total volume of the supramolecular ellagic acid ion salt composition, and the average molecular weight of the PEG is 200 to 400; an antioxidant, the concentration of which is 0.1% w / v to 0.5% w / v based on the total volume of the supramolecular ellagic acid ion salt composition; A basic ionic ligand, which is 1 to 6 times the molar amount of the ellagic acid; Ultrapure water is used as a solvent for preparing the supramolecular ellagic acid ion salt composition together with the PEG.

2. The supramolecular ellagic acid ion salt composition according to claim 1, characterized in that: The invention comprises ellagic acid, an antioxidant, PEG, ultrapure water and an alkaline ion ligand in a mass ratio of (0.02-0.15):(0.01-0.03):(5.6-16.8):(5-15):(0.1-0.3).

3. The supramolecular ellagic acid ion salt composition according to claim 1 or 2, characterized in that: Meet at least one of the following requirements: The concentration of ellagic acid in the total volume of the supramolecular ellagic acid ion salt composition is 0.5% w / v to 1.5% w / v; The concentration of PEG in the total volume of the supramolecular ellagic acid ion salt composition is 25% w / v to 75% w / v; The antioxidant is selected from gallic acid, propyl gallate, ascorbic acid, tocopherol, sodium sulfite or a combination thereof.

4. The supramolecular ellagic acid ion salt composition according to claim 1 or 2, characterized in that: The alkaline ion ligand is selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, tromethamine, triethanolamine, lysine, arginine or a combination thereof.

5. The supramolecular ellagic acid ion salt composition according to claim 3, characterized in that: The concentration of the propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.5% w / v.

6. The supramolecular ellagic acid ion salt composition according to claim 3, characterized in that: The concentration of the propyl gallate in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.3% w / v.

7. The supramolecular ellagic acid ion salt composition according to claim 4, characterized in that: Meet at least one of the following requirements: The molar ratio of the ellagic acid to the alkaline ion ligand is 1:(1-4); The concentration of lysine in the total volume of the supramolecular ellagic acid ion salt composition is 0.1% w / v to 0.75% w / v.

8. The supramolecular ellagic acid ion salt composition according to claim 1, characterized in that: The solubility of ellagic acid in the supramolecular ellagic acid ion salt composition is 1.5 mg / ml to 7.5 mg / ml.

9. A method for preparing the supramolecular ellagic acid ion salt composition according to any one of claims 1 to 8, characterized in that: Providing the ellagic acid, antioxidant, PEG, ultrapure water, and alkaline ion ligand; wherein the average molecular weight of the PEG is 200 to 400; Dispersing the ellagic acid, antioxidant, and PEG according to a ratio to obtain a first dispersion; The ultrapure water and the alkaline ion ligand are added to the first dispersion liquid for dispersion to obtain an ellagic acid supramolecular ion salt composition.

10. Use of the supramolecular ellagic acid ion salt composition according to any one of claims 1 to 8 for preparing cosmetics.

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