Stable compositions containing epigallocatechin gallate, their preparation methods and applications

Abstract

This invention discloses a stable composition containing epigallocatechin gallate, its preparation method, and its applications. The stable composition comprises glycerol, vitamin C, chlorogenic acid, ethoxydiethylene glycol, and epigallocatechin gallate. The preparation method includes mixing glycerol and epigallocatechin gallate at room temperature, stirring to disperse evenly, heating to 75-80°C, and stirring until completely dissolved to obtain a transparent solution, phase A; stirring vitamin C, chlorogenic acid, and ethoxydiethylene glycol evenly at room temperature to obtain a transparent solution, phase B; and mixing phase A and phase B evenly to obtain the stable composition. The composition of this invention has the characteristics of high temperature and light resistance, high stability, and the preparation method is simple and inexpensive.

Description

Technical Field

[0001] This invention relates to a composition containing epigallocatechin gallate, particularly a stable composition containing epigallocatechin gallate, its preparation method, and its application. Background Technology

[0002] Epigallocatechin gallate (EGCG) is a type of catechin, with the highest content, reaching up to 50%. The structural characteristics of catechins are two or three phenolic hydroxyl groups on the B-ring and a 5,7-diphenolic hydroxyl group on the A-ring, thus possessing antioxidant activity. In addition to the phenolic hydroxyl groups on the two rings mentioned above, EGCG also has three phenolic hydroxyl groups on the D-ring (structural formula 1), making it the most potent antioxidant among the four major catechins. EGCG has good water solubility, and its antioxidant activity is more than 100 times that of vitamin C and 25 times that of vitamin E. In skincare products, it has antioxidant and moisturizing, brightening, anti-inflammatory and soothing, anti-pollution, and anti-aging effects, making it a highly recognized active ingredient among consumers.

[0003] However, EGCG's unique structure is extremely unstable, especially in water where it readily undergoes reactions such as auto-oxidation, hydrolysis, polymerization, and isomerization, making it difficult to stably apply in cosmetics. Attempts to add EGCG to cosmetics have been made to adjust pH, add chelating agents, and antioxidants, but these methods fail to maintain stability over shelf life, often resulting in noticeable discoloration, off-flavors, and deactivation. Furthermore, some raw material suppliers attempt to modify EGCG molecularly by incorporating glucosides, palmitoyl groups, or other molecules for encapsulation, hoping to address its stability issues. However, these methods have proven ineffective, with stability remaining unsatisfactory. Moreover, the complex molecular modification processes lead to significant increases in raw material prices, resulting in high costs and low cost-effectiveness.

[0004] In the prior art, application number 202110118899.7 discloses an apple polyphenol mouthwash for eliminating bad breath and its preparation method, which states that "the apple polyphenol mouthwash is prepared by adding the following components by mass percentage: chlorogenic acid 0.05%–0.08%, catechin 0.07%–0.1%, phlorizin 0.1%–0.2%, anthocyanins 0.06%–0.08%, xylitol 1%–3%, potassium sorbate 0.1%–0.2%, vitamin C 0.02%–0.04%, salt 0.1%–0.3%, ethanol 5%–8%, glycerin 8%–10%, and deionized water to 100%."

[0005] However, the mouthwash in the aforementioned patent is an aqueous formula, and the catechins in it are easily oxidized and deactivated, resulting in poor light and heat resistance. Summary of the Invention

[0006] The purpose of this invention is to provide a stable composition containing epigallocatechin gallate, its preparation method, and its applications. The composition of this invention exhibits high stability and resistance to high temperatures and light exposure. The preparation method of the composition is simple and inexpensive.

[0007] The technical solution of the present invention is a stable composition containing epigallocatechin gallate, which is composed of glycerol, vitamin C, chlorogenic acid, ethoxydiethylene glycol and epigallocatechin gallate.

[0008] The aforementioned stable composition containing epigallocatechin gallate comprises the following components in parts by weight: 80 to 100 parts of glycerol, 0.1 to 0.5 parts of vitamin C, 0.001 to 0.04 parts of chlorogenic acid, 1 to 13 parts of ethoxydiethylene glycol, and 0.01 to 30 parts of EGCG.

[0009] The aforementioned stable composition containing epigallocatechin gallate comprises the following components in parts by weight: 84.15 parts glycerol, 0.33 parts vitamin C, 0.02 parts chlorogenic acid, 13 parts ethoxydiethylene glycol, and 2.5 parts EGCG.

[0010] The aforementioned stable composition containing epigallocatechin gallate comprises the following components in parts by weight: 76.65 parts glycerol, 0.33 parts vitamin C, 0.02 parts chlorogenic acid, 13 parts ethoxydiethylene glycol, and 10 parts EGCG.

[0011] The method for preparing the above-mentioned stable composition includes the following steps:

[0012] A. Glycerin and epigallocatechin gallate are mixed at room temperature and stirred until evenly dispersed. The mixture is then heated to 75-80°C and stirred until completely dissolved to obtain a transparent solution, which is phase A.

[0013] B. Stir vitamin C, chlorogenic acid, and ethoxydiethylene glycol at room temperature until homogeneous to obtain a transparent solution, which is phase B.

[0014] C. Mix phase A and phase B evenly to obtain a stable composition.

[0015] The above-mentioned stable composition can be used in cosmetics.

[0016] A cosmetic product is provided in a two-compartment form, wherein one compartment stores a stable composition containing epigallocatechin gallate, and the other compartment stores an aqueous composition; the cosmetic product is used by mixing the two compositions while using it.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The composition of this invention uses four specific cosmetic ingredients: glycerin, vitamin C, chlorogenic acid, and ethoxydiethylene glycol. The ingredients are safe and reliable. They are combined in a reasonable ratio to fuse substances with different solubilities together to form a stable and homogeneous solution.

[0019] VC, as a super antioxidant, preferentially sacrifices itself to consume oxygen or free radicals present in the system, protecting EGCG from oxidation. It can lower the pH of the system and maintain the pH stability of the system under various test conditions, inhibiting the hydrolysis and oxidation of EGCG, and promoting chlorogenic acid to provide strong antioxidant and chelating effects in the later stage, thus stabilizing the EGCG solution.

[0020] This composition can stabilize EGCG of different concentrations under different storage conditions, especially high concentrations of EGCG up to 10%. It can maintain stability for a long time even under conditions of 45℃+ light and 50℃. It has good water solubility and can be better applied in cosmetics, ensuring that its appearance and content changes are minimal during its shelf life. It can effectively exert its effects of anti-oxidation and moisturizing, brightening and whitening, anti-inflammatory and soothing, anti-pollution and anti-aging.

[0021] The preparation method of this invention is simple and the components are common. Compared with the existing technology, it has the advantages of high efficiency and high cost performance.

[0022] Therefore, the composition of the present invention has the characteristics of high temperature and light resistance, high stability, and the preparation method of the composition is simple and low cost. Attached Figure Description

[0023] Figure 1 These are diagrams showing the initial dissolution state of EGCG in Comparative Examples 1-9 of this invention.

[0024] Figure 2 The graph shows the stability results of comparative examples 1-9 of this invention after 1 month under different conditions.

[0025] Figure 3 The graph shows the stability results of comparative examples 1-9 of this invention after 3 months under different conditions.

[0026] Figure 4 This is a statistical chart showing the EGCG retention rate of comparative examples 1-9 of the present invention after being stored for 3 months under light conditions at 45°C.

[0027] Figure 5 This is a graph showing the stability results of comparative examples 10-17 of the present invention under different conditions for one month.

[0028] Figure 6 The graph shows the stability results of Example 1, Comparative Example 1, Comparative Example 8, and Comparative Examples 18-19 of the present invention under different conditions for one month.

[0029] Figure 7 These are stability results of Examples 1, 1, 8, and 18-19 of the present invention under different conditions for 3 months.

[0030] Figure 8 These are statistical charts showing the EGCG retention rates of Embodiment 1, Comparative Example 1, Comparative Example 8, and Comparative Examples 18-19 of the present invention after storage under different conditions.

[0031] Figure 9 This is a graph showing the stability results of Example 1 and Comparative Example 20 of the present invention after being stored under different conditions for one month.

[0032] Figure 10 The graph shows the stability results of Example 1, Comparative Example 18, Comparative Example 19 and Comparative Example 21 of the present invention after being stored under different conditions for 1 month.

[0033] Figure 11 This is a statistical chart of the IC50 of DPPH free radical scavenging rate after storage for 1 month under different conditions for Examples 1, 18, 19 and 21 of the present invention.

[0034] Figure 12 These are stability results of Examples 1-4 after storage under different conditions for one month. Detailed Implementation

[0035] The present invention will be further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the invention.

[0036] Example 1:

[0037] A stable composition containing epigallocatechin gallate comprises the following ingredients in weight percentages: 84.15% glycerol, 13% ethoxydiethylene glycol, 0.33% vitamin C, 0.02% chlorogenic acid, and 2.5% epigallocatechin gallate.

[0038] The preparation method of the above embodiments includes the following steps:

[0039] A. Mix glycerol and epigallocatechin gallate at room temperature, stir to disperse evenly, heat to 75-80°C, stir until completely dissolved, and obtain a transparent solution. Cool to room temperature to obtain phase A.

[0040] B. Stir vitamin C, chlorogenic acid, and ethoxydiethylene glycol at room temperature until homogeneous to obtain a transparent solution, which is phase B.

[0041] C. Mix phase A and phase B evenly to obtain a stable composition.

[0042] The above composition can be used in cosmetics. The cosmetics contain the ingredients in a two-compartment form, one compartment storing a stable composition containing epigallocatechin gallate, and the other compartment storing an aqueous composition. The cosmetics are used by mixing the two compositions while using them.

[0043] The formulations of different embodiments and comparative examples are shown in Table 1:

[0044] Table 1. Formulations of each embodiment and comparative example

[0045]

[0046]

[0047] Comparative Examples 1-9 were denoted as AI. The solubility and stability of the AI ​​group under different conditions for 1 month and 3 months were measured. The stability testing conditions were: room temperature, -15℃, 45℃, and 45℃ light exposure. The 3-month 45℃ light exposure test conditions were: 1 month of 45℃ light exposure + 2 months of room temperature storage. The solubility test results are shown in Table 2, and the stability test results are shown in... Figure 1-3 .in Figure 1 For the initial state diagram of each group, Figure 2 The degree of color change after one month under different conditions. Figure 3 The degree of color change after 3 months under different conditions.

[0048] Table 2. Dissolution State of EGCG

[0049]

[0050] As can be seen from Table 2, EGCG is not particularly soluble in most polyols and requires heating in a water bath to 80°C for a certain period of time to dissolve. However, it can be dissolved in 1,3-propanediol and ethoxydiethylene glycol by stirring at room temperature.

[0051] from Figure 1-3As can be seen, EGCG shows no significant color change in its corresponding solvents at room temperature and -15℃. However, at -15℃, EGCG precipitates from water, indicating poor low-temperature solubility and a certain degree of lipid solubility. Under heat resistance at 45℃ and light exposure at 45℃, EGCG solutions exhibit some color change, with the latter being more pronounced. After one month of heat resistance at 45℃, the pure glycerol system showed the slightest color change and performed best, followed by glycerol systems containing 10% and 20% alcohol, which showed relatively small color changes. Other solvent systems showed significant color changes, especially the water, ethoxydiethylene glycol, and 1,3-propanediol systems, which exhibited very severe color changes. Under conditions of 45°C and light exposure for 1 month, the discoloration intensified. Under conditions of 45°C and heat resistance for 3 months, the degree of discoloration of each composition was further intensified compared to the condition of 45°C and light exposure for 1 month. Under conditions of 45°C and light exposure for 1 month followed by room temperature for 2 months, the degree of discoloration of each system was further intensified compared to the condition of 45°C and 3 months. Among them, the pure glycerol system was the most stable, while the dipropylene glycol system was the least stable.

[0052] The retention rate of EGCG after 3 months of storage at 45℃ under light was calculated using the HPLC standard curve method. Retention rate = (remaining EGCG content / initial EGCG content) * 100%. The initial EGCG content was 2.5% wt (pure product 2.39% wt). The results are shown in Table 3. Figure 4 As shown.

[0053] Table 3. EGCG content after 3 months of storage under 45℃ light conditions.

[0054]

[0055] From Table 3 and Figure 4 As can be seen, the EGCG retention rate was the highest in the pure glycerol system, with a retention rate of 95.40%; while the retention rate was the lowest in the ethoxydiethylene glycol system, with a retention rate of 62.76%.

[0056] pH values ​​of the AI ​​group were tested under different storage conditions, and the results are shown in Table 4.

[0057] Table 4. pH values ​​of EGCG solutions in each group after 3 months of storage.

[0058]

[0059]

[0060] Note: The 45℃ light exposure test conditions were: 1 month under 45℃ light exposure + 2 months at room temperature.

[0061] As can be seen from the pH values ​​in Table 4, the pH of the system decreased under 45℃ and 45℃ light irradiation, with a greater decrease under 45℃ light irradiation. The pure glycerol system showed the smallest pH change among all systems. Combined with the above experimental results, it can be concluded that the darker the system color, the lower the pH; high temperature and light irradiation accelerate the hydrolysis and oxidation reactions of EGCG. Therefore, using glycerol as a solvent can, on the one hand, reduce the presence of water and oxygen in the system, thus reducing various consumption reactions; on the other hand, it can stabilize the acid-base environment of the system and inhibit the occurrence of related reactions.

[0062] Although the above experiments show that glycerol is the ideal solvent for protecting EGCG, most antioxidants cannot be directly dissolved in glycerol. Therefore, ethoxydiethylene glycol was introduced as a medium solvent to dissolve antioxidants.

[0063] The stability of Comparative Examples 10-17 was tested for one month under different conditions, including 25℃, -15℃, 45℃, and 45℃ light exposure. The results are shown in [the table below]. Figure 5 .from Figure 5 As can be seen, Comparative Example 11 exhibited the best stability. Compared to the system without antioxidants, Comparative Examples 11 and 12, containing Vitamin C, showed less discoloration and better stability under one month of heat and light exposure, particularly with a significant improvement in stability under light exposure. Furthermore, ethoxydiethylene glycol demonstrated better stability for EGCG than water. These experiments indicate that ethoxydiethylene glycol alone, along with antioxidants including chlorogenic acid, ferulic acid, and lipoic acid, accelerates the discoloration of EGCG solutions, while Vitamin C enhances the stability of the EGCG-glycerol system, offsetting the negative effects of ethoxydiethylene glycol.

[0064] Examples 1, 1, 8, and 18-19 were subjected to stability tests for 1 month and 3 months under different conditions, including room temperature, -15°C, 45°C, 45°C under light, and 50°C. The retention rate of EGCG was calculated using the HPLC standard curve method. The EGCG retention rate % was calculated as (remaining EGCG content / initial EGCG content) * 100%, where the initial EGCG content was 2.39 wt%. The results of the 1-month stability test are shown below. Figure 6 The stability results after 3 months are shown in [link to data]. Figure 7 The 3-month test conditions consisted of testing at 45℃ and -15℃ for 3 months, while the other test conditions consisted of 1 month under the corresponding conditions plus 2 months of storage at room temperature.

[0065] Table 5. EGCG retention rate (%) of EGCG solution after storage under different conditions

[0066]

[0067] from Figure 6-7It can be seen that Example 1 exhibits the best stability and the least degree of color change, while Comparative Examples 8 and 19 show severe discoloration due to the presence of water. Previous experiments have shown that ethoxydiethylene glycol and chlorogenic acid, when used alone, negatively impact the stability of the system. Combined with Examples 1 and 18, it is evident that glycerol provides excellent protection for EGCG. Furthermore, the synergistic use of vitamin C and chlorogenic acid not only eliminates the negative effects of chlorogenic acid when used alone but also promotes its stabilizing effect on EGCG.

[0068] The retention rates of EGCG in Example 1, Comparative Example 1, Comparative Example 8, and Comparative Examples 18-19 are shown in Table 5. Figure 8 It can be seen that, except for Comparative Examples 8 and 19 containing water, which precipitate at -15°C, the stability of the other groups is optimal at -15°C. Furthermore, Example 1 exhibits the highest EGCG retention rate under all conditions, demonstrating a significant effect on improving high-temperature and light-induced stability. The addition of chlorogenic acid further enhances the stability of the system under prolonged high temperature and light exposure. In contrast, the aqueous EGCG system exhibits poor stability and a low EGCG retention rate.

[0069] The stability of Examples 1 and 20 was tested for one month under different conditions, including room temperature, -15°C, 45°C, 45°C under light, and 50°C. The retention rate of EGCG was calculated using the HPLC standard curve method. The stability test results are shown in [Figure number missing]. Figure 9 The retention rate test results are shown in Table 5.

[0070] from Figure 9 It can be seen that after one month of testing, Example 1 remained largely unchanged in color, while Comparative Example 20 showed significant color change, especially under 45°C light conditions. This indicates that when the antioxidant in the EGCG system is the same, the solvent glycerol can protect the system's color. However, as glycerol is completely replaced with ethoxydiethylene glycol, the system's heat and light resistance stability deteriorates. Table 5 also shows that under 45°C light conditions, the EGCG retention rate of Example 1 was 95.40%, compared to only 80.75% in Comparative Example 20, demonstrating that glycerol provides better protection than ethoxydiethylene glycol in the composition.

[0071] Examples 1, 18, 19, and 21 were subjected to accelerated storage with the lids open for one month under the conditions of room temperature, -15°C, 45°C + light, and 50°C, respectively. The stability and DPPH radical scavenging rate were then tested. The test results are shown in [Figure number missing]. Figure 10 , Figure 11 As shown in Table 7. For samples precipitated at -15℃, slight heating is required to dissolve them before testing the DPPH radical scavenging rate.

[0072] Table 6. DPPH radical scavenging rate (IC50) of EGCG solution after 1 month of storage

[0073]

[0074]

[0075] The experimental results show that after one month of accelerated testing, Example 1 exhibited the best color change stability, the lowest IC50 value under heat and light, and the strongest free radical scavenging ability. Furthermore, the same antioxidant was less effective in water than in glycerol. In the aqueous system, the combination of chlorogenic acid and vitamin C resulted in a weaker free radical scavenging ability compared to vitamin C alone, indicating that in the aqueous system, chlorogenic acid and vitamin C actually had a negative effect.

[0076] Examples 1-4 were subjected to a one-month stability test under conditions of -15℃, 45℃ light exposure, and 50℃, respectively. The test results are shown in […]. Figure 12 .from Figure 12 It can be seen that the examples containing different EGCG concentrations all exhibit good stability under different storage conditions and are not prone to discoloration.

[0077] Based on the above data, it is evident that the composition of VC, chlorogenic acid, ethoxydiethylene glycol, and glycerol of the present invention has a good protective effect on EGCG and can maintain long-term stability under high temperature and light conditions.

Claims

1. A stable composition containing epigallocatechin gallate, characterized in that: Composed of the following ingredients in parts by weight Composition: 80-100 parts glycerol, 0.1-0.5 parts vitamin C, 0.001-0.04 parts chlorogenic acid, 1-13 parts ethoxydiethylene glycol and 0.01-30 parts EGCG.

2. The stable composition containing epigallocatechin gallate according to claim 1, characterized in that: It consists of the following ingredients in parts by weight: 84.15 parts glycerin, 0.33 parts vitamin C, 0.02 parts chlorogenic acid, 13 parts ethoxydiethylene glycol and 2.5 parts EGCG.

3. The stable composition containing epigallocatechin gallate according to claim 1, characterized in that: It consists of the following ingredients in parts by weight: 76.65 parts glycerin, 0.33 parts vitamin C, 0.02 parts chlorogenic acid, 13 parts ethoxydiethylene glycol, and 10 parts EGCG.

4. A method for preparing the stable composition according to any one of claims 1-3, characterized in that: Includes the following steps: A. Mix glycerol and epigallocatechin gallate at room temperature, stir to disperse evenly, heat to 75~80℃, stir until completely dissolved, and obtain a transparent solution, which is phase A; B. Stir vitamin C, chlorogenic acid, and ethoxydiethylene glycol at room temperature until homogeneous to obtain a transparent solution, which is phase B. C. Mix phase A and phase B evenly to obtain a stable composition.

5. The use of the stable composition according to any one of claims 1-3 in the preparation of cosmetics.

6. A cosmetic product comprising the stable composition according to any one of claims 1-3, characterized in that: The product is formulated in a two-compartment format, with one compartment storing a stable composition containing epigallocatechin gallate and the other compartment storing an aqueous composition. The cosmetic is to be used by mixing the two compositions while applying the product.

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