A deep eutectic solvent for promoting the ultra-high dissolution of curcumin and its preparation method

Abstract

The present application discloses a deep eutectic solvent for promoting the ultra-high solubility of curcumin and a preparation method thereof, which relates to the technical field of chemical preparations and aims to solve the technical problem of the low solubility of curcumin in solvents in the prior art. The preparation method of the deep eutectic solvent for promoting the ultra-high solubility of curcumin comprises the following steps: mixing a hydrogen bond donor, a hydrogen bond acceptor and other components, and heating to a first preset temperature to obtain a clear and transparent deep eutectic solvent; heating the deep eutectic solvent to a second preset temperature, adding curcumin powder, quickly vortexing and dissolving, centrifuging to collect the supernatant to obtain a clear and transparent curcumin solution with high solubility. The method of the present application uses a green solvent as a medium, does not require additional substances to be added, is simple to operate, significantly improves the dissolution performance of curcumin, and thus expands its application scope in the fields of cosmetics, food and pharmaceuticals.

Description

Technical Field

[0001] This application relates to the technical field of chemical preparations, and particularly relates to a deep eutectic solvent for promoting the ultra-high solubility of curcumin and a preparation method thereof. Background Art

[0002] Food-derived bioactive small molecules have received extensive attention due to their potential health benefits in preventing various diseases such as cancer, obesity, cardiovascular diseases, and neurodegenerative diseases. As a natural polyphenol extracted from the rhizomes of Zingiberaceae plants, curcumin has excellent antioxidant, anti-inflammatory, and antibacterial activities. However, due to its poor water solubility and stability, the application of curcumin has been greatly restricted.

[0003] In recent years, green and inexpensive deep eutectic solvents (DES) have shown great application potential in the solubilization and stabilization of water-insoluble active substances. Deep eutectic solvents are essentially high-entropy solutions formed by mixing hydrogen bond donors and hydrogen bond acceptors in a certain stoichiometric ratio through hydrogen bond interactions. The hydrogen bond network formed by them interferes with the crystallization ability of the original compound, keeping it in a liquid state at room temperature. Prior art 1 discloses a solution system for drug-loading and transdermal penetration promotion. The deep eutectic solvent formed by diethyl L-tartrate and choline chloride has an obvious solubilization effect on hydrophobic drugs. Prior art 2 discloses a method for increasing the solubility of polysaccharides. The amino acid-organic acid deep eutectic solvent not only has a solubilization effect on poorly soluble polysaccharides and starch, but also can deliver polysaccharides to the deep layer of the skin. Prior art 3 aims at the solubility of curcumin in water being only 11 ng / mL and discloses an aqueous phase crystalline water-in-oil emulsion. The inner phase of the emulsion is composed of a deep eutectic solvent, which can not only replace hydrogenated oil for food production, but also has a curcumin loading capacity of more than 32 mg / g. Prior art 4 discloses a microemulsion system based on a deep eutectic solvent, and its solubility of curcumin can be increased to 51 mg / mL. In addition to the emulsion system, the solubilization effect of deep eutectic solvents themselves on curcumin has also received attention in recent years. Prior art 5 discloses a method for directly adding curcumin to a mixture of amino acids and glycerol to form a therapeutic deep eutectic solvent by heating and stirring. This deep eutectic solvent not only improves the solubility of curcumin, but also increases the scavenging ability of curcumin for DPPH radicals. On this basis, prior art 6 discloses a preparation method of composite hydrogel beads loaded with curcumin co-crystalline solvent. The mass volume concentration of curcumin in this co-crystalline solvent is as high as 30%, and it has potential therapeutic effects in ulcerative colitis. However, the existing deep eutectic solvents still have relatively limited solubility for curcumin. When the curcumin concentration is too high, the solvent is prone to become unstable, resulting in an opaque supersaturated state of the solution.

[0004] At present, the emulsion system is the main form to improve the solubility of curcumin. Preparing a eutectic solvent with higher solubility not only simplifies the complexity of the dissolution process but also broadens the application scope of curcumin, which is of great significance for fields such as cosmetics, food, and pharmaceuticals. Summary of the Invention

[0005] This application provides a eutectic solvent for promoting ultra-high dissolution of curcumin and its preparation method, aiming to solve the technical problem of low solubility of curcumin in solvents in the prior art.

[0006] To solve the above technical problem, the embodiments of this application provide: a preparation method of a eutectic solvent for promoting ultra-high dissolution of curcumin, including the following steps:

[0007] After mixing a hydrogen bond donor, a hydrogen bond acceptor, and other components, heat to a first preset temperature to obtain a clear and transparent eutectic solvent;

[0008] After heating the eutectic solvent to a second preset temperature, add curcumin powder, quickly vortex and dissolve, centrifuge to collect the supernatant, and obtain a clear and transparent curcumin solution with high solubility;

[0009] The mixing molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 5:1 - 1:5;

[0010] For every 1 part by weight of the eutectic solvent, add 0.01 - 1 part by weight of the other components;

[0011] The first preset temperature is 40°C - 110°C, and the second preset temperature is 30°C - 100°C.

[0012] As some alternative embodiments of this application, the hydrogen bond donor includes at least one of citric acid, ethylene glycol, glycerol, polyethylene glycol, urea, niacinamide, mannose, trehalose, and glucose.

[0013] As some alternative embodiments of this application, the hydrogen bond acceptor includes at least one of choline chloride, betaine, mannose, and sorbitol.

[0014] As some alternative embodiments of this application, the other components include at least one of water and ethanol.

[0015] As some alternative embodiments of this application, the parameters for centrifuging and collecting the supernatant are: 6000 - 12000 rpm, 5 - 15 min.

[0016] On the other hand, the embodiments of this application also provide a eutectic solvent for promoting ultra-high dissolution of curcumin, which is obtained by the method described in any one of the above.

[0017] Compared with the prior art, the method for preparing a eutectic solvent with ultra-high solubility of curcumin according to the present application includes mixing a hydrogen bond donor, a hydrogen bond acceptor and other components, and synthesizing the eutectic solvent by heating. Subsequently, curcumin powder is added to the eutectic solvent under heating conditions, dissolved by rapid vortexing, and the supernatant is collected by centrifugation to obtain a clear and transparent high-concentration curcumin solution. It can be seen that the method of the present application uses a green solvent as a medium, without the need to add additional substances, is easy to operate, significantly improves the solubility of curcumin, and thus expands its application scope in the fields of cosmetics, food and pharmaceuticals. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the specific embodiments of the present application or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0019] Figure 1 It is the standard curve graph for the quantification of curcumin involved in the embodiment of the present application.

[0020] Figure 2 It is the apparent graph of the eutectic solvent containing curcumin involved in the embodiment of the present application.

[0021] Figure 3 It is the result graph of the curcumin content in the eutectic solvent involved in the embodiment of the present application.

[0022] Figure 4 It is the result graph of the stability of curcumin in the eutectic solvent under ultraviolet conditions involved in the embodiment of the present application.

[0023] Figure 5 It is the result graph of the curcumin content dissolved in the eutectic solvents formed with different molar ratios involved in the embodiment of the present application.

[0024] Figure 6 It is the result graph of the curcumin content dissolved in the eutectic solvents with different water contents involved in the embodiment of the present application.

[0025] The realization of the purpose of the present application, functional features and advantages will be further described with reference to the embodiments and the drawings. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] Next, the technical solutions in the embodiments of the present application will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application without creative efforts belong to the scope of protection of the present application.

[0027] As described above, food-derived bioactive small molecules have attracted attention due to their potential health benefits. In particular, curcumin, a natural polyphenol, has antioxidant, anti-inflammatory, and antibacterial activities. However, its poor water solubility and stability limit its application. Deep eutectic solvents (DESs) have attracted attention due to their potential in solubilizing and stabilizing water-insoluble active substances. The prior art has demonstrated the application of DESs in improving the solubility of curcumin, including drug-loaded transdermal penetration-promoting integrated solution systems, methods for increasing the solubility of polysaccharides, aqueous-phase crystalline water-in-oil emulsions, DES-based microemulsion systems, and preparation methods for composite hydrogel beads loaded with curcumin eutectic solvents. Nevertheless, the existing DESs still have limited solubility for curcumin, and the solution stability is poor at high concentrations.

[0028] That is, the present application provides a preparation method of a deep eutectic solvent for promoting the dissolution of curcumin in view of the problem of low solubility of curcumin in solvents. The deep eutectic solvent is synthesized by mixing a hydrogen bond donor, a hydrogen bond acceptor, and other components and heating. Curcumin powder is added under the condition of heating the solvent, and it is rapidly vortex-dissolved. The supernatant obtained by centrifugation is the deep eutectic solvent containing a high concentration of curcumin.

[0029] Specifically, the technical solutions adopted in the embodiments of the present application are as follows:

[0030] A preparation method of a deep eutectic solvent for promoting the ultra-high dissolution of curcumin, comprising the following steps:

[0031] Step S10: After mixing a hydrogen bond donor, a hydrogen bond acceptor, and other components, heat to a first preset temperature to obtain a clear and transparent deep eutectic solvent; the first preset temperature is 40°C - 110°C.

[0032] It should be noted that the hydrogen bond donor includes at least one of citric acid, ethylene glycol, glycerol, polyethylene glycol, urea, nicotinamide, mannose, trehalose, and glucose. The hydrogen bond acceptor includes at least one of choline chloride, betaine, mannose, and sorbitol. The other components include at least one of water and ethanol. Among them, the mixing molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 5:1 - 1:5; for every 1 weight part of the deep eutectic solvent, 0.01 - 1 weight part of the other components is added.

[0033] Step S20: After heating the deep eutectic solvent to the second preset temperature, add curcumin powder, vortex and dissolve quickly, and centrifuge to collect the supernatant to obtain a clear and transparent curcumin solution with high solubility; the second preset temperature is 30°C - 100°C; the parameters for centrifuging and collecting the supernatant are: 6000 - 12000 rpm, 5 - 15 min.

[0034] For the convenience of those skilled in the art to understand the technical solution of the present application, the method of the present application will be described in detail below with reference to the embodiments:

[0035] Examples 1 - 3

[0036] Prepare a deep eutectic solvent for promoting the dissolution of curcumin according to the components described in Table 1:

[0037] Table 1

[0038]

[0039] The preparation method of the deep eutectic solvent for promoting the dissolution of curcumin described in Examples 1 - 3 includes the steps:

[0040] (1) Mix the hydrogen bond donor, hydrogen bond acceptor and other components described in each example, and heat at 80°C until a clear and transparent solution is obtained;

[0041] (2) Heat the solvent to 50°C, add the curcumin described in the example, vortex and dissolve, centrifuge at 8000 rpm for 10 min, and collect the supernatant to obtain a deep eutectic solvent containing a high concentration of curcumin.

[0042] Examples 4 - 8

[0043] The hydrogen bond donor is preferably polyethylene glycol 400, the hydrogen bond acceptor is preferably choline chloride, and the other component is preferably water. Prepare a deep eutectic solvent with a molar ratio of hydrogen bond donor to hydrogen bond acceptor of 3:1 - 1:3 according to the components described in Table 2, and the remaining steps are the same as those in Example 1:

[0044] Table 2

[0045]

[0046] Examples 9 - 13

[0047] The hydrogen bond donor is preferably polyethylene glycol 400, the hydrogen bond acceptor is preferably choline chloride, and the other component is preferably water. Prepare deep eutectic solvents with different water contents (10wt%, 30wt%, 50wt%, 70wt% and 90wt%) according to the components described in Table 3, and the remaining steps are the same as those in Example 1:

[0048] Table 3

[0049]

[0050] Comparative Examples 1-4

[0051] Different from Example 1, the solvent was replaced, and the remaining steps were the same as those in Example 1. Comparative Examples 1-4 were prepared according to Table 4:

[0052] Table 4

[0053]

[0054] Experimental Example 1

[0055] Dissolve curcumin with a known content in ethanol, measure the absorbance at 426 nm under different concentration conditions, and draw a standard curve of curcumin content. The curcumin concentration gradient is 0, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 μg / mL. The standard curve is as Figure 1 shown.

[0056] Experimental Example 2

[0057] Spread the solution with a curcumin concentration of 50 μg / mL evenly in a glass dish, irradiate it under a 185 nm ultraviolet lamp at 35 °C for a gradient time (0, 15, 30, 45, 60, 75 min), take a small amount of the solution at each time node to measure the curcumin content, and observe the stability of curcumin.

[0058] As Figure 2 shown, the colors of the solutions of Comparative Examples 1-3 are lighter than those of Examples 1-3, indicating that the dissolution ability of curcumin in Examples 1-3 is higher than that in Comparative Examples 1-3. It should be noted that after centrifugation in Example 3, there is less precipitation and the color is dark red, indicating its strong dissolution ability for curcumin. As Figure 3 shown, the curcumin concentrations in Comparative Examples 1-3 are 4.03, 0.89 and 1.43 mg / mL respectively, and the curcumin concentrations in Examples 1-3 are 13.14, 11.51 and 21.48 mg / mL respectively. The concentrations of the examples are significantly higher than those of the comparative examples. Since the amphiphilic molecular chain of polyethylene glycol has the property of significantly improving the solubility of natural products or drugs, the deep eutectic solvents based on polyethylene glycol (as shown in Examples 1-3) also have this property.

[0059] As Figure 4As shown, curcumin in Examples 1-3 showed good stability under ultraviolet irradiation, while in Comparative Examples 1-2, there was a trend of rapid decline. When irradiated with ultraviolet light for 30 min, the retention rates of curcumin in Examples 1-3 were 74.38%, 83.45% and 72.39% respectively, while in Comparative Examples 1-2 they were 34.77% and 16.90% respectively, indicating that Examples 1-3 have the ability to stabilize curcumin. The strong stabilizing effect of Examples 1-3 may be due to the hydrogen bond network of the eutectic solvent forming a more stable protective layer around curcumin, preventing direct contact between external factors such as light and curcumin through steric hindrance effects, thereby reducing its degradation rate.

[0060] As Figure 5 shown, Examples 4-8 are respectively solutions with a molar ratio of hydrogen bond donor to hydrogen bond acceptor of 3:1 - 1:3. When the molar ratio changes from 1:3 to 3:1, the solubility of curcumin in the solution increases from 55.14 mg / mL to 92.66 mg / mL. The increase in the proportion of polyethylene glycol helps to increase the solubility of curcumin. This is not only because polyethylene glycol can change the overall polarity of the solvent to make it closer to the polarity characteristics of curcumin, but also because the hydrogen bond network formed by a higher proportion of polyethylene glycol can better wrap curcumin molecules to form a stable solvation layer.

[0061] As Figure 6 shown, Examples 9-13 respectively represent the dissolution ability of eutectic solvents with water contents of 10wt%, 30wt%, 50wt%, 70wt% and 90wt% for curcumin. As the water content decreases, the dissolution ability of the solution for curcumin increases, from 2.19 mg / mL to 110.04 mg / mL, indicating that the lower the water content, the more beneficial it is for the eutectic solvent to dissolve curcumin. The hydrogen bond network of the eutectic solvent is more stable under low water content conditions, and the polarity of its solution is lower, which is beneficial to improving the solubility of curcumin.

[0062] Thus, the technical solution of this application successfully improves the solubility of curcumin by designing a eutectic solvent that promotes the ultra-high dissolution of curcumin, and through a simplified preparation process, makes its application in multiple fields more promising. Compared with the prior art, this technical solution has the following technical progress and its reasons:

[0063] 1) Significantly improved solubility of curcumin: The technical solution of this application utilizes the eutectic solvent system to greatly enhance the solubility of curcumin. For example, by using a mixture of hydrogen bond donors and hydrogen bond acceptors, the solubility of curcumin has been significantly improved. The curcumin concentrations in Examples 1-3 were 13.14, 11.51, and 21.48 mg / mL respectively, while those in the control group were only 4.03, 0.89, and 1.43 mg / mL. This indicates that this method has obvious advantages in the solubility of curcumin. This may be because the unique formulation of the eutectic solvent can form a strong dissolution interaction with curcumin through intermolecular hydrogen bonding, significantly increasing the solubility of curcumin. At the same time, by adjusting the ratio of hydrogen bond donors and hydrogen bond acceptors, the dissolution effect can be optimized.

[0064] 2) Stability of the solution: The technical solution of this application can significantly improve the stability of curcumin under ultraviolet irradiation. After 30 minutes of ultraviolet irradiation, the retention rates of curcumin in Examples 1-3 were 74.38%, 83.45%, and 72.39% respectively, while those in the control group were 34.77% and 16.90% respectively. This shows that this technology can effectively enhance the stability of curcumin under ultraviolet light irradiation. This may be because the components in the eutectic solvent, especially the interaction between hydrogen bond donors and hydrogen bond acceptors, contribute to the formation of a more stable curcumin solution, resisting the degradation caused by ultraviolet light. This provides a longer shelf life for the application of curcumin in cosmetics and pharmaceuticals.

[0065] 3) Simple operation and environmental protection: Compared with traditional dissolution methods, the technical solution of this application is simple to operate and does not rely on expensive or complex equipment. The whole process mainly includes heating and vortex dissolution, which makes the preparation process more efficient and low-cost. This method uses a green and environmentally friendly solvent system (such as natural ingredients like citric acid and ethylene glycol), avoiding the use of harmful chemical solvents, meeting the requirements of the modern pharmaceutical, food, and cosmetics industries for green environmental protection, low pollution, and low cost.

[0066] 4) Broaden the application scope of curcumin: Curcumin solutions with high solubility have broad application prospects in the fields of cosmetics, food, and pharmaceuticals. By enhancing solubility and stability, the application range of curcumin has been expanded, including applications in skin care products, antioxidant foods, and pharmaceutical preparations. As a natural compound with a wide range of biological activities, curcumin has important application potential in multiple fields. By improving its solubility and stability, it can play a greater role in daily consumer products, especially in enhancing functions such as antioxidant, anti-inflammatory, and anti-cancer.

[0067] In summary, compared with the prior art, the technical solution of this application has made remarkable technological progress, especially in terms of the solubility, stability, environmental friendliness, and operational simplicity of curcumin. By ingeniously designing the deep eutectic solvent and adjusting its composition ratio, not only the dissolution ability of curcumin has been improved, but also its stability under ultraviolet light has been enhanced, laying a stronger foundation for the application of curcumin in multiple industries.

[0068] The above are only the preferred embodiments of this application and are not intended to limit this application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of this application shall be included within the protection scope of this application.

Claims

1. A preparation method of a deep eutectic solvent for promoting the ultra-high dissolution of curcumin, characterized in that, It includes the following steps: After mixing a hydrogen bond donor, a hydrogen bond acceptor and water, heat the mixture to 80 °C to obtain a clear and transparent eutectic solvent; After heating the eutectic solvent to 50 °C, add curcumin powder, quickly vortex to dissolve, centrifuge to collect the supernatant to obtain a clear and transparent curcumin solution with high solubility; The hydrogen bond donor is polyethylene glycol 400, the hydrogen bond acceptor is choline chloride, and the mixing molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 3:1; The water content of the eutectic solvent is 10 wt%.

2. The preparation method of the eutectic solvent for promoting the ultra-high dissolution of curcumin according to claim 1, wherein, The parameters for centrifuging and collecting the supernatant are: 6000 - 12000 rpm, 5 - 15 min.

3. A deep eutectic solvent for promoting the ultra-high dissolution of curcumin, characterized in that, Prepared by the method according to any one of claims 1 - 2.

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