Eutectic solvent for promoting ultra-high dissolution of curcumin and preparation method of eutectic solvent

Abstract

The invention discloses a eutectic solvent for promoting ultrahigh dissolution of curcumin and a preparation method of the eutectic solvent, relates to the technical field of chemical preparations, and aims to solve the technical problem of relatively low solubility of curcumin in a solvent in the prior art. The preparation method of the eutecticevaporate solvent for promoting ultrahigh dissolution 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 eutecticevaporate solvent; and heating the eutectic solvent to a second preset temperature, adding curcumin powder, carrying out rapid vortex dissolution, centrifuging, and collecting a supernatant to obtain a clear and transparent high-solubility curcumin solution. According to the method, the green solvent is adopted as a medium, no additional substance needs to be added, operation is easy and convenient, the solubility of the curcumin is remarkably improved, and therefore the application range of the curcumin in the fields of cosmetics, food and pharmacy is expanded.

Description

Technical Field

[0001] The present application relates to the technical field of chemical preparations, and in particular to a low eutectic solvent for promoting ultra-high dissolution of curcumin and a preparation method thereof. Background Art

[0002] Food-derived active small molecules have attracted extensive attention due to their potential health benefits in preventing a variety of diseases, including cancer, obesity, cardiovascular disease, and neurodegenerative diseases. Curcumin, a natural polyphenol extracted from the rhizomes of ginger plants, has excellent antioxidant, anti-inflammatory, and antibacterial activities. However, its application is greatly limited due to its poor water solubility and stability.

[0003] In recent years, green and cheap 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 hydrogen bond donors and hydrogen bond acceptors mixed in a certain stoichiometric ratio through hydrogen bond interactions. The hydrogen bond network formed interferes with the crystallization ability of the original compound, making it remain in a liquid state at room temperature. Prior art 1 discloses a drug-carrying and skin-penetration-promoting integrated solution system, and the low eutectic solvent formed by L-tartrate diethyl ester and choline chloride has a significant solubilization effect on hydrophobic drugs. Prior art 2 discloses a method for increasing the solubility of polysaccharides, and the amino acid-organic acid low eutectic solvent not only has a solubilization effect on poorly soluble polysaccharides and starch, but also can deliver polysaccharides to the deep layers of the skin. Prior art 3 discloses an aqueous crystalline oil-in-water emulsion for curcumin, which has a solubility of only 11 ng / mL in water. The inner phase of the emulsion is composed of a low eutectic solvent, which can not only replace hydrogenated oil for food production, but also has a curcumin loading of up to 32 mg / g or more. Prior art 4 discloses a microemulsion system based on a low eutectic solvent, which can increase the solubility of curcumin to 51 mg / mL. In addition to the emulsion system, the solubilization effect of the low eutectic solvent itself on turmeric has also attracted attention in recent years. Prior art 5 discloses a method of directly adding curcumin to a mixture of amino acids and glycerol, and forming a therapeutic low eutectic solvent by heating and stirring. The low eutectic solvent not only improves the solubility of curcumin, but also increases the scavenging ability of curcumin DPPH free radicals. On this basis, prior art 6 discloses a method for preparing composite hydrogel beads loaded with a curcumin eutectic solvent. The mass volume concentration of curcumin in the eutectic solvent is as high as 30%, which has a potential therapeutic effect in ulcerative colitis. However, the existing low eutectic solvents are still relatively limited in their ability to dissolve curcumin. When the concentration of curcumin is too high, the solvent tends to become unstable, causing the solution to be in an opaque supersaturated state.

[0004] At present, the emulsion system is the main form of improving the solubility of curcumin. The preparation of low-melting solvents with higher solubility not only simplifies the complexity of the dissolution process, but also broadens the application range of curcumin, which is of great significance to the fields of cosmetics, food and pharmaceuticals. Summary of the invention

[0005] The present application provides a low eutectic solvent that promotes ultra-high solubility of curcumin and a preparation method thereof, aiming to solve the technical problem of low solubility of curcumin in solvents in the prior art.

[0006] In order to solve the above technical problems, the present application provides a method for preparing a deep eutectic solvent that promotes ultra-high solubility of curcumin, comprising the following steps: After mixing the hydrogen bond donor, the hydrogen bond acceptor and other components, heating to a first preset temperature to obtain a clear and transparent low eutectic solvent; After heating the deep eutectic solvent to a second preset temperature, adding curcumin powder, rapidly vortexing to dissolve, and centrifuging to collect the supernatant to obtain a clear and transparent high-solubility curcumin solution; The mixing molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 5:1-1:5; For every 1 part by weight of the deep eutectic solvent, 0.01-1 part by weight of the other components are added; The first preset temperature is 40°C-110°C, and the second preset temperature is 30°C-100°C.

[0007] As some optional embodiments of the present application, the hydrogen bond donor includes at least one of citric acid, ethylene glycol, glycerol, polyethylene glycol, urea, nicotinamide, mannose, trehalose and glucose.

[0008] As some optional embodiments of the present application, the hydrogen bond acceptor includes at least one of choline chloride, betaine, mannose and sorbitol.

[0009] As some optional embodiments of the present application, the other components include at least one of water and ethanol.

[0010] As some optional embodiments of the present application, the parameters for collecting the supernatant by centrifugation are: 6000-12000 rpm, 5-15 min.

[0011] On the other hand, an embodiment of the present application also provides a low eutectic solvent that promotes ultra-high solubility of curcumin, which is prepared by any of the methods described above.

[0012] Compared with the prior art, the method for preparing a low eutectic solvent for promoting ultra-high solubility of curcumin involved in the present application includes mixing a hydrogen bond donor, a hydrogen bond acceptor and other components, and synthesizing a low eutectic solvent by heating. Subsequently, curcumin powder is added to the low eutectic solvent under heating conditions, dissolved by rapid vortexing, and then 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, does not require additional substances, is easy to operate, and significantly improves the solubility performance of curcumin, thereby expanding its application range in cosmetics, food and pharmaceutical fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the specific implementation of the present application or the technical solution in the prior art, the following is a brief introduction to the drawings required for the specific implementation or the prior art description. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual scale.

[0014] Figure 1 This is a standard curve diagram for the quantitative determination of curcumin involved in the embodiment of the present application Figure 2 This is an apparent diagram of the low eutectic solvent containing curcumin involved in the embodiments of the present application.

[0015] Figure 3 This is a result diagram of the curcumin content in the low eutectic solvent involved in the examples of this application.

[0016] Figure 4 This is a graph showing the stability results of curcumin in a low eutectic solvent under ultraviolet conditions according to an embodiment of the present application.

[0017] Figure 5 This is a graph showing the results of curcumin dissolution in a low eutectic solvent formed with different molar ratios involved in the examples of the present application.

[0018] Figure 6 This is a graph showing the results of curcumin dissolution in low eutectic solvents with different water contents involved in the examples of the present application.

[0019] The realization of the purpose, functional features and advantages of this application will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0020] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0021] As mentioned above, foodborne active small molecules have attracted attention due to their potential health benefits, especially curcumin, a natural polyphenol with antioxidant, anti-inflammatory and antibacterial activities. However, its poor water solubility and stability limit its application. Deep eutectic solvents (DES) have attracted attention due to their potential in solubilizing and stabilizing water-insoluble active substances. The existing technology demonstrates the application of DES in improving the solubility of curcumin, including an integrated solution system for drug loading and skin penetration promotion, a method for increasing the solubility of polysaccharides, an aqueous crystalline oil-in-water emulsion, a DES-based microemulsion system, and a method for preparing composite hydrogel beads loaded with curcumin eutectic solvent. Despite this, the existing DES has limited solubility for curcumin and poor solution stability at high concentrations.

[0022] That is, in order to solve the problem of low solubility of curcumin in solvent, the present application provides a method for preparing a low eutectic solvent that promotes the dissolution of curcumin, wherein a hydrogen bond donor, a hydrogen bond acceptor and other components are mixed and heated to synthesize a low eutectic solvent; curcumin powder is added under the condition of heating the solvent, and the mixture is rapidly vortexed to dissolve, and the supernatant obtained by centrifugation is the low eutectic solvent containing a high concentration of curcumin.

[0023] Specifically, the technical solutions adopted in the embodiments of the present application are as follows: A method for preparing a deep eutectic solvent that promotes ultra-high solubility of curcumin comprises the following steps: Step S10, after mixing the hydrogen bond donor, the hydrogen bond acceptor and other components, heating to a first preset temperature to obtain a clear and transparent low eutectic solvent; the first preset temperature is 40°C-110°C.

[0024] 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. 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 low eutectic solvent, 0.01-1 weight part of the other components is added.

[0025] Step S20, after heating the low eutectic solvent to a second preset temperature, adding curcumin powder, rapidly vortexing to dissolve, centrifuging to collect the supernatant, and obtaining a clear and transparent high-solubility curcumin solution; the second preset temperature is 30° C.-100° C.; the parameters for centrifuging to collect the supernatant are: 6000-12000 rpm, 5-15 min.

[0026] To facilitate those skilled in the art to understand the technical solution of the present application, the method described in the present application is described in detail below in conjunction with embodiments: Examples 1-3 A deep eutectic solvent for promoting the dissolution of curcumin was prepared according to the components described in Table 1: Table 1

[0027] The method for preparing the deep eutectic solvent for promoting the dissolution of curcumin described in Example 1-3 comprises the steps of: (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; (2) The solvent was heated to 50° C., the curcumin described in the example was added, vortexed to dissolve, centrifuged at 8000 rpm for 10 min, and the supernatant was collected to obtain a low eutectic solvent containing a high concentration of curcumin.

[0028] Embodiment 4-8 The hydrogen bond donor is preferably polyethylene glycol 400, the hydrogen bond acceptor is preferably choline chloride, and the other components are preferably water. A low eutectic solvent having a molar ratio of hydrogen bond donor to hydrogen bond acceptor of 3:1-1:3 is prepared according to the components described in Table 2, and the remaining steps are the same as those in Example 1: Table 2

[0029] Examples 9-13 The hydrogen bond donor is preferably polyethylene glycol 400, the hydrogen bond acceptor is preferably choline chloride, and the other components are preferably water. According to the components described in Table 3, low eutectic solvents with different water contents (10wt%, 30wt%, 50wt%, 70wt% and 90wt%) are prepared, and the remaining steps are the same as in Example 1: Table 3

[0030] Comparative Examples 1-4 The difference from Example 1 is that the solvent is replaced, and the remaining steps are the same as those of Example 1. Comparative Examples 1-4 are prepared according to Table 4: Table 4

[0031] Experimental Example 1 Use ethanol to dissolve curcumin of known content, 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 follows Figure 1 shown.

[0032] Experimental Example 2 A curcumin solution with a concentration of 50 μg / mL was evenly spread in a glass dish and irradiated under a 185 nm ultraviolet lamp at 35°C for gradient time (0, 15, 30, 45, 60, 75 min). A small amount of solution was taken at each time point to determine the curcumin content and observe the stability of curcumin.

[0033] like Figure 2 As shown, the color of the solution of Comparative Example 1-3 is lighter than that of Example 1-3, indicating that the solubility of Example 1-3 for curcumin is higher than that of Comparative Example 1-3. It is worth noting that after centrifugation, Example 3 has less precipitation and is dark red in color, indicating that it has a stronger solubility for curcumin. Figure 3 As shown, the concentrations of curcumin in comparative examples 1-3 are 4.03, 0.89 and 1.43 mg / mL, respectively, and the concentrations of turmeric 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 chains of polyethylene glycol have the property of significantly improving the solubility of natural products or drugs, the low eutectic solvents formed based on polyethylene glycol (as shown in examples 1-3) also have this property. like Figure 4 As shown, curcumin in Examples 1-3 exhibits good stability under ultraviolet irradiation, while Comparative Example 1-2 shows a trend of rapid decline. When ultraviolet irradiation is performed for 30 min, the retention rates of curcumin in Examples 1-3 are 74.38%, 83.45% and 72.39%, respectively, while those in Comparative Example 1-2 are 34.77% and 16.90%, respectively, indicating that Examples 1-3 have the ability to stabilize curcumin. The stronger stabilizing effect of Examples 1-3 may be due to the hydrogen bond network of the deep eutectic solvent forming a more stable protective layer around curcumin, which prevents external factors such as light from directly contacting curcumin through the steric hindrance effect, thereby reducing its degradation rate.

[0034] like Figure 5 As shown, Examples 4-8 are solutions with a molar ratio of hydrogen bond donor to hydrogen bond acceptor of 3:1-1:3, respectively. 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 improve the solubility of curcumin, not only because polyethylene glycol can change the overall polarity of the solvent, making it closer to the polar characteristics of curcumin, but also because the hydrogen bond network formed by a higher proportion of polyethylene glycol can better wrap the curcumin molecules to form a stable solvation layer.

[0035] like Figure 6As shown, Examples 9-13 are respectively expressed as the solubility of 10wt%, 30wt%, 50wt%, 70wt% and 90wt% water content of the deep eutectic solvent for curcumin. As the water content decreases, the solubility 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 conducive it is for the deep eutectic solvent to dissolve curcumin. The hydrogen bond network of the deep eutectic solvent is more stable under low water content conditions, and the polarity of its solution is lower, which is conducive to improving the solubility of curcumin.

[0036] It can be seen that the technical solution of the present application successfully improves the solubility of curcumin by designing a low eutectic solvent that promotes ultra-high solubility of curcumin, and through a simplified preparation process, makes its application in multiple fields more promising. Compared with the prior art, the technical solution has the following technical advances and their reasons: 1) Significant improvement in the solubility of curcumin: The technical solution of the present application utilizes a low eutectic solvent system to greatly improve the solubility of curcumin. For example, by using a mixture of hydrogen bond donors and hydrogen bond acceptors, the solubility of curcumin has been greatly improved. The curcumin concentrations of Examples 1-3 are 13.14, 11.51, and 21.48 mg / mL, respectively, while the control group is only 4.03, 0.89, and 1.43 mg / mL. This shows that this method has a clear advantage in the solubility of curcumin. This may be because the unique formula of the low eutectic solvent can form a strong dissolution interaction with curcumin through intermolecular hydrogen bonding, significantly improving the solubility of curcumin. At the same time, the dissolution effect can be optimized by adjusting the ratio of hydrogen bond donors and hydrogen bond acceptors.

[0037] 2) Stability of the solution: The technical solution of the present 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 the present technology can effectively enhance the stability of curcumin under ultraviolet irradiation. This may be because the components in the low eutectic solvent, especially the interaction between hydrogen bond donors and hydrogen bond acceptors, help to form a more stable curcumin solution that resists degradation caused by ultraviolet light. This provides a longer shelf life for the use of curcumin in cosmetics and pharmaceuticals.

[0038] 3) Easy to operate and environmentally friendly: 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 citric acid, ethylene glycol and other natural ingredients), avoids the use of harmful chemical solvents, and meets the requirements of modern pharmaceutical, food and cosmetics industries for green, low pollution and low cost.

[0039] 4) Broaden the application scope of curcumin: High-solubility curcumin solution has broad application prospects in the fields of cosmetics, food and pharmaceuticals. By improving solubility and stability, the scope of use of curcumin can be expanded, including its application 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 many fields. By improving its solubility and stability, it can play a greater role in daily consumer products, especially in enhancing antioxidant, anti-inflammatory and anti-cancer functions.

[0040] In summary, the technical solution of this application has made significant technical progress compared with the prior art, especially in terms of curcumin solubility, stability, environmental protection and ease of operation. By cleverly designing the low eutectic solvent and adjusting its component ratio, not only the solubility of curcumin is improved, but also its stability under ultraviolet light is enhanced, laying a stronger foundation for the application of curcumin in multiple industries.

[0041] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A method for preparing a deep eutectic solvent that promotes ultra-high solubility of curcumin, characterized in that: The following steps are involved: After mixing the hydrogen bond donor, the hydrogen bond acceptor and other components, heating to a first preset temperature to obtain a clear and transparent low eutectic solvent; After heating the deep eutectic solvent to a second preset temperature, adding curcumin powder, rapidly vortexing to dissolve, and centrifuging to collect the supernatant to obtain a clear and transparent high-solubility curcumin solution; The mixing molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 5:1-1:5; For every 1 part by weight of the deep eutectic solvent, 0.01-1 part by weight of the other components are added; The first preset temperature is 40°C-110°C, and the second preset temperature is 30°C-100°C.

2. The method for preparing the deep eutectic solvent for promoting ultra-high solubility of curcumin according to claim 1, characterized in that: The hydrogen bond donor includes at least one of citric acid, ethylene glycol, glycerol, polyethylene glycol, urea, nicotinamide, mannose, trehalose and glucose.

3. The method for preparing the deep eutectic solvent for promoting ultra-high solubility of curcumin according to claim 1, characterized in that: The hydrogen bond acceptor includes at least one of choline chloride, betaine, mannose and sorbitol.

4. The method for preparing the deep eutectic solvent for promoting ultra-high solubility of curcumin according to claim 1, characterized in that: The other components include at least one of water and ethanol.

5. The method for preparing the deep eutectic solvent for promoting ultra-high solubility of curcumin according to claim 1, characterized in that: The parameters for collecting the supernatant by centrifugation are: 6000-12000 rpm, 5-15 min.

6. A deep eutectic solvent for promoting ultra-high solubility of curcumin, characterized in that: The method is prepared by any one of claims 1 to 5.

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