A nicotinamide-baicalein-polyol ternary eutectic solvent, a preparation method and application thereof

Abstract

The application relates to the technical field of supramolecular, and discloses a nicotinamide-baicalein-polyhydric alcohol ternary eutectic solvent as well as a preparation method and application thereof. Nicotinamide, baicalein, 1,3-propylene glycol and / or glycerol are mixed according to a mass ratio of 10:1:89-20:6:74, heated and stirred to obtain a uniform and transparent DES system. The original crystal structure of baicalein and nicotinamide is destroyed, and an amorphous supramolecular DES system is formed through XRD characterization. The system can improve the solubility of baicalein in water by about 23 times, and no solid is precipitated after being diluted into a 2% aqueous solution and stored at 4 DEG C for two months. The application utilizes the supramolecular technology to form a stable eutectic system through intermolecular hydrogen bonds and other interactions, can solve the problem of poor solubility of baicalein, improve the water solubility and stability of baicalein, and expand the application of baicalein in cosmetics and external preparations.

Description

Technical Field

[0001] This invention relates to the field of supramolecular technology, specifically to a nicotinamide-baicalin-polyol ternary eutectic solvent, its preparation method, and its application. Background Technology

[0002] Baicalin is a natural flavonoid compound extracted from Scutellaria baicalensis Georgi, a plant in the Lamiaceae family. It possesses various biological activities, including antioxidant, anti-inflammatory, antibacterial, and regulation of cell signaling pathways, and shows broad application prospects in pharmaceuticals, functional foods, and cosmetics. However, due to the presence of multiple hydroxyl, carboxyl, and glycosidic groups in its molecular structure, strong intermolecular hydrogen bonding, and stable crystal structure, baicalin exhibits low water solubility. This limits its solubility and stability in aqueous environments, thus hindering its further development and application.

[0003] Currently, methods to improve the solubility of baicalin mainly include organic solvent-assisted dissolution, nanotechnology, lipid carrier encapsulation, and cyclodextrin inclusion. While organic solvent-assisted dissolution can improve the solubility of baicalin, some organic solvents have issues related to safety, volatility, and application limitations. Nanotechnology and lipid delivery technologies typically involve complex preparation processes, and the system stability is easily affected by changes in particle size, component ratios, and storage conditions. Cyclodextrin inclusion technology is limited by molecular structure matching, and there is still room for further optimization in improving solubility and maintaining the effective release of active ingredients. Therefore, developing a novel system with a simple preparation process, adjustable components, and the ability to effectively improve the solubility of baicalin is of great significance.

[0004] Deep eutectic solvents (DES) are eutectic mixtures formed by the interactions of two or more components through hydrogen bonds, van der Waals forces, and other mechanisms. Due to their tunable composition, polarity, viscosity, and solvation ability can be adjusted by optimizing the types and ratios of components, thus showing potential for the dissolution and extraction of poorly soluble natural active substances. Compared to traditional organic solvents, using cosmetic raw materials with a good application foundation as components of DES is beneficial to improving the system's applicability in cosmetics and topical formulations. For example, polyol components have good moisturizing properties and skin compatibility, and can be used as functional solvent components in the construction of DES systems. Therefore, DES systems constructed based on cosmetic raw materials are expected to improve the solubility of poorly soluble active ingredients while also ensuring the system's application safety.

[0005] Baicalin has poor solubility and permeability, making it difficult to apply in cosmetics. Therefore, if DES can be prepared and its solubility utilized, it is hoped that the application prospects of baicalin in cosmetics can be expanded. Summary of the Invention

[0006] The technical problem to be solved by this invention is that baicalin has poor water solubility, poor stability and poor permeability. Existing methods for improving solubility have problems with safety, complexity and stability.

[0007] To address the aforementioned technical problems, this invention provides a nicotinamide-baicalin-polyol ternary eutectic solvent, its preparation method, and its application.

[0008] The technical solution adopted in this invention is as follows: A ternary eutectic solvent comprising nicotinamide, baicalin, and a polyol, wherein the polyol is 1,3-propanediol and / or glycerol, and the mass ratio of nicotinamide, baicalin, and polyol is 10:1:89 to 20:6:74; the eutectic solvent is a homogeneous and transparent liquid.

[0009] As a preferred technical solution, the baicalin content in the ternary eutectic solvent is 1% to 6.0% by mass.

[0010] As a preferred technical solution, when the ternary eutectic solvent is diluted with water to a mass fraction of 2% to 60%, the mass concentration of baicalin in the diluted solution is 0.1% to 4.0%. After standing at 4°C for at least one month, it remains a stable and homogeneous liquid without any solid precipitation.

[0011] As a preferred technical solution, the binding energy of baicalin-nicotinamide-polyol in the ternary eutectic solvent is -194.8 to -202.4 kJ / mol.

[0012] As a preferred technical solution, in the XRD pattern of the ternary eutectic solvent, the characteristic diffraction peaks of baicalin and nicotinamide disappear, and only broad diffuse peaks are observed.

[0013] As a preferred technical solution, the polyol is at least one of 1,3-propanediol and glycerol.

[0014] As a preferred technical solution, the nicotinamide-baicalin-polyol ternary eutectic solvent system can remain stable for two months at 4℃, 25℃, and 48℃ without solid precipitation.

[0015] As a preferred technical solution, the nicotinamide-baicalin-polyol ternary eutectic solvent system can be diluted with water to a baicalin mass concentration of 0.1% to 4.0%, with no solid precipitation.

[0016] As a preferred technical solution, after diluting the DES system to a 10% aqueous solution, the solubility of baicalin was measured by HPLC to be 909.99±1.03 μg / mL, while the solubility of baicalin in pure water was measured by HPLC to be 39.43±0.42 μg / mL. This embodiment achieves the solubility enhancement of baicalin in water by a solubility enhancement factor of 23 times.

[0017] This invention also discloses a method for preparing a ternary eutectic solvent, comprising the following steps: Nicotinamide, baicalin, and polyol were mixed in a mass ratio of 10:1:89-20:6:74 and heated and stirred to obtain a homogeneous and transparent eutectic solvent of nicotinamide-baicalin-polyol; wherein the polyol was 1,3-propanediol and / or glycerol.

[0018] This invention also discloses the application of a ternary eutectic solvent in the preparation of cosmetics or topical formulations.

[0019] This invention also discloses the application of a ternary eutectic solvent in improving the water solubility of baicalin.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention provides a baicalin solubilization system based on a low eutectic solvent (DES). By selecting cosmetic components with good application prospects to construct the DES system, the low solubility caused by the traditional solid crystal structure of baicalin is changed by utilizing the hydrogen bonding, intermolecular interactions, and supramolecular assembly effects formed between the components, enabling baicalin to be effectively dispersed and dissolved in the DES system. Compared with traditional physical mixing, simple solvent dissolution, and solid eutectic techniques, the baicalin-DES system constructed in this invention has the characteristics of liquefaction and component controllability. The interaction between baicalin and the system components can be optimized by adjusting the composition and ratio of DES, thereby improving the solubility and application stability of baicalin in the system.

[0021] (2) This invention constructs a nicotinamide-baicalin-1,3-propanediol and / or glycerol DES system, utilizing the hydrogen bond network and solubilization effect formed within the DES to reduce the intermolecular aggregation tendency of baicalin and improve its dispersion and solubility in the system. Simultaneously, this invention uses whitening ingredients and polyols with good application foundations, such as nicotinamide, 1,3-propanediol, and glycerol, as components of the DES, giving the resulting system both whitening and moisturizing effects, which is beneficial for expanding the application of baicalin in cosmetics and topical preparations.

[0022] (3) This invention utilizes the special liquid supramolecular structure of DES as a delivery carrier for baicalin. By adjusting the polarity, viscosity, and intermolecular interactions of the system, a suitable microenvironment is provided for baicalin, which is beneficial to promoting the uniform dispersion of baicalin in the application system and improving the utilization efficiency of the active ingredient. Compared with traditional aqueous systems, DES can improve the dispersion state of poorly soluble plant active ingredients, providing a new carrier option for subsequent formulation development and transdermal delivery applications.

[0023] (4) XRD analysis showed that the characteristic diffraction peaks of baicalin and nicotinamide disappeared in the XRD spectra of Examples 1-4, and only broad diffuse peaks were shown. This indicates that the original crystal structure of the two components was destroyed, indicating that the system was not a simple physical mixture of the two raw materials, but formed an amorphous supramolecular DES system with a liquid network structure.

[0024] (5) DFT calculations show that the binding energy between baicalin and nicotinamide-1,3-propanediol is -194.8121 kJ / mol, and the binding energy between baicalin, nicotinamide, and glycerol is -202.4261 kJ / mol, indicating that the binding capacity between baicalin, nicotinamide, and glycerol is stronger when the polyol in the system is glycerol. In the glycerol-based DES, the concentration of baicalin can reach 6% without precipitation, and no precipitation occurs after dilution with high-content water.

[0025] (6) Thermal stability analysis showed that the mass change of each system was small at low temperature (<100℃), indicating good thermal stability. The maximum thermal decomposition rate temperature was 186℃ in Example 1, 253℃ in Example 2, 235℃ in Example 3, and 240℃ in Example 4, indicating that the composition ratio of DES has a regulatory effect on the thermal degradation behavior of the system. Attached Figure Description

[0026] Figure 1 The Fourier transform infrared spectra of DES in Embodiments 1, 2, 3, and 4 of this invention are shown below. Figure 2 The above are XRD patterns of DES in Embodiments 1, 2, 3, and 4 of this invention. Figure 3 Differential scanning calorimetry images of DES in Embodiments 1, 2, 3, and 4 of this invention; Figure 4 The TGA dynamic thermogravimetric analysis diagrams of DES in Embodiments 1, 2, 3, and 4 of this invention are shown. Figure 5 This is a diagram showing the interaction forces of the components in the nicotinamide-baicalin-1,3-propanediol eutectic solvent in Example 1 of the present invention. Figure 6This is a diagram showing the interaction forces of each component in the nicotinamide-baicalin-glycerol eutectic solvent in Examples 2, 3, and 4 of this invention. Figure 7 These are comparison diagrams of the products in Examples 1-4 and Comparative Examples 1-7 of the present invention. Detailed Implementation

[0027] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below with reference to specific embodiments.

[0028] Example 1 Nicotinamide, baicalin, and 1,3-propanediol were mixed at a mass ratio of 10:1:89 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 30 min to obtain a homogeneous and transparent DES. The mixture was placed at 4°C, 25°C, and 48°C for two months, respectively, and no phase separation or solid precipitation occurred. DES was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, and 2%) and allowed to stand at 4°C for two months; all solutions maintained a stable and homogeneous liquid state without solid precipitation.

[0029] Example 2 Nicotinamide, baicalin, and glycerol were mixed in a mass ratio of 10:3:87 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 1 h to obtain a homogeneous and transparent DES. The solution was placed at 4°C, 25°C, and 48°C for two months, and no phase separation or solid precipitation occurred. The DES solution was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, 2%) and allowed to stand at 4°C for two months; all solutions maintained a stable and homogeneous liquid state without solid precipitation.

[0030] Example 3 Nicotinamide, baicalin, and glycerol were mixed at a mass ratio of 20:5:75 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 1 h to obtain a homogeneous and transparent DES. The mixture was then placed at 4°C, 25°C, and 48°C for two months, and no phase separation or solid precipitation occurred. The DES solution was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, and 2%) and allowed to stand at 4°C for two months; all solutions maintained a stable and homogeneous liquid state without solid precipitation.

[0031] Example 4 Nicotinamide, baicalin, and glycerol were mixed at a mass ratio of 20:6:74 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 1 h to obtain a homogeneous and transparent DES. The mixture was then placed at 4°C, 25°C, and 48°C for two months, and no phase separation or solid precipitation occurred. The DES solution was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, and 2%) and allowed to stand at 4°C for two months; all solutions maintained a stable and homogeneous liquid state without solid precipitation.

[0032] Comparative Example 1 A mixture of 6% baicalin and 1,3-propanediol was heated to 60°C and magnetically stirred at 400 rpm for 30 min, but a clear and homogeneous solution could not be obtained. Compared with Example 1, only nicotinamide was removed, indicating that the solubilization of baicalin is not achieved by dissolving it in 1,3-propanediol.

[0033] Comparative Example 2 When 5% baicalin was mixed with glycerol and heated to 60°C, then magnetically stirred at 400 rpm for 30 min, a clear and homogeneous solution could not be obtained. Compared to Example 3, only nicotinamide was removed, indicating that the solubilization of baicalin is not achieved by dissolving it in glycerol.

[0034] Comparative Example 3 When 6% baicalin was mixed with glycerol and heated to 60°C, it was magnetically stirred at 400 rpm for 30 min, but a clear and homogeneous solution could not be obtained. Compared with Example 4, only nicotinamide was removed, indicating that the solubilization of baicalin is not achieved by dissolving it in glycerol.

[0035] Comparative Example 4 Nicotinamide, baicalin, and 1,3-propanediol were mixed in a mass ratio of 10:3:87 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 30 min to obtain a homogeneous and transparent DES. This DES was then placed at 4°C, 25°C, and 48°C for two months. Phase separation occurred at the low temperature, while browning occurred at the high temperature. Compared to Example 1, only the baicalin content was increased. The mixture was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, 2%) and allowed to stand at 4°C for two months. At concentrations of 60% and 40%, a yellow solid precipitated; at concentrations of 20%, 10%, 5%, and 2%, the mixture remained a homogeneous and transparent liquid.

[0036] Comparative Example 5 Nicotinamide, baicalin, and 1,3-propanediol were mixed in a mass ratio of 20:3:77 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 30 min to obtain a homogeneous and transparent DES. This DES was then placed at 4°C, 25°C, and 48°C for two months. Crystals precipitated at the low temperature, while the DES system underwent browning at the high temperature. Compared to Example 1, the contents of nicotinamide and baicalin were increased. The mixture was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, 2%) and allowed to stand at 4°C for two months. A yellow solid precipitated when diluted to 60% mass fraction, while the mixture remained a homogeneous and transparent liquid when diluted to 40%, 20%, 10%, 5%, and 2%.

[0037] Comparative Example 6 Nicotinamide, baicalin, and 1,3-propanediol were mixed in a mass ratio of 20:6:74 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 30 min to obtain a homogeneous and transparent DES. This DES was then placed at 4°C, 25°C, and 48°C for two months. Crystals precipitated at the low temperature, while the DES system underwent browning at the high temperature. Compared to Example 1, the contents of nicotinamide and baicalin were increased. The mixture was diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, 2%) and allowed to stand at 4°C for two months. At concentrations of 60% and 40%, a yellow solid precipitated; at concentrations of 20%, 10%, 5%, and 2%, the mixture remained a homogeneous and transparent liquid.

[0038] Comparative Example 7 Nicotinamide, baicalin, and 1,3-butanediol were mixed at a mass ratio of 10:1:89 and heated to 60°C. The mixture was then magnetically stirred at 400 rpm for 30 min to obtain a homogeneous and transparent DES. This mixture was placed at 4°C, 25°C, and 48°C for two months, and no phase separation or solid precipitation occurred. Compared to Example 1, only the type of polyol was changed. Diluted with water to different mass fractions (60%, 40%, 20%, 10%, 5%, 2%) and allowed to stand at 4°C for two months, a yellow solid precipitated when diluted to 60% mass fraction, while homogeneous and transparent liquids remained when diluted to 40%, 20%, 10%, 5%, and 2%.

[0039] Structural characterization and performance testing The homogeneous, transparent, and stable baicalin-nicotinamide-polyol (1,3-propanediol, glycerol) DES systems obtained in Examples 1, 2, 3, and 4 were placed for 24 h and then tested using infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and TGA thermogravimetric analysis. 1. Infrared testing Figure 1 The Fourier transform infrared spectra of DES in Embodiments 1, 2, 3, and 4 of this invention are shown.

[0040] Figure 1 Fourier transform infrared spectroscopy was used for the determination. Baicalin was detected at 3398 cm⁻¹. -1 A broad absorption band is observed in the vicinity, mainly attributed to the -OH stretching vibrations of phenolic and glycosyl hydroxyl groups; it is located at 1722 cm⁻¹. -1 The absorption peak at 1659 cm⁻¹ is attributed to the carbonyl group. -1 and 1610cm -1 The absorption band at 3367 cm⁻¹ is mainly attributed to the C=C and C=O stretching vibrations of the flavonoid conjugated skeleton; the hydroxyl and carbonyl groups in baicalin molecules can participate in intermolecular interactions as hydrogen bond donors and acceptors, respectively. Nicotinamide at 3367 cm⁻¹... -1 and 3160 cm -1 The characteristic absorption peaks at 1679 cm⁻¹ are the asymmetric and symmetric -NH₂ stretching vibration peaks, respectively. -1 The characteristic peak at 1592 cm⁻¹ is the stretching vibration peak of the amide bond (C=O). -1 and 1575 cm -1 The characteristic peaks at this location are attributed to two NH bending vibrations. 1,3-Propanediol and glycerol have peaks at 3338 cm⁻¹. -1 3340 cm -1 Absorption occurs at the -OH stretching vibration. After forming a ternary liquid system, Example 1 shows absorption at 3317-3357 cm⁻¹. -1 Examples 2-4 are at 3310-3407 cm. -1 The strong absorption peak observed at this point is due to the formation of a stable hydrogen bond network in the eutectic system. Importantly, the -OH peak in NaDES shifts to lower wavenumbers relative to the spectrum of the starting component, indicating the formation of hydrogen bonds between the components, suggesting the formation of extensive hydrogen bonds between baicalin, nicotinamide, and the polyol.

[0041] 2. XRD Analysis Figure 2 The images show the XRD patterns of DES in Embodiments 1, 2, 3, and 4 of this invention.

[0042] Figure 2The XRD patterns of baicalin, nicotinamide, and various examples are shown. Baicalin exhibits characteristic diffraction peaks at 2θ = 8.6°, 10.34°, 12.4°, 14.66°, 17.02°, 20.64°, 21.18°, 23.76°, 25.44°, and 28.02°, indicating a distinct crystalline structure. Nicotinamide shows strong characteristic diffraction peaks at 14.78° and 22.2°. However, in the XRD patterns of Examples 1-4, the characteristic diffraction peaks of baicalin and nicotinamide disappear, showing only broad, diffuse peaks. This indicates that the original crystalline structures of the two components have been disrupted, suggesting that the system is not a simple physical mixture of the two raw materials, but rather an amorphous supramolecular DES system with a liquid network structure. Figure 2 The XRD patterns of baicalin, nicotinamide, and Examples 1, 2, 3, and 4 are shown in the table below, from bottom to top.

[0043] 3. Thermal stability analysis Figure 3 Differential scanning calorimetry (DSC) images of DES in Embodiments 1, 2, 3, and 4 of this invention.

[0044] Figure 3 The DSC curves for the DES system are shown. Baicalin exhibited an endothermic transition at 206℃, nicotinamide showed a relatively sharp crystallization transition at 132℃, while 1,3-propanediol and glycerol showed broad endothermic processes in the ranges of approximately 160-210℃ and 200-270℃, respectively. The DSC curves of Examples 1-4 show that the melting peaks corresponding to baicalin and nicotinamide disappeared, but the reappearing endothermic peaks were close to the broad endothermic regions of their corresponding polyols. The endothermic peaks in Examples 2, 3, and 4 shifted to higher temperatures compared to glycerol, indicating that the thermal decomposition temperature of the system increased after the formation of the ternary DES. Figure 3 It can be seen that the wide endothermic region of DSC in each embodiment basically overlaps with the main weight loss region of TG-DTG, indicating that the high-temperature endothermic process mainly comes from the volatilization of polyols and the thermal decomposition of the system, rather than the eutectic transformation.

[0045] Figure 4 The TGA dynamic thermogravimetric analysis diagrams of DES in Embodiments 1, 2, 3, and 4 of this invention are shown.

[0046] Figure 4The TGA dynamic thermogravimetric analysis (TGA) plots for the DES systems show that different DES systems exhibit similar thermal degradation processes, with the main weight loss phase concentrated in the higher temperature region. The mass change of each system is relatively small at low temperatures (<100℃), indicating good thermal stability. As the temperature increases, the samples undergo rapid thermal decomposition, with obvious peaks appearing in the DTG curves. The maximum thermal decomposition rate temperature (Tmax) varies among different systems: 186℃ for Example 1, 253℃ for Example 2, 235℃ for Example 3, and 240℃ for Example 4, demonstrating that the composition ratio of DES has a regulatory effect on the thermal degradation behavior of the system.

[0047] 4. Theoretical Calculations Figure 5 This is a diagram showing the interaction forces of the components in the nicotinamide-baicalin-1,3-propanediol eutectic solvent in Example 1 of the present invention.

[0048] Figure 5 This is a DES analysis diagram of Example 1. Figure 5 (a) is the electrostatic potential distribution diagram of baicalin-nicotinamide-1,3-propanediol DES. The blue area is the negative electrostatic potential distribution area and the red area is the positive electrostatic potential distribution area. This shows that the positive and negative electrostatic potential regions of baicalin, nicotinamide and 1,3-propanediol in the system attract each other and have a strong electrostatic force. Figure 5 (b) and (c) are the indicator function plots (IRI) and sign(λ2)ρ-IRI scatter plots of the intermolecular interaction region of DES. Figure 5 (d) The type and characteristics of isosurface interactions can divide the scatter plot intervals: when -0.04 au < sign(λ2)ρ < -0.005 au (blue area), it indicates that there is a significant strong attraction in the system, with hydrogen bonding as the dominant form; when -0.005 au < sign(λ2)ρ < 0.005 au (green area), it represents a relatively weak van der Waals interaction; when 0.005 au < sign(λ2)ρ < 0.02 au (red area), it indicates that there is a mutual repulsion in the system, such as the steric hindrance effect of cyclic compounds. Figure 5 (b) The red, strongly repulsive regions are mainly located within the ring structure of the baicalin molecule's own backbone. On the contact surface between baicalin and nicotinamide, large areas of green and blue isopleths are densely distributed. Green and blue isopleths also exist between baicalin and 1,3-propanediol, and between nicotinamide and 1,3-propanediol. This indicates that strong hydrogen bonding and extensive van der Waals forces jointly drive the binding between baicalin, nicotinamide, and 1,3-propanediol, overcoming the repulsive forces and thus forming a stable DES system.

[0049] Figure 6 This is a diagram showing the interaction forces of the components in the nicotinamide-baicalin-glycerol eutectic solvent in Examples 2, 3, and 4 of this invention.

[0050] Figure 6 The following are DES analysis diagrams for Examples 2, 3, and 4. Figure 6 (a) is the electrostatic potential distribution diagram of baicalin-nicotinamide-glycerol DES. The blue area is the negative electrostatic potential distribution area and the red area is the positive electrostatic potential distribution area. It can be seen that there is a complementary electrostatic potential region between baicalin, nicotinamide and glycerol, and they have a strong electrostatic force. Figure 6 (b) and (c) are the indicator function plots (IRI) and scatter plots of sign(λ2)ρ-IRI of the intermolecular interaction region of DES. Figure 6 (b) The red, strongly repulsive regions are mainly located within the ring structure of the baicalin molecule's own backbone. On the contact surface between baicalin and nicotinamide, large areas of green and blue isopleths are densely distributed. Green and blue isopleths also exist between baicalin and glycerol, and between nicotinamide and glycerol. This indicates that strong hydrogen bonding and extensive van der Waals forces jointly drive the binding between baicalin, nicotinamide, and glycerol, overcoming the repulsive forces and thus forming a stable DES system.

[0051] Table 1 shows the single-point energies of baicalin, nicotinamide, and polyols, as well as the binding energies of each embodiment. The specific calculation method is as follows: .

[0052] Table 1. Single-point energies of baicalin, nicotinamide, and polyols, and binding energies of each example. ; Calculations show that the binding energy between baicalin and nicotinamide-1,3-propanediol is -194.8121 kJ / mol, and the binding energy between baicalin, nicotinamide, and glycerol is -202.4261 kJ / mol. This indicates that the binding capacity between baicalin, nicotinamide, and glycerol is stronger when the polyol in the system is glycerol. Therefore, in the examples, the concentration of baicalin in the glycerol-based DES can reach 6% without precipitation, and no precipitation occurs after dilution with high-content water. When the polyol is 1,3-propanediol, the highest concentration of baicalin is only 1%, and no precipitation occurs after dilution with water.

[0053] Application Example: Solubilizing Effect Taking the DES system obtained in Example 4 diluted to a 10% aqueous solution as an example, the solubility of baicalin was measured by HPLC to be 909.99±1.03 μg / mL, while the solubility of baicalin in pure water was measured by HPLC to be 39.43±0.42 μg / mL. This example achieves the solubility enhancement of baicalin in water by a factor of 23.

[0054] Product Comparison Figure 7 These are comparison diagrams of the products in Examples 1-4 and Comparative Examples 1-7 of the present invention.

[0055] Figure 7 The appearance of the DES systems obtained in Examples 1-4 is compared with that of the products obtained in Comparative Examples 1-7. The DES systems obtained in Examples 1-4 were all homogeneous and transparent liquids, and showed no phase separation or solid precipitation after two months at 4°C, 25°C, and 48°C. In Comparative Examples 1-3, baicalin mixed with a single polyol could not produce a transparent and homogeneous solution. In Comparative Examples 4-6, at higher baicalin or nicotinamide contents, phase separation or crystal precipitation occurred at low temperatures, and browning occurred at high temperatures. In Comparative Example 7, after replacing 1,3-propanediol with 1,3-butanediol, a yellow solid precipitated when diluted to a 60% mass fraction. The above comparisons demonstrate that the specific ternary DES composition and ratio range of this invention are necessary to obtain a stable, homogeneous, and transparent system.

[0056] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A ternary eutectic solvent of nicotinamide-baicalin-polyol, characterized in that: It includes nicotinamide, baicalin and a polyol, wherein the polyol is 1,3-propanediol and / or glycerol, and the mass ratio of nicotinamide, baicalin and polyol is 10:1:89-20:6:74; the eutectic solvent is a homogeneous transparent liquid.

2. The ternary eutectic solvent according to claim 1, characterized in that: The ternary eutectic solvent contains 1% to 6.0% by mass of baicalin.

3. The ternary eutectic solvent according to claim 1, characterized in that: When the ternary eutectic solvent is diluted with water to a mass fraction of 2% to 60%, it is left to stand at 4°C for at least one month to maintain a stable and homogeneous liquid state without any solid precipitation.

4. The ternary eutectic solvent according to claim 1, characterized in that: The binding energy of baicalin-nicotinamide-polyol in the ternary eutectic solvent is -194.8 to -202.4 kJ / mol.

5. The ternary eutectic solvent according to claim 1, characterized in that: In the XRD pattern of the ternary eutectic solvent, the characteristic diffraction peaks of baicalin and nicotinamide disappeared, and only broad diffuse peaks were observed.

6. A method for preparing a ternary eutectic solvent according to any one of claims 1-5, characterized in that, Includes the following steps: Nicotinamide, baicalin, and polyol were mixed in a mass ratio of 10:1:89-20:6:74 and heated and stirred to obtain a homogeneous and transparent eutectic solvent of nicotinamide-baicalin-polyol; wherein the polyol was 1,3-propanediol and / or glycerol.

7. The method according to claim 6, characterized in that, The heating and stirring treatment is as follows: magnetic stirring at 300-500 rpm, heating at 50-60℃ for 0.5-1.0 h.

8. The use of a ternary eutectic solvent according to any one of claims 1-5 in the preparation of cosmetics or topical formulations.

9. The use of a ternary eutectic solvent according to any one of claims 1-5 in improving the water solubility of baicalin.

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