Cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials, their preparation methods and applications

Abstract

This invention discloses a self-assembled supramolecular raw material of cyclodextrin and a ternary eutectic solvent based on baicalin, its preparation method, and its applications, belonging to the technical fields of pharmaceuticals and daily chemicals. The self-assembled supramolecular raw material of cyclodextrin and a ternary eutectic solvent based on baicalin is formed by the self-assembly of the macromolecular host substance hydroxypropyl-β-cyclodextrin and the guest molecule baicalin-based ternary eutectic solvent through weak interactions such as hydrogen bonds and van der Waals forces. It effectively solves the problems of easy degradation and poor stability of ternary eutectic solvents based on baicalin at high temperatures, improves the bioavailability of baicalin, enabling better absorption and utilization by the skin, and more efficiently exerts anti-inflammatory and whitening effects, thus broadening the application scenarios of baicalin in pharmaceuticals and daily chemicals.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceuticals and daily chemical technology, and in particular to a cyclodextrin and a ternary eutectic solvent-based ternary eutectic solvent self-assembly supramolecular raw material, its preparation method and application. Background Technology

[0002] The ternary eutectic solvent based on baicalin utilizes weak interactions such as hydrogen bonds and van der Waals forces to bridge grape seed oil and matrine, forming a supramolecular eutectic solvent that is liquid at room temperature. The preparation method is simple and environmentally friendly. This ternary eutectic solvent based on baicalin solves the solubility problem of baicalin, significantly improving its solubility in water and oils. Simultaneously, it plays an important role in anti-inflammatory and skin-whitening effects by significantly inhibiting lipopolysaccharide-induced inflammation and protecting against cell damage.

[0003] However, it cannot be ignored that although the ternary eutectic solvent based on baicalin has solved the solubility problem of baicalin, it still has shortcomings in terms of stability. Discoloration will occur after prolonged storage at high temperatures. At the same time, further research and development are needed to address the problem that baicalin is easily degraded under high temperature conditions, thus affecting its bioavailability.

[0004] Therefore, there is an urgent need for a new type of supramolecular raw material to fully address the application problems of baicalin, such as poor stability, easy degradation, and low bioavailability. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent, its preparation method and application, aiming to solve the application problem of low bioavailability caused by the high temperature instability and easy oxidative degradation of existing baicalin-based ternary eutectic solvent.

[0006] The technical solution of the present invention is as follows: In a first aspect, the present invention provides a supramolecular raw material for self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin, wherein the supramolecular raw material for self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin is mainly obtained by self-assembly of hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin through interaction forces.

[0007] Optionally, the interaction forces include hydrogen bonds and / or van der Waals forces.

[0008] Optionally, the molar ratio of the hydroxypropyl-β-cyclodextrin to the ternary eutectic solvent based on baicalin is 1:1 to 3:1.

[0009] A second aspect of the present invention provides a method for preparing a supramolecular raw material that is self-assembled from cyclodextrin and a ternary eutectic solvent based on baicalin, comprising the following steps: S1. Under the protection of an inert gas, distilled water, hydroxypropyl-β-cyclodextrin, and a ternary eutectic solvent based on baicalin are added to an ultrasonic reactor. Under heating and stirring conditions, ultrasonic energy is applied, and the ultrasonic reaction is continued for a predetermined time to obtain a mixed solution. S2. The mixed solution is transferred out of the ultrasonic reactor, pre-frozen, and then freeze-dried. After freeze-drying, it is pulverized to obtain the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin.

[0010] Optionally, in step S1, the heating temperature is 30~50℃; the stirring speed is 200~600rpm; the ultrasonic power is 800~1500w; the ultrasonic frequency is 10~25KHz; and the predetermined reaction time is 1~6h.

[0011] Optionally, step S2 specifically includes: transferring the mixed solution from the ultrasonic reactor, spreading it evenly in an iron pan, pre-freezing it, and then transferring it to a vacuum freeze dryer for freeze drying; after freeze drying, the solid is pulverized, packaged with nitrogen gas, and the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin is obtained.

[0012] Optionally, in step S2, the freeze-drying temperature is -80 ℃ ± 5 ℃, and the time is 12~24h.

[0013] A third aspect of the present invention provides an application of the cyclodextrin described herein and a ternary eutectic solvent-based supramolecular raw material self-assembled in the pharmaceutical and daily chemical fields.

[0014] In a fourth aspect, the present invention provides a cosmetic product with whitening and anti-inflammatory properties, comprising the cyclodextrin described in the present invention and a ternary eutectic solvent-based supramolecular raw material.

[0015] Beneficial effects: Based on the formation of a ternary eutectic solvent based on baicalin, this invention utilizes the host-guest self-assembly of a macromolecular cavity structure of hydroxypropyl-β-cyclodextrin, allowing the ternary eutectic solvent based on baicalin to enter and be encapsulated within the cyclodextrin cavity, thus exhibiting excellent stability and solving the problems of high-temperature discoloration and easy degradation. At the same time, the bioavailability of supramolecular raw materials encapsulated by cyclodextrin is greatly improved, playing an important role in anti-inflammatory and whitening effects, laying the foundation for their wide application in the fields of medicine and daily chemicals. Attached Figure Description

[0016] Figure 1Molecular distribution diagram of cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials; Figure 2 This is a schematic diagram of the binding conformation of each component of the supramolecular raw material that is self-assembled by cyclodextrin and a ternary eutectic solvent based on baicalin. Figure 3 This is a schematic diagram of the interaction forces between cyclodextrin and the components of the ternary eutectic solvent-based supramolecular raw material that are self-assembled; Figure 4 Fourier transform infrared spectra of supramolecular raw materials self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent; Figure 5 Scanning electron micrograph of a supramolecular raw material self-assembled by cyclodextrin and a ternary eutectic solvent based on baicalin; Figure 6 A comparison of the stability of cyclodextrin and baicalin-based ternary eutectic solvents for self-assembling supramolecular raw materials and baicalin-based ternary eutectic solvents. Figure 7 The graph shows the self-assembly supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent, the ternary eutectic solvent based on baicalin, and the retention rate of active ingredients of baicalin. Figure 8 A statistical graph showing the permeation efficiency of cyclodextrin with ternary eutectic solvents based on baicalin for self-assembly of supramolecular raw materials and baicalin. Figure 9 A comparison chart of the relative COX2 content of different samples at a concentration of 0.05%; Figure 10 The graph shows the inhibition rate of tyrosinase (bisphenol) activity by the self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent. Figure 11 The graph shows the inhibition rate of tyrosinase (bisphenol) activity by the ternary eutectic solvent based on baicalin. Figure 12 The graph shows the inhibition rate of baicalin on tyrosinase (bisphenol) activity. Detailed Implementation

[0017] This invention provides a self-assembled supramolecular raw material of cyclodextrin and a ternary eutectic solvent based on baicalin, its preparation method, and its application. To make the objectives, technical solutions, and effects of this invention clearer and more explicit, the invention is further described in detail below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Rather, these embodiments are provided to enable a more thorough understanding of the invention and to fully convey the scope of the invention to those skilled in the art.

[0018] It should be noted that the terms "comprising" or "including" used throughout the specification and claims are open-ended and should therefore be interpreted as "including but not limited to". The following descriptions in the specification are preferred embodiments for carrying out this application; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of this application. The scope of protection of this application shall be determined by the scope defined in the appended claims.

[0019] The ternary eutectic solvent based on baicalin solves the problem of poor water solubility of baicalin. It combines baicalin, which has highly effective anti-inflammatory effects, with grape seed oil, which has strong antioxidant capabilities, achieving a synergistic effect in efficacy, exerting both anti-inflammatory and antioxidant effects. However, its stability remains insufficient; discoloration occurs after prolonged exposure to high temperatures and sunlight. Furthermore, the low bioavailability of baicalin due to its easy oxidation means its application needs further development.

[0020] In the development of supramolecular chemistry, the design and synthesis of various artificial macrocyclic molecules are of paramount importance for achieving selective recognition of guest molecules. Among macrocyclic hosts, classic types such as crown ethers, cyclodextrins, calixarenes, columnar aromatics, and cucurbiturils have long been favored by researchers. The cyclodextrin molecule used in this invention has a slightly conical, hollow cylindrical three-dimensional ring structure, which can serve as a host to encapsulate various suitable guest molecules, such as organic molecules, inorganic ions, and gas molecules. Its hydrophobic inner cavity and hydrophilic outer surface allow it to form inclusion complexes and molecular host-guest self-assembly systems with numerous organic and inorganic molecules through van der Waals forces, hydrophobic interactions, and host-guest molecular matching. Hydroxypropyl-β-cyclodextrin retains the hollow structure of β-cyclodextrin while effectively overcoming the main drawback of poor water solubility in β-cyclodextrin. Therefore, hydroxypropyl-β-cyclodextrin is one of the most thoroughly researched and widely used cyclodextrin derivatives, and it has been widely used in the food, pharmaceutical, and cosmetic industries.

[0021] Therefore, this invention uses hydroxypropyl-β-cyclodextrin as the host molecule, and enables host-guest self-assembly with guest molecules in a ternary eutectic solvent based on baicalin under weak interactions such as hydrogen bonding and van der Waals forces. This perfectly solves the stability problem of baicalin, while significantly improving its solubility and bioavailability, allowing the supramolecular raw material to better exert its anti-inflammatory and whitening effects, laying the foundation for its wide application in the fields of medicine and daily chemicals.

[0022] Specifically, embodiments of the present invention provide a supramolecular raw material for self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin, wherein the supramolecular raw material for self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin is mainly obtained by self-assembly of hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin through interaction forces.

[0023] The cyclodextrin and baicalin ternary eutectic solvent self-assembled supramolecular raw material is a yellow solid powder. The baicalin-based ternary eutectic solvent uses baicalin as a bridge between matrine and grape seed oil, combining them through weak interactions such as hydrogen bonds and van der Waals forces to form a homogeneous and stable ternary eutectic solvent. This significantly solves the solubility problem of baicalin, greatly increasing its solubility in water and oils. To improve the bioavailability of baicalin, baicalin, with its highly effective anti-inflammatory properties, is co-soluble with grape seed oil, which has strong antioxidant effects. This method retains the original anti-inflammatory effects of baicalin while more effectively scavenging free radicals and exerting a powerful antioxidant capacity. Furthermore, the molar ratio of baicalin, matrine and grape seed oil is 1:1:1 to 1:1:6, such as 1:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5, 1:1:6, etc., but not limited to these.

[0024] In this embodiment, the cyclodextrin and the baicalin-based ternary eutectic solvent self-assemble into a supramolecular raw material. The guest substance, the baicalin-based ternary eutectic solvent, enters the cavity structure of the macromolecular host substance, hydroxypropyl-β-cyclodextrin, through weak interactions such as hydrogen bonds and / or van der Waals forces, thus forming a supramolecular structure. This effectively solves the problems of easy degradation and poor stability of baicalin-based ternary eutectic solvents at high temperatures, improves the bioavailability of baicalin, enabling better absorption and utilization by the skin, and more efficiently exerts anti-inflammatory and whitening effects, thus broadening the application scenarios of baicalin in the pharmaceutical, daily chemical, and other fields.

[0025] In one embodiment, the molar ratio of hydroxypropyl-β-cyclodextrin to the ternary eutectic solvent based on baicalin in the self-assembled supramolecular raw material of cyclodextrin and baicalin is 1:1 to 3:1, such as 1:1, 2:1, 3:1, etc.

[0026] This molar ratio range was obtained through extensive experimental screening. Within this range, the cyclodextrin and the baicalin-based ternary eutectic solvent can self-assemble into a stable and high-performance supramolecular raw material. When the molar ratio is 1:1, the baicalin-based ternary eutectic solvent can better enter the cavity of hydroxypropyl-β-cyclodextrin, forming a supramolecular structure with a certain degree of stability, while also improving the bioavailability of baicalin to some extent. As the molar ratio gradually increases to 3:1, the stability of the supramolecular structure is further enhanced, and the bioavailability of baicalin is significantly improved, resulting in more efficient anti-inflammatory and whitening effects. Moreover, a suitable molar ratio can also ensure the stability and effectiveness of the raw material in subsequent applications, providing strong support for expanding the application of the raw material in the pharmaceutical, daily chemical, and other fields.

[0027] This invention provides a method for preparing a supramolecular raw material that self-assembles cyclodextrin with a ternary eutectic solvent based on baicalin, comprising the following steps: S1. Under the protection of an inert gas, distilled water, hydroxypropyl-β-cyclodextrin, and a ternary eutectic solvent based on baicalin are added to an ultrasonic reactor. Under heating and stirring conditions, ultrasonic energy is applied, and the ultrasonic reaction is continued for a predetermined time to obtain a mixed solution. S2. The mixed solution is transferred out of the ultrasonic reactor, pre-frozen, and then freeze-dried. After freeze-drying, it is pulverized to obtain the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin.

[0028] In step S1, hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin are thoroughly dispersed in distilled water. Under heating and stirring, ultrasonic energy is applied, and the ultrasonic reaction is continued for a certain period to ensure sufficient contact and reaction between the two components, thereby obtaining a homogeneous mixed solution.

[0029] In step S2, after the mixed solution is transferred out, the pre-freezing operation should be carried out at a low temperature of -30℃ to -80℃ (e.g., -30℃, -40℃, -50℃, -60℃, -70℃, -80℃, etc.) to rapidly freeze the solution into a solid. Then, a freeze-drying process is used to completely remove moisture. Finally, a pulverization process is used to obtain a cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw material with uniform particle size that meets the requirements.

[0030] In one embodiment, in step S1, the molar ratio of hydroxypropyl-β-cyclodextrin to the ternary eutectic solvent based on baicalin in the self-assembled supramolecular raw material of cyclodextrin and baicalin is 1:1 to 3:1, such as 1:1, 2:1, 3:1, etc.

[0031] This molar ratio range was obtained through extensive experimental screening. Within this range, the cyclodextrin and the baicalin-based ternary eutectic solvent can self-assemble into a stable and high-performance supramolecular raw material. When the molar ratio is 1:1, the baicalin-based ternary eutectic solvent can better enter the cavity of hydroxypropyl-β-cyclodextrin, forming a supramolecular structure with a certain degree of stability, while also improving the bioavailability of baicalin to some extent. As the molar ratio gradually increases to 3:1, the stability of the supramolecular structure is further enhanced, and the bioavailability of baicalin is significantly improved, resulting in more efficient anti-inflammatory and whitening effects. Moreover, a suitable molar ratio can also ensure the stability and effectiveness of the raw material in subsequent applications, providing strong support for expanding the application of the raw material in the pharmaceutical, daily chemical, and other fields.

[0032] In one embodiment, in step S1, the heating temperature is 30~50℃; the stirring speed is 200~600rpm; the ultrasonic power is 800~1500w; the ultrasonic frequency is 10~25KHz; and the predetermined reaction time is 1~6h.

[0033] These process parameters were all obtained through multiple experimental optimizations. The heating temperature was set between 30 and 50°C to ensure that the molecules in the reaction system have sufficient energy for self-assembly without causing molecular structure damage or side reactions due to excessive temperature. The stirring speed was controlled between 200 and 600 rpm to ensure thorough mixing of the components in the reaction system, ensuring uniform reaction and avoiding localized high or low concentrations that could affect product quality. Ultrasonic power of 800 to 1500 W and a frequency of 10 to 25 kHz generated suitable cavitation and mechanical effects, promoting better interaction between cyclodextrin and the ternary eutectic solvent based on baicalin, thus accelerating the self-assembly process. The predetermined reaction time was set between 1 and 6 hours to allow the self-assembly reaction to proceed fully, achieving high product purity and yield, while avoiding energy waste and potential product degradation due to excessively long reaction times.

[0034] In one embodiment, step S2 specifically includes: transferring the mixed solution from the ultrasonic reactor, spreading it evenly in an iron pan, pre-freezing it, and then transferring it to a vacuum freeze dryer for freeze drying; pulverizing the freeze-dried solid, packaging it with nitrogen gas, and obtaining the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin.

[0035] In one embodiment, in step S2, the freeze-drying temperature is -80 ℃ ± 5 ℃, and the time is 12~24h.

[0036] The choice of these freeze-drying conditions is based on multiple considerations. The low temperature range of -80℃±5℃ effectively prevents the active ingredients in the raw materials from being deactivated by high temperatures, maximizing the preservation of their chemical structure and biological activity. The freeze-drying time of 12 to 24 hours ensures sufficient moisture removal, achieving the appropriate degree of dryness for the solid raw materials, guaranteeing their quality stability and long-term storage performance, while avoiding excessively long drying times that would increase energy consumption and production costs.

[0037] This invention provides the application of the above-mentioned cyclodextrin and ternary eutectic solvent self-assembled supramolecular raw materials based on baicalin in the pharmaceutical and daily chemical fields.

[0038] This invention provides a cosmetic with whitening and anti-inflammatory properties, comprising the aforementioned cyclodextrin and a ternary eutectic solvent self-assembled supramolecular raw material based on baicalin.

[0039] This embodiment uses hydroxypropyl-β-cyclodextrin as the host substance and, under weak interactions such as hydrogen bonding and van der Waals forces, a ternary eutectic solvent formed by baicalin as a bridge connecting matrine and grape seed oil as the guest substance to carry out host-guest self-assembly. This solves the problems of high-temperature instability and easy degradation of baicalin, and at the same time better exerts the anti-inflammatory and whitening effects of baicalin and grape seed oil, laying the foundation for their wide application in the pharmaceutical and daily chemical fields.

[0040] The present invention will be further described in detail below through specific embodiments.

[0041] Example 1 provides a cyclodextrin and baicalin ternary eutectic solvent self-assembled supramolecular raw material, which is a yellow solid powder.

[0042] The method for preparing the supramolecular raw material self-assembled in the ternary eutectic solvent of cyclodextrin and baicalin includes the following steps: Under nitrogen protection, hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin, dissolved in distilled water, were added to an ultrasonic reactor in a molar ratio of 1:1. Ultrasonic energy (1000 W, 20 kHz) was applied at a stirring speed of 600 rpm and a heating temperature of 40°C, and the ultrasonic reaction was continued for 3 hours to form a mixed solution. The mixed solution was then transferred from the ultrasonic reactor, spread evenly on an iron tray, pre-frozen, and then transferred to a vacuum freeze dryer for freeze-drying at -80°C for 24 hours. The freeze-dried solid was then pulverized.

[0043] To investigate the hydrogen bonding sites in the self-assembly of supramolecular raw materials by cyclodextrin and baicalin in a ternary eutectic solvent, molecular docking was performed on cyclodextrin and baicalin in the ternary eutectic solvent. The most stable conformation was selected as a reference among the resulting conformations. The results are as follows: Figure 1 and Figure 2 As shown, based on its three-dimensional structure and computational simulation results, hydrogen bonds exist between the ternary eutectic solvents of cyclodextrin and baicalin.

[0044] Simultaneously, the interaction forces between cyclodextrin and baicalin in the ternary eutectic solvent self-assembly of supramolecular raw materials were calculated and analyzed, such as... Figure 3 As shown, there are significant hydrogen bonds, van der Waals forces and other weak interactions between cyclodextrin and the ternary eutectic solvent components of baicalin. These interactions jointly promote the formation of self-assembled supramolecular raw materials of cyclodextrin and baicalin ternary eutectic solvent.

[0045] Example 2: Preparation method of supramolecular raw material self-assembled by cyclodextrin and baicalin ternary eutectic solvent.

[0046] Under nitrogen protection, hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin, dissolved in distilled water, were added to an ultrasonic reactor in a molar ratio of 1:1. Ultrasonic energy (1000 W, 20 kHz) was applied at a stirring speed of 600 rpm and a heating temperature of 40°C, and the ultrasonic reaction was continued for 3 hours to form a mixed solution. The mixed solution was then transferred from the ultrasonic reactor, spread evenly on an iron tray, pre-frozen, and then transferred to a vacuum freeze dryer for freeze-drying at -80°C for 24 hours. The freeze-dried solid was then pulverized.

[0047] Comparative Example 1 The difference between this comparative example and Example 1 is that a ternary eutectic solvent based on baicalin is used as the target guest, and different host substances are screened to form supramolecular raw materials that can achieve host-guest self-assembly with the target guest.

[0048] The preparation steps of the supramolecular raw material in this comparative example are as follows: Under nitrogen protection, the main components (chitosan and carboxymethyl cellulose, respectively) in a 1:1 molar ratio and a ternary eutectic solvent based on baicalin were added to an ultrasonic reactor and dissolved in distilled water. Ultrasonic energy (1000 W, 20 kHz) was applied at a stirring speed of 600 rpm and a heating temperature of 40°C for 3 hours to form a mixed solution. The mixed solution was then transferred from the ultrasonic reactor, spread evenly on an iron tray, pre-frozen, and then freeze-dried at -80°C for 24 hours. The resulting substances were tested for their solubility and stability in water.

[0049] The results showed that the raw material formed by chitosan and a ternary eutectic solvent based on baicalin was in a semi-solid state, exhibiting significant hygroscopicity after prolonged storage, and remained difficult to dissolve in water. While the raw material formed by carboxymethyl cellulose and a ternary eutectic solvent based on baicalin showed some solubility in water, it was only about 0.008 g / mL, classifying it as slightly soluble. Furthermore, the aqueous solution showed severe discoloration after being stored at 45°C for 7 days.

[0050] Comparative Example 2 The difference between this comparative example and Example 2 is that different preparation processes are used to prepare cyclodextrin and ternary eutectic solvent self-assembled supramolecular raw materials based on baicalin.

[0051] The preparation steps of the supramolecular raw material in this comparative example are as follows: Under nitrogen protection, hydroxypropyl-β-cyclodextrin and a ternary eutectic solvent based on baicalin, dissolved in distilled water, were added to an ultrasonic reactor in a 1:1 molar ratio. The reactor was heated at 40°C with stirring at 600 rpm, and ultrasonic energy (1000 W, 20 kHz) was applied for 3 hours to form a mixed solution. The solution was then transferred from the ultrasonic reactor to a spray dryer. The feed temperature was set to 150°C, the spray air pressure to 0.25 MPa, and the pump flow rate to 50 prm for spray drying, yielding a self-assembled supramolecular raw material of cyclodextrin and a ternary eutectic solvent based on baicalin. The stability of the aqueous solution was tested.

[0052] The results showed that the cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw material solid powder obtained by spray drying began to change color after being placed at a high temperature of 45°C for 10 days, and obvious color change was observed after 14 days. The stability was far inferior to that of the vacuum freeze-drying preparation method.

[0053] Example 3: Fourier transform infrared spectra of cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials (prepared in Example 2). Fourier transform infrared spectroscopy (FT-IR) was used to analyze the characteristic peak changes of cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials, hydroxypropyl-β-cyclodextrin (HP-β-CD), and baicalin-based ternary eutectic solvent before and after their formation, providing evidence for the formation of supramolecular raw materials self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent. FT-IR can show the characteristic peak changes of host and guest molecules before and after inclusion, providing evidence for the formation of inclusion complexes. The FT-IR results of hydroxypropyl-β-cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials, hydroxypropyl-β-cyclodextrin, and baicalin-based ternary eutectic solvent (also known as baicalin-matrine-grape seed oil ternary eutectic solvent) are shown below. Figure 4 As shown. After supramolecular formation, HP-β-CD is located at 3328.88 cm⁻¹. -1 The -OH stretching vibration peak shifted to 3324.10 cm⁻¹. -1 1012.31cm -1 The CO absorption peak shifted to 1027.47 cm⁻¹. -1 The ternary eutectic solvent based on baicalin is located at 2851.68 cm⁻¹. -1 The CH stretching vibration peak disappeared at 1711.35 cm⁻¹. -1 The CH stretching vibration peak of the benzene ring at that location shifted to 1611.61 cm⁻¹. -1Furthermore, the peak intensity decreased, which may be due to the formation of hydrogen bonds between the CH bond of the benzene ring and the -OH group of HP-β-CD, thereby weakening the stretching vibration of the CH bond of the benzene ring. Based on these changes, it is indicated that the ternary eutectic solvent based on baicalin successfully entered the cyclodextrin cavity. No other characteristic peaks were observed in the self-assembled supramolecular raw material spectrum of hydroxypropyl-β-cyclodextrin and the ternary eutectic solvent based on baicalin, indicating that no new chemical bonds were formed between the host and guest molecules, but rather they were combined through intermolecular forces or hydrogen bonds.

[0054] Example 4: Morphological and structural analysis of cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw material (prepared in Example 2). To investigate the morphological structure of the supramolecular raw material self-assembled from cyclodextrin and baicalin-based ternary eutectic solvent, scanning electron microscopy analysis was performed on the components of the supramolecular raw material self-assembled from hydroxypropyl-β-cyclodextrin and baicalin-based ternary eutectic solvent. Figure 5 As shown, the morphology of baicalin, hydroxypropyl-β-cyclodextrin, matrine, cyclodextrin, and ternary eutectic solvent-based supramolecular raw materials and their physical mixtures were analyzed using scanning electron microscopy. Figure 5 In the image, A to E represent scanning electron microscope (SEM) images of self-assembled supramolecular raw materials and physical mixtures of hydroxypropyl-β-cyclodextrin, baicalin, matrine, cyclodextrin, and baicalin-based ternary eutectic solvents.

[0055] The results showed that baicalin existed as plate-like crystals, matrine as cubic crystals, and hydroxypropyl-β-cyclodextrin as amorphous spheres. Microscopic images of the physical mixture revealed the simultaneous presence of plate-like baicalin, blocky matrine, and amorphous spheres of hydroxypropyl-β-cyclodextrin. The cyclodextrin and the ternary eutectic solvent-based supramolecular raw material self-assembled from baicalin appeared as irregular particles, where the original morphology of each component had disappeared, replaced by amorphous aggregates of varying sizes. These results indicate that when cyclodextrin and the ternary eutectic solvent-based supramolecular raw material self-assemble to form a dual supramolecular structure through host-guest self-assembly, the two components become tightly bound, and baicalin no longer exists in a crystalline state.

[0056] Example 5: Solubility Study of Cyclodextrin in Self-Assembled Supramolecular Raw Material Based on Baicalin in a Ternary Eutectic Solvent (Prepared in Example 2) To investigate the solubility of cyclodextrin in a ternary eutectic solvent-based supramolecular raw material, this example compares the solubility of cyclodextrin in water with the ternary eutectic solvent-based supramolecular raw material, the ternary eutectic solvent-based baicalin, and the baicalin monomer itself. The specific procedure involves dissolving equal masses of the above samples in equal volumes of aqueous solution, stirring at room temperature for 24 hours, and then allowing the mixture to stand for 1 hour before observing the dissolution.

[0057] The results showed that, under normal temperature conditions, the solubility of cyclodextrin self-assembled supramolecular raw materials with baicalin-based ternary eutectic solvents and baicalin-based ternary eutectic solvents in water was significantly better than that of baicalin monomer. Specifically, 1 g / 10 mL of cyclodextrin self-assembled supramolecular raw materials with baicalin-based ternary eutectic solvents and baicalin-based ternary eutectic solvents dissolved completely, and the aqueous solution was clear and transparent, while the 1 g / 10 mL aqueous solution of baicalin was turbid, and the presence of baicalin particles could be clearly seen.

[0058] Furthermore, to improve the solubility concentration of the self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent, and the baicalin-based ternary eutectic solvent sample, the two groups of materials with a concentration of 5 g / mL were dissolved and allowed to stand for observation. It was found that the 5 g / mL cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw material could be completely dissolved under stirring at room temperature, but the 5 g / mL baicalin-based ternary eutectic solvent required heating to 50℃ to completely dissolve and clarify. This indicates that the water solubility of the self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent is better than that of the baicalin-based ternary eutectic solvent.

[0059] Therefore, a comparison of the water solubility tests of cyclodextrin with baicalin-based ternary eutectic solvents, baicalin-based ternary eutectic solvents, and baicalin monomers revealed the following water solubility: cyclodextrin with baicalin-based ternary eutectic solvents > baicalin-based ternary eutectic solvents > baicalin.

[0060] Example 6: Stability Study of Aqueous Solutions of Cyclodextrin and Baicalin-Based Ternary Eutectic Solvent Self-Assembled Supramolecular Raw Material (Prepared in Example 2) The stability of cyclodextrin-based ternary eutectic solvent self-assembled supramolecular raw materials and aqueous solutions of baicalin-based ternary eutectic solvents was compared. In this embodiment, the appearance stability of the aqueous solutions was observed after treating the cyclodextrin-based ternary eutectic solvent self-assembled supramolecular raw materials and aqueous solutions of baicalin-based ternary eutectic solvents with room temperature, high temperature (45℃), and low temperature (5℃) for 30 days, respectively. The stability of the aqueous solutions under different conditions was tested based on appearance, color, odor, and other indicators.

[0061] The results showed that after 30 days of observation, the stability of cyclodextrin with baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials and baicalin-based ternary eutectic solvent aqueous solution was as follows: Figure 6 As shown in the figure, the aqueous solution of the supramolecular raw material self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent showed no significant changes in appearance, color, and odor after treatment at room temperature (RT), high temperature (45℃), and low temperature (5℃) for 30 days. However, the aqueous solution of the ternary eutectic solvent based on baicalin showed a significant color change after treatment at high temperature (45℃) for 30 days, while its appearance and odor remained largely unchanged. This indicates that the aqueous solution of the supramolecular raw material self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent is more stable than the unencapsulated aqueous solution of the ternary eutectic solvent based on baicalin under all temperature conditions.

[0062] Experimental Example 7: Retention Rate of Aqueous Solutions of Cyclodextrin and Baicalin-Based Ternary Eutectic Solvents for Self-Assembly of Supramolecular Raw Materials under High Temperature Conditions This embodiment studies the retention rate of aqueous solutions of cyclodextrin and baicalin-based ternary eutectic solvent-assembled supramolecular raw materials under high-temperature conditions. The cyclodextrin and baicalin-based ternary eutectic solvent-assembled supramolecular raw materials prepared in Example 2 were formulated into a 5% (w / w) aqueous solution. Simultaneously, aqueous solutions of baicalin-based ternary eutectic solvent and saturated baicalin solutions of corresponding concentrations were also prepared. The retention rates of these solutions under high-temperature conditions were tested, and the results are as follows: Figure 7 As shown.

[0063] The results showed that after 90 days of storage at 45℃, the retention rate of the self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent decreased from 100% at day 0 to 93.85%, with a degradation rate of only 6.15%. After 90 days of storage at 45℃, the retention rate of the ternary eutectic solvent based on baicalin decreased from 100% to 85.43%, with a degradation rate of 14.57%. After 90 days of storage at 45℃, the retention rate of saturated baicalin aqueous solution decreased from 100% to 75.87%, with a degradation rate of 24.13%. The results showed that after high-temperature treatment at 45℃, the aqueous solution retention rate of the supramolecular raw material self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent was significantly higher than that of the ternary eutectic solvent based on baicalin and baicalin itself. This indicates that under high-temperature conditions, the stability of the supramolecular raw material self-assembled by cyclodextrin and baicalin-based ternary eutectic solvent is better than that of the ternary eutectic solvent based on baicalin and baicalin itself.

[0064] Example 8: Study on the transdermal permeation capability of cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw materials This embodiment studies the transdermal permeation effect of cyclodextrin and a ternary eutectic solvent-based supramolecular raw material self-assembled using baicalin. The cyclodextrin and baicalin-based ternary eutectic solvent-based supramolecular raw material prepared in Example 1 were formulated into a 5% (w / w) aqueous solution, and a corresponding concentration of baicalin solution was prepared simultaneously (using ethanol-water as the solvent). The transdermal permeation effect of the above solutions was tested using the following method: I. Microscopic examination: Under a dissecting microscope, select undamaged pig skin, cut out 6 pieces of skin of the same size, wash them once with physiological saline, and blot dry the surface moisture with filter paper.

[0065] II. Skin fixation: Fix the skin onto the Franz diffusion pool with the stratum corneum facing the drug delivery chamber and the dermis facing the receiving pool. Add 15 mL of physiological saline to the receiving pool and remove any air bubbles to ensure there are no air bubbles between the dermis and the receiving solution.

[0066] III. Drug Administration: Turn on the instrument in advance, adjust the water bath temperature to 32±1℃, add 1.0mL of drug to the administration chamber, seal with sealing film, and cover with tin foil to prevent liquid evaporation. The effective permeation area is 0.36πcm². 2 .

[0067] IV. Infiltration: Set the stirring speed to 350 rpm.

[0068] V. Sampling: Samples were taken at specific time points (2h, 4h, 6h, 22h, 23h, 24h), filtered through a 0.22μm organic membrane, and then analyzed by HPLC. The cumulative transdermal permeation was calculated, and the results are as follows: Figure 8 As shown.

[0069] The results showed that, 24 hours after percutaneous infiltration, the permeation rates per unit area of ​​the 5% self-assembled supramolecular raw material aqueous solution and the corresponding baicalin solution, based on baicalin content, were 92.10 and 45.86 μg / cm², respectively. 2 After 24 hours of transdermal permeation, the permeation capacity per unit area of ​​baicalin in the self-assembled supramolecular raw material aqueous solution was twice that of the corresponding baicalin solution, indicating that the transdermal permeation capacity of the self-assembled supramolecular raw material aqueous solution is superior to that of baicalin monomer.

[0070] Test Example 1: The soothing effects of cyclodextrin self-assembled supramolecular raw material (prepared in Example 2) with a ternary eutectic solvent based on baicalin, the ternary eutectic solvent based on baicalin, and baicalin monomer. Evaluation of the soothing efficacy of the sample: LPS-induced mouse macrophages RAW264.7 are a classic cell model for studying inflammatory factors. The effect of the test substance in inhibiting COX2 secretion was evaluated by comparing the COX2 secretion levels in mouse macrophages RAW264.7 after administration of the test substance to the control group and the control group. COX2 levels were determined using enzyme-linked immunosorbent assay (ELISA).

[0071] Test standard: T / SHRH 033-2020 "Testing of Soothing Efficacy of Cosmetics - Determination of In Vitro TNF-α Inflammatory Factor Content - Lipopolysaccharide-Induced Macrophage RAW264.7 Assay Method" Results Interpretation: The t-test was used for analysis, with a significance level of α=0.05; P≥0.05 indicates no statistical difference, meaning the sample did not promote changes in inflammatory factor levels; P<0.05 indicates a significant difference and a decrease in inflammatory factor levels, meaning the sample has a soothing effect.

[0072] Specific experimental steps: Ⅰ (Cell Plating): Mouse macrophage RAW264.7 suspension was seeded into 24-well plates and incubated for 24 h.

[0073] II (Liquid Preparation): Prepare working solutions for the test substances according to the test protocol (Table 1).

[0074] III (Drug Addition): According to the test protocol (Table 1), drugs were added to groups, with 1 mL of sample added to each well, 3 replicates per group, and incubation for 2 hours. Except for the NC group, which was given culture medium, the other groups were given drug-containing culture medium containing LPS.

[0075] IV (ELISA test): Collect the supernatant and perform the test according to the ELISA kit instructions.

[0076] The COX2 content of the samples was measured in mouse RAW264.7 macrophages, with dexamethasone as a control. The relative COX2 content of different groups is shown in Table 2, and the comparison of relative COX2 content is shown in [Table 2]. Figure 9 .

[0077] Table 1 COX2 Test Protocol

[0078] Table 2. Detection results of relative COX2 content in different samples at a concentration of 0.1%.

[0079] The results showed that, compared with the NC group, the relative COX2 content in the M group was significantly increased (P<0.05), indicating that the stimulation conditions in this experiment were effective; compared with the M group, the relative COX2 content in the PC group was significantly decreased (P<0.05), indicating that the experiment was effective; compared with the M group, the relative COX2 content of the self-assembled supramolecular raw material, the ternary eutectic solvent based on baicalin, and baicalin at a test concentration of 0.05% was significantly reduced (P<0.05), with inhibition rates of 23.71%, 19.85%, and 12.78%, respectively. This indicates that the self-assembled supramolecular raw material, the ternary eutectic solvent based on baicalin, and baicalin at a mass concentration of 0.05% can inhibit COX2 secretion and achieve a soothing effect.

[0080] In summary, at a concentration of 0.05%, the self-assembled supramolecular raw material showed better COX2 secretion inhibition than the ternary eutectic solvent based on baicalin and baicalin itself (P<0.05), indicating that at this concentration, the soothing effect was: self-assembled supramolecular raw material > ternary eutectic solvent based on baicalin > baicalin.

[0081] Test Example 2: Whitening Efficacy of Cyclodextrin with a Ternary Eutectic Solvent Based on Baicalin for Self-Assembling Supramolecular Raw Material (Prepared in Example 2), a Ternary Eutectic Solvent Based on Baicalin, and Baicalin Monomer Evaluation of the skin-whitening effect of the samples: In the biosynthesis of melanin in the skin, tyrosinase is a key enzyme that acts on dopa to form dopaquinone, which then spontaneously undergoes a series of reactions to finally form melanin. Tyrosinase catalyzes the conversion of dopa to dopaquinone in a pH 6.8 NaHPO4-citrate buffer, and the absorbance can be measured at 475 nm using a spectrophotometer. Raw materials that inhibit tyrosinase activity can reduce the conversion of dopa to dopaquinone, thereby lowering the absorbance. The inhibitory effect of the raw materials on tyrosinase activity is evaluated based on the change in absorbance.

[0082] Test standard: T / SHRH 015-2018 "Cosmetics - Test method for inhibition of tyrosinase activity".

[0083] Results Interpretation: The t-test was used for analysis, with a significance level of α=0.05. P≥0.05 indicated no statistical difference, meaning no inhibitory effect on tyrosinase; P<0.05 indicated a significant difference, meaning an inhibitory effect on tyrosinase, i.e., a whitening effect. Furthermore, a smaller IC50 value indicates a stronger inhibitory effect on tyrosinase.

[0084] Specific experimental steps: Set up sample tubes (T), sample background (T0), enzyme reaction tubes (C), and solvent background (C0). For each sample, three parallel tubes are required for each test concentration in the sample tube (T). Add 1 mL of the same concentration of sample solution to each of the sample tubes (T) and sample background (T0). Add 0.5 mL of tyrosinase solution to each of the sample tubes (T) and enzyme reaction tubes (C), mix well, and incubate in a 37 ℃ water bath for 10 min. Add 2 mL of levodopa solution to each tube sequentially, react for 5 min, and immediately transfer the reaction solution to a cuvette and measure the absorbance at 475 nm.

[0085] Tyrosinase inhibition rate (%) X = (1- ) × 100% The activity of tyrosinase (bisphenol) in the samples was detected, and the results are shown in Tables 3 and 4.

[0086] Table 3 Inhibition rate of self-assembled supramolecular raw materials on tyrosinase (bisphenol) activity

[0087] Table 4. Inhibition rate of tyrosinase (bisphenol) activity by ternary eutectic solvent based on baicalin.

[0088] Table 5. Inhibition rate of baicalin on tyrosinase (bisphenol) activity

[0089] The inhibition rates of the samples on tyrosinase (bisphenol) activity are shown in Tables 3, 4, and 5, and the inhibition curves are shown in Tables 3, 4, and 5. Figure 10 , 11As shown in Figures 1 and 12, the self-assembled supramolecular raw material of the sample showed an IC50 of 5.59% (95% confidence interval IC50 = 4.27%~6.97%) for inhibiting tyrosinase (bisphenol) activity, indicating a whitening effect; the ternary eutectic solvent based on baicalin showed an IC50 of 7.28% (95% confidence interval IC50 = 6.27%~9.16%) for inhibiting tyrosinase (bisphenol) activity, indicating a whitening effect; and the baicalin in the sample showed an IC50 of 8.94% (95% confidence interval IC50 = 7.14%~11.14%) for inhibiting tyrosinase (bisphenol) activity, indicating a whitening effect. Furthermore, the self-assembled supramolecular raw material has a stronger inhibitory effect on bisphenol tyrosinase activity than the ternary eutectic solvent based on baicalin and monomeric baicalin at the same concentration. Therefore, the whitening effect of supramolecular self-assembled supramolecular raw material > ternary eutectic solvent based on baicalin > baicalin.

[0090] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A supramolecular raw material for self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin, characterized in that, The supramolecular raw material for the self-assembly of cyclodextrin and baicalin-based ternary eutectic solvent is mainly obtained by the self-assembly of hydroxypropyl-β-cyclodextrin and baicalin-based ternary eutectic solvent through interaction forces.

2. The cyclodextrin and baicalin-based ternary eutectic solvent self-assembled supramolecular raw material according to claim 1, characterized in that, The interaction forces include hydrogen bonds and / or van der Waals forces.

3. The self-assembled supramolecular raw material of cyclodextrin and baicalin-based ternary eutectic solvent according to claim 1, characterized in that, The molar ratio of the hydroxypropyl-β-cyclodextrin to the ternary eutectic solvent based on baicalin is 1:1 to 3:

1.

4. A method for preparing a supramolecular raw material by self-assembly of cyclodextrin and a ternary eutectic solvent based on baicalin, as described in any one of claims 1 to 3, characterized in that, Includes the following steps: S1. Under the protection of an inert gas, distilled water, hydroxypropyl-β-cyclodextrin, and a ternary eutectic solvent based on baicalin are added to an ultrasonic reactor. Under heating and stirring conditions, ultrasonic energy is applied, and the ultrasonic reaction is continued for a predetermined time to obtain a mixed solution. S2. The mixed solution is transferred out of the ultrasonic reactor, pre-frozen, and then freeze-dried. After freeze-drying, it is pulverized to obtain the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin.

5. The method for preparing supramolecular raw materials by self-assembly of cyclodextrin and ternary eutectic solvent based on baicalin according to claim 4, characterized in that, In step S1, the heating temperature is 30~50℃; the stirring speed is 200~600rpm; the ultrasonic power is 800~1500w; the ultrasonic frequency is 10~25KHz; and the predetermined reaction time is 1~6h.

6. The method for preparing supramolecular raw materials by self-assembly of cyclodextrin and ternary eutectic solvent based on baicalin according to claim 4, characterized in that, Step S2 specifically includes: transferring the mixed solution from the ultrasonic reactor, spreading it evenly in an iron pan, pre-freezing it, and then transferring it to a vacuum freeze dryer for freeze drying; after freeze drying, the solid is pulverized, packaged with nitrogen gas, and the self-assembled supramolecular raw material of cyclodextrin and ternary eutectic solvent based on baicalin is obtained.

7. The method for preparing supramolecular raw materials by self-assembly of cyclodextrin and ternary eutectic solvent based on baicalin according to claim 4, characterized in that, In step S2, the freeze-drying temperature is -80 ℃ ± 5 ℃, and the time is 12~24h.

8. The application of the cyclodextrin described in any one of claims 1 to 3 and the ternary eutectic solvent-based supramolecular raw material based on baicalin in the fields of medicine and daily chemicals.

9. A cosmetic product with whitening and anti-inflammatory properties, characterized in that, It includes the cyclodextrin described in any one of claims 1 to 3 and the ternary eutectic solvent-based supramolecular raw material based on baicalin for self-assembly.

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