Supramolecular eutectic solution as well as preparation method and application thereof

Abstract

The invention discloses a supramolecular eutectic solution as well as a preparation method and application thereof. The supramolecular eutectic solution provided by the invention is formed by dissolving hydroxypropyl-beta-cyclodextrin and 2-hydroxychalcone in an ethanol water solution. When the supramolecular eutectic solution is used for extracting chalcone, the chalcone can be specifically recognized and wrapped, so that the extraction rate of the chalcone is increased, the extraction efficiency is improved, the extraction time is shortened, the purity of the extracted chalcone is improved, and a foundation is laid for preparing high-purity chalcone; when the supramolecular eutectic solution provided by the invention is used for extracting chalcone, the whole process and conditions are mild, and the loss of chalcone activity caused by adverse factors such as high temperature, intense stirring or excessive oxidation can be avoided, so that the extracted chalcone has higher biological activity and quality stability; and compared with other organic solvents, the supramolecular eutectic solution provided by the invention is lower in toxicity and safer, and the emission of the organic solvents and the pollution to the environment are also reduced.

Description

Technical Field

[0001] This application relates to the field of supramolecular eutectic technology, and particularly to a supramolecular eutectic solution, its preparation method and application. Background Art

[0002] Angelica keiskei, as a natural plant with great health care potential, the chalcone compounds it contains are the key active ingredients, showing important physiological activities in many health fields such as antioxidant, anti-tumor, and lipid-lowering. However, the current conventional methods for extracting chalcone from Angelica keiskei, such as solvent extraction method, ultrasonic-assisted extraction method, and microwave-assisted extraction method, all have obvious drawbacks.

[0003] The traditional solvent extraction method faces problems such as long extraction time, large solvent consumption, and low extraction efficiency. Although the ultrasonic-assisted extraction method and the microwave-assisted extraction method have improved the extraction efficiency to a certain extent, due to the special properties of chalcone being thermosensitive and easily oxidizable, it is extremely easy to cause a large loss of this active ingredient during the extraction process due to local overheating or excessive contact with air. At the same time, the chalcone in the extract is often mixed with various impurities, and the subsequent separation and purification work is extremely difficult, seriously restricting the further in-depth development and wide application of chalcone.

[0004] Supramolecular self-assembly drug eutectic technology, as an emerging and cutting-edge technology, relying on non-covalent intermolecular interactions, including hydrogen bonds, π-π stacking, and van der Waals forces, can promote the spontaneous assembly of drug molecules with other eutectic formers to construct a eutectic system with specific structures and functions. However, up to now, there has been no relevant research and report on applying supramolecular self-assembly eutectic technology to the extraction of chalcone from Angelica keiskei.

[0005] Therefore, developing a new simple, efficient, and high-purity extraction technology for chalcone from Angelica keiskei has important value and significance for the further in-depth development and wide application of chalcone from Angelica keiskei. Summary of the Invention

[0006] The purpose of this application is to provide a new supramolecular eutectic solution, its preparation method and application.

[0007] This application adopts the following technical solutions:

[0008] One aspect of this application discloses a supramolecular eutectic solution formed by dissolving hydroxypropyl-β-cyclodextrin and 2-hydroxy chalcone in an ethanol aqueous solution.

[0009] It should be noted that in this application, hydroxypropyl-β-cyclodextrin (HP-β-CD) with special functional groups is selected as the supramolecular host molecule, and 2-hydroxy chalcone is used as the ligand. The combination of the two can form specific interactions, thereby obtaining a stable supramolecular self-assembled eutectic solution. More importantly, the research in this application finds that when using the supramolecular eutectic solution of this application for chalcone extraction, especially for extracting angelica keiskei koidzumi chalcone from angelica keiskei koidzumi, the eutectic host molecule HP-β-CD can highly specifically recognize and encapsulate chalcone. Compared with traditional extraction methods, the extraction rate can be increased by 30 - 50% significantly, greatly improving the extraction efficiency and shortening the extraction time. Moreover, through specific adsorption and combined with subsequent column chromatography purification, various impurities in the extract can be effectively removed, significantly improving the purity of the obtained angelica keiskei koidzumi chalcone, which can reach more than 90%. While the purity of chalcone obtained by traditional extraction methods is usually only between 70 - 80%, providing higher-quality raw materials for subsequent applications. When using the supramolecular eutectic solution of this application for chalcone extraction, the entire extraction process is always carried out under mild conditions, including relatively low temperature, moderate stirring speed, etc., which can fully avoid the loss of chalcone activity caused by adverse factors such as high temperature, strong stirring or excessive oxidation, thus ensuring that the extracted chalcone has higher biological activity and quality stability. In addition, the ethanol aqueous solution used in the supramolecular eutectic solution of this application has lower toxicity compared with other organic solvents. The methanol desorbent used later can also be recycled through effective means such as vacuum concentration, significantly reducing the emission of organic solvents and environmental pollution, meeting the concepts of green chemistry and sustainable development.

[0010] Preferably, the molar ratio of hydroxypropyl-β-cyclodextrin to 2-hydroxy chalcone is (1:1)-(1:3).

[0011] Preferably, the volume ratio of ethanol to water in the ethanol aqueous solution is (3:1)-(5:1).

[0012] Preferably, in the supramolecular eutectic solution, the concentration of hydroxypropyl-β-cyclodextrin is 25 - 30 mg / mL, and the concentration of 2-hydroxy chalcone is 3 - 15 mg / mL.

[0013] On the other hand, this application discloses a preparation method of the supramolecular eutectic solution of this application, including placing hydroxypropyl-β-cyclodextrin and 2-hydroxy chalcone in an ethanol aqueous solution under the conditions of 40 - 50 °C and a stirring speed of 300 - 500 r / min, and continuously stirring and reacting at a constant temperature for 12 - 24 hours to obtain the supramolecular eutectic solution.

[0014] On yet another aspect, this application discloses the application of the supramolecular eutectic solution of this application in the extraction of chalcone.

[0015] It should be noted that the supramolecular eutectic solution of the present application is mainly developed for the extraction of angelica keiskei koidzumi chalcone. It can be understood that the supramolecular eutectic solution of the present application is not limited to the extraction of angelica keiskei koidzumi chalcone, but can also be used for the extraction of chalcone from other raw materials.

[0016] Another aspect of the present application discloses a method for extracting angelica keiskei koidzumi chalcone, including soaking and extracting angelica keiskei koidzumi with the supramolecular eutectic solution of the present application, and separating chalcone from the soaking extract.

[0017] Preferably, the method for extracting angelica keiskei koidzumi chalcone of the present application includes the following steps:

[0018] Adding angelica keiskei koidzumi powder into the supramolecular eutectic solution of the present application, and under the conditions of 25-35 °C and a stirring speed of 200-400 r / min, treating for 1-3 hours, removing the angelica keiskei koidzumi powder to obtain a eutectic solution adsorbed with angelica keiskei koidzumi chalcone;

[0019] Adding methanol as a desorbing liquid to the eutectic solution adsorbed with angelica keiskei koidzumi chalcone for desorption treatment. The conditions for desorption treatment are constant temperature treatment at 30-40 °C and a stirring speed of 300-500 r / min for 2-4 hours;

[0020] After the desorption treatment is completed, separating the solid eutectic from the liquid in the solution, collecting the liquid, and obtaining a desorbing liquid containing angelica keiskei koidzumi chalcone;

[0021] Concentrating the desorbing liquid containing angelica keiskei koidzumi chalcone to obtain a concentrated liquid, purifying the concentrated liquid by column chromatography, and using a mixed solvent of petroleum ether and ethyl acetate as an eluent to elute and collect angelica keiskei koidzumi chalcone.

[0022] Preferably, in the desorption treatment, the volume ratio of methanol to the eutectic solution is (1:5)-(1:10).

[0023] Preferably, to separate the solid eutectic from the liquid in the solution, the specific method adopted includes centrifuging the solution at 5000-8000 r / min for 10-20 minutes after the desorption treatment is completed, and collecting the supernatant, which is the desorbing liquid containing angelica keiskei koidzumi chalcone.

[0024] Preferably, the concentration method adopted in the present application is vacuum concentration, and the concentrated liquid is concentrated to a volume of (1 / 5)-(1 / 10) of the original volume.

[0025] Preferably, column chromatography purification is carried out using silica gel column chromatography.

[0026] Preferably, the specification of the silica gel column is diameter: length = (1:5)-(1:10).

[0027] Preferably, in the eluent of the present application, the volume ratio of petroleum ether to ethyl acetate is (1:4)-(1:8).

[0028] Preferably, the Angelica keiskei powder is obtained by sequentially washing, drying and pulverizing the Angelica keiskei.

[0029] Preferably, after the Angelica keiskei is crushed, it is passed through a 40-60 mesh sieve to obtain the Angelica keiskei powder of the present application.

[0030] It should be noted that after the Angelica keiskei is crushed and passed through a 40-60 mesh sieve, Angelica keiskei powder with uniform particle size can be obtained, which provides a good raw material basis for the subsequent extraction step.

[0031] The beneficial effects of this application are:

[0032] The supramolecular eutectic solution of the present application, when used for chalcone extraction, can specifically identify and encapsulate chalcone, thereby improving the extraction rate of chalcone, enhancing the extraction efficiency, and shortening the extraction time; and, through specific identification and encapsulation, the purity of the extracted chalcone can be improved, laying a foundation for the preparation of high-purity chalcone; when the supramolecular eutectic solution of the present application is used for chalcone extraction, the entire process and conditions are relatively mild, and the loss of chalcone activity caused by adverse factors such as high temperature, strong stirring or excessive oxidation can be avoided, thereby ensuring that the extracted chalcone has higher biological activity and quality stability, and compared with other organic solvents, the supramolecular eutectic solution of the present application is less toxic and safer, and also reduces organic solvent emissions and pollution to the environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the elution peak diagram of the Angelica keiskei chalcone standard in the examples of the present application;

[0034] Figure 2 It is a high performance liquid chromatogram of the Angelica keiskei chalcone extracted in the examples of the present application. DETAILED DESCRIPTION

[0035] In order to completely overcome the inherent defects of existing extraction technologies, the present application innovatively provides an efficient extraction method for tomorrow leaf chalcone based on supramolecular self-assembly drug co-crystal technology, so as to achieve the multiple goals of greatly improving the extraction efficiency and purity of tomorrow leaf chalcone and minimizing the loss of active ingredients during the extraction process.

[0036] The present application first develops a new supramolecular eutectic solution. In one implementation of the present application, the construction of the supramolecular eutectic solution mainly includes the following contents:

[0037] Precise Screening of Supramolecular Host Molecules: Through in-depth research and experimental verification, HP-β-CD with special functional groups is selected as the supramolecular host molecule. Its unique structure and properties can provide stable and effective binding sites for subsequent cocrystal formation.

[0038] Careful Selection of Ligands: 2-Hydroxychalcone is carefully selected as the ligand. Specific interactions can form between this ligand and the supramolecular host molecule, which is beneficial to the stable construction of the cocrystal.

[0039] Precise Formation Process of Cocrystal: HP-β-CD and 2-hydroxychalcone are dissolved in a specific ratio of ethanol-water mixed solvent (ethanol: water = 3:1 - 5:1, v / v) according to the optimal molar ratio of 1:1 - 1:3. Under precisely controlled temperature (40 - 50 °C) and stirring speed (300 - 500 r / min), the reaction is continuously stirred for 12 - 24 hours, thus successfully obtaining the supramolecular self-assembled drug cocrystal, that is, the supramolecular cocrystal solution of this application. At the same time, it is clear that the concentration of HP-β-CD is 25 - 30 mg / mL, and the concentration of 2-hydroxychalcone is 3 - 15 mg / mL. The obtained supramolecular cocrystal solution has good consistency and repeatability.

[0040] Based on the supramolecular cocrystal solution of this application, this application further developed a method for extracting angelica keiskei koidzumi chalcone. In one implementation of this application, it specifically includes:

[0041] Pretreatment of Angelica Keiskei Koidzumi: Angelica keiskei koidzumi is systematically processed. After steps such as washing, drying, and pulverizing, it is sieved through a 40 - 60 mesh sieve, and finally, evenly sized angelica keiskei koidzumi powder is obtained, providing a good raw material basis for subsequent extraction steps.

[0042] Adsorption Extraction: The carefully prepared angelica keiskei koidzumi powder is added to the saturated solution of the supramolecular self-assembled drug cocrystal. Under strictly controlled temperature (25 - 35 °C) and stirring speed (200 - 400 r / min), it is fully adsorbed for 1 - 3 hours, so that the cocrystal can efficiently and specifically adsorb the chalcone in angelica keiskei koidzumi, thereby obtaining a cocrystal solution adsorbed with angelica keiskei koidzumi chalcone.

[0043] Desorption and Separation:

[0044] 1) Precise Operation in the Desorption Process: An appropriate amount of methanol is added to the cocrystal solution adsorbed with angelica keiskei koidzumi chalcone as the desorbent. The volume ratio of methanol to the cocrystal solution is precisely controlled (1:5 - 1:10). Under suitable temperature (30 - 40 °C) and stirring speed (300 - 500 r / min), sufficient desorption is carried out for 2 - 4 hours to effectively separate the chalcone from the cocrystal.

[0045] 2) Strict implementation of the separation step: After the desorption is completed, the solid eutectic in the solution is completely separated from the supernatant by centrifugation technology at a precisely set rotation speed (5000-8000r / min) and centrifugation time (10-20 minutes), thereby obtaining a desorption solution rich in Angelica keiskei chalcone.

[0046] Elution purification: The desorption liquid containing angelica keiskei chalcone is concentrated to 1 / 5-1 / 10 of the original volume by vacuum concentration, and then deep purification is performed by silica gel column chromatography. The specification of the silica gel column is specified as diameter: length = 1:5-1:10, and a petroleum ether-ethyl acetate mixed solvent with a specific volume ratio (1:4-1:8) is selected as the eluent. By accurately collecting the elution peak containing angelica keiskei chalcone, high-purity angelica keiskei chalcone is finally obtained.

[0047] Compared with the existing chalcone extraction method, the extraction method of the present application has the following advantages:

[0048] Significantly improve extraction efficiency: By carefully constructing a supramolecular self-assembled drug co-crystal system, the co-crystal main molecule HP-β-CD can accurately encapsulate the chalcones in tomorrow leaves with its highly specific recognition ability. Compared with traditional extraction methods, the extraction rate can be greatly increased by 30-50%, greatly improving the extraction efficiency and shortening the extraction time.

[0049] Greatly improve the purity: The present invention cleverly utilizes the specific adsorption characteristics of the eutectic system, combined with the efficient purification effect of subsequent silica gel column chromatography, to effectively remove various impurities in the extract, so that the purity of the obtained tomorrow leaf chalcone is significantly improved to more than 90%, while the purity of the chalcone obtained by the traditional extraction method is usually only between 70-80%, providing higher quality raw materials for subsequent applications.

[0050] Effectively reduce the loss of active ingredients: The entire extraction process is always carried out under mild conditions, including relatively low temperature, moderate stirring speed, etc., which can fully avoid the loss of activity of tomorrow leaf chalcone caused by adverse factors such as high temperature, strong stirring or excessive oxidation, thereby ensuring that the extracted chalcone has higher biological activity and quality stability.

[0051] The environmentally friendly advantages are outstanding: in the process of constructing the eutectic system, the ethanol-water mixed solvent used has lower toxicity than other organic solvents; the desorbent methanol can also be recycled and reused through effective means such as vacuum concentration, which significantly reduces the emission of organic solvents and pollution to the environment, and is in line with the concepts of green chemistry and sustainable development.

[0052] The present application is further described in detail below through specific examples. The following examples are only used to further illustrate the present application and should not be construed as limiting the present application.

[0053] The materials and reagents used in the following examples can be obtained commercially without special instructions. The experimental methods used in the following examples are conventional methods without special instructions.

[0054] Example 1

[0055] The supramolecular eutectic solution of this example, its preparation method, and the extraction method of angelicin chalcone based on this supramolecular eutectic solution are as follows in detail:

[0056] 1. Preparation of supramolecular eutectic solution

[0057] Hydroxypropyl-β-cyclodextrin (HP-β-CD) (purchased from Deli Biochemical Industry, CAS No. 128446-35-5) was selected as the supramolecular host molecule, and 2-hydroxy chalcone (purchased from Jianchu Biopharmaceuticals, CAS No. 1214-47-7) was used as the ligand. HP-β-CD and 2-hydroxy chalcone were accurately dissolved in an ethanol-water mixed solvent at a molar ratio of 1:1, with ethanol:water = 3:1 (v / v). The concentration of HP-β-CD was 25 mg / mL, the concentration of 2-hydroxy chalcone was 3 mg / mL, and the amount of the ethanol-water mixed solvent used was 10 mL. Under the conditions of accurately controlling the temperature at 40 °C and strictly setting the stirring speed at 500 r / min, the reaction was continuously stirred for 24 hours to obtain a supramolecular self-assembled drug eutectic, that is, the supramolecular eutectic solution of this example.

[0058] The supramolecular eutectic solution prepared in this example was detected by X-ray diffraction (XRD). At the same time, HP-β-CD dissolved in the same ethanol-water mixed solvent was subjected to XRD detection, and 2-hydroxy chalcone dissolved in the same ethanol-water mixed solvent was subjected to XRD detection.

[0059] The results showed that the characteristic diffraction peak of the eutectic was significantly different from the XRD patterns of HP-β-CD, 2-hydroxy chalcone, and their simple physical mixture, indicating that a supramolecular self-assembled eutectic structure was successfully obtained.

[0060] 2. Analysis of the elution peak of the angelicin chalcone standard

[0061] Angelicin chalcone mainly includes four chalcone components: isobavachaclone, xanthonagelol B, 4-hydroxyderricin, and xanthonagelol. Therefore, in this example, four chalcones were purchased as standards to analyze their elution peaks.

[0062] Specifically, 0.5 mg of isobavachalcone (Aladdin, CAS No. 20784-50-3) was dissolved in 2 mL of methanol, adsorbed by silica gel column chromatography. The silica gel column (Macklin, CAS No. 112926-00-8) had a specification of diameter:length = 1:5, and a petroleum ether-ethyl acetate mixed solvent with a volume ratio of 1:4 was used as the eluent to observe its elution peak. 0.5 mg of xanthoangelol B (ChemFaces, CAS No. 132998-81-3) was dissolved in 2 mL of methanol, and adsorption and elution were carried out using the same method to observe the elution peak. 0.5 mg of 4-hydroxyderricin (Abbexa Biotech Co., Ltd., CAS No. 55912-03-3) was dissolved in 2 mL of methanol, and adsorption and elution were carried out using the same method to observe the elution peak. 0.5 mg of xanthoangelol (Yuanye Biotech Co., Ltd., CAS No. 62949-76-2) was dissolved in 2 mL of methanol, and adsorption and elution were carried out using the same method to observe the elution peak. Then, 0.5 mg of each of the four chalcones was dissolved in 8 mL of methanol, and adsorption and elution were carried out using the same method to observe the elution peak. Figure 1 Among them, the curves from A to D are the elution peak diagrams of isobavachalcone, xanthoangelol B, 4-hydroxyderricin, and xanthoangelol in sequence, and the E curve is the elution peak diagram of the mixed sample of the four chalcones.

[0063] Figure 1 The results presented in detail the specific positions and relative intensities of the elution peaks of the four chalcones, intuitively reflecting the effective separation of the four chalcones from Angelica keiskei by silica gel column chromatography, and providing an important reference for the elution and purification estimation of actual samples.

[0064] 3. Pretreatment of Angelica keiskei

[0065] The washed and dried Angelica keiskei was crushed and then passed through a 40-mesh sieve to obtain Angelica keiskei powder.

[0066] 4. Extraction of chalcones from Angelica keiskei

[0067] 1) Adsorption extraction: 1 g of Angelica keiskei powder was accurately added to 10 mL of the saturated solution of the supramolecular self-assembled drug cocrystal, that is, the saturated supramolecular cocrystal solution prepared in this example; under the conditions of a temperature of 25 °C and a stirring speed of 400 r / min, it was fully adsorbed for 1 hour to obtain a cocrystal solution adsorbed with chalcones from Angelica keiskei.

[0068] 2) Desorption and separation: 2 mL of methanol was added to the cocrystal solution adsorbed with chalcones from Angelica keiskei as the desorbent, and desorption operation was carried out for 2 hours under the conditions of a temperature of 30 °C and a stirring speed of 500 r / min. After desorption was completed, centrifugal separation was carried out at a rotation speed of 5000 r / min for 20 minutes to separate the solid cocrystal in the solution from the supernatant, and the supernatant was taken to obtain a desorbed solution containing chalcones from Angelica keiskei.

[0069] 3) Elution and purification: The desorbed solution containing angelica-chalcone is precisely concentrated to 1 / 5 of the original volume by reduced-pressure concentration, and then purified by silica gel column chromatography. The specifications of the silica gel column are diameter: length = 1:5, and the eluent is a mixed solvent of petroleum ether - ethyl acetate with a volume ratio of 1:4. According to the elution peak information obtained from "2. Analysis of the elution peak of angelica-chalcone standard", angelica-chalcone is collected.

[0070] Meanwhile, the conventional ultrasonic method is used to extract chalcone from the same amount of angelica keiskei powder. Specifically, 1 g of angelica keiskei powder is added to 30 mL of ethanol with a concentration of 70%, and extracted for 1 hour under the conditions of ultrasonic wave with a power of 300 W and a temperature of 50 °C; after extraction, the filtrate is collected, and the filter residue is extracted again by the same method, and the two filtrates are combined. It is precisely concentrated to 1 / 10 of the original volume by reduced-pressure concentration, and then purified by silica gel column chromatography. The specifications of the silica gel column are diameter: length = 1:5, and the eluent is a mixed solvent of petroleum ether - ethyl acetate with a volume ratio of 1:4. According to the elution peak information obtained from "2. Analysis of the elution peak of angelica-chalcone standard", angelica-chalcone is collected.

[0071] 5. Detection of angelica-chalcone

[0072] High performance liquid chromatography (HPLC) is used to detect angelica-chalcone extracted from the supramolecular eutectic solution and by the ultrasonic method respectively, and analyze the content and purity of chalcone.

[0073] The results show that four kinds of angelica-chalcone are separated from the angelica-chalcone extracted by both methods, and the results are consistent with the expectations. The contents of the four kinds of angelica-chalcone extracted by the ultrasonic method are in sequence: isobavachalcone 0.31 mg, xanthoangelol B 0.12 mg, 4-hydroxyderricin 1.87 mg, xanthoangelol 3.24 mg. In total, 5.54 mg of angelica-chalcone is obtained, and the purity is 79%.

[0074] The contents of the four kinds of angelica-chalcone extracted from the supramolecular eutectic solution are in sequence: isobavachalcone 0.41 mg, xanthoangelol B 0.20 mg, 4-hydroxyderricin 2.75 mg, xanthoangelol 4.13 mg. In total, 7.49 mg of angelica-chalcone is obtained, and the purity is 92%. The HPLC chromatogram of the four kinds of angelica-chalcone extracted from the supramolecular eutectic solution is as Figure 2 shown, where 1 is isobavachalcone, 2 is xanthoangelol B, 3 is 4-hydroxyderricin, and 4 is xanthoangelol.

[0075] Example 2

[0076] All the reagents and raw materials used in this example are the same as those in Example 1, except that the ratio and preparation method of the supramolecular eutectic solution are different from those in Example 1, which are detailed as follows:

[0077] HP-β-CD and 2-hydroxy chalcone were accurately dissolved in an ethanol-water mixed solvent (ethanol: water = 4:1, v / v) at a molar ratio of 1:2. The concentration of HP-β-CD was 30 mg / mL, the dosage of 2-hydroxy chalcone was 9 mg / mL, and the dosage of the ethanol-water mixed solvent was 20 mL. Under the conditions of a temperature of 45 °C and a stirring speed of 400 r / min, the reaction was continuously stirred for 18 hours to obtain a supramolecular self-assembled drug eutectic, that is, the supramolecular eutectic solution of this example.

[0078] The supramolecular eutectic solution prepared in this example was detected by X-ray diffraction (XRD). The results were similar to those in Example 1, with diffraction peaks unique to the eutectic, indicating that a supramolecular self-assembled eutectic structure was successfully prepared in this example.

[0079] The supramolecular eutectic solution prepared in this example was used to extract chalcone from Angelica keiskei. The specific pre-treatment, adsorption extraction, desorption separation, and elution purification of Angelica keiskei were the same as those in Example 1. Similarly, HPLC was used to detect the Angelica keiskei chalcone prepared in this example.

[0080] The HPLC results showed that the contents of the four Angelica keiskei chalcones extracted with the supramolecular eutectic solution prepared in this example were, in sequence, isobavachalcone 0.39 mg, xanthoangelol B 0.21 mg, 4-hydroxyderricin 2.73 mg, and xanthoangelol 4.19 mg. A total of 7.52 mg of Angelica keiskei chalcone was obtained, with a purity of 95%.

[0081] Example 3

[0082] All the reagents and raw materials used in this example are the same as those in Example 1, except that the ratio and preparation method of the supramolecular eutectic solution are different from those in Example 1, which are detailed as follows:

[0083] HP-β-CD and 2-hydroxy chalcone were accurately dissolved in an ethanol-water mixed solvent (ethanol: water = 5:1, v / v) at a molar ratio of 1:3. The concentration of HP-β-CD was 30 mg / mL, the concentration of 2-hydroxy chalcone was 12 mg / mL, and the dosage of the ethanol-water mixed solvent was 30 mL. Under the conditions of a temperature of 50 °C and a stirring speed of 300 r / min, the reaction was continuously stirred for 12 hours to obtain a supramolecular self-assembled drug eutectic, that is, the supramolecular eutectic solution of this example.

[0084] The supramolecular eutectic solution prepared in this example was detected by X-ray diffraction (XRD). The results were similar to those of Example 1, showing diffraction peaks characteristic of the eutectic, indicating that the supramolecular self-assembled eutectic structure was also successfully prepared in this example.

[0085] The chalcone of Angelica keiskei was extracted using the supramolecular eutectic solution prepared in this example. Specifically, the pretreatment, adsorption extraction, desorption separation, and elution purification of Angelica keiskei were the same as those in Example 1. Similarly, the chalcone of Angelica keiskei prepared in this example was detected by HPLC.

[0086] The HPLC results showed that the contents of the four chalcones of Angelica keiskei extracted using the supramolecular eutectic solution prepared in this example were, in sequence, isobavachalcone 0.38 mg, xanthoangelol B 0.19 mg, 4-hydroxyderricin 2.70 mg, and xanthoangelol 4.21 mg. A total of 7.48 mg of chalcone of Angelica keiskei was obtained, with a purity of 93%.

[0087] Example 4

[0088] In this example, the same supramolecular eutectic solution as in Example 1 was used for the extraction of chalcone of Angelica keiskei. The only difference was that some parameters were adjusted during the extraction process, and the rest were the same as in Example 1.

[0089] The specific method for the extraction of chalcone of Angelica keiskei is as follows:

[0090] Pretreatment of Angelica keiskei: The washed and dried Angelica keiskei was pulverized and then passed through a 60-mesh sieve to obtain Angelica keiskei powder.

[0091] Extraction of chalcone of Angelica keiskei:

[0092] 1) Adsorption extraction: 1 g of Angelica keiskei powder was accurately added to 10 mL of the saturated solution of the supramolecular self-assembled drug eutectic, that is, the saturated supramolecular eutectic solution prepared in this example. Under the conditions of a temperature of 35°C and a stirring speed of 200 r / min, adsorption was carried out for 3 hours to obtain a eutectic solution adsorbed with chalcone of Angelica keiskei.

[0093] 2) Desorption separation: 1 mL of methanol was added to the eutectic solution adsorbed with chalcone of Angelica keiskei as a desorbent, and desorption was carried out for 4 hours under the conditions of a temperature of 40°C and a stirring speed of 300 r / min. After desorption, centrifugal separation was carried out at a speed of 8000 r / min for 10 minutes to separate the solid eutectic in the solution from the supernatant. The supernatant was taken to obtain a desorbed solution containing chalcone of Angelica keiskei.

[0094] 3) Elution and purification: The desorbing solution containing apterin is accurately concentrated to 1 / 10 of the original volume by means of reduced pressure concentration, and then purified by silica gel column chromatography. The specification of the silica gel column is diameter:length = 1:5, and the eluent is a mixed solvent of petroleum ether - ethyl acetate with a volume ratio of 1:8. According to the elution peak information obtained from "2. Analysis of the elution peak of apterin reference substance", apterin is collected.

[0095] The apterin prepared in this example was detected by HPLC.

[0096] The HPLC results showed that the contents of the four apterins extracted by the supramolecular eutectic solution prepared in this example were in sequence: isobavachalcone 0.40 mg, xanthoangelol B 0.21 mg, 4 - hydroxydicoumarol 2.73 mg, xanthoangelol 4.16 mg. A total of 7.50 mg of apterin was obtained, and the purity was 90%.

[0097] The above content is a further detailed description of the present application in combination with specific implementation manners, and it cannot be determined that the specific implementation of the present application is only limited to these descriptions. For those of ordinary skill in the technical field to which the present application pertains, without departing from the concept of the present application, several simple deductions or substitutions can still be made.

Claims

1. A supramolecular eutectic solution, characterized in that: It is formed by dissolving hydroxypropyl-β-cyclodextrin and 2-hydroxy chalcone in an ethanol aqueous solution.

2. The supramolecular eutectic solution according to claim 1, wherein: The molar ratio of hydroxypropyl-β-cyclodextrin to 2-hydroxy chalcone is (1:1)-(1:3).

3. The supramolecular eutectic solution according to claim 1, wherein: In the ethanol aqueous solution, the volume ratio of ethanol to water is (3:1)-(5:1).

4. The supramolecular eutectic solution according to any one of claims 1-3, characterized in that: In the supramolecular eutectic solution, the concentration of hydroxypropyl-β-cyclodextrin is 25-30 mg / mL, and the concentration of 2-hydroxy chalcone is 3-15 mg / mL.

5. The preparation method of the supramolecular eutectic solution according to any one of claims 1-4, characterized in that: It includes placing hydroxypropyl-β-cyclodextrin and 2-hydroxy chalcone in an ethanol aqueous solution under the conditions of 40-50 °C and a stirring speed of 300-500 r / min, and continuously stirring and reacting at a constant temperature for 12-24 hours to obtain the supramolecular eutectic solution.

6. Use of the supramolecular eutectic solution according to any one of claims 1-4 in the extraction of chalcone.

7. A method for extracting angelica keiskei koidzumi chalcone, characterized in that: It includes soaking and extracting Angelica keiskei Koidz. with the supramolecular eutectic solution according to any one of claims 1-4, and separating chalcone from the soaking extract.

8. The method according to claim 7, wherein: It includes the following steps, Adding Angelica keiskei Koidz. powder to the supramolecular eutectic solution, and treating it for 1-3 hours under the conditions of 25-35 °C and a stirring speed of 200-400 r / min, removing the Angelica keiskei Koidz. powder to obtain a eutectic solution adsorbed with Angelica keiskei Koidz. chalcone; Adding methanol as a desorbing solution to the eutectic solution adsorbed with Angelica keiskei Koidz. chalcone for desorption treatment. The conditions for the desorption treatment are constant temperature treatment at 30-40 °C and a stirring speed of 300-500 r / min for 2-4 hours; After the desorption treatment is completed, separating the solid eutectic in the solution from the liquid, and collecting the liquid to obtain a desorbing solution containing Angelica keiskei Koidz. chalcone; Concentrating the desorbing solution containing Angelica keiskei Koidz. chalcone to obtain a concentrated solution, purifying the concentrated solution by column chromatography, and using a mixed solvent of petroleum ether and ethyl acetate as an eluent to elute and collect Angelica keiskei Koidz. chalcone.

9. The method according to claim 8, characterized in that: In the desorption treatment, the volume ratio of methanol to the eutectic solution is (1:5)-(1:10); Preferably, separating the solid eutectic in the solution from the liquid. The specific method used includes centrifuging the solution at 5000-8000 r / min for 10-20 minutes after the desorption treatment, and collecting the supernatant, which is the desorbing solution containing Angelica keiskei Koidz. chalcone; Preferably, the concentration is vacuum concentration, and the volume of the concentrated solution is (1 / 5)-(1 / 10) of the original volume; Preferably, the column chromatography purification uses silica gel column chromatography; Preferably, the specification of the silica gel column is diameter:length = (1:5)-(1:10); Preferably, in the eluent, the volume ratio of petroleum ether to ethyl acetate is (1:4)-(1:8).

10. The method according to claim 8 or 9, characterized in that: The Angelica keiskei Koidz. powder is obtained by successively washing, drying, and crushing Angelica keiskei Koidz.; Preferably, the Angelica keiskei Koidz. powder is obtained by passing the crushed Angelica keiskei Koidz. through a 40-60 mesh sieve.

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