Preparation method and application of trilobatin-glycyrrhizic acid co-amorphous substance

Abstract

The invention provides a co-amorphous substance co-loaded with trilobatin and glycyrrhizic acid as natural sweeteners, which does not need to add any auxiliary materials, does not relate to special processes and equipment, and is simple, convenient and efficient in preparation method, easy to industrialize and low in cost. According to the double-drug-loading co-amorphous substance prepared by the invention, the water solubility of the two components can be remarkably improved at the same time, the sweetness of the double-drug-loading co-amorphous substance is superior to that of the original components, and the double-drug-loading co-amorphous substance can be used for improving the solubility of other insoluble components; the compound can be used as a multifunctional flavoring agent and has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of medicine and food, and in particular to a preparation method of trilobatin-glycyrrhizic acid co-amorphous material and application thereof. Background Art

[0002] Trilobatin belongs to the dihydrochalcone class of compounds, which can be extracted and separated from a variety of plants or produced by chemical synthesis. As one of the natural sweeteners, trilobatin is not only highly sweet (300 times sweeter than sucrose), but also has no metallic taste or aftersweetness, and has excellent food safety. In addition, it also shows good hypoglycemic, hypolipidemic, anti-inflammatory and antioxidant activities. However, its solubility in water is poor (2.72-3.91 mg / mL), which is not conducive to its effectiveness in the food industry and also limits its absorption and efficacy in the body.

[0003] Glycyrrhizic acid is the main active ingredient of the traditional Chinese medicine licorice and belongs to the triterpenoid saponins. Glycyrrhizic acid is a white crystalline powder with a special sweet taste (about 200 times sweeter than sucrose), and has anti-inflammatory, antiviral, liver-protecting, detoxifying, antispasmodic, and neuroprotective effects. However, glycyrrhizic acid is difficult to dissolve in cold water (0.12 mg / mL), easily soluble in hot water, and insoluble in oils and fats. Glycyrrhizic acid is an amphiphilic natural product and can be used as a surfactant or solid dispersion carrier.

[0004] In order to improve the solubility of poorly soluble drugs, nano-crystal, amorphous, molecular inclusion complex, co-crystal and other technologies are often used in pharmaceutical preparation. Among them, amorphous technology has a significant effect on improving the water solubility and bioavailability of poorly soluble drugs. Co-amorphous drugs can usually be prepared by grinding, melt quenching, solvent volatilization, freeze drying and spray drying. Traditional amorphous drugs are highly dispersed in a large amount of carrier materials, which have the disadvantages of easy hygroscopicity, easy crystallization when placed, and low drug content.

[0005] The prior art forms a drug-drug co-amorphous with glycyrrhizic acid and paeonol, and the dissolution and release of paeonol are improved, which is conducive to further improving bioavailability (CN115645425A); due to the characteristics of glycyrrhizic acid as a surfactant and the fact that glycyrrhizic acid itself can be injected, the prior art prepares itraconazole loaded in the hydrophobic core of glycyrrhizic acid self-assembled micelles to obtain itraconazole nano-micelles, thereby increasing the solubility of itraconazole, and the micelles have good stability and can significantly increase the solubility of itraconazole (CN117731612A); there is an invention that mixes glycyrrhizic acid with berberine hydrochloride to improve the solubility of berberine hydrochloride (CN114306640A). Although glycyrrhizic acid can increase the solubility of more drugs, there is no prior art that can simultaneously improve the solubility of glycyrrhizic acid after another poorly soluble drug is compounded with glycyrrhizic acid.

[0006] The existing technology prepares trilobatin and stevioside into a solid dispersion (Liu Yuezhen. Nanchang University, 2021), with a mass ratio of trilobatin to stevioside of 9:25. After dissolving in ethanol and evaporating, a trilobatin-stevioside solid dispersion is obtained. The solubility of trilobatin increases by 6-9 times, but the effect of this system on the solubility and sweetness of stevioside is unknown. Another technology disperses trilobatin in sterile water, slowly heats it to 55-60°C, and adds a nano-micelle to the suspension while stirring until it becomes transparent. The solubility in water is significantly improved, nearly 100 times, and the efficacy can be increased by 2-5 times compared with traditional oral preparations (CN111467308A). There is also a technology that increases the solubility of trilobatin in water by 300 times after glycosylation (CN110184317A). The former improves its solubility by adding a carrier, and the latter is through chemical synthesis, but both have shortcomings such as low drug loading and complex process.

[0007] On the other hand, compound sweeteners can give full play to the maximum efficacy of sweeteners. They can not only maintain the special effects of single sweeteners, but also introduce new flavors. Through the synergistic effects and physiological characteristics of various sweeteners, they can reduce unpleasant flavors and improve sweetness stability.

[0008] Existing sweetener compounding technologies include compounding stevioside, mogroside V, and xylitol to improve their taste and increase sweetness (CN118160913A). Sweeteners compounded with mogroside, glycyrrhizinate, glucosyl steviol glycoside, xylitol, erythritol, etc. have the characteristics of strong front sweetness, middle sweetness, and after sweetness, and the sweetness lasts for a long time, which is suitable for use in products such as betel nut and chewing gum (Ye Yuwen et al., Journal of Food Science and Technology, 2020, 38(03):111-118). The compounding of these natural products is limited to improving sweetness, and there is no suggestion of increasing solubility.

[0009] The prior art (CN201910747737) discloses a cefpodoxime proxetil-naringenin co-amorphous material and a preparation method thereof. Cefpodoxime proxetil and naringenin are prepared into a co-amorphous material by a solvent method, which can significantly mask the bitter taste of cefpodoxime proxetil and improve its compressibility, but the effect on solubility and dissolution rate is unknown.

[0010] The drug-drug co-amorphous product involved in the present invention is based on the interaction between trilobatin and glycyrrhizic acid, does not require the addition of any carrier or excipient, has a simple process, improves the solubility of both drugs, and improves the sweetness. Summary of the invention

[0011] The purpose of the present invention is to provide a two-component co-amorphous material co-loaded with trilobatin and glycyrrhizic acid. The above system can form a co-amorphous material without adding any auxiliary materials, the drug loading reaches 100%, and the cost and dosage of the preparation are greatly reduced.

[0012] The co-amorphous material can significantly improve the water solubility and sweetness of the two drug components at the same time, does not add any functional excipients, and has a simple preparation method. Specifically, the water solubility of trilobatin and glycyrrhizic acid in the co-amorphous material is higher than that of the single component and its physical mixture, and the sweetness of the co-amorphous material is better than that of the single component and its physical mixture.

[0013] Another object of the present invention is to provide a method for preparing the above-mentioned drug-drug co-amorphous compound.

[0014] Another object of the present invention is to provide the use of trilobatin and glycyrrhizic acid co-amorphous product, which can improve sweetness, reduce the amount of addition, and be used in the fields of medicine, food, etc., and can generate greater economic and social value.

[0015] Specifically, the co-amorphous substance is used as a sweetener; or the co-amorphous substance is used to improve the water solubility of trilobatin and / or glycyrrhizic acid. More surprisingly, the co-amorphous substance is also used to improve the solubility of other poorly soluble ingredients in water and mask their taste. Further, the co-amorphous substance can be used as a taste masking agent.

[0016] Specifically, the present invention provides the following technical solutions: A drug-drug co-amorphous substance, which is composed of trilobatin and glycyrrhizic acid, active ingredients of traditional Chinese medicine, without adding any functional excipients.

[0017] Preferably, the molar ratio of trilobatin to glycyrrhizic acid is less than or equal to 2: 1. Since glycyrrhizic acid itself is amorphous, the mixed system of the two is more inclined to form a co-amorphous substance by continuously increasing the proportion of glycyrrhizic acid.

[0018] More preferably, the molar ratio of trilobatin to glycyrrhizic acid is 1:1.

[0019] The present invention also provides a method for preparing the above-mentioned co-amorphous material, namely, a solvent evaporation method, a grinding method, etc. The solvent evaporation method is to take trilobatin and glycyrrhizic acid raw materials in a molar ratio, add a solvent to make it fully solvent, and then evaporate the solvent to obtain; the ball milling method is to take trilobatin and glycyrrhizic acid raw materials in a molar ratio, and continue to grind to obtain an amorphous material. Preferably, the preparation method is a solvent evaporation method.

[0020] Specifically, the solvent evaporation method is to weigh appropriate amounts of trilobatin and glycyrrhizic acid, completely dissolve them in the solvent and mix them evenly, recover most of the solvent under reduced pressure and naturally evaporate the remaining solvent at room temperature, and crush them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous. The preferred solvent is one or more of methanol, ethanol, 1,4-dioxane, etc. The more preferred solvent is methanol and ethanol.

[0021] Specifically, the grinding method is to weigh an appropriate amount of trilobatin and glycyrrhizic acid, place them in a container, add an appropriate amount of grinding media of suitable size and material, grind them together for 3 hours or more, and pass through an 80-mesh sieve to obtain a trilobatin-glycyrrhizic acid co-amorphous substance.

[0022] The method for preliminary inspection and confirmation of whether it is a co-amorphous product is to place the powder under a microscope and polarized light to observe the morphology and the presence of crystal luster. Further, powder X-ray, differential calorimetry, infrared spectroscopy and other methods can be used to check whether the crystalline state of trilobatin and glycyrrhizic acid is converted into an amorphous state.

[0023] The inventors have verified through experiments that the co-amorphous material obtained by the solvent evaporation method has the highest product yield, a simple preparation process, and the obtained product has the best water solubility.

[0024] The trilobatin-glycyrrhizic acid co-amorphous material provided by the invention has a simple preparation method, good reproducibility and improved sweetness.

[0025] The inventors have verified that trilobatin-glycyrrhizic acid co-amorphous compound can solubilize other poorly soluble bitter drugs and also has a taste-masking effect.

[0026] In summary, the inventors have found through unexpected research that the co-amorphous substance prepared by mixing trilobatin and glycyrrhizic acid components can produce an extremely significant effect of improving water solubility, which is far greater than the solubilization effect of a simple mixture of trilobatin and glycyrrhizic acid. At the same time, this co-amorphous substance can solubilize other poorly soluble drugs, which is beneficial to improve their dissolution and absorption. In addition, no auxiliary materials are required in the process of preparing the co-amorphous substance, which saves costs, has good repeatability and excellent stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 These are the microscopic and polarized images of the trilobatin-glycyrrhizic acid co-amorphous product prepared in Examples AG, A1 is a 40×10 optical micrograph, A2 is a 10×10 optical micrograph, A3 is a 10×10 polarized micrograph, and the following images are the same as above.

[0028] Figure 2(ad) are evaluation diagrams of Example 2 of the present invention; 2a is a solubility comparison diagram of the trilobatin-glycyrrhizic acid co-amorphous product (molar ratio 1:1) prepared in Example 2, the raw material drug and the physical mixture; 2b is an X-ray diffraction diagram; 2c is a differential calorimetry scanning diagram; and 2d is a Fourier transform infrared scanning diagram.

[0029] Figure 3 These are the microscopic and polarized images of the single or mixed products of trilobatin-glycyrrhizic acid prepared in Comparative Examples AF, A1 is a 40×10 optical microscopic image, A2 is a 10×10 optical microscopic image, A3 is a 10×10 polarized microscopic image, and the following figures are the same as above.

[0030] Figure 4 The following are the appearance comparison diagrams of the co-amorphous prepared in Example 2 of the present invention after solubilization of other poorly soluble drugs. A1 / A2 are the appearance comparison diagrams of the co-amorphous solubilization of mangiferin (the left tube contains the co-amorphous, and the right tube does not); B1 / B2 are the appearance and darkroom laser comparison diagrams of glycyrrhizic acid solubilizing mangiferin in an amount equal to that of the co-amorphous; C1 / C2 are the appearance and darkroom laser comparison diagrams of whether trilobatin solubilizes mangiferin.

[0031] Figure 5 This is a comparison chart of the saturated solubility of mangiferin in the co-amorphous material prepared in Example 2 of the present invention and in aqueous solutions of glycyrrhizic acid of different concentrations. DETAILED DESCRIPTION

[0032] Example 1: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 2:1), dissolve them completely in methanol and mix them evenly, evaporate them naturally at room temperature, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 A1-A3 in .

[0033] Example 2: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), dissolve them completely in methanol and mix them evenly, evaporate them naturally at room temperature, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 B1-B3 in.

[0034] Example 3: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:2), dissolve them completely in methanol and mix them evenly, evaporate them naturally at room temperature, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 C1-C3 in .

[0035] Example 4: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), add zirconium oxide microbeads and grind for 3 hours, and collect the powder through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 D1-D3 in.

[0036] Example 5: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:3), dissolve them completely in ethanol and mix them evenly, evaporate them naturally at room temperature, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 E1-E3 in .

[0037] Example 6: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), completely dissolve in a 1:1 mixed solvent of methanol and ethanol, mix evenly, evaporate to dryness at room temperature, and grind through an 80-mesh sieve to obtain a trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 F1-F3 in.

[0038] Example 7: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), dissolve them completely in 1,4-dioxane solvent and mix them evenly, evaporate them naturally at room temperature, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid co-amorphous product. Figure 1 G1-G3 in.

[0039] Example 8: Weigh an equal amount of the sample to be tested, place it in a conical flask, add 200 mL of ultrapure water, ultrasonicate for 30 minutes, and stir with a magnetic stirrer for 30 minutes. Place it in a high-speed centrifuge, centrifuge for 5 minutes, take the upper clear liquid, and measure 60 mL of each and place it in the electronic tongue measuring cup for measurement. The results are shown in the table below. The sweetness value of the co-amorphous substance with a molar ratio of glycyrrhizic acid: trilobatin of 1:1 is higher than that of the raw material and the physical mixture, which may be due to the increased solubility of the co-amorphous substance, resulting in an increase in its sweetness value.

[0040] sample Trilobatin Glycyrrhizic acid Glycyrrhizic acid: trilobatin (molar ratio 1:1) physical mixture Glycyrrhizic acid:trilobatin (molar ratio 1:1) co-amorphous Sweetness value 12.8 13.49 12.5 33.99

[0041] Example 9: Determination of equilibrium solubility of trilobatin and glycyrrhizic acid: The equilibrium solubility of trilobatin and glycyrrhizic acid in Example 2 of the present invention was investigated: an excess of trilobatin and glycyrrhizic acid API, trilobatin-glycyrrhizic acid co-amorphous substance, and a physical mixture of equal proportions of the co-amorphous substance were taken, respectively, and an appropriate amount of water was added, and the mixture was placed in a constant temperature air bath shaker (37°C, 120r / min), shaken for 72 h, taken out and immediately centrifuged, the supernatant was taken, and diluted with the corresponding solvent, and the absorption peak area was determined by HPLC, and the equilibrium solubility of trilobatin and glycyrrhizic acid (Mean±SD, n=3) was calculated. The results are as follows Figure 2 As shown in a. In the product prepared by the co-amorphous technology, the solubility of trilobatin increased significantly, about 20 times compared with the raw material drug. In addition, when trilobatin and glycyrrhizic acid were treated in a physical mixing manner, its solubility also increased, about 4 times. These results show that the application of co-amorphous technology has a significant effect in improving the solubility of trilobatin. At the same time, after glycyrrhizic acid formed a co-amorphous system with trilobatin, its solubility was also improved to a certain extent.

[0042] Example 10: Characterization of properties of trilobatin-glycyrrhizic acid co-amorphous compound.

[0043] Take an appropriate amount of the co-amorphous material obtained in Example 2 and scan it with a powder X-ray diffractometer (PXRD). The measurement conditions are: scanning angle 5θ, step length 0.05°, scanning speed 5° / min, and scanning range 3-75°. The results are shown in Figure 2 b. The characteristic peaks of the product formed in Experimental Example 1 disappeared, confirming that it was amorphous, that is, glycyrrhizic acid-trilobatin amorphous; while the trilobatin API and its physical mixture with glycyrrhizic acid both showed characteristic diffraction peaks, confirming that it was crystalline. After trilobatin and glycyrrhizic acid were co-evaporated with methanol in a ratio of 1:1, the characteristic peaks between 10-30° disappeared significantly, while the characteristic peaks under the physical mixture did not disappear, indicating that the product prepared by co-evaporation was amorphous.

[0044] Take an appropriate amount of the co-amorphous material obtained in Example 2 and scan it with a differential scanning calorimeter (DSC). The measurement conditions are: using a blank crucible as a reference, heating rate 10°C / min, test temperature range 30-350°C, testing under nitrogen protection conditions, and gas flow rate 10mL / min. The results are shown in Figure 2 c. Figure 2 c shows that after the co-evaporation product was prepared in a 1:1 ratio, the melting point peak of trilobatin at 180 °C disappeared, indicating that the co-evaporation product prepared was amorphous.

[0045] Take an appropriate amount of the amorphous material obtained in Example 2 and grind it into fine powder; take an appropriate amount of dry gel powder, add a certain amount of KBr, grind it evenly and press it into tablets; use Fourier transform infrared spectrometer to measure the sample at 4000~400cm -1 The results are as follows: Figure 2 d, the amorphous product prepared in Example 1 was 3412, 2850, 1650, 1400, 1045 cm -1 There are characteristic absorptions in other places, which are obviously different from the spectra of raw materials and physical mixtures, indicating the formation of new images.

[0046] Example 11: Weigh 1.5 mg of mangiferin, weigh an equal amount of mangiferin and mix with 15 mg of the co-amorphous substance prepared in Example 2, and then disperse them in 2 mL of water respectively; similarly, weigh 30 mg of glycyrrhizic acid or trilobatin, mix with mangiferin (3 mg) respectively, and disperse them in 4 mL of water. By comparing the clarity of the two solutions, i.e. observing their transparency and particle suspension, the appearance is as shown in the figure below. Figure 4It can be clearly seen that the co-amorphous material prepared by the method of the present invention significantly improves the solubility of the poorly soluble drug mangiferin in water, thereby making the solution appearance clearer, while in the appearance picture with glycyrrhizic acid added, the sample forms an opaque gel, and in the appearance picture with trilobatin added, the sample is extremely turbid. Therefore, the co-amorphous material of the present invention can increase the solubility of poorly soluble drugs. The bitter drug after adding the co-amorphous product of the present invention changes from slightly bitter to sweet, indicating that the co-amorphous product of the present invention has excellent taste masking function.

[0047] Example 12: The co-amorphous substance prepared in Example 2 and glycyrrhizic acid were prepared into a series of aqueous solutions of different concentrations, and an excess of mangiferin API was added thereto. At the same time, a supersaturated mangiferin suspension was prepared separately as a blank group; it was placed in a constant temperature air bath shaker (37°C, 120r / min), and shaken continuously for 72 h. It was taken out and immediately centrifuged. The supernatant was taken and diluted with the corresponding solvent. The absorption peak area was determined by HPLC, and the equilibrium solubility of mangiferin was calculated (Mean±SD, n=3). The results showed that the solubility of mangiferin API was 0.128±0.0002 mg / mL; and the co-amorphous substance and glycyrrhizic acid obtained in the present invention can significantly improve the saturated solubility of mangiferin, such as Figure 5 , and the solubilization ability of the co-amorphous substance on mangiferin is significantly better than that of glycyrrhizic acid at the same concentration, indicating that the product of the present invention improves the solubility of poorly soluble drugs and has better performance than glycyrrhizic acid.

[0048] During the screening process, the following experiments were also conducted, which are used as comparative examples: Comparative Example 1: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 3:1), dissolve them completely in methanol and mix them evenly, place them at room temperature to evaporate naturally, and crush them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid recrystallized product. Microscopic and polarized light Figure 3 A1-A3 in .

[0049] Comparative Example 2: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 4:1), dissolve them completely in methanol and mix them evenly, place them at room temperature to evaporate naturally, and crush them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid recrystallized product. Figure 3 B1-B3 in.

[0050] Comparative Example 3: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), physically mix them evenly, and grind them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid product. Figure 3 C1-C3 in .

[0051] Comparative Example 4: Weigh an appropriate amount of trilobatin, dissolve it completely in methanol and mix it evenly, place it at room temperature to evaporate naturally, and crush the trilobatin recrystallized product through an 80-mesh sieve. Figure 3 D1-D3 in.

[0052] Comparative Example 5: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), dissolve them completely in dichloromethane and mix them evenly, evaporate them naturally at room temperature, and crush them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid recrystallized product. Figure 3 E1-E3 in .

[0053] Comparative Example 6: Weigh appropriate amounts of trilobatin and glycyrrhizic acid (molar ratio of 1:1), dissolve them completely in ethyl acetate and mix them evenly, place them at room temperature to evaporate naturally, and crush them through an 80-mesh sieve to obtain trilobatin-glycyrrhizic acid recrystallized product. Figure 3 F1-F3 in.

Claims

1. A trilobatin-glycyrrhizic acid co-amorphous compound, characterized in that: The invention is composed of two components, trilobatin and glycyrrhizic acid, and does not need to add any other auxiliary materials. The water solubility of trilobatin and glycyrrhizic acid in the co-amorphous material is higher than that of a single component and a physical mixture thereof, and the sweetness of the co-amorphous material is better than that of a single component and a physical mixture thereof.

2. The trilobatin-glycyrrhizic acid co-amorphous material according to claim 1, characterized in that: The molar ratio of trilobatin to glycyrrhizic acid is not higher than 2:

1.

3. The trilobatin-glycyrrhizic acid co-amorphous material according to claim 2, characterized in that: The molar ratio of trilobatin to glycyrrhizic acid is 1:

1.

4. The trilobatin-glycyrrhizic acid co-amorphous material according to claim 1, characterized in that: The co-amorphous material is in an amorphous state, has no birefringence phenomenon under a polarizing microscope, and has no characteristic diffraction peak on a powder X-ray diffraction spectrum.

5. A method for preparing the trilobatin-glycyrrhizic acid co-amorphous product according to claim 1, characterized in that: The preparation method is prepared by a solvent volatilization method or a ball milling method; the solvent volatilization method is to take trilobatin and glycyrrhizic acid raw materials in a molar ratio, add a solvent to make it fully solventized, and then evaporate the solvent to obtain the product; the ball milling method is to take trilobatin and glycyrrhizic acid raw materials in a molar ratio, continuously grind, and obtain an amorphous substance.

6. The method for preparing trilobatin-glycyrrhizic acid co-amorphous material according to claim 5, characterized in that: The solvent is one or more of methanol, ethanol and 1,4-dioxane.

7. Use of the trilobatin-glycyrrhizic acid co-amorphous product according to claim 1 in the preparation of medicines or foods, characterized in that: The co-amorphous material is used to improve the solubility of other poorly soluble components in water.

8. The use according to claim 7, characterized in that: The other poorly soluble component is mangiferin.

9. Use of the trilobatin-glycyrrhizic acid co-amorphous product according to claim 1 in the preparation of medicines or foods, characterized in that: The co-amorphous material is used as a sweetener; or the co-amorphous material is used as a taste masking agent; or the co-amorphous material is used to improve the water solubility of trilobatin and / or glycyrrhizic acid.

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