A ternary amorphous compound of baicalin-piperine-resveratrol, its preparation method and application

Abstract

This invention discloses a ternary amorphous compound of baicalin, piperine, and resveratrol, its preparation method, and its applications. The ternary amorphous compound is prepared from baicalin, piperine, and resveratrol in a molar ratio of 1:(1-4):1. Powder X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy show that the prepared ternary amorphous compound is an amorphous form distinct from individual components and physical mixtures. Compared to individual components, the apparent solubility of baicalin, piperine, and resveratrol in the ternary amorphous compound is significantly improved, its physical stability is superior to that of binary amorphous compounds, and it exhibits significantly enhanced antibacterial, antioxidant, and anti-inflammatory activities, demonstrating an enhanced synergistic pharmacological effect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a ternary amorphous compound of baicalin-piperine-resveratrol, its preparation method, and its application. Background Technology

[0002] Baicalein, chemically known as 5,6,7-trihydroxyflavone, is primarily derived from the root extract of Scutellaria baicalensis (a member of the Lamiaceae family). Its chemical formula is C1. 15 H 10 O5. Baicalein possesses a wide range of pharmacological effects, including antitumor, antibacterial, antioxidant, and anti-inflammatory properties, as well as effects on improving cerebral blood circulation and inhibiting platelet aggregation. It also has positive effects on obesity-related complications and non-alcoholic fatty liver disease. However, baicalein has poor water solubility and low oral bioavailability, which greatly limits its clinical application.

[0003] Resveratrol is a non-flavonoid polyphenol compound and a bioactive component found in wine and grape juice. Its chemical formula is C2. 14 H 12 O3. Resveratrol possesses a wide range of pharmacological activities, such as antioxidant, anti-inflammatory, and anti-tumor effects. Furthermore, resveratrol is considered one of the most effective anti-aging substances and also has effects in improving metabolic syndrome, Alzheimer's disease, and kidney disease. However, its poor solubility, low bioavailability, and rapid metabolism limit its application.

[0004] Piperine, also known as piperamide, is extracted from the mature fruit of the pepper plant (Piper nigrum), a member of the Piperaceae family. Its chemical formula is C1. 17 H 19 NO3. Piperine possesses various pharmacological activities, such as antitumor, antibacterial, antioxidant, and anti-inflammatory effects. Furthermore, piperine is a natural bioavailability enhancer; when used in combination with other drugs, it can improve drug efficacy and increase bioavailability. However, the fact that piperine is almost insoluble in water limits its clinical application.

[0005] Co-amorphous compounds are amorphous systems composed of two or more small molecules linked by intermolecular forces (such as hydrogen bonds, π-π stacking, and van der Waals forces). Compared to crystalline substances, amorphous compounds possess higher Gibbs free energy and are more easily hydrated, thus they are used to improve the solubility and dissolution rate of poorly soluble drugs, thereby enhancing their bioavailability. Furthermore, co-amorphous systems composed of two or more drugs may produce synergistic pharmacological effects or reduce adverse reactions caused by single-drug administration. Therefore, the combined preparation of multiple drugs into co-amorphous systems has attracted considerable attention in the pharmaceutical industry, especially given the synergistic drug use characteristics of traditional Chinese medicine involving multiple components, targets, and pathways. However, co-amorphous systems are thermodynamically unstable, and their physical stability requires further consideration. Studies have shown that ternary co-amorphous systems are more stable than binary systems. Based on this, this invention designs a ternary co-amorphous compound from baicalein, piperine, and resveratrol to improve drug solubility and dissolution rate. Summary of the Invention

[0006] One objective of this invention is to provide a ternary amorphous compound of baicalin-piperine-resveratrol, which is made of baicalin, piperine and resveratrol, wherein the molar ratio of baicalin, piperine and resveratrol is 1:(1-4):1.

[0007] In their early experiments, the inventors discovered that increasing the proportion of baicalein or resveratrol did not yield a pure amorphous solid.

[0008] Furthermore, the glass transition temperature of the baicalin-piperine-resveratrol ternary amorphous compound is 40-110℃.

[0009] Furthermore, the ternary amorphous compound of baicalin-piperine-resveratrol does not exhibit sharp crystalline diffraction peaks in its powder X-ray diffraction pattern.

[0010] The second objective of this invention is to provide a method for preparing the above-mentioned ternary amorphous compound of baicalin-piperine-resveratrol, wherein baicalin, piperine and resveratrol are mixed and dissolved in an organic solvent, the solvent is removed by rotary evaporation and then dried to obtain the compound.

[0011] Furthermore, the organic solvent is one or a mixture of several of methanol, acetone or anhydrous ethanol, preferably a mixture of methanol and acetone (1:2-2:1, v / v).

[0012] Furthermore, the temperature of the rotary evaporation is 50-70°C, preferably 50-60°C.

[0013] A third objective of this invention is to provide a pharmaceutical formulation comprising the above-mentioned ternary amorphous compound of baicalein-piperine-resveratrol, and pharmaceutically acceptable excipients and / or carriers.

[0014] The pharmaceutically acceptable excipients and / or carriers are those known to those skilled in the art, such as lactose, microcrystalline cellulose, starch, etc. The dosage form of the pharmaceutical preparation may be tablets, capsules, etc.

[0015] The beneficial effects of this invention are as follows:

[0016] 1. The ternary amorphous compound of baicalin-piperine-resveratrol provided by the present invention has a simple preparation method, requires no other excipients, and has good reproducibility.

[0017] 2. Compared with the three crystalline drugs baicalein, piperine, and resveratrol, the apparent solubility of the drugs in the ternary co-amorphous compound of baicalein-piperine-resveratrol is significantly improved; compared with the binary co-amorphous systems of baicalein-piperine and resveratrol-piperine, the ternary co-amorphous compound has improved physical stability during dissolution and storage.

[0018] 3. Antibacterial, anti-inflammatory, and antioxidant tests showed that the baicalin-piperine-resveratrol ternary amorphous compound had enhanced antibacterial, anti-inflammatory, and antioxidant activities. Attached Figure Description

[0019] Figure 1 The powder X-ray diffraction (PXRD) pattern of the ternary amorphous compound of baicalin-piperine-resveratrol (1:1:1) in Example 1 is shown.

[0020] Figure 2 The PXRD pattern of the ternary amorphous compound of baicalin-piperine-resveratrol (1:2:1) in Example 2 is shown.

[0021] Figure 3 The PXRD pattern of the ternary amorphous compound of baicalin-piperine-resveratrol (1:3:1) in Example 3 is shown.

[0022] Figure 4 The PXRD pattern of the ternary amorphous compound of baicalin-piperine-resveratrol (1:4:1) in Example 4 is shown.

[0023] Figure 5 The PXRD pattern of the baicalin-piperine (1:1) binary co-amorphous compound in Comparative Example 1 is shown.

[0024] Figure 6 The PXRD pattern of the resveratrol-piperine (1:1) binary co-amorphous compound in Comparative Example 2 is shown.

[0025] Figure 7The modulated differential scanning calorimetry (MDSC) spectrum of the ternary co-amorphous compound of baicalein-piperine-resveratrol (1:1:1) in Example 1 is shown.

[0026] Figure 8 The Fourier transform infrared (FTIR) spectrum of the ternary amorphous compound of baicalin-piperine-resveratrol (1:1:1) in Example 1 is shown.

[0027] Figure 9 The image shows the supersaturated dissolution curves of baicalein-piperine-resveratrol (1:1:1) ternary amorphous compound, physical mixture, and baicalein in pH 6.8 phosphate buffer solution in Example 1.

[0028] Figure 10 The image shows the supersaturated dissolution curve of piperine in pH 6.8 phosphate buffer, representing the ternary amorphous compound, physical mixture, and piperine from Example 1 (baicalin-piperine-resveratrol (1:1:1)).

[0029] Figure 11 The image shows the supersaturated dissolution curves of resveratrol in pH 6.8 phosphate buffer, representing the amorphous and physical mixture of the baicalein-piperine-resveratrol (1:1:1) ternary co-amorphous compound, resveratrol, and resveratrol in Example 1.

[0030] Figure 12 The PXRD patterns of the baicalein-piperine-resveratrol (1:1:1) ternary co-amorphous compound, the baicalein-piperine (1:1) binary co-amorphous compound, and the resveratrol-piperine (1:1) binary co-amorphous compound in Example 1 after being placed at 40°C for a certain period of time.

[0031] Figure 13 The diagram shows the inhibition zones of the ternary amorphous compound of baicalein-piperine-resveratrol (1:1:1), baicalein-piperine (1:1) amorphous compound, baicalein, piperine, and resveratrol against (A) Escherichia coli and (B) methoxyaureus-resistant Staphylococcus aureus (MRSA) in Example 1.

[0032] Figure 14 The graph shows the antioxidant capacity of the ternary amorphous compound of baicalein-piperine-resveratrol (1:1:1) in Example 1 compared with that of the raw materials of baicalein, piperine and resveratrol, as determined by the ABTS method.

[0033] Figure 15 The graph shows the antioxidant capacity of the ternary amorphous compound of baicalein-piperine-resveratrol (1:1:1) in Example 1 compared with that of the raw materials of baicalein, piperine, and resveratrol, as determined by the DPPH method.

[0034] Figure 16The graph shows the anti-inflammatory activity of the ternary amorphous compound of baicalein-piperine-resveratrol (1:1:1) in Example 1 compared with that of the raw materials of baicalein, piperine, and resveratrol, as determined by the NO method. Detailed Implementation

[0035] The preferred embodiments of the present invention will now be described in detail with reference to specific examples. It should be understood that the following examples are given for illustrative purposes only and are not intended to limit the scope of the invention. Those skilled in the art can make various modifications and substitutions to the present invention without departing from its spirit and essence.

[0036] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0037] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0038] Example 1

[0039] 108.1 mg baicalein (0.4 mmol), 114.1 mg piperine (0.4 mmol), and 91.3 mg resveratrol (0.4 mmol) were weighed into 100 mL round-bottom flasks, and 50 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0040] Example 2

[0041] 54.0 mg of baicalein (0.2 mmol), 114.1 mg of piperine (0.4 mmol), and 45.6 mg of resveratrol (0.2 mmol) were weighed into 100 mL round-bottom flasks, and 30 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0042] Example 3

[0043] 54.0 mg of baicalein (0.2 mmol), 171.2 mg of piperine (0.6 mmol), and 45.6 mg of resveratrol (0.2 mmol) were weighed into 100 mL round-bottom flasks, and 30 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and placed in a desiccator containing calcium chloride, stored at 4 °C.

[0044] Example 4

[0045] 54.0 mg of baicalein (0.2 mmol), 228.2 mg of piperine (0.8 mmol), and 45.6 mg of resveratrol (0.2 mmol) were weighed into 100 mL round-bottom flasks, and 30 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and placed in a desiccator containing calcium chloride, stored at 4 °C.

[0046] Example 5

[0047] 135.1 mg baicalein (0.5 mmol), 142.7 mg piperine (0.5 mmol), and 114.1 mg resveratrol (0.5 mmol) were weighed into 250 mL round-bottom flasks, and 80 mL of methanol was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 50 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0048] Example 6

[0049] 162.1 mg baicalein (0.6 mmol), 171.2 mg piperine (0.6 mmol), and 136.9 mg resveratrol (0.6 mmol) were weighed into 250 mL round-bottom flasks, and 80 mL of acetone was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 50 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0050] Example 7

[0051] 108.1 mg baicalein (0.4 mmol), 114.1 mg piperine (0.4 mmol), and 91.3 mg resveratrol (0.4 mmol) were weighed into 100 mL round-bottom flasks, and 50 mL of acetone-methanol (50:50, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 60 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0052] Comparative Example 1

[0053] 108.1 mg of baicalein (0.4 mmol) and 114.1 mg of piperine (0.4 mmol) were weighed into 100 mL round-bottom flasks, and 50 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The solutions were sonicated at room temperature until clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powders. The powders were dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powders were then pulverized through an 80-mesh sieve and stored in a desiccator containing calcium chloride at 4 °C.

[0054] Comparative Example 2

[0055] 91.3 mg of resveratrol (0.4 mmol) and 114.1 mg of piperine (0.4 mmol) were weighed into 100 mL round-bottom flasks, and 50 mL of acetone-methanol (1:1, v / v) mixed solvent was added. The mixture was sonicated at room temperature until the solution became clear. The solvent was removed by rotary evaporation under reduced pressure at 55 °C to obtain the corresponding solid powder. The powder was dried in a vacuum drying oven at room temperature for 24 h to remove residual solvent from the rotary evaporation product. The resulting powder was then pulverized through an 80-mesh sieve and placed in a desiccator containing calcium chloride, and stored at 4 °C.

[0056] The samples prepared in the above embodiments and comparative examples will now be tested.

[0057] Test Example 1

[0058] PXRD spectra of the samples were collected using an X-ray diffractometer (Malvern Panalytical, United Kingdom) within the range of 2θ from 5° to 40°. The radiation source for the instrument was Cu-Kα. The tube voltage and tube current were set to 45kV and 40mA, respectively, the scan rate was 4° / min, and the step size was 0.02°.

[0059] like Figures 1-4 As shown, in the PXRD spectrum of the ternary amorphous compound of baicalein-piperine-resveratrol prepared by rotary evaporation, the crystallization peak of the active pharmaceutical ingredient completely disappeared, and a single diffuse diffraction ring was observed, proving that a new amorphous solid morphology was successfully prepared.

[0060] like Figure 5 and Figure 6 As shown, baicalin-piperine binary co-amorphous compounds and resveratrol-piperine binary co-amorphous compounds were also prepared.

[0061] Test Example 2

[0062] The MDSC spectrum of the samples was detected using a modulated differential scanning calorimeter (DSC 250, TA Instruments, USA). 3-5 mg of sample was heated in the temperature range of 5℃ to 300℃ at a heating rate of 2℃ / min, and the curves of total heat flux, reversible heat flux, and irreversible heat flux versus temperature were recorded.

[0063] like Figure 7 As shown, a single glass transition temperature was observed in the MDSC spectrum of the ternary co-amorphous compound of baicalin-piperine-resveratrol, which is different from the melting peak of the crystalline component, proving the successful formation of the ternary co-amorphous compound.

[0064] Test Example 3

[0065] Approximately 2 mg of sample was compressed with 200 mg of KBr into a tablet, and Fourier transform infrared spectroscopy (FTIR) was performed at 4000–500 cm⁻¹. -1 The sample was measured within the specified range, with a resolution of 4.0 cm. -1 The number of scans was 64.

[0066] like Figure 8 As shown, compared with the active pharmaceutical ingredient and the ternary physical mixture of baicalein-piperine-resveratrol (1:1:1), the stretching vibration peak of the phenolic hydroxyl group of baicalein in the FTIR spectrum of the ternary co-amorphous compound of baicalein-piperine-resveratrol (1:1:1) is significantly higher (3409.5 cm⁻¹). -1 The peak of the stretching vibration of the piperine carbonyl group (1633.9 cm⁻¹) disappears. -1 The resveratrol phenolic hydroxyl group disappears, and the in-plane bending vibration of the resveratrol hydroxyl group decreases from 1384.2 cm⁻¹. -1 Moved to 1369.2cm -1 Furthermore, the benzene rings of the three components also underwent peak shifts, indicating that there was an interaction between the molecules of baicalin, piperine, and resveratrol in the ternary co-amorphous compound, further proving the formation of the new solid form.

[0067] Test Example 4

[0068] The supersaturated dissolution rate of the sample in pH 6.8 phosphate buffer solution was determined using a dissolution analyzer. The sample was added to 200 mL of phosphate buffer solution (pH = 6.8) at 25 °C with a stirrer speed of 100 rpm. Samples (3 mL) were taken at 1, 2, 4, 8, 12, 16, and 24 hours, and an equal volume of dissolution medium at the same temperature was immediately added. The collected solutions were filtered through a 0.22 μm microporous membrane, appropriately diluted with methanol, and the drug concentration was determined by HPLC. Each sample was measured in triplicate.

[0069] High-performance liquid chromatography (HPLC) determination conditions: The detection system was a Shimadzu LC-2050, the chromatographic column was an Ultimate XB-C18 (250 mm × 4.6 mm, 5 μm), the mobile phase was acetonitrile-0.1% phosphoric acid aqueous solution (50:50, v / v), the flow rate was 1 mL / min, the column temperature was 30 ℃, and the detection wavelengths for baicalein, piperine, and resveratrol were 280 nm, 342 nm, and 306 nm, respectively; the injection volume was 10 μL.

[0070] like Figures 9-11 As shown, compared with baicalein, piperine, and resveratrol crystals, the apparent solubilities of the three components in the baicalein-piperine-resveratrol (1:1:1) ternary co-amorphous compound are 26.0 μg / mL, 22.6 μg / mL, and 53.3 μg / mL, respectively, which are 3.2 times, 5.3 times, and 4.3 times that of their corresponding crystals, and they maintain a high supersaturation for at least 24 hours.

[0071] Test Example 5

[0072] The newly prepared ternary amorphous compound of baicalin-piperine-resveratrol was placed in a high-temperature environment of 40℃ for stability testing, and samples were taken at fixed time points to test the crystallization of the samples by PXRD.

[0073] like Figure 12 As shown, compared with the baicalein-piperine binary co-amorphous compound and the resveratrol-piperine binary co-amorphous compound, the baicalein-piperine-resveratrol ternary co-amorphous compound retains its amorphous form for at least 30 days, exhibiting a single diffuse diffraction ring and demonstrating better physical stability.

[0074] Test Example 6

[0075] The antibacterial activity of the ternary amorphous compound of baicalin-piperine-resveratrol was evaluated using the paper disc diffusion method. 100 μL (10 6E. coli and MRSA bacterial suspensions (CFU / mL) were evenly spread on the surface of LB agar plates. 15 μL of sample solution (7.4 mM) was added dropwise onto a circular sterile paper disc (6 mm in diameter, 0.7 mm thick), which was then placed on the LB agar plate and incubated at 37°C for 16 h. DMSO solution was used as a negative control. The antibacterial activity of the samples was assessed by measuring the diameter (mm) of the inhibition zone formed around the sample. The experiment was repeated three times.

[0076] like Figure 13 As shown, compared with baicalin, piperine, and resveratrol crystals, the ternary amorphous compound of baicalin-piperine-resveratrol exhibits a synergistically enhanced antibacterial effect.

[0077] Test Example 7

[0078] The antioxidant capacity of the baicalein-piperine-resveratrol ternary amorphous compound was evaluated using the ABTS and DPPH methods. For the ABTS assay, 10 μL of a series of sample solutions of varying concentrations was mixed with 190 μL of ABTS working solution in a 96-well plate. After reacting for 6 minutes, the absorbance at 734 nm was measured using a microplate reader. For the DPPH assay, 400 μL of a series of sample solutions of varying concentrations was mixed with 600 μL of DPPH working solution in a 96-well plate. After reacting for 30 minutes, the absorbance at 517 nm was measured using a microplate reader. Each experiment was repeated three times.

[0079] like Figure 14 and Figure 15 As shown, compared with baicalein, piperine, and resveratrol crystals, the ternary amorphous compound of baicalein-piperine-resveratrol has superior antioxidant capacity compared with each of the raw materials.

[0080] Test Example 8

[0081] Mouse mononuclear macrophages (Raw 264.7) in the logarithmic growth phase were harvested at a concentration of 2 × 10⁻⁶. 5 Cells were seeded at a density of 1 μg / mL in 24-well plates and incubated for 24 hours. Cells were then pretreated with different concentrations of sample for 2 hours, followed by treatment with lipopolysaccharide (1 μg / mL) for 24 hours. The culture supernatant was collected, and NO was measured using Griess reagent according to the kit instructions. Each sample was measured in triplicate.

[0082] like Figure 16 As shown, compared with baicalein, piperine, and resveratrol crystals, the ternary amorphous compound of baicalein-piperine-resveratrol exhibits increased anti-inflammatory activity within a certain concentration range.

Claims

1. A ternary amorphous compound of baicalin-piperine-resveratrol, characterized in that, It is made from baicalin, piperine and resveratrol. The preparation process is as follows: baicalin, piperine and resveratrol are mixed and dissolved in an organic solvent, the solvent is removed by rotary evaporation and then dried. The molar ratio of baicalein, piperine and resveratrol is 1:(1-4):

1.

2. The ternary amorphous compound of baicalin-piperine-resveratrol according to claim 1, characterized in that, The glass transition temperature of the ternary amorphous compound of baicalin-piperine-resveratrol is 40-110 °C.

3. The ternary amorphous compound of baicalin-piperine-resveratrol according to claim 1, characterized in that, The ternary amorphous compound of baicalin-piperine-resveratrol showed no sharp crystalline diffraction peaks in its powder X-ray diffraction pattern.

4. The method for preparing the ternary amorphous compound of baicalin-piperine-resveratrol according to claim 1, characterized in that, Baicalein, piperine, and resveratrol are mixed and dissolved in an organic solvent, the solvent is removed by rotary evaporation, and then dried to obtain the final product.

5. The preparation method according to claim 4, characterized in that, The organic solvent is one or a mixture of several of methanol, acetone or anhydrous ethanol.

6. The preparation method according to claim 5, characterized in that, The organic solvent is a mixture of methanol and acetone.

7. The preparation method according to claim 6, characterized in that, The volume ratio of methanol to acetone in the mixed solvent is 1:2 to 2:

1.

8. The preparation method according to claim 4, characterized in that, The temperature of the rotary evaporation is 50-70 ℃.

9. The preparation method according to claim 8, characterized in that, The temperature of the rotary evaporation is 50-60 ℃.

10. A pharmaceutical preparation, characterized in that, It includes the ternary amorphous compound of baicalein-piperine-resveratrol as described in claim 1, and pharmaceutically acceptable excipients.

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