A flufenamic acid-ichimbine co-amorphous substance, a preparation method and application thereof

Abstract

The application provides a flufenamic acid-oxymatrine co-amorphous substance and a preparation method and application thereof, and belongs to the technical field of medicines.The flufenamic acid-oxymatrine co-amorphous substance is composed of flufenamic acid and oxymatrine in a molar ratio of 3:1-1:3, and the co-amorphous substance is prepared by a grinding method or a solution crystallization method.The flufenamic acid-oxymatrine co-amorphous substance has good stability, can significantly improve the solubility of flufenamic acid in water, thereby improving the bioavailability of flufenamic acid, and can also have synergistic effects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a flufenamic acid-sticky alkaloid co-amorphous compound, its preparation method, and its application. Background Technology

[0002] Flufenamic acid (Flu) is a nonsteroidal anti-inflammatory drug (NSAID) that exerts its anti-inflammatory, analgesic, and antipyretic effects by inhibiting cyclooxygenase (COX) activity and reducing the synthesis of inflammatory mediators (prostaglandins). Flufenamic acid is mainly used for short-term symptom relief of inflammatory diseases such as osteoarthritis, rheumatoid arthritis, and soft tissue injuries.

[0003] According to the Biopharmaceutics Classification System (BCS), flufenamic acid belongs to BCS Class II drugs, which are characterized by poor water solubility, resulting in low oral bioavailability. Therefore, improving the solubility of flufenamic acid is of great significance. Summary of the Invention

[0004] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a flufenamic acid-matrine co-amorphous compound, its preparation method and application. The co-amorphous compound has good stability, can significantly improve the solubility of flufenamic acid in water, thereby improving the bioavailability of flufenamic acid, and can also have a synergistic effect.

[0005] To achieve this objective, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides a flufenamic acid-stigmaine co-amorphous compound, wherein the flufenamic acid-stigmaine co-amorphous compound is composed of flufenamic acid and stigmaine in a molar ratio of 3:1 to 1:3.

[0007] The molar ratio of flufenamic acid to picrophylline can be, for example, 3:1, 2.8:1, 2.6:1, 2.5:1, 2.3:1, 2.2:1, 2:1, 1.8:1, 1.6:1, 1.5:1, 1.3:1, 1.2:1, 1:1, 1:1.2, 1:1.3, 1:1.5, 1:1.6, 1:1.8, 1:2, 1:2.2, 1:2.3, 1:2.5, 1:2.6, 1:2.8, or 1:3, etc. However, the invention is not limited to this, and other unlisted values ​​within this range are also applicable.

[0008] The molecular formula of flufenamic acid is C2 14 H 10 F3NO2 has the structural formula shown in Formula I.

[0009]

[0010] Aloperine (Alo) has the molecular formula C0. 15 H 24 N2, whose structural formula is shown in Formula II.

[0011]

[0012] Sophora flavescens is a quinoline alkaloid extracted from sophora flavescens. It is often used clinically to treat dysentery and has good anti-inflammatory, antioxidant, antiviral and analgesic effects.

[0013] This invention uses flufenamic acid as the active pharmaceutical ingredient and stigmine as the drug ligand to prepare a co-amorphous compound. This co-amorphous compound exhibits good stability under high temperature (60℃), high humidity (75% relative humidity at 25℃), and light exposure (4500 lx ± 500 lx). Its solubility in water at 37℃ (based on flufenamic acid) is more than 100 times that of the flufenamic acid raw material, significantly improving the bioavailability of flufenamic acid. Furthermore, since stigmine itself also has certain anti-inflammatory effects, the formation of the co-amorphous compound between flufenamic acid and stigmine also has a certain synergistic effect.

[0014] In some preferred embodiments of the present invention, the molar ratio of flufenamic acid to picrophylline is 1:1.

[0015] In some embodiments of the present invention, the equilibrium solubility of the flufenamic acid-sticky alkaloid co-amorphous compound in water at 37°C, calculated as flufenamic acid, is 1.01 mg / mL.

[0016] In a second aspect, the present invention provides a method for preparing the flufenamic acid-matrine co-amorphous compound as described in the first aspect, wherein the preparation method is a grinding method or a solution crystallization method;

[0017] The grinding method includes the following steps: flufenamic acid and physostigmine are soaked in a first solvent and ground until the first solvent is completely evaporated to obtain flufenamic acid-physostigmine co-amorphous product;

[0018] The solution crystallization method includes the following steps: dissolving flufenamic acid and picrophylline in a second solvent, drying, and obtaining flufenamic acid-picrophylline co-amorphous compound.

[0019] In some embodiments of the present invention, the first solvent is a combination of a 60-95 vol% aqueous ethanol solution and ethyl acetate. The concentration of the 60-95 vol% aqueous ethanol solution can be, for example, 60 vol%, 65 vol%, 70 vol%, 75 vol%, 80 vol%, 85 vol%, 90 vol%, or 95 vol%. However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0020] In some embodiments of the present invention, the volume ratio of 60-95 vol% aqueous ethanol to ethyl acetate in the first solvent is 2-3:1; for example, it can be 2:1, 2.2:1, 2.3:1, 2.5:1, 2.6:1, 2.8:1, or 3:1. However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0021] In some embodiments of the present invention, the volume ratio of the first solvent to the total mass of flufenamic acid and picrophylline is 1.8-5 mL / g; for example, it can be 1.8 mL / g, 2 mL / g, 2.2 mL / g, 2.5 mL / g, 2.8 mL / g, 3 mL / g, 3.2 mL / g, 3.5 mL / g, 3.8 mL / g, 4 mL / g, 4.2 mL / g, 4.5 mL / g, 4.8 mL / g, or 5 mL / g, etc. However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0022] In some embodiments of the present invention, the second solvent is one or a combination of 60-95 vol% aqueous ethanol solution, ethyl acetate, acetonitrile, acetone, and methanol. The concentration of the 60-95 vol% aqueous ethanol solution can be, for example, 60 vol%, 65 vol%, 70 vol%, 75 vol%, 80 vol%, 85 vol%, 90 vol%, or 95 vol%. However, the present invention is not limited thereto, and other unlisted values ​​within this range are equally applicable.

[0023] In some embodiments of the present invention, the ratio of the total mass of flufenamic acid and picrophylline to the volume of the second solvent is 1-80 mg / mL; for example, it can be 1 mg / mL, 3 mg / mL, 5 mg / mL, 8 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, or 80 mg / mL, etc. However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0024] In some embodiments of the present invention, the step of dissolving flufenamic acid and picrophylline in a second solvent includes: mixing flufenamic acid with picrophylline and a second solvent, and stirring at a speed of 500-1000 rpm (e.g., 500 rpm, 550 rpm, 600 rpm, 650 rpm, 700 rpm, 750 rpm, 800 rpm, 850 rpm, 900 rpm, 950 rpm, or 1000 rpm, etc.) for 8-10 hours (e.g., 8 hours, 8.2 hours, 8.5 hours, 8.8 hours, 9 hours, 9.2 hours, 9.5 hours, 9.8 hours, or 10 hours, etc.). However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0025] In some embodiments of the present invention, the drying method is vacuum drying, and the drying temperature is 50-70°C; for example, it can be 50°C, 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, 68°C, or 70°C, etc. However, the present invention is not limited thereto, and other unlisted values ​​within this range are also applicable.

[0026] Thirdly, the present invention provides the use of the flufenamic acid-grossine co-amorphous compound as described in the first aspect or the flufenamic acid-grossine co-amorphous compound prepared by the preparation method described in the second aspect in the preparation of analgesic and / or anti-inflammatory drugs.

[0027] Fourthly, an analgesic and / or anti-inflammatory drug comprising the flufenamic acid-grossine co-amorphous compound as described in the first aspect or the flufenamic acid-grossine co-amorphous compound prepared by the method described in the second aspect, and a pharmaceutically acceptable carrier, diluent, or excipient.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] This invention uses flufenamic acid as the active pharmaceutical ingredient and picrine as the drug ligand to prepare a co-amorphous compound. This co-amorphous compound exhibits good stability under high temperature (60℃), high humidity (75% relative humidity at 25℃), and light exposure (4500 lx ± 500 lx). Its solubility in water at 37℃ (based on flufenamic acid) is more than 100 times that of the flufenamic acid raw material, significantly improving the bioavailability of flufenamic acid. Furthermore, since picrine itself also has certain anti-inflammatory effects, the formation of the co-amorphous compound between flufenamic acid and picrine also has a synergistic effect. Therefore, the flufenamic acid-picrine co-amorphous compound provided by this invention has promising application prospects. Attached Figure Description

[0030] Figure 1AA comparison of the PXRD spectra of flufenamic acid, physostigmine, a mixture of flufenamic acid powder and physostigmine powder, and the flufenamic acid-physostigmine co-amorphous compound provided in Example 2.

[0031] Figure 1B The PXRD pattern of the powder prepared in Comparative Example 1 is shown.

[0032] Figure 2 A comparison of the DSC spectra of flufenamic acid, physostigmine, and the flufenamic acid-physostigmine co-amorphous compound provided in Example 2;

[0033] Figure 3 Infrared spectra of flufenamic acid, physostigmine, and the flufenamic acid-physostigmine co-amorphous compound provided in Example 2;

[0034] Figure 4A PXRD spectra of the flufenamic acid-matrine co-amorphous compound provided in Example 2 after being placed at high temperature for 0, 5, and 10 days;

[0035] Figure 4B PXRD spectra of the flufenamic acid-matrine co-amorphous compound provided in Example 2 after being placed under high humidity conditions for 0, 5, and 10 days;

[0036] Figure 4C PXRD spectra of the flufenamic acid-matrine co-amorphous compound provided in Example 2 after being placed under light for 0, 5, and 10 days;

[0037] Figure 5 Solubility curves of flufenamic acid and the flufenamic acid-misocyanate co-amorphous compound provided in Example 2. Detailed Implementation

[0038] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. Those skilled in the art should understand that the specific embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0039] Example 1

[0040] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0041] Accurately weigh 28.12 mg (0.1 mol) flufenamic acid and 23.23 mg (0.1 mol) picrine, place them in a mortar, add 100 μL of 95 vol% ethanol aqueous solution and 50 μL of ethyl acetate, grind for 15 min, and after the solvent has evaporated, obtain flufenamic acid-picrine co-amorphous powder.

[0042] Example 2

[0043] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0044] Accurately weigh 28.12 mg (0.1 mol) of flufenamic acid and 23.23 mg (0.1 mol) of picroline, place them in a vial, add 2 mL of 95 vol% ethanol aqueous solution, the solution is transparent, add a magnetic stir bar and place on a magnetic stirrer and stir continuously for 8 hours at a speed of 800 rpm, the solution is still transparent, place the solution in a vacuum drying oven and vacuum dry at 60℃ for 2 hours to obtain flufenamic acid-picroline co-amorphous powder.

[0045] Example 3

[0046] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0047] Accurately weigh 28.12 mg (0.1 mol) flufenamic acid and 69.69 mg (0.3 mol) picrine, place them in a mortar, add 200 μL of 60 vol% ethanol aqueous solution and 100 μL of ethyl acetate, grind for 15 min, and after the solvent has evaporated, obtain flufenamic acid-picrine co-amorphous powder.

[0048] Example 4

[0049] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0050] Accurately weigh 84.36 mg (0.3 mol) flufenamic acid and 23.23 mg (0.1 mol) picrine, place them in a mortar, add 300 μL of 85 vol% ethanol aqueous solution and 100 μL of ethyl acetate, grind for 15 min, and after the solvent has evaporated, obtain flufenamic acid-picrine co-amorphous powder.

[0051] Example 5

[0052] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0053] Accurately weigh 28.12 mg (0.1 mol) of flufenamic acid and 46.46 mg (0.2 mol) of picrophylline, place them in a vial, add 1 mL of acetone, the solution is transparent, add a magnetic stir bar and place on a magnetic stirrer and stir continuously for 9 hours at a speed of 500 rpm, the solution is still transparent, place the solution in a vacuum drying oven and vacuum dry at 50 °C for 3 hours to obtain flufenamic acid-picrophylline co-amorphous powder.

[0054] Example 6

[0055] This embodiment provides a flufenamic acid-grossroots alkaloid co-amorphous compound, the preparation method of which is as follows:

[0056] Accurately weigh 56.24 mg (0.2 mol) of flufenamic acid and 23.23 mg (0.1 mol) of picroline, place them in a vial, add 8 mL of methanol, the solution is transparent, add a magnetic stir bar and place on a magnetic stirrer and stir continuously for 10 h at a speed of 1000 rpm, the solution is still transparent, place the solution in a vacuum drying oven and vacuum dry at 70 °C for 1 h to obtain flufenamic acid-picroline co-amorphous powder.

[0057] Example 7

[0058] This embodiment provides a flufenamic acid-bitterine co-amorphous compound, the preparation method of which differs from that of Example 2 only in that the solvent of 95 vol% ethanol aqueous solution is replaced with ethyl acetate.

[0059] Example 8

[0060] This embodiment provides a flufenamic acid-bitterine co-amorphous compound, the preparation method of which differs from that of Example 2 only in that the solvent of 95 vol% ethanol aqueous solution is replaced with acetonitrile.

[0061] Comparative Example 1

[0062] The difference between this comparative example and Example 1 is that the solvent is water, while the total volume of the solvent remains unchanged.

[0063] Characterization of flufenamic acid-matrine co-amorphous compounds

[0064] 1. Powder X-ray Diffraction (PXRD)

[0065] PXRD analysis was performed on flufenamic acid (Flu), physostigmine (Alo), a mixture of flufenamic acid powder and physostigmine powder in a 1:1 molar ratio (Flu+Alo), the flufenamic acid-physostigmine co-amorphous powder provided in the examples (Flu-Alo), and the powder prepared in the comparative example.

[0066] Testing instrument: Rigaku D / max-2550 X-ray powder diffractometer.

[0067] Detection conditions: Cu / K-alpha 1, 40kV-200mA, I(max)=2244, 2θ=4°-40°, λ=1.54056nm.

[0068] The comparison diagram of the PXRD spectra of Flu, Alo, Flu+Alo, and Flu-Alo provided in Example 2 is shown below. Figure 1A As shown.

[0069] from Figure 1A It can be seen that the powder X-ray diffraction pattern of flufenamic acid has characteristic diffraction peaks at 2θ = 13.23°, 17.869°, 18.930°, 19.749°, 24.342°, and 26.700°; the powder X-ray diffraction pattern of picroline has characteristic diffraction peaks at 2θ = 9.5°, 15.29°, 18.24°, 21.99°, 22.38°, and 29.67°. However, the flufenamic acid-picroline co-amorphous compound provided in Example 2 only showed one large diffraction ring, and the powder X-ray diffraction pattern was diffuse. The characteristic peaks of flufenamic acid and picroline disappeared, indicating that the product is a co-amorphous form. The X-ray diffraction patterns of the flufenamic acid-picroline co-amorphous compounds provided in Examples 1 and 3-8 are similar, showing a diffuse pattern.

[0070] The X-ray diffraction pattern of the powder prepared in Comparative Example 1 is as follows: Figure 1B As shown, from Figure 1B It can be seen that the diffraction peaks are not diffuse and characteristic peaks have appeared, indicating that the powder prepared in Comparative Example 1 did not form amorphous material.

[0071] 2. Differential Scanning Calorimetry (DSC)

[0072] Testing instrument: Mettler Toledo DSC3 / 700 / 200 differential scanning calorimeter.

[0073] Detection conditions and methods: Approximately 3 mg of flufenamic acid (Flu), physostigmine (Alo), and the flufenamic acid-physostigmine co-amorphous compound (Flu-Alo) provided in Example 2 were weighed and tested from 30°C to 140°C at a heating rate of 10°C / min.

[0074] A comparison of the DSC spectra of Flu, Alo, and Flu-Alo provided in Example 2 is shown in the figure below. Figure 2 As shown. From Figure 2 It can be seen that flufenamic acid (Flu) has an endothermic peak at 135.07℃, and physostigmine (Alo) has an endothermic peak at 73℃, while the endothermic peak of the flufenamic acid-physostigmine co-amorphous compound (Flu-Alo) provided in Example 2 is at 65.17℃. The endothermic peak temperatures of the flufenamic acid-physostigmine co-amorphous compound are different from those of flufenamic acid and physostigmine alone, indicating the formation of a new phase.

[0075] 3. Fourier Transform Infrared Spectroscopy (IR)

[0076] Testing instrument: Perkin Elmer Spectrum 400 infrared spectrometer.

[0077] Determination conditions and methods: Appropriate amounts of flufenamic acid (Flu), physostigmine (Alo), and the flufenamic acid-physostigmine co-amorphous powder (Flu-Alo) provided in Example 2 were taken and analyzed using infrared absorption spectroscopy at 4000–400 cm⁻¹. -1 Scan within the range and record the infrared absorption spectrum.

[0078] Test results as follows Figure 3 As shown. From Figure 3 It can be seen that the amino (NH) stretching vibration peak of flufenamic acid (Flu) appears at 3322 cm⁻¹. -1 The carbonyl (C=O) stretching vibration peak is at 1652 cm⁻¹. -1 The NH stretching vibration peak of maltodextrin (Alo) appears at 2920 cm⁻¹. -1 When flufenamic acid and strychnine form a co-amorphous compound, the C=O stretching vibration peak of flufenamic acid and the NH stretching vibration peak of strychnine shift to 1582 cm⁻¹, respectively. -1 and 2931cm -1 The above changes may be due to the formation of hydrogen bonds.

[0079] 4. Stability Test

[0080] Testing instruments: HPP260 constant temperature and humidity incubator, Rigaku D / max-2550 X-ray powder diffractometer.

[0081] Detection conditions and methods:

[0082] 4.1 High temperature: Take a small amount of the flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in Example 2, place it in a weighing bottle, and place the weighing bottle in a drying oven at 60°C. Perform PXRD detection after 0, 5 and 10 days respectively.

[0083] 4.2 High humidity: Take a small amount of flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in Example 2, place it in a weighing bottle, and place the weighing bottle in a constant temperature and humidity incubator at a temperature of 25°C and a relative humidity of 75%. Perform PXRD detection after 0, 5, and 10 days, respectively.

[0084] 4.3 Irradiation: Take a small amount of the flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in Example 2, place it in a weighing bottle, and place the weighing bottle under a white light source with a temperature of 25°C and an irradiation intensity of 4500 lx ± 500 lx. Perform PXRD detection after 0, 5, and 10 days.

[0085] The test results under high temperature, high humidity, and light conditions are as follows: Figure 4A , Figure 4B , Figure 4C As shown in the figure, under the three conditions of high temperature, high humidity, and light, the PXRD spectra of the flufenamic acid-matrine co-amorphous compound provided in Example 2 remained diffuse after 5 and 10 days of storage, and there was no significant change compared with the initial (day 0) PXRD spectra, indicating that the flufenamic acid-matrine co-amorphous compound has good stability.

[0086] 5. Equilibrium solubility determination

[0087] The equilibrium solubility of flufenamic acid (Flu) and the flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in the examples were determined by the shake flask method.

[0088] Take 5 mL of deionized water and place it in a 15 mL centrifuge tube. Add an excess of powder sample, seal the tube, and place it on a shaker at 37°C with a stirring speed of 120 r / min. Collect the supernatant at 2 h, 4 h, 8 h, 24 h, 48 h, and 60 h, filter the supernatant through a filter membrane, and detect the content using high performance liquid chromatography (HPLC). Calculate the equilibrium solubility.

[0089] The solubility curves of flufenamic acid (Flu) and the flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in Example 2 are shown in the figure. Figure 5 As shown.

[0090] Figure 5 The results showed that the equilibrium solubility of flufenamic acid (Flu) raw material in water at 37°C was 0.01 mg / mL, while the equilibrium solubility (based on flufenamic acid) of the flufenamic acid-matrine co-amorphous compound (Flu-Alo) provided in Example 2 was 1.01 mg / mL, which is more than 100 times that of flufenamic acid (Flu) raw material. This obviously helps to improve the bioavailability of flufenamic acid.

[0091] The above description is merely a specific embodiment of this disclosure, enabling those skilled in the art to understand or implement it. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this disclosure. Therefore, this disclosure is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A flufenamic acid-matrine co-amorphous compound, characterized in that, The flufenamic acid-matrine co-amorphous compound is composed of flufenamic acid and matrine in a molar ratio of 3:1 to 1:

3.

2. The flufenamic acid-matrine co-amorphous compound according to claim 1, characterized in that, The molar ratio of flufenamic acid to picrophylline is 1:

1.

3. The flufenamic acid-matrine co-amorphous compound according to claim 1 or 2, characterized in that, The equilibrium solubility of the flufenamic acid-matrine co-amorphous compound in water at 37°C, calculated as flufenamic acid, is 1.01 mg / mL.

4. A method for preparing the flufenamic acid-matrine co-amorphous compound as described in any one of claims 1-3, characterized in that, The preparation method includes the following steps: Flufenamic acid and phytic acid were soaked in a first solvent and ground until the first solvent was completely evaporated to obtain a flufenamic acid-phytic acid co-amorphous product. Alternatively, flufenamic acid and strychnine can be dissolved in a second solvent and dried to obtain a flufenamic acid-strychnine co-amorphous compound.

5. The preparation method according to claim 4, characterized in that, The first solvent is a combination of 60-95 vol% aqueous ethanol and ethyl acetate.

6. The preparation method according to claim 5, characterized in that, In the first solvent, the volume ratio of 60-95 vol% aqueous ethanol to ethyl acetate is 2-3:

1.

7. The preparation method according to claim 5 or 6, characterized in that, The volume ratio of the first solvent to the total mass of flufenamic acid and picrine is 1.8-5 mL / g.

8. The preparation method according to claim 4, characterized in that, The second solvent is one or a combination of 60-95 vol% aqueous ethanol solution, ethyl acetate, acetonitrile, acetone and methanol.

9. The preparation method according to claim 8, characterized in that, The ratio of the total mass of flufenamic acid and picrophylline to the volume of the second solvent is 1-80 mg / mL.

10. The preparation method according to claim 4, characterized in that, The step of dissolving flufenamic acid and physostigmine in a second solvent includes: mixing flufenamic acid with physostigmine and the second solvent, and stirring at a speed of 500-1000 rpm for 8-10 hours.

11. The preparation method according to claim 4, characterized in that, The drying method is vacuum drying, and the drying temperature is 50-70℃.

12. The use of a flufenamic acid-grossine co-amorphous compound as described in any one of claims 1-3 or a flufenamic acid-grossine co-amorphous compound prepared by the preparation method described in any one of claims 4-11 in the preparation of analgesic and / or anti-inflammatory medicaments.

13. A pain-relieving and / or anti-inflammatory drug, characterized in that, The drug comprises the flufenamic acid-stearin co-amorphous compound as described in any one of claims 1-3 or the flufenamic acid-stearin co-amorphous compound prepared by the preparation method described in any one of claims 4-11, as well as a pharmaceutically acceptable carrier, diluent or excipient.

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