New fusidic acid crystal form as well as preparation method and application thereof

Abstract

The invention discloses novel fusidic acid crystal forms as well as a preparation method and application thereof. The novel fusidic acid crystal forms are NY01 and NY02. The fusidic acid new crystal form NY01 or NY02 provided by the invention can be prepared into preparation forms such as capsules, tablets, emulsifiable paste, gel and the like with other pharmaceutically acceptable auxiliary materials so as to adapt to different administration routes; the pharmaceutical composition is used for treating osteomyelitis, septicemia, endocarditis, pneumonia, cystic fibrosis, skin and soft tissue infection, surgical operation infection or trauma infection caused by sensitive microorganisms, especially staphylococcus.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and more specifically, relates to two new fusidic acid crystal forms and preparation methods and applications thereof. Background Art

[0002] Fusidic acid is a drug used to treat osteomyelitis, sepsis, endocarditis, pneumonia, cystic fibrosis, skin and soft tissue infections, surgical infections or traumatic infections caused by sensitive microorganisms, especially staphylococci.

[0003] Due to the different molecular arrangements, drug polymorphism will occur, and different crystal forms have different physical and chemical properties. At present, no less than 6 polymorphs of fusidic acid have been reported. Patent GB 930,786 discloses salts formed by fusidic acid with organic bases and inorganic bases, and solvates of fusidic acid, including benzene solvates, methanol solvates, and hemihydrates of fusidic acid. British patent GB 999,794 also discloses solvates and salts of fusidic acid. Patent ES 2208110 discloses two solvent-free fusidic acid crystal forms called type I and type II and a crystalline hemihydrate called type III, respectively, and type III is the same as the hemihydrate currently on the market. CN101351471B proposes an anhydrous crystal form. The document (Samuel E.et. al. The solid-state characterization of fusidic acid) summarizes four crystal forms of fusidic acid (crystal forms I~IV), of which II and IV are metastable crystal forms.

[0004] Although there are many reports on fusidic acid crystal forms, on the one hand, crystal forms containing toxic solvents such as benzene cannot be marketed as active pharmaceutical ingredients; on the other hand, there are very few reports on crystal forms with a certain stability and high apparent solubility.

[0005] Therefore, it is more important to develop more commercially available fusidic acid crystal forms with higher stability and higher apparent solubility. Summary of the invention

[0006] Based on this, the purpose of the present invention is to provide two new crystalline forms of fusidic acid and preparation methods and applications thereof. The present invention prepares two new crystalline forms of fusidic acid, which have high stability and apparent solubility.

[0007] The technical solutions for achieving the above-mentioned invention objectives include the following.

[0008] In a first aspect of the present invention, a fusidic acid crystalline form NY01 is provided, whose characteristic peaks in the X-ray powder diffraction spectrum are expressed as 2θ±0.2° and are located at 8.4°±0.2°, 9.2°±0.2°, 11.8°±0.2°, 12.1°±0.2°, 13.8°±0.2°, 15.3°±0.2°, 15.9°±0.2°, 16.4°±0.2°, 18.7°±0.2°, 19.1°±0.2°, 21.6°±0.2°, and 22.1°±0.2°.

[0009] The second aspect of the present invention provides a method for preparing the above-mentioned fusidic acid crystalline form NY01, comprising the following steps: (1) Dissolve fusidic acid completely in alcohol; (2) While stirring, add water at a rate of 0.5 mL / min~5 mL / min, continue stirring for 0.5 h~3 h, filter to obtain a filter cake; dry the filter cake; (3) Heat to 140℃~160℃ and heat for 5 min~90 min.

[0010] In a third aspect of the present invention, a fusidic acid crystalline form NY02 is provided, whose characteristic peaks in the X-ray powder diffraction spectrum are expressed as 2θ±0.2° and are located at 7.0°±0.2°, 11.4°±0.2°, 12.6°±0.2°, 14.0°±0.2°, 16.0°±0.2°, 16.8°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 18.1°±0.2°, 18.5°±0.2°, and 20.5°±0.2°.

[0011] In a fourth aspect of the present invention, a method for preparing the above-mentioned fusidic acid crystalline form NY02 is provided, comprising the following steps: adding fusidic acid to a mixed solvent of methanol and water, stirring for 0.5 d to 7 d, and filtering to obtain.

[0012] The fifth aspect of the present invention provides a preparation containing fusidic acid, which is prepared from the above-mentioned fusidic acid crystal form NY01 or fusidic acid crystal form NY02, and pharmaceutically acceptable excipients.

[0013] The sixth aspect of the present invention provides use of the above-mentioned preparation containing fusidic acid in treating inflammation or infection.

[0014] The inventors of the present invention selected methanol from a variety of alcohols and mixed it with water in a certain volume ratio as a mixed solvent, and at the same time controlled the mass volume ratio of fusidic acid to the mixed solvent to prepare a new crystalline form of fusidic acid NY02 (in the X-ray powder diffraction pattern measured using Cu-Kα rays, at diffraction angles 2θ of 7.0°±0.2°, 11.4°±0.2°, 12.6°±0.2°, 14.0°±0.2°, 16.0°±0 .2°, 16.8°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 18.1°±0.2°, 18.5°±0.2°, and 20.5°±0.2°). The new crystalline form NY02 has a higher dissolution rate than the stable crystalline form III under the conditions of small intestine or skin simulated pH (pH 6.8), has better solubility properties, is beneficial to improving bioavailability, and has broad application prospects.

[0015] In addition, the inventors first completely dissolved fusidic acid in an alcohol solvent, then added a certain amount of water to the solution at a certain speed, continued to stir, and then heated to a specific temperature to prepare another new fusidic acid crystal form NY01 (in the X-ray powder diffraction pattern measured using Cu-Kα rays, the diffraction angles 2θ were 8.4°±0.2°, 9.2°±0.2°, 11.8°±0.2°, 12.1°±0.2°, 13.8 The new crystal form NY01 has characteristic peaks at 14.4°±0.2°, 15.3°±0.2°, 15.9°±0.2°, 16.4°±0.2°, 18.7°±0.2°, 19.1°±0.2°, 21.6°±0.2°, and 22.1°±0.2°. The new crystal form NY01 is a crystalline form without crystals. It does not undergo crystal transformation when placed under accelerated conditions (40°C, 75%RH) for at least 30 days. It has high stability and good application prospects.

[0016] The new crystalline form of fusidic acid NY01 or NY02 of the present invention can be prepared into capsules, tablets, creams, gels and other preparations with other pharmaceutically acceptable excipients to adapt to different administration routes, and is used to treat osteomyelitis, sepsis, endocarditis, pneumonia, cystic fibrosis, skin and soft tissue infections, surgical infections or traumatic infections caused by sensitive microorganisms, especially staphylococci. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the PXRD pattern of the fusidic acid crystal form NY01 prepared in Example 1 of the present invention.

[0018] Figure 2 This is the DSC spectrum of the fusidic acid crystal form NY01 prepared in Example 1 of the present invention.

[0019] Figure 3This is the TGA spectrum of the fusidic acid crystal form NY01 prepared in Example 1 of the present invention.

[0020] Figure 4 This is the Raman spectrum of the fusidic acid crystal form NY01 prepared in Example 1 of the present invention.

[0021] Figure 5 This is the PXRD pattern of the fusidic acid crystalline form NY02 prepared in Example 3 of the present invention.

[0022] Figure 6 This is the DSC spectrum of the fusidic acid crystalline form NY02 prepared in Example 3 of the present invention.

[0023] Figure 7 This is the TGA spectrum of the fusidic acid crystalline form NY02 prepared in Example 3 of the present invention.

[0024] Figure 8 This is the Raman spectrum of the fusidic acid crystal form NY02 prepared in Example 3 of the present invention.

[0025] Fig. 9 This is the PXRD pattern of the crystalline form of fusidic acid prepared in Comparative Example 4 of the present invention.

[0026] Fig.10 This is a dissolution comparison chart of fusidic acid crystal form NY02, crystal form I and crystal form III in Test Example 1 of the present invention at pH = 6.8.

[0027] Fig.11 This is a PXRD comparison chart of the sample of fusidic acid crystal form NY01 sampled under accelerated conditions within 30 days and 0 day in Experimental Example 2 of the present invention. DETAILED DESCRIPTION

[0028] In order to facilitate the understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0029] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0030] The experimental methods in the following examples where specific conditions are not specified are generally carried out under conventional conditions, such as those described in Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 2013, or according to the conditions recommended by the manufacturer. The various commonly used chemical reagents used in the examples are all commercially available products.

[0031] In some embodiments of the present invention, a fusidic acid crystal form NY01 is disclosed, and its characteristic peaks of the X-ray powder diffraction spectrum are expressed as 2θ±0.2° and are located at 8.4°±0.2°, 9.2°±0.2°, 11.8°±0.2°, 12.1°±0.2°, 13.8°±0.2°, 15.3°±0.2°, 15.9°±0.2°, 16.4°±0.2°, 18.7°±0.2°, 19.1°±0.2°, 21.6°±0.2°, and 22.1°±0.2°.

[0032] In other embodiments of the present invention, a method for preparing the above-mentioned fusidic acid crystalline form NY01 is disclosed, comprising the following steps: (1) Dissolve fusidic acid completely in alcohol; (2) While stirring, add water at a rate of 0.5 mL / min~5 mL / min, continue stirring for 0.5 h~3 h, filter to obtain a filter cake; dry the filter cake; (3) Heat to 140℃~160℃ and heat for 5 min~90 min.

[0033] In some embodiments, the water is added at a rate of 0.5 mL / min to 1 mL / min in step (2).

[0034] In some embodiments, the heating temperature in step (3) is 145°C to 155°C, more preferably 148°C to 152°C.

[0035] In some embodiments, the heating time in step (3) is 5 min to 50 min, preferably 5 min to 30 min, and more preferably 5 min to 25 min.

[0036] In some embodiments, the alcohol in step (1) is ethanol.

[0037] In some embodiments, the mass volume ratio of fusidic acid to ethanol in step (1) is 0.01 g to 0.15 g: 1 mL, more preferably 0.1 g to 0.15 g: 1 mL.

[0038] In some embodiments, the volume ratio of the deionized water in step (2) to the ethanol in step (1) is 1.5-2.5:1.

[0039] In other embodiments of the present invention, a fusidic acid crystalline form NY02 is disclosed, and its characteristic peaks in the X-ray powder diffraction spectrum are expressed as 2θ±0.2° and are located at 7.0°±0.2°, 11.4°±0.2°, 12.6°±0.2°, 14.0°±0.2°, 16.0°±0.2°, 16.8°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 18.1°±0.2°, 18.5°±0.2°, and 20.5°±0.2°.

[0040] In other embodiments of the present invention, a method for preparing the above-mentioned fusidic acid crystal form NY02 is disclosed, comprising the following steps: adding fusidic acid to a mixed solvent of methanol and water, magnetically stirring for 0.5 d to 7 d, and filtering to obtain.

[0041] In some embodiments, the volume ratio of methanol to water in the mixed solvent is 1-4:1, preferably 1-2:1, and more preferably 1:1.

[0042] In some embodiments, the mass volume ratio of fusidic acid to the mixed solvent is 0.01 g~1 g:1 mL, more preferably 0.05 g~0.5 g:1 mL.

[0043] In other embodiments of the present invention, a preparation containing fusidic acid is disclosed, which is prepared from the above-mentioned fusidic acid crystal form NY01 or fusidic acid crystal form NY02, and pharmaceutically acceptable excipients.

[0044] In some embodiments, the formulation is a cream, capsule, tablet or gel.

[0045] In other embodiments of the present invention, use of the above-mentioned preparation containing fusidic acid in treating inflammation or infection is disclosed.

[0046] In some embodiments, the inflammation is osteomyelitis, sepsis, endocarditis, pneumonia or cystic fibrosis caused by Staphylococcus.

[0047] In some embodiments, the infection is a skin and soft tissue infection, a surgical infection or a traumatic infection caused by Staphylococcus.

[0048] In the following embodiments, the detection instruments and methods involved are as follows: X-ray diffraction (PXRD): PANalytical X-ray powder diffractometer (PW3040 / 60, PANalytical Analytical Instruments, the Netherlands), Cu-Kα radiation, wavelength 1.542 Å, equipped with Bragg-Brentano High Definition. Incident light path: divergence slit 1 / 8°, Soller slit 0.04 rad, light shielding frame Mask 10 mm, anti-scatter slit 1 / 2°; diffraction light path: anti-scatter slit P7.5; X-ray sample stage: rotation mode; scanning detector: PIXcel1D-Medipix3; X-ray tube voltage 45 kV, X-ray tube current 40 mA, scanning range 2-40° (2θ), step length 0.026°, step time: 36.465 s. Data acquisition software Data Collector, data viewing software HighScore Plus.

[0049] Raman spectroscopy: Renishaw inVia Raman microspectroscopy, equipped with a near-infrared diode laser source and a Rencam charge-coupled device (CCD) silicon detector. The sample was placed flat on a microscope slide, focused and observed under a 20x objective lens, and Raman single-point detection was performed. The detection conditions were as follows: detection wavelength 785 nm, detection range 100 cm -1 ~1800 cm -1 , laser intensity 100%, exposure time 3 s, cumulative number 2 times; data acquisition and analysis software wire 4.3.

[0050] Differential Scanning Calorimeter (DSC): A differential scanning calorimeter Q2000 (TA Instruments, USA) was used to analyze the thermal properties of the samples. The nitrogen purge gas flow in the sample chamber was set to 50 mL / min, balanced at 25°C, and the heating rate was heated to 190°C at a rate of 10°C / min. The data analysis software was TA Universal Analysis (TA Instruments, USA).

[0051] Thermogravimetric analyzer (TGA): Thermogravimetric analyzer Q500 was used to analyze the thermal weight loss of the samples. The nitrogen purge gas flow in the sample chamber was set to 60 mL / min, the heating rate was heated to 350°C at a rate of 10°C / min, and the data analysis software was TA Universal Analysis (TA Instruments, USA).

[0052] The starting crystalline form of fusidic acid is crystalline form III (hemihydrate), which was purchased from Chengdu Kanghong Pharmaceutical Group Co., Ltd.

[0053] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0054] Example 1 Preparation of Fusidic Acid Crystalline Form NY01 This embodiment provides fusidic acid crystalline form NY01, which is prepared by the following method: At room temperature, add 1 g of fusidic acid to 10 mL of ethanol and stir until completely dissolved; Under stirring, 20 mL of deionized water was added dropwise to the solution at a rate of 1 mL / min, and stirring was continued for 2 h; filtration was performed, and the filter cake was dried in a forced air drying oven at 60°C for 2 h to obtain fusidic acid hemihydrate; Spread fusidic acid hemihydrate on a watch glass, raise the temperature of the forced air drying oven to 150°C and maintain it for 10 min to obtain a fusidic acid powder sample.

[0055] The powder samples were characterized by PXRD, DSC, TGA and Raman, and the results were as follows: Figure 1~Figure 4 The crystalline form NY01 is an anhydrous crystalline form, with a decomposition temperature of about 184.7°C, a melting point of about 180.7°C, and no obvious weight loss from room temperature to 150°C.

[0056] Example 2 Preparation of Fusidic Acid Crystalline Form NY01 This example provides a fusidic acid crystal form NY01. Except for heating to 145° C. for 60 min in step (3), the other steps are the same as those in Example 1.

[0057] The prepared fusidic acid powder sample was characterized by PXRD. The results are as follows: Figure 1 As shown, the results show that the crystal form prepared in this example is NY01.

[0058] Example 3 Preparation of Fusidic Acid Crystalline Form NY02 This embodiment provides fusidic acid crystalline form NY02, which is prepared by the following method: At room temperature, 200 mg of fusidic acid was added to a mixed solution of 3 mL of methanol: water (1:1, v / v), magnetically stirred for 16 h, and filtered to obtain the product.

[0059] The powder samples were characterized by PXRD, DSC, TGA and Raman, and the results were as follows: Figure 5~Figure 8 The crystal form prepared in this example is a new crystal form NY02, which has a weight loss of about 11.7% from room temperature to 150°C, is a solvate, and has a melting point at about 131°C (peak).

[0060] Example 4 Preparation of Fusidic Acid Crystalline Form NY02 This embodiment provides fusidic acid crystalline form NY02, which is prepared by the following method: At room temperature, 600 mg of fusidic acid was added to 3 mL of methanol: water (1:1, v / v), magnetically stirred for 7 days, and filtered to obtain the product.

[0061] The powder samples were characterized by PXRD. Figure 5 As shown, the results show that the crystal form prepared in this example is NY02.

[0062] Example 5 Preparation of Fusidic Acid Cream In this example, fusidic acid crystalline form NY02 prepared in Example 3 was used to prepare fusidic acid cream, and its formula is shown in Table 1.

[0063]

[0064] The preparation method is as follows: (1) Preparation of aqueous phase: Heat purified water to 75°C, add butylated hydroxyanisole and glycerol, stir and mix, and keep warm for later use; (2) Preparation of the oil phase: Heat the oily matrix (white vaseline, liquid paraffin, hexadecanol) and polysorbate 60 until they are melted to obtain the oil phase, homogenize for 10 min, and keep warm at 70°C-75°C for later use; (3) Total mixing: Add the aqueous phase to the oil phase at 75°C and homogenize for 20 min to obtain a blank emulsion. Further add an appropriate amount of hydrochloric acid to adjust the pH value of the total mixture to 4.0-6.5; add fusidic acid crystal form NY02 and continue homogenizing for 10 min to obtain a crude fusidic acid cream.

[0065] (4) Cooling: Cool the crude fusidic acid cream to room temperature, and obtain the finished fusidic acid cream by cooling and filling.

[0066] Comparative Example 1 This comparative example provides a method for preparing fusidic acid crystal form I, comprising the following steps: Add 1 g of fusidic acid to 10 mL of acetonitrile, heat to 55 °C, and stir magnetically for 30 min; Cool to room temperature, filter, and dry the filter cake in a forced air drying oven at 60°C for 4 h.

[0067] The powder sample was characterized by PXRD, and the results showed that the obtained crystal form was fusidic acid crystal form I.

[0068] Comparative Example 2 In this comparative example, except that 20 mL of deionized water is directly and quickly poured into step 2, the remaining steps are the same as those of Example 1, and a yellow slurry substance is obtained, which is amorphous.

[0069] Comparative Example 3 In this comparative example, except that the temperature in step 3 is 100° C., the remaining steps are the same as those in Example 1. The obtained powder sample is characterized by PXRD, and the results show that the obtained crystal form is fusidic acid crystal form III.

[0070] Comparative Example 4 This comparative example provides fusidic acid crystal forms prepared in different solvent systems, which are prepared by the following methods: At room temperature, 200 mg of fusidic acid was added to different solvents (as shown in Table 2), magnetically stirred for 16 h, and filtered. The obtained powder was characterized by PXRD. The results are shown in Fig. 9 And as shown in Table 2.

[0071]

[0072] from Fig. 9 As can be seen from the results in Table 2, when water, ethanol: water (1:1, v), isopropanol: water (1:1, v), and methanol: water (1:8, v) are used as solvents, the prepared fusidic acid is Form I or Form III, or a mixed crystal of Form I and Form III, and the new fusidic acid form NY02 of the present invention cannot be prepared.

[0073] Test Example 1 Dissolution test of fusidic acid crystals This test example investigated the dissolution rate of fusidic acid crystalline form NY02 at pH = 6.8. 50 mg of crystalline form NY02 was weighed, and 50 mg each of crystalline form III (semihydrate, commercially available) and crystalline form I (anhydrous, prepared in Comparative Example 1) were used as reference substances.

[0074] 500 mL of phosphate buffer solution with a pH of 6.8 was used as the dissolution medium, the dissolution temperature was 37±0.5℃, the dissolution method was the paddle method, and the stirring paddle speed was 100 rpm. After the feeding was completed, the timing began, and 2.5 mL of samples were taken at the time points of 5 min, 10 min, 15 min, 30 min, 45 min, and 60 min, and an equal amount of dissolution medium was added at the same time. After sampling, it was filtered with a 0.22 micron microporous membrane and used as the sample to be tested.

[0075] The sample absorbance was detected by ultraviolet spectrophotometer at a wavelength of 210 nm, and the release amount of each sample at different times was calculated by ultraviolet absorbance according to the external standard method. The results are as follows: Fig.10As shown. The test results show that in a dissolution medium with a pH of 6.8, when the dissolution time is 60 minutes, the solubility of crystalline form NY02 is about 80%, while the solubility of crystalline form III is about 35%, and the solubility of crystalline form I is about 56%. The solubility of crystalline form NY02 is about 2.3 times higher than that of crystalline form III, and 1.4 times higher than that of crystalline form I. That is, the crystalline form NY02 prepared by the present invention has a significant improvement in instantaneous solubility and dissolution rate relative to crystalline form III and crystalline form I.

[0076] Test Example 2 Stability of Fusidic Acid Crystalline Form According to the 9001 Stability Guidelines for Drug Substances and Preparations of Part IV of the 2020 edition of the Chinese Pharmacopoeia, the fusidic acid crystalline form NY01 prepared in Example 1 was placed under 40°C and 75% RH conditions for 30 days, and samples were taken on the 5th, 10th, 15th and 30th days, and the samples were characterized by PXRD. The results are as follows: Fig.11 shown.

[0077] The results showed that fusidic acid crystalline form NY01 did not undergo crystal transformation under accelerated conditions for 30 days.

[0078] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0079] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A fusidic acid crystal form NY01, characterized in that: The characteristic peaks of its X-ray powder diffraction spectrum are expressed as 2θ±0.2°, and are located at 8.4°±0.2°, 9.2°±0.2°, 11.8°±0.2°, 12.1°±0.2°, 13.8°±0.2°, 15.3°±0.2°, 15.9°±0.2°, 16.4°±0.2°, 18.7°±0.2°, 19.1°±0.2°, 21.6°±0.2°, and 22.1°±0.2°.

2. A method for preparing the fusidic acid crystalline form NY01 according to claim 1, characterized in that: The following steps are involved: (1) Dissolve fusidic acid completely in alcohol; (2) While stirring, add water at a rate of 0.5 mL / min~5 mL / min, continue stirring for 0.5 h~3 h, filter to obtain a filter cake; dry the filter cake; (3) Heat to 140℃~160℃ and heat for 5 min~90 min.

3. The method for preparing the fusidic acid crystal form NY01 according to claim 2, characterized in that: The water addition rate in step (2) is 0.5 mL / min~1 mL / min; And / or, the heating temperature in step (3) is 145°C to 155°C, more preferably 148°C to 152°C; And / or, the heating time is 5 min to 50 min, preferably 5 min to 30 min, more preferably 5 min to 25 min.

4. The method for preparing the fusidic acid crystal form NY01 according to claim 2, characterized in that: The alcohol in step (1) is ethanol; Preferably, the mass volume ratio of fusidic acid to ethanol is 0.01 g to 0.15 g: 1 mL, more preferably 0.1 g to 0.15 g: 1 mL; And / or, the volume ratio of the deionized water in step (2) to the ethanol in step (1) is 1.5-2.5:1, more preferably 1.8-2.2:

1.

5. A fusidic acid crystalline form NY02, characterized in that: The characteristic peaks of its X-ray powder diffraction spectrum are expressed as 2θ±0.2°, and are located at 7.0°±0.2°, 11.4°±0.2°, 12.6°±0.2°, 14.0°±0.2°, 16.0°±0.2°, 16.8°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 18.1°±0.2°, 18.5°±0.2°, and 20.5°±0.2°.

6. A method for preparing the fusidic acid crystalline form NY02 according to claim 5, characterized in that: The following steps are involved: Add fusidic acid to a mixed solvent of methanol and water, stir for 0.5 d to 7 d, and filter to obtain the product.

7. The method for preparing the fusidic acid crystal form NY02 according to claim 6, characterized in that: The volume ratio of methanol to water in the mixed solvent in step (1) is 1-4:1, preferably 1-2:1, and more preferably 1:

1.

8. The method for preparing the fusidic acid crystalline form NY02 according to claim 6, characterized in that: The mass volume ratio of fusidic acid to the mixed solvent in step (1) is 0.01 g to 1 g: 1 mL, more preferably 0.05 g to 0.5 g: 1 mL.

9. A preparation containing fusidic acid, characterized in that The invention is prepared from the fusidic acid crystal form NY01 according to claim 1 or the fusidic acid crystal form NY02 according to claim 5, and pharmaceutically acceptable excipients.

10. Use of the preparation containing fusidic acid according to claim 9 in treating inflammation or infection.

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