Prednisolone-containing composition as well as preparation method and application thereof

Abstract

The invention relates to the field of medicaments, and provides a prednisolone-containing composition and a preparation method and application thereof, the composition comprises a matrix and prednisolone dispersed in the matrix; wherein the matrix comprises a first matrix and colloidal silicon dioxide, and the first matrix is selected from at least one of hydroxypropyl methyl acetate succinate, hydroxypropyl methylcellulose phthalate, polyacrylic resin L100-55 and polyacrylic resin L100. The composition disclosed by the invention not only can take effect quickly, but also has a better absorption effect, and the method disclosed by the invention can be used for quickly forming the microspheres, so that the preparation time of the microspheres is greatly shortened.

Description

Field of the Invention

[0001] The present application belongs to the field of pharmaceutical preparations. Specifically, the present application provides a prednisolone-containing composition and a preparation method and application thereof. Background Art

[0002] Prednisolone, chemical name 11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione, is an organic compound with the chemical formula C 21 H 28 O 5 It is a cortical hormone drug mainly used for allergic and autoimmune inflammatory diseases, collagen diseases, such as rheumatism, rheumatoid arthritis, lupus erythematosus, severe bronchial asthma, nephrotic syndrome, thrombocytopenic purpura, granulocytopenia, acute lymphocytic leukemia, various adrenal insufficiency, exfoliative dermatitis, non-herpetic neurodermatitis, eczema-like, etc.

[0003] The main problems with the clinical use of prednisolone include: it may be used frequently and for a long time in specific populations such as children, the elderly, critically ill bedridden patients and some patients using gastric tubes, but the above-mentioned special groups generally have swallowing disorders, and the only prednisolone preparations available in China are ordinary tablets. There is a lack of suitable dosage forms for special groups in clinical applications. Suitable dosage forms are urgently needed in the clinic to improve the compliance, safety and scientificity of the medication for the above-mentioned people with swallowing disorders; in addition, prednisolone itself tastes bitter, and the development of ordinary liquid preparations such as oral solutions will cause the bitter taste to remain in the mouth due to its fat solubility, which poses a huge challenge to children's medication compliance; finally, the adverse reactions of prednisolone are closely related to the course of treatment, dosage, type of medication, usage and route of administration, especially gastric irritation, which is the most serious, and can easily cause peptic ulcers and progress rapidly. In severe cases, it manifests as sudden massive gastrointestinal bleeding and perforation, ulcerative esophagitis, vomiting and other adverse reactions.

[0004] Therefore, there is an urgent need for an enteric-coated preparation that can solve the above problems and has better effects. Summary of the invention

[0005] In view of the above situation, the present application provides a prednisolone-containing composition and a preparation method and application thereof.

[0006] In a first aspect, the present application provides a prednisolone-containing composition, comprising a matrix and prednisolone dispersed in the matrix; the matrix comprises a first matrix and colloidal silicon dioxide, and the first matrix is ​​selected from at least one of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyacrylic acid resin L100-55 and polyacrylic acid resin L100.

[0007] In the present invention, the polyacrylic acid resin L100-55 is a copolymer of methacrylic acid and ethyl acrylate in a molar ratio of 1:1, and the polyacrylic acid resin L100 is a copolymer of methacrylic acid and methyl methacrylate in a molar ratio of 1:1.

[0008] Furthermore, the composition is a microsphere, and the particle size of the microsphere is 50-500 μm, which can be 50 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm or a range formed by any two of the above values ​​and a value within the range.

[0009] The circularity of the microspheres is not less than 0.9, and can be 0.9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, 1 or a range formed by any two of the above values ​​and a value within the range (the circularity is the degree of proximity between the particle projection and the circle, and the circularity of a perfect circle is 1.0).

[0010] Further, the weight ratio of prednisolone to matrix in the composition is 1:2.5-19, and can be 1:2.5, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19 or a range formed by any two of the above values ​​and a value within the range.

[0011] Furthermore, the weight ratio of the colloidal silica to the first matrix is ​​1:100-1000, and can be 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, or 1:700.

[0012] In a second aspect, a method for preparing a prednisolone-containing composition is provided, the method comprising: (1) mixing prednisolone and a matrix in the presence of an organic solvent; (2) adding the mixed product of step (1) into water in the presence of an emulsifier for molding; wherein the matrix comprises a first matrix and colloidal silicon dioxide, and the first matrix is ​​selected from at least one of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyacrylic acid resin L100-55 and polyacrylic acid resin L100.

[0013] Furthermore, the content of prednisolone in the mixed system of step (1) is 0.5-10% by weight, and can be 0.5% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, or 10% by weight.

[0014] Furthermore, the dosage ratio of prednisolone to matrix is ​​1:2.5-19, and can be 1:2.5, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19 or a range formed by any two of the above values ​​and a value within the range.

[0015] Furthermore, the usage ratio of the colloidal silica to the first matrix is ​​1:100-1000, and can be 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000 or a range formed by any two of the above values ​​and a value within the range.

[0016] Furthermore, the weight ratio of the emulsifier to water in step (2) is 1:10-1000, and can be 1:10, 1:50, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000 or a range formed by any two of the above values ​​and a value within the range.

[0017] Furthermore, the mixing conditions include: a temperature of 10-25°C, which can be 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 25°C or a range formed by any two of the above values ​​and a value within the range; a time of 0.1-3h, which can be 0.1h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h or a range formed by any two of the above values ​​and a value within the range.

[0018] In the present invention, the mixed product of step (1) is in a relatively soft form after adding water. This soft form is easy to destroy the shape of the ball in subsequent processing, and it takes a period of time to harden. After hardening, it will not affect subsequent processing. The change from a relatively soft state to a relatively hard state is called molding. The hardening standard in the present invention is that after suction filtration under a relative vacuum pressure of -0.06 to -0.09Mpa, the sphere does not deform or undergoes very little deformation, and the roundness can reach not less than 0.9, which can be considered to have been hardened and will no longer affect subsequent processing. The molding conditions include: a temperature of 10-25°C, which can be 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 25°C or any two of the above values ​​and a value within the range; a time of 0.5-2.5h, which can be 0.5h, 1h, 1.5h, 2h, 2.5h or any two of the above values ​​and a value within the range.

[0019] In the present invention, in order to prevent the formed spheres from piling up during the forming process, the stirring state is maintained during the forming process.

[0020] Furthermore, the organic solvent is not limited, as long as the matrix and prednisolone can be dissolved therein. Preferably, the organic solvent is selected from at least one of dichloromethane, 1,4-dioxane, ethyl formate, ethyl acetate, methyl formate, methyl acetate, butyl acetate, isoamyl acetate, methyl isobutyl ketone, methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, tert-butanol, ethylene glycol and glycerol.

[0021] Furthermore, the emulsifier is not limited and is the common emulsifier in the art selected from at least one of sodium dodecyl sulfate, Tween 20, Tween 80, Span 60, Span 80, polyvinyl alcohol, sucrose fatty acid ester and poloxamer, preferably at least one of Tween 80, sodium dodecyl sulfate and polyvinyl alcohol.

[0022] Furthermore, the method further comprises performing solid-liquid separation on the product obtained in step (2), wherein the solid-liquid separation method is preferably vacuum filtration, and the pressure of the vacuum filtration is -0.06 to -0.09 MPa.

[0023] Furthermore, the method may also include washing the solid obtained by solid-liquid separation.

[0024] The third aspect of the present invention provides a prednisolone-containing composition prepared by the above method.

[0025] In the present invention, prednisolone and each matrix used in the above method are basically all prepared into a composition, and the loss is very small and can be ignored. Therefore, the content of each component in the composition has been described above and will not be repeated here.

[0026] The fourth aspect of the present invention provides use of the above-mentioned prednisolone-containing composition in the preparation of a pharmaceutical preparation.

[0027] Furthermore, the pharmaceutical preparation is prepared into at least one of a dry suspension, a tablet, a capsule, a dispersible tablet and an orally disintegrating tablet by adding different pharmaceutical excipients.

[0028] The pharmaceutical preparation of the present invention can be used to treat various related diseases for which prednisolone is known to be effective, including but not limited to various allergic and autoimmune diseases, such as rheumatism, rheumatoid arthritis, lupus erythematosus, etc., as well as nephrotic syndrome, thrombocytopenic purpura, granulocytopenia, polar lymphocytic leukemia, etc. These uses can be determined by those skilled in the art with reference to diagnosis and treatment specifications and related research.

[0029] In the present invention, the polyacrylic acid resin L100-55 is a copolymer of methacrylic acid and ethyl acrylate in a molar ratio of 1:1, and the polyacrylic acid resin L100 is a copolymer of methacrylic acid and methyl methacrylate in a molar ratio of 1:1.

[0030] Through the above technical scheme, the composition of the present invention can not only take effect quickly, but also has a better absorption effect, and the method of the present invention can make the microspheres quickly molded, greatly shortening the preparation time of the microspheres.

[0031] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is the blood drug concentration of each group of beagle dogs in the test case. DETAILED DESCRIPTION

[0033] The present invention will be described in detail below by way of examples. In the following examples,

[0034] Source of colloidal silicon dioxide: Anhui Shanhe Pharmaceutical Excipients Co., Ltd.

[0035] Hydroxypropyl methylcellulose acetate succinate Source: Deqing Weikang Biotechnology Co., Ltd.;

[0036] Hydroxypropyl methylcellulose phthalate Source: Lotte Fine Chemicals Co., Ltd.;

[0037] Polyacrylic acid resin L100-55 Source: Evonik Degussa (China) Investment Co., Ltd. Shanghai Branch;

[0038] Polyacrylic acid resin L100 Source: Evonik Degussa (China) Investment Co., Ltd. Shanghai Branch;

[0039] Magnesium stearate Source: Hunan Erkang Pharmaceutical Co., Ltd.

[0040] Polyacrylic acid resin S100 (copolymer of methacrylic acid and methyl methacrylate in a molar ratio of 1:2) Source: Evonik Degussa (China) Investment Co., Ltd. Shanghai Branch;

[0041] Commercially available prednisolone tablets source: Pfizer AB.

[0042] Example 1

[0043] (1) dissolving prednisolone and a matrix (the weight ratio of colloidal silicon dioxide and hydroxypropyl methylcellulose acetate succinate is 1:500) in dichloromethane at a weight ratio of 1:5 to form an oil phase, wherein the content of prednisolone in the oil phase is 2%, the temperature is 20° C., and the time is 1 hour;

[0044] (2) mixing polyvinyl alcohol and water in a weight ratio of 1:200 to form an aqueous phase;

[0045] (3) At a temperature of 20° C., the oil phase in step (1) is added to the water phase in step (2) for stirring and molding. The molding time is shown in Table 1;

[0046] (4) The stirred and molded product in step (3) is filtered under a vacuum degree of -0.08 MPa to obtain microspheres with a particle size of 50-500 μm and a circularity greater than 0.9.

[0047] Example 2

[0048] (1) dissolving prednisolone and a matrix (a weight ratio of colloidal silicon dioxide and hydroxypropyl methylcellulose acetate succinate is 1:500) in dichloromethane at a weight ratio of 1:5 to form an oil phase, wherein the content of prednisolone in the oil phase is 1%, the temperature is 25° C., and the time is 1 hour;

[0049] (2) mixing sodium lauryl sulfate and water in a weight ratio of 1:50 to form an aqueous phase;

[0050] (3) At a temperature of 25° C., the oil phase in step (1) is added to the water phase in step (2) for stirring and molding. The molding time is shown in Table 1;

[0051] (4) The stirred and molded product in step (3) is filtered under a vacuum degree of -0.08 MPa to obtain microspheres with a particle size of 50-500 μm and a circularity greater than 0.9.

[0052] Example 3

[0053] (1) dissolving prednisolone and a matrix (colloidal silicon dioxide and hydroxypropyl methylcellulose acetate succinate in a weight ratio of 1:500) in dichloromethane in a weight ratio of 1:5 to form an oil phase, wherein the content of prednisolone in the oil phase is 5%, the temperature is 10° C., and the time is 1.5 h;

[0054] (2) mixing Tween 80 and water at a weight ratio of 1:100 to form an aqueous phase;

[0055] (3) At a temperature of 10° C., the oil phase in step (1) is added to the water phase in step (2) for stirring and molding. The molding time is shown in Table 1;

[0056] (4) The stirred and molded product in step (3) is filtered under a vacuum degree of -0.08 MPa to obtain microspheres with a particle size of 50-500 μm and a circularity greater than 0.9.

[0057] Example 4

[0058] The method of Example 1 was followed, except that hypromellose acetate succinate was replaced with hypromellose phthalate to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0059] Example 5

[0060] The method of Example 1 was followed, except that hydroxypropyl methylcellulose acetate succinate was replaced with polyacrylic acid resin L100-55 to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0061] Example 6

[0062] The method of Example 1 was followed, except that hydroxypropyl methylcellulose acetate succinate was replaced with polyacrylic acid resin L100 to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0063] Example 7

[0064] The method of Example 1 is followed, except that the weight ratio of colloidal silicon dioxide to hydroxypropyl methylcellulose acetate succinate is 1:1000. Microspheres with a particle size of 50-500 μm and a circularity higher than 0.9 are obtained.

[0065] Example 8

[0066] The method of Example 1 is followed, except that the weight ratio of colloidal silicon dioxide to hydroxypropyl methylcellulose acetate succinate is 1:100. Microspheres with a particle size of 50-500 μm and a circularity higher than 0.9 are obtained.

[0067] Example 9

[0068] The method of Example 1 was followed, except that the weight ratio of prednisolone to the matrix was 1:10, and microspheres with a particle size of 50-500 μm and a circularity higher than 0.9 were obtained.

[0069] Example 10

[0070] The method of Example 1 was followed, except that the weight ratio of prednisolone to matrix was 1:15, and microspheres with a particle size of 50-500 μm and a circularity higher than 0.9 were obtained.

[0071] Comparative Example 1

[0072] The method of Example 1 was followed, except that colloidal silicon dioxide was not added to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0073] Comparative Example 2

[0074] The method of Example 1 was followed, except that the colloidal silicon dioxide was replaced with magnesium stearate to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0075] Comparative Example 3

[0076] The method of Example 1 was followed, except that hydroxypropyl methylcellulose acetate succinate was replaced with polyacrylic acid resin S100 to obtain microspheres with a particle size of 50-500 μm and a circularity higher than 0.9.

[0077] Test Case

[0078] 1. Molding hardening time

[0079] Method: In the above embodiment and comparative example step (3), the timing starts immediately after the oil phase is added to the water phase, and samples are taken every half an hour. The samples are filtered under a vacuum pressure of -0.08Mpa, and the obtained solid is observed and tested using a particle size and shape analyzer. The detection is stopped when the circularity reaches 0.9 or above, and the time recorded is the molding time. The results are shown in Table 1:

[0080] Table 1 Molding test results

[0081] Example Molding time (h) Example 1 1.0 Example 2 1.0 Example 3 1.5 Example 4 1.5 Example 5 2.0 Example 6 2.0 Example 7 1.5 Example 8 1.5 Example 9 1.5 Example 10 2.0 Comparative Example 1 8.0 Comparative Example 2 8.5 Comparative Example 3 10.0

[0082] From the results in Table 1, it can be seen that when the method of the present invention is used to prepare microspheres, the molding and hardening time of the microspheres is shorter, and the time for preparing the microspheres is shorter.

[0083] 2. In vitro dissolution

[0084] Method: The above examples and comparative examples were measured according to the dissolution and release determination method (Chinese Pharmacopoeia 2020 General Rules 0931 Method 2). The dissolution conditions are as follows:

[0085] Test method in acid: Use 500ml of 0.1mol / L hydrochloric acid solution as dissolution medium, rotate at 50 revolutions per minute, operate according to the law, take samples after 2 hours, and replenish with an equal volume of 0.1mol / L hydrochloric acid solution at the same time. The limit shall not exceed 10% of the feed amount. The results are shown in Table 2.

[0086] Small Intestine Enteric Coating Test Method: Use pH 6.8 phosphate buffer as dissolution medium, rotate at 50 revolutions per minute, operate according to the law, take samples after 30 hours, and replenish with an equal volume of pH 6.8 phosphate buffer at the same time. The limit is not less than 70% of the feed amount. The results are shown in Table 2:

[0087] Table 2 Dissolution test results

[0088]

[0089] According to Table 2, the composition of the present invention has a lower dissolution in acid for 2 hours (lower than 10%), and a higher dissolution in small intestinal fluid (higher than 70%). Although Comparative Examples 1 and 2 have a higher dissolution in the small intestine, they also have a higher dissolution in acid (higher than 10%). Although Comparative Example 3 has a lower dissolution in acid, it also has a lower dissolution in small intestinal fluid (lower than 70%), which obviously cannot meet the conditions for enteric dissolution.

[0090] 3. Pharmacokinetic parameters:

[0091] Six beagle dogs (weight 10kg) were randomly divided into two groups and orally administered with the prednisolone test preparation T (microspheres containing a specific amount of drug in gastric soluble capsules) or reference preparation R for a single cycle. Fasting for 12 hours before administration, food was provided 4 hours after administration on the day of the test, and water was not prohibited during the test. The oral dose of prednisolone for dogs was 5 mg / dog. 2 mL of blood was collected from the veins of the four limbs before administration (0h) and 0.167h (10min), 0.333h (20min), 0.666h (40min), 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (a total of 13 points) after administration, and placed in an EDTA-K2 vacuum blood collection tube, and immediately gently inverted and mixed 5-8 times to mix the blood with the anticoagulant and then centrifuged. Within 1 hour after blood sample collection, centrifuge at 1700g for 10 minutes at 4°C to separate the upper plasma. The separated plasma sample is stored in a refrigerator at a temperature below -60°C; or temporarily stored in a refrigerator at -20°C and transferred to a refrigerator at a temperature below -60°C within 24 hours. The blood sample should be collected and placed in the refrigerator within 2 hours.

[0092] Biological sample analysis: The LC-MS / MS method was used to detect the prednisolone content in plasma. The results are shown in Table 3 and Figure 1 .

[0093] Data processing: WinNonlin software was used to calculate pharmacokinetic parameters. The results are shown in Table 4. max It indicates the time required to reach the peak concentration of the drug after administration. This parameter reflects the speed at which the drug enters the body. The faster the absorption rate, the shorter the peak time. The unit is h; C max Indicates the highest blood drug concentration after administration. This parameter is an important indicator reflecting the absorption rate and degree of the drug in the body. The unit is ng / mL; AUC lastIt represents the area enclosed by the blood drug concentration curve on the time axis from the start of drug administration to the last point, which is used to evaluate the degree of drug absorption. The unit is h*ng / mL. AUCINF_obs represents the area enclosed by the blood drug concentration curve on the time axis in the 0-infinity time period, which is used to predict the degree of drug absorption.

[0094] Table 3 Blood drug concentration test results

[0095]

[0096] Table 4 Pharmacokinetic parameter test results

[0097] Pharmacokinetic parameters Example 1 Example 4 Comparative Example 1 Comparative Example 3 Prednisolone tablets available on the market <![CDATA[T max ]]> 1 1 0.6 2 1 <![CDATA[C max ]]> 226.98 230.42 240.51 59.88 177.54 <![CDATA[AUC last ]]> 553.74 489.32 438.19 214.59 358.80 AUCINF_obs 573.95 505.66 456.87 235.42 376.17

[0098] It can be seen from Tables 3 and 4 that the C max and AUC were significantly better than those of commercially available prednisolone tablets, and T max Comparable to commercially available preparations, while Examples 1 and 4 not only max and AUC are significantly better than those of comparative example 3, T max It is also shorter than Comparative Example 3, although the C max It is lower than that of Comparative Example 1, but the AUC is significantly better than that of Comparative Example 1.

[0099] It can be seen from the above results that the preparation time of microspheres in Examples 1-10 is shorter, the microsphere molding and hardening time is significantly shorter than that of the comparative example, and the in vitro dissolution can meet the requirements of enteric-coated preparations, and the drug absorption degree is also higher. The microspheres prepared by the comparative example formula are not easy to be molded and hardened, and the in vitro dissolution of comparative examples 1 and 2 in acid exceeds the limit requirements. Although the in vitro dissolution of comparative example 3 meets the requirements in acid, the dissolution rate in intestinal fluid is too slow, and the drug absorption degree is lower.

[0100] It can be seen that the prednisolone enteric-coated microsphere preparation of the present invention is not restricted by the pyloric emptying of the stomach after oral administration, can quickly enter the intestine to be released and absorbed by the body and has a good absorption effect.

[0101] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A composition containing prednisolone, characterized in that The composition includes a matrix and prednisolone dispersed in the matrix; The matrix comprises a first matrix and colloidal silicon dioxide, wherein the first matrix is ​​selected from at least one of hypromellose acetate succinate, hypromellose phthalate, polyacrylic acid resin L100-55 and polyacrylic acid resin L100.

2. The composition according to claim 1, wherein the composition is microspheres, and the particle size of the microspheres is 50-500 μm; and / or, the weight ratio of prednisolone to matrix in the composition is 1:2.5-19; And / or, the weight ratio of the colloidal silica to the first matrix is ​​1:100-1000.

3. The composition according to claim 2, wherein the circularity of the microspheres is not less than 0.

9.

4. A method for preparing a composition containing prednisolone, characterized in that: The method comprises: (1) mixing prednisolone and a matrix in the presence of an organic solvent; (2) adding the mixed product of step (1) into water in the presence of an emulsifier for molding; The matrix comprises a first matrix and colloidal silicon dioxide, wherein the first matrix is ​​selected from at least one of hypromellose acetate succinate, hypromellose phthalate, polyacrylic acid resin L100-55 and polyacrylic acid resin L100.

5. The method according to claim 4, wherein: The content of prednisolone in the mixed system of step (1) is 0.5-10% by weight; and / or, the dosage ratio of prednisolone to matrix is ​​1:2.5-19; And / or, the usage ratio of the colloidal silica to the first matrix is ​​1:100-1000.

6. The method according to claim 4 or 5, wherein: The weight ratio of the emulsifier to water in step (2) is 1:10-1000; And / or, the mixing conditions include: temperature of 10-25°C, time of 0.1-3h; And / or, the molding conditions include: temperature of 10-25° C. and time of 0.5-2.5 h.

7. The method according to claim 4 or 5, wherein: The organic solvent is selected from at least one of dichloromethane, 1,4-dioxane, ethyl formate, ethyl acetate, methyl formate, methyl acetate, butyl acetate, isoamyl acetate, methyl isobutyl ketone, methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, tert-butanol, ethylene glycol and glycerol; And / or, the emulsifier is selected from at least one of sodium dodecyl sulfate, Tween 20, Tween 80, Span 60, Span 80, polyvinyl alcohol, sucrose fatty acid ester and poloxamer.

8. The method according to claim 4 or 5, wherein: The method further comprises performing solid-liquid separation on the product obtained in step (2).

9. A prednisolone-containing composition prepared by the method according to any one of claims 4 to 8.

10. Use of the prednisolone-containing composition according to any one of claims 1 to 3 and 9 in the preparation of a pharmaceutical preparation.

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