Pharmaceutical composition for treating osteoarthritis and preparation method thereof

Abstract

The invention discloses a pharmaceutical composition for treating osteoarthritis as well as a preparation method and application thereof. The preparation method comprises the following steps: preparing selenized epigallocatechin gallate; the preparation method comprises the following steps: preparing a 3-acetyl-11-ketone-beta-masticinic acid phospholipid complex; mixing a sodium alginate solution with the two active components, and adding a CaCl2 cross-linking accelerant to form a medicine carrying solution; preparing sodium alginate-chitosan core-shell drug-loaded microspheres by adopting a coaxial electrostatic spraying technology; modifying the surface of the microsphere by using arginine-glycine-aspartic acid peptide; and curing by CaCl2, and freeze-drying to obtain a final product. The drug stability is remarkably improved through selenylation modification and phospholipid complex technologies, long-acting slow release of the drug is achieved through core-shell microspheres constructed through coaxial electrostatic spraying, and cartilage targeting is enhanced by combining RGD peptide modification. The pharmaceutical composition has excellent anti-inflammatory and cartilage protection effects, is suitable for preparing articular cavity injection preparations, and provides a new solution for osteoarthritis treatment.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to a pharmaceutical composition for treating osteoarthritis, a preparation method thereof, and an application thereof in preparing a preparation for intra-articular injection. Background Art

[0002] Osteoarthritis (OA) is a common, chronic, degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, and osteophyte formation at the joint margins, severely impacting patients' quality of life. Current clinical treatments for OA include medication, physical therapy, and surgery, but these methods often only alleviate symptoms and are unable to fundamentally repair damaged articular cartilage.

[0003] Selenated epigallocatechin gallate (Se-EGCG) and 3-acetyl-11-keto-β-boswellic acid (AKBA) have anti-inflammatory and cartilage-protective effects, but they suffer from poor stability and low solubility. Existing drug delivery systems, such as liposomes or conventional microspheres, struggle to achieve long-term retention and targeted delivery in the joint cavity. Summary of the Invention

[0004] In view of this, the main purpose of the present invention is to provide a method for preparing a pharmaceutical composition for treating osteoarthritis, so as to solve the problem that drug-carrying systems such as liposomes or ordinary microspheres are difficult to achieve long-term retention and targeted delivery in the joint cavity.

[0005] The present invention also aims to provide a pharmaceutical composition for treating osteoarthritis prepared by the above-mentioned preparation method, as well as the use of the above-mentioned pharmaceutical composition for treating osteoarthritis in the preparation of a joint cavity injection preparation.

[0006] To achieve the above object, the technical solution of the present invention is implemented as follows: a method for preparing a pharmaceutical composition for treating osteoarthritis, characterized in that the method specifically comprises the following steps:

[0007] S1. preparing selenated epigallocatechin gallate;

[0008] S2, preparing 3-acetyl-11-keto-β-boswellic acid phospholipid complex;

[0009] S3, mixing the sodium alginate solution, the selenated epigallocatechin gallate obtained in S1, and the 3-acetyl-11-keto-β-boswellic acid phospholipid complex obtained in S2, and then adding a cross-linking accelerator to obtain a sodium alginate drug-loaded solution;

[0010] S4, using the chitosan solution as the outer layer and the sodium alginate drug-loaded solution obtained in S3 as the inner layer, and using coaxial electrostatic spraying technology to prepare sodium alginate drug-loaded microspheres;

[0011] S5, dissolving the arginine-glycine-aspartic acid peptide (RGD peptide) in 2-(N-morpholino)ethanesulfonic acid (MES) buffer, and then adding the sodium alginate drug-loaded microspheres obtained in S4 to react to obtain a peptide-modified drug-loaded microsphere solution;

[0012] S6. Add the peptide-modified drug-loaded microsphere solution obtained in S5 into a CaCl2 solution for solidification, wash with ultrapure water, and then freeze-dry to obtain a pharmaceutical composition for treating osteoarthritis.

[0013] Preferably, the specific preparation method of selenated epigallocatechin gallate in S1 is: under nitrogen protection, epigallocatechin gallate (EGCG) and selenocysteine ​​are mixed in a molar ratio of 1:1-1:3, and reacted at 40-60° C. for 4-8 hours to obtain selenated epigallocatechin gallate.

[0014] Preferably, in S2, the specific preparation method of the 3-acetyl-11-keto-β-boswellic acid phospholipid complex is: dissolving 3-acetyl-11-keto-β-boswellic acid and soybean lecithin in ethanol at a mass ratio of 1:2-1:4, stirring at 40-50°C for 2-4 hours, and then evaporating under reduced pressure to remove the solvent to obtain the 3-acetyl-11-keto-β-boswellic acid phospholipid complex.

[0015] Preferably, in S3, the concentration of the sodium alginate solution is 1-3%, the added amounts of the selenized epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complex are both controlled at 1-3% of the mass of the sodium alginate solution, the cross-linking accelerator is a CaCl2 solution, the concentration of the CaCl2 solution is 2-4%, and the volume ratio of the sodium alginate solution to the CaCl2 solution is 10:1-5:1.

[0016] Preferably, in S4, the concentration of the chitosan solution is 0.5%-2%, and the parameters of the coaxial electrostatic spray technology are: inner layer flow rate 0.5-1.5 mL / h, outer layer flow rate 1-3 mL / h, voltage 10-20 kV, and receiving distance 10-20 cm.

[0017] Preferably, in S5, when the sodium alginate drug-loaded microspheres are added, the ratio of 1-5 grams of the sodium alginate drug-loaded microspheres per 100 ml of reaction solution is carried out; the concentration of the arginine-glycine-aspartic acid peptide is 0.5-2 mg / mL; the pH of the 2-(N-morpholino)ethanesulfonic acid buffer is 6.0-7.0; and the reaction time is 1-3 hours.

[0018] Preferably, in S6, the volume ratio of the peptide-modified drug-loaded microsphere solution to the CaCl2 solution is 1:1-1:3, the concentration of the CaCl2 solution is 2.5-3.5%, the curing time is 25-35 minutes, the freezing temperature is -40 to -50°C; the freezing time is 4 to 6 hours; the drying temperature is -20 to -30°C, and the drying time is 24 to 48 hours.

[0019] Preferably, in S4, the particle size of the sodium alginate drug-loaded microspheres is 5-20 μm, and the drug loading amount is 5-15%.

[0020] The second technical solution of the present invention is achieved as follows: a pharmaceutical composition for treating osteoarthritis is prepared by the above-mentioned preparation method.

[0021] The third technical solution of the present invention is achieved as follows: the above-mentioned pharmaceutical composition for treating osteoarthritis is used in the preparation of a joint cavity injection preparation.

[0022] Compared with the existing technology, the present invention synergistically encapsulates selenated epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complexes in sodium alginate-chitosan coaxial microspheres, and uses arginine-glycine-aspartic acid peptide for surface modification, which not only significantly improves the stability and bioavailability of the drug, but also achieves targeted delivery to the joint cavity and long-term sustained release; the core-shell structure microspheres of the composition constructed by coaxial electrostatic spraying technology can effectively prolong the retention time of the drug in the joint cavity. At the same time, the phospholipid complex technology and selenization modification enhance the anti-inflammatory and cartilage protective effects of the active ingredients, providing a new preparation for the treatment of osteoarthritis with anti-inflammatory, cartilage repair and targeted drug delivery functions. BRIEF DESCRIPTION OF THE DRAWINGS DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0024] An embodiment of the present invention provides a method for preparing a pharmaceutical composition for treating osteoarthritis, the method specifically comprising the following steps:

[0025] S1. Preparation of selenated epigallocatechin gallate: Under nitrogen protection, epigallocatechin gallate and selenocysteine ​​are mixed in a molar ratio of 1:1-1:3, and reacted at 40-60° C. for 4-8 hours to obtain selenated epigallocatechin gallate;

[0026] S2. Preparing a 3-acetyl-11-keto-β-boswellic acid phospholipid complex: dissolving 3-acetyl-11-keto-β-boswellic acid and soybean lecithin in ethanol at a mass ratio of 1:2-1:4, stirring at 40-50° C. for 2-4 hours, and then evaporating the solvent under reduced pressure to obtain a 3-acetyl-11-keto-β-boswellic acid phospholipid complex;

[0027] S3, mixing the sodium alginate solution, the selenated epigallocatechin gallate obtained in S1, and the 3-acetyl-11-keto-β-boswellic acid phospholipid complex obtained in S2, and then adding a cross-linking accelerator to obtain a sodium alginate drug-loaded solution, wherein the concentration of the sodium alginate solution is 1-3%, the amount of the selenated epigallocatechin gallate and the 3-acetyl-11-keto-β-boswellic acid phospholipid complex added is controlled to be 1-3% of the mass of the sodium alginate solution, the cross-linking accelerator is a CaCl2 solution, the concentration of the CaCl2 solution is 2-4%, and the volume ratio of the sodium alginate solution to the CaCl2 solution is 10:1-5:1;

[0028] S4, using a chitosan solution with a concentration of 0.5%-2% as the outer layer and the sodium alginate drug-loaded solution obtained in S3 as the inner layer, and using a coaxial electrostatic spraying technique to prepare sodium alginate drug-loaded microspheres, wherein the parameters of the coaxial electrostatic spraying technique are: inner layer flow rate 0.5-1.5 mL / h, outer layer flow rate 1-3 mL / h, voltage 10-20 kV, and receiving distance 10-20 cm; the obtained sodium alginate drug-loaded microspheres have a particle size of 5-20 μm and a drug loading of 5-15%;

[0029] S5. Dissolving the arginine-glycine-aspartic acid peptide in 2-(N-morpholino)ethanesulfonic acid buffer, and then adding the sodium alginate drug-loaded microspheres obtained in S4 to react to obtain a peptide-modified drug-loaded microsphere solution, wherein the sodium alginate drug-loaded microspheres are added at a ratio of 1-5 grams per 100 ml of reaction solution; the concentration of the arginine-glycine-aspartic acid peptide is 0.5-2 mg / mL; the pH of the 2-(N-morpholino)ethanesulfonic acid buffer is 6.0-7.0; and the reaction time is 1-3 hours;

[0030] S6. Add the peptide-modified drug-loaded microsphere solution obtained in S5 to a CaCl2 solution, solidify, wash with ultrapure water, and then freeze-dry to obtain a pharmaceutical composition for treating osteoarthritis, wherein the volume ratio of the peptide-modified drug-loaded microsphere solution to the CaCl2 solution is 1:1-1:3, the concentration of the CaCl2 solution is 2.5-3.5%, the solidification time is 25-35 minutes, the freezing temperature is -40 to -50°C; the freezing time is 4 to 6 hours; the drying temperature is -20 to -30°C, and the drying time is 24 to 48 hours.

[0031] An embodiment of the present invention further provides a pharmaceutical composition for treating osteoarthritis, which is prepared using the above-mentioned preparation method.

[0032] The embodiments of the present invention also provide the use of the above-mentioned pharmaceutical composition for treating osteoarthritis in the preparation of a joint cavity injection preparation.

[0033] The following are specific examples.

[0034] Example 1

[0035] S1. Preparation of selenated epigallocatechin gallate

[0036] Under nitrogen protection, epigallocatechin gallate and selenocysteine ​​were mixed in a molar ratio of 1:1 and reacted at 40° C. for 4 hours to obtain selenated epigallocatechin gallate.

[0037] S2. Preparation of 3-acetyl-11-keto-β-boswellic acid phospholipid complex

[0038] 3-acetyl-11-keto-β-boswellic acid and soybean lecithin were dissolved in ethanol at a mass ratio of 1:2, stirred at 40°C for 2 hours, and the solvent was evaporated under reduced pressure to obtain a 3-acetyl-11-keto-β-boswellic acid phospholipid complex.

[0039] S3. Preparation of sodium alginate drug-loaded solution

[0040] A 1% sodium alginate solution was mixed with the products obtained from S1 and S2, and the addition amount of the selenized epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complex was controlled to 1-3% of the mass of the sodium alginate solution. Then, a 2% CaCl2 solution (volume ratio 10:1) was added and stirred evenly to obtain a sodium alginate drug-loaded solution.

[0041] S4. Preparation of drug-loaded microspheres by coaxial electrostatic spraying

[0042] Coaxial electrostatic spraying technology was used, with an inner layer flow rate of 0.5 mL / h, an outer layer chitosan solution with a concentration of 0.5% at a flow rate of 3 mL / h, a voltage of 10 kV, a receiving distance of 10 cm, to prepare drug-loaded microspheres with a particle size of 5-10 μm and a drug loading capacity of approximately 5%.

[0043] S5. Peptide-modified drug-loaded microspheres

[0044] Arginine-glycine-aspartic acid peptide (0.5 mg / mL) was dissolved in MES buffer at pH 6.0, and drug-loaded microspheres were added at a ratio of 1 g microspheres / 100 mL. The reaction was carried out for 1 hour to obtain a peptide-modified drug-loaded microsphere solution.

[0045] S6. Curing and drying

[0046] The peptide-modified drug-loaded microsphere solution was mixed with a 2.5% CaCl2 solution (volume ratio 1:1), solidified for 25 minutes, washed with ultrapure water, frozen at -40°C for 4 hours, and then dried at -20°C for 24 hours to obtain the final pharmaceutical composition for treating osteoarthritis.

[0047] Example 2

[0048] S1. Preparation of selenated epigallocatechin gallate

[0049] Under nitrogen protection, epigallocatechin gallate and selenocysteine ​​were mixed in a molar ratio of 1:2 and reacted at 50° C. for 6 hours to obtain selenated epigallocatechin gallate.

[0050] S2. Preparation of 3-acetyl-11-keto-β-boswellic acid phospholipid complex

[0051] 3-acetyl-11-keto-β-boswellic acid and soybean lecithin were dissolved in ethanol at a mass ratio of 1:3, stirred at 45°C for 3 hours, and the solvent was evaporated under reduced pressure to obtain a 3-acetyl-11-keto-β-boswellic acid phospholipid complex.

[0052] S3. Preparation of sodium alginate drug-loaded solution

[0053] A 2% sodium alginate solution was mixed with the products obtained from S1 and S2, and the addition amount of the selenized epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complex was controlled to 2% of the mass of the sodium alginate solution. Then, a 3% CaCl2 solution (volume ratio 7:1) was added and stirred evenly to obtain a sodium alginate drug-loaded solution.

[0054] S4. Preparation of drug-loaded microspheres by coaxial electrostatic spraying

[0055] Using coaxial electrostatic spray technology, the inner layer flow rate is 1mL / h, the outer layer concentration is 1% chitosan solution flow rate is 2mL / h, the voltage is 15kV, the receiving distance is 15cm, and the drug-loaded microspheres with a particle size of 10-15μm and a drug loading capacity of about 10% are prepared.

[0056] S5. Peptide-modified drug-loaded microspheres

[0057] Arginine-glycine-aspartic acid peptide (1 mg / mL) was dissolved in MES buffer at pH 6.5, and drug-loaded microspheres were added at a ratio of 3 g microspheres / 100 mL. The reaction was carried out for 2 hours to obtain a peptide-modified drug-loaded microsphere solution.

[0058] S6. Curing and drying

[0059] The peptide-modified drug-loaded microsphere solution was mixed with a 3% CaCl2 solution (volume ratio 1:2), solidified for 30 minutes, washed with ultrapure water, frozen at -45°C for 5 hours, and then dried at -25°C for 36 hours to obtain the final pharmaceutical composition for treating osteoarthritis.

[0060] Example 3

[0061] S1. Preparation of selenated epigallocatechin gallate

[0062] Under nitrogen protection, epigallocatechin gallate and selenocysteine ​​were mixed in a molar ratio of 1:3 and reacted at 60° C. for 8 hours to obtain selenated epigallocatechin gallate.

[0063] S2. Preparation of 3-acetyl-11-keto-β-boswellic acid phospholipid complex

[0064] 3-acetyl-11-keto-β-boswellic acid and soybean lecithin were dissolved in ethanol at a mass ratio of 1:4, stirred at 50°C for 4 hours, and the solvent was evaporated under reduced pressure to obtain a 3-acetyl-11-keto-β-boswellic acid phospholipid complex.

[0065] S3. Preparation of sodium alginate drug-loaded solution

[0066] A 3% sodium alginate solution was mixed with the products obtained from S1 and S2, and the addition amount of the selenized epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complex was controlled to 3% of the mass of the sodium alginate solution. Then, a 4% CaCl2 solution (volume ratio 5:1) was added and stirred evenly to obtain a sodium alginate drug-loaded solution.

[0067] S4. Preparation of drug-loaded microspheres by coaxial electrostatic spraying

[0068] Coaxial electrostatic spraying technology was used, with an inner layer flow rate of 1.5 mL / h, an outer layer chitosan solution with a concentration of 2% at a flow rate of 1 mL / h, a voltage of 20 kV, a receiving distance of 20 cm, to prepare drug-loaded microspheres with a particle size of 15-20 μm and a drug loading capacity of approximately 15%.

[0069] S5. Peptide-modified drug-loaded microspheres

[0070] Arginine-glycine-aspartic acid peptide (2 mg / mL) was dissolved in MES buffer at pH 7.0, and drug-loaded microspheres were added at a ratio of 5 g microspheres / 100 mL. The reaction was carried out for 3 hours to obtain a peptide-modified drug-loaded microsphere solution.

[0071] S6. Curing and drying

[0072] The peptide-modified drug-loaded microsphere solution was mixed with a 3.5% CaCl2 solution (volume ratio 1:3), solidified for 35 minutes, washed with ultrapure water, frozen at -50°C for 6 hours, and then dried at -30°C for 48 hours to obtain the final pharmaceutical composition for treating osteoarthritis.

[0073] In order to verify the performance of the pharmaceutical composition for treating osteoarthritis obtained in the examples of the present invention, the performance of the pharmaceutical composition for treating osteoarthritis obtained in Examples 1 to 3 was tested. The test results are shown in Table 1 below:

[0074] Table 1 Properties of the pharmaceutical compositions for treating osteoarthritis obtained in Examples 1-3 of the present invention

[0075] Performance indicators Example 1 Example 2 Example 3 Drug loading 5％ 10％ 15％ Microsphere particle size (μm) 5-10 10-15 15-20 Drug release (24h) 40％ 30％ 20％ Drug release (72h) 75％ 60％ 50％ RGD peptide modification concentration 0.5 mg / mL 1mg / mL 2mg / mL Joint cavity retention time Shorter (small particle size, easy to diffuse) Medium (better sustained-release balance) Longest (large particle size, optimal sustained release) Applicable treatment cycle Short-term (1-2 weeks) Mid-term (2-4 weeks) Long-term (more than 4 weeks)

[0076] As can be seen from the data in Table 1, the process of the present invention comprises the following steps: preparing selenized epigallocatechin gallate; preparing a 3-acetyl-11-keto-β-boswellic acid phospholipid complex; mixing a sodium alginate solution with the above two active ingredients, and adding a CaCl2 cross-linking promoter to form a drug-loaded solution; preparing sodium alginate-chitosan core-shell drug-loaded microspheres using a coaxial electrostatic spraying technique; modifying the surface of the microspheres with an arginine-glycine-aspartic acid peptide; and obtaining a pharmaceutical composition for treating osteoarthritis through CaCl2 solidification and freeze-drying. The process not only significantly improves the stability and bioavailability of the drug, but also effectively prolongs the retention time of the drug in the joint cavity. Simultaneously, the phospholipid complex technology and selenization modification enhance the anti-inflammatory and cartilage-protective effects of the active ingredients. The composition is suitable for preparing a joint cavity injection preparation, providing a new solution for the treatment of osteoarthritis.

[0077] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for preparing a pharmaceutical composition for treating osteoarthritis, characterized in that: The method specifically comprises the following steps: S1. preparing selenated epigallocatechin gallate; S2, preparing 3-acetyl-11-keto-β-boswellic acid phospholipid complex; S3, mixing the sodium alginate solution, the selenated epigallocatechin gallate obtained in S1, and the 3-acetyl-11-keto-β-boswellic acid phospholipid complex obtained in S2, and then adding a cross-linking accelerator to obtain a sodium alginate drug-loaded solution; S4, using the chitosan solution as the outer layer and the sodium alginate drug-loaded solution obtained in S3 as the inner layer, and using coaxial electrostatic spraying technology to prepare sodium alginate drug-loaded microspheres; S5, dissolving the arginine-glycine-aspartic acid peptide in 2-(N-morpholino)ethanesulfonic acid buffer, and then adding the sodium alginate drug-loaded microspheres obtained in S4 to react to obtain a peptide-modified drug-loaded microsphere solution; S6. Add the peptide-modified drug-loaded microsphere solution obtained in S5 into a CaCl2 solution for solidification, wash with ultrapure water, and then freeze-dry to obtain a pharmaceutical composition for treating osteoarthritis.

2. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: The specific preparation method of the selenated epigallocatechin gallate in S1 is as follows: under nitrogen protection, epigallocatechin gallate and selenocysteine ​​are mixed in a molar ratio of 1:1-1:3, and reacted at 40-60° C. for 4-8 hours to obtain the selenated epigallocatechin gallate.

3. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: In S2, the specific preparation method of the 3-acetyl-11-keto-β-boswellic acid phospholipid complex is: dissolving 3-acetyl-11-keto-β-boswellic acid and soybean lecithin in ethanol at a mass ratio of 1:2-1:4, stirring at 40-50° C. for 2-4 hours, and then evaporating under reduced pressure to remove the solvent to obtain the 3-acetyl-11-keto-β-boswellic acid phospholipid complex.

4. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, wherein: In S3, the concentration of the sodium alginate solution is 1-3%, and the added amounts of the selenized epigallocatechin gallate and 3-acetyl-11-keto-β-boswellic acid phospholipid complex are both controlled to be 1-3% of the mass of the sodium alginate solution; the cross-linking accelerator is a CaCl2 solution, the concentration of the CaCl2 solution is 2-4%, and the volume ratio of the sodium alginate solution to the CaCl2 solution is 10:1-5:

1.

5. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: The parameters of the coaxial electrostatic spray technology in S4 are: inner layer flow rate 0.5-1.5 mL / h, outer layer flow rate 1-3 mL / h, voltage 10-20 kV, and receiving distance 10-20 cm.

6. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: In S5, when the sodium alginate drug-loaded microspheres are added, the ratio of 1-5 grams of the sodium alginate drug-loaded microspheres per 100 ml of reaction solution is carried out; the concentration of the arginine-glycine-aspartic acid peptide is 0.5-2 mg / mL; the pH of the 2-(N-morpholino)ethanesulfonic acid buffer is 6.0-7.0; and the reaction time is 1-3 hours.

7. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: In S6, the volume ratio of the peptide-modified drug-loaded microsphere solution to the CaCl2 solution is 1:1-1:3, the concentration of the CaCl2 solution is 2.5-3.5%, the solidification time is 25-35 minutes, the freezing temperature is -40 to -50°C; the freezing time is 4 to 6 hours; the drying temperature is -20 to -30°C, and the drying time is 24 to 48 hours.

8. The method for preparing a pharmaceutical composition for treating osteoarthritis according to claim 1, characterized in that: In the above-mentioned S4, the particle size of the sodium alginate drug-loaded microspheres is 5-20 μm, and the drug loading amount is 5-15%.

9. A pharmaceutical composition for treating osteoarthritis, characterized in that: The method is described in any one of claims 1 to 8.

10. Use of the pharmaceutical composition for treating osteoarthritis according to claim 9 in the preparation of a preparation for intra-articular injection.