Application of benzenesulfonamide compound in preparation of medicine for preventing and / or treating osteoarthritis

Abstract

The invention discloses an application of a benzenesulfonamide compound in preparation of a medicine for preventing and / or treating osteoarthritis. The invention provides the application of the benzenesulfonamide compound in the medicine for preventing and / or treating osteoarthritis for the first time. Experiments show that joint swelling and abrasion of osteoarthritis mice can be remarkably improved by administration of the benzenesulfonamide compound; meanwhile, the benzenesulfonamide compound can obviously relieve cartilage injury of osteoarthritis mice and inhibit the joint fibrosis process; in addition, the benzenesulfonamide compound significantly inhibits expression of inflammation-related markers in serum of osteoarthritis model mice. The experiment shows that the benzenesulfonamide compound can achieve the purpose of improving osteoarthritis, and has very important significance on drug development, prevention and treatment of the diseases in the future.

Description

Technical Field

[0001] The invention relates to use of a benzenesulfonamide compound in preparing a medicine for preventing and / or treating osteoarthritis, and belongs to the technical field of biomedicine. Background Art

[0002] Osteoarthritis (OA) is a chronic total joint disease that affects articular cartilage, synovium and subchondral bone. Articular cartilage degeneration is the main pathological feature of OA. At present, the number of people suffering from osteoarthritis worldwide has exceeded 500 million, and the number of arthritis patients in my country is conservatively estimated to exceed 100 million, with a total prevalence of 15%. With the acceleration of the aging process of the global population, the incidence and disability rate of OA have increased year by year, and it has become one of the important public health issues facing the world.

[0003] At present, the treatments for osteoarthritis mainly include drug therapy, physical therapy, and surgical treatment. In terms of drug therapy, although commonly used non-steroidal anti-inflammatory drugs can relieve pain symptoms to a certain extent, long-term use has risks such as gastrointestinal adverse reactions and liver and kidney damage; the efficacy of chondroprotective agents is relatively slow, and the effect is poor for patients in the middle and late stages. Physical therapy such as hot compresses, massage, acupuncture, etc. can only temporarily relieve symptoms and cannot fundamentally prevent the progression of the disease. Surgical treatment includes joint replacement, etc., which can significantly improve joint function, but the surgery is traumatic and expensive, and there is a risk of complications such as infection and thrombosis. It also requires a high physical condition for patients and is not suitable for all patients. There is still a clear lack of understanding of the pathogenesis of OA, and the existing treatments for osteoarthritis also have many limitations. There is an urgent need for a safer, more effective, and more convenient treatment method or technology to improve this situation. Summary of the invention

[0004] The main purpose of the present invention is to provide a use of a benzenesulfonamide compound in the preparation of a medicament for preventing and / or treating osteoarthritis, so as to overcome the deficiencies in the prior art.

[0005] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention includes:

[0006] The present invention provides a use of a benzenesulfonamide compound in the preparation of a drug for preventing and / or treating osteoarthritis. The structure of the benzenesulfonamide compound is shown in formula (I):

[0007]

[0008] The embodiment of the present invention also provides a pharmaceutical composition for preventing and / or treating osteoarthritis, comprising: a benzenesulfonamide compound represented by formula (I) or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and / or excipient;

[0009]

[0010] Wherein, the pharmaceutically acceptable derivative is selected from at least one of pharmaceutically acceptable salts, polymorphs, co-crystals, radiolabeled forms and combinations thereof.

[0011] The embodiments of the present invention also provide use of the aforementioned pharmaceutical composition in preparing a drug for preventing and / or treating osteoarthritis.

[0012] Compared with the prior art, the beneficial effect of the present invention is that the present invention proposes for the first time the use of benzenesulfonamide compounds or pharmaceutically acceptable derivatives thereof in drugs for preventing and / or treating osteoarthritis. Experiments show that administration of benzenesulfonamide compounds can significantly improve joint swelling and cartilage wear in osteoarthritis mice; at the same time, benzenesulfonamide compounds significantly increase the number of chondrocytes and counteract bone and joint tissue fibrosis; in addition, benzenesulfonamide compounds significantly inhibit the expression of inflammation-related markers in the serum of osteoarthritis model mice. The above experiments show that benzenesulfonamide compounds can improve osteoarthritis, which is of great significance for the future drug development and prevention and treatment of such diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0014] Figure 1 This is a comparison diagram of bone anatomy of mice in a control group and mice given a benzenesulfonamide compound in an osteoarthritis model in a typical embodiment of the present invention;

[0015] Figure 2 This is a comparison diagram of H&E staining between control mice and mice given a benzenesulfonamide compound in an osteoarthritis model in a typical embodiment of the present invention;

[0016] Figure 3 This is a comparison of Sirius red staining of the bones of mice in a control group and mice given a benzenesulfonamide compound in an osteoarthritis model in a typical embodiment of the present invention;

[0017] Figure 4 This is a comparison of bone safranin fast green staining of mice in a control group and mice given a benzenesulfonamide compound in an osteoarthritis model in a typical embodiment of the present invention;

[0018] Figure 5-Figure 7 This is a graph showing the levels of serum inflammatory indicators in mice in a control group and mice given a benzenesulfonamide compound under an osteoarthritis model in a typical embodiment of the present invention. DETAILED DESCRIPTION

[0019] In view of the defects of the prior art, the inventor of this case has proposed the technical solution of the present invention after long-term research and extensive practice. In order to facilitate the understanding of the present application, the present application will be described in more detail as follows. However, it should be understood that the present invention can be implemented in many different forms and is not limited to the embodiments or examples described herein. On the contrary, the purpose of providing these embodiments or examples is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0020] Specifically, as one aspect of the technical solution of the present invention, it involves the use of a benzenesulfonamide compound in the preparation of a drug for preventing and / or treating osteoarthritis, and the structure of the benzenesulfonamide compound is shown in formula (I):

[0021]

[0022] The benzenesulfonamide compounds of the present invention synergistically treat osteoarthritis through the following multiple pathways:

[0023] (1) Fight joint swelling (bone and joint anatomy diagram, such as Figure 1 ) and reduced cartilage wear (H&E staining of bone joints, as Figure 2 shown);

[0024] (2) Protect cartilage: Maintain the arrangement of collagen fibers (Sirius red staining, such as Figure 3 ), reduced proteoglycan loss and cartilage damage (Safranin fast green staining, as Figure 4 shown);

[0025] (3) Inhibit inflammation: reduce serum MMP13, IL-1β and TNF-α levels (such as Figure 5-Figure 7 shown).

[0026] In some embodiments, the osteoarthritis is mechanical anisotropy-induced bone joint damage.

[0027] Furthermore, the drug can alleviate the degree of joint swelling and cartilage wear of bone and joint injuries induced by uneven mechanical forces.

[0028] Furthermore, the drug can reduce the levels of serum inflammatory factors in bone and joint injuries induced by uneven mechanical forces.

[0029] In some embodiments, when the drug is applied to an osteoarthritis mouse model, the drug can at least inhibit joint swelling in the mouse.

[0030] In some embodiments, when the drug acts on an osteoarthritis mouse model, the drug can at least reduce joint wear of the mouse. In some embodiments, when the drug acts on an osteoarthritis mouse model, the drug can at least reduce the serum inflammatory factor content of the mouse.

[0031] In some embodiments, when the drug acts on an osteoarthritis mouse model, the drug can at least reduce the expression of osteoarthritis-related inflammatory markers in the mouse by more than 30%.

[0032] Furthermore, the osteoarthritis-related inflammatory markers include any one or more combinations of MMP13, IL-1β, and TNF-α, but are not limited thereto.

[0033] In some embodiments, when the drug acts on an osteoarthritis mouse model, the drug can at least promote stabilization of the cartilage structure of the mouse.

[0034] In some embodiments, when the drug acts on an osteoarthritis mouse model, the drug can at least promote and inhibit cartilage fibrosis in the mouse.

[0035] The drug of the present invention improves osteoarthritis through at least one of the following mechanisms: (a) inhibiting joint swelling and reducing articular cartilage wear; (b) protecting the structural integrity of cartilage and inhibiting fibrosis; (c) reducing the level of serum inflammatory factors and counteracting the progression of osteoarthritis.

[0036] The drug of the present invention can significantly improve the joint pathological indicators in the bone and joint injury model induced by uneven mechanical force.

[0037] As another aspect of the technical solution of the present invention, it relates to a pharmaceutical composition for preventing and / or treating osteoarthritis, which comprises: a benzenesulfonamide compound represented by formula (I) or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and / or excipient;

[0038]

[0039] Wherein, the pharmaceutically acceptable derivative is selected from at least one of pharmaceutically acceptable salts, polymorphs, co-crystals, radiolabeled forms and combinations thereof.

[0040] In some embodiments, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least inhibit joint swelling and reduce cartilage wear in the mouse.

[0041] In some embodiments, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least promote stabilization of the cartilage structure of the mouse.

[0042] In some embodiments, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least promote and inhibit cartilage fibrosis in the mouse.

[0043] In some embodiments, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least reduce the serum inflammatory factor content of the mouse.

[0044] In some embodiments, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least reduce the expression of osteoarthritis-related inflammatory markers in the mouse by more than 30%.

[0045] Furthermore, the osteoarthritis-related inflammatory markers include any one or more combinations of MMP13, IL-1β, and TNF-α, but are not limited thereto.

[0046] As another aspect of the technical solution of the present invention, it also relates to the use of the aforementioned pharmaceutical composition in the preparation of a drug for preventing and / or treating osteoarthritis.

[0047] The present invention is further described by the following examples: The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the specific material ratios, process conditions and results described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0048] Unless otherwise specified, the various raw materials, reaction equipment, testing equipment and testing methods used in the following examples are all well known in the art.

[0049] 1. Experimental steps

[0050] Experimental Animals:

[0051] The male C57BL / 6 mice used in this example were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., license number SCXK (Beijing) 2007-0001. The mice were placed under standard conditions of 50±10% humidity and 23±2°C for 12 hours per day and night to adapt to survival. The mice were free to drink water and eat. All animal management and treatment protocols were approved by the Animal Ethics Committee of Xuzhou Medical University. All experiments were conducted in accordance with the recommendations of the Code of Ethics for the Management and Use of Animals.

[0052] Example 1 Construction of osteoarthritis model

[0053] 1. Animals: C57BL / 6 mice (male, 12 weeks old) were used and randomly divided into a control group (n=8) and a drug-treated group (n=8).

[0054] 2. Surgical induction of OA: A mechanical force unevenness model was established by anterior cruciate ligament transection (ACLT), and the OA phenotype was confirmed 8 weeks after surgery.

[0055] Example 2 H&E staining

[0056] Specific experimental methods include:

[0057] 1. Preparation of paraffin sections

[0058] (1) Bone tissue fixation: bone tissues of mice in each group in Example 1 were taken, soft tissues were removed, and then fixed in 4% paraformaldehyde at room temperature for 24 hours, wrapped with gauze, marked, and rinsed with running water overnight;

[0059] (2) Dehydration and clearing: Place the dehydration box in a dehydrator and dehydrate with graded alcohols in sequence: 75% alcohol for 4 h, 85% alcohol for 2 h, 90% alcohol for 2 h, 95% alcohol for 1 h, anhydrous ethanol I for 30 min, anhydrous ethanol II for 30 min, alcohol benzene for 5-10 min, xylene I for 5-10 min, and xylene II for 5-10 min;

[0060] (3) Wax dipping and embedding: melt paraffin I at 65° for 1 hour, melt paraffin II at 65° for 1 hour, and melt paraffin III at 65° for 1 hour. Embed the wax-dipped tissue in an embedding machine. First, put the melted wax into the embedding frame. Before the wax solidifies, take the tissue out of the dehydration box and put it into the embedding frame according to the requirements of the embedding surface and attach the corresponding label. Cool in a -20° freezer. After the wax solidifies, take the wax block out of the embedding frame and trim the wax block;

[0061] (4) Sectioning and spreading: Cut slices with a microtome to a thickness of 5 μm, spread the slices in a 50°C water bath, pick up the slices and mount them on a clean glass slide, and bake them in a 60°C oven overnight. After sectioning, mark them and save them for later use.

[0062] 2. Perform H&E staining

[0063] (1) Dewaxing and rehydration: The sections were dewaxed twice in xylene (15 min / time), dehydrated in 100%, 95%, 90%, 80%, 70%, and 50% alcohol for 5 min each, and finally rehydrated in distilled water for 3 min.

[0064] (2) Hematoxylin staining: The sections were placed in hematoxylin stain for 15 minutes, rinsed with tap water for 3 minutes, and separated with hydrochloric acid alcohol (70% alcohol 99 ml + concentrated hydrochloric acid 1 ml) for 10 seconds;

[0065] (3) Blueing and dehydration: Rinse with tap water for 10 minutes to turn it blue. Dehydrate the slices in 50%, 70%, 80%, and 90% alcohol for 5 minutes each;

[0066] (4) Eosin counterstaining: stain with 1% eosin solution for 2 minutes, dehydrate in 95% alcohol and 100% alcohol for 3 minutes respectively until the boundary is clear;

[0067] (5) Transparent and sealing: After xylene is transparent for 3 minutes, the slides are sealed with neutral gum;

[0068] (6) After sealing, the slides were placed in a 50°C oven for drying and the changes in the tissue structures were observed under a light microscope.

[0069] Example 3 Observation of cartilage tissue fibrosis by picrosirius red staining

[0070] Specific experimental methods include:

[0071] 1. Preparation of paraffin sections

[0072] (1) Fixation of tissue specimens: bone tissues of mice in each group in Example 1 were fixed in 4% paraformaldehyde at room temperature for 24 hours, wrapped with gauze, marked, and rinsed with running water overnight;

[0073] (2) Dehydration and transparency: Place the dehydration box in a dehydrator and dehydrate with graded alcohols in sequence: 75% alcohol for 4 hours, 85% alcohol for 2 hours, 90% alcohol for 2 hours, 95% alcohol for 1 hour, anhydrous ethanol I for 30 minutes, anhydrous ethanol II for 30 minutes, alcohol benzene for 5-10 minutes, xylene I for 5-10 minutes, xylene II for 5-10 minutes

[0074] (3) Wax dipping and embedding: melt paraffin I at 65° for 1 hour, melt paraffin II at 65° for 1 hour, and melt paraffin III at 65° for 1 hour. Embed the wax-dipping tissue in an embedding machine. First, put the melted wax into the embedding frame. Before the wax solidifies, take the tissue out of the dehydration box and put it into the embedding frame according to the requirements of the embedding surface and attach the corresponding label. Cool in a -20° freezer. After the wax solidifies, take the wax block out of the embedding frame and trim the wax block;

[0075] (4) Sectioning and spreading: Cut slices with a microtome to a thickness of 5 μm, spread the slices in a 50°C water bath, pick up the slices and mount them on a clean glass slide, and bake them in a 60°C oven overnight. After sectioning, mark them and store them for later use.

[0076] 2. Sirius red staining

[0077] (1) Dewaxing and rehydration: The sections were dewaxed twice in xylene (15 min / time), dehydrated in 100%, 95%, 90%, 80%, 70%, and 50% alcohol for 5 min each, and finally rehydrated in distilled water for 3 min.

[0078] (2) Staining: Immerse in picrosirius red stain (1% in saturated picric acid solution) for 60 minutes.

[0079] (3) Differentiation and washing: Rapid acid ethanol differentiation (1% HCl-ethanol, 1 to 3 seconds), and rinse with running water for 5 minutes.

[0080] (4) Dehydration and sealing: Dehydration with gradient ethanol, transparentization with xylene, and sealing with neutral resin.

[0081] Example 4 Observation of bone tissue by safranin fast green staining

[0082] 1. Preparation of paraffin sections

[0083] Same as above-mentioned embodiment 2.

[0084] 2. Safranin Fast Green Dyeing

[0085] (1) Dewaxing and rehydration: The sections were dewaxed twice in xylene (15 min / time), dehydrated in 100%, 95%, 90%, 80%, 70%, and 50% alcohol for 5 min each, and finally rehydrated in distilled water for 3 min.

[0086] (2) Safranin staining: Add safranin stain solution, incubate at room temperature for 2 hours, and rinse with running water;

[0087] (3) Fast green staining: Fast green staining for about 1 minute;

[0088] (4) Dehydration, transparency, and sealing: Dehydrate the sections in 50%, 70%, 80%, 90%, 95%, and 100% alcohol for 5 minutes each. Transparentize with xylene for 3 minutes, and then seal the sections with neutral gum.

[0089] (5) After sealing, the slides were placed in a 50°C oven for drying and the changes in the tissue structures were observed under a light microscope.

[0090] Example 5 Mouse ELISA detection kit for detecting serum inflammation-related indicators

[0091] (1) After equilibration at room temperature for 20 min, take out the required strips from the aluminum foil bag and seal the remaining strips in a ziplock bag and place them back at 4°C.

[0092] (2) Set up standard wells and sample wells, and add 50 μL of standards of different concentrations to each standard well;

[0093] (3) First add 10 μL of the sample to be tested to the sample well, and then add 40 μL of the sample diluent; do not add anything to the blank well.

[0094] (4) Except for the blank wells, add 100 μL of horseradish peroxidase (HRP)-labeled detection antibody to each well of the standard and sample wells, seal the wells with a sealing film, and incubate at 37°C in a water bath or incubator for 60 min.

[0095] (5) Discard the liquid, pat dry on absorbent paper, fill each well with washing solution, let stand for 1 min, shake off the washing solution, pat dry on absorbent paper, and repeat this process 5 times.

[0096] (6) Add 50 μL of substrate A and B to each well and incubate at 37°C in the dark for 15 min.

[0097] (7) Add 50 μL of stop solution to each well. Within 15 min, measure the OD value of each well at a wavelength of 450 nm and calculate relevant indicators according to the instructions.

[0098] 2. Experimental Results

[0099] 1. Benzenesulfonamide compounds significantly improve joint swelling in osteoarthritis model mice

[0100] Mice of appropriate age were selected and anterior cruciate ligament transection (ACLT) surgery was performed to construct an osteoarthritis model. The mice after surgery were randomly divided into two groups, one group was given saline and the other group was given benzenesulfonamide compounds. Samples were collected and analyzed 8 weeks after administration. The results showed that the joints of mice in the saline group were significantly swollen, showing typical symptoms of arthritis. In contrast, the joint swelling of mice in the drug group was significantly improved, such as Figure 1 This suggests that benzenesulfonamide compounds may play a protective role against joint damage in osteoarthritis mice.

[0101] 2. Benzenesulfonamide compounds significantly reduce the degree of bone tissue wear in osteoarthritis model mice

[0102] Subsequently, the fixed bone tissue was further subjected to paraffin sectioning and H&E staining. The staining revealed that the bone joints in the saline group were significantly swollen and the articular cartilage was severely worn, showing typical arthritis symptoms, such as Figure 2 In contrast, after administration of benzenesulfonamide compounds, the swelling and wear of the bone joints of mice were significantly reduced, as shown in Figure 2. Figure 2 As shown, Figure 1 These results once again confirm that benzenesulfonamide compounds have a significant protective effect on bone damage caused by osteoarthritis.

[0103] 3. Benzenesulfonamide compounds significantly reduce the degree of fibrosis in osteoarthritis model mice

[0104] Healthy articular cartilage has a smooth extracellular matrix, but once the cartilage is damaged, chondrocytes proliferate abnormally. Eventually, the proliferating chondrocytes transform into a fibroblast-like phenotype, forming a thick layer of fibrocartilage-like tissue by synthesizing type I collagen and inducing the degradation and dedifferentiation of nearby hyaline cartilage. These changes cause the cartilage to become harder and less durable, and ultimately change the phenotype of the articular cartilage, accelerating the progression of OA. Subsequently, picrosirius red staining revealed that the degree of fibrosis in arthritic mice after administration of benzenesulfonamide compounds was significantly reduced compared with that in the saline control group mice, such as Figure 3 This suggests that benzenesulfonamide compounds may counteract the progression of fibrosis during arthritis.

[0105] 4. Benzenesulfonamide compounds can reduce cartilage damage in arthritic mice

[0106] The typical feature of osteoarthritis is cartilage damage. Subsequently, the effect of benzenesulfonamide compounds on chondrocytes in arthritic mice was tested. Through safranin fast green staining, it was found that the positive staining of chondrocytes in the drug-treated group was significantly more than that in the control group. Figure 4 As shown, it suggests that benzenesulfonamide compounds play a counteracting role in the damage of chondrocytes during arthritis.

[0107] 5. Benzenesulfonamide compounds can inhibit the inflammatory process in arthritic mice

[0108] The process of osteoarthritis is often accompanied by the release of inflammatory factors. These pro-inflammatory factors promote the production of proteolytic enzymes, which degrade the extracellular matrix and further damage joint tissue. ELISA detection found that the levels of MMP13, IL-1β and TNF-α, the hallmark molecules of inflammation, in the serum of mice were significantly reduced after administration of benzenesulfonamide compounds. Figure 5-Figure 7 As shown, this suggests that the drug has an inhibitory effect on the inflammatory process of osteoarthritis.

[0109] In addition, the inventors of this case also referred to the aforementioned embodiments and conducted experiments with other raw materials, process operations, and process conditions described in this specification, and obtained relatively ideal results.

[0110] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of the present invention to be protected.

Claims

1. Use of a benzenesulfonamide compound in the preparation of a medicament for preventing and / or treating osteoarthritis, wherein the structure of the benzenesulfonamide compound is shown in formula (I):

2. The use according to claim 1, characterized in that: When the drug acts on an osteoarthritis mouse model, the drug can at least inhibit the joint swelling of the mouse.

3. The use according to claim 1, characterized in that: When the drug acts on an osteoarthritis mouse model, the drug can at least reduce the joint wear of the mouse.

4. The use according to claim 1, characterized in that: When the drug acts on an osteoarthritis mouse model, the drug can at least reduce the serum inflammatory factor content of the mouse; And / or, when the drug acts on an osteoarthritis mouse model, the drug can at least reduce the expression of osteoarthritis-related inflammatory markers in the mouse by more than 30%; preferably, the osteoarthritis-related inflammatory markers include any one or more combinations of MMP13, IL-1β, and TNF-α.

5. The use according to claim 1, characterized in that: When the drug acts on an osteoarthritis mouse model, the drug can at least promote stabilization of the cartilage structure of the mouse; And / or, when the drug acts on an osteoarthritis mouse model, the drug can at least promote and inhibit cartilage fibrosis in the mouse.

6. A pharmaceutical composition for preventing and / or treating osteoarthritis, characterized in that: include: A benzenesulfonamide compound represented by formula (I) or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and / or excipient; Wherein, the pharmaceutically acceptable derivative is selected from at least one of pharmaceutically acceptable salts, polymorphs, co-crystals, radiolabeled forms and combinations thereof.

7. The pharmaceutical composition according to claim 6, characterized in that: When the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least inhibit the joint swelling and articular cartilage wear of the mouse.

8. The pharmaceutical composition according to claim 6, characterized in that: When the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least promote stabilization of the cartilage structure of the mouse; And / or, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least promote and inhibit cartilage fibrosis in the mouse.

9. The pharmaceutical composition according to claim 6, characterized in that: When the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least reduce the serum inflammatory factor content of the mouse; And / or, when the pharmaceutical composition acts on an osteoarthritis mouse model, the pharmaceutical composition can at least reduce the expression of osteoarthritis-related inflammatory markers in the mouse by more than 30%; preferably, the osteoarthritis-related inflammatory markers include any one or more combinations of MMP13, IL-1β, and TNF-α.

10. Use of the pharmaceutical composition according to any one of claims 6 to 9 in the preparation of a medicament for preventing and / or treating osteoarthritis.

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