Composition for treating osteoarthritis and application thereof

Abstract

The invention provides a composition for treating osteoarthritis and application thereof, and belongs to the technical field of medicines. The composition is prepared from baicalin and alpha-ketoglutaric acid, the molar ratio of the baicalin to the alpha-ketoglutaric acid is 800: (3-5). The baicalin and the alpha-ketoglutaric acid have a remarkable synergistic effect in the specific ratio range, the osteoarthritis is treated by protecting cartilage cell damage, relieving cartilage fibrosis and inhibiting cartilage protein polysaccharide and cartilage collagen fiber loss, and in the proper ratio range, the reduction and synergistic effects are achieved on the treatment of the osteoarthritis.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines and provides a composition for treating osteoarthritis and application thereof. Background Art

[0002] Osteoarthritis (OA) is a common degenerative joint disease that causes damage to cartilage and surrounding tissues and is characterized by pain, stiffness, and loss of joint function. Current treatments for OA are very limited, with nonsteroidal anti-inflammatory drugs (NSAIDs) used to relieve pain and swelling. NSAIDs are available in gel or cream form and are rubbed into the skin of the hands and knees (such as 1% diclofenac gel) to help relieve symptoms. Oral NSAIDs carry the risk of serious side effects, so use should be kept as short as possible. People who take oral NSAIDs also usually take medications to protect the stomach lining and may have their kidney function and blood pressure monitored. For people with OA who cannot take NSAIDs, current treatment options are even more limited.

[0003] Baicalin is a flavonoid compound extracted from the dried root of Scutellaria baicalensis, a dicotyledonous plant of the Labiatae family. Studies have shown that it has antibacterial, diuretic, anti-inflammatory, anti-allergic and antispasmodic effects, and has strong anti-cancer effects and other physiological effects. Chinese invention patent CN101491533B discloses the application of baicalin in pharmaceutical manufacturing, pointing out that Huanqingan promotes the transformation of T cells into Tregs with immunosuppressive effects by upregulating the expression of Foxp3, while inhibiting Th17, which promotes inflammation, and inhibits Th17-mediated vasculitis; at the same time, experiments have also proved that baicalin, as a new immunomodulator, has a good therapeutic effect in the treatment of lupus nephritis and rheumatoid arthritis.

[0004] Chinese invention patent CN101700249B discloses a pharmaceutical composition for preventing and treating rheumatoid arthritis. The Chinese medicinal raw materials used to make the active ingredients are composed of the following weight ratios: berberine 5.5-6.0 mg, bamipine 0.3-0.4 mg, jatrorrhizine 1.5-2.0 mg, magnoliavine 1.5-1.8 mg, phellodendron 0.1-0.2 mg, coptisine 0.2-0.3 mg, baicalin 55-60 mg, baicalein 1.5-2.0 mg, wogonin 5.0-7.0 mg, wogonin 0.03-0.05 mg, gardenia glycoside 20-25 mg, crocin 0.1-0.2 mg, and chlorogenic acid 0.25-0.3 mg. The results of pharmacological experiments show that the drug composition can significantly reduce the severity of rheumatoid arthritis CIA mice, and the inflammation and immune damage in the lesion area are significantly improved compared with the control group, and can be used to prepare drugs for treating rheumatoid arthritis. However, the composition is relatively complex, and the compatibility between the various components is not clear, which may result in the inability to fully exert the efficacy of each component.

[0005] At present, there are relatively few studies on such compositions containing baicalin for the prevention and treatment of arthritis. Baicalin has excellent anti-inflammatory and anti-apoptosis properties, and its application is expected to be further expanded when combined with other effective ingredients. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides a composition for treating osteoarthritis. The composition consists of baicalin (BAI) and α-ketoglutaric acid (AKG), which have significant synergistic effects in protecting chondrocyte damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycans and cartilage collagen fibers, and has potential application in the treatment of osteoarthritis.

[0007] The technical solution of the present invention is as follows: The invention provides a composition for osteoarthritis, which consists of baicalin and alpha-ketoglutaric acid; the molar ratio of baicalin to alpha-ketoglutaric acid is 800:3-5.

[0008] Preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3, 200:1 or 160:1.

[0009] More preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3 or 160:1.

[0010] Further preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3.

[0011] The present invention also provides the use of the above composition in preparing a drug for treating osteoarthritis.

[0012] The present invention also provides the use of the above composition in preparing medicines for protecting cartilage cell damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers.

[0013] Furthermore, the composition protects chondrocyte damage by improving the survival rate of chondrocytes.

[0014] Furthermore, the medicine also includes pharmaceutically acceptable excipients.

[0015] Furthermore, the dosage form of the drug is any one of tablets, suspensions, granules, powders, emulsions, capsules and injections.

[0016] Compared with the prior art, the beneficial effects of the present invention are: The present invention expands the composition medicine containing baicalin (BAI) for preventing and treating osteoarthritis, verifies that baicalin (BAI) and α-ketoglutaric acid (AKG) have significant synergistic effects in protecting chondrocyte damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers, and has potential application in the treatment of osteoarthritis. In addition, the optimal ratio of baicalin (BAI) and α-ketoglutaric acid (AKG) is also clarified. Compared with the use of either alone, under this ratio, the composition also achieves the effect of reducing dosage and increasing efficacy in the treatment of osteoarthritis. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The results of rat primary chondrocyte isolation are shown in Figure 1. (A) is the result of Safranin O staining; (B) is the result of Toluidine Blue staining; (C) is the result of Alcian Blue staining. Figure 2 This is the screening result of the toxic dose of MIA on chondrocytes; * p <0.05, compared with the Control group, there is a significant difference; Figure 3 Results of the effects of different concentrations of BAI (A), AKG (B) and BAI+AKG combination (C) on the survival rate of MIA-induced chondrocytes ( * p <0.05, compared with the control group, there is a significant difference; # p <0.05, compared with the model group, there is a significant difference); Figure 4 Comparison of the survival rate of MIA-induced chondrocytes by BAI, AKG alone, and BAI+AKG combination therapy ( * p <0.05, ** p<0.01); Figure 5 Results of changes in rat body weight (A) and knee joint diameter (B); Figure 6 The results of morphological observation of cartilage repair in rat knee joints are shown in Figure 2. Figure 7 Pelletier score for rat knee cartilage repair ( * p <0.05, compared with the Control group, there is a significant difference; # p <0.05, compared with the MIA group, there was a significant difference); Figure 8 This is the Micro-CT scan result of the lower end of the rat femur; Fig. 9 This is the HE staining result of the distal femoral joint of rats; Fig.10 This is the result of SO staining of the distal femoral joint of rats; Fig.11 This is the Masson staining result of the distal femoral joint of rats; Fig.12 The OARSI score results of femoral lesions in rats ( * P <0.05, compared with the Control group, there is a significant difference; # p <0.05, compared with the MIA group, there was a significant difference; a p <0.05, compared with the BAI group, there was a significant difference). DETAILED DESCRIPTION

[0018] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present application.

[0019] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the operating methods used are conventional operating methods, and the equipment used are conventional equipment.

[0020] 1. The therapeutic effect of BAI+AKG combination on chondrocyte injury induced by sodium iodoacetate (MIA) (1) Isolation, culture and identification of primary rat chondrocytes 1.1 Isolation and culture of primary chondrocytes Two SD rats were killed and soaked in 75% ethanol for 15 minutes. The skin was cut from the navel to the sternum to expose the costal cartilage, which was cut and placed in PBS buffer. Then the muscles and soft tissues on the surface of the cartilage were removed, the cartilage was cut into pieces, and transferred to a centrifuge tube with a Pasteur pipette. Then 2 mL of 0.25% trypsin (Trypsin-EDTA) was added, and after digestion at 37°C for 30 minutes, the supernatant was discarded and 4 mL of DMEM medium containing 15% fetal bovine serum (FBS) was added to terminate the digestion. After centrifugation at 1200 rpm for 5 minutes, the supernatant was discarded, 2 mL of 0.2% type II collagenase was added, and digestion was performed at 37°C for 2 hours. After centrifugation at 1200 rpm for 5 minutes, the supernatant was discarded, and 4 mL of DMEM medium containing 15% FBS was added to resuspend. Finally, after the cartilage fragments were precipitated to the bottom of the tube, the supernatant was aspirated into a culture dish and cultured at 37°C and 5% CO2. The medium was changed every 3 days, and the cells were digested with trypsin and passaged when the cells grew to 90%.

[0021] 1.2 Identification of chondrocytes The second generation chondrocytes were taken at 2×10 5 The cells were inoculated at a density of 100 / mL in a six-well plate. When the cells grew to 70-80%, the culture medium was discarded, and the cells were fixed with 4% paraformaldehyde for 30 minutes. Then, the cells were washed with PBS buffer and stained with safranin O staining solution, toluidine blue staining solution and Alcian blue staining solution for 30 minutes respectively. After rinsing with PBS for 3 times, the cells were observed under a microscope.

[0022] 1.3 Experimental Results like Figure 1 As shown in Figure 1, the morphology of chondrocytes is irregular, such as long spindles or polygons. The results of safranin O staining are as follows Figure 1 As shown in (A), the cytoplasm and nucleus are stained red, indicating that the isolated primary cells can secrete proteoglycans; the results of toluidine blue staining are as follows Figure 1 As shown in (B), the cells are stained blue, indicating that the cells can secrete glycosaminoglycans. The results of Alcian blue staining are as follows Figure 1 As shown in (C), Alcian blue can form a complex with sulfate groups (such as chondroitin sulfate) containing anionic groups in chondrocytes and appear light blue. The three staining results all indicate that the enzymatic digestion method was used to successfully isolate and culture primary chondrocytes in rats.

[0023] (2) Effects of MIA and small molecule compounds on chondrocyte viability 2.1 Establishment of MIA-induced chondrocyte injury model The cell suspension was obtained by digesting the chondrocytes with trypsin, and the cell concentration was adjusted to 6×10 4 / mL and inoculated into a 96-well plate, 100μL cell suspension per well. Then, place in a cell culture incubator and culture for 24 hours, discard the culture medium, add MIA solutions with concentrations of 1μM, 2μM, 3μM, 4μM, 5μM, 5.5μM, and 6μM, respectively, continue to culture for 24 hours, and discard the original culture medium. Add DMEM culture medium containing 10% CCK-8 to each well, incubate for 1 hour, measure the OD value at a wavelength of 450nm with an enzyme reader, and calculate the cell survival rate as follows: Cell survival rate = (OD value of drug group - OD value of blank group) / (OD value of control group - OD value of blank group) × 100% Results Figure 2 It can be seen that 5.5μM MIA caused the viability of chondrocytes to drop significantly to 50%-60%. Subsequent experiments selected 5.5μM as the modeling concentration of MIA-induced chondrocyte injury in vitro.

[0024] 2.2 Protective effects of BAI and AKG on MIA-induced chondrocyte injury The cell suspension was obtained by digesting the chondrocytes with trypsin, and the cell concentration was adjusted to 6×10 4 / mL and inoculated into 96-well plates, with 100μL cell suspension in each well. Then, they were cultured in a cell culture incubator for 24h. The cells were grouped, with 4 replicates in each group. The control group (Control group) did not add MIA, the blank group had no cells and did not add MIA, the model group (MIA group) added 5.5μM MIA solution, and the experimental groups (AKG group and BAI group) added 5.5μM MIA solution to induce cell damage. Then, equal volumes of different concentrations of AKG (0.5, 2, 4, 8, 12, 16mM) and different concentrations of BAI (5, 15, 25, 50, 100μM) were added, and the culture was continued for 24h. The culture medium was discarded, and DMEM culture medium containing 10% CCK-8 was added to each well. After incubation for another 1h, the OD value was measured at a wavelength of 450nm using an enzyme reader, and the cell survival rate was calculated to screen out the best concentration for single administration.

[0025] The experimental results are as follows Figure 3 As shown in (A) and (B), after 24 hours of intervention with 5.5μM MIA, the cell survival rate of chondrocytes was significantly reduced to about 50%. When administered alone, 4mM AKG and 8mM AKG can significantly increase the survival rate of chondrocytes; 25uM BAI significantly increases the survival rate of chondrocytes.

[0026] 2.3 Protective effect of BAI+AKG combination on MIA-induced chondrocyte injury The cell suspension was obtained by digesting the chondrocytes with trypsin, and the cell concentration was adjusted to 6×10 4 / mL and inoculated into 96-well plates, with 100μL of cell suspension per well. Then placed in a cell culture incubator for 24h. The cells were grouped, with 4 replicates in each group. The control group (Control group) did not add MIA, the blank group had no cells and did not add MIA, the model group (MIA group) added 5.5μM MIA solution, and the experimental group (BAI+AKG group) added 5.5μM MIA solution to induce cell damage, and then administered according to Table 1, continued to culture for 24h, discarded the culture medium, added DMEM culture medium containing 10% CCK-8 to each well, and incubated for another 1h, and the OD value was measured at a wavelength of 450nm using an enzyme reader to calculate the cell survival rate.

[0027] Table 1 Dosage of combined medication

[0028] Results Figure 3 As shown in (C), it can be seen that when used in combination, 15uM BAI, 25uM BAI and 4mM AKG can significantly protect the survival rate of chondrocytes.

[0029] In addition, the comparison results of cell survival rate after single administration of 15uM BAI and 4mM AKG and combined administration of 15uM BAI + 4mM AKG are shown in Figure 4 As can be seen from the figure, at this concentration, the cell survival rate of the combined drug treatment was significantly different from that of BAI alone and AKG alone. Therefore, at this concentration, AKG and BAI have a significant synergistic effect on the protection of chondrocytes from MIA-induced damage.

[0030] 2. Study on the treatment of osteoarthritis rats with BAI+AKG combination therapy (1) Experimental groups and drug administration Fifty SD rats were randomly divided into control group (Control group), model group (MIA group), baicalin group (BAI group), α-ketoglutarate group (AKG group), and combined administration group (BAI+AKG group), with 10 rats in each group. All rats were fasted for 12 hours, weighed, and anesthetized with isoflurane. The hair on the right knee joint was shaved and disinfected with alcohol. The knee joint was flexed, the needle was inserted into the joint cavity, and the injection was slowly pushed. After the needle was removed, it was disinfected with alcohol. Except for the right knee joint of the rats in the Control group, which was injected with 50μL of normal saline, the right knee joints of the rats in the other groups were injected with 50μL of MIA (2mg / 50μL). Two weeks after the rats in each group were injected with MIA into the right knee joint to establish the model, drug injections were started. The Control group and the MIA group were injected with 50 μL of normal saline, the BAI group was injected with 50 μL of 15uM BAI aqueous solution, the AKG group was injected with 50 μL of 4mM AKG aqueous solution, and the BAI+AKG group was injected with 50 μL of an aqueous solution containing 15uM BAI and 4mM AKG. The drugs were administered once every 7 days for 3 consecutive times.

[0031] (2) Detection indicators 2.1 Measurement of rat knee joint diameter The body weight and knee joint diameter of rats in each group were measured before modeling, on the 1st, 4th and 7th days after modeling, before each administration and when the animals were finally sampled. The measurements were made three times and the average value was taken to evaluate the degree of joint swelling.

[0032] 2.2 Morphological observation and Pelletier score of rat knee cartilage The right lower limb of the rat was taken, the muscles were carefully stripped, the femur and tibia were separated, the cartilage platform was observed and photographed under a stereomicroscope, and the bone tissue was fixed in 4% paraformaldehyde for 24 hours. The Pelletier score was used to evaluate the degree of repair of the rat knee cartilage. The scoring criteria are shown in Table 2.

[0033] Table 2 Pelletier scoring criteria

[0034] 2.3 Bone tissue decalcification, paraffin embedding and sectioning Place the bone tissue sample in 10 times the volume of decalcification solution, and change the decalcification solution every 3 days. Use a 1mL syringe needle to puncture the cortical bone. If you feel no resistance, you can pierce it, indicating that the tissue decalcification is complete. After decalcification, rinse with tap water for 12 hours and then use 75% ethanol, 80% ethanol, 95% ethanol, and 100% ethanol for gradient dehydration. After xylene is transparent for 40 minutes, the bone tissue is fully immersed in wax for 6 hours before embedding. After embedding, the bone tissue is sliced.

[0035] 2.3.1 Hematoxylin-eosin (HE) staining ① Baking: Place the slices in a 60℃ oven for 2 hours to increase the adhesion between the bone tissue and the slide; ② Dewaxing: After the slices have cooled to room temperature, place them in xylene twice for 15 minutes each time, 100% ethanol twice for 5 minutes each time, 95% ethanol, 85% ethanol and 75% ethanol for 5 minutes each, and distilled water three times for 3 minutes each time; ③HE staining: hematoxylin staining for 8 minutes, running water anti-blueing for 10 minutes, 95% ethanol washing for 5 minutes; eosin staining for 10 seconds, 95% ethanol washing for 3 seconds, 100% ethanol washing twice, 1 minute each time, xylene washing twice, 2 minutes each time; finally, seal the slides with neutral gum and dry them in a fume hood overnight; ④After 24 hours, observe the morphological changes of bone tissue under an inverted microscope and take photos.

[0036] 2.3.2 Safranin-Fast Green (SO) staining ① The steps of baking and dewaxing are the same as those of HE staining. The other experimental steps are as follows: ② Staining: Stain with hematoxylin for 10 minutes, place in acidic ethanol for 5 seconds, and wash with distilled water for 10 seconds; stain with fast green for 10 minutes, and wash with 1% acetic acid for 10 seconds; stain with safranin O at 55°C for 1 hour, wash with 95% ethanol for 3 seconds, then wash with 100% ethanol twice, each time for 1 minute, wash with xylene twice, each time for 2 minutes, and finally seal with neutral gum and dry in a fume hood overnight; ③After 24 hours, observe the morphological changes of bone tissue under an inverted microscope and take photos.

[0037] 2.3.3 Masson staining ① The steps of baking and dewaxing are the same as those of HE staining. The other experimental steps are as follows: ②Hematoxylin staining for 10 minutes, acid ethanol differentiation solution treatment for 5 seconds, distilled water washing for 10 seconds; Masson blue solution staining for 3 minutes, distilled water washing for 1 minute; Ponceau fuchsin solution staining for 10 minutes, weak acid working solution treatment for 30 seconds, phosphomolybdic acid differentiation for 30 seconds, and then weak acid working solution treatment for 30 seconds; aniline blue staining for 1 minute, weak acid working solution treatment for 1 minute, successively washed with 95% ethanol for 3 seconds, 100% ethanol for 2 times, 1 minute each time, and xylene for 2 times, 2 minutes each time; finally, seal the slides with neutral gum and dry them in a fume hood overnight; ③After 24 hours, the changes in collagen fibers in the bone tissue were observed under an inverted microscope and photographed.

[0038] (3) Experimental results: 3.1 Changes in rat body weight and knee joint diameter during the experiment Results Figure 5 Compared with the control group, the diameter of the knee joint of each group of rats increased significantly and the knee joint swelled within 1-4 days after the injection of MIA, indicating that the MIA-induced rat knee arthritis model was successfully established. During the experiment, the weight of rats in each group increased steadily, and the weight of rats in the other groups was slightly lower than that of rats in the control group.

[0039] 3.2 Morphological observation and Pelletier score of rat knee cartilage repair Rat articular cartilage morphology Figure 6 The surface of articular cartilage in the Control group was intact and smooth, while obvious ulcers formed on the surface of femoral condyle cartilage in the MIA group, the tibial plateau cartilage was stripped and the subchondral bone was exposed. Although the cartilage surfaces of the other drug-treated groups were damaged to varying degrees, the degree of damage was lighter than that in the MIA group. Among them, the repair effect of articular cartilage in the BAI+AKG group was significantly higher than that in the BAI group and the AKG group.

[0040] Pelletier score results are shown in Figure 7 Compared with the Control group, the MIA group had significant differences, indicating that the MIA-induced rat knee arthritis model was successfully established. Compared with the MIA group, the BAI group, the AKG group, and the BAI+AKG group all had significant differences, indicating that BAI and AKG alone or in combination could repair MIA-induced rat knee cartilage damage, among which the combined group had a lower score than the single-drug group, and had a better repair effect on MIA-induced rat knee cartilage damage.

[0041] 3.3 Micro-CT scan results of the lower end of the rat femur like Figure 8 As shown in the figure, compared with the Control group, the bone tissue of the subarticular bone in the MIA group was severely lost and the number of trabeculae was reduced, indicating that the MIA-induced rat knee arthritis model was successfully established. The other drug-treated groups recovered after treatment, and the recovery of the subarticular bone in the BAI+AKG group was the most obvious.

[0042] 3.4 Histopathological observation of distal femur of rats HE staining results of rat femur tissue sections are as follows Fig. 9As shown in the figure, the surface of the articular cartilage in the Control group was covered with a thin layer of flat chondrocytes, the middle layer was round chondrocytes, and the deep layer and calcified layer were hyperplastic chondrocytes, which were arranged in an orderly manner and had a complete cartilage structure; the articular surface cartilage in the MIA group was eroded and replaced by a thick layer of inflammatory fibrous tissue, the cartilage fibrosis was severe, and there were many hypertrophic chondrocytes in the deep layer; the articular surface of the BAI+AKG group was intact, the surface fibrous tissue became thinner, and the deep hypertrophic chondrocytes were less than those in the MIA group. Compared with the MIA group, the degree of fibrosis of the articular surface in the AKG group was inhibited, but its cartilage structure was basically not repaired. The articular cartilage structure in the BAI group was improved to a certain extent, but compared with the BAI+AKG group, the regeneration rate of the cartilage layer was slow and the number of hypertrophic chondrocytes was large.

[0043] The results of SO staining of rat femoral tissue sections are as follows Fig.10 As shown, the area of ​​the red region reflects the content of proteoglycan in cartilage. The results showed that BAI+AKG can effectively inhibit the loss of proteoglycan in articular cartilage of rats with osteoarthritis.

[0044] Masson staining is a selective staining method for collagen fibers. Normal cartilage is blue because it is rich in collagen fibers. The blue color of the MIA group is seriously lost (appearing red). The results of Masson staining of rat femoral tissue sections are shown in Figure 2. Fig.11 As shown, the results showed that BAI+AKG could effectively inhibit the loss of collagen fibers in articular cartilage of rats with osteoarthritis.

[0045] The OARSI score is a standard for evaluating the progression of OA cartilage pathology. The higher the score, the more severe the cartilage lesions. Based on the results of the above HE staining, SO staining and Masson staining, the OARSI score was performed on the specimens of each group.

[0046] The results are as follows Fig.12 As shown in the results, BAI+AKG can significantly reduce the OARSI score, and is significantly better than the single drug group, and there is a significant difference compared with the AKG group.

[0047] In summary, baicalin (BAI) and α-ketoglutarate (AKG) have significant synergistic effects in protecting chondrocyte damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycans and cartilage collagen fibers, and have potential applications in the treatment of osteoarthritis. The combination of the two also plays a role in reducing dosage and increasing efficacy in the treatment of osteoarthritis.

[0048] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for treating osteoarthritis, characterized in that: The composition consists of baicalin and α-ketoglutaric acid; the molar ratio of baicalin to α-ketoglutaric acid is 800:3-5.

2. The composition according to claim 1, characterized in that The molar ratio of baicalin to α-ketoglutaric acid is 800:

3.

3. The composition according to claim 1, characterized in that The molar ratio of baicalin to α-ketoglutaric acid is 200:

1.

4. The composition according to claim 1, characterized in that The molar ratio of baicalin to α-ketoglutaric acid is 160:

1.

5. Use of the composition according to any one of claims 1 to 4 in the preparation of a drug for treating osteoarthritis.

6. Use of the composition according to any one of claims 1 to 4 in the preparation of a drug for protecting chondrocyte damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers.

7. The use according to claim 6, characterized in that: The composition protects chondrocyte damage by improving the survival rate of chondrocytes.

8. The use according to claim 5 or 6, characterized in that: The drug also includes pharmaceutically acceptable excipients.

9. The use according to claim 5 or 6, characterized in that: The dosage form of the drug is any one of tablets, suspensions, granules, powders, emulsions, capsules and injections.

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