A composition for treating osteoarthritis and its application

Abstract

The present invention provides a composition for treating osteoarthritis and its application, belonging to the technical field of medicine. The composition is composed of baicalin and α-ketoglutaric acid; the molar ratio of baicalin to α-ketoglutaric acid is 800:3-5. Within this specific ratio range, baicalin and α-ketoglutaric acid have a significant synergistic effect, and the treatment of osteoarthritis is achieved by protecting chondrocyte damage, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers. Moreover, within the appropriate ratio range, it has the effect of reducing dosage and increasing efficacy for the treatment of osteoarthritis.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, and provides a composition for treating osteoarthritis and its application. Background Art

[0002] Osteoarthritis (OA) is a common joint degenerative disease that causes damage to cartilage and surrounding tissues, characterized by pain, stiffness, and loss of joint function. Currently, the treatment for osteoarthritis is very limited. Non-steroidal anti-inflammatory drugs (NSAIDs) are mainly used to relieve pain and swelling. NSAIDs are available in both gel and cream formulations and can be rubbed into the skin of the hand and knee joints (such as 1% diclofenac gel) to help relieve symptoms. Oral NSAIDs carry the risk of serious side effects, so the use time should be shortened as much as possible. Patients taking oral non-steroidal anti-inflammatory drugs usually also take drugs to protect the gastric mucosa and may undergo renal function and blood pressure monitoring. For patients with osteoarthritis who cannot take NSAIDs, the current treatment methods are even more limited.

[0003] Baicalin is a flavonoid compound extracted from the dried roots of the dicotyledonous Labiatae plant Scutellaria baicalensis. Studies have shown that it has antibacterial, diuretic, anti-inflammatory, anti-allergic, and antispasmodic effects, and also has strong anti-cancer responses and other physiological effects. Chinese Patent CN101491533B discloses the application of baicalin in pharmaceuticals, indicating that Qing'an promotes the transformation of T cells into immunosuppressive Tregs by upregulating the expression of Foxp3, while inhibiting Th17 with pro-inflammatory effects and suppressing Th17-mediated vasculitis. At the same time, experiments have also proven that baicalin, as a new immunomodulator, has good curative effects 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 traditional Chinese medicine raw materials made into the active ingredients are composed of the following weight ratios: berberine 5.5 - 6.0 mg, palmatine 0.3 - 0.4 mg, jatrorrhizine 1.5 - 2.0 mg, magnoflorine 1.5 - 1.8 mg, phellodendrine 0.1 - 0.2 mg, coptisine 0.2 - 0.3 mg, baicalin 55 - 60 mg, baicalein 1.5 - 2.0 mg, wogonoside 5.0 - 7.0 mg, wogonin 0.03 - 0.05 mg, geniposide 20 - 25 mg, crocin 0.1 - 0.2 mg, chlorogenic acid 0.25 - 0.3 mg. The results of pharmacological experiments show that this pharmaceutical composition can significantly reduce the severity of rheumatoid arthritis in CIA mice, and the inflammation and immune damage in the lesion site are significantly improved compared with the control group, and it can be used to prepare drugs for treating rheumatoid arthritis. However, the composition of this composition is relatively complex, and the compatibility of various components is not clear, which may lead to the failure to fully exert the efficacy of each component.

[0005] At present, there are relatively few studies on such compositions containing baicalin for preventing and treating arthritis. Baicalin has excellent anti-inflammatory and anti-apoptotic properties. When combined with other active ingredients, its application is expected to be further expanded. Summary of the Invention

[0006] Aiming at the problems existing in the prior art, the present invention provides a composition for treating osteoarthritis, which is composed of baicalin (BAI) and α-ketoglutaric acid (AKG). The two have significant synergistic effects in protecting chondrocyte injury, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers, and have potential applications in the treatment of osteoarthritis.

[0007] The technical solution of the present invention is as follows:

[0008] The present invention provides a composition for osteoarthritis, which is composed of baicalin and α-ketoglutaric acid; the molar ratio of baicalin to α-ketoglutaric acid is 800:3 - 5.

[0009] Preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3, 200:1 or 160:1.

[0010] More preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3 or 160:1.

[0011] Further preferably, the molar ratio of baicalin to α-ketoglutaric acid is 800:3.

[0012] The present invention also provides the application of the above composition in the preparation of drugs for treating osteoarthritis.

[0013] The present invention also provides the use of the above-mentioned composition in the preparation of a drug for protecting chondrocyte injury, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers.

[0014] Furthermore, the composition protects chondrocyte injury by enhancing the survival rate of chondrocytes.

[0015] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0016] Furthermore, the dosage form of the drug is any one of tablets, suspensions, granules, powders, emulsions, capsules, and injections.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The present invention expands the drugs of the composition for preventing and treating osteoarthritis containing baicalin (BAI), verifies that baicalin (BAI) and α-ketoglutaric acid (AKG) have significant synergistic effects in protecting chondrocyte injury, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan and cartilage collagen fibers, and has potential applications in the treatment of osteoarthritis. In addition, the optimal ratio of baicalin (BAI) and α-ketoglutaric acid (AKG) is also determined. Compared with the use of the two alone, at this ratio, the composition also achieves the effect of reducing dosage and increasing efficacy in the treatment of osteoarthritis. Description of the Drawings

[0019] Figure 1 Shows the isolation results of primary chondrocytes of rats; among them, (A) shows the safranin O staining result; (B) shows the toluidine blue staining result; (C) shows the alcian blue staining result;

[0020] Figure 2 Shows the screening results of the cytotoxic dose of MIA on chondrocytes; * p <0.05, indicating a significant difference compared with the Control group;

[0021] Figure 3 Shows the survival rate results of chondrocytes induced by MIA with different concentrations of BAI (A), AKG (B), and combined use of BAI + AKG (C) ( * p <0.05, indicating a significant difference compared with the control group; # p <0.05, indicating a significant difference compared with the model group);

[0022] Figure 4Comparison results of the survival rates of chondrocytes induced by MIA with BAI, AKG administered alone, and BAI + AKG administered in combination ( * p < 0.05, ** p < 0.01);

[0023] Figure 5 Results of changes in rat body weight (A) and knee joint diameter (B);

[0024] Figure 6 Results of morphological observation of cartilage repair in rat knee joints;

[0025] Figure 7 Results of Pelletier scores for cartilage repair in rat knee joints ( * p < 0.05, significantly different compared with the Control group; # p < 0.05, significantly different compared with the MIA group);

[0026] Figure 8 Results of Micro-CT scans of the lower end of the rat femur;

[0027] Figure 9 Results of HE staining of the lower end of the rat femur joint;

[0028] Figure 10 Results of SO staining of the lower end of the rat femur joint;

[0029] Figure 11 Results of Masson staining of the lower end of the rat femur joint;

[0030] Figure 12 Results of OARSI scores for the degree of rat femoral lesions ( * P < 0.05, significantly different compared with the Control group; # p < 0.05, significantly different compared with the MIA group; a p < 0.05, significantly different compared with the BAI group). Specific implementation manners

[0031] The following non-limiting examples can enable those of ordinary skill in the art to more comprehensively understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the invention of the present invention according to the disclosed content, and it should also fall within the scope claimed by this application.

[0032] The present invention will be further described below by way of specific embodiments. All kinds of chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the operating methods used are all conventional operating methods, and the equipment used is all conventional equipment.

[0033] I. Therapeutic effect of BAI + AKG combination on chondrocyte injury induced by sodium iodoacetate (MIA)

[0034] (1) Isolation, culture and identification of primary rat chondrocytes

[0035] 1.1 Isolation and culture of primary chondrocytes

[0036] After sacrificing 2 neonatal SD rats, soak them in 75% ethanol for 15 min. Cut the skin along the navel to the sternum to expose the costal cartilage, cut it off and place it in PBS buffer. Then remove the muscle and soft tissue on the surface of the cartilage, cut the cartilage into pieces, and transfer it to a centrifuge tube with a Pasteur pipette. Then add 2 mL of 0.25% trypsin (Trypsin - EDTA), digest at 37 °C for 30 min, discard the supernatant and add 4 mL of DMEM medium containing 15% fetal bovine serum (FBS) to terminate digestion. After centrifugation at 1200 rpm for 5 min, discard the supernatant, add 2 mL of 0.2% type II collagenase, and digest at 37 °C for 2 h. After centrifugation at 1200 rpm for 5 min again, discard the supernatant, and resuspend with 4 mL of DMEM medium containing 15% FBS. Finally, after the cartilage fragments precipitate to the bottom of the tube, aspirate the supernatant into a culture dish and culture it at 37 °C and 5% CO 2 2. Incubate. Change the medium every 3 days. When the cells grow to 90%, digest and passage them with trypsin.

[0037] 1.2 Identification of chondrocytes

[0038] Take the second-generation chondrocytes and inoculate them in a six-well plate at a density of 2×10 5 cells / mL. When the cells grow to 70 - 80%, discard the medium, fix with 4% paraformaldehyde for 30 min, wash with PBS buffer, and then add safranin O staining working solution, toluidine blue staining working solution and alcian blue staining working solution respectively for staining for 30 min. After rinsing 3 times with PBS, observe under a microscope.

[0039] 1.3 Experimental results

[0040] As Figure 1 shown, the morphology of chondrocytes is irregular, such as long spindle-shaped or polygonal. The results of safranin O staining are as Figure 1As shown in (A) therein, it can be seen that both the cytoplasm and the nucleus are stained red, indicating that the isolated primary cells can secrete proteoglycans; the result of toluidine blue staining is as Figure 1 shown in (B) therein. It can be seen that the cells are stained blue, indicating that the cells can secrete glycosaminoglycans; the result of alcian blue staining is as Figure 1 shown in (C) therein. It can be seen that alcian blue can form a complex with sulfate groups (such as chondroitin sulfate) containing anionic groups in chondrocytes and present as light blue. All three staining results indicate that the primary rat chondrocytes were successfully isolated and cultured by the enzyme digestion method in this experiment.

[0041] (2)Effects of MIA and small molecule compounds on chondrocyte viability

[0042] 2.1 Establishment of a chondrocyte injury model induced by MIA

[0043] After digesting chondrocytes with trypsin, a cell suspension was obtained. After cell counting, the cell concentration was adjusted to 6×10 4 cells / mL and seeded into 96-well plates, 100 μL of cell suspension per well. Then, after culturing in a cell incubator for 24 h, the culture medium was discarded, and MIA solutions with concentrations of 1 μM, 2 μM, 3 μM, 4 μM, 5 μM, 5.5 μM, and 6 μM were added respectively. After continuing to culture for 24 h, the original culture medium was discarded. 10% CCK-8-containing DMEM culture medium was added to each well. After incubating for 1 h, the OD value was measured at a wavelength of 450 nm with an enzyme-linked immunosorbent assay (ELISA) reader, and the cell survival rate was calculated according to the following formula:

[0044] Cell survival rate = (OD value of the drug administration group - OD value of the blank group) / (OD value of the control group - OD value of the blank group) × 100%

[0045] The results are shown in Figure 2 , and it can be seen that 5.5 μM MIA caused a significant decrease in the viability of chondrocytes to 50% - 60%. 5.5 μM was selected as the modeling concentration for in vitro induction of chondrocyte injury by MIA in subsequent experiments.

[0046] 2.2 Protective effects of BAI and AKG on MIA-induced chondrocyte injury

[0047] After digesting chondrocytes with trypsin, a cell suspension was obtained. After cell counting, the cell concentration was adjusted to 6×10 4Cells were counted after trypsin digestion to adjust the cell concentration to 6×10

[0048] The experimental results are shown in Figure 3 (A) and (B) below. After chondrocytes were intervened with 5.5 μM MIA for 24 h, the cell viability decreased significantly to about 50%. When administered alone, 4 mM AKG and 8 mM AKG could significantly increase the viability of chondrocytes; 25 μM BAI significantly increased the viability of chondrocytes.

[0049] 2.3 Protective effect of combined administration of BAI + AKG on MIA-induced chondrocyte injury

[0050] Cells were counted after trypsin digestion to adjust the cell concentration to 6×10 4 cells / mL and inoculated into 96-well plates with 100 μL of cell suspension per well. Then they were cultured in a cell incubator for 24 h. The cells were grouped with 4 replicates in each group. Among them, 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 5.5 μM MIA solution, and the experimental group (BAI+AKG group) added 5.5 μM MIA solution to induce cell injury, and then administered drugs according to Table 1 and continued to culture for 24 h. The culture medium was discarded, 10% CCK-8-containing DMEM medium was added to each well, and after incubation for 1 h, the OD value was measured at a wavelength of 450 nm with an enzyme-linked immunosorbent assay (ELISA) reader, and the cell viability was calculated.

[0051] Table 1 Dosage of combined administration

[0052]

[0053] The results are shown in Figure 3 (C) below. It can be seen that when used in combination, 15 μM BAI, 25 μM BAI and 4 mM AKG can significantly protect the viability of chondrocytes.

[0054] In addition, the comparison results of cell viability after single administration of 15 uM BAI and 4 mM AKG and combined administration of 15 uM BAI + 4 mM AKG are shown in Figure 4 , as can be seen from the figure, at this concentration, there are extremely significant differences in cell viability between the combined drug use and single drug use of BAI and single drug use of AKG. Therefore, at this concentration, AKG and BAI have a significant synergistic effect on protecting chondrocytes from MIA-induced damage.

[0055] II. Therapeutic study of combined use of BAI + AKG on osteoarthritis rats

[0056] (1) Experimental grouping and drug administration

[0057] Fifty SD rats were randomly divided into a control group (Control group), a model group (MIA group), a baicalin group (BAI group), an α-ketoglutaric acid group (AKG group), and a combined drug administration group (BAI + AKG group), with 10 rats in each group. After fasting all rats for 12 h, the body weights of the rats were weighed and they were anesthetized with isoflurane. After shaving the hair on the right knee joint, it was disinfected with alcohol. The knee joint was flexed, the needle was inserted into the joint cavity, and the injection was slowly pushed. After removing the needle, it was disinfected with alcohol. Except for injecting 50 μL of normal saline into the right knee joint of the rats in the Control group, 50 μL of MIA (2 mg / 50 μL) was injected into the right knee joint of the rats in the other groups. Two weeks after modeling by injecting MIA into the right knee joint of the rats in each group, drug injection was started. Among them, the Control group and the MIA group were injected with 50 μL of normal saline, the BAI group was injected with 50 μL of an aqueous solution of 15 uM BAI, the AKG group was injected with 50 μL of an aqueous solution of 4 mM AKG, and the BAI + AKG group was injected with 50 μL of an aqueous solution containing 15 uM BAI and 4 mM AKG. The drug was administered once every 7 days for 3 consecutive times.

[0058] (2) Detection indexes

[0059] 2.1 Measurement of the diameter of the rat knee joint

[0060] Before modeling, on the 1st, 4th, and 7th days after modeling, before each drug administration, and at the time of final animal sampling, the body weights and the diameters of the knee joints of the rats in each group were measured three times and the average value was taken to evaluate the degree of joint swelling.

[0061] 2.2 Morphological observation of the cartilage of the rat knee joint and Pelletier score

[0062] Take the right lower limb of the rat. After carefully stripping the muscles, separate the femur and tibia. Observe the cartilage platform under a stereomicroscope and take pictures. Then fix the bone tissue in 4% paraformaldehyde for 24 h. Perform Pelletier scoring on the articular cartilage of each group to evaluate the repair degree of the rat knee joint cartilage. The scoring criteria are shown in Table 2.

[0063] Table 2 Pelletier Scoring Criteria

[0064]

[0065] 2.3 Decalcification, paraffin embedding and sectioning of bone tissue

[0066] Put the bone tissue samples into decalcifying solution with a volume 10 times that of the samples, and change the decalcifying solution once every 3 days. Pierce the cortical bone with a 1 mL syringe needle. If no resistance is felt, it means the tissue decalcification is completed. After decalcification, rinse with tap water for 12 h, then perform gradient dehydration with 75% ethanol, 80% ethanol, 95% ethanol, and 100% ethanol. After clearing with xylene for 40 min, fully infiltrate the bone tissue with wax for 6 h and then embed it. After embedding, section the bone tissue.

[0067] 2.3.1 Hematoxylin-eosin (HE) staining

[0068] ① Baking the sections: Place the sections in an oven at 60 °C for 2 h to increase the adhesion between the bone tissue and the glass slides;

[0069] ② Dewaxing: After the sections are cooled to room temperature, place the sections in xylene twice, 15 min each time, 100% ethanol twice, 5 min each time, 95% ethanol, 85% ethanol, and 75% ethanol for 5 min each, and distilled water three times, 3 min each;

[0070] ③ HE staining: Stain with hematoxylin for 8 min, blue with running water for 10 min, wash with 95% ethanol for 5 min; stain with eosin stain for 10 s, wash with 95% ethanol for 3 s, wash with 100% ethanol twice, 1 min each time, wash with xylene twice, 2 min each time; finally, mount with neutral gum and air-dry the sections overnight in a fume hood;

[0071] ④ After 24 h, observe the morphological changes of the bone tissue under an inverted microscope and take pictures.

[0072] 2.3.2 Safranin-fast green (SO) staining

[0073] ① The steps of baking the sections and dewaxing are the same as those of HE staining. The other experimental steps are as follows:

[0074] ② Staining: Hematoxylin staining for 10 min, placed in acidic ethanol for 5 s, washed with distilled water for 10 s; Fast Green staining for 10 min, washed with 1% acetic acid for 10 s; Safranin O staining at 55 °C for 1 h, washed with 95% ethanol for 3 s, then washed with 100% ethanol twice, 1 min each time, washed with xylene twice, 2 min each time, and finally sealed with neutral balsam and air-dried in the fume hood overnight;

[0075] ③ After 24 h, place it under an inverted microscope to observe the morphological changes of bone tissue and take pictures.

[0076] 2.3.3 Masson Staining

[0077] ① The steps of baking the slides and dewaxing to obtain water are the same as those of HE staining. The other experimental steps are as follows:

[0078] ② Hematoxylin staining for 10 min, treated with acidic ethanol differentiation solution for 5 s, washed with distilled water for 10 s; Masson blueing solution staining for 3 min, washed with distilled water for 1 min; Ponceau fuchsin solution staining for 10 min, treated with weak acid working solution for 30 s, differentiated with phosphomolybdic acid for 30 s, and then treated with weak acid working solution for 30 s; Aniline blue staining for 1 min, treated with weak acid working solution for 1 min, washed with 95% ethanol for 3 s, 100% ethanol twice, 1 min each time, washed with xylene twice, 2 min each time; Finally sealed with neutral balsam and air-dried in the fume hood overnight;

[0079] ③ After 24 h, place it under an inverted microscope to observe the changes of collagen fibers in bone tissue and take pictures.

[0080] (3)Experimental results:

[0081] 3.1 Changes in rat body weight and knee joint diameter during the experiment

[0082] The results are shown in Figure 5 , compared with the Control group, the knee joint diameters of rats in each group were significantly increased within 1 - 4 days after MIA injection, and the knee joints were swollen, indicating that the rat knee arthritis model induced by MIA was successfully established. During the experiment, the body weights of rats in each group increased steadily, and the body weights of the remaining groups of rats were slightly lower than those of the Control group rats.

[0083] 3.2 Morphological observation of rat knee joint cartilage repair and Pelletier score

[0084] The morphology of rat articular cartilage is shown in Figure 6, The articular cartilage surface of the Control group was intact and smooth. In the MIA group, obvious ulcers formed on the femoral condyle cartilage surface, the cartilage of the tibial plateau was exfoliated and the subchondral bone was exposed. Although the cartilage surfaces of the other drug-administered groups were damaged to varying degrees, the degree of damage was less than that of the MIA group. Among them, the repair effect of the BAI+AKG group on articular cartilage was significantly higher than that of the BAI group and the AKG group.

[0085] The results of the Pelletier score are shown in Figure 7 , Compared with the Control group, there were significant differences in the MIA group, indicating that the rat knee arthritis model induced by MIA was successfully established. Compared with the MIA group, there were significant differences in the BAI group, the AKG group and the BAI+AKG group, indicating that BAI and AKG administered alone and in combination could repair the cartilage damage of the rat knee joint induced by MIA. Among them, the score of the combined drug group was lower than that of the single drug administration group, and the repair effect on the cartilage damage of the rat knee joint induced by MIA was better.

[0086] 3.3 Results of Micro-CT scanning of the distal femur of rats

[0087] As Figure 8 shown, compared with the Control group, there was severe loss of bone tissue in the subchondral bone of the MIA group, and the number of trabeculae decreased, indicating that the rat knee arthritis model induced by MIA was successfully established. The other drug-administered groups recovered after treatment, and the recovery of the subchondral bone in the BAI+AKG group was the most obvious.

[0088] 3.4 Results of histopathological observation of the distal femur of rats

[0089] The HE staining results of the rat femur tissue sections are as Figure 9 shown. In the Control group, the articular cartilage surface was covered with a thin layer of flat chondrocytes, the middle layer was round chondrocytes, and the deep and calcified layers were proliferating chondrocytes, arranged in an orderly manner, and the cartilage structure was complete; in the MIA group, the articular surface cartilage 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; in the BAI+AKG group, the articular surface was intact, the surface fibrous tissue was thinned, and the number of hypertrophic chondrocytes in the deep layer was relatively less than that in the MIA group, and the entire cartilage surface was better restored compared with 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. In the BAI group, the cartilage structure was improved to a certain extent, but compared with the BAI+AKG group, the regeneration speed of the cartilage layer was slow and the number of hypertrophic chondrocytes was large.

[0090] The SO staining results of the rat femur tissue sections are as Figure 10 shown. The area of the red region reflects the content of proteoglycans in the cartilage, and the results show that BAI+AKG can effectively inhibit the loss of proteoglycans in the articular cartilage of osteoarthritis rats.

[0091] Masson staining is a staining method for selectively showing collagen fibers. Normal cartilage is blue due to rich collagen fibers. In the MIA group, the blue staining was severely lost (showing red). The Masson staining results of rat femoral tissue sections are as Figure 11 shown, and the results show that BAI + AKG can effectively inhibit the loss of collagen fibers in articular cartilage of osteoarthritis rats.

[0092] OARSI score is a standard for evaluating the pathological progression of OA cartilage. The higher the score, the more severe the cartilage lesion. According to the above results of HE staining, SO staining and Masson staining, OARSI scores were performed on each group of specimens.

[0093] The results are as Figure 12 shown. BAI + AKG can significantly reduce the OARSI score, and is significantly better than the group using drugs alone, with significant differences compared with the AKG group.

[0094] In summary, baicalin (BAI) and α-ketoglutaric acid (AKG) have significant synergistic effects in protecting chondrocyte injury, alleviating cartilage fibrosis, and inhibiting the loss of cartilage proteoglycan 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 efficiency in the treatment of osteoarthritis.

[0095] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than limiting the protection scope of the present invention. Simple modifications or equivalent replacements made by those of ordinary skill in the art to the technical solution of the present invention do not depart 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. The use according to claim 5, characterized in that: The composition has the effects of protecting cartilage cell 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 any one of claims 5 to 7, characterized in that: The drug also includes pharmaceutically acceptable excipients.

9. The use according to any one of claims 5 to 7, 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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