Application of purine deoxynucleotide in preparation of medicine for treating osteoarthritis

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of purine deoxynucleotide in preparation of a medicine for treating osteoarthritis, the purine deoxynucleotide comprises any one of deoxyguanosine monophosphate and deoxyadenosine monophosphate, the molecular formula of the deoxyguanosine monophosphate is C10H12N5Na2O7P, and the molecular formula of the deoxyadenosine monophosphate is C10H12N5Na2O7P. The molecular formula of the deoxyadenosine monophosphate is C10H14N5O6P. A research result shows that the purine deoxynucleotide has an inhibiting effect on the activity of cartilage cells; animal model tests show that the purine deoxynucleotide can significantly reduce the cartilage injury degree of osteoarthritis mice and relieve osteoarthritis, and a new way is provided for improvement of osteoarthritis conditions.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of purine deoxynucleotides in the preparation of drugs for treating osteoarthritis. Background Technology

[0002] Osteoarthritis is a common chronic inflammatory and disabling disease of the joints, often leading to a significant decline in limb function, quality of life, and mobility. The main pathological changes in osteoarthritis include articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Currently, the pathological process and mechanisms of osteoarthritis are not fully understood. The generally accepted view is that the occurrence and development of osteoarthritis are closely related to articular cartilage degeneration, chondrocyte apoptosis, and extracellular matrix degradation caused by inflammatory and immune factors. As a physiological structure at the bone-bone interface, cartilage plays a role in weight-bearing, stress conduction, and buffering of bony structures. Due to its important physiological location and function, cartilage damage and degeneration are the main causes of weakened or lost joint function and are the core pathological features of osteoarthritis development.

[0003] Currently, the main medications for treating osteoarthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, and acetaminophen, primarily used to relieve pain and inflammation. Long-term use of NSAIDs may lead to gastrointestinal ulcers, cardiovascular events, and kidney damage. Opioid use carries risks of addiction, constipation, and falls, especially in elderly patients.

[0004] While current osteoarthritis medications can relieve pain and inflammation, they still cannot stop cartilage damage and degeneration. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides the application of purine deoxynucleotides in the preparation of medicaments for treating osteoarthritis.

[0006] The use of purine deoxynucleotides in the preparation of drugs for treating osteoarthritis, wherein the purine deoxynucleotides include either deoxyguanosine monophosphate or deoxyadenosine monophosphate; The structures of deoxyguanosine monophosphate are shown in formula 1), and the structures of deoxyadenosine monophosphate are shown in formula 2). Formula 1); Formula 2).

[0007] The molecular formula of the deoxyguanosine monophosphate is C 10 H 12 N5Na2O7P, the molecular formula of the deoxyadenosine monophosphate is C 10 H 14N5O6P, the purine deoxynucleotide provided by this invention, inhibits the expression of key catabolism enzymes (such as matrix metalloproteinases) and blocks the chondrocyte apoptosis signaling pathway mediated by inflammatory factors, fundamentally reversing the pathological process of osteoarthritis and achieving the protection and repair of cartilage structure. It breaks through the technical bottleneck of existing drugs that only have anti-inflammatory and analgesic effects but cannot prevent cartilage degeneration. In this way, it can solve the problem that although the existing osteoarthritis treatment drugs can relieve pain and inflammation, they still cannot prevent cartilage damage and degeneration.

[0008] Preferably, the drug is prepared from the purine deoxynucleotide and pharmaceutically acceptable excipients.

[0009] Preferably, the pharmaceutically acceptable excipient is physiological saline or PEG 300.

[0010] Preferably, the drug is a liquid formulation.

[0011] Preferably, the drug is an injectable form.

[0012] Preferably, the concentration of deoxyguanosine monophosphate in the drug is 1 mg / mL to 5 mg / mL.

[0013] Preferably, the concentration of deoxyadenosine monophosphate in the drug is 1 mg / mL to 2.5 mg / mL.

[0014] Preferably, the drug is used to relieve cartilage damage in osteoarthritis.

[0015] Preferably, the drug is used to inhibit the expression of the inflammatory cytokine IL-6 protein.

[0016] Preferably, the drug is used to inhibit the expression of matrix metalloproteinase MMP13 protein.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides the application of purine deoxynucleotides in the preparation of drugs for treating osteoarthritis, offering a novel treatment strategy for osteoarthritis. The purine deoxynucleotide solution in this invention can simultaneously inhibit the protein expression of the inflammatory cytokine IL-6 and matrix metalloproteinase MMP13 in chondrocytes. By inhibiting key factors mediating joint inflammation and chondrocyte degradation, it provides early intervention for cartilage degeneration caused by osteoarthritis. Iodoacetic acid-induced rat osteoarthritis model experiments showed that intra-articular injection of 5 mg / mL deoxyguanosine monophosphate saline or 2.5 mg / mL deoxyadenosine monophosphate saline significantly reduced the degree of cartilage damage compared to the model group, demonstrating that deoxyguanosine monophosphate has the function of reversing cartilage degeneration.

[0018] The purine deoxynucleotides provided by this invention inhibit the expression of key catabolism enzymes (such as matrix metalloproteinases) and block the chondrocyte apoptosis signaling pathway mediated by inflammatory factors, fundamentally reversing the pathological process of osteoarthritis and achieving the protection and repair of cartilage structure. This breakthrough overcomes the technical bottleneck of existing drugs that only have anti-inflammatory and analgesic effects but cannot prevent cartilage degeneration. In this way, it can solve the problem that current osteoarthritis treatments can relieve pain and inflammation but still cannot prevent cartilage damage and degeneration. Attached Figure Description

[0019] Figure 1 This invention relates to the CCK-8 assay used to detect the effect of deoxyguanosine monophosphate on the viability of SW1353 cells.

[0020] Figure 2 The figure shows the effect of deoxyguanosine monophosphate on IL-6 protein expression in SW1353 cells detected by ELISA in this invention; in the figure: - indicates no addition, + indicates addition.

[0021] Figure 3 The figure shows the effect of deoxyguanosine monophosphate on MMP13 protein expression in SW1353 cells detected by ELISA in this invention; in the figure: - indicates no addition, + indicates addition.

[0022] Figure 4 This invention relates to the effect of CCK-8 assay on the viability of SW1353 cells.

[0023] Figure 5 The figure shows the effect of deoxyadenosine monophosphate on IL-6 protein expression in SW1353 cells detected by ELISA in this invention; in the figure: - indicates no addition, + indicates addition.

[0024] Figure 6 The figure shows the effect of deoxyadenosine monophosphate on MMP13 protein expression in SW1353 cells detected by ELISA in this invention; in the figure: - indicates no addition, + indicates addition.

[0025] Figure 7 This invention describes the effects of purine deoxynucleotides on cartilage degeneration in rats with knee osteoarthritis; wherein: A is a description of the experimental treatment time; B is photographs of the degree of damage to the articular cartilage surface of rats in different treatment groups. Detailed Implementation

[0026] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods.

[0027] The materials used are as follows: Deoxyadenosine monophosphate was purchased from Shanghai Yuanye Biotechnology Co., Ltd., S18087-1g.

[0028] Deoxyguanosine monophosphate was purchased from Shanghai Yuanye Biotechnology Co., Ltd., S18101-1g.

[0029] SW1353 cells were purchased from Wuhan Pronosei Life Sciences Co., Ltd. SW1353 cells exhibit a good cartilage phenotype and are suitable for studies on cartilage cell structure and function.

[0030] Example 1. Effects of purine deoxynucleotides on the viability of SW1353 cells Prepare a cell concentration of 5 × 10⁻⁶ 4 SW1353 cell suspension was prepared at 100 μL / mL and seeded into 96-well plates. The cells were then cultured at 37°C and 5% CO2 for 36 h.

[0031] Deoxyguanosine monophosphate was dissolved in DMEM to prepare a high-concentration stock solution (10 mM). Then, 2.5 μL, 5 μL, 10 μL and 20 μL of the high-concentration stock solution were taken and added to 97.5 μL, 95 μL, 90 μL and 80 μL of basic DMEM medium, respectively. Then, 10 μL of fetal bovine serum was added to each solution to prepare a complete medium, thus obtaining deoxyguanosine monophosphate solutions with final concentrations of 0.25 mM, 0.5 mM, 1 mM and 2 mM, respectively.

[0032] Deoxyadenosine monophosphate was dissolved in DMEM to prepare a high-concentration stock solution (10 mM). Then, 5 μL, 10 μL and 20 μL of the high-concentration stock solution were added to 95 μL, 90 μL and 80 μL of basic DMEM medium, respectively. Then, 10 μL of fetal bovine serum was added to each solution to prepare a complete medium, thus obtaining deoxyadenosine monophosphate solutions with final concentrations of 0.5 mM, 1 mM and 2 mM.

[0033] SW1353 cells cultured in 96-well plates at 37℃ and 5% CO2 were divided into control and treatment groups. The control group was given 100 μL of fresh complete culture medium (basal DMEM medium containing 10% serum by volume, prepared by adding 10 μL of fetal bovine serum to 90 μL of basic DMEM medium).

[0034] The deoxyguanosine monophosphate treatment groups were treated with 100 μL of 0.25 mM, 0.5 mM, 1 mM and 2 mM deoxyguanosine monophosphate solutions, respectively.

[0035] The deoxyadenosine monophosphate treatment groups were treated with 100 μL of 0.5 mM, 1 mM, and 2 mM deoxyadenosine monophosphate solutions, respectively.

[0036] SW1353 cells in the 96-well plates of the control and treatment groups were added to their respective culture media and cultured at 37°C and 5% CO2 for 24 hours. After 24 hours, the culture media added to the control and treatment groups was removed, and 100 μL of complete culture medium (basal DMEM medium containing 10% serum) was added to each well. 10 μL of CCK8 solution was then added to each well, and the cells were cultured at 37°C and 5% CO2 for another hour. The absorbance (OD) value at 450 nm was read using a microplate reader. 450 ).

[0037] The principle behind CCK8 assays for cell viability is based on the positive correlation between the activity of dehydrogenases in mitochondria and cell viability. Under the action of dehydrogenases in mitochondria, WST8 in the CCK8 solution is reduced to water-soluble formazan, with the maximum absorption peak of formazan at 450 nm. Increased cell viability corresponds to enhanced dehydrogenase activity, leading to increased formazan production. Therefore, changes in absorbance at 450 nm are used to characterize cell viability.

[0038] 2. Effects of purine deoxynucleotides on IL-6 protein expression in SW1353 cells Prepare a cell concentration of 6 × 10⁶ 4 SW1353 cell suspension was prepared by layering the SW1353 cell suspension into 24-well plates, with 500 μL added to each well. After 36 h, the medium was replaced with DMEM medium containing 1% serum for serum starvation.

[0039] SW1353 cells starved of serum for 24 hours were divided into control group 1, control group 2 and treatment group.

[0040] After pretreatment with 0.25 mM, 0.5 mM and 1 mM deoxyguanosine monophosphate solutions for 3 h, the inflammatory stimulant IL-1β was added to achieve a final IL-1β concentration of 10 ng / mL.

[0041] After pretreatment with 0.5 mM and 1 mM deoxyadenosine monophosphate solutions for 3 h, the deoxyadenosine monophosphate treatment groups were then treated with the inflammatory stimulant IL-1β to achieve a final IL-1β concentration of 10 ng / mL.

[0042] Control group 2 was treated with either no deoxyguanosine monophosphate solution or no deoxyadenosine monophosphate solution for 3 hours under the same conditions, and then the inflammatory stimulant IL-1β was added to make the final concentration of IL-1β 10 ng / mL.

[0043] Control group 1 received no IL-1β and deoxyguanosine monophosphate solution or no IL-1β and deoxyadenosine monophosphate solution.

[0044] After the above groups of SW1353 cells were treated at 37℃ and 5% CO2 for 24 h, the protein expression level of the cellular inflammatory factor IL-6 was detected by ELISA (Human IL-6 ELISA Kit, purchased from Wuhan Sanying Biotechnology Co., Ltd.).

[0045] 3. Effects of purine deoxynucleotides on MMP13 protein expression in SW1353 cells Prepare a cell concentration of 6 × 10⁶ 4 SW1353 cell suspension was prepared by layering the SW1353 cell suspension into 24-well plates, with 500 μL added to each well. After 36 h, the medium was replaced with DMEM medium containing 1% serum for serum starvation.

[0046] SW1353 cells starved of serum for 24 hours were divided into control group 1, control group 2 and treatment group.

[0047] After pretreatment with 0.25 mM, 0.5 mM and 1 mM deoxyguanosine monophosphate solutions for 3 h, the inflammatory stimulant IL-1β was added to achieve a final IL-1β concentration of 10 ng / mL.

[0048] After pretreatment with 0.5 mM and 1 mM deoxyadenosine monophosphate solutions for 3 h, the deoxyadenosine monophosphate treatment groups were then treated with the inflammatory stimulant IL-1β to achieve a final IL-1β concentration of 10 ng / mL.

[0049] Control group 2 was treated with either no deoxyguanosine monophosphate solution or no deoxyadenosine monophosphate solution, and then the inflammatory stimulant IL-1β was added after 3 hours of pretreatment under the same conditions, so that the final concentration of IL-1β was 10 ng / mL.

[0050] Control group 1 received no IL-1β and deoxyguanosine monophosphate solution or no IL-1β and deoxyadenosine monophosphate solution.

[0051] After the cells in each group were treated at 37℃ and 5% CO2 for 24 h, the protein expression level of the cellular inflammatory factor MMP13 was detected by ELISA (Human MMP13 ELISA Kit, purchased from Wuhan Sanying Biotechnology Co., Ltd.).

[0052] 4. Effects of purine deoxynucleotides on cartilage degeneration in iodoacetic acid-induced knee osteoarthritis in rats Both the deoxyguanosine monophosphate group and the deoxyadenosine monophosphate group consisted of 6-week-old male SD rats (200g ± 20g) that were acclimatized for 7 days and then randomly divided into four groups: control group, model group, treatment group 1, and treatment group 2. The 6-week-old male SD rats were purchased from Spiford (Beijing) Biotechnology Co., Ltd.

[0053] Weigh 20 mg of deoxyguanosine monophosphate and dissolve it in 20 mL of physiological saline solution to prepare a 1 mg / mL deoxyguanosine monophosphate physiological saline solution; weigh 100 mg of deoxyguanosine monophosphate and dissolve it in 20 mL of physiological saline solution to prepare a 5 mg / mL deoxyguanosine monophosphate physiological saline solution.

[0054] Weigh 20 mg of deoxyadenosine monophosphate and dissolve it in 20 mL of physiological saline solution to prepare a deoxyadenosine monophosphate physiological saline solution with a concentration of 1 mg / mL; weigh 50 mg of deoxyadenosine monophosphate and dissolve it in 20 mL of physiological saline solution to prepare a deoxyadenosine monophosphate physiological saline solution with a concentration of 2.5 mg / mL.

[0055] On day 1, rats in treatment group 1 were injected intra-articularly with either 1 mg / mL deoxyguanosine monophosphate saline or 1 mg / mL deoxyadenosine monophosphate saline, 50 μL / rat; rats in treatment group 2 were injected intra-articularly with either 5 mg / mL deoxyguanosine monophosphate saline or 2.5 mg / mL deoxyadenosine monophosphate saline, 50 μL / rat; rats in the model group and control group were injected intra-articularly with the same amount of saline.

[0056] On day 2, rats in the model group, drug treatment group 1, and drug treatment group 2 were injected with 20 mg / mL iodoacetic acid solution (50 μL / rat) into the right knee joint cavity to establish a knee osteoarthritis model; the control group was injected with an equal volume of physiological saline into the right knee joint cavity of rats.

[0057] On days 3, 5, 7, 9, 11, and 13, rats in treatment group 1 received an intra-articular injection of 1 mg / mL deoxyguanosine monophosphate saline or 1 mg / mL deoxyadenosine monophosphate saline, 50 μL / rat; rats in treatment group 2 received an intra-articular injection of 5 mg / mL deoxyguanosine monophosphate saline or 2.5 mg / mL deoxyadenosine monophosphate saline, 50 μL / rat; and rats in the control and model groups received an equal volume of saline injected into the intra-articular injection of the right knee joint.

[0058] On day 15, right knee joint samples were collected from rats in the control group, model group, drug treatment group 1, and drug treatment group 2. The cartilage damage in the right knee joint of each group of rats was dissected and observed.

[0059] result 1. Deoxyguanosine monophosphate inhibits the viability of SW1353 cells. The CCK8 assay results of SW1353 cells are as follows: Figure 1 As shown. When deoxyguanosine monophosphate solutions were added to final concentrations of 0.25 mM, 0.5 mM, 1 mM, and 2 mM, the OD... 450 All were significantly different from the control group. P <0.05), but there was no difference between these concentrations ( Figure 1 This indicates that deoxyguanosine monophosphate has a certain inhibitory effect on the cell viability of SW1353 cells.

[0060] 2. Deoxyguanosine monophosphate inhibits the expression of IL-6 and MMP13 proteins in SW1353 cells. IL-1β, as an inflammatory stimulant, was used in this invention to construct an osteoarthritis model of SW1353 cells. ELISA results showed that, compared to control group 2 (IL-1β only), the protein content of IL-6 in the treatment group (with added deoxyguanosine monophosphate solution and IL-1β) gradually decreased with increasing concentration of deoxyguanosine monophosphate solution, and both were significantly different from control group 2. P <0.05)( Figure 2 Compared to control group 2 (IL-1β only), the protein content of MMP13 in the treatment group (deoxyguanosine monophosphate solution and IL-1β) gradually decreased with increasing concentration of deoxyguanosine monophosphate solution, and both were significantly different from control group 2. P <0.05)( Figure 3 This indicates that deoxyguanosine monophosphate can inhibit the expression of inflammatory cytokines IL-6 and matrix metalloproteinase MMP13 proteins.

[0061] 3. Deoxyguanosine monophosphate alleviates iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis. Test treatment plan as follows Figure 7 In section A, the experimental results showed that, compared with the control group, the model group rats injected with 20 mg / mL iodoacetic acid solution showed significant damage to the knee joint cartilage, indicating that the rat knee osteoarthritis model was successfully established; while compared with the model group, the degree of knee joint cartilage damage in the second treatment group (adding 5 mg / mL physiological saline solution) was significantly reduced. Figure 7 (B in the figure), indicating that deoxyguanosine monophosphate can alleviate iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis.

[0062] The above experimental results show that deoxyguanosine monophosphate solution can inhibit the protein expression of inflammatory factors IL-6 and matrix metalloproteinase MMP13 in chondrocytes and alleviate iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis.

[0063] 4. Deoxyadenosine monophosphate inhibits the viability of SW1353 cells. The CCK8 assay results of SW1353 cells are as follows: Figure 4 As shown. When deoxyadenosine monophosphate solutions with final concentrations of 0.5 mM, 1 mM, and 2 mM were added, OD 450 All were significantly different from the control group. P <0.05). This indicates that deoxyadenosine monophosphate has a certain inhibitory effect on the cell viability of SW1353 cells.

[0064] 5. Deoxyadenosine monophosphate inhibits the expression of IL-6 and MMP13 proteins in SW1353 cells. IL-1β, as an inflammatory stimulant, was used in this invention to construct an osteoarthritis model of SW1353 cells. ELISA results showed that, compared to control group 2 (IL-1β only), the protein content of IL-6 in the treatment group (addition of deoxyadenosine monophosphate solution and IL-1β) gradually decreased with increasing concentration of deoxyadenosine monophosphate solution, and both were significantly different from control group 2. P <0.05)( Figure 5 Compared to control group 2 (IL-1β only), the protein content of MMP13 in the treatment group (addition of deoxyadenosine monophosphate solution and IL-1β) gradually decreased with increasing concentration of deoxyadenosine monophosphate solution, and both were significantly different from control group 2. P <0.05)( Figure 6 This indicates that deoxyadenosine monophosphate can inhibit the expression of inflammatory cytokines IL-6 and matrix metalloproteinase MMP13 proteins.

[0065] 6. Deoxyadenosine monophosphate alleviates iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis. Test treatment plan as follows Figure 7 In section A, the experimental results showed that, compared with the control group, the rats in the model group injected with 20 mg / mL iodoacetic acid solution showed significant damage to the knee joint cartilage, indicating that the rat knee osteoarthritis model was successfully established; while compared with the model group, the degree of knee joint cartilage damage in the second treatment group (adding 2.5 mg / mL physiological saline solution) was significantly reduced. Figure 7 The B in the figure indicates that deoxyadenosine monophosphate can alleviate iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis.

[0066] The above experimental results show that deoxyadenosine monophosphate solution can inhibit the protein expression of inflammatory factors IL-6 and matrix metalloproteinase MMP13 in chondrocytes and alleviate iodoacetic acid-induced cartilage degeneration in rat knee osteoarthritis.

[0067] The purine-based deoxynucleotide solution in this invention can simultaneously inhibit the protein expression of inflammatory cytokines IL-6 and matrix metalloproteinase MMP13 in chondrocytes. By inhibiting key factors mediating joint inflammation and chondrocyte degradation, it provides early intervention for cartilage degeneration caused by osteoarthritis. The rat osteoarthritis model experiment induced by iodoacetic acid showed that after intra-articular injection of 5 mg / mL deoxyguanosine monophosphate saline or 2.5 mg / mL deoxyadenosine monophosphate saline, the degree of cartilage damage was significantly reduced compared with the model group, indicating that both deoxyguanosine monophosphate and deoxyadenosine monophosphate have the function of reversing cartilage degeneration.

[0068] This invention provides the application of purine deoxynucleotides in the preparation of drugs for treating osteoarthritis, offering a novel treatment strategy for osteoarthritis. The deoxyguanosine monophosphate (DMP) and deoxyadenosine monophosphate (DAP) solutions in this invention can simultaneously inhibit the protein expression of the inflammatory cytokine IL-6 and matrix metalloproteinase MMP13 in chondrocytes. By inhibiting key factors mediating joint inflammation and chondrocyte degradation, it provides early intervention for cartilage degeneration caused by osteoarthritis. Iodoacetic acid-induced rat osteoarthritis model experiments showed that intra-articular injection of 5 mg / mL DMP saline solution or 2.5 mg / mL DAP saline solution significantly reduced the degree of cartilage damage compared to the model group, demonstrating that both DMP and DAP have the function of reversing cartilage degeneration.

[0069] It should be noted that when numerical ranges are mentioned in the claims of this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, the present invention describes preferred embodiments.

[0070] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0071] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. The application of purine deoxynucleotides in the preparation of drugs for treating osteoarthritis, characterized in that, The purine deoxynucleotides include either deoxyguanosine monophosphate or deoxyadenosine monophosphate. The structures of deoxyguanosine monophosphate are shown in formula 1), and the structures of deoxyadenosine monophosphate are shown in formula 2). Formula 1); Formula 2).

2. The application according to claim 1, characterized in that, The drug is prepared from the purine deoxynucleotide and pharmaceutically acceptable excipients.

3. The application according to claim 2, characterized in that, The pharmaceutically acceptable excipients are physiological saline or PEG 300.

4. The application according to claim 3, characterized in that, The drug is a liquid preparation.

5. The application according to claim 4, characterized in that, The drug is an injectable form.

6. The application according to claim 5, characterized in that, The concentration of deoxyguanosine monophosphate in the injection is 1 mg / mL to 5 mg / mL.

7. The application according to claim 5, characterized in that, The concentration of deoxyadenosine monophosphate in the injection is 1 mg / mL to 2.5 mg / mL.

8. The application according to claim 1, characterized in that, The drug is used to relieve cartilage damage in osteoarthritis.

9. The application according to claim 1, characterized in that, The drug is used to inhibit the expression of the inflammatory cytokine IL-6 protein.

10. The application according to claim 1, characterized in that, The drug is used to inhibit the expression of matrix metalloproteinase MMP13 protein.

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