Application of 2-deoxy-D-glucose in preparation of anti-rheumatoid arthritis drugs
By using 2-deoxy-D-glucose to treat CIA model mice, the joint swelling, inflammation score, synovial inflammation and cartilage destruction of rheumatoid arthritis were significantly alleviated, and the disadvantages of existing drugs were solved, achieving safe and efficient therapeutic effect.
Patent Information
- Application Number
- CN202411823192.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-12
- Publication Date
- 2025-02-21
AI Technical Summary
The existing rheumatoid arthritis treatment drugs have the disadvantages of infection and serious complications, and it is difficult to effectively alleviate joint swelling, reduce joint inflammation scores, inhibit synovial inflammation and relieve cartilage destruction.
2-deoxy-D-glucose was used as the active ingredient and treated with intraperitoneal injection, which significantly alleviated joint swelling, reduced joint inflammation score, inhibited synovial inflammation and relieved cartilage destruction.
2-Deoxy-D-glucose can effectively improve the symptoms of rheumatoid arthritis, and has the advantages of simple treatment process, non-toxic and side effects, and is safe and reliable.
Smart Images
Figure CN119488528A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the application of 2-deoxy-D-glucose, in particular to the application in preparing anti-rheumatoid arthritis medicine. Background Art
[0002] Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a complex pathogenesis that is not yet fully understood. The average prevalence of RA worldwide is about 1%. RA patients are usually accompanied by synovitis, synovial hyperplasia, and pannus formation. Severe RA patients can be disabled, which brings a huge burden to themselves and society. RA is difficult to prevent and cure. Currently, clinical drug treatment mainly aims to reduce disease activity. Although it can achieve certain therapeutic effects, it also has disadvantages such as infection and serious complications. Therefore, it is particularly important to find more effective therapeutic drugs. 2-Deoxy-D-glucose (2DG) is a glucose analogue that has been widely studied as a glycolysis inhibitor. It has been shown to have multiple effects, including anti-tumor and antiviral properties, but its role in rheumatoid arthritis has not been reported. Summary of the invention
[0003] The present invention finds that 2-deoxy-D-glucose has the effect of resisting rheumatoid arthritis, and further invents the application of 2-deoxy-D-glucose in anti-rheumatoid arthritis drugs.
[0004] The technical solution of the present invention is: application of 2-deoxy-D-glucose in the preparation of anti-rheumatoid arthritis drugs.
[0005] The invention is specifically used in the preparation of medicines for relieving joint swelling.
[0006] Specifically, the invention is used in the preparation of drugs for reducing joint inflammation scores.
[0007] Specifically, it is used in the preparation of drugs for inhibiting synovial inflammation.
[0008] Specifically, it is used in the preparation of drugs for alleviating cartilage destruction.
[0009] The present invention finds that 2-deoxy-D-glucose acts on CIA model mice, has the effects of relieving joint swelling, reducing joint inflammation scores, inhibiting synovial inflammation and relieving cartilage destruction, and can comprehensively improve the symptoms of rheumatoid arthritis. It can be used as a drug for preparing a drug for treating rheumatoid arthritis, and has the advantages of a simple treatment process, no toxicity and side effects, safety and reliability, etc. BRIEF DESCRIPTION OF THE DRAWINGS
[0010] Figure 1 This is a schematic diagram of the effect of 2-deoxy-D-glucose on joint swelling in CIA model mice.
[0011] Figure 2 This is a schematic diagram of the effect of 2-deoxy-D-glucose on the joint inflammation score of CIA model mice.
[0012] Figure 3 This is a schematic diagram of the effect of 2-deoxy-D-glucose on synovial inflammation in CIA model mice.
[0013] Figure 4 This is a schematic diagram of the effect of 2-deoxy-D-glucose on synovial cartilage destruction in CIA model mice. DETAILED DESCRIPTION
[0014] experiment: Experimental Example 1: Effect of 2-deoxy-D-glucose on joint swelling in CIA model mice.
[0015] 1.1 Experimental Materials DBA / 1J mice, male, were provided by Shanghai Slack Company.
[0016] Bovine type II collagen, complete adjuvant and incomplete adjuvant were provided by Chondrex, and 2-deoxy-D-glucose was provided by Solebol.
[0017] 1.2 Experimental methods 1.2.1 Experimental Grouping Blank control group: normal DBA / 1J mice, no treatment.
[0018] CIA model group: CIA model group induced by bovine type II collagen, complete adjuvant and incomplete adjuvant, PBS was injected intraperitoneally.
[0019] Experimental group: CIA model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0020] 1.2.2 Experimental methods Male DBA / 1J mice aged 6-8 weeks were randomly divided into groups, and bovine type II collagen and Freund's complete adjuvant were emulsified at a ratio of 1:1. Each DBA / 1J mouse was injected with 100 μl for tail immunization, and 100 μl of a mixture of bovine type II collagen and Freund's incomplete adjuvant was injected again on day 21 to boost immunization for modeling. After the CIA model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat CIA mice, 3 times a week, and the toe thickness of CIA mice was measured 2 weeks after treatment.
[0021] 1.2.3 Experimental Results The thickness of the toes of CIA model mice decreased significantly after treatment with 2-deoxy-D-glucose. Figure 1 .
[0022] Experimental Example 2: Schematic diagram of the effect of 2-deoxy-D-glucose on joint inflammation scores in CIA model mice.
[0023] 2.1 Experimental Materials DBA / 1J mice, male, were provided by Shanghai Slack Company.
[0024] Bovine type II collagen, complete adjuvant and incomplete adjuvant were provided by Chondrex, and 2-deoxy-D-glucose was provided by Solebol.
[0025] 2.2 Experimental methods 2.2.1 Experimental Grouping Blank control group: normal DBA / 1J mice, no treatment.
[0026] CIA model group: CIA model group induced by bovine type II collagen, complete adjuvant and incomplete adjuvant, PBS was injected intraperitoneally.
[0027] Experimental group: CIA model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0028] 2.2.2 Experimental methods Male DBA / 1J mice aged 6-8 weeks were randomly divided into groups, and bovine type II collagen and Freund's complete adjuvant were emulsified at a ratio of 1:1. Each DBA / 1J mouse was injected with 100 μl for tail immunization, and 100 μl of a mixture of bovine type II collagen and Freund's incomplete adjuvant was injected again on day 21 to boost immunization for modeling. After the CIA model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat CIA mice, 3 times a week, and the CIA mice were scored for joint inflammation 2 weeks after treatment.
[0029] 2.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, the synovial inflammation score of CIA model mice was significantly decreased. Figure 2 .
[0030] Experimental Example 3: Effect of 2-deoxy-D-glucose on synovial inflammation in CIA model mice.
[0031] 3.1 Experimental Materials DBA / 1J mice, male, were provided by Shanghai Slack Company.
[0032] Bovine type II collagen, complete adjuvant and incomplete adjuvant were provided by Chondrex, and 2-deoxy-D-glucose was provided by Solebol.
[0033] 3.2 Experimental methods 3.2.1 Experimental Grouping Blank control group: normal DBA / 1J mice, no treatment.
[0034] CIA model group: CIA model group induced by bovine type II collagen, complete adjuvant and incomplete adjuvant, PBS was injected intraperitoneally.
[0035] Experimental group: CIA model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0036] 3.2.2 Experimental methods Male DBA / 1J mice aged 6-8 weeks were randomly divided into groups, and bovine type II collagen and Freund's complete adjuvant were emulsified at a ratio of 1:1. Each DBA / 1J mouse was injected with 100 μl for tail immunization, and 100 μl of a mixture of bovine type II collagen and Freund's incomplete adjuvant was injected again on day 21 to boost immunization for modeling. After the CIA model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat CIA mice, three times a week, and synovial inflammation of CIA mice was detected after 2 weeks of treatment.
[0037] 3.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, synovial inflammation in CIA model mice was significantly alleviated. Figure 3 .
[0038] Experimental Example 4: Effect of 2-deoxy-D-glucose on synovial cartilage destruction in CIA model mice.
[0039] 4.1 Experimental Materials DBA / 1J mice, male, were provided by Shanghai Slack Company.
[0040] Bovine type II collagen, complete adjuvant and incomplete adjuvant were provided by Chondrex, and 2-deoxy-D-glucose was provided by Solebol.
[0041] 4.2 Experimental methods 4.2.1 Experimental Grouping Blank control group: normal DBA / 1J mice, no treatment.
[0042] CIA model group: CIA model group induced by bovine type II collagen, complete adjuvant and incomplete adjuvant, PBS was injected intraperitoneally.
[0043] Experimental group: CIA model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0044] 4.2.2 Experimental methods Male DBA / 1J mice aged 6-8 weeks were randomly divided into groups, and bovine type II collagen and Freund's complete adjuvant were emulsified at a ratio of 1:1. Each DBA / 1J mouse was injected with 100 μl for tail immunization, and 100 μl of a mixture of bovine type II collagen and Freund's incomplete adjuvant was injected again on day 21 to boost immunization for modeling. After the CIA model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat CIA mice, three times a week, and the destruction of synovial cartilage in CIA mice was detected after 2 weeks of treatment.
[0045] 4.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, the destruction of synovial cartilage in CIA model mice was significantly alleviated. Figure 4 .
[0046] The sample detection method of the above experiment of the present invention is to measure and score the toes of the blank control group and the positive control group and take pictures, take decalcified embedded sections of the rat toes for HE staining and TNF-α histochemical staining to detect inflammatory infiltration, and use safranin fast green staining to detect cartilage damage.
[0047] Statistical analysis: GraphPad Prism 6 was used for statistical analysis and graphing. T-test was used for statistical analysis according to the experimental groups. Data are expressed as mean ± standard error (SEM). P < 0.05 was considered statistically significant, and asterisks indicate significant differences (*P < 0.05, **P < 0.01).
[0048] It can be seen from the above experiments that 2-deoxy-D-glucose can comprehensively improve the symptoms of rheumatoid arthritis and can be used to prepare drugs for treating rheumatoid arthritis.
Claims
1. Use of 2-deoxy-D-glucose in the preparation of anti-rheumatoid arthritis drugs.
2. The use of 2-deoxy-D-glucose in the preparation of an anti-rheumatoid arthritis drug according to claim 1, characterized in that: Application in the preparation of medicines for relieving joint swelling.
3. The use of 2-deoxy-D-glucose in the preparation of an anti-rheumatoid arthritis drug according to claim 1, characterized in that: Application in the preparation of drugs for reducing joint inflammation scores.
4. The use of 2-deoxy-D-glucose in the preparation of an anti-rheumatoid arthritis drug according to claim 1, characterized in that: Application in the preparation of drugs for inhibiting synovial inflammation.
5. The use of 2-deoxy-D-glucose in the preparation of an anti-rheumatoid arthritis drug according to claim 1, characterized in that: Application in the preparation of drugs for alleviating cartilage destruction.