Application of sulfadiazine in the preparation of drugs for treating osteoarthritis

Abstract

This invention discloses the application of sulfadimidine in the preparation of drugs for treating osteoarthritis. This invention is the first to demonstrate the significant efficacy of intra-articular injection of sulfadimidine in the treatment of osteoarthritis (OA); the results show that sulfadimidine can not only significantly relieve the symptoms of osteoarthritis but also improve the metabolic function of chondrocytes, thereby slowing the progression of arthritis. Traditional treatment methods mainly include intra-articular injection of anesthetic drugs, joint lubricants (such as sodium hyaluronate), glucocorticoids, and platelet-rich plasma (PRP). However, these methods each have limitations, such as significant short-term effects but potential long-term side effects. Sulfamidine, as a novel treatment method, not only has good efficacy but also fewer side effects, providing a new approach to the drug treatment of osteoarthritis.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the use of sulfadiazine in the preparation of drugs for treating osteoarthritis. Background Technology

[0002] Osteoarthritis (OA) is a non-inflammatory degenerative joint disease, primarily characterized by joint pain and stiffness, especially after prolonged activity. It commonly affects middle-aged and elderly individuals over 50 years of age, impacting their quality of life to varying degrees. In the late stages of OA, severe joint damage often necessitates total joint replacement surgery to restore joint function. However, artificial joints have a limited lifespan, and not all patients achieve satisfactory results through surgery. Therefore, conservative treatment is particularly important, aiming to alleviate symptoms, slow disease progression, and extend the lifespan of the joint.

[0003] Intra-articular injection is currently the main method of conservative treatment. Commonly used intra-articular injection drugs include: 1) Anesthetic drugs: such as lidocaine, used to temporarily relieve joint pain, suitable for short-term pain management and diagnostic procedures. 2) Joint lubricants: such as sodium hyaluronate (HA), which enhances joint lubrication and reduces joint friction by supplementing hyaluronic acid in synovial fluid, thereby relieving pain and improving joint function, but cannot slow the progression of the disease. 3) Glucocorticoids: such as prednisolone, which reduces joint swelling and pain by inhibiting the inflammatory response; although the effect is significant in the short term, it should be used with caution because long-term use may cause cartilage damage. 4) Platelet-rich plasma (PRP): by extracting the patient's own blood, concentrating the platelets, and injecting it into the diseased joint; the growth factors released by platelets can promote cartilage repair and regeneration, and have shown good therapeutic prospects in recent years; however, it is relatively expensive and requires the extraction of a certain amount of autologous blood, which poses a certain degree of harm to the patient.

[0004] The sulfonamide group in sulfadiazine can replace the sulfate group of sulfatase, inhibiting its function. It is suitable for treating bacterial dysentery and enteritis, or for preventing postoperative infections after intestinal surgery. However, there are no reports of sulfadiazine being used to treat osteoarthritis. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of the prior art by providing the application of sulfadiazine in the preparation of drugs for treating osteoarthritis.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This provides information on the use of sulfadiazine in the preparation of drugs for treating osteoarthritis.

[0008] Furthermore, the medication for treating osteoarthritis is sulfadiazine injection.

[0009] Furthermore, the sulfadiazine injection comprises the sole active ingredient sulfadiazine, and a solvent.

[0010] Furthermore, the solvent is physiological saline.

[0011] Furthermore, the concentration of the sulfadiazine injection is 200 μM.

[0012] The present invention adopts the above technical solution and has the following technical effects compared with the prior art:

[0013] This invention is the first to demonstrate the significant efficacy of intra-articular injection of sulfadimidine in the treatment of osteoarthritis (OA). The results show that sulfadimidine can not only significantly relieve the symptoms of osteoarthritis, but also improve the metabolic function of chondrocytes, thereby slowing the progression of arthritis.

[0014] Traditional treatments primarily include intra-articular injections of anesthetic drugs, joint lubricants (such as sodium hyaluronate), corticosteroids, and platelet-rich plasma (PRP). However, these methods each have limitations; for example, while they may show significant short-term effects, long-term use can lead to side effects. Sulfamicin, as a novel treatment, not only offers good efficacy but also fewer side effects, providing a new approach to the drug treatment of osteoarthritis. Attached Figure Description

[0015] Figure 1 Alcian blue staining results for mouse chondrocytes stimulated with IL1 and Sulfaguanidine.

[0016] Figure 2 Histological staining results of a mouse OA model after treatment with Sulfaguanidine. Detailed Implementation

[0017] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but this is not intended to limit the invention. It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of the present invention can be combined with each other.

[0018] Pharmaceuticals and Biomaterials:

[0019] Sulfaguanidine, MedChemExpress, Cat:HY-B1267;

[0020] Laboratory mice, C57BL / 6J, Vitaliva;

[0021] Recombinant mouse IL-1β, Suzhou Nearshore Protein Technology Co., Ltd.

[0022] Example 1

[0023] Preparation of 200 μM sulfadimidine injection: It was prepared by dissolving 42.8 μg of sulfadimidine in 1 ml of physiological saline.

[0024] Example 2

[0025] Cellular experiments:

[0026] 1) For newborn mice, after euthanasia by carbon dioxide asphyxiation, the skin of the knee joint was cut open, and the knee cartilage was directly separated. The separated tissue was washed five times with sterile PBS, digested with 0.25% trypsin for 30 min, and then digested with 0.15% type II collagenase for 2 h. Subsequently, the digestion solution was passed through a 70 μm cell sieve, centrifuged, reselected, and cultured in DMEM medium containing 10% FBS and 1% penicillin antibiotics at 37°C in a 5% CO2 incubator for routine culture. When the cells reached 80-90% confluence, they were digested with trypsin and passaged for subsequent experiments.

[0027] 2) Sulfamethidine stimulation: Primary mouse chondrocytes reached 2×10 4 Cells were seeded in 12-well plates and, when the cells reached 60-70% confluence, chondrocytes were treated with 10 ng / ml IL-1β. The sulfadiazine treatment group simultaneously treated chondrocytes with a 200 μM sulfadiazine solution.

[0028] 3) Alcian blue staining: After fixing cell culture plates with 4% PFA for 15 min, staining was performed with Alcian blue (AB) solution for 15 min. The plates were then washed with distilled water until colorless and observed under a stereomicroscope. Alcian blue staining revealed that chondrocytes stimulated with Sulfaguanidin for 48 h showed increased AB staining, suggesting reduced extracellular matrix degradation. Figure 1 ).

[0029] Example 3

[0030] Animal experiments:

[0031] Ten-week-old male wild-type C57 mice were used in the experiment. Thirty mice were randomly divided into three groups: sham-operated group, control group, and intra-articular treatment group, with 10 mice in each group. The control and intra-articular treatment groups established mouse osteoarthritis (OA) models through anterior cruciate ligament (ACLT) transection. For mice in the sham-operated and control groups, the knee joint injection site was disinfected before inserting the needle into the joint cavity, and 5 μL of physiological saline was injected into the joint cavity the following day. For mice in the intra-articular treatment group, the knee joint injection site was disinfected before inserting the needle into the joint cavity, and 5 μL of prepared 200 μM sulfadiazine injection solution was injected into the joint cavity the following day. The area was disinfected after needle withdrawal. Four weeks later, mice were euthanized by carbon dioxide asphyxiation. Knee joint tissue was isolated, fixed in 4% PFA solution for 24 weeks, decalcified in 10% EDTA for one week, then dehydrated with graded ethanol and embedded in paraffin. Sections were cut into 5 μm thick sections, and cartilage degeneration in the knee joint was assessed by Safranin O-Fixed Green (SO-FS) staining. SO-FS staining showed that the severity of osteoarthritis (OA) in mice treated with Sulfaguanidine was significantly lower than that in the control group. Figure 2 This suggests its therapeutic effect on OA.

[0032] The above description is merely a preferred embodiment of the present invention and does not limit the implementation and protection scope of the present invention. Those skilled in the art should realize that any equivalent substitutions and obvious changes made based on the content and illustrations of the present invention should be included within the protection scope of the present invention.

Claims

1. The use of sulfadiazine in the preparation of a medicament for the treatment of osteoarthritis for intra-articular injection, characterized in that, The medication for treating osteoarthritis is sulfadiazine injection, which comprises sulfadiazine as the sole active ingredient and physiological saline.

2. The application according to claim 1, characterized in that, The concentration of the sulfadiazine injection is 200 μM.

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