Application of sulphaguanidine in preparation of medicine for treating osteoarthritis

Abstract

The invention discloses an application of sulphaguanidine in preparation of a medicine for treating osteoarthritis. According to the invention, the obvious curative effect of the sulfadimidine (sulfadimidine) in the aspect of treating the osteoarthritis (OA) through intraarticular injection is confirmed for the first time; research results show that the sulphaguanidine not only can remarkably relieve the symptoms of osteoarthritis, but also can improve the metabolic function of cartilage cells, so that the progress of arthritis is slowed down. Traditional treatment methods mainly include intraarticular injection of anesthetic drugs, joint lubrication drugs (such as sodium hyaluronate), glucocorticoid and platelet rich plasma (PRP). However, these methods have limitations, such as significant effects in short periods but may cause side effects in long-term use. As a novel treatment means, sulphaguanidine not only has a good curative effect, but also has small side effects, and provides a new thought for drug treatment of osteoarthritis.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to the application of sulfaguanidine in the preparation of a drug for treating osteoarthritis. Background Art

[0002] Osteoarthritis (OA) is a non-inflammatory degenerative joint disease, which is mainly manifested by joint pain and stiffness, especially after long-term activities. The disease is common in middle-aged and elderly people over 50 years old, affecting the quality of life of patients to varying degrees. In the late stages of OA, joint damage is severe, and artificial joint replacement surgery is often required to restore joint function. However, artificial joints have a certain service life limit, and not all patients can achieve satisfactory treatment results through surgery. Therefore, conservative treatment is particularly important, with the aim of relieving symptoms, delaying disease progression, and prolonging the service life of joints.

[0003] Intra-articular drug injection is the main method of conservative treatment at present. Commonly used intra-articular injection drugs include: 1) Anesthetic drugs: such as lidocaine, which is used to temporarily relieve joint pain and is suitable for short-term pain management and diagnostic operations. 2) Joint lubricating drugs: such as sodium hyaluronic acid (HA), which can relieve pain and improve joint function by replenishing hyaluronic acid in synovial fluid, enhancing joint lubrication, and reducing joint friction, but it cannot delay the progression of the disease. 3) Glucocorticoids: such as prednisolone, which can reduce joint swelling and pain by inhibiting 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 in it, and injecting it into the diseased joint; the growth factors released by platelets can promote cartilage repair and regeneration, and have shown good treatment prospects in clinical practice in recent years; but the price is relatively expensive, and a certain amount of autologous blood needs to be extracted, which is harmful to the patient.

[0004] The sulfonamide group of sulfaguanidine can replace the sulfate group of sulfatase, inhibiting the action of sulfatase, and is suitable for treating bacterial dysentery and enteritis, or for preventing infection after intestinal surgery. However, there is no report on the use of sulfaguanidine in treating osteoarthritis. Summary of the invention

[0005] The purpose of the present invention is to provide the use of sulfaguanidine in preparing a drug for treating osteoarthritis in view of the deficiencies in the prior art.

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

[0007] Provided is the use of sulfaguanidine in preparing a drug for treating osteoarthritis.

[0008] Furthermore, the drug for treating osteoarthritis is sulfaguanidine injection.

[0009] Furthermore, the sulfaguanidine injection comprises sulfaguanidine as the only active ingredient, and a solvent.

[0010] Furthermore, the solvent is physiological saline.

[0011] Furthermore, the concentration of the sulfamethoxazole 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] The present invention confirms for the first time the significant therapeutic effect of intra-articular injection of sulfadimidine in treating osteoarthritis (OA); the research results show that sulfadimidine can not only significantly alleviate the symptoms of osteoarthritis, but also improve the metabolic function of chondrocytes, thereby slowing down the progression of arthritis.

[0014] Traditional treatments mainly include intra-articular injections of anesthetics, joint lubricants (such as sodium hyaluronate), glucocorticoids, and platelet-rich plasma (PRP). However, each of these methods has its limitations. For example, they are effective in the short term, but long-term use may cause side effects. As a new treatment method, sulfaguanidine not only has good efficacy, but also has fewer side effects, providing a new idea for the drug treatment of osteoarthritis. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The results of Alcian blue staining of mouse chondrocytes after stimulation with IL1 and Sulfaguanidine.

[0016] Figure 2 The histological staining results of mouse OA model after Sulfaguanidine treatment. DETAILED DESCRIPTION

[0017] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments, but is not intended to be limiting of the present invention. It should be noted that the embodiments and features in the embodiments of the present invention may be combined with each other without conflict.

[0018] Pharmaceuticals and biomaterials:

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

[0020] Experimental mice, C57BL / 6J, Vitallife;

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

[0022] Example 1

[0023] Preparation of 200 μM sulfaguanidine injection: Dissolve 42.8 μg sulfaguanidine in 1 ml of normal saline.

[0024] Example 2

[0025] Cell experiments:

[0026] 1) For newborn mice, cut the knee joint skin after carbon dioxide asphyxiation and directly separate the knee joint cartilage. The separated tissue was washed 5 times with sterile PBS, digested with 0.25% trypsin for 30 minutes, and then replaced with 0.15% type II collagenase for 2 hours. Subsequently, the digestion solution was passed through a 70μm cell sieve, centrifuged and re-selected, and cultured in a DMEM medium containing 10% FBS and 1% double antibody at 37°C and 5% CO2 incubator for routine culture. When the cells are 80-90% attached to the wall, trypsin digestion and subculture are used for subsequent experiments.

[0027] 2) Sulfamidine stimulation: 2×10 primary mouse chondrocytes were cultured 4 / well were inoculated in a 12-well plate, and when the cells adhered to the wall to 60-70%, 10 ng / ml IL-1β was added to treat the chondrocytes. The sulfamethoxazole treatment group was also treated with 200 μM sulfamethoxazole solution.

[0028] 3) Alcian blue staining: The cell culture plate was fixed with 4% PFA for 15 minutes, then stained with Alcian blue (AB) solution for 15 minutes, washed with distilled water until colorless, and observed under a stereo microscope. Alcian blue staining showed that the AB staining of chondrocytes after 48 hours of sulfaguanidin stimulation deepened, indicating that the degradation of the extracellular matrix was reduced ( Figure 1 ).

[0029] Example 3

[0030] Animal Experimentation:

[0031] Ten-week-old male wild-type C57 mice were used in the experiment. Thirty mice were randomly divided into three groups: sham operation group, control group and joint cavity treatment group, with 10 mice in each group. The control group and joint cavity treatment group established the mouse OA model by anterior cruciate ligament transection (ACLT) in mice. For the mice in the sham operation group and the control group, the knee joint needle point was disinfected locally and the needle was inserted into the joint cavity, and 5μL of normal saline was injected into the joint cavity every other day; for the mice in the joint cavity treatment group, the knee joint needle point was disinfected locally and the needle was inserted into the joint cavity, and 5μL of the prepared 200μM sulfaguanidine injection was injected into the joint cavity every other day, and the local disinfection was performed after the needle was removed. After 4 weeks, the mice were killed by carbon dioxide asphyxiation, and their knee joint tissues were isolated and fixed in 4% PFA solution for 24 hours, decalcified in 10% ethylenediaminetetraacetic acid for 1 week, and then dehydrated in graded ethanol and embedded in paraffin. The sections were cut into 5 μm thick sections, and the degeneration of the mouse knee cartilage was evaluated by safranin O-fast green staining (SO-FS). By SO-FS staining, it was observed that the severity of OA in mice treated with Sulfaguanidine was significantly milder than that in the control group ( Figure 2 ), suggesting its role in the treatment of OA.

[0032] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the contents of the specification and illustrations of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of sulfaguanidine in the preparation of drugs for treating osteoarthritis.

2. The use according to claim 1, characterized in that: The medicine for treating osteoarthritis is sulfaguanidine injection.

3. The use according to claim 2, characterized in that: The sulfaguanidine injection comprises sulfaguanidine as the only active ingredient and a solvent.

4. The use according to claim 3, characterized in that: The solvent is physiological saline.

5. The use according to claim 2, characterized in that: The concentration of the sulfamethoxazole injection is 200 μM.

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