Application of regulatory factor inhibitor in preparation of medicine for treating scapulohumeral periarthritis
By using regulatory factor inhibitors to suppress the expression of interleukin-6 and matrix metalloproteinases, macrophage polarization is regulated, overcoming the problems of side effects and limited efficacy in existing treatments for frozen shoulder, and achieving a more effective treatment for frozen shoulder.
Patent Information
- Application Number
- CN202511124445.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-12
- Publication Date
- 2025-11-21
AI Technical Summary
Existing treatments for frozen shoulder, such as oral NSAIDs and intra-articular corticosteroids, have side effects or limited efficacy. Surgical treatment involves large incisions and has a high recurrence rate, and there is a lack of effective drug treatment options.
By using regulatory factor inhibitors such as triphenylantimonium and tocilizumab, the expression of interleukin-6 and matrix metalloproteinases 2/9 is inhibited, and sustained release is achieved using a hydrogel carrier to regulate macrophage polarization and suppress inflammation and fibrosis in shoulder joint tissues.
It effectively inhibits the progression of frozen shoulder, improves treatment outcomes, reduces shoulder joint range of motion and tissue lesions, and provides a new direction for drug treatment.
Smart Images
Figure CN120983629A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of biopharmacy, in particular to the application of a regulatory factor inhibitor in the preparation of a drug for treating periarthritis. BACKGROUND
[0002] Periarthritis, also commonly known as fifty shoulder, shoulder drop, frozen shoulder, etc., the main symptoms are shoulder joint stiffness, unable to raise the arm, and turning the shoulder will cause pain. At present, periarthritis with mild symptoms is mainly treated by oral non-steroidal anti-inflammatory drugs (NSAIDs) or intra-articular injection of glucocorticoids, and severe periarthritis is mainly treated by mechanical release of adhesion through surgery. However, oral NSAIDs can easily cause gastrointestinal / kidney toxicity, which can cause great damage to the body. Intra-articular injection of glucocorticoids can relieve inflammation in the short term, but cannot block the fibrosis process, and repeated injection can accelerate the degeneration of cartilage. Surgical treatment has a large incision and high cost, and the recurrence rate is high. In summary, the efficacy of the current treatment methods has room for improvement. SUMMARY
[0003] The purpose of the present application is to provide the application of a regulatory factor inhibitor in the preparation of a drug for treating periarthritis, so as to improve the efficacy of periarthritis.
[0004] To achieve the above-mentioned purpose, the present application provides the following technical scheme: The application of a regulatory factor inhibitor in the preparation of a drug for treating periarthritis, wherein the regulatory factor inhibitor is used to inhibit the expression of interleukin 6, and / or is used to inhibit the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
[0005] Optionally, the regulatory factor inhibitor is ammonium triphenylstibonium and / or tocilizumab.
[0006] Optionally, when the regulatory factor inhibitor is ammonium triphenylstibonium, the dosage is any value in the range of 20 mg / kg to 30 mg / kg.
[0007] Optionally, when the regulatory factor inhibitor is tocilizumab, the dosage is any value in the range of 3 mg / kg to 5 mg / kg.
[0008] Optionally, the regulatory factor inhibitor is carried on a hydrogel carrier.
[0009] Optionally, the hydrogel carrier is a methacrylated hyaluronic acid hydrogel.
[0010] Optionally, the regulatory factor inhibitor is used to inhibit the activity of M1 macrophages.
[0011] Optionally, the regulatory factor inhibitor is used to regulate macrophage polarization.
[0012] Optionally, the modulator of the regulatory factor is used to inhibit inflammation and fibrosis of the shoulder joint tissue.
[0013] The present application has the beneficial effect of inhibiting the development of periarthritis from a pathological perspective by inhibiting the expression of interleukin 6 or inhibiting the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9, which helps to improve the universality and provides a new direction for the drug treatment of periarthritis.
[0014] The above description is only a summary of the technical solutions of the present application. In order to more clearly understand the technical means of the present application, and to implement the content of the specification, the following will be described in detail with the preferred embodiments of the present application and with the accompanying drawings. BRIEF DESCRIPTION OF DRAWINGS
[0015] Figure 1 A schematic diagram of the periarthritis model construction method shown in embodiment one of the present application; Figure 2 A quantitative analysis diagram of the shoulder joint activity of each group of rats shown in embodiment one of the present application; Figure 3 A hematoxylin-eosin staining diagram of each group of samples shown in embodiment one of the present application; Figure 4 A quantitative analysis diagram of the shoulder joint capsule thickness of each group of samples shown in embodiment one of the present application; Figure 5 A Masson trichrome staining diagram of each group of samples shown in embodiment one of the present application; Figure 6 A Papanicolaou staining diagram of each group of samples shown in embodiment one of the present application; Figure 7 An immunohistochemical staining experimental result diagram of each group of samples shown in embodiment one of the present application. DETAILED DESCRIPTION
[0016] The technical solutions of the present application will be described in detail below with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.
[0017] In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application. In addition, the terms "first", "second", "third" are only for descriptive purposes and cannot be understood as indicating or implying relative importance.
[0018] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.
[0019] In addition, the technical features involved in the different embodiments of the application described below can be combined with each other as long as there is no conflict between them.
[0020] The present application claims the use of a regulatory factor inhibitor in the preparation of a medicament for treating periarthritis of shoulder, the regulatory factor inhibitor being used to inhibit the expression of interleukin 6, and / or to inhibit the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
[0021] By inhibiting the expression of interleukin 6 or inhibiting the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9, the development process of periarthritis of shoulder is inhibited from a pathological point of view, which helps to improve the universality and provides a new direction for the drug treatment of periarthritis of shoulder.
[0022] In some embodiments, the regulatory factor inhibitor is triphenyl antimony ammonium and / or tocilizumab. Triphenyl antimony ammonium is a matrix metalloproteinase inhibitor that can effectively inhibit the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Tocilizumab is an interleukin 6 inhibitor that can effectively inhibit the expression of interleukin 6.
[0023] In some embodiments, when the regulatory factor inhibitor is triphenyl antimony ammonium, the dosage is any value in the range of 20mg / kg to 30mg / kg, for example, it can be any value in the range of 20mg / kg, 22mg / kg, 24mg / kg, 26mg / kg, 28mg / kg and 30mg / kg.
[0024] In some embodiments, when the regulatory factor inhibitor is tocilizumab, the administration amount is any value in the range of 3 mg / kg to 5 mg / kg, for example, any value in the range of 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg and 5 mg / kg.
[0025] In some embodiments, the regulatory factor inhibitor is carried on the hydrogel carrier, which helps to achieve sustained release of the drug.
[0026] In some embodiments, the hydrogel carrier is a methacrylated hyaluronic acid hydrogel. The methacrylated hyaluronic acid (HAMA) hydrogel has temperature-sensitive injectability, biodegradability and sustained release characteristics, which helps to sustain the release of the drug and improve the therapeutic effect.
[0027] In some embodiments, the regulatory factor inhibitor is used to inhibit the activity of M1 type macrophages. M1 type macrophages are responsible for producing pro-inflammatory cytokines and mediators, which can lead to the intensification of inflammation and induce fibrotic changes in the case of periarthritis. On the contrary, M2 type macrophages release anti-inflammatory cytokines and growth factors, which promote tissue repair and resolution of inflammation. By inhibiting the activity of M1 type macrophages, it helps to inhibit the occurrence and progression of periarthritis.
[0028] In some embodiments, the regulatory factor inhibitor is used to regulate macrophage polarization, which helps to reshape the immune homeostasis and thus plays a therapeutic effect.
[0029] In some embodiments, the regulatory factor inhibitor is used to inhibit inflammation and fibrosis of the shoulder joint tissue.
[0030] For details, please refer to the following examples.
[0031] Example 1: Thirty-two healthy female clean SD rats were taken, the body weight of the rats was in the range of 200 g to 250 g, and the rats were 8 to 10 weeks old, provided by the animal experiment center of Suzhou University. The rats were bred in an environment with room temperature of 18℃ to 20℃, humidity of 50% to 60%, and good ventilation, 6 rats per cage, and free access to food and water. The rats were randomly divided into four groups and named as Control group, Model group, HAMA+SB-3CT group and HAMA+Tocilizumab group. The Model group, HAMA+SB-3CT group and HAMA+Tocilizumab group of mice were constructed with rat periarthritis model, and all procedures in the present application were carried out according to the Animal Care Committee and the Guide for the Care and Use of Animals of the National Institutes of Health. For construction method, please refer to Figure 1The rats were anesthetized by intraperitoneal injection of sodium pentobarbital, and the anesthetic dose was 40 mg / kg. The anesthetized rats were fixed on the table in a lateral position, and a longitudinal incision of about 3 cm was made along the lower edge of the scapula to expose the scapula and humerus. A suture needle was passed through the lower edge of the scapula, and a 2-0 suture was passed around the humeral shaft and tightened to stabilize the shoulder joint. The skin incision was then sutured. No muscle tissue was separated during the operation, and the construction of the rat periarthritis humeroscapularis model was completed on the same day for each group of rats.
[0032] In this embodiment, each group of rats woke up within 30-60 minutes after the operation, could move freely in the cage, eat normally, and had no obvious changes in mental state. There was no inflammatory reaction such as redness and swelling, and exudation at the incision, and the incision healed in one stage. No animals died during the model construction process, and the postoperative rats moved freely in the cage.
[0033] Within two weeks after the model construction, the rats were given drugs once a week. The rats in the Model group were injected with normal saline into the fixed shoulder joint, the rats in the HAMA+SB-3CT group were injected with hydrogel loaded with SB-3CT into the fixed shoulder joint, the dose of SB-3CT was 25 mg / kg, the rats in the HAMA+Tocilizumab group were injected with hydrogel loaded with Tocilizumab into the fixed shoulder joint, the dose of Tocilizumab was 4 mg / kg. The preparation method of the hydrogel loaded with Tocilizumab or SB-3CT is as follows.
[0034] The interleukin 6 (IL-6) inhibitor Tocilizumab and the matrix metalloproteinase (MMP) inhibitor SB-3CT purchased from Celleck Chemicals were used to prepare the therapeutic solution. The molecular weight of Tocilizumab is 148KD, which was dissolved in sterile water to obtain a solution with a concentration of 1mg / ml. SB-3CT was used to inhibit the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and was dissolved in a 10% dimethyl sulfoxide (DMSO) aqueous solution to obtain a concentration of 6.25mg / ml. The methyl acrylate hyaluronic acid (HAMA) powder with a molecular weight of 100KD-200KD purchased from Suzhou Yongqinquan Intelligent Equipment Co., Ltd. (Engineering For Life) was dissolved in the SB-3CT and Tocilizumab solutions, respectively, and magnetically stirred for 2h to fully dissolve the HAMA. The cystamine hydrochloride solution was added slowly under ice bath conditions to obtain a final concentration of 1mmol / ml of cystamine hydrochloride and a final concentration of 5% of HAMA. The resulting hydrogel agent carried Tocilizumab and SB-3CT, respectively. This hydrogel agent is temperature-sensitive, and is in a liquid state at low temperatures. After injection into the body, it undergoes crosslinking under the action of body temperature and changes to a gel-like state.
[0035] After two administrations, the rats were sacrificed by lethal dose of sodium pentobarbital at 8 weeks after surgery. The sutures of each rat were removed, and the shoulder joint range of motion (ROM) of each group of rats was evaluated. The abduction angle of each rat's shoulder joint was detected as the ROM. The ROM of the Control group was 132.13°±3.10°, the ROM of the Model group was 98.88°±12.14°, the ROM of the HAMA+SB-3CT group was 119.63°±5.66°, and the ROM of the HAMA+Tocilizumab group was 123.88°±4.57°. Please refer to Figure 2 The above data was analyzed and a bar graph was generated. The data analysis in this example was performed using GraphPad Prism 9.0 software, and Student-t test was used for comparison between two groups. Single factor analysis of variance and post-hoc test were used for comparison among multiple groups. When the difference was statistically significant, it was marked in the figure as When the difference was not statistically significant, it was marked as "ns" in the figure. In this experiment, the difference was considered statistically significant when p < 0.0001. As can be seen from the figure, the ROM of the rats in the Model group decreased significantly compared with the Control group, indicating that by depriving the joint of physical activity, the shoulder joint can be induced to degenerate, thereby simulating similar pathological changes to human periarthritis humeroscapularis, proving the reliability of the model. After treatment intervention by SB-3CT or Tocilizumab, the rat shoulder joint activity was significantly restored, indicating that the intervention of IL-6 inhibitors and MMP inhibitors can inhibit the decrease in activity induced by joint lack of movement.
[0036] After completing the ROM evaluation, the shoulder joint tissues of the rats in each group were collected. The collected shoulder joint tissues were fixed with 4% paraformaldehyde for 48 h. After fixation, they were decalcified in 10% EDTA for 5 weeks. After decalcification, the excess muscle tissue was removed, the samples were embedded with paraffin and sectioned for subsequent analysis.
[0037] The shoulder joint tissue section samples of the rats in each group were subjected to various histological staining.
[0038] The steps of hematoxylin-eosin (H&E) staining include: immersing the sample in xylene for deparaffinization, with a soaking time of 10 min, repeating twice, then immersing in ethanol solutions with concentrations of 100%, 100%, 95%, 90%, and 85%, with a soaking time of 10 min each, immersing in distilled water, taking out after 10 min and rinsing with distilled water for 3 min, immersing in hematoxylin solution for staining for 5 min, rinsing with tap water for 2 min. After rinsing the sample, immerse it in 1% hydrochloric acid ethanol solution for differentiation for 30 s, take it out and rinse with tap water for 1 min, immerse it in 10% ammonia water for counterstaining for 30 s, take it out and rinse with tap water for 1 min, then immerse it in 1% eosin solution for re-staining for 5 min, take it out and rinse with tap water for 1 min, dehydrate, transparentize, mount, and place it under a microscope for observation. The scale in the histological staining experiment of this embodiment is 100 μm and 500 μm.
[0039] See Figure 3As can be seen from the sample images of the Control group and the Model group, shoulder joint fixation leads to obvious cell infiltration and shoulder joint capsule thickening, while there is no obvious pathological change in the samples of the HAMA+SB-3CT group and the HAMA+Tocilizumab group. The shoulder joint capsule thickness of each sample was statistically analyzed by using the image analysis software ImageJ, and it was found that the shoulder joint capsule thickness of the Control group was 103.50 pm ± 7.19 pm, the shoulder joint capsule thickness of the Model group was 211.88 pm ± 11.71 pm, the shoulder joint capsule thickness of the HAMA+SB-3CT group was 125.00 pm ± 6.12 pm, and the shoulder joint capsule thickness of the HAMA+Tocilizumab group was 129.38 pm ± 10.14 pm. The data was analyzed and plotted as a bar chart, please see Figure 4 , which proves that the intervention of IL-6 inhibitors and MMP inhibitors can inhibit the thickening of the shoulder joint capsule.
[0040] The steps of Masson trichrome staining include: soaking the sample in Masson A liquid overnight, heating the sample with Masson A liquid in a 37°C oven for about 30 min after about 15 hours, while preheating Masson D liquid and Masson F liquid in a 37°C oven. After taking out the heat-treated sample, wash it with tap water for about 30S until the tissue is yellow. Mix equal amounts of Masson B liquid and Masson C liquid, and immediately immerse the washed sample in the mixed solution for 3 minutes. After taking out, wash it with running water, add 1% hydrochloric acid ethanol solution for 1 min, and observe the cell nucleus under a microscope. The background is almost colorless or light gray. Wash it with tap water and drain the excess water. Immerse it in Masson D liquid for 6 minutes to make the entire tissue appear bright red. If the red color is too light, you can extend the staining time appropriately. After draining the excess water as much as possible while ensuring that the tissue does not dry out, treat it with Masson E liquid for 2 min. Do not wash after removing it. Drain the excess Masson E liquid and directly immerse it in Masson F liquid for 5 min. After taking it out, immerse it in 1% glacial acetic acid for about 5s, repeat three times, then immerse it in anhydrous ethanol for dehydration, the first dehydration is 5s, the second and third dehydrations are 10s, immerse it in n-butanol for 30s, then treat it with n-butanol again for 2 min, then treat it with xylene for 10s, repeat twice, then seal it with neutral balsam under a microscope.
[0041] Please see Figure 5 As can be seen from the sample images of the Control group and the Model group, shoulder joint fixation leads to obvious cell infiltration and shoulder joint capsule thickening, while there is no obvious pathological change in the samples of the HAMA+SB-3CT group and the HAMA+Tocilizumab group. The shoulder joint capsule thickness of each sample was statistically analyzed by using the image analysis software ImageJ, and it was found that the shoulder joint capsule thickness of the Control group was 103.50 pm ± 7.19 pm, the shoulder joint capsule thickness of the Model group was 211.88 pm ± 11.71 pm, the shoulder joint capsule thickness of the HAMA+SB-3CT group was 125.00 pm ± 6.12 pm, and the shoulder joint capsule thickness of the HAMA+Tocilizumab group was 129.38 pm ± 10.14 pm. The data was analyzed and plotted as a bar chart, please see Figure 4 , which proves that the intervention of IL-6 inhibitors and MMP inhibitors can inhibit the thickening of the shoulder joint capsule.
[0040] The steps of Masson trichrome staining include: soaking the sample in Masson A liquid overnight, heating the sample with Masson A liquid in a 37°C oven for about 30 min after about 15 hours, while preheating Masson D liquid and Masson F liquid in a 37°C oven. After taking out the heat-treated sample, wash it with tap water for about 30S until the tissue is yellow. Mix equal amounts of Masson B liquid and Masson C liquid, and immediately immerse the washed sample in the mixed solution for 3 minutes. After taking out, wash it with running water, add 1% hydrochloric acid ethanol solution for 1 min, and observe the cell nucleus under a microscope. The background is almost colorless or light gray. Wash it with tap water and drain the excess water. Immerse it in Masson D liquid for 6 minutes to make the entire tissue appear bright red. If the red color is too light, you can extend the staining time appropriately. After draining the excess water as much as possible while ensuring that the tissue does not dry out, treat it with Masson E liquid for 2 min. Do not wash after removing it. Drain the excess Masson E liquid and directly immerse it in Masson F liquid for 5 min. After taking it out, immerse it in 1% glacial acetic acid for about 5s, repeat three times, then immerse it in anhydrous ethanol for dehydration, the first dehydration is 5s, the second and third dehydrations are 10s, immerse it in n-butanol for 30s, then treat it with n-butanol again for 2 min, then treat it with xylene for 10s, repeat twice, then seal it with neutral balsam under a microscope.
[0041] Please see Figure 5 , which proves that the intervention of IL-6 inhibitors and MMP inhibitors can inhibit the thickening of the shoulder joint capsule.
[0042] The steps of S&F staining include: immersing the sample in the fast green dye solution for about 1.5 min, washing the excess dye with water, observing the color of the sample, re-staining if the color is too light, immersing in water to fade the color and re-staining if the color is too dark, shortening the staining time to obtain a sample with moderate color, and then immersing in the differentiation solution for 10 s. After taking out, washing with water, immersing in the ponceau dye solution for 1.5 min, rapidly dehydrating with anhydrous ethanol for 3 times, immersing in xylene for 1.5 min for transparency treatment, sealing with neutral balsam, and observing under a microscope.
[0043] See Figure 6 It can be seen that there is a large amount of collagen deposition in the samples of the Model group, and the content of collagen in the samples of the Control group, the HAMA+SB-3CT group and the HAMA+Tocilizumab group is less, which supports the result of Masson staining.
[0044] Immunohistochemical staining experiments were performed using an immunohistochemical kit purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. to detect the expression of inducible nitric oxide synthase (iNOS) and mannose receptor (CD206) in the samples. In this experiment, the antibodies were purchased from Wuhan Servicebio Biotech Co., Ltd. (Servicebio) and were diluted at a ratio of 1:50.
[0045] The steps of the immunohistochemical staining experiment include: immersing the sample in an environmentally friendly dewaxing solution for 10 min, repeating three times, immersing in anhydrous ethanol for 5 min, repeating three times, and then washing with distilled water. Citrate buffer at pH 6.0 is preheated to boiling, and after the sample is added, microwave treatment is performed to keep it slightly boiling for 15 min for antigen repair. After natural cooling to room temperature, place it in phosphate buffer (PBS) at pH 7.4, and shake it on a decolorizing shaker for 3 times, 5 min each time. Pay attention to the liquid during microwave treatment, which should always cover the sample to prevent dry pieces. After antigen repair, immerse the sample in a 3% hydrogen peroxide solution, incubate at room temperature for 25 min in the dark, and then place the slide in PBS and shake it on a decolorizing shaker for 3 times, 5 min each time, to block endogenous peroxidase. Add 3% bovine serum albumin (BSA) evenly to the sample in the group, and incubate at room temperature for 30 min to complete serum blocking. Gently shake off the blocking solution, and add the diluted primary antibody on the slice. Place the sample in a wet box and incubate at 4°C overnight. Place the sample in PBS and shake it on a decolorizing shaker for 3 times, 5 min each time. Gently shake off the liquid, and add the secondary antibody matching the primary antibody to cover the tissue in the circle, and incubate at room temperature for 50 min. The secondary antibody is labeled with horseradish peroxidase (HRP). Place the sample in PBS and shake it on a decolorizing shaker for 3 times, 5 min each time. Gently shake off the liquid, and add freshly prepared diaminobenzidine (DAB) developing solution in the circle. Control the developing time under a microscope, and the positive display is brownish yellow. After observing that the developing is complete, rinse the sample with tap water. Stain the sample with hematoxylin for 3 min, then rinse with tap water, and then differentiate with hematoxylin differentiation solution for 10 s. Rinse with tap water, and then return blue with hematoxylin return blue solution for 10 s. After rinsing with running water, complete the re-staining of the cell nucleus. Place the sample in ethanol with concentrations of 75% and 85% for 5 min each, then treat with anhydrous ethanol for 5 min, repeat twice, and then treat with n-butanol and xylene for 5 min each. After taking out, dry slightly, mount with mounting medium, and observe under a microscope.
[0046] iNOS is significantly up-regulated only in M1-type macrophages, and is a classic marker of M1-type macrophages. CD206 is highly expressed in M2-type macrophages, and is one of the characteristic markers of M2-type macrophages. See Figure 7, the expression of iNOS and CD206 was quantified by data analysis with immunoreactive score (IRS) respectively, and a column chart was drawn to analyze the polarization of macrophages. In this experiment, the difference was considered statistically significant when p < 0.00001. The analysis results showed that the IRS of iNOS in the Control group sample was 2.38 ± 0.99, the IRS of iNOS in the Model group sample was 7.88 ± 1.45, the IRS of iNOS in the HAMA+SB-3CT group sample was 3.25 ± 0.97, and the IRS of iNOS in the HAMA+Tocilizumab group sample was 2.50 ± 0.87. The IRS of CD206 in the Control group sample was 1.25 ± 0.43, the IRS of CD206 in the Model group sample was 1.00 ± 0.50, the IRS of CD206 in the HAMA+SB-3CT group sample was 1.25 ± 0.43, and the IRS of CD206 in the HAMA+Tocilizumab group sample was 1.13 ± 0.33. Comparison showed that after the construction of the periarthritis model, the expression level of iNOS increased significantly, while the expression level of CD206 did not change significantly, indicating that the occurrence of periarthritis led to the prevalence of M1 type macrophages. After treatment intervention with IL-6 inhibitors and MMP inhibitors, the activity of M1 type macrophages was inhibited, while the activity of M2 type macrophages did not change significantly.
[0047] In summary, IL-6 inhibitors and MMP inhibitors can reduce inflammation and fibrosis of shoulder joint tissue, and inhibit the activity of M1 type macrophages, thereby effectively delaying the progression of periarthritis.
[0048] The technical features of the above-described embodiments can be combined in any manner. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described, but as long as the combinations of the technical features do not contradict, they should be considered within the scope of the present disclosure.
[0049] The above-described embodiments only express several embodiments of the present application, and the description is more specific and detailed, but it should not be understood as limiting the scope of the patent. It should be noted that for those skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are within the scope of the present application. Therefore, the scope of protection of the present application should be subject to the appended claims.
Claims
1. The application of regulatory factor inhibitors in the preparation of drugs for treating frozen shoulder, wherein the regulatory factor inhibitors are used to inhibit the expression of interleukin-6 and / or to inhibit the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
2. The application as described in claim 1, characterized in that, The regulatory factor inhibitor is triphenylantimonium and / or tocilizumab.
3. The application as described in claim 2, characterized in that, When the regulatory factor inhibitor is triphenylantimonium, the dosage is any value between 20 mg / kg and 30 mg / kg.
4. The application as described in claim 2, characterized in that, When the regulatory factor inhibitor is tocilizumab, the dosage is any value between 3 mg / kg and 5 mg / kg.
5. The application as described in claim 1, characterized in that, The regulatory factor inhibitor is carried on a hydrogel carrier.
6. The application as described in claim 5, characterized in that, The hydrogel carrier is methacrylated hyaluronic acid hydrogel.
7. The application as described in claim 1, characterized in that, The regulatory factor inhibitor is used to suppress the activity of M1 macrophages.
8. The application as described in claim 7, characterized in that, The regulatory factor inhibitor is used to regulate macrophage polarization.
9. The application as described in claim 1, characterized in that, The regulatory factor inhibitor is used to suppress inflammation and fibrosis in shoulder joint tissues.