Application of interleukin-13 in promoting repair after muscle injury
Through the combination of IL13 and Musclin, the problem of lack of effective drugs for the treatment of muscle degenerative diseases in the prior art was solved, and the effect of remediation of muscle damage was achieved, and the toxicity and side effects of the drug were reduced.
Patent Information
- Application Number
- CN202510539266.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-27
- Publication Date
- 2025-06-20
AI Technical Summary
The prior art lacks effective drugs for the treatment of muscle degenerative diseases, and the side effects of steroid hormones are relatively large and difficult to use for a long time.
By detecting the effects of IL13 and Musclin, it was found that administration of IL13 and Musclin alone can promote repair after muscle injury, and combining the two can significantly improve the therapeutic effect.
Combination medication can significantly promote repair after muscle damage, and its effect is better than medication alone. The drug is low in toxicity and has fewer side effects, which can delay the occurrence of drug resistance and reduce the economic burden on patients.
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Figure CN120168610A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technologies, and particularly to the application of interleukin-13 in promoting the repair after muscle injury. Background Art
[0002] Currently, it is estimated that hundreds of millions of people worldwide suffer from muscle degenerative diseases due to injuries or diseases (up to more than 100 kinds), resulting in problems such as inconvenient movement, impaired respiratory and cardiac functions of patients, seriously affecting the quality of life and survival rate of patients, imposing a great economic burden on patients and their families. Only sarcopenia related to aging accounts for 1.5% of the total healthcare expenditure. At present, the treatment strategies for muscle degenerative diseases mainly use steroid hormones for relief, lacking other effective therapeutic drugs; however, steroid hormones have relatively large side effects. Therefore, it is very necessary to develop drugs for promoting muscle regeneration to alleviate and treat muscle degenerative diseases.
[0003] Muscle is a kind of tissue with the ability of regeneration. Under conditions of injury or some diseases, the muscle regeneration ability will be activated, while aging will reduce the muscle regeneration ability. Normally, damaged muscles secrete various factors to provide a good microenvironment for muscle regeneration. Multiple secreted factors have become emerging therapeutic targets for promoting muscle regeneration. Currently, the treatment strategies for muscle degenerative diseases mainly focus on relieving symptoms, lacking effective therapeutic drugs. Summary of the Invention
[0004] The present invention provides the application of interleukin-13 in promoting the repair after muscle injury. By detecting the effects of single treatment with IL13 and Musclin, it is found that single administration of IL13 and Musclin can promote the treatment effect of repairing muscle injury. And, comparatively speaking, the combined use of the two has a more significant synergistic effect in promoting the drug treatment effect of muscle injury. The drugs adopting the above application method and administration mode have advantages such as low drug toxicity, small side effects, being able to delay the generation of drug resistance, and reducing the economic burden of patients. The technical solution of the present invention is specifically achieved through the following techniques.
[0005] In the first aspect of the present invention, there is provided the application of interleukin-13 in the preparation of a preparation for promoting the repair after muscle injury, or for preventing, alleviating or treating muscle degenerative diseases.
[0006] In the second aspect of the present invention, there is provided the application of interleukin-13 and Musclin in the preparation of a combined preparation for promoting the repair after muscle injury, or for preventing, alleviating or treating muscle degenerative diseases.
[0007] Further, the combined preparation is a drug or a functional food for promoting the repair after muscle injury.
[0008] In a third aspect of the present invention, a preparation is provided, which is used to promote the repair after muscle injury, or to prevent, alleviate or treat muscle degenerative diseases; the preparation comprises interleukin-13 (IL13).
[0009] Interleukin-13 is a cytokine secreted by immune cells and has been reported to have various protective effects, such as promoting small intestine smooth muscle contraction, inhibiting macrophage immune senescence, promoting angiogenesis, promoting cold-induced adaptive thermogenesis, and resisting intestinal nematode infection, etc. Musclin is a muscle-secreted factor and is very important for maintaining muscle health. Musclin can improve endurance exercise performance, reduce the accumulation of fat and fibrous tissue in muscles after exercise, alleviate muscle loss in cachexia, and relieve the inflammatory responses of adipocytes, monocytes and endothelial cells. There has been no research
[0010] on the association between the combined use of interleukin-13 and Musclin and the repair effect after muscle injury. By separately administering interleukin-13 or Musclin to a C57BL / 6 mouse muscle injury model, and by combining interleukin-13 and Musclin in the present invention, it is found that the combined use of the two can significantly promote the repair after muscle injury.
[0011] The "muscle degenerative diseases" claimed in the present invention are a class of diseases caused by aging or diseases, resulting in the gradual loss of muscle tissue and loss of function, including sarcopenia, muscular dystrophy, myasthenia gravis (MG), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), polymyositis (PM), tendon degenerative diseases (tendinopathy), etc.
[0012] Furthermore, the preparation further comprises Musclin.
[0013] More specifically, the mass ratio of the interleukin-13 to Musclin is 1:(10 - 200)
[0014] Optionally, the mass ratio of the interleukin-13 to Musclin is 1:100.
[0015] Furthermore, the dosage form of the preparation is any pharmaceutically acceptable dosage form.
[0016] More specifically, the dosage form can be in the form of an oral preparation, such as tablets, capsules, pills, powders, granules, suspensions, syrups, etc.; or it can be a dosage form for injection, such as injection solutions, powder for injection, etc., through intravenous, intraperitoneal, subcutaneous or intramuscular routes. All the dosage form forms used are well-known to those of ordinary skill in the pharmaceutical art.
[0017] Furthermore, the preparation comprises any one or more pharmaceutically acceptable excipients.
[0018] Furthermore, the preparation is a single compound preparation or a combination of two separate preparations of interleukin-13 and Musclin.
[0019] Furthermore, the preparation is a combined preparation loaded on a pharmaceutical carrier.
[0020] Even further, the pharmaceutical carrier includes liposomes, micelles, dendrimers, microspheres or microcapsules.
[0021] The product provided by the present invention can be administered to a subject by means known in the art, including but not limited to oral, parenteral, subcutaneous, intramuscular, intravenous, intraperitoneal, intrahepatic, intramyocardial, intrarenal, vaginal, rectal, buccal, sublingual, intranasal, transdermal methods, etc.
[0022] Furthermore, the administered dose will depend on the age, health and weight of the recipient, the types of combined drugs, the treatment frequency, the administration route, etc. The drug can be administered in a single daily dose, or the total daily dose can be administered in divided doses two, three or four times a day. The dose can be administered once or multiple times, and the administration time can range from a single day to several months or longer.
[0023] The product provided by the present invention can be administered to any human or animal (such as a pet or livestock, etc.) that has or has had muscle injury or muscle degenerative disease.
[0024] Compared with the prior art, the advantages of the present invention are as follows: After studying the repair and treatment effects of IL13 and Musclin on muscle injury, it is found that the cross-sectional area of muscle fibers in the group administered with IL13 or Musclin alone is significantly larger than that in the non-administered group. This indicates that administration of IL13 or Musclin alone can promote the repair after muscle injury.
[0025] More importantly, compared with the group administered alone and the non-administered group, the cross-sectional area of muscle fibers in the group administered with IL13 and Musclin in combination is significantly larger. This indicates that the combined use of IL13 and Musclin can further promote the repair after muscle injury, and the effect is better than that of single use, and it can be widely applied to muscle injury or other muscle degenerative diseases of humans or animals. Description of the Drawings
[0026] Figure 1 Schematic diagram of the treatment of muscle injury with IL13 recombinant protein ( Figure 1 A) and result diagram ( Figure 1 B). Figure 1The left figure of B is a stained section of the tibialis anterior muscle, and the right figure shows the change in the cross-sectional area of newly formed muscle fibers after administration of the IL13 recombinant protein. Saline represents the saline group.
[0027] Figure 2 Schematic diagram of Musclin treatment for muscle injury ( Figure 2 A) and result diagram ( Figure 2 B). Figure 2 The left figure of B is a stained section of the tibialis anterior muscle, and the right figure shows the change in the cross-sectional area of newly formed muscle fibers after administration of Musclin.
[0028] Figure 3 Schematic diagram of the treatment protocol for muscle injury by combined administration of IL13 recombinant protein and Musclin.
[0029] Figure 4 Result diagram of the promotion of muscle regeneration after combined administration of IL13 and Musclin for muscle injury. Among them, the left figure is a stained section of the tibialis anterior muscle, and the right figure shows the change in the cross-sectional area of newly formed muscle fibers after administration of the IL13 recombinant protein and Musclin. Detailed implementation manners
[0030] The technical solutions of the present invention will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.
[0031] The following detailed implementation manners were directed to a C57BL / 6 mouse model of muscle injury for modeling, and interleukin-13, Musclin were administered alone, and interleukin-13 and Musclin were administered in combination, and the effects of these three administration methods on the repair of muscle injury in the model were verified.
[0032] 1. Experimental materials and equipment
[0033] In this embodiment, the interleukin-13 (IL13) used was the IL13 recombinant protein provided by medchemexpress company and dissolved in sterile saline at a concentration of 2.5 μg / ml.
[0034] Musclin was synthesized by our laboratory. The murine Musclin 26-130 amino acid sequence (NCBI publicly available sequence) was cloned into the pET-15b vector, and the positive clone was transferred into E. coli, and protein expression was induced in E. coli, and separation and purification were carried out using metal affinity chromatography (Ni2+-NTA affinity column) to obtain the Musclin recombinant protein.
[0035] The C57BL / 6 mice were provided by Hubei Center for Disease Control and Prevention.
[0036] 2. Establishment of a C57BL / 6 muscle injury mouse model
[0037] The C57BL / 6 mice were anesthetized by inhaling isoflurane. 50 μl of 1 mg / ml cardiotoxin (CTX, dissolved in sterile saline) was intramuscularly injected into the tibialis anterior muscle to induce muscle injury and establish a muscle injury mouse model.
[0038] 3. Administration methods for each group
[0039] (1) IL13 recombinant protein treatment group
[0040] On days 0, 2, 4, and 6 after establishing the muscle injury mouse model, 50 μL of 5 μg / ml or 2.5 μg / ml IL13 recombinant protein (dissolved in sterile saline) was intramuscularly injected respectively, as shown in Figure 1 and Figure 4 respectively.
[0041] (2) Musclin recombinant protein treatment group
[0042] On the days after establishing the muscle injury mouse model, 50 μL of 0.5 μg / μl or 0.25 μg / μl Musclin recombinant protein (dissolved in sterile saline) was subcutaneously injected every day, as shown in Figure 2 and Figure 4 respectively.
[0043] (3) Combined administration group
[0044] On days 0, 2, 4, and 6 after establishing the muscle injury mouse model, 50 μL of 2.5 μg / ml IL13 recombinant protein was intramuscularly injected, and at the same time, 50 μL of 0.25 μg / μl Musclin was injected every day, as shown in Figure 3 respectively.
[0045] (4) Normal saline group (control group)
[0046] In the control group, 50 μL of sterile saline was subcutaneously injected every day after establishing the C57BL / 6 muscle injury mouse model, and 50 μL of sterile saline was intramuscularly injected on days 0, 2, 4, and 6.
[0047] In all the above experimental groups, the tibialis anterior muscles of the mice were harvested on the 7th day after injury; embedded, sectioned, and stained with H&E; the newly formed myofibers with central nuclei were selected and their cross-sectional areas were counted. The results are as shown in Figures 1-4 respectively.
[0048] From Figure 1 and Figure 2 It can be seen that after separately administering the IL13 recombinant protein or the Musclin recombinant protein, the average cross-sectional area of the newly formed muscle fibers in the mice was significantly increased compared with the control group, and the muscle regeneration was better. This indicates that separately administering the IL13 recombinant protein or Musclin can both promote the repair after muscle injury.
[0049] From Figure 4 It can also be seen that after separately administering, such as Figure 1 half the dose of the IL13 recombinant protein or such as Figure 2 half the dose of the Musclin recombinant protein, the average cross-sectional area of the newly formed muscle fibers in the mice was significantly increased compared with the control group, and the muscle regeneration was better. This indicates that separately administering the IL13 recombinant protein or Musclin, even when the dose is halved, can promote the repair after muscle injury.
[0050] From Figure 4 It can further be seen that after co-administering the IL13 recombinant protein and Musclin at the same dose, the average cross-sectional area of the newly formed muscle fibers in the mice was further increased, and the muscle regeneration was better. The improvement effect was significantly enhanced compared with separately administering the IL13 recombinant protein or the Musclin recombinant protein.
[0051] The above specific embodiments have described in detail the implementation of the present invention. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the claims and the technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple variations all fall within the protection scope of the present invention.
Claims
1. An application of interleukin-13 in the preparation of a preparation, characterized in that: The preparation is used for promoting repair of muscle after injury, or for preventing, alleviating or treating muscle degenerative diseases.
2. An application of interleukin-13 and Musclin in the preparation of a combined preparation, characterized in that: The combined preparation is used for promoting repair of muscle after injury, or for preventing, alleviating or treating muscle degenerative diseases.
3. A preparation, characterized in that The preparation is used for promoting repair of muscle after injury, or for preventing, alleviating or treating muscle degenerative diseases; the preparation comprises interleukin-13.
4. The preparation according to claim 3, characterized in that The formulation also includes Musclin.
5. The preparation according to claim 4, characterized in that The mass ratio of interleukin-13 to Musclin is 1:(10-200).
6. The preparation according to claim 4, characterized in that The mass ratio of interleukin-13 to Musclin is 1:
100.
7. The preparation according to claim 4, characterized in that The dosage form of the preparation is any pharmaceutically acceptable dosage form.
8. The preparation according to any one of claims 3 to 7, characterized in that The preparation includes any one or more pharmaceutical excipients that are pharmaceutically acceptable.
9. The preparation according to any one of claims 3 to 7, characterized in that The preparation is a single compound preparation, or a combination of two separate preparations of interleukin-13 and Musclin.
10. The preparation according to any one of claims 3 to 7, characterized in that The preparation is a combined preparation loaded on a pharmaceutical carrier.