Use of il7r inhibitors in the preparation of a medicament for treating rosacea

Abstract

The present application relates to the field of biological medicine, and particularly relates to application of IL7R inhibitor in preparation of a drug for treating rosacea. The IL7R inhibitor includes preparations for inhibiting the IL7R at the gene level and the protein level, the preparation for inhibiting the IL7R at the gene level is shRNA, siRNA, dsRNA, miRNA, cDNA, antisense RNA / DNA, and the preparation for inhibiting the IL7R at the protein level is a small molecule compound, a peptide and an antibody. It is found for the first time that targeting IL7R has a significant therapeutic effect on rosacea, can effectively reduce the recurrence rate and reduce the degree of skin lesions. This finding not only opens up a new direction for the basic research of rosacea, but also provides a brand-new and breakthrough solution for the clinical treatment of rosacea, and is expected to bring more persistent and stable therapeutic effect for patients.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biological medicine, and particularly relates to application of an IL7R inhibitor in preparation of a rosacea treatment drug. BACKGROUND

[0002] Rosacea is a common chronic inflammatory skin disease, with an average international prevalence rate of about 5.46%. It is usually manifested as paroxysmal flushing of facial skin, persistent erythema or papules, pustules, telangiectasia, and so on. A small number of patients may also have hypertrophy and ocular changes, which seriously affect the daily life of patients.

[0003] Current treatment methods for rosacea include anti-inflammatory, targeted blood vessels, targeted nerves, and antimicrobial, etc., but these methods often have the problem of high recurrence rate.

[0004] Previous studies have found that rosacea has excessive activation of Th1 / Th17 signals. IL-7R (interleukin 7 receptor) is a heterodimeric complex that plays a crucial role in the development of T cells and B cells, differentiation and survival of naive T cells, and generation and maintenance of memory T cells, and recruitment of effector T cells. In addition, IL-7R is also very important for the development and maintenance of innate lymphocytes (ILC), and plays a key regulatory role in the generation of lymphoid structures and barrier defense mechanisms.

[0005] However, there is currently no research on IL7R in rosacea, and its targeted treatment effect is also not clear, which provides a new direction for future research and treatment. SUMMARY

[0006] In view of the problems in the prior art, the present application provides application of an IL7R inhibitor in preparation of a rosacea treatment drug.

[0007] The treatment of rosacea focuses on controlling symptoms and signs. The existing anti-inflammatory, targeted blood vessels, targeted nerves, and antimicrobial treatment methods often have the problem of recurrence. In view of the high recurrence rate and the difficulty in effectively alleviating skin lesions in the prior art in treating rosacea, the present application is dedicated to providing an innovative treatment idea. The present application first discovers that targeting IL7R has a significant therapeutic effect on rosacea, which can effectively reduce the recurrence rate and alleviate the degree of skin lesions. This discovery not only opens up a new direction for the basic research of rosacea, but also provides a completely new and breakthrough solution for the clinical treatment of rosacea, which is expected to bring more persistent and stable treatment effect to patients.

[0008] In some embodiments, the IL7R inhibitor includes a preparation that inhibits the IL7R at the gene level and the protein level.

[0009] In some embodiments, the agent for inhibiting the IL7R at the genetic level is shRNA, siRNA, dsRNA, miRNA, cDNA, antisense RNA / DNA.

[0010] In some embodiments, the agent for inhibiting the IL7R at the protein level is a small molecule compound, a peptide, an antibody.

[0011] In some embodiments, the antibody is IL7Ra mab.

[0012] In some embodiments, the medicament further comprises a pharmaceutically acceptable excipient.

[0013] In some embodiments, the excipient comprises a diluent.

[0014] In some embodiments, the diluent comprises water for injection.

[0015] Compared with the prior art, the present application has the following beneficial effects:

[0016] The present application discloses, for the first time, the important role of targeting IL7R in the treatment of rosacea, providing a new research direction for tackling this chronic inflammatory skin disease. In the treatment experiment targeting IL7R, the redness and vascular dilation of the rosacea animal model are significantly improved, and the redness area and redness index score are greatly reduced, which strongly proves that the targeted treatment can effectively inhibit the inflammatory response of rosacea. Therefore, IL7R is extremely likely to become a key target for future rosacea treatment, providing more effective treatment options for patients. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 Timeline for IL7R alpha antibody treatment of LL37-induced rosacea animal model.

[0018] Figure 2 General photograph and dermoscopy photograph of IL7R alpha antibody treatment of LL37-induced rosacea animal model.

[0019] Figure 3 HE staining, CD31 immunohistochemistry, CD4 immunohistochemistry, and toluidine blue staining pictures of IL7R alpha antibody treatment of LL37-induced rosacea animal model.

[0020] Figure 4 Statistical graph of IL7R alpha antibody treatment of LL37-induced rosacea animal model (n=5), wherein A is the redness score, B is the redness area, C is the average epidermal thickness, D is the dermal infiltrating cells, E is CD31 + vascular endothelial cells, F is CD4 + T cells, G is mast cells. Detailed Implementation

[0021] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.

[0022] The IL7Ra mab in the following examples was purchased from BioXCell, catalog number #BE0065, and the LL37 was purchased from MedChemExpress (MCE), catalog number HY-P1222A.

[0023] Example 1: Treatment of Rosacea with Targeted IL7R

[0024] I. Experimental Methods

[0025] Model construction: LL37-induced rosacea-like phenotype in mice was treated with IL7R antibody.

[0026] Experimental design: such as Figure 1 As shown, an intradermal injection of LL37 was used to induce a rosacea-like mouse model in 8-week-old female BALB / c mice. Specifically, 48 hours before treatment, mice were shaved and given a first intraperitoneal injection of IL7Ra mab (diluted with water for injection), 150 μg per mouse, followed by repeated injections every 24 hours for a total of 4 times. Simultaneously with the third IL7Ra mab injection, 40 μl of LL37 (320 μM concentration) was injected intradermally into their backs for 2 days. This was done twice daily for two days. Photographs were taken using a camera and dermoscopy to assess skin inflammation 24 hours after the last LL37 injection. Mice were then sacrificed and tissues were collected for further experiments.

[0027] Grouping: Control, IL7Ra mab, LL-37, LL-37+IL7Ra mab.

[0028] II. Experimental Results

[0029] Apparent improvement: such as Figure 2 As shown, the erythema and vasodilation were significantly reduced in the IL7R-targeted treatment group. This result indicates that IL7R-targeted therapy has a significant effect on improving the appearance of rosacea. The reduction in erythema reflects a decrease in the inflammatory response.

[0030] Quantitative data: such as Figure 3As shown, hematoxylin-eosin (HE) staining of paraffin-embedded skin sections from different groups of mice revealed that the IL7Rα monoclonal antibody (IL7Rα mab) effectively improved epidermal thickening and significantly reduced the infiltration of immune cells in the dermis. This finding further confirms the potential of IL7Rα mab in alleviating skin inflammation.

[0031] Furthermore, immunohistochemical and toluidine blue staining analyses of CD31 and CD4 cells indicated that IL7Rα mab effectively reduced vascular density, CD4 T cell infiltration, and mast cell infiltration in rosacea-like inflammation. These results not only support the anti-inflammatory effects of IL7Rα mab at the histological level but also reveal its potential mechanism of action: mitigating the inflammatory response by regulating immune cell infiltration.

[0032] like Figure 4 As shown, both the erythema area and the erythema index score were significantly reduced, further demonstrating that IL7Rα mab can effectively inhibit the inflammatory response of rosacea. The reduction in erythema area not only reflects a significant improvement in skin erythema but may also be related to the reduction in vasodilation. The decrease in the erythema index score comprehensively reflects the improvement in the severity and extent of erythema, providing strong evidence for the clinical application of IL7Rα mab.

[0033] In summary, these experimental results demonstrate that IL7Rα mab has significant efficacy in improving the apparent symptoms of rosacea and reducing the inflammatory response. These findings not only provide a new strategy for the treatment of rosacea but also lay a solid foundation for future research and clinical applications.

[0034] It should be noted that when numerical ranges are mentioned in the claims of this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, the present invention describes preferred embodiments.

[0035] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

Claims

1. The application of IL7R inhibitors in the preparation of rosacea treatment drugs, characterized in that, The IL7R inhibitor is IL7Ra mab.

2. The application of the IL7R inhibitor according to claim 1 in the preparation of a rosacea treatment drug, characterized in that, The drug also includes pharmaceutically acceptable excipients.

3. The application of the IL7R inhibitor according to claim 2 in the preparation of a rosacea treatment drug, characterized in that, The excipients include a diluent.

4. The use of the IL7R inhibitor according to claim 3 in the preparation of a rosacea treatment drug, characterized in that, The diluent includes water for injection.

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