Use of compound ys434 in the preparation of a medicament for the prevention and / or treatment of pulmonary fibrosis and pharmaceutical compositions thereof

Abstract

The application belongs to the field of biological medicine, and particularly relates to the use of a compound YS434 in the preparation of a drug for preventing and / or treating pulmonary fibrosis and a pharmaceutical composition thereof. The small-molecule compound YS434 can treat pulmonary fibrosis by reducing collagen fiber deposition, alleviating inflammatory response, promoting alveolar epithelial tissue repair, and inhibiting the progression of pulmonary tissue fibrosis, thereby providing a new option for a drug for treating pulmonary fibrosis in clinic, and having a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to the use of compound YS434 in the preparation of medicaments for the prevention and / or treatment of pulmonary fibrosis and pharmaceutical compositions thereof. Background Technology

[0002] Pulmonary fibrosis is a lung disease characterized by the destruction of the normal structure of lung tissue, which is gradually replaced by fibrous tissue. Idiopathic pulmonary fibrosis (IPF) is a specific type of pulmonary fibrosis. It is a chronic, progressive, fibrotic interstitial lung disease with an unknown etiology. It is characterized by lung tissue scarring (fibrosis), leading to irreversible decline in lung function. It is more common in people over 50 years of age and is currently incurable. The treatment goals are to slow disease progression, improve quality of life, and reduce acute exacerbations. In fibrotic lung tissue, the content of β-catenin protein is significantly increased. It promotes tissue fibrosis by promoting epithelial-mesenchymal transition (EMT) in epithelial cells and promoting fibroblast proliferation and secretion of matrix proteins. Current treatment methods mainly include the following aspects: 1. Drug therapy: The main drugs approved for IPF treatment are pirfenidone and nintedanib. Nintedanib is a tyrosine kinase inhibitor that can slow the decline in lung function (reduce the annual decline rate of FVC by about 50%). Pirfenidone can inhibit fibrosis and inflammatory response and is suitable for mild to moderate IPF. However, these drugs have many side effects, such as gastrointestinal reactions, abnormal liver function, and photosensitivity (pirfenidone), which affect patient tolerance and compliance. 2. Symptomatic and supportive treatment, mainly including oxygen therapy, pulmonary rehabilitation, and vaccination. 3. Complication management. 4. Lung transplantation is suitable for end-stage IPF (severe decline in FVC or DLCO) and patients with extremely poor prognosis, but there are problems such as donor shortage, high surgical risk, and postoperative rejection. Because idiopathic pulmonary fibrosis is a difficult-to-cure disease, the efficacy of current treatment methods is limited.

[0003] The small molecule compound YS434 has the molecular formula [missing information]. It has been reported that the synthesis of this small molecule compound and its use in treating tumors, ulcerative colitis, and familial multiple intestinal adenomatosis have been granted invention patents, but there are currently no reports on the use of the small molecule compound YS434 in treating pulmonary fibrosis. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides the use of compound YS434 in the preparation of medicaments for the prevention and / or treatment of pulmonary fibrosis, and pharmaceutical compositions thereof.

[0005] This invention provides the use of compound YS434 or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a geometric isomer thereof, in the preparation of a medicament for the prevention and / or treatment of pulmonary fibrosis; the structural formula of compound YS434 is as follows: .

[0006] Preferably, the pulmonary fibrosis is idiopathic pulmonary fibrosis.

[0007] Preferably, the drug can reduce collagen fiber deposition.

[0008] Preferably, the drug can reduce inflammatory cell infiltration.

[0009] Preferably, the drug can promote the repair of alveolar epithelial tissue.

[0010] The present invention also provides a pharmaceutical composition for the prevention and / or treatment of pulmonary fibrosis, which is a formulation prepared by adding pharmaceutically acceptable excipients to compound YS434 or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a geometric isomer thereof as the active ingredient.

[0011] Preferably, the preparation is at least one of an injection, an oral preparation, or a topical preparation.

[0012] Preferably, the oral preparation is an ointment, pill, oral liquid, powder, tablet, granule or capsule; the injectable preparation is an injection solution or powder for injection; the external preparation is a spray, lotion, liniment, ointment, plaster, paste or patch.

[0013] Preferably, the topical preparation is selected from sprays.

[0014] This invention is the first to discover that the small molecule compound YS434 has a therapeutic effect on pulmonary fibrosis, especially idiopathic pulmonary fibrosis. Through experiments, this invention has demonstrated that YS434 can reduce collagen fiber deposition, alleviate inflammatory response, promote alveolar epithelial tissue repair, and effectively inhibit the progression of pulmonary fibrosis, providing a new drug option for the clinical treatment of pulmonary fibrosis and showing good application prospects.

[0015] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0016] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0017] Figure 1 H&E staining was used to show the effects of different treatment groups on mouse lung tissue.

[0018] Figure 2 Masson staining was used to show the effects of different treatment groups on lung fibrosis in mice. Detailed Implementation

[0019] In the following examples and experimental cases, reagents and raw materials not specifically described are all commercially available products.

[0020] Example 1: The small molecule compound YS434 can be used to treat pulmonary fibrosis.

[0021] I. Experimental Methods

[0022] C57 / BL6J mice weighing 20g-22g, aged 6-8 weeks, were used to establish a mouse model of pulmonary fibrosis by intratracheal administration of bleomycin at a dose of 1.1mg / kg. In the bleomycin + YS434 group, starting 14 days after modeling, YS434 was administered every other day via nebulization. The YS434 used for nebulization was dissolved in DMSO at a concentration of 160μg / ml, with each nebulization lasting 30 minutes. In the bleomycin group, only DMSO nebulization was administered after modeling, with each nebulization lasting 30 minutes. Each group consisted of 12 mice. On day 21 after modeling (after a total of 4 treatments), lung tissue from the saline group, bleomycin group, and bleomycin + YS434 treatment group was collected, paraffin sections were prepared, and H&E staining and Masson's trichrome staining were performed. (The synthesis method of small molecule compound YS434 is based on: Application No. CN201810380559.X Flavonoids for the Prevention and Treatment of Colorectal Cancer)

[0023] II. Experimental Results

[0024] like Figure 1 As shown, the lung tissue structure in the saline group was normal, with clearly visible alveoli and thin alveolar walls, and no obvious signs of inflammatory cell infiltration or fibrosis. Compared with the saline group, the lung tissue structure in the bleomycin group was disordered, including alveolar wall thickening, collagen fiber deposition, and inflammatory cell infiltration, indicating that the pulmonary fibrosis model was successfully established. Compared with the bleomycin group, the bleomycin + YS434 group showed reduced alveolar wall thickening and collagen fiber deposition, and reduced inflammatory cell infiltration, indicating that YS434 treatment can inhibit pulmonary fibrosis in mice and promote the restoration of normal lung tissue structure in mice with pulmonary fibrosis.

[0025] like Figure 2As shown, compared with the saline group, the lung tissue structure of the bleomycin group was disordered and the collagen fibers were significantly increased (increased in the blue area), indicating that bleomycin successfully induced pulmonary fibrosis. Compared with the bleomycin group, the bleomycin + YS434 group had reduced collagen fiber deposition (reduced in the blue area), alveolar wall thickening and inflammatory cell infiltration were reduced, indicating that YS434 has a therapeutic effect on bleomycin-induced pulmonary fibrosis.

[0026] The above results indicate that the small molecule compound YS434 can inhibit the process of pulmonary fibrosis and treat pulmonary fibrosis by reducing collagen fiber deposition, alleviating inflammatory response, and promoting alveolar epithelial tissue repair.

Claims

1. Use of a compound YS434 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of pulmonary fibrosis; the compound YS434 has the structural formula of .

2. Use according to claim 1, characterized in that, The pulmonary fibrosis is idiopathic pulmonary fibrosis. The pulmonary fibrosis is idiopathic pulmonary fibrosis. The pulmonary fibrosis is idiopathic pulmonary fibrosis. The pulmonary fibrosis is idiopathic

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