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Application of dipyridamole or pharmaceutically acceptable salt thereof in preparation of medicine for preventing and/or treating pulmonary inflammation

A dipyridamole, pharmaceutical technology, applied in the direction of drug combinations, medical preparations containing active ingredients, antipyretics, etc., can solve problems such as limited research, reduce inflammation infiltration, improve respiratory function, reduce fibroblasts Effects of hyperplasia and collagen accumulation

Active Publication Date: 2021-11-05
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Phosphodiesterase (PDE) is a specific hydrolase of cAMP and cGMP, and its inhibitor can effectively increase the concentration of cAMP / cGMP and is used in the treatment of various diseases, but it is currently used as a new target drug for anti-pulmonary fibrosis. Research is still very limited, including only a small number of relevant studies on PDE4 and PDE5 inhibitors
However, there are no relevant reports of this drug in pulmonary fibrosis and other pulmonary inflammatory diseases

Method used

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  • Application of dipyridamole or pharmaceutically acceptable salt thereof in preparation of medicine for preventing and/or treating pulmonary inflammation
  • Application of dipyridamole or pharmaceutically acceptable salt thereof in preparation of medicine for preventing and/or treating pulmonary inflammation
  • Application of dipyridamole or pharmaceutically acceptable salt thereof in preparation of medicine for preventing and/or treating pulmonary inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Effect of dipyridamole on transformation of HLF-1 cells into myofibroblasts induced by TGF-β

[0047](1) Experimental materials: HLF-1 (human embryonic lung fibroblasts), purchased from the Cell Bank of the Chinese Academy of Sciences; DMEM medium (Gibco, USA); fetal bovine serum (BI, Israel); TGF-β (Proteintech, USA); Pyridamole (2,2',2",2"'-[(4,8-dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)secondary nitrogen] tetra Ethanol, Beide, China); PMSF (Beyond, China); RIPA (Beyond, China); BCA (thermo Fisher Scientific, USA); FN primary antibody (abcam, UK); α-SMA primary antibody (abcam, UK); GAPDH primary antibody (abcam, UK); HRP-goat anti-mouse IgG (BOSTER, China).

[0048] (2) Experimental method: HFL-1 cells were divided into 5×10 5 / mL inoculated in a cell culture dish and cultured overnight to allow the cells to adhere to the wall. The cells were divided into blank control group, model group, and drug administration group. Except for the blank group, ...

Embodiment 2

[0050] Example 2 Effect of dipyridamole on TGF-β-induced fibroblast transformation of NIH / 3T3 cells

[0051] (1) Experimental materials: NIH / 3T3 (mouse embryonic fibroblasts), purchased from the Cell Bank of the Chinese Academy of Sciences; DMEM medium (Gibco, USA); fetal bovine serum (BI, Israel); TGF-β (Proteintech, USA); Pyridamole (2,2',2",2"'-[(4,8-dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)secondary nitrogen] tetra Ethanol, Biide); PMSF (BYT); RIPA (BYT); BCA (thermo Fisher Scientific, USA); FN primary antibody (British abcam); α-SMA primary antibody (British abcam); GAPDH primary antibody (British abcam ); HRP-goat anti-mouse IgG (China BOSTER).

[0052] (2) Experimental method: NIH / 3T3 cells were treated with 5×10 5 / mL inoculated in a cell culture dish and cultured overnight to allow the cells to adhere to the wall. The cells were divided into blank control group, model group, and drug administration group. Except for the blank group, 5 μM TGF-β was added, and...

Embodiment 3

[0054] Example 3 Effect of dipyridamole on bleomycin-induced pulmonary fibrosis model rats

[0055] (1) Experimental materials: 60 SPF grade SD rats, 6-8 weeks old, weighing 200-250g, male, purchased from the Experimental Animal Center of Sun Yat-sen University (permit number: SYXK (Guangdong) 2016-0112), environment Temperature: 20-25°C, humidity 50-70%, free to eat and drink. Dipyridamole (2,2',2",2"'-[(4,8-dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitro] Tetraethanol, Bi De); Pirfenidone (Shanghai McLean Biochemical Technology Co., Ltd.); Carboxymethylcellulose Sodium CMC-Na (Shanghai Aladdin Biochemical Technology Co., Ltd.); Bleomycin Hydrochloride for Injection (Sea Pfizer Pharmaceuticals Co., Ltd.).

[0056] (2) Experimental method:

[0057] Animal grouping: get 60 male SD rats, randomly divided into: blank group (0.5% CMC-Na), model group (0.5% CMC-Na), pirfenidone administration group (150mg / kg), dipyrim Low-dose administration group of dipyridamole (10 mg...

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PUM

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Abstract

The invention discloses the application of dipyridamole or a pharmaceutically acceptable salt thereof in the preparation of medicines for preventing and / or treating pulmonary inflammation. The dipyridamole of the present invention can inhibit the transformation of fibroblasts into myofibroblasts; meanwhile, it can also improve the respiratory function of the bleomycin-induced pulmonary fibrosis model rats, reduce the inflammatory infiltration of lung tissue, and reduce the Pathological conditions such as fibroblast proliferation and collagen accumulation; and it has a strong binding strength with the 2019 novel coronavirus-induced pneumonia target 3CL enzyme, and has a strong inhibitory effect on the 3CL enzyme of the coronavirus and the infection of Vero E6 cells by the coronavirus activity, indicating that the dipyridamole has the effect of preventing and treating pulmonary fibrosis and pneumonia caused by the 2019 novel coronavirus, and can be prepared as a pneumonia drug for application.

Description

technical field [0001] The present invention relates to the fields of pharmaceutical technology and pulmonary disease technology, and more specifically relates to the application of dipyridamole or a pharmaceutically acceptable salt thereof in the preparation of drugs for preventing and / or treating pulmonary inflammation. Background technique [0002] Idiopathic pulmonary fibrosis (IPF) refers to chronic, progressive fibrotic interstitial lung disease of unknown etiology. die. The disease mainly occurs in middle-aged and elderly people over 55 years old, with an incidence rate of about 4.6-16.3 per 100,000 people. my country currently lacks epidemiological statistics of IPF patients, but as a country with a serious aging population, the number of patients is estimated to be more than 500,000 and is increasing year by year. The etiology of IPF is unknown and it is difficult to diagnose. Patients have no symptoms at the early stage. After diagnosis, they are in the middle an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/519A61P11/00A61P29/00A61P31/14
CPCA61K31/519A61P11/00A61P29/00A61P31/14
Inventor 罗海彬吴一诺李哲田怡婧陈健文周倩
Owner SUN YAT SEN UNIV