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Use of aspirin and derivative thereof in preparation of drug for treating airway mucus hypersecretion

A technology of aspirin and its derivatives, which is applied in the field of clinical medicine, can solve problems such as airflow limitation, increased risk of bacterial infection, and progressive decline in lung function, achieving credible experimental results

Inactive Publication Date: 2020-06-30
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Normal bronchial mucosal glands and goblet cells only secrete a small amount of mucus to keep the respiratory mucosa moist. When the respiratory tract is stimulated by pathogenic microorganisms or physical and chemical factors, the secretion of airway mucus increases and is discharged through ciliary movement and coughing. Persistent mucus hypersecretion can lead to airway obstruction, airflow limitation, progressive decline in lung function, and increased risk of bacterial infection

Method used

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  • Use of aspirin and derivative thereof in preparation of drug for treating airway mucus hypersecretion
  • Use of aspirin and derivative thereof in preparation of drug for treating airway mucus hypersecretion
  • Use of aspirin and derivative thereof in preparation of drug for treating airway mucus hypersecretion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Aspirin regulates the expression of FOXA2

[0053] 1. Cell level research

[0054] 1.1 Cell culture

[0055] A549 cells were placed in DMEM medium containing 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin, at 37°C, 5% CO 2 Subculture in an incubator. The medium was changed every two days, and the cultures were subcultured every 4 days.

[0056] 1.2 Drug handling

[0057] Dexamethasone (Dexamethasone, 10 -6 M, 48h), ambroxol (Ambroxol, 2.1 μg / ml, 48h), tiotropium bromide (tiotropium, 20nM, 48h), aspirin (aspirin, 4mM, 48h) to stimulate A549 cells.

[0058] 1.3 RNA level detection

[0059] 1.3.1 Total RNA extraction

[0060] 1) Wash the cells once with 1ml of phosphate buffer solution pre-cooled in a 4°C refrigerator, add 1ml TRIzol to each well, and act for 2 minutes to fully lyse the cells. Freeze the lysed samples in a -80°C refrigerator. Freezing and thawing can make the cells lyse more fully. ;

[0061] 2) Thaw the TRIzol-t...

Embodiment 2

[0111] Example 2 Study on Lysine Pirin Regulating Airway Mucus Secretion

[0112] 1. Animal handling

[0113] BALB / c female mice (4-6 weeks) were randomly divided into control group (WT), OVA sensitized group (OVA), wild type + lysine-pirin group (WT + L-ASA), OVA sensitized + In the lysinepirin group ((OVA+L-ASA) 4-6 rats in each group), the lysinepirin was administered by nebulization. The left lung was stained with HE and PAS, and the right lung was lavaged with normal saline. The cells in the lavage fluid were counted, sliced, and Swiss-Giemsa stained. The right lung tissue was extracted for RNA and protein detection.

[0114] 1) Preparation of mouse abdominal cavity sensitization mixture

[0115] Configure the corresponding total amount of sensitization mixture according to the number of experimental mice, and prepare according to the following ratio: immune adjuvant Al(OH)3-Mg(OH)2(Imject TM Alum Adjuvant) 0.5ml and 200 micrograms of chicken ovalbumin (dissolved in ph...

Embodiment 3

[0149] Example 3 Regulation of aspirin on the expression of MUC5AC and MUC5B in human primary airway epithelial cells

[0150] 1. Human primary airway epithelial cell culture

[0151]Preparation of Feeder cell: Culture NIH / 3T3 (mouse embryonic fibroblast cell line) in a 15cm culture dish with DMEM (H) medium (containing 10% FBS and 1% PS), and use Mitomycin C (4mg / L) after treating the cells for three hours, freeze them with cell preservation solution for future use.

[0152] 2. Isolation and expansion of primary human airway epithelium

[0153] Resuscitate the prepared Feeder cell (2M) in a 15cm culture dish (treated with PureCol) one day in advance, and replace it with CRCY medium the next day;

[0154] Microdissect a section of human bronchus and cut it longitudinally. Dilute pronase with Accutase to 8-10ml of 0.5mg / ml digestive solution. Add 1ml of FBS to stop the digestion, centrifuge at 3000g for 3min, discard the supernatant, resuspend in CRCY medium, add to the pre-...

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PUM

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Abstract

The invention discloses use of aspirin and a derivative thereof in preparation of a drug for treating airway mucus hypersecretion. The aspirin derivative is lysine aspirin (aspirin-DL-lysine). Cell experiments and animal experiments prove that the aspirin-DL-lysine is capable of regulating and controlling expression of FOXA2, MUC5AC and MUC5B so as to realize a function of inhibiting airway mucushypersecretion. By virtue of research results of the invention, novel methods and thoughts are provided for clinic treatment.

Description

technical field [0001] The invention belongs to the field of clinical medicine and relates to the use of aspirin or its derivatives in treating airway mucus hypersecretion. Background technique [0002] Respiratory mucus is an important part of the first defense barrier of the airway, and plays an important role in maintaining airway humidification and assisting the function of airway epithelial cells. However, if the mucus secretion is abnormal, long-term excessive mucus secretion (also known as chronic mucus hypersecretion) can block the airway lumen, induce bronchopulmonary infection, and lead to the destruction of the bronchi and lung parenchyma structure, resulting in a chronic and irreversible decrease in lung function. [0003] Airway mucus is a dilute solution of lipids, carbohydrate conjugates, and proteins. It is generally believed that the airway mucus is composed of a thin sol layer and a relatively viscous gel layer. The sol layer is only 7 μm, and the cilia ar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/616A61K31/198A61P11/00
CPCA61K31/198A61K31/616A61P11/00A61K2300/00
Inventor 罗凤鸣汤小菊孙凌魏传琦
Owner WEST CHINA HOSPITAL SICHUAN UNIV