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Application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia

A technology for glucocorticoids and viral pneumonia, which is applied in biological, clinical and medical fields, and can solve the problems of undiscovered drug effects of bisphosphonates

Active Publication Date: 2022-02-11
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of bisphosphonate drugs (and / or in combination with other active agents) in viral pneumonia has not been found in the prior art

Method used

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  • Application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia
  • Application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia
  • Application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Example 1. Alendronate combined with dexamethasone can increase the endosomal pH of macrophages both in vivo and in vitro

[0110] 1. Experimental steps

[0111] In vitro pH measurement: take mouse alveolar macrophages, according to 5×10 per well 4 The cells were plated in confocal small dishes, and then 1 mL of 50 μM alendronate sodium or 0.2 μM dexamethasone was added to each well, or both were cultured for 24 hours. Then add pHrodo TM Red dextran was labeled for 10 min, and photographed with a confocal microscope.

[0112] pH determination in vivo: after nasal administration of 150 μg alendronate sodium, or 1 μg dexamethasone or a combination of the two for 24 hours, the alveolar macrophages of the mice were taken out, and 50 μg / mL pHrodo TM Red dextran marked with 10min after use NxT Acoustic Focusing Flow Cytometry Detection.

[0113] 2. Experimental results

[0114] Alendronate sodium combined with dexamethasone treated mouse alveolar macrophages in vitro c...

Embodiment 2

[0115] Example 2. Alendronate sodium combined with dexamethasone can promote macrophages to clear SARS-CoV-2Delta mutant strains in vitro

[0116] 1. Experimental steps

[0117] Take mouse alveolar macrophages, according to 5×10 per well 4 cells were plated in 24-well plates. The next day according to 2.5×10 4 After 2 hours of TCID50 virus infection, the culture medium was discarded, washed twice with PBS, and the PBS was discarded for the last time. Add 1mL of 50μM alendronate sodium or 0.2μM dexamethasone to each well, or a combination of the two to continue culturing for 22h or 46h, then wash twice with PBS, discard the PBS for the last time, add 1mL TRIZOL to each well, extract RNA, and reverse transcription. Analysis of viral gene ORF1ab( Figure 2B ) and copy number of N (Fig. 2A).

[0118] 2. Experimental results

[0119] qPCR analysis showed that alendronate combined with dexamethasone could reduce the viral load of macrophage SARS-CoV-2Delta strain in vitro ( ...

Embodiment 3

[0120] Example 3. Alendronate combined with dexamethasone can down-regulate the expression of IL-1, TNF-α, IL-6 and other inflammatory cytokines in macrophages infected by the Delta mutant strain in vitro

[0121] 1. Experimental steps

[0122] Take mouse alveolar macrophages, according to 5×10 per well 4 cells were plated in 24-well plates. The next day according to 2.5×10 4 After 2 hours of TCID50 virus infection, the culture medium was discarded, washed twice with PBS, and the PBS was discarded for the last time. Add 1 mL of 50 μM alendronate sodium or 0.2 μM dexamethasone to each well, or a combination of both to continue culturing for 22 h or 46 h, then wash twice with PBS, and discard the PBS for the last time. Add 1mL TRIZOL to each well, extract RNA, and perform reverse transcription. The expression of IL-6 was analyzed by qPCR.

[0123] 2. Experimental results

[0124] Alendronate combined with dexamethasone can down-regulate the expression of IL-6, IL-1 and TNF...

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Abstract

The invention provides application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia. In particular, the nitrogenous bisphosphonate combined glucocorticoid is used to treat or ameliorate coronavirus infections, wherein the nitrogen-containing bisphosphonate is selected from pamironate, alendronate, risedronate, ibandronate, zoledronate, minodronate and pnaphonate, and the glucocorticoid is selected from the group consisting of dexamethasone, rimesolone, prednisolone, fluorometholone, hydrocortisone, mometasone, fluticasone, beclomethasone, flunivoxone, antiphlogistic, fluticasone propionate, beclomethasone dipropionate, budesonide and mometasone furoate.

Description

technical field [0001] This application relates to biological, medical and clinical fields. Specifically, it relates to the use of nitrogen-containing bisphosphonates combined with glucocorticoids in the prevention or treatment of viral pneumonia infection. Background technique [0002] Novel coronavirus pneumonia (COVID-19) is an acute respiratory infectious disease caused by 2019 novel coronavirus (SARS-CoV-2) infection. The main route of transmission is respiratory droplet transmission and contact transmission, with an incubation period of 1-14 days, mostly 3-7 days. [0003] Typical 2019-nCoV pneumonia mainly manifests as fever, dry cough, and fatigue, and a small number of patients are accompanied by upper respiratory and gastrointestinal symptoms such as nasal congestion, runny nose, and diarrhea. Severe patients often develop dyspnea within a week, and severe cases rapidly progress to acute respiratory distress syndrome, septic shock, coagulation dysfunction, and mu...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/663A61K31/573A61P31/14A61P11/00
CPCA61K45/06A61K31/663A61K31/573A61P31/14A61P11/00A61K2300/00A61K31/675A61K31/57A61K31/58A61K31/56A61P31/12Y02A50/30A61P37/06A61K9/0019A61K9/0043A61K31/569A61K31/575
Inventor 黄波
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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