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Application of nitrogen-containing bisphosphonate in prevention or treatment of viral pneumonia

A technology for viral pneumonia and bisphosphonates, which can be used in biological, clinical, and medical fields to solve problems such as the effects of bisphosphonates that have not yet been discovered

Pending 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 in viral pneumonia has not been found in the prior art

Method used

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  • Application of nitrogen-containing bisphosphonate in prevention or treatment of viral pneumonia
  • Application of nitrogen-containing bisphosphonate in prevention or treatment of viral pneumonia
  • Application of nitrogen-containing bisphosphonate in prevention or treatment of viral pneumonia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Example 1. Alendronate sodium can promote macrophages to eliminate SARS-CoV-2Delta strains in vitro

[0093] 1. Experimental steps

[0094] Take mouse alveolar macrophages, according to 5×10 per well 4 cells were plated in 24-well plates. The next day follow 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 to each well, continue to culture for 22h or 46h, 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. Analysis of viral gene ORF1ab( Figure 1A ) and N( Figure 1B ) copy number.

[0095] 2. Experimental results

[0096] qPCR analysis showed that alendronate sodium can reduce the viral load of SARS-CoV-2Delta strain in macrophages in vitro ( Figure 1A with Figure 1B ).

Embodiment 2

[0097] Example 2. Alendronate sodium can down-regulate the expression of IL-6 in macrophages infected with Delta strain in vitro

[0098] 1. Experimental steps

[0099] Take mouse alveolar macrophages, according to 5×10 per well 4 cells were plated in 24-well plates. The next day follow 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 to each well, continue to culture for 22h or 46h, 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.

[0100] 2. Experimental results

[0101] Alendronate sodium can down-regulate the expression of IL-6 in macrophages infected with Delta strain in vitro ( figure 2 ).

Embodiment 3

[0102] Example 3. Alendronate sodium can increase the endosomal pH value of macrophages both in vivo and in vitro

[0103] 1. Experimental steps

[0104] In vitro pH measurement: take mouse alveolar macrophages, according to 5×10 per well 4 The cells were plated into confocal small dishes, and then 1 mL of 50 μM alendronate sodium was added to each well, and cultured for 24 hours. Then add pHrodo TM Red dextran was labeled for 10 min and photographed with a confocal microscope.

[0105] In vivo pH measurement: intranasally administered 150 μg alendronate sodium to each mouse, 24 hours later, the alveolar macrophages of the mice were taken out, and 50 μg / mL pHrodo TM Red dextran labeled for 10min with NxT Acoustic Focusing Flow Cytometry Detection.

[0106] 2. Experimental results

[0107] Alendronate sodium treatment of mouse alveolar macrophages in vitro can increase the pH value of the endosome ( Figure 3A , Figure 3B ). In vivo administration of alendronate sodi...

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Abstract

The invention provides application of nitrogen-containing bisphosphonates in prevention or treatment of viral pneumonia. In particular, the present regimen relates to new uses of nitrogen-containing bisphosphonates in the treatment or amelioration of coronavirus infection; wherein the nitrogen-containing bisphosphonate is selected from pamironate, alendronate, risedronate, ibandronate, zoledronate, minodronate and pnaphonate. The invention further discloses a preparation method of the nitrogen-containing bisphosphonate.

Description

technical field [0001] This application relates to biological, medical and clinical fields. Specifically, it relates to the use of nitrogen-containing bisphosphonates in preventing or treating 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 routes of transmission are respiratory droplet transmission and contact transmission. Typical 2019-nCoV pneumonia mainly manifests as fever, dry cough, and fatigue. 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 multiple organ failure, which eventually lead to the death of the patient. The novel coronavirus is highly ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/663A61K31/675A61P31/14A61P11/00A61P29/00A61P31/16
CPCA61K31/663A61K31/675A61P31/14A61P11/00A61P29/00A61P31/16
Inventor 黄波
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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