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Diltiazem for use in the treatment of microbial infections

A technology of diltiazem and pathogenic microorganisms, applied in the fields of compounds for pathogenic microorganism infection, compounds for preventing and/or treating pathogenic microorganism infection, and capable of solving problems such as unexplored beneficial effects of diltiazem and incompletely clear technical effects

Pending Publication Date: 2021-05-11
UNIV CLAUDE BERNARD LYON 1 +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0034] However, all of the beneficial effects of diltiazem may have been left unexplored, and the technical effects most likely related to diltiazem as a drug are not yet fully understood

Method used

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  • Diltiazem for use in the treatment of microbial infections
  • Diltiazem for use in the treatment of microbial infections
  • Diltiazem for use in the treatment of microbial infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0277] Example 1 Characterization of diltiazem-induced type III interferon gene expression by RNAseq and RT-qPCR.

[0278] A-diltiazem applied to the basolateral pole of the reconstructed human airway epithelium ( HAE, Epithelix)

[0279] Reconstituted human airway epithelium was maintained in culture at the air-liquid interface according to the instructions of the supplier Epithelix ( HAE, Epithelix), treated or not with diltiazem (90 μM) at its basolateral pole through its culture medium. Diltiazem treatment was repeated for 3 consecutive days (a total of 3 applications).

[0280] Treated and untreated epithelium were then lysed with 150 [mu]L RLT buffer (Qiagen). Total ARN was extracted using the RNeasy kit (Qiagen) according to the supplier's instructions.

[0281] According to the vendor's instructions, use ScriptSeq TM Complete Gold Kit-Low Input (SCL6EP, Epicentre), cADN library was prepared from 200ng total ARN. Use ScriptSeq TM Primers provided in the Index P...

Embodiment 2

[0295] Example 2 Confirmation of diltiazem-induced expression of 8 genes related to "type III interferon" response by Rt-qPCR.

[0296] Reconstituted human airway epithelium was maintained in culture at the air-liquid interface according to the instructions of the supplier Epithelix ( HAE, Epithelix), treated or not with diltiazem (90 μM) at its basolateral pole through its culture medium. Diltiazem treatment was repeated for 3 consecutive days (a total of 3 applications).

[0297] Treated and untreated epithelium were then lysed with 150 [mu]L RLT buffer (Qiagen). Total ARN was extracted using the RNeasy kit (Qiagen) according to the supplier's instructions. After the reverse transcription step, use the StepOnePlus TM A real-time PCR system (Applied Biosystems) performed real-time quantitative PCR reactions on 96-well plates.

[0298] 定量PCR引物(GAPDH:Hs02758991_g1,IFNL1:Hs00601677_g1,IFNL2:Hs00820125_g1,IFIT1:Hs01675197_m1,IFIT2:Hs00533665_m1,IFIT3:Hs00382744_m1,IFI27:Hs01...

Embodiment 3

[0302] Example 3 ELISA measures diltiazem-stimulated secretion of type III interferon lambda 1 (IL-29).

[0303] Reconstituted human airway epithelium was maintained in culture at the air-liquid interface according to the instructions of the supplier Epithelix ( HAE, Epithelix), treated or not with diltiazem (90 μM) at its basolateral pole through its culture medium. Diltiazem treatment was repeated for 3 consecutive days (a total of 3 applications).

[0304] After 72 hours of treatment, interferon λ1 ( IL-29) secretion level (pg / mL).

[0305] image 3 Representative of the results obtained: After treatment with diltiazem by the epithelial culture medium, the secretion of IFNλ1 (IL-29) was sharply increased in the apical pole; a significant increase was also observed in the basolateral pole of the treated epithelium, but to a lesser degree.

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Abstract

The present invention relates to diltiazem for use as an agent activating the expression of at least one gene coding for type III interferon, for the prevention and / or treatment of infections involving at least one pathogenic micro-organism affecting the epithelia of the respiratory and / or intestinal tracts.

Description

technical field [0001] The present invention relates to compounds for preventing and / or treating infections by pathogenic microorganisms. [0002] More specifically, the present invention relates to compounds for the prevention and / or treatment of pathogenic microbial infections of the respiratory and / or intestinal epithelium. Background technique [0003] Infection of respiratory and / or intestinal epithelial pathogens [0004] Acute respiratory infection (IRA) is one of the leading causes of consultation, hospitalization and death worldwide, especially among young children, with nearly 2 million deaths per year. The cost to society of treating these different respiratory infections is estimated to be between 1.5 billion and 2 billion euros per year. [0005] Among the pathogens that cause IRA, viruses dominate. Viruses are found in most cases of pneumonia in children, and they are the cause of bacterial pneumonia in adults. The most representative viruses in terms of fr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/554A61P31/00A61P31/04A61P31/10A61P33/00A61K9/00A61P31/12
CPCA61K31/554A61P31/00A61P31/04A61P31/10A61P31/12A61P33/00A61K9/0073A61K2300/00A61K45/06A61P37/04A61P31/14
Inventor M·罗莎-卡拉特拉瓦O·特利尔C·尼古拉斯德拉姆G·博文M·A·皮佐诺
Owner UNIV CLAUDE BERNARD LYON 1
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