Composition comprising a peptide and an inhibitor of viral neuraminidase

A neuraminidase and composition technology, which can be used in antiviral agents, drug combinations, medical preparations containing active ingredients, etc., and can solve problems such as high variability of influenza virus

Pending Publication Date: 2021-04-30
阿佩普蒂科研究和开发有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the high variability of influenza viruses, vaccines must be improved each year for currently circulating virus subtypes or subtype variants

Method used

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  • Composition comprising a peptide and an inhibitor of viral neuraminidase
  • Composition comprising a peptide and an inhibitor of viral neuraminidase
  • Composition comprising a peptide and an inhibitor of viral neuraminidase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Influenza virus infection can cause the development of pneumonia

[0067] Laboratory mice (C57BL / 6 strain, 8 weeks old) were infected nasally with an influenza A strain (PR8 / 34) and a dose of 150 PFU. On days 3, 5, 7, and 9 post-infection, lungs were removed from 8 mice each, and relative lung weights were determined as a measure of pneumonia.

[0068] Examination showed that the weight of the lungs increased more compared to the control lungs as the duration of the mice's infection with the influenza virus increased. The results are shown in figure 1 middle.

Embodiment 2

[0070] Treatment of pneumonia by administration of a neuraminidase inhibitor or a combination of a neuraminidase inhibitor and peptide AP301

[0071] Laboratory mice (C57BL / 6 strain, 8 weeks old) were infected nasally with an influenza A strain (PR8 / 34) and a dose of 150 PFU. Subsequently, the test animals received oral administration of 10 mg / kg oseltamivir (neuraminidase inhibitor) and intratracheal administration of 10 µg peptide AP301 / test animal, respectively. On test days 2 and 4, the treatment was repeated.

[0072] On days 5, 7, and 9 post-infection, lungs were removed from 30 mice each, and relative lung weights were determined as a measure of pneumonia. The results are shown in figure 2 middle.

[0073] Examinations indicated that neuraminidase inhibitors produced only a moderate reduction in pneumonia as measured by lung weight. However, if the peptide AP301 was administered to influenza virus-infected mice in addition to the neuraminidase inhibitor, pneumonia ...

Embodiment 3

[0075] The pro-inflammatory properties of the AP301 peptide were assessed ex vivo in human whole blood

[0076] An ex vivo-in vitro-safety pharmacology study of the AP301 peptide was performed in human whole blood to determine whether the AP301 peptide resulted in the release of the pro-inflammatory marker interleukin-6 (IL-6) (i.e. APN 301 Will exhibit TNF-specific inflammatory activity (ie TNF-receptor-binding activity)). In this study, fresh whole blood, which is a recognized predictive model for assessing inflammatory responses in vivo, has been used.

[0077] Method summary

[0078] The goal of this study was to determine the pro-inflammatory signaling capacity of the AP301 peptide. Whole blood cultures were used here and the secretion of interleukin-6 (IL-6), a very sensitive marker of proinflammatory stimuli, was quantified by means of ELISA.

[0079] test system

[0080] test system 25 ml of freshly collected heparinized blood from 5 healthy subjects (GP) were u...

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Abstract

The invention relates to a composition comprising a peptide and an inhibitor of viral neuraminidase. Described is a composition comprising a peptide which consists of 7-17 adjacent amino acids and comprises the hexamer TX1EX2X3E, where X1, X2 and X3 can be any natural or non-natural amino acid, and the peptide is cyclized and does not exhibit TNF receptor binding activity, and an inhibitor of viral neuraminidase.

Description

[0001] The present invention is a divisional application of a Chinese patent application with the same title as November 15, 2011 and application number 201180055463.2. technical field [0002] The present invention relates to a pharmaceutical composition for treating influenza. Background technique [0003] In humans, influenza is a severe disease of the respiratory tract and the entire organism caused by influenza viruses. Influenza viruses belong to the Orthomyxoviridae family and are characterized by a segmented RNA genome in a negative-strand orientation. The types relevant to humans are influenza-A and -B viruses, of which subtype A in particular is known to be the causative agent of respiratory hyperthermia. In addition to veterinary importance, all influenza viruses have zoonitic potential, ie the possibility of transfer from chickens or pigs to humans. [0004] Influenza periodically emerges as a pandemic, originating in most cases in Southeast Asia and China, fro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19A61K45/06A61K31/351A61K31/215A61P31/16A61P11/00
CPCA61K38/191A61K45/06A61P11/00A61P31/16A61P43/00A61K2300/00A61K38/10A61K38/12A61K31/351A61K31/167A61K9/0073C07K7/64
Inventor B.菲舍尔R.卢卡斯H.菲舍尔
Owner 阿佩普蒂科研究和开发有限责任公司
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