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Use of active ingredients for the prophylaxis and/or therapy of viral diseases

a technology of active ingredients and viral diseases, applied in the field of test systems, can solve the problems of large number of fatalities, huge economic cost factor, and substantial threat to the health of man and animal, and achieve the effect of reducing the risk of infection

Inactive Publication Date: 2006-11-02
INAMED GMBH INST FUR AEROSOLMEDIZIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Infections by RNA or DNA viruses are a substantial threat for the health of man an animal.
Infections by influenza viruses still belong to the big epidemics of mankind and cause year for year a large number of fatalities.
They are an immense cost factor for the economy, for instance by inability to work because of illness.
The problem of controlling in particular RNA viruses is the adaptability of the viruses caused by a high fault rate of the viral polymerases, thus the preparation of suitable vaccines as well as the design of antiviral substances being very difficult.
The hopes placed on this therapeutic agent thus could not be fulfilled.
Due to their in most cases very small genomes and therefore limited coding capacity for replication-necessary functions, all viruses have to rely to a strong extent on functions of their host cells.
Since, however, in a cell the signal transduction pathways have hardly any function closed in itself, but with activation of the one signal transduction pathway, further signal transduction pathways are additionally activated by cross linkages, it can in principle not be excluded that an inhibited signal transduction pathway can be bypassed by the cell as well as by the viruses, and the therapeutic effect of an active ingredient inhibiting a virus multiplication by inhibition of a certain signal transduction pathway could be limited thereby.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Test System for Identifying Antiviral Active Ingredients

[0047] By means of retroviral transduction of the human lung epithelial cells A549, the canine kidney epithelial cells MDCK and the monkey cells Vero, cell lines were prepared, which stably express either a dominant-negative form of the IKK (IKK KD) or a dominant-interfering mutated form of the inhibitor of NF-kB, mIkB. Furthermore, corresponding lines were also generated, which express an active form of the IKK (IKK EE). The constructs as well as their efficiency with regard to the NF-kB mediated gene expression in cells were already described (Denk et al., J Biol Chem 276, 28451-28458, 2001).

[0048] For generating the stable cell lines, the respective cDNAs for IKK KD, mIkB and IKK EE were cloned in sense orientation into the retroviral expression vector pCFG5 IEGZ (Kuss et al., Eur J Immunol 29, 3077-3088, 1999). Beside the messenger RNA of the ‘gene of interest’, the vector DNA also codes for the messenger RNA of the “gree...

example 2

Inhibition of the Viral NF-kB Activation and Reduction of the Influenza Viruses In Vitro

2.1: Acetylsalicylic Acid (ASA).

[0052] Salicylates, such as ASA or sulfasalazines are widely clinically used as pain alleviating and inflammatory agents. Newer publications show that these substances are direct and effective inhibitors of the IKK (Yin et al., Nature 396, 77-80, 1998; Weber et al., Gastroenterology 119, 1209-1218, 2000) and can inhibit in vitro the multiplication of influenza viruses (Huang and Dietsch, New Engl J Med 319, 797, 1988). Thus, as a positive control, ASA was used. Lung epithelial cells A549 were treated with increasing concentrations of ASA in the range from 0.01 mM-5 mM. These concentrations remained in the culture medium during the full experiment. One hour after treatment the infection by the influenza A virus strain fowl plague virus (FPV) with a multiplicity of the infection of 1 (M.O.I.=1) was performed. Another 24 h after the infection, the titers of the new...

example 3

Effect of ASA on the Influenza Infection in the Mouse

3.1 IP / Parenteral Administration.

[0057] C57 Bl / 6 mice were nasally infected by 5,000 pfu / 20 μl influenza virus (fowl plague virus, FPV). 30 min before the infection, 500 μl ASA (50 mM=9 mg / ml PBS, Sigma-Aldrich Steinheim) were i.p. injected, then ASA (50 mM=9 mg / ml) was administered continuously in drinking water. For control purposes, PBS was injected or administered. Body weight, death rate and survival time were determined. 30 mice per group were treated.

[0058] The following results were obtained. Whereas in the control group, all animals died of influenza, in the ASA group approx. 20% of the animals survived the infection. Further, the average survival time of the dead animals was clearly longer than in the control group. ASA in concentrations of 50 mM, however, led to a distinct reduction of the body weight because of the toxic dose.

3.2 Aerogenic Administration.

[0059] C57 Bl / 6 mice were nasally infected by 5,000 pfu / 20...

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Abstract

The invention relates to the use preferably of at least one active ingredient for the prophylaxis and / or therapy of a viral disease, wherein this active ingredient inhibits at least one component of the cellular signal transduction pathway for the activation of the transcription factor NF-kB such that the virus multiplication is inhibited. The present invention relates furthermore to the local, preferably aerogenic administration of the active ingredient according to the invention for inhibiting a virus multiplication. The active ingredient according to the invention may be combined with at least one further antivirally effective substance for the prophylaxis and / or therapy of a viral disease.

Description

FIELD OF THE INVENTION [0001] The invention relates to a test system for identifying active ingredients, which are suitable for the prophylaxis and / or treatment of viral diseases, the uses of such active ingredients for preparing a pharmaceutical composition for the prophylaxis and / or treatment of viral diseases, formulations for such pharmaceutical compositions and methods for preparing such pharmaceutical compositions. PRIOR ART AND BACKGROUND OF THE INVENTION [0002] Infections by RNA or DNA viruses are a substantial threat for the health of man an animal. To the RNA viruses belong the negative-strand-RNA viruses, such as for instance influenza viruses or the Borna disease virus. Infections by influenza viruses still belong to the big epidemics of mankind and cause year for year a large number of fatalities. They are an immense cost factor for the economy, for instance by inability to work because of illness. Of substantial economic importance are also infections by the Borna dise...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61K31/7056A61K31/7048A61K31/63A61K31/60A61K31/56A61K31/401A61K31/13A61K31/355A61K31/353A61K31/00A61K31/19A61K31/335A61K31/35A61K31/40A61K31/54A61K31/70A61K36/82A61K45/06A61P31/12A61P31/16G01N33/50
CPCA61K31/00A61K31/13G01N33/5041A61K31/19A61K31/335A61K31/35A61K31/40A61K31/54A61K31/60A61K31/70A61K36/82A61K45/06G01N33/5008A61K2300/00
Inventor PLANZ, OLIVERPLESCHKA, STEPHANSEDLACEK, HANS-HARALDLUDWIG, STEPHAN
Owner INAMED GMBH INST FUR AEROSOLMEDIZIN
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