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Preventive or therapeutic agent for herpesvirus-related disease

A herpes virus and virus agent technology, applied in antiviral agents, medical preparations containing active ingredients, organic active ingredients, etc., can solve problems such as unclear combined effects, achieve excellent therapeutic effects, high safety, and reduce adverse effects The effect of action

Inactive Publication Date: 2008-01-23
ASTELLAS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] However, there has been no report on the combined use of this compound and a polymerase inhibitor so far, and the effect of the combined use is completely unclear.

Method used

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  • Preventive or therapeutic agent for herpesvirus-related disease
  • Preventive or therapeutic agent for herpesvirus-related disease
  • Preventive or therapeutic agent for herpesvirus-related disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] Example 1 Helicase-primer inhibitory activity

[0109] Baculovirus (Dr. Nigel D.Stow, Medical Research Council, provided by UK) for expression of UL5, UL52, and UL8 proteins constituting the helicase-priming enzyme complex of HSV-1, by papers such as Crute The method described in (JBC, 1991, Vol.266, P21252-21256) prepared the recombinant HSV-1 helicase-prime enzyme complex. Detection of DNA-dependent ATPase activity, which is the enzymatic activity of the HSV-1 helicase-primerase complex, was carried out according to the method described in Crute et al. (JBC, 1991, Vol. 266, P4484-4488). In summary, 520ng of HSV-1 helicase-prime enzyme complex was reacted at 30°C for 30 minutes in a reaction solution containing 20 μg / mL of DNA from heat-denatured bovine sperm and 2mM ATP, and the ATPase activity was passed. ATP is hydrolyzed into ADP and monophosphoric acid, adding malachite green reagent (0.03% malachite green, 0.1% ammonium molybdate, 4.8% sulfuric acid) equal to th...

Embodiment 2

[0112] Embodiment 2 HSV-1 skin infection mouse model (test in vivo)

[0113] The in vivo activity of the pharmaceutical composition of the present invention was tested using a mouse model of HSV-1 skin infection using the method according to H. Machida et al. (Antiviral Res. 1992 17 133-143). Brush the skin of HR-1 hairless mice (female, 7 weeks old) under ether anesthesia vertically and horizontally with an injection needle several times, and drop the virus liquid (HSV-1 WT-51 strain 1.5×10 4 PFU / 15μL) to make it saturated, so that it can be infected with HSV-1.

[0114] The compounds to be tested are: using the methylcellulose suspension of VCV as a polymerase inhibitor, and in addition, using the compound of Production Example 2 described later, that is, N-(4-methylphenyl)-N-(2-{ [4-(1,3-oxazol-4-yl)phenyl]amino}-2-oxoethyl)1,1-dioxotetrahydro-2H-thiopyran-4-carboxamide methyl cellulose The plain suspension was used as a helicase-priming enzyme inhibitor, and the dosage in...

manufacture example

[0132] Production examples of the compound (I) as a helicase-prime enzyme inhibitor of the present invention are shown below. In addition, many raw material compounds used in the following reactions are disclosed in patent documents (International Publication No. 02 / 38554 pamphlet) and the like, and can be easily obtained by methods described in these known documents. Production examples of novel compounds among starting compounds are shown as reference examples.

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PUM

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Abstract

To provide a medicine, particularly a pharmaceutical composition useful for preventing or treating a variety of diseases caused by infection of a virus of the Herpesviridae family. [MEANS FOR SOLVING PROBLEMS] The present invention relates to an anti-herpesvirus agent characterized by combining a helicase-primase inhibitor with a polymerase inhibitor. By combining the helicase-primase inhibitor with the polymerase inhibitor having different action mechanisms, the anti-herpesvirus agent of the present invention achieves a dramatically superior anti-herpesvirus action compared with conventional administration of a polymerase inhibitor alone. Therefore, it is particularly effective in a case in which a sufficient therapeutic effect cannot be achieved only with a polymerase inhibitor. Further, the doses of both agents can be kept low, therefore it is also possible to perform treatment by lowering the effect of an adverse reaction to be concerned.

Description

technical field [0001] The present invention relates to a medicine, in particular to a medicine useful for the prevention and treatment of herpes virus-related diseases. Background technique [0002] Viruses of the herpesviridae family cause a wide variety of infectious diseases in humans and animals. For example, it is well known that varicella zoster virus (varicella zoster virus; VZV) causes chickenpox, herpes zoster, herpes simplex virus type-1 and -2 (herpes simplex virus type-1 and -2; HSV-1 and HSV- 2) Infections such as herpes labialis and genital herpes were caused respectively. In addition, in recent years, infectious diseases caused by herpes viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6, 7, and 8 have also been clarified. [0003] Nucleic acid drugs called polymerase inhibitors such as acyclovir (ACV) and its prodrugs valacyclovir (VCV) and famciclovir (FCV) are now used as drugs against herpes viruses such as VZV and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/422A61K45/06A61K31/4245A61K31/52A61K31/522A61P31/22A61P43/00C07D413/12
CPCA61K31/422A61K31/4245C07D413/12A61K31/52A61K31/522A61K45/06A61P31/22A61P43/00A61K2300/00
Inventor 鈴木弘周藤健治
Owner ASTELLAS PHARMA INC
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