JPH0129A - antiviral agent - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to an antiviral agent against a special pathogen for which no effective treatment has yet been found.

<Prior art> Acyclovir (
Acyclovir, Ara-A, and the like are known. These drugs are based on inhibiting some step of the viral replication process.

However, since the virus propagation process is dependent on the metabolic system of the host cell, use of the above drugs leads to inhibition of the normal cellular metabolic system, resulting in side effects. Under these circumstances, there is a desire to develop antiviral agents that selectively inhibit viral enzymes, constituent proteins, nucleic acid synthesis processes, and the like.

<Problems to be Solved by the Invention> Special pathogens are dangerous international infectious diseases that have recently attracted attention. This is a class IV (class I) pathogen such as viral hemorrhagic fever, Lassa fever, Marburg disease, and Ebola hemorrhagic fever.
V) pathogenic virus and Hantan virus (Han
Taan Virus (HV) is a virus for which no effective prevention or treatment has been found, although it is relatively highly infectious to humans and has a high fatality rate. experiment,
Research will also be conducted in high-security laboratories for classes ■ to IV.

1) is an epidemic hemorrhagic fever (epidemic hemorrhagic fever).
rhagic fever (EHF) or Korean hemorrhagic fever (KOr(!an hemorrhagic fev)
er: The causative virus of Kf-(F), which causes renal symptoms and caused a disease with similar symptoms worldwide in 1982.
At the Wl-to workshop in 2017, renal symptomatic hemorrhagic fever (h)
emorrhagic fever with ren
al syndrome: HFR3). This virus persistently infects field mice and then infects humans. Currently, there are repeated epidemics in China, the Soviet Union, and almost all of Europe, and the disease has a fatality rate of around 5%. Clinically, it is an acute disease characterized by sudden high fever, proteinuria, and bleeding tendency, accompanied by gastrointestinal symptoms such as severe symptoms, headache, myalgia, diarrhea, and vomiting. In severe cases, shock, hemorrhage, and uremia may also occur. No effective prevention or treatment methods have been found yet.

An object of the present invention is to provide an antiviral agent effective against the above-mentioned special pathogens.

Means for Solving the Problems> The present invention is an antiviral agent against special pathogens, especially HV, which contains interferon (IFN) as an active ingredient.

The IFN used in the present invention is of the α, β, or γ type, and may be any of the natural type, those produced by chemical synthesis, and those produced by genetic recombination technology. Natural types include human IFN-α produced by human leukocytes, human IFN-β produced by human diploid fibroblasts, and recombinant ones include human IFN-α and human IFN-β. , human IFN-γ, and the like. It is also effective to use these α, β, and γ types of IFN in combination.

A stabilizer can be added to the antiviral agent of the present invention if necessary. Such stabilizers include human serum albumin, polyols disclosed in JP-A No. 58-92619, and polyols disclosed in JP-A-58-92621.
Examples include acid buffers and the like. Furthermore, it goes without saying that formulations can be prepared by appropriately mixing commonly used carriers, etc., depending on the administration method. I contained as an active ingredient of the present invention
Since FN has species specificity, when administering to humans, it is necessary to use human IFN, and when administering to other animals, it is necessary to use IFN from the same species of animal. Various dosage forms are used, such as injections, capsules, oral preparations, and ointments.

The dosage is determined appropriately depending on the subject, administration method, symptoms, etc., but is generally 500,000 to 3,500,000 units, particularly 80 to 3,500,000 units.
1.2 million units will be administered in three doses.

Experimental Example> Experimental Example 1 Vero cells E 6 (VeroE 6 ) were incubated with human IF
N-(2, treated with human IFN-β or human IFN-γ at various concentrations for 24 hours at 37°C. The cells were then infected with HV for 1 hour at 37°C.

The human IFN-α used was the natural type provided by Dr. Cantell, and the human IFN-β was the natural type “
Feron'' (manufactured by Toshi Co., Ltd.), human IFN-γ, was produced by genetic recombination technology as described in JP-A-58-90514.

The relationship between the IFNI degree and the inhibition rate was as shown in Figure 1. From this result, the inhibition rate is IFN-β>IFN-γ>
It can be seen that the order is IFN-α.

Experimental Example 2 First, the susceptibility of ICR mice (Nippon Yurea Co., Ltd.) to HV was investigated. ICR mice 24 hours after birth, ICR mice 24 to 48 hours after birth, 48 hours after birth
H for the three groups of ICR mice over time
When infected with V, the oral change in survival rate was shown in Figure 2 (
It was shown in A>. These results show that ICR mice that are 24 hours or more old have lower susceptibility to HV and a lower mortality rate. Based on this result, in the following experiments, we conducted the following experiments.
ICR mice aged within 1 hour were used. Approximately 18 years old
Mouse IFN-β was administered to ICR mice at 5X10S units/mouse or 5X104 units/mouse for 6 hours.
After hours HV[3,8X103 plaque forming units (PF
LI)/mice] and examined oral changes in mouse survival rate. The mouse IFN-β used here was published in Japanese Patent Publication No. 6
It was produced by genetic recombination technology according to the description of 1-19488@. The results are shown in FIG. 2 (B) and (C). (B) 5X105 mouse IFN-β
unit/mouse, (C) is 5X104 units/mouse.
This is the case when administered to mice. In all cases, a significant life-prolonging effect was observed.

Experimental Example 3 Mouse 1FN-β was administered to ICR mice within 24 hours after birth.
HV (3,
8x103 PFU/717] was infected on the same side or contralateral side to the interferon administration [Figure 3 (A)]. Separately, H
V (3,8×103 PFU/mouse) and infected with 6
Mouse IF after hours and 1°2.3, 4.6.8 days
N-β was administered at 5 x 10 units/mouse [Figure 3 (B
)].

The mouse IFN-β used here was produced by the method described in Experimental Example 2. Oral changes in survival rate in each case were investigated. Figure 3 (A> shows mouse IFN-β in HV
When administered at the same time as infection, the same figure (B) shows that mouse IFN
The results are shown when -β was administered to patients infected with HV. These results showed that in the case of simultaneous administration, a remarkable effect was observed in the case of ipsilateral inoculation. Furthermore, even after administration of the virus, a therapeutic effect was observed if IFN was administered frequently.

[Brief explanation of the drawing]

FIG. 1 shows the relationship between IFN concentration and inhibition rate. Figures 2 and 3 show the relationship between the number of days elapsed after HV infection and the survival rate of ICR mice. Patent applicant Toshi Co., Ltd. Inhibition rate (%) Figure 2 = 1 - ICR mouse 24 hours after birth - Ichigo - ICR mouse 24 to 48 hours after birth -
〇-ICC mom mouse 6 10 1 over 48 hours old
4 18 22 26 Number of days since infection

Claims (1)

[Claims] (1) Antiviral agent against special pathogens containing interferon as an active ingredient.