JPS6115841A - Antiviral agent for hematherm - Google Patents

Abstract

PURPOSE:To provide the titled antiviral agent containing leupeptin or its salt as an active component. CONSTITUTION:An antiviral agent for hematherms can be prepared by using the leupeptin of formula (R is acyl) or its salt (e.g. mineral acid salt such as sulfate, etc. or carboxylic acid salt such as citrate, etc.) as an active component. The hematherm is e.g. man, domestic animals such as cattle, horse, sheep, pig, etc. or domestic poultry such as chicken, etc. It is administered at a rate of 0.1-10mg/ kg daily. There is no particular restriction in the method of administration, however, it is preferable to be orally administered. The period of administration is usually the affected period of the viral disease, however, it may be administered through the period liable to be affected with the viral disease (e.g. a suckling or an infant) for the prevention of the viral disease. The agent is prepared in the form of solid or liquid preparation such as tablet, capsule, granule, syrup, etc. or it may be added to a food or drink such as water, milk, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an antiviral agent for warm-blooded animals containing leupeptin or its salts as an active ingredient.

The antiviral agent of the present invention is expected to be a preventive and therapeutic agent for various viral diseases.

[Conventional technology]

Viruses are one of the pathogens of warm-blooded animals such as humans and livestock, and vaccines are usually used for them.

[Problem that the invention seeks to solve]

However, no vaccines have been developed, and even if vaccines have been developed, many have not yet been put into practical use. For example, rotavirus multiplies in the intestinal epithelium of human infants and young domestic animals such as cows, pigs, and sheep, often causing severe non-bacterial diarrhea. Rotavirus is highly contagious, and nosocomial infections in maternity hospitals have become a problem in the medical world. In addition, in the livestock industry, the current intensive rearing system of multiple animals causes great damage when it occurs frequently, and has become a serious industrial problem.

Currently, there is no vaccine for this virus in practical use, and the only countermeasure is to administer oral or parenteral fluids as a symptomatic treatment for dehydration caused by diarrhea, and no fundamental treatment has yet been established. Not yet.

[Means for solving problems]

As a result of various studies on antiviral agents for warm-blooded animals, the present inventors discovered that leupeptin or its salts have an antiviral effect.

The present invention has been completed based on the above findings.

The leukinbutin used in the present invention was developed by one of the inventors, Hanai et al., from Streptomyces roseus MA-
8397A, ], (Streptomyces r
oseusMA839-Al Microtechnical Research Institute No. 3017)
An enzyme inhibitor that was discovered to be produced by various types of actinomycetes, including strains (see Japanese Patent Publication No. 171.54 of 1972).
Its chemical structure is represented by the following general formula m leupeptin Pr: R-CH3CH2CO-leupeptin y Ac: R=CH3Co- (in the formula, R represents an acyl group).

Among them, propionyl-leucyl-leucyl-argininal is called leupeptin Pr-LL L , and the corresponding acetyl compound is called leupeptin A, c-LL L .

Salts of leupeptin include, for example, salts with mineral acids such as sulfate, hydrochloride, and phosphate, and salts with carboxylic acids such as citrate, acetate, tartrate, fumarate, and naphthoate. can give.

Next, the acute toxicity of leupeptin used in the present invention (L D
50) are shown in Table 1.

Table 1 The warm-blooded animals to which the antiviral agent of the present invention is administered are not particularly limited, and examples thereof include humans, livestock such as cows, horses, sheep, and pigs, and poultry such as chickens. The dosage may be about 0.1 to 10 η/day per ky of body weight of a warm-blooded animal, and the route of administration is not particularly limited, but oral administration is preferable. The administration period is usually the period during which the virus disease occurs, but it may also be administered throughout the period during which the patient is susceptible to the virus disease, for example, in the case of rotavirus disease, during infancy or early childhood.

The anti-irritant agent for homeothermic animals of the present invention is a preparation prepared by preparing the compound represented by (1) above and its salts as is or by mixing them with a physiologically harmless solid or liquid carrier, such as tablets or capsules. It may be administered as it is in the form of solid or liquid preparations such as granules, powders, and syrups, or may be administered by adding it to food or feed such as water, milk, and artificial milk. Examples of solid carriers used here include lactose, cornstarch, calcium carbonate, and cellulose, and examples of liquid carriers include water, physiological saline, and syrup. In addition, auxiliary agents or additives such as emulsifiers, dispersants, suspending agents, wetting agents, stabilizers, and sweeteners may be used as necessary.

Note that there is no problem in adding other drugs to the antiviral agent for homeothermic animals of the present invention.

Example 1 A manufacturing example of the powder will be explained as follows.

1 part by weight of leupeptin sulfate, 4 parts by weight of corn starch
Parts by weight were placed in a type mixer and thoroughly stirred and mixed to obtain a powder.

Example 2 Leupeptin sulfate 2% (W/V) was dissolved in simple syrup having a white sugar content of 65% to obtain a syrup.

〔effect〕

The excellent effects of the antiviral agent for warm-blooded animals of the present invention will be explained below using experimental examples.

Experimental Example (1) Experimental Method The antiviral effect against rotavirus was investigated using a cultured cell system.

The virus used was human rotavirus (MO strain), and this virus was injected into MA104 cells derived from monkey fetal kidneys.
After infection with , io, 5, the cells were cultured in serum-free MEM medium supplemented with leupeptin Ac-LL for 20 hours while changing the medium every 5 hours.

The amount of virus released into the medium was then measured using a fluorescence focus assay.
cus assay) method.

(2) Experiment results The results are shown in Table 1.

Table 1 This table shows that leupeptin significantly inhibits virus proliferation at concentrations of 50 μg Anl or higher.

Therefore, the preparation of the present invention is expected to be an antiviral agent for warm-blooded animals.

Claims (1)

[Claims] Antiviral agent for warm-blooded animals containing leupeptin or its salts as an active ingredient