JPH03112929A - Antiviral agent and anti-anaerobic bacterial pharmaceutical - Google Patents

Abstract

PURPOSE:To obtain a preventive and treating agent containing 3- acetoxymethyl-5-fluorouracil and useful as a preventive and treating agent for viral and anaerobic microbism. CONSTITUTION:An antiviral and anti-anaerobic bacterial agent containing a compound, expressed by the formula and having a powerful antiviral activity and also anaerobic microbial activity together as an active ingredient. The dose of the compound expressed by the formula is preferable about 30-1500mg/ day in the case of oral administration and about 10-500mg/day in the case of parenteral administration. The compound expressed by the formula is obtained by reacting 5-fluorouracil with an alpha-halogenalkyl carboxylate in the presence of a dehydrohalogenating agent in a basic solvent.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to an antiviral agent and an antianaerobic agent.

[Problems to be solved by conventional techniques and inventions] In recent years,
Diseases caused by viruses tend to increase, and, for example, sexually transmitted diseases (S, T, D) and opportunistic infections such as those caused by AIDS patients are becoming social problems, and are a major problem for humanity. As antiviral agents, vidarabine, acyclovir, etc. have been developed, but they are not definitive as resistant strains have already appeared. Generally, when trying to develop antiviral agents and antibacterial agents, it is necessary to constantly develop a large number of new antiviral and antibacterial agents, taking into consideration the occurrence of resistant strains.

Therefore, an object of the present invention is to provide an effective new antiviral agent and antianaerobic agent.

[Means to solve the problem]

In view of the above circumstances, the present inventors conducted intensive research to develop a new antiviral agent and found that a compound represented by the following formula (I) has strong antiviral activity and also has antianaerobic effects. They discovered this and completed the present invention.

That is, the present invention provides an antiviral agent and an antianaerobic agent characterized by containing 3-acetoxymethyl-5-fluorouracil represented by the following formula (1) H as an active ingredient. .

The compound (1) which is the active ingredient of the present invention is, for example,
As described in Japanese Patent No. 4-122281, it can be produced by the following method (1) or (2).

The following blank space (wherein,
is a carboxylic acid α to 5-fluorouracil (I [I)
- A method in which a halogenoalkyl ester (II>) is reacted in a basic solvent such as ammonia or pyridine in the presence of a dehydrohalogenating agent, and method (2) is a method in which the compound (rV) is hydrolyzed, preferably in weak alkalinity. It's a method.

Compound (I) may be isolated by a conventional method such as column chromatography.

When the compound (r) obtained in this way is used as an antiviral agent or an antianaerobic agent, the dosage will vary depending on the patient's weight, age, sex, administration method, physical condition, medical condition, etc. Appropriate doses are 30 to 1500 mg per day for oral administration, and 10 to 500 mg per day for parenteral administration.

Incidentally, even when compound (I) was administered to mice at 100 mg/kg intraperitoneally or orally, no abnormality or death was observed.

The antiviral agent and antianaerobic agent of the present invention can be prepared into tablets, granules, powders, capsules, suspensions, injections,
It can be made into various dosage forms such as small portions. To produce a solid preparation, compound (I) is added with an excipient, and if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, a filler, a coating agent, a sugar coating agent, etc. After adding, it is preferable to form into tablets, granules, powders, capsules, small pieces, etc. by a conventional method.

When preparing an injection, compound (I) is dissolved, dispersed, emulsified, etc. in advance in an aqueous carrier such as distilled water for injection, or
Alternatively, it may be made into an injectable powder and dissolved for use. Administration methods for injections include intravenous administration, intraarterial administration, intraportal administration, intraperitoneal administration, intramuscular administration, and subcutaneous administration.

[Example] Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Antiviral effect: Vero cells (monkey kidney cells) were prepared at 2×10 5 cells/rd and cultured at 37° C. in a 5% CO□ atmosphere for - days to form a monolayer. Add to this the H3V virus (H3V virus) diluted with PBS.
erpes 5inplex virus type
I) was infected at a multiplicity of infection (M, O, r, ) 0.3. On the other hand, compound (I) was mixed with dimethyl sulfoxide (
DMSO) and Eagle's IBM medium containing 2% tallow serum (2% FBS MBM medium) at 100. ug
/rd, 10 μg/mI! and 1 μg/rnl ([the final concentration of 1M5O was 1%)]. This was added to the H3V virus-infected cells and cultured for one day at 37°C in a C(]2 incubator. Thereafter, the cytopathic effect was observed under a microscope.
CT) was observed, stained with crystal purple, and evaluated according to the following criteria. Note that acyclovir was used as a control. The results are shown in Table 1. Evaluation criteria: Most of the cells are dead. 10: About half of the cells are dead. I) was found to be a useful antiviral agent with an antiviral effect equivalent to that of acyclovir.

Example 2 Anti-anaerobic effect: Medium contains GAM containing 100 μg/rnl of compound (I)
Using a plate in which the agar medium was diluted several times, the table 2 below was prepared.
A loopful of each strain was inoculated, cultured under anaerobic conditions, and the minimum inhibitory concentration (MIC) was determined. Table 2 shows the results.
Shown below.

From the results in Table 2 below, compound (I) is effective against anaerobic bacteria, especially Bacillus.
It was found that it exhibited good antibacterial effects against anaerobic bacteria of the genus Teroides.

〔Effect of the invention〕

The antiviral agent and antianaerobic agent of the present invention have strong antiviral and antibacterial effects, so they are effective against various viruses and bacteria.
It is useful as a preventive and therapeutic agent for anaerobic bacterial infections.

that's all

Claims (2)

[Claims] 1. An antiviral agent characterized by containing 3-acetoxymethyl-5-fluorouracil as an active ingredient, which is represented by the following formula (I) ▼There are mathematical formulas, chemical formulas, tables, etc.▼ (I). 2. An antianaerobic agent comprising 3-acetoxymethyl-5-fluorouracil according to claim 1 as an active ingredient.