JPS5817167B2 - Pharmaceutical composition with antiviral action - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a pharmaceutical composition having an antiviral effect, more specifically a 3-aminosulfonyl-4 compound represented by the general formula (1): (wherein, X represents a halogen). -Relating to a pharmaceutical composition having anti-viral activity containing halogenobenzoic acid or a salt thereof as a main component.

In recent years, research and development of antiviral agents for viral diseases has been actively conducted, but no one with sufficient efficacy and toxicity has been discovered, and its development has been desired.

From this perspective, the present inventors have conducted research for many years to find compounds that suppress the proliferation of viruses, particularly compounds that are effective against myxoviruses.

As a result, it was discovered that 3-aminosulfonyl-4-hyrogesobenzoic acid met this purpose, and the present invention was completed.

3-aminosulfonyl-4-halogenbenzoic acid, which is a pharmaceutical composition of the present invention, is a known compound and can generally be produced by the following steps.

That is, it is produced by chlorosulfonating 4-halogenobenzoic acid with chlorosulfonic acid, and then reacting the obtained 3-chlorosulfonyl-4-halogenbenzoic acid with ammonia.

Table 1 shows the physicochemical properties of 3-aminosulfo-4-halogenobenzoic acid thus produced.

Furthermore, the 3-aminosulfonyl-4-halogenbenzoic acid thus produced can be made into a pharmacologically acceptable salt form.

Examples of the salt form include sodium salt, potassium salt, lithium salt, lamb salt, ammonium salt, calcium salt, barium salt, and the like.

Next, the effectiveness and toxicity of 3-aminesulfo-4-halogenbenzoic acid will be explained using experimental examples.

Experimental Example 1 Antiviral effect in cultured cells Monolayer cultured monkey kidney cells (Vero), dog kidney cells (M
DOK) and human fetal lung cells were added with Eagle's medium containing 0.2% bovine serum albumin and a diluted solution of the test compound, and after culturing for 1 hour, a virus solution diluted with the same Eagle's medium was added. The cells were cultured for 2 or 3 days at 37°C under carbon dioxide gas.

The minimum inhibitory concentration of the test compound was determined using the degree of cell degeneration caused by the virus as an index.

The results are shown in Table 2. □ Compounds I to ■ have a minimum inhibitory concentration of 30 μg/ml against myxoviruses such as line and parainfluenza, especially influenza virus.
It showed a strong antiviral effect.

Experimental Example 2 Preventing viral infection in mice Influenza virus was inoculated intranasally into a group of 10 mice, and the test compound was intraperitoneally administered twice a day for 14 days.
The survival rate of each day was observed.

The results are shown in Table 3.

Compound 1-IV showed a remarkable effect on preventing infection.

Experimental Example 3 Acute toxicity in mice A group of 10 ddY male mice weighing 25 g @e,
Add the test compound to 10 ml/5% gum arabic solution. The suspension was administered orally or intraperitoneally.

The LD5o value was determined from the number of deaths 7 days after administration using the Wilcoxon and Litchfield calculation method.

The results are shown in Table 4. Table 4 As is clear from the experimental examples of acute toxicity or higher in mice, compounds I to ■ have antiviral effects, especially anti-influenza effects, and are extremely safe, so they are clinically considered to be caused by myxovirus. It is extremely useful in the treatment of various infectious diseases, such as upper respiratory tract inflammation, pneumonia, and bronchitis.

When Compounds I to 1■ are administered to the human body, the daily dose for Compound I and ■ is usually 10 to 5000 mg, and the daily dose for Compound III is 10 to 5000 mg.
, IV is 30 to 500 o=1, but it may be increased or decreased as appropriate depending on the medical condition etc.

Compounds I-1 can be prepared into pharmaceutical formulations in a conventional manner with any optional conventional pharmaceutical carriers, bases or excipients.

For oral administration, capsules, tablets, powders, or oral liquid preparations (including dry syrup); for intrarectal administration, rectal suppositories; for injections, for example, dissolve in distilled water for injection before use. It can also be used as a freeze-dried injection, other nasal drops, or an inhaler.

The formulations are shown below as examples, but the formulations are not limited thereto.

Example 1 Tablet I) Compound 1 50g11) Lactose
Appropriate amount 111) Crystalline cellulose 60g1V)
Potato starch 54g ■) Magnesium stearate 2g Among the above, (1) to (I
Mix V) and add a portion of (1■) separated in advance to 10
It is added as a glue to make granules and dried.

Next, (V) was added and mixed to make 200 tablets per tablet.
” ? tablets.

The tablets may be coated with sugar by a conventional method, if necessary.

Example 2 5 Dispersant Compound II 50g Lactose
940g Magnesium stearate 10g 000g The above components were weighed and mixed uniformly to form a 5% powder.

Example 3 Capsule I) Compound III 50g II) Calcium hydrogen phosphate 50g 111) Aluminum silicate appropriate amount iV) Crystalline cellulose 60g V) Magnesium stearate 2g (1) above
-(V) are mixed, passed through a sieve and mixed thoroughly, and then prepared into capsules of 2001"9 each according to a conventional method.

Example 4 Injection Take 100 g of the sodium salt of Compound (1), dissolve it in distilled water for injection (21), and prepare an injection of 100"if/2 ml per ampoule using a conventional method.

Example 5 1% Nasal Drop Compound Monosodium Salt 10g Sodium Chloride 5° Chlorobuknol
Total amount with 5g distilled water 1.0
After weighing each of the above components and dissolving them in 950 ml of water,
Dilute the total amount i and ooo to make a 1% nasal spray.

Claims (1)

[Scope of Claims] 1 An antiviral agent containing 3-aminosulfonyl-4-halogenobenzoic acid or a salt thereof as a main component, represented by the general formula (1) (wherein, X represents a halogen) Pharmaceutical composition.