JPH0826980A - Antiviral agent - Google Patents

Abstract

PURPOSE:To obtain an antiviral agent, containing a compound selected from alpha-plnene, beta-plnene, d-limonene and sandalwood oil as an active ingredient and capable of manifesting inhibiting activities against the proliferation of viruses. CONSTITUTION:This antiviral agent contains at least one selected from alpha-pinene, beta-pinene, d-limonene and sandalwood oil used as perfume ingredients as an active ingredient. The active ingredient can suitably be blended with a usually used pharmaceutical preparation carrier to prepare an oral agent such as a tablet, a capsule, a granule, a fine granule or a powder or a parenteral agent such as a parenteral injection or a suppository according to a conventional method. The daily dose thereof for an adult is 5mg to 1g, expressed in terms of weight of the active ingredient and administered in several divided portions. The antiviral agent can be used as bathing agents, cosmetics, aromatic agents, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a compound having an inhibitory effect on virus growth and useful as an antiviral agent.

[0002]

[Prior Art and Problems] Acquired Immunodeficiency Syndrome (AIDS)
Human immunodeficiency virus (HIV-1), which is the pathogen of
Currently, very few drugs act effectively against human retroviruses such as HTLV-1, which is a pathogenic virus for cell leukemia, and their effects are not fully satisfactory.

Therefore, it has been desired to develop an effective drug against the above viruses.

[0004]

Means for Solving the Problems The inventors of the present invention have surprisingly studied to solve the above-mentioned problems with terpenes and plant-derived essential oils conventionally used as a fragrance ingredient, and as a result, surprisingly, these compounds It was found that some of them have an excellent antiviral effect, and thus completed the present invention.

That is, the present invention provides an antiviral agent containing at least one selected from α-pinene, β-pinene, d-limonene and sandalwood oil as an active ingredient (hereinafter, referred to as
It is called the active ingredient of the present invention. ).

The active ingredient of the present invention is a compound which has been conventionally used as a perfume ingredient. Α-pinene, β-pinene and d-limonene are available from Yasuhara Chemical Co., Ltd. and sandalwood oil from PAYAN & BERTRAND. It is commercially available and can be easily obtained.

Next, the effects of the present invention will be described with reference to experimental examples.

Experimental Example 1 HIV-1 and HTLV-1 viruses are present in the natural environment of tropical Africa in the culture of virus-infected cells, and are considered to be involved in the localized occurrence of malignant tumors. A plant-derived tumor promoter, 4-DPE (4-deoxyphorbol ester)
It was added at a concentration of ng / ml to induce virus growth.

At the same time, a system was prepared in which the active ingredient of the present invention coexisted at various concentrations, and the difference in virus growth was observed after culturing for 2 days.

The active ingredient of the present invention is PBC34 [polyoxyethylene (2
0) Polyoxypropylene (4) ethyl ether].

The detection of virus growth is carried out by staining the cells with a fluorescently labeled monoclonal antibody against each virus and then measuring the fluorescence intensity of the cells using a flow cytometer, or by measuring the virus antigen positive cell rate under a fluorescence microscope. Was calculated.

The results are shown in Table 1.

Table 1

It can be seen from Table 1 that the active ingredient of the present invention significantly suppresses virus growth when PD34 which is a tumor promoter is added, as compared with PBC34 which is a reference substance.

The active ingredient of the present invention has been conventionally used as a fragrance, and as a result of an acute toxicity test by oral administration in rats, the LD ₅₀ of α-pinene was 3.7 g / kg,
Since LD ₅₀ of β-pinene and d-limonene is 5 g / kg and LD _{50 of} sandalwood oil is 5.58 g / kg, it is clear that they are highly safe.

Next, the dose and formulation of the active ingredient of the present invention will be explained.

The active ingredient of the present invention can be administered to animals and humans as it is or together with a conventional pharmaceutical carrier. The dosage form is not particularly limited and may be appropriately selected and used as needed, and examples thereof include oral preparations such as tablets, capsules, granules, fine granules and powders, parenteral preparations such as injections and suppositories. To be

In order to exert a desired effect as an oral preparation, it varies depending on the age, body weight, and degree of disease of the patient, but usually 5 mg to 1 g as the weight of the active ingredient of the present invention is administered to an adult several times daily. It seems that it is appropriate to take them separately.

Oral preparations include, for example, starch, lactose, sucrose,
Mannitol, carboxymethyl cellulose, corn starch, inorganic salts and the like are used in a conventional manner.

In addition to the above-mentioned excipients, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a flavoring agent, a coloring agent, a flavoring agent, etc., may be appropriately used in this type of formulation. You can
Specific examples of each are as follows.

[Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, crystalline cellulose,
Ethyl cellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low-substituted hydroxypropyl cellulose.

[Surfactant] sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 8
0.

[Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.

[Fluidity promoter] Light anhydrous silicic acid, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

The active ingredient of the present invention can also be administered as a suspension, emulsion, syrup or elixir, and these various dosage forms contain a flavoring agent and a coloring agent. Good.

Furthermore, the active ingredient of the present invention can be used in cosmetics such as bath agents, cosmetics and fragrances.

When used in a bath salt, components such as inorganic salts, inorganic acids, organic acids, oils and fats, polyhydric alcohols, and surfactants which are usually used in bath salts are appropriately used in addition to the active ingredient of the present invention. It can be selected and compounded. In this case, the compounding amount of the active ingredient of the present invention may be 0.01 to 1% of the total amount of the preparation.

Next, the present invention will be described in more detail with reference to examples of preparations, but the present invention is not limited thereto.

Example 1

According to the above formulation, the ingredients (1) to (2) were uniformly mixed and compression-molded with a tableting machine to give tablets (200 mg each).

Each tablet contains 20 mg of α-pinene, and 1 to 5 tablets for adults are to be taken in several divided doses per day.

Example 2 Crystalline cellulose 84.5 g Magnesium stearate 0.5 g Carboxymethyl cellulose calcium 5 g β-pinene 10 g Total 100 g

According to the above formulation, a part of and was uniformly mixed, compression-molded, crushed, and the remaining amount of and was added and mixed, and compression-molded with a tableting machine to give one tablet.
0 mg tablets were obtained.

One tablet of this tablet contains 20 mg of β-pinene, and 1 to 5 tablets for adults are to be taken in several divided doses per day.

Example 3 Crystalline cellulose 79.5 g 10% Hydroxypropyl cellulose ethanol solution 50 g Carboxymethyl cellulose calcium 5 g Magnesium stearate 0.5 g d-limonene 10 g Total 145 g

According to the above formulation, and were uniformly mixed, the mixture was kneaded by a conventional method, granulated by an extrusion granulator, dried and crushed, and then mixed, and compressed by a tableting machine. It was molded to obtain a tablet of 200 mg each.

One tablet of this tablet contains 20 mg of d-limonene, and 1 to 5 tablets for adults are to be taken in several divided doses per day.

Example 4

According to the above recipe, the components (1) to (4) are uniformly mixed, compression-molded by a compression molding machine, and then crushed by a crusher,
Sieve to obtain granules.

1 g of this granule contains 100 mg of sandalwood oil, and 0.5 to 1 g of an adult is taken in several divided doses per day.

Example 5 Crystalline cellulose 86.5 g 10% Hydroxypropyl cellulose ethanol solution 35 g α-pinene 10 g Total 131.5 g

According to the above-mentioned recipe, the ingredients (1) to (4) were uniformly mixed and kneaded. After granulating with an extrusion granulator, it was dried and sieved to obtain granules.

1 g of this granule contains 100 mg of α-pinene, and 0.5 to 1 g of an adult is taken in several divided doses per day.

Example 6 Corn starch 89.5 g Light anhydrous silicic acid 0.5 g β-pinene 10 g Total 100 g

According to the above-mentioned formulation, 1 to 3 were mixed uniformly, and 200 mg was filled in a No. 2 capsule.

One capsule of this capsule contains 20 mg of β-pinene, and 1 to 5 capsules for adults are to be taken in several divided doses per day.

Example 7 (Effervescent tablet form) Sodium hydrogen carbonate 40.0 parts by weight Succinic acid 40.0 parts by weight Dextrin 19.0 parts by weight Pigment 0.5 parts by weight d-limonene 0.5 parts by weight

According to the above formulation, the effervescent tablet-shaped bath agent obtained by a conventional method was dissolved in a bath water at 40 ° C. and used so that the concentration (150 ppm) of 30 g / 200 l was obtained.

Example 8 (Liquid) 1,3-BG 30.0 parts by weight Jojoba oil 20.0 parts by weight Pigment 4.0 parts by weight Sandalwood oil 0.5 parts by weight Purified water 45.5 parts by weight

According to the above-mentioned formulation, the effervescent tablet-like bath agent obtained by a conventional method was dissolved in a bath water at 40 ° C. so that the concentration was 30 g / 200 l (150 ppm).

Example 9 (Powder) Sodium hydrogen carbonate 45.0 parts by weight Sodium sulfate 48.0 parts by weight Titanium oxide dextrin coating 5.0 parts by weight Jojoba oil 0.5 parts by weight Pigment 1.0 parts by weight α-pinene 0.5 parts by weight

According to the above-mentioned formulation, the effervescent tablet-like bath agent obtained by a conventional method was used by dissolving it in a bath water at 40 ° C. so as to have a concentration of 30 g / 200 l (150 ppm).

Example 10 (Bead colon) Silica gel beads 90 parts by weight α-pinene 10 parts by weight

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Yoshimi Kawasaki, 392 Tsukiji Tsuji, Fujieda, Shizuoka Prefecture, In Tsumura Co., Ltd. (72) Inventor, Katsusuke Nagai 392 Tsukiji, Fujieda, Shizuoka, Tsumura

Claims (1)

[Claims] 1. An antiviral agent containing as an active ingredient at least one selected from α-pinene, β-pinene, d-limonene and sandalwood oil.