JPH024711A - Antiparasitic agent - Google Patents

Abstract

PURPOSE:To obtain an antiparasitic agent, containing [6]-shogaol and/or [6]- gingerol as an active ingredient and capable of exhibiting excellent anthelmintic effects on parasites, such as oxyurids or roundworms of Anisaxis spp., parasitic on human digestive tracts. CONSTITUTION:An antiparasitic agent, containing [6]-shogaol expressed by formula I and/or gingerol expressed by formula II as an active ingredient and having the above-mentioned effects. The afore-mentioned compound is directly used or, together with a normally used pharmaceutical carrier, formed into an oral agent, e.g., tablet, capsule, granule, fine granule or powder, or a parenteral agent, such as injection, and can be administered to animals and humans and the following daily dose is considered as normally suitable for an adult. 100-500mg in the case of oral administration and 0.5-100mg in the case of parenteral administration.

Description

[Detailed description of the invention] [Industrial application fields] The present invention relates to antiparasitic agents.

[Prior Art and Section II] Parasites infect humans through various mediums, and many parasites are known, including pinworms that occur in the lower gastrointestinal tract of children.

Recently, a parasitic disease called anisakiasis has been on the rise. Anisakiasis is an extremely painful disease caused by the parasite Anisakis hiding in fish and penetrating the stomach or intestine walls of humans who eat the fish. In the case of gastric anisakiasis, there are radical treatments such as endoscopy, but for intestinal anisakiasis, no diagnosis or treatment methods have been established, and issues remain.

Therefore, there was a desire for a t5n shot of Yakusei 1 to exterminate these parasites.

[Means for Solving the Problems] The present inventors conducted intensive research to find an effective antiparasitic agent, and as a result, they discovered one that has an anthelmintic effect.

That is, the present invention is an antiparasitic agent (hereinafter referred to as the drug of the present invention) containing [6]-shogaol and/or [6]-gingerol as an active ingredient.

In addition, [6]-Shogaol ((6)-Shogaol
ol) and [6]-gingerol ((6)-Gin
The +1■ formula for (gerol) is as shown below.

[[6]-Shogaol] [[6]-Gingerol].

The above compounds [6]-shogaol and [6]-gingerol can be obtained, for example, from ginger, which is a plant of the Zingiberaceae family, by the following method. That is, dried ginger rhizomes were extracted with ether, and the extract obtained by concentrating this was subjected to column chromatography using silica gel, developed in the order of hexane, a hexane/ether mixed solvent, and ether.・Ether mixing ratio 3:l~
The solvent is distilled off from the elution part of the mixed solvent of tit
% crude [6]-shogaol fraction is obtained, and the solvent is distilled off from the ether eluate to obtain a crude (6)-gingerol fraction of about 0.34%. Next, the carrier [6]-shogaol fraction was subjected to separation thin layer chromatography using silica gel, developed with a hexane/ether mixed solvent, and [6]
]-Shogaol is scraped off, extracted with a mixed solvent of chloroform and methanol, and the solvent is distilled off from this extract to obtain [6]-shogaol. Also, coarse [
6]-Gingerol fraction was subjected to separation thin layer chromatography using silica gel, developed with a mixed solvent of hexane and acetone, and the [6]-gingerol portion was scraped off.
This is extracted with a mixed solvent of chloroform and methanol, and the solvent is distilled off from this extract to obtain [6]-gingerol. [6]-Shogaol and [6] by this method
]-A specific example of the production of gingerol is as follows.

Specific Example: 5 kg of dried ginger rhizomes were extracted twice with 8e ether, and the ether extracts were combined and concentrated under reduced pressure to obtain 134 g of extract. Add this extract to silica gel
Column chromatography using 2509 was carried out using hexane, a hexane/ether mixed solvent in which the mixing ratio of ether to hexane was increased sequentially, and then ether, and fractionated by IQ, with a hexane/ether mixing ratio of 3. :
1~1:! The eluted portion of the mixed solvent was combined and the solvent was distilled off to obtain a yellow oil containing 13.79 [6]-shogaol.The eluted portion of the ether was combined and the solvent was distilled off to obtain [6]- 16.99 yellow oil containing gingerol was obtained. Next, 5.489 of the yellow oil containing [6]-shogaol obtained as above was subjected to thin layer chromatography for separation using silica gel, and hexane and
It was developed with an ether mixed solvent (1:2), the [6]-shogaol portion was scraped off, this was extracted with a chloroform/methanol mixed solvent (4:1), and the solvent was distilled off from this extract to give a 0. [6]-Shogaol 89 was obtained as a pale yellow oil. In addition, 6.779 of a yellow oil containing [6]-gingerol was subjected to thin layer chromatography for separation using silica gel, and a hexane/acetone mixed solvent (7
:3), scrape off the [6]-gingerol part, and add it to a mixed solvent of chloroform and methanol (4:I).
The solvent was distilled off from this extract to obtain 4.2 g of [6]-gingerol as a pale yellow curved product.

The properties of [6]-shogaol and [6]-gingerol obtained as described above were consistent with literature values. [
[6]-Shogaol: D, Il, Connela
nd M, D, 5uLherland, Au5t, J.
Chem, 22.1033 (1969) [6]-gingerol: D, W, Connel and M, D,
5uLherland,＾ust,J,chem,,2
2.1033 (1969) and T, MuraLa,
M, 5hinohara and M, Miyamot
o.

Chcm, I'ham, Bull, (Tokyo), 2
0,2291 (1972)].

Next, the excellent antiparasitic effect of the drug of the present invention will be explained using experimental examples.

[6]-Shogaol and [6]gingerol obtained in the specific experimental example were each prepared in a two-fold dilution series with ethanol, and each solution was added to physiological saline at a concentration of 1% (w/v). , 2d each in a serum tube ((ircine
r, Solingen, II-Germany).

The final concentration of each component is 15.625 rinsing/d from IJIy/d.
Up to mQ.

Next, 8 to 12 Anisakis larvae obtained by pepsin digestion of pollack viscera were distributed into each tube. These were kept at 37° C., and survival or death was determined after 24 hours. As a result, [6]-shogaol and [6]-shogaol obtained in the specific example were found.
]-The minimum effective concentrations of gingerol that led to the disappearance of all worm movements were 62.5//IF/m and 250/#/ml, respectively, indicating antiparasitic effects.

As described above, the drug of the present invention has an antiparasitic effect and is effective against parasites that infect the human gastrointestinal tract.

LDS of [6]-shogaol and [6]-gingerol. is 50.9!9/9 and 2 for intravenous administration.
9 to 5.0 m97, and 687.0 my by oral administration.
/9 and 250.0119/9.

Next, the dosage and formulation of [6]-shogaol and [6]-gingerol will be explained.

[6]-Shogaol and [6]-gingerol can be administered to animals and humans as is or together with a conventional pharmaceutical carrier. The dosage form is not particularly limited and may be appropriately selected and used as required, and includes oral dosage forms such as tablets, capsules, granules, fine granules, and powders, and parenteral dosage forms such as injections.

In order to exert the desired effect as an oral agent, it depends on the age, weight, and severity of the disease of the patient, but it is usually administered in adults [6
]-Shogaol or [6]-gingerol It seems appropriate to take it in several doses.

Oral preparations such as tablets, capsules, and granules of [6]-shogaol and [6]-gingerol can be prepared using, for example, starch, lactose, sucrose, mannitol, carboxymethyl cellulose, cornstarch, inorganic salts, etc. according to conventional methods. Manufactured.

In addition to the excipients mentioned above, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, fragrances, and the like can be used in this type of preparation as appropriate. Specific examples of each are shown below.

[Binder] Starch, dextrin, gum arabic powder, gelatin,
Hydroxypropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroquinepropyl starch, sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, low substituted hydroxypropylcellulose.

[Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80° [Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, Polyethylene glycol.

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

[6]-Shogaol and [6]-gingerol can also be administered as suspensions, emulsions, syrups, and elixirs, and these various dosage forms may include flavorings and colorants. It may include r.

In order to exert the desired effect as a parenteral agent, it depends on the age, weight, and severity of the disease of the patient, but it is usually used in adults.
6]-Shogaol or [6]-gingerol may be administered intravenously, intravenously, subcutaneously, or intramuscularly at a dose of 0.5 to 100119 mg/day.

This parenteral preparation is manufactured according to a conventional method, and generally uses distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol, etc. as a diluent. be able to. Furthermore, a bactericide, a preservative, and a stabilizer may be added as necessary.

Furthermore, as necessary, tonicity agents, stabilizers, preservatives,
A soothing agent or the like may be added.

Example 1 ■Corn starch 449 ■Crystalline cellulose 409 ■Carboxymethyl cellulose calcium 59 ■Light silicic anhydride 0.5 g ■Magnesium stearate 0.5 g ■[6-shogaol
to9 total 1001i+ According to the above recipe, ■ to ■ were mixed uniformly and compression molded using a tablet machine to obtain some tablets of 200119.

This tablet contains 2°g of [6]-shogaol, and adults should take 5 to 25 tablets a day in several doses.

Example 2 ■ Crystalline cellulose 84.5y ■ Magnesium stearate 0.5g ■ Calcium carboxymethyl cellulose, 59 ■ [6]-gingerol tog Total 1009 According to the above recipe, ■, ■ and part of ■ were uniformly mixed and compressed. After molding, pulverize, add the remaining m of ■ and ■, mix, and compression mold with a key press to make a portion of 200 Il!
Tablets of ti were obtained.

This tablet contains [6]-gingerol 20 and 9, and adults should take 5 to 25 tablets a day in several doses.

Example 3 ■Crystalline cellulose 34.59■10% hydroxypropyl cellulose ethanol solution 501F ■Carboxymethyl cellulose calcium 59 ■Magnesium stearate 0.5g■[6]-Shogaol! 09 total 100g Mix ■, ■, and ■ uniformly according to the above recipe, make a netting using a conventional method, granulate it with an extrusion granulator, dry and crush it, mix ■ and ■, and press the key. A portion of the mixture was compression molded using a machine to obtain 20,031 g of tablets.

This tablet contains 20 pieces of [6]-shogaol, and adults should take 5 to 25 tablets a day in several doses.

Example 4 ■Corn starch 84g■Magnesium stearate 0.5g■Carboxymethylcellulose calcium 59■Light silicic anhydride 0.59■[6]-gingerol 10g Total 100g Mix ■~■ uniformly according to the above recipe and compression mold. After compression molding in a machine, it was crushed in a crusher and sieved to obtain granules.

1 g of this granule contains [6]-gingerol IOQ m
It contains y, and adults should take 1 to 5 g a day in several doses.

Example 5 ■Corn starch 89.59■Light silicic anhydride o, sg■[6]-Shogaol
10g total 100g Mix ■～■ uniformly according to the old recipe, 200 m
y was filled into a No. 2 capsule.

This capsule contains [6]-shogaol 2019, and adults should take 5 to 25 capsules a day in several doses.

Example 6 ■ Soybean oil 59 ■ Distilled water for injection 89.59 ■ Soybean phospholipid
2.5g ■Glycerin 29■
[6]-Gingerol 19 total
100g Dissolve ■ in ■ and ■ according to the above recipe, and add ■
The solutions of (1) and (2) were added and emulsified to obtain an injection.

Claims (1)

[Scope of Claims] An antiparasitic agent containing [6]-shogaol and/or [6]-gingerol as an active ingredient.