JPH04145076A - Preventive for anisakiasis - Google Patents

Abstract

PURPOSE:To obtain a preventive for anisakiasis showing strongly inhibitory effects on anisakiasis motion free from side effects, comprising costunolide or dehydrocostuslactone derived from a natural-occurring substance or a derivative thereof as an active ingredient. CONSTITUTION:A preventive for anisakiasis comprising costunolide, dehydrocostuslactone or a derivative thereof as an active ingredient. The ingredient can be isolated from Saussurea lappa Clarke (Compositae), costunolide is considered to have formula I and dehydrocostuslactone to have formula II. alpha-Cyclocostunolide or beta-cyclocostunolide may be cited as the derivative thereof. A dose of the compound and the derivative thereof is 50-300mg/day, preferably 100-200mg/day.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a drug for preventing anisakiasis.

(Prior Art) Anisakis parasitizes mammals as the final host in marine animals, marine crustaceans including krill as intermediate hosts, and fish and squid as secondary hosts. If this is eaten raw in the form of sashimi or sushi, it can infect humans. Specifically, the disease occurs when live worms enter the mouth and penetrate the gastrointestinal wall, causing symptoms such as nausea, vomiting, and abdominal pain. It is said that it is not possible to alleviate the symptoms of anisakiasis unless the worm body is directly removed. Therefore, even if there is an insecticidal drug, its effect cannot be expected if administered after the onset of symptoms.

Therefore, there has been interest in foods, drugs, etc. that can weaken the ability of Anisakis to infect through simultaneous ingestion or pretreatment. For example, Kasuya et al. (Journal of Infectious Diseases, Vol. 62, 1152-
1156.198B) reported that ginger (6-shogaol) and Aojiso (berylaldehyde) have strong insecticidal activity against Anisakis. Also, Yasuda et al.
Tokyo Metropolitan Institute of Health Research Annual Report Volume 39 24-27.19
88) found similar effects on the herbal medicines anethole and cinnamon. but,
Ginger, perilla, etc. cannot be eaten in large quantities. In addition, it is necessary to search for new and even more powerful effective substances.

(Problems to be Solved by the Invention) The present invention provides a preventive agent for anisakiasis that is derived from natural products and has no side effects.

(Means for solving the problem) We extracted components from various herbal medicines and examined their effect on suppressing Anisakis movement.
A strong effect was found on costunolide, dehydrocostaslactone, or its derivatives isolated from Asteraceae ppa C1arke (Asteraceae). That is, the present invention provides anisakiasis preventive agent containing costunolide, dehydrocostaslactone or a derivative thereof as an active ingredient.

Costunolide used in the present invention is generally considered to have the formula, and dehydrocostus sulfone is considered to have the formula.

These derivatives include σ-cyclocostunolide (a-cycJo-
cosLunol 1de), β-cyclocostunolide (βcyclocostunol 1de), indehydrocostus lactone (isodehydrocostunol
tuslactone), insarzanin C (isoz
aluzanin C), Alan Trafton (alan
tolactone), inalan tolactone (iso
-alantolactone), etc. Mixtures of the above compounds may be used if necessary.

It has been confirmed that costunolide, dehydrocostas lactone, or its derivatives used in the present invention are contained in various herbal medicines, especially wood aroma [Govindan, S.
, V et al., Indian J Chem, 15B, 965
(1977), etc., and are prepared from these using conventional purification methods, specifically, solvent extraction and the like.

These substances are essential oil components, so when administering them, dissolve (disperse) them in an emulsifier such as glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, or a quality preservation agent such as propylene glycol. improves. Furthermore, these active substances may be processed into various solid preparations, liquid preparations, etc. by adding excipients, lubricants, sweeteners, fillers, flavoring agents, etc., and then administered.

Examples of the excipient include microcrystalline cellulose, lactose, sucrose, corn starch, and silicic anhydride.

Examples of the lubricant include talc, magnesium stearate, and silica. Examples of sweeteners include sorbitol, glucose, maltose, starch syrup, and the like. Extending agents include soybean protein, wheat starch, potato starch, and the like. Examples of fragrances include menthol, peppermint, eucalyptus oil, cinnamon, lemon oil, and the like.

The dosage of costunolide, dehydrocostaslactone or its derivatives in this case is 50-300 mg/d
It is preferable to mix so that ays is preferably 1 OO-200+og/day.

The parasites targeted here include Anisakis, which may be involved in anisakiasis.
akis) genus, Terranova genus,
Included are the genera Contracaecum, Raphidascaris, and Thynnascaris. In particular, it is said that cases of disease are often caused by Anisakis larva type I and Terranova larva type II. (
Manufacture et al.: Okayama Saiseikai General Hospital Magazine, Volume 20, 129-1
33.1988).

(Effect) The drug of the present invention effectively prevents anisakiasis. It is particularly effective in deworming Anisakis type 1 larvae, Terranova type I larvae, etc.

(Example) Materials: Anisakis type I larvae and Terranova type larvae, which actively move in eight figures, were removed from the internal organs of cod and mackerel.
It was stocked in 0.4% physiological saline.

Preparation of test solution: Wood incense was crushed, 3 times the amount of ethyl acetate was added, and the mixture was subjected to ultrasonic treatment at room temperature for 30 minutes to obtain a filtrate. The same extraction operation was repeated again, and the resulting filtrates were combined and dried under reduced pressure at 40°C to obtain an extract.

Next, the extract was dissolved in hexane-ethyl acetate (2:1) and column fractionated using the same solvent (silica gel [Fuco-gel C-3
00, Wako Pure Chemical Industries, Ltd.], 44440 cm column. The obtained fractions were transferred to a thin layer plate (silica gel 60F-25
The components were checked by spotting on 4Nimelk) and developing with a developing solvent, n-hexane-ethyl acetate (5:2).

Of these, fractions containing two components with Rf values around 0°4 to 0.5 were collected. Both parts were roughly separated using preparative liquid chromatography (DevelosilLopODS 24s).
Two components were isolated using a 2-4×3.6 cm column (manufactured by Kouchi Kagaku Co., Ltd.) and eluted with 80% methanol.

From the results of physical constants and instrumental analysis, it was confirmed that the two components obtained were costunolide and dehydrocostaslactone, respectively. Next, costunolide and dehydrocostas lactone were added to a solution containing 1% propylene glycol and 0.4% salt to a final concentration of 250 μg/11112, and then ultrasonication was performed for 2 to 5 minutes to uniformly dissolve the components ( Dispersion) to prepare a test solution.Evaluation method: Take 20ml of the test solution in a petri dish, add 7 to 10 Anisakis,
The motility of Anisakis was observed over time using the evaluation method shown in Table 1. The results are shown in Table-2. The scoring result is the average -i:s
Represented by D.

For comparison, 6-shogaol, which has already been recognized to have a strong insecticidal effect (Kasuya et al.; Journal of Infectious Diseases 62@
1152-1156.1988) and anethole (Yasuda et al.; Annual Report of the Tokyo Metropolitan Institute of Health, Vol. 39, 24-27)
．． 1988) was also considered.

Table 1 From these results, costunolide and dehydrocostaslactone showed a strong inhibitory effect on Anisakis motility. Its effects have already been reported (Yasuda et al.; Annual Report of the Tokyo Metropolitan Institute of Health, Vol. 39, 24-27, 1988) and 6
-Shi Ugaol (Kasuya et al.; Journal of Infectious Diseases, Vol. 62, 11)
52-1156.1988).

Claims (1)

[Claims] 1. Anisakiasis preventive agent containing costunolide, dehydrocostas lactone or a derivative thereof as an active ingredient.