WO2002060258A1

WO2002060258A1 - Fish anthelmintics and anthelmintic method

Info

Publication number: WO2002060258A1
Application number: PCT/JP2002/000711
Authority: WO
Inventors: Jun Morita; Mamoru Ishihara; Hideki Mizoguchi; Hideki Hatakeyama
Original assignee: Meiji Seika Kaisha, Ltd.
Priority date: 2001-01-31
Filing date: 2002-01-30
Publication date: 2002-08-08
Also published as: JP4695766B2; JP2004331498A

Abstract

It is intended to provide anthelmintics and an anthelmintic method for parasites in the field of fish farming, in particular, heterobothriums living on globefish and pseudodactylus living on eel. Namely, anthelmintics for parasites (excluding gyrodactylus) living on fishes (excluding herrings and carps such as rainbow trout) characterized by containing as the active ingredient nitroscanate or its pharmaceutically acceptable salt; and an anthelmintic method characterized by administering these anthelmintics to farmed fishes. By using these anthelmintics, parasites living on farmed fishes can be effectively exterminated. Also, infection with parasites can be prevented or treated by feeding farmed fishes with feeds containing these anthelmintics.

Description

Description Biocide and control method for fish parasites Technical field

The present invention relates to a parasiticide and a method for controlling parasites in aquaculture fish in the field of aquaculture. Background art

Due to the remarkable damage of parasites outside the fish body in fish farming, there is a demand for its proper control.

For example, in pufferfish cultivation such as torafugu, parasitism is a very serious problem because it hinders stable production. Among parasitosis, in particular, heterotrophic infectious disease is one of the most infectious diseases in the cultivation of troughs, etc. because it occurs at any farm in Japan.

Heterobothium (Heterobothrium okamotoi, a solitary creature), which is a parasite of pufferfish such as torafugu, parasitizes puffer fish and sucks blood from the gills and surrounding fleshy parts, causing blowfish to grow poorly. Sometimes, they die (Fishology [Infectious Diseases & Parasites], Shuzo Egusa, Koseisha Koseikaku, 1983, P 284-286). The life history of this insect is thought to end its life four to five months after hatching from the egg. Hatching larvae hatched from eggs swim and parasitize the gills to become larvae. When they grow to about 5-6 mm, they migrate to the tissues surrounding the gills, become larvae, and lay eggs.

Since both the larva on the gill flap and the adult on the gill cavity wall are extremely resistant to changes in drugs and osmotic pressure, methods for controlling the parasites so far have been limited to 2-cyclohexylcarbonyl-1,2,3,3. 6, 7, lib—Hexahydro— 4 It has been reported that oral administration of H-birazino-1 [2, 1-a]-isoquinolin-1 4-one (generic name: Praziquantel, manufactured by Bayer K.K.) for 200 days 111 days is effective. However, (JP-A-11-92309), an effective anthelmintic method has not been developed.

The only countermeasure against this insect at the aquaculture site is to regularly bathe the fish in formalin at around 800 ppm for about one hour. However, formalin is a substance that emits cancer, and poses a problem in terms of environmental pollution. In addition, a hydrogen peroxide formulation (JP-A-06-046878), which was approved for this disease in 1998, has a narrow range of effective and toxic concentrations and is difficult to use. There is such a problem.

On the other hand, scleroderma hirsutidae of the eel is often a problem in the one-mouthed papa eel, but with the spread of house-style eel, large infestation of the two eel has also been observed (Fish Disease Picture Book, Hatai Kishio, Kazuo Ogawa, Kazumi Hirose, Ed., Midori Shobo, 1988, p. (4) The causal parasites of the eel, Pseudo-dactychidism, are two monophytes, Pseudodactylo-gilus-bini and Pseudodacty-gilus-angire. Both parasites are distinguished by the size of a pair of hooks located in the center of the fixation disc.

Large infestation of girds in the mouth causes poor feeding and growth, which is an industrial problem. As a treatment for this disease, (2,2,2-triclo-or-hid-or-quiche) for phospho-dactyl-Gills' bis-monophosphonic acid dimethyl ester (generic name: Trichlorfon, manufactured by Bayer Ltd.) ) Is effective at 0.5 ppm pond spraying, but has little effect on Pseudodactylus girus angile. Trichlorfon also makes complete anthelminosis difficult and sometimes recurs, so more effective drugs are needed.

Based on the above, it is useful for proper elimination of fish ectoparasites in fish farming. The development of effective drugs is strongly desired.

An object of the present invention is to provide a pesticide and a method for controlling fish parasites in the field of aquaculture. In particular, it is an object of the present invention to provide a pesticide and a method for controlling Heteroborim spp., Which is a parasite of pufferfish such as troughfish, and Pseudodactyrogirus, which is a parasite of eel. Disclosure of the invention

The present invention provides the following inventions described in the claims.

(1) A pesticidal agent for fish parasites, characterized in that nitroskanet or a pharmaceutically acceptable salt thereof is used as an active ingredient (except for fish, excluding rainbow trout, etc. , And parasites excluding girodactylus.).

(2) The pesticide according to claim 1, wherein the fish parasite is solitary.

(3) The pesticide according to claim 2, wherein the solitary organism is Heterobium okamotoi, a parasite of blowfish.

(4) The pesticide according to claim 2, wherein the solitary organism is Pseudospermia gills vini, which is a parasite of a salmon.

(5) The pesticide according to claim 3, wherein the blowfish is trough.

(6) The pesticide according to claim 4, wherein the persimmon is perilla.

(7) A method for controlling fish parasites, which comprises administering nitroskanate or a pharmaceutically acceptable salt thereof to fish (however, fish excluding dicines such as rainbow trout and koi). , And parasites excluding girodactylus.).

(8) The method according to claim 7, wherein the fish parasite is a solitary.

(9) The extermination method according to claim 8, wherein the solitary organism is Heterobollium okamotoi, a parasite of blowfish.

(10) The extermination method according to claim 8, wherein the solitary organism is a giant beetle, which is a parasite of a salmon. (11) The extermination method according to claim 9, wherein the puffer fish is trough.

(12) The extermination method according to claim 10, wherein the persimmon is perilla.

(13) A feed for fish comprising the pesticide according to claim 1.

(14) A feed for puffer fish, comprising the pesticide according to claim 3.

(15) The puffer fish feed according to claim 14, wherein the puffer fish is trough.

(16) A feed for eel, which contains the pesticide according to claim 4.

(17) The feed for eel according to claim 16, wherein the eel is eel.

(18) An injection for the treatment of Heteroborium okamotoii infection, which is a parasite of puffer fish, comprising an effective amount of nitroskanate or a pharmaceutically acceptable salt thereof.

(19) The injection according to claim 18, wherein the puffer fish is trough. (20) Injection for the treatment of pseudo-dactylogis / bini infection, a parasite of eel, characterized by containing an effective amount of nitroskanet or a pharmaceutically acceptable salt thereof. Agent.

(21) The injection according to claim 20, wherein the persimmon is perilla. BEST MODE FOR CARRYING OUT THE INVENTION

“Nitroskanate” (Nitroscanate, manufactured by Sankyo Co., Ltd.) used in the present invention (Sankyo Pharmaceutical Equipment Handbook, 1998 edition, edited by the Japan Pharmaceutical Affairs Association, p. 244-245) is a 4- (412-trophenoxy) phenyl A compound called sotiocyanate, which is used in nematodes such as dogs and cats (C. Genchi, G. Traldi, and MT Manfredi.Field trials of the anthelmintinc efficacy of nitroscanate and mebendazole in dogs.Veterinary Rec., 1990, 27, 77-80), tapeworm (JC Boray, MB Strong, JR Allison, M. von Orelli) , G. Saras in, and W. Gfeller.Nitroscanate a new broad spectrum anthelmintic against nematode and cestode of dogs and cats.Aust.Vet.J Li 1979, 55, 45-53) and fluke (RA Cornish, and C. Bryant) Changes in energy metabolism due to anthemintics in Fascila hepatica maintained in vitro. Int. J. ParasitoL, 1976, 6, p393-398).

Parasites such as tapeworms and nematodes to be dewormed are mainly in the digestive tract and liver, and the parasites are dewormed by oral administration of nitroskanet. This mechanism of action is thought to be inhibition of adenosine triphosphate synthesis (RA Cornish, and C. Bryant.Changes in energy metabolism due to anthelmintics in Fascila hepatica maintained in vitro.Int. J. Parasitol , 1976, 6, p393-398).

Therefore, the present inventors examined the effect of ditroskanet on the control of fish parasites, such as Heterobium okamotoi, which is known as a puffer parasite, and found that this substance was effective in controlling fish parasites. I found that it could be used.

In the present invention, in addition to nitroskanate, a pharmaceutically acceptable salt thereof can be used as an active ingredient. Here, pharmaceutically acceptable salts are inorganic salts such as hydrochloride, sulfate, nitrate, and phosphate; acetate, tartrate, citrate, fumarate, maleate, and toluenesulfone. Organic salts such as acid salts and metasulfonates; metal salts such as sodium salts, potassium salts and calcium salts; salts with bases such as trimethylamine salts, guanidine salts and ammonium salts. The nitroskanate according to the present invention or a pharmaceutically acceptable salt thereof is a known compound.

The fish parasites to which the present invention is applied include, for example, solitary, nematodes, tapeworms, and trematodes. Of these, monoplasias belong to the flatworm phylum Monoplasia (Fishology [Infectious Diseases and Parasites], Shu Egusa, ed.

198 3, p 2 3 5-2 8 9).

Monoplans are hermaphroditic and are mostly fish ectoparasites. Body length

They range from small species of 1 mm or less to several cm. Primarily based on the structure of the fish-fixing organs at the rear end, they can be divided into single-post and multi-post.

The taxonomic groups and species names of the main parasites belonging to the polypodal suckers include Microcotyle sebastisci, Bivagina tai, Heteraxine heterocerca, and Hetea. Lobodium 'Okamotoi (Heterobothrium okamotoi), Eidiplozoon nipponicum (Eudiplozoon nipponicum), Neoheterobolimum flounder (Neoheterobothrium hirame) and the like, but in the present invention, parasites belonging to heterobotium Is the main subject.

The taxonomic groups and species names of the main parasites belonging to single suckers are Dactyrogyrus extensus j (Pactorogyrus extensus j, Pseudoductylogyrus bini), Peudoductylogyrus anguillae), Tetraonchus awakurai, Benedenia 'Seriolae', and Neobenedenia 'Gillerellae' (Neobenedenia girellae), etc. Introduction to science, edited by Kiyokuni Muroga and Shuzo Egusa, Koseisha Koseikaku, 1996, p98), Classification of main parasites of this genus Group and species names include Proteocephalus neglectus and the like.

In addition, nematodes belong to the nematode phylum (Introduction to fish pathology, edited by Kiyokuni Muroka and Shuzo Egusa, Koseisha Koseikaku, 1996, p98), and the main parasites of this genus Classification groups and species names include Anguillicola crassus.

The trematodes belong to the flatworm genus Lepidoptera (Introduction to fish pathology, edited by Kiyokuni Muroka and Shuzo Egusa, Koseisha Koseikaku, 1996, p98). The taxonomic groups and species names of the main parasites belonging to the trematodes include the vascular fluke paradeon parasiteon silicus grandispinus (Paradaeontacylix grandispinus) and the paradeon parasiteon parasitee parasitism (Paradaeontacylix kampachi). It is.

Next, the fish to which the present invention is applied belong to the teleosts of teleost fish excluding rainbow trout and other dicins and koi, and include sea bass, pufferfish, curry, and eel. Can be Specific examples include sea buckthorn, amberjack, larch, Thailand, and swordfish belonging to sea bass; pufferfish swordfish, boxfish, torafugu, norisenbong, sabifugu; flatfish belonging to flatfish; scallop eel, and the like.

Among these fishes, those that are infected with the above parasites or those that are likely to be infected are covered by the present invention.

The nitroskanate according to the present invention or a pharmaceutically acceptable salt thereof is used in the form of a pesticide and a method for controlling fish parasites, as well as a feed and an injection containing the same. Therefore, there are various methods of administering these substances to fish, and when used as a pesticide, a method of putting the target fish directly into breeding water in which the insecticide is dissolved and directly contacting the same is applied. When used as a feed, oral administration is applied, and when used as an injection For this, a method of injecting an appropriate site in fish is adopted. When applied as an extermination method, any of the various methods described above can be used alone or in combination.

For the control of parasites, the above-mentioned active compound is used alone or, if necessary, in combination with other substances such as carriers, stabilizers, solvents, excipients, and diluents, as appropriate. Can be used.

Examples of the carrier include sodium alginate, lactose, cellulose, starch, gluten, casein, calcium phosphate monobasic, gelatin, polyethylene glycol, light acid anhydride and the like.

Examples of the stabilizer include propylene glycol, magnesium chloride, calcium ascorbate, tocopherol acetate, ethoxyquin, sodium pyrosulfite and the like.

The carrier used when dissolving the pesticide in the breeding water includes a solvent or a solubilizing agent. Examples of the solvent include, in addition to water, alcohols such as ethanol, butanol, benzyl alcohol, and glycerol; propylene glycol, polyethylene glycol, N-methylbilidone, and mixtures thereof. Can be

Examples of the dissolution aid include polyvinylpyrrolidone, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, polyvinyl alcohol, and polyoxyethylene sorbitan fatty acid ester.

The pesticide of the present invention may contain the compound described above in an amount effective for controlling a target fish parasite.The compound may be used alone, or may be used in combination with a carrier or other components. May be used. Generally, the concentration of the compound, which is the active ingredient in the parasiticidal agent, is between 0.01% and 20%, preferably between 0.05% and 10%, but if necessary, Further, the aforementioned stabilizer 0.5 -10% and excipients 0.1-10% may be added as appropriate. In the case of a pesticide using the compound alone, it is preferable to use the compound after diluting it with an auxiliary component so as to have the above concentration at the time of use.

When the parasiticidal agent of the present invention is incorporated into feed, ditroskanet, which is an active ingredient of the insecticide, or a pharmaceutically acceptable salt thereof, may be gelatin, methylcellulose, ethylcellulose, or acetic acid acetate. It is preferable to use the composition after coating it with a coating agent such as cellulose phosphate and hydroxypropylmethylcellulose.

Examples of the coating method include known methods such as fluidized bed coating, worster coating, and jet air flow dispersion coating. The use of the above-mentioned coated compound is preferable because it has the effect of preventing a decrease in the palatability of the feed and the effect that the compound as an active ingredient hardly leaks from the fed feed.

The feed containing the parasite control agent of the present invention may be any feed containing components used for breeding fish, such as fish meal, squid meal, okiami meal, feed yeast, sardine minced, and moist pellet. These may be used alone or in combination of two or more. The amount of the compound, which is an active ingredient, in feed is the same as in the case of the above pesticide o

When the parasiticidal agent of the present invention is used as an injection (intramuscular, subcutaneous, intravenous, intraperitoneal), the compound as an active ingredient is dissolved or suspended in a suitable solvent, and Produced by adding additives such as solubilizers, acids, bases or buffer salts as tonicity agents, antioxidants and preservatives as appropriate, sterilizing, and, if necessary, filtering. Fill bottles, bottles and other containers.

Solvents used in this case include physiologically acceptable solvents, e.g. Examples include water, alcohols (eg, ethanol, butanol, benzyl alcohol, glycerol), propylene glycol, polyethylene glycols, N-methylpiperidone, and mixtures thereof. Further, the compound which is an active ingredient can be dissolved in physiologically acceptable vegetable oils or synthetic oils for injection.

Any dissolving agent may be used as long as it promotes dissolution of the active ingredient nitroskanate or a pharmaceutically acceptable salt thereof in a solvent, or prevents precipitation thereof. Examples thereof include ridone, polyoxyethylated castor oil, and polyoxyethylene sorbin ester. These may be used alone or in combination.

Examples of preservatives include benzyl alcohol, trichloroethanol, p-hydroxybenzoic acids and n-butanol. These may be used alone or in combination.

Regarding the dose of the parasiticidal agent of the present invention, in the case of oral administration, 1 mg to 2 g, preferably lmg to lg of the above-mentioned compound as an active ingredient per 1 kg of fish body weight per day is used. Administer in the range. The pesticide is administered once or in several divided doses. The administration period is suitably 1 to 10 days.

In addition, when a parasiticide is dissolved in breeding water, and the fish is immersed in the breeding water and brought into direct contact with the breeding water, the target substance must be dissolved in breeding water so that the active ingredient concentration is 0.5 to 500 ppm. Fish for 10 minutes to 2 days. In the case of injection administration, 0.1 mg to 200 mg, preferably 0.5 mg to 100 mg at a time is administered. In this case, the administration period is preferably 1 to 3 days.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 The test group consisted of a total of 2 groups: 100 mg of nitroskanate / kg body weight intraperitoneally and a control group in which saline containing 3% polyoxyethylene sorbitan monolaurate was intraperitoneally administered. . In the test, two troughs were used per group to which nitros was added and three were used per control group. After adding 100 mg of nitroskanate or 150 / L of polyoxyethylene sorbitan monolaurate to the container, physiological saline was added to make a final volume of 5 mL, and each injection solution was prepared.

In the test, five tiger puffer fish infected with Heterobacterium okamotoi and having an average fish weight of 171 g were used.

The above-mentioned injection solution was administered to the intraperitoneal cavity of the pufferfish infected with Heterobollium okamotoi so that the fish weight became 1 mL / 200 g. On the 4th day after the administration, the pufferfish was taken out, the necropsy was performed, the aorta was cut off, the blood was exsanguinated, the gills were taken out, the gills were cut into small pieces, and immersed in a 10% formalin solution. Stirred well for 10 minutes.

The stirred gill flap was poured over a net placed with plankton net, and the remaining gill flap was washed well so as to rub against the net. Next, the net was removed, the blanket net was washed well, and when the seawater had sufficiently flowed out, the seawater remaining on the blankton net was recovered. This operation was repeated three times. The collected seawater was poured into a petri dish and examined under a stereomicroscope to determine the number of parasites of Heterobium okamotoi.

Table 1 shows the results. The anthelmintic rate due to nitroskanate was calculated as the ratio of the number of parasites in the control group to the number of parasites in the control group, and was 98.3%. (Beauty 亏 flat odd king number \ 7o)

IT

Lonely right gi 丄 Q Π π u

2 8 3

3 5 3

Nitroskanet 4 1 1. 0 98.3 Dosage group 5 1 Example 2

Infested two eels of the eel gill parasite Pseudodactylus gillus vinii were exposed to nitrosane at a concentration of 10 ppm for 24 hours while airing, and the anthelmintic effect was examined.

That is, a suspension was prepared by suspending 40 L of polyoxyethylene sorbitan fatty acid ester (Zine 20) and breeding water so that the amount of nitroskane per 1 L of the chemical bath was 0.01 g. After that, this suspension was suspended in 5 L of breeding water so that the concentration of nitroskanate became 10 ppm, and one penguin was bathed for 24 hours. The number of parasitoids was measured under a microscope on the gills of Pseudodactychia remaining on the gills after bathing. The number of insects that fell into the breeding water after the chemical bath was determined by collecting the parasite from the breeding water after the chemical bath using a plankton net and measuring it under a stereoscopic microscope. The anthelmintic rate was calculated by adding the number of parasites remaining on the gills and the number of deparasites, and dividing the number of parasites by the total number of parasites as the total number of parasites.

Table 2 shows the results. As a result of this test, it was clarified that the medicinal bath for 2'4 hours at a concentration of 10 pm ditroskanate had an anthelmintic effect of about 62.2% on average. Table 2

Industrial applicability

ADVANTAGE OF THE INVENTION According to this invention, the parasiticide of the cultured fish and the control method are provided. By using these pesticides, the parasites of cultured fish can be effectively controlled.

In addition, feeding the feed containing the pesticide to cultured fish can prevent or treat parasite infection.

Claims

The scope of the claims

1. A pesticidal agent for fish parasites, characterized in that nitroskanet or a pharmaceutically acceptable salt thereof is used as an active ingredient (except for fish, exotic fishes such as rainbow trout, etc. And parasites except gyrodactylus.).

2. The pesticide according to claim 1, wherein the fish parasite is solitary.

3. The pesticide according to claim 2, wherein the solitary organism is Heterobium okamotoi, a parasite of blowfish.

4. The pesticidal composition according to claim 2, wherein the solitary organism is Pseudospermia gills vine, which is a parasite of eel.

5. The pesticide according to claim 3, wherein the blowfish is trough.

6. The pesticide according to claim 4, wherein the persimmon is perilla.

7. A method for controlling fish parasites, which comprises administering nitroskanet or a pharmaceutically acceptable salt thereof to fish (except for fish, excluding dicins such as rainbow trout and carp, And parasites except gyrodactylus.).

8. The extermination method according to claim 7, wherein the fish parasite is solitary.

9. The extermination method according to claim 8, wherein the solitary organism is Heterobacterium okamotoi, a pufferfish parasite.

10. The extermination method according to claim 8, wherein the solitary organisms are girdlings of the mouth of parasites.

11. The extermination method according to claim 9, wherein the blowfish is trough.

12. The extermination method according to claim 10, wherein the persimmon is perilla.

13. A feed for fish, comprising the pesticide according to claim 1.

14. A blowfish feed that contains the pesticide according to claim 3.

15. The puffer fish feed according to claim 14, wherein the puffer fish is trough.

16. An eel feed containing the pesticide according to claim 4.

17. The feed for eel according to claim 16, wherein the eel is eel.

18. An injectable agent for treating heteropourium 'okamotoi infection, which is a pufferfish parasite, comprising an effective amount of nitroskanet or a pharmaceutically acceptable salt thereof.

19. The injection according to claim 18, wherein the puffer fish is trough.

20. An injection for the treatment of Pseudodactyrogillus vini infection, which is a parasite of eel, characterized by containing an effective amount of nitroskanate or a pharmaceutically acceptable salt thereof. .

21. The injection according to claim 20, wherein the persimmon is perilla.