KR20090047491A - Method of removing parasites on body surface of fishes - Google Patents

Abstract

By orally administering 50-250 mg / kg body weight / day of vithionol to fish, the body parasites of fish are eliminated without expressing a side effect. Vithionol is administered orally for 1 to 3 days, continuous or every other day. This method is a skin insect parasitic larvae, defense, bushy, longfin siamese, flying, horse mackerel, white horse mackerel, sea bass, red snapper, yellow tang, red barley, bellows, flounder, yellow flounder, cocksucking, stone bream, river bream It is suitable for fish of perch, flounder, puffer fish, etc., reference mackerel, rodent, turbot, tilapia. When controlling the surface parasites of fish, the feed for fish farms to which the required amount of vithionol is added can be used.

Description

How to get rid of fish surface parasites {METHOD OF REMOVING PARASITES ON BODY SURFACE OF FISHES}

The present invention relates to a method for controlling parasites of fish (especially farmed fish) and a feed for fish farming for parasite control. Specifically, the present invention relates to a method for controlling body surface parasites such as neobenedenia and Benedenia by oral administration of a medicament, and a feed for fish farming for controlling such parasites.

Parasites in sponge culture are a major problem because they interfere with stable production. Among parasitic diseases, skin respiratory infections, in particular, occur in any of the Japanese aquaculture farms and are considered to be one of the biggest problems in aquaculture farming. Typically, skin parasites called a trematode is neo-Venetian Denia (planar dongmulmun only raised ginger danhu sucker current cap Oradea (capsalidae) and the neo-Venetian Denia, paper relre (Neobenedenia girellae )) I, Benedenia (quasi-monocytes short-lived short-lived resorption capsalidea and Benedenia-seriole) seriolae )), and other species of fish such as white horse mackerel, yellowtail, sea bream, red snapper, yellow tang, red barley, barley, flounder, and jerky. As a diagnostic method in the field, in addition to mortality accompanied by symptoms such as epidermal redness of the abdomen, peeling of the fin and clouding of the eye, a large body of parasitic fish may appear cloudy due to the large secretion of mucus. . In addition, abnormal swimming, such as rubbing the body of the reed nets are often seen. Symptoms worsen by rubbing the body on live reeds and the like, and the chance of infection of pathogens from parasitic sites increases, so the damage may be increased. When parasites of the main insect are confirmed, it can be repelled by performing a fresh water bath or hydrogen peroxide bath for about 1 to 3 minutes while paying attention to the water temperature. However, since the labor force required for processing such as a place shift of the fish and the stress on the fish are large, treatment with a drug that can be orally administered is strongly desired.

As a drug that can be used for oral administration to skin insects, the generic name praziquantel (isoquinoline pyrazine derivative) is sold by Bayer Medical Co., Ltd. and Kyowa Fermentation Co., Ltd. for the control of skin insects parasitic on the body surface of perch fish. have. They are mixed and administered to aquaculture feeds.

Bithionol (bisithol, bis (2-hydroxy-3,5-dichlorophenyl) sulfide) is the name of Sirnak paste, animal bitine, which is used by Dainippon Pharmaceutical Co., Ltd. and Tanabe Pharmaceutical Co., Ltd. It is sold as).

Non-patent document 1 reports that the number of Benedenia parasites has decreased to 10-15% of the control as a result of continuous oral administration of bithiool for 3 to 5 days in defense under conditions of 300 mg / kg fish body weight / day. Although this document is a report of 1965, there have been no reports on anti-parasitic effects on fish of vithionol since, and it has not reached practical use. Practical antiparasitic drugs should be those that can completely control parasites. If half of the parasites are killed, half of the parasites will multiply if you stop taking the medication. Non-Patent Document 1 confirms the antiparasitic effect of bithionol, but complete hookworm is not. Non-patent document 1 does not describe or suggest about the dosage amount which can fully control parasites, what side effects in that case, and it fully eliminates and minimizes the side effects. In other words, Non Patent Literature 1 indicates that many problems still remain to completely exterminate the external parasitic insect repellent (Benedenia) of fish, but does not teach the solution.

[Non-Patent Document 1] Tsukuo Takada, Shogoro Kasahara (1965): "A Study on the Control of External Parasitic Insects of Defense". Fisheries propagation, 13, 23-27.

Disclosure of the Invention

Problems to be Solved by the Invention

An object of this invention is to provide the rescue method by the oral administration agent of the body surface parasite in fish (especially aquaculture fish).

Means to solve the problem

The inventors have searched for various oral antiparasitic drugs and natural-derived substances for animals in search of oral medicaments effective for skin insects, which are an important problem in the defense of defense products such as scab and defense. As a result, it was found out that an effect was observed for the vithionol sold as an antiparasitic drug for animals, and the present invention was completed.

This invention is a body surface parasite control method of the fish of (1)-(6).

(1) A method for controlling body surface parasites of fish, characterized by orally administering 50 to 250 mg / kg body weight / day of vithionol to the fish.

(2) The method for controlling the body surface parasites of (1), wherein oral administration of bithiol is performed for 1 to 3 days.

(3) The method for controlling the body surface parasites of (1), wherein oral administration of bithionol is performed every other day.

(4) The method for controlling body surface parasites according to any one of (1) to (3), wherein the fish is a fish of flatfish or perch.

(5) Fish spearfish, defense, bushley, longfin snailfish, flying, horse mackerel, white horse mackerel, sea bass, red snapper, yellow tang, red barley, bellfish, flounder, yellow flounder, jerky fish, stone bream, river bream, reference shark The method for controlling body surface parasites according to any one of (1) to (3), which is any one of?

(6) The method for controlling body surface parasites according to any one of (1) to (3), wherein the fish is caterpillar, defense, bushley or flounder.

Moreover, this invention is a feed for fish farming for body surface parasite control of (7)-(11).

(7) Fish feed for body surface parasite control, characterized in that it has been added so that fish can ingest 50-250 mg / kg body weight / day of bithionol.

(8) The fish feed for body surface parasite control according to (7), wherein the fish is added to the fish feed for the sea bass fish so that the bass fish can ingest the 60-250 mg / kg body weight / day of the biotin.

(9) Fish feed for the control of body surface parasites according to (8), wherein the fish is caterpillar, defense or bushley.

(10) Fish farming for controlling parasites parasites according to (7), characterized in that bitiolin is added to the feed for the flounder fish so that the flounder fish can ingest 50 to 200 mg / kg of body weight / day. feed.

(11) The feed for fish farming for body surface parasite control of (10) in which the fish is flounder.

Effects of the Invention

According to the method of the present invention, the antiparasitic action can be exerted without expressing adverse effects such as poor feeding of bithionol in fish. In addition, the feed added with the necessary amount of bithionol can control parasites only by feeding a fixed amount of food as usual.

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which shows the antiparasitic effect and oral effect on the food intake of oral administration of bithionol to the neobenedenia parasitic to flounder in Example 1.

FIG. 2 is a diagram showing the effect on the insecticidal effect and food intake of oral administration of bitionol to neobenedenia parasitic on flounder in Example 2. FIG.

FIG. 3 is a diagram showing the total length of neobenedenia as an index showing the antiparasitic effect of oral administration of bithionol to neobenedenia parasitic on flounder in Example 2. FIG.

FIG. 4 is a diagram showing the antiparasitic effect and oral effect on the food intake of oral administration of bithionol to neobenedenia parasitic in scabbard in Example 3. FIG.

FIG. 5 is a diagram showing the total length of neobenedenia as an index of the antiparasitic effect of oral administration of bithionol to neobenedenia parasitic sputum in Example 3. FIG.

FIG. 6 is a diagram showing the antiparasitic effect of oral administration of bithionol to oral administration of neobenedenia parasitic scabbard in Example 4, and its effect on food intake. 2% and 4 days were fed with no added drug at 4% of fish body weight).

FIG. 7 is a diagram showing the antiparasitic effect of oral administration of bithionol to neobeneddenia parasitic worms and the effect on food intake in Example 5. FIG.

FIG. 8 is a diagram showing the relationship between the size of the body length of neobenedenia parasitic in scaber and the dosage required for the expression of an antiparasitic effect in Example 6. FIG.

FIG. 9 is a diagram showing the relationship between the size of the body length of neobenedenia parasitic in scaber and the dosage required for expression of an antiparasitic effect in Example 7. FIG.

FIG. 10 is a diagram showing the antiparasitic effect of oral administration of bithionol to neobenedenia parasitic in lye (large fish) in Example 8. FIG.

FIG. 11 is a diagram showing changes over time of parasitic water after oral administration of bithionol to neobenedenia parasitic in scabbard in Example 9. FIG.

FIG. 12 is a photograph showing the change of the carcass after oral administration of bithionol to neobenedenia parasitic in scaber in Example 9. FIG.

FIG. 13 is a diagram showing the effect on the insecticidal effect and food intake of oral administration of bithionol to neobenedenia parasitic in defense in Example 11. FIG.

FIG. 14 is a diagram showing the effect on the insecticidal effect and food intake of oral administration of bithionol to neobenedenia parasitic in defense in Example 12. FIG.

Best Mode for Carrying Out the Invention

Bithionol used in the present invention is a compound represented by bis (2-hydroxy-3,5-dichlorophenyl) sulfide. As a drug containing bithionol, it is marketed as an antiparasitic drug of cattle and horses, respectively, from Dainippon Pharmaceutical Co., Ltd. and Tanabe Pharmaceutical Co., Ltd. under the trade names Sirnak paste and animal bitin.

The antiparasitic effect of the bithionol of the present invention is parasitic parasites on the body surface of fish, neobenedenia, benedenia, generally called skin fluke, such as parasitic girodactylus (salmon and fish, flounder, carp, cockfish, goldfish, Effective mainly in guppy). In particular, it is effective for neo-Venedenia, Benedenia, etc. which are generally called skin fluke.

The fish which are the object of this invention are the fish of the flounder and perch which these skin insects parasitic in a body surface, and are the fish of a defensive fish, a flounder, a blowfish, a sea bream. Specifically, catfish, defense, perch, yellow tang, bushley, long fin ashfish, flying, horse mackerel, white horse mackerel, red snapper, red snapper, bellfish, cocksack, flounder, yellow flounder, stone bream, river bream, reference shark , Fish, turbot, tilapia and the like are exemplified.

Vithionol is added to feeds, which can lead to eating disorders and death. Therefore, it is important to observe and use the dosage amount that is effective and does not cause side effects. As shown in the examples, vithionol obviously causes eating disorders in excess of 300 mg / kg / day in flounder and sputum. Particularly in defense, eating disorders and death were observed even at 200 mg / kg / day. From the examples, it is considered that the single oral dose at which mortality is observed in scaber is in the range of 300 to 400 mg / kg / day, and in the range of 100 to 200 mg / kg / day in defense. In addition, the effect is not observed at 50 mg / kg / day or less. Therefore, when vitrionol is used for parasite control, it is administered within a dose range of 50 to 250 mg / kg / day in any fish. As a usage, a high dose (eg, 140 to 250 mg / kg / day) is administered only for 1 day, or a slightly lower dose (eg, 50 to 140 mg / kg / day) is administered for 2 days or 3 days. It is preferable. Particularly in fish species that are prone to side effects such as defense, it is preferable to administer a low dose of 50 to 150 mg / kg / day every other day. Eating disorders and mortality, which are side effects of vithionol, are observed immediately after administration, and therefore, whether or not fish are susceptible to side effects can be judged by administering high or low doses to a few fish for one to three days.

Specifically, in the case of cutaneous insect repellent control of flounder species such as flounder, it is appropriate to administer 50-100 mg / kg / day for 3 days or 100-100 mg / kg / day for 1 day. In addition, in the case of skin repellent control such as perch scab, 100-200 mg / kg / day for 1-3 days or 140-250 mg / kg / day for 1 day is appropriate. Similarly, in defense, etc. where side effects tend to occur even in perch, it is appropriate to administer 50 to 150 mg / kg / day every other day.

In addition, as shown by Examples 5-8, the effect of a bithionol is an antiparasitic effect obtained with a small dose, so that the fish body size is large. For example, in the case of caterpillar, the dose of totally inhibiting parasites is reduced to 166 mg / kg / day in 43 g size, 136 mg / kg / day in 116 g size and 123 mg / kg / day in 220 g size, It is confirmed that even 480g size is fully suppressed at 144 mg / kg / day. Since 200 mg / kg / day daily administration does not cause side effects, even if the same amount is administered, there is no problem. However, a small dose may be used when administering to a fish of a large fish body size.

As confirmed in Examples 6 and 7, the smaller the size of the parasite, the lower the dose. Therefore, it is desirable to administer vithionol promptly when a parasite infection is confirmed.

In the case of fish, oral administration agents are commonly used in addition to feed. When adding bithionol to the feed, it is desirable to use a nutritionally considered feed for each fish species. The feed for the flounder or perch fish is considered to have nutritional properties and properties required for the fish of the flounder or perch. Usually, pellets are prepared by mixing fish meal, crude oil, starch, minerals, vitamins, fish oil, etc., or pellets by mixing powdered fish (mash) added with vitamins to frozen fish such as sardines and fish meal. And the like are used. Since the daily food intake is determined depending on the type and size of the fish, the amount of bitionol converted to the above dosage amount is added to the feed. Vithiool may be administered once a day, or may be administered by dividing several times. In the case where there is a tendency to show a decrease in food intake by vithionol, the effect on food intake can be reduced by administering one dose rather than several times a day. For example, for a fish that is fed once a day, for example, a daily dose of bithionol is added to an amount of food that is about 80% of the total food supply, and the food is first fed and reliably fed. Get the necessary amount of Vithionol. In addition, in the case of the fish to be fed multiple times in a day, a daily dose of bithionol is added to and fed to the first feed therein. Since a bithionol is a stable substance with melting | fusing point 188 degreeC, it can be added also in the manufacturing process of the feed which has a heating process.

Although the Example of this invention is described below, this invention is not limited to these at all.

The skin worms ( Neobenedenia girellae ) used in the following examples are those which keep and raise the larvae as hosts, and collect and cultivate the eggs spawned from the adults, and use the obtained hatching larvae for testing.

Example 1

Insecticidal Effect of Oral Administration of Vithionol on Neobenedenia Parasites of Olive Flounder-1

Test method: 60 flounder with an average fish weight of about 78 g were bred in a 200 liter water tank for about 7 days, and was tamed at 25 degreeC water temperature. In the meantime, the food was supplied with commercial feed, and the feeding rate was 1.5% of the fish body weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index and adding about 1.2 million neo-Venedenia hatched larvae to expose the fish to the parasite for 1 hour. After infection, each 10 were housed in 6 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, a commercial feed was fed and the feeding rate was 1.5% of the fish body weight. Each test diet was fed 8 to 10 days after infection. The feed rate of the test feed was 1% of the fish body weight. On day 11 after infection, all fish were sampled and neobenedenia parasitic on the body surface was counted.

Specimen: 4 mg Vitonol administered orally with Vithionol for 3 days at 66 mg, 128 mg, 197 mg, 312 mg / kg fish body weight / day after parasite exposure, 155 mg / day from 8 days after parasite exposure. A total of 6 balls of a positive control group administered with Praziquantel (commercially available anti-skin insect repellent) and a control group (0 mg) fed a drug-free feed for 3 days at kg body weight / day were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of mortality, and the number of parasites.

The results are shown in FIG. In Fig. 1, * means that 5 animals died after 1 day of feeding. The positive control group administered Fraziquantel had significantly less parasitic counts than the control group (p <0.01). However, a decrease in appetite was observed, and furthermore, the parasites could not be completely eliminated. On the other hand, all the non-thionol treated groups were able to completely exterminate the parasites, indicating the effectiveness of the agent (p <0.01 compared with the number of parasites in the positive control group). In particular, no decrease in appetite was observed at the 66 mg / kg administration dose. In the 312 mg / kg administration group, 5 deaths occurred after administration, and side effects were observed. 128 mg / kg and 197 mg / kg of the bulbs were observed to have a clear appetite after 2 days of administration, but since a complete antiparasitic effect was observed, it was considered effective at a single dose at these concentrations.

Example 2

Insecticidal Effect of Oral Bithionol on Neobenedenia Parasites of Olive Flounder-2

Test method: 50 flounder with an average fish body weight of about 29 g were bred in a 200 liter water tank for about 7 days, and tamed at 25 degreeC water temperature. In the meantime, the food was supplied with commercial feed, and the feeding rate was 1.5% of the fish body weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index, and injecting about 10,000 individuals of the neo-Venedenia hatching larvae and exposing the fish to the parasites for 1 hour. After infection, each 10 were housed in five 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feed was supplied and the feeding rate was 1.5%. Each test diet was fed 8 to 10 days after infection. The feed rate of the test feed was 1%. On day 11 after infection, all fish were sampled to count neobenedenia parasitic on the body surface, and the total length of neobenedenia parasitic on each sphere was measured (n = 30).

Experimental group: 4 groups of Vithionol administration group administered orally with vithionol for 3 days at 6 mg, 18 mg, 52 mg, 66 mg / kg fish body weight / day from 8 days after parasite exposure, control group fed with no additives (0) Mg) was set in total. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of mortality, the number of parasites, and the length of a parasite.

The results are shown in FIG. At a dose of 52 mg / kg or 66 mg / kg of bithionol, no appetite loss was observed, and an obvious antiparasitic effect was observed. The parasitic number of the 52 mg / kg administration group showed a significant difference of p <0.05 compared to the control group, and the 66 mg / kg administration group showed a significant difference of p <0.01. In particular, the 66 mg / kg administration group clearly showed a low parasitic number, and the result of Example 1 was reproduced. Parasite length was 2.59 ± 0.55 mm (mean ± standard deviation), 6 mg / kg, 2.68 ± 0.44 mm, 18 mg / kg, 2.41 ± 0.54 mm, 52 mg / kg, 2.30 ± 0.42 mm, respectively. , 66 mg / kg spheres were 2.12 ± 0.27 mm (FIG. 3). Significant differences were observed in 52 mg / kg (p <0.05) and 66 mg / kg (p <0.01) compared to the parasite lengths of the control. In addition, in FIG. 3, * means significant difference in p <0.05 compared with control (0 mg), ** means significant difference in p <0.01 compared with control (0 mg), respectively.

Example 3

Insecticidal Effect of Oral Vithionol on Parasite Neobenedenia Parasite-1

Test method: 50 lychees with an average fish weight of about 24 g were bred in a 200 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food was supplied with commercial feed, and the feeding rate was 4% of the fish body weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index, and injecting about 10,000 individuals of hatched larvae from Neovenedenia, exposing the fish to the parasite for 1 hour. After infection, each 10 were housed in five 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feeds were fed and the feeding rate was 4% of the fish body weight. Each test diet was fed 8 to 10 days after infection. The feed rate of the test feed was 2% of the fish body weight. On day 11 after infection, all fish were sampled to count neobenedenia parasitic on the body surface, and the total length of neobenedenia parasitic on each sphere was measured (n = 30).

Experimental group: Four groups of non-thiothol-administered oral administration of 63-, 127-mg, 193-mg, 332-mg / kg fish body weight / day for 3 days from the 8th day after parasite exposure. Mg) was set in total. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of mortality, the number of parasites, and the length of a parasite.

The results are shown in FIG. In FIG. 4, * means that 1 animal died 1 day after food supply. The 63 mg / kg and 127 mg / kg bitionol administrations resulted in less parasitic counts than the control (p <0.05). Parasite length was significantly increased in the control group at 3.85 ± 0.22mm, 63mg / kg and 3.73 ± 0.28mm, and 127mg / kg, and 3.59 ± 0.23mm, respectively. It was inhibited (FIG. 5).

However, these doses did not completely eliminate the parasites, and it has been found that the optimal dose of the protective agent requires more than the flounder. On the other hand, the 193 mg / kg administration group almost completely eliminated the parasites. The 332 mg / kg administration group completely exterminated the parasite, but mortality occurred one day after the feeding, and extreme appetite was observed on the second day of the feeding, and side effects were observed. In the 193 mg / kg administration group, apparent appetite was observed on the 3rd day of administration, but a complete antiparasitic effect was observed. Therefore, single or two administrations were considered effective at this concentration. Obvious side effects were observed with the 332 mg / kg administration group, but despite the decreased appetite from the second day of administration, a full antiparasitic effect was observed, so a single administration is considered effective at such high doses. In addition, in FIG. 5, * means significant difference by p <0.01 compared with the control (0mg).

Example 4

Insecticidal Effect of Oral Administration of Vithionol on Neo-Venedenia Parasites of Caterpillar-2

Test Method: Sixty squids with an average fish weight of about 26 g were bred in a 200 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food was supplied with commercial feed, and the feeding rate was 4% of the fish body weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index, and injecting about 1.20,000 neo-Venedenia hatched larvae and exposing the fish to the parasite for 1 hour. After infection, each 10 were housed in 6 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feeds were fed and the feeding rate was 4% of the fish body weight. Each test diet was fed 8 to 10 days after infection. The feed rate of the test feed was 2% of the fish body weight. All of the feeds on the 11th day of infection were fed without chemicals, and the feed rate was 4%. All fish were sampled on day 12 after infection and counted neobenedenia parasitic on the body surface.

Specimen: Oral administration of thiotin 3 days at 137 mg / kg fish body weight / day from day 8 after parasite exposure, oral administration of 1-98 mg / kg fish body weight / day at day 8 after parasite exposure for 1 day Dose, oral administration of 198 mg / kg fish body weight / day for 2 days or more at 198 mg / kg fish body weight / day from 8 days after parasite exposure. Administration group, positive control group administered Praziquantel (commercial anti-skin insecticide) for 3 days at 162 mg / kg fish body weight / day from day 8 after parasite exposure, control group supplying no additives (0 mg) 6 spheres in total were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. No mortality was observed throughout the test period. The positive control group treated with Fraziquantel was clearly less parasitic than the control group (p <0.05), but the parasites did not completely exterminate and were less effective than when administered to flounder. On the other hand, at the 198 mg / kg administration group of the bithionol, the main insect can be fully exterminated, and the previous test result was reproduced. In addition, almost all the insects were abolished without causing appetite deterioration in the bithionol 198 mg × 1 day administration group, and the efficacy of single administration at the high dose was shown. Even in the case of 198 mg × 2 daily administration of bithionol, almost no appetite was caused, and all the insects were killed. From the above results, Vithionol has an anti-dermal insecticidal effect, and in defense, a single dose at 137-300 mg / kg fish body weight is effective for controlling insects and does not cause a decrease in appetite. It proved to be superior to Quantel.

Example 5

Insecticidal Effect of Oral Vithionol on Parasite Neovenedenia Parasites-3

Test Method: Sixty squids with an average fish weight of about 43 g were reared in a 200 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food was supplied with commercial feed, and the feeding rate was 4% of the fish body weight. Water injection was at 2.4 liters / minute. Infection of parasites was performed by exposing fish to a parasite for 1 hour by introducing a 200 liter water tank as an index, and injecting about 1.2 million individuals of the hatched larvae of neobenedenia. After infection, each 10 were housed in 6 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feeds were fed and the feeding rate was 4% of the fish body weight. Each test diet was fed on day 8 after infection. The feed rate of the test feed was 2% of the fish body weight. After that, commercial feed was supplied for 2 days, and the feeding rate was 4% of the fish body weight. On day 11 after infection, all fish were sampled and neobenedenia parasitic on the body surface was counted.

Specimen: Five thiotin-administered diets containing 126 mg, 147 mg, 166 mg, 185 mg, 215 mg / kg fish body weight / day in a single oral dose of vitionol at 8 days after parasite exposure. A total of six spheres of the control (0 mg) were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. The parasitic number of 166 mg / kg and 185 mg / kg fish body weight biotinol groups was almost 0 (p <0.01), and the parasitic number of 215 mg / kg fish body weight biotin group was 0 (p <0.01). In addition, no death or loss of appetite was observed during the test period. Thus, single doses of 166 mg, 185 mg and 215 mg / kg fish body weight biotinol have a clear antiparasitic effect and have been found to be safe doses.

In addition, in the upper graph of Fig. 7, * denotes that the total food intake at the time of administration of the drug is 2% of the fish body weight, and then 4% of the body weight of the fish. Fish body weight) is 43 g, and in the lower graph of FIG. 7, * means significant difference as p <0.01 compared to the control (0 mg).

Example 6

Insecticidal Effect of Oral Vithionol Administration on Neo-Venedenia Parasite

Test Method: 54 lychees with an average fish weight of about 116 g were bred in a 200 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food supply gave a commercial feed, and the feed rate was 3% of the fish weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index, and adding about 8000 neobenedenian hatched larvae to expose the fish to the parasite for 1 hour. In addition, on day 4 from the first infection, 8000 Neovenedenia individuals were added again to expose fish to parasites for 1 hour. After the second infection, each 8 were housed in 6 100 liter tanks. In addition, in order to investigate the parasite length at the time of drug administration, the remaining 6 were housed in a 100 liter water tank. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feed was supplied, and the feeding rate was 3% of the fish body weight. Each sphere test diet was fed on day 8 from the first infection. The feed rate of the test feed was 2% of the fish body weight. At the same time (8 days from the first infection), all the fish were sampled from the bulb containing 6 fish in a 100 liter water tank, and parasitic parasites were collected. Parasites of the first infected parasitic 8 days and parasites of the next infected parasitic 4 days were divided, and the length of carcasses of each 50 individuals was examined. About six 100-liter tanks continued to be fed, commercial feed was supplied for 2 days thereafter, and the feeding rate was 3% of the fish body weight. On day 11 after infection, all fish were sampled and neobenedenia parasitic on the body surface was counted.

Experimental group: Five groups of non-thiothol-administered, five-dose oral drug-free diets with oral administration of vitionol at 81 mg, 103 mg, 125 mg, 136 mg, 157 mg / kg fish body weight / day 8 days after parasite exposure. A total of six spheres of the control (0 mg) were set. In addition, a sphere for determining the size of the parasites at the time of administration of the drug-containing feed was set (6 animals in a 100 liter tank). A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. The parasite length at 4 days of parasitic feeding with drug addition was 0.84 ± 0.11 mm. The parasitic effect of vithionol on parasites on day 4 was clearly manifested from a single dose of 125 mg / kg fish body weight (p <0.05), resulting in a parasitic number of 136 mg and 157 mg / kg fish body weight biotinol groups being nearly zero. Was (p <0.01). Parasite length of 8 days parasitic was 2.61 ± 0.27 mm. The parasitic effect of vithionol on parasites on day 8 was clearly manifested from 136 mg / kg fish body weight (p <0.01), and the parasitic number of 157 mg / kg fish body weight biotinol was zero. From the above results, it was found that the antiparasitic effect of orally administered bithionol depends on the size of the parasite, and that the smaller the parasite, the lower the dose, the antiparasitic effect is obtained. In addition, no decrease in food intake or death were observed in each test group. 8 is a graph showing the antiparasitic effect on N. girellae (body length 0.84 ± 0.11 mm) of parasitic day 4, where n = 8 and AV is 116 g. 8 is a graph showing the antiparasitic effect on N.girellae (body length 2.61 ± 0.27 mm) of parasitic 8 days, n = 8, AV is 116g, and * is p < Significant difference of 0.05, ** means significant difference of p <0.01 compared to the control (0 mg), respectively.

Example 7

Insecticidal Effect of Oral Vithionol Administration on Neo-Venedenia Parasite

Test Method: 47 lychees with an average fish weight of about 220 g were reared in a 500 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food supply gave a commercial feed, and the feed rate was 3% of the fish weight. Water injection was at 4.8 liters / minute. Parasite infection was carried out by using a 500 liter water tank as an index, and adding about 8000 neobenedenian hatched larvae to expose the fish to the parasite for 1 hour. In addition, on day 4 from the first infection, 8000 Neovenedenia individuals were added again, and the fish were exposed to the parasites for 1 hour. After the second infection, each 7 were housed in 6 200 liter tanks. In addition, in order to check the parasite length at the time of drug administration, the remaining five were housed in a 200 liter water tank. The water injection during the breeding period was 2.4 liters / minute. Seven days after infection, commercial feed was supplied, and the feeding rate was 3% of the fish body weight. Each sphere test diet was fed on day 8 from the first infection. The feed rate of the test feed was 1.5% of the fish body weight. Parasitic parasites were collected by sampling the entire fish from a 200 liter tank containing 5 fish at the same time (8 days from the first infection). Parasites of the first infected parasitic 8 days and parasites of the next infected parasitic 4 days were divided, and the length of carcasses of each 50 individuals was examined. About six 200-liter tanks continued to be fed, commercial feed was supplied for 2 days thereafter, and the feeding rate was 3% of the fish body weight. On day 11 after infection, all fish were sampled and neobenedenia parasitic on the body surface was counted.

Test Specimen: Five (5) non-thiothol-administered oral supplements containing 78 mg, 93 mg, 106 mg, 123 mg, 151 mg / kg fish body weight / day in a single oral dose of fish on 8 days after parasite exposure. A total of six spheres of the control (0 mg) were set. In addition, a sphere for determining the size of the parasites at the time of administration of the drug-added feed was set (to accommodate 5 in a 200 liter tank). A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. The parasite length at 4 days of parasitic feeding with chemicals was 0.88 ± 0.10 mm. The parasitic effect of vithionol on the parasitic number at 4 days of parasite was evident from a single dose of 123 mg / kg fish body weight (p <0.01) and the parasitic number of the 151 mg / kg fish body weight biotin group was nearly zero ( p <0.01). The parasite length of 8 days parasite was 2.82 ± 0.013 mm. The parasitic effect of vithionol on parasites on day 8 was clearly manifested from 123 mg / kg fish body weight (p <0.01), and the parasitic number of 151 mg / kg fish body weight biotinol was zero. From the above results, the antiparasitic effect of orally administered bithionol varies depending on the size of the parasite, and it is reproduced that the parasitic effect is obtained at a lower dose as the parasite is smaller. In addition, no decrease in food intake or death were observed in each test group. In addition, the upper graph of FIG. 9 is a graph showing the insecticidal effect on N. girellae (body length 0.88 ± 0.10 mm) of parasitic 4 days, n = 7, AV is 220g, and 1.5% feeding. The lower graph of FIG. 9 is a graph showing the antiparasitic effect on N.girellae (body length 2.82 ± 0.13 mm) of parasitic 8 days, n = 7, AV is 220g, and * is p < 0.01 means significant difference.

Comparing the results of Examples 5-7, the insecticidal rate was 35% (Example 5) for the main insect on the 8th day of parasite with single dose of 147 mg / kg fish body weight at 43 g size (Example 5), and 42.7 at 136 mg at 100 g size. % (Example 6) and the 200g size, the worm rate was 70% at 123 mg (Example 7). Therefore, it was considered that the larger the fish body size, the more the pesticidal effect is obtained at a lower dose.

Example 8

Insecticidal Effect of Oral Vithionol on Parasite Neovenedenia Parasite-6

Test method: Ten lychees with an average fish weight of about 480 g were bred in a 500 liter water tank for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food was supplied with commercial feed, and the feeding rate was 1% of the fish body weight. Water injection was at 4.8 liters / minute. Parasite infection was carried out by using a 500-liter water tank as an index, and adding about 6000 individuals of neo-Nedenia hatching larvae and exposing the fish to the parasite for 1 hour. After infection, three were housed in two 200 liter water baths and four in one 200 liter water bath. The water injection during the breeding period was 2.4 liters / minute. Seven days after infection, commercial feed was supplied, and the feeding rate was 1% of the fish body weight. Each test diet was fed on day 8 after infection. The feed rate of the test feed was 0.5% of the fish body weight. After that, commercial feed was supplied for 2 days, and the feeding rate was 1% of the fish body weight. On day 11 after infection, all fish were sampled and neobenedenia parasitic on the body surface was counted.

Test group: 2 groups of thiotin-administered group treated with oral vitionol in a single oral dose of 144 mg, 151 mg / kg fish body weight / day at 8 days after parasite exposure, and 3 groups of control (0 mg) fed with no additives. Was set. In addition, the number of animals provided for the test was 144 mg administration group 4, 151 mg administration group and 3 control groups. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of mortality, and the number of parasites.

The results are shown in FIG. The parasitic number of the 144 mg / kg and 151 mg / kg fish body weight biotinol doses was 0 (p <0.01). In addition, no death or loss of appetite was observed during the test period. Therefore, the insecticidal effect of vithionol was reproduced even in large fish. In addition, this result supports the result of Example 7 that the larger the fish body size is, the less the insecticidal effect is obtained. In Fig. 10, n = 3,144 mg / kg B.W. N = 4,151 mg / kg B.W. N = 3 and AV 480g for the non-thionol-administered group, and * means significant difference of p <0.01 compared to the control group (0 mg).

Example 9

Effect of Vithionol Administration on Neovenedenia Parasitic in Slum Defense (Changes in Parasitic Numbers After Administration)

Test method: 18 lychees with an average fish weight of about 44 g were reared in a 100 liter water bath for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food supply gave a commercial feed, and the feed rate was 3% of the fish weight. Water injection was at 1.2 liters / minute. Parasite infection was carried out by using a 100-liter water tank as an index, and adding about 3000 individuals of neo-Venedenia hatched larvae and exposing the fish to the parasite for 1 hour. Seven days after infection, commercial feed was supplied, and the feeding rate was 3% of the fish body weight. On day 8 from infection the test diet was fed to 180 mg bitionol / kg fish body weight. The feed rate of the test feed was 2% of the fish body weight. The test feed was fed and each of the three animals was sampled at 0, 4, 8, 12, 16, 24 hours later to examine the parasitic numbers. In addition, the drainage was filtered through a dense net and the dropped worms were collected to investigate the condition of the larvae.

The results are shown in FIG. In Fig. 11, AV 44 g, administration condition is 2% feeding in a single dose of 180 mg / kg fish body weight, n = 3 / each time. The parasitic number decreased sharply at 12 hours after administration and became nearly zero at 16 hours. In addition, the dropping insects in the breeding drainage were observed 6 hours after administration. The decaying larvae apparently had a white cloud and a constriction of the adhering phase (Fig. 12a (Adult N.girellae adult in breeding drainage 6 hours after administration)). In addition, when the insects parasitic in the fish were examined 8 hours after administration, turbidity of the carcasses was observed (FIG. 12C (N.girellae adult after 8 hours of administration)). Therefore, it was evident that orally administered vithionol appeared in the body surface of the scaber within 6 hours, and exerted its effect. In addition, the metabolism of the administered drug was estimated to be fast. It was found that the antiparasitic effect of vithionol is exhibited by the inhibition of homeostasis maintenance and atrophy of the fixing phase in that the carcass is clouded. 12B also shows N. girellae adults (control) at 0 hours of administration.

Example 10

Effect of Vithionol Administration on Cattle Defense

Test method: Each 10 squids with an average fish weight of about 75 g were housed in three 100-liter tanks, bred for about seven days, and tamed at a water temperature of 25 ° C. In the meantime, the food supply gave a commercial feed, and the feed rate was 3% of the fish weight. Water injection was at 1.2 liters / minute. After tame the test feed was fed. The feed rate of the test feed was administered once at 2% of the fish body weight. After that, commercial feed was supplied for 3 days, and the feeding rate was 3% of the fish body weight.

Test District: 200 mg, 300 mg, 400 mg / kg Fish body weight / day, three groups of non-thiothol administration groups in which oral administration of bithiol was orally administered. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing the occurrence of death and appetite trend.

The results are shown in Table 1. ○ indicates no appetite deterioration in the appetite deterioration column of Table 1. In the 200 mg and 300 mg / kg fish body weight biotinol single doses, no mortality occurred and no appetite loss was observed. On the other hand, in a single dose of 400 mg / kg fish body weight biotinol, 9 out of 10 died 2 to 3 hours after administration. However, the loss of appetite was not observed in one surviving animal, and the state was recovered. Thus, it has been found that the minimum toxic oral dose that exhibits apparent toxicity, such as the death of Vithionol fish, ranges from 300 to 400 mg / kg fish body weight. In addition, in the single dose of 400 mg / kg fish body weight biotinol, 9 out of 10 mice died 2 to 3 hours after administration, indicating that metabolism of orally administered vithionol was rapid, and that of Example 9 The results were supported.

              Single dose condition after administration 0 One 2 3 result 200mg / kg fish body weight Our number 0 0 0 0 0/10 Loss of appetite ○ ○ ○ ○ 300mg / kg fish body weight Our number 0 0 0 0 0/10 Loss of appetite ○ ○ ○ ○ 410mg / kg fish body weight Our number 9 0 0 0 9/10 Loss of appetite ○ ○ ○ ○

※ AV 75g, 2% food supply in single dose

* In an appetite deterioration column, ○ indicates no appetite deterioration.

Example 11

Insecticidal Effect of Oral Vithionol on Defensive Neo-Benedenia Parasite-1

Test method: 48 defense | guards with an average fish weight of about 54 g were bred in a 200 liter water tank for about 7 days, and was domesticated at the water temperature at 25 degreeC. In the meantime, the food was supplied with commercial feed, and the feeding rate was 4% of the fish body weight. Water injection was at 2.4 liters / minute. Infection of parasites was carried out by using a 200 liter water tank as an index, and adding about 1.80,000 individuals of hatched larvae of Neovenedenia, exposing the fish to parasites for 1 hour. After infection, each eight were housed in six 100 liter tanks. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feeds were fed and the feeding rate was 4% of the fish body weight. The vithionol administration group was given a single dose of the test feed 8 days after infection, and the feed rate of the test feed was 2% of the fish body weight. After that, commercial feed was supplied for 3 days, and the feeding rate was 4% of the fish body weight. All fish were sampled on day 12 after infection and counted neobenedenia parasitic on the body surface.

Experimental group: Four groups of non-thionol-administered oral doses of 70-, 139-mg, 196-mg, 333-mg / kg fish body weight / day for a single oral dose of vitionol at 8 days after parasite exposure, and 171-mg / day after 8-day parasite exposure. A total of 6 balls of the control group (0 mg), the positive control group administered with Praziquantel (commercially available anti-skin insecticide) for 3 days, and the control group (0 mg) fed with no drug feed were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. For 196 mg / kg and 333 mg / kg fish body weight biotinol doses, death occurred about 4 hours after administration. The mortality was 5 out of 8 at 196 mg and 8 out of 8 at 333 mg. The parasitic number of the 139 mg / kg fish body weight biotinol administered group was clearly less than the control group (p <0.05), and the parasitic number of the 196 mg / kg fish body weight biotinol surviving fish group was zero. In addition, the number of parasitic groups in the control group, Fraziquantel feeding, was less than that of the control, but there was no statistically significant difference between the control and the control. From the above results, it was found that the optimal single dose of bithionol in the defense was around 139 mg / kg fish body weight, and the effect was higher than that administered for 3 days at Praziquantel 171 mg / kg fish body weight / day. In addition, in the case of defense, the dose of vithionol, which exhibits apparent toxicity, is low compared to spearfish, and is also toxic at 196 mg / kg fish body weight. Thus, it has been clarified that oral doses of virutinol that are toxic vary depending on the species. In addition, in the upper graph of FIG. 13, the feeding amount at the time of feeding the drug-added feed is 2% of the fish body weight, other than 4% of the fish body weight, and n = 8, AV is 54g. 13, 70 mg / kg B.W., 139 mg / kg B.W., 196 mg / kg B.W. (5/8 row (5 out of 8)) and 333 mg / kg B.W. Each dose of (8/8 lo (5 of 8) dead) is all administered for 1 day, and the Praziquantel (praziquantel) dose is for 3 days. In the lower graph of FIG. 13, * means significant difference as p <0.05 compared to control (0 mg), and ** means significant difference as p <0.01 as compared to control (0 mg).

Example 12

Insecticidal Effect of Oral Vitonol Administration on the Defensive Neobenedenia Parasite-2

Test Method: 20 defense fish having an average fish weight of about 105 g were bred in a 200 liter water tank for about 7 days and tamed at a water temperature of 25 ° C. In the meantime, the food supply gave a commercial feed, and the feed rate was 3% of the fish weight. Water injection was at 2.4 liters / minute. Parasite infection was carried out by using a 200-liter water tank as an index, and adding about 6000 individuals of neobenedenian hatched larvae and exposing the fish to the parasite for 1 hour. After infection, each five were housed in four 100 liter water baths. The water injection during the breeding period was 1.2 liters / minute. Seven days after infection, commercial feed was supplied, and the feeding rate was 3% of the fish body weight. The bithionol administration group administered the test feed every other day on the 8th and 10th days after infection, and made the feed rate of the test feed 1%. On the 9th day and 11th day after the infection, commercial feed was supplied, and the feeding rate was 3% of the fish body weight. All fish were sampled on day 12 after infection and counted neobenedenia parasitic on the body surface.

Specimen: 8-day and 10-day post-parasite exposure, 57 mg, 90 mg, 104 mg / kg fish body weight / day Vitonol every other day in three dose groups, control supplements (0 mg) Four spheres in total) were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing appetite trend, the occurrence of death, and parasitic number.

The results are shown in FIG. The parasitic number of the 104 mg / kg fish body weight biotinol every other day treatment group was 0, clearly showing an antiparasitic effect (p <0.01). In addition, in all the spheres, neither death nor appetite was observed during the test period. From the above results, the apparent antiparasitic effect was not obtained by a single administration such as 104 mg / kg fish body weight / day administration conditions, but instead, even at low doses without toxicity, the effect was obtained by administering the bithionol every other day. have. In addition, these results also show that the insecticidal effect is obtained by continuous administration even at a low dose such as 104 mg / kg fish body weight. In addition, in each graph of FIG. 14, the feeding amount at the time of feeding a chemical | medical agent addition feed is 1% of fish body weight, otherwise it is 3% of fish body weight, n = 5 and AV are 105 g. In addition, in the upper graph of FIG. 14, 57 mg / kg B.W., 90 mg / kg B.W., and 104 mg / kg B.W. Each dose of is administered every other day for 2 days.

Example 13

Effect of Vithionol Administration on Defense

Test method: Each of three defenses of an average fish weight of about 650 g was housed in three 500-liter tanks, reared for about 7 days, and tamed at a water temperature of 25 ° C. In the meantime, the food was supplied with commercial feed, and the feeding rate was 1% of the fish body weight. Water injection was at 4.8 liters / minute. After tame the test feed was fed. The feed rate of the test feed was administered once at 0.5% of the fish body weight. Thereafter, commercial feed was given for 8 days, and the feeding rate was 1% of the fish body weight.

Test group: A total of three groups of two groups of non-thiothone administered with a single oral dose of bithionol at 200 mg, 300 mg / kg fish body weight / day and a control (0 mg) fed a drug-free feed were set. A predetermined amount of each drug was added to the moist feed to make a test feed.

Judgment of effect: It was performed by comparing the occurrence of death and appetite trend.

The results are shown in Table 2. In the column of appetite deterioration of Table 1, (circle) shows no appetite deterioration, and x represents appetite deterioration. For 200 mg / kg and 300 mg / kg fish body weight biotinol doses, death occurred about 3 hours after administration. The number of deaths was 2 out of 3 at 200 mg and 3 out of 3 at 300 mg. In addition, 200 mg bulb surviving fish showed no appetite recovery during the test period. In the case of defense, the results of Example 11 were reproduced, in which the virulence dose showing obvious toxicity was low compared to slumber.

           Single dose condition after administration 0 One 2 3 4 5 6 7 8 result 0mg / kg fish weight Our company 0 0 0 0 0 0 0 0 0 0/3 Loss of appetite ○ ○ ○ ○ ○ ○ ○ ○ ○ 200mg / kg fish body weight Our company One 0 0 0 One 0 0 0 0 2/3 Loss of appetite ○ × × × × × × × × 300mg / kg fish body weight Our company 3 3/3 Loss of appetite ○

※ AV 650g, drug administration conditions are supplied 0.5% by single dose

※ In appetite deterioration column, ○ indicates no appetite deterioration, and × represents appetite deterioration.

INDUSTRIAL APPLICABILITY According to the present invention, an antiparasitic drug capable of controlling oral administration of surface parasites such as farmed fish can be provided. By adjusting the dosage and the duration of administration, the effect can be exerted without expressing the side effects of the bithionol.

Claims (11)

A method for controlling body surface parasites of fish, characterized by orally administering 50 to 250 mg / kg body weight / day of vithionol to the fish. The method of claim 1, A method for controlling body surface parasites, which is administered orally for 1 to 3 days. The method of claim 1, Body parasite control method characterized in that oral administration of bithionol every other day. The method according to any one of claims 1 to 3, A method for controlling body surface parasites in which fish is either perch, flounder or puffer fish. The method according to any one of claims 1 to 3, Fish spearfish, defense, bushley, longfin snailfish, flying, horse mackerel, white horse mackerel, perch, red snapper, yellow tang, red barley, bellow, halibut, yellow flounder, cockfish, stone bream, river bream, reference shark, fish, Body parasite control method of any of the turbot, tilapia. The method according to any one of claims 1 to 3, A method of controlling parasitic parasites in which fish is caterpillar, defense, bushley or flounder. A feed for fish farming for body surface parasites, characterized by the addition of bithionol so that fish can ingest 50 to 250 mg / kg body weight / day. The method of claim 7, wherein A fish feed for body surface parasite control, in which bithione is added to a bass fish feed so that bass fish can ingest 60 to 250 mg / kg body weight / day. The method of claim 8, A fish-based feed for body parasites, where the fish is caterpillar, defense or bushley. The method of claim 7, wherein A fish feed for body surface parasite control, in which viburnum is added to the feed for the flounder fish so that the flounder can ingest 50 to 200 mg / kg of body weight / day. The method of claim 10, Fish farming for the control of parasitic parasites in which fish are flounder.

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