KR20020028060A - Treatment of gill monogenean disease in fish using praziquantel and cimetidine - Google Patents

Abstract

PURPOSE: A method for treatment of gill disease of fishes by orally administrating a mixture liquid of praziquantel and cimetidine through feed is provided which is economical and has an increased treatment effect with a small amount of praziquantel as compared to prior art. CONSTITUTION: Feed is prepared by using praziquantel and cimetidine as a therapeutically effective drug and the feed is taken to fishes infected with gill disease in an amount of 5 to 300mg/kg of praziquantel and cimetidine respectively. The fishes are Sebastes schlegeli, red sea bream, sea bass, yellow tail, carp, catfish, eel and the like.

Description

Treatment of gill monogenean disease in fish using praziquantel and cimetidine}

The present invention relates to a method for treating gill aphids of fish using a combination of praziquantel and cimetidine, and more particularly, praziquantel and human body, which are conventionally used as anti-enteritises of humans and veterinary animals. The present invention relates to a new method for treating gill repellents that is economical and maximizes the therapeutic effect by using cimetidine, which is used as a therapeutic agent for duodenal ulcer, as a combination and applying it to gill repellents of fish with very low therapeutic efficiency. .

Among the diseases that occur during the benign process of fish, gill respiratory disease is caused by several types of monogenea, such as Microcotyle sebastis , Bivagina tai, and Dactylogyrus genus. Refers to a disease that causes parasites in gills and damages fish. The parasites push their heads into blood vessels distributed in the gills of parasitic gills, sucking blood or sucking tissue, causing severe anemia and necrotic tissue necrosis in fish, as well as wounds caused by their parasites. Secondary to facilitate the invasion of pathogens, such as bacteria, and cause a lot of harm, such as causing severe stress on fish.

The gill larvae of fish go through the life cycle of the common larvae, and the eggs spawned from the larvae parasites in the gills of the fish are attached to the cage by the filament structure at both ends of the gills. It hatches into cilia larvae called oncomiracidium and parasitises in the gills of fish. This direct living environment can lead to severe infection in a short time, which causes severe productivity loss, such as the death of fish and impede growth.

The treatment of gillsporosis, which has been used in conventional aquaculture sites, has mainly used chemotherapeutic agents such as formalin or masotene, which are known to have pesticidal properties against a wide range of parasitic species. However, formalin is currently not only regulated as a fishery drug due to environmental pollution and human health problems, but is also known to have poor treatment efficiency for fish gill respiratory disease through a formalin bath. Masoten is also used for the treatment of gillsworms in fish by using a method of bathing, but the treatment efficiency is very weak.

Recently, however, the present inventors have developed a method for treating fish gill insufficiency through oral administration of praziquantel, and has been published in a famous foreign journal [Fish Pathology, Diseases of Aquatic Organisms] to suggest a new treatment for gill slits. .

Fraziquantel is the result of a cooperative study by two German pharmaceutical companies, Bayer A.G. and E. Merck, Darmstadt. The antiparasitic activity of pyrazinoisoquinoline derivatives was discovered in Bayer Laboratories in 1972 and was continuously studied by researchers at Merck, including J. Seubert and others. These studies validated the anti-entermal effect of Fraziquantel's broad range of human insecticides, and patents were granted in Germany in December 1973 and in the United States in 1977. Fraziquantel has been widely used in Europe since 1978, and has been used worldwide in the 1980s. Praziquantel was also recognized for its importance as a veterinary drug and was approved for use as a veterinary drug in the United States in 1980, and was approved and registered as a human drug in 1982 by the US Food and Drug Administration.

Fraziquantel is the first anti-entrepreneur to meet all of the requirements of WHO as a chemotherapeutic agent for treating a wide range of parasitic diseases in humans. Its advantages include high therapeutic efficiency, low toxicity, and a single oral administration. Remains the only medication to treat it.

Psychological, clinical, neurological, hematological and other studies of 36 healthy volunteers at Merck in 1978 based on the results of many animal studies on the toxicity and antiparasitic effects of Fraziquantel. Clinical and biochemical investigations revealed no changes related to drug administration [Leopold et al., 1978]. These pharmacokinetic studies have led to Fraziquantel's toxic changes in major functions and organs of the human body. It was confirmed that it does not cause Praziquantel's suitability as a therapeutic agent. In addition, comprehensive toxicity studies on praziquantel through various test systems have been conducted by WHO in collaboration with the International Agency for Research on Cancer (IARC), which has resulted in harmful effects on mutagenesis, cancer induction, malformations and embryos. No problem was identified [WHO, 1985].

Examples of the application of such praziquantel to fish include the cyst larvae of the Diplostomum spathaceum (Blyund and Sumari, 1981), which are parasitic in the eyes of trout, and the clinostium dryness parasitic in the muscles of channel catfish. Encapsulated larvae of Clinostomum marginatum [Lorio, 1989] and worms parasitic in the gut of marine and freshwater fish [Pool et al., 1984; Moser et al., 1986; Sanmartin Duran et al., 1989] have been used to treat parasitic diseases. However, these parasites are all internal parasitic species that are parasitic in the body of fish, and there are no reports of oral administration of Fraziquantel to control external parasites such as gill insects.

It is clear that treatment of fish gillsworms with oral administration of Fraziquantel is very useful in that it does not stress the fish at all and saves labor. However, despite the fact that Praziquantel's oral administration has been shown to be an effective treatment for gillsworms in fish, it is very costly for the aquaculture industry to use because it is quite expensive. Giving is the biggest disadvantage. Therefore, in order to solve these shortcomings, it is necessary to develop a technology that can achieve an effective therapeutic effect at the minimum possible concentration of praziquantel.

In order to reduce the dosage of praziquantel and at the same time increase the therapeutic effect, it may be possible by slowing down the rate at which praziquantel is broken down in the liver and excreted in the kidneys. Recently, there have been reports of good results obtained by simultaneous administration of cimetidine in order to increase the therapeutic efficiency in treating cysticidercosis using praziquantel. Cimetidine is a type of histamine H2-receptor antagonist that has been used originally to suppress gastric acid secretion in the treatment of gastric ulcers in humans, but it also slows down the excretion rate by inhibiting the metabolism of some specific drugs in the liver, It has been found to have an effect of increasing the concentration. The effect of cimetidine is mainly due to the inhibition of the metabolism of the drug by inhibiting the activity of cytochrome P450 present in the liver or kidney, and this function is suppressed the metabolism and excretion of praziquantel in the blood when used simultaneously with praziquantel It has been shown to increase the concentration of prazicantel and also increase the pesticidal effect of the parasite by allowing prazicantel to stay in the blood for longer than administered alone.

Therefore, the present invention not only improves the treatment efficiency of gillal insecticidal disease through simultaneous oral administration of praziquantel and cimetidine combination, but also with the administration of a much smaller dose of praziquantel than the amount of praziquantel previously disclosed by the present inventors. The purpose of the present invention is to provide a treatment method for gillsworms of fish that greatly reduces the economic burden, which is the biggest disadvantage of Fraziquantel, by developing a method capable of high therapeutic effect.

The present invention is characterized by a method for the treatment of gillsworms through oral administration of praziquantel and cimetidine combination to fish infected with gills.

Hereinafter, the present invention will be described in detail.

The oral administration of the praziquantel and cimetidine combinations for gill insufficiency of fish according to the present invention is the world's first treatment for the treatment of ectoparasites of fish including gills. In other words, the present invention can not only increase the therapeutic effect of gill insufficiency by concurrently administering cimetidine in the treatment of gillal insufficiency of fish through oral administration of praziquantel, but also greatly reduces the dosage of praziquantel. Because it can be obtained, there is an advantage that can greatly reduce the economic burden. As in the present invention, in the treatment of gills, it is a new treatment technology that has not been reported worldwide by praziquantel and cimetidine combination.

In the present invention, a combination of praziquantel, which is conventionally used as an anti-enteritiser of humans and veterinary animals, and cimetidine, which is used as a therapeutic agent for stomach and duodenal ulcers in humans, is used as a combination of By applying it to gillsworms, we have developed a new method for treating gillsworms that is economical and has excellent therapeutic effects.

Praziquantel used in the present invention has been verified through a number of pharmacokinetic studies that do not cause toxic changes in the main functions and organs of the human body has been validated as a therapeutic drug and safety, even in the case of cimetidine no harm to the human body It has been proven to be a safe drug that does not have a prescription and is currently registered as a drug without a doctor's prescription in countries such as the United States. Therefore, when used in fish that are consumed raw, since it does not harm the human body is very suitable drugs for the treatment of raw fish.

In the present invention, a specific method for applying the praziquantel and cimetidine mixture to fish is an oral administration method added and administered in a feed, which will be described in detail below.

First, in order to determine the correct effective therapeutic concentration when administered orally alone, Fraziquantel orally administered Fraziquantel in various concentrations to fish infected with gills. As a result, it has been found through the present invention that it is preferable to administer Fraziquantel at 50 to 300 mg / Kg per body weight of fish, and more preferably at 100 to 200 mg / Kg per body weight of fish. The reason for limiting the concentration of oral administration in the above range is that the remedy effect is lower than the above range, the concentration above this does not have a significant difference in the remedy effect.

In order to slow the metabolic rate and excretion of phagequattel in the body and increase the concentration of phagequattel in the blood, the treatment of phagequattel and cimetidine is orally administered to the fish. As a result, it was shown that the concentration of cimetidine is effective to be administered at a concentration of 50 to 300 mg / Kg per weight of fish at each concentration of praziquantel, and more preferably 100 to 200 per weight of fish. It is administered in mg / Kg. The reason for limiting the concentration of oral administration in the above range is that the relief effect is lower than the above range, the concentration above this does not have a significant difference in the relief effect.

In order to use the above oral administration method according to the actual cage farming, a feed containing praziquantel and cimetidine mixture is prepared, and the fish infected with gill insecticidal is ingested by ingesting the above feed. Use the method.

The production of the feed is prepared by mixing the raw powder of praziquantel and cimetidine raw powder, and the feed mixed with the drug is produced by pellets by adjusting the diameter to fit the size of the fish to be treated with a pellet maker or It can be administered by adsorbing on a commercial feed.

It is preferable that the feed prepared as described above is administered to fish infected with gill insects 3 to 6 times at intervals of 2 to 5 days. At this time, the reason for giving a time interval in the above range when administering the feed is to relieve the re-infected insects hatching from the spawned eggs, limited to this range of the time interval and the number of feed administration The reason for this is that a significant therapeutic effect can be obtained by this administration method.

Fishes that can be applied to treatment of gillsworms using praziquantel and cimetidine combination include zodiac rock, dome, sea bass, defense, carp, catfish, eel, etc., and all other fish that can be consumed by circuit You can.

As described above, when the combination of praziquantel and cimetidine is used as a method for treating gill insufficiency of fish, it is economically very useful because it shows the same therapeutic effect with only half the concentration of prajiquantel alone. .

Although this invention is demonstrated in detail based on an Example, this invention is not limited to a following example.

Example

Fishes from the Jeolbolak Hatchery in Tongyeong were purchased from Jeolbolak Cheer [length: 13-16 cm] and used for 1 week in a laboratory tank. Seventy fish were divided into seven groups of 10 fish and incubated in a laboratory tank (50 L). At the time of the experiment, the water temperature was 20 ± 1 ℃ and salinity was 33 ‰.

Fish were anesthetized with MS222 and gastrointestinal tubes were used to administer 200 mg of Fraziquantel per kg body weight in the first group, 100 mg in the second group, 50 mg in the third group, and kg in the fourth group. The praziquantel 200 mg and cimetidine 200 mg, the fifth group was treated with 100 mg of praziquantel and 200 mg of cimetidine, and the sixth group was administered 50 mg of praziquantel and 200 mg of cimetidine. The seventh group received the same amount of normal saline as control.

To determine the therapeutic effect of the drug, 84 hours after oral administration, all fish in each group were caught, and all gills were separated from each individual, and the number of gill worms parasitic in gills under the dissecting microscope was quantitatively counted.

As a result, all of the experimental groups showed significantly lower infection intensity than the control group except the experimental group administered 50 mg / kg of body weight of Praziquantel. In particular, the experimental group administered with Fraziquantel 200 mg and cimetidine 200 mg simultaneously showed 100% therapeutic effect. The therapeutic effect of the experimental group administered with cimetidine in combination with praziquantel showed the same level as the therapeutic effect of the experimental group administered with praziquantel alone even at the concentration of praziquantel 1/2 [Table 1 and Table 2]. .

As described above, in the case of treating gill aphids for reproductive fish using a combination of praziquantel and cimetidine according to the present invention, oral administration is an excellent method first developed in the treatment of monolithic diseases of fish. In addition, it is possible to effectively treat gill sludge in fish farms without stress or fish labor due to bathing in the cage, and it can greatly contribute to productivity improvement and cost reduction of reproductive fish.

Claims (4)

Praziquantel (cizitidine) combination of cimetidine (fish), characterized in that the treatment of gill respiratory disease of fish characterized in that applied to the fish infected. The method of claim 1, wherein after preparing a feed containing the combination of praziquantel and cimetidine as an effective drug, the feed is treated orally by feeding the feed to the fish infected with gillworms. . The fish of claim 2, wherein the oral administration administers a Fraziquantel concentration at 5 to 300 mg / Kg per fish body weight, and the cimetidine concentration at 5 to 300 mg / Kg per body weight of fish. Method of treatment of gillsworm. The method according to claim 1 or 2, wherein the fish comprises zombolac, dome, perch, yellowtail, carp, catfish, eel and common fish that can be consumed by circuit.