&#; &#;&#;&#; &#;&#;&#;&#;&#;(praziquantel)&#; &#;&#;&#;&#;(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. .
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&#;&#;&#; &#;&#;&#;&#; &#; &#;&#;&#;&#; &#;&#; &#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;(Microcotyle sebastis), &#;&#;&#;&#; &#;&#;(Bivagina tai), &#;&#;&#;&#;&#;&#;&#;&#;&#;(Dactylogyrus) &#; &#;&#; &#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;&#;(Monogenea)&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;. &#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#; &#;&#; 2&#;&#;&#;&#; &#;&#; &#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;, &#;&#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#; &#;&#; &#;&#;&#;.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.
&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;, &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#; &#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#;(oncomiracidium)&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;. &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#; &#;&#;&#;, &#;&#; &#;&#; &#;&#;&#; &#;&#; &#; &#;&#;&#;&#; &#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;.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.
&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;(formalin)&#;&#; &#;&#; &#;&#;&#;(masoten)&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;. &#;&#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#; &#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#;. &#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;, &#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;.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.
&#;&#;&#; &#;&#; &#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;(praziquantel) &#;&#;&#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;[Fish Pathology,Diseases of Aquatic Organisms]&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;.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. .
&#;&#;&#;&#;&#;&#; &#;&#;&#; &#; &#;&#;&#;&#;[Bayer A.G.&#; E. Merck, Darmstadt]&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;. &#;&#;&#;&#;&#;&#;&#;&#;&#;(pyrazinoisoquinoline) &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#;, J. Seubert &#;&#; &#;&#;&#; Merck&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;. &#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#;, &#; 12&#; &#;&#;&#;&#; &#;&#;&#; &#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;. &#;&#;&#;&#;&#;&#; &#; &#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;, &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#;. &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#;, &#;&#; &#;&#;&#;(Food and Drug Administration)&#; &#;&#; &#; &#;&#;&#; &#;&#;&#; &#;&#;, &#;&#;&#;&#;&#;.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 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 and in the United States in . Fraziquantel has been widely used in Europe since , and has been used worldwide in the s. 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 , and was approved and registered as a human drug in by the US Food and Drug Administration.
&#;&#;&#;&#;&#;&#; WHO&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;, &#;&#; &#;&#; &#; &#; 1&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;.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.
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&#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#; Merck&#;&#; 36&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;, &#;&#;&#;&#;, &#;&#;&#;&#;, &#;&#;&#;&#; &#; &#; &#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#; &#; &#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#; &#;&#;&#;[Leopold et al., ].&#;&#;&#; &#;&#;&#;&#;&#;&#;(pharmacokinetic) &#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;. &#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#;&#; WHO&#; IARC(International Agency for Research on Cancer)&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#;, &#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;, &#;&#;&#;, &#;&#; &#;&#; &#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;[WHO, ].Psychological, clinical, neurological, hematological and other studies of 36 healthy volunteers at Merck in 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., ]. 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, ].
&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;(Diplostomum spathaceum)&#; &#;&#;&#;&#;[Blyund and Sumari, ], &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#;(Clinostomum marginatum)&#; &#;&#;&#;&#;[Lorio, ] &#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#;[Pool et al., ; Moser et al., ; Sanmartin Duran et al., ] &#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#;. &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#;, &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;.Examples of the application of such praziquantel to fish include the cyst larvae of the Diplostomum spathaceum (Blyund and Sumari, ), 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, ] and worms parasitic in the gut of marine and freshwater fish [Pool et al., ; Moser et al., ; Sanmartin Duran et al., ] 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.
&#;&#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#; &#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#; &#;&#;. &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;&#;(neurocysticercosis)&#; &#;&#;&#; &#;&#;&#; &#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#;&#;&#; &#;&#;. &#;&#;&#;&#;&#; &#;&#;&#;&#;(histamine) H2-&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#; &#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;, &#;&#; &#;&#; &#;&#;&#; &#; &#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#;. &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#;&#;&#; &#;&#; &#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; P450&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;, &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#;&#;&#; &#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#;&#;&#;&#; &#; &#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#;&#; &#;&#;&#; &#;&#; &#; &#;&#; &#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#;&#;&#; &#;&#;&#;&#; &#;&#;&#; &#;&#;&#; &#;&#;.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.
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