JP2012067022A - Treating agent for edwardsiellosis of fish containing fosfomycin as active component - Google Patents
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Abstract
Description
本発明は、魚類のエドワジエラ症治療剤に関する。 The present invention relates to a therapeutic agent for fish edwardieriasis.
エドワジエラ症はグラム陰性桿菌であるエドワジエラ・タルダ（Edwardsiella tarda）によって引き起こされる養殖魚の感染症であり、魚齢に関係なく周年発生し、慢性化しやすくなることから、ヒラメやマダイなどの養殖魚の出荷量が減少させられるため、養殖現場においては大きな問題となっている。
従前から予防治療対策の研究開発は進められているが、本症に対する有効な治療薬はなく、ワクチンも実用化されていない状況である。従来、魚類のエドワジエラ症に対する治療剤として、塩酸オキシテトラサイクリンが使用されているが、十分な治療効果が得られず、また耐性菌を発生させてしまうという問題がある。
その他にもエドワジエラ症の治療剤として、生薬を用いた予防治療剤（特許文献１）や抗菌活性を有する中鎖脂肪酸を含む魚類用飼料（特許文献２）、あるいは、エドワジェラ・タルダ由来株の不活化菌体を用いたワクチン（特許文献３）などが研究されているが、いまだ製品化されたものはない。
そのため、養殖現場からは魚類養殖に甚大な経済的損失を与えるエドワジエラ症に対する有効な治療剤の開発を切望されている。
Edwardsiellosis is an infectious disease of cultured fish caused by the Gram-negative gonococcus Edwardsiella tarda, which occurs every year regardless of the age of the fish and is likely to become chronic. This is a major problem at aquaculture sites.
Research and development of preventive treatment measures has been underway for a long time, but there is no effective therapeutic drug for this disease, and no vaccine has been put into practical use. Conventionally, oxytetracycline hydrochloride has been used as a therapeutic agent for fish edwardieriasis, but there is a problem that a sufficient therapeutic effect cannot be obtained and resistant bacteria are generated.
In addition, as a therapeutic agent for Edwardsiellosis, prophylactic and therapeutic agents using herbal medicine (Patent Document 1), fish feed containing medium chain fatty acids having antibacterial activity (Patent Document 2), A vaccine using activated cells (Patent Document 3) has been studied, but none has been commercialized yet.
For this reason, the aquaculture site is eager to develop an effective therapeutic agent for edwardiadiosis that causes enormous economic loss to fish culture.
本発明の課題は、マダイなどの養殖魚のエドワジエラ症に対する有効な治療剤を提供することにある。 An object of the present invention is to provide an effective therapeutic agent for Edwardsiellasis in cultured fish such as red sea bream.
前記の課題を解決するために研究を重ねた結果、ホスホマイシンが魚類のエドワジエラ症に対して優れた治療効果を示すことを見出した。すなわち、本発明はホスホマイシンを有効成分として含有する魚類のエドワジエラ症治療剤を提供するものである。 As a result of repeated studies to solve the above-mentioned problems, it has been found that fosfomycin exhibits an excellent therapeutic effect on fish edwardierosis. That is, the present invention provides a therapeutic agent for fish edwardieriasis containing fosfomycin as an active ingredient.
本発明は、
［１］ホスホマイシンを有効成分として含有する魚類のエドワジエラ症治療剤、
［２］前記［１］の魚類がマダイ、ブリ、カンパチ、マアジ、シマアジ、キジハタまたはヒラメである魚類のエドワジエラ症治療剤、
［３］ホスホマイシンの有効量を投与することを特徴とする魚類のエドワジエラ症治療方法、
［４］投与方法が、経口、注射または薬浴である、前記［３］のエドワジエラ症治療方法
に関する。
The present invention
[1] A therapeutic agent for fish edwardieriasis containing fosfomycin as an active ingredient,
[2] A therapeutic agent for edwardiadiosis of fish, wherein the fish of [1] is red sea bream, yellowtail, amberjack, horse mackerel, striped horse mackerel, pheasant grouper, or flounder.
[3] A method for treating Edwardsia disease in fish, comprising administering an effective amount of fosfomycin,
[4] The present invention relates to the method for treating Edwardsia disease according to the above [3], wherein the administration method is oral, injection or drug bath.
本発明の魚類のエドワジエラ症治療剤は、従来の抗菌剤による耐性菌にも抗菌力を示し、養殖飼料に含有させる等の投与方法により、早い摂餌活性の回復を図りながら、エドワジエラ症に感染した魚類の治療を行うことができる。 The therapeutic agent for fish edwardieriasis of the present invention exhibits antibacterial activity against bacteria resistant to conventional antibacterial agents, and infects edwardiaerosis while recovering fast feeding activity by an administration method such as inclusion in cultured feed. Can be used to treat fish.
本発明の治療剤はホスホマイシンを有効成分とするものである。ホスホマイシンは医薬品として、グラム陰性菌やグラム陽性菌による感染症の治療に用いられており、他の抗生物質と交差耐性が無いことが知られている。また、ヒト以外に牛の大腸菌性下痢症やサルモネラ症の治療に用いられている。さらに、魚類のパスツレラ属細菌性類結節症の治療に用いられている（特許第２９９３８１２号）。ホスホマイシンとしては、フェネチルアンモニウム塩、ナトリウム塩（ホスホマイシン・ナトリウム）またはカルシウム塩（ホスホマイシン・カルシウム）等の塩を用いることができる。 The therapeutic agent of the present invention contains fosfomycin as an active ingredient. Fosfomycin is used as a pharmaceutical for the treatment of infections caused by Gram-negative and Gram-positive bacteria, and is known to have no cross-resistance with other antibiotics. In addition to humans, it is used to treat bovine Escherichia coli diarrhea and salmonellosis. Furthermore, it is used for the treatment of fish Pasteurella spp. Bacterial nodules (Japanese Patent No. 2993812). As fosfomycin, salts such as phenethylammonium salt, sodium salt (fosfomycin / sodium) or calcium salt (fosfomycin / calcium) can be used.
本剤が適用できる魚類としては、エドワジエラ・タルダ（Edwardsiella tarda）に感染する魚類であれば、特に制限されないが、例えば、マダイ、ブリ、カンパチ、マアジ、シマアジ、キジハタ、ヒラメ等があげられる。
ここでいうエドワジエラ・タルダ（Edwardsiella tarda）は定型および非定型を問わない全ての株が含まれる。
The fish to which this agent can be applied is not particularly limited as long as it is a fish that is infected with Edwardsiella tarda.
Edwardiella tarda here refers to all stocks, both regular and atypical.
本発明の治療剤の投与方法は特に限定されず、経口、注射、薬浴（海水または淡水に溶解）等、様々な方法によって行うことができる。その中でも養殖魚飼育形態から経口投与が好ましい。経口投与の方法も特に制限されないが、一般にはホスホマイシンを賦形剤に混合し、製剤化したものを餌料（例えば魚肉ミンチ、モイストペレット、ドライペレット等）に含有させて経口投与する方法が好ましい。 The administration method of the therapeutic agent of this invention is not specifically limited, It can carry out by various methods, such as oral, injection, and a chemical bath (dissolving in seawater or fresh water). Among these, oral administration is preferable from the farmed fish breeding form. The method for oral administration is not particularly limited, however, generally preferred is a method in which fosfomycin is mixed with an excipient and formulated into a feed (eg, fish mince, moist pellets, dry pellets, etc.) for oral administration.
また、粉剤、散剤、顆粒剤などの製剤とした上で、餌料と混合して用いることができる。製剤に配合される成分は特に限定されないが、例えば、界面活性剤として、ポリオキシエチレン硬化ヒマシ油６０、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、大豆リン脂質及びプロピレングリコール脂肪酸エステルなど、結合剤として、ヒドロキシプロピルセルロース（Ｍ、Ｌ）、カルボキシルメチルセルロースナトリウム、アルギン酸ナトリウム及びポリビニールアルコール、防腐剤として、パラオキシ安息香酸メチル及びパラオキシ安息香酸プロピル、賦形剤として、白糖、精製白糖、粉糖、コーンスターチ、乳糖、グルコース及びＤ−マンニトールなどを配合することができる。製剤の製造方法は常法によって行うことができる。 In addition, it can be used as a preparation such as powder, powder, granule and the like and mixed with feed. Although the component mix | blended with a formulation is not specifically limited, For example, as surfactant, polyoxyethylene hydrogenated castor oil 60, glycerol fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, soybean phospholipid, propylene glycol fatty acid ester, etc. As binders, hydroxypropylcellulose (M, L), sodium carboxymethylcellulose, sodium alginate and polyvinyl alcohol, as preservatives, methyl paraoxybenzoate and propyl paraoxybenzoate, as excipients, white sugar, purified white sugar, powdered sugar Corn starch, lactose, glucose, D-mannitol and the like can be blended. The preparation method of a formulation can be performed by a conventional method.
本発明の治療剤の投与量は、魚体重１ｋｇ当たりホスホマイシンとして１０〜６０ｍｇ（力価）の範囲で適宜調整することができるが、より好ましくは、３０〜５０ｍｇ（力価）の範囲で行うことができる。投与回数や投与日数は特に限定されないが、１日１〜３回に分けて、４〜８日間程度投与することができる。 The dose of the therapeutic agent of the present invention can be appropriately adjusted within the range of 10 to 60 mg (titer) as fosfomycin per kg of fish body weight, more preferably within the range of 30 to 50 mg (titer). Can do. Although the frequency | count of administration and the administration days are not specifically limited, It can divide into 1 to 3 times per day and can be administered for about 4 to 8 days.
次に本発明の魚類のエドワジエラ症治療剤の効果を以下の実施例により更に詳細に説明するが、本発明はこれらの実施例に限定されるものではない。 Next, the effects of the therapeutic agent for fish Edwardsia disease of the present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
（試験例１）ホスホマイシンの試験管内抗菌活性
エドワジエラ症の原因菌エドワジエラ・タルダ（Edwardsiella tarda）に対するホスホマイシンの最小発育阻止濃度（ＭＩＣ）を、日本化学療法学会のＭＩＣ測定法に準じて測定した。その結果を表１に示した。ホスホマイシンのＭＩＣは、塩酸オキシテトラサイクリンに対する感受性株（１５株：E08-18、E09-10、E09-14、E09-15、E09-19、E09-20、E09-25、E09-28、E09-32、E09-36、E09-37、E09-38、E09-40、E09-43、E09-44の株）及び耐性株（７株：E09-2、E09-16、E09-21、E09-24、E09-30、E09-31、E09-39の株）に対しても、１〜２μｇ／ｍＬであり、一定の抗菌力を示した。すなわち、ホスホマイシンは塩酸オキシテトラサイクリンに対する耐性株に対しても強い抗菌活性を示すことが確認された。
(Test Example 1) In vitro antibacterial activity of fosfomycin The minimum growth inhibitory concentration (MIC) of fosfomycin against Edwardsiella tarda, the causative bacterium of Edwardsiella disease, was measured according to the MIC measurement method of the Japanese Society of Chemotherapy. The results are shown in Table 1. MIC of fosfomycin is sensitive to oxytetracycline hydrochloride (15 strains: E08-18, E09-10, E09-14, E09-15, E09-19, E09-20, E09-25, E09-28, E09-32). , E09-36, E09-37, E09-38, E09-40, E09-43, E09-44 strains) and resistant strains (7 strains: E09-2, E09-16, E09-21, E09-24, E09-30, E09-31, and E09-39 strains) were 1 to 2 μg / mL and showed a certain antibacterial activity. That is, it was confirmed that fosfomycin exhibits a strong antibacterial activity even against a strain resistant to oxytetracycline hydrochloride.
（試験例２）マダイのエドワジエラ症原因菌エドワジエラ・タルダ（Edwardsiella tarda）の人工感染治療試験（１）
平均体重２９ｇのマダイ稚魚を、１水槽に２０尾ずつ２群に分けて収容し、エドワジエラ・タルダ（Edwardsiella tarda）（Ｅ０８−１８株：2008年7月愛媛県のマダイの腎臓から分離）浮遊液を１個体当たり３．６×１０６ＣＦＵ／ｍＬ腹腔内注射し、流水で飼育した。試験群は、ホスホマイシン・カルシウム４０ｍｇ（力価）／ｋｇ魚体重を投薬した１群と無投薬対照群１群の計２群に設定した。
菌接種後、ホスホマイシン・カルシウムの１０％製剤を、水を吸着させた市販の養魚用ドライペレットに所定の濃度になるように展着し、これの１日量を１日に１〜３回に分けて、６日間連続して自由摂餌により経口投与した。感染後１４日目までの供試魚の死亡率を計測した。死亡魚についてはエドワジエラ症原因菌で使用する選択培地（ＳＳ寒天培地）へ腎臓から菌分離を行った。なお、試験期間中の水温は２３．８〜２４．６℃であった。
その結果を表２に示した。無投薬対照群での死亡率は、９５％であった。死亡魚１９尾中１８尾からエドワジエラ・タルダが分離され、エドワジエラ症による死亡率が９０％であることが確認された。一方、投薬群の死亡率は１０％であり、菌分離によりエドワジエラ症による死亡であることが確認され、ホスホマイシンの優れた治療効果が認められた。
また、魚の摂餌は菌接種後に低下したが、ホスホマイシンの投薬により摂餌活性の回復が早まることが認められた。
(Test Example 2) Artificial infection treatment test of red sea bream Edwardsiella tarda (1)
A fish of red sea bream with an average weight of 29 g is housed in two groups of 20 fish in one aquarium. Edwardsiella tarda (E08-18 strain: separated from the kidney of red sea bream in Ehime Prefecture in July 2008) Was injected intraperitoneally with 3.6 × 10 6 CFU / mL per animal and reared in running water. The test groups were set to two groups, one group administered with fosfomycin / calcium 40 mg (titer) / kg body weight of fish and one group with no administration control.
After inoculation with bacteria, a 10% formulation of fosfomycin / calcium was spread on a commercially available dry pellet for fish farming to which water was adsorbed to a predetermined concentration, and the daily dose was reduced to 1 to 3 times a day. Separately, it was orally administered by free feeding for 6 consecutive days. The mortality of the test fish was measured up to 14 days after infection. For dead fish, the bacteria were isolated from the kidney to a selective medium (SS agar medium) used for the causative bacteria of Edwardsiella disease. The water temperature during the test period was 23.8 to 24.6 ° C.
The results are shown in Table 2. The mortality rate in the untreated control group was 95%. Edwardsiella tarda was isolated from 18 of 19 dead fish, and it was confirmed that the mortality due to Edwardsiellosis was 90%. On the other hand, the mortality rate of the dosing group was 10%, and it was confirmed that the death was due to Edwardsiellosis by bacterial isolation, and an excellent therapeutic effect of fosfomycin was recognized.
Fish feeding decreased after inoculation with bacteria, but it was observed that fosfomycin administration accelerated recovery of feeding activity.
（試験例３）マダイのエドワジエラ症原因菌エドワジエラ・タルダ（Edwardsiella tarda）の人工感染治療試験（２）
平均体重２７ｇのマダイ稚魚を、１水槽に２０尾ずつ３群に分けて収容し、エドワジエラ・タルダ（Edwardsiella tarda）（Ｅ０８−１８株；塩酸オキシテトラサイクリン感受性株）浮遊液を１個体当たり４．６×１０６ＣＦＵ／ｍＬ腹腔内注射し、流水で飼育した。
試験群は、ホスホマイシン・カルシウム４０ｍｇ（力価）／ｋｇ魚体重投薬群、塩酸オキシテトラサイクリン５０ｍｇ（力価）／ｋｇ魚体重投薬群及び無投薬感染対照群１群の計３群を設定した。菌接種後、ホスホマイシン・カルシウムの１０％製剤及び市販の塩酸オキシテトラサイクリン製剤（「水産用ＯＴＣ散「コーキン」」、コーキン化学社製）を、水を吸着させた市販の養魚用ドライペレットに所定の濃度になるように展着し、これの１日量を１日に１〜３回に分けて、ホスホマイシン・カルシウムでは６日間、塩酸オキシテトラサイクリンでは７日間、連続して自由摂餌により経口投与した。感染後１４日目までの供試魚の死亡率を計測した。死亡魚についてはエドワジエラ症原因菌の選択培地（ＳＳ寒天培地）に腎臓から菌分離を行った。なお、試験期間中の水温は２４．１〜２６．０℃であった。
その結果を表３に示した。無投薬対照群での死亡率は、９５％であった。死亡魚からはエドワジエラ・タルダが分離され、エドワジエラ症により死亡したことが確認された。一方、投薬群の死亡率は、ホスホマイシン・カルシウム４０ｍｇ（力価）／ｋｇ魚体重投薬群で２５％、塩酸オキシテトラサイクリン５０ｍｇ（力価）／ｋｇ魚体重投薬群で１００％である。よって、従来の抗生物質よりもホスホマイシンが優れた投薬効果を示すことが確認された。
また、魚の摂餌は菌接種後に低下したが、ホスホマイシンの投薬の方が塩酸オキシテトラサイクリンや無投薬の群よりも摂餌活性の回復が早まることが認められた。
(Test Example 3) Artificial infection treatment test of red sea bream Edwardsiella tarda (2)
A red sea bream with an average weight of 27 g is housed in 3 groups of 20 fish per fish tank, and Edwardsiella tarda (E08-18 strain; oxytetracycline hydrochloride-sensitive strain) suspension is 4.6 per individual. × 10 6 CFU / mL was injected intraperitoneally and kept in running water.
The test groups consisted of a total of 3 groups: fosfomycin / calcium 40 mg (titer) / kg fish body weight dosing group, oxytetracycline hydrochloride 50 mg (titer) / kg fish body weight dosing group, and 1 untreated infection control group. After inoculation with bacteria, a 10% formulation of fosfomycin / calcium and a commercially available oxytetracycline hydrochloride formulation (“OTC powder for fisheries“ Kawkin ””, manufactured by Kokin Chemical Co., Ltd.) are placed on a commercially available dry pellet for fish farming that has been adsorbed with water. It was spread to a concentration, and the daily dose was divided into 1 to 3 times a day, and was orally administered by continuous free intake for 6 days for fosfomycin calcium and 7 days for oxytetracycline hydrochloride. . The mortality of the test fish was measured up to 14 days after infection. For the dead fish, bacteria were isolated from the kidneys on a selection medium (SS agar medium) for causative bacteria of Edwardsiella disease. The water temperature during the test period was 24.1 to 26.0 ° C.
The results are shown in Table 3. The mortality rate in the untreated control group was 95%. From the dead fish, Edwardsiella tarda was isolated and confirmed to have died due to Edwardsiellosis. On the other hand, the mortality rate of the dosing group is 25% in the fosfomycin calcium 40 mg (titer) / kg fish body weight group, and 100% in the oxytetracycline hydrochloride 50 mg (titer) / kg fish body weight group. Therefore, it was confirmed that fosfomycin exhibits a superior dosing effect than conventional antibiotics.
In addition, although feeding of the fish decreased after inoculation with the fungus, it was found that the administration of fosfomycin accelerated recovery of the feeding activity faster than the oxytetracycline hydrochloride or non-administered group.
本発明は、マダイなどの養殖魚のエドワジエラ症に対する治療剤として利用することができる。 INDUSTRIAL APPLICABILITY The present invention can be used as a therapeutic agent for Edwardsiella disease in cultured fish such as red sea bream.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6475425A (en) * | 1987-09-17 | 1989-03-22 | Nisshin Flour Milling Co | Prophylactic acid remedy for edwardsiella infection in fishes |
| WO2000010558A1 (en) * | 1998-08-25 | 2000-03-02 | Nippon Suisan Kaisha, Ltd. | Natural physiologically active substances efficacious against fish diseases and fish feeds containing the same |
| JP2008050300A (en) * | 2006-08-24 | 2008-03-06 | Kawasaki Mitaka Seiyaku Kk | Vaccine for edwardsiellasis and streptococcosis of fish |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6475425A (en) * | 1987-09-17 | 1989-03-22 | Nisshin Flour Milling Co | Prophylactic acid remedy for edwardsiella infection in fishes |
| WO2000010558A1 (en) * | 1998-08-25 | 2000-03-02 | Nippon Suisan Kaisha, Ltd. | Natural physiologically active substances efficacious against fish diseases and fish feeds containing the same |
| JP2008050300A (en) * | 2006-08-24 | 2008-03-06 | Kawasaki Mitaka Seiyaku Kk | Vaccine for edwardsiellasis and streptococcosis of fish |
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| Title |
|---|
| JPN6014034054; Ａｎｔｉｍｉｃｒｏｂ． Ａｇｅｎｔｓ Ｃｈｅｍｏｔｈｅｒ． Ｖｏｌ．４５ Ｎｏ．８, 2001, ｐｐ．２２４５-２２５５ * |
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