CN111132676A - Ten-fold eye composition containing 5-aminolevulinic acid - Google Patents
Ten-fold eye composition containing 5-aminolevulinic acid Download PDFInfo
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- CN111132676A CN111132676A CN201880060955.2A CN201880060955A CN111132676A CN 111132676 A CN111132676 A CN 111132676A CN 201880060955 A CN201880060955 A CN 201880060955A CN 111132676 A CN111132676 A CN 111132676A
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- decapod
- vibrio parahaemolyticus
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Fodder In General (AREA)
- Feed For Specific Animals (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention provides a decapod oral administration composition containing 5-aminolevulinic acid (5-ALA) and a method comprising causing the decapod to ingest 5-aminolevulinic acid. The oral administration composition for the ten-foot mesh can be used for feeding the ten-foot meshCulturing and breeding, and can effectively prevent and treat vibrio parahaemolyticus (Vibrio parahaemolyticus)Vibrio parahaemolyticus) EMS/AHPND (early death syndrome/acute hepatopancreatic necrosis disease) which is a pathogenic bacterium. In addition, the oral administration composition for decapod targets can promote the growth of decapod targets by administering a predetermined amount of the composition.
Description
Technical Field
The present invention relates to an orally administrable composition for decapod subjects, feed and feed additive, which contains at least one selected from 5-aminolevulinic acid (5-ALA) or an ester thereof, or a salt thereof, and more particularly, to an orally administrable composition for prophylaxis and treatment of decapod subject early death syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND), which contains at least one selected from 5-ALA or an ester thereof, or a salt thereof. The present invention also relates to a method for preventing and treating the decapod early death syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) comprising causing the decapod order to bioabsorb at least one selected from 5-ALA or an ester thereof, or a salt thereof, and more particularly, to a method for preventing and treating the decapod order early death syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) comprising causing the decapod order to bioabsorb at least one selected from 5-ALA or an ester thereof, or a salt thereof.
Background
The production of shrimp worldwide has proliferated from 301 ten thousand tons in the year of "4 (1992)" to 768 ten thousand tons in the year of "24 (2012)". In recent years, the development of shrimp farming has been attracting attention from 30% in 4(1992) to 56% in 24(2012) over the half of the production amount in view of the proportion of the production amount by farming (non-patent document 1). In shrimp farming, unlike in natural environments, various diseases have been observed in shrimp farms for reasons such as raising shrimp at high density and applying excessive stress. Since the survival rate of cultured aquatic animals and plants has a great influence on the culture operation, proper treatment of diseases is required in the culture industry.
In recent years, shrimp farming is in a state of crisis in some countries due to diseases of shrimps called EMS (early mortality syndrome) which occur among young shrimps and have a mortality rate of approximately 100%. The disease was first reported in china in 2009, then spread to southeast asia such as vietnamese, thailand, malaysia, etc., and was reported to occur in mexico in 2013. In EMS, since the liver and pancreas of shrimp show symptoms such as discoloration and Necrosis, this early death syndrome is also called EMS/AHPND (Acute hepatopanctional Necrosis Disease). Moreover, it is also known that the EMS/AHPND is due to a specific type of Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Is caused by infection (non-patent document 2).
A method of using a vaccine for vibrio infection of prawn has been developed (patent document 1). However, in patent document 1, Vibrio parahaemolyticus is suggested as a target bacteriumVibrio parahaemolyticus) However, there is no specific disclosure about Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Moreover, it is not clear at all that the vaccine therapy is effective for the prevention and treatment of EMS/AHPND. Furthermore, it has been clarified that this method is preferable if the method is a method for preventing and treating EMS/AHPND using a substance which is cheaper and more easily available than a special vaccine. It is further preferable that the prevention and treatment of EMS/AHPND and the culture of shrimp are advantageous.
It is known that 5-ALA is present in mitochondria of cells, is biosynthesized in mitochondria in animals, binds to iron components to become heme, a raw material for cytochrome, and the like, and is a component necessary for metabolism, and is biosynthesized in chloroplasts in plants, binds to magnesium to become chlorophyll, and is a component necessary for photosynthesis. Further, patent document 2 discloses a method for producing 5-ALA phosphate, and further discloses a method for synthesizing 5-ALA hydrochloride. Further, a method for producing 5-ALA using a microorganism is also known (patent document 3).
Documents of the prior art
Patent document
Patent document 1: japanese patent laid-open publication No. 2015-137254
Patent document 2: japanese patent laid-open No. 2006 and 182753
Patent document 3: japanese patent laid-open publication No. 2005-333907
Patent document 4: japanese laid-open patent publication No. 2001-316255
Non-patent document
Non-patent document 1: white paper of aquatic products of 25 years and (6) production conditions of breeding industry of the world
Non-patent document 2: mohammad Jalil Zorriehzahra, Reza Banaederakhshan; EarlyMortability Syndrome (EMS) as new Emerging thread in Stirp Industry; advances in animal and Veterinary Sciences, March 2015, Volume 3, speciality 2, Pages 64-72
Disclosure of Invention
Therefore, there has been a strong demand for the development of a decapod oral administration composition which is useful for raising and breeding decapod organisms including prawn family organisms, particularly for preventing and treating EMS/AHPND. In addition, there is a demand for the development of a decapod orally administrable composition that can not only prevent and treat EMS/AHPND of a decapod organism, but also promote its growth. However, such a composition for oral administration for a sufficient purpose has not been achieved.
The present inventors have intensively studied a composition for oral administration which can solve the above-mentioned problems and have found that a composition containing at least one selected from 5-ALA or an ester thereof, or a salt thereof is extremely useful, and have completed the present invention based on this finding.
Namely, the present invention is as follows.
[1] An oral composition for decapod use comprises at least one selected from 5-aminolevulinic acid (5-ALA) or an ester thereof, or a salt thereof.
[2] An orally administered composition for preventing and treating early mortality syndrome/acute hepatopancreatic necrosis (EMS/AHPND) of the order of ten comprises at least one selected from 5-aminolevulinic acid (5-ALA), an ester thereof, and a salt thereof.
[3] The composition according to the above [1] or [2], wherein the order decapod is a family prawn.
[4] The composition according to any one of the above [1] to [3], wherein the composition is a feed or a feed additive.
[5] A method comprising causing a decapod organism to ingest at least one member selected from the group consisting of 5-aminolevulinic acid (5-ALA) or an ester thereof, or a salt thereof.
[6] A method for preventing and treating early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) of the order decapod comprises allowing bioabsorption of at least one selected from 5-aminolevulinic acid (5-ALA) or its ester, or its salt by the order decapod.
[7] The method according to the above [5] or [6], wherein the order decapod is a family prawn.
[8] A method for promoting the growth of a decapod organism, comprising causing the decapod organism to ingest at least one selected from the group consisting of 5-aminolevulinic acid (5-ALA), an ester thereof, and a salt thereof per 1g of body weight of the decapod organism and in an amount of 0.25 to 2.5. mu.g/g-day per 1 day, the amount being in terms of 5-ALA phosphate.
The present invention provides an oropodal oral composition containing at least one selected from 5-ALA, an ester thereof, and a salt thereof, which is capable of providing an effect of preventing and treating uropodal EMS/AHPND in the breeding and culture of uropodal organisms. As a result, EMS/AHPND having a mortality rate of approximately 100% in the past can be prevented and treated, and economic contribution can be made to the breeding and cultivation of organisms of the order of ten. The oral composition for decapod eye of the present invention brings about an advantageous effect of promoting growth when administered to a decapod organism in a predetermined administration amount. This advantageous effect is an effect that has not been known in the past and cannot be expected by those skilled in the art of breeding and culturing of organisms of the order of ten.
Drawings
FIG. 1 shows pathogenic bacteria (Vibrio parahaemolyticus: (Vibrio parahaemolyticus) (Vibrio parahaemolyticus)) using EMS/AHPND for Litopenaeus vannamei administered with 5-ALA phosphateVibrio parahaemolyticus) Graph of results of challenge test compared to a control group not administered 5-ALA phosphate and shown over time.
FIG. 2 is a graph showing the cumulative frequency of peeling of litopenaeus vannamei given 5-ALA during a 3-month feeding period, compared with a control group not given 5-ALA.
FIG. 3 is a graph showing the ATP levels of the liver and pancreas of Litopenaeus vannamei given 5-ALA for 2 weeks, compared with a control group not given 5-ALA.
FIG. 4 shows the utilization of Litopenaeus vannamei given 5-ALA for 3 monthsPathogenic bacteria (Vibrio parahaemolyticus) (II) with high EMS/AHPND dosageVibrio parahaemolyticus) Graph of results of challenge test compared to a control group not administered 5-ALA and shown over time.
FIG. 5 is a pathogenic bacterium (Vibrio parahaemolyticus: (Vibrio parahaemolyticus) < in detail >Vibrio parahaemolyticus) Graph of results of challenge test compared to a control group not administered 5-ALA and shown over time.
FIG. 6 shows that pathogenic bacteria (Vibrio parahaemolyticus: (Vibrio parahaemolyticus) (Vibrio parahaemolyticus)) using EMS/AHPND were administered to Litopenaeus vannamei given 5-ALA for 3 monthsVibrio parahaemolyticus) In haemolymph at the time of infection treatment) as compared with a control group to which 5-ALA was not administered.
FIG. 7 shows that pathogenic bacteria (Vibrio parahaemolyticus: (Vibrio parahaemolyticus) (Vibrio parahaemolyticus)) using EMS/AHPND were administered to Litopenaeus vannamei given 5-ALA for 3 monthsVibrio parahaemolyticus) Graph showing gene expression of heme oxygenase-1 (HO-1) in liver pancreas at the time of infection treatment of (1) compared to a control group to which 5-ALA was not administered.
FIG. 8 shows pathogenic bacteria (Vibrio parahaemolyticus: (Vibrio parahaemolyticus) (Vibrio parahaemolyticus)) using EMS/AHPND on Litopenaeus vannamei administered with 5-ALA for 3 monthsVibrio parahaemolyticus) In the liver and pancreas, respectively) was compared with a control group to which 5-ALA was not administered.
FIG. 9 is a graph showing the gene expression of nuclear receptor E75 in the hepatopancreas of litopenaeus vannamei administered with 5-ALA for 3 months, compared with a control group not administered with 5-ALA.
FIG. 10 is a graph showing the gene expression of nitric oxide synthase in the liver and pancreas of Litopenaeus vannamei administered 5-ALA for 3 months, compared with that of a control group to which 5-ALA was not administered.
FIG. 11 is a graph showing the gene expression of nitric oxide synthase in the liver and pancreas of Litopenaeus vannamei administered 5-ALA for 2 weeks, compared with that of a control group not administered 5-ALA.
FIG. 12 is a graph showing the gene expression of C-type lectin in the liver and pancreas of litopenaeus vannamei administered 5-ALA for 2 weeks, compared with that of a control group to which 5-ALA was not administered.
Detailed Description
One embodiment of the present invention is a decapod orally administrable composition containing at least one selected from 5-ALA or an ester thereof, or a salt thereof.
In the present invention, 5-aminolevulinic acid (5-ALA) is a compound also called delta-aminolevulinic acid. In the present invention, "5-ALA or an ester thereof" is "5-ALA or a 5-ALA ester", and may be represented by the following formula (I). In the present invention, the phrase "a salt thereof" in the phrase "5-ALA, an ester thereof, or a salt thereof" means a salt of 5-ALA or a salt of a 5-ALA ester. Examples of the salt include, but are not limited to, hydrochloride, hydrobromide, hydroiodide, phosphate, methylphosphoric acid, ethylphosphoric acid, phosphite, hypophosphite, nitrate, sulfate, acetate, propionate, tosylate, succinate, oxalate, lactate, tartrate, glycolate, mesylate, butyrate, valerate, citrate, fumarate, maleate, malate and other acid addition salts, and sodium, potassium, calcium and other metal salts, ammonium salts, alkylammonium salts, and the like.
In the above formula (I), R1Is a hydrogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group or an aralkyl group. R1When hydrogen is used, the formula (I) represents 5-ALA. R1In the case of a straight-chain or branched alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, the above formula (I) represents a 5-ALA ester.
R1The straight-chain or branched alkyl group shown in (1) is preferably an alkyl group having 1 to 18 carbon atoms, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, a 2-methylbutyl group, an n-hexyl group, an isohexyl group, a 3-methylpentyl group, an ethylbutyl group, an n-heptyl group, a 2-methylhexyl group, an n-octyl group, an isooctyl group, a tert-octyl group, a 2Nonyl, isononyl, 1-methyloctyl, ethylheptyl, n-decyl, 1-methylnonyl, n-undecyl, 1-dimethylnonyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, etc. Examples of the cycloalkyl group include, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group, and also include a cycloalkyl group having an alkyl substituent, for example, a cycloalkyl group having an alkyl substituent having 1 to 6 carbon atoms, for example, a 3-methylcyclohexyl group, a 4-ethylcyclohexyl group, and a 2-methylcyclooctyl group. The straight-chain or branched alkyl group is more preferably an alkyl group having 1 to 16 carbon atoms, and particularly preferably a methyl group, an ethyl group, an n-butyl group, an n-hexadecyl group or a 2-ethylhexyl group.
As R1Examples of the aryl group in (1) include phenyl and naphthyl. The aryl group may be substituted with 1 to 3 substituents such as alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl and cyclohexyl, alkoxy group having 1 to 6 carbon atoms such as methoxy, ethoxy, n-propoxy, n-butoxy, isobutoxy and tert-butoxy, halogen atom such as hydroxyl, amino, nitro, cyano, fluorine, chlorine, bromine and iodine, and carboxyl.
As R1The aralkyl group shown in (1) is preferably an aralkyl group composed of an alkyl group having 1 to 6 carbon atoms and an aryl group having 6 to 20 carbon atoms. Examples of the alkyl group having 1 to 6 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl, and cyclohexyl, and examples of the aryl group having 6 to 20 carbon atoms include phenyl and naphthyl. Among the aralkyl groups, a benzyl group or a phenethyl group is preferable, and a benzyl group is particularly preferable. The aryl group of the aralkyl group may be substituted with 1 to 3 substituents such as an alkyl group having 1 to 6 carbon atoms described above, a methoxy group, an ethoxy group, an n-propoxy group, an n-butoxy group, an isobutoxy group, a tert-butoxy group, a C1-6 alkoxy group, a hydroxyl group, an amino group, a nitro group, a cyano group, a fluorine, chlorine, bromine, iodine, and other halogen atoms, and a carboxyl group.
In the present invention, at least one selected from 5-ALA, an ester thereof, and a salt thereof may be used as the active ingredient, and only one of the active ingredients may be used, or a combination of two or more of the active ingredients may be used. For example, the active ingredient used in the present invention may be any of 5-ALA, 5-ALA ester, 5-ALA salt or 5-ALA ester salt. Further, for example, a combination of 5-ALA and a salt of a 5-ALA ester may be used. At least one selected from 5-ALA, an ester thereof and a salt thereof used in the present invention may be in a purified state, a roughly purified state or a synthesized mixture state. In the present invention, it is preferable to use 5-ALA salt as the active ingredient, and it is more preferable to use 5-ALA hydrochloride and/or 5-ALA phosphate as the active ingredient.
The "Octopus" in the present invention is also called "OctopusDecapoda) One of the crustacean classification groups in (1) is a biological group including shrimp, crab and colonizing crab. The object of the present invention is preferably a shrimp, more preferably also called branchiomyales (A)Dendrobranchiata) The organism of the suborder prawn. More preferably, the organisms of the order decapod as subject of the present invention are of the family Penaeidae (A.) (A.Penaeidae) The organism of (1). Even more preferably, the organisms of the order of the decapod as the subject of the present invention include Penaeus vannamei (Litopenaeus vannamei, Penaeus vannamei, family Penaeaceae) (II)Litopenaeus vannamei) Japanese prawn (1)Marsupenaeus japonicus) Grass shrimp (Black tiger shrimp) ()Penaeus monodon) Chinese prawn (prawn) (II)Fenneropenaeus chinensis) Penaeus vannamei Boone (A) and (B)Melicertus latisulcatus) Prawns of Yangqian (A. Megaloba)Metapenaeus ensis) Red shrimp (Red shrimp, Hu Wei)Metapenaeopsis barbata) Penaeus vannamei (II)Penaeus semisulcatus) And the like, but are not limited thereto. In addition, a still more preferred decapod organism to be subjected to the present invention is litopenaeus vannamei. In addition, from the viewpoint of occurrence of EMS/AHPND in the order of decapod in juvenile shrimps, it is preferable that the organism of decapod order to be the object of the present invention is juvenile shrimps, and it is more preferable that the organism of decapod order to be the object of the present invention is juvenile shrimps of the family prawn.
In the present invention, the oral composition for decapod order is not particularly limited as long as it is a composition orally administered to a decapod order organism. For example, the composition may be in a form in which at least one selected from 5-ALA, an ester thereof, and a salt thereof as an active ingredient is dissolved in a medium such as water and administered to an environment in which the decapod organisms are bred. In this case, the effective ingredient in the administered environment is orally ingested by the decapod organism, and the effect thereof can be obtained.
The orally administrable composition of the present invention is preferably a decapod feed or a decapod feed additive, from the viewpoint of allowing a decapod organism to more efficiently take at least one selected from 5-ALA or an ester thereof, or a salt thereof. The feed for decapod order may contain any component as long as it is a component generally used in breeding and cultivating organisms of decapod order, and may be a feed produced by any production method. The feed of the present invention may be made of substantially the same raw materials as those of conventional shrimp feeds, and may contain, for example, protein sources such as cuttlefish powder, krill powder, whitefish powder, soybean oil residue, and corn gluten meal, binders such as gluten and starch, other vitamin mixtures, mineral mixtures, and trace metals, which are used in general shrimp feeds, but not limited thereto. The decapod feed of the present invention may have any shape and size depending on the type and size of the decapod organism to be fed. The feed for the ten-item purpose of the present invention can be produced in various forms. For example, the feed for a full-size purpose of the present invention may be a powdery feed obtained by mixing and pulverizing dry raw materials, a solidified feed obtained by solidifying the powdery feed, for example, a dry pellet feed or a water-containing solidified feed, for example, a pasty feed or a wet pellet feed. For example, a general powdered shrimp-farming feed and at least one active ingredient selected from 5-ALA or an ester thereof, or a salt thereof are optionally mixed together with a mixing medium such as water, the mixture is molded, for example, the mixture is extruded from a 50mL syringe, and the molded product is dried, for example, at about 60 to 65 ℃ for about 2 hours, whereby the full-purpose feed containing at least one selected from 5-ALA or an ester thereof, or a salt thereof of the present invention can be produced. The form of the feed, the degree of drying, and the like are not particularly limited as long as they are not inconvenient to administer. From the viewpoint of sufficiently exerting the effect of the active ingredient in the decapod organism, the total amount of the active ingredients contained in the feed (that is, the 5-ALA ester, the salt of 5-ALA, and the salt of 5-ALA ester that may be contained in the feed) is preferably 1 to 100ppm, more preferably 2 to 50ppm, and still more preferably 3 to 20ppm, in terms of 5-ALA phosphate. Particularly, from the viewpoint of promoting the growth of decapod organisms, the total amount of the active ingredients contained in the feed is preferably 5 to 50ppm, more preferably 10 to 40ppm, and still more preferably 15 to 30ppm, in terms of 5-ALA phosphate.
In addition, the oral administration composition for decapod mesh may be a feed additive for decapod mesh. The feed additive is not particularly limited as long as it can be added to a general feed for a full-size purpose. For example, the feed additive of the present invention may contain at least one selected from 5-ALA or an ester thereof, or a salt thereof, a spreading agent capable of adhering the active ingredient to a feed for a decapod purpose, or the like, may contain a medium for absorbing the active ingredient into the feed for a decapod purpose, or may contain a medium for easily mixing the active ingredient with a raw material for the feed for a decapod purpose. The feed additive of the present invention is preferably added to the feed so that the total amount of the active ingredients contained in the feed falls within the above range.
Another embodiment of the present invention is a method comprising causing the decapod organism to ingest at least one selected from 5-ALA or an ester thereof, or a salt thereof. The intake here is oral intake. The method is not particularly limited as long as it enables the decapod organism to ingest at least one selected from 5-ALA or an ester thereof, or a salt thereof as an active ingredient. For example, a method of adding at least one selected from 5-ALA or an ester thereof, or a salt thereof to an environment where organisms belonging to the order Nopoda are bred, and allowing the organisms to take in the active ingredient is known. However, from the viewpoint of more efficiently ingesting at least one selected from 5-ALA or an ester thereof, or a salt thereof as an active ingredient, it is preferable that the feed containing at least one selected from 5-ALA or an ester thereof, or a salt thereof is ingested by the order decapod.
Another embodiment of the present invention is a method for promoting the growth of organisms of the order decapod comprising causing the organisms of the order decapod to ingest a specified amount of at least one selected from the group consisting of 5-ALA or an ester thereof, or a salt thereof. In this embodiment, the total amount of at least one selected from 5-ALA, an ester thereof, and a salt thereof as an active ingredient to be ingested by a decapod order organism is preferably 0.25 to 2.5. mu.g/g.day, more preferably 0.5 to 2.0. mu.g/g.day, and still more preferably 0.75 to 1.5. mu.g/g.day per 1g of the body weight of the decapod order organism and per 1 day in terms of 5-ALA phosphate. Although not being bound by theory, it is believed that 5-ALA improves the efficiency of energy extraction from ingested bait in the organism of the decapod order organism as one of the mechanisms of growth promotion of the decapod order organism of this embodiment of the invention.
Another embodiment of the present invention is an oral administration composition for preventing and treating early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) of the order decapod, comprising at least one selected from 5-ALA or an ester thereof, or a salt thereof. In addition, another embodiment of the present invention is a method for preventing/treating early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) of the order decapod comprising causing an organism of the order decapod to ingest at least one selected from 5-ALA or an ester thereof, or a salt thereof. The "prevention/treatment" of "decapod early death syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND)" in the present invention refers to Vibrio parahaemolyticus (Vibrio parahaemolyticus), (A) which is a serious problem in the culture of decapod organismsVibrio parahaemolyticus) Prevention and/or treatment of shrimp disease known as early death syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) that is a pathogenic bacterium. Here, prevention means that the onset of EMS/AHPND is inhibited, i.e., the onset is completely inhibited or the incidence is reduced, by administering at least one selected from 5-ALA or an ester thereof, or a salt thereof. In addition, the treatment refers to infection with Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Or the sensation of the Tenpoda organism in which EMS/AHPND has occurredThe infection was cured by EMS/AHPND. In this embodiment of the present invention, at least one selected from 5-ALA, an ester thereof, and a salt thereof as the active ingredient has an advantageous effect of being able to prevent and/or treat the full purpose EMS/AHPND. This effect is clearly shown in the examples in the form of a reduction in mortality following pathogen challenge. The advantageous effect of at least one selected from 5-ALA, an ester thereof, and a salt thereof as an active ingredient is an effect that has not been known so far and cannot be expected by those skilled in the art of breeding and farming for a full purpose. In the prevention and treatment of EMS/AHPND of the order Nopodales, the total amount of at least one selected from 5-ALA, an ester thereof, and a salt thereof as an active ingredient ingested by organisms of the order Nopodales is preferably 0.05 to 5. mu.g/g.day, more preferably 0.1 to 2.5. mu.g/g.day, and even more preferably 0.15 to 1. mu.g/g.day per 1g of body weight of the organisms of the order Nopodales in terms of 5-ALA phosphate.
The environment for raising and culturing the decapod organisms to which the present invention is applied is not particularly limited, and the present invention can be applied to large-scale pond culture in south-east asia and the like, and can also be applied to small-scale culture in a water tank and the like.
The present invention will be described in detail below with reference to examples, but the present invention is not limited to the scope of the examples.
Examples
Example 1: preparation of feed containing 5-ALA
With 5-ALA phosphate (C)5H9NO3·H3PO4) The feed was mixed with a powdered feed (a general commercial bait for breeding litopenaeus vannamei in thailand was powdered) to a concentration of 15ppm, and the mixture was mixed with distilled water in an amount equivalent to that of the powdered feed. Subsequently, the obtained mixture was filled in a 50mL syringe and extruded to prepare a pasta-like shaped feed. Drying the mixture at 60-65 ℃ for about 2 hours. After drying, the pasta-like shaped feed is finely pulverized in a manner that facilitates administration, and is granulated. The granules are stored in a refrigerator until the granules are frozenThe application is as follows.
Example 2: the 5-ALA pair is subjected to a treatment based on Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Influence of the survival rate of the attacking Litopenaeus vannamei
Litopenaeus vannamei with a weight of about 2g was used. Putting 20 litopenaeus vannamei in each group into a 100L water tank, and feeding for 28 days. The feed prepared in example 1 was administered to the 5-ALA drug administration group, and the same feed was administered to the control group except that 5-ALA was not contained. The amount of bait was set to 5% of the weight of the shrimp, and the bait was thrown 4 times a day using an automatic bait-throwing device.
At 2 weeks from the start of the test, litopenaeus vannamei was transferred to a container filled with litopenaeus vannamei at 3X 105cfu/ml amount of Vibrio parahaemolyticus: (Vibrio parahaemolyticus) The sea water of (2) is subjected to Vibrio parahaemolyticus in a 15L tankVibrio parahaemolyticus) Infection treatment of litopenaeus vannamei. The survival rate of litopenaeus vannamei was further confirmed at 2 weeks after the infection treatment. The results are shown in FIG. 1. In FIG. 1, "Control" represents a Control group and "ALA" represents a 5-ALA administration group.
As shown in FIG. 1, in the control group to which 5-ALA was not administered, a significant decrease in survival rate was shown from day 7 after infection, and all of the litopenaeus vannamei died at day 13 after infection. On the other hand, in the group administered with 5-ALA in advance, only 1 death occurred during the observation period, and a significant survival rate was shown relative to the control group (p value < 0.0001). Thus, it was clarified that 5-ALA is responsible for Vibrio parahaemolyticus in the order decapod organisms: (Vibrio parahaemolyticus) Is effective preventive/therapeutic agent for pathogenic bacteria EMS/AHPND. Since almost 100% of shrimps died if EMS/AHPND was generated in an actual shrimp farm, the experimental conditions of example 2 were considered to simulate the generation of EMS/AHPND in an actual shrimp farm. Therefore, it is assumed that 5-ALA is effective for the prevention and treatment of EMS/AHPND in actual shrimp farms.
Example 3: the conditions for feeding Litopenaeus vannamei used in the following experiments
400 litopenaeus vannamei with the average weight of 0.84 +/-0.33 g are divided into the following 4 groups per 100 litopenaeus vannamei, and the groups are raised in different water tanks. At the start of feeding, 2 weeks and 3 months from the start of feeding, the following items were measured.
(a) The 5-ALA-administered group at 15ppm was administered with a feed containing 15ppm of 5-ALA.
(b) The 30ppm 5-ALA-administered group was administered with a feed containing 30ppm 5-ALA.
(c) The 5-ALA-administered group at 60ppm was administered with a feed containing 60ppm of 5-ALA.
(d) Control groups were given feed without 5-ALA.
The feeding amount per day for litopenaeus vannamei is 5% of the average weight of litopenaeus vannamei. The amount of bait feed per day was divided into 4 times (8:00, 13:00, 18:00 and 23:00) to provide feed for litopenaeus vannamei. The weight of litopenaeus vannamei was monitored by measuring the total weight of litopenaeus vannamei in each group every week, and the amount of bait administered per day was adjusted based on the measured weight. The remaining feed and excrement were removed once a day. Water quality parameters were also monitored during the feeding.
A feed containing 15ppm of 5-ALA was prepared as follows. 150mg of 1% 5-ALA powder (containing 5-ALA phosphate (C)5H9NO3·H3PO4) Dissolving the solution in 100ml of water, and thoroughly mixing the obtained solution with 100 g of shrimp powder feed (used by powdering general commercial baits for litopenaeus vannamei in thailand), to obtain a feed mixture. Next, the feed mixture is granulated using a masher. Drying the granules in a constant temperature oven at 60-65 deg.C for about 2-3 hr to obtain feed containing 15ppm 5-ALA. The feed was stored in a refrigerator at 4 ℃ until use. A feed containing 5-ALA in an amount of 30ppm and a feed containing 5-ALA in an amount of 60ppm were produced in the same manner as the production of the feed containing 5-ALA in an amount of 15ppm, except that the amounts of the 5-ALA powder added were 300mg and 600mg, respectively. The feed containing no 5-ALA used in the control group was prepared in the same manner as the feed containing 15ppm of 5-ALA, except that 1% of 5-ALA powder was not added.
Example 4: effect of 5-ALA on the growth of Litopenaeus vannamei
In the breeding of litopenaeus vannamei under the conditions described in example 3, the effect of 5-ALA on the growth of litopenaeus vannamei was investigated by measuring the weight gain during the 3-month breeding period. The individual body weights of the litopenaeus vannamei in each group were measured at the beginning of feeding and at 3 months from the beginning of feeding. The results are shown in table 1 below. In the table, the initial body weight was the body weight at the start of feeding (day 0), the final body weight was the body weight at month 3, the body weight gain was the final body weight — initial body weight, SGR was the instantaneous Growth Rate (%), calculated from the formula of SGR ═ lnal final weight-lnal initial weight/days on bait casting ] × 100, FCR was the Feed Conversion Rate (Feed Conversion Rate), and FCR ═ Feed consumption/body weight gain. The values for initial body weight, final body weight, body weight gain and SGR in the tables are mean. + -. standard deviation (mean. + -. SD). The descriptions of 15ppm, 30ppm and 60ppm in the table indicate the 15ppm 5-ALA administration group, the 30ppm 5-ALA administration group and the 60ppm 5-ALA administration group, respectively.
[ Table 1]
| Parameter(s) | Control group | 15ppm | 30ppm | 60ppm |
| Initial weight (g) | 0.84±0.36 | 0.84±0.27 | 0.83±0.34 | 0.84±0.35 |
| Final body weight (g) | 6.54±2.77 | 7.39±3.01 | 7.46±3.10 | 6.26±3.37 |
| Weight gain (g) | 5.70±2.93 | 6.55±3.20 | 6.63±3.11 | 5.42±3.23 |
| SGR(％) | 2.44±0.31 | 2.59±0.32 | 2.61±0.23 | 2.39±0.41 |
| FCR | 2.04 | 2.02 | 1.93 | 2.24 |
As shown in Table 1, the 5-ALA-administered group at 15ppm and the 5-ALA-administered group at 30ppm showed large weight gain and large transient growth rate (SGR) compared to the control group. Thus, the fact that the 5-ALA with 15ppm and the 5-ALA with 30ppm are given to the litopenaeus vannamei to promote the growth of the litopenaeus vannamei is clear. In addition, the Feed Conversion Ratio (FCR) was slightly decreased in the 15ppm 5-ALA-administered group and the 30ppm 5-ALA-administered group as compared with the control group. Thus, although not being bound by theory, it is assumed that one of the reasons why the growth of litopenaeus vannamei is promoted by 5-ALA in the 15ppm 5-ALA-administered group and the 30ppm 5-ALA-administered group is likely to be the improvement of the efficiency of energy extraction from the feed by 5-ALA in the litopenaeus vannamei organism.
In addition, the frequency of peeling of litopenaeus vannamei during the feeding period of 3 months was measured, and the cumulative frequency of this peeling is shown in fig. 2. The 15ppm, 30ppm and 60ppm descriptions in FIG. 2 represent the 15ppm 5-ALA administration group, the 30ppm 5-ALA administration group and the 60ppm 5-ALA administration group, respectively. In FIG. 2, the cumulative frequency of desquamation in each group was represented by assuming that the cumulative frequency of desquamation at week 12 in the group to which 30ppm of 5-ALA having the highest cumulative frequency of desquamation was administered was 100%. As shown in FIG. 2, the cumulative frequency of desquamation was highest in the 30ppm 5-ALA-administered group, followed by 15ppm 5-ALA-administered group, and the lowest frequency of desquamation was the control group. Since shrimps peeled with growth, it is assumed that the increase in cumulative frequency of peeling caused by the administration of 5-ALA at 30ppm and 15ppm also indicates that the growth of litopenaeus vannamei was promoted by the administration of 5-ALA.
Example 5: effect of 5-ALA on ATP levels in the liver and pancreas
ATP levels in the liver pancreas of litopenaeus vannamei were measured 2 weeks from the start of feeding. The ATP level was determined for 3 litopenaeus vannamei cells per group. The samples for measuring ATP concentration were prepared as follows. Approximately 10mg of liver and pancreas was collected from each litopenaeus vannamei. The collected liver and pancreas were washed with phosphate buffered saline (1 × PBS). The washed liver pancreas was homogenized in ice-cold 100. mu.l of 2N perchloric acid (PCA), the homogenate was kept on ice for 30 minutes, followed by centrifugation at 13000 Xg at 4 ℃ for 2 minutes to obtain a supernatant. The supernatant was diluted to 500. mu.l with ATP reaction buffer. Subsequently, 50 to 100. mu.l of ice-cold KOH (2M) was added to the diluted supernatant to precipitate an excess of PCA. The pH was adjusted by adding 0.1M KOH or PCA to the supernatant as necessary. The obtained sample was then centrifuged at 13000 Xg for 15 minutes, and the supernatant was collected and used as a sample for measuring the ATP concentration. ATP concentration was measured using an ATP colorimetric assay kit (catalog No.: ab 83355: Abcam (registered trademark), Cambridge, Mass., USA). The ATP concentration is determined according to the instructions of the manufacturer of the kit. The results are shown in FIG. 3. The 15ppm, 30ppm and 60ppm descriptions in FIG. 3 represent the 15ppm 5-ALA administration group, the 30ppm 5-ALA administration group and the 60ppm 5-ALA administration group, respectively.
As shown in FIG. 3, the ATP level in the liver and pancreas of litopenaeus vannamei was higher in all of the 5-ALA-administered groups than in the control group. ATP levels in the hepatopancreas of litopenaeus vannamei increased in a 5-ALA dose-dependent manner. Statistically significant differences were observed in the increased ATP levels relative to the control group in the 30ppm and 60ppm 5-ALA-administered groups. Significant difference test using t-test method, asterisks in FIG. 3 indicate p < 0.05. In the 60ppm 5-ALA-administered group, the increase in ATP level was not correlated with weight gain. While not being bound by theory, it is believed that this is because the electron transport system is activated excessively due to the excess of 5-ALA, and a large amount of lipids and carbohydrates are consumed by the TCA circuit that supplies the electron transport system with reducing power. However, the increase in ATP levels in the 15ppm and 30ppm 5-ALA-administered groups supported the 5-ALA-derived efficiency of energy extraction from feed in the litopenaeus vannamei organism, which is presumed to be one of the causes of the growth promotion of litopenaeus vannamei by 5-ALA.
Example 6: based on Vibrio parahaemolyticus: (Vibrio parahaemolyticus) EMS/AHPND infection assay
For the 5-ALA pair, the treatment is based on Vibrio parahaemolyticus: (Vibrio parahaemolyticus) The influence of the survival rate of the attacked litopenaeus vannamei was studied.
Is prepared for each group to put in 3 × 106The amount of cfu/ml (high amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) And a 10L water tank containing 3X 10 of seawater5The amount of cfu/ml (low amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) A 10L water tank for seawater. Transferring 10 litopenaeus vannamei groups of 3 months from the beginning of feeding to these water tanks, and performing Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Infection treatment of litopenaeus vannamei. Litopenaeus vannamei in each group was fed the same feed (feed containing 5-ALA at 15ppm, 30ppm or 60ppm, or feed containing no 5-ALA) as that given before the infection treatment at 2 weeks from the infection treatment. Each group and each Vibrio parahaemolyticus were confirmed every day within 2 weeks from the infection treatment: (Vibrio parahaemolyticus) Survival rate of Litopenaeus vannamei at the given amount. Will be used at 3 × 106The amount of cfu/ml (high amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) The results of seawater treatment of Litopenaeus vannamei (L.) with water at 3X 10 are shown in FIG. 45The amount of cfu/ml (low amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) The results of seawater treatment of litopenaeus vannamei are shown in figure 5. The 15ppm, 30ppm and 60ppm descriptions in FIGS. 4 and 5 indicate the 15ppm 5-ALA administration group, the 30ppm 5-ALA administration group and the 60ppm 5-ALA administration group, respectively.
As shown in fig. 4, for 3 × 106The amount of cfu/ml (high amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) When litopenaeus vannamei was treated with seawater, 60ppm of 5-ALA-administered group showed a very high survival rate compared to the control group. The 5-ALA-administered groups at 15ppm and 30ppm showed low survival rate compared to the 5-ALA-administered group at 60ppm, but showed high survival rate compared to the control group. For 3 x 105The amount of cfu/ml (low amount) contains Vibrio parahaemolyticus: (Vibrio parahaemolyticus) When litopenaeus vannamei was treated with seawater, as shown in fig. 5, 15ppm, 30ppm and 60ppm of 5-ALA-administered groups all showed very high survival rates compared to the control group. Thus, it was clarified that 5-ALA is responsible for Vibrio parahaemolyticus in the order decapod organisms: (Vibrio parahaemolyticus) Is effective preventive/therapeutic agent for pathogenic bacteria EMS/AHPND.
Example 7: based on Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Influence of 5-ALA on the Total blood cell count in the treatment of infection of (1)
Utilization of Vibrio parahaemolyticus by the same method as that in example 6: (Vibrio parahaemolyticus) (high dose) litopenaeus vannamei was infected at month 3 from the start of feeding. Before (0 hour) infection treatment, after 6 hours from infection treatment, and after 12 hours from infection treatment, 200. mu.l of hemolymph (hemolymph) was collected from the ventral sinuses (ventral sinus) of 3 litopenaeus vannamei boone each group, and diluted with 800. mu.l of anticoagulant. The total blood cell count in haemolymph was determined using a C-chip (C-chip) haemocytometer (NanoEntek, Germany). 1 in FIG. 6The descriptions of 5ppm, 30ppm and 60ppm represent the 15ppm 5-ALA administration group, the 30ppm 5-ALA administration group and the 60ppm 5-ALA administration group, respectively. As shown in FIG. 6, the 5-ALA-administered group showed an increase in total blood cell count as compared with the control group at all times before and after the infection treatment. The 5-ALA-administered group at 60ppm after 6 hours from the infection treatment showed a statistically significantly high total blood cell count compared with the other groups. The significant difference test uses the t-test method. Although not being bound by theory, since blood cells such as granulocytes play an important role as immunocompetent cells in shrimp, it is considered that one of the causes of the preventive/therapeutic effect on EMS/AHPND by the administration of 5-ALA is likely to be activation of the natural immune system by the increase in the total blood cell count by 5-ALA.
Example 8: based on Vibrio parahaemolyticus: (Vibrio parahaemolyticus) Influence of 5-ALA on Gene expression of Heheme oxygenase-1 and Prophenol oxidase in the treatment of infection
Utilization of Vibrio parahaemolyticus by the same method as that in example 6: (Vibrio parahaemolyticus) (high dose) litopenaeus vannamei was infected at month 3 from the start of feeding. Before (0 hour) infection treatment, after 6 hours from infection treatment, and after 12 hours from infection treatment, liver and pancreas were collected from 5 litopenaeus vannamei each group, and total RNA was extracted from the liver and pancreas of each litopenaeus vannamei using rnaasso Plus reagent (Takara Bio, japan) according to the instructions of the manufacturer of the reagent. cDNA was synthesized from 1. mu.g of total RNA extract using a High-Capacity reverse transcription kit (Applied Biosystems, USA) according to the instructions of the manufacturer of the kit. The synthesized cDNA was diluted 5-fold and used as template for qPCR. The gene expression of heme oxygenase-1 (HO-1) and prophenoloxidase (proPO) was determined by applying real-time Polymerase Chain Reaction (PCR) using SYBR green fluorescent dye to the cDNA. The assay was performed using a Thunderbird (registered trademark) SYBR qPCR Mix (tokyo, japan). The amplification reaction was performed using a MicroAmp Optical 96-well reaction plate (applied biosystems, usa). Each well contained 10. mu.l of qPCRMix, 0.6. mu.l of each primer, 0.4. mu.l of ROX reference dye and 2. mu.l of cDNA template. The cycling conditions were as follows. Cycles of 1 minute at 95 ℃ followed by 15 seconds at 90 ℃ and 60 seconds at 60 ℃ were carried out for 40 cycles. At the end of each qPCR reaction, dissociation analysis was performed, confirming that only 1 product was detected. Use 2-ΔΔCtThe method (Livak and schmitgen, 2001) determines the relative change in gene expression data based on qPCR to calculate Ct values (Cycle Threshold: Threshold Cycle), determine gene expression of EF1 α as an internal standard, calculate the ratio normalized using the relative expression of the control group, perform log (base ═ 2) conversion of the data prior to analysis, use the forward primer with sequence 1 (5'-CTGAGGAGCTCGATGAGGAG-3') and the reverse primer with sequence 2 (5'-CATGGCCACAACACTACCAG-3') to determine expression of heme oxygenase-1, use the forward primer with sequence 3 (5'-GGAATTGTTTTACTACATGCATCAGC-3') and the reverse primer with sequence 4 (5'-GGAACAAGTCATCCACGAGCTT-3') to determine expression of prophenoloxidase, use the forward primer with sequence 5 (5'-ATTGCCACACCGCTCACA-3') and the reverse primer with sequence 6 (5'-TCGATCTTGGTCAGCAGTTCA-3') to determine expression of EF1 α, the results are shown in fig. 7-8, the mean value of the gene expression of the control group at each time is set to 0, the relative value of the gene expression of each group is relative to the relative value, the error in fig. 7-8 is shown in the bar 7-8, the error of the administration of the bar set at 0ppm, 5-30 ppm, 5ppm, and 15ppm, 5 ppm.
As shown in FIG. 7, after 6 hours from the infection treatment, the gene expression of heme oxygenase-1 was increased in a dose-dependent manner in the 5-ALA-administered group compared with the control group. As shown in FIG. 8, 6 hours after the infection treatment, the 5-ALA-administered group showed an increase in the expression of the prophenoloxidase gene as compared with the control group. Heme oxygenase-1, 1 known as a heme protein, is an enzyme involved in heme metabolism and is a cytoprotective protein that protects cells from damage due to oxidative stress. Suggests that phenol oxidizing enzymes may participate in the mechanism of recognizing cell wall components of fungi and bacteria and correlating the recognition result with the generation of ligands of toll receptors. Therefore, while not being bound by theory, it is considered that one of the reasons for the preventive/therapeutic effect on EMS/AHPND by the administration of 5-ALA is likely to be the increase in gene expression of heme oxygenase-1 and prophenoloxidase by 5-ALA.
Example 9: effect of 5-ALA on Gene expression of Nuclear receptor E75 and nitric oxide synthase
The method comprises collecting the liver pancreas from 3 to 4 litopenaeus vannamei groups at month 3 from the start of feeding, extracting total RNA from the liver pancreas of each litopenaeus vannamei, synthesizing cDNA from the total RNA, measuring the gene expression of the nuclear receptor gene E75 and nitric oxide synthase by applying real-time Polymerase Chain Reaction (PCR) using SYBR green fluorescent dye to the cDNA, measuring the gene expression of EF1 α as an internal standard for calculating the Ct value, measuring the expression of the nuclear receptor gene E75 using a forward primer having the sequence 7 (5'-GCCTACAACAAGCCCCATAA-3') and a reverse primer having the sequence 8 (5'-GCCAGAGAGGAAGTCTGGTG-3') for measuring the expression of the nuclear receptor gene E75, using a forward primer having the sequence 9 (5'-GGAAGACCCACGTCTGGAAG-3') and a reverse primer having the sequence 10 (5'-TCGAGCGATCTCCTTGAAGC-3') for measuring the expression of nitric oxide synthase, setting the average value of the gene expression of the control group to 0, setting the relative values of the gene expression of the respective groups to 0, setting the bars in FIGS. 9 to 10 as the relative values, setting the error values of the bars in FIGS. 9 to 10, and setting the amounts of the bars in the amounts of 30ppm, 5 to 15ppm, and 5 to 15ppm, respectively, 30ppm of ALA, and 5 to 5ppm, and 5ppm, respectively, and 30ppm, 30 to 5, respectively.
As shown in fig. 9, the gene expression of nuclear receptor E75 was statistically significantly increased in all 5-ALA-administered groups compared to the control group. The significant difference test uses the t-test method. As shown in FIG. 10, the gene expression of nitric oxide synthase was increased in the 5-ALA-administered group compared to the control group. It is known that nuclear receptor E75 is a protein required for ecdysone synthesis, contains heme as a prosthetic group, functions as a sensor of intracellular heme concentration, and is also likely to sense nitric oxide as an intracellular signaling molecule. Nitric oxide synthase is known as an enzyme involved in the synthesis of nitric oxide required for the production of peroxynitrite having a potent antibacterial activity against bacterial infection and the like, and is a hemoprotein. E75 requires heme to stabilize its structure and further serves as a sensor for heme concentration, and NO synthase itself is a heme protein, and therefore, by examining the expression thereof, it is possible to serve as an index for confirming that the administration of 5-ALA is related to heme synthesis in the body of shrimp.
Example 10: effect of 5-ALA on Gene expression of nitric oxide synthase and C-type lectin
In the 2 weeks from the start of feeding, hepatopancreas were collected from 3 to 4 litopenaeus vannamei groups, total RNA was extracted from the hepatopancreas of each litopenaeus vannamei, cDNA was synthesized from the total RNA, gene expression of nuclear receptor gene E75 and nitric oxide synthase was measured by applying real-time Polymerase Chain Reaction (PCR) using SYBR green fluorescent dye to the cDNA, gene expression of EF1 α was measured as an internal standard for the calculation of Ct value, a forward primer having sequence 9 (5'-GGAAGACCCACGTCTGGAAG-3') and a reverse primer having sequence 10 (5'-TCGAGCGATCTCCTTGAAGC-3') were used for the measurement of nitric oxide synthase expression, a forward primer having sequence 11 (5'-CAAGATGGCTCCCACCAACA-3') and a reverse primer having sequence 12 (5'-GTCGAACTCGGCGTTATCGG-3') were used for the measurement of C-type lectin, the apparatus, conditions and the like used in the measurement were the same as those in example 8, the results are shown in fig. 11 to 12, the average value of gene expression of the control group was set to 0, and the relative values of the respective groups were relative values of the relative values, the error bars in fig. 11 to 12, the error bars of the groups, the error bars of 5 to 30ppm, the ALA groups, and the error bars of the groups of 5 to 15ppm, and 30ppm, to 15ppm, respectively, to 15ppm, to 30ppm, and.
As shown in FIG. 11, the gene expression of nitric oxide synthase was increased in a dose-dependent manner in the 5-ALA-administered group compared to the control group. As shown in FIG. 12, 15ppm of 5-ALA-administered group showed an increase in the gene expression of C-type lectin as compared to the control group. It is suggested that C-type lectins may induce the most important nodal response in the primary immune response. Although not being bound by theory, C-type lectins are thought to play an important role in the nodule formation reaction, which is a reaction in which the uptake of bacteria into granulocytes and the further spread of bacteria is prevented, suggesting that one reason for the effectiveness of EMS may be the nodule reaction promoting effect of increased expression of C-type lectins by administration of 5-ALA. Nitric oxide synthase is an enzyme involved in the synthesis of nitric oxide, is a heme protein, and its synthesis is promoted by the administration of 5-ALA.
Industrial applicability
The decapod oral administration composition containing at least one selected from 5-ALA or an ester thereof, or a salt thereof according to the present invention can be used for feeding and breeding decapod organisms, and is effective for preventing and treating Vibrio parahaemolyticus (Vibrio parahaemolyticus) ((Vibrio parahaemolyticus))Vibrio parahaemolyticus) EMS/AHPND, which is a pathogenic bacterium. The oral composition for decapod use according to the present invention, which contains at least one selected from 5-ALA, an ester thereof, and a salt thereof, can promote the growth of an organism of the decapod order in a predetermined administration amount.
Sequence listing
<110> soaring medicine of Nippon N Ltd
National university of French human Tokyo ocean university
<120> Ten-fold objective composition containing 5-aminolevulinic acid
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<150>JP 2017-179379
<151>2017-09-19
<150>JP 2018-168668
<151>2018-09-10
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<170>PatentIn version 3.5
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<400>5
attgccacac cgctcaca 18
<210>6
<211>21
<212>DNA
<213> Litopenaeus vannamei
<400>6
tcgatcttgg tcagcagttc a 21
<210>7
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>7
<210>8
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>8
<210>9
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>9
<210>10
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>10
tcgagcgatc tccttgaagc 20
<210>11
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>11
<210>12
<211>20
<212>DNA
<213> Litopenaeus vannamei
<400>12
Claims (8)
1. An oral composition for decapod use comprises at least one selected from 5-ALA (5-aminolevulinic acid), an ester thereof, and a salt thereof.
2. An orally administered composition for preventing and treating EMS/AHPND, which is an early death syndrome/acute hepatopancreatic necrosis disease in the order of ten-legged, contains 5-ALA, which is 5-aminolevulinic acid, or an ester or salt thereof.
3. The composition according to claim 1 or 2, wherein the order decapod is of the family prawn.
4. The composition according to any one of claims 1 to 3, wherein the composition is a feed or a feed additive.
5. A method comprising causing a decapod organism to ingest at least one member selected from the group consisting of 5-aminolevulinic acid (5-ALA) or an ester thereof, or a salt thereof.
6. A method for preventing and treating early mortality syndrome/acute hepatopancreatic necrosis disease EMS/AHPND of the order decapod comprising biologically ingesting at least one selected from 5-aminolevulinic acid (5-ALA) or an ester thereof, or a salt thereof.
7. The method according to claim 5 or 6, wherein the order decapod is of the family prawn.
8. A method for promoting the growth of a decapod organism, comprising causing the decapod organism to ingest at least one selected from 5-ALA, which is 5-aminolevulinic acid, or an ester thereof, or a salt thereof, in an amount of 0.25 to 2.5 [ mu ] g/g-day per 1g of the body weight of the decapod organism, the amount being in terms of 5-ALA phosphate.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017179379 | 2017-09-19 | ||
| JP2017-179379 | 2017-09-19 | ||
| PCT/JP2018/033494 WO2019059027A1 (en) | 2017-09-19 | 2018-09-10 | Composition for order decapoda, including 5-aminolevulinic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111132676A true CN111132676A (en) | 2020-05-08 |
Family
ID=66107090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880060955.2A Pending CN111132676A (en) | 2017-09-19 | 2018-09-10 | Ten-fold eye composition containing 5-aminolevulinic acid |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2019055943A (en) |
| CN (1) | CN111132676A (en) |
| BR (1) | BR112020005255A2 (en) |
| TW (1) | TWI791045B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022063295A1 (en) * | 2020-09-28 | 2022-03-31 | 天津博菲德科技有限公司 | Additive for increasing survival rate of aquaculture animals and application thereof |
| CN115399271A (en) * | 2022-10-14 | 2022-11-29 | 杭州师范大学 | Domestication method for improving molt rate of prawns and composition for improving molt rate of prawns |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010053796A1 (en) * | 2000-05-08 | 2001-12-20 | Hyeungrak Kim | Delta-aminolevulinic acid for prevention and treatment of infection microorganisms and parasite |
| KR20090027269A (en) * | 2007-09-12 | 2009-03-17 | 주식회사 이지바이오 시스템 | Feed composition replacing antibiotics using delta-aminolevulinic acid |
| KR20140106116A (en) * | 2013-02-26 | 2014-09-03 | 한남바이오 주식회사 | Feed composition for Crustacean |
| CN107106597A (en) * | 2014-08-01 | 2017-08-29 | 石油-德里美国有限公司 | Clay product reduces the purposes of the effect of the bacteriosis in shrimp |
| CN107114608A (en) * | 2017-05-25 | 2017-09-01 | 乐清益昌食品技术有限公司 | One kind preventing and treating prawn white body disease feed and preparation method thereof |
-
2018
- 2018-09-10 BR BR112020005255-8A patent/BR112020005255A2/en not_active IP Right Cessation
- 2018-09-10 JP JP2018168668A patent/JP2019055943A/en active Pending
- 2018-09-10 CN CN201880060955.2A patent/CN111132676A/en active Pending
- 2018-09-19 TW TW107133024A patent/TWI791045B/en active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010053796A1 (en) * | 2000-05-08 | 2001-12-20 | Hyeungrak Kim | Delta-aminolevulinic acid for prevention and treatment of infection microorganisms and parasite |
| KR20090027269A (en) * | 2007-09-12 | 2009-03-17 | 주식회사 이지바이오 시스템 | Feed composition replacing antibiotics using delta-aminolevulinic acid |
| KR20140106116A (en) * | 2013-02-26 | 2014-09-03 | 한남바이오 주식회사 | Feed composition for Crustacean |
| CN107106597A (en) * | 2014-08-01 | 2017-08-29 | 石油-德里美国有限公司 | Clay product reduces the purposes of the effect of the bacteriosis in shrimp |
| CN107114608A (en) * | 2017-05-25 | 2017-09-01 | 乐清益昌食品技术有限公司 | One kind preventing and treating prawn white body disease feed and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 安本信哉等: "5-アミノレブリン酸の経口投与がウナギに及ぼす効果", 《水産増殖》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022063295A1 (en) * | 2020-09-28 | 2022-03-31 | 天津博菲德科技有限公司 | Additive for increasing survival rate of aquaculture animals and application thereof |
| CN115399271A (en) * | 2022-10-14 | 2022-11-29 | 杭州师范大学 | Domestication method for improving molt rate of prawns and composition for improving molt rate of prawns |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2019055943A (en) | 2019-04-11 |
| BR112020005255A2 (en) | 2020-09-24 |
| TW201914440A (en) | 2019-04-16 |
| TWI791045B (en) | 2023-02-01 |
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Application publication date: 20200508 |