EP3145521A1 - Verbindung oder zusammensetzung zur verwendung bei der vorbeugung und/oder behandlung eines ektoparasitischen ruderfusskrebsbefalls oder infektion bei fischen - Google Patents

Verbindung oder zusammensetzung zur verwendung bei der vorbeugung und/oder behandlung eines ektoparasitischen ruderfusskrebsbefalls oder infektion bei fischen

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Publication number
EP3145521A1
EP3145521A1 EP15716476.5A EP15716476A EP3145521A1 EP 3145521 A1 EP3145521 A1 EP 3145521A1 EP 15716476 A EP15716476 A EP 15716476A EP 3145521 A1 EP3145521 A1 EP 3145521A1
Authority
EP
European Patent Office
Prior art keywords
quillaja saponaria
saponaria saponins
saponins
fish
ppm
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP15716476.5A
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English (en)
French (fr)
Inventor
Alin Ximena Casado Zelaya
Michael Andrew ADLER EGGERS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biomar Group AS
Original Assignee
Biomar Group AS
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Filing date
Publication date
Application filed by Biomar Group AS filed Critical Biomar Group AS
Publication of EP3145521A1 publication Critical patent/EP3145521A1/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides

Definitions

  • the present invention relates to Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for use in the prevention and/or treatment of ectoparasitic infection or infestation in fish.
  • the present invention also relates to a method for the manufacture of a fish feed comprising Quillaja Saponaria saponins.
  • Ectoparasitic copepods are copepods that feed on the mucus, epidermal tissue and/or blood of fish.
  • Ectoparasitic copepods include sea lice, which includes copepods within the family Caligidae. This family includes around 162
  • Ectoparasitic copepods such as sea lice may cause physical and enzymatic damage at the site of attachment on the fish which results in abrasion-like lesions that may vary in their nature and severity.
  • a sea lice infection itself may cause a generalized chronic stress response in fish since feeding and attachment cause changes in the mucus consistency and damage the epithelium resulting in the loss of blood and fluids, electrolyte changes and Cortisol release. These changes can decrease the immune response and affect negatively the feed intake leading to a significant reduction of growth and performance.
  • Sea lice infections also make the fish susceptible to other diseases and may as a secondary infection be a possible vector for other pathogens like salmon alphe virus (Pancreatic disease), Infectious Salmon Anamis virus (ISAv) and Piscirickettsia salmonis.
  • the degree of damage is also dependent on the species of sea lice, the developmental stages of the sea lice present, and the number of sea lice on the fish. Economic losses caused by ectoparasitic copepods such as sea lice can be tremendous and significant research effort has been dedicated to treat, control and prevent such diseases in aquaculture production.
  • ectoparasitic infestations/infections in farmed fish are not only harmful for the cultivated fish, they also represent a constant and severe thread for wild populations, which can be infected by the farmed fish. This is another reason why an effective control and treatment of ectoparasitic copepods and other infectious diseases is of great importance.
  • Ectoparasitic copepods of the family Caligidae was first identified in Chile during 1997 in Atlantic salmon. From 1997 and until a few years ago sea lice of the family Lepeophtheirus and Caligus was treated with emamectin benzoate.
  • emamectin benzoate Unfortunately, the efficiency of emamectin benzoate has diminished significantly due to the excessive use and lack of rotation with other fish-specific antiparasitic compounds. Such compounds include organophosphates, pyrethroids, hydrogen peroxides and chitin synthesis inhibitors.
  • organophosphates such as organophosphates, pyrethroids, hydrogen peroxides and chitin synthesis inhibitors.
  • the strategy applied to decrease infestations/infections with sea lice is a combination of emamectin benzoate and newer pesticides such as Deltamethrin, Cypermethrin, Azametofos and Hydrogen peroxide administrated by immersion.
  • the effectiveness of this strategy however, has not reached the level expected and infestations/infections caused by sea lice still poses a huge problem to the farming industry.
  • Newer strategies to decrease infestations with ectoparasitic copepods includes immunestimulants such as beta-glucans, essential oils (carvacrol, thymol and their combinations), and other nutraceuticals such as nucleotides and mannan- oligosaccharides, organic minerals like zinc and therapeutic levels of vitamin C.
  • immunestimulants such as beta-glucans, essential oils (carvacrol, thymol and their combinations), and other nutraceuticals such as nucleotides and mannan- oligosaccharides, organic minerals like zinc and therapeutic levels of vitamin C.
  • Such strategies may be applied alone or in combination with the chemical strategies mentioned above.
  • Fish-specific antiparasitic compounds such as compounds capable of preventing and/or treating ectoparasitic copepods like sea lice, should preferably be non-toxic for the fish in the applied concentrations and from an environmental point of view, the compounds should be fast and easily degradable in the natural environment without any unfavourable and harmful accumulation in the nutritional chain. When supplied
  • infestations/infections such as infestations/infections caused by sea lice
  • an object of the present invention relates to a compound or composition for use in the prevention and/or treatment of ectoparasitic infestations or infections in fish.
  • one aspect of the invention relates to Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for use in the prevention and/or treatment of ectoparasitic infection or infestation in fish.
  • Another aspect of the present invention relates to the use of Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for the manufacture of a medicament for the treatment and/or prevention of ectoparasitic copepod infection or infestation in fish.
  • Yet another aspect of the present invention is to provide a method of treating and/or preventing ectoparasitic copepod infection or infestation in fish, said method comprising oral administering to said fish Quillaja Saponaria or a composition comprising Quillaja Saponaria saponins.
  • Still another aspect of the present invention is to provide a method for the manufacture of a fish feed, comprising the steps of combining Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins with approved and/or authorised fish feed ingredients and obtaining a fish feed comprising Quillaja Saponaria saponins.
  • Figure 1 shows the toxicity of Quillaja saponaria saponins on Caligus.
  • the dose "ppm" in figure 1 refers to experiments conducted with Quillaja high extract which comprises 20% Quillaja saponaria saponins - the dose thus corresponds to 0, 0.1, 10 and 100 ppm Quillaja saponaria saponins.
  • Figure 2 shows the effect of Quillaja saponaria saponins on the infection rate with Caligus in Atlantic salmon (Salmo salar).
  • FIG. 3A-3C shows the SGR (specific growth rate); SFR (specific feed rate) and FCR (feed conversion rate) between two groups.
  • Figure 4 shows the chemical formula of s triterpenoid saponin.
  • FIG. 5 shows that Quillaja saponaria saponins reduce the infestation rate with Caligus under commercial conditions.
  • Fish from a seawater site were divided in two groups; unit 1 that was fed with a Control Diet and unit 2, fed with a Test Diet added, which corresponds to the Control Diet with the addition of Quillaja saponaria saponins.
  • the counting considered the following life cycle stages: Chalimus, adult females and males and gravid females.
  • the infestation rate calculated is expressed as a percentage. The values represent the mean of 5 cages per condition ⁇ SE. (*) statistically significant difference.
  • One Way ANOVA analysis at P ⁇ 0.050 The present invention will now be described in more detail in the following.
  • the present inventors have surprisingly discovered that saponins from Quillaja saponaria in vitro presents a high toxicity to Caligus. Moreover in vivo studies performed by the present inventors show a significant reduction of Caligus in Atlantic salmon fed with a feed comprising Quillaja saponaria saponins compared to a control group fed with a traditional feed . Thus, one embodiment the present invention pertains to Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for use in the prevention and/or treatment of ectoparasitic infection or infestation in fish.
  • the present invention pertains to the use of Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for the manufacture of a medicament for the treatment and/or prevention of ectoparasitic copepod infection or infestation in fish.
  • a further embodiment of the present invention pertains to a method of treating and/or preventing ectoparasitic copepod infection or infestation in fish, said method comprising administering to said fish Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins.
  • prevention also covers prophylactic use of the compound, the medicament or method disclosed above.
  • Quillaja (Quillaja saponaria) is a tree native to Chile.
  • the inner bark of Quillaja saponaria can be reduced to powder and employed as a substitute for soap due to the presence of saponins.
  • Quillaja Saponaria saponins may also be referred to as inner bark of Quillaja saponaria. They may be provided as a powder or liquid, and may be in a purified, partly purified or native state. Saponins are mainly produced by plants, but also by lower marine animals and some bacteria (Yoshiki et al., 1998; Riguera, 1997). Saponins derive their name from their ability to dissolve in water to form colloidal solutions that produce foam upon shaking.
  • Quillaja Saponaria saponins consist of a sugar moiety, usually comprising glucose, galactose, glucuronic acid, xylose, rhamnose or methyl pentose, glycosidically linked to a hydrophobic aglycone also refeered to as a sapogenin.
  • the sapogenin can be a triterpenoid or a steroid or derivative thereof (Francis et al., 2005).
  • Saponins from Quillaja saponaria belongs to the group of triterpenoid saponins and will in the following be termed Quillaia saponins or Quillaja Saponaria saponins.
  • the Quillaja Saponaria saponins are terpenoid saponins.
  • Terpenoid saponins may be selected from the group consisting of monoterpenoid saponins, diterpenoid saponins and triterpenoid saponins.
  • the terpenoid saponins are triterpenoid saponins.
  • ectoparasitic copepods are copepods that feed on the mucus, epidermal tissue and/or blood of fish.
  • Sea lice are ectoparasitic copepods and belong to the family Caligidae. This family includes around 162 Lepeophtheirus and 268 Caligus species.
  • the ectoparasitic copepod may be sea lice.
  • the sea lice may be of the family Caligidae.
  • the sea lice may be of the species Lepeophtheirus or Caligus and more specifically they may be selected from the group consisting of Lepeophtheirus salmonis, Caligus elongatus and Caligus rogercresseyi.
  • L. salmonis has a high specificity for salmonids, including the widely farmed Atlantic salmon (Salmo salar). L. salmonis may also parasitize other salmonids to varying degrees, including brown trout (sea trout: Salmo trutta), arctic char (Salvelinus alpinus) and all species of Pacific salmon.
  • Caligus rogercresseyi has been recognized as the major parasite of farmed salmon in Chile. It was first reported in 1997 in Atlantic salmon. Currently the most susceptible reported hosts are Atlantic salmon and rainbow trout. Caligus rogercresseyi also parasitizes wild species, being the Patagonian blenny
  • the terms "infestation” and “infection” are used herein interchangeably since some scientific articles written in English use the terms “infection” or “infestation” to develop a matter that explains diseases caused by parasites.
  • the fish is of the family Salmonidae or may be of the subfamily Salmoninae.
  • the fish may be of a genus selected from the group consisting of Salmo, Oncorhynchus and Salvelinus.
  • the fish may be selected from the group consisting of Atlantic salmon ⁇ Salma salar L), Adriatic trout ⁇ Salmo obtusirostris), Flathead trout (Salmo platycephalus), Marble trout (Salmo marmoratus), Ohrid trout (Salmo letnica) and Sevan trout (Salmo ischchan).
  • Salmon is produced by mixing the eggs from one female salmon with the milt of one male salmon for fertilization. Once the eggs have hardened, they are transported to a hatchery for incubation . Each egg batch is incubated separately in Heath trays for approximately 5-6 weeks until they reach the eyed stage and will hatch after a total of approximately 9 weeks.
  • the alevins or sac fry Upon hatch, the alevins or sac fry will continue to develop using the nutrients in their yolk sacs. When their yolk sacs are almost consumed, the young fry are ready to feed . Once the young fry are onto feed they grow quickly over the next 6 to 12 months in freshwater. The fry grow to become parr/fingerlings and finally undergo developmental changes that prepare them for life in saltwater as smolts. Smolts ready for saltwater are transported from the hatchery to the marine farms, where they are transferred to the net pens to begin the seawater/saltwater phase of their life cycle. Smolts entered at the sea sites adjust to the saltwater environment and begin feeding. They are fed a high quality diet specially formulated to match the optimal seasonal and life stage requirements of salmon in the wild . Once onto feed, smolts grow quickly in seawater/saltwater, reaching a kilogram in size in 6 to 8 months.
  • the fish may be selected from the group consisting of smolts and adult fish. Therefore, the compound, composition and/or feed of the present invention may be administered to fish in the freshwater phase or the seawater/saltwater phase.
  • the invention may be useful to control e.g. parasitic infection with sea lice during the
  • the compound, composition and/or feed of the present invention is administered during the last period of the freshwater phase with the objective to prepare fish before the transfer to seawater/saltwater i.e. as a prevention of a potential ectoparasitic infection or infestation.
  • the fish may be selected from the group consisting of Chinook salmon (Oncorhynchus tshawytscha), Chum salmon
  • Oncorhynchus keta Coho salmon (Oncorhynchus kisutch), Pink salmon (Oncorhynchus gorbuscha), Sockeye salmon (Oncorhynchus nerka), Masu salmon (Oncorhynchus masou), Biwa trout (Oncorhynchus rhodurus), Cutthroat trout (Oncorhynchus clarkii), Rainbow trout (Oncorhynchus mykiss) and Mexican Golden Trout (Oncorhynchus chrysogaster).
  • the fish may be Arctic char (Salvelinus alp in us).
  • the fish may be selected from the group consisting of Atlantic salmon (Salma salar L.) and Rainbow trout (Oncorhynchus mykiss) .
  • One preferred administration form of the Quillaja Saponaria saponins, the composition comprising Quillaja Saponaria saponins and/or the medicament comprising Quillaja Saponaria saponins is oral dosing.
  • the dosing may preferably be in the form of a feed comprising Quillaja Saponaria saponins - i.e. a fish feed .
  • the Quillaja Saponaria saponins, the composition comprising Quillaja Saponaria saponins and/or the medicament comprising Quillaja Saponaria saponins may be part of a fish feed or may be formulated as a fish feed .
  • Such feed may be selected from the group consisting of pressed fish feed, pelleted fish feed, expanded fish feed, extruded fish feed and wet semimoist feed . Which of the feed types to choose depends on the fish species, the maturity of the fish and to which environment the feed is to be applied .
  • the compositon and/or fish feed of the present invention comprise Quillaja Saponaria saponins in combination with approved and/or authorised fish feed ingredients.
  • the approved fish feed ingredients may selected from the group consisting of a carbohydrate source, a protein source, a lipid source, ash, water and any combinations thereof.
  • approved fish feed ingredients may selected from the group consisting of a carbohydrate source, a protein source, a lipid source, ash, water and any combinations thereof.
  • ingredients and "authorised fish feed ingredients” are used interchangeably.
  • approved fish feed ingredients and “authorised fish feed ingredients” have the following meaning : fish feed ingredients covering feed materials such as products of vegetable or animal origin, whose principal purpose is to meet animals' nutritional needs, in their natural state, fresh or preserved, and products derived from the industrial processing thereof, and organic or inorganic substances, whether or not containing feed additives, which are intended for use in oral animal-feeding either directly as such, or after processing, or in the preparation of compound feed, or as carrier of premixtures.
  • carrier can be a substance used to dissolve, dilute, disperse or otherwise physically modify a feed additive in order to facilitate its handling, application or use without altering its technological function and without exerting any technological effect itself.
  • the protein source may constitute from 25-55% (w/w) of the
  • composition and/or fish feed such as from 26-54% (w/w), e.g . from 27-53% (w/w), such as from 28-52% (w/w), e.g. from 27-51% (w/w), such as from 28- 50% (w/w), e.g. from 29-49% (w/w), such as from 30-48% (w/w), e.g. from 31- 47% (w/w), such as from 32-46% (w/w), e.g. from 33-45% (w/w), such as from 34-44% (w/w), e.g. from 35-43% (w/w), such as from 36-42% (w/w), such as from 37-41% (w/w), e.g .
  • the carbohydrate source may constitute from 5-25% (w/w) of the composition and/or fish feed, such as from 6-24% (w/w), e.g. from 7-23% (w/w), such as from 8-24% (w/w), e.g. from 9-23% (w/w), such as from 10-24% (w/w), e.g. from 11-23% (w/w), such as from 12- 22% (w/w), e.g. from 13-21% (w/w), such as from 14-20% (w/w), e.g. from 15-19% (w/w), such as from 16-18% (w/w), e.g. from 17-19% (w/w), preferably in the range from 10-15% (w/w).
  • the lipid source may constitute from 14-40% (w/w) of the composition and/or fish feed, such as from 15-39% (w/w), e.g. from 16-38% (w/w), e.g. 17-37% (w/w), such as from 18-36% (w/w), e.g. from 19-35% (w/w), such as from 20-36% (w/w), e.g. from 21-35% (w/w), such as from 22-36% (w/w), e.g. from 23-35% (w/w), such as from 24-34% (w/w), e.g. from 25-33%, such as from 26-32% (w/w), e.g.
  • Typical protein sources may be processed animal protein or plant protein.
  • the processed animal protein may be selected from the group consisting of fish meal, blood meal, pork meal, feather meal, meat meal, bone meal and any
  • the plant protein may be selected from the group consisting of soybean, peanut, corn, gluten, raps, lupine, sunflower, wheat, sorghum, pea, oat and any combination thereof.
  • the carbohydrate sources may be selected from the group consisting of corn, wheat, beans, peas, tapioca, potato starch, sorghum, oat and any combination thereof.
  • the lipid sources may selected from the group consisting of fish oils, plant oils, poultry oil and any combinations thereof and the plant oil may be selected from the group consisting of soybean, rapeseed, sunflower, linseed oil and any combinations thereof.
  • the fish feed may comprises an ingredient selected from the group consisting of nucleotides, prebiotics, probiotics, vitamins, minerals, antioxidants, liposoluble and hydrosoluble molecules extracted from vegetables, liposoluble and hydrosoluble molecules extracted from marine sources, immune stimulants and any combinations thereof. Which ingredient(s) to choose depends on the fish species, the maturity of the fish and to which environment the feed is to be applied .
  • Example 1 and figure 1 the present inventors shows that the mortality of Caligus presented a dose response pattern achieving a 50, 85 and 100% mortality at 0.1, 10 and 100 ppm of Quillaja Saponaria saponins
  • Example 2 and figure 2 the present inventors showed that feeding Atlantic salmon comprising 200 ppm of Quillaja Saponaria saponins lead to a 44.3% reduction of the number of Caligus per fish compared with the group of fish fed with a control diet. Moreover it can be seen from figures 3A-3C that there are no statistically significant differences on specific growth rate (SGR), specific feed rate (SFR) and feed conversion rate (FCR) between the groups in Example 2.
  • SGR specific growth rate
  • SFR specific feed rate
  • FCR feed conversion rate
  • the composition and/or fish feed may comprise at least 0.1 ppm Quillaja Saponaria saponins, e.g. at least 0.2 ppm Quillaja Saponaria saponins, such as at least 0.3 ppm Quillaja Saponaria saponins, e.g . at least 0.4 ppm Quillaja Saponaria saponins, such as at least 0.5 ppm Quillaja Saponaria saponins, e.g. at least 0.6 ppm Quillaja Saponaria saponins, such as at least 0.7 ppm Quillaja Saponaria saponins, e.g.
  • At least 0.8 ppm Quillaja Saponaria saponins such as at least 0.9 ppm Quillaja Saponaria saponins, e.g . at least 1 ppm Quillaja Saponaria saponins, such as at least 5 ppm Quillaja Saponaria saponins, e.g. at least 10 ppm Quillaja Saponaria saponins, such as at least 50 ppm Quillaja Saponaria saponins, e.g. at least 100 ppm
  • Quillaja Saponaria saponins such as at least 200 ppm Quillaja Saponaria saponins, e.g. in the range from 0.1 - 200 ppm Quillaja Saponaria saponins, such as in the range from 0.2 - 180 ppm Quillaja Saponaria saponins, e.g. in the range from 0.3 - 170 ppm Quillaja Saponaria saponins, such in the range from 0.4 - 160 ppm Quillaja Saponaria saponins, e.g.
  • Quillaja Saponaria saponins in the range from 0.9 - 90 ppm Quillaja Saponaria saponins, such in the range from 1 - 80 ppm Quillaja Saponaria saponins, e.g. in the range from 5 - 70 ppm Quillaja Saponaria saponins, such in the range from 10 - 60 ppm Quillaja Saponaria saponins, e.g. in the range from 20 - 50 ppm Quillaja Saponaria saponins, such in the range from 30 - 40 ppm Quillaja Saponaria saponins.
  • Saponins may be measured by means of Ultra Performance Liquid
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise at least 0.1 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 0.1 - 200 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 0.4 - 160 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 0.8 - 120 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 1 - 80 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 5 - 70 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 10 - 60 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 20 - 50 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 30 - 40 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 0,1 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 10 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 100 ppm Quillaja Saponaria saponins.
  • composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25-55% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (iii) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 200 ppm Quillaja Saponaria saponins.
  • the fish are continuously fed Quillaja Saponaria saponins, a composition comprising Quillaja Saponaria saponins or a fish feed comprising Quillaja Saponaria saponins as part of their daily diet. It may further be preferred that the Quillaja Saponaria saponins, the composition comprising Quillaja Saponaria saponins or the fish feed comprising Quillaja Saponaria saponins is supplied to fish for at least 7 days.
  • the feed may be administered in the freshwater stage (as a prevention) or in the seawater/saltwater phase (as a prevention and/or treatment) - such administration may be for at least 7 days in order to obtain a sufficient preventive effect or treatment.
  • the Quillaja Saponaria saponins the composition comprising Quillaja Saponaria saponins or the fish feed comprising Quillaja Saponaria saponins is administered orally.
  • the sea lice life cycle consists of 10 different stages (plus the egg stage), with a moult between each one.
  • Saponaria saponins or the fish feed comprising Quillaja Saponaria saponins is effective on Chalimus I, Chalimus II, Chalimus III, Chalimus IV, pre-adult, adult sea lice stages and gravid females infested or re-infested on fish.
  • one aspect of the present invention pertains to the use of Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for the manufacture of a medicament for the treatment and/or prevention of ectoparasitic copepod infection or infestation in fish.
  • Another aspect of the present invention pertains to a method of treating and/or preventing ectoparasitic copepod infection or infestation in fish, said method comprising oral administering to said fish Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins.
  • the use or the prevention or the treatment according to the present invention may be a reduction of the total number of Chalimus I, Chalimus II, Chalimus III, Chalimus IV and adult sea lice stages infested or re-infested on fish compared to a population of fish fed an approved fish feed comprising no Quillaja Saponaria saponins.
  • the use or the prevention or the treatment may be combined with other traditional fish-specific antiparasitic compounds or other chemical, medical or natural agents against ectoparasites.
  • Such strategies include but is not limited to oral treatments such us emamectin benzoate and diflubenzuron.
  • Chemical or medical agents include but is not limited to immersion treatments such as hydrogen peroxide, deltamethrin, cypermethrin and azametiphos.
  • Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins may be used as a dry powder or solubilized in liquids including but not limited to oil before applied to the feed (e.g. pellet).
  • Including Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins in fish feed includes using state of the art technology well known for the person skilled in the art.
  • compositions such as fish feed
  • these methods include steps of provising a composition comprising Quillaja
  • Quillaja Saponaria saponins may be mixed together with the fish feed ingredients prior to formation of the fish feed pellets.
  • the invention provides a method for manufacturing a fish feed, comprising the steps of:
  • the present invention pertains to the manufacture of a fish feed, comprising the steps of:
  • the fish feed may be formulated as a pressed fish feed, pelleted fish feed, expanded fish feed, extruded fish feed and wet semimoist feed .
  • the combining of Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins with approved fish feed ingredients may be performed by use of mixing the ingredients in a feed mixer prior to further processing of the feed into fish feed . It goes without saying that the fish feed obtained may comprise the ingredients, constituents etc. stated under the heading "administration and formulation”.
  • the experiment was carried out under in vitro conditions. Ten adults Caligus rogercresseyi in total, five females plus five males, were deposited in a Petri plaque and incubated with 0, 0.5, 50 and 500 ppm of Quillaja high extract, and maintained in an incubator chamber at 12° C + 0.5 and under controlled oxygen saturation. Survival of Caligus was evaluated 24 hours after challenge. Each challenge condition was assessed in duplicate.
  • the Quillaja high extract comprises 20 % w/w Quillaja Saponaria saponins.
  • control diet with the commercial name "CPK 4mm”
  • CPK 4mm commercial name "CPK 4mm”
  • Later fish from this group were fed to satiation with : (i) control (diet 1) or (ii) 1000 ppm of Quillaja high extract (which corresponds to 200 ppm Quillaja saponaria saponins (diet 2) during 42 days.
  • Fish were challenged by immersion with Caligus rogercresseyi (42 copepodids per fish) by adding the said copepodids to the water in the tanks where the fish were maintained, with the objective to evaluate the effect of each diet on growth fish were weighted at the start, and at day 52 of the trial.
  • Uneaten feed was collected in all tanks after finishing the feeding, weighted and stored . Each experimental condition was carried out in five replicates.
  • Atlantic salmon maintained in a productive seawater site were distributed in two units each one conformed by 12 cages, unit 1 and unit 2, establishing two groups with similar characteristics. Each of these units where fed with either a commercial standard diet (Control) or a test diet which included Quillaja saponaria saponins. At the start of the trial the average body weight of fish was 2.5 kg in both groups. The recording of the number of Caligus was done in five cages per unit, selected according to their location : two index cages and three central cages. The counting of Caligus was carried out at the start of the feeding regimen and 33 days after to a continuous feeding regimen .
  • 100-56.44 43.56 or 43.6% less Caligus in the group fed with the diet added with Quillaja saponaria saponins. 127% and 225% are the infestation rates expressed in percentage, presented in figure 5.
  • Yoshiki, Y., Kudou, S and Okubo, K Relationship between chemical structures and biological activities of triterpenoid saponins from soybean [review] . Biosci.

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EP15716476.5A 2014-04-09 2015-04-09 Verbindung oder zusammensetzung zur verwendung bei der vorbeugung und/oder behandlung eines ektoparasitischen ruderfusskrebsbefalls oder infektion bei fischen Withdrawn EP3145521A1 (de)

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WO2015061755A1 (en) 2013-10-25 2015-04-30 Phibro Animal Health Corporation Combination and/or composition comprising bacillus, and yucca, quillaja or both and a method for making and using
EP3452027B1 (de) * 2016-05-02 2020-09-16 Evolva SA Verwendung von nootkaton zur behandlung von seeläusen
WO2018018171A1 (es) 2016-07-29 2018-02-01 Saponin Research Center S.A. Uso de extractos de quillaja saponaria para la prevención y control de infecciones virales en peces
US20180325970A1 (en) 2016-07-29 2018-11-15 Saponin Research Center S.A. Use of quillaja saponaria extracts for the prevention and control of bacterial infections in fish
NO346318B1 (en) * 2019-10-05 2022-06-07 Previwo As Method for treating and/or preventing a parasitic infection in a teleost
NO346319B1 (en) * 2019-10-05 2022-06-07 Previwo As Method for treating and/or preventing a sea lice infection in a teleost

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