• 专利附录
  • 专利说明
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    • 专利摘要:
    The invention relates to Quillaja Saponaria saponins or a composition comprising Quillaja Saponaria saponins for use in the prevention and/or treatment of an 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.
    公开号:DK201670845A1
    申请号:DKP201670845
    申请日:2016-10-28
    公开日:2016-11-14
    发明作者:Alin Ximena Casado Zelaya；Michael Andrew Adler Eggers
    申请人:Biomar Group As；
    IPC主号:
    专利说明:

    ::€OMp6uND OR COMPOSITION FOR USE m THE PREVENTION ANP/ØR TREATMENT OF AN EéTOPAimSITIÉ COPETOO INFESTATION OR INFECTION IN FISH.
    Field of the invention
    The present invention relates to QuHlaja Sapomna; saponins or a composition comprising -Qpøap Saponarta 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 OuiPaja Saponana saponins.
    Background of the invention
    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 Cailgldae, This family includes around 162 Lepeophtheirus and 268 Caiigus species,
    Ectoparasitic copepods .such as sea lice may cause physleai and enzymatic damage at thesite of attachment on the fish which results in ahrasion-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 ioss 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 d possible^ vector for other pathogens like salmon aiphs virus (Pancreatic disease), infectious Salmon Anamis virus (ISAv) and Piscinckettsia salfoonis. The degree of damage is also dependent on the species of sea lice, the developmental: stages df the sea lice present, and the number of sea lice Oh 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. Moreover, ectoparasitic infestations/infeetions 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 fey 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 Callgidae was first Identified in Chile during i 997 in Atlantic salmon, From 1997 and until a few years ago; sea lice of the family Lepeophtheiras and Csfigus was treated with emamectin benzoate. Unfortunately, the efficiency of emamectin benzoate has diminished significantly ;due to the excessive use and lack of rotation with other fish-specific anfiparasitic compounds. Such compounds include organophosphates, pyrethroids, hydrogen peroxides and chitl.n synthesis inhibitors. At present, the strategy applied to decrease Infestations/infeetions 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/infeetions caused by sea Ice still poses a huge problem to the farming industry.
    Hewer strategies to decrease infestations with ectoparasitic copepods includes immunestimuiants such as beta-glucans, essentia! oils (carvacrdi, thymol and their combinations), and other outraceuticals such as nucleotides and mannan-oiigosaechatides, 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 unfeyourabie and harmful accumulation in the nutritional chain. When supplied with the diet, such compounds should either be degraded or excreted fey the organism after a reasonable time period. This is especially important since fa rmed fish will eventually be consumed by humans .
    In Chile over the last couple of years,, the economic losses recorded doe to the management of sea lice outbreaks has beco.me:όdedf'the^most impoH^ntdtems-'In· the Salmon and Trout production costs. In this scenario the development of alternative treatments for the control of ectoparasitic copepod infestations/infectlons such as infestations/lnfections caused by sea lice, is urgent
    In this respect, it would be especially advantageous if such treatment could be included in: the fish feed«
    Summary of the invention
    Thus, do object of the present invention relates to a compound or composition for use id the prevention and/or treatment of ectoparasitic infestations or infections in fish.
    In particular, it may be seen as an object of the present invention to provide a compound or composition that solves the above mentioned problems of the prior art ~ e,g, by being essentially non-toxic for the fish in the applied concenthations when incorporated into a fish feed,
    Thus, one aspect of the invention relates ta Qu$&ja Ssponaria saponlns or a composition comprising QuiifajéJBapppiøti$ ^pdftfns' for: use in the prevention and/or treatment of ectoparasitic infection Of infestation In fish .
    Another aspect of the present mvention relates to the use of QuPlaj& S&ponaria sapdnms or a composition comprising Quiilaja Saponaria saponlns 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 Quiliaja Saponaria or a composition comprising Quiliaja 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 Quiliaja Saponaria saponins or a composition comprising Quiliaja Saponaria saponins with approved and/or authorised fish feed ingredients and obtaining a fish feed comprising Quiliaja Saponaria' saponins,
    Description of the figures
    Figure X shows thetoxldty of Quiliaja saponaria saponins on Ceiigus. the:dose *ppm'f'1d: figure 1 refers to experiments conducted: with Quiliaja high extract which comprises 20% Quiliaja saponaria saponins - the ddsc thus corresponds to 0, U-L· 10 and :i 00 ppm Quiliaja saponaria saponins.
    Figure 2 shows the effect of QwPaja saponaria saponins oh the infection rate with Caiigus in Atlantic salmon (Saimo safer) >
    Figure 3A-3C shows the SGR (specific growth rate); SFR (specific feed rate) and FCR (feed conversion rate) between two groups.
    Figure 4 shows the.chemlcaS formula of s tritefpsnoid saponin.
    Figure 5 shows that Quiliaja sapmaria saponins reduce the infestation rate with Caiigus under commercial conditions, Fish from a seawater site were divided in two groupsunit X 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 Quiliaja saponaria saponins, At the start:of the: feeding strategy and 33 days: after the starting of the feeding regimen, the number of Caiigus attached to the skin of fish and those parasites present in the tens of counting were recorded. The counting considered the following life cycle stages: Chalimvst 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 £ BE. (*) statisticaiiy significant difference. One way AMOWA analysis at P<0.050. the present invention will now be described in more detail in the following, Detailed description of the' invention
    The present inventors have surprisingly discovered: that saponins from Quiiiaja saponaria m vitro presents a high toxicity to Caiigus. Moreover in vivo studies performed by the present inventors show a significant, reduction of Caiigus in Atlantic salmon; fed with a feed comprising Quiiiaja saponaria saponins compared to a control group fed with a traditional feed.
    Thus., one embodiment the present invention pertains to Quiiiaja Saponaria saponins or a composition comprising Quiiiaja Saponaria". saponins for use In the prevention and/or treatment oflectoparésltic infection or Infestation in fish. in another embodiment; the present Invention pertains to the use of Quiiiaja Saponaria saponins Or a composition comprising Quiiiaja Saponaria saponins for the manufacture of a medicament for the treatment and/or prevention of ectoparasitlc copepod infection or infestation in fish. A further embodiment of the present invention pertains to a method of treating and/or preventing ectoparasitlc copepod infection or infestation in fish, said method comprising administering to said fMxQmiiaja Saponaria saponins or a composition comprising Quiiiaja Saponaria saponins,
    It is to be understood that the term "prevention" also covers prophylactic use of the compound, the medicament or method disclosed above.
    Quiiiaja Saponaria saponins
    Quiiiaja (Qaiiiaja saponaria) is a tree native to Chile, The inner bark of Quiiiaja saponaria can be reduced to powder and employed as a substitute for soap due to the presence of saponimiThm, Quiiiaja Saponaria saponins may also be referred to as inner bark of Quiiiaja saponaria. They may be provided as a powder or liquid, and may be in 0 purified, partly purified or native state, Saponins are mainly produced by plants, but also by lower marine animals and some bacteria (Yøshiki et al., 1998; Riguers, 1997), Saponins derive their name from: their ability to dissolve in water to form colloidal solutions that produce foam upon shaking:, these: molecules consists of a group of glycosides with surface active properties that distinguish these compounds from other glycosides. Quitt&amp;ja Sapanana saponins consist of a sugar moiety,: usually comprising glucose, galactose, glucuronic acid,: xylose, rhamnose or methyl pentose, glycosidicaily linked to a hydrophobic agiyeone also refee red to as a sapogenin. The sapogenih can be a triferpenoid or a steroid or derivative thereof (Francis at ah, 2005), Saponins from QuiM&amp;ja saponan'a belongs to the group of triterpenoid saponins and wiil in the following be termed Quiiiala saponins or QuMaja Saponaria saponins.
    Although saponins play a key role in the defence response of plants against the, insects attack, &amp; is believed that saponins exert a negative effect,on animals if present in an animal diet in moderate to high concentrations (Cheeke, 19%), in fact dietary saponins derived from different plants have been considered as the etlologlcai factor of a significant reduction of feed intake and impairment of productive performance of saimonid fish (Mswinger, 1994;Bureau et ai., 1998). thus, in one embodiment of the present invention the QuIHajaSapomm saponins are terpenoid saponins. Terpenoid saponins may be selected from the group consisting of mo noterpenoid saponins, diterpenoid saponins and triterpenoid saponins. In a preferred embodiment the terpenoid saponins are triterpenoid saponins:.
    The chemicai formula of a triterpenoid saponin is shown in figured, B&amp;apamsitic ccpapod
    As mentioned above ectoparasitic copepods are copepods that feed on the mucus, epidermal tissue ahb/or blood of fish.
    Sea lice are ectoparasltic copepods and belong to the family Caligidae, This family includes around 162 LepeophtPems aM 288 Caligm species.
    Thus, in an embodiment of the present invention the ectoparasihc copepod may be sea Hee. In a further embodiment the sea lice may be of the family Caligidae.
    In a further embodiment the sea dice may be of the speciestMpeaphthBiFm or Caligus and more specifically they may be selected from the group consisting of Lepeophtheirus saim&amp;ais, Caiigus eiongalus and Caligus rogercrmseyL
    Sea lice of different iife stages has been found on fish - such life stages include but is not limited to Cfialimus /, Chaiimus IJ, Chaiimus II!y Chaiimus IV, pre-adults, adult sea iice and gravid females,
    Many ectoparasites such as sea lice are specific with regards to host genera . For example X, saimonis has a high specificity før salmon Ids, Including the widely farmed Atlantic salmon (Satmo salar), L saimonis may also parasitize other salrhonids to varying degrees, Including brown trout (sea trout: Salma irutta), arctic char (Se/ve/mgs aipinus) and all species of Pacific salmon.
    Cailgm 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 mgsrcresseyi also parasitizes wild species, being the Patagonian bienny (Bieginops m&amp;clovinus) one of the most important due to Its role as reservoir and spreader of Caligus to farmed: salmonid fish,
    Fish with sea iice occur In fish.
    In ths present context 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. Thus,: in am-embodiment of the present invention the fish is of the family Salmon ieiae or may he of the subfamily Saimomnae, In a preferred embodiment the fish may be of a genus selected from the group consisting of SaimOf Qnmrhymhusand Saiveiinus.
    If the fish is of the genus Saimo the fish may be selected from tbe group consisting of Atlantic salmon {Salma satar'L), Adriatic trout (Salmo obtusimsMs}f
    Flathead trout {Salmoplatycaphalas}, Marble trout (Salmo ietoica) and Sm/an trout {Salmo ischchan),
    Salrnoh is produced by mixing the eggs from one female saimon With the miit of onetmele salmon for fertilization, Once the eggs have· hardened, they are transported to a hatchery for incubation, Each egg; batch: is incubated se paratoly in Heath trays for appfoxfmafeiy S~8 weeks until they reach the eyed stage and wii! hatch after a total of approximately 9 weeks. Upon hatch, the aievins or sac fry Will continue to develop using the nutrients m their yoik 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 dyer the next 6 to 12 months in freshwater. The foy grow to become parr/fingeriings and finally undergo developments! changes that prepare them 'for iife In saltwater: as smolts. Smoits ready for saltwater are transported'foom· the hatchery to the marine farms, where they are transferred to the net pens to begin the seawater/saitwater 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 saimon in the wild . Once onto feed, smoits grow quickly in seawaterysaitwater, reaching a kilogram in size in 8 to 8 months.
    Thus, in an embodiment of the present invention the fish rnay be seieoted from the group consisting of smelts and adult fish. Therefore, the compound, composition and/or feed of the present invention may he administered to fish in the freshwater phase or the seawater/saitwater phase. The invention may be useful to control e.g. parasitic infection with sea lice during the seawater/saitwater stage. However, it may be preferred that 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/saitwater i.e< as a prevention of a potential ectoparasltic infection or infestation.
    If the fish is of the genus Oncomyndws the fish may be selected from the group consisting of Chinook salmon {Oncorhynchus tshawytscha), Churn salmon (Oncorhynciws keta$*Coho salmon (Sm&amp;rbynchas klsutch), Pink saimon χφ&amp;ΡόφγηΦυ$ §orbtméa)i' saimoh $Omårftfåehti&amp;nerka^ Iviaéu salmon
    Ønmrhynchus mssou)f Biwa trout (Qmarpynchus rfrodums), Cutthroat tmut 0nm&amp;yn^usoiarkiijf&amp;3inhaw trout (Onmrhynchus mykissj arid Mexican Golden Trout (Oncorhynchus chrysogastérT
    If the fish is of the genus Saiyeiinm the fish may be Arctic char (SaimUnus alpin us).
    In a particular preferred embodiment, the fish may be selected from the group: consisting of Atlantic salmon '(S&amp;fffia safari.) and Rainbow trout (Qncorhynckijs; myklss).
    Administration and forniuiapon
    One preferred administration form of the Quiiiaja Saponaria saponins, the composition comprising Quiiiaja Saponaria saponins and/or the medicament comprising Quiiiaja Saponaria saponins is oral dosing. The dosing may preferably be in the form of a feed comprising Quiiiaja Saponaria saponins ~ be. a fish feed,
    In one embodiment of the: present invention the Qutffaja Saponaria saponins, the composition comprising Qwiiaja Saponaria saponins and/or the medicament comprising Quiiiaja Saponam saponins may be part of a fish feed or may he 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,
    In a particular embodiment the compositon and/or fish feed of the present: invention comprise Quiiiaja 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,
    In-the context of the present application the terms "approved, fish feed ingredients" and "authorised fish feedJrtgr€d'ients:"'am'dsecl intercnarsgeaOSy, in the context of the present application the tertns'^appmved':^shfeeci'Jlnfredfents'r and "authorised :frsh 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 industriai processing thereof, and organic or inorganic substances, whether or not containing feed additives, which are intended for use In ora! animat-feeding either directly as such, or after processing, or in the preparation of compound feed, or as carrier of premixtures. In this context, "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 tselfr
    Typically 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 29-45% '(w/w), such as from 30-48% (w/w), e.g. from 31-47% (w/w), such as from 32-40% (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, from 38-40% (w/w), such as from 39-40% (w/w), preferably in the range from 30-55% (w/w).
    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), ei)' from 9-23% (w/w), such as from 10-24% (w/w), e.g. from 11-23% (w/w), such asfrom 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 16-36% (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 22-38% (w/w), e.g. from 23-35% (w/-w)t such as from24-34% (w/w), e.g. from 25-33%, such as from 26-32% (w/w}f e.g. from 27-33%, such ss from 2S~32% (w/w}, e.g. from 29-31%, such as from 30-31% (w/w), preferabiy 'in the range from 2s -40% (w/w).
    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 meai, meat meal, bone meal and any combinations thereof whereas 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 com, 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 combroadens thereof.
    In a preferred embodiment the fish feed may comprises an ingredient selected from the group consisting of nucleotides, probiotics, probiotics, vitamins, minerals, antioxidants, liposoiuble and hydrosolubie molecules extracted from vegetables, liposoiuble and hydrosoluble molecules extracted from marine sources, immune stimulants and any combinations thereof. Which ingredientfs) to choose depends on the fish species, the maturity of the fish and to which environment the feed Is to be applied.
    As can be seen in Example l and figure x the present inventors shows that the mortality of CaMgus presented a dose response pattern achieving a 50, 85 and 190% mortality at. 0.1, 10 and xOO ppm of QuiPaja Saponana sapomns respectively, in Example 2 and figure 2 the present inventors showed that feeding Atlantic salmon composing 200 ppm of QuiPaja Saponarm saponins lead to a 44.3% reduction of the number of CaPgus 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 «ο: statisticaliy significant differences on specific growth rate (SiSfr), specific feed rate pFR) and feed conversion rate (PCR) between the groups In Example 2.
    Thus, in a preferred embodiment off he; present invention the composition and/or fish feed may comprise at least 0.1 ppm QuMaja Saponaria saponins, e.g. at feast 0.2 ppm Quliiaja Saponaria saponins., such as at feast 0.3 ppm Quliiaja Saponaria saponins, e.g, at least 0.:4 ppm Quiilaja Saponam saponins, such as at least 0,5 ppm Quiliaja Saponaria saponins, e.g, at least 0.6 ppm Quiliaja Saponam saponins, such as at least 0.7 ppm Quiliaja Sapomria .saponins, e.g. atleast Q.S ppm Quiilaja Saponam saponins, such as at least 0.9 ppm Quiliaja Sapm&amp;rta· saponins, e.;g. at least 1 ppm Saponam saponins, such as at least 5 ppm
    Quiilaja Saponaria saponins, e.g, at least 10 ppm Quiilaja Saponam saponins, such as at least :50 ppm Quiilaja Saponaria saponins, e.g, at least 108 ppm Quiliaja Saponaria saponins, such as at least 200 ppm Quiliaja Saponaria saponins, e.g. in the range from 0.1 - 200 ppm Quiliaja Saponaria saponins, such as in the range from 0,2 - ISO ppm Quiilaja Saponaria sapohins, e.g, in the range from 0.3 - 170 ppm Quiliaja Saponaria .saponins, .such in the: range from 0,4 -- 160 ppm Quiilaja Saponaria saponins, e,g, in the range from 0.5 -- ISO ppm Quiliaja Saponaria saponins, such in the range from 0,6 -- 140 ppm Quiilaja Saponaria saponins, e.g. in the range from 0.7 - 100 ppm Quiilaja Saponariasaponins,such in the range from 0,8 -120ppm Quliiaja Saponaria saponins, e,g. In the range from 0.9 - 1:10 ppm Quiilaja Saponaria saponins, such in the range from 0.8 ~ 100 ppm Quiilaja Saponaria saponins, e,g. in the range from 0,9 - 90 ppm Quiiiaø Saponaria saponins, such in the range from 1 ~ 80 ppm Quiliaja Saponaria saponins, e.g. in the range from 5 - 70 ppm Quiiiap SaponarU sapomm, sucP in the range from 10 - 60 ppm Quiilaja Saponaria saponins, e.g, in the range from 20 - SO ppm Quiilaja Sapomria saponins, such in the range from 30 - 40 ppm Quiilaja Saponaria saponins,
    Saponins may be measured by means of Ultra Performance Ugyid Chromatography he. UPhC (a modified HPLC method).
    In a preferred embodiment the composition and/or fish feed comprise the follow i ng co nst ituen ts in t h e: fei i owl ng a mounts: (i) pr ote i n: so urce const itutesi from 25-5.5% (w/w) of the composition and/or fish feed, (ii) carbohydrate source constitutes from 5-25¾¾ (w/w) of the composition and/or fish feed, (ill) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv)the composition and/or fish feed comprise at feast 0.1 ppm Quiiiaja Saponaria saponins.
    In a preferred embodiment the composition and/or fish feed comprise the folio wing constituents in the following amounts: (j) protein source constitutes from 25-55% (w/w) of the com position; and/or fish feed, .(if) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (in) 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 Quiiiaja Saponaria saponins. in a preferred embodiment the 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,, (li) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (ill) lipid source constitutes from 24-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 0,4 - 260 ppm Qniiiaja Saponaria saponins.
    In a preferred embodiment the 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, (ti) 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 comprlsefr.S -120 ppm Qiuiliaja Sapon&amp;fia saponins. in a preferred: embodiment the 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, (il) carbohydrate soured: constitutes from S-25% (w/w) of the composition and/or fish feed, (iii) hpsd source.: gohstitutes from 14-40% (w/w) Of the composition and/or fish feed (iy): the composition and/or fish feed comprise !: - 80 ppmQpiii&amp;ja Saponaria saponins. in a preferred embodiment the composition and/or fish feed comprise thé: following constituents in the following:amounts: (j) protein source constitutes from 25-55% (w/w) of the composition and/or fishfeed, (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 Qulilaja Saponatia saponins.
    In a preferred embodiment the composition and/or fish feed comprise the following constituents in the following: amounts: (i) protein source constitutes trom 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, .{in) lipid source constitutes from 14-40% (w/w:)N©fi'ihe:x©mpeslt(oh'ahd/or''frSh feed (Iv) the composition and/or fish feed comprise 10 - 60 ppm Quiilaja Saponana saponins. in a preferred embodiment the icompositson 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, (ill) 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 Quiitaja Saponaria saponins. in a preferred embodiment the 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, (it) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (HI) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 20 - 40 ppm QuHbja Sapanaria saponins.
    In a preferred embodiment the composition and/or fish feed comprise the following constituents In the foliowing amounts: (I) protein source constitutes from 2S-SS% (w/W) of the composition and/or fish feed, (H) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (ill) 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 Quiiiaja Sapaparia saponins.
    In a preferred embodiment the composition and/or fish feed comprise the following constituents in the following amounts: (i) protein source constitutes from 25--55% (w/w) ofthe composition and/or fish feed, (;i) carbohydrate source constitutes from 5 - 2.5% (w/w) of the composition and/or fish feed, (m) lipid source constitutes from 14-40% (w/w) ofthe composition and/or fish feed (iv) the composition and/or fish feed comprise 10 ppm Quiiiaja Saponaria saponins.
    In a preferred embodiment the composition aml/or fish feed comprise the following constituents in the following: amounts: (i| protein source constitutes from 25-55% (w/w) of the com position' and/or fish feed, (li) carbohydrate source constitutes from 5-25% (w/w) of the composition and/or fish feed, (in) lipid source constitutes from 14-40% (w/w) of the composition and/or fish feed (iv) the composition and/or fish feed comprise 3.00 ppm Quiiiaja Saponaria saponins, in-8 preferred embodiment the composition and/or fish feed comprise the following constituents in the following amounts: (I) protein source constitutes from 25-55% (w/w) ofthe composition and/or fish feedvfii) carbohydrate source constitutes from 5-25% (w/w) ofthe composition and/or fish feed:, (Hi) lipid source constitutes from 14-40% (w/w) ofthe composition and/or fish feed (iv) the composition and/or fish feed comprise 200 ppm Quiiiaja Saponaria saponins.
    In. order to obtain a satisfactory result, it may be preferred that the fish are continuously fed QuiiiajaSaponaria saponins;, a composition comprising Quiiiaja Saponaria saponins or a fish feed comprising Quiiiaj&amp; Saponaria saponins as part of their daily diet. It may further be preferred that the Quiiiaja Saponaria saponins, the composition comprising: Quiiiaja: Saponaria saponins or the fish feed comprising Quiiiaja Saponaria saponins Is supplied to fish for at least days.
    As mentioned previously the feed may be administered in the freshwater stage (as a prevention) or In the seawater/saitwater 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, it. may further be preferred that the Quiiiaja Sappo&amp;ria saponins, the composition comprising Quiiiaja Saponaria saponins, or the fish feed comprising Quiiiaja Saponaria saponins is administered orally. %e sea lice life cycle consists vbf 10: dlfferenbstages (plus the egg stage), With a nfeuit between each one, Thus, in a preferred embodiment it may be preferred that the Quiliaja S&amp;ponaHa saponins, the composition comprising Quiliaja Sapanana saponins or the fish feed comprising Quåipja Saponaria saponins is effective on Wfraitmus I, ChaUmus II, Chaiimm 111, Qhailmus t/( pre~adu!tf adult sea lice stages and gravid females infested or re-infested on fish .
    Thus, one aspect of the present invention pertains to the use of Quiliaja Saponaria saponins. or a composition comprising. φίύ0Ά Sapmatia saponins for the manufacture of a medicament for the treatment and/or prevention of ectoparasstic copepod infection or' infestation in fish,
    Another aspect of the .present invention pertains to a method of treating and/or preventing ectoparasitie copepad infection or infestation in fish, said method comprising oral administering to said fish Quiliaja Saponaria saponins or a composition comprising Qulilaja Saponaria saponins.
    The use or the prevention or the treatment according to the present invention may be a reduction of thetotal number of Chaiimw I, ChaUmus II, Cha!imu$ III, ChaUmus IV and adult sea lice stages infested or reHOfested on fish compared to a population of fish fed an approved fish feed comprising no Quiliaja 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 difiubenzuron. Chemical or medica! agents include but is not limited to immersion treatments such as hydrogen peroxide, delta metltrlh:, cypermethfln and azametiphos.
    Method for the manufacture of a fish feed
    There are numerous recipes for making fish feed. When combined with approved fish feed ingredients QuMaja Saponaria saponins or a composition comprising
    Quiiiaja Saponaria saponins may bé used as a dry powder or solubilised in liquids including but not limited to oil before: applied to the feed (eg. pellet).
    Including Quiiiaja Saponam saponins of a composition comprising Quillaja Saponaria saponins in fish feed includes using state of the art technology weli known for the person skilled in the art.
    Thus, in a further aspect the present invention pertains to methods for the manufacture of compositions (such as fish feed) as defined above. In generai these methods include steps of "provising a composition comprising Quiiiaja Saponaria saponins together with any of the fish feed ingredients defined above, in an embodiment Quiiiaja Saponaria saponins may be mixed together with the %h feed ingredients prior to formation of the fish feed pellets*
    Thus,, in an even further embodiment the invention provides a method for manufacturing a fish feed, comprising the steps of: i) combining Quiiiaja Sap on aria $a pon i n s or a composition comprising Quiiiaja Saponaria saponins with approved fish feed ingredients*· and (if) obtaining a fish feed comprising Quiiiaja Saponaria saponins.
    In another embodiment the present invention pertains to the manufacture of a fish feed, comprising the steps of: i) combining Quiiiaja Saponaria saponins or a composition comprising Quiiiaja Saponaria saponins with approved fish feed ingredients, ii) forming fish feed and (iii) obtaining a fish feed comprising Quillaja Saponaria saponins.
    The fish feed may be formulated as a pressed fish feed, pelleted fish feed, expanded fish feed, extruded fish feed and wet semifooist feed,
    Thd: comblhlhg: of Quiiiaja: Saponaria saponins or a composition comprising Quiiiaja Saponana saponins with approved fish feed' ingredients may be performed by use of hlixfhg the ingredients In a feed mixer prior to further processing of the feed into fish feed.
    It goes without saying that theilsih feed obtained may comprise the ingredients,, constituents etc. stated under the heading "administration and formulation".
    It should be noted that embodiments and features described In the context of one of the aspects of the present invention also apply to the other aspects of the invention.
    All patent and non-patent references cited in the present application, are hereby incorporated by reference in their entirety.
    The invention will now be described in further details in the following non-limiting examples and figure,: wherein
    Examples
    Toxidfty of Quiiiaja saponaria saponins on Caiigus,
    The ex peri ment was carried out under in vitro conditions. Ten adults Caiigus r&amp;gércressayf miotai, five females plus five males, were deposited in a Petri plaque and incubated with 0, . Q,5> 50 and 500 ppm of Quiiiaja high extract, and maintained in an incubator chamber at 12° C 4 0,5 and under controlied Oxygen saturation. Survival of Caiigus was evaluated 24 hours after challenge. Each challenge condition was assessed In dupilcate.
    The Quiiiaja high extract comprises 20 % w/w Quif^a Saponaria saponins.
    Survival of Caiigus was evaluated 24 hours after challenge. Each challenge condition was assessed in duplicate.
    As can be seen from Figure I, it was observed that mortally of Caiigus presented a dose response pattern achieving a 50:, 85 and 100% of mortaiity at 0.5,. 50 and 500 ppm of Quiiiaja high extract (which thus corresponds to 0.1,10 and 100 ppm of Qmiiaja Saponaria saponins): respectively. Both females and: males presented; a; ;sittilaf sensitivity to each dose of Quiiiaja Saponaria saponins tested.
    Example 2
    Effect of QuiBajB saponarm sapommon the infection rate with Caiigus in Atlantic salmon {Salmo s&amp;iarj.
    The experiment was carried out at Pundacidn Chile aquaculture research facilities (Puerto Montt, Chile;). X2SQ Atlantic salmon smolt of 120 g which had no previous contact with Caiigus were distributed in 25 fiberglass tanks of 0.4 rnf with full salinity water and acciimatedrduring :2l days fed:with a commercial diet (i.e. control diet with the commercial name "CPK 4mm"). Later fish from this group were fed to satiation with: (i) control (diet X) or (ii) 1000 ppm of Quiiiaja high extract (which corresponds to 200 ppm Qmliaja sapmaria saponins (diet 2) during 42 days.
    Fish were .challenged by immersion with €&amp;jigmrogmt*res$eyt'.(42·©opepodids 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 ail tanks after finishing the feeding, weighted and stored. Each experimental condition was carried out in five replicates.
    As can be seen from Figure 2, feeding with diet 2 resulted in a 44.3% of reduction of number of Caiigus per fish compared with the group fish fed diet 1,
    Prom figures 3A-3C it is clear that there are no statistically significant dlfiferences on SCR (specific growth rate); SFR (specific:feed rate) and FCR (feed conversion rate) between both groups: diet 1 ~ control diet and diet 2 ~ 1300 ppm; of Quitlaja high extract (which corresponds to 200 ppm Qaiiiaja sapomrM saponins). hxample.3.
    Atlantic salmon maintained in a productive seawater; sit# were distributed in two units each one confbnbsd 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 QafUaja sdponaria saponins. At the start: of the trial the average body weight offish was 2,5 kg in: both groups. The recording of the number of Caiigus 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, .Considering· the average values of the infestation rate ofeachgroup, in figure 5 it is shown that consistently with the results obtained with the to wud trial (Example 2), fish from Unit 2, fed with the Test Diet, presented a 43,6% of reduction of the infestation rate with Caligus compared with fish from Unit 1 {fed with Control Diet) 127% and 225% of infestation rate, respectively, By way of exemplification these·percentages are calculated as follows: the difference between the infestation rate of both groups, expressed in percentage is (127/225)^10© ώ 56.44%, 100-56,44^43,56 or 43,6% less Caligus in the group fed with the diet added with Qulilaja saponarie saponins, 127% and 225% are the infestation rates expressed in percentage!, presented in figure 5,
    The infestation rate was calculated as follows: (Number of Caligus at day 33)-(Number of Caiigus at basal time) = X, then the infestation rate will be X/f Number of Caiigus at basal time), Then the infestation: rate expressed as percentage is: X/(Humber of Caiigus at basal time)*:! 00.
    Even more, similar to the results of the to vivo trial (Example 2), the effect exerted by Test Diet on the infestation rate with Caiigus, was attributable to the reduction of ail stages of Chalt mas, The productive parameters SGfC SFR and FCR were not affected by any of the treatments,
    References
    Bureau, D.,. Harris, A, and Cho, C, The effects of purified alcohol extracts from soy products on feed intake and growth of Chinook salmon (Oncorhynchus tshawytscha) and rainbow trout (Oncorhynchus rti.yk.iss), Aguacuitute: 161: 27 -43, 1998.
    Gbeeke, F.R. Bioiogioai effects of feed and forage sapohlns and their impact on animal production, in: Saponlns Used in Food and Agriculture. Plenum Press, New York, pp, 377-386, 1996,
    Francis, 0,, Makkar, -ft., and Becker, k. Effects of cyclic and regular feeding of a Qutiiaja saponin supplemented diet on growth and metabolism of common carp (Cyprtnus carpio L.). Fish Physiology and Biochemistry 24: 343 -350, 2002.
    Newinger, HVD, Fish poisoning plants in Africa, Bot, Acta 107^263-270, 1994.
    Riguera, R, Isolating Oioactlve compounds from marine organisms. 3, Mar, Biqteehnoi, 5:187-193, 1997,
    Yoshiki, ¥,, Ktidou, 5 and Okuho, K, Relationship between chemical 'structures and bioiogicai activities of triterpen old saponins from soybean [review]. Biosci. Biotechnoi Blachem, 62: 2291-2299, 1998,
    权利要求:
    Claims (12)
    [1] t, Qaiilaja SapomrJa saponlns or a composition comprising Qulllaja Saponaria sapohihs for use in the prevention and/or treatment of an ecto parasi tic infection or infestation in fish:, 2. the compound or composition according to:claim i* wherein the ectoparasitlc cop apod is a sea iice,
    [3] 3. The compound or composition according to claim 2, wherein the sea iice is selected from the group consisting of Lepaopfiifialrm safmonls, Cailgus &amp;fongatus Caiigm ci&amp;memt and mgererasseyi,
    [4] 4. The compound or composition according to any one of the preced ing claims.* wherein said fish is of the family Saimonidae.
    [5] 5. The compound or composition according to any one of the preceding claims, wherein the fish is of the genus selected from the group consisting of Salma, Oncorhynchm a n d Salveiimts, C The compound or composition according to any one of the preceding claims, wherein the fish is selected from the group consisting of Atlantic salmon {Salma mlar L) and Rainbow troPiiOmorhynchus myklssT
    [7] 7, The compound or composition according to any one of the preceding claims, wherein in said compound or composition is part of a fish feed or formulated as a fish feed.
    [8] 8, The compound or composition according to claim 7, wherein said fish feed is selected from the group consisting of pressed fish feed, pelleted fish feed, expanded fish feed, extruded fish feed and wet semi mo 1st feed.
    [9] 9, The compound or corn position according: to claim 7, wherein: said fish feed: comprises: approved fish feed ingredients.
    [10] 10. The compound or composition according to any one of the proceeding claims* wherein the feed comprises an ingredient selected from the group consisting of nucleotides, preblotlcs, probiotics, vitamins, minerals, antioxidants, iiposoiuble and hydrosoiubie moiecules extracted from vegetables, iiposolubie and hydrosoiubie moiecuies extracted from marine sources, immune stimulants and any combinations thereof. X X. The compound or composition according to any one of the preceding ciaims, wherein said composition comprises at least 0.1 ppm Quiiiaja Saponaria saponins, e,g. at ieast 0.2ppm QuiiiajaSaponaria saponins, such as at ieast 0.3 ppm Quiiiaja Saponaria sapooms, e.g, at least 0.4 ppmQuiiiaja Saponaria saponins, such as at ieast 0.5 ppm Quiiiaja Saponaria saponins, e.g. at least 0.6 ppm Quiiiaja Saponaria saponins, such asat least 0.7 ppm Quiiiaja Saponaria saponins, e,g. at least 0,8 ppm Quiiiaja Saponaria saponins, such as at least 0.9 ppm Quiiiaja Saponaria saponins, e.g. at least l ppm Quiiiaja Saponaria saponins, such as at least 5 ppm Quiiiaja Saponaria saponins, e,§. at ieast 10 ppmQmiiaja Saponaria saponins, such as at least SO ppm Quiiiaja Saponaria saponins, e,g. at least i00 ppm Quiiiaja Saponaria saponins, such as at least 200 ppm Quiiiaja Saponaria saponins, e.g. in the range from 0,1 - 200 ppm Quiiiap Saponaria saponins, such as in the range from 0.2 -- 180 ppm Quiiiaja Saponaria saponins, e.g, in the range from 0.3 - 170 ppm Quiiiaja Saponaria saponins, such In the range from 0 ,4 -160 ppm Quiilap Saponaria saponins, e.g, in the range from 0.5 - 150 ppm Quiiiaja SapOnaria saponins, such in the range from 0,6 -140 ppm Quiiiaja Saponaria saponins, e,g. in the range: from 0.7 ~ 130 ppm Quiiiaja Saponaria saponins, such in the range:from: 0,8 -120; ppm Quiiiaja Saponaria saponins, e.g. in the range from 0,9 ~ 110 pprn Quiiiaja Saponaria saponins, such in the range from 0 ,8 -100 ppm Quiiiaja Saponaria saponins,. e,g, in the range ftarh 0,9 - SO ppm Quiiiaja Saponaria saponins, such: in the range from 1 · 80 ppm Quiiiaja Saponaria. saponins, e.g. in the range from 5 » 70 ppm Quiiiaja Sapanaha saponins, such In the range from 10 - 60 ppm Quiiiaja Saponaria saponins, e.g. in the range from 20 - SO ppm Quiiiaja Saponaria saponins, such in the range from 30 - 40 ppm Quiiiaja Saponaria saponins.
    [12] 12. The compound or composition Becoming to any of the preceding claims, wherein said QuHiaja Saponaria saponins Is a terpenoid saponin,
    [13] 13. The compound or composition according to claim 12, wherein said terpenoid saponins is triterpenoid saponin,
    [14] 14. The compound or composition according:1 to any one of the proceeding claim, wherein said prevention and/or treatment is::combined with other traditional anti ectoparasite strategies or other chemical, medical or natural agents against ectoparasites,
    [15] 15. A method for the manufacture of a fish feed, comprising the steps:of; 1) combining QuHlaja Sap ana na saponins or a composition comprising :QuHiaja Saponøriø: saponins with approved fish feed ingredients, and obtaining a fish feed comprising QuMaja Saponana saponins,:
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    同族专利:
    公开号 | 公开日
    WO2015155293A1|2015-10-15|
    EP3145521A1|2017-03-29|
    CA2945249A1|2015-10-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JP4127864B2|1994-09-29|2008-07-30|太陽化学株式会社|Gram-negative bacterial growth inhibitor|
    US6485734B1|1999-04-07|2002-11-26|Bradley Baker|Topical composition for the treatment of head lice and nits and method|
    JP2002370993A|2001-06-13|2002-12-24|Bussan Biotech Kk|Herb-containing immunopotentiator|
    KR101391911B1|2010-12-20|2014-05-07|비센|Bee venom composition having improved growth rate and immune function|JP6045895B2|2012-10-01|2016-12-14|株式会社トプコン|Ophthalmic observation device|
    WO2015061755A1|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|2016-05-02|2020-09-16|Evolva SA|Use of nootkatone to treat sea lice|
    US20180325971A1|2016-07-29|2018-11-15|Saponin Research Center S.A.|Use of quillaja saponaria extracts for the prevention and control of viral infections in fish|
    US20180325970A1|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|
    NO20191193A1|2019-10-05|2021-04-06|Previwo As|Method for treating and/or preventing a parasitic infection in a teleost|
    NO20191194A1|2019-10-05|2021-04-06|Previwo As|Method for treating and/or preventing a sea lice infection in a teleost|
    法律状态:
    2018-07-16| PHB| Application deemed withdrawn due to non-payment or other reasons|Effective date: 20180626 |
    优先权:
    申请号 | 申请日 | 专利标题
    EP14164022|2014-04-09|
    PCT/EP2015/057732|WO2015155293A1|2014-04-09|2015-04-09|Compound or composition for use in the prevention and/or treatment of an ectoparasitic copepod infestation or infection in fish|
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