WO2014051440A1 - Procédé et composition de traitement des ectoparasites - Google Patents

Procédé et composition de traitement des ectoparasites Download PDF

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Publication number
WO2014051440A1
WO2014051440A1 PCT/NZ2013/000180 NZ2013000180W WO2014051440A1 WO 2014051440 A1 WO2014051440 A1 WO 2014051440A1 NZ 2013000180 W NZ2013000180 W NZ 2013000180W WO 2014051440 A1 WO2014051440 A1 WO 2014051440A1
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WO
WIPO (PCT)
Prior art keywords
spinosyn
animal
lice
sheep
administered
Prior art date
Application number
PCT/NZ2013/000180
Other languages
English (en)
Inventor
Warwick Mitchell SMITH
Fadil Al Alawi
Original Assignee
Bayer New Zealand Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bayer New Zealand Limited filed Critical Bayer New Zealand Limited
Publication of WO2014051440A1 publication Critical patent/WO2014051440A1/fr
Priority to ZA2015/02205A priority Critical patent/ZA201502205B/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/22—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom rings with more than six members
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • 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

  • This invention relates to an ectoparasitic treatment method and composition.
  • the present invention relates to the treatment of biting lice on sheep, although it should be appreciated that aspects of the present invention can be extended to related matters.
  • Lice are typically categorised into those that feed directly on the blood of the host, i.e. sucking lice, and those that feed on the skin surface (e.g. on secretions and skin debris), i.e. biting (or chewing) lice.
  • sucking louse Three species of sucking louse are known to occur on sheep but are rarely identified or implicated in production losses or disease in Australia. These are Linognathus ovillus (the face louse) and
  • Linognathus pedalis the foot louse
  • Linognathus africanus O'Callaghan et al., 1989.
  • the sheep show signs of pruritus (itchiness) such as rubbing, biting and scratching and these behaviours damage the integrity of the fleece (e.g. causing 'pulled' or cotted wool).
  • pruritus can be intense and the irritation can manifest as changes to the skin, including increased scurf and thickening of the epidermis and overlying lipid layer (Britt et al. 1986; Heath et al. 1995b).
  • There is variation between individual sheep susceptibility to lice and this may be linked to an immune response to infestation James 1999; James et al. 2002).
  • Lice are transmitted between sheep via direct contact. Lice control relies upon effective chemical treatment of an entire flock and subsequent biosecurity measures to prevent re-infestation (i.e. exclusion of lice-infested sheep). Due to the surface-feeding habits of B. ovis, all successful chemical treatments previously used have involved topical delivery of the lousicidal chemical.
  • the methods used can be broadly categorised into high-volume application of diluted chemical (i.e. in water) or low-volume delivery of concentrated chemical formulations. High-volume application methods used in the past have included plunge dips, shower dips, jetting races and hand jetting. These methods require prolonged wetting of the animal or high-pressure jets to ensure adequate penetration or saturation of the fleece with the chemical solution (Rothwell, 2005).
  • a method of treating an animal infested with biting lice characterised by the step of administering internally to the animal a pharmaceutically effective amount of at least one spinosyn such that the spinosyn is present systemically within the animal.
  • a composition when used for internal administration to an animal to treat biting lice including at least one spinosyn in the order of 0.1 % to 65 w/v.
  • a use of a composition including a pharmaceutically effective amount of at least one spinosyn wherein the use includes administering the composition internally to the animal such that the spinosyn is present systemically within the animal, characterised in that the use of the composition is for the treatment or prevention of biting lice.
  • a dosage regime to treat biting lice on an animal characterised by the step of administering at least one spinosyn internally to the animal with a total dosage of equal to or less than 100 milligrams per kilogram animal.
  • Bovicola ovis the principles in the present invention could apply to and be useful for other situations - for example treating biting insects on other ruminant and camelid species.
  • Many of the problems associated with sheep are also present in, for example, cows, goats, and alpaca, albeit with different species of biting lice.
  • the medicament can be administered to the animal by a variety of means.
  • the medicament may be administered orally, for example with a drench gun such as that used for other medicaments.
  • an injectable liquid may be used and delivered via an injector - for example such as that used to deliver antibiotics.
  • solid dose forms e.g. tablets, pellets, boluses, implants
  • routes of administration/absorption e.g. transcutaneous, transmucosal
  • a critical aspect of the invention is that regardless of the mode of administration, the spinosyn is present systemically within the animal.
  • MLs The next major class of parasiticides to be developed with systemic activity were the MLs. These chemicals have been used extensively for control of internal and external parasites of sheep and cattle since abamectin was introduced in Australia in 1985 (Holdsworth, 2005). The term 'endectocide' was coined to describe the MLs because they have been so successful for control of both internal (endo-) and external (ecto-) parasites.
  • Abamectin, ivermectin, doramectin eprinomectin and moxidectin have all demonstrated activity against biting lice on cattle, i.e.
  • Bovicola bovis (Titchener et al, 1994; Clymer et al, 1998; Colwell, 2002; Holste, 1997; Lloyd et al, 2001 ; Lloyd et al, 1996).
  • B. bovis are more susceptible to the topical formulations of MLs applied on or near the sites of infestation than those administered by injection (Logan et al, 1993; Cleale, 2004). Consistent with this observation is the fact that "sucking lice are typically more susceptible to injectable formulations of macrocyclic lactones than are chewing lice" (Cleale et al, 2004).
  • B. bovis and B. ovis are distinct species of biting lice, which are known to be very host-specific. This means that each louse species is highly adapted to its particular host animal species. In other words, B. bovis cannot infest sheep and B. ovis cannot infest cattle. Given that the lice are host-adapted, there may be differences in their biology (e.g. preferred skin substrates to feed on, frequency of feeding, proximity to skin surface, mobility) that make B. bovis on cattle more susceptible to MLs (and perhaps OPs) delivered via the systemic route.
  • some chemicals present in the blood stream may be delivered to the skin surface by diffusion between cells of the skin (intercellular), diffusion through cells of the skin (intracellular), diffusion into the hair follicles, secretion in sweat, secretion in sebum or by accumulation inside epidermal cells which gradually move towards the skin surface (Patzelt et al 2008). It is not known precisely which of these mechanisms are responsible for the delivery of ML and OP chemicals to the skin surface of cattle where they can exert an effect on B. bovis. However, marked differences in the skin layers and appendages (i.e. hair follicles, sebaceous glands and sweat glands) are known to occur between different species.
  • cattle skin may have around 890 follicles/cm 2 whereas a Merino sheep can have up to 10,000 follicles/cm 2 (Mills & Cross, 2006).
  • the density of blood vessels, thickness of the skin, and the rate and composition of the sebaceous secretions can also differ (Mills & Cross, 2006). It is evident that the significant structural and physiological differences between the skin of cattle and sheep could certainly influence the delivery of chemicals to biting lice feeding on the skin surface.
  • WO 01 11961 and WO 01 11962 (Eli Lilly and Company) both describe formulations containing spinosyn for controlling insects/pests in small ruminants, such as sheep and goats. The formulations and methods of controlling these insects/pests are described as being topically applied to a ruminant.
  • NZ 516790 describes an oral formulation for controlling an ectoparasite infestation on a companion animal for a prolonged time, said formulations comprising a spinosyn component. NZ 516790 follows conventional wisdom in that it describes
  • Pages 7-8 of NZ 516790 provides a good overview on the understanding and spinosad usage for treating lice:
  • WO 03024223 describes the use of a synergistic combination of spinosad and a macrocyclic lactone.
  • the trials therein show that systemic use of spinosad is more effective than contact application.
  • the term "systemic" is used in regard to the pest (i.e lice) rather than the host (e.g. sheep). While the trials did determine that ingestion of sheep epidermis treated with the composition is effective in killing the lice, it does not teach that systemic administration to the host is effective at killing the lice. Given the different structure of the skin between sheep and cattle, and the general understanding in the art, as discussed above, it would be unexpected that systemic administration of a spinosyn would provide a therapeutic effect by killing biting lice such as those on sheep.
  • spinosyn also known as fermentation product A83543
  • spinosyn should be taken as meaning any compound, a derivative or analogue thereof, either naturally derived or synthetically derived, generally having a 5,6,5-tricyclic ring system, fused to a 12-membered macrocyclic lactone, a neutral sugar (2N,3N,4N-tri-0-methylrhamnose) and an amino sugar (forosamine).
  • the meaning of spinosyn is further outlined in NZ 531787, the contents of which are incorporated herein in its entirety for reference.
  • R 2 , R 4 , R 3 , R 5 and R 6 are hydrogen or methyl; or an acid addition salt thereof when R 1 is other than hydrogen.
  • Spinosyns are known to occur in over 20 natural forms and currently can be provided in over 200 synthetic forms. Incorporated herein by reference, Kirst et al and NZ 516790 further outlines the scope and variants of spinosyns. As discussed in Kirst er al and NZ 516790, one such example is Spinosad which includes a racemic mix of two spinosyns, Spinosyn A, the major component and Spinosyn D (the minor component), an approximate 17:3 ratio.
  • spinosyn derivative is 'spinetoram' which, when compared to Spinosad, has been found to be effective against a greater spectrum of insect pests with an increased potency and duration of efficacy 3,4 .
  • Spinetoram includes a major component (3'ethoxy-5,6-dihydro spinosyn J) and a minor component (3'-ethoxy spinosyn L).
  • biting/chewing lice should be taken as meaning ectoparasites whose mouthparts are adapted for chewing, and eat skin fragments, skin secretions, feathers, hair and/or wool.
  • sucking lice should be taken as meaning ectoparasites whose mouthparts are adapted for sucking the blood of their host.
  • systemic treatment should be taken as meaning any treatment which is applied internally to an animal and which reaches different areas of the body primarily through the bloodstream.
  • this may include oral, parenteral, and anal delivery.
  • topical treatment should be taken as meaning any treatment which is applied onto an external surface of an animal such as the skin or hair/wool of an animal.
  • biting lice is the species Bovicola ovis (B.ovis).
  • the animal is a sheep.
  • Bovicola ovis is a species of lice specific to sheep, known to be biting lice rather than sucking lice. With knowledge of the present invention, the inventors extrapolated that spinosyn may also be effective for systemic treatment of biting lice present in other animals beyond sheep.
  • the administration route is oral.
  • composition may be provided as a suspension, tablet, powder, drench or the like.
  • the administration route is via injection.
  • the main advantage of systemic administration is that it helps to ensure the total dosage is being given to the animal.
  • topical administration as per conventional wisdom with spinosyns used for biting lice, the disadvantage is the dosed medicament may be licked off by other animals, rubbed off by the animal or possibly be washed away in rain.
  • the spinosyn is spinosad.
  • spinosad is a mixture of spinosyn A and spinosyn D. These two spinosyns are currently known as very effective types of spinosyn insecticides.
  • spinosad is beneficial to use as per the present invention, as it is already used both topically (for biting lice) and systemically (for sucking lice). Therefore, it is known to be safe to use, has low side effects and has widespread approval amongst the farming industry.
  • spinosyn any suitable form of spinosyn (whether currently available or developed in future) may be used in the present invention without departing from the scope thereof.
  • One such preferred example of a spinosyn derivative, more recently identified as being particularly effective, is spinetoram.
  • the present invention can be co-formulated with other active ingredients, for example anthelmintic treatments, vaccines, vitamins/mineral supplements and the like. Not only does this offer advantages by having two or more treatments being delivered in a single dose, but there may also be complementary effects resulting. For example, the inclusion of vitamins and minerals may assist the skin recovery of an animal once the biting lice have disappeared as a result of the insecticide treatment.
  • active ingredients for example anthelmintic treatments, vaccines, vitamins/mineral supplements and the like.
  • compositions will include spinosyn in the order of 0.1 % to 65 % w/v as.
  • the concentration.of.spinosyn- is ⁇ %-to'35% " w/v. More preferably, the concentration of spinosyn is approximately 9 % w/v.
  • dispersing agents in addition to the active there may be provided dispersing agents, preservatives, anti-foaming agents and humectants.
  • the composition is prepared as an oral composition.
  • this may be in the format of a tablet, powder, drench, gel and so forth.
  • the composition may be in the form of an injectable composition or sustained release composition such as a bolus or implant, or the like.
  • the daily dosage administered is less than about 2000 mg/sheep/day.
  • the dosage may be between 100 - 2000 mg/sheep/day.
  • the spinosyn is administered at total dosage of equal to or less than 100 milligrams per kilogram of animal.
  • the dosage regime may also vary significantly.
  • the inventors identified that either a single or double dosage of 6.75 mg/kg/day (i.e. just on day 0, or on both day 0 and day 1) regime was sufficient to eradicate the lice.
  • this may include the administration of a number of discrete dosages over a few days, or alternate embodiments could involve the use of a slow release device.
  • a sustained release product which releases the active at low levels over a given period of time, such as 3-7 days.
  • composition being administered will vary dependent upon the administration route and whether a single dose will be used or the active is to be administered over time. Further, as discussed previously, the present invention can be used with other actives as well.
  • Example 1 Injectable composition
  • composition suitable for administration by injection is provided in Table 1.
  • composition for a 1000 mg tablet, suitable for oral administration is provided in Table 2.
  • a further composition for a tablet, suitable for oral administration is provided in Table 3.
  • composition suitable for administration as an oral drench is provided in Table 4.
  • lousicide agents were tested to determine their efficacy for treating biting lice on sheep (B. ovis) when administered systemically. It was expected as per conventional wisdom that systemic administration would not present the active compound in vectors which would be consumed by the biting lice.
  • Plasma and fleece concentrations of spinosad were determined for two of the groups, as shown in Tables 8 and 9. Plasma and fleece concentrations correlated with the dose administered.
  • Table 8 Assessment of mean spinosad concentration in wool over time treatment groups 2 and 4.
  • Example 7 Spinosad injectable solution 5%w/v

Abstract

La présente invention concerne un procédé de traitement d'un animal infesté par des poux piqueurs, caractérisé par l'étape d'administration à l'intérieur de l'animal d'une quantité pharmaceutiquement efficace de spinosyne de telle sorte que la spinosyne soit présente de façon systémique dans l'animal.
PCT/NZ2013/000180 2012-09-28 2013-09-26 Procédé et composition de traitement des ectoparasites WO2014051440A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
ZA2015/02205A ZA201502205B (en) 2012-09-28 2015-03-27 Ectoparasitic treatment method and composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NZ602723 2012-09-28
NZ60272312 2012-09-28

Publications (1)

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WO2014051440A1 true WO2014051440A1 (fr) 2014-04-03

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AR (1) AR092719A1 (fr)
AU (2) AU2012233000B2 (fr)
UY (1) UY35059A (fr)
WO (1) WO2014051440A1 (fr)
ZA (1) ZA201502205B (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2557986C1 (ru) * 2014-07-31 2015-07-27 Федеральное государственное бюджетное научное учреждение "Всероссийский научно-исследовательский институт ветеринарной энтомологии и арахнологии" (ФГБНУ ВНИИВЭА) Способ защиты крупного рогатого скота от иксодовых клещей
WO2021122513A1 (fr) 2019-12-16 2021-06-24 Intervet International B.V. Composition pour lutter contre les poux
WO2021122515A1 (fr) 2019-12-16 2021-06-24 Intervet International B.V. Lutte contre les parasites chez les ruminants

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994020518A1 (fr) * 1993-03-12 1994-09-15 Dowelanco Nouveaux composes a83543 et procede de production desdits composes
US5591606A (en) * 1992-11-06 1997-01-07 Dowelanco Process for the production of A83543 compounds with Saccharopolyspora spinosa

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5591606A (en) * 1992-11-06 1997-01-07 Dowelanco Process for the production of A83543 compounds with Saccharopolyspora spinosa
WO1994020518A1 (fr) * 1993-03-12 1994-09-15 Dowelanco Nouveaux composes a83543 et procede de production desdits composes

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2557986C1 (ru) * 2014-07-31 2015-07-27 Федеральное государственное бюджетное научное учреждение "Всероссийский научно-исследовательский институт ветеринарной энтомологии и арахнологии" (ФГБНУ ВНИИВЭА) Способ защиты крупного рогатого скота от иксодовых клещей
WO2021122513A1 (fr) 2019-12-16 2021-06-24 Intervet International B.V. Composition pour lutter contre les poux
WO2021122515A1 (fr) 2019-12-16 2021-06-24 Intervet International B.V. Lutte contre les parasites chez les ruminants

Also Published As

Publication number Publication date
AU2016202546A1 (en) 2016-05-19
ZA201502205B (en) 2017-11-29
UY35059A (es) 2014-03-31
AU2012233000B2 (en) 2016-01-21
AR092719A1 (es) 2015-04-29
AU2012233000A1 (en) 2014-04-17

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