NZ758435B2 - Delayed release feed-through veterinary compositions with ovicidal and larvicidal activity against susceptible and resistant strains of parasites in ruminants' feces, use of these compositions, method for delaying the release of these compositions - Google Patents
Delayed release feed-through veterinary compositions with ovicidal and larvicidal activity against susceptible and resistant strains of parasites in ruminants' feces, use of these compositions, method for delaying the release of these compositions Download PDFInfo
- Publication number
- NZ758435B2 NZ758435B2 NZ758435A NZ75843518A NZ758435B2 NZ 758435 B2 NZ758435 B2 NZ 758435B2 NZ 758435 A NZ758435 A NZ 758435A NZ 75843518 A NZ75843518 A NZ 75843518A NZ 758435 B2 NZ758435 B2 NZ 758435B2
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- NZ
- New Zealand
- Prior art keywords
- composition
- ruminant
- benzimidazole compound
- present
- feed
- Prior art date
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003853 activation of bipolar cell growth Effects 0.000 description 1
- 230000000996 additive Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000240 adjuvant Effects 0.000 description 1
- 229950010075 albendazole sulfoxide Drugs 0.000 description 1
- 230000000111 anti-oxidant Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 230000001488 breeding Effects 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000000994 depressed Effects 0.000 description 1
- 201000008286 diarrhea Diseases 0.000 description 1
- SEKVTWKYOIVNGT-UHFFFAOYSA-L disodium;dodecan-1-ol;sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O.CCCCCCCCCCCCO SEKVTWKYOIVNGT-UHFFFAOYSA-L 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 244000079386 endoparasites Species 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002346 eprinomectin Drugs 0.000 description 1
- ZAFFWOKULJCCSA-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate;trimethylazanium;chloride Chemical compound [Cl-].C[NH+](C)C.CCOC(=O)C(C)=C ZAFFWOKULJCCSA-UHFFFAOYSA-N 0.000 description 1
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 229960005282 febantel Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002209 hydrophobic Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000000366 juvenile Effects 0.000 description 1
- 230000002147 killing Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000002267 larvicidal agent Substances 0.000 description 1
- 230000003902 lesions Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- HMCCXLBXIJMERM-UHFFFAOYSA-N methyl N-[[2-[(2-methoxyacetyl)amino]-4-phenylsulfanylanilino]-(methoxycarbonylamino)methylidene]carbamate Chemical compound C1=C(NC(NC(=O)OC)=NC(=O)OC)C(NC(=O)COC)=CC(SC=2C=CC=CC=2)=C1 HMCCXLBXIJMERM-UHFFFAOYSA-N 0.000 description 1
- 230000004274 microtubule-based process Effects 0.000 description 1
- WTERNLDOAPYGJD-SFHVURJKSA-N monepantel Chemical compound C([C@@](C)(NC(=O)C=1C=CC(SC(F)(F)F)=CC=1)C#N)OC1=CC(C#N)=CC=C1C(F)(F)F WTERNLDOAPYGJD-SFHVURJKSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 201000001181 parasitic helminthiasis infectious disease Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrugs Drugs 0.000 description 1
- 230000001681 protective Effects 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001502 supplementation Effects 0.000 description 1
- YFNCATAIYKQPOO-UHFFFAOYSA-N thiophanate Chemical compound CCOC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OCC YFNCATAIYKQPOO-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
- A23K20/147—Polymeric derivatives, e.g. peptides or proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/174—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/20—Inorganic substances, e.g. oligoelements
- A23K20/22—Compounds of alkali metals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/20—Inorganic substances, e.g. oligoelements
- A23K20/26—Compounds containing phosphorus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K40/00—Shaping or working-up of animal feeding-stuffs
- A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
Abstract
veterinary composition is disclosed and is based on anthelmintic compounds, particularly from the benzimidazole group, with delayed release properties, preferably in the form of granules or pellets, to be added to feed or feed supplements offered to ruminants in order to control eggs and larvae of helminths, preferably from the genusHaemonchusspp. helminths, preferably from the genusHaemonchusspp.
Description
DELAYED RELEASE FEED-THROUGH VETERINARY COMPOSITIONS WITH
OVICIDAL AND LARVICIDAL ACTIVITY AGAINST SUSCEPTIBLE AND
RESISTANT STRAINS OF PARASITES IN RUMINANTS’ FECES, USE OF THESE
COMPOSITIONS, METHOD FOR DELAYING THE RELEASE OF THESE
COMPOSITIONS
FIELD OF INVENTION
The present invention regards a veterinary composition, to be mixed with animal
feed or salt, preferably in the form of granules or pellets, based on anthelmintic compounds,
particularly from the benzimidazole group, with delayed release properties, to control eggs and
larvae of helminths, preferably from the genus Haemonchus spp., in ruminants’ feces.
The blood sucking nematodes of Haemonchus genus are probably the most
economically important parasites in ruminants raised in warm damp climates of tropics and
sub tropics (BASSETTO, 2015). Also known as red stomach worms, wire worms or barber's
pole worms, their incidence and pathology is well known in cattle (SANTOS, 2010;
AMARANTE, 2011), goats (LEITE-BROWNING, 2006) and sheep (BOWIE, 2014). As with
many other endoparasites, Haemonchus spp. show elevated resistance to traditional
anthelmintics (DAS NEVES, 2014; BASSETTO, 2015).
The life cycle of gastrointestinal nematodes (among which figures Haemonchus
spp.) comprises two different phases: a parasitic phase and a nonparasitic or free-living phase.
The free-living phase begins after egg shedding among the host’s feces —a single adult female
Haemonchus can release between 5,000 and 10,000 eggs per day. Pastured animals will infect
themselves by grazing on contaminated grass. The more animals are grazing in the same area,
the higher the chance of worms to spread themselves among the herd.
18192324_1 (GHMatters) P45573NZ00
After egg shedding, eggs develop in moist conditions in the feces and continue to
develop into the L1 (rhabditiform) and L2 juvenile stages by feeding on bacteria in the dung.
The L2 rhabditiform sheds its cuticle and then develops into the L3 filiariform infective larvae.
Under favorable conditions of temperature and humidity, the period between egg shedding and
the presence of the first infective larvae (L3) is 5-7 days. Infective larvae have a protective
cuticle that helps them withstand heat and avoid desiccation for some time. They will crawl up
blades of wet grass and wait to be ingested by a grazing animal. Sheep, goats and cattle
become infected when they graze and eat contaminated grass. Infective larvae (L3) pass
through the ruminants’ digestive tract until they reach the abomasum (fourth, or ‘true’,
stomach). The larvae will then shed their cuticle and burrow into the internal layer of the
abomasum where they develop into L4, usually within 48 hours. In the final stage, L4 larvae
molt and develop into the adult form (L5). The male and female adults mate and live in the
abomasum, where they feed upon the host’s blood and copulate.
The pre-patent period, i.e., the period of time between infective larvae ingestion by
the host and the appearance of the first eggs among the host’s feces is 21-28 days
(Haemonchus contortus) and 28 days (Haemonchus placei). Similar life cycles and pre-patent
periods are present in the vast majority of gastrointestinal nematodes that parasitizes
ruminants.
The nematode piercing the abomasum causes a number of significant
complications in the infected ruminants that can lead to death. The infected animals can
display severe dehydration, diarrhea, unthrifty appearance, lethargy, depressed low energy
behavior, rough hair coat and uncoordinated movements. Furthermore, significantly reduced
growth and poor reproductive performance have been observed. The accumulation of fluid in
18192324_1 (GHMatters) P45573NZ00
the abdomen, gut wall, thoracic cavity and submandibular tissue – a phenomenon commonly
called "bottle jaw”, also is a common association with this infection. Severe blood loss, white
mucous membranes, and anemia/low PCV are common complications of the infection.
The infection, called haemonchosis, causes large economic losses for farmers
around the world, especially for those living in the warmer climates. Anthelmintics have been
used in order to control these and other worm infections for a long time, but anthelmintic
resistance among parasites is rapidly growing.
According to HOSSETTO (2000), dairy cattle with high incidence of worms can
show a substantial loss in milk yield, up to 25% of the daily production. A 5%-10% raise in
the annual mortality rate may be expected (Marques, 2003), especially among calves, as well
as 12% less births per year (FADIL, n/a.).
Existing anthelmintics work by killing the adult forms and immature species by
means of its toxic effect, although they don’t possess enough residual power that leads to re-
infestation cycle elimination. So, after 28-35 days an estimated 70% of worm infestation will
be back. Moreover, existing anthelmintics leave toxic residues on beef and milk of the treated
animals, and are more likely to be affected by anthelminthic resistance.
Parasitic resistance to anthelmintics is a phenomenon whereby members of a
population are selected and become dominant after constant use of a chemical compound. The
diagnosis will be positive for "resistance" when a certain drug that used to show 99% efficacy
over the parasite burden reduction starts showing less than 95% efficacy against the same
parasites after certain period of time (MOLENTO, 2004).
In recent years, the problem of anthelmintic resistance has reached new heights
where it can no longer be ignored as a major issue in the control of parasites of livestock. It is
18192324_1 (GHMatters) P45573NZ00
an inconvenient truth that reports of resistance are no longer noteworthy; anthelmintic
resistance is the status quo. In many parts of the world, multiple-resistant parasites are highly
prevalent, and it is no longer uncommon to find sheep or goat farms where resistance exists to
all available anthelmintic drugs (Cezar et al., 2010; da Cruz et al., 2010; Howell et al., 2008).
In general, levels and spectrum of anthelmintic resistance are less severe in parasites of horses
and cattle, but the same problems exist and seem to be worsening (Kaplan, 2004; Kaplan et al.,
2004; Soutello et al., 2007; Suarez and Cristel, 2007; Traversa et al., 2009; Waghorn et al.,
2006a). Thus, in some regions, high levels of multiple-drug resistance threaten the health and
productivity of these species as well.
Until the recent introduction of monepantel (Kaminsky et al., 2008) in New
Zealand and the United Kingdom, there had not been a new class of anthelmintics delivered to
the livestock market since ivermectin almost 30 years ago. This new drug and others, such as
derquantel (Little et al., 2010), may offer a temporary reprieve from the problems created by
mounting failures of older anthelmintics. However, the development of new anthelmintic drug
classes is not likely to solve the problem of anthelmintic resistance. The great cost associated
with the development of new drugs and the trends of reduced levels of investment into new
animal drug research over the past few decades make it extremely unlikely that we are
entering a new phase where a continuous supply of new anthelmintic compounds will follow
(Geary et al., 2004).
Over the past decade there have been increasing numbers of reports of
anthelmintic resistance in gastrointestinal nematodes of cattle worldwide, most of which
concern resistance to the avermectin/milbemycin drugs (Anziani et al., 2001, 2004; Condi et
18192324_1 (GHMatters) P45573NZ00
al., 2009; Demeler et al., 2010; Edmonds et al., 2010; Familton et al., 2001; Fiel et al., 2001;
Gasbarre et al., 2009; Mejia et al., 2003; Mena et al., 2008).
The most comprehensive studies investigating the prevalence of anthelmintic
resistance in cattle parasites have been performed in New Zealand (Waghorn et al., 2006a) and
in South America (Soutello et al., 2007; Suarez and Cristel, 2007). In all three studies,
injectable avermectin/milbemycin products were used, with data indicating that resistance is
becoming a very serious problem in these regions.
The predominant genera infecting these cattle were Cooperia spp. and
Haemonchus spp. and both genera were consistently found associated with resistance. In
addition, there was evidence on two farms for moxidectin-resistance in Oesophagostomum
spp. Resistance in Oesophagostomum spp. was subsequently confirmed using FECRT
combined with a controlled efficacy test (using injectable moxidectin) on a cattle farm in
Brazil (Condi et al., 2009). An interesting observation in this study was that 98.5% of the
Cooperia spp. females recovered at necropsy (14 days after treatment) from the control
animals had eggs inside the uterus, as compared to only 48.2% of the females recovered from
the moxidectin treated group (P < 0.001). A temporary suppression of egg output by worms
surviving moxidectin treatment has been reported previously in sheep (Sutherland et al.,
1999). These data indicate that moxidectin treatment may cause a temporary suppression in
egg output; suggesting that FECRT data from moxidectin (and other macrocyclic lactone
drugs) should be interpreted with caution to avoid mis- or under-diagnosis of anthelmintic
resistance. These data also suggest that 14 days may not be a sufficient interval following
moxidectin treatment for post-treatment feces collection, and that 17–21 days may be
preferred.
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To apply any of these anti-parasite drugs it’s necessary to gather the herd and lead
them to the corral.
A roundup is an extremely laborious activity that involves many people and has a
long duration. Essentially, the herding of animals to the corral leads to a disorganization of
their activities (PARANHOS DA COSTA & NETO, 2003), animals cannot feed, are
subjected to stress, and this can lead to weight loss up to 15 kg per animal per roundup
(ARENALES, 2004). Stressful roundup activities also raise the risk of accidents, which may
lead to bruised carcasses (PARANHOS DA COSTA et al., 2004).
Further, the existing anthelmintics are known to leave residues in beef and milk,
being necessary to establish their withdrawal periods.
18192324_1 (GHMatters) P45573NZ00
Commonly Used Deworming Products
Warnings and
Withdrawals**
Type Trade Name Active Dairy & Beef &
Ingredient Milk Slaughter
Block SafeGuard Cattle Block Fenbendazole Note 1 11d
Drench Prohibit Levamisole Note 1 48h
Synanthic 9.06% Oxfendazole Note 1 7d
Synanthic 22.5% Oxfendazole Note 1 7d
Panacur Fenbendazole 0 8d
SafeGuard Fenbendazole 0 8d
Valbazen Albendazole Note 1, 2 27d (Note 2)
Feed SafeGuard Fenbendazole 0 13d
additives Rumatel Morantel Tartrate 0 14d
Injectable Levamisol Levamisole Note 1 7d
Ivermectin Containing Ivermectin Note 1 35d
Ivomec Plus, Noromectin Ivermectin/Clors Note 1 49d
Plus ulon Note 3 35d
Dectomax Doramectin Note 1 21d
Cydectin Moxidectin
Paste Panacur Fenbendazole 0 8d
SafeGuard Fenbendazole 0 8d
Pour-on Ivermectin Containing Ivermectin Note 1 48d
Pouron Eprinomectin 0 0
Eprinex Doramectin Note 3 45d
Dectomax Pouron Moxidectin 0 0
Cydectin Pouron
Mineral SafeGuard Mineral Fenbendazole 0 13d
dewormer
*Local feed dealerships may independently market feed mixes and blocks containing
additive products.
18192324_1 (GHMatters) P45573NZ00
Note 1: Not to be used on dairy cattle of breeding age.
Note 2: Not to be used during the first 45 days of pregnancy or for 45 days after bull
removal.
Note 3: Safe in dairy heifers up to 20 months of age.
**Withdrawals are subject to change.
SUMMARY OF THE PRESENT INVENTION
[0018A] Provided herein is a method of controlling eggs and larvae of a helminth that
develops in ruminant feces, comprising administering to a ruminant an efficacious amount of a
composition comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer;
wherein the composition is administered to the ruminant, by oral route through means of feed
or feed supplement, at a dosage of 50 mg to 125 mg of the benzimidazole compound per
ruminant per day.
[0018B] Also provided herein is a method of controlling eggs and larvae of a helminth that
develops in ruminant feces, comprising administering to a ruminant a feed or feed supplement
composition, comprising
i) feed or feed supplement offered to animals and;
ii) an efficacious amount of a composition comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer;
18192324_1 (GHMatters) P45573NZ00
wherein the feed or feed supplement composition is given to the ruminant in such amount that
the ruminant is administered a dosage of 50 mg to 125 mg of the benzimidazole compound per
ruminant per day.
[0018C] Also provided herein is a composition for controlling eggs and larvae of a helminth
that develops in ruminant feces, the composition comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer;
wherein the composition is formulated for administration to a ruminant by oral route,
through means of feed or feed supplement,
and wherein the composition is formulated for delayed release with respect to the
benzimidazole compound such that release occurs in the feces of the ruminant.
[0018C] Also provided herein is a composition for controlling eggs and larvae of a helminth
that develops in ruminant feces, the composition comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer;
wherein the composition is formulated for administration to a ruminant by oral route,
through means of feed or feed supplement,
18192324_1 (GHMatters) P45573NZ00
and wherein the composition is formulated for delayed release with respect to the
benzimidazole compound such that delayed release is from about 10 hours to 72 hours from
consumption of the composition by a ruminant.
[0018D] Also provided herein is a composition for controlling eggs and larvae of a helminth
that develops in ruminant feces, the composition comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer;
wherein the composition is formulated for administration to a ruminant by oral route,
through means of feed or feed supplement,
and wherein said composition is formulated for delayed release with respect to the
benzimidazole compound such that the ruminant after 10 hours to 72 hours has a residue of the
benzimidazole compound of less than 100 ppm.
[0018E] Also provided herein is a feed or feed supplement composition, comprising
i) feed or feed supplement offered to animals and;
ii) a composition as defined herein;
wherein the feed or feed supplement composition is formulated for administration at a
dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day.
[0018F] Also provided herein is a kit for controlling nematodes that develop in ruminant’s
feces comprising a canister containing a composition as defined herein and a dosing device,
when used in a method as defined herein.
18192324_1 (GHMatters) P45573NZ00
The compositions of the present invention offer one or more advantages over
common anthelmintics, including one or more of the following aspects:
1) By mixing said composition, in its granule or pelletized form, with salt, feed or
any other nutritional supplement offered to cattle, one avoids: the inconvenient costs that arise
from rounding up the cattle into the corral, stress on the cattle, food deprivation and/or lesions;
2) By utilizing delayed-release technology, the active ingredient is essentially
deployed only in the feces, therefore avoiding residues on the animal’s living tissues and milk;
and/or
3) By having the activity of the composition released or concentrated in the feces,
the active ingredient has nearly or about 100% of its potency employed against immature
nematode forms (larvae and eggs) present in the dung pat, with in loco ovicide and larvicide
action, avoiding future infections.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
Different from the prior art, including commercial uses available in the literature,
the present invention pertains in part to a composition, preferably a veterinary composition,
and method of treatment. The composition preferably is in the form of granules or pellets.
The composition can be added to animal feed, or salt or any other nutritional supplement
8c followed by Page 9
18192324_1 (GHMatters) P45573NZ00
offered to animals, such as ruminants. The composition is effective in controlling helminths’
eggs and larvae, especially of the Haemonchus genus, present in the animal’s feces.
Administration of the composition of the present invention through feed or feed
supplements allows for feces expelled by treated animals to contain the benzimidazole-based
composition.
Benzimidazoles, the active ingredient, are a class of heterocyclic aromatic organic
compounds that include a fusion of benzene and imidazole, as in the formula below:
The benzimidazoles are characterized by a broad spectrum of activity against
roundworms (nematodes), an ovicidal effect, and a wide safety margin. Examples of the
benzimidazole compounds or benzimidazole drugs are: mebendazole, flubendazole,
fenbendazole, oxfendazole, oxibendazole, albendazole, albendazole sulfoxide, thiabendazole,
thiophanate, febantel, netobimin, and/or triclabendazole or any combination thereof. The
benzimidazoles generally have one or more substitutions of groups off of the benzene ring
and/or the imidazole ring.
The anti-parasitic main mode of action of benzimidazole drugs is to impair the
tubulin polymerization into microtubules, therefore disrupting microtubule-based processes.
Through a specially developed formulation, the present invention allows for the
availability of these benzimidazole compounds essentially only after their excretion alongside
feces, which can take place from about 10 hours to about 72 hours after ingestion (e.g., 12
hours to 72 hours, 20 hours to 72 hours, 30 hours to 72 hours, 40 hours to 72 hours),
depending on the ruminant species that received the treatment. Therefore, there generally will
18192324_1 (GHMatters) P45573NZ00
not be any absorption of the active ingredient by treated animals, before the 10 hours to 72
hours. The composition containing benzimidazole compounds will be expelled from the
ruminant organism through defecation. The delayed release or delayed availability of the
active ingredient is due to the combining of the active ingredient with the other ingredients of
the composition.
Therefore, generally, the active ingredient will be active only in the feces, sparing
the animals from exposure to benzimidazole compounds. This delayed release mechanism
avoids unwanted residues in milk or meat. Due to the present invention, the residue in the
animal or milk of the animal after 10 hours to 72 hours of ingesting can be below 100 ppm or
below 50 ppm or below 5 ppm or about 0 ppm, such as from 0 ppm to 1 ppm or 0 ppm. These
ppm ranges are also applicable after 72 hours or more of ingesting the composition of the
present invention.
Having the feces treated with the present invention’s composition, and being that
the feces practically are the only medium where helminth worms’ eggs and larvae develop,
particularly of the Haemonchus genre, and being that benzimidazole compounds have efficacy
against eggs and larvae of helminths, the reproductive cycle of said parasites can be broken.
Delayed release of the benzimidazole compound or benzimidazole-containing
compound means that the combination of ingredients used to form the composition of the
present invention protects the benzimidazole from being activated, released or destroyed by
gastric acids of the stomach(s) and avoids absorption in the intestine and/or other parts of the
animal, so that the benzimidazole is present in the feces exiting the animal and then is released
in the feces. For purposes of the present invention, the composition can be considered a
targeted-release composition as the target of release is the feces. For purposes of the present
18192324_1 (GHMatters) P45573NZ00
invention, the composition can be considered an extended release composition in view of the
hour to 72 hour delay in the benzimidazole efficacy being activated.
With the elimination of eggs and larvae, the adult worms population will decrease,
since there will be no immature larvae to develop into adults.
The composition of the present invention can include:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer (e.g., hydrophobic binding polymer);
(c) at least one hydrophilic polymer; and
(d) at least one particulate solid carrier.
Examples of benzimidazole compounds or benzimidazole containing compounds
are thiabendazole, fenbendazole, albendazole, triclabendazole, cambendazole, parbendazole,
mebendazole, flubendazole, oxfendazole, carbendazin, fuberidazole, triazoxide,
ricobendazole, oxibendazole, and/or one of its derivatives or salts thereof or prodrugs thereof.
Most preferably, the benzimidazole compound is thiabendazole and/or fenbendazole and/or
albendazole.
The amount of the active ingredient in the present invention’s composition may
vary according to the selected active ingredient. For example, the amount of the benzimidazole
containing compounds can be from about 0.1% to about 30% in weight of benzimidazole
compounds, based on the total weight of the composition. The wt% can be above 30 wt% if
desired.
The at least one hydrophobic polymer for the present invention can be
ethylcelulose, a zein, or a polymethacrylate copolymer, or any combination thereof. The
18192324_1 (GHMatters) P45573NZ00
hydrophobic polymer can be present in an amount of from 5 wt% to 55 wt%, based on the
total weight of the composition, such as from 7.5 wt% to 30 wt% or from 10 wt% to 20 wt%.
The at least one hydrophilic polymer can be any hydrophilic polymer or polymers.
The hydrophilic polymer can, as an option, be considered an adjuvant. The hydrophilic
polymer in combination with the hydrophobic polymer preferably have the ability to achieve
the delayed release of the active ingredient as described herein.
Examples of the hydrophilic polymer include, but are not limited to, hypromellose,
polyvinylpyrrolidone, carragenine, hydroxipropilmethylcellulose, or any combination thereof.
The hydrophilic polymer can be present in an amount of from about 0 wt% or from
0 wt% to 40 wt%, based on the total weight of the composition, such as from 2.5 wt% to 30
wt% or from 5 wt% to 20 wt%.
The particulate solid carrier can be any commonly used carrier. Examples of the
solid carrier include microcrystalline cellulose, calcium phosphate, calcium sulfate, mannitol,
kaolin, or any combination thereof. The carrier can be present in an amount of from 20 wt%
to 80 wt%, based on the total weight of the composition, such as from 30 wt% to 70 wt% or
from 40 wt% to 65 wt%.
Additionally, the composition of the present invention may further include, if
desired, one or more stabilizers, tensoactives, flavor enhancers, preservatives, and/or
antioxidants. The composition can contain, as an option one or more diluents. Examples
include starch, talcum powder, and/or calcium carbonate. The composition can contain one or
more other ingredients as an option, such as a lubricant(s). An example of a lubricant is silicon
dioxide. The composition can contain one or more pH adjustment agents or pH buffers, such
as, but not limited to, an acid or base, such as, an organic simple acid. An example of a
18192324_1 (GHMatters) P45573NZ00
specific agent is ethyl citrate. The total amount of the optional ingredients can be, in total
amounts (by wt% of the composition) of from about 0.1 wt% to about 10 wt%.
Generally, each of the components that form the composition of the present
invention are in solid form, but this is not a requirement. The composition of the present
invention can be prepared by mixing together each of the ingredients, for instance, in a tank to
form a mixture that can be pelletized, granulated, or otherwise aggregated to form a whole
host of sizes and/or shapes, such as spheres, rods, pellets, that can range in size from 3.5 mm
to 0.05 mm or other sizes. When forming the composition by mixing the ingredients, a
solvent can be used, such as an alcohol, like ethanol which can evaporate away. The
composition can be a combination of dry ingredients, and if so, the composition can be
considered a dry mix or a formulation. If one or more of the ingredients are liquid, the
components can be mixed and so achieve a binding of the various ingredients. Generally, the
mixture of components is a physical mixture where the components are homogenously
distributed amongst each other.
When the composition is formed, it can be considered a matrix or agglomerate or
aggregate.
The present invention further relates to a nematode controlling feed or feed
supplement that comprises a) the composition of the present invention, as described herein,
and b) a feed or a feed supplement. The feed and/or feed supplement can be mixed with the
composition of the present invention or otherwise combined to form the nematode controlling
feed or feed supplement.
Thus, the present invention also relates to a compound capable of controlling
nematodes that use feces as a medium for their reproductive cycle, through the addition of said
18192324_1 (GHMatters) P45573NZ00
compound to feed or feed supplements offered to animals, in a quantity of the composition
described above that is efficacious against such nematodes.
The feed to be offered to animals may be ground or pelletized. Nutritional
supplementation can be selected — without limitations — from: sodium chloride, mineralized
salt, calcium phosphate, vitamins concentrates, protein supplements, among others.
The present invention further relates to an auxiliary kit for controlling nematodes
that use feces as a medium for their reproductive cycle, that comprises a canister containing
the present invention’s composition and a dosing device. The canister may have any capacity,
but being particularly one that contains from about 100 g to 500 g, or 300 g of said
composition, or a pail containing from 1 kg to 15 kg, or 6 kg of said composition. Particularly,
the dosing device can dose up to 100 g of said compound according to the present invention’s
requirements.
In a particular realization, the kit may comprise usage instructions for said
compound according to the present invention’s requirements.
The amount of said composition to be mixed with feed or feed supplement is to be
established based on the estimated intake of the feed or feed supplement in use, which, in
livestock operations, is common knowledge.
For purposes of the present invention, the controlling of eggs and larvae, or the
controlling of eggs and larvae of a helminth or helminths means that the eggs and larvae are
substantially or completely killed in the feces due to the composition of the present
invention. The kill rate can be over a 90% kill rate based on the nematode or egg or larvae
population of helminth in the feces, or over a 95% kill rate, or over a 98% kill rate, or about a
100% kill rate or a 100% kill rate of the eggs and larvae.
18192324_1 (GHMatters) P45573NZ00
As an example, the dosage of the composition of the present invention to an animal
can be from about 50 mg to 125 mg of active ingredient/animal/day or from about 60 mg to
100 mg, or from about 70 mg to 80 mg of active ingredient/animal/day. If included in a feed or
feed supplement, the composition can be present in an amount to achieve this dosage range.
By way of illustration, the following quantities can be added to feed or feed
supplement to achieve the desired dosage range with about 2 wt% of active ingredient present:
a) for feed supplement with daily intake between 60 - 120 g per head, 66g to 80g
of the present invention’s composition are to be mixed with each 1 kg of the feed supplement.
b) for feed with daily intake between 3 - 6 kg per head, 1350 g to 1620 g of the
present invention’s composition are to be mixed with each 1,000 kg of the feed.
Presented below are further examples of particular formulations of the present
invention, with no limitations whatsoever to its scope besides those contained in the attached
claims.
Examples of compositions for 1 kg of product:
EXAMPLE 1 – COMPOSITIONS CONTAINING BENZIMIDAZOLE COMPOUNDS
EXAMPLE 1A
Components Quantity
Thiabendazole 20 g
Ethyl Acrylate Copolymer, Methyl metacrilate and
trimethylammonium ethyl methacrylate chloride – 550 g
Eudragit RS - CAS [334341]
Triethyl citrate 25 g
Microcrystalline Cellulose 405 g
18192324_1 (GHMatters) P45573NZ00
EXAMPLE 1B
Components Quantity
Fenbendazole 100 g
Ethyl Acrylate Copolymer and Methyl metacrilate 2 : 1 -
300 g
Eudragit NM - [90102]
Triethyl citrate 10 g
Calcium Phosphate 590 g
EXAMPLE 1C
Components Quantity
Fenbendazole 100 g
Ethyl Acrylate Copolymer and Methyl metacrilate 2 : 1 -
250 g
Eudragit NM - [90102]
Triethyl citrate 10 g
Cellulose 200 g
Kaolin 440 g
EXAMPLE 1D
Components Quantity
Albendazole 100 g
Ethyl Acrylate Copolymer and Methyl metacrilate 2 : 1 -
150 g
Eudragit NE - [90102]
Triethyl Citrate 10 g
Calcium Phosphate 290 g
Microcrystalline cellulose 450 g
EXAMPLE 1E:
Components Quantity
Thiabendazole 20 g
Zein 400 g
Starch 40 g
Microcrystalline cellulose 300 g
Kaolin 240 g
18192324_1 (GHMatters) P45573NZ00
EXAMPLE 1F:
Components Quantity
Fenbendazole 100 g
Ethylcellulose 100 g
Hypromellose 50 g
Microcrystalline cellulose 200 g
Kaolin 550 g
EXAMPLE 1G:
Components Quantity
Albendazole 100 g
Ethylcellulose 150 g
Carragenine 200 g
Calcium carbonate 100 g
Calicum Phosphate 450 g
EXAMPLE 1H:
Components Quantity
Thiabendazole 200 g
Ethylcellulose 50 g
Hypromellose 400 g
Sodium lauryl ether sulfate 20 g
Microcrystalline cellulose 330 g
EXAMPLE 1I:
Components Quantity
Fenbendazol 100 g
Ethyl Acrylate Copolymer and Methyl metacrilate 2 : 1 -
300 g
Eudragit NM - [90102]
Triethyl Citrate 15 g
Microcrystalline cellulose 135 g
Kaolin 450 g
EXAMPLE 1J:
Components Quantity
Albendazole 100 g
Zein 400 g
Starch 40 g
Microcrystalline cellulose 460 g
18192324_1 (GHMatters) P45573NZ00
EXAMPLE 1K:
Components Quantity
Thiabendazole 20 g
Zein 300 g
Starch 50 g
Microcrystalline cellulose 500 g
Calcium sulfate 130 g
EXAMPLE 1L:
Components Quantity
Fenbendazole 100 g
Zein 350 g
Polyvinylpyrrolidone 30 g
Microcrystalline cellulose 170 g
Kaolin 350 g
EXAMPLE 1M:
Components Quantity
Albendazole 300 g
Ethylcellulose 50 g
Hypromellose 350 g
Sodium Lauryl Benzene Sulfonate 30 g
Kaolin 270 g
EXAMPLE 1N:
Components Quantity
Thiabendazole 20 g
Ethylcellulose 150 g
Hypromellose 50 g
Silicon dioxide 40 g
Microcrystalline cellulose 740 g
EXAMPLE 1O:
Components Quantity
Fenbendazole 100 g
Ethylcellulose 200 g
Hypromellose 50 g
Silicon dioxide 50 g
Microcrystalline cellulose 600 g
18192324_1 (GHMatters) P45573NZ00
The present invention includes the following aspects/embodiments/features in any
order and/or in any combination:
1. A composition for the control of eggs and larvae of a helminth that develops in
ruminant feces, comprising:
(a) at least one benzimidazole compound;
(b) at least one hydrophobic polymer;
(c) at least one particulate solid carrier, and
(d) optionally, at least one hydrophilic polymer.
2. The method of any preceding or following embodiment/feature/aspect, wherein said
helminth is of the Haemonchus genre, and the ruminant feces is from the suborder of
Ruminantia.
3. The method of any preceding or following embodiment/feature/aspect, wherein the
benzimidazole compound is thiabendazole, fenbendazole, albendazole, triclabendazole,
cambendazole, parbendazole, mebendazole, flubendazole, oxfendazole, carbendazim,
fuberidazole, triazoxide, ricobendazole, oxilbendazole, or a derivative thereof, or any
combination thereof.
4. The method of any preceding or following embodiment/feature/aspect, wherein the
benzimidazole compound is thiabendazole, fenbendazole, or albendazole, or any combination
thereof.
. The method of any preceding or following embodiment/feature/aspect, wherein the
hydrophobic polymer is ethylcellulose, zein, a methyl methacrylate copolymer, or any
combination thereof.
18192324_1 (GHMatters) P45573NZ00
6. The method of any preceding or following embodiment/feature/aspect, wherein the
hydrophilic polymer is present.
7. The method of any preceding or following embodiment/feature/aspect, wherein the
particulate solid carrier is microcrystalinne cellulose, calcium phosphate, calcium sulfate,
mannitol, kaolin, or any combination thereof.
8. The method of any preceding or following embodiment/feature/aspect, further
comprising a stabilizer, a flavoring agent, a flavor enhancer, a preservative, a tensoactive, a
lubricant, a diluent, a lubricant, a pH adjustment agent, or an antioxidant, or any combination
thereof.
9. A feed or feed supplement composition comprising a) feed or feed supplement offered
to animals and b) an efficacious amount of any preceding or following
embodiment/feature/aspect.
. The feed or feed supplement composition of any preceding or following
embodiment/feature/aspect, wherein the feed is ground or pelletized.
11. The feed or feed supplement composition of any preceding or following
embodiment/feature/aspect, wherein the feed supplement is sodium chloride, mineralized salt,
calcium phosphate, a vitamin concentrate, a protein supplement, or any combination thereof.
12. A kit for controlling nematodes that develop in ruminant’s feces comprising a canister
containing the composition of any preceding or following embodiment/feature/aspect and a
dosing device.
13. The kit of any preceding or following embodiment/feature/aspect further comprising
written instructions for its use.
18192324_1 (GHMatters) P45573NZ00
14. The kit of any preceding or following embodiment/feature/aspect, wherein the canister
contains about 300 g of said composition and a 25g-dosing device for dosing of said
composition.
. The kit of any preceding or following embodiment/feature/aspect, wherein said
canister is a pail containing about 6 kg of said composition and a 25g-dosing device for dosing
of said composition.
16. A method to control eggs and larvae of helminths present in ruminants’ feces, said
method comprising administering to an animal, by oral route, through means of feed or feed
supplement, the composition of any preceding or following embodiment/feature/aspect.
17. The method of any preceding or following embodiment/feature/aspect, wherein said
method enhances zootechnical performance of ruminants by means of controlling eggs and
infective larvae in their habitat.
18. The composition of any preceding or following embodiment/feature/aspect, wherein
said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%,
based on the total weight of said composition.
19. The composition of any preceding or following embodiment/feature/aspect, wherein
said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said
hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said
hydrophilic polymer is present in an amount of from 0 wt% to about 40 wt% and said
particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a
total weight of said composition.
. The method of any preceding or following embodiment/feature/aspect, wherein said
composition is administered to said animal in an amount of from about 4 g to about 8 g.
18192324_1 (GHMatters) P45573NZ00
21. The composition of any preceding or following embodiment/feature/aspect, wherein
said benzimidazole compound in said composition is bioactively released on a delayed release
basis.
22. The composition of any preceding or following embodiment/feature/aspect, wherein
said delayed release is from about 10 hours to 72 hours from consumption of the composition
by an animal.
23. The method of any preceding or following embodiment/feature/aspect, wherein said
composition is delayed released with respect to said benzimidazole compound such that the
release occurs in the feces of said ruminant.
24. The method of any preceding or following embodiment/feature/aspect, wherein said
animal after 10 hours to 72 hours has a residue of said benzimidazole compound of less than
100 ppm.
. The method of any preceding or following embodiment/feature/aspect, wherein said
animal after 10 hours to 72 hours has a residue of said benzimidazole compound of less than 1
ppm.
26. The composition of any preceding or following embodiment/feature/aspect, wherein
said hydrophilic polymer is present and is hypromellose, polyvinylpyrrolidone, carragenine,
hydroxipropilmethylcellulose, or any combination thereof.
27. The composition of any preceding or following embodiment/feature/aspect, wherein
one or more of the following is additional present in the composition: starch, talcum powder,
calcium carbonate, silicon dioxide, ethyl citrate, or any combination.
28. The composition of any preceding or following embodiment/feature/aspect, wherein
said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said
18192324_1 (GHMatters) P45573NZ00
hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said
hydrophilic polymer is present in an amount of from 2.5 wt% to about 30 wt% and said
particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a
total weight of said composition.
The present invention can include any combination of these various features or
embodiments above and/or below as set forth in sentences and/or paragraphs. Any
combination of disclosed features herein is considered part of the present invention and no
limitation is intended with respect to combinable features.
Applicants specifically incorporate the entire contents of all cited references in this
disclosure. Further, when an amount, concentration, or other value or parameter is given as
either a range, preferred range, or a list of upper preferable values and lower preferable values,
this is to be understood as specifically disclosing all ranges formed from any pair of any upper
range limit or preferred value and any lower range limit or preferred value, regardless of
whether ranges are separately disclosed. Where a range of numerical values is recited herein,
unless otherwise stated, the range is intended to include the endpoints thereof, and all integers
and fractions within the range. It is not intended that the scope of the invention be limited to
the specific values recited when defining a range.
Other embodiments of the present invention will be apparent to those skilled in the
art from consideration of the specification and practice of the invention disclosed herein. It is
intended that the specification and examples be considered exemplary only, with a true scope
and spirit of the invention being indicated by the following claims.
18192324_1 (GHMatters) P45573NZ00
Claims (43)
- CLAIMS 1. A method of controlling eggs and larvae of a helminth that develops in ruminant feces, comprising administering to a ruminant an efficacious amount of a composition comprising: (a) at least one benzimidazole compound; (b) at least one hydrophobic polymer; (c) at least one particulate solid carrier, and (d) optionally, at least one hydrophilic polymer; wherein the composition is administered to the ruminant, by oral route through means of feed or feed supplement, at a dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day.
- 2. The method of claim 1, wherein said helminth is of the Haemonchus genre, and the ruminant feces is from the suborder of Ruminantia.
- 3. The method of claim 1 or 2, wherein the benzimidazole compound is thiabendazole, fenbendazole, albendazole, triclabendazole, cambendazole, parbendazole, mebendazole, flubendazole, oxfendazole, carbendazim, fuberidazole, triazoxide, ricobendazole, oxilbendazole, or a derivative thereof, or any combination thereof.
- 4. The method of claim 3, wherein the benzimidazole compound is thiabendazole, fenbendazole, or albendazole, or any combination thereof. 18192324_1 (GHMatters) P45573NZ00
- 5. The method of any of claims 1 to 4, wherein the hydrophobic polymer is ethylcellulose, zein, a methyl methacrylate copolymer, or any combination thereof.
- 6. The method of any of claims 1 to 4, wherein the hydrophilic polymer is present.
- 7. The method of claim 5, wherein the hydrophilic polymer is polyvinylpyrrolidone, carragenine, hydroxypropylmethylcellulose, or any combination thereof.
- 8. The method of any of claims 1 to 7, wherein the particulate solid carrier is microcrystalline cellulose, calcium phosphate, calcium sulfate, mannitol, kaolin, or any combination thereof.
- 9. The method of any of claims 1 to 8, further comprising a stabilizer, a flavoring agent, a flavor enhancer, a preservative, a tensoactive, a lubricant, a diluent, a lubricant, a pH adjustment agent, or an antioxidant, or any combination thereof.
- 10. The method of any of claims 1 to 9, wherein one or more of the following is additionally present in the composition: starch, talcum powder, calcium carbonate, silicon dioxide, ethyl citrate, or any combination.
- 11. The method of any of claims 1 to 10, wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, based on the total weight of said composition. 18192324_1 (GHMatters) P45573NZ00
- 12. The method of claim 11, wherein the composition contains a hydrophilic polymer and a separate particulate solid carrier wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said hydrophilic polymer is present in an amount of from 0 wt% to about 30 wt% and said particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a total weight of said composition.
- 13. The method of claim 12, wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said hydrophilic polymer is present in an amount of from 2.5 wt% to about 30 wt% and said particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a total weight of said composition.
- 14. The method of any of claims 1 to 13, wherein said method enhances zootechnical performance of ruminants by means of controlling eggs and infective larvae in their habitat.
- 15. The method of any of claims 1 to 14, wherein said benzimidazole compound in said composition is bioactively released on a delayed release basis.
- 16. The method of claim 15, wherein said delayed release is from about 10 hours to 72 hours from consumption of the composition by a ruminant. 18192324_1 (GHMatters) P45573NZ00
- 17. The method of claim 15 or 16, wherein said composition is delayed released with respect to said benzimidazole compound such that the release occurs in the feces of said ruminant.
- 18. The method of any of claims 15 to 17, wherein said ruminant after 10 hours to 72 hours has a residue of said benzimidazole compound of less than 100 ppm.
- 19. The method of claim 18, wherein said ruminant after 10 hours to 72 hours has a residue of said benzimidazole compound of less than 1 ppm.
- 20. A method of controlling eggs and larvae of a helminth that develops in ruminant feces, comprising administering to a ruminant a feed or feed supplement composition, comprising i) feed or feed supplement offered to animals and; ii) an efficacious amount of a composition comprising: (a) at least one benzimidazole compound; (b) at least one hydrophobic polymer; (c) at least one particulate solid carrier, and (d) optionally, at least one hydrophilic polymer; wherein the feed or feed supplement composition is given to the ruminant in such amount that the ruminant is administered a dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day.
- 21. The method of claim 20, wherein the feed is ground or pelletized. 18192324_1 (GHMatters) P45573NZ00
- 22. The method of claim 20 or 21, wherein the feed supplement is sodium chloride, mineralized salt, calcium phosphate, a vitamin concentrate, a protein supplement, or any combination thereof.
- 23. A composition for controlling eggs and larvae of a helminth that develops in ruminant feces, the composition comprising: (a) at least one benzimidazole compound; (b) at least one hydrophobic polymer; (c) at least one particulate solid carrier, and (d) optionally, at least one hydrophilic polymer; wherein the composition is formulated for administration to a ruminant by oral route, through means of feed or feed supplement, at a dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day, and wherein the composition is formulated for delayed release with respect to the benzimidazole compound such that release occurs in the feces of the ruminant.
- 24. The composition of claim 23, wherein the composition is formulated for delayed release with respect to the benzimidazole compound such that delayed release is from about 10 hours to 72 hours from consumption of the composition by a ruminant.
- 25. The composition of claim 23 or 24, wherein said composition is formulated for delayed release with respect to the benzimidazole compound such that the ruminant after 10 hours to 72 hours has a residue of the benzimidazole compound of less than 100 ppm. 18192324_1 (GHMatters) P45573NZ00
- 26. The composition of claim 25, wherein said composition is formulated for delayed release with respect to the benzimidazole compound such that the ruminant after 10 hours to 72 hours has a residue of said benzimidazole compound of less than 1 ppm.
- 27. The composition of any of claims 23 to 26, wherein the benzimidazole compound is thiabendazole, fenbendazole, albendazole, triclabendazole, cambendazole, parbendazole, mebendazole, flubendazole, oxfendazole, carbendazim, fuberidazole, triazoxide, ricobendazole, oxilbendazole, or a derivative thereof, or any combination thereof.
- 28. The composition of claim 27, wherein the benzimidazole compound is thiabendazole, fenbendazole, or albendazole, or any combination thereof.
- 29. The composition of any of claims 23 to 28, wherein the hydrophobic polymer is ethylcellulose, zein, a methyl methacrylate copolymer, or any combination thereof.
- 30. The composition of any of claims 23 to 29, wherein the hydrophilic polymer is present.
- 31. The composition of any of claims 23 to 30, wherein the hydrophilic polymer is polyvinylpyrrolidone, carragenine, hydroxypropylmethylcellulose, or any combination thereof. 18192324_1 (GHMatters) P45573NZ00
- 32. The composition of any of claims 23 to 31, wherein the particulate solid carrier is microcrystalline cellulose, calcium phosphate, calcium sulfate, mannitol, kaolin, or any combination thereof.
- 33. The composition of any of claims 23 to 32, further comprising a stabilizer, a flavoring agent, a flavor enhancer, a preservative, a tensoactive, a lubricant, a diluent, a lubricant, a pH adjustment agent, or an antioxidant, or any combination thereof.
- 34. The composition of any of claims 23 to 33, wherein one or more of the following is additionally present in the composition: starch, talcum powder, calcium carbonate, silicon dioxide, ethyl citrate, or any combination.
- 35. The composition of any of claims 23 to 34, wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, based on the total weight of said composition. 37.
- The composition of claim 36, wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said hydrophilic polymer is present in an amount of from 2.5 wt% to about 30 wt% and said particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a total weight of said composition.
- 37. The composition of claim 36, wherein said benzimidazole compound is present in an amount of from 0.1 wt% to about 20 wt%, said hydrophobic polymer is present in an amount of from about 5 wt% to about 55 wt%, said hydrophilic polymer is present in an amount of 18192324_1 (GHMatters) P45573NZ00 from 2.5 wt% to about 30 wt% and said particulate solid carrier is present in an amount of from 40 wt% to about 75 wt%, based on a total weight of said composition.
- 38. A feed or feed supplement composition, comprising i) feed or feed supplement offered to animals and; ii) a composition according to any of claims 23 to 37; wherein the feed or feed supplement composition is formulated for administration at a dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day. wherein the composition is administered to the ruminant, by oral route through means of feed or feed supplement, at a dosage of 50 mg to 125 mg of the benzimidazole compound per ruminant per day
- 39. The feed or feed supplement composition of claim 38, wherein the feed supplement is sodium chloride, mineralized salt, calcium phosphate, a vitamin concentrate, a protein supplement, or any combination thereof.
- 40. A kit for controlling nematodes that develop in ruminant’s feces comprising a canister containing a composition of any of claims 23 to 39 and a dosing device, when used in a method according to any of claims 1 to 22.
- 41. The kit when used of claim 40 further comprising written instructions for its use. 18192324_1 (GHMatters) P45573NZ00
- 42. The kit when used of claim 40 or 41, wherein the canister contains about 300 g of said composition and a 25g-dosing device for dosing of said composition.
- 43. The kit when used of any of claims 40 to 42, wherein said canister is a pail containing about 6 kg of said composition and a 25g-dosing device for dosing of said composition. 18192324_1 (GHMatters) P45573NZ00
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR102017010598-9 | 2017-05-19 | ||
BR102017010598-9A BR102017010598A2 (en) | 2017-05-19 | 2017-05-19 | delayed release veterinary compositions for control of helminth eggs and larvae in ruminant feces, use of compositions, use of anthelmintics for this purpose |
US15/823,965 US10300045B2 (en) | 2017-05-19 | 2017-11-28 | Delayed release feed-through veterinary compositions with ovicidal and larvicidal activity against susceptible and resistant strains of parasites in ruminants' feces, use of these compositions, method for delaying the release of these compositions |
US15/823,965 | 2017-11-28 | ||
PCT/US2018/029492 WO2018212954A1 (en) | 2017-05-19 | 2018-04-26 | Delayed release feed-through veterinary compositions with ovicidal and larvicidal activity against susceptible and resistant strains of parasites in ruminants' feces, use of these compositions, method for delaying the release of these compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ758435A NZ758435A (en) | 2021-11-26 |
NZ758435B2 true NZ758435B2 (en) | 2022-03-01 |
Family
ID=
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