WO2003004059A1 - Treatment of parasitic disease - Google Patents
Treatment of parasitic disease Download PDFInfo
- Publication number
- WO2003004059A1 WO2003004059A1 PCT/AU2002/000867 AU0200867W WO03004059A1 WO 2003004059 A1 WO2003004059 A1 WO 2003004059A1 AU 0200867 W AU0200867 W AU 0200867W WO 03004059 A1 WO03004059 A1 WO 03004059A1
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- WO
- WIPO (PCT)
- Prior art keywords
- sustained release
- parasitic
- mini
- implant
- blood level
- Prior art date
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Classifications
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Definitions
- the present invention relates to a method of treatment of parasitic diseases, including external (ecto-) and internal (endo-) parasites and to a sustained release pharmaceutical composition for such treatment. More specifically, the present invention relates to the use of a sustained release pharmaceutical composition which provides a significant increase in the bio- availability of the pharmaceutical composition with a corresponding increase in the blood levels of the pharmaceutical agent.
- Parasitic diseases are of particular concern in domestic and farm animals, in particular cattle, sheep, pigs, dogs, cats, rats, mice, birds and fish.
- Numerous forms of treatment are known including oral tablets, pour-ons, injectables and the like.
- many of the known treatments suffer from the fact that exposure to an infected environment leads to a high level of re-infection as soon as the effect of the treatment wears off.
- a particularly useful anti-parasitic agent is ivermectin.
- This product first became available in an injectable formulation, and later as a pour-on.
- both methods of drug administration require animals to be treated on several occasions. For example, once at the start of grazing and again about six weeks later.
- drug levels in the blood are high immediately after administration, but drop substantially after about four weeks. This often results in re-infection developing within six to eight weeks after the second treatment.
- ivermectin is not indicated for the treatment of parasitic infestations for smaller animals with the exception of heartworm, particularly cats and dogs, as the high levels required using the conventional methods of application named above to generate protection may be toxic, even lethal, to such animals. Accordingly, where a disease indication requires the achievement of a high threshold blood plasma level and/or requires the delivery of multiple pharmaceuticals and/or requires sustained release to be continued over an extended period at high levels, the drug delivery systems known in the prior art generally exhibit insufficient drug carrying capacity.
- such drug delivery implants may be placed subcutaneously in the ear of an animal. This may be physically impossible where the size of the implant becomes too large.
- an object of the present invention to overcome or at least alleviate one or more of the difficulties and deficiencies related to the prior art.
- the present invention provides for use of an anti-parasitic agent in a sustained release form, in the treatment of external parasites.
- the anti-parasitic agent may include a macrocyclic lactone, for example ivermectin, moxidectin, eprinomectin, doramectin, an insect growth regulator, or mixtures thereof.
- a macrocyclic lactone for example ivermectin, moxidectin, eprinomectin, doramectin, an insect growth regulator, or mixtures thereof.
- the anti-parasitic agent may be used in the treatment of any and all animals, including domestic and farm animals, including sheep, cattle, horses, pigs, goats, dogs, cats, ferrets, rodents, including mice and rats, birds, including chicken, geese and turkeys, marsupials, fish, primates and reptiles.
- domestic and farm animals including sheep, cattle, horses, pigs, goats, dogs, cats, ferrets, rodents, including mice and rats, birds, including chicken, geese and turkeys, marsupials, fish, primates and reptiles.
- an anti-parasitic agent e.g. ivermectin
- a sustained release (i.e. solid) form permits the achievement of ectoparasitic, and optionally endoparasitic protection to animals, without reaching harmful or toxic levels.
- a method of treating parasitic diseases in animals which method includes administering to an animal a prophylactically or therapeutically effective, but non-toxic, amount of an anti-parasitic agent in a sustained release form.
- the anti-parasitic agent may include a macrocyclic lactone, as described above.
- the parasitic disease to be treated may include an external (ecto-) parasitic infestation, for example fleas, ticks, mites, lice and the like.
- an external (ecto-) parasitic infestation for example fleas, ticks, mites, lice and the like.
- the method may provide for the concomitant treatment of internal (endo-) parasitic infestations including worms, e.g. heartworm.
- the present invention provides for use of an anti-parasitic agent in a sustained release form in the concomitant treatment of external and internal parasites.
- the present invention provides for the concomitant treatment of internal parasites (including worms, e.g. heartworm, roundworms) and external parasites (including fleas, ticks and mites) in animals, including domestic and farm animals including in particular cats and dogs.
- internal parasites including worms, e.g. heartworm, roundworms
- external parasites including fleas, ticks and mites
- the anti-parasitic agent may be provided in a sustained release delivery apparatus including a plurality of sustained release mini-implants or pellets; each mini implant or pellet including an anti-parasitic composition including at least one anti-parasitic agent; a carrier therefor; and optionally a sustained release support material; the anti-parasitic composition carried in or on the sustained release support material, when present; each implant being of insufficient size individually to provide a predetermined desired threshold blood level of anti-parasitic active for treatment of a selected disease indication.
- each mini-implant includes a pharmaceutical active-containing inner layer; and a water-impermeable outer layer.
- each mini-implant takes the form of an extruded rod bearing a water-impermeable coating thereover.
- the plurality of sustained release mini-implants or pellets in combination may provide a blood level of pharmaceutical active at least equal to a predetermined threshold for an extended period, e.g. of approximately 1 to 24, preferably 1 to 4 weeks for ivermectin active.
- the plurality of sustained release mini-implants or pellets may be of two or more different sizes and provides for the concomitant treatment of ectoparasites and endoparasites.
- the mini-implants or pellets may be provided in a first size which provides a blood level of pharmaceutical active of approximately 1.25 to 3 times the desired threshold blood level for an extended, though relatively short, period, e.g. of approximately 1 to 4 weeks, and in a second size which provides a blood level at or near the desired threshold blood level over a longer time period, e.g. of approximately 4 to 52 weeks.
- the present invention provides a method of treating fleas in animals, which method includes administering to an animal a prophylactically or therapeutically effective, but non-toxic amount of an anti-parasitic agent, preferably a macrocyclic lactone, in a sustained release form.
- the animals to be treated preferably include cats, dogs, ferrets and rodents.
- the sustained release form utilised in the present invention may include a sustained release apparatus.
- the present invention in this form provides a method for the therapeutic or prophylactic treatment of a parasitic condition in an animal (including a human) requiring such treatment, which method includes administering to the animal a sustained release delivery apparatus including a plurality of sustained release mini-implants or pellets; each mini implant or pellet including an anti-parasitic composition including at least one anti-parasitic agent; a carrier therefor; and optionally a sustained release support material; the anti-parasitic composition carried in or on the sustained release support material, when present; each implant being of insufficient size individually to provide a predetermined desired threshold blood level of anti-parasitic active for treatment of a selected disease indication; and administering the sustained release delivery apparatus to the animal to be treated.
- the threshold blood level of the anti- parasitic agent required to treat external, and optionally internal parasites may be achieved utilising a series of mini-implants or pellets which individually may be of insufficient or no value in treating the disease.
- the sustained release apparatus may provide approximately zero order release of pharmaceutical active.
- each mini-implant includes a pharmaceutical active-containing inner layer; and a water impermeable outer layer.
- each mini-implant takes the form of an extruded rod bearing a water-impermeable coating thereover.
- the mini-implants or pellets are provided in at least two different sizes and provides for the concomitant treatment of ectoparasites and endoparasites.
- the mini-implants or pellets are provided in a first size which provides a blood level of pharmaceutical active of approximately 1.25 to 3 times the desired threshold blood level for a first relatively short time period; and in a second size which provides a blood level of pharmaceutical active at or near the desired threshold blood level for a second longer time period.
- the sustained release apparatus may be provided as a sustained release kit.
- the method according to the present invention includes providing a sustained release kit including a plurality of sustained release mini implants or pellets packaged for delivery in a single treatment; each mini-implant or pellet including an anti-parasitic composition including at least one pharmaceutically active component including an anti-parasitic agent; a carrier therefor; and optionally a sustained release support material; the anti-parasitic composition carried in or on the sustained release support material; each implant being of insufficient size individually to provide a predetermined desired threshold blood level of anti-parasitic agent for treatment of external parasites; and administering the mini implants or pellets in a single treatment.
- the sustained release kit further includes a sustained release delivery apparatus.
- an injector instrument for subcutaneous delivery of standard size pellets may be used as the sustained release delivery apparatus.
- the multiple mini-pellets may be provided in a single cartridge for use in a standard injector instrument which in turn disperse as individual mini-pellets within the body of the animal to be treated.
- the plurality of sustained release implants may be provided in a biodegradable sheath.
- the biodegradable sheath may be formed of a water-soluble material.
- the water-soluble material utilised in the biodegradable sheath may be selected from one or more of the water-soluble substances described below.
- Each sustained release mini-pellet according to the present invention may be biodegradable.
- Each sustained release mini-pellet according to the present invention may be of the covered rod or matrix type.
- a rod-like shape is preferred.
- each sustained release mini-pellet may be approximately 0.1 to 0.5 times, preferably approximately 0.20 to 0.25 times, the length of a single rod shaped implant, capable of providing the desired threshold blood level of anti- parasitic agent.
- a typical cattle implant is the product sold under the trade designation "Revalor", and containing as pharmaceutical actives trembolone acetate and estradiol.
- This implant has the dimensions 4 mm x 4 mm.
- the equivalent implant according to the present invention may have dimensions of 4 mm x 2 mm.
- the sustained release delivery apparatus may take the form of a covered rod or dispersed matrix structure.
- a multi mini-pellet system permits the treatment of diseases over an extended period with pharmaceutically active components which have heretofore not been applicable to such diseases as it has not been possible to achieve the required threshold blood plasma levels to be efficacious and to maintain those blood levels over an extended period of time.
- the sustained release delivery apparatus may provide approximately zero order release of pharmaceutical active.
- the pharmaceutically active component ivermectin is a mixture of not less than 90% ivermectin H 2 B ⁇ a and not more than 5% ivermectin H 2 B ⁇ b having the respective molecular weights 875.10 and 861.07.
- Ivermectin is a potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against both internal and external parasites as well as being effective against arthropods, insects, nematodes, filarioidea, platyhelminths and protozoa.
- the sustained release support material may take the form of a support matrix or rod, preferably a covered rod structure.
- the sustained release support material may be formed from a biodegradable or biocompatible material, preferably a biocompatible hydrophobic material.
- the biocompatible material may be selected from the group consisting of polyesters, polyamino acids, silicones, ethylene-vinyl acetate copolymers and polyvinyl alcohols.
- the sustained release support material is a silicone material.
- a silicone rod is preferred.
- the silicone material may be a porous silicon or Biosilicon material, for example as described in International patent application PCT/GB99/01185, the entire disclosure of which is incorporated herein by reference. A mesoporous, microporous or polycrystalline silicon or mixtures thereof may be used.
- Biodegradable polymers that may be employed in the present invention may be exemplified by, but not limited to, polyesters such as poly(lactic acid- glycolic acid) copolymers (PLGA), etc. and by hydrophobic polyamino acids such as polyaranin, polyleucine, polyanhydride, poly(glycerol-sebacate)(PGS), Biopol and the like.
- the hydrophobic polyamino acids mean polymers prepared from hydrophobic amino acids.
- Nonbiodegradable polymers that may be employed in the present invention may be exemplified by, but not limited to, silicones, polytetrafluoroethylenes, polyethylenes, polypropylenes, polyurethanes, polyacrylates, polymethacrylates such as polymethylmethacrylat.es, etc., ethylene-vinyl acetate copolymers, and others. More preferably a silicone elastomer as described in copending Australian provisional patent application PR7614, to applicants (the entire disclosure of which is incorporated herein by reference), may be used.
- the anti-parasitic composition may, in a preferred embodiment, further include at least one pharmaceutically active component.
- the pharmaceutically active component may be exemplified by, but not limited to, one or more selected from the group consisting of:
- the pharmaceutically active component may include a water-insoluble pharmaceutical, a water-soluble pharmaceutical or mixtures thereof.
- the water-soluble pharmaceutical actives useful in the sustained release delivery apparatus according to the present invention include such drugs as peptides, proteins, glycoproteins, polysaccharides, and nucleic acids.
- the present invention is particularly appropriate for delivery of pharmaceuticals, in addition to parasitic agents, that are very active even in extremely small quantities and whose sustained long-term administration is sought. When used in substantially increased quantities, such pharmaceuticals may be applied to disease indications heretofore untreatable over an extended period.
- the pharmaceuticals may be exemplified by, but not limited to, one or more selected from the group consisting of cytokines (eg. interferons and interleukins), hematopoietic factors (eg. colony-stimulating factors and erythropoietin), hormones (eg. growth hormone, growth hormone releasing factor, calcitonin, leuteinizing hormone, leuteinizing hormone releasing hormone, and insulin), growth factors (eg.
- cytokines eg. interferons and interleukins
- hematopoietic factors eg. colony-stimulating factors and erythropoietin
- hormones eg. growth hormone, growth hormone
- somatomedin nerve growth factor
- neurotrophic factors fibroblast growth factor
- hepatocyte proliferation factor cell adhesion factors
- immunosuppressants enzymes (eg. asparaginase, superoxide dismutase, tissue plasminogen activating factor, urokinase, and prourokinase), blood coagulating factors (eg. blood coagulating factor VIII), proteins involved in bone metabolism (eg. BMP (bone morphogenetic protein)), and antibodies.
- enzymes eg. asparaginase, superoxide dismutase, tissue plasminogen activating factor, urokinase, and prourokinase
- blood coagulating factors eg. blood coagulating factor VIII
- proteins involved in bone metabolism eg. BMP (bone morphogenetic protein)
- the interferons may include alpha, beta, gamma, or any other interferons or any combination thereof.
- the interleukin may be IL-1 , IL-2, IL-3, or any others, and the colony-stimulating factor may be multi-CSF (multipotential CSF),
- GM-CSF granulocyte-macrophage CSF
- G-CSF granulocyte CSF
- Vaccines are particularly preferred.
- the vaccines useful in the sustained release delivery apparatus according to the present invention may be exemplified by, but not limited to, one or more selected from the group consisting of
- Diphtheria-Tetanus (DT for children) Diphtheria-Tetanus (tD for adults)
- the anti-parasitic composition according to the present invention further includes a carrier for the anti-parasitic agent component.
- the carrier may be selected to permit release of the pharmaceutically active component over an extended period of time from the composition.
- the carrier may include a water-soluble substance.
- a water-soluble substance is a substance which plays a role of controlling infiltration of water into the inside of the drug dispersion. There is no restriction in terms of the water-soluble substance so long as it is in a solid state (as a form of a preparation) at the body temperature of an animal or human being to which it is to be administered, and a physiologically acceptable, water-soluble substance.
- the water-soluble substance specifically may be selected from one or more of the group consisting of synthetic polymers (eg. polyethylene glycol, polyethylene polypropylene glycol), sugars (eg. sucrose, mannitol, glucose, sodium chondroitin sulfate), polysaccharides (e.g. dextran), amino acids (eg. glycine and alanine), mineral salts (eg. sodium chloride), organic salts (eg. sodium citrate) and proteins (eg. gelatin and collagen and mixtures thereof).
- synthetic polymers eg. polyethylene glycol, polyethylene polypropylene glycol
- sugars eg. sucrose, mannitol, glucose, sodium chondroitin sulfate
- polysaccharides e.g. dextran
- amino acids eg. glycine and alanine
- mineral salts eg. sodium chloride
- organic salts eg. sodium citrate
- proteins eg. gelatin and collagen and
- amphipathic substance when the water-soluble substance is an amphipathic substance, which dissolves in both an organic solvent and water, it has an effect of controlling the release of, for example, a lipophilic drug by altering the solubility thereof.
- An amphipathic substance includes, but not limited to, polyethylene glycol or a derivative thereof, polyoxyethylene polyoxypropylene glycol or a derivative thereof, fatty acid ester and sodium alkylsulfate of sugars, and more specifically, polyethylene glycol, polyoxy stearate 40, polyoxyethylene[196]polyoxypropylene- [67]glycol, polyoxyethylene[105]polyoxypropylene[5]glycol, polyoxyethylene- [160]polyoxypropylene[30]glycol, sucrose esters of fatty acids, sodium lauryl sulfate, sodium oleate, sodium desoxycholic acid (sodium deoxycholic acid (DCA)) of which mean molecular weights are more than 1500.
- the water-soluble substance may include a substance which is water-soluble and has any activity in vivo such as low molecular weight drugs, peptides, proteins, glycoproteins, polysaccharides, or an antigenic substance used as vaccines, i.e. water-soluble drugs.
- the pharmaceutical carrier may constitute from approximately 5% to 30% by weight, preferably approximately 10% to 20% by weight based on the total weight of the pharmaceutically active composition.
- Each sustained release implant or mini-pellet may include additional carriers or excipients, lubricants, fillers, plasticisers, binding agent, pigments and stabilising agents.
- Suitable fillers may be selected from the group consisting of talc, titanium dioxide, starch, kaolin, cellulose (microcrystalline or powdered) and mixtures thereof.
- Suitable binding agents include polyvinyl pyrrolidine, hydroxypropyl cellulose and hydroxypropyl methyl cellulose and mixtures thereof.
- the sustained release implant according to the present invention may have a rod-like shape, for example it is selected from circular cylinders, prisms, and elliptical cylinders.
- a circular cylindrical device is preferred since the injector body and the injection needle typically have a circular cylindrical shape.
- the sustained release implant according to the present invention may be manufactured according to the method described in copending Australian provisional patent application PR7614 referred to above.
- the inner layer of the pharmaceutical formulation of the present invention may contain two or more layers containing different anti- parasitic agents and/or pharmaceuticals. These layers may take the form of concentric circles with a single center of gravity or may appear as a plural number of inner layers whose respective centers of gravity lie at different points in the cross section.
- the formulation contains more than one inner layer there may be one or more anti-parasitic agents or pharmaceuticals present in the inner layers.
- the actives may be present such that each layer contains a different active or there is more than one active in one or all of the inner layers.
- the size of the sustained release anti-parasitic formulation of the present invention may, in the case of subcutaneous administration, be relatively small, e.g. 1/4 to 1/10 normal size.
- the configuration may be circular cylindrical, and the cross-sectional diameter in the case is preferably 0.2 to 4 mm, the axial length being preferably approximately 0.2 to 30 mm, preferably approximately 0.5 to 15 mm, more preferably approximately 1 to 10 mm.
- the thickness of the outer layer should be selected as a function of the material properties and the desired release rate.
- the outer layer thickness is not critical as long as the specified functions of the outer layer are fulfilled.
- the outer layer thickness is preferably 0.05 mm to 3 mm, more preferably 0.05 mm to 0.25 mm, and even more preferably 0.05 mm to 0.1 mm.
- Sustained release implants according to the present invention may preferably have a double-layer structure, in order to achieve long-term zero-order release.
- the anti-parasitic-containing inner layer and the water-impermeable outer layer may be fabricated separately or simultaneously.
- a circular cylindrical sustained release apparatus with a single centre of gravity in the device cross section may be fabricated, for example, by the following methods:
- the fabrication method is not limited to these examples.
- a water-impermeable outer layer cannot be obtained in a single operation, it will then be necessary, for example, to repeat the outer layer fabrication process until water permeation can be prevented.
- the resulting composition is subsequently cut into suitable lengths. Successive cutting yields a sustained release apparatus according to the present invention having both ends open.
- An anti-parasitic formulation with an open end at one terminal may be fabricated by dipping one terminal of the anti-parasitic formulation into a solution which dissolves the outer-layer material and drying it, or by covering one terminal end of the anti-parasitic formulation with a cap made from the outer-layer material.
- the fabrication may comprise insertion of the inner layer into an outer- layer casing with a closed-end at one terminal, which are separately produced, and also formation of the inner layer in said casing.
- a method for the therapeutic or prophylactic treatment of a parasitic condition in an animal (including a human) requiring such treatment includes administering to the animal a sustained release delivery apparatus including a plurality of sustained release mini-implants or pellets; each implant including the anti-parasitic composition including at least one anti-parasitic agent; and a carrier therefor; and optionally a sustained release support material; and the anti-parasitic composition carried in or on the sustained release support material, when present; each implant being of insufficient size individually to provide a predetermined desired threshold blood level of anti-parasitic active for treatment of a selected disease indication.
- the pharmaceutical payload may be increased by the sustained release delivery apparatus according to the present invention when compared to the prior art.
- Infestations and diseases which were therefore untreatable may now be treated over an extended period of time utilising the apparatus of the present invention.
- treatment with ivermectin in dogs may result in protection levels, e.g against fleas and endoparasites such as worms for up to an entire season (e.g. three to six months), with protection against heartworm for up to 12 months.
- the animals may be treated utilising the sustained release delivery apparatus including an anti-parasitic drug such a ivermectin.
- an anti-parasitic drug such as a ivermectin.
- the method of administration may include subcutaneous or intramuscular injection, intradermal injection, intraperitoneal injection, intranasal insertion or indwelling, intrarectal insertion or indwelling, for example as a suppository or utilising oral administration.
- the animals to be treated may be selected from the group consisting of sheep, cattle, horses, pigs, goats, dogs, cats, ferrets, rodents, including mice and rats, birds, including chicken, geese and turkeys, marsupials, fish, primates and reptiles.
- each mini implant takes the form of a compressed tablet or extruded rod bearing a silicone coating thereover.
- each mini implant is approximately 0.1 to 0.5 times the length and/or diameter of a standard full size tablet.
- the method further includes providing a sustained release kit including a plurality of sustained release mini implants or pellets packaged for delivery in a single treatment; each mini-implant or pellet including an anti-parasitic composition including at least one pharmaceutically active component including an anti-parasitic agent; a carrier therefor; and optionally a sustained release support material; the anti-parasitic composition carried in or on the sustained release support material; each implant being of insufficient size individually to provide a predetermined desired threshold blood level of anti-parasitic agent for treatment of external parasites; and administering the mini implants or pellets in a single treatment.
- the plurality of sustained release mini implants or pellets are provided in a biodegradable sheath and administered as a single cartridge via an injector instrument.
- a mixture of ivermectin and carrier material in proportions specified in Table 1 below was produced.
- the obtained solid was milled and passed through a sieve (212 ⁇ m).
- a portion of a powder thus obtained and SilasticTM Medical Grade ETR Elastomer Q7-4750 Component A and SilasticTM Medical Grade ETR Elastomer Q7-4750 component B were mixed to give a drug dispersion component.
- SilasticTM Medical Grade ETR Elastomer Q7-4750 Component A and SilasticTM Medical Grade ETR Elastomer Q7-4750 Component B were mixed to give a coating layer component.
- the cylindrical preparation 1 is then cut into various lengths as shown in
- Table 1 to provide the sustained release mini-pellets according to the present invention.
- Preparation 1 was subcutaneously administered to dogs, whole blood was collected from the animal via the jugular vein and the dogs periodically challenged with fleas.
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ529857A NZ529857A (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
AU2002344687A AU2002344687B2 (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
CA002451742A CA2451742A1 (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
JP2003510068A JP2005505513A (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic diseases |
BR0210632-9A BR0210632A (en) | 2001-07-04 | 2002-07-01 | Parasitic disease treatment |
US10/482,058 US20040247634A1 (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
EP02742517A EP1411985A4 (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPR6105A AUPR610501A0 (en) | 2001-07-04 | 2001-07-04 | Treatment of parasitic disease |
AUPR6105 | 2001-07-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003004059A1 true WO2003004059A1 (en) | 2003-01-16 |
Family
ID=3830069
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/AU2002/000867 WO2003004059A1 (en) | 2001-07-04 | 2002-07-01 | Treatment of parasitic disease |
Country Status (9)
Country | Link |
---|---|
US (1) | US20040247634A1 (en) |
EP (1) | EP1411985A4 (en) |
JP (1) | JP2005505513A (en) |
CN (1) | CN1522158A (en) |
AU (2) | AUPR610501A0 (en) |
BR (1) | BR0210632A (en) |
CA (1) | CA2451742A1 (en) |
NZ (1) | NZ529857A (en) |
WO (1) | WO2003004059A1 (en) |
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WO2005117934A1 (en) * | 2004-05-31 | 2005-12-15 | Smart Drug Systems Inc | Sustained release composition |
DE102007002872A1 (en) * | 2007-01-15 | 2008-07-17 | Alpha-Biocare Gmbh | Use of avermectin with derivation of epi-methylamino group (emamectin) or epi-acetylamino group (epinomectin) and/or salts, for treatment of fish against parasites, nematode, Acanthocephala or Crustacea |
WO2010106046A1 (en) * | 2009-03-17 | 2010-09-23 | Intervet International B.V. | Macrocyclic lactone drug delivery system |
EP3351546A1 (en) * | 2011-12-02 | 2018-07-25 | Merial, Inc. | Long-acting injectable moxidectin formulations |
EP2598151B1 (en) | 2010-07-30 | 2018-12-26 | CEVA Santé Animale SA | Compositions for treating heartworm infestation |
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EP1835938B1 (en) | 2004-12-27 | 2013-08-07 | Baxter International Inc. | Polymer-von willebrand factor-conjugates |
US7645860B2 (en) | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
CA2647314A1 (en) | 2006-03-31 | 2007-11-08 | Baxter International Inc. | Pegylated factor viii |
CN104984334B (en) * | 2015-06-26 | 2018-06-26 | 金宇保灵生物药品有限公司 | A kind of rabies Attenuate vaccine-praziquantel complexing agent and preparation method and application |
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- 2002-07-01 NZ NZ529857A patent/NZ529857A/en not_active IP Right Cessation
- 2002-07-01 WO PCT/AU2002/000867 patent/WO2003004059A1/en active IP Right Grant
- 2002-07-01 US US10/482,058 patent/US20040247634A1/en not_active Abandoned
- 2002-07-01 AU AU2002344687A patent/AU2002344687B2/en not_active Ceased
- 2002-07-01 CA CA002451742A patent/CA2451742A1/en not_active Abandoned
- 2002-07-01 CN CNA028131193A patent/CN1522158A/en active Pending
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Also Published As
Publication number | Publication date |
---|---|
US20040247634A1 (en) | 2004-12-09 |
EP1411985A4 (en) | 2006-06-07 |
CA2451742A1 (en) | 2003-01-16 |
EP1411985A1 (en) | 2004-04-28 |
AUPR610501A0 (en) | 2001-07-26 |
BR0210632A (en) | 2004-07-27 |
NZ529857A (en) | 2005-01-28 |
AU2002344687B2 (en) | 2008-04-10 |
CN1522158A (en) | 2004-08-18 |
JP2005505513A (en) | 2005-02-24 |
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