WO2017100825A1 - Composition pharmaceutique et ses utilisations - Google Patents

Composition pharmaceutique et ses utilisations Download PDF

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Publication number
WO2017100825A1
WO2017100825A1 PCT/AU2016/050306 AU2016050306W WO2017100825A1 WO 2017100825 A1 WO2017100825 A1 WO 2017100825A1 AU 2016050306 W AU2016050306 W AU 2016050306W WO 2017100825 A1 WO2017100825 A1 WO 2017100825A1
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WIPO (PCT)
Prior art keywords
pharmaceutical composition
animal
wound
therapeutically effective
effective amount
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PCT/AU2016/050306
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English (en)
Inventor
Robert GILLIGAN
Wayne Daley
Original Assignee
Gilligan Robert
Wayne Daley
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority claimed from AU2015905241A external-priority patent/AU2015905241A0/en
Application filed by Gilligan Robert, Wayne Daley filed Critical Gilligan Robert
Publication of WO2017100825A1 publication Critical patent/WO2017100825A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/241—Lead; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions

Definitions

  • This invention relates generally to compositions and methods for treating an infectious ocular disease and/or for treating wounds. More particularly, this invention relates to compositions to therapeutically or prophylactically treat infectious keratoconjunctivitis and promote ocular wound healing resulting from infectious keratoconjunctivitis in domestic livestock.
  • Infectious keratoconjunctivitis is a common ocular disease caused by bacterial infection of domestic livestock and in particular, cattle, sheep and goats. The clinical symptoms of this disease are characterized by blepharospasm, conjunctivitis, lacrimation and varying degrees of corneal opacity, ulceration and wounding. Infectious bovine keratoconjunctivitis (IBK; otherwise known as 'pinkeye') in cattle is usually associated with infection by the bacterium Moraxella bovis, of which there are seven different serogroups of varying degrees of pathogenicity.
  • IBK Infectious bovine keratoconjunctivitis
  • keratoconjunctivitis can be associated with Chlamydia pecorum, Mycoplasma spp (notably M. conjunctivae), Moraxella ovis, Colesiota conjunctivae, Listeria monocytogenes, Acholeplasma oculi, and Thelazia spp.
  • An outbreak of infectious keratoconjunctivitis is potentially debilitating to a domestic livestock herd and can affect up to 80% of a herd.
  • the disease is typically acute and spreads rapidly, with one or both eyes becoming affected.
  • the impaired vision, constant pain and irritation experienced by the animal severely effects the animal's ability to source water and food.
  • the animal may also develop corneal ulceration that may persist without healing during infection and after the infection has resolved.
  • corneal ulceration may persist without healing during infection and after the infection has resolved.
  • damage to the eye can be severe enough for blindness to be permanent.
  • the causative agents of infectious keratoconjunctivitis persist in a herd through asymptomatic carrier animals.
  • Short term treatment for this condition varies from good management practices that reduce or prevent spread of infection (such as isolation of infected animals or controlling numbers of face flies) to systemic or topical administration of antibiotics alone or in combination with corticosteroids, and physical methods such as suturing the eye and application of eye patches that can be glued over the affected eye that offer protection from irritation caused by dust, flies and sunlight. All such methods suffer from one or more disadvantages such as cost, ease of use and effectiveness.
  • Eye patches are also costly and burdensome to apply since the animal's head needs to be firmly restrained to effectively administer the glue evenly and without a break to the perimeter of the eye. The patch then needs to be carefully applied such that no gap or ingress is left for flies to enter. Furthermore, patches are administered to one eye only and are generally single use. A further disadvantage of the protection afforded by an eye patch is the value probably only relates to an individual animal in the early stages of the disease when there is still a chance of saving sight in the eye.
  • the invention provides pharmaceutical compositions for therapeutic uses in the fields of wound healing and/or infectious keratoconjunctivitis that comprise a synergistic combination of agents having an astringent property, a styptic property and/or an anti-infective/antiseptic property.
  • the agents used in the composition also preferably have one or more of the following properties: a sanative, relief of inflammation, breaking down and removing the milky film associated with infectious keratoconjunctivitis and a natural repellent to deflect flies who transfer the infection from animal to animal.
  • the invention relates to infectious bovine keratoconjunctivitis.
  • the invention provides a pharmaceutical composition suitable for administration to an animal, comprising a therapeutically effective amount of a zinc salt, a lead salt of acetic acid, and an alum, together with a pharmaceutically acceptable carrier, diluent or excipient.
  • the pharmaceutical composition of the first aspect is a composition suitable for administration to an animal for preventing and/or treating an infectious keratoconjunctivitis-associated disease, disorder or condition or an infectious keratoconjunctivitis infection.
  • the pharmaceutical composition of the first aspect is a composition suitable for administration to an animal for treating a wound or promoting healing or closure of a wound in an animal.
  • the composition is particularly suited to treating a wound in an animal having or suspected to have an infectious keratoconjunctivitis-associated disease, disorder or condition.
  • the therapeutically effective amount of a lead salt of acetic acid is a concentration of between about 1 gram per litre and about 20 grams per litre. More preferably, the therapeutically effective amount of a lead salt of acetic acid is a concentration of between about 5 grams per litre and 15 grams per litre. Even more preferably, the therapeutically effective amount of a lead salt of acetic acid is a concentration of a lead salt of acetic acid is about 10 grams per litre.
  • the lead salt of acetic acid is selected from lead(II) acetate and lead(IV) acetate, and any combination thereof. More preferably, the lead salt of acetic acid is lead(II) acetate.
  • the therapeutically effective amount of a zinc salt is a concentration between about 1 gram per litre and about 20 grams per litre. More preferably, the therapeutically effective amount of a zinc salt is between about 5 grams per litre and about 15 grams per litre. Even more preferably, the therapeutically effective amount of a zinc salt is a concentration between about 9 grams per litre and about 12 grams per litre. Yet even more preferably, the therapeutically effective amount of a zinc salt is a concentration of about 11 grams per litre.
  • the zinc salt is selected from zinc sulphate, zinc chloride, zinc acetate and zinc oxide, and any combinations thereof. More preferably, the zinc salt is selected from zinc sulphate and zinc oxide. Even more preferably, the zinc salt is zinc sulphate
  • the therapeutically effective amount of an alum is a concentration of between about 1 gram per litre and about 20 grams per litre. More preferably, the therapeutically effective amount of an alum is a concentration of between about 5 grams per litre and about 15 grams per litre. Even more preferably, the therapeutically effective amount of an alum is a concentration of between about 7 grams per litre and about 10 grams per litre. Yet even more preferably, the therapeutically effective amount of an alum is a concentration of about 8.5 grams per litre.
  • the alum is selected from the group consisting of potassium aluminium sulphate, sodium alum (sodium aluminium sulphate), ferric alum (ferric ammonium sulphate) and ammonium alum (ammonium aluminium sulphate), and any combinations thereof.
  • the alum is potassium aluminium sulphate and/or ammonium aluminium sulphate.
  • the pharmaceutical composition of the aforementioned aspect comprises at least one additional pharmaceutically-active agent.
  • the invention provides a method of treating and/or preventing an infectious keratoconjunctivitis-associated disease, disorder or condition, in an animal having or suspected to have an infectious keratoconjunctivitis infection, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby treat and/or prevent the disease, disorder or condition in the animal.
  • the invention provides a method of treating and/or preventing an infectious keratoconjunctivitis infection in an animal, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby treat and/or prevent the infectious keratoconjunctivitis infection in the animal.
  • the invention provides a method of promoting healing or closure of a wound in an animal, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby promote healing or closure of the wound in the animal.
  • Particular embodiments of the fourth aspect relate to a method of promoting healing or closure of a wound in an eye of an animal having or suspected to have an infectious keratoconjunctivitis infection, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby promote healing or closure of the wound in the eye of the animal.
  • the invention provides a method of treating a wound in an animal, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby treat the wound in the animal.
  • Particular embodiments of the fifth aspect related to a method of treating a wound in an eye of an animal having or suspected to have an infectious keratoconjunctivitis infection, the method including the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of the first mentioned aspect, to thereby treat the wound in the eye of the animal.
  • the wound is an internal wound or an external wound.
  • the external wound is a cutaneous (skin) wound.
  • the external wound is an ocular wound, and more preferably, the ocular wound is in an eye of animal having or suspected to have an infectious keratoconjunctivitis infection.
  • the invention provides use of the pharmaceutical composition of the first aspect in the manufacture of a medicament for the treatment of an infectious keratoconjunctivitis infection, and/or an infectious keratoconjunctivitis-associated disease, disorder or condition in an animal and/or a wound.
  • administration is topical administration and more preferably, topical administration to an eye of an animal.
  • the animal is a mammal.
  • the mammal is a veterinary subject and more preferably, a livestock animal.
  • the livestock animal is selected from a bovine species, an ovine species, a capra species, a porcine species and an equine species.
  • the livestock animal is a bovine species.
  • the livestock animal is an ovine species.
  • the livestock animal is a capra species.
  • the livestock animal is a domestic livestock animal.
  • the pharmaceutical composition is suitable for delivery as an aerosol, a swab, a spray or a mist. More preferably, the sprayable composition is a solution.
  • the infectious keratoconjunctivitis-associated disease, disorder or condition is an infectious bovine keratoconjunctivitis-associated disease, disorder or condition.
  • the infectious keratoconjunctivitis infection is an infectious bovine keratoconjunctivitis.
  • the present invention is predicated, at least in part, on development of a pharmaceutical composition that is surprisingly able to (i) treat, promote or improve wound healing; and/or (ii) treat or prevent an infectious keratoconjunctivitis in an animal; and/or (ii) minimise spread of an infectious keratoconjunctivitis.
  • Preferred embodiments of the pharmaceutical compositions and methods of the invention relate to infectious bovine keratoconj uncti viti s .
  • Administration of the pharmaceutical composition of the invention provides an attractive alternative to antibiotics for the treatment of an infectious keratoconjunctivitis infection, especially in the case of multidrug-resistant IBK infection.
  • Antibiotic use also decreases the opportunity for development of bacterial resistance in treated animals (and human populations consuming cattle by-products), and avoids local and systemic side effects associated with antibiotic administration.
  • compositions and therapeutic methods of the invention also have particular utility in treating, healing and/or closing wounds generally, and in particular, wounds present in an eye of an animal with, or suspected to have, an infectious keratoconjunctivitis infection.
  • the invention is broadly directed to pharmaceutical compositions and therapeutic methods utilising said pharmaceutical compositions that confer particular benefits of decreasing, arresting or otherwise eliminating the incidence or spread of an infectious keratoconjunctivitis from one animal to another, and/or treating or preventing an infectious keratoconjunctivitis-associated disease, disorder or condition in a subject in need thereof.
  • the infectious keratoconjunctivitis is infectious bovine keratoconjunctivitis or alternatively, is preferably infectious keratoconjunctivitis of an ovine species, a capra species, a porcine species or an equine species.
  • the invention has utility as a broad-spectrum wound healing formulation by treating or promoting healing or closure of a wound.
  • the wound is in an animal with an infectious keratoconjunctivitis and preferably, an ocular wound in an animal with an infectious keratoconjunctivitis.
  • the invention provides a pharmaceutical composition (and methods of use of said pharmaceutical composition) with a synergistic combination of agents that reduces an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection in a subject. It is preferable that in conjunction to a reduction of infectious keratoconjunctivitis-associated disease, disorder or condition, the incidence of an infectious keratoconjunctivitis infection is decreased amongst subjects.
  • the conventional treatment time for infectious bovine keratoconjunctivitis of about 5-10 days may be reduced to about 3-5 days with the pharmaceutical compositions and methods described herein, with a concomitant reduction in or complete elimination of transmission of an infectious keratoconjunctivitis infection/s in a herd.
  • a further benefit of the particular combination of active agents is their long lasting effect, which is beneficial for animals exposed to the environment.
  • reduction as in reducing an infectious keratoconjunctivitis-associated disease, disorder or condition in a subject, it is meant a lessening or shortening of a symptom, aspect or characteristic associated with an infectious keratoconjunctivitis infection, or an infectious keratoconjunctivitis-associated disease, disorder or condition, or the length of time a subject experiences a symptom, aspect or characteristic associated with an infectious keratoconjunctivitis infection, or an infectious keratoconjunctivitis-associated disease, disorder or condition and more preferably, infectious bovine keratoconjunctivitis.
  • a reduction may correspond to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and up to 90% (and all integers in between) shortening or lessening or otherwise improvement of one or a plurality of symptoms, aspects or characteristics associated with an infectious keratoconjunctivitis infection, or an infectious keratoconjunctivitis-associated disease, disorder or condition, or in the length of time a subject experiences one or a plurality of symptoms, aspects or characteristics associated with an infectious keratoconjunctivitis infection, or an infectious keratoconjunctivitis-associated disease, disorder or condition, typically measured relative to conventional therapeutic treatments or when no therapeutic intervention has occurred.
  • a reduction can include a complete arrest of a symptom, aspect or characteristic associated with an infectious keratoconjunctivitis infection or an infectious keratoconjunctivitis-associated disease, disorder or condition.
  • Reduction in a subject can be determined using any methods or standards known to a person of skill in the art, including both quantitative or qualitative methods or standards.
  • an infectious keratoconjunctivitis infection is decreased
  • the decrease can be partial or absolute ⁇ i.e., no subjects infected).
  • the decrease is absolute with complete elimination of incidence of an infectious keratoconjunctivitis infection amongst subjects.
  • the decrease can be 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and up to 90% (and all integers in between) relative to untreated subjects or alternatively, subjects treated with conventional therapies for example.
  • a decrease in incidence of an infectious keratoconjunctivitis infection can be determined using any methods or standards known to a person of skill in the art, including both quantitative or qualitative methods or standards.
  • the infectious keratoconjunctivitis infection is an infectious bovine keratoconjunctivitis infection.
  • the invention provides a pharmaceutical composition suitable for administration to an animal, comprising a therapeutically effective amount of a zinc salt, a lead salt of acetic acid and an alum, together with a pharmaceutically acceptable carrier, diluent or excipient.
  • terapéuticaally effective amounf describes a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. For example, in general embodiments, this can be the amount of a specified agent or composition comprising said specified agent necessary to treat or prevent an infectious keratoconjunctivitis- associated disease, disorder or condition, or an infectious keratoconjunctivitis infection. In some embodiments, a "therapeutically effective amounf is sufficient to treat a wound, or promote wound healing or wound closure in an animal.
  • a "therapeutically effective amounf is sufficient to treat a wound, or promote healing or closure of a wound in an animal with or suspected to have an infectious keratoconjunctivitis-associated disease, disorder or condition (and in particular an ocular wound, although without limitation thereto).
  • a "therapeutically effective amounf is an amount sufficient to achieve a desired biological effect, for example an amount that is effective to reduce, decrease, minimise and/or arrest incidence or spread of an infectious keratoconjunctivitis infection from one animal to another.
  • a therapeutically effective amount of an agent is an amount sufficient to induce the desired result without causing a substantial adverse effect (such as a cytotoxic effect or allergic effect, but without limitation thereto) in a subject.
  • the therapeutically effective amount will vary depending upon the health and physical condition of the subject and the taxonomic group of individual to be treated, the formulation of the composition, the assessment of the medical situation, manner of administration, the severity of the disease, disorder and/or condition being treated, and other relevant factors.
  • Administration of a therapeutically effective amount of an active agent to a subject may either in a single dose or as part of a series (for example daily) or slow release system, during a course of treatment. However, the frequency of administration is dependent on the preparation applied, the subject being treated, the severity of disease, disorder and/or condition or infection and the manner of administration of the therapy or composition.
  • the term "agenf as used herein includes a compound that induces a desired pharmacological and/or physiological effect.
  • the term also encompasses pharmaceutically acceptable and pharmacologically active ingredients of those compounds specifically mentioned herein including but not limited to salts, esters, amides, prodrugs, active metabolites, analogues and the like.
  • salts esters, amides, prodrugs, active metabolites, analogues and the like.
  • pharmaceutically-acceptable carrier diluent or excipienf
  • a pharmaceutical vehicle comprised of a material that is not biologically or otherwise undesirable, i.e., the material may be administered to a subject along with the selected active agent without causing any or a substantial adverse reaction.
  • Such pharmaceutical vehicles may include excipients such as water, saline, dextrose, glycerol, propylene glycol, ethanol, and the like, or combinations thereof and other additives such as diluents, detergents, colouring agents, saline, wetting or emulsifying agents, pH buffering agents, preservatives, and the like or combinations thereof.
  • the composition of the present invention may contain any such additional ingredients so as to provide the composition in a form suitable for administration.
  • the "pharmaceutically-acceptable carrier, diluent or excipienf is suitable for veterinary purposes.
  • infectious keratoconjunctivitis-associated disease, disorder or condition any clinical pathology resulting from an infection by a causative infectious agent (known or potential) associated with an infectious keratoconjunctivitis and includes blepharospasm, conjunctivitis (with or without varying degrees of keratitis), lacrimation, inflammation, epiphora, ocular discharge, concurrent polyarthritis, varying degrees of corneal opacity, ocular wounding, corneal ulceration, cornel lesions and corneal wounding, although without limitation thereto.
  • An infectious keratoconjunctivitis-associated disease, disorder or condition can be determined using any methods or standards known to an ordinarily skilled artisan, including both quantitative or qualitative methods or standards.
  • Infectious keratoconjunctivitis can be associated with any one or a plurality of different causative agents depending on, for example, the animal species.
  • Causative infectious agents that may be associated with an infectious keratoconjunctivitis in bovine species include the bacterium Moraxella bovis, of which there are seven different serogroups of varying degrees of pathogenicity.
  • Rickettsiae and a virus may also be associated with infectious bovine keratoconjunctivitis as well as Moraxella bovoculi.
  • Other preferred embodiments relate to infectious keratoconjunctivitis of other species as described herein.
  • infectious keratoconjunctivitis can be associated with Chlamydia pecorum, Mycoplasma spp (notably M. conjunctivae), Moraxella ovis, Colesiota conjunctivae, Listeria monocytogenes, Acholeplasma oculi, and Thelazia spp, although without limitation thereto.
  • an "infectious keratoconjunctivitis infection" is an infection caused by, associated with or a result of a known (as described herein) or putative causative infectious agent.
  • the infectious keratoconjunctivitis is an infectious bovine keratoconjunctivitis associated with a Moraxella bovis or caused by a Moraxella bovis.
  • a subject may or may not display symptoms of an infectious keratoconjunctivitis infection.
  • An infectious keratoconjunctivitis infection can be determined using any methods or standards known to an ordinarily skilled artisan, including both quantitative or qualitative methods or standards.
  • the pharmaceutical compositions of the invention comprise a therapeutically- effective amount of a lead salt of acetic acid and more preferably, the lead salt of acetic acid is lead(II) acetate.
  • Lead(II) acetate is colloquially known as sugar of lead, salt of Saturn, lead sugar, Goulard's powder and lead diacetate.
  • Lead(II) acetate is represented by the chemical formula Pb(CH 3 COO) 2 and may be hydrated (e.g. Pb(C 2 H 3 0 2 ) 2 3H 2 0).
  • Pb(CH 3 COO) 2 may be hydrated (e.g. Pb(C 2 H 3 0 2 ) 2 3H 2 0).
  • lead(II) acetate acts as a styptic to contract organic tissues and stop or reduce haemorrhage and bleeding.
  • a further potentially useful therapeutic property of lead(II) acetate is an astringent with sedative properties that may act in the relief, reduction or alleviation of inflammation when brought directly into contact with an affected surface.
  • the lead salt of acetic acid is synthesised from lead and acetic acid by methods as are known in the art.
  • the therapeutically effective amount of a lead salt of acetic acid is a concentration of between about 1 and about 20 g/L, preferably between about 5 and about 15g/L or more preferably about lOg/L.
  • compositions of the invention also comprise a therapeutically effective amount of an alum.
  • alum as used herein and as understood in the art denotes a class of chemical compounds typically having the formula ;4M(S0 4 ) 2 .xH 2 0 where A is a monovalent cation such as potassium, sodium or ammonium, and Mis a trivalent metal ion such as aluminium and x is typically 12, although the extent of hydration may vary as will be understood by a person of skill in the art.
  • the dodecahydrate form of potassium aluminium sulphate (KA1(S0 4 ) 2 ) is represented by the chemical formula KA1(S0 4 ) 2 12H 2 0.
  • the dodecahydrate form of ammonium aluminium sulphate ( H 4 A1(S0 4 ) 2 ) has the chemical formula H 4 A1(S0 4 ) 2 12H 2 0.
  • H 4 A1(S0 4 ) 2 has the chemical formula H 4 A1(S0 4 ) 2 12H 2 0.
  • a person of skill in the art will readily appreciate which form of an alum is more suited for formulation of the pharmaceutical composition administered by a particular route.
  • Alum has several properties useful for the invention including, but not limited to, antiseptic and astringent properties and an insect repellent. Accordingly, aluminium ammonium sulphate is an effective repellent for flies, which are main vectors for infectious keratoconjunctivitis.
  • Potassium aluminium sulphate is a highly astringent agent that prevents infectious agents from entering tissues, skin and the like.
  • Alum has antiseptic properties and prevents the growth of bacteria.
  • the alum is selected from the group consisting of potassium aluminium sulphate, sodium alum (sodium aluminium sulphate), ferric alum (ferric ammonium sulphate) and ammonium alum (ammonium aluminium sulphate), and combinations thereof.
  • the alum is selected from potassium aluminium sulphate and ammonium aluminium sulphate, and any combinations thereof.
  • the alum is ammonium aluminium sulphate.
  • the alum is potassium aluminium sulphate.
  • the alum can either be naturally occurring or may be synthesised using methods as are well known in the art. It will be appreciated by a person of skill in the art that naturally occurring alum may require purification for use in the compositions and methods of the invention.
  • the therapeutically effective amount of an alum is at a concentration of between about 1-20 g/L, preferably about 5-15 g/L and more preferably about 7-10 g/L.
  • the concentration of the alum is about 8.5 g/L.
  • the term “purified” refers to material that is substantially free of other contaminating material from the source from which the material is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. “Substantially free” means that a preparation of a material is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% pure. In a preferred embodiment, the preparation of a material has less than about 40%, 30%, 20%, 10% and more suitably 5%, 4%, 3%), 2%), 1%) (by dry weight), of non-material components or of chemical precursors or of non- material chemicals (also referred to herein as a "contaminating components").
  • the pharmaceutical compositions of the invention include a therapeutically effective amount of a zinc salt.
  • the zinc salt is an agent that supports and accelerates a healthy immune system as well as playing a role in protecting against infection by way of assisting with vitamin A absorption.
  • the zinc salt may have further properties and/or activities that make it useful for inclusion in the pharmaceutical composition of the invention, for example an antiseptic astringent activity, although limitation thereto.
  • the zinc salt is an inorganic zinc salt or an organic zinc salt.
  • the zinc salt is an inorganic zinc salt. It will be appreciated that the zinc salt may have one or more hydrated forms and the extent of the hydrated form may vary.
  • zinc sulphate has three (3) hydrate forms in addition to the anhydrous form: a monohydrate, a hexahydrate and a heptahydrate.
  • a person of skill in the art will readily appreciate which form of a zinc salt is more suited for formulation of the pharmaceutical composition administered by a particular route.
  • an anhydrous form may be more suited for formulation into a systemically administered composition.
  • the zinc salts contemplated by the invention are suitably soluble and preferably, soluble in water.
  • the zinc salt is selected from zinc sulphate, zinc chloride, zinc acetate and zinc oxide, and combinations thereof. More preferably, the zinc salt is selected from zinc oxide and zinc sulphate. Even more preferably, the zinc salt is zinc sulphate.
  • the therapeutically effective amount of a zinc salt is at a concentration of between about 1-20 g/L, preferably about 5-15 g/L and more preferably about 9-12 g/L.
  • the zinc salt is at a concentration of about 11 g/L.
  • concentrations recited herein may in certain embodiments refer to a final concentration of an agent that is present in a composition (e.g., a final concentration of a powder that has dissolved in a solution) or in alternative embodiments, may refer to the amount of an agent that is added to reach a desired concentration in a composition (e.g., x grams of an agent added to one litre of an aqueous solution to reach x g per litre). It will be appreciated that suitably these two values may be substantially the same but it is contemplated that these values may vary (e.g., by 10, 20 or up to 30%, although without limitation thereto).
  • salts used herein are suitable for inclusion into a pharmaceutical composition of the invention.
  • a "pharmacologically acceptable” salt, ester, amide, prodrug or derivative of a compound as provided herein is a salt, ester, amide, prodrug or derivative that this not biologically or otherwise undesirable.
  • “about” is meant a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 % to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.
  • the invention provides therapeutic methods that include the step of administering a pharmaceutical composition as described herein, to a subject in need thereof.
  • patient refers to any animal, particularly a vertebrate animal, and even more particularly a mammalian subject, and even more preferably a veterinary subject, for whom therapy or prophylaxis is desired.
  • a vertebrate animal refers to any animal, particularly a vertebrate animal, and even more particularly a mammalian subject, and even more preferably a veterinary subject, for whom therapy or prophylaxis is desired.
  • the invention is particularly suited to domestic livestock animals and more preferably, a bovine species, an ovine species, a caprine species, a porcine species and an equine species.
  • Types of animals that may benefit from the practice of the invention include any that are susceptible to infection by a causative agent of infectious keratoconjunctivitis.
  • exemplary animals include but are not limited to: members of the biological subfamily Bovinae which includes medium- to large-sized ungulates such as domestic dairy and beef cattle, bison, African buffalo, the water buffalo, the yak, and the four-horned and spiral-horned antelopes, etc.
  • Representative bovine species include Bos frontalis, Bos gaurus, Bos grunniens, Bos mutus, Bos indicus, Bos javanicus, Bos sauveli and Bos taurus (cattle).
  • the therapy and compositions of the invention are particularly suited to Bos taurus.
  • the invention also relates to members of the biological subfamily Caprinae, genus Copra Representative goat species include Copra aegagrus (goat) and more particularly, Copra aegagrus hircus (domestic goat). Also included are members of the biological subfamily Caprinae, genus Ovis (sheep). Illustrative sheep species includes Ovis aries (domestic sheep). The invention also relates to members of the porcine family.
  • the animals may be so-called livestock raised in an agricultural setting for the production of dairy products or meat; or may be raised to perform work; or may be in another setting, e.g., in a zoo, animal reserve, etc., or raised for some other reason, e.g., as pets, show animals, for breeding purposes, etc.
  • compositions and methods of the present invention are suitable for administration to an individual who has been diagnosed with an infectious keratoconjunctivitis- associated disease, disorder, or condition, or an infectious keratoconjunctivitis infection, who is suspected of having an infectious keratoconjunctivitis-associated disease, disorder, infection or condition, or an infectious keratoconjunctivitis infection, who is known to be susceptible and who is considered likely to develop an infectious keratoconjunctivitis-associated disease, disorder, or condition, or an infectious keratoconjunctivitis infection, or who is considered likely to develop a recurrence of a previously treated infectious keratoconjunctivitis-associated disease, disorder, or condition, or an infectious keratoconjunctivitis infection.
  • the invention provides a method of treating and/or preventing an infectious keratoconjunctivitis-associated disease, disorder or condition, in an animal having or suspected to have an infectious keratoconjunctivitis infection wherein the method includes the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition described herein, to thereby treat and/or prevent the disease, disorder or condition in the animal.
  • treating refers to a therapeutic intervention that at least partly ameliorates, eliminates or reduces a symptom or pathological sign of an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection, or a wound, after it has begun to develop.
  • These terms include: (a) inhibiting the disease or condition, i.e., arresting its development; or (b) relieving the disease, disorder or condition, i.e., causing regression of the disease, disorder or condition.
  • the term “ameliorating” with reference to the invention refers to any observable beneficial effect of the treatment.
  • compositions and methods of the invention are also suitable for use in preventive measures.
  • preventive measures for example, in case of an outbreak of infection, administration of the composition of the invention to non-affected animals, especially those which are in close contact with those showing clinical signs of disease, could prevent the spread of the infection.
  • prophylactic treatment might be undertaken in animals considered to be vulnerable to infection and/or in whom infection could have grave consequences, e.g., young/baby animals, show animals, pregnant females, prize animals, breeding stock, etc., whether or not an outbreak is known to have occurred.
  • preventing refers to a course of action initiated prior to infection by, or exposure to, a causative agent (or a potential causative agent) of an infectious keratoconjunctivitis and/or before the onset of a symptom or pathological sign of an infectious keratoconjunctivitis-associated disease, disorder or condition, or infection, so as to prevent infection and/or reduce the symptom or pathological sign. It is to be understood that such preventing need not be absolute to be beneficial to a subject.
  • a “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection, or exhibits only early signs for the purpose of decreasing the risk of developing a symptom or pathological sign of an infectious keratoconjunctivitis-associated disease, disorder or condition.
  • prophylactic treatment includes treatment of asymptomatic carriers of an infectious keratoconjunctivitis.
  • prevention includes cessation or reduction of the incidence, spread or transmission of an infectious keratoconjunctivitis-associated disease, disorder or condition, or infection, from one animal to another.
  • the pharmaceutical compositions disclosed herein have surprising utility as a therapeutic wound healing composition. Therefore, other particular aspects of the invention relate to therapeutic methods of promoting healing or closure of a wound, or treating a wound.
  • the pharmaceutical compositions are capable of treating a wound in an animal upon administration to the subject.
  • Particular preferred embodiments relate to wound healing in an animal having or suspected to have an infectious keratoconjunctivitis infection.
  • wound is meant any breach, injury, loss, erosion or deterioration to a surface, an epithelium or a membrane that compromises or potentially compromises the integrity of the surface, an epithelium or a membrane. It can be partial or total.
  • wound is used herein interchangeably with “ulcer” or “lesion”.
  • the wound may be acute or chronic (otherwise known as non-healing).
  • a wound may be a result of a physical intervention such trauma, violence, a thermal injury such as burning, accident, or surgery.
  • a wound may be a result of a disease such as an infection (such as infectious keratoconjunctivitis, although without limitation thereto) or diseases such as to diabetes; skin diseases such as psoriasis and dermatitis; diseases of internal organs, including but not limited to, diseases of the liver, kidneys or lungs; cancer; virus or any other condition, although without limitation thereto.
  • a wound may occur due to laceration or breaking of a membrane (such as the skin in the form of cutaneous wounds) and usually damage to underlying tissues.
  • a wound may occur in a topical location (otherwise referred to as 'external wound') or internally.
  • a topical wound may be present anywhere on an external surface of a subject.
  • a topical external wound may occur on skin (a cutaneous wound) or on the topical surface of an eye (an ocular wound).
  • wound healing is meant to include augment, increase, improve, induce, accelerate, facilitate or initiate wound healing or wound closure, and/or increase the rate of wound healing or wound closure, relative to an untreated subject.
  • wound healing is considered to be promoted, for example, if the time of healing a wound treated with a therapeutic agent or a pharmaceutical composition compared to a wound not treated with the agent or the composition is reduced by about 10%, about 20%, about 25%, about 30%, about 40%), about 50%, about 75%.
  • the degree of scar formation can be used to ascertain whether wound healing is promoted.
  • wound healing refers to a regenerative process with the induction of a healing program comprising wound closure and the processes involved in wound closure.
  • wound healing encompasses but is not limited to the processes of granulation, neovascularization, fibroblast, endothelial and epithelial cell migration, extracellular matrix deposition, re-epithelialization, and remodelling.
  • wound closure refers to the healing of a wound wherein sides of the wound are re-joined to form a continuous barrier ⁇ e.g., intact skin).
  • the invention can be generally applied to a wide variety of wounds.
  • the wound is acute.
  • the wound is chronic.
  • Types of wounds that may be treated are internal and external wounds.
  • such wounds may require promotion of cell migration and/or proliferation for healing or closure to occur.
  • a wound is an external wound such as cuts, tears, lacerations, punctures, surgical wounds, a burn, a scar, a wound caused by a skin disease such as psoriasis, an inflammatory skin disease, an eczema and dermatitis (e.g., splits, dry skin, and roughness of the skin).
  • the external wound is a cutaneous wound or is an ocular wound, caused by a disease or a physical injury, although without limitation thereto.
  • the animal that has or is suspected to have an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection.
  • the wound is a cutaneous wound in an animal that has or is suspected to have an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection.
  • the wound is in an eye of an animal having or suspected to have an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection.
  • the invention encompasses administration to one or both eyes of said animal, as is necessary.
  • administration of the pharmaceutical composition of the invention in methods described herein is to a diseased eye of an animal with an infectious keratoconjunctivitis.
  • the wound is either a direct or indirect result of an infectious keratoconjunctivitis-associated disease, disorder or condition, or an infectious keratoconjunctivitis infection.
  • a cutaneous wound will typically require topical administration with a suitable pharmaceutical composition, be it a solution, a gel, a dressing impregnated with the pharmaceutical composition.
  • a suitable pharmaceutical composition be it a solution, a gel, a dressing impregnated with the pharmaceutical composition.
  • local injection to a cutaneous wound may be a suitable route of administration. Suitable routes of administration are described herein.
  • administering or “administration” is meant the introduction of a composition disclosed herein into a subject by a particular, chosen route.
  • any safe route of administration may be employed for providing a patient with the composition of the invention.
  • oral, rectal, topical, parenteral, sublingual, buccal, intravenous, intra-articular, intra-muscular, intra-dermal, subcutaneous, inhalational, intraocular ⁇ e.g., topical or injectable intraocular administration), intraperitoneal, mucosal administration ⁇ e.g., intranasal and oral routes), transdermal and the like may be employed.
  • the prophylactic or therapeutic compositions may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, ocular mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other pharmaceutically-active agents. Administration can be systemic or local. In particularly preferred embodiments, administration is contacting the composition of the invention to a surface in need thereof such as a wound, a wounded skin, an eye, a diseased eye or a wound in an eye of an animal having, or suspected to have, an infectious keratoconjunctivitis infection.
  • a surface in need thereof such as a wound, a wounded skin, an eye, a diseased eye or a wound in an eye of an animal having, or suspected to have, an infectious keratoconjunctivitis infection.
  • compositions of the invention may be administered by any of the many suitable means which are known to those of skill in the art, generally administration will be topical, including administration to any accessible surface that is wounded, diseased, afflicted or infected or liable to infection, e.g. intraocular, intranasal, or to the skin, etc.
  • prophylactic or therapeutic compositions of the invention are administered by intraocular or intranasal administration and more preferably, the mode of administration is intraocular.
  • the mode of administration is topical intraocular.
  • the pharmaceutical compositions may be administered to the eye by means of conventional topical ophthalmic formulations, such as solutions, suspensions or gels.
  • the preferred formulation for topical ophthalmic administration of the pharmaceutical composition is a solution.
  • the solution is administered as an aerosol, eye drops, spray or mist.
  • compositions such as tablets, pills, powders (e.g., lyophilized preparations) and the like are also contemplated, especially solid forms suitable for solution in, or suspension in, liquids prior to administration.
  • the preparation may also be emulsified or aerosolized.
  • the preparation of such compositions is generally known to those of skill in the art.
  • the invention encompasses an ophthalmic formulation (using eye drops, sprays, mists, aerosols etc.) for the treatment of animals infected with, or suspected of being infected with, an infectious keratoconjunctivitis. It is contemplated that this formulation releases a therapeutically effective amount concentration on preferably the eye surface for up to 24 hours or longer.
  • affected animals may optionally be physically restrained in a chute or other suitable stanchion device.
  • the ingredients of the compositions of the invention are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachet indicating the quantity of active agent.
  • a sprayable composition it can be dispensed in a suitably designed spray bottle.
  • the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.
  • an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.
  • the prophylactic or therapeutic compositions and agents of the invention may be desirable to administer locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion, a swab, by injection, or by means of an implant, said implant being of a porous or non-porous material, including membranes and matrices, such as sialastic membranes, polymers, fibrous matrices (e.g., TissuelTM), or collagen matrices.
  • the prophylactic or therapeutic agent can be delivered in a controlled release or sustained release system.
  • polymers used in sustained release formulations include, but are not limited to, poly(2-hydroxy ethyl methacrylate), poly(methyl methacrylate), poly(acrylic acid), poly(ethylene-co-vinyl acetate), poly(methacrylic acid), polyglycolides (PLG), polyanhydrides, poly(N- vinyl pyrrolidone), poly(vinyl alcohol), polyacrylamide, poly(ethylene glycol), polylactides (PLA), poly(lactide- co-glycolides) (PLGA), and polyorthoesters.
  • a pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration as will be known to a person of skill in the art. If the compositions of the invention are to be administered topically, the compositions can be formulated in the form of an ointment, cream, transdermal patch, lotion, gel, shampoo, spray, aerosol, solution, sprayable solution, swab, mist, emulsion, or other form well-known to one of skill in the art.
  • viscous to semi-solid or solid forms comprising a carrier or one or more excipients compatible with topical application and having a dynamic viscosity preferably greater than water are typically employed.
  • Suitable formulations include, without limitation, solutions, suspensions, emulsions, creams, ointments, powders, liniments, salves, and the like, which are, if desired, sterilized or mixed with auxiliary agents (e.g., preservatives, stabilizers, wetting agents, buffers, or salts) for influencing various properties, such as, for example, osmotic pressure.
  • auxiliary agents e.g., preservatives, stabilizers, wetting agents, buffers, or salts
  • suitable topical dosage forms include sprayable aerosol preparations wherein the active ingredient, preferably in combination with a solid or liquid inert carrier, is packaged in a mixture with a pressurized volatile (e.g., a gaseous propellant, such as fireon) or in a squeeze bottle.
  • Moisturizers or humectants can also be added to pharmaceutical compositions and dosage forms if desired. Examples of such additional ingredients are well known in the art.
  • routes of administration include, but are not limited to, parenteral, e.g., intravenous, intradermal, subcutaneous, oral, intranasal (e.g., inhalation), transdermal (e.g., topical), transmucosal, and rectal administration.
  • the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous, subcutaneous, intramuscular, oral, intranasal, or topical administration to human beings.
  • compositions for intravenous administration are solutions in sterile isotonic aqueous buffer.
  • the composition may also include a solubilizing agent and a local anaesthetic such as lignocaine to ease pain at the site of the injection.
  • the methods of the invention comprise intranasal administration of a composition
  • the composition can be formulated in an aerosol form, spray, mist or in the form of drops.
  • prophylactic or therapeutic agents for use according to the present invention can be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas).
  • a suitable propellant e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas.
  • the dosage unit may be determined by providing a valve to deliver a metered amount.
  • Capsules and cartridges for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
  • a powder mix of the compound and a suitable powder base such as lactose or starch.
  • suitable powder base such as lactose or starch.
  • Tablets or capsules can be prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose, or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate).
  • binding agents e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropyl methylcellulose
  • fillers e.g., lactose, microcrystalline cellulose, or calcium hydrogen phosphate
  • lubricants e.g., magnesium stearate, talc, or silica
  • disintegrants e.g., potato starch or sodium starch
  • Liquid preparations for oral administration may take the form of, but not limited to, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives, or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid).
  • the preparations may also contain buffer salts, flavouring, colouring, and sweetening agents as appropriate.
  • Preparations for oral administration may be suitably formulated for slow release, controlled release, or sustained release of a prophylactic or therapeutic agent(s).
  • the methods of the invention may comprise administration of compositions formulated for parenteral administration by injection (e.g., by bolus injection or continuous infusion).
  • Formulations for injection may be presented in unit dosage form (e.g., in ampoules or in multi-dose containers) with an added preservative.
  • the compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
  • the active ingredient may be in powder form for constitution with a suitable vehicle (e.g., sterile pyrogen- free water) before use.
  • compositions formulated as depot preparations may additionally comprise administration of compositions formulated as depot preparations.
  • long acting formulations may be administered by implantation (e.g., subcutaneously or intramuscularly) or by intramuscular injection.
  • the compositions may be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives (e.g., as a sparingly soluble salt).
  • compositions formulated as neutral or salt forms include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.
  • compositions are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachet indicating the quantity of active agent.
  • a hermetically sealed container such as an ampoule or sachet indicating the quantity of active agent.
  • composition can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.
  • an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.
  • the invention also provides that one or more of the prophylactic or therapeutic agents, or pharmaceutical compositions of the invention is/are packaged in a hermetically sealed container such as an ampoule or sachet indicating the quantity of the agent.
  • a hermetically sealed container such as an ampoule or sachet indicating the quantity of the agent.
  • one or more of the prophylactic or therapeutic agents, or pharmaceutical compositions of the invention is/are supplied as a dry sterilized lyophilized powder or water free concentrate in a hermetically sealed container and can be reconstituted (e.g., with water or saline) to the appropriate concentration for administration to a subject.
  • the present invention encompasses co-administration of the pharmaceutical composition of the invention in conjunction with at least one additional pharmaceutically-active agent.
  • the pharmaceutical composition of the present invention comprises at least one additional pharmaceutically-active agent.
  • additional pharmaceutically-active agent include an anti-infective agent (such as an anti-protozoal or an anti -viral), a stabiliser, a preservative, an antioxidant, an anti-inflammatory agent (such as a corticosteroid), a vitamin (or analogue thereof), an anti-allergic agent, a corneal moisture restorer, although without limitation thereto.
  • the present invention also contemplates combination therapies, which employ a pharmaceutical composition as described herein and concurrent administration of an ancillary therapy (e.g., medical treatment), non-limiting examples of which include radiotherapy, surgery, chemotherapy and immunotherapy, and the like.
  • an ancillary therapy e.g., medical treatment
  • co-administering refers to the administration of a single composition containing two or more active agents, or the administration of each active as separate compositions and/or delivered by separate routes either contemporaneously or simultaneously or sequentially within a short enough period of time that the effective result is equivalent to that obtained when all such actives are administered as a single composition.
  • simultaneous is meant that the active agents are administered at substantially the same time, and desirably together in the same formulation.
  • temporary it is meant that the active agents are administered closely in time, e.g., one agent is administered within from about one minute to within about one day before or after another. Any contemporaneous time is useful.
  • the agents when not administered simultaneously, the agents will be administered within about one minute to within about eight hours and suitably within less than about one to about four hours. When administered contemporaneously, the agents are suitably administered at the same site on the subject.
  • the term "same site” includes the exact location, but can be within about 0.5 to about 15 centimetres, preferably from within about 0.5 to about 5 centimetres.
  • “separately” as used herein means that the agents are administered at an interval, for example at an interval of about a day to several weeks or months.
  • the active agents may be administered in either order.
  • the term “sequentially” as used herein means that the agents are administered in sequence, for example at an interval or intervals of minutes, hours, days or weeks. If appropriate the active agents may be administered in a regular repeating cycle.
  • IBK is most apparent in herds during summer and more so during dry periods. In particular, it is during drought periods that less nutrients in the grasses (thus lowering the immune system), more thistles and course grasses damage the eye and plays host to IBK infection carried by dust and flies. The movement of stock from paddock to yards for treatment is not always practical and only adds to the potential spread of the infection, particularly with drought effected stock. Returning drought effected (most prone to contracting IBK) stock to the stock yards is rarely an option. Over a 3.5-year period, a herd of 900 drought effected cattle owned by an inventor of the invention were treated for IBK with various conventional infectious keratoconjunctivitis therapies and the composition of the invention.
  • a particularly useful formulation had the following composition in 500mL of filtered water: 5 grams of lead (II) acetate, 5.5 grams of zinc sulphate powder and 4.2 grams of alum (potassium aluminium phosphate and ammonium aluminium sulphate).
  • Administration of the composition comprised spraying the composition via a soft wide mist to saturate the entire surface of the animal's eye.
  • the inventors found a surprising and substantial improvement in the healing of IBK in affected / diseased animals as follows: (i) able to treat both eyes, which cannot be achieved with antibiotic cream and patches; (ii) very easy to administer by way of a spray mist to both eyes, which proved to be a very low stress level experience for the animal; and (iii) the relatively low cost of the formulation permitted treatment of every eye of every animal which, at least in part, assisted with reducing or halting incidence or reinfection rates in the herd and treating asymptomatic carriers (which are the primary reason for elevated incidence or reinfection rates in an IBK-affected herd). Treatment using the formulation resulted in a marked improvement in treatment time.
  • the treatment time using the formulation of the invention reduced to about 3 days compared to the normal 5-10 days with the conventional therapies detailed above.
  • the inventor/s recognised the speed of recovery of the animals treated with the composition of the invention.
  • the animals had decreased stress and pain compared to the conventional treatments.
  • the composition of the invention was tested as a wound healing agent and in particular, a broad-spectrum wound healing agent.
  • the wounds tested varied and were typical of wounds animals experience within any animal grazing operation, such as animals partially blinded by an IBK infection that were wounded by walking into and becoming entangled in fencing material, lacerations caused in mustering and yarding of stock, wild dog attacks and the wound caused by the castration of the male portion of the herd.
  • the inventor/s recognised the additional therapeutic benefit that use of the invention would bring to the grazier in their day to day operation.
  • the invention was used on all size wounds and the inventor/s found the same quick healing characteristics that were experienced with the invention for the treatment of infectious bovine keratoconjunctivitis as described in Example 1.
  • the composition is presented in a 500 ml plastic spray bottle with finger grips similar plastic container used with most household cleaning products.
  • the composition is administered to each and every eye of the herd or group of animals to be treated with the mist spray composition form of the invention. Both eyes are treated each day for 3 days.
  • Each application is sprayed via a soft wide mist to saturate the entire surface of the animal's eye.
  • Two (2) spray mists are administered to each eye. The infectious keratoconjunctivitis that is present or is suspected to be present in the animal's eye will resolve.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique qui est efficace dans le traitement prophylactique et/ou thérapeutique de maladies ou d'affections associées à la kératoconjonctivite infectieuse et, en particulier, mais sans s'y limiter, à la kératoconjonctivite infectieuse bovine. Les compositions pharmaceutiques de l'invention sont également utiles pour le traitement d'une plaie ou d'une lésion, et en particulier d'une plaie ou d'une lésion associée à la kératoconjonctivite infectieuse. D'autres applications desdites compositions pharmaceutiques comprennent, entre autres, la réduction ou l'interruption de la transmission de la kératoconjonctivite infectieuse bovine dans un troupeau.
PCT/AU2016/050306 2015-12-17 2016-04-29 Composition pharmaceutique et ses utilisations WO2017100825A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB247018A (en) * 1925-02-28 1926-02-11 Adde Van Der Wal Improved manufacture of a remedy for foot-and-mouth disease
US20040223932A1 (en) * 2003-05-05 2004-11-11 Closure Medical Corporation Adhesive treatment for acne
US20050095222A1 (en) * 2003-10-29 2005-05-05 Taro Suzuki Allergen inhibitor, allergen-inhibiting method, allergen-inhibiting fiber and allergen-inhibiting sheet

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB247018A (en) * 1925-02-28 1926-02-11 Adde Van Der Wal Improved manufacture of a remedy for foot-and-mouth disease
US20040223932A1 (en) * 2003-05-05 2004-11-11 Closure Medical Corporation Adhesive treatment for acne
US20050095222A1 (en) * 2003-10-29 2005-05-05 Taro Suzuki Allergen inhibitor, allergen-inhibiting method, allergen-inhibiting fiber and allergen-inhibiting sheet

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MEREDITH PA ET AL.: "The Effects of Aluminium, Lead and Zinc on delta-Aminolaevulinic Acid Dehydratase", BIOCHEMICAL SOCIETY TRANSACTIONS, vol. 2, no. 6, 1 December 1974 (1974-12-01), pages 1243 - 1245, XP055391290 *

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