OA20893A - Method of disease control. - Google Patents

Abstract

A method of treating a subject having a disease caused by a pathogen, preferably an acid-labile pathogen, said method comprising the step of applying to the subject a therapeutically effect amount of a topical composition having biocidal properties or both pain-relieving and biocidal properties. The composition can be used to treat or control bacterial, viral, fungal or infestational pathogens, and related diseases. The disease can be fool and mouth disease (FMD) or scabby mouth (orf), caused by an acid-labile virus. The topical composition can be used to treat hoof rot/footrot/foot abscess and viral lesions.

Description

Method of Disease Control

Related Applications

This application daims priority of Australian Provisional Patent Application No. 2019901824, filed 28 May 2019, and Australian Provisional Patent Application No. 2019901837, filed 28 May 2019, the contents of which are incorporated herein by reference.

Technical Field

This invention relates to a method of a treating a subject having a pathogenic disease. In one embodiment, the invention concems a method of treating a subject having a skin or mucous membrane disease caused by a pathogen. In another embodiment, the invention concems a method of treating an ulcerative disease such as foot and mouth disease.

Background of the Invention

Foot and mouth disease (FMD), also known as hoof and mouth disease (HMD), is a highly contagious degenerative viral disease of cloven-hoofed animais such as cattle, buffalo, sheep, swine, goats, antelope, deer and bison. It is caused by a Picomavirus, and its symptoms include fever, loss of appetite and weight, blistering or boils on mucous membranes, particularly those of the mouth, feet and udder, animais walking in short tripping steps, lameness (hoof disease), and death.

Infection occurs when the virus is taken into a cell of the animal. The cell then manufactures copies of the virus and eventually bursts, releasing thousands of virus particles. Discharge from blisters on the skin, cavity of the mouth and fissures ofthe hoof is heaviiy infected with the virus. The disease is readily transmitted by contact or as an aérosol.

There is no effective treatment for FMD. Recovery rates are slow, animais may faîl to recover, and infected animais may be slaughtered. An animal survivîng the disease will acquire immunity for several months but only against the spécifie virus strain with which it was infected. Likewise, vaccines are only effective against spécifie virus strains.

The disease is most prévalent in Asia, Africa, and South America. Infected animais are usually quarantined and slaughtered together with healthy ones so as to limit contagion. The entire farm is then usually subjected to thorough disinfection.

Scabby mouth, also known as contagious pustular dermatitis, contagious ecthyma and orf, is a viral disease of goats and sheep. It is caused by a Parapoxvirus, and its symptoms include scabs and pustules, usually around the mouth and face of affected animais. Most commonly, raised scabs with a red ulcerated area undemeath the scab occur around the lips, muzzle and nostril. Less commonly, raised scabs and ulcerated areas occur around the eyes, feet, lower leg, anus, vulva, udder, scrotum and pizzle. In severe cases, infected animal may stop eating, animais may become lame and animais with udder lésions may develop mastîtis.

Abrasions in the skin enable virus to infect. Infection may also occur upon prolonged wetting of the feet. The disease can be transmitted by contact from sheep to sheep. More commonly, scabs shed from infected sheep spread the disease.

There is no spécifie treatment for scabby mouth, but infected animais usually recover spontaneously, with scabs healing in about 3^4 weeks. Animais can develop immunity provîded that there is regular exposure to the virus. Animais can be vaccinated against the virus, usually for a 12-month period. The disease is prévalent in ail sheep-raising countries.

Hoof rot/footrot is a catch-ail term for a fungal or bacterial infection in the hoof of an animal, such as sheep, goats, cattle, horses and deer.

Footrot ïs caused by a combination of the bacteria Fusobacterium necrophorum and Dichelobacter nodosus (more common in sheep), and Bacteroides melaninogenicus (more common in cattle). Its symptoms include a foul-smelling necrotic lésion of the interdigîtai skin, swelling, reduced weight gain, decreased milk and wool production, and lameness. It is extrcmely painful and contagions.

Irritation of the interdigital area provides entry of the bacteria for infection. The disease is transmitted prîmarily from foot to foot via moîst pastures, laneways and muddy yards.

Footrot is treated by foot bathing, hoof trimming, use of antibiotîcs and vaccination.

Animais that hâve been infected with or exposed to footrot do not develop any significant natural immunity or résistance. Vaccines hâve been developed, but theîr efficacy is unreliable and the immunity they provide is of short duration.

The product Trî-Solfen™ (Animal Ethics Pty Ltd) is a local anaesthetic and antiseptie gel spray for use on animais to provide pain relief following animal husbandry procedures such as mulesing, tail dockîng and castration. The product contaîns two topîcal local anaesthetics, being fast-acting lignocaine for immédiate pain relief and long-acting bupîvacaine for prolonged pain relief. The product's gel base adhères well to open wounds and acts as a barrier to environmental stimuli to improve wound healing. The Tri-Solfen™ product contaîns adrenalîn, to both localise the anaesthetic effect and prevent or minîmîze systemic absorption, and is of acidic pH. See US Patent Nos. 8,960,128, 8,822,416 and 9,592,318 (Animal Ethics Pty Ltd), the entire contents of which are incorporated herein b y way of reference.

Detailed Description of the Invention

Varions aspects and embodiments of the présent invention are described below.

The présent inventors hâve made a surprising discovery that the Tri-Solfen™ product is particularly effective in treating and controlling foot and mouth disease (FMD) in cattle when applied to a diseased area of the animal. Although it was anticipated that the gel-based product might alleviate pain caused by the virus when applied to FMD blistering and boils, what was not anticipated was that animais treated with the Tri-Solfen™ product would show markedly hastened healing of their lésions as well as rapidly regain their appetite, gain weight, overcome lameness and survive the disease.

The inventors postulate that the Tri-Solfen™ product provided immédiate pain relief and, in addition, displayed unexpected viricidal properties, both of which contributed to rapid animal recovery from the disease.

The inventors postulate that the Tri-Solfen™ product exposed the virus to viricidal properties of the product, including acidic pH, with immédiate effect, as well as for a prolonged period of time, enabled by the concomitant numbing of tissues by the local anaesthetic agents which prevented acid burning or stinging cffect, and further effectively coated blistering and boils to lower the potential for virus discharge and transmission.

The inventors found that an anaesthetic agent could fonction as an acidic biocidal agent, yet any pain or discomfort caused by the acidic nature of the agent/composition was quickly countered by the fast-aetîng anaesthetic agent îtself.

In view of the surprising effïcacy of the Tri-Solfen™ product, the inventors postulate that similar compositions having both rapidly acting pain-relieving and viricidal properties can be used to treat and control FMD.

Based on the findings in cattle with FMD, the inventors hâve identîfied the potential to treat other infections or inflammatory disease caused by a pathogen that results in épithélial or mucosal inflammation, ulcération, sloughing, peeling, excoriation or lésions such as vesicles or blisters that may rupture and form ulcers.

The inventors postulate that the Tri-Solfen™ product and like products can be used to treat and control other foot or mouth-type pathogenic diseases, including scabby mouth and hoof rot/footrot/foot abscess.

The inventors also postulate that the Tri-Solfen™ product and like products could be used to treat and control other bacterial, viral or fungal pathogens, particularly acid-labile pathogens that resuit in épithélial lésions or ulcérations of the skin or mucous membranes such as Herpesvirus lésions including shingles, cold-sores and génital herpes, and diseases caused by Rhinovirus and Horse Equine Rhinitis A virus (ERAV), Candida such as oral candidîasîs, and Tinea.

The inventors also postulate that the Tri-Solfen™ product and like products could be used to treat and control infestational pathogens such as Lucilia cuprina blowfly larvae. Flystrike lésions are very painful, being caused b y the blowfly larvae. Larvae are killed by 0.5% hydrochlorîc acid. Applying acidic treatment however is likely to be painful. Therefore, a product like Tri-Solfen™ may inactivate larvae while also preventing or treating pain. Flystrike lésions may occur as examples in the breech, perineum, tail, poil pizzle or body of sheep.

According to a first aspect of the présent invention, there is provided a method of treating a subject having a pathogenic disease, said method comprising the step of applying to the subject a therapeutically effect amount of a topical composition having biocidal properties or both painrelieving and biocidal properties.

According to a second aspect of the présent invention, there is provided a method of treating a diseased area of a subject caused by a pathogen, said method comprising the step of applying to the diseased area a topical composition having biocidal properties or both painrelieving and biocidal properties.

According to a third aspect of the présent invention, there is provided a method of treating or controlling a disease in a subject caused by an acid-labile pathogen, said method comprising the step of applying to the subject a therapeutically effect amount of a topical composition having biocidal properties or both pain-relievîng and biocidal properties.

According to a fourth aspect of the présent invention, there is provided a method of treating or controlling foot and mouth disease (FMD) in a subject, scabby mouth in a subject, hoof rot/footrot in a subject, or foot abscess in a subject, said method comprising the step of applying to the subject a composition having biocidal properties or both pain-relieving and biocidal properties.

According to a fifth aspect of the présent invention, there is provided a method of treating or controlling viral lésions in a subject, said method comprising the step of applying to the subject a composition having biocidal properties or both pain-relieving and biocidal properties.

According to a sixth aspect of the présent invention, there is provided a method of treating or controlling Parapoxvirus, Herpes virus, Picomovirus or Equine Rhinitis A lésions in a subject, said method comprising the step of applying to the subject a composition having biocidal properties or both pain-relieving and biocidal properties.

According to a seventh aspect of the présent invention, there is provided a method of treating or controlling fungal lésions or bacterial lésions in a subject, said method comprising the step of applying to the subject a composition having biocidal properties or both pain-relieving and biocidal properties.

According to an eighth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and bîocidal properties in the préparation of a médicament for treating a subject having a pathogenic disease.

According to a ninth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating a diseased area of a subject caused by a pathogen.

According to a tenth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating or controlling a disease in a subject caused by an acidlabile pathogen.

According to an eleventh aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating or controlling foot and mouth disease (FMD) in a subject, scabby mouth in a subject, hoof rot/footrot in a subject, or foot abscess in a subject.

According to a twelfth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating or controlling viral lésions in a subject.

According to a thirteenth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating or controlling Parapoxvirus, Herpes virus, Picomovirus or Equine Rhinitis A lésions in a subject.

According to a fourteenth aspect of the présent invention, there is provided use of a topical composition having biocidal properties or both pain-relieving and biocidal properties in the préparation of a médicament for treating or controlling fungal lésions or bacterial lésions in a subject.

According to a fifteenth aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating a subject having a pathogenic disease.

According to a sixteenth aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating a diseased area of a subject caused by a pathogen.

According to a seventeenth aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating or controlling a disease due to an acid-labile pathogen in a subject.

According to an eighteenth aspect of the présent invention, there is provided a topical composition or médicament having biocidal properties or both pain-relîeving and biocidal properties, formuiated for treating a subject having a pathogenic disease,

According to a nineteenth aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating or controlling foot and mouth disease (FMD) in a subject, scabby mouth in a subject, hoof rot/footrot in a subject, or foot abscess in a subject,

According to a twentieth aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating or controlling viral lésions in a subject.

According to a twenty-first aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating or controlling Parapoxvirus, Herpes virus, Picornovirus or Equine Rhinitis A lésions in a subject.

According to a twenty-second aspect of the présent invention, there is provided a topical composition having biocidal properties or both pain-relieving and biocidal properties for use in treating or controlling fungal lésions, bacterial lésions or lésions caused by an infestational pathogen in a subject.

In each of the aspects, the composition or médicament is topîcally applied to a diseased area of the subject caused by or aggravated by the pathogen.

In each of the aspects, preferably the composition or médicament has both pain-relieving and biocidal properties. In each of the aspects, preferably the composition or médicament has rapid pain-relieving properties.

In each of the aspects, preferably at least one ingrédient of the composition or médicament provides both biocidal activity and pain-relieving activity, preferably rapidly-acting pain relief. Such an ingrédient can be a local anaesthetic agent (as described elsewhere in this spécification). Such an ingrédient can be a local anaesthetic agent having a rapid onset of action.

In some embodiments, the pathogenic disease is a skin or mucous membrane disease caused by a pathogen. In some embodiments, the diseased area is the skin or mucous membrane of the subject.

In some embodiments, the diseased area corresponds to épithélial or mucosal denuding, inflammation, excoriation, ulcération, sloughing, peeling or lésions such as pustules, pox lésions, éruptions, vesicles or blisters that may rupture and form ulcers.

Preferably the diseased area corresponds to significant épithélial or mucosal denuding, inflammation, excoriation, ulcération, sloughing, peeling or lésions such as pustules, pox lésions, éruptions, vesicles or biisters that may rupture and fonn ulcers, as opposed to mînor épithélial or mucosal denuding, inflammation, excoriation, ulcération, sloughing, peeling or lésions such as pustules, pox lésions, éruptions, vesicles or biisters that may rupture and form ulcers. That is, for example, the composition is used on significant pathogenic ulcerative lésions, as opposed to minor pathogenic ulcers or skin excoriation.

In some embodiments the diseased area corresponds to a mouth and/or nasal area of the subject. In some embodiments the diseased area corresponds to the génital and/or anal area of a subject. In some embodiments the diseased area corresponds to a hand, arm, foot, hoof or leg of the subject. In some embodiments the diseased area corresponds to a face or thorax (including abdomen and back) of a subject. In some embodiments the diseased area corresponds to perineum, annpîts, under folds of the breasts, in creases or folds of skin on the abdomen etc of a subject. In some embodiments the diseased area corresponds to feet, scalp, skin, or skin folds or creases of a subject. In some embodiments the diseased area corresponds to lésions (due to flystrike, for example) in the breech, perineum, tail, poil pizzle or body of a subject.

The composition can be used to treat or control bacterial and/or viral and/or fungal and/or infestational pathogens, and/or related diseases. The composition can be used to treat or control any suitable type of bacterial, viral, fungal or infestational pathogen or related disease. Examplcs of suitable viral pathogens include Parvovirus, Parapoxvirus, Picomavirus, Herpesvirus and Rhinovirus. Examples of suitable fungal pathogens include Candida and Tinea. Examples of suitable infestational pathogens include insects, such as insect larvae, preferably screw worm or blowfly larvae. Examples of suitable bacterial pathogens include those that cause infection or ulcers on the skin or mucous membrane (eg. including épithélial or mucosal inflammation, ulcération, sloughing, peeling, excoriation or lésions such as vesicles or biisters that may rupture and form ulcers), including those that may be involved in hoof rot/footrot. Examples of suitable infestational pathogens include insects, such as insect larvae, preferably screw worm or blowfly larvae

The composition can be used to treat or control hoof rot/footrot. “Hoof rot/footrot” as used herein includes withîn its scope a fungal or bacterial infection in the hoof of an animal, such as sheep, goats, cattle, horses and deer. “Hoof rot/footrot” as used herein also includes within its scope any type of foot abscess.

In some embodiments the composition can be used to treat or control foot abscess. In some embodiments the composition can be used to treat or control other aphthous or foot or mouth-type pathogenic diseases.

The composition can be used to treat or control acid-labile bacterial, acid-labile viral, acid-labile fungal pathogens and/or acid-labile infestational pathogens and/or related diseases. The composition can be used to treat or control any suitable type of acid-labile bacterial, acidlabile viral, acid-labile fungal or acid-labile infestational pathogen or related disease. In some embodiments the acid-labile pathogen can be, but is not limited to, Parvovirus, Parapoxvirus and Picomavirus. In some embodiments the acid-labile pathogen can be, but is not limited to, Herpesvirus and Rhi no virus. In some embodiments the acid-labile pathogen can be, but is not limited to, Candida and Tinea. In some embodiments the acid-labile pathogen can be, but is not limited to bacterial pathogens include those that cause infection or ulcers on the skin or mucous membrane (eg. încluding épithélial or mucosal inflammation, ulcération, sloughing, peeling, excoriation or lésions such as vesicles or blisters that may rupture and form ulcers), încluding those that may be involved in hoof rot/footrot. In some embodiments the acid-labile pathogen can be, but is not limited to, an infestational pathogen such as an insect, preferably screw worm or blowfly larvae. (Larvae may be killed by 0.5% hydrochloric acid.)

In some embodiments the composition can be used to treat or control viral pathogens, particularly acid-labile viruses, încluding diseases caused by those viruses. Examples include Herpes (simplex and zoster), Parvovirus, Rhinovîrus and Equine Rhinitis A virus.

In some preferred embodiments the composition can be used to treat or control viral pathogens that lack a lipid membrane, încluding diseases caused by those viruses. Examples include Herpes (simplex and zoster), Parvovirus, Rhinovîrus and Equine Rhinitis A virus.

In some embodiments the composition can be used to treat or control pathogens, încluding diseases caused by those pathogens, încluding:

Rhinovîrus - human and animal virus - that can resuit in sore throat ulcers and nose lésions.

Equine Rhinitis A virus (ERAV) - horse virus sîmilar to FMD (causes horse version of FMD also called ERV 1 ERV 2 apthovirus).

Herpes viruses - shingles (herpes varicella zoster) or génital herpes (herpes simplex virus 2) or cold sores (herpes simplex virus 1).

Candida, being a fungus that is acid labile and can infect wounds, cause mouth ulcers, cause skin ulcération of perineum, armpits, under folds of the breasts, in creases or folds of skin on the abdomen and delay healing.

Tinea, which causes skin ulcération and lésions of the feet, scalp, skin, skin folds and creases.

Infestational pathogens, such as Lucilia cuprina blowfly larvae and Cochlioinyia hominîvorax screw wonn fl y larvae that cause ulcerative lésions.

Described features of the composition can also be features of the médicament, context permitting.

The composition (or médicament) can be of any suitable form. The composition can be, for example, in the form of a liquid, ointment, gel, lotion, cream, crème, émulsion, paste, film or suspension.

Depending on the form of the composition, the composition can include one or more of the following types of ingrédients: adhesive; aqueous or oily diluent; carrier; excipient; base; buffer; pH adjuster; bittering agent (i.e. foul-tasting agent); suspending agent; thickening agent; gelling agent; viscosity increasing agent; emulsifier; emollient; humectant; stabilising agent; dispersing agent/dîspersant; solubiliser; skin conditioning agent; skin protectant; skin pénétration enhancer; fragrance; preservative; sunscreen agent; surfactant; textural modifier; colourant; propellant; réfrigérant; and, waterproofing agent.

Suitable oily or aqueous bases, carriers, diluents and excipients are inert and physiologically acceptable and include, for example: bacteriostatic saline (saline containing benzyl alcohol), cetomacrogol, cetyl alcohol, glycérine, lanolin, petrolatum based creanis, gels, hydrogels, saline, short chain alcohols and glycols (e.g. ethyl alcohol and propylene glycol), and water.

Either water in oil or oil in water émulsions can be used. Examples of suitable surfactants and emulsifying agents include: non-ionic ethoxylated and non-ethoxylated surfactants, abietic acid, almond oil PEG, beeswax, butylglucoside caprate, Cig-C^ô acid glycol ester, C9-C15 alkyl phosphate, caprylic/capric triglycéride PEG-4 esters, cetomacrogol, ceteareth7, cetereth-20, cetyl phosphate, cetyl stearyl alcohol, corn oil PEG esters, DEA-cetyl phosphate, dextrin laurate, dilaureth-7 citrate, dimyristyl phosphate, glycereth-17 cocoate, glyceryl erucate, glycerol, glyceryl laurate, G.M.S. acid stable, hydrogenated castor oil PEG esters, isosteareth-11 carboxylic acid, lecithîn, lysolecithin, nonoxynol-9, octyldodeceth-20, palm glyceride, PEG diisostearate, PEG stearamine, poloxamines, polyglyceryls, potassium linoleate, PPGs, raffinose myristate, sodium caproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate, sodium tocopheryl phosphate, steareths, TEA-C12-C13 pareth-3 sulfate, tri-Ci2-Ci5 pareth-6 phosphate, and trideceths.

The composition can comprise one or more types of preservative. A suitable preservative, for example, can be: benzalkonium chloride, benzoic acid, beuzothonium chloride, benzyl alcohol, 2-bromo-2-nitropropane-l,3-diol, bronopol, butylated hydroxyanisole, butylated hydroxytoluene, butyl paraben, chlorophene, chlorphenesin, diazolidinyl urea, DMDM hydantoin, ethyl paraben, formai dehyde-releasing preservative, hydroquinone, iodopropynyl butyl carbamate, imidazolidinyl urea, methyldibromo glutaronitrile, methylhydroquinone, methylisothiazolinone, methyl paraben, nitrosamines, o-cymen-5-ol, phenoxyethanol, propyl paraben, quatemium-15, sodium benzoate, sodium dehydroacetate, sodium hydroxymethylglycinate, sodium mctabisulfite, and sodium sulfite. Preferably, the composition includes the reducing agent such as sodium metabisulfite. Any suitable amount of sodium metabisulfïte can be used, eg. up to about 3.5mg/ml.

The composition can include a colourant so that its application can be verified visually. The colourant can be a pigment and/or dye. Suitable colourants include, for example, common food dyes or the ORCODERM®, ORCOBRITE® and ORCOFUR® lines of pigments and dyes sold by the Organic Dyestuffs Corporation. Preferably, the colourant is non-toxic and will not permanently stain the skin or animal hide or surrounding hair, fur or wool.

A skin conditioning agent, as defined herein, improves dry or damaged skin. Such agents, for example, include: acetyl cysteine, N-acetyl dihydrosphingosine, acrylates/behenyl acrylate/dimethicone acrylate copolymer, adenosine, adenosîne cyclic phosphate, adensosine phosphate, adenosine triphosphate, alanine, albumen, algae extract, allantoin and dérivatives, aloe barbadensis extracts, aluminum PCA, amyloglucosidase, arbutin, arginine, azulene, bromelain, buttermilk powder, butylène glycol, caffeine, calcium gluconate, capsaicin, carbocysteine, carnosine, beta-carotene, casein, catalase, cephalins, ceramides, chamomilla recutita (mairicaria) flower extract, cholecalciferol, cholesteryl esters, coco-betaine, coenzyme A, com starch modified, crystallins, cycloethoxymethicone, cysteine DNA, cytochrome C, darutoside, dextran sulfate, dimethicone copolyols, dimethylsilanol hyaluronate, DNA, elastin, elastin amino acids, epidermal growth factor, ergocalciferol, ergosterol, ethylhexyl PCA, fibronectin, folie acid, gelatin, gliadin, beta-glucan, glucose, glycine, glycogen, glycolipids, glycoproteins, glycosaminoglycans, glycosphingolipids, horseradish peroxidase, hydrogenated proteins, hydrolyzed proteins, jojoba oil, keratin, keratin amino acids, kinetin, lactoferrin, lanosterol, lauryl PCA, lecîthin, linoleic acid, linolenic acid, lipase, lysine, lysozyme, malt extract, maltodextrin, melanin, méthionine, minerai salts, nîaein, niacinamide, oat amino acids, oryzanol, palmitoyl hydrolyzed proteins, pancreatin, papain, PEG, pepsin, phospholipids, phytosterols, placental enzymes, placenta! lipids, pyridoxal 5-phosphate, quercetîn, resorcinol acetate, riboflavîn, RNA, saccharomyces lysate extract, silk amino acids, sorbitol, sphingolipîds, stearamidopropyl betaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl lînoleate, ubiquinone, vitis vinifera (grape) seed oil, wheat amino acids, xanthan gum, and zinc gluconate.

The composition can include a skin pénétration enhancer for enhancing the pénétration of active ingrédients. Any suitable type of enhancer can be used. Examples of suitable enhancers may include solvents, détergents or low carbon alcohols such as dimethylsulfoxide, oleyl alcohol, propylene glycol, methyl pyrrolidone and dodecylazyl cycloheptan 2-one.

The composition can comprise one or more of the following adhesives, thickening agents, gelling agents and/or viscosîty increasing agents: acrylamides copolymer, agarose, amylopectîn, calcium alginate, calcium carboxymethyl cellulose, carbomer, carboxymethyl chitin, castor oil dérivatives, cellulose gum, cellulosic préparation, cetyl alcohol, cetostearyl alcohol, dextrin, gelatin, hydroxy cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxpropyl starch, inert sugar, magnésium alginate, methylcellulose, microcrystalline cellulose, pectin, PEG's, polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, quatemîum ammonium compound of bentonite or zinc stéarate, sorbitol, PPG's, sodium acrylates copolymer, sodium carrageenan, xanthum gum, and yeast beta-glucan.

The composition can comprise an insecticide or insect repellent to stop insect infestation. Any suitable type of insecticide or insect repellent can be used. Ex amples of suitable insecticides include: trichlorfon, triflumeron, fenthion, bendiocarb, cyromazîne, dîslubenzuron, dicyclanil, fluazuron, amitraz, deltamethrin, cypermethrin, chlorfenbinphos, flumethrin, ivermectin, abermectin, avermectin, doramectin, moxidectin, zeti-cypermethrin, diazinon, spinosad, imîdacloprid, nitenpyran, pyriproxysen, sipronil, cythioate, lufenuron, selamectin, milbemycin oxime, chlorpyrifos, coumaphos, propetamphos, alpha-cypermethrin, high cis cypermethrin, ivermectin, diflubenzuron, cyclodiene, carbamate and benzoyl urea.

The composition can be applied to the subject (or diseased area of the subject) in any suitable form. The composition can be applied in a liquid form or other free-flowîng form. The composition can be applied as a spray-on liquid or spray-on gel so as to minimise pain related to touching a subject, minimise the risk of infection from skin contamination and so that the diseased area need not be disturbed more than necessary. Altemativeiy, the composition can be applied as a gel by hand, or squeezed from a tube.

In some embodiments the composition is adhesive or sticky or tenacious.

Once applied, the composition can be, for example, in the form of an ointment, gel, foam, lotion, crème, cream, émulsion, paste, solution or suspension, or may set and /or form a physical barrier, ‘skin’, coating or film.

Once applied, the composition can be, for example, in the form of an adhesive/sticky/tenacious ointment, gel, foam, lotion, crème, cream, émulsion, paste, solution or suspension, or may set and /or form an adhesive physical barrier, ‘skin’, coating or film.

For example, if applied to a diseased area such as a leg or hoof, the composition may form an adhesive coat or coating, layer, barrier, skin or film. That is, the composition can be adhesive.

For example, if applied to a diseased wet area such as a mouth and/or nasal région, the composition may foam and spread over those wet surfaces, or otherwise coat and spread over those wet surfaces.

The composition can be in a sustained-release form, whereby one or more actives of the composition are slowly released to provide a therapeutic effect over an extended period of time (eg. biocidal activity, pain relief, antiviral activity).

The composition can be incorporated into a bandage, plaster, dressing, wipe or tissue.

The composition can be applied as a metered dose.

The composition can form or can be in the fonn of an adhesive gel after being applied to the subject.

The composition can form or can be in the form of a foam after being applied to the subject.

The composition can be both adhesive/sticky in a relatively dry diseased area and/or form a foam in a relatively wet diseased area.

The composition can comprise a hydrophilîc or hydroalcoholic gelling agent. The composition can comprise about 1 to 20 g per litre of at least one type of gum or cellulosic préparation, including ail about 0.1 g incréments between 1 and 20, including 1.1, 1.2 etc. The composition can comprise a polyhydric aicohol in combination with a cellulosic préparation; for example, hydroxy cellulose (eg. hydroxyethyl cellulose, ethylhydroxy cellulose) in combination with non-crystallising liquid sorbitol. The composition can comprise about 5 mg/ml hydroxy cellulose (eg. hydroxyethyl cellulose) in combination with about 100 mg/ml non-crystallising liquid sorbitol (70%).

Preferably, the composition is in the form of a liquid prier to having been applied to a subject. Preferably, the composition forms, or is in the form of, a stick y, viscous, adhesive gel when applied to a subject. Preferably, the composition is in the form of a spray-on gel that can coat the diseased area of the subject and can maximise delivery of actives to the diseased area of the subject, preferably by way of stayîng moist and viscous (i.e. “sticky”).

Preferably, the composition forms, or is in the form of, a foam when applied to a subject. Preferably, the composition is in the form of a foam that can coat the diseased area ofthe subject and can maximise delivery of actives to the diseased area of the subject. Preferably the composition, as a foam, can spread throughout the diseased area.

Preferably, the composition forms an effective long-lasting barrier over the diseased area. The tenu long-lasting barrier is to be understood as meaning a barrier/seal that is substantially capable of remaining intact over a diseased area for hours, days, a week or even weeks, or until the wound has naturally sealed or the pain has otherwise abated by way of the natural healing process — eg. about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours, or about one, two, three, four, fïve, six or seven days, or one, two, three, four or more weeks.

The barrier preferably aids in the healing process, presumably by minimising or preventing water loss from the diseased area and by acting as a barrier against microbial contamination.

In some embodiments the composition is in the form of a liquid that thickens to an adhesive gel when reacting with physiological fluids of the diseased area of the subject.

The composition can provide prolonged pain relief, including pain relief for about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23 or 24 hours, or about one, two, three, four, fïve, six or seven days, or one, two, three, four or more weeks, or until the wound has naturally sealed or the pain has otherwise abated by way of the natural healing process.

The composition can provide prolonged pain relief, including pain relief for about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours, or about one, two, three, four, fïve, six or seven days, or one, two, three, four or more weeks.

The composition can provide prolonged release of a biocidal agent or exposure to a biocidal property, including for about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8,

9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours, or about one, two, three, four, fïve, six or seven days, or one, two, three, four or more weeks.

Regardîng the pain-relieving properties of the composition or médicament, the composition or médicament can comprise at least one pain relieving agent. The at least one pain relieving agent can be an anaesthetic agent or an analgésie agent, such as an anti-inflammatory agent. In some embodiments, at least one anaesthetic agent is used. In some embodiments at least one analgésie agent is used. In some embodiments, at least one analgésie agent is used in combination with at least one anaesthetic agent. Ex amples of anaesthetic agents include:

lignocaine, chloroprocaine, mepivacaine, bupîvacaine, articaine, etîdocaine, levobupivacaîne, tetracaine, prilocaine, benzocaine, ropivacaine, cocaïne, oxyprocaine, hexylcaine, dibucaine, piperocaîne and procaine and phannaceutically acceptable acids, bases and salts (including acidic salts) thereof. In some embodiments the anaesthetîc agent is in the form of an acidic sait or acidic solution. (Local anaesthetîc solutions typically hâve an acidic pH to maximise their water solubility and Chemical stability.)

Examples of other potentially suitable anaesthetîc agents include: butamben, butambenpicrate, dimethisoquin hydrochloride, diperodon, diphenhydramine, dyclonine, ketamine, methapyriline, p-buthylaminobenzoic acid, 2- (die-ethylamino) ethyl ester hydrochloride, pramoxine and tripelennamine.

The composition preferably provides maximum anaesthesia with minimal risk of toxicity. The fonnulation ofthe composition can be varied, as required, for potency, speed of onset and duration of anaesthetîc action.

In some embodiments, the composition comprises at least one local anaesthetîc agent. In some embodiments, the composition comprises at least one local anaesthetîc agent having a rapid onset of action (ie. rapidly acting). In some embodiments, the composition comprises at least one local anaesthetîc agent having a long duration of action. In some embodiments, the composition comprises both at least one local anaesthetîc agent having a rapid onset of action and at least one local anaesthetîc agent having a long duration of action. It is to be understood that some local anaesthetîc agents can provide both a rapid onset of action and long duration of action, such as amethocaine / tetracaine, so the local anaesthetîc agent providing a rapid onset of action and local anaesthetîc agent providing a long duration of action can be one and the same.

Anaesthetîc agents that usually hâve a rapid onset of action (usually between about 5-10 minutes) include lignocaine, prilocaine, amethocaine / tetracaine and cocaine.

Anaesthetîc agents that often hâve a much slower onset of action but a much greater duration of action (usually between about 4-12 hours of anaesthesia) include bupîvacaine, ropivacaine, levo-bupivacaine, and amethocaine ! tetracaine. Bupîvacaine may typically provide up to about 6-12 hours of anaesthesia, depending on the method of administration.

Any suitable amount of anaesthetîc agent can be used in the composition but preferably about 0.01-10 weight/volume % of anaesthetîc agent is used (as well as ail 0.01 incréments between 0.01 and 10, eg. 0.01, 0.02 etc).

Any suitable amount of rapid onset anaesthetîc agent can be used in the composition but preferably about 0.01-10 weight/volume % of anaesthetîc agent is used (as well as ail 0.01 incréments between 0.01 and 10). Preferably, about 2-8 weight/volume % anaesthetîc agent is used in those situations where a rapid onset of action is required (as well as ail 0.01 incréments between 2 and 8). More preferably, about 5 % weight/volume anaesthetic agent is used.

In some embodiments, about 1-10 weight/volume % lignocaine is used (as well as ail 0.01 incréments between 1 and 10, eg. 0.01, 0.02 etc). In some embodiments, about 2-8 weight/volume % lignocaine is used as the anaesthetic agent in those situations where a rapid onset of action is required (as well as ail 0.01 incréments between 2 and 8). In some embodiments, about 5 % lignocaine is used.

Any suitable amount of long duration of action anaesthetic agent can be used in the composition but preferably about 0.01-10 weight/volume % of anaesthetic agent is used (as well as ail 0.01 incréments between 0.01 and 10). Preferably, about 0.1-5 weight/volume % anaesthetic agent is used in those situations where a long duration of action is required (as well as ail 0.01 incréments between 0.1 and 5). More preferably, about 0.5 % weight/volume anaesthetic agent is used.

In some embodiments, the composition can comprise any suitable amount of bupivacaine if lignocaine or other rapid onset anaesthetic agent has an inadéquate duration of action. Preferably, the composition comprises about 0.1 -5 weight/volume % bupivacaine (as well as ail 0.ÜI incréments between 0.1 and 5), and more preferably about 0.5% bupivacaine.

In some embodiments, the composition can comprise any suitable amount of tetracaine. Preferably, the composition comprises about 1-10 weight/volume % tetracaine (as well as ail 0.01 incréments between 1 and 10).

In some embodiments, at least one analgésie agent and/or at least one anti-inflammatory agent can be used. Examples of potentially suitable analgésie and/or anti-inflammatory agents include: 1-menthol, acetaminophen, alclofenac, aspirin, bendazac, betamethasone, bufexemacpiroxicam, camphor, cholîne salicylate, clidanac, clofezone, corticosterone, cortisone, déxaméthasone, diclofenac, diflunisal, fenbufen, fenoprofen, fentiazac, fludrocortisone, fluocinolone, fluphenamic acid, flurandrenolide, flurbiprofen, glycol salicylate, halcinonide, hydrocortisone, ibuprofen, indomethacin, indoprofen, ketoprofen, meclofenamate sodium, mefenamic acid, medrysone, mepirizole, méthylprednisolone, methyl salicylate, naproxene, oxyphenbutazone, paramethasone, pentazoeîne, phenylbutazone, piroxicam, prednisone, prednisolone, protizidic acid, pranoprofen, salicylic acid, sulindac, suprofen, tiaprofenîc acid, tolmetin and triamcinolone.

Potentially suitable analgésie agents include one or more of the following: acetaminophen, aspirin, salicylic acid, methyl salicylate, choline salicylate, glycol salicylate, 1menthol, camphor, mefenamic acid, fluphenamic acid, indomethacin, diclofenac, alclofenac, ibuprofen, ketoprofen, pranoprofen, fenoprofen, sulindac, fenbufen, clidanac, flurbiprofen, indoprofen, protizidic acid, fentîazac, tolmetin, tîaprofenic acid, bendazac, bufexemacpiroxicam, phenylbutazone, oxyphenbutazone, clofezone, pentazocine, mepirizole, hydrocortisone, cortisone, dexamethasone, fluocinolone, triamcînolone, medrysone, prednisolone, flurandrenolide, prednisone, halcinonide, méthylprednisolone, fludrocortisone, corticosterone, paramethasone, betamethasone, naproxen, suprofen, piroxicam, diflunisal, meclofenamate sodium, carprofen, flunixin, tolfenamîc acid and meloxîcam.

Pûtentially suitable non-steroidal anti-inflammatory drug (NSAlDs) include one or more of the following: salicylate (e.g. aspirîn (acetylsalicylîc acid), diflunisal (dolobid), salicylic acid and other salicylates, salsalate (disalcid)), propionic acid dérivative (e.g. ibuprofen, dexibuprofen, naproxen, fenoprofen, ketoprofen, dexketoprofen, flurbiprofen, oxaprozin, loxoprofen), acetic acid dérivative (e.g. indomethacin, tolmetin, sulindac, etodolac, ketorolac, dîclofenac, aceclofenac, nabumetone), enolic acid (oxicam) dérivative (e.g. piroxicam, meloxîcam, tenoxicam, droxicam, lomoxicam. isoxicam, phenylbutazone), anthranilic acid dérivative (fenamate) (e.g. mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamîc acid), sélective COX-2 inhibitor (e.g. celecoxib, rofecoxib, valdecoxib, parecoxib, lumîracoxîb, etoricoxib, firocoxib), sulfonanilide (e.g. nimesulide), or other (e.g. clonixin, licofelone, Hharpagide in Figwort or Devil's Claw).

In some embodiments approximately 0.1% (Img/ml) meloxîcam or other NSAID is used, Any suitable amount of analgésie or anti-inflammatory agent can be used in the composition but preferably about 0.01-10 weight/volume % of agent is used (as well as al! 0.01 incréments between 0.01 and 10).

The composition can further include a vasoconstrictor to decrease the rate of vascular absorption of the pain relieving agent, so to improve the depth and duration of pain relieving agent, to reduce bleeding from a wound of the subject, as well as to reduce systemic toxicity. The vasoconstrictor can also lower the pH. Any suitable type of vasoconstrictor can be used, including any suitable sait or form thereof. Suitable vasoconstrictors include, for instance, adrénaline (epinephrine), noradrenalin (norepinephrine) and fenylpressin, including any suitable sait or form thereof. Preferably, the composition includes about 1:1000-1:10,000 vasoconstrictor (as well as ail 10 factor incréments between 1000 to 10,000), and more preferably 1:2,000 vasoconstrictor. Preferably the vasoconstrictor is adrénaline.

Regarding the biocidal properties of the composition or médicament, the composition or médicament can comprise at least one biocidal agent. However, dependîng on the type of pathogen/s, the composition or médicament can hâve biocidal properties attributable to any one or more of the following: low pH (below about pH 4.0, but more preferably below about pH 3.0); antiseptie agent; antimicrobial agent; viricidal agent (eg. at least one anaesthetic agent such as lidocaine, preferably in high doses); antifungal agent; antibiotic; and, vaccine antîgen spécifie for the pathogen. (Local anaesthetic solutions typically hâve an acidic pH to maximise their water solubility and Chemical stability.)

The composition can include one or more other active ingrédients. An active ingrédient, as defined herein, is a compound that provides benefit to the subject. The active ingrédient can be, for instance, an anticoagulant, antiproliférative, cytokine, cytotoxin, growth factor, interferon, haemostatic agent, hormone, lipid, déminerai ized boue or bone morphogenetic protein, cartilage inducing factor, oligonucleotide, polymer, polysaccharide, polypeptide, protease inhibitor, vitamin, minerai, and, insecticide or insect repellent.

The composition can hâve a pH below about 4.0, which includes a pH of about 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.2, 3.1, 3.0 .2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1 and 2.0.

The composition preferably includes an antiseptie agent to, amongst other things, minîmize wound contamination and infection, and act as an anti-viral agent. Any suitable type of antiseptie agent can be used. Suitable antiseptie agents include cetrimide, povidone-iodine, chlorhexidine, iodîne, benzalkonium chloride, benzoic acid, nitrofiirazone, benzoyl peroxide, hydrogen peroxide, hexachlorophene, phénol, resorcinol and cetylpyridinium chloride.

The subject can be a human. The subject can be an animal. The subject can be any member of the mammalian order Artiodactyla. The subject can be any relevant type of hoofed animal. The subject can be any relevant type of hoofed African animal. Hoofed animais include, for example: cattle, reindeer, giraffe, deer, sheep, moose, camel, hippopotamus, goat, pig, boar, elk, llama, bison, alpaca, okapi, yak, ruminants of the saborder Ruminantia, buffalo, gaur, antelope, gazelle, ox, gnu and suid. The animal is preferably a sheep, horse, cow, goat, pig, deer, antelope, bison or buffalo.

Preferably the composition is capable of coating and adhering to a diseased area of the subject.

Preferably the composition is capable of controlled and/ or prolonged release of a biocidal agent or exposure to a biocidal property.

Preferably the composition is capable of providîng rapid pain relief. Preferably the composition is capable of providîng prolonged pain relief. Preferably the composition is capable of providîng both rapid pain relief and prolonged pain relief.

Preferably the composition is capable of providîng rapid pain relief so as to relief pain caused by an acidic composition.

Preferably the composition is biocompatible and absorbable such that it does not require removal.

Preferably the composition comprises an adhesive gel base capable of coating and adhering to a diseased area and providing prolonged contact with the dîseased area and controlled and/or prolonged release of a biocîdal agent or exposure to a biocidal property.

In some embodiments, the biocidal property is that the composition comprises a pH less than about 3.0. In some embodiments, the biocidal agent is lignocaine. In some embodiments, the biocidal property is that the composition is acidic and can inactivate a pathogenic virus. In some embodiments, the biocidal agent is substantially uniformly dispersed throughout the composition. In some embodiments, the biocidal agent is an antiseptie, such as cetrimide. In some embodiments, the composition comprises a gelling agent or thickener, such as hydroxyethyl cellulose. In some embodiments, the composition comprises a gelling agent or thickener, such as non-crystallising liquid sorbitol (70%). In some embodiments, the composition comprises a colourant, such as a dye. In some embodiments, the composition comprises a pH less than about 4.0, preferably less than about 3.0. In some embodiments the composition is in the form of a liquid that sets as a sticky viscous gel when exposed to the diseased area.

In some embodiments, the composition comprises: a liquid gel matrix that contains the following: lidocaine; adrenalin; and cetrimide, and the composition is optionally coloured; or a liquid gel matrix that contains the following: tetracaine; adrenalin; and cetrimide, and the composition is optionally coloured; or a liquid gel matrix that contains the following: lidocaine; bupivacaine; adrenalin; and cetrimide, and the composition is optionally coloured, wherein said composition has a pH lower than about 4.0.

In a first preferred embodiment, the composition (“Composition 1”) comprises: about 100 mg/ml non-crystallising liquid sorbitol (70%);

about 50.0 mg/ml lignocaine HCI;

about 5.0 mg/ml bupivacaine HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.0 mg/ml cetrimide;

about 45.0 pg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose; and optionally colourant such as a dye.

If desired, lignocaine can be swapped out and tetracaine swapped in at about 1-10%, but preferably about 5% (50mg/mI) (“Composition 2”).

In a second preferred embodiment, the composition (“Composition 3”) comprises:

about 100 mg/ml non-crystallising Iiquid sorbitol (70%);

about 40.0 mg/ml lignocaine HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.0 mg/ml cetrimide;

about 36.0 pg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose; and optionally colourant such as a dye.

If desired, lignocaine can be swapped out and tetracaîne swapped in at about 1-10%, but preferably about 5% (50mg/ml) (“Composition 4”).

In a third preferred embodiment, the composition (“Composition 5”) comprises:

about 100.0 mg/ml purified water sorbitol Iiquid 70% non-crystallising;

about 50.0 mg/ml (5%) tetracaîne HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.0 mg/ml cetrimide;

about 45.0 pg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose;

to 1 ml purified water; and optionally colourant such as a food dye (quantity to suit (q.s.)).

In a fourth preferred embodiment, the composition (“Composition 6”) comprises: lignocaine, bupivacaine, adrénaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, Iiquid sorbitol (70%), buffer, and, optionally colourant such as a dye.

If desired, lignocaine can be swapped out and tetracaîne swapped in at about 1-10%, but preferably about 5% (50mg/ml) (“Composition 7”).

In a fifth preferred embodiment, the composition (“Composition 8”) comprises: amethocaine / tetracaîne, adrénaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, Iiquid sorbitol (70%), buffer, and, optionally, colourant such as a dye.

In a preferred embodiment, the composition (“Composition 9”) is as described or substantially as described in US Patent Nos. 8,960,128, 8,822,416 and 9,592,318 (to Animal Ethics Pty Ltd), the entire contents of which are incorporated herein by way of reference.

Any suitable dosage and dosage régime can be used. This will dépend on, amongst other things, the ingredients/actives/properties of the composition, the size/weight of the subject being treated, the size of the diseased area/lesîon area being treated, and the frequency of reapplication of the composition that is required (if any).

Suitable dosages can be gleaned, for ex ample, from the Best Mode section of this spécification.

Preferably, the entire diseased area of the subject is coated with the composition, eg. hoof and mouth régions, in the case of foot and mouth disease. The amount applied will vary according to the number and size of the diseased areas/lesions.

In the case of Compositions 1 to 9 and similar compositions, in some embodiments this will usually amount to application of between about 5ml and 60ml of Composition per subject, including ail 0.1 ml values between 5 and 60. However, more or less could be applied.

In the case of Compositions 1 to 9 and similar compositions, in some embodiments this will amount to application of between about 6ml and 20ml of Composition per subject, including ali 0.1 ml values between 6 and 20. However, more or less could be applied.

For any one of the Compositions and similar compositions containing lidocaine but no adrenalin, about 2.6g lidocaine (without adrenalin) can be applied to cattle or other subjects weighing 600-800kg = approximately 3-4mg/kg.

The application dose of a said Composition (containing lidocaine plus adrenalin) may be up to about 50mg lidocaine/kg of subject body weight, which equals about 1ml Composition/kg subject body weight. In some embodiments, this could amount to about up to about 4mg lidocaine/kg subject weight, which equals about 0.08ml/kg of the Composition. In some embodiments, this could amount to about: cattle or other subjects (eg. from the bovine group) 500kg plus = up to about 40ml of a said Composition. In some embodiments, this could amount to about: calves or other subjects 20-500kg = up to about 12 ml of a said Composition. In some embodiments, this could amount to about: calves or other subjects 20-500kg = up to about 20 ml of a said Composition. In some embodiments, this could amount to about: cattle or other subjects 500kg plus = up to about 50ml or 60ml of a said Composition.

Any of the features described herein can be combined in any combination with any one or more of the other features described herein within the scope of the invention.

Preferred features, embodiments and variations of the invention may be discemed from the following Best Modes section which provides sufficient information for those skilled in the art to perform the invention. The Best Modes section is not to be regarded as limiting the scope of the preceding Detailed Description in any way.

Brief Description of Figures

Figure 1 shows typical lésions (mouth and hoof) and body habitus (lameness) caused by FMD, prior to treatment with Tri-Solfen™ gel product.

Figure 2 shows how the Tri-Solfen™ gel product was applied to animais suffering from FMD, using a liquid-gel applicator.

Best Modes for Carrying Ont the Invention

Example 1 -Supervised Observational Field Trial of Tri-Solfen™ for Foot and Mouth Disease -Discovery of Anti-Viral Effects - Laos 2019

Background

Foot and mouth-disease (FMD) is a highly infections viral disease that affects animais with cloven hooves such as cattle, pigs, sheep, goats and artiodactyl wildlife species. The disease is characterized by fever, salivation and vesicles in the mouth, muzzle, dental pad, tongue, teats and feet. The rupture of the vesicles results in marked painful swelling of the coronary band, dépréssion, innapetence, lameness, recumbency, loss of body condition, severe mastitis and abortions (Radostitis et al. 2000).

The global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animais affected. There are direct losses due to a réduction in production and changes in herd structure; and indirect losses that relate to the signîficant costs of FMD control and management and poor access to markets and limited use of improved production technologies. The annual impact of FMD in terms of production losses and vaccination alone are estîmated as in the région of US$5 billion (Knight-Jones and Rushton 2013). Much of the global FMD burden of production losses falls on the world’s poorest communities, particularly those most dépendent on livestock in developing countries. The direct losses limit hvestock productivity creating a food insecurity and contributing to malnutrition.

The FMD virus belongs to the Aphthovirus genus of Picornaviridae family, and its classification has seven serotypes (O, A, Asia 1, C, SAT 1, SAT 2, and SAT 3) and about 80 subtypes (Kahn et al. 2005). The serotypes hâve a large number of strains that hâve a spectrum of antigenic characteristics requirîng more than one vaccine strain for each serotype (Kahn et al. 2005). There is no cross immunity between serotypes and this présents difficulties to vaccination programs (Radostitis et al. 2000).

The disease is highly contagions. The mode of transmission from infected animal to susceptible one is by inhalation, or direct contact with infected lésions or sécrétions. Exhaled air containing the virus infects susceptible animais via the respiratory or oral route. Ail body excrétions and sécrétions from infected animal may contaîn the virus. Transmission to calves is via infected milk and fodder contaminated from contact with infected animais. Other sources of infection include: milk tankers, mechanical animal vectors like horses, cat, dogs, avian species and humans. Pigs are considered ‘amplifying hosts’; often infected by contaminated feed derived from infected animais, spreading large volumes of virus that may spread the disease via aérosol to the cattle and other species (Kahn et al, 2005).

Disinfection during an outbreak can prevent the virus from spreading. The virus is known to be highly acid labile, FMD virus does not hâve an outer membrane and therefore is destroyed rapidly in conditions below pH 5.0 and above pH 11.0. At pH < 4 it undergoes rapid and complété destruction (Bachrach et al., 1957). Citric acid is commonly used for disinfection of animal housing and surrounding contaminated environments (Sellers et al., 1968).

FDM lestons are extremely painful for animais and results in lameness and pain on eating and drinking. Together these resuit in rapid loss of condition. Ulcers often take weeks to heal and foot lésions may become secondarily infected, compounding morbidity. There is no spécifie curative treatment for FMD. The conventional method of treating infected animais, where available, mainly involves the use of antibiotics, flunixin meglumine and mild disinfectants (Radostitis et al. 2000). In some countries FMD has been managed traditionally by use of natural soda ash solution for washing of the lésions and other communities hâve applied honey and even fmger millet flour to the lésions (Gakuya et al., 2010). There are recent reports of improved healing following topical treatment of lésions with varions agents încluding some antiseptics, phenytoin and lidocaine (Misk et al., 2015, Al-lethie et al., 2018)

Tri-Solfen™ (developed by Animal Ethics Pty Ltd) is a proprietary topical anaesthetic and antiseptie wound-care product that is applied directly to wounds in animais to mitigate pain, bleeding and infection. It contains two local anaesthetîcs; lidocaine/lignocaine, for rapid onset and bupivacaine, for prolonged duration of local anaesthetic effect, as well as adrenalin, to prevent systemic absorption of local anaesthetic actives, and cetrimide for antiseptie activity. Although not used to treat FMD cases until as described herein, Tri-Solfen™ is registered and widely used in livestock species (sheep and cattle) in Australia and New Zealand to mitigate pain due to wounds from surgical husbandry procedures such as castration, docking and dehoming and mulesing. It is applied directly to wounds using a “no touch” technique as a metered dose “spray and stay” formulation that adhères to the wound, providing a long-lasting coating over the wound to pro vide prolonged delivery of the actives. Numéro us studies hâve reported significant réductions in pain associated with wounds in sheep, cattle and pigs (Lomax et al., 2008, 2010 and 2013, 2017). In cattle, as well as mîtigating pain associated with castration, disbudding and dehoming wounds, it has also proven effective to mitigate pain associated with hoof lésions, resulting in improved management of bovine lameness (Stilwell et al., 2018).

Observational Field Trial

A supervisée! observational trial of Tri-Solfen™ use for pain mitigation was performed during an FMD outbreak in buffalo in Laos in March 2019.

An outbreak of FMD in northern Laos was reported involving Ban Muangkhi, in Luang Prabang district ofthe Luang Prabang province. The outbreak involved 99 buffalo and 37 cows of a population of 194 buffalo and 44 cows, from 136 households. Clinical examination îdentified that the animais were affected with moderate to severe FMD lésion. Ail affected animais were treated with Tri-Solfen™ product (on oral and foot lésions). The Tri-Solfen™ product is a blue coloured liquid gel matrix that contains the following components: lidocaine hydrochloride; bupivacaîne hydrochloride; adrenalin; and cetrimide. In particular, the TriSolfen™ commercial product contains:

Lidocaine hydrochloride 50g/L

Bupivacaîne hydrochloride 5g/L

Adrenalin 1: 2000

Cetrimide 5g/L

Tri-Solfen™ product was applied using the “no-touch” metered-dose spray applicator directly to coat ulcerative lésions where-ever présent in or around the mouth, nose or on the hooves. Applications were suffi ci ent to coat the wounds without run-off, with total doses between 10-30ml applied per animal.

It was intended that in the affected animais, only a third of the pedal lésions would bc treated with Tri-Solfen™, a third would be treated with chlortctracycline, and third left untreated, to enable collection of data on the rate of healing. However, once the clinical response to TriSolfen™ product was observed, ail farmers însisted that ail lésions were to be treated ‘with this new medicine that really works’.

Results

On April 12th, we requested that ail interested farmers with FMD affected animais that agreed to trial the ‘new medicine’, assemble their affected animais for examination, collection of samples and potentially treatment of the FMD lésions with the wound therapy formulation. Following the initial treatments and the observations of very positive clinical effects, ail the fanners (n=15) in the village with FMD-affected buffalo (n=99) and cattle (n=37) presented their animais for treatment. This was from a village population of 194 buffalo and 44 cows and involved only 15 of 136 households. The lowcrrate of households impacted with FMD than expected, was considered attributable to FMD vaccination that had been conducted in the village 5 months previously. Although présent in the village, no goats or pigs were reported to hâve been affected by FMD.

On arrivai at the village, the initial observations were thaï the normally quiet and passive animais were hyperaesthetic and agitated, reluctant to move, with several preferring recumbency to being restrained b y the ‘bleeding pôle’ method commonly used in developing countries where cattle crushes are largely absent. Although both F MD-vaccinai ed and unvaccinated buffalo and cattle were présent in the village, clinical signs were only observed in the unvaccinated animais.

Clinical examinations confirmed the presence of lésions of severe, subacute, ulcerative glossitis extending to in volve the nasal muvosa, plus moderate subacute ulcerative interdigital dermatitis. These lésions were considered typical of FMD of a few days’ duration. Oral ulcérations were between 5 and 15cm in diameter. Pedal lésions were most commonly located in interdigital issue but were occasionally spread across the coronary band and were between 5 and 10cm in diameter. Following aseptie collection of necrotic oral mucosal tissue from 10 animais, between 10-30 millilitres of Tri-Solfen™ product per animal was sprayed directly onto the oral and feet lésions (no teat lésions were observed). This resulted in immédiate împrovement in demeanour and locomotion of the animais. No adverse events were observed or reported.

The clinical impacts of treatment of a large number of FMD-affected large ruminants (n=l 36) with the pain-relief topical anaesthetic wound formulation Tri-Solfen™, were readily observable by ail présent on April 12th. Further, the follow-up interviews with the farmers also indîcated that the expected response and recovery from the disease was considered markedly improved from known disease progression and recovery times for FMD-affected animais following use of other treatments.

On interview a week later, ail 15 farmers advised that their animais were eating within 2 days and lésions had recovered within 5 days. They ail also advised they were keen to purchase the product for future use. Farmers described that the treatment had clearly provîded a rapid împrovement in behaviour indicative of a dramatic réduction in pain, as well as an împrovement in healing rates, with animais eating within 2 days and lésions having recovered within 3-5 days. Although the laboratory reported that the tissue samples were unsuitabie for antigen testing or submission for virus isolation, samples collected from a previous outbreak in a nearby village identified the FMD invol ved în recent outbreaks as serotype O (Panasian topo type).

As a resuit of these fmdings, the Lao veterinary Chemical authority rapidly registered the product for the purpose of treating FMD. At the time of writing, a similar positive épisode of treatment with this new therapy had recently occurred, involving a large outbreak of FMD in the adjacent province in Laos (Huaphan).

Applications were extremely well tolerated by animais and noted to resuit in a rapid improvement in habitus, locomotion, and behaviour. There were no adverse events observed on application or reported during follow-up interviews.

Farmers described that treatment provided a rapid improvement in behaviour indicative of a dramatic réduction in pain, as well as a rapid improvement in healing, with animais able to eat within 2 days and lésions having recovered within 3-5 days.

These were consîdered markedly improved from known disease progression and recovery times for FMD-affected animais.

Discussion

The pain-alleviation effects of Tri-Solfen™ product observed in this trial, along with absence of adverse effects, are highly consistent with positive pain relieving effects reported in cattle with wounds from other sources as detailed above. The flow-on effects in buffalo/cattle with FMD hâve resulted in markedly improved locomotion feeding and recovery, with dramatic potential benefits for health and welfare of cattle/buffalo and communities in FMD outbreaks.

Furthermore, a dramatic effect on the speed of resolution of the FMD lésions has been observed. This is a novel discovery indicative of likely direct anti-viral activity of Tri-Solfen™ product against FMD virus. This anti-viral activity should limit virus transmission during outbreaks. Further, the positive clinical impacts encourage farmers to seek treatment, increasing the proportion of the affected population that is administered an antiviral médication. These positive impacts are likely to influence the spread of the disease, mînimising the extent of suffering and économie losses.

Direct anti-viral activity of Tri-Solfen™ product is thought to proceed from a unique synergistîc combination of factors. As noted, FMD virus has high sensitivity to acid environments and is rapidly destroyed at pH <4. Tri-Solfen™ product has a pH of 2.7 and thus has direct viricidal activity against FMD virus when applied to exposed lésions where virus is still présent. In general, the application of acidic solutions to open wounds and ulcers, such as présent in FMD, is contraîndîcated as the acidîty may exacerbate pain and be poorly tolerated. In the case of Tri-Solfen™ product however the relatively high concentration of lidocaine (5%) applied with adrenalin is known to resuit in rapid and prolonged wound anaesthesia. This combination therefore, uniquely delivers to the lésion, a long-lasting solution with acidity suffi ci ent to destroy the virus, without causing pain to the animal.

Furthermore, lidocaine, at concentrations présent in Tri-Solfen™ product, should hâve direct viricidal effects. Although it has not been tested for activity against FMD until now, lidocaine and its pharmaceutically active salts are known to exhibît antiviral activity against

Herpes Virus in cell culture and animal model Systems at concentrations ranging from 0.5mg/ml (0.05%) to lOOmg/ml (10%) (Haines et al., 1986). Cetrimide, another active in Tn-Solfen™ product, is a quatemary ammonium antiseptie also with known antiviral activity, however may or may not hâve activity against FMD virus, as quaternary ammonium compounds are général!y considered ineffective against viruses without lipid membranes (such as FMD) (Shirai 2012).

The combined effect of the acidic pH, with the antiseptie and antiviral effects of the actives appears to hâve eradicated the virus from exposed lésions and associated inflammatory sécrétions, as well as minimising secondary bacterial infection. This, in tum, may not only reduce viral and bacterial load on the animal (and hence hasten healîng and recovery) but should also eliminate viral shedding from wounds, and prevent spread of the disease to other animais or the environment via contact with infected lésions or inflammatory sécrétions from wounds.

Such a combination of effects may be anticipated to deliver profound benefits for the well-being of animais, herds and communities affect ed b y FMD outbreaks. The potential to not only reduce animal suffering and speed recovery but also to greatly reduce the extent and severity of outbreaks may hâve profound health, welfare and économie benefits.

Since this outbreak in Laos in April 2019, clinical trials with Tri-Solfen™ product hâve been conducted in several countries in Africa, with al! reports indicating very high level (100%) acceptance by farmers, of the application of this wound pain-relief therapeutic compound to FMD lésions.

Example 2 - Effect of a topical anaesthetic formulation on viral load in lambs naturally infected with orf virus

Objectives

Orf is a highly contagions eruptive skin condition of sheep and goats, caused by a Parapoxvirus with a worldwide distribution. It affects mainly lambs and kids, with more serious outbreaks often associated with intensive husbandry, causing significant financial losses to livestock production. It is also a zoonotic disease, affecting mainly people via direct or indirect contact with infected animais. Vaccination remains the preferred option to control the disease. However, currently in Spain and many other countries, no orf vaccine is available. The treatment of this disorder referred to as Contagions Ecthyma and Scabby Mouth, involves standard hygiene practices and management of presumptive secondary infections.

Materials and methods

Fourteen one-month-old Rasa Aragonesa lambs, naturally infected with orf, were recruited from a farm where an outbreak of orf disease was occurring. The animais were divided into two cohorts: Group A (n=l 1) consisting of animais with orf lésions treated with TriSol fen™ product and Group B (n=3), a control group without treatment.

Cotton swabs were obtained before treatment (TO) and days 1 (Tl), 3 (T2) and 5 (T3) post-treatment, then submitted to direct DNA extraction and real-time PCR quantification (Exopol) or to incubation with primary tissue cultures from ovine skin fibroblasts (OSF) and Timmortalized goat embryonic fibroblasts (TIGEF). Orf quantification was performed by real time PCR on DNA from cultured cells at day 0 and 5 post-treatment. Data were analyzed using the non-parametric Wilcoxon test for paired samples and by T-Student’s test for unrelated samples.

Results

In the study carried out using quantitative PCR, no significant différences were found between day 0 pre-treatment (TO) and day 5 post-treatment (T3) (p=0.722). However, when the viral load was assessed in primary tissue cultures of ovine skin fibroblasts (OSF) and Timmortalized goat embryonic fibroblasts (TIGEF), there was a réduction in both groups between TO and T3 that was significant in the OSF cell cultures (p<0.05).

Conclusions

These results suggest that despite the presence of the viral DNA in the orf lésions at 5 days post-treatment, this may belong to inactivated virus as the viral load obtained after cell culture ofthe samples of the treated animais was significantly less than that obtained from Controls. These findings suggest that as treatment of orf lésions with Tri-Solfen™ product reduces the viral load présent in lésions, such therapy may also alter the clinical progression and transmission in outbreaks of Contagions Ecthyma.

Example 3 - Use of Tri-Solfen™ Product for Other Pathogenic Diseases

The inventors hâve made a surprising discovery that the Tri-Solfen™ gel product is particularly effect in treating and controlling FMD in bovine species when applied to a diseased area of the animal. In view of the surprising efficacy ofthe Tri-Solfen™ product, the inventors postulats that similar compositions having both viricidal and rapidly acting pain-relieving properties can be used to treat and control FMD - especially compositions that are adhesive/sticky in relatively dry diseased areas and/or foam in relatîvely wet diseased areas. The inventors also postulate that the Tri-Solfen™ product and like products can be used to treat and control other foot or mouth-type pathogenic diseases, including scabby mouth and hoof rot/footrot/foot abscess.

The inventors also postulate that the Tri-Solfen™ product and like products can be used to treat and control other viral, bacterial or fungal diseases in humans and animais - particularly those that are acid-labile, such as Herpes, Parvovirus, Rhino-vîrus and Equine rhinitis A virus, and Candida and Tinea.

The inventors further postulate that the Tri-Solfen™ product and like products can be used to treat and control diseases in humans and animais caused by infestational pathogens, such as those causing flystrike - particularly those that are acid-labile, such as screw worm and blowfly larvae.

Treatment of diseased animais or humans could be carried ont, largely as described for FMD, by applying the composition/solution topically to ail exposed lésions (denuded, excoriated, inflamed, blistered, erupted or ylcerated skin or mucous membranes) in sufficient amount to coat the surface of the lésions.

Throughout this spécification, unless in the context of usage an alternative interprétation is required, the term “comprise” (and variants thereof such as “comprising” and “comprised”) dénotés the inclusion of a stated integer or integers but does not exclude the presence of another integer or other integers.

Any reference to publications cited in this spécification is not an admission that the disclosures constitute comme n general knowledge in Australîa or in other countries.

It will be appréciâted by one of skill in the art that many changes can be made to the composition and uses exemplified above without departing from the broad ambit and scope of the invention.

References

Radostitis OM, Gay CC, Blood DC, Hinchcliff KW. Veterinary medicine: A textbook of the diseases of cattle, sheep, pigs, goats and horses. Ninth édition. London. UK: W.B. Saunders company. Harcourt publishers; 2000. pp. 1059-1066.

Knight-Jones, T.J.D., and J. Rushton. “The Economie Impacts of Foot and Mouth Disease - What Are They, How Big Are They and Where Do They Occur?” Préventive Veterinary Medicine 112, no. 3—4 (November 1, 2013): 161—73.

https://doi.Org/10.1016/i.prevetmed.20I3.07.013·

Kahn CN, Line S. The Mercks Veterinary Manual. Ninth Edition. New Jersey, USA: Merck and Company Incorporated, White Flouse Station; 2005. pp. 507-510.

Bachrach, H. L., S. S. Breese, J. J. Callis, W. R. Hess, and R. E. Patty. “Inactivation of Foot-and-Mouth Disease Virus by PH and Température Changes and by Formaldéhyde.” Proceedings of the Society for Experimental Biology and Medicine 95, no. 1 (May 1, 1957): 147-52. https://d0i.0rg/l 0.3181/00379727-95-23148.

Sellers, R. F. “The Inactivation of Foot-and Mouth Disease Virus by Chemicals and Disînfectants.” The Veterinary Record 83, no. 20 (November 16, 1968): 504—6.

Gakuya, DW, CM Mulei, and S B Wekesa. “Use of Ethnoveterinary Remedies in the Management of Foot and Mouth Disease Lésions in a Diary Herd. African Journal of Traditional, Complementary, and Alternative Medicines 8, no. 2 (December 30, 2010): 165-69. https : //w ww .ncbi .nlm .nih. go v/pmc/arti cl es/PMC3 252696/.

Misk, Nabil, Tarik Misk, and H Z Rateb. “Assessment and topical treatment of lésions of foot and mouth disease in cattle.” Assiut Vet. Med. J. Vol. 61 No. 145, April 1, 2015.

Aï-lethie, Al-Lethie, Sayed F El-Hawari, Khaled El-Khabaz, Enas Elmeligy, Arafat Khalphallah, and Usama Mahmoud. “Evaluation of clinical recovery and healing of oral lésions by 3 different therapeutic regimens in cattle with foot and mouth disease (FMD)” 64 (January 1, 2018).

Lomax, S, M Sheil, and P A Windsor. “Impact of Topical Anaesthesia on Pain Alleviation and Wound Healing in Lambs after Mulesing ” Australian Veterinary Journal 86, no. 5 (May 2008): 159-68. https://doi.Org/10.l 11 l/j.1751-0813.2008.00285.x.

Lomax, S., and P. A. Windsor. “Topical Anesthésia Mitigates the Pain of Castration in Beef Calves.” Journal of Animal Science 91, no. 10 (October 1, 2013): 4945-52. https://doi.org/10.2527/ias.2012-5984.

Lomax, S, M Sheil, and Pa Windsor. “Duration of Action of a Topical Anaesthetic Formulation for Pain Management of Mulesing in Sheep.” Australian Veterinary Journal 91, no, 4 (April 2013): 160-67. https://doi.0rg/lO.l 111/avi. 12031.

Lomax, S, H Dickson, M Sheil, and P A Windsor. “Topical Anaesthesia Alleviates ShortTerm Pain of Castration and Tail Docking in Lambs.” Australian Veterinary Journal 88, no. 3 (Mardi 2010): 67-74. https://doi.Org/10.lllVi.1751-0813.2009.00546.x.

Lomax, Sabrina, Charissa Harris, Peter A. Windsor, and Peter J. White. “Topical Anaesthesia Reduces Sensitivity of Castration Wounds in Néonatal Piglets.” PloS One 12, no. 11 (2017): e0187988.

Stilwell, G.T., A.M. Ferrador, M.S. Santos, J.M. Domingues, and N. Carolino. “Use of Topical Local Anesthetics to Control Pain during Treatment of Hoof Lésions in Dairy Cows.” Journal of Dairy Science, April 2019. https://doi.Org/10.3168/ids.2018-15 820.

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Claims (17)

1. A topical composition having both pain-relieving and biocidal properties, wherein the topical composition comprises at least one pain relieving agent that counters pain caused by an acidic nature of the composition, for use in a method of treating or controlling foot and mouth disease (FMD) in a subject, scabby mouth in a subject, hoof rot/footrot in a subject, or foot abscess in a subject caused by an acid-labile pathogen, said method comprising the step of applying to the subject a therapeutically effect amount of the topical composition.

2. A topical composition having both pain-relieving and biocidal properties, wherein the topical composition comprises at least one pain relieving agent that counters pain caused by an acidic nature of the composition, for use in a method of treating or controlling a diseased area of a subject caused by an acid-labile pathogen, wherein the disease is foot and mouth disease (FMD), scabby mouth (orf), hoof rot/footrot, or foot abscess, said method comprising the step of applying to the diseased area the topical composition.

3. The topical composition for use of claim 1 or claim 2, wherein the acid-labile pathogen is a virus, bacterium, fungus, or infestational pathogen.

4. The topical composition for use of claim 3, wherein the acid-labile pathogen is Parapoxvirus, Picornavirus, Ilerpes virus, Parvovirus, Rhinovirus, or Equine Rhinitis A virus.

5. The topical composition for use of claim 3, wherein the acid-labile pathogen is Candida fungus, Tinea fungus or insect larvae.

6. The topical composition for use of any one of the preceding daims, wherein the composition has a pH lower than about 4.0.

7. The topical composition for use of any one of the preceding daims, wherein the composition comprises at least one anaesthetic agent.

8. The topical composition for use of daim 7, wherein the at least one anaesthetic agent has biocidal activity against the pathogen.

9. The topical composition for use of claim 7 or claim 8, wherein the at least one anaesthetic agent has a rapid onset of action.

10. The topical composition for use of any one of the preceding daims, wherein the composition comprises an antiseptie agent.

11. The topical composition for use of any one of the preceding daims, wherein the composition comprises a vasoconstrictor.

12. The topical composition for use of any one of the preceding daims, wherein the composition is gel-based.

13. The topical composition for use of any one of the preceding claims, wherein the composition is a spray-on gel.

14. The topical composition for use of any one of the preceding claims, wherein the composition is coloured so that its topical application is readily détectable.

15. The topical composition for use of any one of the preceding claims, wherein the composition is biocompatible and need not be removed from a diseased area of the subject.

16. The topical composition for use of any one of the preceding claims, wherein the composition forms a long-lasting barrier over a diseased area of the subject.

17. The topical composition for use of any one of the preceding claims, wherein the composition comprises:

(a) Composition 1 comprising:

about 100 mg/ml non-crystallising liquid sorbitol (70%);

about 50.0 mg/ml lignocaine HCl;

about 5.0 mg/ml bupivacaine HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.0 mg/ml cetrimide;

about 45.0 pg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose; and optionally colourant;

(b) Composition 2 whereby lignocaine of Composition 1 is replaced by tetracaine at about 10 mg/ml - 100 mg/ml;

(c) Composition 3 comprising:

about 100 mg/ml non-crystallising liquid sorbitol (70%);

about 40.0 mg/ml lignocaine HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.0 mg/ml cetrimide;

about 36.0 μg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose; and optionally colourant;

(d) Composition 4 whereby lignocaine of Composition 3 is replaced by tetracaine at about 10 mg/ml -100 mg/ml;

(e) Composition 5 comprising:

about 100.0 mg/ml purified water sorbitol liquid 70% non-crystallising;

about 50.0 mg/ml (5%) tetracaine HCl;

about 1.5 mg/ml sodium metabisulfite;

about 5.Ü mg/ml cetrimide;

about 45.0 pg/ml adrénaline tartrate;

about 5.0 mg/ml hydroxy cellulose;

to 1 ml purified water; and optionally colourant (quaniity to suit);

(f) Composition 6 comprising: lignocaine, bupivacaine, adrénaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, Iiquid sorbitol (70%), buffer, and, optionally colourant;

(g) Composition 7 whereby lignocaine of Composition 6 îs replaced by tetracaîne at about lOmg/ml - 100 mg/ml;

(h) Composition 8 comprising: amethocaine / tetracaîne, adrénaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, Iiquid sorbitol (70%), buffer, and, optionally, colourant;

(i) Composition 9 comprising a Iiquid gel matrix that contains the following: lidocaine; adrenalin; and cetrimide, and the composition is optionally coloured, wherein said composition has a pH lower than about 4.0;

(j) Composition 10 comprising Iiquid gel matrix that contains the following: tetracaîne; adrenalin; and cetrimide, and the composition is optionally coloured, wherein said composition has a pH lower than about 4.0; or (k) Composition 11 comprising a Iiquid gel matrix that contains the following: lidocaine; bupivacaine; adrenalin; and cetrimide, and the composition is optionally coloured, wherein said composition had a pH lower than about 4.0.