Method of Disease Control

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 foot 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.

Claims

1. A method of treating a subject having a pathogenic disease caused by an acid-labile pathogen, said method comprising the step of applying to the subject a therapeutically effective amount of a topical composition having biocidal properties or both pain-relieving and biocidal properties.

2. (canceled)

3. (canceled)

4. (canceled)

5. (canceled)

6. (canceled)

7. The method of claim 1, wherein the composition comprise at least one pain relieving agent that counters pain caused by an acidic nature of the composition.

8. The method of claim 1, wherein the composition has a pH lower than about 4.0.

9. The method of claim 7, wherein the at least one pain relieving agent comprises at least one anaesthetic agent that has biocidal activity against the pathogen.

10. The method of claim 9, wherein the at least one anaesthetic agent has a rapid onset of action.

11. The method of claim 1, wherein the composition comprises an antiseptic agent.

12. The method of claim 1, wherein the composition comprises a vasoconstrictor.

13. The method of claim 1, wherein the composition is gel-based.

14. The method of claim 1, wherein the composition is a spray-on gel.

15. The method of claim 1, wherein the composition is colored so that topical application of the composition is readily detectable.

16. The method of claim 1, wherein the composition is biocompatible and need not be removed from a diseased area of the subject.

17. The method of claim 1, wherein the composition forms a long-lasting barrier over a diseased area of the subject.

18. The method of claim 1, wherein the composition is selected from the group consisting of: (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 μg/ml adrenaline tartrate; and about 5.0 mg/ml hydroxy (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 adrenaline tartrate; and about 5.0 mg/ml hydroxy cellulose; (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 non-crystallising liquid sorbitol (70%); about 50.0 mg/ml (5%) tetracaine HCl; about 1.5 mg/ml sodium metabisulfite; about 5.0 mg/ml cetrimide; about 45.0 μg/ml adrenaline tartrate; and about 5.0 mg/ml hydroxy cellulose; (f) Composition 6 comprising: lignocaine, bupivacaine, adrenaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, liquid sorbitol (70%), and buffer; (g) Composition 7 whereby lignocaine of Composition 6 is replaced by tetracaine at about 10 mg/ml 100 mg/ml; (h) Composition 8 comprising: amethocaine/tetracaine, adrenaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, liquid sorbitol (70%), and buffer; (i) Composition 9 comprising a liquid gel matrix that contains the following: lidocaine; adrenalin; and cetrimide, wherein said composition has a pH lower than about 4.0; (j) Composition 10 comprising a liquid gel matrix that contains the following: tetracaine; adrenalin; and cetrimide, wherein said composition has a pH lower than about 4.0; (k) Composition 11 comprising a liquid gel matrix that contains the following: lidocaine; bupivacaine; adrenalin; and cetrimide, wherein said composition has a pH lower than about 4.0.

19. A method of treating or controlling in a subject a pathogenic disease caused by an acid-labile pathogen selected from the group consisting of foot and mouth disease (FMD), scabby mouth, hoof rot/footrot, foot abscess, and viral lesions, said method comprising the step of applying to the subject a therapeutically effect amount of a topical composition having a pH lower than about 4.0 and comprising at least one anaesthetic agent having a rapid onset of action that has biocidal activity against the pathogen and counters pain caused by an acidic nature of the composition.

20. (canceled)

21. The method of claim 18, wherein the composition is colored so that topical application of the composition is readily detectable.

22. The method of claim 1, wherein the disease is selected from the group consisting of foot and mouth disease (FMD), scabby mouth (orf), hoof rot/footrot, and foot abscess.

23. The method of claim 1, wherein the acid-labile pathogen is selected from the group consisting of a virus, bacterium, fungus, and infestational pathogen.

24. The method of claim 21, wherein the acid-labile pathogen is selected from the group consisting of Parapoxvirus, Picornavirus, Herpes virus, Parvovirus, Rhinovirus, and Equine Rhinitis A virus.

25. The method of claim 21, wherein the acid-labile pathogen is selected from the group consisting of Candida fungus, Tinea fungus and insect larvae.

26. The method of claim 19, wherein the composition is selected from the group consisting of: (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 μg/ml adrenaline tartrate; about 5.0 mg/ml hydroxy cellulose; and colorant; (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 adrenaline tartrate; about 5.0 mg/ml hydroxy cellulose; and colorant; (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 5.0 mg/ml cetrimide; about 45.0 μg/ml adrenaline tartrate; about 5.0 mg/ml hydroxy cellulose; and colorant; (f) Composition 6 comprising: lignocaine, bupivacaine, adrenaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, liquid sorbitol (70%), buffer, and colorant; (g) Composition 7 whereby lignocaine of Composition 6 is replaced by tetracaine at about 10 mg/ml 100 mg/ml; (h) Composition 8 comprising: amethocaine/tetracaine, adrenaline, cetrimide, 2-ethyl hydroxycellulose, sodium metabisulfite, liquid sorbitol (70%), buffer, and colorant; (i) Composition 9 comprising a liquid gel matrix that contains the following: lidocaine; adrenalin; and cetrimide, and the composition is colored; (j) Composition 10 comprising a liquid gel matrix that contains the following: tetracaine; adrenalin; and cetrimide, and the composition is colored; and (k) Composition 11 comprising a liquid gel matrix that contains the following: lidocaine; bupivacaine; adrenalin; and cetrimide, and the composition is colored.

Description

BRIEF DESCRIPTION OF FIGURES

[0172] FIG. 1 shows typical lesions (mouth and hoof) and body habitus (lameness) caused by FMD, prior to treatment with Tri-Solfen™ gel product.

[0173] FIG. 2 shows how the Tri-Solfen™ gel product was applied to animals suffering from FMD, using a liquid-gel applicator.

BEST MODES FOR CARRYING OUT THE INVENTION

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

Background

[0174] Foot and mouth-disease (FMD) is a highly infectious viral disease that affects animals 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, depression, innapetence, lameness, recumbency, loss of body condition, severe mastitis and abortions (Radostitis et al. 2000).

[0175] The global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animals affected. There are direct losses due to a reduction in production and changes in herd structure; and indirect losses that relate to the significant 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 estimated as in the region 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 dependent on livestock in developing countries. The direct losses limit livestock productivity creating a food insecurity and contributing to malnutrition.

[0176] The FMD virus belongs to the Aphthovirus genus of Picornaviridae family, and its classification has seven serotypes (0, A, Asia 1, C, SAT 1, SAT 2, and SAT 3) and about 80 subtypes (Kahn et al. 2005). The serotypes have a large number of strains that have a spectrum of antigenic characteristics requiring more than one vaccine strain for each serotype (Kahn et al. 2005). There is no cross immunity between serotypes and this presents difficulties to vaccination programs (Radostitis et al. 2000).

[0177] The disease is highly contagious. The mode of transmission from infected animal to susceptible one is by inhalation, or direct contact with infected lesions or secretions. Exhaled air containing the virus infects susceptible animals via the respiratory or oral route. All body excretions and secretions from infected animal may contain the virus. Transmission to calves is via infected milk and fodder contaminated from contact with infected animals. 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 animals, spreading large volumes of virus that may spread the disease via aerosol to the cattle and other species (Kahn et al. 2005).

[0178] Disinfection during an outbreak can prevent the virus from spreading. The virus is known to be highly acid labile. FMD virus does not have 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 complete destruction (Bachrach et al., 1957). Citric acid is commonly used for disinfection of animal housing and surrounding contaminated environments (Sellers et al., 1968).

[0179] FDM lesions are extremely painful for animals and results in lameness and pain on eating and drinking. Together these result in rapid loss of condition. Ulcers often take weeks to heal and foot lesions may become secondarily infected, compounding morbidity. There is no specific curative treatment for FMD. The conventional method of treating infected animals, 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 lesions and other communities have applied honey and even finger millet flour to the lesions (Gakuya et al., 2010). There are recent reports of improved healing following topical treatment of lesions with various agents including some antiseptics, phenytoin and lidocaine (Misk et al., 2015, Al-lethie et al., 2018)

[0180] Tri-Solfen™ (developed by Animal Ethics Pty Ltd) is a proprietary topical anaesthetic and antiseptic wound-care product that is applied directly to wounds in animals to mitigate pain, bleeding and infection. It contains two local anaesthetics; 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 antiseptic 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 dehorning and mulesing. It is applied directly to wounds using a “no touch” technique as a metered dose “spray and stay” formulation that adheres to the wound, providing a long-lasting coating over the wound to provide prolonged delivery of the actives. Numerous studies have reported significant reductions in pain associated with wounds in sheep, cattle and pigs (Lomax et al., 2008, 2010 and 2013, 2017). In cattle, as well as mitigating pain associated with castration, disbudding and dehorning wounds, it has also proven effective to mitigate pain associated with hoof lesions, resulting in improved management of bovine lameness (Stilwell et al., 2018).

[0181] Observational Field Trial

[0182] A supervised observational trial of Tri-Solfen™ use for pain mitigation was performed during an FMD outbreak in buffalo in Laos in March 2019.

[0183] An outbreak of FMD in northern Laos was reported involving Ban Muangkhi, in Luang Prabang district of the 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 identified that the animals were affected with moderate to severe FMD lesion. All affected animals were treated with Tri-Solfen™ product (on oral and foot lesions). The Tri-Solfen™ product is a blue coloured liquid gel matrix that contains the following components: lidocaine hydrochloride; bupivacaine hydrochloride; adrenalin; and cetrimide. In particular, the Tri-Solfen™ commercial product contains:

[0184] Lidocaine hydrochloride 50 g/L

[0185] Bupivacaine hydrochloride 5 g/L

[0186] Adrenalin 1: 2000

[0187] Cetrimide 5 g/L

[0188] Tri-Solfen™ product was applied using the “no-touch” metered-dose spray applicator directly to coat ulcerative lesions where-ever present in or around the mouth, nose or on the hooves. Applications were sufficient to coat the wounds without run-off, with total doses between 10-30 ml applied per animal.

[0189] It was intended that in the affected animals, only a third of the pedal lesions would be treated with Tri-Solfen™, a third would be treated with chlortetracycline, and third left untreated, to enable collection of data on the rate of healing. However, once the clinical response to Tri-Solfen™ product was observed, all farmers insisted that all lesions were to be treated ‘with this new medicine that really works’.

[0190] Results

[0191] On April 12th, we requested that all interested farmers with FMD affected animals that agreed to trial the ‘new medicine’, assemble their affected animals for examination, collection of samples and potentially treatment of the FMD lesions with the wound therapy formulation. Following the initial treatments and the observations of very positive clinical effects, all the farmers (n=15) in the village with FMD-affected buffalo (n=99) and cattle (n=37) presented their animals for treatment. This was from a village population of 194 buffalo and 44 cows and involved only 15 of 136 households. The lower rate of households impacted with FMD than expected, was considered attributable to FMD vaccination that had been conducted in the village 5 months previously. Although present in the village, no goats or pigs were reported to have been affected by FMD.

[0192] On arrival at the village, the initial observations were that the normally quiet and passive animals were hyperaesthetic and agitated, reluctant to move, with several preferring recumbency to being restrained by the ‘bleeding pole’ method commonly used in developing countries where cattle crushes are largely absent. Although both FMD-vaccinated and unvaccinated buffalo and cattle were present in the village, clinical signs were only observed in the unvaccinated animals.

[0193] Clinical examinations confirmed the presence of lesions of severe, subacute, ulcerative glossitis extending to involve the nasal muvosa, plus moderate subacute ulcerative interdigital dermatitis. These lesions were considered typical of FMD of a few days' duration. Oral ulcerations were between 5 and 15 cm in diameter. Pedal lesions were most commonly located in interdigital issue but were occasionally spread across the coronary band and were between 5 and 10 cm in diameter. Following aseptic collection of necrotic oral mucosal tissue from 10 animals, between 10-30 millilitres of Tri-Solfen™ product per animal was sprayed directly onto the oral and feet lesions (no teat lesions were observed). This resulted in immediate improvement in demeanour and locomotion of the animals. No adverse events were observed or reported.

[0194] The clinical impacts of treatment of a large number of FMD-affected large ruminants (n=136) with the pain-relief topical anaesthetic wound formulation Tri-Solfen™, were readily observable by all present on April 12th. Further, the follow-up interviews with the farmers also indicated that the expected response and recovery from the disease was considered markedly improved from known disease progression and recovery times for FMD-affected animals following use of other treatments.

[0195] On interview a week later, all 15 farmers advised that their animals were eating within 2 days and lesions had recovered within 5 days. They all also advised they were keen to purchase the product for future use. Farmers described that the treatment had clearly provided a rapid improvement in behaviour indicative of a dramatic reduction in pain, as well as an improvement in healing rates, with animals eating within 2 days and lesions having recovered within 3-5 days. Although the laboratory reported that the tissue samples were unsuitable for antigen testing or submission for virus isolation, samples collected from a previous outbreak in a nearby village identified the FMD involved in recent outbreaks as serotype O (Panasian topotype).

[0196] As a result of these findings, the Lao veterinary chemical authority rapidly registered the product for the purpose of treating FMD. At the time of writing, a similar positive episode of treatment with this new therapy had recently occurred, involving a large outbreak of FMD in the adjacent province in Laos (Huaphan).

[0197] Applications were extremely well tolerated by animals and noted to result in a rapid improvement in habitus, locomotion, and behaviour. There were no adverse events observed on application or reported during follow-up interviews.

[0198] Farmers described that treatment provided a rapid improvement in behaviour indicative of a dramatic reduction in pain, as well as a rapid improvement in healing, with animals able to eat within 2 days and lesions having recovered within 3-5 days.

[0199] These were considered markedly improved from known disease progression and recovery times for FMD-affected animals.

Discussion

[0200] 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 have resulted in markedly improved locomotion feeding and recovery, with dramatic potential benefits for health and welfare of cattle/buffalo and communities in FMD outbreaks.

[0201] Furthermore, a dramatic effect on the speed of resolution of the FMD lesions 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 medication. These positive impacts are likely to influence the spread of the disease, minimising the extent of suffering and economic losses.

[0202] Direct anti-viral activity of Tri-Solfen™ product is thought to proceed from a unique synergistic 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 lesions where virus is still present. In general, the application of acidic solutions to open wounds and ulcers, such as present in FMD, is contraindicated as the acidity 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 result in rapid and prolonged wound anaesthesia. This combination therefore, uniquely delivers to the lesion, a long-lasting solution with acidity sufficient to destroy the virus, without causing pain to the animal.

[0203] Furthermore, lidocaine, at concentrations present in Tri-Solfen™ product, should have direct viricidal effects. Although it has not been tested for activity against FMD until now, lidocaine and its pharmaceutically active salts are known to exhibit antiviral activity against Herpes Virus in cell culture and animal model systems at concentrations ranging from 0.5 mg/ml (0.05%) to 100 mg/ml (10%) (Haines et al., 1986). Cetrimide, another active in Tri-Solfen™ product, is a quaternary ammonium antiseptic also with known antiviral activity, however may or may not have activity against FMD virus, as quaternary ammonium compounds are generally considered ineffective against viruses without lipid membranes (such as FMD) (Shirai 2012).

[0204] The combined effect of the acidic pH, with the antiseptic and antiviral effects of the actives appears to have eradicated the virus from exposed lesions and associated inflammatory secretions, as well as minimising secondary bacterial infection. This, in turn, may not only reduce viral and bacterial load on the animal (and hence hasten healing and recovery) but should also eliminate viral shedding from wounds, and prevent spread of the disease to other animals or the environment via contact with infected lesions or inflammatory secretions from wounds.

[0205] Such a combination of effects may be anticipated to deliver profound benefits for the well-being of animals, herds and communities affected by 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 have profound health, welfare and economic benefits.

[0206] Since this outbreak in Laos in April 2019, clinical trials with Tri-Solfen™ product have been conducted in several countries in Africa, with all reports indicating very high level (100%) acceptance by farmers, of the application of this wound pain-relief therapeutic compound to FMD lesions.

Example 2—Effect of a Topical Anaesthetic Formulation on Viral Load in Lambs Naturally Infected with Orf Virus

[0207] Objectives

[0208] Orf is a highly contagious 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 animals. 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 Contagious Ecthyma and Scabby Mouth, involves standard hygiene practices and management of presumptive secondary infections.

[0209] Materials and Methods

[0210] 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 animals were divided into two cohorts: Group A (n=11) consisting of animals with orf lesions treated with Tri-Solfen™ product and Group B (n=3), a control group without treatment.

[0211] Cotton swabs were obtained before treatment (T0) and days 1 (T1), 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 T-immortalized 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.

[0212] Results

[0213] In the study carried out using quantitative PCR, no significant differences were found between day 0 pre-treatment (T0) 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 T-immortalized goat embryonic fibroblasts (TIGEF), there was a reduction in both groups between T0 and T3 that was significant in the OSF cell cultures (p<0.05).

CONCLUSIONS

[0214] These results suggest that despite the presence of the viral DNA in the orf lesions at 5 days post-treatment, this may belong to inactivated virus as the viral load obtained after cell culture of the samples of the treated animals was significantly less than that obtained from controls. These findings suggest that as treatment of orf lesions with Tri-Solfen™ product reduces the viral load present in lesions, such therapy may also alter the clinical progression and transmission in outbreaks of Contagious Ecthyma.

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

[0215] The inventors have 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 of the Tri-Solfen™ product, the inventors postulate 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 relatively 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.

[0216] 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 animals particularly those that are acid-labile, such as Herpes, Parvovirus, Rhino-virus and Equine rhinitis A virus, and Candida and Tinea.

[0217] The inventors further postulate that the Tri-Solfen™ product and like products can be used to treat and control diseases in humans and animals caused by infestational pathogens, such as those causing flystrike particularly those that are acid-labile, such as screw worm and blowfly larvae.

[0218] Treatment of diseased animals or humans could be carried out, largely as described for FMD, by applying the composition/solution topically to all exposed lesions (denuded, excoriated, inflamed, blistered, erupted or ulcerated skin or mucous membranes) in sufficient amount to coat the surface of the lesions.

[0219] Throughout this specification, unless in the context of usage an alternative interpretation is required, the term “comprise” (and variants thereof such as “comprising” and “comprised”) denotes the inclusion of a stated integer or integers but does not exclude the presence of another integer or other integers.

[0220] Any reference to publications cited in this specification is not an admission that the disclosures constitute common general knowledge in Australia or in other countries.

[0221] It will be appreciated 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

[0222] Radostitis O M, Gay C C, Blood D C, Hinchcliff K W. Veterinary medicine: A textbook of the diseases of cattle, sheep, pigs, goats and horses. Ninth edition. London. UK: W.B. Saunders company. Harcourt publishers; 2000. pp. 1059-1066. [0223] Knight-Jones, T. J. D., and J. Rushton. “The Economic Impacts of Foot and Mouth Disease What Are They, How Big Are They and Where Do They Occur?” Preventive Veterinary Medicine 112, no. 3-4 (Nov. 1, 2013): 161-73. [0224] Kahn C N, Line S. The Mercks Veterinary Manual. Ninth Edition. New Jersey, USA: Merck and Company Incorporated, White House Station; 2005. pp. 507-510. [0225] 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 Temperature Changes and by Formaldehyde.” Proceedings of the Society for Experimental Biology and Medicine 95, no. 1 (May 1, 1957): 147-52. [0226] Sellers, R. F. “The Inactivation of Foot-and Mouth Disease Virus by Chemicals and Disinfectants.” The Veterinary Record 83, no. 20 (Nov. 16, 1968): 504-6. [0227] Gakuya, D W, CM Mulei, and S B Wekesa. “Use of Ethnoveterinary Remedies in the Management of Foot and Mouth Disease Lesions in a Diary Herd.” African Journal of Traditional, Complementary, and Alternative Medicines 8, no. 2 (Dec. 30, 2010): 165-69. [0228] Misk, Nabil, Tarik Misk, and H Z Rateb. “Assessment and topical treatment of lesions of foot and mouth disease in cattle.” Assiut Vet. Med. J. Vol. 61 No. 145, Apr. 1, 2015. [0229] Al-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 lesions by 3 different therapeutic regimens in cattle with foot and mouth disease (FMD)” Assiut Vet. Med. J. 64, no. 156 (Jan. 1, 2018): 89-95. [0230] 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. [0231] Lomax, S., and P. A. Windsor. “Topical Anesthesia Mitigates the Pain of Castration in Beef Calves.” Journal of Animal Science 91, no. 10 (Oct. 1, 2013): 4945-52. [0232] 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. [0233] Lomax, S, H Dickson, M Sheil, and P A Windsor. “Topical Anaesthesia Alleviates Short-Term Pain of Castration and Tail Docking in Lambs.” Australian Veterinary Journal 88, no. 3 (March 2010): 67-74. [0234] Lomax, Sabrina, Charissa Harris, Peter A. Windsor, and Peter J. White. “Topical Anaesthesia Reduces Sensitivity of Castration Wounds in Neonatal Piglets.” PloS One 12, no. 11 (2017): e0187988. [0235] 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 Lesions in Dairy Cows.” Journal of Dairy Science, April 2019. [0236] Haines et al. Antiviral pharmaceutical preparations and methods for their use—U.S. Pat. No. 4,628,063 45: Dec. 9, 1986. [0237] Shirai, Junsuke. “Disinfection Against the Outbreaks of Foot and Mouth Disease (FMD).” Journal of Disaster Research 7, no. 3 (Apr. 1, 2012): 264-73.