Liquid dressing compositions and uses thereof

Abstract

A liquid dressing composition comprising shellac, an anti-infective metal active agent, and a solvent is described for use in the treatment or prevention of infection and / or wounds. When topically applied to a subject, the composition can form a barrier to provide an easily applied barrier to protect lesions and other wounds from foreign infectious agents.

Description

[Technical Field]

[0001] The present invention relates to a liquid dressing composition and its medical uses, particularly for preventing and / or treating wounds and / or infections. The present invention further relates to a device for delivering or applying the liquid dressing composition. [Background technology]

[0002] There is an unmet need for liquid dressings that are easy to apply, effective, remain sterile, and protect lesions and other wounds from foreign infectious agents. Also, when topical application of antibiotics (or other materials) to a lesion is required, such a liquid dressing should ideally "contain" such materials in their environment, preventing their loss from the outside, and therefore increasing the efficacy of the treatment.

[0003] Digital dermatitis (DD) is an infectious disease of the hoof that affects as many as 40% of dairy cows. It is caused by indoor rearing of dairy cows, which is necessary due to the increased dietary requirements of highly efficient milking cows. It is characterized by painful ulcerative or vegetative lesions, which cause lameness, reduce milk production, and increase mortality, resulting in economic inefficiencies and animal welfare concerns. Treatment of digital dermatitis is challenging because the wounds associated with digital dermatitis are typically chronically infected with multiple species of anaerobic bacteria, particularly spirochetes. Animal hooves are often in constant contact with fecal slurry, which also allows for disease spread among cattle within a herd and reinfection of previously treated animals.

[0004] Existing treatments for digital dermatitis include the application of topical antibiotics or metal-based antimicrobial agents to the lesions. However, all of these treatments are not very effective because the hooves are in constant contact with fecal slurry, resulting in rapid loss of the antimicrobial or antibiotic agent to the external environment. It is impractical to re-bandage the antibiotic or similar treatment after each application to prevent its loss from the applied area of ​​the animal to the external environment. Such bandages must be removed after several days anyway, or they may have negative effects as a precursor to infection. Aside from the economic loss, these repeated cycles of infection and antibiotic application promote the development of antibiotic-resistant bacteria, which is a serious public health problem.

[0005] In addition to traditional antibiotics, other antimicrobial treatments include the use of formalin or ionic copper footbaths, or the application of copper and zinc EDTA gel. Treating heavily infected herds with footbaths can help control the spread of infection, but does not treat the infected animals. This also has the disadvantage of generating large amounts of environmentally toxic waste, which is expensive to dispose of in a safe manner. Formalin is also carcinogenic. Copper and zinc EDTA gel has limited antimicrobial activity and, like antibiotics, requires multiple applications, and in severe infections, additional bandaging. Some formulations of copper and zinc EDTA gel are highly viscous, requiring application with a brush, with the attendant risk of cross-infection between treated animals. These products lack long-lasting qualities beyond relying on their viscosity, and therefore their longevity on wounds is expected to be limited in such problematic environments. Given these disadvantages, effectively treating digital dermatitis continues to be a problem in the industry.

[0006] U.S. Patent No. 8,648,082 (Jaleva, LLC) describes a biological dressing for treating skin lesions such as athlete's foot, impregnated with a composition containing mastic gum resin and an antimicrobial, antiviral, or anti-inflammatory agent, applied in a volatile solvent. The mastic gum resin used is a tree-derived resin, such as benzoin. This is then covered with a conventional dressing.

[0007] U.S. Patent No. 5,178,870 (Explore) describes an antimicrobial composition comprising a low-viscosity varnish (sandarac) and an antimicrobial compound dissolved in ethanol. This composition is coated onto teeth to inhibit bacterial growth in the oral cavity. EP 0900560A (Oka) describes a tooth coating composite comprising an antimicrobial agent and shellac dissolved in alcohol to cover tooth surfaces with a very thin, almost tacky coating to help prevent periodontal disease. US 2010 / 0297043 describes a cosmetic composition for coating skin containing a natural resin and a non-drying or semi-drying oil as an emollient. WO 2019 / 0176124 discloses a porous cosmetic skin coating composition containing shellac or leucine, a solvent, and silica.

[0008] Alzahrani et al. (Journal of International Medical Research, 41(3)795-803, 2013, doi:10.1177 / 0300060513483391) describe the effect of applying gauze impregnated with shellac to diabetic patients with dry gangrene to prevent infection and progression to wet gangrene. WO2011 / 129781 (Bedir and Alhayani) offers a similar proposal to use shellac to mummify dead tissue in diabetic foot ulcers by placing the patient's foot inside a treatment chamber under pressure in situations where amputation is not possible.

[0009] Antic et al. (Meat Science, 88:498-502, 2011) describe the application of shellac to bovine hides to limit microbial cross-contamination of raw bovine meat during the hide-skinning operation. Summary of the Invention

[0010] Generally, the present invention provides liquid dressing compositions capable of forming a self-supporting barrier when topically applied to a subject for the prevention and / or treatment of wounds and / or infections, including, for example, wounds and / or infected sites or lesions associated with digital dermatitis. In some cases, the dressing is expected to be anti-infective and thus resistant to biofilm formation from the environment or from the wound itself. Advantageously, the barrier may be hydrophobic, and in some circumstances, the dressing may be capable of releasing its antimicrobial ions to the wound at concentrations compatible with antimicrobial activity in the wound itself. Alternatively, the liquid dressing compositions of the present invention may not themselves have substantial microbial repellent activity but may help prevent microbial colonization of the wound by providing a physical barrier to infection. Typically, the liquid dressing composition comprises shellac and a metal-based active in a volatile solvent, such as ethanol, and is capable of forming a self-supporting, solid hydrophobic barrier after topical application as a liquid to a subject. The metal-based active can improve barrier function and, optionally, additionally, provide inherent repellent properties against environmental pathogens. Because shellac compositions that do not contain metal-based actives are soluble under alkaline conditions (>pH 7), the compositions of the present invention are surprisingly capable of forming a barrier that can withstand high pH, ​​such as that found in alkaline environments such as fecal slurries.

[0011] In some cases, metal-based active agents can impart anti-infective properties to the liquid dressing compositions of the present invention. Alternatively, or in addition, the metal active agent can help improve one or more properties of the liquid dressing composition, for example, improving the barrier properties of the composition and / or physicochemical properties such as the viscosity of the composition.

[0012] Alternatively, or in addition, the liquid dressing composition used in accordance with the methods of the present invention provides a self-adhesive, fast-setting chemical barrier capable of sealing in a previously applied treatment to a subject, for example, at the site of a wound, lesion, or infection. Thus, the compositions of the present invention can be used in combination with other agents, such as antibiotics, anti-infectives, or agents that promote lesion healing, or other materials with potential benefits to the host. The barrier formed by the composition can also protect lesions, such as digital dermatitis, resulting from the environment, while providing a temporary barrier that can withstand extreme conditions, such as alkaline slurries, yet still self-degrade over time. The barrier formed by the compositions of the present invention can have the additional advantage of not requiring additional forms of dressing material or dressing to physically support barrier function or efficacy. In preferred applications, the components of the antimicrobial composition and the barrier formed therefrom are compatible with the food chain.

[0013] Thus, the present invention is aimed at improving animal welfare, ensuring optimal milk production, and reducing losses of antimicrobial agents to the environment and food chain, as well as finding application for the prevention and treatment of wounds and / or infections in other situations as further described below. The compositions of the present invention are also biocompatible, and their pH can be controlled to maintain the composition at a pH above 3, preferably above 4, and most preferably above 4.5, allowing for safe, biologically compatible topical use.

[0014] Thus, in one aspect, the present invention provides a liquid dressing composition for use in treating or preventing infection and / or wounds, the liquid dressing composition comprising shellac, a metal active agent, and a solvent, and capable of forming a barrier when topically applied to a subject. In some aspects, the liquid dressing composition consists of shellac, a metal active agent, and a solvent. Alternatively, or in addition, the barrier formed when the composition is applied to a subject is a hydrophobic barrier.

[0015] Although these compositions have been developed specifically to provide treatment for digital dermatitis, particularly as it occurs in cattle, the compositions and medical uses described herein have application in the treatment of human and non-human animal subjects, as well as for the treatment of other types of wounds and / or infections and topical requirements.

[0016] In a further aspect, the present invention provides a liquid dressing composition for use in treating or preventing digital dermatitis, the composition comprising shellac, a metal active agent, and a solvent, the composition being capable of forming a barrier when topically applied to a subject.

[0017] In a further aspect, the present invention provides the use of a liquid dressing composition in the manufacture of a medicament for treating or preventing infection and / or wounds, the composition comprising shellac, a metal active agent and a solvent, the composition being capable of forming a barrier when topically applied to a subject.

[0018] In a further aspect, the present invention provides the use of a liquid dressing composition in the manufacture of a medicament for treating or preventing digital dermatitis, the composition comprising shellac, a metal active agent, and a solvent, the composition being capable of forming a barrier when topically applied to a subject.

[0019] In a further aspect, the present invention provides a method for treating or preventing infection and / or wounds, comprising the steps of: (a) topically applying to a subject a liquid dressing composition comprising shellac, an anti-infective metal active agent, and a solvent, the composition being capable of forming a barrier when topically applied to a subject; and (b) allowing the solvent to evaporate so that the composition forms the barrier.

[0020] In a further aspect, the present invention provides a method for treating or preventing digital dermatitis, comprising the steps of: (a) topically applying to a subject a liquid dressing composition comprising shellac, an anti-infective metal active, and a solvent, the composition being capable of forming a barrier when topically applied to a subject; and (b) allowing the solvent to evaporate so that the composition forms the barrier.

[0021] In a further aspect, the present invention provides a method for treating or preventing a localized infection in a subject, the method comprising the steps of: (a) topically applying to the subject a liquid dressing composition comprising shellac, a metal active agent, and a solvent, the composition being capable of forming a barrier when topically applied to a subject; and (b) allowing the solvent to evaporate so that the composition forms the barrier.

[0022] In the medical applications and methods described herein, the topically deposited barrier produced by the compositions of the present invention may be employed in conjunction with conventional treatment, for example, by using the barrier composition over an area or location on a subject where an antibiotic or other anti-infective, a therapeutic agent to promote healing, or other therapeutic agent has been previously applied. This means that the barrier provides a protective layer that keeps the previously applied therapeutic agent contained. In practice, it may be advantageous to have an ointment or other substance pre-applied to the skin or wound that acts to prevent "solvent sting" of the liquid dressing compositions of the present invention when applied topically.

[0023] Generally, the compositions used in the present invention have the advantages of being easily applied as a liquid or gel, rapidly curing to form an insoluble, water-resistant (hydrophobic) barrier, and / or being sufficiently robust to provide resistance to mechanical damage and harsh environmental pressures. While these advantages are particularly useful for veterinary applications of the present invention, as well as for human applications, given their ease of application, a robust barrier is required, for example, for military, leisure, or sports use, or other traumatic situations such as burns and surgery. The properties of the compositions, such as their ability to form a self-supporting barrier and therefore not requiring the use of bandages or other dressings, are particularly advantageous for use in harsh environments, such as outdoor activities or sports, such as hiking, camping, fishing, rock climbing, or canoeing, or for military activities or work involving sudden trauma. This is because the barrier formed by the compositions generally has sufficient physical strength to withstand physical damage (e.g., knocks), is water-resistant, and can be conveniently transported and applied in a simple liquid format. The present invention may be an all-in-one solution for a localized problem, at least until further intervention can be performed, ie the material is also useful for first aid.

[0024] The barrier-forming properties of the compositions used in the present invention also make them suitable for rapid wound or lesion or plaque coverage.This can be useful in time-saving situations, such as surgical interventions, or for accessing difficult-to-reach areas of the subject's body, and can help avoid the need for repeated dressing applications, especially in anatomical areas that are otherwise difficult to dress, thereby improving patient compliance.Surgical wounds, diabetic wounds and ulcers, intertrigo or skin fold dermatitis, skin lesions, traumatic lesions, abscesses, and small scratches or lesions (such as those caused by animal fights) are examples where a simple but effective chemical barrier may be preferable to other treatment options.

[0025] In a further aspect, the present invention is also particularly useful for surgical wounds, skin lesions, ulcers, cuts, abrasions, and other traumatic wounds. The present invention may be used, for example, by doctors, surgeons, nurses, other medical professionals, military personnel, extreme sports enthusiasts, veterinarians, livestock farmers, pet owners, or zoos and similar facilities. Its versatility and ease of application allow for rapid use and access to difficult areas of the body, particularly lesions, wounds, or sores that may become infected if left untreated. Examples of topical conditions that can be treated according to the present invention include folliculitis, cellulitis, hot bath folliculitis, impetigo, ringworm, rain scabies, foot and mouth disease, bluetongue, scabies, and / or lice infestation.

[0026] In a further embodiment, unpleasant tasting compounds may be added to compositions intended for veterinary use to discourage animals from biting or chewing at the barrier site. In some cases, such taste deterrent compounds may also be added to compositions intended to treat small children.

[0027] Preferably, the composition used in the present invention also provides a barrier that can inhibit the further development of infection at the site of existing wounds, lesions or plaques or at risk areas.In one example, the composition of the present invention can be used to treat or prevent acne, for example, by preventing bacterial infection of acne lesions.Other types of wounds that can be treated according to the present invention include pustules, blisters, sores, fissures and maceration.

[0028] The compositions of the present invention may also be used to treat surgical wounds, including incisional wounds, excision wounds, as well as wounds from different types of surgery, such as appendectomy, breast biopsy, Caesarean section, cholecystectomy, coronary artery bypass, dilation and curettage, skin graft, hemorrhoidectomy, hip replacement, hysterectomy, hysteroscopy, inguinal hernia repair, knee replacement, lower back pain surgery, mastectomy, colectomy, prostatectomy, reconstruction, or tonsillectomy.

[0029] Treatment of "wound" as used herein includes chronic wounds, acute wounds, lesions, cuts, sores, bites, ulcers, rashes, burns, abscesses, bumps, warts, cracked skin, blisters, scaly skin, pimples, vesicles, nodules, plaques, fistulas, scabs, scratches, wheals or scars.

[0030] Examples of topical diseases and injuries that may be associated with or caused by wounds and therefore can be treated or prevented by the invention described herein include dermatitis, insect bites, other animal bites, traumatic wounds, post-surgical wounds, self-inflicted wounds, skin cancer, burns, electrical burns, chemical burns, radiation burns, ice burns, pox, bruises, papules, pustules, comedones, sores, pitting, emphysematous cysts, scales, petechiae, viral infections, bacterial infections, fungal infections, yeast infections, acne, seborrhea, scabies, insect hypersensitivity, allergic eczema, non-allergic eczema, hyperpigmentation, glossitis, nail disease, viral rashes, tattoo-related lesions, and dandruff.

[0031] Additional skin diseases and injuries that can be treated or subsequent wounds prevented by the compositions disclosed herein include, but are not limited to, lacerations, abrasions, puncture wounds or abrasions, first-degree burns, second-degree burns, third-degree burns, frostbite, epidermal necrotizing dermatitis, stasis dermatitis, dyshidrotic dermatitis, seborrheic dermatitis, contact dermatitis, psoriasis, cutaneous leishmaniasis, measles, hand, foot and mouth disease, athlete's foot, onychomycosis, cutaneous lupus erythematosus, tick bites, flea bites, tick bites, eczema, ear plaque, papillomatosis, Buruli ulcer, Besnoitiosis, urticaria, myiasis, contagious pustular dermatitis, digital dermatitis (dematitis), photosensitization, sheep pox, goat pox, chicken pox, swinepox, worm nodule disease, and the like. disease), canine pyoderma, cowpox, sarcoid, onchocerciasis, heartworm, intertrigo, dermatophilosis, folliculitis, impetigo, ringworm, rain scab, foot rot, foot and mouth disease, bluetongue, ovine scabies, eczema and / or pediculosis, Malassezia dermatitis, carbuncles, boils, eosinophilic granuloma with collagen degeneration, skin inflammation, red leg syndrome, melanoma, non-melanoma skin cancer, contagious ecthyma, skin or gill flukes, scale or gill infections, winter ulcer disease, crustacean parasites, feather plucking, scaly face, foot mites, feather mites, back and wing diseases, feather loss, feather injuries, skin neoplasms, lice, flies, blood-sucking fly, mites, digital swarms, split keels keel), wingtip edema, ichthyosis, myiasis, cracked coat, shedding disorder, scale rot, blister disease, erythema, petechiae, ecchymoses, leeches, gum disease, cellulitis, tinea versicolor, candidiasis, herpes zoster, hot-bath folliculitis, filariasis caused by W. loa, peeling skin syndrome, rosacea, adult linear IgA disease, Dühring's disease, Grover's disease, pemphigus foliaceus, pemphigus nodularis, pemphigus vegetans, pemphigus vulgaris, acne gangrenous, Fox-Fordyce disease, alopecia folliculitis, perforated nasal folliculitis, lichen planus, red crescent lunulae), perforated folliculitis, mucosal squamous cell carcinoma, leukoplakia, scrotal tongue, acute necrotizing ulcerative gingivitis, pyogenic granuloma, xanthomas of the eyelids, trench fever, sweaty sock syndromesyndrome), pseudofolliculitis barbae, perioral dermatitis, paronychia, epidermolysis pitting, necrobiosis lipoidica, Morgellons disease, bubonic plague, diabetic ulcer, erythrasma, hidradenitis suppurativa, jellyfish sting, lichen planus, or lichen simplex chronicus.

[0032] Lesions that may be treated or prevented by the present invention may have a variety of appearances and contours, for example, linear, circular, nummular, target, serpentine, herpetic and / or zoster-like.

[0033] In some cases, superficial skin conditions, if untreated, can lead to progression to more severe wounds, for example, a rash can lead to self-inflicted skin perforations caused by scratching, biting, rubbing, or other physical actions by the subject. Thus, the present invention can be used with such superficial skin conditions.

[0034] In some cases, the compositions of the present invention can help maintain healthy skin and thus prevent lesions in the subject. Thus, examples of skin care actions of the compositions of the present invention include, but are not limited to, cleansing, hydrating, moisturizing, refining, smoothing, exfoliating, softening, restoring, unclogging, sunscreen, sun protection, heat protection, moisturizing, absorbing, desensitizing, rejuvenating, removing impurities, reducing skin irritation, soothing, and refreshing.

[0035] For the avoidance of doubt, skin care, infection and / or wound treatment or prevention includes, but is not limited to, preventative or corrective measures, treatments or adjunct treatments on the skin, mucous membranes, hair and / or nails. In veterinary subjects, treatment or prevention of infection and / or wounds includes treatment of the skin, mucous membranes, hair, coat, nails, bones, claws, hooves, coat, scales, horns, feathers, tusks, antlers or teeth of live veterinary subjects.

[0036] Preferably, the compositions of the present invention are made from safe (e.g., GRAS-compliant) biocompatible ingredients, for example, ingredients already present in the food chain. For veterinary use, this is important for livestock-derived foods (milk, cheese, meat) that enter the human food chain. This also means that the barrier produced using the compositions of the present invention can be left to slowly self-degrade, avoiding the need for medical technicians, veterinarians, or dairy farmers to remove it at the end of the treatment protocol. Other advantages include inherent safety properties for application and increased appetite for use by users.

[0037] In some applications, the composition of the present invention is colored either by the ingredients of the composition or by including dyes or other pigments in the composition.Advantageously, this can be used to allow color tracking when applying the composition (for example, to determine the extent of application to the subject's body), and / or to allow the subsequent biodegradation of the barrier, for example, to determine when the composition needs to be reapplied.Examples of pigments that can be used according to the present invention include synthetic pigments such as Patent Blue V, or Brilliant Blue FCF, or Brilliant Black BN, or Sunset Yellow FCF, or Quinoline Yellow, or Ponceau 4R, or indigo carmine, natural pigments such as lutein, or riboflavin, or caramel, or chlorophyllin, or carotene, or betanin, or anthocyanin, and / or mineral pigments such as titanium dioxide, or iron oxide and iron hydroxide.

[0038] As demonstrated in the examples, the raw materials used to produce the compositions of the present invention are relatively inexpensive and do not involve complex synthesis, as manufacturing is accomplished by dissolving and mixing the various components in ethanol or a similar solvent, followed by ready-to-use packaging.

[0039] In use, treatment using the compositions of the present invention will typically involve optionally applying a pre-administered therapeutic agent, e.g., an antibiotic compound, to a treatment site on a subject, and then applying a barrier composition to that same site so that a hydrophobic barrier forms via evaporation of the volatile solvent. In the case of treatment of bovine digital dermatitis, or indeed for other situations, the method may include an initial step of cleaning the treatment site (i.e., the hoof or leg of an animal with digital dermatitis).

[0040] Embodiments of the present invention will now be described by way of example, and not limitation, with reference to the accompanying drawings, in which: It is anticipated, however, that further various forms and embodiments of the invention will be apparent to those skilled in the art in view of the present disclosure.

[0041] "And / or," as used herein, shall be construed as a specific disclosure of two specified features or components, each with or without the other. For example, "A and / or B" shall be construed as a specific disclosure of (i) A, (ii) B, and (iii) each of A and B, when each is individually set forth herein.

[0042] Unless the context dictates otherwise, the feature descriptions and definitions set forth above are not limited to any particular aspect or embodiment of the invention, but apply equally to all aspects and embodiments described. [Brief explanation of the drawings]

[0043] [Figure 1] Loss of antibiotic spray into simulated slurries in the presence or absence of a protective barrier ex vivo. [Figure 2] Metal release (Zn and Cu) from the barrier. Samples were collected directly from the contact lethality assay after 24 hours at 30°C in LB (bacteriological medium) with gentle agitation. The top graph shows absolute concentrations (ppm), whereas the bottom graph shows relative release. [Figure 3] Contact lethality results. K12 in Log CFU / ml after 24 hours of incubation with E. coli in LB. F0 consisted of a shellac-only composition, which had the same bacterial growth as the control experiment (no shellac). Note: For materials (F4, F6, F8, F11, F13, F14, F26, F27 and F30, see Table 7) that had 1.7 Log CFU / ml as the detection limit and therefore had this result, no bacterial colonies formed. [Figure 4] Improvement in mobility score (n=7) between day 0 and day 7 of treatment in vivo. Statistical analysis was performed via one-sided Wilcoxon matched-pairs test. DETAILED DESCRIPTION OF THE INVENTION

[0044] Compositions of the Invention Shellac or shellac derivatives may be used in the compositions of the present invention, and references to "shellac" herein include both shellac and shellac derivatives. This may include wax-free shellac, dewaxed shellac, dewaxed and bleached shellac, dewaxed and bleached shellac, shellac esters, or wax-containing shellac. Additionally, the shellac used may be in powder, flake, chunk, or, in certain cases, supplied as a solution. Shellac is a resin secreted by female lac insects on trees and is commonly produced in India and Thailand. It is processed and typically sold as dried flakes, or can be dissolved in a solvent such as alcohol to produce liquid shellac. Shellac is readily commercially available from suppliers such as Sigma or AF Suter & Co. Preferably, the barrier compositions of the present invention comprise 10% w / w to 70% w / w shellac, more preferably 20% w / w to 70% w / w shellac, more preferably 30% to 70% shellac, more preferably 35% to 70% shellac, more preferably 35% to 60% shellac, and most preferably 40% to 60% shellac, where the amount of shellac is expressed relative to the % w / w amount in the composition before it is applied. In some embodiments, it is preferred that the type of shellac used is one that is approved as a food additive.

[0045] Advantageously, the pH of the composition of the present invention can be controlled, for example, by using a component with buffering properties.This is generally done so that the composition has a pH suitable for topical application to a subject.A pH of more than pH 3, preferably more than pH 4, most preferably more than pH 4.5 is suitable for safe and biologically compatible topical use.As the upper limit of pH, the composition used according to the present invention preferably has a pH of less than pH 9.0, more preferably less than pH 8.5, more preferably less than pH 8.0, more preferably less than pH 7.4, most preferably less than pH 6.5.

[0046] The inventors have found that the use of shellac or shellac derivatives is preferable to the use of other resins which have some undesirable properties, such as rosin, which presents allergy concerns. Generally, the compositions used in the present invention can be obtained by mixing the ingredients in a volatile solvent to produce a homogeneous mixture. It is usually advantageous to dissolve the metal active substance in the volatile solvent, followed by any additives, and then add the shellac last. This order allows the metal compound to be properly dissolved before adding the additives (e.g., PEG, TEC, and glycerol) and helps avoid the resulting mixture becoming inhomogeneous due to clumps of shellac, for example. This order of steps also ensures that the additives are well dispersed before adding the shellac, as some additives may precipitate shellac at higher concentrations before being dispersed in the composition. In some cases, the metal active substance is expected to be an anti-infective metal active substance.

[0047] In most cases where additives were added to the compositions described herein, values ​​were recorded by mass. Consequently, concentrations are sometimes referred to as mMolal (mmol / kg) rather than mM (mmol / L). Additionally, when % is used, it refers to mass w / w %.

[0048] In the present invention, the hydrophobic barrier produced using the composition of the present invention is "self-supporting," i.e., it is mechanically robust and does not require stabilization with a structural matrix, such as a woven or nonwoven matrix, such as a bandage or gauze, as used in the prior art. However, in some cases, it may be desirable to provide a barrier with increased mechanical strength, and in these situations, the barrier composition may further comprise fibers. Examples of fiber components include, but are not limited to, cellulose, preferably 1.0 to 15 wt %, more preferably 2.5 to 5.0 wt % cellulose.

[0049] Preferably, the volatile solvent used to produce the composition of the present invention is ethanol, acetone-water mixture, isopropanol, propanol, or butanol, and combinations thereof. The use of ethanol, acetone-water mixture, propanol, butanol, and isopropanol may be preferred for biocompatibility reasons. When alcohol is used as a solvent, it may be primary, secondary, or tertiary alcohol.

[0050] Examples of other volatile solvents (e.g., those with a boiling point below 100°C) that can be employed in the present invention include ethers such as diethyl ether or tetrahydrofuran, ketones such as methyl ethyl ketone, primary alcohols such as methyl alcohol, ethyl alcohol, or benzyl alcohol, secondary alcohols such as isopropanol, tertiary alcohols such as tert-butyl alcohol, acetone-water mixtures, ethyl acetate-ethanol mixtures, and / or glycol mixtures with any of the above-mentioned solvents. Other possible solvents include aldehydes such as benzaldehyde, carboxylic acids such as acetic acid, lactic acid, or propionic acid, ethers such as diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, ethylene glycol butyl ether, ethylene glycol ethyl ether, ethylene glycol methyl ether, or dioxane, ketones such as cyclohexanone, primary alcohols such as amyl alcohol, secondary alcohols such as sec-butyl alcohol or isobutylcarbinol, tertiary alcohols such as diacetone alcohol, terpenoids such as citronellol, and / or glycol mixtures with any of the above.

[0051] In some cases, the metal active substance may be an anti-infective metal active substance, while in other cases, the metal active substance may be added for other purposes, such as to modulate the viscosity of the composition. The degree of anti-infective properties imparted by the metal active substance may also depend on the concentration of the metal active substance in the composition. The anti-infective element may have any chemical speciation, including, for example, a combination thereof, such as Ag, Cu, Zn, Fe, Se, Al, Cr, Mo, Ga, Co, Bi, Sb, Li, Ge, Ti, and / or Ce, more preferably Cu, Zn, Ag, Fe, and / or Mo, and most preferably Cu or Zn. A more general list of metal active materials includes Ag, Cu, Zn, Fe, Se, Al, Cr, Mo, Ga, Co, Bi, Sb, Li, Ge, Ti, Ce, Na, K, Rb, Be, Mg, Ca, Sr, Sc, Ti, Zr, Hf, V, Nb, W, Mn, Re, Ru, Ir, Pd, Pt, In, La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, and / or Er, more preferably Cu, Zn, Fe, Mg, Ca, Sr, Ti, Mn, Ce, Mo, Ga, Zr, Gd, La, Sm, Gd, Er, W and / or Al, more preferably Cu, Zn, Fe, Mg, Ca, Sr, Ti, Al, and / or Mn, most preferably Cu, Zn, Mg, Ca, and / or Fe.

[0052] Examples of anti-infective metal actives used to produce the anti-infective compositions of the present invention include copper, zinc, silver, bismuth, and / or cobalt compounds, and may include selenium. Metal actives include copper carboxylate complexes or zinc carboxylate complexes. Examples of suitable anti-infective metal active compounds include copper chloride, copper acetate, copper oxide, copper oxohydroxide, copper hydroxide, zinc chloride, zinc acetate, nano-zinc oxide, normal zinc oxide, iron chloride, aluminum chloride, molybdenum acetate, or kaolin. In some cases, combinations of anti-infective metal actives may be used, such as a combination of copper and zinc, which may optionally further include selenium. In other cases, one or more anti-infective-based metal actives may be combined with one or more metal-based excipients, which may or may not have some anti-infective properties. As shown in the examples, the anti-infective metals used in these materials may or may not result in a final anti-infective composition. This will depend on the exact formulation, including but not limited to, the concentration and selection of the metal, as well as its chemical speciation. If having anti-infective properties is not desirable for these compositions, other metals may be used to modulate the physical properties of the final composition.

[0053] Preferably, the metal active agent or excipient is present in the composition at a concentration of 5 mMol to 3.5 mol, more preferably 25 mMol to 3.5 mol, more preferably 50 mMol to 3.5 mol, more preferably 75 mMol to 3.5 mol, more preferably 100 mMol to 3.5 mol, more preferably 100 mMol to 2 mol, more preferably 100 mMol to 1.5 mol, more preferably 100 mMol to 1 mol, more preferably 100 mMol to 750 mMol, more preferably 100 mMol to 500 mMol, more preferably 150 mMol to 500 mMol, and most preferably 150 to 350 mMol. In some cases, the metal active agent or anti-infective metal active agent has the advantage of increasing the viscosity and / or barrier thickness of the composition compared to a corresponding composition excluding the metal active agent, i.e., a composition comprising shellac alone.

[0054] Specific examples of copper metal active substances include copper EDTA, copper tartrate, copper citrate, copper adipate, copper benzoate, copper maleate, copper malonate, copper gluconate, copper aspirin, copper citraconate, copper fumarate, copper glutarate, clioquinol copper, copper salicylaldehyde benzoylhydrazone, copper picolinate, copper alanine, copper arginine, copper aspartate, copper gluconate, copper glycinate, copper histidine, copper isoleucine, copper leucine, copper lysine, copper methionine, copper phenylalanine, copper Copper proline, copper serine, copper threonine, copper tyrosine, copper valine, copper formate, copper propionate, copper isovalerate, copper pivalate, copper phenylacetate, copper cyanoacetate, copper chloroacetate, copper hydroxyacetate, copper 2-hydroxypropanoate, copper 2-hydroxybutanoate, copper quinate, copper pyruvate, copper ethoxyacetate, copper sulfate, copper thiocyanate, copper sulfide, copper bromide, copper fluoride, copper nitrate, copper carbonate, copper carbonate hydroxide, copper selenite, copper peroxide, copper tetraammine sulfate, copper phosphate, or elemental copper.

[0055] Specific examples of zinc metal active substances include zinc EDTA, zinc tartrate, zinc citrate, zinc adipate, zinc benzoate, zinc maleate, zinc malonate, zinc gluconate, zinc aspirin, zinc citraconate, zinc fumarate, zinc glutarate, zinc clioquinol, zinc salicylaldehyde benzoylhydrazone, zinc picolinate, zinc alanine, zinc arginine, zinc aspartate, zinc gluconate, zinc glycinate, zinc histidine, zinc isoleucine, zinc leucine, zinc lysine, zinc methionine, zinc phenylalanine, zinc proline, zinc serine, zinc threonine, zinc tyrosine, zinc valine, zinc formate, zinc propionate, zinc isovalerate, zinc pivalate, zinc hydroxyacetate, zinc sulfate, zinc phosphate, or elemental zinc.

[0056] It is expected that those skilled in the art will know that, in general, grinding an otherwise insoluble metal active material can aid in the formulation of a homogeneous material. It has been found that the compositions used in accordance with the present invention have a viscosity suitable for topical application to a subject while forming a protective hydrophobic barrier. Examples of suitable viscosities include viscosities greater than 50 cP, more preferably greater than 75 cP, more preferably greater than 100 cP, more preferably greater than 200, more preferably greater than 500, more preferably greater than 750, more preferably greater than 1000 cP, more preferably greater than 2500 cP, more preferably greater than 5000 cP, and most preferably greater than 10,000 cP. Generally, for compositions applied as a spray, the viscosity may be 10 cP to 3000 cP. For compositions applied as a paint, more viscous compositions may be used, for example, compositions having a viscosity greater than 1000 cP, more preferably greater than 2000 cP. Viscosity measurements may be performed at room temperature, i.e., 25°C. In some embodiments, the addition of the metal active material serves to increase the viscosity of the composition, for example, by at least 50%, more preferably at least 100%, even more preferably at least 200%, and most preferably at least 500%, as measured at 25° C., compared to a corresponding composition without the metal active material.

[0057] In use, the compositions of the present invention may be used in combination with or co-administered with other therapeutic or non-therapeutic agents, such as one or more antibiotics and / or therapeutic agents. In some cases, the additional active agent may be an antibiotic preparation, an antimicrobial agent (e.g., oxytetracycline or chlorhexidine), and / or a hemostatic active substance. In some embodiments, the composition can be applied to a site where one or more antibiotics or other anti-infective or therapeutic agents, disinfectants, or other agents have already been applied, thereby providing a protective barrier over the treatment site together with the therapeutic agent, helping to prevent the loss of the therapeutic agent, for example, due to washing away from contact with the environment. Alternatively, or in addition, the compositions of the present invention may be formulated to contain one or more antibiotics. Examples of antibiotic compounds approved for use in animals include various natural compounds, such as penicillin (produced by fungi of the Penicillium genus), cephalosporins, and semi-synthetic modifications of lactam antibiotics, such as carbapenems. Antibiotics still isolated from living organisms include aminoglycosides, whereas other antibiotics, such as sulfonamides, quinolones, and oxazolidinones, are produced only by chemical synthesis. Many antibacterial compounds are classified based on their chemical / biosynthetic origin: natural, semisynthetic, and synthetic. Ansamycins are a class of antibiotics that inhibit bacterial RNA polymerase and have excellent efficacy against Gram-positive and selective Gram-negative bacteria. Examples include rifamycin, rifampin, rifampicin, rifabutin, rifanetin, rifalazil, ABI-1657, and their analogs. Beta-lactams include penicillins (e.g., benzylpenicillin, amoxicillin), carbapenems (e.g., meropenem, imipenem), and cephalosporins (e.g., cephalexin, cefuroxime). Naturally occurring aminoglycosides, such as streptomycin, neomycin, tobramycin, gentamicin, or semi-synthetic derivatives, such as amikacin, netilmicin.Fluoroquinolones (e.g., ciprofloxacin, norfloxacin), macrolides (e.g., erythromycin, clarithromycin), ketolides (e.g., telithromycin), tetracyclines such as tetracycline, oxytetracycline, chlortetracycline, or doxycycline, glycopeptides (e.g., vancomycin, teicoplanin), lincomycins (e.g., lincomycin, pirlimycin), amphenicols (e.g., thiamphenicol, chloramphenicol), streptogramins (e.g., pristinamycin), oxazolidinones (e.g., linezolid, cycloserine), pleuromutilins (e.g., tiamulin, retapamulin), mupirocin, fusidic acid, polymyxin B, or bacitracin are often used topically and can also be used in combination with the invention described herein. Preferred antibiotics, such as those employed topically for hoof and superficial wound infections (eg, digital dermatitis), include chlortetracycline, oxytetracycline, and thiamphenicol.

[0058] In some cases, the compositions described herein can be used in combination with metal-based therapeutic agents, such as copper (II) sulfate, copper EDTA, zinc EDTA, zinc pyrithione, silver, silver nitrate, silver sulfadiazine, and mixtures of these metal-based therapeutic agents. In this situation, the compositions for use in the present invention can be applied after the application of the metal-based therapeutic agent.

[0059] In some cases, topical antimicrobial agents (non-antibiotics) may be used, such as parabens, biguanides such as chlorhexidine, diamines, hydrogen peroxide, phenols such as triclosan, halophenols such as chloroxylenol, iodine, or benzoates such as benzoic acid.

[0060] In some cases, antifungal agents may be used.Examples of antifungal agents include polyenes (for example, amphotericin B, nystatin), azoles such as fluconazole, ketoconazole, clotrimazole, miconazole, terconazole, butoconazole, clotrimazole, econazole, oxiconazole, tioconazole, or sulconazole, allylamines and related compounds such as terbinafine, tolnaftate, butenafine, or naftifine, morpholine-related compounds such as amorolfine, and also ciclopirox, gentian violet, selenium sulfide, zinc pyrithione, zinc undecylenate, and piroctone olamine.

[0061] In some cases, antiprotozoal drugs may be used, such as metronidazole (which is also an antibiotic) or nitazoxanide (which is also active as an antiviral agent). In some cases, combinations of the above antibiotics or other therapeutic agents, such as neomycin, polymyxin, and bacitracin, can also be used to increase efficacy.

[0062] In some cases, the antimicrobial composition preferably further comprises one or more hydrophilic additives to be used as plasticizers or to promote barrier formation, or both, after application of the composition to a treatment site on a subject or individual. Examples of hydrophilic additives include TEC (in which case the composition preferably comprises 2-30%, more preferably 3-20%, and most preferably 5-15%), polyalkylene glycol, e.g., PEG such as PEG-400 (in which case the composition preferably comprises 2-30%, more preferably 3-20%, and most preferably 5-15%), glycerol (in which case the composition preferably comprises 1-20%, more preferably 2-15%, and most preferably 3-10%), hexylene glycol (in which case the composition preferably comprises 1-20%, more preferably 2-15%, and most preferably 3-10%), and triacetin (in which case the composition preferably comprises 1-20%, more preferably 2-15%, and most preferably 3-10%).

[0063] The inventors have observed that in some cases, a non-solvent for shellac (i.e., a solution in which shellac is insoluble) may be mixed with a solution containing shellac at the time of application to induce the immediate formation of a solid barrier. For example, when an ethanolic solution of shellac is contacted with a sufficient amount of glycerol, the barrier immediately forms. In situ mixing can also be achieved using a two-component cartridge, where one chamber contains the shellac solution and another non-solvent (see Example 2.1), such as PEG or glycerol. The inventors have also observed that this process requires a larger amount of non-solvent compared to its use as a hydrophilic additive, as described above. For example, upon mixing the two components, the resulting PEG concentration is expected to be 30-75%, most preferably 33-66%. As an additional example, the resulting glycerol concentration is expected to be 20-75%, most preferably 25-50%.

[0064] In some cases, the anti-infective composition preferably further comprises one or more hydrophobic barrier-enhancing substances, for example, to enhance the water resistance of the barrier layer formed when the anti-infective composition is applied to a subject or individual and at least some of the volatile solvent has evaporated. Examples of hydrophobic barrier-enhancing substances include decanoic acid (in which case the composition preferably comprises 2-30%, more preferably 3-20%, and most preferably 4-10%), octanoic acid (in which case the composition preferably comprises 2-20%, more preferably 3-15%, and most preferably 5-12%), oleic acid (in which case the composition preferably comprises 2-20%, more preferably 3-15%, and most preferably 5-12%), or lauric acid (in which case the composition preferably comprises 2-20%, more preferably 3-15%, and most preferably 5-12%).

[0065] In some cases, the composition preferably further comprises one or more buffers to inhibit degradation of the barrier, which might otherwise degrade too rapidly. This is particularly advantageous in digital dermatitis, since the barrier degrades relatively quickly in contact with alkaline fecal slurry, and the inclusion of an additional buffer slows down the degradation of the barrier. This is because shellac can become water-soluble under alkaline conditions, and fecal slurry has a pH of about pH 8, which has a buffering capacity of about 100 mM, which is expected to contribute to the degradation of the barrier over time due to the solubilization of shellac. For this reason, compositions used in accordance with the present invention preferably have a pH above 4.0 for topical application, but may be maintained below pH 6.0 or 6.5 during use, provided such losses can be avoided. One elegant solution to this problem is to include a buffer in the composition, preferably one with a pKa of 4.0 to 6.5. Examples of suitable buffering components include carboxylic acids, including monocarboxylic acids such as benzoic acid, lauric acid, glycolic acid, levulinic acid, lactic acid, pyruvic acid, or glyceric acid; adipic acid (preferably 0.5% to 5%); azelaic acid (preferably 0.5% to 5%); dicarboxylic acids such as succinic acid, pimelic acid, or decanoic acid; or tricarboxylic acids such as citric acid. Those skilled in the art will recognize that various categories of molecules, including but not limited to amino acids, fatty acids, and alphahydroxy acids, may contain carboxylic acid pendant groups. Such molecules may also be suitable as buffers in the present invention.

[0066] In some cases, the composition preferably further comprises an anti-inflammatory agent or a complexing agent to enhance the loading or solubility of the metal active agent. Examples of suitable anti-inflammatory agents or complexing agents are salicylic acid, sodium salicylate, and propionic acid, or chemical derivatives thereof.

[0067] In some cases, the composition preferably further comprises a hemostatic agent. For applications where wound treatment involves blood clotting, such as acute wound treatment, e.g., military, sports, or acute veterinary use, kaolin, aluminum sulfate, or zeolite may be included. Examples of suitable concentrations of hemostatic agents such as kaolin include 1% to 40%, more preferably 2% to 35%, more preferably 3 to 30%, and most preferably 5 to 30%.

[0068] In some cases, the composition further comprises an analgesic, such as acetylsalicylic acid, salicylic acid, trolamine salicylate, magnesium salicylate, and / or methyl nicotinate. Natural analgesics, such as capsaicin, may also be added.

[0069] In some cases, the composition further comprises an anti-inflammatory agent, such as ibuprofen, diclofenac, felbinac, ketoprofen, and / or piroxicam. In some cases, the composition further comprises a soothing agent, such as menthol, eucalyptus oil, cinnamon oil, and / or camphor.

[0070] In some cases, the composition further comprises an anti-itch agent, such as hydrocortisone. Preferably, all ingredients of the composition are approved food or feed additives and / or qualify as GRAS agents ("Generally Recognized As Safe").

[0071] Formulations and Uses The compositions for use according to the present invention can be employed for the prevention or treatment of infections and / or wounds. When the compositions are used to treat or prevent infections, the infections can be bacterial, fungal, parasitic, or viral infections. Generally, the compositions are particularly suitable for treating or preventing bacterial infections, i.e., the compositions are antimicrobial compositions. Generally, compositions used according to the present invention, comprising shellac and a metal active or an anti-infective metal active in a volatile solvent, are capable of forming a hydrophobic barrier when topically applied to a human or non-human animal (e.g., mammalian) subject. When topically applied to a subject, the compositions of the present invention generally form a solid interface. However, this is not required, as contact with environmental moisture, or, in the case of treating livestock such as cattle, contact with fecal slurry, will result in the immediate formation of a hydrophobic barrier, making the present invention well suited for use in problematic environments, such as digital dermatitis (e.g., bovine digital dermatitis) and udder infections, such as udder ulcerations, udder dermatitis, or udder lesions. Additional veterinary uses include the use of the liquid dressing composition for sealing or dehorning teats.

[0072] The anti-infective compositions used in medical and veterinary applications according to the present invention can be used in general wound management, especially when infection is a potential burden. Examples include chronic ulcers and acute wounds, including traumatic or postoperative wounds. Examples of wounds for which the compositions of the present invention are useful include open wounds (lacerations, abrasions, puncture wounds, or abrasions), or chronic ulcers such as diabetic ulcers, Buruli ulcers, or other types of wounds, such as traumatic lesions, abscesses, and small scratches, when used to aid in the treatment of burns, surgical wounds, or foot rot. The compositions used according to the present invention are also advantageous in aiding the treatment of closed wounds that have already undergone healing by providing a protective environment and further preventing reinfection. Therefore, the compositions can also be used in wound prevention. In some embodiments, the liquid dressing composition is expected to be supplied in the form of an over-the-counter (OTC) composition. Other veterinary conditions that can be treated in accordance with the present invention include folliculitis, impetigo, ringworm, rain scab, foot rot, foot and mouth disease, bluetongue, eczema and / or pediculosis.

[0073] The anti-infective compositions of the present invention are well suited for veterinary applications, where wound management in animals can be particularly problematic. These problems include high microbial loads (both pathogenic and non-pathogenic) in the surrounding environment and the fact that frequent wound cleaning and reapplication of antimicrobial agents are generally impractical or excipients. The use of standard dressings is generally discouraged due to the problem of accumulated feces or other waste products. In contrast to the use of dressings, which require isolation of the animal for dressing application and removal, the compositions used in the present invention can be used to form a robust, self-supporting hydrophobic barrier that protects the wound and is robust enough to contain any pre-applied antibiotic or antimicrobial agent, but that degrades over time. This reduces the need for frequent reapplication of antibiotics or antimicrobial agents and obviates the need for subsequent barrier removal. The present invention also allows for the use of reduced antibiotic doses. Typically, the hydrophobic barrier formed from the compositions of the present invention requires 1 to 20 days, more preferably 2 to 10 days, and most preferably 3 to 7 days, to degrade. The rate of degradation is usually higher when the barrier is in contact with a fecal slurry.

[0074] In some cases, the compositions used in the present invention are substantially free of silicon dioxide (silica). Alternatively or in addition, the composition used in the present invention does not substantially contain softening agents, such as oil, for example, non-drying or semi-drying oil.Examples of softening agents are triglyceride oils, for example, triglyceride oils of animal, vegetable, mineral or synthetic origin.Examples of suitable non-drying or semi-drying oils include pine oil, eucalyptus oil, tea tree oil, rosehip oil, soybean oil, coconut oil, castor oil, olive oil, safflower oil and sunflower oil.

[0075] In this application, "substantially free" means that the compositions of the present invention are free of the stated component, or if they do contain, they contain minimal or trace amounts of the component in question, e.g., less than 1.0% w / w, more preferably less than 0.5% w / w, and even more preferably less than 0.1% w / w.

[0076] In some cases, the compositions of the present invention consist of or consist essentially of the stated components. One advantage of the compositions of the present invention is that the barrier is non-porous to water. When the composition forms a barrier with pores, the pores are generally small in size, for example, pores with an average diameter of 1 μm or less.

[0077] The compositions used in the present invention can be applied using any device capable of delivering a viscous liquid. Generally, the viscous nature of a composition means that it is not sprayable. Prior art sprays on dressings can form relatively thin films, and the aerosols used to deposit films are disadvantageous in that they cannot retain a high percentage of solids, have a high drying time:mass of deposited solids ratio, and are generally non-biodegradable. Therefore, the compositions of the present invention are preferably administered using a squeezable bottle, a squeezable or collapsible tube, an adhesive dispenser, a cartridge and plunger kit using a manual, pneumatic, or electric cartridge gun, or a liquid dispenser. In some cases, it may be preferable to administer the composition using a disposable spatula, brush, or the like. In some cases, application may be combined with dispensing the composition onto the area to be treated, for example, by using a brush or other applicator.

[0078] In other cases, the compositions of the present invention may be formulated for spray delivery, which may be useful in circumstances where a thinner dressing is appropriate to aid in wound treatment or to help manage infection.

[0079] Thus, in a further aspect, the present invention provides a device for applying a liquid dressing composition for use in the treatment of infections and / or wounds, comprising: a first chamber containing a composition comprising shellac and a metal active (e.g., an anti-infective metal active) in a volatile solvent as defined herein and a second chamber containing a non-solvent; a mixing chamber in communication with the first and second chambers; an actuation means for delivering the composition and the non-solvent to the mixing chamber to provide a mixed composition; and an applicator in communication with the mixing chamber for applying the mixed composition to a location on a target; wherein the composition is capable of forming a hydrophobic barrier when topically applied to a subject.

[0080] In these devices, examples of non-solvents include glycerol or polyalkylene glycols, such as PEG. These devices may take the form of a dual or two-component cartridge applicator device. In another embodiment, the present invention provides a device for delivering the composition in the form of a spray, for example, a device using pressurized gas or air delivery.

[0081] The liquid dressing compositions of the present invention may be formulated for use as antimicrobial agents, for example, to treat or prevent bacterial or microbial infections and / or for wound treatment. Thus, in addition to the materials described above, the compositions of the present invention may contain pharmaceutically acceptable excipients, carriers, buffers, stabilizers, or other materials known to those skilled in the art. Such materials are expected to be non-toxic and not significantly interfere with the efficacy of the solid phase material for the application in question.

[0082] For example, it is known in the art that the incorporation and subsequent release of antimicrobial agents into a dressing is beneficial for preventing the invasion and proliferation of microorganisms at the wound site. Effectively / surprisingly, the compositions of the present invention can maintain a sterile dressing (through contact lethality) by minimizing the release of antimicrobial metals, thereby avoiding side effects and / or off-target effects. This differs from previous compositions in the art that employed resins as a delivery matrix for antimicrobial agents. In another embodiment, the compositions of the present invention may be formulated to release their antimicrobial metal ions into the wound at concentrations that are active in the wound environment.

[0083] The term "anti-infective" as used herein includes the treatment or prevention of infections caused by bacteria, fungi, parasites or viruses. The term "antimicrobial" as used herein includes the treatment or prevention of infections caused by gram-negative and gram-positive microorganisms, and particularly refers to preventing the entry of microorganisms from the environment into the wound or the colonization of the dressing by microorganisms, including Spirochaete species, Escherichia species such as E. coli, Staphylococcus species such as S. epidermis, S. aureus and methicillin-resistant S. aureus ("MRSA"), Bacillus species, For example B. subtilis or B. anthracis, Pseudomonas species, for example P. aeruginosa, Vibrio species, for example V. fisheri, Streptococcus species, for example S. zooepidemicus, S. equi, S. suis, S. uberis, S. pyogenes and S. pneumoniae, Klebsiella species, for example K. pneumoniae pneumoniae, Micrococcus species, for example M. luteus, Clostridium species, for example C. difficile or C. perfringens, Acinetobacter species, for example A. baumannii, Mycobacterium species, for example M. tuberculosis and M. bovis, Salmonella species, Erysipelothrix species, for example E. rhusiopathiae or E. insidiosa, Corynebacterium species, for example C.minutissimum, Leptospira spp., e.g., L. interrogans, Cutibacterium spp., e.g., C. acnes, Gardnerella spp., e.g., G. vaginalis, Campylobacter spp., e.g., C. fetus, Klebsiella spp., e.g., K. pneumoniae, K. rhinoscleromatis, Capnocytophaga species such as C. canimorsus, Vibrio species such as V. vulnificus, Pasteurella species such as P. multocida, Aeromonas species such as A. hydrophila, Eikenella species such as E. corrodens, Mycoplasma species such as M. pneumoniae, Calymmatobacterium species such as C. dallanulomatis (C granulomatis, Helicobacter spp., for example H. pylori, Clostridium spp., for example C. perfringens, Listeria spp., for example L. monocytogenes, Treponema spp., for example T. carateum or T. vincentii or T. maltophilum or T. lecithinolyticum, Bartonella spp., for example B. henselae, Nocardia spp., for example N. brasiliensis (N.brasiliensis, Yersinia species, for example Y. pestis, Serratia species, for example S. marcescens, Burkholderia species, for example B. pseudomallei, Actinomyces species, for example A. israelii, Borrelia species, for example B. burgdorferi, Enterococcus species, for example E. faecalis, or fungi such as Candida species, for example C. albicans, Malassezia species lassezia species, for example M. furfur and M. pachydermatis, Trycophyton species, for example T. rubrum or T. interdigitale, Microsporum species, for example M. canis, M. equinum, M. audouinii, M. gypseum, or M. nanum, Epidermophyton species, for example E. floccosum, Fusarium species, for example F. solani, Rhizopus microspores, Rhizomucor spp. such as R. pusillis, Mucor spp. such as M. indicus, Syncephalastrum spp. such as S. racemosumm, Cunninghamella spp. such as C. bertholletiae, Apophysomyces spp. such as A. elegans, Lichtheimia spp. such as L. corymbifera,corymbifera, Saxenaea spp., for example S. erythrospora, Aspergillus spp., for example A. glaucus, Blastomyces spp., for example B. dermatitidis, Coccidioides spp., for example C. immitis, Cryptococcus spp., for example C. neoformans, Histoplasma spp., for example H. capsulatum ulatum, Cochliobolus species such as C. lunatus, Cladophialophora species such as C. bantiana, Exophiala species such as E. jeanselmei, Pyrenochaeta species such as P. romeroi, Pneumocystis species such as P. romeroi, Pneumocystis species such as P. ulcerans, ... is species, such as P. jirovecii, Paracoccidioides species, such as P. brasiliensis, Sporothrix species, such as S. schenckii, Talaromyces species, such as T. marneffei, or parasites such as Sarcoptes species , for example S. scabiei, Leishmania species, for example L. donovani, L. braziliensis, L. panamensis, Ancylostomatidae, for example Ancylostoma species or Necator species, Strongyloides species, for example S.stercoralis, Onchocerca species such as O. volvulus, Diptera larvae such as Lucilia sericata, Protophormia terraenovae, Cochliomyia hominivorax, Cordylobia anthropophaga, or Sarcophaga bercaea, Balamuthia species such as B. mandrillaris, or Acanthamoeba species, or viruses such as papillomaviruses, enteroviruses such as Coxsackieviruses, Molluscum contagiosum, Wallicerovirus, or Herpesvirus. The term "antimicrobial," as used herein, is understood to apply to substances such as those that inhibit the attachment of microorganisms to surfaces, kill microorganisms, and / or inhibit the reproduction of microorganisms, particularly those that prevent the entry of microorganisms from the environment into a host, or the colonization or biofilm formation of a dressing by microorganisms. The term "microorganism" is understood to include all microorganisms, including bacteria as detailed above, as well as fungi such as yeasts, archaea, and protists and viruses. The terms "microbial" and "antimicrobial" are to be interpreted accordingly.

[0084] In some embodiments, the liquid dressing compositions of the present invention can be used to treat or prevent infections and / or wounds where the infection is caused by a virus. Examples of viruses that can infect a subject and that can be treated or prevented using the compositions of the present invention include respiratory viruses, gastrointestinal viruses, and skin viruses.

[0085] Respiratory viruses: rhinoviruses, canine adenoviruses (CAV1 and CAV2), adenoviruses (HAdV B and C), canine parainfluenza virus (type 5), bovine parainfluenza virus type 3, influenza viruses (e.g., influenza A viruses H3N2, H1N1, H2N2, H5N1, H1N2, H9N2, H7N9, and influenza B viruses), respiratory syncytial viruses (human RSV A, human RSV B, bovine RSV, pneumonia virus of mice), naturally circulating alpha- and beta-coronaviruses (e.g., 229E, OC43, SARS-CoV-2 (COVID-19), SARS-CoV-1, MERS-CoV, and HCoV) HKU1, canine CoV, feline CoV, bovine CoV), Epstein-Barr virus, Coxsackie A virus (e.g., A21, A24), cytomegalovirus, human metapneumovirus, herpes simplex virus, bovine herpesvirus type 1, varicella-zoster virus, and enterovirus D68.

[0086] Gastrointestinal viruses: rotaviruses (e.g. human groups A, B and C, avian and bovine), bovine adenoviruses, human adenoviruses (HAdV-types F40, 41 and HAdV-type G52), bovine viral diarrhea virus, caliciviruses and astroviruses.

[0087] Cutaneous viruses: measles virus, rubella virus, parvovirus B19, canine parvovirus, human herpesvirus 6, echoviruses (9 and 16), coxsackieviruses (A9, A16, B5, etc.), Epstein-Barr virus, cytomegolavirus, dengue virus, Zika virus, chikungunya virus, monkeypox virus, cowpox virus, bovine and human papillomavirus, foot-and-mouth disease virus, hand-foot-and-mouth disease virus.

[0088] The group of viruses includes respiratory viruses, gastrointestinal viruses and skin viruses.Accordingly, the liquid dressing composition for use in aiding in the treatment or prevention of infection and / or wounds, wherein the infection is caused by a virus of the Adenoviridae family, such as human mastadenovirus A, or HAdV-F40, or HAdV-F41, or HAdV-G52, or AdV-B, or HAdV-C, or canine adenovirus 1, or a virus of the Caliciviridae family, such as norovirus, or feline calicivirus, or sapovirus, or a virus of the Coronaviridae family, such as canine CoV, or feline CoV, or bovine CoV, or porcine epidemic diarrhea virus, or HCoV229E, or HCoVOC43, or SARS CoV-1, or SARS CoV-2, or MERS-CoV, or HCoV HKU1, or by a virus of the Flaviviridae family, such as dengue fever virus, or Japanese encephalitis, or yellow fever virus, or hepatitis C virus, or Zika virus, or West Nile virus, or pestivirus C, or by a virus of the Herpesviridae family, such as Marek's disease virus, boar herpesvirus-1, equine herpesvirus-1, or herpes simplex virus 2, or varicella-zoster virus, or Epstein-Barr virus, or cytomegalovirus, or by a virus of the Matonaviridae family, such as rubella virus, or by a virus of the Orthomyxoviridae family by viruses such as influenza A virus H3N2, or influenza A virus H1N1, or influenza A virus H2N2, or influenza B virus, or by viruses of the papillomaviridae family, such as human or bovine papillomavirus type 1, or type 2, or type 6, or type 11, or type 18, or type 31, or type 33, or type 45, or type 52, or type 58, or by viruses of the paramyxoviridae family, such as bovine parainfluenza virus type 3, or measles, or mumps, or avian orthovulavirus 1,or by a small ruminant morbillivirus, or by a virus of the Parvoviridae family, such as HBoV1, or parvovirus B19, or canine parvovirus, or porcine parvovirus, or by a virus of the Picornaviridae family, such as poliovirus, or enterovirus D68, or rhinovirus A, or rhinovirus B, or rhinovirus C, or human coxsackievirus A9, or human coxsackievirus B5, or by a virus of the Pneumoviridae family, such as human metapneumovirus or human It is caused by a virus of the Poxviridae family, such as lumpy skin disease virus, sheeppox virus, goatpox virus, monkeypox virus, or cowpox virus, or by a virus of the Reoviridae family, such as bluetongue virus, African horse sickness virus, rotavirus A, rotavirus B, or rotavirus C, or by a virus of the Phenuiviridae family, such as Rift Valley fever virus, or by a virus of the Togaviridae family, such as chikungunya virus.

[0089] A liquid dressing composition for use in the treatment or prevention of infection and / or wounds, wherein the infectious agent can induce a viral hemorrhagic fever, such as Marburg virus, or Ebola virus, or an Arenavirus, such as Lassa virus.

[0090] The uses of the liquid dressing compositions of the present invention will vary depending on whether the composition is intended to treat or prevent infection in a human or animal subject. However, in addition to applications related to the treatment or prevention of conditions in human subjects, the present invention also has applications in the veterinary field, for example, for use in treating non-human animals, more particularly non-human mammals, such as companion animals such as dogs, cats, and horses, as well as livestock species such as cattle, goats, and sheep. Rare / orphan species (e.g., mums, rare use and minor use species), including those used in agriculture, such as alpacas or llamas, exotic pets, zoo animals, and safari park animals, may also benefit from these new materials. In one specific application, the antimicrobial compositions of the present invention are used to treat bovine digital dermatitis, more particularly in dairy cows. In further applications, the antimicrobial compositions of the present invention are used for udder dermatitis and post-amputation claw amputation in cattle; foot rot in sheep; and mud fever in horses. The compositions of the present invention can also be used to protect wounds and stitches after surgery, such as castration, in dogs, cats, and horses, as well as sheep, pigs, and cattle. Examples of species that can be treated using the present invention include humans, cattle, water buffalo, yaks, pigs, horses, sheep, goats, llamas, alpacas, deer, donkeys, zebu cats, zebras, elephants, orangutans, chimpanzees, gorillas, lemurs, gibbons, baboons, chickens, turkeys, ducks, emus, geese, ostriches, cats, dogs, ferrets, gerbils, hamsters, chinchillas, rats, rabbits, reptiles, amphibians, parrots, canaries, galliformes, anseriformes, and passerines.

[0091] In some veterinary applications where animals may bite, chew, or peck at the barrier formed by the compositions of the present invention, it may be desirable to include a taste deterrent in the composition, e.g., a bitter ingredient, to discourage such behavior and extend the life of the barrier or eliminate the need for reapplication.

[0092] In embodiments where the composition is intended for administration to a subject, for example, in the treatment of a wound or skin infection, the precise nature of the carrier or other ingredients may be related to the mode or route of administration of the composition, typically via a topical route.

[0093] In one embodiment, the compositions of the present invention may be formulated for topical administration, useful in treating wounds, ulcers, or treating or preventing bacterial infections. Application of the present invention using topical products aids in therapeutic use for wound healing.

[0094] In some cases, an effective amount of the antimicrobial compositions herein may be formulated for topical application to the skin, hair, nails, hide, fur, feathers, or wattles of a human or animal. Generally, "topical administration," according to the present invention, does not include application to the teeth of a subject.

[0095] For example, in some cases where the composition is used to treat or prevent a respiratory viral infection, the composition may be administered intranasally, for example, using a loaded swab that lines the inside of the nasal passages or follows the outside of the nose.

[0096] Example The following examples are provided to illustrate preferred embodiments of the invention and are not intended to limit the scope of the invention. [Example]

[0097] Example 1: Primary Formulation Example 1.1.S1B1 30% dewaxed shellac in ethanol, 100 mM copper acetate, and 100 mM zinc chloride. The copper acetate and zinc chloride were weighed into a 50 mL Falcon tube, and then the ethanol was added. The mixture was manually homogenized and allowed to mix for approximately 1 hour. The shellac was then added to the plastic bottle, and the mixture was again allowed to mix until homogenous.

[0098] Example 1.2.S1B2 40% dewaxed shellac in ethanol, 100 mMol copper acetate, 100 mMol zinc chloride. Example 1.1 was followed except that the shellac concentration was 40% instead of 30%.

[0099] Example 1.3.S1B3 50% dewaxed shellac in ethanol, 80 mM copper acetate, 20 mM copper chloride, 100 mM zinc chloride. The copper acetate, copper chloride, and zinc chloride were weighed into a 500 ml plastic bottle, and then ethanol was added. The mixture was hand-homogenized and allowed to mix for approximately 1 hour. The shellac was then added to the plastic bottle, and the mixture was again allowed to mix until completely homogenous.

[0100] Example 1.4.S1B4 60% dewaxed shellac in ethanol, 50 mM copper acetate, 50 mM copper chloride, 100 mM zinc chloride. The copper acetate, copper chloride, and zinc chloride were weighed into a 500 ml plastic bottle, and then ethanol was added. The mixture was hand-homogenized and allowed to mix for approximately 1 hour. The shellac was then added to the plastic bottle, and the mixture was again allowed to mix until completely homogenous.

[0101] Example 1.5.S1B5 40% dewaxed shellac (pre-blended) in ethanol, 12% PEG-400, 5% glycerol, 100 mM copper acetate, 100 mM zinc chloride. Example 1.2 was followed, except that the PEG-400 and glycerol were added to the ethanolic solution of the metals and mixed well before adding the shellac.

[0102] Example 1.6.S1B6 40% dewaxed shellac (pre-blended), 8% triethyl citrate (TEC), 1% ZnO, 100 mMol copper acetate, 100 mMol zinc chloride in ethanol. Example 1.2 was followed except that the TEC and ZnO were added to the ethanolic solution of metals and mixed well before adding the shellac.

[0103] Example 1.7.S1B7 50% dewaxed shellac (blended) in ethanol, 10% triethyl citrate (TEC), 5% decanoic acid, 100 mMol copper acetate, 100 mMol zinc chloride. The formulation was according to Example 1.2, except that the concentration of shellac was 50% instead of 60%, and the TEC and decanoic acid were also mixed before adding the shellac.

[0104] Example 1.8.S1B8 The formulation was according to Example 1.5, except that higher metal concentrations (190 mMol zinc chloride, 126 mMol copper acetate) and 109 mMol salicylic acid were used. 1.204 g of copper acetate, 1.236 g of zinc chloride, and 0.7147 g of salicylic acid were added to 17.38 g of ethanol and mixed well. Glycerol (2.1236 g), PEG-400 (5.1359 g), and shellac (19.75 g) were then added, and the slurry was mixed until homogeneous.

[0105] Example 1.9.S1B9 43% shellac, 174 mM copper acetate, 174 mM zinc chloride, 101 mM salicylic acid, 8% glycerol, 10.5% PEG-400, 4.3% azelaic acid, 2.2% decanoic acid, and 1.8% adipic acid. 1.2093 g of copper acetate, 0.8273 g of zinc chloride, and 0.4843 g of salicylic acid were added to 7.82 g of ethanol and mixed thoroughly. Then, 1.5053 g of azelaic acid, 0.756 g of decanoic acid, 0.642 g of adipic acid, 2.802 g of glycerol, 3.6421 g of PEG-400, and 15.1195 g of shellac were added and the slurry was mixed until homogeneous.

[0106] Example 1.10: Large Amount of Metal Salts 500mMolal copper chloride, 450mMolal zinc chloride, 50mMolal zinc oxide, shellac 40%.

[0107] Example 1.11: Shellac plus metal hydroxide 500 mMol copper chloride and 500 mMol zinc chloride (according to final concentrations) were neutralized with KOH to pH 4, then shellac was added to 40% w / w.

[0108] Example 1.12: Kaolin-shellac blend 3.92 g of kaolin was added to 15.65 g of 50% (w / w) esterified shellac in ethanol and mixed well. Kaolin has been used as a source of antimicrobial aluminum and as a hemostatic agent.

[0109] Example 1.13: S1B5 with Kaolin 40% dewaxed shellac (pre-blended), 12% PEG-400, 5% glycerol, 100 mM copper acetate, and 100 mM zinc chloride in ethanol. The copper acetate and zinc chloride were weighed into a 50 mL Falcon tube, and then ethanol was added. The mixture was manually homogenized and allowed to mix for approximately 1 hour. PEG-400 and glycerol were added to the metal ethanol solution and mixed well before adding the shellac. After the shellac was completely dispersed, kaolin was added at 11% (w / w). [Example]

[0110] Example 2. Two-component formulation Example 2.1 The material produced in Example 1.4 was loaded into one chamber of a two-component cartridge, while the other chamber contained glycerol, and applied to active digital dermatitis lesions with a manual applicator gun. Upon mixing the two components, a rubber-like barrier immediately formed. This demonstrates the feasibility of using an applicator gun device to deliver the composition of the present invention.

[0111] Composition Editing Table Abbreviations for sources and types of shellac: Wax-free shellac from S-Sigma AFD-AF Dewaxed (<0.5%) shellac from Suter & Co. AFW-AF Wax-containing shellac from Suter&Co Pre-esterified shellac (shellac esters) from AFE-AF Suter&Co F - Shellac used as obtained from the source, i.e. flakes (as obtained from the source) B-Shelac used after blending flakes into powder.

[0112] Metal source abbreviations: CuAc - cupric acetate hydrate (Cu(CH3COO)2.xH2O) FeCl - Ferric chloride hexahydrate (FeCl3.6H2O) CuCl - Copper(II) chloride (CuCl2.2H2O) ZnCl - Zinc chloride (ZnCl2) ZnAc - Zinc Acetate Dihydrate (Zn(CH3COO)2.2H2O) AlCl - Aluminum chloride (AlCl3.6H2O) MoAc - Molybdenum acetate (Mo2(CH3COO)4).

[0113] [Table 1-1]

[0114] [Table 1-2]

[0115] [Table 1-3]

[0116] [Table 1-4]

[0117] [Table 1-5] [Example]

[0118] Example 3. Effect of concentration on compatibility Example 3.1 A 70% solution of shellac in ethanol was prepared, which gave a clear, amber, viscous solution. A five-fold dilution with ethanol gave a free-flowing, clear, yellow solution with no visible precipitate.

[0119] Example 3.2 Dissolving 200 mM copper acetate in ethanol produced a dark blue / green solution. When this was diluted 1:10 with ethanol, a clear light blue solution was produced. However, when it was diluted 1:10 with 17% shellac solution, a cloudy greenish solution with a large amount of precipitate was produced.

[0120] Example 3.3 Solid shellac can be added to an ethanolic solution of copper acetate (100 mMol) to obtain a homogeneous solution containing 40% shellac with no visible precipitate.

[0121] Concentrated shellac ethanol solutions can be easily diluted with ethanol. However, shellac plus copper acetate ethanol solutions form a shellac precipitate upon dilution. This is surprising because high-concentration materials are stable, whereas lower concentrations are not. Additionally, this is advantageous because (1) these solutions can be produced at high concentrations to allow thick barriers to form, and (2) upon dilution (which is expected to occur upon application), the material may precipitate in situ, resulting in faster barrier formation. [Example]

[0122] Example 4. Testing Retention of Rosin vs. Shellac with and without Metals material Copper acetate and zinc chloride were weighed into a Falcon tube and dissolved in ethanol. Shellac or rosin was then added and allowed to dissolve overnight on a roller mixer. Equivalent materials without copper acetate and zinc were prepared by simply dissolving shellac (40 and 60%) or rosin (40%) in ethanol overnight on a roller mixer. Table 2 lists the materials prepared and their compositions.

[0123] [Table 2]

[0124] Retention Test composition We used moistened carpet squares (5.5 cm x 5.5 cm) with a bitumen secondary backing (i.e., backside; details in the table below) to approximate the environment encountered by wet bovine hooves. Briefly, the squares were immersed in a beaker of tap water for 5–10 seconds and then secured on a stand at a 27° vertical angle using clamps, with the backside (i.e., bitumen backing) facing upwards.

[0125] [Table 3]

[0126] Applicable A new carpet surface was used for each test. The composition was always applied to the same area using a plastic syringe (5 mL). The amount applied and the percentage subsequently lost (i.e., the percentage that did not adhere to the carpet) were determined gravimetrically (Table 4).

[0127] [Table 4]

[0128] observation The composition containing 40% shellac with CuAc and ZnCl formed the best barrier. The second best was 60% shellac. The other materials were less viscous and formed a thin, brittle barrier.

[0129] conclusion Surprisingly, the addition of antimicrobial metals allowed for increased viscosity and improved retention while using less shellac. The results of these experiments showed that only compositions containing metal actives and shellac had the necessary viscosity and adhesive properties to form a self-supporting hydrophobic barrier with adhesive properties. In contrast, the addition of metal actives to rosin failed to provide a practical barrier. [Example]

[0130] Example 5. Viscosity Enhancement The inventors have discovered that metals can also be used to induce viscosity increases in shellac compositions. The following table (extracted from the main compilation table) provides some examples of compositions whose viscosity has been enhanced through the addition of metals. For the avoidance of doubt, this table is intended merely to illustrate the viscosity enhancements that can be achieved with various metal combinations and / or concentrations.

[0131] [Table 5] [Example]

[0132] Example 6. Resistance to alkaline degradation Shellac compositions are soluble under alkaline conditions (pH > 7). Physiological fluids generally have a pH above 7.0, limiting their usefulness as a topical barrier. In addition, external environments are often alkaline, particularly in veterinary applications. In the case of digital dermatitis, the barrier must withstand contact with typically alkaline manure slurries (up to pH 9.0) (see Salazar et al., Characterization of dairy slurry in southern Chile farms. Agricultura Tecnica, 67(2), 155, 2007; Fordham and Schwertmann, Composition and Reactions of Liquid Manure (Gulle), with Particular Reference to Phosphate: III. pH-Buffering Capacity and Organic Components 1. Journal of Environmental Quality, 6(2), 140–144, 1977; and UC Manure Technical Guide Series; Dairy Manure Nutrient Content and Forms). Contact with such solutions is expected to rapidly destroy the integrity of the shellac barrier.

[0133] The inventors have discovered that the addition of metal dramatically increases the resistance of the barrier to simulated slurry (SS). Surprisingly, the compositions described herein performed better than non-metallic barriers containing higher amounts of shellac (Table 6). This feature of the present invention is economically advantageous in that it allows for the use of lower amounts of shellac, resulting in lower manufacturing costs.

[0134] Furthermore, the inventors found that wet barriers from the compositions of the present invention (i.e., before solvent evaporation) were very resistant to SS. In contrast, shellac-only barriers that were not allowed to dry for 24 hours performed very poorly. The alkali resistance provided by wet barriers is particularly advantageous in a feedlot environment, since the hoof comes into contact with the wet slurry soon after application of the barrier.

[0135] [Table 6]

[0136] method The SS consisted of 75 mmolal ammonium carbonate (pH 8.9) because this has previously been shown to be the chemical range for fecal slurries in cattle feedlots (see Fordham and Schwertmann et al., and the UC manure Technical Guide series mentioned above).

[0137] 1.0 g of the shellac composition was added to the bottom of a tube with a total volume of 22 mL. 20 g of freshly prepared SS was added either immediately ("wet") or after a 24-hour drying period (open tube at room temperature; "dry"). Exposure of the barrier to SS was carried out on a roller mixer at room temperature for 24 hours, after which the SS fraction was discarded and the mass of the remaining barrier was determined. The recovery rate was calculated relative to a control not exposed to SS. [Example]

[0138] Example 7. Antibiotic Containment The compositions of the present invention are effective in preventing the loss of antibiotics to the surrounding environment. This is exemplified in Example 7.1, in which a solution of oxytetracycline (0.5%) was applied to the surface of a simulated lesion. Furthermore, in the absence of a barrier, 42% of the antibiotic was lost from the surface of the simulated lesion within 90 minutes, despite exposure to only 1 ml of fluid. In contrast, when a protective barrier was applied over the antibiotic, less than 0.2% of the oxytetracycline was lost to the surrounding fluid. In Example 7.2, chlortetracycline spray (commonly used to treat digital dermatitis) was applied to the limbs (between the interdigital grooves and the upper toes) of bovine cadavers and exposed to the simulated slurry for 1 hour. In the absence of a barrier (n=4), substantial loss was observed (93%±3.6%). Application of a barrier (n=4) reduced loss to 18%±3.5% (5-fold).

[0139] Example 7.1 Antibiotic loss experiments were performed in 24-well plates. 1 ml of 10% bovine gelatin solution (prepared at 50°C) was added to the bottom of each well and allowed to stand at 7±2°C for 90 minutes. 20 μL of 0.5% oxytetracycline in ethanol was then added to the bottom of each well and allowed to dry for 5–10 minutes. 0.50±0.05 g of S1B2 (prepared according to Example 1.2) was then added to half of the experimental wells (N=6 per group) to form a protective barrier over the antibiotic and allowed to dry for 5–10 minutes (appropriate OTC-free wells were also prepared for background correction). 1 mL of UHP water was then added to all wells. These wells were kept in the dark for 90 minutes, after which aqueous fraction samples were collected for fluorescence measurement on a plate reader (355 / 590) against oxytetracycline standards (curve fitting by Graphpad). Antibiotic loss to the aqueous phase was determined to be 42% for antibiotic alone and 0.1% for antibiotic plus barrier.

[0140] Example 7.2 An ex vivo antibiotic loss experiment was conducted using bovine cadaver limbs. An antibiotic spray suspension (Animedazon spray, containing chlortetracycline as the active ingredient and patent blue V as the dye) used to treat digital dermatitis was applied to each limb by spraying for 2 seconds onto commonly affected areas (the area between the interdigital grooves and the upper toes). The mass of the spray can was recorded before and after each application to control the amount of spray applied. The applied antibiotic spray was allowed to dry for 60 seconds, and then limbs were either (a) a control group (n = 4): directly immersed in 1 liter of simulated slurry (SS; 75 mM ammonium carbonate) or (b) a barrier group (n = 4): treated with a barrier formulation (15 ± 5 g of S1B2 from Example 1.2) applied over the antibiotic spray site, allowed to dry for an additional 120 seconds, and then immersed in 1 liter of SS. After 1 hour of immersion, a 10 mL sample of SS was taken from each limb to terminate the assay. The samples were analyzed for absorbance to determine the percentage of the antibiotic formulation lost to the simulated slurry fluid; the strong and characteristic spectrochemical profile of Patent Blue V (λmax H2O= 639 nm [J. Chem. Sci. (2018) 130:12]), absorbance measurements provided a convenient surrogate for antibiotic loss. Absorbance standards were prepared by serial dilution of a measured mass of antibiotic spray in a simulated slurry solution. Six replicate aliquots (200 μL each) from each standard and assay sample were then plated (Corning Co-star 96-well) and absorbance was measured between 350 and 850 nm. The raw spectra had a somewhat noisy and variable baseline (due to organic contaminants on the surface) and required processing in MATLAB® (Savitsky-Golay filtering, followed by baseline subtraction with a second-order polynomial) to obtain reliable absorbance maxima. Finally, a linear standard curve (concentration vs. absorbance at 639 nm) was used to generate loss data for each assay sample. In the absence of barrier protection, 93% of the applied patent blue was lost to the assay fluid; when the barrier formulation was used, loss was reduced by more than five-fold to 18%. [Example]

[0141] Example 8. Barrier-mediated contact lethality and metal release Many of the compositions disclosed herein release very low levels of metals when contacted with fluids. Nevertheless, these compositions have bactericidal activity upon contact. In contrast, a shellac-only barrier was found to have no measurable contact lethal activity.

[0142] Contact lethality / metal release method 1 mL of each material was transferred to a well on a 12-well plate and left to stand overnight. The next day, 1 mL of E. coli culture (approximately 10 6 ~10 7 CFU / ml) was added on top of each material and incubated for 24 hours at 30°C with gentle agitation (100 rpm). After 24 hours, samples from the bacterial cultures were collected to quantify bacterial concentration (counts on agar plates) and metal release (ICP-OES).

[0143] Materials tested for contact lethality and metal release

[0144] [Table 7]

[0145] Consequences of metal release Samples were collected directly from the contact lethality assay after 24 hours at 30°C in LB (bacteriological medium) with gentle agitation. Figure 2 shows the release of Zn and Cu from the barrier. The top graph refers to absolute concentrations (ppm), whereas the bottom graph refers to relative release.

[0146] Contact lethality results Figure 3 shows the contact lethality results for K12 in Log CFU / ml after 24 hours of incubation with E. coli in LB. F0 consisted of a shellac-only composition, which had the same bacterial growth as the control experiment (no shellac). For materials F4, F6, F8, F11, F13, F14, F26, F27, and F30, which had a detection limit of 1.7 Log CFU / ml and therefore this result, no bacterial colonies were formed. [Example]

[0147] Example 9. Application in cows with digital dermatitis S1B2 was applied to eight hooves of dairy cows with digital dermatitis. Briefly, the hooves were immobilized and hosed down to remove slurry and other debris. Chlortetracycline was applied (sprayable formulation) and allowed to dry for several seconds. Five to ten grams of S1B2 was then applied to the digital dermatitis lesions to ensure complete coverage. After one minute, the cows were released and returned to their pens, where the hooves were exposed to the slurry and immersed in a formaldehyde bath several times daily (after the cows were robotically milked). Two days after application, six hooves were assessed for barrier integrity; four had nearly complete wound coverage, one had some barrier residue, and one had no visible barrier. In contrast, on day 7, only one of the seven hooves evaluated had any residue, and the other six had no visible barrier at all. [Example]

[0148] Example 10. Application Strategy Several formulations (Table 8) were applied onto the hooves of dairy cows suffering from digital dermatitis. The products were applied using various application strategies according to Example 9.

[0149] [Table 8] [Example]

[0150] Example 11. Application to tinea lesions S1B2 was applied to two ringworm lesions on a dairy cow. Five to ten grams of S1B2 was applied directly onto each wound (i.e., no antibiotics were applied). After seven days, the barrier was completely absent from one lesion (in the thigh region), while partial coverage (approximately 50% of the lesion area) was observed in the other lesion (in the back section of the cow). [Example]

[0151] Example 12. Use in breast infections A cow exhibiting extensive ulcerations on its udder was treated with S1B2. The lesions were first cleaned and disinfected with 0.5% chlorhexidine. Chlortetracycline spray was applied, and then the lesions were covered with S1B2 using a brush. No obvious loss of product was observed during application. [Example]

[0152] Example 13. Use in breast infections The experiment designed in Example 12 was repeated using the S1B1 composition in place of S1B2. [Example]

[0153] Example 14. Use in breast infections The experiment designed in Example 12 was repeated, except that the lesions were simply wiped with a paper towel and then chlortetracycline spray was applied (i.e., no chlorhexidine was used). After 3 days, approximately 75% of the lesion area was still covered by the barrier, and the lesions showed visible improvement. [Example]

[0154] Example 15. Clinical Improvement in Mobility in Treated Cows Cows suffering from digital dermatitis were treated with chlortetracycline spray and then administered an S1B2 barrier according to Example 9. On the day of treatment (day 0) and 7 days later, their mobility (lameness) was assessed by a veterinarian using a standard mobility scoring system (Griffiths et al., 2018) described in Table 9. The results are shown in Figure 4. In this system, lower scores indicate better mobility; on day 0, mobility scores ranged from 1 (incomplete) to 3 (severely impaired). On day 7, a statistically significant improvement in mobility score was observed, which was normalized to 0 (excellent mobility) or 1.

[0155] [Table 9]

[0156] Description of methods for mobility studies Animal mobility was assessed by a veterinarian using a standard scoring system described in Table 9. A one-sided Wilcoxon matched-pairs signed-rank test was employed to test for statistical significance. A P value of <0.05 was considered statistically significant. Mobility scoring is described in Griffiths, B.E., Grove White, D., and Oikonomou, G. A Cross-Sectional Study Into the Prevalence of Dairy Cattle Lameness and Associated Herd-Level Risk Factors in England and Wales. Front. Vet. Sci. 5, 65 (2018).

[0157] All documents cited herein are expressly incorporated by reference in their entirety for all purposes.

Claims

1. A liquid dressing composition for the treatment or prevention of infection and / or wounds, the composition comprising shellac, a metal active material and a volatile solvent, the metal active material being an anti-infective metal active material selected from one or more of Cu, Zn, Fe, Al, Mo and Ca, and the composition being capable of forming a self-supporting hydrophobic barrier when topically applied to a subject.

2. 10. The liquid dressing composition of claim 1, applied to the subject at the site of a wound or infection or at risk of developing a wound or infection.

3. 3. A liquid dressing composition according to claim 1 or 2 for the treatment or prevention of bacterial, fungal, parasitic or viral infections.

4. 4. A liquid dressing composition according to claim 3 for the treatment or prevention of infections caused by gram-negative or gram-positive bacteria.

5. (a) the bacterial infection is Spirochete spp., Escherichia spp., Staphylococcus spp., Bacillus spp., Pseudomonas spp., Vibrio spp., Streptococcus spp., Klebsiella spp., Micrococcus spp., Clostridium spp., Acinetobacter spp., Mycobacterium spp., Salmonella spp., Chlamydia spp., Erysipelothrix spp., Corynebacterium spp., Leptospira spp., Cutibacterium spp., Gardnerella spp., Campylobacter spp., caused by Klebsiella species, Klebsiella species, Capnocytophaga species, Vibrio species, Pasteurella species, Aeromonas species, Eikenella species, Mycoplasma species, Kalimatobacterium species, Helicobacter species, Clostridium species, Listeria species, Treponema species, Bartonella species, Nocardia species, Yersinia species, Serratia species, Burkholderia species, Actinomyces species, Borrelia species, or Enterococcus species; or (b) the fungal infection is caused by Candida spp., Malassezia spp., Trichophyton spp., Microsporum spp., Epidermophyton spp., Fusarium spp., Rhizopus spp., Rhizomucor spp., Mucor spp., Syncephalastrum spp., Cunninghamella spp., Apophysomyces spp., Lichtheimia spp., Saxenaea spp., Aspergillus spp., Blastomyces spp., Coccidioides spp., Cryptococcus spp., Histoplasma spp., Cochliobolus spp., Cladophialophora spp., Exophiala spp., Madurella spp., Pyrenocheta spp., Pneumocystis spp., Paracoccidioides spp., Sporothrix spp., or Talaromyces spp.; or (c) the parasitic infection is caused by a hookworm, such as Sarcoptes spp., Leishmania spp., Ancylostoma spp. or Ancylostoma spp., Strongyloides spp., Onchocerca spp., Diptera larvae, blowflies, screwworm flies, human flies, or flesh flies, Balamuthia spp. or Acanthamoeba spp.; or (d) the viral infection is caused by a papillomavirus, an enterovirus, such as a Coxsackievirus, a Mollasipoxvirus species, a Wallaceavirus, or a herpesvirus; or (e) the infection is caused by a virus from the Adenoviridae family, Caliciviridae family, Coronaviridae family, Flaviviridae family, Herpesviridae family, Orthomyxoviridae family, Papillomaviridae family, Paramyxoviridae family, Parvoviridae family, Poxviridae family, Reoviridae family, Matonaviridae family, Picornaviridae family, Pneumoviridae family, Togaviridae family, or Phenuiviridae family; 4. The liquid dressing composition of claim 3.

6. The liquid dressing composition of any one of claims 1 to 5, wherein the treatment comprises applying a second active agent to an area on the subject and applying the liquid dressing composition over the area to seal in the second active agent.

7. 7. The liquid dressing composition of claim 6, wherein the second active agent comprises an antibiotic agent, an antimicrobial agent and / or a hemostatic active agent, or wherein the second active agent comprises iodine.

8. 8. The liquid dressing composition of claim 6 or 7, wherein the self-supporting hydrophobic barrier reduces loss of the second active agent by at least 20% compared to treatment in which the self-supporting hydrophobic barrier is not applied.

9. 9. The liquid dressing composition of claim 1, wherein the liquid dressing composition is applied as a liniment composition, and the liniment composition may have a viscosity of from 1000 cP to 5000 cP at 25°C.

10. 9. The liquid dressing composition of claim 1, wherein the liquid dressing composition is applied as a spray composition, and the spray composition may have a viscosity of from 10 cP to 3000 cP at 25°C.

11. 11. A liquid dressing composition according to any one of claims 1 to 10 for the treatment of bovine digital dermatitis, udder infections, leishmaniasis, diabetic or Buruli ulcers, teat sealing, dehorning, udder dermatitis, post-declawing, foot rot in sheep or mud fever in horses.

12. A liquid dressing composition according to any preceding claim, wherein the shellac is wax-free shellac, dewaxed shellac, dewaxed and bleached shellac, dewaxed and decolorized shellac, shellac esters or wax-containing shellac.

13. A liquid dressing composition according to any preceding claim, wherein the composition comprises 10 to 70% w / w of shellac.

14. The liquid dressing composition of any one of claims 1 to 13, wherein the volatile solvent is ethanol, an acetone-water mixture, isopropanol, propanol and butanol, or a combination thereof.

15. 15. The liquid dressing composition of any one of claims 1 to 14, wherein the anti-infective metal active is copper chloride, copper acetate, copper oxide, copper oxohydroxide, copper hydroxide, zinc chloride, zinc acetate, nano zinc oxide, normal zinc oxide, iron chloride, aluminum chloride, molybdenum acetate, or kaolin.

16. A liquid dressing composition according to any preceding claim, wherein the anti-infective metal active is present in a concentration of from 20 mMolal to 500 mMolal.

17. 17. A liquid dressing composition according to any preceding claim, wherein the addition of the metal active material increases the viscosity of the composition and / or the thickness of the barrier compared to a composition comprising shellac alone.

18. 18. The liquid dressing composition of any one of claims 1 to 17, wherein the composition may be co-administered with one or more antibiotics and applied to a subject at a location where the antibiotics have already been applied.

19. The liquid dressing composition of any preceding claim, wherein the liquid dressing composition comprises or is co-administered with an antibiotic, antifungal, and / or antiseptic.

20. 20. The liquid dressing composition of any one of claims 1 to 19, wherein the barrier formed when the composition is applied to a subject is resistant to environments having a pH greater than pH 9.

0.

21. A liquid dressing composition according to any preceding claim, which comprises an additional resin component.

22. A liquid dressing composition according to any preceding claim, wherein the liquid dressing composition further comprises fibres, such as cellulose fibres, in an amount of 1 to 15% w / w.

23. 23. A liquid dressing composition according to any preceding claim, further comprising one or more hydrophilic additives as plasticisers and / or to promote the formation of the self-supporting hydrophobic barrier.

24. 24. The liquid dressing composition of claim 23, wherein the hydrophilic additive is selected from TEC, polyalkylene glycols such as polyethylene glycol, glycerol, hexylene glycol, and / or triacetin.

25. A liquid dressing composition according to any preceding claim, further comprising one or more hydrophobic barrier enhancing substances to enhance water resistance.

26. 26. The liquid dressing composition of claim 25, wherein the hydrophobic barrier enhancing agent is selected from decanoic acid, octanoic acid, oleic acid and / or lauric acid.

27. The liquid dressing composition of any preceding claim, further comprising one or more buffering agents to inhibit or reduce degradation of the barrier.

28. 28. The liquid dressing composition of claim 27, wherein the buffering agent is a dicarboxylic acid such as adipic acid, azelaic acid, succinic acid, pimelic acid, or decanoic acid.

29. The liquid dressing composition of any preceding claim, further comprising an anti-inflammatory or complexing agent to enhance the loading or solubility of the metal active agent.

30. 30. The liquid dressing composition of claim 29, wherein the anti-inflammatory agent or the complexing agent is selected from salicylic acid, sodium salicylate and / or propionic acid.

31. A liquid dressing composition according to any preceding claim, further comprising a hemostatic agent, such as kaolin, aluminium sulphate or zeolite.

32. 32. The liquid dressing composition of claim 31, wherein the hemostatic agent enhances clotting for use in acute wound care.

33. 33. The liquid dressing composition of any one of claims 1 to 9 and 11 to 32, which has a droplet size of 1 mm or greater and is non-sprayable.

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