Liquid bandage agent composition and use thereof

Abstract

To provide a liquid bandage agent whose application is easy and effective and which maintains a sterilization state and protects a lesion and other wounds from a foreign infectious substance.SOLUTION: A liquid bandage agent composition is intended to use in treatment or prevention of infection and / or a wound, and includes shellac, a metal active material, and a solvent. The composition is capable of forming a barrier when locally applied to an object.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to liquid bandage compositions and their medical uses, in particular to the prevention and / or treatment of wounds and / or infections. The present invention further relates to devices for delivering or applying liquid bandage compositions.

Background Art

[0002] There is still an unmet need for a liquid bandage that is easy to apply, effective, maintains sterility, and protects lesions and other wounds from exogenous infectious agents. Also, when local application of an antibiotic (or other material) to a lesion is required, such a liquid bandage should ideally "contain" such a material in its environment, prevent loss from the outside, and thus increase the efficacy of treatment.

[0003] Digital dermatitis (DD) is a hoof infection that affects up to 40% of dairy cows. It is caused by the indoor housing of dairy cows required due to the increased dietary requirements of cows milked at high efficiency. It is characterized by painful ulcerative or proliferative lesions, causes lameness, reduces milk production, increases mortality, and is accompanied by economic inefficiencies and animal welfare concerns. Treatment of digital dermatitis is a difficult problem because wounds associated with digital dermatitis are typically chronically infected with multiple species of anaerobic bacteria, especially Spirochaeta. Since the hooves of animals are often in constant contact with manure slurry, this also allows for the spread of disease among cows in the herd and reinfection of previously treated animals.

[0004] Existing treatments for interdigital dermatitis involve the application of topical antibiotics or metal-based antimicrobials to the lesions. However, these treatments are not very effective because the hoof is constantly in contact with fecal slurry, so the antimicrobial or antibiotic is quickly lost to the external environment. It is not practical to reapply a bandage every time after applying an antibiotic or similar treatment to prevent it from being lost from the applied area of the animal to the external environment. Such bandages must be removed after a few days anyway, or they may have a negative effect as a harbinger of infection. In addition to economic losses, 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 conventional antibiotics, other antimicrobial treatments include the use of formalin or ionized copper foot baths, or the application of copper and zinc EDTA gels. Treating a severely infected herd in a foot bath 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. The antimicrobial activity of copper and zinc EDTA gels is limited, requires multiple applications like antibiotics, and may also require bandaging in cases of severe infection. Some formulations of copper and zinc EDTA gels are highly viscous, require application with a brush, and carry an associated risk of cross-infection between treated animals. There is no quality that lasts beyond reliance on the viscosity of these products, and thus their lifespan on the wound is expected to be limited in such problematic environments. Considering these disadvantages, treating interdigital dermatitis in an effective way continues to be a problem in the industry.

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

[0007] U.S. Patent No. 5,178,870 (Explore) describes an antimicrobial composition in which a low-viscosity varnish (sandarac) and an antimicrobial compound are dissolved in ethanol. This composition is coated on teeth to inhibit oral bacterial growth. EP0900560A (Oka) describes a dental coating composite material containing an antimicrobial agent and shellac dissolved in alcohol for covering the tooth surface with a very thin coating having little adhesiveness to assist in preventing periodontal disease. US2010 / 0297043 describes a cosmetic composition for coating the skin, containing a natural resin and a non-drying or semi-drying oil as a softening agent. WO2019 / 0176124 discloses a porous cosmetic skin coating composition containing shellac or rosin, 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 the application of a gauze impregnated with shellac to diabetic patients with dry gangrene to prevent infection and progression to wet gangrene. WO2011 / 129781 (Bedir and Alhayani) provides a similar proposal to use shellac to mummify the necrotic tissue of diabetic foot ulcers by placing the patient's foot inside a treatment chamber under pressure in situations where treatment by amputation is not possible. 、

[0009] ​Antic et al. (Meat Science, 88:498-502, 2011) describe the application of shellac to cowhide to limit cross-contamination of microorganisms during hide removal of bovine raw meat. SUMMARY OF THE INVENTION

[0010] Generally, the present invention provides a liquid bandage composition that can form a self-standing barrier when topically applied to a subject for the prevention and / or treatment of wounds and / or infections, including, for example, wounds and / or infections associated with lesions including wounds and / or infected sites or interdigital dermatitis. In some cases, the bandage 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 situations, the bandage can release its antimicrobial ions to the wound at a concentration compatible with antimicrobial activity in the wound itself. Alternatively, the liquid bandage composition of the present invention may not itself have substantial microbiostatic activity, but can help prevent microbial colonization of the wound by providing a physical barrier against infection. Generally, the liquid bandage composition contains shellac and a metal-based active substance in a volatile solvent such as ethanol and can form a self-standing solid hydrophobic barrier after topical application as a liquid to a subject. The metal-based active ingredient can improve the barrier function and, optionally, can also provide inherent repellent properties against environmental pathogens in addition. Since shellac compositions without metal-based active substances are soluble under alkaline conditions (>pH 7), surprisingly, the compositions of the present invention can form barriers that can withstand high pHs such as those found in alkaline environments such as fecal slurries.

[0011] ​In some cases, the metal-based active substance can impart anti-infective properties to the liquid bandage composition of the present invention. Alternatively, or in addition thereto, the metal active substance can assist in improving one or more properties of the liquid bandage composition, such as improving physicochemical properties such as the barrier properties and / or the viscosity of the composition.

[0012] Alternatively, or in addition thereto, the liquid bandage composition used according to the method of the present invention can encapsulate, for example, a treatment previously applied to a subject at the site of a wound, lesion or infection by providing a sticky and rapidly hardening chemical barrier. Thus, the composition of the present invention can be used in combination with other agents such as antibiotics, anti-infective agents or agents that promote lesion healing, or other materials that have a potential benefit to the host. The barrier formed by the composition can also protect lesions, such as interdigital dermatitis, resulting from the environment, while at the same time providing a temporary barrier that can withstand extreme conditions such as an alkaline slurry but is still capable of self-degradation over time. The barrier formed by the composition of the present invention may have the further advantage that it does not require an additional form of a dressing material or dressing agent to physically support the barrier function or efficacy. In a preferred application, the components of the antimicrobial composition and the barrier formed therefrom are compatible with the food chain.

[0013] Thus, the present invention aims to improve animal welfare, ensure optimal milk production, reduce the loss of antimicrobial agents to the environment and food chain, and also find applications for the prevention and treatment of wounds and / or infections in other situations as further described below. The composition of the present invention is also biocompatible and can control its pH so that safe biologically compatible topical use is possible by maintaining the composition at a pH higher than 3, preferably higher than 4, most preferably higher than 4.5.

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

[0015] These compositions were developed particularly for treating interdigital dermatitis, especially as it occurs in cattle, but the compositions and medical uses described herein have applications in treating human and non-human animal subjects, as well as treating other types of wounds and / or infections and for applications due to local requirements.

[0016] In a further form, the present invention provides a liquid bandage composition for use in treating or preventing interdigital dermatitis, comprising shellac, a metal active substance, and a solvent, which is capable of forming a barrier when topically applied to a subject.

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

[0018] In a further form, the present invention provides the use of a liquid bandage composition in the manufacture of a medicament for treating or preventing interdigital dermatitis, the composition comprising shellac, a metal active substance, and a solvent, which is capable of forming a barrier when topically applied to a subject.

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

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

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

[0022] In the medical uses and methods described herein, the locally deposited barrier produced by the composition of the present invention may be employed in conjunction with conventional treatments, for example, by using the barrier composition over a site or location on a subject to which an antibiotic or other anti-infective agent, a therapeutic agent for promoting 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, an ointment or... applied to the skin or wound that acts to prevent the "solvent sting" of the liquid bandage composition of the present invention when applied topically. It may be advantageous to have other substances.

[0023] Generally, the compositions used in the present invention have the advantage of being readily applicable as liquids or gels, curing rapidly to form insoluble water-resistant (hydrophobic) barriers, and / or being robust enough to provide resistance to mechanical damage and harsh environmental pressures. These advantages are particularly useful for veterinary applications of the present invention when readily applicable, and also for human applications, but are required, for example, in military, leisure, or sports use, or in other situations of trauma such as burns and surgery, where a robust barrier is needed. The properties of the composition are such that it is possible to form a self-standing barrier and thus does not require the use of a dressing material or other dressing agent, which is particularly advantageous for use in rough environments such as outdoor activities or outdoor sports such as hiking, camping, fishing, rock climbing or canoeing, or for military activities or work related to sudden trauma. This is because the barrier formed by the composition generally has a physical strength to withstand physical damage (e.g., knocks), is water-resistant, and can be transported and applied in a convenient form, as a simple liquid format. The present invention may be an all-in-one solution for local problems until at least further intervention can be carried out, i.e., the material is also useful for first aid.

[0024] Also, due to the properties that form a barrier for the compositions used in the present invention, they are suitable for rapidly covering wounds or lesions or patches. This can be useful in time-saving situations, such as in surgical interventions, or when attempting to access difficult-to-reach parts of a subject's body, especially in anatomical areas where it is difficult to apply a bandage in other ways, thereby helping to avoid the need for repeated bandage application and improving patient compliance. Surgical wounds, diabetic wounds and ulcers, intertrigo or skin fold dermatitis, skin lesions, traumatic lesions, abscesses and small scratches or lesions (e.g., due to animal fights) are examples where a simple but effective chemical barrier may be preferred over other treatment options.

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

[0026] In a further form, a compound having an unpleasant taste may be added to a composition intended for veterinary use to prevent an animal from biting or chewing at the barrier site. In some cases, such a taste deterrent compound may also be added to a composition intended for treating small children.

[0027] Preferably, the compositions used in the present invention also provide a barrier capable of inhibiting the progression of further infection at the site of existing wounds, lesions or patches or in areas at risk of such. In one example, the composition of the present invention may be used to treat or prevent acne, for example, by preventing bacterial infection of acne sites. Other types of wounds that can be treated according to the present invention include pustules, blisters, abrasions, lacerations and maceration.

[0028] The compositions of the present invention can also be used in the treatment of surgical wounds. These wounds include wounds by incision, wounds by excision, and in addition, wounds by different types of surgical operations such as appendectomy, breast biopsy, cesarean 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 wounds by tonsillectomy.

[0029] Treatment of "wounds", as used herein, includes chronic wounds, acute wounds, lesions, bruises, abrasions, bites, ulcers, rashes, burns, abscesses, boils, warts, skin cracks, blisters, scaly skin, eruptions, vesicles, nodules, plaques, fistulas, crusts, scratches, wheals or scars.

[0030] Examples of local diseases and injuries that may be associated with or caused by wounds and thus can be treated or prevented by the inventions described herein include dermatitis, insect bites, bites of other animals, traumatic wounds, postoperative wounds, self-inflicted wounds, skin cancer, burns, electrical burns, chemical burns, radiation burns, frostbite, smallpox, birthmarks, papules, pustules, pimples, abrasions, depressions, emphysematous cysts, scales, petechiae, viral infections, bacterial infections, fungal infections, yeast infections, acne, seborrhea, scabies, hypersensitivity to insects, allergic eczema, non-allergic eczema, hyperpigmentation, glossitis, nail diseases, viral rashes, tattoo-related lesions, dandruff.

[0031] Additional skin diseases and injuries that can be treated by the compositions disclosed herein or subsequent wounds prevented include, but are not limited to, lacerations, abrasions, puncture wounds or scratches, first-degree burns, second-degree burns, third-degree burns, frostbite, epidermal necrolytic dermatitis, congestive dermatitis, dermatitis of sweating disorders, seborrheic dermatitis, contact dermatitis, psoriasis, cutaneous leishmaniasis, measles, hand, foot and mouth disease, athlete's foot, onychomycosis, cutaneous lupus erythematosus, bedbug bites, flea bites, mite bites, ringworm, ear plaques, papillomatosis, Buruli ulcer, besnoitiosis, jinmashin, myiasis, infectious pustular dermatitis, interdigital dermatitis, photosensitivity, sheep pox, goat pox, fowl pox, swine pox, worm nodule disease, canine pyoderma, cowpox, sarcoid, onchocerciasis, filariasis, intertrigo, dermatophilosis, folliculitis, impetigo, tinea, rain scald, foot rot, foot-and-mouth disease, bluetongue, sheep scab, ringworm and / or lice infestation, Malassezia dermatitis, carbuncle, swelling, eosinophilic granuloma with collagen degeneration, skin inflammation, red leg syndrome, melanoma, non-melanoma skin cancer, infectious pustules, skin or ear flukes, scale or ear infections, winter ulcer disease, crustacean parasites, plucked feathers, scaly face, foot mites, feather mites, back and feather diseases, feather loss, feather damage, skin neoplasms, lice, flies, blood-sucking winged insects, mites, interdigital tumors, split keel, wing tip edema, ichthyosis, myiasis, outer covering cracks, desquamation disorders, scale rot, vesicle diseases, erythema, petechiae, ecchymosis, hill, gum diseases, cellulitis, vitiligo, candidiasis, herpes zoster, warm bath folliculitis, filariasis due to Loa loa, peeling skin syndrome, dermatographia, adult linear IgA disease, Duhring's disease, Grover's disease, pemphigus foliaceus, pemphigus nodularis, proliferative pemphigus, pemphigus vulgaris, acne necrotica, Fox-Fordyce disease, folliculitis decalvans, folliculitis perforans nasi, lichen planus, red lunulae, folliculitis perforans, mucosal squamous cell carcinoma ​, vitiligo, scrotal tongue, acute necrotizing ulcerative gingivitis, pyogenic granuloma, eyelid xanthelasma, trench fever, sweaty sock syndrome, pseudofolliculitis barbae, perioral dermatitis, paronychia, punctate epidermal exfoliation, necrobiosis lipoidica, Morgellons disease, bubonic plague, diabetic ulcer, erythrasma, hidradenitis suppurativa, jellyfish sting, penile phimosis or lichen simplex chronicus, etc.

[0032] The lesions that can be treated or prevented by the present invention may have various appearances and contours, for example, they may be linear, annular, nummular, targetoid, serpiginous, herpes-like and / or zosteriform.

[0033] In some cases, the surface skin condition, if untreated, may lead to progression to more severe wounds. For example, a rash may lead to self-inflicted skin perforation by scratching, biting, rubbing, or other physical actions by the subject. Therefore, the present invention can be used for such surface skin conditions.

[0034] In some cases, the composition in the present invention can help maintain healthy skin and thus prevent lesions in the subject. Therefore, examples of skin care operations by the composition of the present invention include, but are not limited to, cleansing, moisturizing, humidifying, refining, smoothing, exfoliating, softening, resurfacing, unclogging, sunscreen, sunburn prevention, protection from heat, moisturizing, absorption, desensitization, rejuvenating, removing impurities, reducing skin irritation, pain relief, and refreshing. To avoid misunderstanding, skin care, treatment or prevention of infection and / or wounds include, but are not limited to, preventive or corrective measures, treatment, or assistance in treatment on the skin, mucous membranes, hair and / or nails.

[0035] ​In veterinary subjects, for the treatment or prevention of infections and / or wounds, there are treatments in the skin, mucous membranes, hair, fur, claws, bones, hooves, outer coverings, scales, horns, feathers, teeth, antlers or teeth of living veterinary subjects.

[0036] Preferably, the composition of the present invention is made from safe (e.g., in compliance with GRAS standards) biocompatible components, for example, components already present in the food chain. In the case of veterinary use, this is important for foods of livestock origin (milk, cheese, meat) that enter the human food chain. This also means that the barrier produced using the composition of the present invention can be left to gradually self-degrade, avoiding the need for medical technicians, veterinarians or farmers to remove it at the end of the treatment protocol. It also includes having unique properties in terms of application safety and being more appetizing for use by the user.

[0037] In some uses, the composition of the present invention is colored either by the components that are the raw materials of the composition or by including dyes or other pigments in the composition. Advantageously, this can be used to enable tracking by color when applying the composition (e.g., to determine the extent of application to the subject's body) and / or to enable biodegradation of the barrier to occur subsequently, for example, to determine when reapplication of the composition is necessary. Examples of dyes that can be used according to the present invention include synthetic dyes 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 origin dyes such as lutein, or riboflavin, or caramel, or chlorophyllin, or carotene, or betanin, or anthocyanin, and / or mineral dyes such as titanium oxide, or iron oxide and iron hydroxide.

[0038] As demonstrated in the examples, the raw materials used to produce the composition of the present invention are relatively inexpensive, and the composition is manufactured by dissolving and mixing various components in ethanol or a similar solvent and then packaging them for immediate use, so the composition does not involve complex synthesis.

[0039] In use, the procedure of using the composition of the present invention will typically, optionally, involve applying a therapeutically active agent, such as an antibiotic compound, which is administered in advance, to the treatment site of interest, and then applying the barrier composition to the same site such that a hydrophobic barrier is formed through evaporation of the volatile solvent. In the case of the treatment of bovine digital dermatitis, or in fact for other situations, the method may include an initial step of cleaning the treatment site (i.e., the hoof or leg of an animal having digital dermatitis).

[0040] Embodiments of the present invention are described herein by way of example only, with reference to the accompanying drawings, but are not limiting. However, various further forms and embodiments of the present invention are expected to be apparent to those skilled in the art in view of the disclosure of the present invention.

[0041] "And / or" as used herein shall be construed as a specific disclosure of each of two specified features or components being included or not included in the other. For example, "A and / or B" shall be construed as a specific disclosure of (i) A, (ii) B, and (iii) A and B, respectively, as individually recited herein.

[0042] Unless otherwise indicated in the context, the descriptions and definitions of the features set forth above are not limited to any particular embodiment or form of the present invention and apply equally to all of the embodiments and forms described.

Brief Description of the Drawings

[0043]

Figure 1

Figure 2

Figure 3

Figure 4

DETAILED DESCRIPTION OF THE INVENTION

[0044] The composition of the present invention In the composition of the present invention, shellac or a shellac derivative may be used, and the reference to "shellac" in this specification includes both shellac and shellac derivatives. This may include wax-free shellac, dewaxed shellac, dewaxed bleached shellac, dewaxed decolorized shellac, shellac ester or wax-containing shellac. In addition, the shellac used may be in the form of powder, flakes, lumps, or in certain cases, may be supplied as a solution. Shellac is a resin secreted by female lac insects on trees and is generally produced in India and Thailand. It is processed and generally sold as dry 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 It is preferred that the barrier composition of the present invention comprises 10% w / w to 70% w / w of shellac, more preferably 20% w / w to 70% w / w of shellac, more preferably 30% to 70% of shellac, more preferably 35% to 70% of shellac, more preferably 35% to 60% of shellac, and most preferably 40% to 60% of shellac, where the amount of shellac is indicated 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 components having buffering properties. This is generally done so that the composition has a pH suitable for topical application to the subject. A pH above 3, preferably above pH 4, and most preferably above pH 4.5 is suitable for safe and biocompatible topical use. As an upper limit for the pH, the composition used according to the present invention preferably has a pH of less than 9.0, more preferably less than 8.5, more preferably less than 8.0, more preferably less than 7.4, and most preferably less than 6.5.

[0046] The inventors have found that the use of shellac or shellac derivatives is preferred over the use of other resins having some undesirable properties such as rosin which has allergy concerns. Generally, the compositions used in the present invention can be obtained by mixing the components in a volatile solvent to produce a homogeneous mixture. This is usually advantageous to dissolve the metal active substance in the volatile solvent, followed by any additives, and finally adding shellac. This order allows the metal compound to be properly dissolved before the addition of additives (such as PEG, TEC and glycerol), and helps to avoid the resulting mixture becoming heterogeneous, for example by lumps of shellac. The order of the process also means that the additives are well dispersed before adding shellac, since 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 are added to the compositions described herein, the values are recorded based on mass. Consequently, the concentration may sometimes be referred to as mMolal (mmol / kg) rather than mM (mmol / L). In addition, 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-standing", i.e., it is mechanically robust and does not require stabilization in a structural matrix such as a woven or non-woven matrix as used in the prior art, such as a bandage or gauze. 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 contain 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, an acetone - water mixture, isopropanol, propanol or butanol, and combinations thereof. The use of ethanol, an acetone - water mixture, propanol, and butanol, and isopropanol may be preferred for biocompatibility reasons. When alcohol is used as the solvent, it may be a primary, secondary or tertiary alcohol.

[0050] Examples of other volatile solvents (e.g., those having a boiling point of less than 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, or ethyl alcohol, or benzyl alcohol, secondary alcohols such as isopropanol, tertiary alcohols such as tert - butyl alcohol, an acetone - water mixture, an ethyl acetate - ethanol mixture, and / or a glycol mixture with any of the solvents described above. Other possible solvents include aldehydes such as benzaldehyde, carboxylic acids such as acetic acid, or lactic acid, or propionic acid, diethylene glycol butyl ether, or diethylene glycol ethyl ether, or diethylene glycol methyl ether, or ethylene glycol butyl ether, or ethylene glycol ethyl ether, or ethylene glycol methyl ether, or ethers such as dioxane, ketones such as cyclohexanone, primary alcohols such as amyl alcohol, secondary alcohols such as sec - butyl alcohol, or isobutyl carbinol, tertiary alcohols such as diacetone alcohol, terpenoids such as citronellol, and / or a glycol mixture 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, for example, 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 elements may have any chemical species formation, examples of which include their combinations, 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, most preferably Cu or Zn. A more general listing of metal active substances 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 active substances used to produce the anti-infective composition of the present invention include copper, zinc, silver, bismuth and / or cobalt compounds, and may include selenium. Examples of metal active substances include copper carboxylate complexes or zinc carboxylate complexes. Examples of suitable anti-infective metal active compounds include copper chloride, copper acetate, copper oxide, oxo-hydroxide copper (copper oxo-hydroxide), copper hydroxide, zinc chloride, zinc acetate, nano zinc oxide, normal zinc oxide, iron chloride, aluminum chloride, molybdenum acetate, and It is kaolin. In some cases, a combination of anti-infective metal active substances may be used, for example, a combination of copper and zinc, which may optionally further contain selenium. In other cases, one or more anti-infective base metal active substances may be combined with one or more metal-based excipients, and in this case, the latter 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 is expected to depend on the exact formulation, including but not limited to the concentration and selection of the metal, as well as its speciation. If it is not desirable for these compositions to have anti-infective properties, other metals may be used to modulate the physical properties of the final composition.

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

[0054] Specific examples of the copper metal active substance 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, copper chloroquine, copper salicylaldehyde benzoyl hydrazone, 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 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-hydroxypropionate, copper 2-hydroxybutyrate, 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, tetraammine copper sulfate, copper phosphate, or elemental copper.

[0055] Specific examples of the zinc metal active substance 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 chloroquine, zinc salicylaldehyde benzoyl hydrazone, zinc picolinate, alanine zinc, arginine zinc, aspartate zinc, 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] Generally, it is expected to be known to those skilled in the art that grinding an otherwise insoluble metal active substance can help with the blending of a homogeneous material. The composition used according to the present invention has a viscosity suitable for topical application to the subject and maintains it. It has been found that a protective hydrophobic barrier is formed. 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 cP, more preferably greater than 500 cP, more preferably greater than 750 cP, more preferably greater than 1000 cP, more preferably greater than 2500 cP, more preferably greater than 5000 cP, and most preferably greater than 10000 cP. Generally, for compositions applied as sprays, the viscosity may be from 10 cP to 3000 cP. When the composition is applied as a coating agent, a more viscous composition may be used, for example, a composition having a viscosity greater than 1000 cP, more preferably greater than 2000 cP. The viscosity measurement may be made at room temperature, i.e., 25 °C. In some embodiments, the addition of the metal active substance serves to increase the viscosity of the composition, when measured at 25 °C, by, for example, at least 50%, more preferably at least 100%, even more preferably at least 200%, and most preferably at least 500% compared to the corresponding composition without the metal active substance.

[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, or may be applied over a site where one or more antibiotics and / or other anti-infective agents, disinfectants or other agents have already been applied, thereby providing a protective barrier over the site of treatment together with the therapeutic agent and helping to prevent loss of the therapeutic agent, for example by being washed away by contact with the environment. Alternatively, or in addition, the compositions of the present invention may be formulated so that they contain one or more antibiotics. Examples of antibiotic compounds approved for use in animals include various natural compounds, such as semi-synthetic modifications of lactam antibiotics such as penicillin (produced by fungi of the genus Penicillium), cephalosporin, and carbapenem. Antibiotics still isolated from 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 origin of chemical synthesis / biosynthesis into natural, semi-synthetic, and synthetic. Ansamycin is a class of antibiotics that inhibit bacterial RNA polymerase and have excellent efficacy against Gram-positive and select Gram-negative bacteria, examples of which include the following. Rifamycin, rifampin, rifampicin, rifabutin, rifanethine, rifalazil, ABI-1657, and analogs thereof. Beta-lactams, such as penicillin (e.g., benzylpenicillin, amoxicillin), carbapenem (e.g., meropenem, imipenem), cephalosporin (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), lincosamides (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 topically employed for hoof and surface wound infections (e.g., interdigital 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 context, 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 antibacterial agents (non-antibiotics) may be used. For example, 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, an antifungal agent may be used. Examples of antifungal agents include polyenes (e.g., 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 further ciclopirox, gentian violet, selenium sulfide, zinc pyrithione, zinc undecylenate, and piroctone olamine.

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

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

[0063] The inventors have observed that in some cases, at the time of application, a non-solvent for shellac (i.e., a solution in which shellac does not dissolve) may be mixed with the solution containing shellac to induce the immediate formation of a solid barrier. For example, when an ethanol solution of shellac comes into contact with a sufficient amount of glycerol, a barrier is formed immediately. In-situ mixing can also be achieved using a two-component cartridge, in which case one chamber contains the shellac solution and the other 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 the hydrophilic additive described above. For example, when the two components are mixed, the resulting concentration of PEG is expected to be 30 to 75%, most preferably 33 to 66%. As a further example, the resulting concentration of glycerol is expected to be 20 to 75 %, most preferably 25 to 50%.

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

[0065] In some cases, preferably, the composition further comprises one or more buffering agents to inhibit the degradation of the barrier which might otherwise degrade too rapidly. This is particularly advantageous in interdigital dermatitis since the barrier in contact with alkaline fecal slurries degrades relatively rapidly and further, the degradation of the barrier can be slowed by including additional buffering agents. This is because shellac can become water-soluble under alkaline conditions, fecal slurries have a pH of about pH8 and have a buffering capacity of about 100 mM which is expected to contribute to the degradation of the barrier over time due to solubilization of shellac. For this reason, the compositions used according to the invention preferably have a pH higher than 4.0 to be locally suitable, but may be maintained below pH6.0 or below pH6.5 during use as long as such loss can be avoided. One sophisticated solution to this problem is to include in the composition a buffer solution, preferably a buffer solution having a pKa of 4.0 to 6.5. Examples of suitable buffering components include carboxylic acids containing monocarboxylic acids such as benzoic acid, lauric acid, glycolic acid, levulinic acid, lactic acid, pyruvic acid, or glyceric acid, dicarboxylic acids such as adipic acid (preferably 0.5% to 5%), azelaic acid (preferably 0.5% to 5%), succinic acid, pimelic acid or decanoic acid, or tricarboxylic acids such as citric acid. Without being limited thereto, it is expected to be known to those skilled in the art that various categories of molecules such as amino acids, fatty acids, and alpha-hydroxy acids may contain carboxylic acid pendant groups. Such molecules may also be suitable as buffering agents in the present invention.

[0066] In some cases, preferably, the composition further comprises an anti-inflammatory agent, or a complexing agent to enhance the loading or solubility of a metal active substance. 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, preferably, the composition further comprises a hemostatic agent. In applications where wound treatment involves blood clotting, such as in the treatment of acute wounds, for example in military, sports or acute veterinary use, for example kaolin, aluminum sulfate, or zeolite may be included. Examples of suitable concentrations of hemostatic agents such as kaolin are 1% - 40%, more preferably 2% - 35%, more preferably 3 - 30%, and most preferably 5 - 30%.

[0068] In some cases, the composition further comprises an analgesic, such as acetylsalicylic acid, salicylic acid, tromethamine salicylate, magnesium salicylate and / or methyl nicotinate. Also, natural analgesics, such as capsaicin, may 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 an anesthetic, 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 components of the composition are approved food or feed additives and / or have the status of GRAS reagents (Generally Recognised As Safe).

[0071] Formulations and Uses The composition for use in accordance with the present invention can be employed for the prevention or treatment of infections and / or wounds. When the composition is used to treat or prevent an infection, the infection can be a bacterial, fungal, parasitic or viral infection. Generally, the composition is particularly suitable for treating or preventing bacterial infections, i.e., the composition is an antimicrobial composition. Generally, the composition used in accordance with the present invention, which comprises shellac and a metal active substance or an anti-infective metal active substance in a volatile solvent, is capable of forming a hydrophobic barrier when topically applied to a human or non-human animal (e.g., mammalian) subject. When topically applied to the subject, the composition of the present invention generally forms a solid interface. However, contact with the moisture of the environment, or in the case of treatment of livestock such as cows, contact with the fecal slurry, will result in the immediate formation of a hydrophobic barrier, thereby making the present invention suitable for use in problem environments such as interdigital dermatitis (e.g., bovine interdigital dermatitis) and udder infections, e.g., udder ulceration, udder dermatitis or udder lesions, although this is not essential. Further veterinary uses include the use of a liquid bandage composition for teat sealing or horn removal.

[0072] The anti-infective composition for use in medical and veterinary use according to the present invention can be used in general wound management, particularly when the infection is a potential burden. Examples of this include chronic ulcers and acute wounds including traumatic wounds or postoperative wounds. Examples of wounds for which the composition of the present invention is 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 minor scratches in the treatment of burns, surgical wounds, or foot rot, or in the case of assisting in the treatment of traumatic lesions, pustules and minor scratches. The composition used according to the present invention is also advantageous in assisting in the treatment of closed wounds that have already healed by providing a protective environment, and further in preventing reinfection. Therefore, the composition can also be used for wound prevention. In some embodiments, the liquid bandage composition is expected to be supplied in the form of an over-the-counter (OTC) composition. Other veterinary conditions treatable according to the present invention include folliculitis, impetigo, ringworm, rain scald, foot rot, foot-and-mouth disease, bluetongue, dermatophytosis and / or lice infestation.

[0073] The anti-infective composition according to the present invention is well-suited for veterinary applications where wound management in animals can be particularly problematic. These problems include a high microbial load (pathogenic and non-pathogenic) in the surrounding environment, and the fact that frequent wound cleaning and reapplication of antimicrobial agents are generally not feasible or are excipients. Generally, the use of standard dressings is hampered by these accumulating fecal or other waste problems. In contrast to the use of dressings that require isolation of the animal for application and removal of the dressing, the composition used in the present invention can be used to form a robust yet biodegradable self-standing hydrophobic barrier that is sufficient to protect the wound and also encapsulate any pre-applied antibiotic or antimicrobial agent. This reduces the need for frequent reapplication of the antibiotic or antimicrobial agent and obviates the need for subsequent removal of the barrier. The present invention also enables the use of reduced dosages of antibiotics. Generally, the hydrophobic barrier formed from the composition of the present invention takes 1 to 20 days, more preferably 2 to 10 days, most preferably or 3 to 7 days to degrade. The rate of degradation is usually higher when the barrier is in contact with fecal slurry.

[0074] In some cases, the composition used in the present invention is substantially free of silicon dioxide (silica). Alternatively, or in addition, the composition used in the present invention is substantially free of softening agents such as oils, such as non-drying or semi-drying oils. Examples of softening agents are triglyceride oils, such as 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, rose hip oil, soybean oil, coconut oil, castor oil, olive oil, safflower oil and sunflower.

[0075] In the present application, "substantially free of" means that the composition of the present invention either does not contain the stated component or, if it does contain it, contains a minimal or trace amount of the component in question, for example 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 composition of the present invention consists of or consists essentially of the stated components. One advantage of the composition of the present invention is that the barrier is non-porous to water. When the composition forms a barrier with pores, they generally have a small 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 fact that the composition is viscous means that it is not sprayable. Sprays on dressings in the prior art can form relatively thin films, so the aerosol used to deposit the film cannot hold a high percentage of solids, has a high ratio of drying time: mass of deposited solid, and generally suffers from the disadvantage of being non-biodegradable. Accordingly, the compositions of the present invention are preferably administered by means of an extrudable bottle, an extrudable or collapsible tube, an adhesive dispenser, a manual, pneumatic or electric cartridge gun using a cartridge and plunger kit, or a liquid dispenser. In some cases, it may be preferable for the composition to be administered via the use of a disposable spatula or brush or the like. In some cases, the application may be combined with, for example, distributing the composition over the area to be treated by using a brush or other applicator.

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

[0079] Accordingly, 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, the device comprising: a first chamber containing a composition comprising shellac and a metal active agent (e.g., an anti-infective metal active agent) 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; actuating 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 subject, wherein the composition is capable of forming a hydrophobic barrier when topically applied to a subject. In these devices, examples of non-solvents include glycerol or polyalkylene glycols, such as PEG. These devices may be in the form of a dual or two-component cartridge applicator device. In other embodiments, 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.

[0080]

[0081] ​The liquid bandage composition of the present invention may be formulated for use as an antimicrobial agent or for treating, for example, bacterial or microbial infections and / or for treating wounds to prevent such infections. Thus, in addition to the materials described above, the composition of the present invention may contain pharmaceutically acceptable excipients, carriers, buffers, stabilizers or other materials well known to those skilled in the art. Such materials are expected to be non-toxic and not to significantly interfere with the efficacy of the solid phase materials for the intended application.

[0082] For example, it is known in the art that the uptake and subsequent release of antimicrobial agents within a bandage is advantageous for preventing the entry and growth of microorganisms at the wound site. Advantageously / surprisingly, the composition of the present invention can maintain a sterile bandage (through contact lethality) by minimizing the release of antimicrobial metals, thereby avoiding side effects and / or off-target effects. This is different from previous compositions in the art that employed a resin as a delivery matrix for antimicrobial agents. In another embodiment, the composition of the present invention may be formulated to release its antimicrobial metal ions to the wound at an active concentration 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 in particular refers to preventing the entry of microorganisms from the environment into the wound or their colonization on the bandage. Such microorganisms include the following: Spirochaete species, Escherichia species, such as Escherichia coli, Staphylococcus species, such as Staphylococcus epidermis, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus ( "(MRSA), Bacillus species, such as Bacillus subtilis or Bacillus anthracis, Pseudomonas species, such as Pseudomonas aeruginosa, Vibrio species, such as Vibrio fisheri, Streptococcus species, such as Streptococcus zooepidemicus, S. equi , S. suis, S. uberis, S. pyogenes and Streptococcus pneumoniae, Klebsiella species, such as Klebsiella pneumoniae, Micrococcus species, such as Micrococcus luteus (M. luteus), Clostridium species, such as Clostridium difficile or Clostridium perfringens, Acinetobacter species, such as Acinetobacter baumannii, Mycobacterium species, such as Mycobacterium tuberculosis and M. bovis, Salmonella species, Erysipelothrix species, such as Erysipelothrix rhusiopathiae or Erysipelothrix insidiosa, Corynebacterium species, such as Corynebacterium minutissimum, Lepto spira species, such as Leptospira interrogans, Cutibacterium species, such as Cutibacterium acnes, Gardnerella Genus (Gardnerella) species, such as G. vaginalis (G.vaginalis), Campylobacter species, such as C. fetus (C.fetus), Klebsiella species, such as K. pneumoniae (K.pneumoniae), K. rhinoscleromatis, Capnocytophaga species, such as C. canimorsus (C.canimorsus), Vibrio species, such as V. vulnificus (V.vulnificus), Pasteurella species, such as P. multocida (P.multocida), Aeromonas species, such as A. hydrophila (A.hydrophila), Eikenella species, such as E . corrodens (E.corrodens), Mycoplasma species, such as M. pneumoniae (M.pneumoniae), Calymmatobacterium species, such as C. granulomatis (C granulomatis), Helicobacter species, such as H. pylori (H.pylori), Clostridium species, such as Welch bacterium (C.perfringens), Listeria species, such as L. monocytogenes (L.monocytogenes), Treponema, such as T. carateum (T.carateum) or T. vincentii or T. maltophilum or T. lecithinolyticum, Bartonella species, such as B. henselae, Nocardia species, such as N. brasiliensis, Yersinia species, such as Y. pestis, Serratia species, such as S. marcescens, Burkholderia species, such as B. pseudomallei, Actinomyces species, such as A. israelii, Borrelia species, such as Borrelia burgdorferi, Enterococcus species, such as E. faecalis, or fungi such as Candida species, such as C. albicans, Malassezia species, such as M. furfur and M. pachydermatis, Trichophyton species, such as T. rubrum or T. interdigitale, Microsporum species, such as M. canis, M. equinum, M. audouinii, M. gypseum, or M. nanum, Epidermophyton species, such as E. floccosum, Fusarium species, such as F. solani, Rhizopus microspores, Rhizomucor species, such as R. pusillis, Mucor species, such as M . M. indicus, Syncephalastrum species such as S. racemosum, Cunninghamella species such as C. bertholletiae, Apophysomyces species such as A. elegans, Lichtheimia such as L. corymbifera, Saksenaea species such as S. erythrospora, Aspergillus species such as A. glaucus, Blastomyces species such as B. dermatitidis, Coccidioides species such as C. immitis , Cryptococcus species such as C. neoformans, Histoplasma species such as H. capsulatum , Cochliobolus species such as C. lunatus, Clad ophialophora species such as C. bantiana, Exophiala species such as E. jeanselmei, Pyrenochaeta species such as P. romeroi, Pneumocystis species such as P. jirovecii, Paracoccidioides species such as P. brasiliensis, Sporothrix species such as S. schenckii, Talaromyces species such as T. marneffei, etc., or parasites such as the following, e.g .. For example, species of the genus Sarcoptes, such as Sarcoptes scabiei, Leishmania species, such as Leishmania donovani, Leishmania braziliensis, L. panamensis, the family Ancylostomatidae, such as species of the genus Ancylostoma or Necator americanus, Strongyloides species, such as Strongyloides stercoralis, Onchocerca species, such as Onchocerca volvulus, dipterous larvae, such as Lucilia sericata, Protophormia terraenovae, Cochliomyia hominivorax, Cordylobia anthropophaga, or Sarcophaga bercaea, Balamuthia species, such as B. mandrillaris, or Acanthamoeba species, etc., or viruses such as papillomavirus, enterovirus, such as coxsackievirus, Molluscipoxvirus genus species, such as infectious molluscum contagiosum, Varicellovirus genus, or Herpesvirus genus, etc. The term "antimicrobial", as used herein, is understood to apply to substances that inhibit the attachment of microorganisms to a surface, kill microorganisms, and / or inhibit the reproduction of microorganisms, particularly substances that prevent the entry of microorganisms from the environment into the host, or the establishment or biofilm formation of microorganisms on dressings. The term "microorganism" is understood to include all microorganisms, including bacteria as detailed above, in addition to fungi such as yeast, archaea and protists and viruses. The terms "microbial" and "antimicrobial" shall be construed as such.

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

[0085] Respiratory viruses: Rhinovirus, Canine adenovirus (CAV1 and CAV2), Adenovirus (HAdV B and C), Canine parainfluenza virus (type 5), Bovine parainfluenza virus type 3, Influenza virus (e.g., Influenza A virus H3N2, H1N1, H2N2, H5N1, H1N2, H9N2, H7N9 and Influenza B virus), Respiratory syncytial virus (Human RSV A, Human RSV B, Bovine RSV, Mouse pneumonia virus), 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, Coxsackievirus A (e.g., A21, A24), Cytomegalovirus, Human metapneumovirus, Herpes simplex virus, Bovine herpesvirus type 1, Varicella-zoster virus, Enterovirus D68.

[0086] Gastrointestinal viruses: Rotavirus (e.g., Human group A, B and C, Avian and Bovine), Bovine adenovirus, Human adenovirus (HAdV-F40, 41 and HAdV-G52), Bovine viral diarrhea virus, Calicivirus and Astrovirus.

[0087] Skin viruses: measles virus, rubella virus, parvovirus B19, canine parvovirus, human herpesvirus 6, echovirus (9 and 16), coxsackievirus (A9, A16, B5, etc.), Epstein-Barr virus, cytomegalovirus, dengue virus, Zika virus, chikungunya virus, monkeypox virus, vaccinia virus, bovine and human papillomavirus, foot-and-mouth disease virus, hand, foot and mouth disease virus.

[0088] Virus groups include respiratory viruses, gastrointestinal viruses and skin viruses Therefore, a liquid bandage composition for use in assisting in the treatment or prevention of infection and / or wounds, wherein the infection is caused by a virus of the family Adenoviridae, 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 by a virus of the family Caliciviridae, such as norovirus, or feline calicivirus, or sapovirus, or by a virus of the family Coronaviridae, 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 family Flaviviridae, such as dengue 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 family Herpesviridae, such as Marek's disease virus, swine 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 family Matonaviridae, such as rubella virus, or by a virus of the family Orthomyxoviridae, such as influenza A virus H3N2, or influenza A virus H1N1, or influenza A virus H2N2, or influenza B virus, or by a virus of the family Papillomaviridae, such as human or bovine papillomavirus type 1, or 2, or 6, or 11, or 18, or 31, or 33, or 45, or 52, or 58, or by a virus of the family Paramyxoviridae, such as bovine parainfluenza virus 3, or measles, or mumps, or orthovulavirus 1, or peste des petits ruminants morbillivirus, or by a virus of the family Parvoviridae,For example, by HBoV1, or parvovirus B19, or canine parvovirus, or porcine parvovirus, or by a virus of the family Picornaviridae, 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 family Pneumoviridae, such as human metapneumovirus or human orthopneumovirus, or by a virus of the family Poxviridae, such as lumpy skin disease virus, sheep pox virus, goat pox virus, monkey pox virus, or vaccinia virus, or by a virus of the family Reoviridae, such as bluetongue virus, African horse sickness virus, rotavirus A or rotavirus B, or rotavirus C, or by a virus of the family Phenuiviridae ( ), such as Rift Valley fever virus, or by a virus of the family Togaviridae, such as chikungunya virus.

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

[0090] The use of the liquid bandage composition of the present invention is expected to vary depending on whether the composition is intended to treat or prevent infection in human or animal subjects. However, in addition to being applicable for the treatment or prevention of conditions in human subjects, the present invention has applications regarding use in the veterinary field, for example in the treatment of non-human animals, more particularly non-human mammals, such as companion animals like dogs, cats and horses, in addition to livestock species such as cows, goats and sheep. Rare / less common species (e.g., M.U.M.S., minor use minor 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 particular application, the antimicrobial composition of the present invention is used for the treatment of bovine digital dermatitis, more particularly for the treatment of dairy cows. In a further application, the antimicrobial composition of the present invention is used for dermatitis of the udder and post-cut, post-clipping in cows; foot rot in sheep; and mud fever in horses. The compositions of the present invention can also be used for the protection of post-operative wounds and sutures such as castration in dogs, cats and horses, in addition to sheep, pigs and cows. Examples of species treatable using the present invention include humans, cows, pigs, yaks, pigs, horses, sheep, goats, llamas, alpacas, deer, donkeys, water buffalo, zebras, elephants, orangutans, chimpanzees, gorillas, squirrel monkeys, spider monkeys, baboons, chickens, ducks, geese, ostriches, emus, cats, dogs, ferrets, guinea pigs, hamsters, chinchillas, rats, rabbits, reptiles, amphibians, parrots, canaries, pheasants, wild ducks and sparrows.

[0091] In some veterinary applications where the animal may bite, chew or puncture the barrier formed by the composition of the present invention, it may be desirable to include a taste deterrent, e.g., a bitter component, in the composition to deter such behavior, 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 wounds or skin infections, the exact nature of the carrier or other components may be related to the manner or route of administration of the composition, typically the manner or route of administration via a topical route.

[0093] In one embodiment, the composition of the present invention may be formulated for topical administration useful in the treatment of wounds, ulcers, or the treatment or prevention of bacterial infections. The application of the present invention using topical products aids in the therapeutic use for wound healing.

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

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

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

Examples

[0097] Example 1: Primary formulation Example 1.1.S1B1 30% de-waxed shellac in ethanol, 100 mMolal copper acetate, 100 mMolal zinc chloride. Copper acetate and zinc chloride were weighed into a 50 mL Falcon tube, and then ethanol was added. The mixture was manually homogenized and mixed as such for about 1 hour. Next, shellac was added to a plastic bottle, and the mixture was mixed as such again until homogeneous.

[0098] Example 1.2.S1B2 40% de-cerased shellac in ethanol, 100 mMolal copper acetate, 100 mMolal zinc chloride. Conducted except that the shellac concentration was 40% instead of 30%. Followed Example 1.1.

[0099] Example 1.3.S1B3 50% de-cerased shellac in ethanol, 80 mMolal copper acetate, 20 mMolal copper chloride, 100 mMolal zinc chloride. Copper acetate, copper chloride and zinc chloride were weighed into a 500 ml plastic bottle, and then ethanol was added. The mixture was manually homogenized and mixed for about 1 hour as it was. Next, shellac was added to the plastic bottle, and the mixture was mixed as it was until it became completely homogeneous again.

[0100] Example 1.4.S1B4 60% de-cerased shellac in ethanol, 50 mMolal copper acetate, 50 mMolal copper chloride, 100 mMolal zinc chloride. Copper acetate, copper chloride and zinc chloride were weighed into a 500 ml plastic bottle, and then ethanol was added. The mixture was manually homogenized and mixed for about 1 hour as it was. Next, shellac was added to the plastic bottle, and the mixture was mixed as it was until it became completely homogeneous again.

[0101] Example 1.5.S1B5 40% de-cerased shellac (blended) in ethanol, 12% PEG-400, 5% glycerol, 100 mMolal copper acetate, 100 mMolal zinc chloride. Followed Example 1.2., except that PEG-400 and glycerol were added to the metal ethanol solution and mixed well before adding shellac.

[0102] Example 1.6.S1B6 40% de-waxed shellac (blended) in ethanol, 8% triethyl citrate (TEC), 1% ZnO, 100 mMolal copper acetate, 100 mMolal zinc chloride. Followed Example 1.2, except that TEC and ZnO were added to the metal ethanol solution and mixed well before adding the shellac.

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

[0104] Example 1.8.S1B8 The formulation followed Example 1.5, except that higher metal concentrations (190 mMolal zinc chloride, 126 mMolal copper acetate) and 109 mMolal 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. Then, glycerol (2.1236 g), PEG-400 (5.1359 g) and shellac (19.75 g) were added and the slurry was mixed until homogeneous.

[0105] Example 1.9.S1B9 43% shellac, 174 mMolal copper acetate, 174 mMolal zinc chloride, 101 mMolal salicylic acid, 8% glycerol, 10.5% PEG400, 4.3% azelaic acid, 2.2% decanoic acid, 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 well. Then, azelaic acid (1.5053 g), decanoic acid (0.756 g), adipic acid (0.642 g), glycerol (2.802 g), PEG-400 (3.6421 g) and shellac (15.1195 g) were added and the slurry was made homogeneous until mixed

[0106] Example 1.10: Large amount of metal salt 500 mMolal copper chloride, 450 mMolal zinc chloride, 50 mMolal zinc oxide, shellac 40%.

[0107] Example 1.11: Metal hydroxide in addition to shellac 500 mMolal copper chloride and 500 mMolal zinc chloride (according to the final concentration) were neutralized to pH 4 with KOH, and then shellac was added to 40% w / w.

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

[0109] Example 1.13: S1B5 containing kaolin 40% dewaxed shellac (blended) in ethanol, 12% PEG-400, 5% glycerol, 100 mMolal copper acetate, 100 mMolal zinc chloride. Copper acetate and zinc chloride were weighed into a 50 mL Falcon tube, and then ethanol was added. The mixture was manually homogenized and mixed for about 1 hour as it was. PEG-400 and glycerol were added to the metal ethanol solution and mixed well before adding shellac. After completely dispersing the shellac, 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, the other chamber contained glycerol, and it was applied to active interdigital dermatitis lesions with a manual applicator gun. When the two components were mixed, a rubber-like barrier was immediately formed. This demonstrates the feasibility of delivering the composition of the present invention using an applicator gun device.

[0111] Composition editing table Abbreviations of sources and types of shellac: Wax-free shellac from S-Sigma Degreased (<0.5%) shellac from AFD-AF Suter&Co Wax-containing shellac from AFW-AF Suter&Co Pre-esterified shellac (shellac ester) from AFE-AF Suter&Co Shellac used as obtained from the F-supplier, i.e., flakes (as obtained from the supplier) Shellac used after blending flakes into powder.

[0112] Abbreviations of metal sources: 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. Influence of Concentration on Compatibility Example 3.1 When a 70% solution of shellac in ethanol was prepared, it was a clear amber-colored viscous solution. When diluted 5-fold with ethanol, a freely flowing clear yellow solution was obtained with no visible precipitate.

[0119] Example 3.2 When 200 mMolal of copper acetate was dissolved in ethanol, a dark blue / green solution resulted. When this was diluted 1:10 with ethanol, a clear pale blue solution resulted. However, when it was diluted 1:10 with a 17% shellac solution, a turbid greenish solution with a large amount of precipitate resulted.

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

[0121] The ethanol solution of concentrated shellac can be easily diluted with ethanol. However, an ethanol solution of copper acetate in addition to shellac forms a precipitate of shellac when diluted. This is surprising because the high-concentration material is stable while the low-concentration is not. In addition, this is for the following reasons: (1) These solutions can be produced at high concentrations so that a thick barrier can be formed, and (2) when diluted (which is expected to occur during application), the material can precipitate in situ, which is advantageous for the barrier to form faster.

Example

[0122] Example 4. Test of rosin-to-shellac retention with and without metal Materials Copper acetate and zinc chloride were weighed into a Falcon tube and dissolved in ethanol. Next, shellac or rosin was also added and dissolved overnight using a roller mixer. Equivalent materials without copper acetate and zinc were prepared by simply dissolving shellac (40 and 60%) or rosin (40%) in ethanol using a roller mixer overnight. Table 2 lists the prepared materials and their compositions.

[0123]

Table 2

[0124] Retention test Composition As an environment close to the environment where a wet cow's hoof encounters, a humidified square carpet (5.5 cm × 5.5 cm) with a secondary backing of bitumen (i.e., the back side; details are as shown in the following table) was used. Briefly, the square was immersed in a beaker filled with tap water for 5 - 10 seconds and then fixed on a stand with the back side (i.e., bitumen backing) facing upward at a vertical angle of 27° using a clamp.

[0125]

Table 3

[0126] Application 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 applied amount and the subsequent loss rate (i.e., the rate that did not adhere to the carpet) were determined by weighing (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 not very viscous and formed thin and brittle barriers.

[0129] Conclusion Surprisingly, the addition of the antimicrobial metal enabled the achievement of increased viscosity and improved retention while using a smaller amount of shellac. The results of these experiments showed that only the compositions containing the metal active substance and shellac had the necessary viscosity and adhesion properties to form a self-standing hydrophobic barrier with adhesive properties. In contrast, the addition of the metal active substance to rosin could not provide a practical barrier. [Examples]

[0130] Example 5. Viscosity Enhancement The inventors have found that metals can also be used to cause an increase in viscosity in shellac compositions. The following table (extracted from the main compilation table) provides some examples of compositions whose viscosities were enhanced through the addition of metals. To avoid misunderstanding, this table is for the sole purpose of exemplifying that viscosities can be achieved with various metal combinations and / or concentrations.

[0131]

Table 5

Example

[0132] Example 6. Resistance to Alkaline Decomposition The cerac composition is under soluble alkaline conditions (pH > 7). Since physiological fluids generally exceed pH 7.0, this limits its usefulness for topical barriers. In addition, the external environment is often alkaline, particularly in veterinary applications. In the case of interdigital dermatitis, the barrier must usually withstand contact with an alkaline compost slurry (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 lose the integrity of the cerac barrier. The integrity of the rack barrier is expected to be rapidly lost.

[0133] The inventors have discovered that the addition of metals dramatically increases the resistance of the barrier to simulated slurry (SS). Surprisingly, the compositions described herein showed superior performance compared to metal-free barriers containing higher amounts of cerac (Table 6). This feature of the present invention is economically advantageous in that it allows for the use of even less cerac content, thus reducing manufacturing costs.

[0134] Furthermore, the inventors have found that the wet barrier from the compositions of the present invention (i.e., before solvent evaporation) had very high resistance to SS. In contrast, the barrier performance of shellac alone that had not been dried for 24 hours was extremely poor. Since the hoof will come into contact with the wet slurry immediately after the application of the barrier, the resistance to alkali by the wet barrier is particularly advantageous in the feedlot environment.

[0135]

Table 6

[0136] Method Since 75 mmolal ammonium carbonate (pH 8.9) has been shown to be within the chemical range of manure slurries in dairy feedlots, SS consisted of 75 mmolal ammonium carbonate (pH 8.9) (see Fordham and Schwertmann et al., and the above UC manure Technical Guide series).

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

Example

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

[0139] Example 7.1 The antibiotic loss experiment was conducted in a 24-well plate. 1 ml of a 10% bovine gelatin solution (prepared at 50 °C) was added to the bottom of each well and left to stand at 7 ± 2 °C for 90 minutes. Next, 20 μL of a 0.5% ethanol solution of oxytetracycline was added to the bottom of each well and left to dry for 5 - 10 minutes. Then, 0. 50 ± 0.05 g of S1B2 (prepared according to Example 1.2) was added to form a protective barrier over the antibiotic and left to dry for 5 - 10 minutes (appropriate OTC-free wells were also prepared for background correction). Next, 1 mL of UHP water was added to all wells. These were maintained in the dark for 90 minutes, after which samples of the aqueous fraction were collected for fluorescence measurement with a plate reader (355 / 590) against an oxytetracycline standard (curve fitting by Graphpad). The loss of antibiotic to the aqueous phase was determined to be 42% for antibiotic only and 0.1% for antibiotic plus barrier.

[0140] Example 7.2 Ex vivo antibiotic loss experiments were performed using bovine cadaver limbs. An antibiotic spray suspension used to treat digital dermatitis (Animedazon spray, containing chlortetracycline as the active substance and patent blue V as the dye) was applied to each limb by spraying for 2 seconds in the 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 the limbs were either (a) control group (n=4): directly immersed in 1 liter of simulated slurry (SS; 75 mM ammonium carbonate) or (b) 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 for 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; a strong and characteristic spectrochemical profile of Patent Blue V (λmax H2O = 639 nm [J. Chem. Sci. (2018) 130:12]), Photometric measurements served as a convenient surrogate for antibiotic loss. Absorbance standards were prepared by serial dilution with a measured mass of the antibiotic spray mock slurry solution. Sextuplicate aliquots (200 μL each) from each standard and assay sample were then plated (Corning Co-star 96-well) and absorbance was measured at 350-850 nm. The remaining spectrum had a variable baseline with some noise (due to organic contaminants on the limb) and required processing in MATLAB® (Savitsky Golay filtering, followed by baseline subtraction with a second-degree polynomial) to obtain a reliable maximum absorbance value. Finally, a linear standard curve (concentration vs. absorbance at 639 nm) was used to generate the 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, the loss was reduced to 18%, less than one-fifth.

Example

[0141] Example 8. Contact lethality and metal release by the barrier Many of the compositions disclosed herein release very low levels of metal when in contact with a fluid. Nevertheless, these compositions have bactericidal activity upon contact. In contrast, a barrier of shellac alone was found to have no measurable contact lethality activity.

[0142] Contact lethality / metal release method 1 mL of each material was transferred to a well on a 12-well plate and left standing overnight. The next day, 1 ml of an E. coli culture in LB (about 10 6 ~10 7 CFU / ml) was added on top of each material and incubated at 30 °C for 24 h with gentle stirring (100 rpm). After 24 h, samples were collected from the bacterial medium and the bacterial concentration (number on agar plates) and metal release (ICP-OES) were quantified.

[0143] Materials tested for contact lethality and metal release

[0144]

Table 7

[0145] Results of metal release After 24 hours at 30 °C with gentle stirring in LB (bacterial medium), samples were collected directly from the contact lethality assay. Figure 2 shows the release of Zn and Cu from the barrier. The upper graph refers to the absolute concentration (ppm), while the lower graph refers to the relative release.

[0146] Results of contact lethality Figure 3 shows K12 at Log CFU / ml 24 hours after incubation with E. coli in LB, which is the result of contact lethality. F0 consists of only the composition of cerac, which had the same bacterial growth as the control experiment (without cerac). 1.7 Log CFU / ml was the detection limit, and therefore, for the materials (F4, F6, F8, F11, F13, F14, F26, F27, and F30) having this result, no bacterial colonies were formed.

Example

[0147] Example 9. Application in cows with digital dermatitis S1B2 was applied to the eight hooves of dairy cows suffering from digital dermatitis. Briefly, the hooves were fixed, water was run over them with a hose, and slurry and other waste were removed. Chlortetracycline was applied (sprayable formulation) and allowed to dry for a few seconds. Then, 5 - 10 g of S1B2 was applied so that the digital dermatitis lesions were completely covered. After 1 minute, the cows were released and returned to the pen, where the hooves were brought into contact with the slurry and immersed several times a day (after milking the cows with a robot) in a formaldehyde bath. Two days after application, the integrity of the barrier was evaluated for six hooves, four of which almost completely covered the wound, one had some barrier residue, and one had no visible barrier. In contrast, on the seventh day, 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 to the hooves of dairy cows suffering from interdigital 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 tinea lesions on a dairy cow. 5 - 10 g of S1B2 was applied directly onto each wound (i.e., no antibiotic was applied). After 7 days, the barrier had completely disappeared from one lesion (in the thigh region), while partial coverage (about 50% of the lesion site) was observed in the other lesion (in the section of the cow's back).

Example

[0151] Example 12. Use in Udder Infections Cows presenting large - scale ulceration in their udders were treated with S1B2. The lesions were first washed and disinfected with 0.5% chlorhexidine. Chlorotetracycline spray was applied, and then a brush was used to cover the lesions with S1B2. No obvious loss of the product was observed during application.

Example

[0152] Example 13. Use in Udder Infections The experiment planned in Example 12 was repeated using the S1B1 composition instead of S1B2.

Example

[0153] Example 14. Use in Udder Infections The experiment planned in Example 12 was repeated, but the lesions were only wiped with a paper towel and then a chlorotetracycline spray was applied (i.e., chlorhexidine was not used). After 3 days, approximately 75% of the lesion sites were still covered by the barrier and the lesions showed a visible improvement.

Example

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

[0155]

Table 9

[0156] Description of the method for the mobility study Animal mobility was evaluated by a veterinarian using the standard scoring system described in Table 9. The one-sided Wilcoxon matched-pairs signed-rank test was employed to test for statistical significance. A P-value < 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 hereby incorporated by reference in their entirety for all purposes.

Claims

1. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds, comprising shellac, a metal active agent and a solvent, the composition being capable of forming a barrier when topically applied to a subject.

2. 2. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 1, applied to the site of a wound or infection or to an area at risk of developing a wound or infection in the subject.

3. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 1 or 2, wherein the metal active substance is an anti-infective metal active substance.

4. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 3, which is capable of forming a self-supporting hydrophobic barrier when topically applied to a subject.

5. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 4 which is free of silicon dioxide (silica) and / or softening agents.

6. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 5, which is for use in the treatment or prevention of bacterial, fungal, parasitic or viral infections.

7. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 6, wherein the infection is caused by gram-negative or gram-positive bacteria.

8. The bacterial infection is selected from the group consisting of 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., Klebsiella spp., Capnocytophaga spp., and the like.

8. The liquid dressing composition for use in the treatment or prevention of infections and / or wounds according to claim 7, caused by Bacillus subtilis spp., Vibrio spp., Pasteurella spp., Aeromonas spp., Eikenella spp., Mycoplasma spp., Kalimatobacterium spp., Helicobacter spp., Clostridium spp., Listeria spp., Treponema spp., Bartonella spp., Nocardia spp., Yersinia spp., Serratia spp., Burkholderia spp., Actinomyces spp., Borrelia spp., or Enterococcus spp.

9. 6. The infection and / or fungal infection according to any one of claims 1 to 5, wherein the fungal infection is caused by Candida spp., Malassezia spp., Trichophyton spp., Microsporum spp., Epidermophytes 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., Mazurella spp., Pyrenocheta spp., Pneumocystis spp., Paracoccidioides spp., Sporothrix spp., or Talaromyces spp. A liquid dressing composition for use in the treatment or prevention of wounds.

10. 6. The liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 5, wherein 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, Bucconidae, Screwworm flies, Musculus mortis or Flesh flies, Balamuthia spp. or Acanthamoeba spp.

11. 6. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 5, wherein the viral infection is caused by a papillomavirus, an enterovirus, such as a Coxsackievirus, a Mollasipoxvirus species, a Wallicerovirus, or a herpesvirus.

12. 6. The liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 5, wherein 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.

13. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 12, wherein the treatment comprises applying a second active agent to a site on the subject and applying the liquid dressing composition over the site to seal in the second active agent.

14. 14. The liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 13, wherein the second active agent comprises an antibiotic agent, an antimicrobial agent and / or a haemostatic active substance.

15. 15. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 13 or 14, wherein the self-supporting hydrophobic barrier reduces loss of the second active agent by at least 20%, optionally at least 30%, compared to treatment in which the self-supporting hydrophobic barrier is not applied.

16. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 15, for treating a non-human animal subject.

17. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 16, wherein said topical application is application to a non-human animal subject.

18. 18. The liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 17, wherein the liquid dressing composition is for the treatment of cattle, buffalo, yak, pig, horse, sheep, goat, llama, alpaca, deer, donkey, zebu, zebra, elephant, orangutan, chimpanzee, gorilla, lemur, gibbon, baboon, chicken, turkey, duck, emu, goose, ostrich, cat, dog, ferret, gerbil, hamster, chinchilla, rat, rabbit, parrot, canary, galliformes, anseriformes or passerines.

19. 19. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, which is applied as a liniment composition, which liniment composition may have a viscosity of from 1000 cP to 5000 cP at 25°C.

20. 20. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, which is applied as a spray composition, said spray composition optionally having a viscosity of from 10 cP to 3000 cP at 25°C.

21. 21. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 20 which is for the treatment of bovine digital dermatitis, udder infections, leishmaniasis, diabetic or Buruli ulcers, teat sealing, horn removal, udder dermatitis, post amputation, foot rot in sheep or mud fever in horses.

22. 22. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 21, wherein the shellac is wax-free shellac, dewaxed shellac, dewaxed and bleached shellac, dewaxed and decolorized shellac, shellac esters or wax-containing shellac.

23. 23. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims comprising 10 to 70% w / w of shellac, optionally comprising 40% w / w to 60% w / w of shellac.

24. 24. The liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 23, wherein the solvent is ethanol, acetone-water mixture, isopropanol, propanol and butanol, or combinations thereof.

25. The metal active material is an anti-infective metal active material selected from one or more of Ag, Cu, Zn, Fe, Se, Al, Cr, Mo, Ga, Co, Bi, Sb, Li, Ge, Ti, and / or Ce, or Ag, Cu, Zn, Fe, Se, Al, Cr, Mo, Ga, Co, Bi, Sb, Li, Ge, Ti, Ce, Na, K, Rb, Be, Mg, Ca, S 25. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims comprising a metal active material selected from one or more of: r, 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.

26. 26. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 25, wherein the metal active material comprises one or more of Cu, Zn, Ag, Fe, Se and / or Mo.

27. 27. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 26, 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, aluminium chloride, molybdenum acetate or kaolin.

28. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 27, wherein the anti-infective metal active is present in a concentration of from 20 mMolal to 500 mMolal.

29. The addition of the metal active material improves the viscosity and viscosity of the composition compared to a composition containing shellac alone.

29. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 28, which increases the thickness of the barrier and / or

30. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 29, wherein the antimicrobial composition is co-administered with one or more antibiotics.

31. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 30, applied to a subject at a location where the antibiotic has already been applied.

32. 32. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 31 comprising or co-administered with an antibiotic, an antifungal and / or an antiseptic.

33. 33. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, wherein the barrier formed when the composition is applied to a subject is resistant to environments having a pH above pH 9.

0.

34. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 33 comprising a further resin component.

35. 35. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims comprising fibres, preferably at 1 to 15% w / w, more preferably 2.5 to 10%, most preferably 2.5% to 7.5%.

36. 36. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 35, wherein the fibres are cellulose fibres.

37. 37. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, further comprising one or more hydrophilic additives as plasticizers and / or to promote the formation of said self-supporting hydrophobic barrier.

38. 38. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 37, wherein the hydrophilic additive is selected from TEC, polyalkylene glycols, such as polyethylene glycol, glycerol, hexylene glycol, and / or triacetin.

39. 39. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, further comprising one or more hydrophobic barrier enhancing substances to enhance water resistance.

40. 40. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 39, wherein the substance which enhances the hydrophobic barrier of the antimicrobial composition is selected from decanoic acid, octanoic acid, oleic acid and / or lauric acid.

41. 41. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 40, further comprising one or more buffering agents to inhibit or reduce degradation of the barrier.

42. 42. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 41, wherein the buffering agent is a dicarboxylic acid, optionally wherein the dicarboxylic acid is adipic acid, azelaic acid, succinic acid, pimelic acid or decanoic acid.

43. 43. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 42, wherein the antimicrobial composition further comprises an anti-inflammatory or complexing agent to enhance the loading or solubility of the metal active agent.

44. 44. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to claim 43, wherein the anti-inflammatory agent or complexing agent is selected from salicylic acid, sodium salicylate and / or propionic acid.

45. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 44, further comprising a haemostatic agent such as kaolin, aluminium sulphate or zeolite.

46. 46. ​​A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of claims 1 to 45, wherein the hemostatic agent enhances clotting action for use in acute wound care.

47. A liquid dressing composition for use in the treatment or prevention of infection and / or wounds according to any one of the preceding claims, which has a droplet size of 1 mm or greater and is non-sprayable.

48. 1. 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 material in a volatile solvent as defined in any one of claims 1 to 47 and a second chamber containing a non-solvent; a mixing chamber in communication with said first and second chambers; an actuation means for delivering the composition and a 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 barrier upon topical application to a subject.

49. 49. The device of claim 48, wherein the non-solvent is glycerol or a polyalkylene glycol, such as PEG.

50. 50. The device of claim 48 or 49 which is a dual cartridge applicator.

51. 48. A pressurized spray delivery device comprising a composition comprising shellac and a metal active agent in a volatile solvent as defined in any one of claims 1 to 47, and a propellant for delivering said composition.

Images