Composition for preventing and treating moisture-related skin lesions

Abstract

Therapeutic compositions, kits and methods and uses thereof are provided. The composition comprises zinc oxide, hydrocortisone and / or clotrimazole.

Description

Background Art

[0001] Moisture-associated skin damage (MASD) is a term for a range of lesions characterized by epidermal inflammation and erosion. Excessive exposure of the skin to moisture compromises its integrity, and once compromised, the skin is more susceptible to penetration and impact by irritants such as urine, feces, sweat, wound exudate, stomal discharge, etc. In addition, moist skin has a high coefficient of friction, making it susceptible to friction and shear injury. MASD encompasses a variety of clinical entities such as incontinence-associated dermatitis (IAD), intertrigo (ITD), periwound skin lesions, and peristomal MASD.

[0002] Patients with MASD experience intense, persistent symptoms such as pain, burning, and itching, especially when the skin breakdown involves partial-thickness erosions and peeling. Emerging evidence highlights the association between MASD and other dermatologic conditions such as dermatitis, fungal / bacterial skin infections, and pressure injuries.

[0003] The development and severity of MASD depends on many intrinsic and extrinsic factors. It is common in individuals with excessive sweating, increased dermal metabolism, abnormal skin pH, a history of allergies, deep body folds, dermal atrophy, and insufficient sebum secretion. Extrinsic factors that may trigger and exacerbate MASD are chemical / biological irritants, mechanical stress on the skin, fungal / candidal proliferation, seasonal or environmental factors, incontinence (urinary, fecal, or both), and hygiene habits.

[0004] Prevention and treatment of MASD is of great importance to many patient populations. The present disclosure provides compositions for this purpose. Summary of the invention

[0005] Compositions and methods for preventing and treating moisture-related skin damage, including but not limited to intertrigo and incontinence-related dermatitis, are provided for human and veterinary use. The composition, which may be referred to as "Dr. Gordon's Bum Cream," is based on petrolatum and comprises, consists essentially of, or consists of as active ingredients: about 5% to about 20% zinc oxide by weight; about 0.2% to about 2.5% hydrocortisone by weight; and about 0.1% to about 1% clotrimazole; and the remainder is petrolatum by weight. Optionally, dimethicone is present at about 0.01% to about 2.5% by weight.

[0006] In one embodiment, a method for preventing or treating MASD is provided, the method comprising topically applying an effective dose of a composition comprising, consisting essentially of, or consisting of as an active ingredient: about 5% to about 20% zinc oxide by weight; about 0.5% to about 2.5% hydrocortisone by weight; and about 0.1% to about 1% clotrimazole; and the remainder being petrolatum by weight. Optionally, polydimethylsiloxane is present at about 0.01% to about 2.5% by weight. The volume of the amount applied will vary with the size of the surface to be treated, but may generally include the amount required to form a thin layer of the therapeutic preparation on the skin. It may be applied repeatedly as needed, daily, twice a day, every other day, every three days, every four days, every week, etc. In some embodiments, the duration of application of the pharmaceutical preparation does not exceed about 10 days, and in some embodiments does not exceed about 7 days.

[0007] In some embodiments, the therapeutic preparation is provided as a lotion. The lotion is optionally packaged for single use, for example, in a stick package, etc., with a volume of about 0.1 ml to 10 ml. Larger, multiple-use packaging is also worthy of consideration. In some embodiments, the preparation is embedded in a disposable wipe, which can be packaged for single use, or in the form of a co-pack. The therapeutic preparation can also be provided in the form of a sprayer.

[0008] In addition to the healing benefits provided by the formulations of the present invention of shortening the length of time required for skin recovery, the formulations of the present invention also provide aesthetically acceptable formulations that do not damage bedding, clothing, etc., thereby allowing continued use over a longer period of time to promote healing. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Embodiments of compositions, devices, methods, and kits are described with reference to the accompanying drawings.

[0010] Figure 1 A graph showing the results of treating a rabbit model of incontinence-associated dermatitis with a therapeutic cream consisting of 1.0% hydrocortisone, 1.0% clotrimazole, and 15.0% zinc oxide.

[0011] Figure 2 Shown is a linear regression analysis of the enzyme assay test results for the 3% soy extract cream samples.

[0012] Figure 3 The results of a first test to determine the inhibitory effect of soy extract with and without cream are shown.

[0013] Figure 4 The results of a second test to determine the inhibitory effect of soy extract with and without cream are shown. DETAILED DESCRIPTION

[0014] The compositions of the present invention can help alleviate the effects of MASD and reduce the time it takes for the skin to recover. The therapeutic formulations are cosmetically acceptable and provide improved barrier and healing properties.

[0015] The benefits of the formulations described herein include clinically proven comprehensive healing and protection in a safe, physiologically and aesthetically acceptable formulation. The pH of the formulation is substantially similar to normal skin pH. The formulation is mild, does not contain parabens, phthalates, fragrances, alcohol, and is easy to apply. The aesthetically acceptable formulation does not stain fabrics. The formulation is transparent once applied to facilitate skin inspection. The formulation remains in place once applied, but can be easily removed with just gentle cleansing. By providing a cost-effective single formulation for MASD, the number of products, resources and time required to complete a skin care regimen can be minimized.

[0016] definition

[0017] In the following description, a number of commonly used terms are used. In order to provide a clear and consistent understanding of the specification and claims, and the scope of such terms, the following definitions are provided.

[0018] The terminology and notation used herein follows that in standard treatises and texts in the art, e.g., Kornberg and Baker, DNA Replication, 2nd ed. (WH Freeman, New York, 1992); Lehninger, Biochemistry, (Worth Publishers, New York, 1975); Strachan and Read, Human Molecular Genetics, 2nd ed. (Wiley-Liss, New York, 1999); Eckstein, ed., Oligonucleotides and Analogs: A Practical Approach (Oxford University Press, New York, 1991); Gait, ed., Oligonucleotide Synthesis: A Practical Approach (IRL Press, Oxford, 1984); etc.

[0019] The terms "therapeutic agent" or "drug" are used interchangeably herein and include the pharmaceutically active compositions of the present invention as described herein.

[0020] Moisture-associated skin damage (MASD) is a term for a spectrum of lesions characterized by inflammation and erosion of the epidermis. Specific conditions treated include, for example, incontinence-associated dermatitis. IAD results from the creation of an alkaline environment by ammonia in urine and / or feces that enhances the proteolytic activity of fecal enzymes (proteases and lipases) on the skin. These enzymes disrupt the skin's acidic protective mantle, allowing irritants to easily penetrate the skin and initiate an inflammatory response. Current estimates of the prevalence of IAD range from 5.6% to 50% across different healthcare settings, patient populations, and age groups; the highest rates are seen in patients with severe disease.

[0021] Intertriginous dermatitis (ITD), also known as intertriginous, is a type of moisture-related skin lesions between skin folds, commonly found in the inframammary, pannus, groin, perianal, and interdigital areas. A combination of excess moisture from sweating, airflow restriction obstruction, and friction between opposing epidermal surfaces may lead to ITD. Intertriginous dermatitis is initially characterized by mirror-image erythema, inflammation, and surrounding scaling, but over time the epidermis becomes macerated, edematous, crusted, and eroded and provides an optimal environment for the proliferation of microorganisms such as Candida albicans, leading to secondary infection.

[0022] Periwound skin damage. Wound fluids contain endogenous protein-degrading enzymes that are corrosive and can damage intact skin. Periwound skin is particularly susceptible to MASD when drainage exceeds the fluid-handling capacity of the dressing. In addition, repeated application and removal of tapes and dressings may strip the stratum corneum around the wound, leading to further skin damage.

[0023] Peristomal moisture-related skin injury is characterized by inflammation and erosions at the mucocutaneous junction and surrounding areas. Despite various containment strategies, fecal effluent may leak and spill onto the peristomal skin, particularly in patients with hyperactive bowel movements, diarrhea, and fistulas connecting the intestine to the skin surface. A contoured abdomen due to excess subcutaneous fat, poor muscle tone, hernias, fissures (linear breaks in the skin from the dermal base), or clefts associated with skin / muscle defects can present challenges, often resulting in poor appliance adhesion and pouch leakage. Maceration after establishment of a secure pouching system is a major complication associated with peristomal MASD as it creates a vicious cycle: eroded epidermis produces moisture that prevents the pouching system from adhering to the skin and forming a tight seal, leading to further contact of effluent with the skin, which in turn leads to greater maceration and pouching difficulties.

[0024] The severity of MASD and its improvement can be assessed by various clinical indicators. Administration of the disclosed therapeutic formulations reduces one or more of these signs, for example, by reducing scores on standardized tests by at least about 10%, at least about 25%, at least about 50%, or more.

[0025] For example, IAD often presents with diffuse erythema but may also be characterized by erosions, edema, scaling, papules, or bullae containing serous exudate and may be associated with pruritus, burning, or pain. The Incontinence-Associated Dermatitis and Severity Instrument is a tool that assesses redness, skin lesions, and rash on 13 body sites affected by IAD. A score of 0 to 52 is generated to guide practice. In addition, Beeckman et al developed the Incontinence-Associated Dermatitis Skin Condition Assessment Tool to describe the surface area (in square centimeters), severity of redness, and depth of any perineal skin lesions.

[0026] Recently, a global IAD classification tool was developed. First, the affected skin is evaluated to determine if there is persistent redness or skin loss. Next, clinical infection or intertrigo is assessed based on a range of signs and symptoms. From this, IAD is classified into 4 categories: persistent redness without clinical signs of infection; persistent redness with clinical signs of infection; skin loss without clinical signs of infection; and persistent redness with clinical signs of infection.

[0027] Although ITD and IAD are caused by similar factors, ITD affects areas other than those affected by incontinence. Areas affected by ITD may appear erythematous with scaling. Based on the characteristic appearance of satellite lesions, secondary intertriginous candidiasis seems plausible. However, there is currently no validated measurement scale to describe the severity of ITD.

[0028] Skin damage around the wound is obvious, showing varying degrees of skin maceration, erythema, edema, inflammation, blistering, excoriation and erosion. White maceration refers to white skin and swelling, while erythema maceration refers to redness and inflammation of the skin. Characteristic manifestations of skin damage around the wound include erosion, erythema, edema, blister formation, itching, edema and pain.

[0029] Peristomal MASD is moisture-related inflammation and erosion of the skin that begins at the stoma / skin junction and may extend outward. The Stoma Skin Tool is designed to assess peristomal skin in two ways. First, it assigns a score based on discoloration, erosions, and tissue overgrowth. Photographic references are provided to assist the assessor. Second, the Stoma Skin Tool provides a diagnostic guide that guides caregivers through an interview with the patient to determine the possible cause of the skin disorder (e.g., chemical irritation, mechanical irritation, or infection).

[0030] Urinary incontinence: The main effects of urinary incontinence on affected skin are related to chronic overexposure to water and the generally elevated pH of urine. Skin pH for healthy skin is typically in the range of 5.0 to 5.9. This pH supports healthy skin physiology and is essential for normal skin processes. Studies have shown that exposure to higher pH (from urine or cleansers formulated with a higher pH) may lead to skin damage due to factors including increased water loss and disruption of stratum corneum production due to disrupted barrier function.

[0031] Fecal incontinence : Along with bile acids, waste products, and bacteria, digestive enzymes are also typically found in feces as a result of their intended passage through the intestines. These digestive enzymes can be from many different classes of enzymes (i.e., lipases for digesting fats, proteases for digesting proteins, etc.), each with a specific desired biological role. As part of the digestive process, they work by cleaving / breaking down key bonds in food into smaller units. However, when these enzymes are present in unintended areas or tissues (such as skin or wounds), they can cause significant damage by cutting unintended targets in other tissues that would not normally be exposed to these enzymes. This enzymatic activity can cause new lesions and prevent effective healing of injured skin, and can provide an environment that promotes microbial growth, as some of the smaller units formed during digestion can act as food for the microorganisms.

[0032] Some examples of digestive proteases present in feces include chymotrypsin, trypsin, and pancreatic elastase, all of which help digest proteins by cutting at different locations on the protein chain. In addition, other enzymes may be present, such as lipase, which generally aids in the digestion of fats. Although these enzymes are generally expected to be present in feces to varying degrees, when feces comes into contact with wounds or is in contact with the skin for a long time, these enzymes can cleave unintended targets, resulting in new or worsening skin lesions.

[0033] Combined urinary and fecal incontinence : When urine and feces are present together, in addition to their respective effects on the skin and skin structure, the increased urine pH further enhances the enzymatic activity of digestive enzymes, many of which have maximal activity at alkaline pH (>7). For example, the pH maxima of trypsin (7.8 to 8.7) and pancreatic lipase (8.0) are within the range of normal to alkaline urine pH levels (4.5 to 8.0 and above).

[0034] Biofilm formation is an established feature of microbial infections. As a microbial (fungal, bacterial, etc.) infection matures, a protective matrix forms to help support the microbial colony, the biofilm. This biofilm matrix can not only impede wound healing, but can also prevent or interfere with antimicrobial compounds and / or the body’s own immune response factors from reaching their targets, thereby helping to clear the infection. Ideally, the production of biofilm in wounds should be minimized for better overall outcomes.

[0035] The terms "subject," "individual," and "patient" are used interchangeably herein to refer to a mammal for which treatment is being evaluated and / or is being treated. In one embodiment, the mammal is a human. The terms "subject," "individual," and "patient" encompass, but are not limited to, individuals who suffer from or are at risk of developing adhesions. The subject can be a human, but also includes other mammals, particularly those that can be used as laboratory models of human disease, such as mice, rats, and the like.

[0036] As used herein, the term "diagnosis" refers to the identification of a pathological state, disease or condition, such as the identification of MASD and its subtypes.

[0037] As used herein, the terms "treatment" and the like refer to the administration of an agent or the performance of a procedure for the purpose of achieving an effect on a subject (e.g., a patient). The effect may be preventive, i.e., completely or partially preventing an adverse condition, disease, or its symptoms, and / or may be therapeutic, i.e., achieving partial or complete improvement, relief, or cure of an adverse condition, disease, and / or its symptoms. Thus, treatment encompasses the administration of a formulation before an adverse condition, disease, or its symptoms occur, during an adverse condition, disease, or its symptoms occur, and / or after an adverse condition, disease, or its symptoms occur. Treatment may refer to any sign of success in treating, improving, or preventing an adverse condition or disease, including any objective or subjective parameter, such as relief; relief; symptom relief or making an adverse condition more tolerable to the patient; a slower rate of deterioration or decline; or making the final point of deterioration less debilitating. The treatment or improvement of symptoms may be based on objective or subjective parameters; including the results of a doctor's examination. Thus, the term "treatment" includes the administration of a formulation of the present disclosure to prevent or delay, alleviate, or prevent or inhibit the development of a symptom or adverse condition. The term "therapeutic effect" refers to the reduction, elimination, or prevention of an adverse condition, disease, or its symptoms or side effects.

[0038] In certain embodiments, "combination", "combination therapy" and "combination product" refer to the simultaneous administration of a first therapeutic agent and a second therapeutic agent to a patient. When administered in combination, the components can be administered simultaneously or sequentially in any order at different time points. Thus, the components can be administered separately but sufficiently close in time to provide the desired therapeutic effect.

[0039] As used herein, the term "correlation" or "correlated with..." and similar terms refer to a statistical association between instances of two events, where the events include numbers, data sets, etc. For example, when the events involve numbers, a positive correlation (also referred to herein as a "direct correlation") means that as one event increases, the other also increases. A negative correlation (also referred to herein as an "inverse correlation") means that as one event increases, the other decreases.

[0040] "Dosage unit" refers to physically discrete units suited as unitary dosages for a specific individual to be treated. Each unit may contain a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specifications for the dosage unit form may be determined by (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of formulating such an active compound.

[0041] "Pharmaceutically acceptable excipients" refer to excipients that can be used to prepare generally safe, non-toxic and desirable pharmaceutical compositions, and include excipients that are acceptable for veterinary use as well as human pharmaceutical use. These excipients can be solid, liquid, semisolid, or, in the case of aerosol compositions, can be gases.

[0042] The terms "pharmaceutically acceptable," "physiologically tolerable," and grammatical variations thereof, when referring to compositions, carriers, diluents, and agents, are used interchangeably and indicate that the material is capable of being administered to a human or human being without producing an adverse physiological reaction to an extent that would prohibit administration of the composition.

[0043] A "therapeutically effective amount" refers to an amount sufficient to treat an adverse condition, symptom, or disease in a subject when administered to the subject. An effective dose is sufficient to reduce adhesions by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more. The dosage of the therapeutic antibody can be, for example, from about 1 mg / kg body weight to about 100 mg / kg body weight, and can be administered immediately after surgery or other events expected to result in adhesion formation; or to reduce existing adhesions. Dosing can be repeated every day, every two days, every three days, every half week, every week, etc. DETAILED DESCRIPTION

[0045] As described above, the present disclosure provides methods for treating adhesions in a subject, including, for example, preventing adhesion formation, stopping or reducing adhesion formation, and / or reversing or eliminating adhesions that have already occurred in the subject. Compositions and kits for performing such methods are also provided.

[0046] Before describing various aspects of the present invention in more detail, it should be understood that the present invention is not limited to the specific embodiments described, and therefore may of course vary. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments and is not intended to be limiting, as the scope of the present invention will only be limited by the appended claims.

[0047] Where a numerical range is provided, it is understood that unless the context clearly indicates otherwise, each intervening value is encompassed within the invention, between the upper and lower limits of the range and any other specified value or intervening value, to one-tenth of the unit of the lower limit. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, but are subject to the impact of any specifically excluded limitations in the range. When the range includes one or two limits, ranges excluding one or both of the included limits are also encompassed within the invention.

[0048] Certain ranges of values ​​given herein are preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that follows it, as well as for numbers that are close to or approximately the number that follows the term. In determining whether a number is close to or approximately a specifically recited number, a close or approximate unrecited number may be a number that, in the context in which it is presented, provides a substantial equivalence to the specifically recited number.

[0049] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

[0050] All publications and patents cited in this specification are incorporated herein by reference as if each individual publication or patent was specifically and individually indicated to be incorporated by reference, and are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the publication dates provided may be different from the actual publication dates which may need to be independently confirmed.

[0051] It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should also be noted that the claims may be drafted to exclude any optional elements. Thus, this statement is intended to serve as antecedent basis for using exclusive terminology such as "solely," "only," and the like in connection with the recitation of claim elements, or for using a "negative" limitation.

[0052] As will be apparent to those skilled in the art after reading this disclosure, each individual embodiment described and illustrated herein has discrete components and features that can be easily separated or combined with the features of any of the other several embodiments without departing from the scope or spirit of the invention. Any described method may be performed in the order of events described or in any other order that is logically possible.

[0053] preparation

[0054] The therapeutic formulation, which may be referred to as "Dr. Gordon's Bum Cream" (DGBC), is based on petrolatum and, in some embodiments, comprises, consists essentially of, or consists of as active ingredients: about 5% to about 20% zinc oxide by weight; about 0.2% to about 2.5% hydrocortisone by weight; and about 0.1% to about 1% clotrimazole; and the remainder is petrolatum by weight. Optionally, polydimethylsiloxane is present at about 0.01% to about 2.5% by weight. When formulated, zinc oxide may be mixed with petrolatum, optionally with polydimethylsiloxane, to form a paste. Hydrocortisone and clotrimazole powders are then mixed into the paste to obtain the final formulation.

[0055] In other embodiments, the therapeutic formulation comprises, consists essentially of, or consists of as active ingredients: about 5% to about 20% zinc oxide by weight; about 0.2% to about 2.5% hydrocortisone by weight; about 0.1% to about 1% clotrimazole; about 30% to 60%, preferably about 40% to 50%, petrolatum by weight; the remainder being inactive ingredients.

[0056] Zinc oxide (CAS No. 1314-13-2) is an inorganic compound with the chemical formula ZnO. It is a white powder that is insoluble in water. Although it occurs naturally in the form of zinc ore, most zinc oxide is produced synthetically. Zinc oxide is present in a concentration of about 5%, about 6%, about 7%, about 8%, about 9%, about 10% to about 20%, about 19%, about 18%, about 17%, about 16%, about 15% by weight. In some embodiments, zinc oxide is present in a concentration of about 10% to about 15%, about 11% to about 14%, about 12% to about 13% by weight, and may be present in a concentration of about 12.5% ​​by weight.

[0057] Hydrocortisone, 11β, 17α, 21-trihydroxypregnane-4-ene-3, 20-dione (CAS No. 50-23-7) is a synthetic or semi-synthetic analog of the natural hydrocortisone hormone produced by the adrenal glands, with primary glucocorticoid and secondary mineralocorticoid effects. As a glucocorticoid receptor agonist, hydrocortisone promotes protein catabolism, gluconeogenesis, capillary wall stability, and renal calcium excretion, and suppresses immune and inflammatory responses. Hydrocortisone is present in a concentration of about 0.2%, about 0.3%, about 0.4%, about 0.5% to about 2.5%, about 2%, about 1.5%, about 1% by weight. In some embodiments, hydrocortisone is present in a concentration of about 0.2% to about 0.5% by weight. In other embodiments, hydrocortisone is present in a concentration of about 0.5% to about 1.5%, about 0.75% to about 1.25% by weight, and may be present in a concentration of about 1% by weight.

[0058] Clotrimazole (CAS No. 23593-75-1) is a synthetic imidazole derivative with a broad spectrum of antifungal activity. Clotrimazole inhibits the biosynthesis of sterols, especially ergosterol, an important component of fungal cell membranes, thereby destroying and affecting the permeability of cell membranes. By weight, clotrimazole is present in a concentration of about 0.1%, about 0.2%, about 0.3%, about 0.4% to about 1%, about 0.9%, about 0.8%, about 0.7%. In some embodiments, clotrimazole is present in a concentration of about 0.25% to about 0.75%, about 0.4% to about 0.6% by weight, and may be present in a concentration of about 0.5% by weight.

[0059] Polydimethylsiloxane (dimethicone; CAS No. 63148-62-9) is used as a defoaming agent, emollient, and skin protectant. It prevents water loss by forming a moisturizing barrier on the skin. Dimethicone may be absent or present. If present, dimethicone is present in a concentration of about 0.01%, about 0.02%, about 0.03%, about 0.04% to about 2.5%, about 2%, about 1%, about 0.5% by weight. In some embodiments, dimethicone is present in a concentration of about 0.025% to about 0.075%, about 0.04% to about 0.06% by weight, and may be present in a concentration of about 0.05% by weight.

[0060] In one embodiment, the therapeutic formulation comprises 1.0% hydrocortisone, 1.0% clotrimazole, and 15.0% zinc oxide.

[0061] Petrolatum (CAS No. 8009-03-8) is a complex combination of hydrocarbons and is a semisolid obtained from dewaxed paraffin residues. It consists mainly of saturated crystalline and liquid hydrocarbons with carbon numbers substantially greater than C25. Petrolatum constitutes the remainder of the formulation and is therefore usually present at about 80% to 90% by weight, depending on the specific ranges of the other ingredients.

[0062] In some embodiments, inactive ingredients include, but are not limited to, cetearyl alcohol, mineral oil, lanolin, paraffin, water, sodium phosphate, EDTA, modified corn starch, chlorocresol.

[0063] In one embodiment, the pH of the formulation is adjusted to about 6.5 to 7.5 using sodium hydroxide.

[0064] In some embodiments, the formulation comprises additives such as, but not limited to, enzyme inhibitors, pH buffers, moisturizers or wetting agents, antibacterial agents or antifungal agents. Examples of enzyme inhibitors include, but are not limited to, inhibitors of chymotrypsin, trypsin, pancreatic elastase or lipase. In one embodiment, enzyme inhibitors include fecal enzyme inhibitors. Examples of fecal enzyme inhibitors include botanicals, such as Balmex adult cream (active ingredients: 11.3% zinc oxide, inactive ingredients: beeswax, benzoic acid, polydimethylsiloxane, fragrance, soybean oil, magnesium aspartate, methylparaben, microcrystalline wax, mineral oil, evening primrose seed extract, olive leaf extract, panthenol, potassium aspartate, potassium hydroxide, propylparaben, sarcosine, sodium cocoyl amino acid, sorbitan sesquioleate, synthetic beeswax, tocopherol), soybean Bowman-Birk inhibitor, protease inhibitors of natural origin. Examples of pH buffers include acidic buffers such as citrate. In some embodiments comprising a pH buffer, the buffer maintains the pH between 5.0 and 5.9, taking into account that an alkaline pH facilitates skin decomposition and fecal protease activity. Examples of moisturizers or humectants include, but are not limited to, hyaluronic acid or polyglutamic acid. Examples of antimicrobial agents include silver-containing PGA nanoparticles. Many essential oils have antifungal or antibacterial effects and do not cause side effects like some synthetic ingredients. Examples of antifungal and / or antimicrobial agents include essential oils from thyme, cinnamon, oregano, cloves, mint, citronella, geranium, lemongrass, eucalyptus, mint, or Grosso lavender; and tea tree oil, clove oil, sage oil, jasmine oil, lavender oil, ylang-ylang oil, eucalyptus oil, cinnamon oil, lemon oil, lemongrass oil, thieves oil, wild oregano oil, jojoba oil, or manuka tree oil. In one embodiment, the formulation comprises oregano oil and lavender oil. Plant extracts have antiseptic, anti-inflammatory, astringent, and bactericidal properties. Some can stimulate the growth of new cells. These properties work together to form a natural remedy for fungal skin infections. Some moisture-related skin lesions include: ringworm, athlete's foot, tinea versicolor, onychomycosis, and jock itch.

[0065] In some embodiments, the preparation comprises a proteolytic enzyme inhibitor. The proteolytic enzyme inhibitor family has been isolated from various plants and beans. Proteolytic enzyme inhibitors are generally referred to as plant inhibitory peptides, which can reduce the proteolytic activity of trypsin and chymotrypsin. Exemplary plant inhibitor peptides include, but are not limited to, soybean tyrosine inhibitor (STI), Birk-Bowman inhibitor (BBI), potato inhibitor I, potato inhibitor II, pumpkin trypsin inhibitor, cereal-derived α-amylase and trypsin inhibitor, mustard trypsin inhibitor, serine protease inhibitor, plant cystatin, carboxypeptidase inhibitor, cyclic peptide, α-hairpin inhibitor. In some embodiments, the proteolytic enzyme inhibitor is a tyrosine inhibitor (see Table A). In some embodiments, the proteolytic enzyme inhibitor includes soybean tyrosine inhibitor (STI), Birk-Bowman inhibitor (BBI), non-denatured soybean extract or a combination thereof. In some embodiments, the formulations or compositions described herein include 0.1% to 30%, 1% to 25%, 0.5% to 3%, 5% to 15%, 7% to 15%, about 3%, about 7% or about 15% proteolytic enzyme inhibitors by weight. In some embodiments, proteolytic enzyme inhibitors, such as tyrosine inhibitors, are provided for preventing or treating MASD. In some embodiments, a composition comprising a proteolytic enzyme inhibitor (such as a tyrosine inhibitor) and a carrier is provided for preventing or treating MASD. The composition may further include clotrimazole, hydrocortisone and / or zinc oxide. The composition may be a sprayable composition (wet or dry spray formulation), optionally including zinc oxide.

[0066]

[0067] In some embodiments, the formulation comprises a soy tyrosine inhibitor (STI) at a concentration of 0% to 25% by weight (i.e., 1% by weight); a Birk-Bowman inhibitor (BBI), a Birk-Bowman related protease inhibitor, and / or a Birk-Bowman family protease inhibitor at a concentration of 0% to 25% (i.e., 1% by weight); or a non-denatured soy extract (i.e., 10% by weight). Loose stools and diarrhea increase the risk of MASD when stool is in contact with the skin for a long time. Diarrhea is associated with an increased likelihood of incontinence-associated dermatitis in children, and clinical experience strongly suggests that contact with loose stools is often associated with severe MASD and extensive erosions of the affected skin. Loose stools contain higher concentrations of proteolytic enzymes, such as trypsin and chymotrypsin, which may impair the moisturizing effects of filaggrin and the emollient effects of inherent lipids in the stratum corneum. More alkaline pH and higher concentrations of active fecal enzymes associated with diarrhea can exacerbate harmful effects on the skin. Unprecipitated and unfermented soybeans produce severe gastric discomfort due to the inhibitory activity of soybean trypsin inhibitor (STI) and Birk-Bowman inhibitor (BBI), which inhibit the action of trypsin, chymotrypsin, and other proteases required for protein digestion. It is the heat inactivation of STI and BBI during soybean processing that makes soybeans edible. BBI reduces the proteolytic activity of trypsin, chymotrypsin, elastase, cathepsin G and chymase, serine protease-dependent matrix metalloproteinases, urokinase protein activator, mitogen-activated protein kinase, and PI3 kinase, and enhances the expression of connexin 43 (Cx43).

[0068] Product use, form and packaging

[0069] When used, a certain amount of the composition, for example 1 ml to 100 ml, is applied to the site of interest from a suitable container or applicator, and if necessary, it is applied to the site and / or rubbed into the site by hand or fingers or a suitable device. The site where the covering technique is used includes various areas of the skin. Reapplication is performed as needed, and the treatment can last for 1 day, 3 days, 5 days, 7 days, 10 days.

[0070] The therapeutic composition of the present invention can be formulated into any form suitable for application to the site of interest, usually as a lotion. The composition can be packaged in any suitable container to adapt to its viscosity and the intended use of the consumer. For example, it is packaged in an aerosol device driven by a bottle, a propellant, or a container equipped with a pump suitable for finger operation. When the composition is a gel, it can be simply stored in a non-deformed bottle or squeeze container, such as a tube or a covered jar. Thus, the present invention also provides a closed container for accommodating an acceptable composition of the aesthetic aspect defined herein. The closed container may include, for example, a tube containing 15, 30, 50 or 100 grams of the therapeutic preparation.

[0071] The following examples are presented to provide a person of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what is considered to be the present invention. Every effort has been made to ensure the accuracy of the numbers used (e.g., amounts, temperatures, concentrations, etc.), but some experimental errors and deviations should be allowed for. Unless otherwise indicated, parts are parts by weight, molecular weight is weight average molecular weight, temperature is degrees Celsius, and pressure is atmospheric pressure or near atmospheric pressure.

[0072] Example A - Formulation 1

[0073] Compound Weight Percent Zinc oxide (CAS No. 1314-13-2) 12.5％. Hydrocortisone (CAS No.: 50-23-7) 1％. Clotrimazole (CAS No. 23593-75-1) 0.5％. Polydimethylsiloxane (CAS No. 63148-62-9) 0.05％. Vaseline (CAS No. 8009-03-8) 85.95％

[0074] Example B - Formulation 2

[0075] Compound Weight Percent Vaseline 45％ Cetearyl Alcohol and Ceteareth-20 4％ Mineral Oil USP 11％ Lanolin USP 2％ paraffin 4.5％ Purified water 10％ Sodium phosphate dibasic heptahydrate USP 0.2％ Disodium EDTA 0.2％ Modified corn starch 6％ Zinc Oxide 15％ Clotrimazole 1％ Hydrocortisone 1％ Chlorocresol 0.1％

[0076] This formulation uses a safe and effective low dose of active agents to address the common problems of wet damaged skin. Proper treatment of damaged skin due to IAD (incontinence associated dermatitis) and intertrigo reduces the risk of pressure injuries, and this cream addresses both MASD conditions. Conventional regimens require the use of separate agents in sequence, while the single formulation of the present invention requires only a single application, thereby reducing the need for professional care. In short, this formulation provides a simple, safe, and effective one-step skin care regimen.

[0077] The inactive agents, namely zinc oxide and emollients, keep the active agents in contact with the skin and provide a barrier. The inactive agents effectively keep the active agents “in place” so that they can provide healing rather than being rubbed off on sheets and clothing, resulting in wasted time and product and slowed or ineffective healing. Nurses and physicians note that healing times are up to two times faster than with traditional single-agent use. The emollients and zinc also protect the skin from moisture damage that can reappear after treatment and can wash the active agents off the skin, requiring reapplication. The emollients and zinc oxide moisturize the skin while protecting it. This provides relief to the patient. Additionally, fewer products are needed compared to using multiple products. The formulation can be packaged in small quantities for travel or economical use. Using an effective, one-step product saves both product and nursing / caregiver time needed to treat the patient. Simple, yet effective, one-step solutions are important for addressing complex, chronic, and recurring skin care issues.

[0078] The blended mixture is very gentle and light, making it very easy to apply and remove. This reduces patient discomfort and skin damage from manipulation, rubbing and pulling. It is blended to be clear or "vanish" for easy inspection.

[0079] In another formulation, the cream is layered or embedded onto a disposable wipe. The wipes offer the same one-step process in one package. By combining three steps into one, one-step incontinence care helps reduce the time and effort spent by caregivers. It is efficient. Administration does not require caregivers to come into direct contact with the skin or latex. It is an ideal and hygienic solution that avoids the risk of direct contact with the spread of infection or other contamination, or contact with latex in the case of allergies.

[0080] The wipes are suitable for institutional, home use, and are easy to carry in a purse or pocket for a day trip. The wipes provide the convenience of a prescribed dose, uniform, controlled distribution, no rubbing, non-stickiness, moisture saturation, and easy application. Polydimethylsiloxane and aloe vera may be present in the wipe formulation. In some formulations, biodegradable wipes are provided.

[0081] In other embodiments, an aerosol, spray pump or continuous spray bottle formulation is provided. Aerosol spray is an effective and hygienic way of administering medicine, suitable for very delicate damaged skin, and can be provided in the form of dry spray, wet spray, foam or gel. It is very suitable for medical products. The formulation can be sealed, which helps to prevent infection and contamination of patients and caregivers. Since there is no need for contact, this helps to prevent pain and further skin damage to patients and evenly distribute the medicine over the surface area. Aerosols can be sprayed on any part of the body in any direction. The right amount of medicine can be easily sprayed exactly where it is needed in a resource-efficient manner. Aerosols can also be sprayed on three-in-one cleaning wipes so that medicine can be added when needed. Aerosols or sprays can control particle size, spray pattern and concentration to achieve maximum effect, so they are cost-effective. Aerosol containers are available in institutional sizes and travel sizes.

[0082] In certain embodiments, the therapeutic preparation is a sprayable composition comprising one or more spray components. As used herein, "spray component" refers to a spray as one or more added ingredients, and its specific purpose is to help spray in liquid, gel or foam form. After spraying, gelling or foaming are completed, the spray component may volatilize. The spray component can be inactive or can have supplementary activity, such as anti-infective and anti-inflammatory properties, which can be added or coordinated with the active ingredient of the present invention. Some spray components, such as lower alcohols, can serve as penetration enhancers and increase the transdermal delivery of active ingredients. Exemplary spray components include but are not limited to gelling agents, foaming agents or spray support solvents. In certain embodiments, the preparation can be sprayed in liquid, gel, foam or powder form.

[0083] The composition includes a gelling agent to promote gel formation and stability. In one or more embodiments, the gelling agent includes natural gums such as tragacanth, carrageenan, pectin, agar, and alginic acid; semi-synthetic materials such as methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and polymers such as carbomer ( 940). These may be water-based or hydroalcoholic. In one embodiment, one or more gelling agents are independently selected from the group consisting of natural gums such as tragacanth, carrageenan, pectin, agar, and alginic acid; semi-synthetic materials such as methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carbomer polymers. Exemplary gelling agents are also described in US 4,534,958 and EP 0679309, the entire contents of which are incorporated herein by reference.

[0084] The composition includes a foaming agent to improve the foaming ability of the preparation and to increase the stability of the foam for the intended purpose. In one or more embodiments, the foaming agent includes fatty alcohols, fatty acids and mixtures thereof. The foaming agent may include at least one fatty alcohol and at least one fatty acid. Suitable fatty alcohols include alcohols with 15 or more carbons in the carbon chain, such as hexadecanol and stearyl alcohol (or mixtures thereof). Other examples of fatty alcohols are eicosanol (C20), behenyl alcohol (C22), 1-triacontanol (C30), and alcohols with longer carbon chains (up to C50). Fatty alcohols derived from beeswax, including mixtures of alcohols, most of which have at least 20 carbon atoms, are particularly suitable for use as foam adjuvants of the present invention. In one embodiment, one or more foaming agents are independently selected from the group consisting of fatty alcohols, fatty acids and mixtures thereof. Exemplary foaming agents are also described in EP 0613728, US 4,534,958, US 6,126,920 and US 8,336,737, all of which are incorporated herein by reference.

[0085] Suitable fatty acids include acids with 16 or more carbons in the carbon chain, such as hexadecanoic acid (C16), stearic acid (C18), arachidic acid (C20), behenic acid (C22), octacosanoic acid (C28), and fatty acids with longer carbon chains (up to C50), or mixtures thereof. The concentration of fatty alcohols and fatty acids required to support the foaming system is generally inversely proportional to the length of their carbon chains. Alternatively, the carbon atom chain of the fatty alcohol or fatty acid may have at least one unsaturated site, may be branched or may be optionally substituted with hydroxyl groups, such as 12-hydroxystearic acid. In certain embodiments, the foaming agent may include a mixture of any ratio of fatty alcohols, fatty acids, and hydroxy fatty acids and alcohols. The total amount of foam adjuvant is from about 0.1% to about 5% (w / w) of the carrier mass, and typically, the total amount is from about 0.4% to about 2.5% (w / w) of the carrier mass.

[0086] A spray supporting solvent is included in the composition to improve flow characteristics, droplet size, atomization ability, thereby facilitating liquid spraying. The spray supporting solvent can be volatile to support volatilization during spraying or after application to the treatment area. In one or more embodiments, the spray supporting solvent includes water, a lower alcohol with a maximum of 5 carbons, such as ethanol and isopropanol, a lower ketone with a maximum of 5 carbons, such as acetone, methyl ethyl ketone and 3-pentanone, or a mixture thereof. In one embodiment, one or more spray supporting solvents are independently selected from the group consisting of water, a lower alcohol with a maximum of 5 carbons, such as ethanol and isopropanol, a lower ketone with a maximum of 5 carbons, such as acetone, methyl ethyl ketone and 3-pentanone, or a mixture thereof.

[0087] In one embodiment, the therapeutic formulation comprises hydrocortisone, clotrimazole, zinc oxide, petrolatum, water, cetearyl alcohol, ceteareth-20, sodium phosphate, and one or more spray components. In one embodiment, the sprayable composition comprises hydrocortisone, clotrimazole, zinc oxide, petrolatum, water, cetearyl alcohol, ceteareth-20, sodium phosphate, and one or more spray components, wherein the formulation can be sprayed in liquid, gel, or foam form.

[0088] In some embodiments, a set of sprayable compositions is provided, wherein 1) a first part that contacts the treatment area comprises hydrocortisone, clotrimazole, petrolatum, water, cetearyl alcohol, ceteareth-20, sodium phosphate and one or more spray components; 2) a second part of a protective layer comprises zinc oxide, petrolatum and one or more spray components, wherein the preparation can be sprayed independently in the form of liquid, gel or foam. The first part that contacts the treatment area is sprayed directly on the treatment area, and the second part of the protective layer is sprayed on the first part that contacts the treatment area.

[0089] In one embodiment, the one or more spray components of the first portion contacting the treatment area are independently selected from the group consisting of a gelling agent, a foaming agent, and a spray-supporting solvent. In one embodiment, the one or more spray components of the second portion of the protective layer are independently selected from the group consisting of a gelling agent, a foaming agent, and a spray-supporting solvent.

[0090] In some embodiments, the therapeutic formulation or sprayable composition is delivered using a manual pump, a spray pump, or in metered doses.

[0091] In other embodiments, applicators with higher fluid content are provided for hard-to-reach damaged areas, which avoids the risk of direct contact and contamination, and also avoids the use of latex.

[0092] In another embodiment, a protective mask is provided in which the therapeutic agent is embedded in the seal of the protective mask, such as a protective mask used by caregivers in hospitals, long-term care homes, and other occupations requiring protection. This helps to treat skin damage caused by sweating and friction caused by long-term use of closed masks (and other protective clothing), and provides protection and reduces risks in infectious environments.

[0093] In some embodiments, a kit containing one or more separate creams is provided. These separate face creams can be applied separately, or mixed together and then applied. In one embodiment, a cream is a therapeutic preparation as described herein, which contains hydrocortisone, clotrimazole and zinc oxide, and optionally one or more of the enzyme inhibitors, pH buffers, moisturizers or wetting agents, antibacterial agents, antifungal agents or peptides described herein. In some embodiments, two or more creams are mixed together to prepare a therapeutic preparation containing hydrocortisone, clotrimazole and zinc oxide as described herein. In one embodiment, the kit contains three or four separate creams. In one embodiment, the first cream contains non-medicinal ingredients for skin protection. In one embodiment, the second cream contains 0.1% to 1.1%, preferably 1% hydrocortisone by weight. In another embodiment, the second cream contains hydrocortisone and zinc oxide. In one embodiment, the third cream contains 0.1% to 1.1%, preferably 1% clotrimazole by weight. In one embodiment, the third cream contains clotrimazole and zinc oxide. In some embodiments, the second cream and the third cream are separate creams. In other embodiments, the second cream and the third cream are manufactured together as a single product. In one embodiment, the fourth cream contains one or more of the enzyme inhibitors, pH buffers, moisturizers or wetting agents, antibacterial agents, antifungal agents, or peptides described herein. In one embodiment, the first cream, the second cream, and / or the third cream contain one or more of the enzyme inhibitors, pH buffers, moisturizers or wetting agents, antibacterial agents, antifungal agents, or peptides described herein. In one embodiment, the fourth cream is formulated to specifically treat the problem of risk factors associated with the occurrence of MASD in patients with diarrhea, and contains one or more of the following: soybean tyrosine inhibitors (TSI) at a concentration of 0% to 25% (i.e., 1% by weight); Birk-Bowman inhibitors, Birk-Bowman-related protease inhibitors, and / or Birk-Bowman family protease inhibitors at a concentration of 0% to 25% (i.e., 1% by weight); or non-denatured soy extracts (i.e., 10% by weight).

[0094] In some embodiments, the compositions and formulations described herein are provided in the form of freeze-dried powders, comprising 1% to 100% of the compositions or formulations by weight, the remainder comprising corn starch, tapioca starch, kudzu starch, kaolin, oatmeal, talc, or a combination thereof. The powder is dry-sprayed onto a cream formulation described herein that has been topically applied to the skin. This dry spray adheres to the local area and forms a crust or film after drying, which physically prevents additional incontinence attacks during cleaning. The dry spray or wet spray will contain anti-fecal peptides or any peptide from the plant protease inhibitor family. The preparation will contain an adhesive, which may contain any of the above-mentioned dry powders.

[0095] Treatment and options

[0096] The present disclosure relates to compositions and methods for treating a subject to reduce MASD, such as surgical adhesions, and includes administering to the subject a therapeutic formulation described herein. In some embodiments, the MASD is intertrigo. In some embodiments, the MASD is associated with incontinence.

[0097] The compositions and preparations described herein can also be used to prevent or treat tinea pedis, tinea cruris and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton floccosum; (2) candidiasis caused by Candida albicans; (3) tinea versicolor caused by Malassezia furfur, or anorectal pruritus.

[0098] The method comprises administering to a subject in need of treatment an effective therapeutic amount or effective dose of a therapeutic formulation. In some embodiments, the effective dose of the therapeutic entity described herein varies according to many different factors, including the mode of administration, the target site, the physiological state of the patient, whether the patient is human or animal, other drugs administered, and whether the treatment is preventive or therapeutic. Typically, the patient is human, but non-human mammals can also be treated. The therapeutic dose can be adjusted to optimize safety and efficacy. The reduction of skin lesions can be monitored.

[0099] The effective dosage of the agent may vary with the agent, but typically ranges from up to about 0.1 ml, 0.5 ml, 1 ml, 5 ml, 10 ml, 20 ml, 30 ml, 50 ml, or more depending on the surface area to be treated.

[0100] The therapeutic agent may be administered for one or more days, and in some embodiments, daily, every other day, semi-weekly, weekly, etc., for about 1 to 2 weeks.

[0101] In some embodiments, for prophylactic administration, an amount of a therapeutic formulation sufficient to eliminate or reduce the risk, lessen the severity, or delay the onset of a condition is administered to a patient susceptible to or at risk for MASD.

[0102] In other embodiments, for therapeutic administration, an amount of the therapeutic formulation sufficient to cure or at least partially arrest skin damage (including its complications and pathological sequelae) is administered to a patient already suffering from MASD. An amount sufficient to accomplish therapeutic or prophylactic treatment is defined as a therapeutically or prophylactically effective dose.

[0103] In some embodiments, when the therapeutic formulation comprises an enzyme inhibitor and / or a pH buffer, the therapeutic formulation is administered to a patient suffering from urinary incontinence and / or fecal incontinence.

[0104] Pharmaceutical compositions are generally formulated in full compliance with all Good Manufacturing Practice (GMP) regulations of the U.S. Food and Drug Administration.

[0105] In some embodiments, the therapeutic formulation is administered to the patient in combination with a biofilm treatment, for example using hyperosmotic conditions and / or surfactants. Exemplary biofilm treatments are described in WO2013052958, US10 / 021876, US7976875, and US7959943, the entire contents of which are incorporated herein by reference.

[0106] In certain embodiments, corn starch is applied after applying compositions as herein described or therapeutic preparations to prevent the removal of the compositions or therapeutic preparations. In one embodiment, corn starch is applied by blowing or dry spraying (i.e. using a squeeze bottle). After the compositions or therapeutic preparations are applied to the skin area, corn starch is blown or dry sprayed to the area and adhered to the compositions or therapeutic preparations to form a natural protective film, while also preventing the compositions or therapeutic agents from being removed. This natural protective film can protect the skin from diarrhea. When covered with corn starch film, the skin area through the application can be cleaned with a wipe, and when necessary, the corn starch film can be removed with mineral oil. Then the skin below can be cleaned and observed, and the compositions or therapeutic preparations can be re-applied as needed. As needed, the corn starch film can be re-applied.

[0107] There are multiple skin care products available for the treatment of MASD; however, the wide variety of skin care products makes it difficult for bedside nurses or caregivers to select the best product for a specific condition. This challenge is compounded by the lack of consistency in product names and the lack of a grading system designed to help clinicians select products based on the severity of IAD, irritants, and presence of complications. (Doughty 2012). Interestingly, patients often apply multiple products to their skin due to a lack of assessment, poor understanding of barrier products, and care plans, which can lead to worsening of the skin condition (Mahoney et al., 2019). Due to the lack of well-established clinical trials, recommendations for MASD are based on expert opinion, consensus statements, and best practices. Gentle cleansing, the use of moisturizing topicals, and the application of barrier products are the main elements of preventing and treating IAD (Beele H2018). IAD was the subject of a Cochrane Systemic Review 2016 that aimed to elucidate the effects of various skin care products and procedures on the treatment and prevention of IAD. They found no evidence to suggest that one skin care product is better than another.

[0108] In accordance with the present disclosure, exemplary protocols for improving the treatment of MASD using the compositions and therapeutic formulations provided herein are provided.

[0109] Example C - Scheme 1

[0110] Four unique medicated and non-medicated topical cream products are used alone or in combination. Cream A is non-medicated and is used daily to protect the skin and prevent MASD. Cream B is medicated (containing 0.1% to 1.1%, preferably 1% hydrocortisone by weight, optionally zinc oxide), and is applied for 7 days if signs of redness, itching, pain or burning persist. If additional skin protection is needed, further cover the skin area where Cream B was applied with Cream A. After the rash has healed, resume daily use of Cream A alone. Cream C is medicated (containing 0.1% to 1.1%, preferably 1% clotrimazole by weight, optionally zinc oxide), and is applied for 7 days if severe itching occurs, especially between skin folds, or flaky skin or small red spots appear at the edge of the rash, or if a fungal infection is suspected. If additional skin protection is needed, further cover the skin area where Cream C was applied with Cream A. After the rash has healed, resume daily use of Cream A alone. Cream D is non-medicated (contains one or more enzyme inhibitors, pH buffers, moisturizers or wetting agents, antibacterial agents, antifungal agents, or peptides) and is applied for 7 days if redness, itching, pain, or burning occurs as a result of liquid diarrhea. If additional skin protection is needed, further cover the skin area where Cream D was applied with Cream A. After the rash has healed, resume daily use of Cream A alone.

[0111] Example D - Additional Combination 3

[0112] Three or four medicinal and non-medicinal topical cream products are used alone or in combination. Cream A is as described in Example C. If there is persistent and / or intense redness, itching, pain or burning, creams B and C as described in Example C can be made together as a single product and applied for 7 days. If additional skin protection is needed, the skin area where creams B and C are applied is further covered with cream A. After the rash heals, resume daily use of only cream A. Cream D is as described in Example C, and if there is persistent and / or intense redness, itching, pain or burning, it can be prepared and applied for 7 days alone or in combination with B, in combination with C, or in combination with B and C. If additional skin protection is needed, the skin area where cream D is applied is further covered with cream A. After the rash heals, resume daily use of only cream A.

[0113] Example E - Alternative 2

[0114] When it is necessary to speed up healing, reduce nursing time and prevent skin damage caused by the application of multiple agents, equal amounts of creams A, B and C, or A, B, C and D as described in Example C can be combined together and applied in a single step for 7 days. After the rash heals, resume daily use of cream A only.

[0115] A rabbit model of IAD was also studied. The combination cream (DGBC) was used to evaluate healing in an animal model of IAD compared to the three active ingredients of the cream. Twenty-six IAD lesions were induced, and each lesion was treated with the individual ingredients and the combination cream. Although the combination cream containing the three drugs showed the fastest synergistic healing, all single-agent treatment groups were effective in treating IAD, with all lesions completely healed by day 5 of treatment.

[0116] Example F - Incontinence-associated dermatitis rabbit model

[0117] Rabbits were purchased from Charles River for use in these experiments. Rabbits were chosen because they have large, relatively hairless ears that are suitable for topical application of IAD-inducing agents as well as treatment of incontinence-associated dermatitis (IAD). Additionally, the animals' ears were utilized to maximize sample size, effectively halving the number of animals required for the project. Twenty-two female rabbits were purchased: two for the pilot phase and 18 for Phase II of the project. The study was conducted in accordance with CCAC guidelines, and the animals were housed at the AVC research facility. The experimental treatment used a therapeutic cream consisting of 1.0% hydrocortisone, 1.0% clotrimazole, and 15.0% zinc oxide (DGBC).

[0118] Phase I trial: To determine the best compound to induce IAD, IAD was induced in one ear with 5% pancreatic enzymes (fecal enzymes) and in the other ear with 1% ammonium hydroxide (synthetic urine). Sterile 3x3 gauze was used as a carrier for the irritant. The gauze was soaked with 5 ml of artificial urine or pancreatic enzymes. This amount of irritant was sufficient to soak each gauze. The soaked gauze was covered with an occlusive dressing (Opsite) and left in place for 72 hours. An Elizabethan collar was placed on any rabbit that attempted to move or remove the covering gauze. After 72 hours, the occlusive dressing and gauze were removed. Treatments were applied vertically on the ears in sequence and the order was rotated for each rabbit: Rabbit 1 (R1): A (BDGC Treatment Cream), B (Clotrimazole), C (Hydrocortisone), D (Zinc Oxide); Rabbit 2 (R2): D, A, B, C. The results are summarized in Table 1. Table 1 Phase I Study Results for Rabbit 1 and Rabbit 2 Rabbit 1:

[0119]

[0120]

[0121] Rabbit 2:

[0122]

[0123] IAD classification: 1A persistent redness without clinical symptoms of infection, 1B persistent redness with clinical symptoms of infection, 2A skin defect without clinical symptoms of infection, 2B skin defect with clinical symptoms of infection.

[0124] Phase II clinical trial.

[0125] Induction of IAD. 1. Rabbit anesthesia: Intramuscular (IM) midazolam 0.5 mg / kg plus buprenorphine 0.03 mg / kg. Animals were assessed for anesthesia before gauze was applied. For animals that required further anesthesia, ketamine 5 mg / kg IM was used for anesthesia. 2. Ear cleaning: The skin of both inner ears of each animal was cleaned with 2x2 gauze soaked with 3 ml of isopropyl alcohol, and the skin was allowed to air dry for 5 minutes before applying the soaked gauze. Before induction of IAD, the animals were grasped for 5 minutes to ensure that the ears were dry. 3. Induction of IAD with gauze containing 5% pancreatin: The following stimulation was performed on both ears of the animal: Sterile 2x2 gauze was used as a carrier of the stimulant. The gauze was soaked with 3 ml of pancreatin. 4. Ear wrapping: Gauze containing pancreatin was applied to the inner surface of both ears of each animal. The soaked gauze was covered with an occlusive dressing (OpSite), VetWrap was loosely applied on the gauze roll, and it was left in place for 24 hours. 5.24 hour monitoring period: After 24 hours, remove the bandage and occlusive dressing and assess the ear for adequate stimulation. If the stimulation is clearly insufficient, a new 2x2 gauze is soaked in 3 ml of pancreatin and reapplied as above. 6. Removal of wraps and gauze: Once adequate stimulation is achieved, remove the occlusive dressing and gauze. 7. Adequate stimulation for treatment: Perform a first visual assessment of the skin lesions using the erythema and edema assessment and the Ghent Global IAD classification tool. The classification of lesions takes into account "redness", "skin loss" and the percentage of lesion area. Take photos of the skin lesion area. The Ghent scale file is used in the pilot study for additional stimulation assessment. 8. Pain management: Rabbits were treated with gabapentin 20 mg / kg PO once daily during IAD induction and on the first day of treatment. Rabbits assessed as painful 1 hour after gabapentin administration were treated with buprenorphine 0.03 mg / kg SC and pain was reassessed within 1 hour.

[0126] Treatments: 1. Photo Collection: Both ears Day "n": Rabbits were held by the same researcher in the same area of ​​the same room, and a second researcher took photos of the stimulation of each ear. 2. Photos and data for each ear and each animal were entered into the Ghent Scale file. 3. One researcher held each rabbit, and another researcher delineated and marked the IAD stimulation area using the same standard ruler (see attachment). In turn, the IAD area was divided into four equal areas for treatment. 4. Compounds were applied to the designated areas of the IAD on each ear. The four treatments were as follows: DGBC Treatment Cream (A); 1.0% Clotrimazole (B); 1.0% Hydrocortisone (C), 15.0% Zinc Oxide (D). The order of treatments was randomized for each subject.

[0127] Synergy Analysis: The synergy between the three compounds will be analyzed using Multidimensional Combinatorial Synergy (MuSyC), which is based on a two-dimensional (2D) extension of the Hill equation derived from mass action kinetics.

[0128] Analysis: The results will be analyzed considering the results of synergistic efficacy (b), synergistic effectiveness (a) and synergistic synergy (g) of each compound. These three parameters will determine the synergistic properties of the compound.

[0129] Adverse Events / Risks: Hydrocortisone and clotrimazole are among the most commonly used drugs on the World Health Organization (WHO) Essential Medicines List

[10] . Long-term administration of hydrocortisone may cause local allergic reactions, skin irritation / pain, and skin atrophy. Clotrimazole may cause blistering, discomfort / pain, edema, erythema, irritation, peeling / flaking, itching, rash, and stinging / burning sensations in humans. Zinc oxide may cause mild irritation when applied topically to animals.

[0130] Results: Twenty Australian white rabbits were purchased for clinical trials of "Dr. Gordon's Bum Cream". Two rabbits were used in trial #21-039 to complete the main clinical trial. Eighteen female rabbits weighing 1.4±0.079 kg were used in protocol #21-051, the purpose of which was to evaluate the safety, efficacy and synergy of the therapeutic cream (DGBC). Incontinence-associated dermatitis (IAD) lasting 24 hours was artificially induced in 18 rabbits using 1 ml 5% pancreatin and each ear was occluded with Opsite. After achieving sufficient irritation (see results of protocol #21-039), the rabbits were treated with DGBC (A), 1% clotrimazole (B), 1% hydrocortisone (C) and 15% zinc oxide (D). According to the protocol, the left and right ears were divided into four vertical sections (one for each compound) and treated with the four compounds for 7 days. The order of the compounds was randomized, and each rabbit received a specific and unique order. The median daily dosage of DGBC treatment cream (A), 1% clotrimazole (B), 1% hydrocortisone (C), and 15% zinc oxide (D) was 37 cm 2 0.13 g / d (range 0.1 g / d to 0.15 g / d) was used on the area of ​​​​(average ear area). A thin layer of each compound was applied to the marked area. During the first three days of the clinical trial, gabapentin was given to rabbits for analgesia; after the third day, only three rabbits had a pain score of 1, and analgesia was no longer given.

[0131] Efficacy: Results showed that the DGBC treatment cream completely cured 70% of the ears in an average of three days; 16.6% of the ears could not be evaluated, while 13% of the ears were cured using a different compound than the DGBC treatment cream and in some cases for longer than seven days. Results showed that hydrocortisone, clotrimazole, and zinc oxide used alone did not produce the same effects as using the DGBC treatment cream containing a combination of these three compounds. The DGBC treatment cream showed superior efficacy when used to treat IAD in rabbits, with no crusting or skin flaking after treatment compared to zinc oxide. See Figure 1 .

[0132] Example G-Proteolytic Enzyme Assay

[0133] Methods. Enzyme assay experiments were conducted to develop a cream containing raw soy extract that could inhibit digestive enzymes commonly found in feces. Pancreatic enzymes were used as the enzyme source and azocasein as the substrate to produce compounds that were UV active at 440 nm. The punitive inhibitor of this reaction was raw soy extract. To measure the proteolytic activity of pancreatic enzymes in solution, spectrometric assays were performed using azocasein. The inhibitor was extracted from raw soybeans in water. The soy extract was prepared by soaking appropriate amounts of soybeans in purified water at 4°C for 24 hours. The mixture was stirred, centrifuged, and the supernatant was retained. The soy extract was incorporated into the cream by a freeze drying process. The creams tested included Dr Gordon's Bum Cream, Dr Gordon's Everyday Cream, and Vaseline cream. The creams were mixed with pancreatic enzymes and subjected to protease inhibition assays.

[0134] Results. When soy extract was added to a standard pancreatin-azocasein solution, the absorbance at 440 nm was reduced. Raw soy extract inhibited the pancreatin-azocasein reaction (PAR) by about 85% (Table 2). Five different creams were tested to determine the inhibitory effect of soy extract with or without creams. For each cream, the cream was tested alone as a control comparator, and then the cream containing 3% soy extract was tested. Comparing the absorbance of the reactions at working concentrations and the reactions with creams, azocasein and pancreatin, it was observed that the reaction between azocasein and pancreatin was not interfered by any interference from the cream (Table 3). In all creams, 3% soy extract showed an inhibitory effect on PAR.

[0135] Table 2: Response and inhibition percentages of assay reactions.

[0136]

[0137] Table 3: Responses of extracts from the cream and responses of those in contact with the cream.

[0138] Absorbance (AU) <![CDATA[1 / 100 dilution Pancreatin / Azocasein Rxn (working concentration)]]> 0.1878 <![CDATA[Cream extract + Azocasein Reaction determination]]> 0.0098 <![CDATA[Cream extract + Azocasein + Pancreatin Reaction determination]]> 0.1834

[0139] Table 2. To determine the percentage of inhibition by raw soy extract, a pancreatin-azocasein (PAR) solution was prepared and incubated with two different volumes (0.5 mL and 1.0 mL) of soy extract. Raw soy extract inhibited PAR by approximately 85%.

[0140] Table 3. Interference of cream alone and with a solution of pancreatin azocasein (PAR) at 440 nm was investigated. Reactions were performed using azocasein and 1.0 mL of cream extract without pancreatin to determine if cream would react with azocasein and with PAR and cream extract. Comparison of the absorbance of the reactions at the working concentrations and the reactions with cream, azocasein, and pancreatin revealed that the reaction between azocasein and pancreatin was not interfered by any cream.

[0141] The raw soybean extract was evaporated and concentrated into a thick paste by heating at 50°C for about three days. Three cream samples containing concentrated soybean extract were prepared, 3%, 7%, and 15% by weight. The reaction was repeated using 1 g of each concentration of cream, azocasein, and pancreatin. Table 4 shows the inhibition percentage results for each cream.

[0142] Table 4: Response of the reaction assay to different percentages of soy in the cream.

[0143] Absorbance (AU) Creams without soy extracts 0.1468 Cream containing 3% soybean extract 0.0525 Cream containing 7% soy extract 0.0526 Cream containing 15% soy extract 0.0592

[0144] Table 4. The extent of inhibition was similar for all three concentrations of soy extract. The absorbance ranged from 0.05 to 0.06 AU, with an overall inhibition of the trypsin-azocasein reaction (PAR) of 65% to 70%.

[0145] Two linear regression analyses were performed to observe the relative concentration of the enzyme solution and the absorbance at 440 nm (see Figure 2 ). The R-squared value is a statistical measure of how well the statistical model predicts the results. The R-squared value in the first regression analysis was 0.998, and the R-squared value in the second regression analysis was 0.994. The absorbance at 440 nm increased almost linearly with the increase in the relative concentration of the enzyme solution.

[0146] Five different creams were also tested to determine the inhibitory effect of soy extract with or without the creams. As a control, the PAR (Pancreatin-Azocasein Reaction) in solution was tested alone. For each cream, the cream was tested alone as a control comparator and then the cream containing 3% soy extract was tested. The difference in absorbance at 440nm was analyzed. 3% soy extract had an inhibitory effect on PAR in all of the following creams: Mediderm 87%, Relieve 99%, Dr Gordon's Bum Cream 67%, Treat 77%, Dr Gordon's Everyday Cream 97%. See Figure 3 and Figure 4 .

[0147] Example H - Natural Formulations

[0148] In various embodiments including dry sprays, Cream D or other natural products will include: 1% to 40% zinc oxide by weight, 0.5% to 100% soybean extract by weight (or any other extract from a plant family, such as those listed in Table A), and other agents selected from the following: acetic acid, zinc salts-zinc acetate, mixed fatty acid glycerides-stearate, aluminum hydroxide, oats-colloidal oats, urea, urea hydrochloride, sodium carbonate salts-baking soda, carbonic acid, zinc salts-zinc carbonate, 2,5-dioxy-4-imidazolidinyl-urea-allantoin, iron oxide and zinc oxide-calamine, kaolin (various), DL-lactic acid, 2-hydroxy-2-methylacetic acid-lactic acid, lanolin, anhydrous lanolin-lanolin, olive-olive oil, 1,2,3-propanediol-glycerol, almond-almond oil, cocoa-cocoa butter, corn-corn starch, cod liver oil.

[0149] Therapeutic formulation: water, cetearyl alcohol, clotrimazole, glyceryl laurate and benzyl alcohol, liquid paraffin, polyethylene glycol monocetyl ether and white petrolatum. Therapeutic formulations may contain additional components or combinations of the components listed above.

[0150] Relief formulation: 1% hydrocortisone, water, cetearyl alcohol, glyceryl laurate and benzyl alcohol, liquid paraffin, polyethylene glycol monocetyl ether, white petrolatum and aloe (i.e., aloe barbadensis leaf juice). The relief formulation may contain additional ingredients or a combination of the ingredients listed above.

[0151] Example I - Individual Case Study Data for Adult and Infant Populations

[0152] Preliminary results show that the cream is effective in relieving intense itching of the skin caused by contact with stool and diarrhea. Preliminary evidence shows that the cream can quickly relieve pain and itching associated with enterocutaneous fistulas. Preliminary results show that the cream appears to reduce and relieve dermatitis associated with chronic diarrhea in infants. The cream is well tolerated. Comments include: "comfortable", "non-sticky", and "long-lasting".

[0153] Case Study #1. Preliminary results suggest that once daily application is sufficient to relieve chronic anal pruritus in individuals experiencing chronic symptoms due to anal surgery.

[0154] Case Study #2. The cream was applied after each bowel movement in an individual with Crohn's disease dilation who had persistent diarrhea for 72 hours. This dilation often resulted in significant perianal itching and burning. Individual reports stated that the cream appeared to prevent skin damage as there was no redness or itching during or after an attack.

[0155] Case Study #3. For an infant with chronic diarrhea and noticeable red, irritated skin, the baby’s perineal rash disappeared after 3 days of applying the cream at every diaper change. The parent noted rapid improvement in skin after diaper changes and the child seemed calmer.

[0156] All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0157] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to one of ordinary skill in the art based on the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims

1. A therapeutic composition comprising: from about 5% to about 20% by weight zinc oxide; from about 0.5% to about 2.5% by weight hydrocortisone; and From about 0.1% to about 1% clotrimazole by weight.

2. The therapeutic composition of claim 1 comprising from about 10% to about 15% by weight zinc oxide.

3. A therapeutic composition according to claim 2 comprising 12.5% ​​by weight zinc oxide.

4. The therapeutic composition of claim 2 comprising 15% by weight zinc oxide.

5. The therapeutic composition of any one of claims 1 to 4 comprising from about 0.2% to about 2.5% by weight of hydrocortisone.

6. The therapeutic composition of claim 5 comprising from about 0.2% to about 0.5% by weight hydrocortisone.

7. The therapeutic composition of claim 5 comprising from about 0.75% to about 1.25% by weight hydrocortisone.

8. The therapeutic composition of claim 5 comprising 1% by weight hydrocortisone.

9. The therapeutic composition of any one of claims 1 to 8 comprising from about 0.25% to about 0.75% clotrimazole by weight.

10. The therapeutic composition of claim 9 comprising 0.5% by weight clotrimazole.

11. The therapeutic composition of claim 9 comprising 0.1% by weight clotrimazole.

12. The therapeutic composition of any one of claims 1 to 11 comprising from about 30% to about 60% by weight petrolatum.

13. The therapeutic composition of claim 12, wherein petrolatum is present in a concentration of about 40% to 50% by weight.

14. The therapeutic composition of claim 13, wherein petrolatum is present at a concentration of 45% by weight.

15. The therapeutic composition of any one of claims 1 to 14, further comprising 0.01% to about 2.5% by weight of polydimethylsiloxane.

16. The therapeutic composition of any one of claims 1 to 15 comprising a proteolytic enzyme inhibitor.

17. The therapeutic composition of claim 16, wherein the proteolytic enzyme inhibitor is a tyrosine inhibitor.

18. The therapeutic composition of claim 16, wherein the proteolytic enzyme inhibitor comprises soy tyrosine inhibitor (STI), Birk-Bowman inhibitor (BBI), non-denatured soy extract, or a combination thereof.

19. The therapeutic composition of any one of claims 16 to 18 comprising about 0.1% to 30% by weight of the proteolytic enzyme inhibitor.

20. The therapeutic composition according to any one of claims 1 to 19, comprising: a) one or more inactive ingredients selected from the group consisting of: cetearyl alcohol, mineral oil, lanolin, paraffin, water, sodium phosphate, EDTA, modified corn starch and chlorocresol; and / or b) one or more additives, and wherein the additive is a pH buffer, a humectant, an antibacterial agent, an antifungal agent, or a peptide.

21. The therapeutic composition of claim 1, comprising: 12.5% ​​by weight zinc oxide; 1% by weight hydrocortisone; 0.5% clotrimazole by weight; 0.05% by weight dimethicone; and 85.95% petrolatum by weight.

22. The therapeutic composition of claim 1, comprising: 15% by weight zinc oxide; 1% by weight hydrocortisone; and 1% Clotrimazole by weight.

23. The therapeutic composition of claim 1, comprising: 45% petrolatum by weight; 4% cetearyl alcohol and ceteareth-20 by weight; 11% by weight mineral oil; 2% lanolin by weight; 4.5% paraffin by weight; 10% water by weight; 0.2% by weight disodium hydrogen phosphate heptahydrate; 0.2% disodium EDTA by weight; 6% by weight modified corn starch; 15% by weight zinc oxide; 1% clotrimazole by weight; 1% by weight hydrocortisone; and 0.1% chlorocresol by weight.

24. A kit comprising: a second cream comprising 0.1% to 1.1% by weight hydrocortisone and optionally zinc oxide; and A third cream comprising 0.1% to 1.1% by weight clotrimazole and optionally zinc oxide.

25. The kit according to claim 24, comprising one or both of the following: A first cream comprising a non-medicinal ingredient for skin protection; and The fourth cream comprises one or more of a pH buffer, a moisturizer or a wetting agent, an antibacterial agent or an antifungal agent.

26. The kit according to claim 24 or 25, wherein one or more of the first cream, the second cream, the third cream, and the fourth cream comprises a proteolytic enzyme inhibitor.

27. The kit according to claim 26, wherein the proteolytic enzyme inhibitor is a tyrosine inhibitor.

28. The kit of claim 26, wherein the proteolytic enzyme inhibitor comprises soy tyrosine inhibitor (STI), Birk-Bowman inhibitor (BBI), non-denatured soy extract, or a combination thereof.

29. The kit of claim 28, wherein the fourth cream comprises a soy tyrosine inhibitor (TSI), a Birk-Bowman inhibitor (BBI), a non-denatured soy extract, or a combination thereof.

30. The kit composition of any one of claims 26 to 29, comprising about 0.1% to 30% by weight of the proteolytic enzyme inhibitor.

31. A kit according to any one of claims 24 to 30, wherein the second cream and / or the third cream comprises one or more of a pH buffer, a moisturizer or humectant, an antibacterial agent or an antifungal agent.

32. A kit according to any one of claims 24 to 31, wherein: The second cream comprises hydrocortisone and zinc oxide; and / or The third cream comprises clotrimazole and zinc oxide.

33. A kit according to any one of claims 24 to 32, wherein: The second cream comprises 1% by weight hydrocortisone; and / or The third cream contains 1% by weight of clotrimazole.

34. A kit according to any one of claims 24 to 33, wherein the second cream and the third cream are mixed together before application to the skin.

35. The therapeutic composition of any one of claims 1 to 23, for use with a cream comprising one or more of: an enzyme inhibitor; a pH buffer; a moisturizer or humectant; an antibacterial agent; an antifungal agent; or a proteolytic enzyme inhibitor selected from soy tyrosine inhibitor (TSI), Birk-Bowman inhibitor (BBI) and non-denatured soy extract.

36. The therapeutic composition according to any one of claims 1 to 23: i.Packaged in sealed containers; ii. Embedded in disposable wipes; iii. packaged in aerosol, spray pump or continuous spray containers; iv. packaged in an applicator; or v.Embedded in the seal of the protective mask.

37. A sprayable composition comprising a therapeutic composition according to any one of claims 1 to 23 or a cream as defined in any one of claims 24 to 34, and one or more spray components.

38. The sprayable composition of claim 37, wherein the one or more spray components comprise one or more gelling agents, foaming agents or spray-supporting solvents.

39. A kit comprising a first sprayable composition and a second sprayable composition, wherein: The first sprayable composition comprises hydrocortisone, clotrimazole, petrolatum, water, cetearyl alcohol, ceteareth-20, sodium phosphate, and one or more spray components; and The second sprayable composition comprises zinc oxide, petrolatum, and one or more spray components.

40. The kit of claim 39, wherein the one or more spray components in the first sprayable composition and the second sprayable composition comprise a gelling agent, a foaming agent, or a spray-supporting solvent.

41. A method for preventing or treating moisture associated skin damage (MASD), comprising: 1 g to 100 g of a composition according to any one of claims 1 to 23 is topically applied to the skin of a subject.

42. A method for preventing or treating moisture associated skin damage (MASD) using the kit described in 37 or 38, comprising: spraying the first sprayable composition onto a treatment area of ​​the subject; and The second sprayable composition is sprayed onto the first sprayable composition and the treatment area.

43. The method of claim 41 or 42, wherein the MASD is intertrigo.

44. The method of claim 43, wherein the MASD is incontinence-associated dermatitis (IAD).

45. The method of claim 44, wherein the IAD is urinary incontinence, fecal incontinence, or combined urinary and fecal incontinence.

46. ​​Use of the therapeutic composition of any one of claims 1 to 23 and 35 to 36, the kit of any one of claims 24 to 34 and 39 to 40, or the sprayable composition of claim 37 or 38 for preventing or treating moisture associated skin damage (MASD).

47. Use of a tyrosine inhibitor for preventing or treating moisture associated skin damage (MASD).

48. The use according to claim 46 or 47, wherein the MASD is intertrigo.

49. The method of claim 48, wherein the MASD is incontinence-associated dermatitis (IAD).

50. The method of claim 49, wherein the IAD is urinary incontinence, fecal incontinence, or combined urinary and fecal incontinence.

51. A composition comprising a tyrosine inhibitor and a carrier for use in preventing or treating moisture associated skin damage (MASD).

52. The composition of claim 51 further comprising clotrimazole, hydrocortisone and / or zinc oxide.

53. The composition of claim 51 which is a sprayable composition and optionally comprises zinc oxide.

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