WO2019108903A1

WO2019108903A1 - Methods of treating skin lesions

Info

Publication number: WO2019108903A1
Application number: PCT/US2018/063261
Authority: WO
Inventors: Ronald V. Nardi; Allen REHA; Jay Barth
Original assignee: Scioderm, Inc.
Priority date: 2017-12-01
Filing date: 2018-11-30
Publication date: 2019-06-06

Abstract

The present disclosure provides methods of treating skin lesions, e.g., of Epidermolysis bullosa (EB), in a subject in need thereof. In some embodiments, the methods comprise topically administering, at least once daily, to a skin area affected by the lesions of EB: a pharmaceutical composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant. In some embodiments, the composition comprises less than 0.5% allantoin or 0% allantoin.

Description

METHODS OF TREATING SKIN LESIONS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application Serial Nos.

62/593,745 filed December 1, 2017; 62/663,937 filed April 27, 2018; and 62/676,212 filed May 24, 2018 each of which is incorporated herein by reference in its entirety.

BACKGROUND OF THE DISCLOSURE

[0002] A skin lesion, or an open area on the skin where the epidermal covering is

disrupted, can include blister erosion, ulceration, scabbing, bullae, and eschars, as well as areas that are weeping, sloughing, oozing, crusted, and denuded. Skin lesions can be caused by various trauma to the skin and certain diseases can make individuals more susceptible to skin lesions.

[0003] Epidermolysis Bullosa (EB) is a rare group of inherited connective tissue

disorders that typically manifest at birth as blisters and lesions on the skin and, in some cases, the epithelial lining of other organs, in response to little or no apparent trauma. The skin of EB patients is extremely fragile, and lesions and blisters on the skin put these patients at high risk of infection.

[0004] EB can result from a genetic mutation in one of several genes related to normal skin structure and function. EB can also be an autoimmune disease in which the body produces antibodies to, e.g., the structural components of the skin.

[0005] In 2017, The Dystrophic Epidermolysis Bullosa Research Association of America

(DEBRA of America) estimated that about 1 out of every 20,000 babies in the United States are bom with some form of EB. There are many genetic and symptomatic variations of EB, but all share the prominent symptom of extremely fragile skin that blisters and tears from minor friction or trauma. All forms of EB are painful, debilitating and life threatening. In some EB subtypes, high mortality occurs before the age of 1 (junctional Herlitz), and others in adolescences to early adulthood, typically due to infection or failure to thrive. In addition, children surviving into their 20’s and 30’s are also at risk for development of a virulent form of squamous cell carcinoma, which is in many cases fatal.

[0006] There is currently no cure for EB. There are no standard of care products

approved to treat the dermal manifestations of EB, and there is no approved drug for EB in either Europe or the United States.

SUMMARY OF THE DISCLOSURE

[0007] Certain aspects of the present disclosure are directed to a method of treating or reducing the incidence of a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin. In some embodiments, the subject suffers from EB.

[0008] Other aspects of the present disclosure are directed to methods of reducing the size of a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin. In some embodiments, the subject suffers from EB.

[0009] Other aspects of the present disclosure are directed to methods of reducing the total burden of skin lesions in a subject in need thereof comprising: topically

administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin. In some embodiments, the subject suffers from EB.

[0010] Other aspects of the present disclosure are directed to methods of accelerating closure of a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin. In some embodiments, the subject suffers from EB.

[0011] Other aspects of the present disclosure are directed to methods of treating a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition, wherein the composition comprises or consists essentially of: (a) about 40% to about 90% water; (b) about 8% to about 30% an emollient; (c) about 1% to about 15% an emulsifier; (d) about 0.01% to about 1% a pH modifier; (e) about 1% to about 10% a viscosity agent; (f) about 1% to about 20% a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof; (g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B,

nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and (i) about 0.01% to about 3.0% a preservative. In some embodiments, the subject suffers from EB.

[0012] In some embodiments, the composition does not comprise allantoin, i.e., the

composition comprises 0% allantoin.

[0013] In some embodiments, the composition comprises or consists essentially of: (a) about 40% to about 90% water; (b) about 8% to about 30% an emollient; (c) about 1% to about 15% an emulsifier; (d) about 0.01% to about 1% a pH modifier; (e) about 1% to about 10% a viscosity agent; (f) about 1% to about 20% a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof; (g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and (i) about 0.01% to about 3.0% a preservative.

[0014] In some embodiments, the composition comprises or consists essentially of: (a) about 40% to about 90% water; (b) about 8% to about 30% emollient selected from the group consisting of lanolin oil, cod liver oil, mineral oil, an alcohol, and any combination thereof; (c) about 1% to about 15% emulsifier selected from the group consisting of sodium lauryl sulfate, a white wax, and a combination thereof; (d) about 0.01% to about 1% pH modifier selected from the group consisting of citric acid, lactic acid, and a combination thereof; (e) about 1% to about 10% viscosity enhancing agent selected from the group consisting of cetyl alcohol, stearyl alcohol, and a combination thereof; (f) about 1% to about 20% solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof; (g) about 0.01% to about 2% chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium

methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) 0.01% to about 1% antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and (i) about 0.01% to about 3.0% preservative selected from the group consisting of methylparaben, propylparaben, and a combination thereof.

[0015] In some embodiments, the composition comprises or consists essentially of: (a) about 40% to about 90% water; (b) about 1% to about 6% cetyl alcohol; (c) about 1% to about 4% stearyl alcohol; (d) about 1.5% to about 3% beeswax; (e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution; (f) about 0.05% to about 0.2% citric acid; (g) about 5% to about 15% lanolin oil; (h) about 2% to about 8% propylene glycol; (i) about 0.05% to about 0.5% tetrasodium EDTA; (j) about 0.05% to about 5% cod liver oil; (k) about 0.05% to about 1% butylated hydroxytoluene; (1) about 0.05% to about 0.5% methylparaben; and (m) about 0.05% to about 0.5% propylparaben.

[0016] In some embodiments, the composition comprises or consists essentially of: (a) about 42% to about 80% water; (b) about 2% to about 6% cetyl alcohol; (c) about 1% to about 3% stearyl alcohol; (d) about 1.5% to about 3% beeswax; (e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution; (f) about 0.06% to about 0.1% citric acid; (g) about 5% to about 15% lanolin oil; (h) about 2% to about 8% propylene glycol; (i) about 0.05% to about 0.35% tetrasodium EDTA; (j) about 0.05% to about 5% cod liver oil; (k) about 0.05% to about 1% butylated hydroxytoluene; (1) about 0.05% to about 0.5% methylparaben; and (m) about 0.05% to about 0.5% propylparaben.

[0017] In some embodiments, the composition comprises or consists essentially of: (a) about 69.16% water; (b) about 5% cetyl alcohol; (c) about 2.45% stearyl alcohol; (d) about 1.9% beeswax; (e) about 1.9% sodium lauryl sulfate in a 30% solution; (f) about 0.09% citric acid; (g) about 10.6% lanolin oil; (h) about 5.7% propylene glycol; (i) about 0.15% tetrasodium EDTA; (j) about 2% cod liver oil; (k) about 0.5% butylated hydroxytoluene; (1) about 0.3% methylparaben; and (m) about 0.25% propylparaben.

[0018] In some embodiments, the method further comprises applying to the skin area affected by the lesion a dressing that covers the lesion. In some embodiments, the dressing is applied to the lesion less than 30 minutes after the composition is applied. In some embodiments, the skin is washed prior to administration of the composition. In some embodiments, necrotic tissue is removed from the skin prior to administration of the composition. In some embodiments, the administration of the composition is done using clean hands.

[0019] In some embodiments, the dressing is a non-adhesive. In some embodiments, the dressing is selected from the group consisting of a bandage, a gauze, a mesh, a tubular bandage, a cohesive bandage, a soft silicone tape, hydrogel, a sheet hydrogel, a hydrogel impregnated gauze, a biosynthetic cellulose, a bordered dressing, a powder, a lipido- colloid, a soft silicone, a soft silicone mesh, a polymeric membrane, a foam, a soft silicone foam, a soft silicone foam with super-absorbers, a super absorbent dressing, emu oil, restore dimethicreme, white petroleum, and any combination thereof.

[0020] In some embodiments, the subject is bathed prior to administration of the

composition in a water comprising bleach, salt (e.g., 0.9% NaCl), vinegar, or

chlorhexidine. In some embodiments, the subject is bathed in a whirlpool bath prior to administration of the composition.

[0021] In some embodiments, the lesion comprises a blister, and wherein the blister is lanced prior to administration of the composition. In some embodiments, the blister is lanced by inserting a needle into the blister, or by cutting a hole in the blister. In some embodiments, the blister comprises a roof, and the roof of the blister is not removed.

[0022] In some embodiments, the method further comprises administering the

composition to the skin using a circular motion, a motion parallel to the axis of the body, a motion perpendicular to the axis of the body, a blotting technique, or any combination thereof. In some embodiments, the lesion comprises a center and a perimeter, and wherein the composition is applied to the center of the lesion and then spread outward to the perimeter of the lesion or wherein the composition is applied to the perimeter of the lesion and then spread inward toward the center of the lesion.

[0023] In some embodiments, the composition is applied to the skin as a layer, wherein the layer is at least about 0.1 mm thick. In some embodiments, the layer is about 0.1 mm to about 2 mm thick. In some embodiments, the layer is about 0.1 mm to about 1.5 mm thick, about 0.1 mm to about 1 mm thick, about 0.1 mm to about 0.9 mm thick, about 0.1 mm to about 0.8 mm thick, about 0.1 mm to about 0.7 mm thick, about 0.1 mm to about 0.6 mm thick, about 0.1 mm to about 0.5 mm thick, about 0.1 mm to about 0.4 mm thick, about 0.1 mm to about 0.3 mm thick, or about 0.1 mm to about 0.2 mm thick.

[0024] In some embodiments, about 0.1 mL to about 2 mL of the composition is applied per 1 cm² of the skin. In some embodiments, about 0.1 mL to about 1.5 mm thick, about 0.1 mL to about 1 mL, about 0.1 mL to about 0.9 mL, about 0.1 mL to about 0.8 mL, about 0.1 mL to about 0.7 mL, about 0.1 mL to about 0.6 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 0.4 mL, about 0.1 mL to about 0.3 mL, or about 0.1 mL to about 0.2 mL of the composition is applied per 1 cm² of the skin. In some embodiments, the a pea-sized amount of the composition is applied to the lesion.

[0025] In some embodiments, the composition is applied to at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or all exposed skin of the subject.

[0026] In some embodiments, the composition is applied 1 time per day. In some

embodiments, the composition is applied 1 time per day, 2 times per day, or 3 times per day. In some embodiments, the dressing is applied 1 time per day. In some embodiments, the dressing is applied 1 time per day, 2 times per day, or 3 times per day. [0027] In some embodiments, the lesion is at least about 1, 2, 3, 4, 5, 6, or 7 days old. In some embodiments, the lesion is about 30 days old or less. In some embodiments, the subject has a total lesion burden of at least about 1, 5, 10, 15, 20, 25, 30, 40, or 50%.

[0028] In some embodiments, the subject suffers from epidermolysis bullosa (EB). In some embodiments, the subject is at least 18 years old. In some embodiments, the subject is about 2 years old. In some embodiments, the subject is less than 2 years old. In some embodiments, the subject is 1 month old to less than 2 years old. In some embodiments, the subject is about 1 month old, about 2 months old, about 3 months old, about 4 months old, about 5 months old, about 6 months old, about 7 months old, about 8 months old, about 9 months old, about 10 months old, about 11 months old, about 12 months old, about 13 months old, about 14 months old, about 15 months old, about 16 months old, about 17 months old, about 18 months old, about 19 months old, about 20 months old, about 21 months old, about 22 months old, about 23 months old, or about 24 months old.

[0029] In some embodiments, the administration of the composition reduces itching associated with the skin lesion in the subject in need thereof. In some embodiments, the administration of the composition reduces pain associated with the skin lesion in the subject in need thereof.

[0030] In some embodiments, the administration of the composition reduces the size of the lesion by at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% relative to the size of the lesion prior to the administration of the composition. In some embodiments, the administration of the composition reduces the size of the lesion within about 2 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 14 weeks, about 16 weeks, or about 18 weeks after the initial administration of the composition relative to the size of the lesion prior to the

administration of the composition. In some embodiments, the administration of the composition reduces the total number of legions on the subject by at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% relative to the total number of legions on the subject prior to the administration.

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG. l is a graphical representation of the mean time to complete target wound closure within 3 months, shown in days (y-axis) for all patients and for patients stratified by EB type, age, target wound age, and BSAI total wound version (X-axis).

[0032] FIGs. 2A-2G are graphical representations of the efficacy of SD-005 treatment of

EB patients. FIG. 2A shows the proportion of all patients (n=87) with target wound closure at day 14, 1 month, 2 months, and 3 months of treatment with SD-005; and FIG. 2B shows the probability (percent) of intent-to-treat patients treated with SD-005 with target wound closure at 2 weeks, 1 month, 2 months, 3 months, 4 months, and 5 months. FIGs. 2C shows the proportion of a subset of EB patients (n=59) with target wound closure over time (up to 3 months) following treatment with SD-005 compared to the target wound closure over time in EB patients 18 years or older treated with either an active agent (n=l4) or vehicle (n=l2) as reported by Patrof et al., British Journal of Dermatology 749: 1025-33 (2013). FIG. 2D shows the proportion of all patients (n=87) with target wound closure at day 14, 1 month, 2 months, and 3 months of treatment with SD-005 based on type of EB (simplex: light grey; recessive dystrophic: dark grey; and junctional non-Herlitz: black). FIG. 2E shows the proportion of all patients (n=87) with target wound closure at day 14, 1 month, 2 months, and 3 months of treatment with SD- 005 based on patient age (1 month to less than 2 years: light grey; 2 years to less than 12 years: dark grey; 12 years to less than 18 years: striped; and 18 years or older: black). FIG. 2F shows the proportion of a subset of EB patients 18 years old or older (h=10) with target wound closure over time (up to 3 months) following treatment with SD-005 compared to the target wound closure over time in EB patients 18 years or older treated with either an active agent (n=l4) or vehicle (n=l2) as reported by Patrof et al. (2013). FIG. 2G shows the proportion of all patients (n=87) with target wound closure at day 14,

1 month, 2 months, and 3 months of treatment with SD-005 based on BSAI total wound burden (less than 5%: grey; 5% or higher: black).

[0033] FIGs. 3 A-3B are graphical representations of the mean % change in target wound size for EB patients 18 years old or older (h=10) (FIG. 3A) and for EB patients (n=59) (FIG. 3B) over time (up to 3 months) following treatment with SD-005 compared to % mean change in target wound size for EB patients treated with either an active agent (n=l4) or vehicle (n=l2) as reported by Patrof et al. (2013).

DETAILED DESCRIPTION OF THE DISCLOSURE

[0034] The present application discloses methods for treating a skin lesion in a subject in need thereof. In certain aspects, the present disclosure is directed to methods of improving the care of EB patients. For example, the methods of administering a composition disclosed herein provides improvements over previous methods, e.g., an increase in healing of lesions and/or a decrease in the number of lesions. In some embodiments, the methods of the disclosure provide improved care to adult patients, e.g., patients 18 years or older, as compared to standard of care therapies. In some

embodiments, the methods of the disclosure provide improved care to infant patients, e.g., patients less than 2 years old, as compared to standard of care therapies.

[0035] The present disclosure provides methods of treating and/or reducing the incidence of a skin lesion in a subject in need thereof, e.g., a subject suffering from EB, comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, an antioxidant, and a preservative; wherein the composition comprises less than 0.5% allantoin, e.g., 0% allantoin. In some embodiments, the disclosed methods reduce the number of lesions in a treated area. In some embodiments, the disclosed methods reduce the size of one or more lesions and reduce the number of lesions in a treated area. In some embodiments, the total lesion burden is reduced by the treatment. In some embodiments, the composition does not comprise allantoin. In particular embodiments, the subject suffers from EB.

[0036] In some embodiments, the lesion count, the size of at least one lesion, and/or the total lesion burden is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or about 100%. [0037] In some embodiments, the administration a composition herein provides a reduction in lesion count in the subject within 2 weeks, 1 month, 2 months, or 3 months after the initial administration of the pharmaceutical composition.

I. Definitions

[0038] It is to be noted that the term "a" or "an" entity refers to one or more of that entity: for example, "a nucleotide sequence" is understood to represent one or more nucleotide sequences. As such, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein.

[0039] The term "about" is used herein to mean approximately, roughly, around, or in the regions of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 10 percent, up or down (higher or lower).

[0040] Also as used herein, "and/or" refers to and encompasses any and all possible

combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or").

[0041] The term "consisting essentially of," as used herein, refers to embodiments which meet all the elements of a given claim yet include additional elements that do not materially change the nature of the claimed embodiment. For example, a composition consisting essentially of elements A, B, and C refers to a composition that has A, B, and C and any additional elements that do not materially change the nature of the

composition.

[0042] A "lesion" as used herein is defined as an open area on the skin where the

epidermal covering is disrupted. In some embodiments, a lesion comprises a blister erosion, ulceration, scabbing, bullae, and eschars, as well as areas that are weeping, sloughing, oozing, crusted, and denuded. In some embodiments, the size of a lesion is represented by the surface are of the lesion, which is typically expressed in cm².

"Complete target lesion closure" or "lesion closure," as used herein, is defined as skin re- epithelialization without drainage.

[0043] A "blister" refers to a fluid filled protrusion of the top layers of the skin and the resulting structure remaining after the fluid has been removed. In some embodiments, the size of a blister is represented by the surface are of the lesion, which is typically expressed in cm².

[0044] The term "dressing," as used herein refers to a material or substance that is applied to a lesion as a barrier to the environment. In some embodiments, the dressing is selected from the group consisting of a bandage, a gauze, a mesh, a tubular bandage, a cohesive bandage, a soft silicone tape, hydrogel, a sheet hydrogel, a hydrogel impregnated gauze, a sodium carboxymethylcellulose-based dressing ( e.g ., HYDROFIBER®), a biosynthetic cellulose, a bordered dressing, a powder, a lipido-colloid, a soft silicone, a soft silicone mesh, a polymeric membrane, a foam, a soft silicone foam, a soft silicone foam with super-absorbers, a super absorbent dressing, emu oil, restore dimethicreme,

AQUAPHOR® (Beiersdorf, Inc.), white petroleum, and any combination thereof. In some embodiments, the dressing is fully or partially occlusive. In other embodiments, the dressing is not occlusive. In some embodiments, the dressing comprises a fluid matrix (e.g., a cream, e.g, AQUAPHOR®). In some embodiments, the dressing comprises a gel matrix (e.g, a gel, e.g, hydrogel). In some embodiments, the dressing comprises a solid matrix (e.g, a bandage, a gauze, a mesh, etc.). In some embodiments, the dressing is applied directly to the skin. In other embodiments, the dressing is applied on top of a another dressing (e.g., a fluid matrix is applied on top of a solid matrix). In some embodiments, multiple types of dressings are layered. In some embodiments, the dressing is loosely administered to a treated area. In some embodiments, a garment is worn over the dressing. In some embodiments, no garment is worn over the dressing.

[0045] The term "subject," as used herein, refers to a human, e.g., a human patient. In some embodiments, the subject has EB. In some embodiments, the subject is an adult. In some embodiments, the adult is at least about 18 years old, at least about 19 years old, at least about 20 years old, or at least about 21 years old. In some embodiments, the subject is at least about 16 years old. In some embodiments, the subject at least about 17 years old. In some embodiments, the subject at least about 18 years old. In some embodiments, the subject is about 16 to about 18 years old. In some embodiments, the subject is about 18 to about 60 years old, about 18 to about 50 years old, about 18 to about 40 years old, about 18 to about 30 years old, about 18 to about 25 years old, about 25 to about 60 years old, about 25 to about 50 years old, about 25 to about 40 years old, about 25 to about 30 years old, about 30 to about 60 years old, or about 30 to about 50 years old. [0046] In some embodiments, the subject is about 2 years old. In some embodiments, the subject is less than 2 years old. In some embodiments, the subject is 1 month old to less than 2 years old. In some embodiments, the subject is about 1 month old, about 2 months old, about 3 months old, about 4 months old, about 5 months old, about 6 months old, about 7 months old, about 8 months old, about 9 months old, about 10 months old, about 11 months old, about 12 months old, about 13 months old, about 14 months old, about 15 months old, about 16 months old, about 17 months old, about 18 months old, about 19 months old, about 20 months old, about 21 months old, about 22 months old, about 23 months old, or about 24 months old.

[0047] The terms "a circular motion," "a motion parallel to the axis of the body," and "a motion perpendicular to the axis of the body" refer to the direction of the motion used to administer a substance to a subject's skin. In some embodiments, the substance is any composition described herein. In some embodiments, the substance is administered by applying the substance to a target area comprising a lesion on the skin of a subject, e.g ., a subject suffering from EB, which can include the area surrounding the lesion.

[0048] A composition applied using "a circular motion" is applied by contacting the skin

(e.g., a target area) with the substance and spreading the substance using circular movements. The circular movements can be of any size necessary to apply the substance to the desired area of the skin. The circular movements do not need to be concentric. In some embodiments, the circular movements are all in one direction, e.g. , all movements are clockwise or counterclockwise. In other embodiments, the circular movements are in either direction, e.g. , alternating between clockwise and counterclockwise movements.

[0049] A composition applied using "a motion parallel to the axis of the body" is applied by contacting the skin (e.g., a target area) with the substance and spreading the substance using linear movements, wherein the linear movements run substantially parallel to the axis of the body. The linear movements do not need to be perfectly parallel to the axis of the body, but rather are more parallel than perpendicular, e.g. , at an angle of 0 45 relative to the axis of the body. For example, a composition applied to a subject's upper arm using a motion parallel to the axis of the body, is applied using linear motions that run substantially parallel to the subject's humerus. In some embodiments, the motion parallel to the axis of the body is unidirectional, e.g. , every motion is proximal to distal or every motion is distal to proximal. In other embodiments, the motion parallel to the axis of the body is bidirectional, e.g, the substance is applied in a back-and-forth manner, wherein the motion alternates between proximal-to-distal and distal-to-proximal motions.

[0050] A composition applied using "a motion perpendicular to the axis of the body" is applied by contacting the skin (e.g., a target area) with the substance and spreading the substance using linear movements, wherein the linear movements run substantially perpendicular to the axis of the body. The linear movements do not need to be perfectly perpendicular to the axis of the body, but rather are more perpendicular than parallel, e.g. , at an angle of 45°-90° relative to the axis of the body. For example, a composition applied to a subject's upper arm using a motion perpendicular to the axis of the body, is applied using linear motions that run substantially perpendicular to the subject's humerus. In some embodiments, the motion perpendicular to the axis of the body is unidirectional, e.g. , every motion is to the left or every motion is right. In other embodiments, the motion perpendicular to the axis of the body is bidirectional, e.g. , the substance is applied in a back-and-forth manner, wherein the motion alternates between leftward and rightward motions.

[0051] The term "total burden," "total lesion burden," or "total wound burden" refers to the percent of the subject's surface area that is affected by the disease, e.g. , the percent of the subject's skin that has one or more lesions associated with EB. In some embodiments, total burden is measured using a Body Surface Area Index (BSAI) score. In some embodiments, the subject has a BSAI of less than about 5%. In some embodiments, the subject has a BSAI of less than about 4.9%, less than about 4.8%, less than about 4.7%, less than about 4.6%, less than about 4.5%, less than about 4.4%, less than about 4.3%, less than about 4.2%, less than about 4.1%, less than about 4.0%, less than about 3.9%, less than about 3.8%, less than about 3.7%, less than about 3.6%, less than about 3.5%, less than about 3.4%, less than about 3.3%, less than about 3.2%, less than about 3.1%, less than about 3.0%, less than about 2.9%, less than about 2.8%, less than about 2.7%, less than about 2.6%, less than about 2.5%, less than about 2.4%, less than about 2.3%, less than about 2.2%, less than about 2.1%, less than about 2.0%, less than about 1.9%, less than about 1.8%, less than about 1.7%, less than about 1.6%, less than about 1.5%, less than about 1.4%, less than about 1.3%, less than about 1.2%, less than about 1.1%, less than about 1.0%, or less than about 0.5%. In certain embodiments, the subject has a BSAI of less than about 4%. In certain embodiments, the subject has a BSAI of less than about 3%. In certain embodiments, the subject has a BSAI of less than about 2%. In certain embodiments, the subject has a BSAI of less than about 1%.

[0052] "Bleach," as used herein, refers to commercially available, household bleach.

Bleach comprises about 3% to about 8% sodium hypochlorite, by weight.

[0053] The term "adverse event" or "AE," as used herein, refers to any untoward medical occurrence in a patient, administered a treatment. The AE does not necessarily have to have a causal relationship with a given treatment. An AE can therefore be any

unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the treatment, whether or not considered related to the treatment. AEs can include the onset of new illness or the exacerbation of pre-existing conditions.

[0054] The term "serious adverse event" or "SAE," as used herein, refers to an AE that results in death, is life threatening (z.e., the patient was at risk of death at the time of the event; but not an event that hypothetically might have caused death if it was more severe), results in hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly / birth defect, or is considered to be an important medical event. Hospitalizations are defined as initial or prolonged admissions that include an overnight stay. Hospitalization or prolonged hospitalization for technical, practical, or social reasons, in the absence of an AE is not an SAE.

[0055] The term "unexpected adverse drug reaction," as used herein, refers to an adverse reaction, the nature or severity of which is not consistent with the treatment. The term "suspected unexpected serious adverse reaction" or "SETSAR," as used herein refers to an SAE that is suspected to be related to the administered the treatment and the nature or severity of which is not consistent with applicable product information.

[0056] A "trace," "negligible," or "insignificant" amount of a substance in a composition, as used herein, refers to a very small amount of a substance in the composition. In certain embodiments, the trace, negligible, or insignificant amount of the substance is so small as to not have an expected effect on the clinical efficacy or activity of the composition. In some embodiments, the trace, negligible, or insignificant amount of the compound is so low that it renders a compound that would otherwise require a prescription from a health care professional safe for over the counter sale, e.g ., as approved by a government agency, e.g. , by the ETnited States Food and Drug Administration. In some embodiments, the amount of allantoin in the composition is a trace amount of allantoin, a negligible amount of allantoin, and/or an insignificant amount of allantoin.

II. Methods of Treatment

[0057] Certain aspects of the present invention are directed to methods of treating or reducing the incidence of a skin lesion in a subject in need thereof. Other aspects of the present invention are directed to methods of reducing the size of a skin lesion in a subject in need thereof, e.g., a subject suffering from EB. Other aspects are directed to methods of reducing the total burden of skin lesions in a subject in need thereof, e.g., a subject suffering from EB. Other aspects are directed to methods of accelerating closure of a skin lesion in a subject in need thereof, e.g., a subject suffering from EB. In certain

embodiments, the method comprises topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, an antioxidant, and a preservative. In certain

embodiments, the composition comprises less than 0.5% allantoin. In particular embodiments, the composition does not comprise allantoin.

[0058] Other aspects of the present invention are directed to methods of treating a skin lesion in a subject in need thereof, e.g., a subject suffering from EB, comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition, wherein the composition comprises or consists essentially of: (a) about 40% to about 90% water; (b) about 8% to about 30% an emollient; (c) about 1% to about 15% an emulsifier; (d) about 0.01% to about 1% a pH modifier; (e) about 1% to about 10% a viscosity agent; (f) about 1% to about 20% a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof; (g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and (i) about 0.01% to about 3.0% a preservative. [0059] In some embodiments, the methods of the present disclosure comprise

administering a composition that consists essentially of (a) about 40% to about 90% water; (b) about 8% to about 30% an emollient; (c) about 1% to about 15% an emulsifier; (d) about 0.01% to about 1% a pH modifier; (e) about 1% to about 10% a viscosity agent; (f) about 1% to about 20% a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof; (g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and (i) about 0.01% to about 3.0% a preservative, wherein the inclusion of additional components that do not materially change the properties of the claimed composition are envisioned. In some embodiments, a composition consisting essentially of the above listed elements further includes a negligible amount of allantoin, e.g ., less than 0.5% allantoin. In some embodiments, a composition consisting essentially of the above listed elements does not comprise allantoin.

[0060] Other aspects of the present invention are directed to methods of reducing the incidence of lesions of Epidermolysis bullosa (EB) in a subject in need thereof. Other aspects of the present disclosure provide methods of dressing a lesion of EB in a subject in need thereof. Other aspects of the present disclosure provide methods of reducing the size of a lesion of EB in a subject in need thereof. Other aspects of the present disclosure provide methods of reducing the number of lesions of EB in a subject in need thereof. Other aspects of the present disclosure provide methods of reducing the total burden of lesions of EB in a subject in need thereof comprising. In some embodiments, the methods comprise topically administering, at least once daily, to a skin area affected by the lesions of EB: (a) a composition disclosed herein, and (b) a dressing that covers the lesions of EB. In certain embodiments, the administration of (a) and (b) provides a significant reduction in lesion count in the subject within 2 weeks, 1 month, 2 months, or 3 months after the initial administration of the composition. In certain embodiments, the administration of (a) and (b) provides a significant reduction in lesion size for the subject within 2 weeks, 1 month, 2 months, or 3 months after the initial administration of the composition. In some embodiments, the lesion comprises a blister.

[0061] In some embodiments, the administration of the composition reduces the total number of lesions, on the skin of the subject relative to the total number of lesions, present prior to the administration. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 2 weeks, within about 1 month, within about 2 months, or within about 3 months. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 2 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 3 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 4 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 5 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 6 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 7 weeks. In some embodiments, the administration of the composition reduces the total number of lesions on the skin of the subject within about 8 weeks.

[0062] In some embodiments, the administration of a composition disclosed herein

reduces the total number of lesions on the skin of the subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.

[0063] In some embodiments, the administration of the composition as disclosed herein reduces the total burden of the subject relative to the total lesion burden prior to the administration. In some embodiments, the administration of the composition as disclosed herein reduces the total burden of the subject within about 2 weeks, within about 1 month, within about 2 months, or within about 3 months. In some embodiments, the administration of the composition as disclosed herein reduces the total lesion burden of the subject within about 2 weeks. In some embodiments, the administration of the composition reduces the total lesion burden of the subject within about 3 weeks. In some embodiments, the administration of the composition as disclosed herein reduces total lesion burden of the subject within about 4 weeks. In some embodiments, the

administration of the composition reduces the total lesion burden of the subject within about 5 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the total lesion burden of the subject within about 6 weeks. In some embodiments, the administration of the composition reduces the total lesion burden of the subject within about 7 weeks. In some embodiments, the administration of the

composition as disclosed herein reduces the total lesion burden of the subject within about 8 weeks.

[0064] In some embodiments, the administration of the composition as disclosed herein reduces the total burden of the subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.

[0065] In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject relative to the size of the same one or more target lesions prior to the administration. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 2 weeks, within about 1 month, within about 2 months, or within about 3 months. In some embodiments, the

administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 2 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 3 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 4 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 5 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 6 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 7 weeks. In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject within about 8 weeks.

[0066] In some embodiments, the administration of the composition as disclosed herein reduces the size of one or more target lesions on the skin of the subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.

[0067] The lesion can be of any size prior to the administration. In some embodiments, the lesion has a surface are of about 1 cm² to about 100 cm². In some embodiments, the lesion has a surface are of about 10 cm² to about 50 cm². In some embodiments, the lesion has a surface are of about 1 cm², about 2 cm², about 3 cm², about 4 cm², about 5 cm , about 10 cm , about 15 cm , about 20 cm , about 25 cm , about 30 cm , about 35 cm², about 40 cm², about 45 cm², or about 50 cm². In certain embodiments, the lesion has a surface are of about 50 cm² to about 100 cm². In some embodiments, the lesion has a surface are of about 10 cm². In some embodiments, the lesion has a surface are of about 20 cm². In some embodiments, the lesion has a surface are of about 30 cm². In some embodiments, the lesion has a surface are of about 40 cm². In some embodiments, the lesion has a surface are of about 50 cm². In some embodiments, the lesion has a surface are of more than about 50 cm².

[0068] In some embodiments, administration of the composition as disclosed herein

induces complete lesion closure of the lesion in less than about 1 week, in less than about 2 weeks, in less than about 3 weeks, in less than about 4 weeks, in less than about 5 weeks, in less than about 6 weeks, in less than about 7 weeks, in less than about 8 weeks, in less than about 9 weeks, in less than about 10 weeks, in less than about 11 weeks, in less than about 12 weeks, in less than about 13 weeks, in less than about 14 weeks, in less than about 15 weeks, in less than about 16 weeks, in less than about 17 weeks, in less than about 18 weeks, in less than about 19 weeks, in less than about 20 weeks, or in less than about 21 weeks. In some embodiments, administration of the composition as disclosed herein induces complete lesion closure of the lesion in less than about 1 month, less than about 2 months, less than about 3 months, less than about 4 months, less than about 5 months, or less than about 6 months.

[0069] In some embodiments, administration of the composition as disclosed herein

increases the probability of wound closure within at least about 2 weeks, within at least about 1 month, within at least about 2 months, within at least about 3 months, within at least about 4 months, or within at least about 5 months. In certain embodiments, the probability of a subject experiencing wound closure within about 1 month of

administration of a composition disclosed herein is at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, or at least about 20%. In some embodiments, the probability of a subject experiencing wound closure within about 2 months of administration of a composition disclosed herein is at least about 10%, at least about 12%, at least about 15%, at least about 17%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50%. In some embodiments, the probability of a subject experiencing wound closure within about 3 months of administration of a composition disclosed herein is at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, or at least about 70%. In some embodiments, the probability of a subject experiencing wound closure within about 4 months of

administration of a composition disclosed herein is at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, or at least about 80%. In some embodiments, the probability of a subject experiencing wound closure within about 5 months of

administration of a composition disclosed herein is at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, or at least about 90%. [0070] In some embodiments, the complete lesion closure is at least about 25%, in at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, at least about 85%, or at least about 90% of the lesions.

[0071] In some embodiments, the administration of the composition as disclosed herein reduces pain experienced by the subject that is related to one or more lesions on the skin of the subject relative pain experienced by the subject prior to the administration. In some embodiments, the pain is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%, relative to the pain prior to the administration.

[0072] In some embodiments, the administration of the composition as disclosed herein reduces itching experienced by the subject that is related to one or more lesions on the skin of the subject relative itching experienced by the subject prior to the administration. In some embodiments, the itching is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%, relative to the itching prior to the administration.

[0073] In some embodiments, the subject is an adult. In some embodiments, the subject is at least about 16 years old, at least about 17 years old, at least about 18 years old, at least about 19 years old, at least about 20 years old, or at least about 21 years old. In some embodiments, the subject is at least about 16 years old. In some embodiments, the subject at least about 17 years old. In some embodiments, the subject at least about 18 years old. In some embodiments, the subject is about 16 to about 18 years old. In some

embodiments, the subject is about 18 to about 60 years old, about 18 to about 50 years old, about 18 to about 40 years old, about 18 to about 30 years old, about 18 to about 25 years old, about 25 to about 60 years old, about 25 to about 50 years old, about 25 to about 40 years old, about 25 to about 30 years old, about 30 to about 60 years old, or about 30 to about 50 years old.

[0074] In some embodiments, the subject is a child. In some embodiments, the subject is an infant. In some embodiments, the subject is about 2 years old. In some embodiments, the subject is less than 2 years old. In some embodiments, the subject is 1 month old to less than 2 years old. In some embodiments, the subject is about 1 month old, about 2 months old, about 3 months old, about 4 months old, about 5 months old, about 6 months old, about 7 months old, about 8 months old, about 9 months old, about 10 months old, about 11 months old, about 12 months old, about 13 months old, about 14 months old, about 15 months old, about 16 months old, about 17 months old, about 18 months old, about 19 months old, about 20 months old, about 21 months old, about 22 months old, about 23 months old, or about 24 months old.

A. Disease Burden Prior to Administration

[0075] In certain embodiments, the methods of the present invention treat one or more lesion present on a subject prior to the administration. The lesions can be lesions that are typical of EB, e.g ., skin lesions of EB.

[0076] The lesions can be in any stage of healing prior to the administration. For

example, in some embodiments, the lesion is an open lesion with no scabbing. In other embodiments, the lesion is an open lesion with some scabbing. In other embodiments, the lesion is completely scabbed. In some embodiments, the lesion comprises a blister that is intact, e.g. , not ruptured. In other embodiments, the blister is ruptured. In some embodiments, the ruptured blister comprises residual fluid. In other embodiments, the ruptured blister is drained. In some embodiments, the blister comprises a roof. In other embodiments, the blister does not comprise a roof, e.g. , the blister is open. In some embodiments, the blister comprises a clear fluid, e.g. , lacking blood. In other

embodiments, the blister comprises a fluid comprising blood, e.g. , a red fluid.

[0077] In some embodiments, the subject has more than 1 lesion prior to the

administration. In some embodiments, the subject has 2 or more lesions. In some embodiments, the subject has 3 or more lesions. In some embodiments, the subject has 4 or more lesions. In some embodiments, the subject has 5 or more lesions. In some embodiments, the subject has 6 or more lesions. In some embodiments, the subject has 7 or more lesions. In some embodiments, the subject has 8 or more lesions. In some embodiments, the subject has 9 or more lesions. In some embodiments, the subject has 10 or more lesions. In some embodiments, the subject has 15 or more lesions. In some embodiments, the subject has 20 or more lesions. In some embodiments, the subject has 25 or more lesions. In some embodiments, the subject has 30 or more lesions.

[0078] In some embodiments, the subject has 1 to 5 lesions prior to the administration. In some embodiments, the subject has 5 to 10 lesions. In some embodiments, the subject has 10 to 15 lesions. In some embodiments, the subject has 15 to 20 lesions. In some embodiments, the subject has 20 to 25 lesions. In some embodiments, the subject has 25 to 30 lesions. In some embodiments, the subject has 30 to 35 lesions. In some

embodiments, the subject has 35 to 40 lesions. In some embodiments, the subject has 40 to 45 lesions. In some embodiments, the subject has 45 to 50 lesions. In some

embodiments, the subject has 50 to 100 lesions.

[0079] In some embodiments, the subject has a total lesion burden of at least about 1% prior to the administration. In some embodiments, the subject has a total lesion burden of at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% prior to the administration. In certain embodiments, the subject has a total lesion burden of at least about 25%. In certain embodiments, the subject has a total lesion burden of at least about 50%. In certain embodiments, the subject has a total lesion burden of at least about 75%.

[0080] In some embodiments, total burden is measured using a Body Surface Area Index (BSAI) score. In some embodiments, the subject has a BSAI of less than about 5%. In some embodiments, the subject has a BSAI of less than about 4.9%, less than about 4.8%, less than about 4.7%, less than about 4.6%, less than about 4.5%, less than about 4.4%, less than about 4.3%, less than about 4.2%, less than about 4.1%, less than about 4.0%, less than about 3.9%, less than about 3.8%, less than about 3.7%, less than about 3.6%, less than about 3.5%, less than about 3.4%, less than about 3.3%, less than about 3.2%, less than about 3.1%, less than about 3.0%, less than about 2.9%, less than about 2.8%, less than about 2.7%, less than about 2.6%, less than about 2.5%, less than about 2.4%, less than about 2.3%, less than about 2.2%, less than about 2.1%, less than about 2.0%, less than about 1.9%, less than about 1.8%, less than about 1.7%, less than about 1.6%, less than about 1.5%, less than about 1.4%, less than about 1.3%, less than about 1.2%, less than about 1.1%, less than about 1.0%, or less than about 0.5%. In certain

embodiments, the subject has a BSAI of less than about 4%. In certain embodiments, the subject has a BSAI of less than about 3%. In certain embodiments, the subject has a BSAI of less than about 2%. In certain embodiments, the subject has a BSAI of less than about 1%.

[0081] The lesion can be of any size prior to the administration. In some embodiments, the lesion has a surface are of about 1 cm² to about 100 cm². In some embodiments, the lesion has a surface are of about 10 cm² to about 50 cm². In some embodiments, the lesion has a surface are of about 1 cm², about 2 cm², about 3 cm², about 4 cm², about 5 cm , about 10 cm , about 15 cm , about 20 cm , about 25 cm , about 30 cm , about 35 cm², about 40 cm², about 45 cm², or about 50 cm². In certain embodiments, the lesion has a surface are of about 50 cm² to about 100 cm². In some embodiments, the lesion has a surface are of about 10 cm². In some embodiments, the lesion has a surface are of about 20 cm². In some embodiments, the lesion has a surface are of about 30 cm². In some embodiments, the lesion has a surface are of about 40 cm². In some embodiments, the lesion has a surface are of about 50 cm². In some embodiments, the lesion has a surface are of more than about 50 cm².

[0082] The lesion can be of any age prior to the administration. In some embodiments, the lesion is at least about 1 day old, at least about 2 days old, at least about 3 days old, at least about 4 days old, at least about 5 days old, at least about 6 days old, at least about 7 days old, at least about 14 days old, at least about 21 days old, or at least about 28 days old. In some embodiments, the lesion is at least about 1 week old, at least about 2 weeks old, at least about 3 weeks old, or at least about one month old. In certain embodiments, the lesion is more than 1 month old, more than 2 months old, more than 3 months old, more than 4 months old, more than 5 months old, more than 6 months old, or more than 12 months old. In certain embodiments, the lesion is more than 1 year old, more than 2 years old, more than 3 years old, more than 4 years old, more than 5 years old, more than 6 years old, more than 7 years old, more than 8 years old, more than 9 years old, or more than 10 years old. In some embodiments, the lesion is about 30 days old or less. In certain embodiments, the lesion is less than about 30 days old, less than about 29 days old, less than about 28 days old, less than about 27 days old, less than about 26 days old, less than about 25 days old, less than about 24 days old, less than about 23 days old, less than about 22 days old, less than about 21 days old, less than about 20 days old, less than about 19 days old, less than about 18 days old, less than about 17 days old, less than about 16 days old, less than about 15 days old, less than about 14 days old, less than about 13 days old, less than about 12 days old, less than about 11 days old, less than about 10 days old, less than about 9 days old, less than about 8 days old, less than about 7 days old, less than about 6 days old, less than about 5 days old, less than about 4 days old, less than about 3 days old, less than about 2 days old, or less than about 1 day old.

B. Preparation of the Subject

[0083] In certain aspects of the present invention, the skin of a subject, e.g., a subject suffering from EB, is prepared prior to the administration of a composition disclosed herein and/or a dressing that covers a lesion. In some embodiments, the subject's skin is washed prior to the administration. The subject's skin can be washed by methods known in the art. In some embodiments, the subject's skin is washed by bathing the skin. In some embodiments, the subject is bathed in a water comprising bleach, salt (e.g., 0.9% NaCl), vinegar, or chlorhexidine.

[0084] In some embodiments, the subject is bathed in a solution comprising a mixture of water and bleach. In some embodiments, the solution comprises about 5 mL of bleach per 5 L of water. In some embodiments, the solution comprising a mixture of water and bleach comprises about 0.005% to about 0.008% sodium hypochlorite.

[0085] In some embodiments, the subject is bathed in a solution comprising a mixture of water and a salt. In some embodiments, the salt comprises NaCl. In some embodiments, the salt comprises table salt. In certain embodiments, the subject is bathed in a solution comprising 9 grams of table salt per 1 liter of water. In some embodiments, the subject is bathed in a solution comprising about 0.9% NaCl.

[0086] In some embodiments, the subject is bathed in a solution comprising a mixture of water and vinegar. In some embodiments, the solution comprises about 0.1% vinegar, about 0.5% vinegar, about 1% vinegar, about 5% vinegar, about 10% vinegar, about 15% vinegar, about 20% vinegar, about 25% vinegar, about 30% vinegar, about 35% vinegar, about 40% vinegar, about 45% vinegar, or about 50% vinegar. In certain embodiments, the vinegar comprises apple cider vinegar. [0087] In some embodiments, the subject is bathed in a solution comprising a mixture of water and chlorhexidine. Chlorhexidine gluconate (or "chlorhexidine") is an antiseptic agent that has broad-spectrum activity against many organisms, including S. aureus and enterococcus species. In some embodiments, the solution comprises about 1% to about 5% chlorhexidine. In certain embodiments, the solution comprises about 0.1%

chlorhexidine, about 0.5% chlorhexidine, about 1% chlorhexidine, about 5%

chlorhexidine, about 10% chlorhexidine, about 15% chlorhexidine, or about 20% chlorhexidine. In certain embodiments, the solution comprises about 1% chlorhexidine. In certain embodiments, the solution comprises about 2% chlorhexidine.

[0088] In some embodiments, the subject is bathed by being partially or fully submerged in a bath of a solution described herein. In other embodiments, the subject is bathed by being washed using a cloth or sponge that is saturated in a solution described herein. In other embodiments, the subject is bathed by pouring a solution described herein over all or a portion of the subject's body. In certain embodiments, the subject is bathed in a whirlpool bath.

C. Preparation of the Skin

[0089] In certain aspects of the present invention, the skin, e.g., the skin of a subject suffering from EB, is prepared prior to the administration of a composition disclosed herein and/or a dressing that covers a lesion.

[0090] In some embodiments, the lesion is fully or partially covered by a previous

dressing, and the previous dressing is removed before the administration. In some embodiments, the prior dressing is selected from the group consisting of a bandage, a gauze, a mesh, a tubular bandage, a cohesive bandage, a soft silicone tape, hydrogel, a sheet hydrogel, a hydrogel impregnated gmze(e.g., HYDROFIBER®, a biosynthetic cellulose, a bordered dressing, a powder, a lipido-colloid, a soft silicone, a soft silicone mesh, a polymeric membrane, a foam, a soft silicone foam, a soft silicone foam with super-absorbers, a super absorbent dressing, emu oil, restore dimethicreme,

AQETAPHOR® (Beiersdorf, Inc.), white petroleum, and any combination thereof.

[0091] In certain embodiments, the prior dressing is removed using a silicone medical adhesive remover (SMAR). In other embodiments, the prior dressing is removed by soaking the prior dressing in a bath and allowing the prior dressing to fall off without mechanical intervention. [0092] In some embodiments, necrotic tissue is removed from the skin, e.g, from the lesion or from the skin surrounding the lesion, prior to administration of the composition and/or the dressing that covers the lesion. Necrotic tissue can be removed using any methods known in the art. In some embodiments, necrotic tissue is removed by methods that enhance autolytic debridement. Autolytic debridement refers to the natural process employed by the body, wherein proteolytic enzymes and macrophages remove necrotic tissue. In some embodiments, necrotic tissue is removed using sharp debridement. Sharp debridement refers to a method of using scissors, scalpels, and other sharp instruments to cut away or remove necrotic tissue. In some embodiments, the necrotic tissue is removed using mechanical debridement. Mechanical debridement refers to lesion cleansing with a solution. In some embodiments, mechanical debridement uses a whirlpool bath, a debridement pad (e.g, DEBRISOFT®, Activa Healthcare, LTD). In some embodiments, the necrotic tissue is removed using larval therapy. Larval therapy refers to the application of live, disinfected larvae, e.g, fly larvae, e.g, maggots, to the surface of a lesion or surrounding tissue to remove necrotic tissue. In certain embodiments, the necrotic tissue is removed using any combination of the methods described above.

[0093] In some embodiments, the lesion comprises a blister, wherein the blister

comprises a fluid. In some embodiments, the blister is lanced prior to the administration of the composition and/or the dressing that covers the lesion. The blister can be lanced using any method known in the art. In some embodiments, the blister is lanced by inserting a needle into the blister. In some embodiments, a needle is passed through the blister, creating an entry hole and an exit hole. In other embodiments, a needle is inserted without passing through the blister, creating only an entry hole.

[0094] In some embodiments, the blister is lanced by cutting a hole in the blister. In

certain embodiments, a hole is cut in the blister using a scalpel or scissors. In certain embodiments, the blister comprises a roof, and the roof is removed prior to administration of the composition and/or the dressing that covers the lesion. In other embodiments, the blister comprises a roof, and the roof is not removed prior to administration of the composition.

[0095] In certain embodiments, the fluid in the blister is removed prior to the

administration of the composition and/or the dressing that covers the lesion. The fluid in the blister can be removed using any method known in the art. In some embodiments, a hypodermic needle is inserted into the blister, and the fluid is aspirated from the blister. In some embodiments, the blister is compressed to expel the fluid present in the blister. In certain embodiments, the blister is compressed using a cloth, a sponge, or hand, or a gloved hand.

[0096] In some embodiments, the blister is dried prior to the administration of the

composition and/or the dressing that covers the lesion. In certain embodiments, the blister is allowed to air-dry. In some embodiments, a dry powder is used to dry the blister. In certain embodiments, the dry powder comprises a corn flour ( e.g ., cornstarch). In other embodiments, the composition and/or the dressing that covers the lesion is administered while the blister is still wet.

I). Administration of the Composition

[0097] Certain aspects of the present invention are directed to methods of topically

administering a composition disclosed herein and/or a dressing that covers the lesion. In some embodiments, the composition is administered without co-administration of another topical treatment.

[0098] In some embodiments, the composition is applied at least once daily, at least twice daily, or at least three times daily. In some embodiments, the composition is applied 1 time per day, 2 times per day, or 3 times per day. In certain embodiments, the

composition is applied 1 time per day. In other embodiments, the composition is applied 2 times per day. In other embodiments, the composition is applied 3 times per day. In certain embodiments, the composition is applied to the lesion or the blister greater than 1 time per day.

[0099] In some embodiments, the composition is applied at the beginning of the day, at the end of the day, or once at the beginning of the day and once at the end of the day. In some embodiments, the composition is applied once at the beginning of the day, once at midday, and once at the end of the day.

[0100] In certain embodiments, the composition is at room temperature when it is applied to the skin. In other embodiments, the composition is below room temperature when it is applied to the skin. In other embodiments, the composition is above room temperature when it is applied to the skin.

[0101] In some embodiments, the composition is applied directly to the lesion. In some embodiments the composition is applied to the skin surrounding the lesion. In some embodiments, the composition is applied to the lesion, and the surrounding skin. In some embodiments, the composition is applied to healthy skin. In some embodiments, the composition is applied to at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or all exposed skin of the subject. In some embodiments, the composition is applied to at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or all skin of the subject. In some embodiments, the composition is applied to the entire body.

[0102] In certain embodiments, the composition is administered using a clean hand, a clean gloved hand, a clean cloth, a clean sponge, or any combination thereof. In some embodiments, the clean hand, the clean gloved hand, or the clean sponge are pretreated to reduce the tensile strength of the clean hand, the clean gloved hand, or the clean sponge prior to the administration. In certain embodiments, a clean hand is used.

[0103] In some embodiments, the composition is administered using a circular motion, a motion parallel to the axis of the body, a motion perpendicular to the axis of the body, a blotting technique, or any combination thereof. More than one motion can be used to apply the composition to a single target lesion, and more than one motion can be used to apply the composition to different target lesions on a single subject.

[0104] In certain embodiments, the composition is applied using a circular motion,

wherein the composition is applied by contacting the lesion, or the surrounding skin with the composition and spreading the composition using circular movements. In some embodiments, the circular movements follow a pattern of concentric circles of increasing size, wherein the circular movements begin in the center of the lesion, and the circular movements gradually increase in size to reach the perimeter of the lesion. In some embodiments, the circular movements follow a pattern of concentric circles of decreasing size, wherein the circular movements begin at the perimeter of the lesion, and the circular movements decrease in size to reach the center of the lesion. In some embodiments, the process of increasing or decreasing the size of the concentric circles is repeated and/or alternated. In some embodiments, the circular movements do not follow a pattern of concentric circles. The circular movements can be of any size necessary to apply the composition to the target area. In some embodiments, the circular movements are clockwise. In other embodiments, the circular movements are counterclockwise. In other embodiments, the circular movements alternate between clockwise and counterclockwise movements.

[0105] In some embodiments, the composition is applied using a motion parallel to the axis of the body, wherein the composition is applied by contacting the lesion, or the surrounding skin with the composition and spreading the composition using linear movements, wherein the linear movements run parallel or substantially parallel to the axis of the body. In some embodiments, each linear movement is more parallel to the axis of the body than perpendicular. In certain embodiments, the linear movements are at an angle of 0° to 45°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 40°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 35°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 30°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 25°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 20°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 15°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 10°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 0° to about 5°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of about 0°, relative to the axis of the body. In some embodiments, the motion parallel to the axis of the body is unidirectional. In certain embodiments, each motion parallel to the axis of the body is proximal to distal. In other embodiments, each motion parallel to the axis of the body is distal to proximal. In other embodiments, the motion parallel to the axis of the body is bidirectional, wherein both proximal -to-distal and distal-to-proximal motions are used.

[0106] In some embodiments, the composition is applied using a motion perpendicular to the axis of the body, wherein the composition is applied by contacting the lesion, or the surrounding skin with the composition and spreading the substance using linear movements, wherein the linear movements run perpendicular or substantially

perpendicular to the axis of the body. In some embodiments, each linear movement is more perpendicular to the axis of the body than parallel. In certain embodiments, the linear movements are at an angle of 45° to 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 50° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 55° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 60° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 65° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 70° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 75° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 80° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of 85° to about 90°, relative to the axis of the body. In other embodiments, the linear movements are at an angle of about 90°, relative to the axis of the body. In some embodiments, the motion perpendicular to the axis of the body is unidirectional. In certain embodiments, each motion perpendicular to the axis of the body is left to right. In other embodiments, each motion perpendicular to the axis of the body is right to left. In other embodiments, the motion perpendicular to the axis of the body is bidirectional, wherein both left-to-right and right-to-left motions are used.

[0107] In certain embodiments, the composition can be applied directly to the center of the lesion, and spread outward from the center to the perimeter of the lesion. In other embodiments, the composition can be applied directly to the tissue surrounding the lesion, and spread inward towards the center of the lesion. In some embodiments, the

composition can be applied directly to the perimeter of the lesion, and spread inward towards the center of the lesion. In some embodiments, the composition is spread using a motion from the perimeter of the lesion towards the center of the lesion.

E. Dosing

[0108] The compositions described herein can be administered at any effective dose or amount. In some embodiments, the composition is applied to the skin as a layer, wherein the thickness of the layer is about 0.01 mm to about 2 mm thick. In some embodiments, the thickness of the layer is about 0.1 mm to about 2 mm thick, about 0.1 mm to about 1.5 mm thick, about 0.1 mm to about 1 mm thick, about 0.1 mm to about 0.9 mm thick, about 0.1 mm to about 0.8 mm thick, about 0.1 mm to about 0.7 mm thick, about 0.1 mm to about 0.6 mm thick, about 0.1 mm to about 0.5 mm thick, about 0.1 mm to about 0.4 mm thick, about 0.1 mm to about 0.3 mm thick, about 0.1 mm to about 0.2 mm thick, about 0.01 mm to about 0.1 mm thick, about 0.01 mm to about 0.05 mm thick, or about 0.05 mm to about 0.1 mm thick. In some embodiments, the thickness of the layer is about 0.1 mm to about 2 mm thick. In certain embodiments, the layer is at least about 0.1 mm thick.

[0109] In some embodiments, the thickness of the layer is about 0.01 mm thick, about

0.02 mm thick, about 0.03 mm thick, about 0.04 mm thick, about 0.05 mm thick, about 0.06 mm thick, about 0.07 mm thick, about 0.08 mm thick, about 0.09 mm thick, about 0.1 mm thick, about 0.2 mm thick, about 0.3 mm thick, about 0.4 mm thick, about 0.5 mm thick, about 0.6 mm thick, about 0.7 mm thick, about 0.8 mm thick, about 0.9 mm thick, about 1 mm thick, about 1.1 mm thick, about 1.2 mm thick, about 1.3 mm thick, about 1.4 mm thick, about 1.5 mm thick, about 1.6 mm thick, about 1.7 mm thick, about 1.8 mm thick, about 1.9 mm thick, or about 2 mm thick. In some embodiments, the layer is about 0.1 mm thick.

[0110] In some embodiments, about 0.01 mL to about 2 mL of the composition is applied per 1 cm² of the skin. In some embodiments, about 0.1 mL to about 2 mL, about 0.1 mL to about 1.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 0.9 mL, about 0.1 mL to about 0.8 mL, about 0.1 mL to about 0.7 mL, about 0.1 mL to about 0.6 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 0.4 mL, about 0.1 mL to about 0.3 mL, about 0.1 mL to about 0.2 mL, about 0.01 mL to about 0.1 mL, about 0.02 mL to about 0.1 mL, about 0.03 mL to about 0.1 mL, about 0.04 mL to about 0.1 mL, about 0.05 mL to about 0.1 mL, about 0.06 mL to about 0.1 mL, about 0.07 mL to about 0.1 mL, about 0.08 mL to about 0.1 mL, or about 0.09 mL to about 0.1 mL of the composition is applied per 1 cm² of the skin. In certain embodiments, about 0.1 mL to about 2 mL of the composition is applied per 1 cm² of the skin.

[0111] In some embodiments, about 0.01 mL, about 0.02 mL, about 0.03 mL, about 0.04 mL, about 0.05 mL, about 0.06 mL, about 0.07 mL, about 0.08 mL, about 0.09 mL, about 0.1 mL, about 0.2 mL, about 0.3 mL, about 0.4 mL, about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, about 1 mL, about 1.1 mL, about 1.2 mL, about 1.3 mL, about 1.4 mL, about 1.5 mL, about 1.6 mL, about 1.7 mL, about 1.8 mL, about 1.9 mL, or about 2 mL of the composition is applied per 1 cm² of the skin.

[0112] In certain embodiments, a pea-sized amount of the composition is applied to the lesion. In some embodiments, a dime-sized amount of the composition is applied to the lesion. In some embodiments, a nickel-sized amount of the composition is applied to the lesion. In some embodiments, a quarter-sized amount of the composition is applied to the lesion. In some embodiments, a half-dollar-sized amount of the composition is applied to the lesion.

F. Dressing

[0113] In certain embodiments, the methods further comprise applying to the skin area affected by the lesion a dressing. In some embodiments, the dressing covers one or more lesions, e.g., a lesions of EB.

[0114] The dressing can be applied at any time after administration of the composition. In some embodiments, the dressing is applied immediately after administration of the composition. In some embodiments the dressing is applied less than about 5 minutes, less than about 10 minutes, less than about 15 minutes, less than about 20 minutes, less than about 25 minutes, less than about 30 minutes, less than about 35 minutes, less than about 40 minutes, less than about 45 minutes, less than about 50 minutes, less than about 55 minutes, or less than about 60 minutes after administration of the composition. In certain embodiments, the dressing is applied less than 30 minutes after administration of the composition. In some embodiments, the dressing is applied after the composition is administered and before the composition dries.

[0115] In some embodiments, the dressing is applied after the composition has been

administered and after the composition has dried. In some embodiments, the dressing is applied at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 minutes, at least about 25 minutes, at least about 30 minutes, at least about 35 minutes, at least about 40 minutes, at least about 45 minutes, at least about 50 minutes, at least about 55 minutes, or at least about 60 minutes after administration of the composition. In certain embodiments, the dressing is applied at least about 2 hours after administration of the composition.

[0116] In some embodiments, the dressing is applied about 1 to about 60 minutes after, about 1 to about 30 minutes after, about 1 to about 15 minutes after, or about 1 to about 5 minutes after administration of the composition. In some embodiments, the dressing is applied about 1 to about 10 minutes after, about 5 to about 15 minutes after, about 10 to about 20 minutes after, about 15 to about 25 minutes after, about 20 to about 30 minutes after, about 25 to about 35 minutes after, about 30 to about 40 minutes after, about 45 to about 55 minutes after, or about 50 to about 60 minutes after administration of the composition. In some embodiments, the dressing is applied about 1 hour to about 2 hours after the administration.

[0117] In some embodiments, the dressing is applied each time the composition is

applied. In some embodiments, the dressing is applied 1 time per day. In some embodiments, the dressing is applied 2 times per day. In some embodiments, the dressing is applied 3 times per day. In certain embodiments, the dressing is applied to a lesion of EB greater than 1 time per day.

[0118] Any dressing known in the art for the treatment of skin lesions can be used in the present methods. Examples of suitable dressings include, but are not limited to, a bandage, a gauze, a mesh, a tubular bandage, a cohesive bandage, a soft silicone tape, hydrogel, a sheet hydrogel, a hydrogel impregnated gauze, HYDROFIBER®, a biosynthetic cellulose, a bordered dressing, a powder, a lipido-colloid, a soft silicone, a soft silicone mesh, a polymeric membrane, a foam, a soft silicone foam, a soft silicone foam with super-absorbers, a super absorbent dressing, emu oil, restore dimethicreme, AQETAPHOR® (Beiersdorf, Inc.), white petroleum, and any combination thereof.

[0119] In some embodiments, more than one dressing is applied. In some embodiments, multiple types of dressing are layered. In some embodiments, the dressing is administered loosely, e.g ., wrapped around the treated area.

[0120] In some embodiments, the lesion is fully occluded by the dressing. In some

embodiments, the lesion is partially occluded by the dressing. In other embodiments, the lesion is not occluded by the dressing. In certain embodiments, the dressing is kept dry following the administration of the composition and the application of the dressing. In some embodiments, the dressing is prevented from drying following the administration of the composition and the application of the dressing.

[0121] In some embodiments, the particular dressing depends on the location and/or nature of the lesion, e.g. , the blister. In certain embodiments, the lesion is located on the subject's hand, and the dressing is designed to allow for increased dexterity, to prevent fusion of the digits, or both.

III. Compositions

[0122] Certain aspects of the present disclosure are directed to methods of topically

administering a composition disclosed herein to a subject, e.g., a subject suffering from EB, to treat a skin lesion. In some embodiments, the composition comprises or consists essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant. In some embodiments, the composition further comprises an additive, a solvent, or both. In certain embodiments, the composition comprises less than 0.5% allantoin. In some embodiments, the composition comprises a trace amount of allantoin, a negligible amount of allantoin, and/or an insignificant amount of allantoin. In particular embodiments, the composition does not comprise allantoin (e.g., comprises 0% allantoin).

[0123] In some embodiments, the emollient is selected from the group consisting of a fatty ester, a fatty alcohol, or a combination thereof. In certain embodiments, the fatty ester or the fatty alcohol is selected from the group consisting of diisopropyl adipate, oleyl alcohol, lanolin, isopropyl myristate, isopropyl palmitate, caprylic/capric triglycerides, cetyl lactate, cetyl palmitate, hydrogenated castor oil, glyceryl esters, hydroxycetyl isostearate, hydroxy cetyl phosphate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, polyoxypropylene (5) poloxyethylene (20) cetyl ether (PPG-5-Ceteth-20), 2-ethylhexyl isononoate, 2-ethylhexyl stearate, C_l2 to C_l6 fatty alcohol, C12 to C_l6 fatty alcohol lactate, isopropyl lanolate, 2-ethyl-hexyl salicylate, and combinations thereof. In some embodiments, the one or more emollients may be a combination of fatty alcohols. In certain embodiments, the one or more emollients may be l-hexadecanol, acetylated lanolin, behenocyl dimethicone, C_l2-i₅ alkyl benzoate, cetearyl octanoate, cocoglycerides, dicaprylate/dicaprate dimethicone copolyol, dimethiconol, dioctyl adipate, glyceryl stearate, isocetyl alcohol, isohexadecane,

isopentylcyclohexanone, isopropyl palmitate, lauryl lactate, mineral oil, methoxy peg- 22/dodecyl glycol copolymer, myristyl lactate, ocryldodecyl neopentanoate, octyl cocoate, octyl palmitate, octyl stearate, octyldodecyl neopentanoate, polyglyceryl-4 isosterate, polyoxyl 40 stearate, polyoxymethylene urea, potassium sorbate, propylene glycol, propylene glycol isoceth-3 acetate, and propylene glycol myristyl ether acetate. In some embodiments, the emollient may be a high molecular weight saturated and unsaturated fatty alcohol such as, but not limited to, carbitol, lauryl alcohol, myristyl alcohol, cetyl alcohol, isocetyl alcohol, stearyl alcohol, isostearyl alcohol, hydroxystearyl alcohol, oleyl alcohol, ricinoleyl alcohol, behenyl alcohol, erucyl alcohol, 2- octyldodecanyl alcohol, cetearyl alcohol, lanolin alcohol, or the like. In some

embodiments, the emollient is selected from the group consisting of lanolin oil, cod liver oil, mineral oil, an alcohol, and any combination thereof. In certain embodiments, the alcohol comprises cetyl alcohol, stearyl alcohol, or a combination thereof. Emollients are well known in the art and are listed, for example, the International Cosmetic Ingredient Dictionary, Eighth Edition, 2000, which is hereby incorporated by reference in its entirety.

[0124] In some embodiments, the composition comprises an emollient in an amount from about 8% to about 30% by weight. In certain embodiments, the composition includes more than one emollient, wherein each emollient is included at about 0.05% to about 15% by weight of any one emollient. In certain embodiments, the composition comprises about 8% to about 30% emollient selected from the group consisting of lanolin oil, cod liver oil, mineral oil, an alcohol, and any combination thereof. In some embodiments, the composition comprises cetyl alcohol in an amount from about 2% to about 6%, stearyl alcohol in an amount from about 1% to about 3%, lanolin in an amount from about 5% to about 15%, cod liver oil in an amount from about 0.05% to about 5% or combinations thereof. In particular embodiments, the composition comprises about 5% to about 15% lanolin oil, about 0.05% to about 5% cod liver oil, or a combination thereof. In certain embodiments, the composition comprises about 10.6% lanolin oil, about 2% cod liver oil, or a combination thereof. In some embodiments, the composition comprises about 1% to about 6% cetyl alcohol, about 1% to about 3% stearyl alcohol, or a combination thereof.

In particular embodiments, the compositions comprises about 3.6% cetyl alcohol, about 1.7% stearyl alcohol, or a combination thereof. In one particular embodiment, the composition comprises about 3.6% cetyl alcohol, about 1.7% stearyl alcohol, about 10.6% lanolin oil, and about 2% cod liver oil.

[0125] In some embodiments, the emulsifier is selected from the group consisting of sodium lauryl sulfate, a white wax, a sesquioleate, an ethoxylated ester of a derivative of a natural oil, a silicone emulsifier, a fatty acid soap, a fatty acid sulphate, an ethoxylated fatty alcohol, a sorbitan ester, an ethoxylated sorbitan ester, an ethoxylated fatty acid ester, an ethoxylated monoglyceride, an ethoxylated diglyceride, an ethoxylated triglyceride, a non-ionic self-emulsifying wax, an ethoxylated fatty acid, a methylglucose ester, and any combination thereof. In certain embodiments, the white wax comprises beeswax, paraffin wax, or a combination thereof. In certain embodiments, the

sesquioleate comprises sorbitan sesquioleate, polyglyceryl-2-sesquioleate, or a combination thereof. In certain embodiments, the ethoxylated ester of a derivative of a natural oil comprises a poly ethoxylated ester of hydrogenated castor oil. In certain embodiments, the silicone emulsifier comprises a silicone polyols. In certain

embodiments, the fatty acid soap comprises potassium stearate. In certain embodiments, the fatty acid sulphate comprises sodium cetostearyl sulphate. In certain embodiments, the ethoxylated fatty acid ester comprises an ethoxylated stearate. In certain

embodiments, the methylglucose ester comprises polyglycerol-3 methyl glucose distearate. Various emulsions suitable for embodiments described herein and methods for preparing such emulsions are well known in the art and are described in, for example, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., USA, which is hereby incorporated by reference in its entirety.

[0126] In some embodiments, the composition comprises an emulsifier in an amount from about 1% to about 15%. In some embodiments, the formulation comprises from about 1% to about 10%, or from about 1% to about 5% emulsifier. If more than one emulsifier is used, the formulation may include from about 1% to about 5% or from about 1.5% to about 3% by weight of the formulation of each emulsifier. In certain

embodiments, the composition comprises about 1% to about 15% emulsifier selected from the group consisting of sodium lauryl sulfate, a white wax, and a combination thereof In particular embodiments, the compositions comprises about 1.5% to about 3% beeswax, about 1.5% to about 3% sodium lauryl sulfate in a 30% solution, or a combination thereof. In certain embodiments, the composition comprises about 2% beeswax, about 2% sodium lauryl sulfate in a 30% solution, or a combination thereof.

[0127] In some embodiments, the antioxidant is selected from the group consisting of amino acids such as glycine, histidine, tyrosine, trytophan and derivatives thereof;

imidazoles such as urocanic acid and derivatives thereof; peptides such as D,L-camosine, D-carnosine, L-carnosine and derivatives thereof such as anserine, carotinoids, carotenes such as alpha-carotone, beta-carotene, lycopene, and derivatives thereof; chlorogenic acid and derivatives thereof; lipoic acid and derivatives thereof such as dihydrlipoic acid, aurothioglycose, propylthiouracil and other thiols such as thioredoxin, glutathione, cysteine, cystine, cystamine and glycosyl; N-acetyl, methyl, ethyl, propyl, amyl, butyl, lauryl, palmitoyl, oleyl, alpha-linoleyl, cholesteryl and glyceryl esters and salts thereof; dilauryl thiodipropionate; distearyl thiodipropionate; thiodipropionic acid and derivatives thereof such as esters, ethers, peptides, lipids, nucleotides, nucleosides, and salts;

sulfoximine compounds such as buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, hepta-thionine sulfoximine; unsaturated fatty acids and derivatives thereof such as alpha-linolenic acid, linoleic acid, oleic acid, folic acid and derivatives thereof; ubiquinone and ubiquinol and derivatives thereof; vitamin C and derivatives thereof such as ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate, tocopherals and derivatives thereof such as vitamin E acetate, vitamin A and derivatives such as vitamin A palmitate, vitamin B and derivatives thereof; coniferyl benzoate of benzoin resin; rutinic acid and derivatives thereof; alpha-glycosylrutin;

ferulic acid; furfurylidene glucitol; camosine; butyl hydroxytoluene; trihydroxy- butyrophenone; uric acid and derivatives thereof; mannose and derivatives thereof;

superoxide dismutase; zinc and derivatives thereof such as ZnO, ZnS0₄; selenium and derivatives thereof such as selenium methionine; stilbene and derivatives thereof such as stilbene oxide, trans-stilbene oxide, and the like; and any combination thereof. In some embodiments, the antioxidant is selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbyl stearate, butyl hydroxyanisole, gallic esters, and any combination thereof. In particular embodiments, the antioxidants comprises BHT.

[0128] The antioxidant can be included in the composition in any suitable amount. In some embodiments, the composition comprises about 0.001% to about 3% by weight of an antioxidant. In some embodiments, the composition comprises about 0.01% to about 1% or about 0.05% to about 1% by weight of an antioxidant. In certain embodiments, the composition comprises about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, gallic esters, and any combination thereof. In particular embodiments, the composition comprises about 0.01% to about 1% antioxidant selected from the group consisting of vitamin B,

nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, gallic esters, and any combination thereof. In particular embodiments, the composition comprises about 0.05% to about 1% butylated

hydroxytoluene. In one particular embodiment, the composition comprises about 0.5% butylated hydroxytoluene.

[0129] In some embodiments, the preservative is selected from the group consisting of pentylene glycol; ethylene diamine tetra acetate (EDTA) and its salts; chlorhexidine and its diacetate, dihydrochloride, di gluconate derivatives; l,l,l-trichloro-2-methyl-2- propanol; parachlorometaxylenol; polyhexamethylenebiguanide hydrochloride;

dehydroacetic acid; diazolidinyl urea; 2,4-dichlorobenzyl alcohol; 4,4-dimethyl-l,3- oxazolidine; formaldehyde, glutaraldehyde; dimethylidantoin; imidazolidinyl urea; 5- chloro-2-methyl-4-isothiazolin-3-one; ortho-phenylphenol; benzyl alcohol; benzoic acid and its salts; 4-hydroxybenzoic acid and its methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-esters (parabens); methylparaben; propylparaben; isopropylparabens;

isobutylparabens; butylparabens; ethylparaben; trichlosan; 2-phenoxy ethanol; phenyl mercuric acetate; quaternium-l5; methylsalicylate; salicylic acid and its salts; sorbic acid and its salts; iodopropanyl butylcarbamate; calcium sorbate; zinc pyrithione; 5-bromo- Snitro-l,3-dioxane, 2-bromo-2-nitropropane-l,3-diol; sulfites; bisulfites; benzalkonium chloride; phenoxy ethanol; 2-phenoxy ethanol; chloroxylenol; diazolidinyl urea; and any combination thereof. In certain embodiments, the composition comprises methylparaben, propylparaben, or a combination thereof.

[0130] Preservatives may be provided in any concentration known in the art. In some embodiments, the composition comprises about 0.01% to about 3.0% of a preservative. In some embodiments, the composition comprises about 0.05% to about 1% or about 0.05% to about 0.5% of a preservative. In some embodiments, the composition comprises about 0.01% to about 3.0% preservative selected from the group consisting of methylparaben, propylparaben, and a combination thereof. In certain embodiments, the composition comprises about 0.05% to about 0.5% methylparaben, about 0.05% to about 0.5% propylparaben, or a combination thereof. In particular embodiments, the composition comprises about 0.3% methylparaben, about 0.25% propylparaben, or a combination thereof.

[0131] In some embodiments, the pH modifier is selected from the group consisting of lactic acid, citric acid, sodium citrate, glycolic acid, succinic acid, phosphoric acid, monosodium phosphate, disodium phosphate, oxalic acid, dl-malic acid, calcium carbonate, sodium hydroxide and sodium carbonate, sodium hydrogen carbonate, and ammonium hydrogen carbonate. In particular embodiments, comprises citric acid, lactic acid, or a combination thereof.

[0132] In some embodiments, the composition comprises about 0.01% to about 1% of a pH modifier. In some embodiments, the composition about 0.05% to about 0.5%, about 0.06% to about 0.15%, about 0.06% to about 0.11%, or about 0.06% to about 0.1% by weight of a pH modifier. In certain embodiments, the composition comprises about 0.01% to about 1% pH modifier selected from the group consisting of citric acid, lactic acid, and a combination thereof. In particular embodiments, the composition comprises about 0.05% to about 0.2% citric acid. In particular embodiments, the composition comprises about 0.06% to about 0.1% citric acid. In one particular embodiment, the composition comprises about 0.09% citric acid.

[0133] In some embodiments, the solubilizing agent is selected from the group consisting of hydrochloric acid, sodium hydroxide, glycine, cyclodextrin, liquid paraffin, hydrogenated castor oil, ethanol, glycerin, propylene glycol, dilute hydrochloric acid, hydrogenated oils, purified water, physiological saline, water for injection, Macrogol 4000, Polysorbate 80, or a combination thereof. In particular embodiments, the solubilizing agent is selected from propylene glycol, glycerin, and a combination thereof.

[0134] In some embodiments, the composition comprises about 1% to about 20% of a solubilizing agent. In some embodiments, the composition comprises about 1% to about 10% or from about 2% to about 8% by weight of a solubilizing agent. In certain embodiments, the composition comprises about 1% to about 20% of a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof. In particular embodiments, the composition comprises about 2% to about 8% propylene glycol. In one particular embodiment, the composition comprises about 5.7% propylene glycol.

[0135] In some embodiments, the viscosity agent is a viscosity modifier. In some

embodiments, the viscosity agent comprises a high molecular weight compound. In certain embodiments, the high molecular weight compound is selected from the group consisting of a carboxyvinyl polymer, carboxymethyl cellulose, polyvinyl pyrrolidone, hydroxy ethyl cellulose, methyl cellulose, a natural gum ( e.g ., a gelatin or tragacanth gum), an alcohol (e.g. polyvinyl alcohol), and any combination thereof. In some embodiments, the viscosity agent comprises ethanol or isopropyl alcohol. In some embodiments, the viscosity agent comprises a high molecular weight saturated and unsaturated fatty alcohol. In certain embodiments, the molecular weight saturated and unsaturated fatty alcohol is selected from carbitol, lauryl alcohol, myristyl alcohol, cetyl alcohol, isocetyl alcohol, stearyl alcohol, isostearyl alcohol, hydroxystearyl alcohol, oleyl alcohol, ricinoleyl alcohol, behenyl alcohol, erucyl alcohol, 2-octyldodecanyl alcohol, cetearyl alcohol, lanolin alcohol, and any combination thereof. In some embodiments, the viscosity agent is selected from the group consisting of cetyl alcohol, stearyl alcohol, or a combination thereof.

[0136] In some embodiments, the composition comprises from about 1% to about 10% of a viscosity agent. In certain embodiments, the composition comprises from about 1 to about 6% of a viscosity agent. In some embodiments, the composition comprises about 1% to about 10% viscosity enhancing agent selected from the group consisting of cetyl alcohol, stearyl alcohol, and a combination thereof. In certain embodiments, the composition comprises about 1% to about 6% cetyl alcohol, about 1% to about 3% stearyl alcohol, or a combination thereof. In certain embodiments, the composition comprises about 2% to about 6% cetyl alcohol, about 1% to about 3% stearyl alcohol, or a combination thereof. In particular embodiments, the compositions comprises about 3.6% cetyl alcohol, about 1.7% stearyl alcohol, or a combination thereof.

[0137] In some embodiments, the chelating agent is selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, ethylenediamine tetra acetic acid (Edetate, EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, and any combination thereof. In particular embodiments, the chelating agent is tetrasodium EDTA.

[0138] The chelating agents may be provided in any effective amount. In some

embodiments, the composition comprises about 0.01% to about 2% by weight of a chelating agent. In some embodiments, the composition comprises about 0.05% to about 0.5% or about 0.05% to about 0.35% by weight of a chelating agent. In certain

embodiments, the composition comprises about 0.01% to about 2% of a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium

methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof. In particular embodiments, the composition comprises about 0.05% to about 0.5% tetrasodium EDTA. In other embodiments, the composition comprises about 0.05% to about 0.35% tetrasodium EDTA. In one particular embodiment, the composition comprises about 0.15% tetrasodium EDTA.

[0139] In some embodiments, the composition further comprises a solvent. In certain embodiments, the solvent comprises water. Generally, the quantity of water used as a solvent may depend on the various other ingredients used. In some embodiments, the composition comprises about 10% to about 95%, about 40% to about 90%, about 42% to about 87%, about 42% to about 80%, about 42% to about 75%, about 42% to about 70%, or about 42% to about 68% water. The exact quantity of solvent may be dependent on the form of the product. In certain embodiments, a composition that is in a lotion form comprises more water than a composition that is in a spray form, and a composition that is in a cream or butter form comprises less water than a composition that is in a spray form. In certain embodiments, the water is a deionized water. Other suitable solvent materials known in the art may also be used.

[0140] In certain embodiments, the composition further comprises allantoin. In some embodiments, the composition comprises a negligible amount of allantoin. In some embodiments, the composition comprises a trace amount of allantoin. In some

embodiments, the composition comprises an insignificant amount of allantoin. In some embodiments, the composition comprises a negligible amount of allantoin. In some embodiments, the composition comprises less than 0.5% allantoin. In some embodiments, the composition comprises less than about 0.45% allantoin. In some embodiments, the composition comprises less than about 0.35% allantoin. In some embodiments, the composition comprises less than about 0.3% allantoin. In some embodiments, the composition comprises less than about 0.25% allantoin. In some embodiments, the composition comprises less than about 0.2% allantoin. In some embodiments, the composition comprises less than about 0.15% allantoin. In some embodiments, the composition comprises less than about 0.1% allantoin. In some embodiments, the composition comprises less than about 0.05% allantoin. In some embodiments, the composition comprises less than about 0.01% allantoin.

[0141] In some embodiments, the composition comprises about 0.01% to less than 0.5% allantoin. In some embodiments, the composition comprises about 0.05% to less than 0.5% allantoin. In some embodiments, the composition comprises about 0.1% to less than

0.5% allantoin. In some embodiments, the composition comprises about 0.2% to less than

0.5% allantoin. In some embodiments, the composition comprises about 0.3% to less than

0.5% allantoin. In some embodiments, the composition comprises about 0.4% to less than

0.5% allantoin.

[0142] In some embodiments, the composition comprises 0.49% allantoin, about 0.45%, about 0.40%, about 0.35%, about 0.3%, about 0.25%, about 0.2%, about 0.15%, about 0.1%, about 0.05%, or about 0.01% allantoin.

[0143] In certain embodiments, the composition does not comprise allantoin. In certain embodiments, the composition comprises 0% allantoin.

[0144] In certain embodiments, the composition comprises or consists essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant, wherein the composition does not comprise an additional active ingredient. An "active ingredient" as used herein refers to any component that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals. In some embodiments, the compositions comprises or consists essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant, wherein the composition does not comprise an additional active ingredient that requires prescription from a healthcare professional for use, e.g ., as required by the United States Food and Drug Administration.

[0145] In some embodiments, the composition further comprises a fragrance. In some embodiments, the composition further comprises an herbal extract.

[0146] In some embodiments, the composition comprises, consists essentially of, or consists of:

(a) about 40% to about 90% water;

(b) about 8% to about 30% an emollient;

(c) about 1% to about 15% an emulsifier;

(d) about 0.01% to about 1% a pH modifier;

(e) about 1% to about 10% a viscosity agent; (f) about 1% to about 20% a solubilizing agent selected from the group

consisting of propylene glycol, glycerin, and a combination thereof;

(g) about 0.01% to about 2% a chelating agent selected from the group

consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof;

(h) about 0.001% to about 3% an antioxidant selected from the group

consisting of vitamin B, nordihydroguaiaretic acid, butylated

hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and

(i) about 0.01% to about 3.0% a preservative.

[0147] In some embodiments, the composition comprises, consists essentially of, or

consists of:

(a) about 40% to about 90% water;

(b) about 8% to about 30% emollient selected from the group consisting of lanolin oil, cod liver oil, mineral oil, an alcohol, and any combination thereof;

(c) about 1% to about 15% emulsifier selected from the group consisting of sodium lauryl sulfate, a white wax, and a combination thereof;

(d) about 0.01% to about 1% pH modifier selected from the group consisting of citric acid, lactic acid, and a combination thereof;

(e) about 1% to about 10% viscosity enhancing agent selected from the group consisting of cetyl alcohol, stearyl alcohol, and a combination thereof;

(f) about 1% to about 20% solubilizing agent selected from the group

consisting of propylene glycol, glycerin, and a combination thereof;

(g) about 0.01% to about 2% chelating agent selected from the group

consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) 0.01% to about 1% antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and

(i) about 0.01% to about 3.0% preservative selected from the group consisting of methylparaben, propylparaben, and a combination thereof.

[0148] In some embodiments, the composition comprises, consists essentially of, or consists of:

(a) about 40% to about 90% water;

(b) about 1% to about 6% cetyl alcohol;

(c) about 1% to about 4% stearyl alcohol;

(d) about 1.5% to about 3% beeswax;

(e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution;

(f) about 0.05% to about 0.2% citric acid;

(g) about 5% to about 15% lanolin oil;

(h) about 2% to about 8% propylene glycol;

(i) about 0.05% to about 0.5% tetrasodium EDTA;

(j) about 0.05% to about 5% cod liver oil;

(k) about 0.05% to about 1% butylated hydroxytoluene;

(l) about 0.05% to about 0.5% methylparaben; and

(m) about 0.05% to about 0.5% propylparaben.

[0149] In some embodiments, the composition comprises, consists essentially of, or consists of:

(a) about 42% to about 80% water;

(b) about 2% to about 6% cetyl alcohol;

(c) about 1% to about 3% stearyl alcohol;

(d) about 1.5% to about 3% beeswax;

(e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution;

(f) about 0.06% to about 0.1% citric acid;

(g) about 5% to about 15% lanolin oil;

(h) about 2% to about 8% propylene glycol; (i) about 0.05% to about 0.35% tetrasodium EDTA;

(j) about 0.05% to about 5% cod liver oil;

(k) about 0.05% to about 1% butylated hydroxytoluene;

(l) about 0.05% to about 0.5% methylparaben; and

(m) about 0.05% to about 0.5% propylparaben.

[0150] In some embodiments, the composition comprises, consists essentially of, or consists of:

(a) about 69.16% water;

(b) about 5% cetyl alcohol;

(c) about 2.45% stearyl alcohol;

(d) about 1.9% beeswax;

(e) about 1.9% sodium lauryl sulfate in a 30% solution;

(f) about 0.09% citric acid;

(g) about 10.6% lanolin oil;

(h) about 5.7% propylene glycol;

(i) about 0.15% tetrasodium EDTA;

(j) about 2% cod liver oil;

(k) about 0.5% butylated hydroxytoluene;

(l) about 0.3% methylparaben; and

(m) about 0.25% propylparaben.

[0151] In some embodiments, the composition consists essentially of or consists of:

(a) about 69.16% water;

(b) about 5% cetyl alcohol;

(c) about 2.45% stearyl alcohol;

(d) about 1.9% beeswax;

(e) about 1.9% sodium lauryl sulfate in a 30% solution;

(f) about 0.09% citric acid;

(g) about 10.6% lanolin oil;

(h) about 5.7% propylene glycol;

(i) about 0.15% tetrasodium EDTA;

(j) about 2% cod liver oil;

(k) about 0.5% butylated hydroxytoluene; (l) about 0.3% methylparaben; and

(m) about 0.25% propylparaben.

IV. Kits

[0152] Certain aspects of the present disclosure are directed to kits comprising a

composition described herein. In certain embodiments, the kit comprises: (1) a composition described herein, (2) a dressing described herein, and (3) instructions for administering (1) and (2) according to a method disclosed herein.

[0153] In some embodiments, the kit further comprises a needle, scissors, or a scalpel. In certain embodiments, the needle is a hypodermic needle. In some embodiments, the kit further comprises one or more solution for washing a subject or a lesion as disclosed herein.

[0154] All of the various aspects, embodiments, and options described herein can be combined in any and all variations.

[0155] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0156] Having generally described this disclosure, a further understanding can be

obtained by reference to the examples provided herein. These examples are for purposes of illustration only and are not intended to be limiting.

EXAMPLES

Example 1

[0157] A phase 3 study was conducted to evaluate the efficacy and safety of SD-005 in the treatment of patients with Epidermolysis Bullosa (EB). SD-005 is an oil in water composition including 5% cetyl alcohol, 2.45% stearyl alcohol, 1.9% beeswax, 1.9% sodium lauryl sulfate in a 30% solution, 0.09% citric acid, 10.6% lanolin oil, 5.7% propylene glycol, 0.15% tetrasodium EDTA, 2% cod liver oil, 0.5% butylated

hydroxytoluene, 0.3% methylparaben, 0.25% propylparaben, and about 69.16% water. Approximately 150 patients were enrolled at study sites worldwide, with 87 subjects randomly assigned to receive SD-005.

[0158] All patients enrolled in the study had a diagnosis of simplex, recessive dystrophic, or junctional non-Herlitz EB; must have 1 target lesion (size 10 to 50 cm²) that has been present for 21 days or more; and the patient must be at least 1 month old.

[0159] Patients were excluded for one or more of the following reasons: (1) the target lesion had clinical evidence of local infection; (2) prior use of any investigational drug within the 30 days before enrollment; (3) prior use of immunotherapy or cytotoxic chemotherapy within the 60 days before enrollment; (4) prior use of systemic or topical steroidal therapy within the 30 days before enrollment (Inhaled steroids and ophthalmic drops containing steroids are allowed); (5) prior use of systemic antibiotics within the 7 days before enrollment; (6) current or former malignancy; (7) arterial or venous disorder resulting in ulcerated lesions; (8) pregnancy or breastfeeding during the study; or (9) females of childbearing potential who are not abstinent and not practicing a medically acceptable method of contraception.

[0160] The primary efficacy endpoints were the time to complete target lesion closure within 3 months and the proportion of patients experiencing complete closure of the target lesion within 3 months. Complete target lesion closure is defined as skin re- epithelialization without drainage.

[0161] The key secondary efficacy endpoints were the proportion of patients

experiencing complete closure of their target lesion within 2 months; the proportion of patients experiencing complete closure of their target lesion within 1 month; and the change in lesional skin based on Body Surface Area Index (BSAI) at Month 3, compared to Baseline. BSAI is a global measure of disease“spread” with weighting factors. The BSA affected with lesional skin was calculated at baseline and at each visit to assess the total affected area before and after using the product.

[0162] Lesional skin for assessment consists of area(s) that contain any of the following: blisters, erosions, ulcerations, scabbing, bullae, and eschars, as well as areas that are weeping, sloughing, oozing, crusted, and denuded. The percent of this area was recorded for each defined body region [(number from 0-100% assigned for each region) - BSA] Other areas categorized as skin that was either healed or scarred were not considered lesional skin. The BSAI was assessed per this by a study physician. The same study physician performed this assessment for each patient visit.

[0163] The change in Total Body Lesion Burden based on BSAI at Month 3 was

determined, compared to Baseline. The change in total body lesion coverage based on BSAI estimates at each visit, compared to baseline was measured using the same principles that underlie the BSAI estimates of lesional skin, the percentage of the total BSA affected by open lesions was calculated at baseline and at each visit to assess the total lesion area before and after using the product. The BSAI of lesions was assessed by a study physician. The same study physician performed this assessment for each patient visit.

[0164] The change in itching was assessed at Week 1 (Day 7), compared to baseline, and itching was measured using the "Itch Man Pruritus Assessment Tool." For patients 1 month to 5 years of age itching was assessed using caretaker’s response, and patients 6 years of age and older self-reported their itching assessments.

[0165] The change in pain was assessed at Week 1 (Day 7), compared to baseline, and pain was measured using the "FLACC scale" for patients 1 month to 3 years of age and the "Wong Faces Pain Scale" for patients 4 years of age and older.

[0166] Other secondary efficacy endpoints included (1) the change in Total Body Lesion

Burden based on BSAI at Week 2 and Months 1, 2, and 3 compared to Baseline; (2) the percent change from Baseline in Total Body Lesion Burden based on BSAI at Week 2 and Months 1, 2, and 3; (3) the change in lesional skin based on BSAI at Week 2 and Months 1, 2, and 3, compared to Baseline; (4) the percent change in lesional skin based on BSAI at Week 2 and Months 1, 2, and 3, compared to Baseline; (5) the presence of scarring of healed target lesion at the visit where the complete closure is documented; (6) the change in target lesion characteristics (i.e., inflammation, blistering, granulation tissue, erythema, exudate) at Week 2 and Months 1, 2, and 3, compared to Baseline; (7) the change in itching and pain at Days 1 to 6, Week 2, and Months 1, 2, and 3, compared to Baseline; and (8) the proportion of patients experiencing target lesion closure within Week 2. A. Study Design

[0167] This Phase 3, multi-center, randomized, double-blind, study assessed the efficacy and safety of SD-005 in the treatment of lesions in approximately 150 patients with simplex, recessive dystrophic, or junctional non-Herlitz epidermolysis bullosa (EB).

[0168] SD-005 was applied topically, once a day to the entire body of 87 patients for a period of 90 days.

[0169] One target lesion, e.g. , a target wound, on each patient was selected at baseline by the Investigator, per the ARANZ SilhouetteStar™ system manuals and training provided. At screening, multiple lesions on the subject were assessed against study

inclusion/exclusion criteria. The selected target lesions were at least 21 days old (size 10 to 50 cm²). Photographic confirmation of the target lesion location was collected at baseline, and the picture saved from the first visit was used to confirm location of the target lesion at subsequent visits. Once the target lesion was identified, it was followed during the subsequent study visits 2, 3, 4 and 5. Only 1 lesion was selected for the study and followed within the ARANZ system.

[0170] Patients who had an eligible target lesion and met all other inclusion/exclusion criteria were randomized. The first dose of treatment was administered during the office visit. Patients randomized were initially given one-month supply of study medication.

[0171] Each patient returned to the study site for visit 2 (14 days ±5 days from baseline), visit 3 (30 days ±7 days from baseline), visit 4 (60 days ±7 days from baseline), and visit 5 (90 days ±7 days from baseline) to have the target lesion, previously identified at baseline, re-assessed for the level of healing. In addition, itching, pain, body surface area index (BSAI), and scarring of healed target lesion were also assessed at each visit. The ARANZ SilhouetteStar™ was used to measure the target lesion area at all visits.

[0172] Safety assessments included monitoring tolerability, AEs, and physical

examinations.

[0173] Baseline demographics and characteristics for subjects randomized to receive SD-

005 are shown in Table 1. Table 1: Baseline Demographics and Characteristics

Data are reported as mean ± standard deviation or n (%).

B. Study Medicine and Administration

[0174] SD-005 cream was supplied in 8-ounce plastic tubes, to be reclosed after use and stored at room temperature. SD-005 was applied topically once a day to the entire body for a period of 90 days. The first dose of study treatment was administered during the first study visit upon randomization and after completion of the physical examination, baseline BSAI, itching, and pain assessments.

[0175] A patient diary was returned at visits 3, 4 and 5 to evaluate compliance.

[0176] Concurrent administration of the following medications was acceptable and did not result in the withdrawal of the patient: oral and topical antihistamines; topical antibiotics; systemic antibiotics; inhaled steroids and ophthalmic drops containing steroids; non-steroidal anti-inflammatory drugs (NSAIDs); limited steroid use is acceptable for planned medical procedures, including but not limited to, esophageal dilatation; morphine or other narcotic pain relievers; and vitamins. Medications considered necessary for the patient’s welfare (intercurrent illness or AEs) were also permissibly at the discretion of the Investigator. The subjects were instructed not to take any medications without prior consultation with the Investigator, as feasible. The administration of all such medication / therapy was recorded and assessed at each visit.

[0177] The use of immunosuppressive agents or corticosteroids (oral, rectal, intravenous, and topical) were prohibited (however, limited steroid use was acceptable for planned medical procedures, including but not limited to, esophageal dilatation). In some cases, use of prohibited medications during the trial resulted in the withdrawal of the subject, which decision was based on the assessment by the Investigator and medical monitor. C. Safety Assessments

[0178] The safety of SD-005 dermal cream, applied daily to the entire skin surface, was assessed by monitoring tolerability, AEs, and physical examinations. Physical examinations were done by a physician, and included examination of the head, eyes, ears, nose, throat, neck, chest, lungs, heart, abdomen, skin, and lymph nodes and assessment of the musculoskeletal and neurological systems. Weight, height/length, and temperature were also recorded.

[0179] Adverse events (AEs) were identified by the patient or as a result of general, non leading questioning. All AEs were recorded in the eCRF. Adverse events were collected after signing the informed consent/assent through Visit 5. The identified AEs were followed up to 30 days after the last dose of study drug has been administered.

[0180] In the case of withdrawal due to an AE/SAE, the patient was followed until

resolution of the AE, or until in the opinion of the Investigator, the event had stabilized, or the Investigator did expect any further improvement or worsening of the subject’s condition, and the patient was referred to their primary physician for appropriate management of the ongoing event. Reasonable efforts were made to contact a patient who fails to attend any follow-up appointments, in order to ensure that he/she was in satisfactory health.

[0181] The severity (intensity) of each AE was classified by the Investigator as (1) mild, wherein the subject was aware of a sign of symptom, which was easily tolerated; (2) moderate, wherein the sign or symptom caused discomfort, but did not interfere with normal activities; or (3) severe, wherein the sign or symptom was of sufficient intensity as to interfere with normal activities.

[0182] The likely relationship of each AE to the medicinal product was assessed by the

Investigator and reported as unrelated, possibly, probably, or definitely related to the treatment. An AE was classified as unrelated was used when the event occurred before dosing or the event or intercurrent illness was due wholly to factors other than drug treatment. An AE was classified as possibly related to the treatment if there was a reasonable temporal relationship with treatment and the event could be explained by patient’s clinical state or other factors. An AE was classified as probably related to the treatment if there was a reasonable temporal relationship with drug treatment, the event was likely to be a known reaction to agent or chemical group, or was predicted based on known pharmacology, and the event could not be easily explained by the patient’s clinical state or other factors. An AE was classified as definitely related to the treatment if there was a distinct temporal relationship with treatment, it was a known reaction to agent or chemical group, or predicted by known pharmacology, and the event could not be explained by the patient’s clinical state or other factors.

I). Results

[0183] Target lesion closure was measured for all EB patients administered SD-005

(n=87) through month 3. The mean time to complete wound closure within 3 months in patients treated with SD-005 was 53.6 days (FIG. 1). The time to complete target wound closure was longer in patients having EB simplex compared with patients having recessive dystrophic or junctional non-Herlitz EB (FIG. 1). The time to complete target wound closure was shorter in patients aged 1 month to <2 years compared with patients in older age groups and in patients with <5% BSAI of total wound burden compared with patients with >5% BSAI of total wound burden (FIG. 1). The time to complete target wound closure was longer when the target wound was >30 days old compared with target wounds present for <30 days (FIG. 1).

[0184] The proportion of the 87 EB patients in the study treated with SD-005 with target lesion (e.g, target wound) closure was about 7.1% at 2 weeks, about 22.6% at 1 month, about 42.9% at 2 months, about 53.6% at 3 months, about 65% at 4 months, and about 82% at 5 months (FIGs. 2A-2B). As a comparison, a historical study, using an unrelated therapy for treating EB in subjects at least 18 years old, reported about 30% of patients administered an active (fibroblast cell therapy) (n=l4) experienced target lesion closure at 3 months in the active arm and less than 20% experienced target lesion closure at 3 months with the vehicle (n=l2) (see Petrof et al. , 2013; FIG. 2C).

[0185] The data for the EB subjects from the SD-005 study was stratified according to

EB type (FIG. 2D), patient age (FIGs. 2E and 2F), and BSAI of total wound burden (FIG. 2G). The proportion of patients with complete target wound closure at each time point was similar regardless of EB type (FIG. 2D). A higher proportion of patients in the 1 month to <2 year age group experienced complete target wound closure compared with older age groups at all time points (FIG. 2E), and patients in the 1 month to <2 year age group on average had a shorter time to wound closure compared to older patients (data not shown). About 70% of subjects at least 18 years old (h=10), treated with SD-005 experienced target lesion closure within 3 months (FIG. 2F), which was about triple the percent experiencing target lesion closure in subjects at least 18 years old administered active (n=l4) or vehicle (n=l2) at 3 months in the Petrof study (FIG. 2G). About 30% of patients at least 18 years old in the SD-005 study showed target wound closure at 1 month and about 60% of these patients showed target wound closure at 2 months, which was more than double the percent of subjects experiencing target lesion closure when administered active (n=l4) or vehicle (n=l2) at 2 months in the Petrof study (FIG. 2F). In addition, a higher proportion of patients with <5% BSAI of total wound burden experienced complete target wound closure compared with patients with >5% BSAI of total wound burden at all time points (FIG. 2G).

[0186] Target lesion size was also monitored for 59 EB patients through month 3.

Subjects at least 18 years old treated with SD-005 showed an average decrease in the size of the target lesions of more than 95% by month 2, which was maintained through month 3 (FIG. 3 A). By 1 month, target lesions decreased in size by an average of over 80%

(FIG. 3 A). These reductions in target wound size were greater than those observed in the Petrof study, where active treatment in EB patients at least 18 years old showed an average decrease in target lesion size of about 60% at month 3 (FIGs. 3 A and 3B). SD- 005 treatment performed better than the Petrof therapy in EB patients (FIG. 3B).

Furthermore, a comparison of the subpopulation of subjects at least 18 year old is shown in FIG. 3 A.

[0187] In addition, treatment with SD-005 was associated with reductions in all other clinical endpoint parameters over the 3 -month period. In particular, the mean change from baseline in BSAI of lesional skin at Month 3 was -5.0%; the mean change from baseline in BSAI of total wound burden at Month 3 was -2.3%; the mean change from baseline in itch at Day 7 was -0.3 (1.2); and the mean change from baseline in pain assessment at Day 7 was -0.6 (3.1) for patients treated with SD-005.

[0188] Treatment with SD-005 was generally well tolerated. Approximately 70% of patients experienced an adverse event (AE), within only about 21.8% experiencing treatment-related AEs (Table 2). About 9.2% of the patients experienced a serious AE, and only three subjects withdrew from the study due to an AE (Table 2). Table 2: Adverse Events

AE=adverse event. 'Defined as an AE that began or changed in severity or relationship to treatment on or after the date of the first dose of study medication. ^*One case of a non- treatment-related death occurred on Day 62 after initiation of treatment due to cardiac disorders and cardiopulmonary failure.

[0189] These results show that treatment of EB patients (including patients less than 2 years old or patients 18 years old or older) with the SD-005 reduces target lesion size in a greater proportion of subjects, to a greater extent, and in less time than other tested compositions.

Claims

WHAT IS CLAIMED IS:

1. A method of treating or reducing the incidence of a skin lesion in a subject in need

thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin.

2. A method of reducing the size of a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin.

3. A method of reducing the total burden of skin lesions in a subject in need thereof

comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin.

4. A method of accelerating closure of a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition comprising or consisting essentially of an emollient, an emulsifier, a pH modifier, a viscosity agent, a solubilizing agent, a preservative, a chelating agent, and an antioxidant; wherein the composition comprises less than 0.5% allantoin.

5. The method of any one of claims 1 to 4, wherein the composition does not comprise allantoin.

6. A method of treating a skin lesion in a subject in need thereof comprising: topically administering, at least once daily, to a skin area affected by the lesion a composition, wherein the composition consists essentially of:

(a) about 40% to about 90% water;

(b) about 8% to about 30% an emollient;

(c) about 1% to about 15% an emulsifier;

(d) about 0.01% to about 1% a pH modifier;

(e) about 1% to about 10% a viscosity agent;

(f) about 1% to about 20% a solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof;

(g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof;

(h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and

(i) about 0.01% to about 3.0% a preservative.

7. The method of any one of claims 1 to 5, wherein the composition comprises:

(a) about 40% to about 90% water;

(b) about 8% to about 30% an emollient;

(c) about 1% to about 15% an emulsifier;

(d) about 0.01% to about 1% a pH modifier;

(e) about 1% to about 10% a viscosity agent;

(g) about 0.01% to about 2% a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof; (h) about 0.001% to about 3% an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and

(i) about 0.01% to about 3.0% a preservative.

8. The method of any one of claims 1 to 7, wherein the composition comprises:

(a) about 40% to about 90% water;

(f) about 1% to about 20% solubilizing agent selected from the group consisting of propylene glycol, glycerin, and a combination thereof;

(g) about 0.01% to about 2% chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, dihydroxyethyl glycine, ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, and a combination thereof;

(h) 0.01% to about 1% antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, ascorbir stearate, butyl hydroxyanisole, and gallic esters; and

9 The method of any one of claims 1 to 8, wherein the composition comprises:

(a) about 40% to about 90% water;

(b) about 1% to about 6% cetyl alcohol; (c) about 1% to about 4% stearyl alcohol;

(d) about 1.5% to about 3% beeswax;

(e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution;

(f) about 0.05% to about 0.2% citric acid;

(g) about 5% to about 15% lanolin oil;

(h) about 2% to about 8% propylene glycol;

(i) about 0.05% to about 0.5% tetrasodium EDTA;

(j) about 0.05% to about 5% cod liver oil;

(k) about 0.05% to about 1% butylated hydroxytoluene;

(l) about 0.05% to about 0.5% methylparaben; and

(m) about 0.05% to about 0.5% propylparaben.

10. The method of any one of claims 1 to 9, wherein the composition comprises:

(a) about 42% to about 80% water;

(b) about 2% to about 6% cetyl alcohol;

(c) about 1% to about 3% stearyl alcohol;

(d) about 1.5% to about 3% beeswax;

(e) about 1.5% to about 3% sodium lauryl sulfate in a 30% solution;

(f) about 0.06% to about 0.1% citric acid;

(g) about 5% to about 15% lanolin oil;

(h) about 2% to about 8% propylene glycol;

(i) about 0.05% to about 0.35% tetrasodium EDTA;

(j) about 0.05% to about 5% cod liver oil;

(k) about 0.05% to about 1% butylated hydroxytoluene;

(l) about 0.05% to about 0.5% methylparaben; and

(m) about 0.05% to about 0.5% propylparaben.

11. The method of any one of claims 1 to 10, wherein the composition comprises:

(a) about 69.16% water;

(b) about 5% cetyl alcohol;

(c) about 2.45% stearyl alcohol;

(d) about 1.9% beeswax; (e) about 1.9% sodium lauryl sulfate in a 30% solution;

(f) about 0.09% citric acid;

(g) about 10.6% lanolin oil;

(h) about 5.7% propylene glycol;

(i) about 0.15% tetrasodium EDTA;

(j) about 2% cod liver oil;

(k) about 0.5% butylated hydroxytoluene;

(l) about 0.3% methylparaben; and

(m) about 0.25% propylparaben.

12. The method of any one of claims 1 to 11, wherein the composition further comprises a fragrance.

13. The method of any one of claims 1 to 12, further comprising applying to the skin area affected by the lesion a dressing that covers the lesion.

14. The method of claim 13, wherein the dressing is applied to the lesion less than 30 minutes after the composition is applied.

15. The method of any one of claims 1 to 14, where the skin is washed prior to administration of the composition.

16. The method of any one of claims 1 to 15, wherein necrotic tissue is removed from the skin prior to administration of the composition.

17. The method of any of claims 1 to 16, wherein the administration of the composition is done using clean hands, a clean gloved hand, a clean cloth or clean sponge.

18. The method of any of one of claims 1 to 17, wherein a previous dressing is removed

before administering the composition.

19. The method of claim 18, where the previous dressing is removed using a silicone medical adhesive remover (SMAR).

20. The method of any one of claims 13 to 19, wherein the dressing is a non-adhesive.

21. The method of any of claims 13 to 20, wherein the dressing is selected from the group consisting of a bandage, a gauze, a mesh, a tubular bandage, a cohesive bandage, a soft silicone tape, hydrogel, a sheet hydrogel, a hydrogel impregnated gauze, a biosynthetic cellulose, a bordered dressing, a powder, a lipido-colloid, a soft silicone, a soft silicone mesh, a polymeric membrane, a foam, a soft silicone foam, a soft silicone foam with super-absorbers, a super absorbent dressing, emu oil, restore dimethicreme, white petroleum, and any combination thereof.

22. The method of any of claims 13 to 21, wherein the dressing is loosely applied.

23. The method of any of claims 13 to 22, wherein the dressing is administered to a single lesion.

24. The method of any of claims 12 to 23, wherein the dressing is applied to an area of skin comprising the lesion.

25. The method of any of claims 1 to 24, wherein the subject is bathed prior to administration of the composition in a water comprising bleach, salt (e.g., 0.9% NaCl), vinegar, or chlorhexidine.

26. The method of any of claims 1 to 25, wherein the subject is bathed in a whirlpool bath prior to administration of the composition.

27. The method of any of claims 13 to 20, wherein the lesion comprises a blister, and wherein the blister is lanced prior to administration of the composition.

28. The method of claim 27, wherein the blister is lanced by inserting a needle into the blister, or by cutting a hole in the blister.

29. The method of claim 27 or 28, wherein the blister comprises a roof, and the roof of the blister is not removed.

30. The method of any one of claims 27 to 29, wherein the blister is compressed to expel fluid present in the blister.

31. The method of any one of claims 27 to 30, wherein the blister is dried before

administration of the composition.

32. The method of claim 31, where a dry powder is used to dry the blister.

33. The method of any one of claims 27 to 30, wherein the composition is administered while the blister is still wet.

34. The method of any of claims 1 to 33, comprising administering the composition to the skin using a circular motion, a motion parallel to the axis of the body, a motion perpendicular to the axis of the body, a blotting technique, or any combination thereof.

35. The method of any of claims 1 to 34, wherein the lesion comprises a center and a

perimeter, and wherein the composition is applied to the center of the lesion and then spread outward to the perimeter of the lesion or wherein the composition is applied to the perimeter of the lesion and then spread inward toward the center of the lesion.

36. The method of any of claims 1 to 35, wherein the composition is applied to the skin as a layer, wherein the layer is at least about 0.1 mm thick.

37. The method of claim 36, wherein the layer is about 0.1 mm to about 2 mm thick.

38. The method of claim 36 or 37, wherein the layer is about 0.1 mm to about 1.5 mm thick, about 0.1 mm to about 1 mm thick, about 0.1 mm to about 0.9 mm thick, about 0.1 mm to about 0.8 mm thick, about 0.1 mm to about 0.7 mm thick, about 0.1 mm to about 0.6 mm thick, about 0.1 mm to about 0.5 mm thick, about 0.1 mm to about 0.4 mm thick, about

0.1 mm to about 0.3 mm thick, or about 0.1 mm to about 0.2 mm thick.

39. The method of any one of claims 36 to 38, wherein the layer is about 0.1 mm thick, about 0.2 mm thick, about 0.3 mm thick, about 0.4 mm thick, about 0.5 mm thick, about 0.6 mm thick, about 0.7 mm thick, about 0.8 mm thick, about 0.9 mm thick, about 1 mm thick, about 1.1 mm thick, about 1.2 mm thick, about 1.3 mm thick, about 1.4 mm thick, about 1.5 mm thick, about 1.6 mm thick, about 1.7 mm thick, about 1.8 mm thick, about

1.9 mm thick, or about 2 mm thick.

40. The method of any of claims 1 to 39, wherein about 0.1 mL to about 2 mL of the

composition is applied per 1 cm² of the skin.

41. The method of any of claims 1 to 40, wherein about 0.1 mL to about 1.5 mm thick, about 0.1 mL to about 1 mL, about 0.1 mL to about 0.9 mL, about 0.1 mL to about 0.8 mL, about 0.1 mL to about 0.7 mL, about 0.1 mL to about 0.6 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 0.4 mL, about 0.1 mL to about 0.3 mL, or about 0.1 mL to about 0.2 mL of the composition is applied per 1 cm² of the skin.

42. The method of any of claims 1 to 41, wherein about 0.1 mL to about 2 mL of the

composition is applied per 1 cm² of the skin.

43. The method of any of claims 1 to 42, wherein a pea-sized amount of the composition is applied to the lesion.

44. The method of any of claims 1 to 43, wherein the composition is applied to at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or all exposed skin of the subject.

45. The method of any of claims 1 to 44, wherein the composition is applied to at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or all skin of the subject.

46. The method of any of claims 1 to 45, wherein the composition is applied 1 time per day.

47. The method of any of claims 1 to 46, wherein the composition is applied 1 time per day, 2 times per day, or 3 times per day.

48. The method of any of claims 1 to 47, wherein the composition is applied to a lesion

greater than 1 time per day.

49. The method of any of claims 13 to 48, wherein the dressing is applied 1 time per day.

50. The method of any of claims 13 to 49, wherein the dressing is applied 1 time per day, 2 times per day, or 3 times per day.

51. The method of any of claims 13 to 50, wherein the dressing is applied to a lesion greater than 1 time per day.

52. The method of any of claims 1 to 51, wherein the lesion is at least about 1, 2, 3, 4, 5, 6, or 7 days old.

53. The method of any of claims 1 to 52, wherein the lesion is greater than one week, two weeks, three weeks, or 1 month old.

54. The method of any of claims 1 to 53, wherein the subject has a total lesion burden of at least about 1, 5, 10, 15, 20, 25, 30, 40, or 50%.

55. The method of claim 54, wherein the subject has a total lesion burden of at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50%.

56. The method of any of claims 1 to 55, wherein the composition is at room temperature, below room temperature, or above room temperature when applied to the skin.

57. The method of any of claims 1 to 56, wherein the composition is applied at the beginning of the day, at the end of the day, or once at the beginning of the day and once at the end of the day.

58. The method of any one of claims 1 to 57, wherein the subject suffers from epidermolysis bullosa (EB).

59. The method of any one of claims 1 to 58, wherein the administration of the composition reduces itching associated with the skin lesion in the subject in need thereof.

60. The method of any one of claims 1 to 59, wherein the administration of the composition reduces pain associated with the skin lesion in the subject in need thereof.

61. The method of any one of claims 1 to 60, wherein the subject is at least 18 years old.

62. The method of any one of claims 13 to 61, wherein the dressing is applied within 30

minutes or within 60 minutes of the composition.

63. The method of any one of claims 1 to 62, wherein the administration of the composition reduces the size of the lesion by at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% relative to the size of the lesion prior to the administration of the composition.

64. The method of any one of claims 1 to 63, wherein the administration of the composition reduces the size of the lesion within about 2 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 14 weeks, about 16 weeks, or about 18 weeks after the initial administration of the composition relative to the size of the lesion prior to the administration of the composition.

65. The method of any one of claims 1 to 64, wherein the administration of the composition reduces the total number of legions on the subject by at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% relative to the total number of legions on the subject prior to the administration.

66. The method of any one of claims 1 to 60 and 63 to 65, wherein the subject is less than 2 years old.

67. The method of claim 66, wherein the subject is at least 1 month old to less than 2 years old.

68. The method of any one of claims 1 to 67, wherein the subject has a BSAI score of less than about 5%.

69. The method of any one of claims 1 to 68, wherein the lesion is about 30 days old or less.

70. The method of any one of claims 1 to 69, wherein administration of the composition

induces complete lesion closure of the lesion in less than about 1 week, in less than about 2 weeks, in less than about 3 weeks, in less than about 4 weeks, in less than about 5 weeks, in less than about 6 weeks, in less than about 7 weeks, in less than about 8 weeks, in less than about 9 weeks, in less than about 10 weeks, in less than about 11 weeks, in less than about 12 weeks, in less than about 13 weeks, in less than about 14 weeks, in less than about 15 weeks, in less than about 16 weeks, in less than about 17 weeks, in less than about 18 weeks, in less than about 19 weeks, in less than about 20 weeks, or in less than about 21 weeks.

71. The method of any one of claims 1 to 69, wherein administration of the composition induces complete lesion closure of the lesion in less than about 1 month, less than about 2 months, less than about 3 months, less than about 4 months, less than about 5 months, or less than about 6 months.

72. The method of claim 70 or 71, wherein the complete lesion closure is in at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, or at least about 85% of the lesions.