WO2025059166A1 - Compositions and methods for treating skin inflammation - Google Patents

Abstract

Disclosed herein are topical compositions and methods for treating skin inflammation, caused by injuries such as from insect bites and stings, exposure to a plant of the genus Toxicodendron, contact dermatitis, and the like. The disclosed topical compositions consist essentially of a surfactant combination comprising polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol or a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer. Methods for treating conditions, such as skin inflammation and associated symptoms, include topical administration of the disclosed composition.

Description

COMPOSITIONS AND METHODS FOR TREATING SKIN INFLAMMATION

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/581,859, filed on September 11, 2023.

FIELD OF THE INVENTION

[0002] The present disclosure relates to compositions and methods for treating skin inflammation.

BACKGROUND OF THE INVENTION

[0003] The skin is the body’s largest organ and functions as an external protection system. This external protective system is at risk for many potential sources of insult and ultimate injury. Examples of various insults and injuries affecting the skin include allergies such as contact dermatitis, rashes such as from poison ivy, insect or bug bites and stings, skin cancer, lesions, wounds, burns, and scars. The body’s immune system is often activated at the site of the injury. [0004] A key attribute of the skin is its ability to protect the body from infectious and other foreign agents, such as, for example but not limited to, poison ivy and insect or bug bites and stings. Skin inflammation symptoms, including itching, redness, swelling, etc., often result as part of the inflammatory response at the site of the insult or injury. These symptoms can vary in severity and by individual but are generally uncomfortable for a significant period of time.

[0005] Rashes from poison ivy exposure are one example of a skin inflammatory symptom or reaction. The poison ivy plant and its relatives, common throughout the United States and other parts of the world, all contain the toxic chemical compound urushiol. Urushiol causes allergic dermatitis in as many as 85% of people. The most commonly encountered species in the United States are of the genus Toxicodendron which comprises poison ivy (T. radicans), poison oak (T. toxicarium), and poison sumac (T. vernix), however examples are also present throughout the world. The American Academy of Dermatology estimates that there are up to 50 million cases of contact dermatitis of urushiol origin in the United States alone. Although the global urushiol induced contact dermatitis cases are unknown, experts estimate that the incidence is likely similar to that of the United States.

[0006] Urushiol is an oleoresin having a mixture of catechol oils with multiple alkyl carbon chains of varying length. Urushiol is a colorless oil when contained within an undisturbed leaf but upon exposure to oxygen, such as when a leaf is broken, it quickly oxidizes and polymerizes to a black insoluble lacquer. Upon exposure, urushiol oil penetrates the stratum comeum of the epidermal skin layer and binds to Langerhans cells. These cells then travel to the lymph nodes where T-Cells enlist multiple cytokines and macrophages that come back to the site of exposure and cause irritation, redness, itching & swelling.

[0007] Following exposure to urushiol, the molecule begins to penetrate the skin within minutes and is completely bound to the skin after about 2-6 hours. This binding results in the clinical manifestation of skin inflammation, including redness and rash occurring within 48 hours. As the irritation persists, redness and swelling are accompanied by additional symptoms of blistering and severe itching. The rash typically reaches its peak within 5 days and may take 2 or more weeks to resolve entirely. Although poison ivy rash may appear in new locations throughout progression, the rash does not “spread” via scratching or from the fluid excreted from the blisters. Additionally, urushiol can remain active on clothing, shoes and tools for up to five years so secondary cases are common.

[0008] Historically, treatment has consisted of immediately washing with soap & water, alcohol or other cleanser after exposure. Unfortunately, many patients are either not able to wash immediately or are not aware of the exposure until many hours or days later. Some poison ivy products rely on harsh solvents or combinations of surfactants/polymers. Currently, there are both prophylactic as well as post-exposure treatments. For example, U.S. Patent No. 4,663,151 to Waali is directed to a prophylactic treatment based upon aluminum chlorohydrate.

Unfortunately, this treatment must be administered prior to exposure to urushiol and has limited success in preventing a reaction. Post-exposure treatments include, for example, Tec-Nu® outdoor skin cleaner manufactured by Tec Laboratories, Inc., and Zanfel ® wash by Zanfel Laboratories, Inc. Tec-Nu skin cleanser relies on the surfactant octylphenoxy-polyethoxyethanol (Triton X-100) and mineral spirits to treat allergic dermatitis resulting from urushiol exposure. The bulky octyl groups may not be able to completely surround the non-polar groups in urushiol and therefore it is not completely efficacious in removing and neutralizing urushiol. Additionally, octylphenoxy-polyethoxyethanol degrades into a product with hormone-like activity and therefore is ccotoxic to the environment. Zanfcl wash utilizes similar ingredients to those found in industrial detergents, i.e., the surfactants 26-(nonylphenoxy)- 3,6,9,12,15,18,21,24-octaoxahexacosan-l-ol (nonoxynol-9), sodium lauroyl sarcosinate (SLS) and C12-15 pareth-9. See, for example, U.S. Patents 6,423,746 and 7,008,963. Similar to Triton X-100, the surfactants used in Zanfel suffer similar steric hindrance from the bulky octyl and long chain carbon groups. These surfactants also have high critical micelle concentrations. Thus, there is a need for improved formulations that bind and inactivate urushiol to treat the resultant skin inflammation symptoms caused by the allergic dermatitis reaction.

[0009] In another example, insect bites create localized pruritic dermatitis reactions that usually result in a raised, itchy “bump” or wheal at the site of the bite, i.e. skin inflammation symptoms. The inflammatory reaction after a mosquito bite, for example, is believed to be driven largely from toxins located in their saliva. Whereas other biting insects leave stingers, fangs, and venom in the skin of victims. A typical skin inflammatory reaction following an insect bite stalls with the formation of a pruritic wheal around the bite, peaking at around 24 hours. If more bites from the same species occur, they develop an immediate reaction, peaking at 30 minutes. This is species-specific due to varying antigens in the insect’s saliva. Available treatments for insect bite symptoms include anti-inflammatory steroids, allergy reducing antihistamines, cold packs, and calamine which only cools the area. These products have variable efficacy.

[0010] Due to the significantly large number of skin inflammatory cases, especially those caused by exposure to plants in the Toxicodendron family and insect bites, and limited available treatments that work safely, quickly, and effectively, there is a need for new treatments.

SUMMARY OF THE INVENTION

[0011] This disclosure is based, at least in part, on at least the following surprising findings:

(1) a topical composition consisting essentially of a surfactant combination of polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol or a polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft co-polymer can treat conditions, such as skin inflammation.

(2) The composition works safely, quickly and effectively.

(3) The composition is economical and readily available. [0011] Thus, this disclosure provides a novel composition and method for treating skin inflammation and associated symptoms.

[0012] In a first aspect, the disclosure features a topical composition consisting essentially of a surfactant combination of polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol or a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer. The surfactant combination or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer is about 0.2 to about 15.0 percent (w/w) of the total composition. The composition may also include at least one of a solvent, an absorbent, a gelling agent, an abrasive, and a preservative. Example components include, for example, water, bentonite, disodium ethylenediaminetetraacetic acid (EDTA), glycerin, sodium lauroyl sarcosinate, carbomer, phenoxyethanol, ethylhexylglycerin, triethanolamine, jojoba esters, or sodium bicarbonate. [0013] In one aspect there is provided a topical composition including about 7 to about 8% (w/w) of the surfactant combination or the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer. The composition may also include about 76 to 77 percent of water, about 3 percent bentonite, about 0.05 to 1 percent of disodium EDTA, about 3 percent of glycerin, about 0.1 to 1 percent of sodium lauroyl sarcosinate, about 0.1 to 1 percent of acrylates/c 10-30 alkyl acrylate crosspolymer- U21, about 0.5 to 1 percent of phenoxyethanol, about 0.05 to 1 percent of ethylhexylglycerin, about 0.1 to 1 percent of triethanolamine, and about 8 percent of jojoba esters. Alternatively, the composition may include about 78 to 80 percent of water, about 3 percent bentonite, about 0.05 to 1 percent of disodium EDTA, about 3 percent of glycerin, about 0.1 to 1 percent of sodium lauroyl sarcosinate, about 0.1 to 1 percent of acrylates/c 10-30 alkyl acrylate crosspolymer- U21, about 0.5 to 1 percent of phenoxyethanol, about 0.05 to 1 percent of ethylhexylglycerin, about 0.1 to 1 percent of triethanolamine, and about 5 percent of sodium bicarbonate. Percentages are (w/w) based on the total composition.

[0014] In a second aspect, the disclosure features a method for treating skin inflammation by administering to a subject suffering from skin inflammation or an associated symptom a composition consisting essentially of a surfactant combination of polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol or a polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft co-polymer. The inflammatory skin condition may be caused, for example, by an insect bite or sting or by exposure to a plant of the genus Toxicodendron. [0015] In one aspect there is provided use of a topical composition as described in the first aspects in the manufacture of a medicament for treating skin inflammation and associated symptoms.

[0016] In one aspect there is provided a topical composition as described in the first aspects for treatment of skin inflammation and associated symptoms.

[0017] In one aspect there is provided use of a topical composition as described in the first aspects for treatment of skin inflammation and associated symptoms.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figs. 1A-F are photographs showing progression of a skin inflammatory reaction, or lesion, caused by poison ivy. Fig. 1A shows the lesion at 6:14pm before treatment at 6:15pm. Figs. IB- IF shows the lesion post-treatment at 6:25pm, e.g. after about 10 minutes (IB), at 6:26pm, e.g. after about 11 minutes (1C), 6:41pm, e.g. after about 26 minutes (ID), 6:52pm, e.g. after about 37 minutes (IE), and at 7:33pm, e.g. after about 78 minutes (IF).

DETAILED DESCRIPTION OF THE INVENTION

[0019] The present disclosure relates to compositions and methods for treating skin inflammatory conditions. Various aspects will be described more fully hereinafter. Such aspects may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey its scope to those skilled in the art.

[0020] The term “condition” is used in this disclosure to mean, and is used interchangeably with, the terms skin inflammation, disease, disorder, injury, or illness, unless otherwise indicated. Conditions may be caused by, for example but not limited to, contact dermatitis, insect bites (also commonly known as bug bites) and stings, including mosquitos, ticks, flies, bed bugs, mites, lice, arachnids, etc., and contact with plants from the genus Toxicodendron, including poison ivy, poison oak, and poison sumac. Other examples include stings, such as from bees, jellyfish, and sea urchins. Contact dermatitis may be caused by allergens or direct contact with substances, such as cosmetics, fragrances, jewelry, plants, etc. Signs and symptoms of skin inflammation include, for example but not limited to, rash, red patches, blisters, abscess, stinging, burning, swelling, and/or itching. [0021] As used herein, the terms “treat,” “treating,” “treatment” and variations thereof refer to partially or completely alleviating, inhibiting, ameliorating, reducing, or relieving the disease or condition and/or symptoms thereof (e.g., skin inflammation, including, without limitation, wheal, itching, swelling, redness, blisters, abscess, rash, etc.) from which the subject is suffering. This can include reversing, reducing, or arresting the symptoms, clinical signs, and underlying pathology of a condition in a manner to improve or stabilize a subject’s condition. The response to treatment using the disclosed methods is evaluated by a number of parameters known in the art and described below.

[0022] The results of treatment with the methods of the present disclosure may be evaluated or determined by any method known to those skilled in the art, including, but not limited to, imaging and physical examination. Results may include enhancing the texture, appearance, color, sensation, hydration, or reduction of fluid discharge from the affected area of the tissue in a subject relative to a subject not receiving the compound or composition.

[0023] As used herein, “composition” and “formulation” are interchangeable and refer to any chemical or biological composition, material, agent, or the like that is capable of inducing a therapeutic effect when properly administered to a subject.

[0024] The terms “effective amount” and “therapeutically effective amount” are used interchangeably in this disclosure and refer to an amount of a composition that, when administered to a subject, is capable of reducing a symptom of a condition in a subject or enhance the texture, appearance, color, sensation, or hydration of the intended tissue treatment area. The actual amount which comprises the “effective amount” or “therapeutically effective amount” will vary depending on a number of conditions including, but not limited to, the severity of the condition, the size and health of the patient, and the route of administration. A skilled medical practitioner can readily determine the appropriate amount using methods known in the medical arts.

[0025] The phrase “pharmaceutically acceptable” or “cosmetically acceptable” is employed herein to refer to those agents of interest, compounds, salts, compositions, dosage forms, etc., which are within the scope of sound medical judgment suitable for use in contact with the tissues of human beings and/or other mammals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. In some aspects, pharmaceutically acceptable means approved by a regulatory agency of the federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals (c.g. animals), and more particularly, in humans.

[0026] The term “salts” as used herein embraces pharmaceutically acceptable salts commonly used to form alkali metal salts of free acids and to form additional salts of free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable.

[0027] The term “patient” and “subject” are interchangeable and may be taken to mean any living organism which may be treated with compounds of the present invention. As such, the terms “patient” and “subject” may include, but is not limited to, any non-human mammal, primate, or human. In some embodiments, the patient or subject is an adult, child or infant. In some embodiments, the patient or subject is a human.

[0028] All percentages, parts and ratios are based upon the total weight of the topical compositions and all measurements made are at about 25 °C, unless otherwise specified.

[0029] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a “polymer” includes a single polymer as well as two or more of the same or different polymers; reference to an “excipient” includes a single excipient as well as two or more of the same or different excipients, and the like.

[0030] The word “about” when immediately preceding a numerical value means a range of plus or minus 10% of that value, e.g. “about 50” means 45 to 55, “about 25,000” means 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation. For example, in a list of numerical values such as “about 49, about 50, about 55,” “about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 52.5. Furthermore, the phrases “less than about” a value or “greater than about” a value should be understood in view of the definition of the term “about” provided herein.

[0031] The terms “administer,” “administering” or “administration” as used herein refer to directly administering or applying a compound (also referred to as an agent of interest) or a composition to the skin of a subject at the site of the condition.

[0032] For convenience, certain terms employed in the specification, examples and claims are collected here. Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0033] Embodiments of the present invention are described below. It is, however, expressly noted that the present invention is not limited to these embodiments, but rather the intention is that modifications that are apparent to the person skilled in the art and equivalents thereof are also included.

[0034] As noted above, urushiol is the broad term for the chemical substances found in the genus Toxicodendron such as poison ivy, oak, and sumac. Urushiol is a mix of phenolic compounds known as catechols that are benzylic compounds having varying side-chain lengths of 15 or 17 carbon atoms. The side chains also have varying degrees of saturation/unsaturation and may have 1-3 double bonds. The poison ivy and sumac plants contain primarily catechols of 15 carbons (pentadecylcatechols) whereas, poison oak contains mostly 17 carbon side-chains (heptadecylcatechols). Upon exposure to oxygen, urushiol readily oxidizes and polymerizes into a highly insoluble shellac-like substance that quickly binds to skin proteins.

[0035] The resulting reaction is a delayed hypersensitivity, allergic dermatitis reaction to urushiol. That is, the resultant skin inflammatory reaction does not present until many hours or even days later after exposure to the antigen, urushiol. After the antigen is metabolized and degraded, the resulting “pieces” are presented to T lymphocytes by antigen presenting cells such as Langerhan’s cells or macrophages. The T lymphocytes then release inflammatory signaling substances called cytokines that directly recruit white blood cells called monocytes that become macrophages. The cytokines activate the macrophages and they attack all cell types in the area causing massive tissue damage that is the hallmark of poison ivy rash.

[0036] Insect bites also create localized dermatitis reactions in sensitive people. Immediate skin inflammatory reactions are postulated, without limitation, to be due to IgE mediated type 1 reactions as they correlate with serum levels. When this IgE binds to insect saliva proteins, mast cells are triggered, causing a release of histamines and leukotrienes responsible for the wheal, itch, and warmth of immediate reactions.

[0037] In one embodiment the compositions and methods described herein are useful for removing urushiol from the skin, before or after a reaction to the urushiol has occurred, to thereby eliminate or reduce the irritant and treat the resulting skin inflammation and at least one of the associated symptoms, e.g. itching, redness, and/or wheal, etc., and allow the skin to heal. Similarly, the compositions and methods disclosed herein are useful for removing mosquito saliva or other insect venom from the skin following insect bites, to thereby treat the resultant skin inflammation. In an example embodiment, the skin inflammation symptom of itching is relieved.

[0038] Various embodiments include a composition containing a surfactant combination of polyethylene glycol, such as PEG 6000, vinyl caprolactam, and vinyl acetate as the active agent. In an alternative embodiment the composition may include a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer as the active agent. The surfactant combination or copolymer has the unique ability to form micelles around highly non-polar molecules, such as the catechol urushiol, and can be easily washed away in polar solvents, such as water. The surfactant combination or copolymer achieves the critical micelle concentration (CMC) at significantly lower concentrations than other surfactants as shown in Table 1. The critical micelle concentration is the concentration of surfactant, above which the surfactant molecules will completely wrap around (create micelles) the solute, for example urushiol, mosquito saliva, or other insect venom. The key feature of micelle formation is the ability of micelles to bind and completely envelop urushiol, for example, while simultaneously creating a water-soluble particle that can be washed away. The very low CMC of the surfactant combination or copolymer embodied herein (7.6 mg/L) is hypothesized without being limiting to result in more efficient inactivation and removal of irritants, such as urushiol, on the skin.

Table 1. Common Surfactant Critical Micelle Concentrations

[0039] In embodiments, the effective amount of polyethylene glycol in the surfactant combination is about 1% to about 90%, about 10% to about 80%, about 20% to about 70%, about 30% to about 60%, about 40% to about 50%, about 2% to about 20%, about 5% to about 15%, and about 12% to about 14%. In one embodiment the amount of polyethylene glycol is about 13% (w/w) of the total surfactant combination or copolymer.

[0040] In embodiments, the effective amount of polyvinyl caprolactam in the surfactant combination is about 1% to about 90%, about 10% to about 80%, about 20% to about 70%, about 30% to about 60%, about 40% to about 50%, about 40% to about 70% and about 50% to about 60%. In one embodiment the amount of polyvinyl caprolactam is about 57% (w/w) of the total surfactant combination or copolymer.

[0041] In embodiments, the effective amount of polyvinyl acetate in the surfactant combination is about 1% to about 90%, about 10% to about 80%, about 20% to about 70%, about 30% to about 60%, about 40% to about 50%, about 15% to about 40% and about 20% to about 40%. In one embodiment, the amount of polyvinyl acetate is about 30% (w/w) of the total surfactant composition or copolymer.

[0042] The surfactant combination of polyethylene glycol, vinyl caprolactam, and vinyl acetate or the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer is comprised of polar and non-polar moieties. The long hydrophilic and hydrophobic strands readily envelop compounds, such as urushiol, within the hydrophobic strands, yet easily attach to water molecules via the hydrophilic strands, allowing for efficient aqueous removal of agents, or irritants, that elicit an immune and/or inflammatory response, such as but not limited to urushiol oil, insect saliva, and insect venom.

[0043] In embodiments, the concentration of the surfactant combination or copolymer in the topical composition should not be less than 0.2% and can be as high as 15% w/w of the total composition. Given the low CMC of the surfactant combination or copolymer, amounts in excess of 2% are thought to be sufficient to fully form micelles around the irritants, for example urushiol, while accounting for dilution in wash water.

[0044] In one embodiment, bentonite, also known as bentonite clay, or a similar absorbent is included in the composition. The bentonite clay aids in absorption of irritants, for example but not limited to urushiol oil, insect saliva, insect venom, and blister fluid, allowing for drying of oozing rashes, blisters, abscesses, and other symptoms. [0045] In another embodiment, inert scrubbing agents, or abrasives, such as, for example but not limited to, perlite, polyethylene, pumice, jojoba, or bamboo may also be included in the composition. The weight percent of abrasive in the composition can be modulated to achieve the desired grittiness in the product. Abrasive ranges of about 3-10% w/w are reasonable. The addition of an inert abrasive/exfoliant agent may enhance the activity of the composition but is not required. The abrasive component provides mechanical agitation of the dead keratinocyte layer of the stratum corneum and therefore may allow for more thorough release of, and binding to, irritants, such as urushiol. Examples of abrasives include, but are not limited to, keratin pumice, perlite, jojoba esters, and polyethylene beads.

[0046] Other components of the composition may include a solvent, such as water, a gelling agent, and/or a preservative. A foam stabilizer, a thinning agent, and/or a buffer/pH adjuster, such as triethanolamine, may also be added to the composition. The composition may also include aloe, lanoline, and the like. Examples of preservatives include, without limitation, phenoxyethanol, ethylhexylglycerin, sodium phytate, ethylenediaminetetraacetic acid (EDTA). Examples of gelling agents include, without limitation, carbomers and acrylates, such as acrylates/c 10-30 alkyl acrylate crosspolymer-U21.

[0047] In one example embodiment, the composition includes perlite, polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft copolymer, carbomer, phenoxyethanol, and ethylhexylglycerin, ethylhexylglycerin, triethanolamine, sodium phytate, and water.

[0048] In another example embodiment, the composition includes polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft copolymer water, disodium EDTA, glycerin, sodium lauroyl sarcosinate, acrylates/c 10-30 alkyl acrylate crosspolymer-U21, phenoxyethanol, ethylhexylglycerin, bentonite, triethanolamine, and jojoba esters 40/60. This composition may be particularly useful for the treatment of conditions, such as skin inflammation and associated symptoms, such as rashes, for example rashes caused by poison ivy.

[0049] In yet another example embodiment, the composition includes polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft copolymer water, disodium EDTA, glycerin, sodium lauroyl sarcosinate, acrylates/c 10-30 alkyl acrylate crosspolymer-U21, phenoxyethanol, ethylhexylglycerin, bentonite, triethanolamine, and sodium bicarbonate. This composition may be particularly useful for the treatment of conditions, such as skin inflammation and associated symptoms caused by insect bites or stings. [0050] In embodiments, the composition is a topical formulation for treatment of conditions, such as skin inflammation. Example embodiments include, for example but not limited to, the treatment of conditions caused by urushiol induced allergic dermatitis and insect bites and stings. [0051] In additional embodiments, methods of treating conditions, such as skin inflammation, and associated symptoms in a subject are provided. Such methods include administering a therapeutically effective amount of the disclosed compositions to a subject in need thereof. Administration may include applying a composition onto the affected area, allowing the composition to remain for a period of time, and removing the composition from the affected area. The composition may also be rubbed into the skin at the affected site.

[0052] In an example embodiment, the composition is applied to the affected area of the skin and distributed evenly around, for example by a scrubbing or circular motion. The composition remains on the affected area for a period of time, such as from one to three minutes, depending on the severity of the reaction, the sensitivity of the individual and particular composition employed, and may then be washed away with water to remove the bound irritant, such as urushiol. For maximal effect, the initial application can be followed by multiple applications, for example a second and third application, waiting for a period of time, such as about 30 to 60 seconds in between applications. In the event that water is not available, the composition may be left on or wiped away with a towel or cloth. Clinical experience has shown that substantial relief of itching and visible inflammation usually occurs within minutes of administering the composition to the skin of the subject having the condition. If the reaction is systemic, subsequent applications may be required over a period of time, e.g. several days. In an example, the composition may be administered approximately every six to ten hours over approximately two to three days or until the condition is improved and/or symptom(s) are resolved. In another example, the product will be administered as needed based on reemergence of symptoms, such as, for example, itching.

[0053] The compositions described herein may be included in a kit, pack, or dispenser, referred to collectively herein as a “kit,” optionally with instructions for administration of such pharmaceutical compositions.

[0054] Optionally, additional compositions and/or components may be included in the kit. The kit may include one or more containers of a pharmaceutically acceptable carrier (e.g., sterile water or saline) suitable for reconstituting or diluting each pharmaceutical composition included in the kit. The compositions and carrier(s) may be housed in tubes or vials or other suitable containers such as syringes. Each composition may be in the form of a solution, a dry powder, a liquid, a suspension in a liquid, frozen, or in any other suitable form.

[0055] It is to be understood that the disclosed methods and compositions may assume various alternative variations and step sequences, except where expressly specified to the contrary. Moreover, other than in any operating examples, or where otherwise indicated, all numbers such as those expressing values, amounts, percentages, ranges, subranges and fractions may be read as if prefaced by the word “about”, even if the term does not expressly appear. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the results desired to be obtained by the disclosed methods. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Where a closed or open-ended numerical range is described herein, all numbers, values, amounts, percentages, subranges and fractions within or encompassed by the numerical range are to be considered as being specifically included in and belonging to the original disclosure of this application as if these numbers, values, amounts, percentages, subranges and fractions had been explicitly written out in their entirety.

[0056] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard variation found in their respective testing measurements.

[0057] As used herein, unless indicated otherwise, a plural term can encompass its singular counterpart and vice versa, unless indicated otherwise. For example, although reference is made herein to “a” composition, a combination (i.e., a plurality) of these components can be used. In addition, in this application, the use of “or” means “and/or” unless specifically stated otherwise, even though “and/or” may be explicitly used in certain instances.

[0058] As used herein, “including”, “containing” and like terms are understood in the context of this application to be synonymous with “comprising” and are therefore open-ended and do not exclude the presence of additional undescribed and/or unrecited elements, materials, ingredients and/or method steps.

[0059] As used herein, “consisting of’ is understood in the context of this application to exclude the presence of any unspecified element, ingredient and/or method step.

[0060] As used herein, “consisting essentially of’ is understood in the context of this application to include the specified elements, materials, ingredients and/or method steps and others that are unspecified, provided that the latter “do not materially affect the basic and novel characteristic(s)” of what is being described.

[0061] The compositions and methods are further supported by the information provided in the following Examples. It is to be understood that the embodiments described in the Examples are merely illustrative and are not intended to limit the scope of the present disclosure, which will be limited only by the appended claims.

EXAMPLES

[0062] The invention is further described in the following examples, which do not limit the scope of what is claimed.

[0063] Example 1: Figure 1 shows the progression of a poison ivy lesion, i.e. skin inflammatory reaction or condition, in one patient following application of the inventive composition. The reaction included symptoms of swelling, redness, blisters, oozing, and itching. Two to three days after exposure to poison ivy, the example formulation (I) shown in Table 2 was applied to the wetted lesion and rubbed in a circular motion for approximately 3 minutes. The product was then rinsed away, and photographs were taken at the intervals specified in Fig. 1A-F. In approximately 45 minutes after administration of formulation (I), the symptoms were remarkably improved and after approximately 1 hour the symptoms were surprisingly almost resolved. Poison ivy rashes typically take 2 to 3 weeks to resolve with self-care and at home remedies. Surprisingly, redness, swelling and inflammation of the lesion was reduced by 90% within approximately 45 minutes after treatment with formulation (I). Table 2: Example formulation (I).

[0064] Other results have shown in cases of contact dermatitis, bites, and stings, for example from insects, arachnids, etc., when used as directed, itching symptoms typically resolve within 10 minutes after administration of the composition. After this initial period, there is a continued reduction in redness and swelling. There is often a remarkable reduction in symptoms within an hour. The composition was applied as needed until symptoms were fully resolved.

[0065] Example 2: Another example formulation, formulation (II), is shown in Table 3. This formulation may be particularly useful for insect bites.

Table 3: Example formulation (II).

[0066] Example 3 : A subject reported having been stung by a bee on the dorsal portion of their foot. The skin inflammatory reaction resulted in a large swollen wheal surrounded by an erythemic red flare. The wheal remained itchy and swollen for multiple days prior to treatment. Formulation I was applied to the reaction site by rubbing in a circular motion for approximately 3 minutes, left on the reaction site, and allowed to dry. The subject reported experiencing dramatic itch relief for approximately 1 to 2 hours post application. Formulation I was reapplied approximately 4 to 5 times per day for two days until the itch symptom resolved entirely (data not shown).

[0067] Whereas particular features of the present invention have been described above for purposes of illustration, it will be evident to those skilled in the art that numerous variations of the details of the methods disclosed herein may be made without departing from the scope in the appended claims.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A topical composition consisting essentially of: a. a surfactant combination consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol; or b. a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer.

2. The topical composition of claim 1, further comprising at least one of a solvent, an absorbent, a gelling agent, an abrasive, and a preservative.

3. The topical composition of claim 1, further comprising at least one of water, bentonite clay, disodium ethylenediaminetetraacetic acid (EDTA), glycerin, sodium lauroyl sarcosinate, carbomer, phenoxyethanol, ethylhexylglycerin, triethanolamine, jojoba esters, and sodium bicarbonate.

4. The topical composition of claim 1, wherein the surfactant combination or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer is about 0.2 to about 15.0 percent (w/w) of the total composition.

5. The topical composition of claim 4, wherein the surfactant combination or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer is about 7 to about 8% (w/w) of the total composition.

6. The topical composition of claim 2, wherein the absorbent is bentonite.

7. The topical composition of claim 6, wherein the bentonite is about 3 percent (w/w) of the total composition.

8. The topical composition of claim 5, wherein the composition further comprises: about 76 to 77 percent (w/w) of water; about 3 percent (w/w) of bentonite; about 0.05 to 1 percent (w/w) of disodium EDTA; about 3 percent (w/w) of glycerin; about 0.1 to 1 percent (w/w) of sodium lauroyl sarcosinate; about 0.1 to 1 percent (w/w) of acrylates/c 10-30 alkyl acrylate crosspolymer- U21; about 0.5 to 1 percent (w/w) of phenoxyethanol; about 0.05 to 1 percent (w/w) of ethylhexylglycerin; about 0.1 to 1 percent (w/w) of triethanolamine; and about 8 percent (w/w) of jojoba esters.

9. The topical composition of claim 5, wherein the composition further comprises: about 78 to 80 percent (w/w) of water; about 3 percent (w/w) of bentonite; about 0.05 to 1 percent (w/w) of disodium EDTA; about 3 percent (w/w) of glycerin; about 0.1 to 1 percent (w/w) of sodium lauroyl sarcosinate; about 0.1 to 1 percent (w/w) of acrylates/c 10-30 alkyl acrylate crosspolymer- U21; about 0.5 to 1 percent (w/w) of phenoxyethanol; about 0.05 to 1 percent (w/w) of ethylhexylglycerin; about 0.1 to 1 percent (w/w) of triethanolamine; and about 5 percent (w/w) of sodium bicarbonate.

10. A method for treating skin inflammation, the method comprising administering to a subject suffering from skin inflammation or a symptom of skin inflammation a topical composition consisting essentially of: a surfactant combination of polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol; or a polyvinyl caprolactam-poly vinyl acetate-polyethylene glycol graft co-polymer, wherein the administration is by topical application at the site of the inflammation or symptom.

11 . The method of claim 10, wherein the skin inflammation is caused by an insect bite or sting.

12. The method of claim 10, wherein the skin inflammtion is caused by exposure to a plant of the genus Toxicodendron .

13. The method of claim 10, wherein the composition further comprises at least one of a solvent, an absorbent, a gelling agent, an abrasive, and a preservative.

14. The method of claim 10, wherein the composition further comprises at least one of water, bentonite, disodium EDTA, glycerin, sodium lauroyl sarcosinate, carbomer, phenoxyethanol, ethylhexylglycerin, triethanolamine, jojoba esters, and sodium bicarbonate.

15. The method of claim 10, wherein the surfactant combination or polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft co-polymer is about 0.2 to about 15.0 percent (w/w) of the total composition.

16. The method of claim 15, wherein the surfactant combination or polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft co-polymer is about 7 to about 8% (w/w) of the total composition.

17. The method of claim 13, wherein the absorbent is bentonite.

18. The method of claim 16, wherein the composition further comprises: about 76 to 77 percent (w/w) of water; about 3 percent (w/w) of bentonite; about 0.05 to 1 percent (w/w) of disodium EDTA; about 3 percent (w/w) of glycerin; about 0.1 to 1 percent (w/w) of sodium lauroyl sarcosinate; about 0.1 to 1 percent (w/w) of acrylates/c 10-30 alkyl acrylate crosspolymer- U21; about 0.5 to 1 percent (w/w) of phenoxyethanol; about 0.05 to 1 percent (w/w) of ethylhexylglycerin; about 0.1 to 1 percent (w/w) of triethanolamine; and about 8 percent (w/w) of jojoba esters.

19. The method of claim 16, wherein the composition further comprises: about 78 to 80 percent (w/w) of water; about 3 percent (w/w) of bentonite; about 0.05 to 1 percent (w/w) of disodium EDTA; about 3 percent (w/w) of glycerin; about 0.1 to 1 percent (w/w) of sodium lauroyl sarcosinate; about 0.1 to 1 percent (w/w) of acrylates/c 10-30 alkyl acrylate crosspolymer- U21; about 0.5 to 1 percent (w/w) of phenoxyethanol; about 0.05 to 1 percent (w/w) of ethylhexylglycerin; about 0.1 to 1 percent (w/w) of triethanolamine; and about 5 percent (w/w) of sodium bicarbonate.

20. The method of claim 10, wherein the administration is by rubbing.