US 20080286299A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0286299 A1 Battaglia (43) Pub. Date: Nov. 20, 2008

(54) FILM-FORMING RESINS ASA CARRIER (60) Provisional application No. 60/734,608, filed on Nov. FOR TOPCAL APPLICATION OF 7, 2005, provisional application No. 60/517,319, filed PHARMACOLOGICALLY ACTIVE AGENTS on Nov. 3, 2003. Publication Classification (75) Inventor: Alex Battaglia, La Jolla, CA (US) (51) Int. Cl. A636/00 (2006.01) Correspondence Address: A6IP 700 (2006.01) DLA PPER US LLP A6IP3L/00 (2006.01) 4365 EXECUTIVE DRIVE, SUITE 1100 (52) U.S. Cl...... 424/195.18 SAN DIEGO, CA 92.121-2133 (US) (57) ABSTRACT (73) Assignee: JALEVA, LLC, San Diego, CA The invention provides a biological dressing for treatment of (US) a dermatological disease comprised of one or more resins or other film-forming agents, a topically acceptable Volatile sol (21) Appl. No.: 12/182,372 vent, and a pharmacologically active agent. The combined one or more resins are present in a Suitable amount Such that (22) Filed: Jul. 30, 2008 the composition, when the solvent evaporates, will dry to form a solid coating that Sticks to the skin, nail or mucosal membrane to which the composition is applied, and maintain Related U.S. Application Data the pharmacologically active agent over a Sustained period of (63) Continuation of application No. 12/091,043, filed on time in contact with sites on the skin or mucosal membranes Jul. 28, 2008, filed as application No. PCT/US2006/ exhibiting symptoms of the disease. Methods are provided for 043572 on Nov. 7, 2006, Continuation of application treating symptoms of dermatological diseases with Such a No. 10/754,430, filed on Jan. 9, 2004. pharmacological composition. Toe Nail Fungus In Vitro - Franz Cell initial Results Ciclopirox Penetration

O6 0.4

O Epidermis Patent Application Publication US 2008/0286299 A1

Patent Application Publication Nov. 20, 2008 Sheet 2 of 2 US 2008/0286299 A1

US 2008/0286299 A1 Nov. 20, 2008

FILM-FORMING RESINSASA CARRIER decreases the necessary time for the treatment. It is preferably FOR TOPCAL APPLICATION OF associated with less waste and lower cost, and ultimately PHARMACOLOGICALLY ACTIVE AGENTS leads to improved treatment of patient symptoms and increased patient satisfaction. CROSS REFERENCE TO RELATED APPLICATION(S) 0008. In medicine, tincture of benzoin and mastic gum (Mastisol) have been employed to form a sticky coating on 0001. This application is a continuation of co-pending skin prior to the placement of adhesive preparations. Tincture U.S. Ser. No. 12/091,043, filed Apr. 21, 2008, which is a 35 of benzoin has also been used to form a biologic dressing over U.S.C. S 371 National Stage application of International Superficial cutaneous wounds as well as aphthous ulcers (can Application No. PCT/US2006/043572, filed Nov. 7, 2006; which claims the benefit under 35 U.S.C. S 119(e) to U.S. ker Sores). However, the general use of resins, such as mastic Application Ser. No. 60/734,608, filed Nov. 7, 2005, now and benzoin gum, as semi-permanently applied carriers for abandoned. Additionally, this application is a continuation of increasing the efficacy and usefulness of topological of phar co-pending U.S. Ser. No. 10/754,430, filed Jan. 9, 2004, macological agents has not been disclosed. A tincture of which claims the benefit under 35 U.S.C. S 119(e) to U.S. benzoin has been used with podophyllin resin (10-25%) in the Application Ser. No. 60/517,319, filed Nov. 3, 2003, now treatment of genital warts. It is considered by many to be abandoned. The disclosures of each of the prior applications cumbersome and inconvenient (see U.S. Pat. Nos. 5,063,065 are considered part of and are incorporated by reference in the and 5,167,649). Unfortunately, podophyllin resin is toxic, disclosure of this application. and even when applied in a tincture of benzoin, this agent must be removed by rigorous washing 1 to 6 hours post BACKGROUND OF THE INVENTION application. Due to the problems associated with using podo 0002 1. Field of the Invention phyllin resin in tincture of benzoin, other carriers have been 0003. The invention relates to resin or other film-forming sought. As an example, in the treatment of genital warts, Goh, agent based biological dressings that adhere to the skin and et al. (Singapore Med J (1998) 39:17-19) reports that podo contain one or more pharmacologically active agents for the phyllin prepared in 0.25% ethanol can be self-applied and is treatment of symptoms relating to dermatological diseases as efficacious as podophyllin prepared in tincture of benzoin and those affecting mucous membranes. The invention is exemplified by biological dressings comprising tincture of and applied in the clinic. Use of tincture of benzoin as a benzoin and clotrimazole for the treatment of athlete's foot biological bandage with compounds that it is desirable to and by biological dressings comprising mastic and ciclopiroX have in long contact with the skin has not been reported. for onychomycosis. 0004 2. Background Information SUMMARY OF THE INVENTION 0005 For many forms of dermatological conditions, the powders, sprays, Solutions, lotions and creams available over 0009 Compositions and methods are provided for the-counter lack effectiveness. The reason for this varies, increasing the effectiveness of treatment of dermatological from poor delivery of the medication to the source or cause of disorders on the skin or a mucous membrane of a mammal by the condition, to loss of the medication through abrasion from using a resin or other film-forming agent as a carrier for a normal activity of the patient, to absorption of medications pharmacologically active agent. The pharmacological com applied to the skin by the patient's socks or clothes. For these various reasons, currently available commercial medications positions are comprised of one or more resins or other film are prone to come offeasily once applied to the affected area, forming agents, at least one topically acceptable pharmaco and consequently much of the medication is wasted, either logically active agent for treatment of a dermatological through over application in an attempt to anticipate the prob disorder other than the resins or other film-forming agents, lem, or in medicine quickly being dispersed away from the wherein the active agent is non-toxic to the mammal being site. The medications for these conditions typically require at treated when left in contact with the lesion of interest for least 2 to 4 weeks of continuous treatment, and thus often fail greater than four hours, and a topically acceptable Volatile due to this poor delivery. Solvent. The compositions optionally can include a penetra 0006. A further problem with the use of existent medica tion enhancer. The methods of treating symptoms of a der tions is the lack of compliance by patients. Due to the mess matological disorder include the steps of contacting affected and difficulty of use, patients will often use these over the counter medications only until their symptoms abate and then sites on the skin or nails of a patient in need thereof with the they will stop the medication, before the recommended pharmacological composition comprised of one or more res course of treatment is completed, and hence often before the ins or other film-forming agents, a pharmacological agent or infection has truly cleared. Though momentarily abated, the agents, and an evaporative solvent, and allowing it to dry to infection then begins to take hold again, and in a matter of form a resin-based biological dressing. The biological dress days or weeks a full blown infection occurs again. In many ing comprises a sticky film of the one or more resins or other cases the patient will repeat using the over the counter medi agents which form a film on the skin and a pharmacologically cation until the symptoms clear, and again stop the medica active agent; the latter remains on the skin, nail or mucous tion with the first sign of abatement, with the whole cycle membrane after the volatile solvent has evaporated from the repeating. one or more resins or other film-forming composition. The 0007 Hence, there is a need for a clean and inexpensive dressing forms a hydrophobic, protective film that provides vehicle/carrier of topically applied medications that increases Sustained release of the pharmacologically active agent at the the convenience and effectiveness of the treatment and site of application. The invention finds use in the treatment of US 2008/0286299 A1 Nov. 20, 2008

dermatological disorders such as infection, inflammation, applied to a lesion needing treatment, and left in place for an and hyperproliferation of epidermal cells. extended period of time, without requiring conventional adhesive bandages. It is intended that the dressing need only BRIEF DESCRIPTION OF THE DRAWINGS be washed from the lesion for purposes of convenience and cleanliness. The biological dressings of the Subject invention 0010 FIG. 1 is a graphical representation showing data are cleaner and easier to apply than conventional dressings from a skin penetration study of a composition of the inven and existing medications, have less waste and are more eco tion. nomical, allowing for more efficient, efficacious and palat 0011 FIG. 2 is a graphical representation showing in vitro able relief of symptoms or recovery from the skin disorder franz cell penetration results. being treated. Overall treatment success is increased by decreasing the time required for therapy, for example for DETAILED DESCRIPTION OF THE INVENTION athlete's foot, from about four weeks to seven to ten days 0012 Compositions and methods are provided for the while decreasing the total amount of medication needed and convenient and effective treatment of at least one symptom of improving patient compliance. a dermatological disorders in a mammal, particularly a 0015. Further advantages of the subject invention include human, in need thereof, with a biological dressing. By “bio that various of the resins that find use, including benzoin and logical dressing or “biologic dressing or “biologic ban mastisol, and wound sealing agents are already approved for dage' is intended a non-occlusive but adherent pharmaco human use and have been tested and found to be safe for logical composition that is formed by drying on the skin a topical application on non-human mammals; the wound seal pharmacologic composition comprised of one or more resins, ing agents have the advantage of being able to deliveralcohol Such as benzoin, mastic or other compositions that can form a insoluble medications while reducing pain during application barrier film on the skin, such as compositions that are used as to an open wound. skin wound sealing agents, one or more pharmacologically 0016. The resin-based biological dressings are prepared active agents and a topically acceptable Volatile solvent, Such by drying on the skin, a pharmacological composition com as ethanol. The resin-based biologic dressing forms a protec prising an agent that can be used to ameliorate the symptoms tive coating at the site(s) on the skin, nails or mucosal mem of a dermatological disease and one or more resins dissolved brane exhibiting symptoms of the disorder and also acts as a in a volatile solvent. Generally, the pharmacological compo reservoir for the pharmacolocally active agent(s) to provide sition is prepared as a Sticky slurry or solution of the com sustained delivery of an appropriate medication or combina bined one or more resins or film-forming agents and the tion of medications to the site. pharmacologically active agent that can be applied to a site on 0013 The skin disorder symptoms to be treated include, the skin or a mucosal membrane. The consistency of the but are not limited to, skin, nail and mucosal membrane pharmacological composition can be varied by adjusting the lesions, inflammation, itching, Scaling and pain. The disor ratio of solvent to the combined one or more resins in the ders include viral, fungal and bacterial infections, inflamma composition to achieve the desired consistency for applica tory conditions, and hyperproliferative disorders. The phar tion to aparticular site. For areas where evaporation of solvent macological agent(s) can include topically active agents that may be slower, for example, application to lesions on a can be used to ameliorate skin disorder symptoms, including mucosal membrane Such as the gums, it may be desirable to antimicrobial and antiviral agents, anti-inflammatory agents, prepare the composition as a paste and to use a more volatile analgesics and anesthetics. As desired, the effectiveness of Solvent, whereas for application to hard to reach areas, such as the pharmacological agent(s) optionally can be increased by between the toes, it may be desirable to prepare a less viscous including a skin or nail penetration enhancer in the pharma composition that can be applied thinly to the affected areas. cologic composition. However, for treatment of more severe lesions in non-visible 0014. The biological bandage is easily removed using a areas, due to an athlete's foot infection for example, applica Solvent such as ethanol. Since the coating that contains the tion of a more viscous preparation may be preferred. It should medication stays in place until Such deliberate removal, the be understood that Some wound sealing agents develop into a effectiveness of the treatment is increased since the skin is dry adhesive layer or film once in contact with tissue, and exposed to the active ingredient for a longer period of time. therefore do not generally require use of a solvent other than This also allows for a decreased treatment time, and, ulti what may be necessary to properly blend in the pharmaco mately, improved treatment of symptoms and increased logically active agent. patient satisfaction. Thus, compositions of the invention can 0017. The relative proportions of the one or more resins or be used to improve delivery of medications that are soluble in other film-forming agents, the pharmacologically active organic solvents such as alcohols that are typically applied agent or agents and the evaporative solvent in the preferred topically for the treatment dermatologic disorders. The composition can vary widely, and depend upon the specific advantages of the Subject invention include a more specifi intended use of the biological dressing. Precise preferred cally directed application of medications to sites affected by ratios depend to some extent on the rate of release of the a skin disorder, and extended retention on the skin of the pharmacologically active agent from the film, the desired medication because the film is resistant to water and abrasion stickiness of the residual film, and the area of application. For by clothing. Additionally, the vehicle is relatively inexpen example, if the intended application is to an affected area on sive, is pleasant Smelling, and the bandage can be conve the face, the preferred composition would have a lower pro niently and easily removed, for example with alcohol, when portion of combined resins or other film-forming agents, to desired. Many dermatological conditions are exacerbated by allow for a more thinly applied, less visible and less sticky moisture so the water repellent qualities of the dressing also medical dressing. Generally, the pharmacological composi protect the skin from further damage. The resin-based bio tions of the subject invention will typically have about 5% to logical dressings of the invention are designed to be directly 90% resin or other film-forming agent, more likely about 20% US 2008/0286299 A1 Nov. 20, 2008

to 85%, 30% to 70% or 40% to 60% resin or other film (a sub-type of polyolefins) are pressure sensitive adhesives forming agent. In one embodiment, the pharmacological made by blending multiple molecular weights to achieve compositions will have about 1% to 15% resin or other film desired adhesive and drug-carrier properties. Silicones are forming agent. available in the form of gels, liquids, or elastomers, depend 0018. The resin-based biological dressings of the inven ing on the nature of side groups and the interchain cross tion may also be comprised of a combination of multiple linking. Other potential adhesive vehicles include hydrogel resins or other film-forming agents, provided that when a polymers such as poly (oxypropylene-co-oxyethene) glycol, non-resin film-forming agent is used in combination with a cellulose bioadhesives such as hydroxypropylmethyl-cellu resin, the resin is the primary matrix of the composition. In lose, synthetic laticies such as polyvinyl acetate and ethylene one embodiment, the compositions of the Subject invention vinyl-acetate, mucosal adhesives such as polyoxyethylene, will comprise a combination of one or more resins, each resin pyroxylin Solutions, and the iodophors. Commercial sources being less than 20% of the total composition. In some of film-forming agents that can be combined directly with a embodiments, the total concentration of the combined resins pharmacologically active agent include Dermabond (Ethi in the compositions of the invention will exceed 20%, and con) which is a formulation of 2-octylcyanoacrylate; Liquid may be as much as 20% to 90% of the total composition. In BandAid (Johnson and Johnson) which is also a formulation other embodiments, the total concentration of the combined of 2-octylcyanoacrylate; Liquiderm, Soothe-N-Seal, Nexa resins may not exceed 20%, and may be as little as 1% to 20% Band (all from Closure Medical Co), all formulations of of the total composition. Accordingly, the concentrations of cyanoacrylate: "New-Skin' (New Skin) containing pyroxy each of the resins or other film forming agents may vary so lin; and hydrogels containing poly (oxypropylene-co-oxy long as toxicity to the Subject is avoided. ethene) glycol (MedLogic). 0019. The stickiness of the biological dressings is pro 0021. A desirable feature of the subject compositions is vided by the use of a combination of one or more resins or that they form an adherent and protective film or biological other film-forming agents. The resins that are useful in the bandage over a dermatologic lesion. To effect this attribute, methods and compositions of the invention include, but are the pharmacological composition is prepared with a volatile not limited to, naturally occurring resins and gums, such as Solvent that evaporates to leave a hydrophobic coating com those that are harvested from trees, although gum resins also prised of the one or more resins or other film-forming agents may be prepared by synthetic means (see for example, U.S. and the pharmacological agent on the skin or nail. Volatile Pat. Nos. 5,644,049, 5,429,590 and 4,307.717). Exemplary Solvents for use in the Subject compositions include ethyl resins include benzoin resinous exudate harvested from Sty acetate, n-propyl acetate, alcohols Such as methanol, ethanol, racaceae trees, including Benzoin Siam from Styrax Tonki propanol, and isopropanol, ketones, such as acetone, and nesis and Benzoin Sumatra from Styrax Benzoin. Tincture of ethers such as dimethyl ether. Other evaporative compounds benzoin and benzoin compound tincture is readily available may also find use, so long as they are compatible with other through numerous commercial sources, including many drug components of the pharmacological composition and topi stores and Suppliers of Surgical goods. Another resinous tree cally acceptable to the majority of patients. The resins of exudate that is preferred and is commonly used in the medical choice are diluted in the volatile solvent such that the concen arts for enhancing the adherence of Surgical bandages, is tration of solvent comprises about 40% to 98% (v/v or V/w), mastic, a hard resin that is harvested from Pistacia lentiscus. more commonly at least about 50% to 95%, 65% to 90%, 70% A tincture of mastic gum (Mastisol) is produced by Ferndale to 85%, preferably about 90% to 95% of the total composi Laboratories in Ferndale, Mich. and is also available through tion. An exemplary composition contains a tincture of ben Suppliers of Surgical goods. Other resins that can be used Zoin, which is comprised of benzoin in about 75% to 83% include the gum resin exudates from Burserceae trees, includ ethanol. ing Boswellia serrata (also known as Boswellin), Boswellia 0022. The pharmacological agent or agents included in the dalzielli, Boswellia Carteri (olibanum gum) and the oleoresin pharmacological compositions will depend upon the derma Canarium luzonicum or Canarium commune (Elemi gum or tological disorder being treated. To allow for extended con resin). Oleoresins useful in the compositions of the invention tact of the biological dressing with the lesion under treatment, include balsam resins. Additional resinous exudates contem pharmacological agents chosen should be efficacious without plated from other tree species include Eucalyptus species being locally or systemically toxic or caustic to the mammal (Eucalyptus globulus) and Myrtaceae "Tea-tree' species to which the medicated dressing is administered. A biological (Melaleuca alternifolia, Leptospermum scoparium, and Kun dressing of the Subject invention is intended to remain at the zea ericoides). Many naturally occurring resins themselves site of application for greater than four hours, more often as have pharmacological properties, and their topical applica long as 8, 10 or 12 hours, sometimes as long as 16, 18 or 20 tion may cause irritation in certain patients or exacerbate hours, and for certain treatments, as long as 24, 36 or 72 hours certain conditions. Prudent choice of the resins to be used in or even longer prior to removal. The time of treatment desired preparing a particular biological dressing takes into consid is based at least in part upon the nature of the condition to be eration the disorder to be treated and the sensitivities of a treated and the pharmacological agent(s) that are being used. particular patient's skin. In general, the pharmacological compositions are formulated 0020. In addition to the resins discussed herein, biologic so that the concentration of the pharmacological agent(s) that dressings can be made from several classes of adhesive poly is in the biological bandage approximates the concentration mers including acrylic polymers (e.g. cyanoacrylates), poly of agent that is used in existing topical formulations. How isobutylenes and silicones. Examples of the acrylic polymers ever, because the adherent properties of a film-forming resin include acrylate-vinylacrylate, dimethylaminoethyl based biological dressing allow for extended and continuous methacrylate, methacrylic esters, N2-butylcyanoacrylate, exposure of a skin lesion to drug, reduced concentration for 2-octylcyanoacrylate, polyacrylic acid, polyaminomethyl mulations are possible and in Some cases preferred. The methacrylate and polymethylmethacrylate. Polyisobutylenes amount to be used can therefore be adjusted as appropriate. US 2008/0286299 A1 Nov. 20, 2008

Generally, the amount used will be within the range of +25% logical dressings having an antibiotic medication as the of the indicated concentration, preferably within +10% of the primary pharmacological agent can be prepared to treat other indicated concentrations. In the following paragraphs, the skin disorders for which such medications are traditionally percentages appearing in parenthesis after the name of a used, including as impetigo contagiosa, acne Vulgaris, other particular agent represent the concentration(s) of agent that is Superficial skin infections of unknown etiology, and post (are) used in existing topical formulations. operative Superficial skin infections (e.g., infections that 0023 The subject biological dressings find particular use occur around the insertion of a catheter). Wound healing can in treating numerous dermatological disorders, including be aided and colonization of wounds (i.e. isolated areas with Superficial infections (fungal, bacterial, viral and parasitic), first-degree burns) can be inhibited by application of a bio and inflammatory skin disorders. As used herein, the term logical dressing comprising silver Sulfadiazine (1%). The “skin’ refers to the membranous tissue forming the external particular antibiotic selected to be included in the biologic covering or integument of an animal and consisting in Verte dressing will of course depend on the agents to which the brates of the epidermis and dermis. As used herein, the term strain of bacteria causing the infection is sensitive, and the “nail” refers to a substructure, composed mainly of the pro specific needs of the patient. tein keratin, of the outer layer of the skin. As such, “nail 0027. A biologic dressing can also be prepared for the includes both “fingernails” and "toenails” of an animal. The treatment of Superficial parasitic infections, such as Scabies, “nail bed' is the skin on the top of which the nail grows. nits and lice (including head lice and crab lice). For treating Additional uses include Sustained delivery of pharmacologi Such infections, pharmacological compositions comprising cal agents for hair growth stimulation and hair growth retar miticides or pediculocides such as crotamiton (10%) or per dation, skin pigmenting and pigmentation removal agents, methrin (5%), lindane (1%), malathion (0.003% to 0.5%), Sunscreens, insect repellents, anti-anginal, anti-perspirant benzylbenzoate (26% to 30%), thiabendazole and pyrethrins. and anti-nausea agents. 0028. For treating pain associated with arthritis, joint 0024 Superficial fungal infections treatable by the subject inflammation and muscle pain a composition of the invention compositions include those caused by mold-like fungi (der can be prepared comprising one or more resins or other film matophytes or tinea) or yeast-like fungi (Candida) that are forming agents and one or more active ingredients such as confined to the stratum corneum or squamous mucosa. Par menthol (10%), methyl salicylate (10%) and capsaicin ticularly considered is the treatment of tinea infections (0.01%-10%) or a corticosteriod (see below for appropriate including onychomycosis (tinea unguium), athlete's foot compounds and dosages). The compositions of the invention (tinea pedis), ringworm (tinea capitis), jockitch (tinea cruris), also find use in the treatment of dermatological inflammatory tinea corporis, tinea manuum and tinea versicolor. Other der disorders, wherein the primary pharmacological agent matological fungal infections treatable with the described included is a corticosteroid. Particularly contemplated is the biological dressings include Candida, Epidermophyton, treatment of corticosteroid-responsive inflammatory condi Microsporum, Trichophyton and Pityrosporum infections. tions, such as atopic dermatitis or eczema, Seborrheic derma 0025 Compositions for the treatment of superficial fungal titis, some forms of psoriasis, aphthous ulcers (canker Sores), infections will include at least one anti-fungal pharmaceutical Superficial skin lesions due to contact with poisonous plants agent. Anti-fungal agents for use in a biological dressing Such as poison oak or poison ivy, insect bites, and other skin composition include those well-known in the art, such as rashes of unknown etiology. Steroidal agents of all different clotrimazole (0.5% to 2.0%), ketoconazole (0.5% to 2%), grades (1-7) that are known in the art can be included in a econazole (1%), miconazole (2%), terconazole (0.4%), buto biological dressing preparation, such as betamethasone conazole (2%). Oxiconazole (1%), Sulconazole (1%), ciclo (0.025% to 0.1%), clobetasol (0.05%), diflorasone (0.05%), pirox olamine (1% to 8%), haloprogin (1%), tolnaftate (1%), amcinonide (0.1%), desoximetasone (0.05% to 0.25%), fluo amphotericin B (3%), butenafine (1.0%), terbinafine (0.5% to cinonide (0.05%), halsinonide (0.1%), triamcinolone 2.0%), naftifine (0.5% to 10%), nystatin and griseofulvin. (0.025% to 0.5%), hydrocortisone (0.1% to 2.5%), flurandre References that can be consulted to aid in the selection of an nolide (0.05%), alclometasone (0.05%), fluocinolone (0.01% appropriate pharmacological agent include Goodman and to 0.2%), desonide (0.05%), desamethasone (0.1%) and Gilman's "The Pharmacological Basis of Therapeutics”, 9" methylprednisolone (1.0%), clocortolone (0.1%), fluticasone Edition, 1996, Pergamon Press, New York, and the lastest (0.005% to 0.05%), mometasone (0.1%), prednicarbate edition of the Physician's Desk Reference published by (0.1%), amcinonide (0.1%), and halobetasole (0.05%). The Medical Economics Company, Montvale, N.J.). particular corticosteriodal agent selected will depend on the 0026. Bacterial infections that may arise can be treated patient and the particular disorder being treated. simultaneously or prophylactically by additionally including 0029. For the treatment of certain skin disorders, non a topically compatible antibiotic pharmacological agent in steroidal drugs may be appropriate. As an example, a com the biological dressing. Antibiotic medications known in the position comprising one or more resins or other film-forming art that will find use in preparation of the Subject composi agents and salicylic acid (0.5% to 60%) and/or retinoic acid tions include clindamycin (1%), erythromycin (1.0% to (Retin-A) (0.025% to 0.05%) would be suitable for the treat 2.0%), tetracycline (1% to 3%), mupirocin (2.0%), gentami ment of acne, psoriasis, warts, and other hyperkeratotoic dis cin (0.1%), metronidizole (0.75%, 1%), bacitracin (250 to orders. Cantharidin (0.7%) and imiquimod (5%) are other 600 units/cc), neomycin (3.5 mg/cc) and polymyxin B (8,000 examples of pharmacological agents for use in a biological to 12,000 units/cc). A composition with a combination of dressing prepared for the treatment of warts, including genital antibiotics against different strains of bacteria will be pre warts. Other pharmacological agents Suitable for the treat ferred for certain treatments. A steroidal pharmacological ment of acne include tretinoin (0.025% to 0.2%), isotretinoin, agent, such as betamethasone (0.025% to 0.1%), in a biologi adapaline (0.1%), azelaic acid (20%), clindamycin, erythro cal dressing intended to treat a fungal infection can addition mycin, tetracycline, benzoyl peroxide (2.5% to 10%), and ally be included to enhance the retraction of the lesion. Bio Sulfacetamide (10%). A composition comprising one or more US 2008/0286299 A1 Nov. 20, 2008 resins or other film-forming agents and metronidazole active agents suitable for use in a resin-based biological (0.75%) finds use in the treatment of rosacea. dressing for Surgical preparations include, but are not limited 0030 Biological dressings comprising anthralin (0.1% to to biguanides Such as chlorhexidene gluconate and alexidine, 0.5%), calcipotriene (0.005%) and/or tazaroteine find use in povione iodine, iodine, halogen releasing agents such as the treatment of psoriasis. iodophor, diamidines, anilides such as triclocarban, phenols, 0031. For certain inflammatory dermatological condi halophenols and bis-phenols such as triclosan, peroxygens tions, it may be desirable to include one or more anti-hista Such as hydrogen peroxide, silver compounds Such as silver mine compounds with a steroidal compound in the biological nitrate and quarternary ammonium compounds. dressing compositions to aid in relieving itching that is often 0036 Compositions comprising one or more resins or associated with inflammatory lesions. Histamine H1 and H2 other film-forming agents and containing synthetic hormones receptor blockers known in the art are of use in the preparation find use in the treatment of indications associated with abnor of biologic dressings for treating certain inflammatory skin mal hormone production as well as contraception. For conditions include the H1 blockers astemizole and terfena example, a biologic dressing containing transdermal test dine, and the H2 blocker cimetidine. osterone, generally about 2.5-5.0 mg per application, or 0032. Dermatological conditions which can be treated equivalent other androgenic compound(s) in an appropriate with pharmacological compositions in which an anti-hista amount can be used to treat young males with congenital or mine is the primary agent include urticaria, and itching asso acquired primary hypogonadism, or congenital or acquired ciated with lymphoproliferative diseases such as poly hypogonadotropic hypogonadism and other similar disor cythemia rubravera and Hodgkin's disease. Oftentimes best ders. In women, a bilogic dressing containing estradiol (an results are achieved when using both an H1 and an H2 active form of estrogen) or other equivalent estrogenic com blocker. Additionally, a medicated biologic dressing compris pound(s) in an appropriate amount, can be used to treat the ing the anti-pruritic doxepin (5%) finds use in relieving the indications and symptoms associated with atrophic vaginitis, itching in patients with certain types of eczema. Topical dox atrophic dystrophy of the Vulva, menopausal symptoms, epin appears to work by preventing the effects of histamine. female hypogonadism, ovariectomy, primary ovarian failure, 0033. A biologic dressing of the invention also finds use in non-steroid dependentinoperable breast cancer and vasomo the treatment of Superficial dematological viral infections, tor symptoms associated with menopause and prevention of whenever topical anti-viral medications would be indicated. post-menopasual osteoporosis. A biologic dressing contain Particularly considered is the administration of acyclovir ing an estrogenic compound. Such as for example estradiol in (5%) for the treatment of viral infections caused by herpes an amount Sufficient for the treatment of Such indications is (type 1 and type 2)simplex viruses, but a biological dressing used. can also be applied to Superficial skin infections caused by 0037. A composition comprising one or more resins or papillomavirus (for example, common and genital warts). other film-forming agents and containing norethindrone Other examples of anti-viral agents for use in a biological (progestin) can be used to prevent pregnancy by inhibiting dressing include gancyclovir, penciclovir (1%), Vidarabine ovulation and thickening the mucosa of the cervix. In addi (3%), idoxuridine (0.5%) and trifluridine. tion, a film-forming resin or other film-forming agent com 0034. A resin-based biological dressing also finds use in position containing a progestin compound Such as norethin providing relief from pain associated with the lesions caused drone (0.14-0.25 mg per application) can be used for treating by some dermatological disorders. Particularly considered is abnormal menstrual disorders such as amenorrhea, abnormal treatment of the dermal pain that can be associated with uterine bleeding and endometriosis, applications generally Varicella-Zoster virus (shingles, chickenpox) with a topically will be to the skin. The site of application of the film-forming compatible local anesthetic. A preferred pharmacological resin or other film-forming agent composition will vary agent for use in a resin-based dressing prepared for treating depending upon the intended use. Generally the site of appli pain associated with dermatological disorders is lidocaine cation will be to the skin at a location that will provide for (0.5% to 25%, see U.S. Pat. Nos. 5,709,869, 5,601,838, absorption into the blood stream. Particularly in the case of 5,589,180 and 5,411,738, incorporated herein by reference). treatments relating to the female genitalia, application can be Other local anesthetics chemically and/or pharmacologically intravaginally. related to lidocaine, or lidocaine hydrochloride, include bupi 0038 Film-forming resin or other film-forming agent vacaine hydrochloride (0.25% to 1.5%), etidocaine hydro compositions are also suitable for Sustained delivery of phar chloride (1.0% to 3.0%), mepivacaine hydrochloride (1.0% to macological agents use for hair growth retardation and stimu 5.0%), prilocalne hydrochloride (4.0% to 8.0%), and tetra lation. For treatments intending to stimulate hair growth, caine hydrochloride (0.5% to 2.0%). Other preferred local compositions comprising minoxidil (1% to 5%) are prepared. anesthetics are those with low solubility in water, and which For other topical formulations that can be used with the one or are particularly Suited for Sustained local anesthetic action more resins or other film-forming agents, see U.S. Pat. No. when topically applied. Examples of local anesthetics with 6,184.249. For treatment intending to retard hair growth com low solubility in water include benzocaine and the hydroio positions comprising eflornithine hydrochloride (13.9%) are dide salt of tetracaine. Additional local anesthetics used in prepared. treating mucous membranes and the skin include dibucaine, 0039. A composition comprising one or more resins or dyclonine hydrochloride (0.5% to 1.0%), and pramoxine other film-forming agents additionally finds use in preparing hydrochloride (1.0%). Another example of a pharmacologi protective compositions comprising one or more Sun protect cal agent used topically to relieve dermatological pain ing, ultraviolet absorptive agents. Sunscreens for use in a includes capsaicin (0.025%). film-forming resin or other film-forming agent-based dress 0035. A composition comprising one or more resins or ing include aminobenzoate agents, such as p-aminobenzoic other film-forming agents additionally finds use in Surgical acid (PABA), ethyl 4-bis(hydroxypropyl)aminobenzoate, preparations for Sustained release of antiseptics. Examples of octyl dimethyl PABA, PABA propoxylate, glyceral PABA, US 2008/0286299 A1 Nov. 20, 2008

2-ethylhexyl PABA and pentyl PABA: cinnamate agents, meronate, N-octyl bicycloheptene, dicarboximide, and 2.3.4. Such as cinoxate, diethanolamine-p-methoxy cinnamate, 5-bis(2-butylene)tetra-hydro-2-furaldehyde. For use as an 2-ethylhexyl-p-methoxycinnamate and octyl methoxycin insect repellent, a resin or other film-forming agent prepara namate; benzones, such as oxybenzone, dioxybenzone, tion is preferably applied as a thin coat to areas of the skin Sulisobenzone; salicylates, such as 2-ethylhexyl salicylate, most likely to be attacked by an insect. Preferably, the insect triethanol amine salicylate, and octyl salicylate; and other repellant compound used repels insects without irritating the Sunscreen agents, such as meradimate (7.5%), octinoxate skin. Advantageously, as with the Sunscreen preparations (7.5%), homosalate (10%), Sulisobenzone (10%), titanium described above, a composition comprising one or more res dioxide and Zinc oxide. For use as a Sunscreen, generally a ins or other film-forming agents and insect repellent is par thin combination of one or more resins or other film-forming agents/ultraviolet absorptive agents is applied to areas of the ticularly effective at providing long-lasting insect repellency skin that will be exposed to the sun. For some situations, on the skin through resisting removal by abrasion or moisture. protection of exposed skin from the sun will be best accom 0043. The compositions of the invention also find use in plished by applying a thicker formulation of the one or more the treatment of drug addiction. Compositions comprising resins or other film forming agents. For example, application one or more resins or other film-forming agents may be pre of Sunscreen to protect the skin of the nose at high altitudes. pared with nicotine, generally about in an amount Sufficient to Advantageously, a formulation comprising one or more res decrease nicotine addition, 14-22 mg per application, or other ins or other film-forming agents and Sunscreen compound is amounts as appropriate, for use in the reduction and/or ces particularly effective at providing long-lasting Sun protection sation of cigarette Smoking, chewing tobacco or other nico to exposed skin through resisting removal by abrasion or tine containing compounds. The compositions are applied to moisture. the skin in a location that provides sufficient absorption of the 0040 Compositions comprising one or more resins or nicotine, typically the upper arm. As the need for nicotine other film-forming agents may be prepared with pharmaco decreases the dosage of nicotine in the composition can be logical agents used for pigmenting or de-pigmenting the skin, adjusted downward. for instance, for use in treating patients with vitiligo. For 0044 Optionally, the biologic dressings of the invention treatments intending to de-pigment or lighten isolated dermal areas, a pharmacologic composition comprising hydro may include a penetration enhancer, i.e., a chemical com quinone (2% to 4%) is prepared. For treatments intending to pound that, when included in a formulation, temporarily pigment desired areas of skin, a composition comprising a increases the permeability of the skin to a drug allowing more psoralen agent. Such as methoxalen (1.0%), for combined use of the drug to be absorbed in a shorter period of time. with UV light, is prepared. Examples of penetration enhancers that can be used include dimethylsulfoxide (DMSO), n-decyl methylsulfoxide, N.N- 0041. A medicated resin-based dressing will also find use in the Sustained delivery of anti-perspirants, anti-anginal, dimethylacetamide, N,N-methyl-2-pyrrolidone and anti-nausea agents and anti-cancer agents. Particularly con octylphenylpolyethylene glycols. templated are compositions comprising aluminum chloride 0045. The biologic dressings of the invention may also (20%), for the inhibition of perspiration of isolated dermal include one or more other pharmaceutically acceptable car areas, for instance to aid in carrying out Surgical procedures. riers as needed that do not adversely affect the effectiveness A composition comprising one or more resins or other film of the drug, or the resinous delivery vehicle and do not dam forming agents and nitroglycerin (0.5% to 2.0%) will find use age the skin to which it is applied. Suitable pharmaceutical in the Sustained transdermal delivery of this anti-anginal carriers include sterile water; Saline, dextrose; dextrose in agent which can provide relief from chest pains. Relief from water or saline; condensation products of castor oil and eth nausea, due to motion sickness for example, can be provided ylene oxide combining about 30 to about 35 moles of ethylene using a biological dressing comprising Scopolamine. Foranti oxide per mole of castor oil; liquid acid; lower alkanols; oils nausea purposes, a composition comprising one or more res Such as corn oil, olive oil, peanut oil, Sesame oil, wintergreen ins or other film-forming agents and Scopolamine would be oil, lanolin oil and the like, with emulsifiers such as mono- or applied, behind the ear for example, before the onset of activ di-glyceride of a fatty acid, or a phosphatide, e.g., lecithin, ity that potentially would induce nausea. Additionally, a resin and the like; glycols; polyalkylene glycols; aqueous media in or other film-forming agent dressing can be prepared for the the presence of a suspending agent, for example, Sodium Sustained delivery of pharmacological agents useful in the carboxymethyl-cellulose; sodium alginate; poly(vinyl pyr treatment of Superficial cancerous and pre-cancerous lesions. rolidone); and the like, alone, or with Suitable dispensing Particularly contemplated is the treatment of isolated actinic agents such as lecithin; polyoxyethylene Stearate; and the keratosis lesions with a biological dressing comprising like. The carrier may also contain adjuvants such as preserv 5-fluorouracil (5-FU; 5% to 10%). ing, stabilizing, wetting, emulsifying agents and the like. 0.042 A composition comprising one or more resins or 0046. The compounds of this invention can be adminis other film-forming agents may also be prepared with an insect tered in conjunction with a transdermal patch that can include repellant as the pharmacologic agent. Examples of insect the pharmacologic agentina Suitable solvent system with the repellant compounds Suitable for inclusion in a resin-based one or more film-forming agents and a polyester patch. The biological dressing include terpenoids, such as citronellal, compounds of the present invention also can be delivered geraniol, terpentine, pennyroyal, cedarwood, eucalyptus and through mucosal membranes. Transmucosal (i.e., Sublingual, wintergreen; benzoquinones; aromatics. Such as cresols, ben buccal, and vaginal) drug delivery provides for an efficient Zaldehyde, cinnamic aldehyde, benzoic acids; and synthetic entry of active Substances to the systemic circulation and insect repelling agents, such as N,N-diethyl-m-toluamide reduces immediate metabolism by the liver and intestinal wall (DEET), ethylhexanediol, dimethyl phthalate, dimethylethyl flora. Transmucosal drug dosage forms are held in contact hexanediol, carbate, butopyronoxyl, di-n-propyl isocinchon with the mucosal membrane where they disintegrate and/or US 2008/0286299 A1 Nov. 20, 2008

dissolve rapidly to allow immediate systemic absorption. The doses. The kits include containers which can also constitute a method of manufacture of these formulations is known in the delivery system, holding a composition comprising an effec art tive agent either as concentrates (including lyophilized com 0047 For aerosol administration, the pharmaceutical positions), which may be further diluted prior to use or they compositions are preferably supplied in finely divided form may be provided at the concentration of use, where the con together with a Surfactant and propellantas pharmaceutically tainers may include one or more dosages. Conveniently, in the acceptable carriers. The Surfactant is nontoxic, and preferably kits single dosages can be provided in sterile containers so soluble in the propellant. Representative of Such agents are that the physician or the patient may employ the containers the esters or partial esters of fatty acids containing from 6 to directly, where the containers have the desired amount and 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, concentration of agents. When the containers contain the Stearic, linoleic, linolenic, olesteric and oleic acids with an formulation for direct use, usually there will be no need for aliphatic polyhydric alcohol or its cyclic anhydride. Mixed other reagents for use with the method. The kits also can be in esters, such as mixed or natural glycerides, can be employed. the form of a transdermal or transmucosal system for single or 0048. In practicing a method of treating the symptoms of a multiple applications. The containers can be made of plastic, dermatological disease in a patient, the pharmacological glass, metal or Such material deemed appropriate for each composition in its original prepared form, is applied directly particular medication and can be light opaque as required for and specifically on the lesions or other damaged areas of skin light sensitive formulations. The containers can be color requiring treatment. The biological dressing composition coded, each color being unique to a particular product and its may initially be prepared in any form suitable for topical respective active ingredient. The containers can also be color application, such as a paste, a liquid, a semi-solid, a gel, a coordinated with the outer packaging to simplify marketing Suspension, an emulsion or the like, provided that the formu and consumer purchasing. Examples of containers that are lation allows the one or more resins or other film-forming also delivery systems are those that facilitate application of agents and the one or more pharmacologically active agent to the Subject compositions to the skin or mucosa. The delivery effectively adhere together to the skin surface to which they systems can be any of a wide assortment of types of applica are applied and to form a protective barrier over the skin once tors (e.g. bottles), shapes and sizes of containers such as the Volatile solvent has evaporated. To minimize waste, appli roll-on, spray with either a manual or aerosolized delivery cation is generally carried out by painting or Swabbing the system, applicators with Small padded applicator tips for the composition at the affected site or sites, but certain prepara delivery ofbuccal mucosal medications or syringe type appli tions can also be applied by spraying on the formulation, and cators for semisolid medication such as are described in U.S. allowing it to dry. Pat. No. 5,531,703 and references cited therein, particularly 0049. The biologic dressing composition can be applied for the delivery of vaginal mucosal medications. wherever the patient has Superficial skin lesions or infections, 0051. The subject compositions can be contained in pack Such as on cutaneous areas, fingernails, toenails, mucous aging material, which comprises a label indicating that the membranes, and mucocutaneous junctions (i.e., perianal, Subject compositions can be used to treat dermatologic dis intertriginous and Vulvovaginal areas). After application, the orders in humans or to treat other disorders in humans using volatile solvent evaporates to leave a protective solidified, transdermal delivery means. adherent and hydrophobic film or coating on the skin Surface 0.052 The invention now being generally described, it will to which it has been applied. The solidified film residue com be more readily understood by reference to the following prises the one or more resins or other film-forming agents, examples which are included for purposes of illustration only and the one or more pharmacologically active agents. By and are not intended to limit the present invention. forming a barrier holding the pharmacologically active agent or agents to the Surface, the combined film-forming resins or EXAMPLE 1. other film-forming agents permit a Sustained, continuous Treatment of Athlete's Foot (Tinea Pedis) with a release and a prolonged exposure to the agent or agents. Resin-Based Biological Dressing Comprised of Tin Continuous exposure of the skin to the medication is main tained as long as the coating stays in place. The biologic ture of Benzoin and Clotrimazole dressing, therefore can effect symptomatic relief with less 0053 Tincture of benzoin compositions are produced with frequent applications. For most dermatological disorders standard tincture of benzoin (3M, Minneapolis, Minn.). Rep treated using a resin or other film-forming agent-based dress licated experiments were performed with a composition com ing, one or two daily applications will be sufficient to promote prising tincture of benzoin with 90% alcohol plus 1% clotri regression or disappearance of the targeted skin lesions. For mazole. The experiments were repeated using mastic gum certain less respondent lesions, three daily applications may and elemi gum tinctures as well. To determine efficacy in be required to effect disappearance of symptoms. Other der treating athlete's foot, the benzoin/clotrimazole composition matological disorders may require application every second was applied to cases of athlete's foot, replicated 5 times. In day to realize symptomatic relief. The composition conve each replicate, the composition led to complete clearance of niently can be removed at will, by application of an appropri the athlete's foot within 1 week, when applied twice daily for ate solvent, normally ethanol. The composition can also be 7 days. No allergic reaction was noted in this test, although removed by Scrubbing with Soap and water. the alcohol component reportedly led to stinging when 0050. The subject compositions can be provided for use in applied to deep fissures. Minimal lint from the socks was one or more applications. For treatment with a pharmaceuti noted on the coating where the composition was applied but cal composition comprising an agent identified as one which was easily removed with ethanol. Efficacy of the benzoin/ is effective in treating the symptoms of a disease amendable clotrimazole composition was compared to controls of tinc to treatment by dermal application of medication, the Subject ture of benzoin alone and no treatment. The benzoin/clotri compositions can be provided as kits for use in one or more mazole composition provided symptomatic relief and led to US 2008/0286299 A1 Nov. 20, 2008

healing more quickly than tincture of benzoin alone, though skilled in the art to which this invention pertains. All publi tincture of benzoin alone improved symptoms and signs more cations and patent applications are herein incorporated by quickly when compared to no treatment. This is likely due to reference to the same extent as if each individual publication the fact that the sticky coating from the tincture tends to repel or patent application was specifically and individually indi moisture. Efficacy of the benzoin/clotrimazole composition cated to be incorporate by reference. also was compared to commercially available medications 0057 Although the invention has been described with ref such as Lamisil.R., Lotrimin R, Mycelex(R) and Tinactin R. In erence to the above example, it will be understood that modi comparison, the benzoin/clotrimazole composition greatly fications and variations are encompassed within the spirit and decreased the time necessary for treatment compared to for Scope of the invention. Accordingly, the invention is limited mulations of each of the commercial medications, particu only by the following claims. larly when the commercial medications were administered in the form of powder, liquid, Solution, spray or gel. The ben What is claimed is: Zoin/clotrimazole composition also decreased the time nec 1. A pharmacological composition comprising: a) a resin; essary for treatment when compared to cream versions of the b) chlorhexidine; and c) a topically acceptable volatile sol above medications and was much less messy than any of the vent for the resin and the chlorhexidine. commercial preparations tested. 2. The composition according to claim 1, further compris ing at least one topically acceptable pharmacologically active EXAMPLE 2 agent other than the resin that is effective as a treatment for ameliorating symptoms of a disease of skin or a mucous Treatment of Onychomycosis (Tinea Unguium) with membrane of a mammal, wherein the pharmacologically a Film-Forming Resin-Based Biological Dressing active agent can remain in contact with the skin, nail or the Comprised of Tinture of Mastic Gum and Ciclopirox mucous membrane for greater than 4 hours without toxic effects to the mammal. 0054 Tincture of mastic gum (Mastisol) compositions are 3. The composition according to claim 1, wherein the resin produced with standard Mastisol (Ferndale Laboratories in Ferndale, Mich.). Replicated experiments were performed is selected from the group consisting of a hard resin, an with a composition comprising tincture of mastic gum with oleoresin, and a gum resin. 82% alcohol plus 8% Ciclopirox. To determine efficacy in 4. The composition according to claim3, wherein the resin treating onychomycosis, the mastic gum?ciclopiroX compo is mastic gum. sition was applied to cases of onychomycosis, replicated 6 5. The composition according to claim 4, wherein the mas times. In each replicate, the composition led to significant tic gum is present at about 1%-15% of the total composition. improvement of the onychomycosis within 6 weeks, when 6. The composition according to claim 5, wherein the mas applied once daily for 6 weeks. No allergic reaction was noted tic gum is 5% of the total composition. in this test. Minimal lint from the socks was noted on the 7. The composition according to claim3, wherein the resin coating where the composition was applied but was easily is benzoin. removed with ethanol. Efficacy of the mastic gum/ciclopirox 8. The composition according to claim3, wherein the resin composition was compared to controls of tincture of mastic is selected from the group consisting of olibanum gum, elemi gum alone and no treatment. The mastic gum/ciclopiroX com gum, and balsam resin. position provided symptomatic relief and led to healing more 9. The composition according to claim 1, wherein the resin quickly than tincture of mastic gum alone, though tincture of is a mixture of two or more resins. mastic gum alone improved symptoms and signs more 10. The composition according to claim 9, wherein the two quickly when compared to no treatment. This is likely due to or more resins are mastic gum and benzoin. the fact that the sticky coating from the tincture tends to repel 11. The composition according to claim 10, wherein the moisture. Efficacy of the mastic gum/ciclopiroX composition mastic gum is present at 4% of the total composition and the also was compared to commercially available medications benzoin is present at 1% of the total composition. Such as PenLac R. In comparison, the mastic gum/ciclopiroX 12. The composition according to claim 10, wherein the composition greatly decreased the time necessary for treat mastic gum is present at 3% of the total composition and the ment compared to formulations of each of the commercial benzoin is present at 2% of the total composition. medications, particularly when the commercial medications 13. The composition according to claim 10, wherein the were administered in the form of powder, liquid, Solution, mastic gum is present at 2% of the total composition and the spray or gel. The mastic gum?ciclopiroX composition also benzoin is present at 3% of the total composition. decreased the time necessary for treatment when compared to 14. The composition according to claim 10, wherein the cream versions of the above medications and was much less mastic gum is present at 1% of the total composition and the messy than any of the commercial preparations tested. benzoin is present at 4% of the total composition. 0055. The above results demonstrate the improved symp 15. The composition according to claim 1, wherein the tomatic relief from a disorder that can be achieved by admin topically acceptable Volatile solvent is ethanol, ethyl acetate, istering a topically acceptable pharmacological agent in a or n-propyl acetate. film-forming resin carrier that forms a biological bandage in 16. The composition according to claim 15, wherein the comparison presently available carriers. With a film-forming topically acceptable Volatile solvent is ethanol and comprises resin-based biological dressing, relief from the unpleasant about 60% to 95% of the composition. symptoms associated with a dermatological lesion is realized 17. The composition according to claim 16, wherein the more efficiently and in a more convenient and palatable man ethanol is 70% of the composition. 18. The composition according to claim 1, wherein the 0056 All publications and patent applications mentioned chlorhexidine is chlorhexidine gluconate and is present at in this specification are indicative of the level of skill of those about 0.01%-5% of the composition. US 2008/0286299 A1 Nov. 20, 2008

19. The composition according to claim 18, wherein the 25. The method of claim 24, wherein the composition chlorhexidine gluconate is 2% of the composition. further comprises at least one topically acceptable pharma 20. The composition according to claim 1, further compris cologically active agent other than the resin that is effective as ing a penetration enhancer. a treatment forameliorating symptoms of a disease of skin or 21. The composition according to claim 1, further compris a mucous membrane of a mammal, wherein the pharmaco ing an oil. logically active agent can remain in contact with the skin or 22. A pharmacological composition comprising: a) mastic mucosal membrane for greater than 4 hours without toxic gum; b) chlorhexidine gluconate; and c) ethanol. effects to the mammal. 26. The method of claim 24, wherein the resin is selected 23. A pharmacological composition comprising: a) tinc from the group consisting of a hard resin, an oleoresin, and a ture of benzoin; b) chlorhexidine gluconate; and c) ethanol. gum resin. 24. A method of treating a subject having or at risk of 27. The method according to claim 24, wherein the resin is having a microbial infection comprising contacting a skin or a mixture of two or more resins. mucosal Surface of the Subject having the microbial infection 28. The method of claim 24, wherein the solvent is ethanol, with a pharmacological composition comprising: ethyl acetate, or n-propyl acetate. (a) a resin; 29. The method of claim 24, wherein the skin or mucosal (b) chlorhexidine; and Surface is oral tissue. (c) a topically acceptable volatile solvent for the one or more resins and the chlorhexidine.