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USOO6585967B2 (12) United States Patent (10) Patent No.: US 6,585,967 B2 Narang et al. (45) Date of Patent: *Jul. 1, 2003

(54) ADHESIVE TREATMENT FORTINEA 5,480,935 A 1/1996 Greff et al. CRURIS 5,514,371 A 5/1996 Leung et al. 5,514,372 A 5/1996 Leung et al. Inventors: Upvan Narang, Raleigh, NC (US); 5.530,037 A 6/1996 McDonnell et al. (75) 5,554,365 A 9/1996 Byram et al. William S. C. Nicholson, Raleigh, NC 5,575.997 A 11/1996 Leung et al. (US); Anthony Sherbondy, Raleigh, 5,580,565 A 12/1996 Tighe et al. NC (US); Gabriel N. Szabo, Raleigh, 5,582,834 A 12/1996 Leung et al. NC (US) 5,613,942 A 3/1997 Lucast et al. 5,624,669 A 4/1997 Leung et al. (73) Assignee: Closure Medical Corporation, 5,653,769 A 8/1997 Barley, Jr. et al. Raleigh, NC (US) 5,661,170 A 8/1997 Chodosh ...... 514/390 5,665,817 A 9/1997 Greff et al. (*) Notice: Subject to any disclaimer, the term of this 5,684,042 A 11/1997 Greff et al. patent is extended or adjusted under 35 5,716,607 A 2/1998 Byram et al. U.S.C. 154(b) by 0 days. 5,716,608 A 2/1998 Byram et al. 5,717.005 A 2/1998 Richardson 5,725,491 A 3/1998 Tipton et al. This patent is Subject to a terminal dis 5,730,994. A 3/1998 Askill et al. claimer. 5,753,699 A 5/1998 Greff et al. 5,755,680 A 5/1998 Ghodsian (21) Appl. No.: 09/898,005 5,762.919. A 6/1998 Greff et al. 5,762.955 A 6/1998 Smith (22) Filed: Jul. 5, 2001 5,783,177 A 7/1998 Greff et al. 5,800,373 A 9/1998 Melanson et al. (65) Prior Publication Data 5,800,831 A 9/1998 Burnett et al. US 2003/000794.6 A1 Jan. 9, 2003 5,807,563 A 9/1998 Askill et al. 5,811,091 A 9/1998 Greff et al. (51) Int. Cl." ...... A61K 31/74; A61K 7/00; 5,811,107 A 9/1998 Gangadharan et al. A61K 31/415 5,827,870 A 10/1998 Chodosh U.S. Cl...... 424/78.31; 424/401; 514/390 5,840,072 A 11/1998 Carey (52) 5,855,208 A 1/1999 Askill et al. (58) Field of Search ...... 424/401, 78.31; 5,981,621 A 11/1999 Clark et al. 514/390 6,001,345 A 12/1999 Askill et al. 6,086,906. A 7/2000 Greff et al. (56) References Cited 6,090,397 A 7/2000 Lee et al. 6,102.205 A 8/2000 Greff et al. U.S. PATENT DOCUMENTS 6,155,265 A 12/2000 Hammerslag 3,577,516 A 5/1971 Gould et al. 6,183,190 B1 2/2001 Raiteri 3,847,155 A 11/1974 Bernaola 6,183,593 B1 2/2001 Narang et al. 3,880,158 A 4/1975 Gurney 6,238,692 B1 5/2001 Smith 3.987,000 A 10/1976 Gleichenhagen et al. 6,433,096 B1 8/2002 Hickey et al. 4,073,291 A 2/1978 Marvel et al. 2001/0038857 A1 11/2001 Smith 4,287.177 A 9/1981 Nakashima et al. 2001/0051179 A1 12/2001 Berman 4,310,509 A 1/1982 Berglund et al. FOREIGN PATENT DOCUMENTS 4,323,557 A 4/1982 Rosso et al. 4,479,933 A 10/1984 Akimova et al. WO WO OO/35276 6/2000 4,560,555 A 12/1985 Snider WO WO O1/32795 A1 5/2001 4,643,180 A 2/1987 Feld et al. 4,752.472 A 6/1988 Kligman * cited by examiner 4,806,614 A 2/1989 Matsuda et al. Primary Examiner Thurman K. Page 4,826,677 A 5/1989 Mueller et al. 4,880,416 A 11/1989 Horiuchi et al. Assistant Examiner Blessing Fubara 4.913,897 A 4/1990 Chvapil et al. (74) Attorney, Agent, or Firm-Oliff & Berridge, PLC 4,981,483 A 1/1991 Akimova et al. (57) ABSTRACT 4,987,893 A 1/1991 Salamone et al. 5,009.224 A 4/1991 Cole A method of treating or preventing tinea cruris, commonly 5,082,663 A 1/1992 Konishi et al. known as Jock Itch, includes applying a polymerizable 5,103,812 A 4/1992 Salamone et al. 5,160.737 A * 11/1992 Friedman et al...... 424/401 monomer adhesive composition to an area of skin afflicted 5,254,132 A 10/1993 Barley et al. with or Susceptible to tinea cruris, optionally with at least 5,306,490 A 4/1994 Barley, Jr. one of an additional anti-fungal agent or a skin care additive, 5,320.838 A 6/1994 Woller and allowing the polymerizable monomer composition to 5,403.591 A 4/1995 Tighe et al. polymerize to form a polymer film over the area of Skin. 5,409,903 A 4/1995 Polak et al. 5,413,780 A 5/1995 Huprich 34 Claims, No Drawings US 6,585,967 B2 1 2 ADHESIVE TREATMENT FORTINEA drugs, Such as anti-fungal agents, to affected parts of the CRURIS skin. U.S. Pat. Nos. 5,716,607 and 5,716,608, both to Byram et al., disclose the use of cyanoacrylate adhesives to prevent ionization radiation damage to skin. Such damage is pre BACKGROUND OF THE INVENTION vented by applying the cyanoacrylate polymer to the skin to be protected. U.S. Pat. No. 5,653,769 to Barkey, Jr., et al., 1. Field of Invention discloses protecting skin areas from irritation due to contact The present invention relates to treatment and prevention with artificial devices Such as prosthetics, bandages and of tinea cruris, commonly known as Jock Itch. casts by applying a cyanoacrylate polymer to the desired 2. Description of Related Art skin areas that otherwise would be prone to ulceration or Monomer and polymer adhesives are used in both indus irritation by the devices. trial (including household) and medical applications. U.S. Pat. No. 4,287.177 to Nakashima et al. discloses a Included among these adhesives are the 1,1-disubstituted protective covering material for forming a film or coat on the ethylene monomers and polymers, Such as the skin or wound Surface, wherein the film may contain an C-cyanoacrylates. Since the discovery of the adhesive prop 15 anti-fungal agent that is controllably released when the erties of Such monomers and polymers, they have found composition is placed in contact with the skin. U.S. Pat. Nos. wide use due to the Speed with which they cure, the Strength 5,684,042; 5,753,699; 5,762,919; 5,783,177; and 5,811,091 of the resulting bond formed, and their relative ease of use. to Greffet al. disclose a cyanoacrylate composition with a These characteristics have made the C-cyanoacrylate adhe compatible anti-fungal agent to form an anti-fungal poly Sives the primary choice for numerous applications Such as meric cyanoacrylate film to be applied on mammalian skin bonding plastics, rubbers, glass, metals, Wood, and, more as wound dressings, wound bandages, Surgical incise drapes, recently, biological tissues. wound closure materials and the like. It is known that monomeric forms of C-cyanoacrylates are Tinea cruris, also referred to generally as jock itch or extremely reactive, polymerizing rapidly in the presence of ringworm of the groin, is a fungal or dermatophy even minute amounts of an initiator, including moisture 25 tosis of the groin, perineum and perineal regions, generally present in the air or on moist Surfaces Such as animal Seen in males, and Sometimes spreading to contiguous areas, (including human) tissue. Monomers of C-cyanoacrylates generally caused by fungal Species Such as those of are anionically polymerizable or free radical polymerizable, MicroSporum, Trichophyton, and Epidermophyton, particu or polymerizable by Zwitterions or ion pairs to form poly larly by the fungal Species of Trichophyton and Epidermo mers. Once polymerization has been initiated, the cure rate phyton. The condition generally includes Severely pruritic, can be very rapid. Sharply demarcated lesions with a raised erythematous mar Medical applications of 1,1-disubstituted ethylene adhe gin and thin, dry Scaling. Tinea cruris often accompanies Sive compositions include use as an alternate or an adjunct tinea pedis, or Athlete’s Foot. to Surgical Sutures and/or Staples in wound closure, as well Physicians commonly prescribe in the form as for covering and protecting Surface wounds Such as 35 of powders, aeroSols, liquids or creams for the treatment of lacerations, abrasions, burns, Stomatitis, Sores, minor cuts tinea cruris. Such medications are also commonly obtained and Scrapes, and other wounds. When an adhesive is applied by individuals “over-the-counter” for treatment of the same to Surfaces to be joined, it is usually applied in its mono skin condition. The source of the affliction often is a public meric form, and the resultant polymerization gives rise to the Safety and health concern, as the occurrence of tinea cruris desired adhesive bond. 40 is higher in public areas Such as locker rooms, public U.S. Pat. Nos. 5,514,371, 5,514,372, 5,575,997, 5,624, showers, Sports facilities, and the like. 669, and 5,582,834 to Leung et al. disclose the addition of Often the condition occurs on the skin areas of the groin, a therapeutic agent in a cyanoacrylate composition. The perineum and perineal regions that are prone to higher levels cyanoacrylate adhesive forms a matrix for the therapeutic 45 of moisture and that come into frequent frictional contact agent, with the therapeutic agent being released in Vivo over with a patient's clothing or with other skin Surfaces. AS a time from the matrix during biodegradation of the polymer. result of this frictional contact, as well as contact with U.S. Pat. No. 5,762.955 to Smith discloses a treatment for clothing and the like, topically applied medications can be healthy, damaged, diseased, or infected biological tissue by more easily removed from the affected areas of a patient's applying a bioadhesive coating in conjunction with a medi 50 skin. Moreover, the topically applied medications are more cation. The treatment is directed, in part, to treating external prone to the affects of moisture that is present at the affected biological tissue that may be affected by harmful afflictions area of skin. These difficulties mean that treatment is Sig Such as bruises, burns, dermatological afflictions, , nificantly reduced, because the is not held in gashes, wounds, herpes Sores, canker Sores, or intra-oral place for a Sufficient time. As a result, the efficacy of the lesions, and Skin cancerS Such as leukemia. Smith further 55 treatment is significantly reduced, and patients must fre discloses Several medications that may be used including quently reapply medications So that the affected area corticosteroids, fluoroouracil, obtundants, anesthetics, receives proper treatment. Furthermore, the inconvenience , fungicides, anti-inflammatory agents, antibacte of bandages due to constant or frequent movement and rial agents, agents, and other medications or flexing of the skin, the Small Surface area usually involved, combinations of medications used in processes for healing 60 friction and moisture, make bandages impractical for mini tissue, promoting or preventing blood clotting, destroying mizing frictional contact that occurs at the affected areas of cancer cells, palliative treatments and killing of bacteria or a patient's skin, as well as impractical as a means to hold the Viruses. medication in place for longer periods of time. U.S. Pat. No. 4,880,416 to Horiuchi et al., discloses a In addition, conventional treatment regimens for tinea dermal bandage of a preformed film-like adhesive material 65 cruris continue to pose significant public health and Safety for preventing dermally applied ointments, creams, concerns. Because conventional treatments have the above Solutions, powders, etc. from falling off, and for delivering described problems of being easily removed from the US 6,585,967 B2 3 4 afflicted Skin and being Susceptible to moisture, there is a tive treatment, and minimize the possibility of re-infection much greater chance that the fungal infection can be spread. or transmission of the fungal infection to other areas of the This spread of the fungus can be either to other parts of the patient's body or to other individuals. Likewise, the same Same patient's body, or to other individuals. benefits can be obtained by applying the composition of the Despite the known use of adhesives, Such as described present invention to an area prone or Susceptible to infection, above, Such adhesives have not been used in the treatment which in turn aids in preventing spread or transmission of of tinea cruris. Instead, the majority of tinea cruris treat the infection. ments currently on the market include topically applied In addition to forming a stronger barrier to keep moisture medications that have the problems of being easily removed away from the affected area while maintaining active agents from the application Site, being prone to moisture effects, in contact with the area, cyanoacrylate compounds are also and resulting in higher spread or transmission rates. desirable for the treatment or prevention of tinea cruris Therefore, there is a need for an alternative tinea cruris because of their inherent anti-fungal properties. In labora treatment that remains at the application Site for longer tory tests, it has been discovered that at least Some periods, that reduces the spread or transmission of the fungal cyanoacrylate compounds or formulations, even in the infection, and that provides fast, effective relief from the 15 absence of an added anti-fungal agent, appears to inhibit Symptoms of tinea cruris. fungal infections. Because of this anti-fungal property, Such cyanoacrylate compounds and formulations may be espe SUMMARY OF THE INVENTION cially desirable for treating or preventing tinea cruris, even The present invention provides methods for preventing without the introduction or pre-application of other anti and/or treating tinea cruris by applying a monomeric adhe fungal agents. Moreover, the anti-fungal properties of Such Sive composition to the affected area, or to areas that are cyanoacrylate compounds and formulations may also be prone to infection. The monomeric adhesive composition of beneficial in instances where an anti-fungal agent is applied the present invention preferably comprises a polymerizable before, or together with, the cyanoacrylate, because the 1,1-disubstituted ethylene monomer Such as a cyanoacrylate cyanoacrylate can continue to provide its anti-fungal effect monomer, that may include or be accompanied by an addi 25 even after the applied anti-fungal agent has been completely tional anti-fungal agent. The composition reduces moisture absorbed or used up. contact with the affected Skin area, keeps any active ingre In addition, cyanoacrylate compounds are also useful as dients in contact with the affected Skin area for a longer time, anti-fungal agent carriers or delivery agents. In this capacity, provides fast and effective treatment of tinea cruris, and can the cyanoacrylate compound provides the same protective act to prevent infection in the first instance, or prevent the and anti-fungal benefits, but also offers the added benefit of Spread of an infection to other areas. enhancing the treatment of the affected area by controllably The present invention provides an unexpected treatment releasing an anti-fungal agent to the affected area, or pro or prevention composition and method for tinea cruris, viding prolonged preventative benefits to an applied area by because polymerizable monomerS Such as 1,1-disubstitutyed controllably releasing an anti-fungal agent to the area. ethylene monomers and cyanoacrylates have not previously 35 The present invention also provides various applicators been used to treat or prevent Such skin conditions. Moreover, that are Suitable for applying the adhesive composition. while Such polymerizable monomers have been variously DETAILED DESCRIPTION OF PREFERRED used on other parts of the body, Such as for Sealing open EMBODIMENTS wounds, their use for treating or preventing tinea cruris, on 40 areas of skin in the groin and Surrounding areas, is an This invention is directed to methods of treating tinea entirely and new and unexpected use of the materials. cruris, commonly known as Jock Itch, by applying a mono The present treatment for or prevention of tinea cruris is meric adhesive composition to an afflicted area of a patient's advantageous for Several reasons. First, because tinea cruris skin, in particular the groin, perineum and perineal regions. affects the skin in a patient's groin and Surrounding areas, it 45 This invention is also directed to methods of preventing is often very difficult for the patient to keep a treatment agent tinea cruris by applying a monomeric adhesive composition in contact with the affected Skin area for an extended period to an area of a patient's skin that is prone or Susceptible to of time. This is either because frictional contact with the Such infection. affected area tends to disturb any applied active agents, or According to embodiments of the present invention, the because higher levels of moisture present in the area tend to 50 adhesive composition can be applied alone, or it can be affect or likewise disturb the applied agent. Furthermore, applied Subsequent to or concurrent with the application of because the treatment and prevention methods of the present a separate anti-fungal agent. Furthermore, in embodiments, invention provide a Stronger physical barrier at the affected the cyanoacrylate composition can itself include an anti skin area, the risks of Spread or transmission of the fungal fungal agent in addition to polymerizable monomer. infection, either to other areas of the patient's body or to 55 According to the present invention, “treat” (or other forms other individuals, is significantly decreased. The present of the word such as “treating” and “treatment”) refers to invention thus provides Significant public health benefits. employment of the methods against an established fungal Because cyanoacrylates tend to polymerize rapidly to infection. “Treat' thus encompasses both amelioration of form a relatively robust polymerized film, cyanoacrylates effects of the fungal infection, Such as by reducing Swelling, applied to an affected area of a patient's groin (or to an area 60 irritation, pain and the like, and active reduction of the prone or Susceptible to infection) can provide fast, effective infection Such as by killing the fungus and preventing protection over the affected area and other Skin Surfaces. By re-growth of the fungus at an infected area. protecting the affected area from moisture and frictional According to the present invention, "prevent” (or other contact, the cyanoacrylate compound can hold any applied forms of the word such as “preventing” and “prevention”) active agents in place for a longer period of time and can 65 refers to employment of the methods against a Subsequent accordingly significantly increase the time of exposure of an fungal infection, Such as at areas of skin that are prone or applied medication to the affected area, ensure more effec Susceptible to fungal infection. “Prevent' thus encompasses US 6,585,967 B2 S 6 both prevention of spread of an established fungal infection, tor or a Stabilizer. Thus, the anti-fungal agent can provide not as well as prevention of infection in the first instance on the only a biological activity, but a chemical one as well. particular patient. Anti-fungal agents that also serve as polymerization ini In embodiments of the invention, an adhesive composi tiators can initiate and/or accelerate the polymerization of tion can be used alone for treating or preventing tinea cruris. In Such embodiments, a patient or care-provider simply the composition when applied to an affected or desired area applies the composition to an area of the Skin, Such as the of skin. Accelerated polymerization reduces the waiting time groin, perineum and perineal regions, afflicted with tinea necessary after application, and makes the composition cruris, or to an area where prevention of infection is desired. more convenient to apply. Suitable anti-fungal agents that The composition then is permitted to polymerize to form a can also serve as initiators include, but are not limited to, robust polymeric coating that effectively covers and protects certain acidic and quaternary ammonium compounds. In the affected or applied area of the patient's skin. Anti-fungal embodiments where the anti-fungal agent also acts as a properties of the composition may inhibit or kill microbes, polymerization initiator or rate modifier, the present inven and the robust polymeric coating that the composition forms tion provides the additional advantage of not requiring that protects the area from frictional contact with clothing or a further, Separate polymerization initiator or rate modifier other skin Surfaces So that prolonged treatment or prevention 15 be used. Furthermore, in these embodiments, the anti-fungal can be achieved. agent is preferably located in a non-contacting relationship Preferably, the composition is applied in a Sufficient with the adhesive composition prior to use, So that premature amount to entirely cover the desired area, which generally polymerization of the adhesive composition does not occur. would correspond to an affected area where tinea cruris is Anti-fungal agents that also serve as Stabilizers can extend present, or to an areas that is prone or Susceptible to tinea the useful life of the composition. By increasing the useful cruris. In embodiments, the composition covers an addi life of the composition, the composition can be stored and tional area around the desired area, for example to prevent packaged for longer periods of time without the risk of further infection. premature polymerization. Suitable anti-fungal agents that According to the present invention, the adhesive compo can also serve as Stabilizers can include, but are not limited sition is preferably permitted to substantially or fully poly 25 to, certain acidic and phenolic compounds Such as phenolic merize to form a polymer film before the treated area is antioxidants. In embodiments where the anti-fungal agent permitted to contact other Surfaces. Thus, for example, when also acts as a Stabilizer for the adhesive composition, the the composition is applied to the groin, the thighs and other present invention provides the additional advantage of not skin areas are preferably kept Separated from each other requiring that a further, Separate Stabilizer be used. until the composition has Substantially or fully polymerized, Furthermore, in these embodiments, the anti-fungal agent is to prevent bonding the thighs and other skin areas together. preferably located in a contacting relationship with the In further embodiments of the present invention, the adhesive composition, Such as being mixed with the adhe adhesive composition can be applied over a medicament for Sive composition, prior to use. treating or preventing tinea cruris. The medicament in this 35 Although a mixture of anti-fungal agent and embodiment is not particularly limited, and can include any cyanoacrylate, according to the present invention, is not of the available medicaments for the skin condition. The limited to a Specific ratio of anti-fungal agent to medicament can also be, or comprise, any Suitable anti cyanoacrylate, the anti-fungal agent is preferably present in fungal agent, as described below. In this embodiment, the an effective amount, preferably a therapeutically effective medicament can be first applied to the affected or desired 40 amount for treating or preventing the tinea cruris. area, followed by application of a polymerizable adhesive When mixed or combined immediately prior to use, the composition. The medicament can be in any Suitable form, anti-fungal agent can be mixed with the polymerizable including liquid, Solid, powder, cream or the like, and can cyanoacrylate composition in a Suitable container and there include only a medicament or can include other Suitable after applied. Alternatively, mixing can be conducted during additives such as diluents, carriers or the like. Where the 45 the application process, for example by using an applicator medicament is in a liquid or a Semi-liquid form, it is that is loaded with anti-fungal agent, which thereby mixes preferred that the medicament be permitted to dry, Substan the agent with the adhesive composition during application. tially or completely, prior to application of the adhesive Suitable anti-fungal agents include, but are not limited to, composition. However, the adhesive composition can also known agents Such as parabens, creSols, , , be immediately applied over the applied medicament, or can 50 polyenes, acidics, mercurials, quaternary ammonium be applied prior to drying of the medicament, if desired. compounds, other agents, non-polymer-Stabilized In embodiments of the present invention, an appropriate, compounds, i.e., that are not complexed with or otherwise preferably monomer-compatible, anti-fungal agent can be part of a polymer Species, mixtures thereof, and the like. mixed with the polymerizable adhesive composition and a Such anti-fungal agents should preferably be present in a resultant composition applied to the affected or desired area. 55 therapeutically effective amount, particularly in cases where In this embodiment, the anti-fungal agent can be mixed with higher amounts may otherwise be toxic to the patient. the polymerizable adhesive composition during manufacture For example, Suitable parabens include, but are not lim (i.e. prior to packaging the materials), or immediately prior ited to, alkyl parabens and Salts thereof, Such as to use. However, the present invention is not limited to Such methylparaben, methylparaben Sodium, , embodiments. Thus, for example, the anti-fungal agent need 60 propylparaben, propylparaben Sodium, butylparaben, and not be monomer-compatible. In these embodiments, the the like. Butyl-paraben is especially preferred as it can also anti-fungal agent can be mixed or combined with the poly act as a Stabilizer for certain polymerizable monomers, Such merizable adhesive composition, usually just prior to as cyanoacrylate monomers, in the adhesive composition. application, and a resultant composition applied to the Suitable cresols include, but are not limited to, creSol, affected or desired area 65 chlorocreSol, and the like. Suitable azoles include, but are In further embodiments of the present invention the not limited to, , , , anti-fungal agent may also Serve as a polymerization initia , , , Saperconazole, US 6,585,967 B2 7 8 , , , , Zinc lactate, nitrate, Silver iodide, Silver acetate, Silver tercanazole, , and the like. Suitable allylamines benzoate, Silver carbonate, Silver chloride, Silver citrate, include, but are not limited to, , SF86-327, and the Silver oxide, Silver Sulfate, and tincture of , as well as like. Suitable polyenes include, but are not limited to, mixtures thereof and the like. Copper peptides are discussed, nyastatin, , pimaricin, and the like. Suitable for example, in “Copper: An Essential Element for Life.” acidics include, but are not limited to, benzoic acid and Salts Pro Cyte Corporation, available at http:// thereof, Sorbic acid and Salts thereof, propionic acids and www.humatech.com/technology.html (Oct. 28, 1999), the Salts thereof, boric acid and Salts thereof, dehydroacetic acid, entire disclosure of which is incorporated herein by refer Sulphurous and Vanillic acids, and alkyl esters of pararhy ence. Further information on anti-fungal activities of metals drobenzoic acid. Suitable mercurials include but are not can be found, for example, in S. Seymour Block, limited to, , phenylmercuric acetate and nitrate, Disinfection, Sterilization and Preservation, 3" Ed., Phila and sodium ethylmercurithiosalicylate. Suitable delphia: Lea & Febiger, 1983, the entire disclosure of which quaternary ammonium compounds include, but are not is incorporated herein by reference. The ions from the metal, limited to, , , which constitute the anti-fungal agent, diffuse into and , and cetyltrimethyl ammonium bro 15 through the adhesive composition. mide. Other known agents that can be used include, but are Other Suitable anti-fungal agents include the various not limited to, hydroquinone, pyrocatechol, resorcinol, 4-n- compounds identified as such in The Merck Index, 12" Ed. hexyl resorcinol, captain (i.e., 3a,4,7,7a-tetrahydro-2- (1996), incorporated herein by reference. Such agents ((trichloromethyl)thio)-1H-isoindole-1,3(2H)-dione), ben include acrisorein, 3-amino-4-hydroxybutyric acid, ammo Zalkonium chloride, benzalkonium chloride Solution, nium mercuric chloride, , amphotericin B, benzethonium chloride, benzoic acid, benzyl alcohol, anthralin, aZaSerine, benzoic acid, , biphenamine, cetylpyridinium chloride, chlorobutanol, dehydroacetic boric acid, bromosalicylchloranilide, buclosamide, acid, o-phenylphenol, , phenylethyl alcohol, potas , , calcium propionate, , sium benzoate, potassium Sorbate, Sodium benzoate, Sodium , , chlorphenesin, , dehydroacetate, Sodium propionate, Sorbic acid, thimerosal, 25 ciclopiro X, cloconazole, clotrima Zole, cloxyquin, thymol, chlorothymol, , chlorobutanol, phenoxy-2- coparaffinate, m-cresyl acetate, cupric Sulfate, dermostatin, , benzyl alcohol, B-phenylethyl alcohol, diamthazole dihydrochloride, , enilconazole, , 6-acetoxy-2,4-dimethyl-m-dioxane 2, etisaZol, exalamide, , filipin, fluconazole, 4,4'trichloro-2'-hydroxy-diphenylether, imidizoldinylether , , fungichromin, , urea compound, bromo-2-nitropropanediol-1,3,5-bromo-5- , halethazole, , heXetidine, isoconazole, nitrol-1,3dioxane 2-methyl 1-4-isothiazolin-3-one and 5 itraconazole, ketoconazole, lanoconazole, loflucarban, chloro derivative 1-(3-chloro allyl)-3, 5,7-triazo lucensomycin, Magenta I, , 2-(methoxymethyl)- 1-azoniaadamantane chloride (Dowicil 200), phenylmercu 5-, miconazole, monensin, myxin, naftifine, ric compounds Such as , phenylmer , neomycin undecylenate, , , curic nitrate and phenylmercuric acetate, formaldehyde, 35 oligomycins, , Ontianil, oxiconazole nitrate, formaldehyde generatorS Such as the preservatives Germall pecilocin, perimycin, phenylmurcuric nitrate (basic), potas II(R) and Germall 115(R) (imidazolidinyl urea, available from sium iodide, propionic acid, pyrithione, pyrrolnitrin, Sutton Laboratories, Charthan, N.J.), morpholines, Salicylic rubijervine, Salicylanilide, , Saperconazole, and benzoic acids, Sodium and potassium iodides, Sertaconzole, Siccanin, Sodium propionate, , flucytosine, 5-flucytosine, griseofulvin, , 40 Sulconazole, tenonitro Zole, terbinafine, , cidofovir, famico clovir, Valacyclovir, , thimerosal, tioconazole, , tolindate, , pneumocandins, pradimicins, benanomicins, nikkomycins, triacetin, 2,4,6-tribromo-m-creSol, tubercidin, ujothion, amorolfine, polyoxins, duanorubicin citrate, doxorubicin , Viridin, Zinc propionate, mixtures thereof, hydrocholride, tolnaftate, , butenafine, and erg and the like. estrol biosynthesis inhibitors. 45 In embodiments of the present invention, the monomer Non-polymer-Stabilized compounds, i.e., that are not composition can also be applied in conjunction with one or complexed with or otherwise part of a polymer Species, more conventional skin care additives. Suitable skin care which can be either soluble or insoluble in the monomeric additives that are typically used in the treatment of tinea composition, can also be used. Where the compounds are cruris and that can be applied in place of or in conjunction insoluble in the monomeric composition, they must gener 50 with the monomer composition and/or the anti-fungal agent ally be capable of releasing Species, Such as ions, which are of the present invention include, but are not limited to, Soluble in the monomer composition and provide the anti miconazole nitrate, poVidone iodine complex, cliquinol, fungal effect. Thus Such compounds either themselves are, , tolnaftate and undecylenic acid, mixtures or provide, the anti-fungal agent. Such Suitable non thereof, and the like. polymer-complexed materials include, but are not limited to, 55 In addition, in embodiments where monomer additives metals and metal compounds. Examples of Such metal including, but not limited to those listed above, are insoluble compounds or elemental metals include, but not limited to, with the monomer composition, the additive can be applied mercurial compounds, Such as phenolmercuric chloride, to a skin area before applying the monomer composition. In phenolmercuric acetate, acetomeroctol, nitromersol, Such embodiments, the additive and the monomer compo thimerosal, mercurochrome, mercuric chloride, and mercu 60 Sition can be provided, for example, in Separate packages in ric iodide, elemental metals, Such as Silver and copper; and a kit. metal compounds, Such as copper chloride, copper Sulfate, In other embodiments, where Such additives are soluble copper peptides, Zinc chloride, Zinc Sulfate, Zinc Salts of with the monomer composition, the additives can be com cyanoacrylic acid, Zinc Salts of cyanoacetic acid, Zinc Salts bined with the monomer composition during manufacture of of dicyanoglutaric acid, Zinc Salts of rosin, Zinc oxide, Zinc 65 the composition. Moreover, in cases where the additive is Salts of polycyanoacrylic acid, Zinc Salts of polyacrylic acid, Soluble with the monomer composition, the additive can be Zinc bacitracin, Zinc Salicylate, Zinc Stearate, Zinc citrate, applied before the monomer composition is applied, it can US 6,585,967 B2 9 10 be pre-mixed with and applied together with the monomer patent application Ser. No. 09/471,392 filed Dec. 23, 1999, composition, it can be mixed together with the monomer which are hereby incorporated in their entirety by reference composition immediately before application, or it can even herein. be applied after the monomer composition has been applied. The C-cyanoacrylates of the present invention can be AS a result, in cases where a Soluble additive is to be applied, prepared according to Several methods known in the art. the additive and the composition can be provided in a kit U.S. Pat. Nos. 2,721,858, 3,254,111, 3,995,641, and 4,364, where the additive and the monomer composition are pre 876, each of which is hereby incorporated in its entirety by mixed, or the additive and the monomer composition can be reference he rein, disclose methods for preparing provided Separately to be applied Separately or mixed C-cyanoacrylates. together immediately prior to, during, or after application. The composition may optionally also include at least one Although a mixture of additive and cyanoacrylate, other plasticizing agent that assists in imparting flexibility to according to the present invention is not limited to a specific the polymer formed from the monomer. The plasticizing ratio of additive to cyanoacrylate, the additive is preferably agent preferably contains little or no moisture and should not present in an effective amount, and preferably in a thera Significantly affect the Stability or polymerization of the peutically effective amount. 15 monomer. Examples of Suitable plasticizers include but are When mixed immediately prior to use, the additive can be not limited to tributyl citrate, acetyl tri-n-butyl citrate mixed with the polymerized cyanoacrylate composition in a (ATBC), polymethylmethacrylate, polydimethylsiloxane, Suitable container and thereafter applied. Alternatively, mix hexadimethylsilaZane and others as listed in U.S. patent ing can be conducted during the application process, for application Ser. No. 09/471,392 filed Dec. 23, 1999, the example by using an applicator loaded with Skin care disclosure of which is incorporated in its entirety by refer additive, which thereby mixes the additive with the adhesive ence herein. composition during application. The composition may also optionally include at least one In addition, as discussed above with respect to Suitable thixotropic agent. Suitable thixotropic agents are known to anti-fungal agents, various skin care additives may also the skilled artisan and include, but are not limited to, Silica Serve as polymerization initiators or rate modifiers. Also, 25 gels Such as those treated with a silyl isocyanate, and Suitable skin care additives may serve as Stabilizers for the optionally Surface treated titanium dioxide. Examples of adhesive composition. Suitable thixotropic agents and thickeners are disclosed in, In embodiments, the monomer composition and/or its for example, U.S. Pat. No. 4,720,513, and U.S. patent packaging can be Sterilized. However, Sterilization is by no application Ser. No. 09/374,207 filed Aug. 12, 1999, the means required, particularly in View of the fact that most disclosures of which are hereby incorporated in their entire commercially available products for the treatment of tinea ties by reference herein. cruris are not sterilized. Furthermore, whether or not the The composition may optionally also include thickeners. composition and container is Sterilized, the composition can Suitable thickeners may include poly (2-ethylhexy further include one or more Suitable preservative, as 35 methacrylate), poly(2-ethylhexyl acrylate) and others as described below. listed in U.S. patent application Ser. No. 09/472,392 filed Sterilization of the monomer composition and/or its pack Dec. 23, 1999, the disclosure of which is incorporated by aging can be accomplished by techniques known to the reference herein in its entirety. skilled artisan, and is preferably accomplished by methods The composition may also optionally include at least one including, but not limited to, chemical, physical, and/or 40 natural or Synthetic rubber to impart impact resistance. irradiation methods. Examples of chemical methods include, Suitable rubbers are known to the skilled artisan. Such but are not limited to, exposure to ethylene oxide or hydro rubbers include, but are not limited to, dienes, Styrenes, gen peroxide vapor. Examples of physical methods include, acrylonitriles, and mixtures thereof. Examples of Suitable but are not limited to, sterilization by heat (dry or moist) or rubbers are disclosed in, for example, U.S. Pat. Nos. 4.313, retort canning. Examples of irradiation methods include, but 45 865 and 4,560,723, the disclosures of which are hereby are not limited to, gamma irradiation, electron beam incorporated in their entireties by reference herein. irradiation, and microwave irradiation. A preferred method The composition may optionally also include one or more is electron beam irradiation, as described in U.S. patent Stabilizers, preferably both at least one anionic vapor phase application Ser. No. 09/025,472, filed on Feb. 18, 1998, the Stabilizer and at least one anionic liquid phase Stabilizer. entire disclosure of which is incorporated herein by refer 50 These Stabilizing agents may inhibit premature polymeriza ence. The composition should also show low levels of tion. Suitable stabilizers may include those listed in U.S. toxicity to living tissue during its useful life. In preferred patent application Ser. No. 09/471,392 filed on Dec. 23, embodiments of the present invention, the composition is 1999, the disclosure of which is incorporated by reference sterilized to provide a Sterility Assurance Level (SAL) of at herein in its entirety. Furthermore, certain Stabilizers may least 10. In embodiments, the Sterility Assurance Level 55 also function as anti-fungal agents, Such as, for example, may be at least 10", or may be at least 10, or may be at various acidic anti-fungals, as identified above. least 10. The stability, and thus the shelf-life, of some monomeric The monomer (including prepolymeric) adhesive compo adhesive compositions can be further enhanced and Sition may include one or more polymerizable monomers. extended through careful regulation of the packaging. Preferred monomers that may be used in this invention are 60 Treated (e.g., fluorinated polymer) packaging Such as that readily polymerizable, e.g. anionically polymerizable or free disclosed in copending U.S. patent application Ser. No. radical polymerizable, or polymerizable by Zwitterions or 09/430,289, filed Oct. 29, 1999, which is hereby incorpo ion pairs to form polymers. Such monomers include those rated by reference herein in its entirety, is preferred and may that form polymers, that may, but do not need to, biodegrade. reduce the amount of stabilizer that is combined into the Such monomers are disclosed in, for example, U.S. Pat. Nos. 65 composition. AS mentioned above, certain Stabilizers 5,328,687 and 5,928,611 to Leung et al., U.S. patent appli including, but not limited to, certain acidics can also func cation Ser. No. 09/430,177, filed on Oct. 29, 1999, and U.S. tion as anti-fungal agents. In this case, the amount of the US 6,585,967 B2 11 12 anti-fungal/stabilizer material is either not reduced below a 09/.430,289, 09/430,290, and 09/430,180 filed Oct. 29, 1999; level to provide the desired anti-fungal effect, or a further 09/343,914 filed Jun. 30, 1999; 09/385,030 filed Aug. 30, anti-fungal/non-Stabilizing agent is added to ensure that the 1999; and 09/176,889 filed Oct. 22, 1998; the entire disclo desired anti-fungal effect is provided. Sures of which are incorporated herein by reference. A The compositions may also include pH modifiers to further Suitable application is described in co-pending U.S. control the rate of degradation of the resulting polymer, as patent application Ser. No. 09/989,006 (Attorney Docket disclosed in U.S. patent application Ser. No. 08/714,288, No. 102250), filed concurrently herewith, the entire disclo filed Sep. 18, 1996, the entire disclosure of which is hereby Sures of which are incorporated herein by reference. incorporated by reference herein in its entirety. EXAMPLES Compositions of the present invention may also include at 1O least one biocompatible agent effective to reduce active Example 1 formaldehyde concentration levels produced during in vivo A 2-octyl cyanoacrylate monomer composition is pre biodegradation of the polymer (also referred to herein as pared by adding 30 mg of haloprogin, an anti-fungal agent, “formaldehyde concentration reducing agents”). Preferably, to 2 mL of 2-octyl cyanoacrylate monomer. The mixture is this component is a formaldehyde Scavenger compound. 15 Sealed in a glass vial and Stirred. Examples of formaldehyde Scavenger compounds useful in The characteristics of the composition are observed at this invention include Sulfites; bisulfites; mixtures of Sulfites about one minute after preparation and later at least twenty and bisulfites, etc. Additional examples of formaldehyde four hours after preparation. The results of the observations Scavenger compounds useful in this invention and methods show that the Solution remains clear, indicating that halo for their implementation can be found in U.S. Pat. Nos. progin is Soluble in the monomer and does not cause 5,328,687, 5,514,371, 5,514,372, 5,575,997, 5,582,834 and premature polymerization. 5,624,669, all to Leung et al., which are hereby incorporated The composition is then applied to an affected area of skin herein by reference in their entireties. showing the characteristics of tinea cruris. The monomer To improve the cohesive strength of adhesives formed composition polymerizes in under one minute, resulting in a from the compositions of this invention, difunctional mono 25 polymerized film of material covering the affected area. The meric croSS-linking agents may be added to the monomer polymerized film will remain in place for at least three dayS. compositions of this invention. Such crosslinking agents are While the invention has been described with reference to known. U.S. Pat. No. 3,940,362 to Overhults, which is preferred embodiments, the invention is not limited to the hereby incorporated herein in its entirety by reference, Specific examples given, and other embodiments and modi discloses exemplary cross-linking agents. fications can be made by those skilled in the art without The compositions of this invention may further contain departing from the Spirit and Scope of the invention. fibrous reinforcement and colorants Such as dyes, pigments, What is claimed is: and pigment dyes. Examples of Suitable fibrous reinforce 1. A method of treating tinea cruris, comprising: ment include PGA microfibrils, collagen microfibrils, and 35 a) applying an adhesive composition comprising a poly others as described in U.S. patent application Ser. No. merizable monomer to an area of Skin that is afflicted 09/471,392 filed on Dec. 23, 1999, the disclosure of which with tinea cruris, and is incorporated by reference herein in its entirety. b) allowing said polymerizable monomer composition to The polymerizable compositions useful in the present polymerize to form a polymer film over Said area of invention may also further contain one or more 40 Skin, preservatives, for prolonging the Storage life of the compo wherein Said polymerizable monomer composition com Sition. Suitable preservatives, and methods for Selecting prises an O-cyanoacrylate monomer. them and incorporating them into adhesive compositions, 2. The method of claim 1, wherein said monomer com are disclosed in U.S. patent application Ser. No. 09/430,180, position comprises at least one member Selected form the the entire disclosure of which is incorporated herein by 45 group consisting of ethyl cyanoacrylate, butyl reference. Such preservatives can be in addition to any cyanoacrylate, and 2-octyl cyanoacrylate. anti-fungal agent that may or may not be added to the 3. The method of claim 1, further comprising combining composition, as described above. Such preservatives can be at least one of an anti-fungal agent or a skin care additive included irrespective of whether the composition and con with the polymerizable monomer composition on the area So tainers are Sterilized. 50 that the at least one agent or additive Serves as a polymer In embodiments of the present invention, the composition ization initiator for Said polymerizable monomer composi and/or its applicator may contain materials. Such as a poly tion. merization initiator, accelerator, rate-modifier, and/or croSS 4. The method of claim 1, wherein said composition linking agent for initiating polymerization and/or croSS further comprises at least one Stabilizing agent for Said linking of the polymerizable monomer material. Suitable 55 polymerizable monomer. materials and applicators and packaging Systems are dis 5. The method of claim 4, wherein said stabilizing agent closed in U.S. Pat. No. 5,928,611 and U.S. patent application is also at least one of an anti-fungal agent or a skin care Ser. Nos. 09/430,177, 09/430,176, 09/430,289, 09/430,290, additive. and 09/430,180 filed Oct. 29, 1999; 09/343,914 filed Jun. 30, 6. The method of claim 1, wherein said composition 1999; 09/385,030 filed Aug. 30, 1999; and 09/176,889 filed 60 comprises at least one plasticizer. Oct. 22, 1998; the entire disclosures of which are incorpo 7. The method of claim 6, wherein the plasticizer is rated herein by reference. Selected from the group consisting of tributyl citrate, acetyl According to the present invention, any Suitable applica tributyl citrate, polymethylmethacrylate, polydimethylsilox tor can be used to apply the composition to the affected areas ane and hexadimethylsilaZane. of Skin. Suitable applicators and packaging Systems are 65 8. The method of claim 1, wherein the composition further disclosed in, for example, U.S. Pat. No. 5,928,611 and U.S. comprises at least one of an anti-fungal agent or a skin care patent application Ser. Nos. 09/430,177, 09/430,176, additive. US 6,585,967 B2 13 14 9. The method of claim 8, wherein the composition further Sulbentine, tenonitrozole, tolciclate, tolindate, triacetin, 2,4, comprises said at least one anti-fungal agent and Said at least 6-tribromo-m-creSol, tubercidin, ujothion, undecylenic acid, one anti-fungal agent is Selected from the group consisting Viridin, and Zinc propionate. of parabens, creSols, azoles, allylamines, polyenes, acidics, 12. The method of claim 8, wherein the composition mercurials, quaternary ammonium compounds, and non further comprises said at least one anti-fungal agent and Said polymer-Stabilized compounds. at least one anti-fungal agent is Selected from the group 10. The method of claim 8, wherein the composition consisting of creSol, clotrimazole, tolnaftate, terbinafine and further comprises said at least one anti-fungal agent and Said tioconazole. at least one anti-fungal agent is a paraben Selected from the 13. The method of claim 8, wherein the composition group consisting of alkyl parabens having an alkyl group of further comprises said at least one anti-fungal agent and Said from 1-4 carbon atoms. at least one anti-fungal agent is Selected from the group 11. The method of claim 8, wherein the composition consisting of benzoic acid and Salts thereof, Sorbic acid and further comprises said at least one anti-fungal agent and Said Salts thereof, propionic acid and Salts thereof, boric acid and at least one anti-fungal agent is Selected from the group Salts thereof, dehydroacetic acid, Sulphurous acids, Vanillic consisting of methylparaben, methylparaben Sodium, 15 acids, phenol, creSol, chlorocreSol, o-phenylphenol, ethylparaben, propylparaben, propylparaben Sodium, chlorothymol, parabens, alkyl esters of parahydroxybenzoic butylparaben, creSol, chlorocre Sol, Voriconazole, acid, methyl-p-hydroxybenzoate S, ethyl-p- ketoconazole, fluconazole, itraconazole, miconazole, hydroxybenzoates, propyl-p-hydroxybenzoates, benzyl-p- clotrimazole, Saperconazole, neticonazole, oxiconazole, hydroxybenzoates and butyl-p-hydroxybenzoates, isoconazole, Sulconazole, tercanazole, tioconazole, naftifine, thimersal, phenylmercuric acetate and phenylmercuric SF86-327, nyastatin, amphotericin B, pimaricin, benzoic nitrate, nitromerSol, Sodium ethylmercurithiosalicylate, ben acid and Salts thereof, Sorbic acid and Salts thereof, propi Zalkonium chloride, cetylpyridinium chloride, benzetho onic acids and Salts thereof, boric acid and Salts thereof, nium chloride, cetyltrimethyl ammonium bromide, dehydroacetic acid, Sulphurous and Vanillic acids, alkyl chlorobutanol, phenoxy-2-ethanol, benzyl alcohol, esters of pararhydrobenzoic acid, thiomersal, phenylmercu 25 3-phenylethyl alcohol, chlorohexidine, chloroform, ric borate, phenylmercuric acetate and phenylmercuric 6-acetoxy-2,4-dimethyl-m-dioxane, 2,4,4'trichloro-2'- nitrate, nitromerSol, Sodium ethylmercurithiosalicylate, ben hydroxy-diphenylether, imidizolidinyl urea compound, Zalkonium chloride, cetylpyridinium chloride, benzetho bromo-2nitropropanediol-1,3,5-bromo-5-nitrol-1,3 dioxane, nium chloride, cetyltrimethyl ammonium bromide, 2-methyl-4-isothiazolin-3-one and 5 chloro derivative, and hydroquinone, pyrocatechol, resorcinol, 4-n-hexyl 1-(3-chloroallyl)-3,5,7-triazo 1-azoniaadamantane chloride. resorcinol, 3a,4,7,7a-tetrahydro-2-((trichloromethyl)thio)- 14. The method of claim 8, wherein the composition 1H-isoindole-1,3(2H)-dione, benzalkonium chloride, benze further comprises Said at least one skin care additive and Said thonium chloride, benzoic acid, benzyl alcohol, cetylpyri at least one skin care additive is selected from the group dinium chloride, chlorobutanol, dehydroacetic acid, consisting of miconazole nitrate, poVidone iodine complex, o-phenylphenol, phenol, phenylethyl alcohol, potassium 35 cliquinol, haloprogin, tolnaftate and undecylenic acid and benzoate, potassium Sorbate, Sodium benzoate, Sodium mixtures thereof. dehydroacetate, Sodium propionate, Sorbic acid, thimerosal, 15. The method of claim 8, wherein the at least one thymol, chlorothymol, alcohols, chlorobutanol, phenoxy-2- anti-fungal agent or skin care additive is mixed with the ethanol, benzyl alcohol, B-phenylethyl alcohol, polymerizable monomer composition immediately prior to chlorhexidine, 6-acetoxy-2,4-dimethyl-m-dioxane 2,4, 40 applying the polymerizable monomer composition to the 4'trichloro-2'-hydroxy-diphenylether, imidizoldinylether area of Skin. urea compound, bromo-2-nitropropanediol-1,3,5-bromo-5- 16. The method of claim 8, wherein the at least one nitrol-1,3 dioxane, 2-methyl 1-4-isothiazolin-3-one and 5 anti-fungal agent or skin care additive is mixed with the chloro derivative, 1-(3-chloroallyl)-3,5,7-triazo polymerizable monomer composition during manufacture of 1-azoniaadamantane chloride, formaldehyde, imidazolidinyl 45 the polymerizable monomer composition. urea, morpholines, Salicylic acids, benzoic acids, Sodium 17. The method of claim 8, wherein the composition iodides and potassium iodides, flucytosine, 5-flucytosine, further comprises said at least one anti-fungal agent and Said griseofulvin, terbinafine, cidofovir, famico clovir, anti-fungal agent is butylparaben. Valacyclovir, echinocandins, pneumocandins, pradimicins, 18. The method of claim 1, wherein said composition has benanomicins, nikkomycins, amorolfine, polyoxins, duano 50 a Sterility Assurance Level (SAL) of 10–10. rubicin citrate, doxorubicin hydrocholride, tolnaftate, 19. The method of claim 1, further comprising applying at ciclopiroX, butenafine, ergestrol biosynthesis inhibitors, least one of an anti-fungal agent or a skin care additive to the acrisorein, 3-amino-4-hydroxybutyric acid, ammonium mer area of Skin before applying the adhesive composition. curic chloride, amorolfine, anthralin, aZaSerine, bifonazole, 20. The method of claim 19, further comprising allowing biphenamine, bromosalicylchloranilide, buclosamide, 55 the at least one applied anti-fungal agent or Skin care butoconazole, calcium propionate, candicidin, chlordantoin, additive to Substantially dry before applying the adhesive chlormidazole, chlorphenesin, chlorquinaldol, cloconazole, composition. cloxyquin, coparaffinate, m-cresyl acetate, cupric Sulfate, 21. The method of claim 19, wherein the anti-fungal agent dermostatin, diamthazole dihydrochloride, econazole, is applied and is Selected from the group consisting of enilconazole, etisaZol, exalamide, fenticonazole, filipin, 60 parabens, creSols, and non-polymer-Stabilized compounds. flutrimaZole, fungichromin, hachimycin, halethazole, 22. The method of claim 19, wherein the anti-fungal agent hamycin, he Xe tidine, lanoconazole, loflucarban, is applied and is Selected from the group consisting of alkyl lucensomycin, Magenta I, mepartricin, 2-(methoxymethyl)- parabens having an alkyl group of from 1-4 carbon atoms. 5-nitrofuran, monensin, myxin, natamycin, neomycin 23. The method of claim 19, wherein the anti-fungal agent undecylenate, nifuratel, oligomycins, omoconazole, 65 is applied and is Selected from the group consisting of ontianil, pecilocin, perimycin, pyrithione, pyrrolnitrin, methylparaben, methylparaben Sodium, ethylparaben, rubijervine, Salicylanilide, Sertacon Zole, Siccanin, propylparaben, propylparaben Sodium, butylparaben, creSol, US 6,585,967 B2 15 16 chlorocreSol, Voriconazole, ketoconazole, fluconazole, 25. The method of claim 19, wherein the anti-fungal agent itraconazole, miconazole, clotrimaZole, Saperconazole, is applied and further comprises at least one of a diluent and neticonazole, oxiconazole, isoconazole, Sulconazole, a carrier. tercanazole, tioconazole, naftifine, SF86-327, nyastatin, 26. The method of claim 19, wherein the anti-fungal agent amphotericin B, pimaricin, benzoic acid and Salts thereof, is applied and is in the form of a liquid, a Solid, a powder, Sorbic acid and Salts thereof, propionic acids and Salts O CC. 27. The method of claim 19, wherein the skin care thereof, boric acid and Salts thereof, dehydroacetic acid, additive is applied and is Selected from the group consisting Sulphurous and Vanillic acids, alkyl esters of pararhydroben of miconazole nitrate, povidone iodine complex, cliquinol, Zoic acid, thimerosal, phenylmercuric borate, phenylmercu haloprogin, tolnaftate and undecylenic acid and mixtures ric acetate and , nitromerSol, Sodium thereof. ethylmercurithiosalicylate, benzalkonium chloride, benze 28. The method of claim 1, wherein said adhesive com thonium chloride, benzoic acid, benzyl alcohol, cetylpyri position is applied directly to Said area of Skin, and Said dinium chloride, chlorobutanol, dehydroacetic acid, adhesive composition does not include an anti-fungal agent o-phenylphenol, phenol, phenylethyl alcohol, potassium or a skin care additive. benzoate, potassium Sorbate, Sodium benzoate, Sodium 15 29. The method of claim 28, wherein said polymer film dehydroacetate, Sodium propionate, Sorbic acid, thimerosal, has anti-fungal effects at Said area of skin. thymol, chlorothymol, alcohols, chlorobutanol, phenoxy-2- 30. The method of claim 1, wherein said area of skin is ethanol, benzyl alcohol, B-phenylethyl alcohol, Selected from the group consisting of a patient's groin, chlorhexidine, 6-acetoxy-2,4-dimethyl-m-dioxane 2,4, perineum and perineal regions. 4'trichloro-2'-hydroxy-diphenylether, imidizoldinylether 31. A method of treating tinea cruris, the method com urea compound, bromo-2-nitropropanediol-1,3,5-bromo-5- prising the Steps of nitrol-1,3 dioxane, 2-methyl 1-4-isothiazolin-3-one and 5 a. applying at least one of an anti-fungal agent or a skin chloro derivative, 1-(3-chloroallyl)-3,5,7-triazo care additive to an area of skin that is afflicted with 1-azoniaadamantane chloride and formaldehyde, imidazo tinea cruris; lidinyl urea, morpholines, Salicylic acids, benzoic acids, 25 Sodium iodides, potassium iodides, flucy to Sine, b. applying a polymerizable monomer composition to Said 5-flucytosine, griseofulvin, terbinafine, cidofovir, area of skin over the at least one applied anti-fungal famicoclovir, Valacyclovir, echinocandins, pneumocandins, agent or skin care additive, wherein Said composition pradimicins, be nanomicins, nikkomycins, amorolfine, comprises an O-cyanoacrylate monomer; and polyoxins, duanorubicin citrate, doxorubicin hydrocholride, c. allowing Said polymerizable monomer composition to tolnaftate, ciclopiroX, butenafine, ergestrol biosynthesis polymerize to form a polymer film over Said area of inhibitors, acrisorein, 3-amino-4-hydroxybutyric acid, skin and Said at least one anti-fungal agent or skin care ammonium mercuric chloride, amorolfine, anthralin, additive. a Za Serine, bifo na Zole, biphen a mine, 32. The method of claim 31, wherein said area of skin is bromosalicylchloranilide, buclosamide, butoconazole, cal 35 Selected from the group consisting of a patient's groin, cium propionate, candicidin, chlordantoin, chlormidazole, perineum and perineal regions. chlorphenesin, chlorquinaldol, cloconazole, cloxyquin, 33. A method of treating tinea cruris, the method com coparaffinate, m-cresyl acetate, cupric Sulfate, dermostatin, prising: diamthazole dihydrochloride, econazole, enilconazole, a. combining a polymerizable monomer composition and etisaZol, exalamide, fenticonazole, filipin, flutrimazole, 40 at least one of an anti-fungal agent or skin care additive fungichromin, hachimycin, haletha Zole, hamycin, to form a mixture; heXetidine, lanoconazole, loflucarban, lucensomycin, b. applying Said mixture to an area of skin that is afflicted Magenta I, mepartricin, 2-(methoxymethyl)-5-nitrofuran, with tinea cruris, and monensin, myxin, natamycin, neomycin undecylenate, c. allowing Said mixture to polymerize to form at least one nifuratel, oligomycins, omoconazole, Ontianil, pecilocin, 45 of an anti-fungal containing polymer film or a skin care perimycin, pyrithione, pyrrol nitrin, rubijervine, additive containing polymer film over Said area of Skin, Salicylanilide, Sertacon Zole, Siccanin, Sulb entine, wherein Said polymerizable monomer composition com tenonitrozole, tolciclate, tolindate, triacetin, 2,4,6-tribromo prises an O-cyanoacrylate monomer. m-creSol, tubercidin, ujothion, undecylenic acid, Viridin, and 34. The method of claim 33, wherein said area of skin is Zinc propionate. 50 Selected from the group consisting of a patient's groin, 24. The method of claim 19, wherein the anti-fungal agent perineum and perineal regions. is applied and is Selected from the group consisting of elemental metals and metal compounds. k k k k k