WO2008133982A2 - Adhesive patch with aversive agent - Google Patents

Abstract

The disclosed subject matter provides an adhesive patch that includes a medicament and an aversive agent. The adhesive patch may be a transdermal patch, suitable for systemically delivering a medicament; or may be a topical patch, suitable for locally delivering a medicament to the surface of the skin.

Description

ADHESIVE PATCH WITH AVERSIVE AGENT

Related Application (s)

This patent application claims the priority benefit of U.S. Provisional Patent Application Serial No. 60/926,483 filed April 27, 2007, which application is incorporated herein by reference.

Background Adhesive patches are devices that are applied to the skin for the transdermal or topical delivery of a medication. Medicated adhesive patches typically include a flexible backing having a front side and a back side, wherein said front side includes a pressure sensitive adhesive and a medicament suitable for topical administration to the skin. Such patches release a therapeutically effective amount of the medicament over a prolonged period of time for the treatment of a disease or disorder in a mammal .

Summary

The adhesive skin patch of the disclosed subject matter may be used by either a child or an adult, with a decreased likelihood that a child or mentally impaired adult will place the patch in his mouth.

Problems associated with a child or mentally impaired adult placing the patch in the mouth, and for example ingesting the patch with all of the accompanying ingredients therein, as well as possibly chocking and suffocating, may be avoided. As such, the patch may be used with a higher comfort level that the risks identified above, that are inherently associated with the use of topical adhesive patches, may be avoided or at least minimized.

The disclosed subject matter provides an adhesive patch that includes an effective amount of an aversive agent. The disclosed subject matter also provides a kit that includes: (a) an adhesive patch that includes an effective amount of an aversive agent and (b) packaging material . The disclosed subject matter also provides for methods of medical and/or cosmetic treatment that include applying the adhesive patches described herein to a patient in need of such treatment. As such, the disclosed subject matter provides for adhesive patches described herein for use in medical and/or cosmetic therapy. Specifically, the disclosed subject matter provides for the use of adhesive patches described herein for the manufacture of a medicament, for treating various diseases or disorders. Suitable diseases or disorders include, e.g., acne, pain, inflammation, corns, canker sores, arthritis, headache, migraine, insect bites, smoking, the common cold, cold sores, fever, cracked skin, hemorrhoids, influenza, wrinkles, warts, obesity, toxin accumulation, sleep disorders, blisters, libido impairment, cough, itching, hypertension, postmenstrual syndrome, hypogonadism, fungal infections, depression, post-herpetic neuralgia, hormone deficiency, angina including angina pectoris, erectile dysfunction, symptoms associated with menopause, hypoestrogenism, vulvar and vaginal atrophy, postmenopausal osteoporosis, motion sickness, attention deficit hyperactivity disorder, fertility, neurological disorders including Parkinson's disease, and incontinence.

The adhesive patch may be a topical patch, that may be topically applied to locally deliver one or more medicaments to the surface of the skin.

Alternatively, the adhesive patch may be a transdermal patch, that may be topically applied to systemically deliver a medicament.

In a specific embodiment of the disclosed subject matter, the adhesive patch may include a flexible backing having a front side and a back side. The adhesive patch may further include a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. The ^'formulation includes the aversive agent, in addition to other substances (e.g., medicament and excipient components) .

Brief Description of the Figures

Embodiments of the invention may be best understood by referring to the following description and accompanying drawings which illustrate such embodiments. The numbering scheme for the Figures included herein are such that the leading number for a given reference number in a Figure is associated with the number of the Figure. For example, an adhesive patch 1 may be located in Figure 1. However, reference numbers are the same for those elements that are the same across different Figures. In the drawings : Figure 1 illustrates the front side of an adhesive patch of the disclosed subject matter.

Figure 2 illustrates the back side of an adhesive patch of the disclosed subject matter. 5 Figure 3 illustrates the front side of an adhesive patch of the disclosed subject matter, with a release liner attached to the adhesive patch.

Figure 4 illustrates the back side of an adhesive patch of the disclosed subject matter, with a release 10. liner attached to the adhesive patch.

Figure 5 illustrates the back side of an adhesive patch of the disclosed subject matter, with a release liner attached to the adhesive patch and the adhesive patch is partially detached from the release liner. 15 Figure 6 illustrates the back side of an adhesive patch of the disclosed subject matter, with a release liner attached to the adhesive patch and the adhesive patch is partially detached from the release liner.

Figure 7 illustrates a top view of a specific 0 adhesive patch of the disclosed subject matter.

Figure 8 illustrates a top view of a specific adhesive patch of the disclosed subject matter.

Figure 9 illustrates a specific adhesive skin patch of the disclosed subject matter, wherein the 5 adhesive patch is in use.

Figure 10 illustrates an enlarged cross-sectional view of a specific adhesive patch of the disclosed subject matter. 0 Detailed Description

The disclosed subject matter provides an adhesive patch that includes an aversive agent. The aversive agent is present in a known, discrete, safe (non- toxic), and effective amount. Having a relatively unpleasant taste, the aversive agent effectively minimizes and discourages the occurrence of an animal (e.g., human) from accidentally ingesting the adhesive patch, after the adhesive patch is orally administered. As such, the adhesive patch of the disclosed subject matter may include substances not intended for oral administration, with a diminished likelihood that an animal will ingest the adhesive patch.

The aversive agent has minimal or no therapeutic activity. Additionally, the aversive agent is both topically and orally safe. As such, the adhesive patch will be permitted by any relevant federal or local authority (e.g., the United States Food and Drug Administration (FDA) ) .

The adhesive patch is convenient to use. The adhesive patch also maintains the stability of the aversive agent over an extended period of time. Likewise, the aversive agent will have minimal or no adverse affects upon the functional characteristics of the adhesive patch. For example, the aversive agent will have minimal or no adverse affects upon the stability of the components present in the adhesive patch. The aversive agent will also have minimal or no adverse affects upon the therapeutic effectiveness of the medicaments present in the adhesive patch. Additionally, the aversive agent will have minimal or no adverse affect upon the requisite adhesiveness of any pressure sensitive adhesives present in the adhesive patch.

References in the specification to "one embodiment", "an embodiment", "an example embodiment", etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment . Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.

Transdermal Patch

In a specific embodiment of the disclosed subject matter, the aversive agent may be included in a transdermal patch.

As used herein, a "transdermal patch" refers to a medicated adhesive patch that is placed on the skin, to deliver a time released dose of medicament through the skin and into the bloodstream. A wide variety of pharmaceuticals may be delivered by transdermal patches. Suitable transdermal patches include, e.g., nicotine patches, which release nicotine to help quitting the habit of tobacco smoking. Other transdermal patches administer estrogen for menopause and to prevent osteoporosis after menopause; nitroglycerin for angina; and lidocaine to relieve the pain of shingles (herpes zoster) . Recent developments expanded their use to the delivery of hormonal contraceptives, antidepressants and even pain killers. Some medicaments are combined with substances, such as alcohol, that increase their ability to penetrate the skin in order to be used in a transdermal patch.

Specific exemplary transdermal patches include, e.g., NicoDerm^®, also known as NicoDerm CQ^®, which are over the counter palliative nicotine replacement therapy used to ameliorate the withdrawal effects involved in quitting smoking. Alternative brand names include Prostep^®, Habitrol^®, Nicotrol^®, Nicorette, and

Commit^®.

In a specific embodiment of the disclosed subject matter, a unique adhesive vehicle is provided. The vehicle has pressure sensitive adhesive qualities due to its composition and viscoelastic nature. The adhesive is hydrophilic and therefore water may dissolve into or evaporate from the adhesive, depending on the conditions to which it is exposed. This water exchange capability implies that if the adhesive is on a suitably porous backing and is applied to the skin, it will not be occlusive as most drug delivery patches are. The occlusive nature of conventional drug delivery patches is thought to play an important role in enhancing drug absorption, but also often results in greater incidence of skin irritation. The relatively low occlusiveness of the disclosed subject matter may be envisioned to be a special adhesive ointment or gel which is water- breathable, such as a water washable or water soluble ointment or gel .

In a specific embodiment of the disclosed subject matter, an ointment or gel on a backing is provided. The ointment or gel includes an aversive agent in a known, discrete, safe, and effective amount. The adhesive patch maintains the stability of the aversive agent over an extended period of time. The backing is pliable and/or stretchable. Since the backing may be porous and/or vapor permeable, many consumers typically refer to the device as a "patch, " a "skin patch," or an "adhesive skin patch." As such, the device (i.e., the ointment or gel on the backing) will herein be referred to as a patch, a skin patch or an adhesive skin patch. It is appreciated that those skilled in the art understand that the term "patch" is used to refer to the device and is not otherwise limiting in any manner.

It is appreciated that those of skill in the art understand that the terms used herein, unless expressly stated otherwise, include the singular as well as the plural. For example, the term "aversive agent" 15 includes the singular (i.e., one aversive agent) as well as the plural (i.e., two or more aversive agents) .

As used herein, "holdout" refers to the physical properties of a backing, relating to the ability of a specific class of gels or ointments to penetrate, cross-link, wet, and/or cure within the matrix of the backing. A specific class of gels or ointments may or may not be able to penetrate a given backing. Upon penetration of a gel or ointment into a backing, the gel or ointment will cross-link, wet, or cure in the backing. As such, the holdout properties are the ability of the gel or ointment to affect the degree of penetration, cross-linking, wetting, and/or curing within the matrix of the backing. Those backings with superior holdout properties will typically prevent, decrease, or lessen the likelihood of the ointment or gel from wetting the backing; will typically increase the likelihood of the ointment or gel to cross-link within the matrix of the backing; will typically increase the likelihood of the ointment or gel to cure within the matrix of the backing; and/or will typically increase the likelihood of the ointment or gel to partially penetrate the matrix of the backing. Referring to Figures 1-10, an adhesive patch 1 of the disclosed subject matter is provided. The adhesive patch 1 includes a formulation 5 located on at least a portion of the front side 3 of the backing 2, in at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. Specifically, the formulation 5 is partially embedded in at least a portion of the front side 3 of the backing 2. In addition to being located in at least a portion of the front side 3 of the backing 2, the formulation 5 is located on a portion of the surface of front side 3 of the backing 2. Specifically, the formulation 5 is located on the entire surface of the front side 3 of the backing 2.

Backing

The backing 2 is defined by a front side 3 (the side exposed to the skin during use) and a back side 4 (the side exposed to the environment during use) . The backing 2 should be nonirritating to human skin. The backing 2 is a self-supporting sheet of water soluble or water insoluble, polymeric or natural material that provides strength and integrity for the formulation 5. The backing 2 of the adhesive patch 1 may be vapor permeable. As such, the backing 2 may be porous, since porosity provides openings for receiving the formulation 5 and it helps to assure that the adhesive skin patch 1 is vapor permeable. Alternatively, in specific embodiments, the backing 2 may be non-porous, such that the adhesive skin patch 1 is relatively occlusive.

Specifically, the backing 2 may retain the formulation 5 while allowing moisture from the skin to pass. The backing 2 may have any suitable thickness, provided the suitable thickness allows for a flexible, bendable, pliable, vapor permeable, and/or a stretchable sheet of water insoluble porous material . Specifically, the thickness of the backing 2 may be about 0.001 mm to about 5.0 mm, about 0.001 mm to about 3.0 mm, or about 0.025 mm to about 1.25 mm.

The backing 2 may be manufactured from any suitable material, provided the suitable material may form a flexible, bendable, pliable, and/or stretchable backing 2. The backing 2 includes a flexible porous sheet of water soluble or water insoluble material that provides support for the adhesive skin patch 1. The backing 2 may include water soluble or -water insoluble polymeric fibers, a porous film, or any other kind of matrix with spaces within the matrix. A specific backing 2 is a lightweight, porous, pliable strip composed of a nonwoven fabric of polymeric or natural fibers such as polyester, polyolefin, cotton or cellulose fibers bonded together with a sizing resin, entanglement, or thermal process. The backing 2 may be woven or nonwoven. Specifically, the backing 2 includes nonwoven fabric. Alternatively, in specific embodiments, the backing 2 may include open cell foam.

Specifically, the backing 2 may include polyester fibers, polyurethane fibers, polyolefin fibers, polyamide fibers, natural fibers, cotton fibers, copolyester fibers, cellulose acetate fibers, polycellulose fibers, or any mixture thereof. Additional stable, water insoluble flexible sheet materials and methods for manufacturing the suitable backings 2 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein, and are suitable as backings 2 according to the disclosed subject matter. The infusion of the formulation 5 into the backing 2 may be accomplished, e.g., with the use of a continuous process mixer, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein; or as discussed herein.

Alternatively, the backing 2 may be a non-woven backing 2 that is treated by coating: the front side 3 of the backing adhesive patch 1, the back side 4 of the backing 2, or both the front side 3 and back side 4 of the backing 2; with a silicone-containing compound, a fluorocarbon solution, or a combination thereof. Suitable silicone-containing compounds include, e.g., polydimethyl siloxanes, dialkylsiloxanes , dimethylsiloxo vinyl alkenes, dialkylsiloxo vinyl alkenes, dimethylsiloxo acrylates, dialkylsiloxo acrylates, vinyl terminated polydimethylsiloxane, and vinyl terminated polydialkylsiloxane . The exemplary silicone- containing compounds are commercially available from, e.g., Goldschmidt Chemical Corp. (Essen, Germany); GE Silicones (Waterford, NY) ; Wacker Silicone Corp. (Adrian, MI) ; and Dow Corning Corp. (Midland, MI) .

The backing 2 may be manufactured from a suitable non-woven fabric that is commercially available from, e.g., Freudenberg Faservliesstoffe KG (Weinham,

Germany) ; Sontara Technologies (division of DuPont Corporation) (Old Hickory, TN); Lystil S. A. (Brignoud Cedex, France) ; Dexter Nonwovens (Windsor Locks, CT) ; and Chicopee (New Brusnwick, NJ) . Other commercial vendors that supply suitable non-woven fabrics may be found at the Technical Textiles and Nonwoven website (http://www.ttna.com.au/) , April 23, 2007.

It has surprisingly been discovered that the use of a treated backing, such as a fluorocarbon treated non-woven backing, typically increases the yield of an adhesive patch. The use of a backing material that has been treated with a sizing agent allows for the effective control of the rate of penetration, such that the gel or ointment has solidified after it has begun to penetrate the backing, but before it has passed completely through the backing. In addition, the use of a backing material that has been treated with a sizing agent allows for the effective control of the depth to which the ointment or gel will easily penetrate before solidifying. It has surprisingly been discovered that increasing the control of the rate at which the ointment or gel penetrates the backing typically improves the overall yield of the production process by reducing the amount of material which must be discarded because the back side of the backing has become too tacky for either processing or for consumer acceptance. At least a portion of the backing 2 may be treated with a sizing agent 8 such that the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm² to about 65 dynes/cm². Specifically, the portion of the backing 2 that is treated with the sizing agent 8 may have a surface energy of about 27 dynes/cm² to about 56 dynes/cm². The sizing agent 8 lowers the surface energy of the portion of the backing 2 that is treated with the sizing agent 8. Any suitable sizing agent 8 may be employed, provided the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm² to about 65 dynes/cm². Suitable sizing agents 8 include, e.g., fluorocarbon solutions, silicone-containing compounds, and combinations thereof. Specifically, the backing 2 may be a non-woven backing 2 that is treated with a fluorocarbon. For example, the fluorocarbon treated backing 2 may be, e.g., Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M1573 F, Vilmed M1573 FH, Vilmed M1577 F, Vilmed M1578 F, or Vilmed M1578 FH; which are all commercially available from Freudenberg Faservliesstoffe KG (Weinham, Germany) . Alternatively, the silicone treated backing 2 may be a non-woven backing 2 that is coated with one or more silicone-containing compounds, e.g., a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkenes, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, and a vinyl terminated polydialkylsiloxane .

At least a portion of the backing 2 may be treated with the sizing agent 8. The portion of the backing 2 that is treated with the sizing agent 8 may be that portion of the backing 2 that may typically include the formulation 5. The entire surface of the front side 3 of the backing 2 may be treated with the sizing agent 8 or a portion of the surface of the front side 3 of the backing 2 may be treated with the sizing agent 8. Specifically, the entire surface of the front side 3 of the backing 2 may be treated with the sizing agent 8. In addition to the surface of the front side 3 of the backing 2 being treated with the sizing agent 8, the sizing agent 8 may penetrate at least a portion of the underlying surface (e.g., one- tenth to about nine-tenths the thickness, or about one-fourth to about nine-tenths the thickness) of the backing 2. Specifically, the sizing agent 8 may penetrate the entire underlying surface of the backing 2.

Suitable fluorocarbon treated backings 2 include, e.g., Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed

M1573 F, Vilmed M1573 FH, Vilmed M1577 F, Vilmed M1578 F, and Vilmed M1578 FH; which are all commercially available from Freudenberg Faservliesstoffe KG (Weinham, Germany) . As shown in Figs. 1-6 and 9-10, the backing 2 includes a front side 3 and a back side 4. The adhesive skin patch 1 includes a formulation 5 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the formulation 5 may be located on the entire surface of the front side 3 of the backing 2 or the formulation 5 may be located on a portion of the surface of the front side 3 of the backing 2.

Specifically, the formulation 5 may be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the formulation 5 may be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the formulation 5 may be partially embedded into the backing 2) .

As shown in Figure 9, the formulation 5 may penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the formulation 5 may penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the formulation 5 may be partially embedded into the backing 2. Specifically, the formulation 5 may be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the formulation 5 is partially embedded into the backing 2) .

Alternatively, a portion of the front side 3 of the backing 2 may include the formulation 5 and other portions of the front side 3 of the backing 2 may include any combination of the pressure sensitive adhesive 14 and solvent 13. For example, a central circular portion of the front side 3 of the backing 2 may include the formulation 5 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14. The formulation 5, when partially embedded into the front side 3 of the backing 2, imparts strength and structure into the adhesive patch 1. For example, when the formulation 5 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized.

When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the formulation 5 may be in continuous contact with the skin surface of the patient .

Specifically, the adhesive skin patch I₇ upon contact with skin, will allow the skin to breathe. More Specifically, the adhesive skin patch 1, upon prolonged contact with skin, will hold in place the formulation 5 and will permit the skin to breathe over prolonged periods of time typically experienced with the use of the patch, e.g., up to about 24 hours, up to about 12 hours, up to about 8 hours, or up to about 6 hours .

As shown in Figs. 3-6 and 9, the adhesive skin patch 1 may be reversibly attached to a release liner 10. The release liner 10 helps to maintain the adhesiveness of the adhesive skin patch 1 prior to use, such as during manufacturing, packaging, shipping, and/or storage. Any suitable release liner 10 may be employed for use in the disclosed subject matter. Suitable release liners 10 are readily known to those of skill in the art. See, e.g., U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein for further descriptions of release liners 10 useful in the disclosed subject matter. The release liner 10 may include a perforation 12 that allows the tab section 11 of the release liner 10 to be removed (see, Figs. 3, 5, and 6) . Removal of the tab section 11 of the release liner 10 allows the adhesive skin patch 1 to be removed from the release liner 10 with relative ease.

Medicament

The formulation 5 includes a medicament 21, suitable for topical administration. Suitable medicaments 21 include, e.g., topical analgesics, anti -pruritic agents, anti- inflammatory agents, anesthetic agents, keratolytic agents, rubrefacient agents, non-steroidal anti -inflammatory drugs (NSAIDs), alkaloids, tropane alkaloids, vasodilators, hormones, antidepressants, opiods, amino amides, antibiotic agents, anti-fungal agents, anti-viral agents, cosmetic agents, steroids, topical antitussives, topical acne drugs, and symptomatic cold relievers.

Suitable topical analgesics include, e.g., paracetamol (acetaminophen) , acetylsalicylic acid, the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, COX-2 inhibitors such as rofecoxib and celecoxib, capsaicinoids such as capsaicin (8-methyl- N-vanillyl-6-nonenamide) , dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin and homocapsaicin; and various others. Some other classes of drugs not normally considered analgesics are used to treat neuropathic pain syndromes; these include tricyclic antidepressants and anticonvulsants. Additional suitable analgesics include, e.g., trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid and capsicum.

Suitable anti-pruritic agents include, e.g., menthol, hydrocortisone and camphor.

Suitable anti-inflammatory agents include, e.g., hydrocortisone. Additionally, herbs have anti- inflammatory qualities, including hyssop, ginger, Arnica montana which contains helenalin, a sesquiterpene lactone, and willow bark, which contains salicylic acid.

Suitable anesthetic agents include, e.g., benzocaine and lidocaine.

Suitable keratolytic agents include, e.g., salicylic acid.

Suitable rubrefacient agents include, e.g., capsicum. Suitable non-steroidal anti -inflammatory drugs (NSAIDs) include, e.g., ibuprofen, especially the S- isomer of ibuprofen.

Suitable alkaloids include, e.g., nicotine and bloodroot (Sanguinaria Mayadensis, Bloodroot promotes the natural self-destruction (apoptosis) of maycer cells, like squamous cell carcinoma) .

Suitable tropane alkaloids include, e.g., scopolamine, also known as hyoscine. Suitable vasodilators include, e.g., nitroglycerin (NG) , also known as nitroglycerine, trinitroglycerin, and glyceryl trinitrate.

Suitable hormones include, e.g., estrogen and testosterone.

Suitable antidepressants include, e.g., Selective serotonin reuptake inhibitors (SSRIs) , Serotonin- norepinephrine reuptake inhibitors (SNRIs) , Noradrenergic and specific serotonergic antidepressants (NASSAs) , Norepinephrine

(noradrenaline) reuptake inhibitors (NRIs) , Norepinephrine-dopamine reuptake inhibitors (NDRIs) , Tricyclic antidepressants (TCAs) , Monoamine oxidase inhibitor (MAOIs), and Augmenter drugs. Suitable Selective serotonin reuptake inhibitors (SSRIs) include, e.g., fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro, Esipram) , citalopram (Celexa) , and sertraline (Zoloft) .

Suitable Serotonin-norepinephrine reuptake inhibitors (SNRIs) include, e.g., venlafaxine (Effexor) and duloxetine (Cymbalta) .

Suitable Noradrenergic and specific serotonergic antidepressants (NASSAs) include, e.g., mirtazapine (Avanza, Zispin, Remeron) . Suitable Norepinephrine (noradrenaline) reuptake inhibitors (NRIs) include, e.g., reboxetine (Edronax) .

Suitable Norepinephrine-dopamine reuptake inhibitors (NDRIs) include, e.g., bupropion (Wellbutrin, Zyban) . Suitable Tricyclic antidepressants (TCAs) include, e.g., amitriptyline, citalopram and venlafaxine . Suitable Monoamine oxidase inhibitor (MAOIs) include, e.g., moclobemide (Manerix) , and selegiline (marketed as Emsam) .

Suitable Augmenter drugs include, e.g., tryptophan (Tryptan) and buspirone (Buspar) .

An additional suitable antidepressant is selegiline (Eldepryl) .

Suitable opioids include, e.g., fentanyl . Suitable amino amides include, e.g., prilocaine and lidocaine.

Suitable topical antitussives include camphor, menthol, eucalyptus oil, turpentine oil, thymol, or a combination thereof.

Suitable cosmetic agents include, e.g., antioxidants, collagen synthesis stimulators, fibroblast growth stimulators, collagen cross -linking inhibitors, caffeine and theophyline.

Suitable antioxidants include, e.g., free radical scavengers, e.g., alpha hydroxy acids, beta hydroxy acids, Vitamin C, Vitamin E, Vitamin A, lycopene, tumeric, green tea, white tea, and acceptable salts thereof.

Suitable alpha hydroxy acids include, e.g., lactic acid, tartaric acid, citric acid, glycolic acid, malic acid, alpha-hydroxy octanoic acid, alpha- hydroxy caprylic acid, mixed fruit acids, sugar maye extracts, and acceptable salts (e.g., ammonium salts) thereof .

Suitable beta hydroxy acid include, e.g., salicylic acid, beta-hydroxybutanoic acid, tropic acid, trethomayic acid, and acceptable salts (e.g., ammonium salts) thereof. Suitable collagen synthesis stimulator include, e.g., plant extracts containing kinetin (6 furfurylaminopurine) , Vitamin C, copper containing peptides, and combinations thereof. Suitable fibroblast growth stimulators include, e.g., copper containing peptides, retin A, cytokines, and combinations thereof.

Suitable cytokines include, e.g., Fibroblast Growth Factors . Suitable collagen cross-linking inhibitors include, e.g., aminoguanidine, carnosine, or a combination thereof.

Suitable vasoconstrictors include, e.g., ephedrine, epinephrine, phenylephrine, and suitable salts thereof.

Suitable antibiotic agents include, e.g., cilastatin, clavulanic acid, folinic acid, probenecid, pyridoxine, sulbactam, dapsone, ethambutol , isoniazid, pyrazinamide, rifampin, streptomycin, capreomycin, ethionamide, para aminosalicylic acid, cycloserine, ciprofloxacin, nalidixic acid, norfloxacin, ofloxacin, imipenam, meropenem, cilistatin, cefadroxil, cefazolin, cephalexin, cephalothin, cefaclor, cefamandole, cefonicid, cefoxitin, cefuroxine, cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, moxalactam, cefepine, bacitracin, vancomycin, aztreonam, amoxicillin, clavulanic acid, benzathine, penicillin g, penicillin v, ampicillin, carbenicillin indamyl , carbenicillin, mezlocillin, piperacillin, ticarcillin, cloxacillin, dicloxacillin, floxacillin, methicillin, nafcillin, oxacillin, colistmethate, polymixin b, trimethoprim, co- trimoxazole, mafenide, sulfadiazine, sodium sulfacetamide, sulfacytine, sulfadiazine, sulfamethoxazole , sulfapyridine, sulfasalazine, sulfisoxazole, chloramphenicol, clindamycin, spectinomycin, azithromycin, clarithromycin, erythrmoycin, erythromycin estolate, spiramycin, chlortetracycline, demeclocycline, doxycycline, minocycline, oxytetracycline, amikacin, kanamycin, neomycin, streptomycin, tobramycin, nitrofurantoin, griseofulvin, potassium iodide, fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole, amphotericin b, nystatin, niclosamide, nifurtimox, piperazine, praziquantel, pyrantel pamoate, ascariasis, pinworm, thiabendazole, amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine, pyrimethamine, quinidine gluconate, fansidar, diloxanide furoate, melarsoprol, nifurtimox, paromomycin, pentamidine, sodium stibogluconate, suramin, metronidazole, foscarnet, 3-deoxythmidin-2 - ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, foscarnet, 3 -deoxythmidin-2 - ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, and pharmaceutically acceptable salts thereof.

Suitable analgesics, antipruritics, and/or anesthetics include, e.g., camphor, menthol, benzocaine, butamben picrate, dibucaine, dibucaine hydrochloride, dimethisoquin hydrochloride, dyclonine hydrochloride, lidocaine, metacresol, lidocaine hydrochloride, pramoxine hydrochloride, tetracaine, tetracaine hydrochloride, benzyl alcohol, camphorated metacresol, juniper tar, phenol, phenolate sodium, resorcinol, diphenhydramine hydrochloride, tripelennamine hydrochloride, hydrocortisone, hydrocortisone acetate, camphorated metacresol, and combinations thereof. Specifically, the anesthetic may be lidocaine, which is commercially available from Hawkins Chemical (Minneapolis, MN), and camphor, which is commercially available from Jiangsu High Hope (Waxi City, China) .

Suitable corticosteroids are known to those of skill in the art and are disclosed, e.g., in Goodman Gilman, Alfred; Goodman, Louis S.; Gilman, Alfred; Goodman and Gilman' s The Pharmacological Basis of Therapeutics, Sixth Edition, pp .1482 -1486 ;

Christophers, Enno; Schόpf, Erwin; Kligman, Albert M. ; Stoughton, Richard B.; and Topical Corticosteroid Therapy; A Novel Approach to Safer Drugs, Raven Press, pp. 3-5. Suitable corticosteroids include, e.g., Cortisol (hydrocortisone); tetrahydrocortisol ; prednisone (cortisone) ; prednisolone (Cortisol) ; Sa- methylprednisolone; fludrocortisone (9α- fluorocortisol) ; 11-desoxycortisol ; cortisone (11- dehydrocortisol) ; corticosterone ; triamcinolone (9α- fluoro-lδα-hydroxyprednisolone) ; paramethasone (βot- fluoro-16α-methylprednisolone) ; betamethasone (9cκ- fluoro-16/3-methylprednisolone) ; dexamethasone (9α- fluoro-lδα-methylprednisolone) ; desoxycorticosterone acetate (doca acetate, percorten acetate); desoxycorticosterone pivalate (percorten pivalate) ; fludrocortisone acetate (florine acetate) ; Cortisol (hydrocortisone) (cortef, hydrocortone) ; Cortisol acetate (cortef acetate, hydrocortone acetate); Cortisol cypionate (cortef) ; Cortisol sodium phosphate (hydrocortone phosphate) ; Cortisol sodium succinate (solu-cortef ) ; beclopmethasone dipropionate (vanceril); betamethasone (celestone) ; betamethasone sodium phosphate and acetate (celestone soluspan) ; betamethasone dipropionate (diprosone) ; betamethasone valerate (valisone) ; betamethasone benzoate (benisone, flurodate) ; cortisone acetate (cortone acetate) ; dexamethasone (decadron, gammacorten) ; dexamethasone sodium phosphate (decadron phosphate, hexadrol phosphate); dexamethasone acetate (decadron-L. A. ) ; fuprednisolone (alphadrol) ; meprednisone (betapar) ; methylprednisolone (medrol) ; methylprednisolone acetate (depo-medrol , medrol acetate); methylprednisolone sodium succinate (solu-medrol) ; paramethasone acetate (haldrone) ; prednisolone (delta- cortef) ; prednisolone acetate (meticortelone acetate) ; prednisolone sodium phosphate (hydeltrasol) ; prednisolone sodium succinate (meticortelone soluble) ; prednisolone tebutate (hydelta-T . B .A. ) ; prednisone (deltasone, paracort) ; triamcinolone (aristocort, kenacort) ; triamcinolone acetonide (aristoderm, kenalog) ; triamcinolone diacetate (aristocort diacetate, kienacort diacetate); triamcinolone hexacotonide (aristospan) ; desonide (tridesilon) ,- desoximetasone (topicort) ; flumethasone pivalate (locorten) ; fluocinolone acetonide (fluonid, synalar) ; fluocinonide (lidex, topsyn) ; fluorometholone (oxylone) ; flurandrenolide (cordran) ; halcinonide (halog) ; and medrysone (HMS liquifilm, medrocort) . See, e.g., Goodman Gilman, Alfred; Goodman, Louis S.; Gilman, Alfred; Goodman and Gilman' s The Pharmacological Basis of Therapeutics, Sixth Edition, pp.1482-1486 (Tables 63-3 and 63-4).

Additional suitable exemplary corticosteroids include aclometasone dipropionate (alclovate) ; betamethasone- 17 -benzoate (benisone, flurobate) ; betamethasone dipropionate (diprosone) ; betamethasone-

17-valerate (valisone) ; clobetasol propionate (temovate) ; desonide (desowen, tridesilon) ; dexamethasone (aeroseb-D) ; desoximetasone (topicort); diflorasone diacetate (florone) ; flumethasone pivalate (locorten) ; fluocinolone acetonide (synalar, synalar-

HP, neosynalar, fluonid) ; fluocinolone acetonide acetate (lidex; lidex-E; topsyn) ; fluorometholone (oxylone) ; flurandrenolide (cordran) ; halcinonide (halog) ; hydrocortisone (cort-dome, lubricort) ; hydrocortisone acetate (cortef, carmol HC, neo- cortef) ; hydrocortisone-17-valerate (westcort) ; prednisolone (meti-derm) ; and triamcinolone acetonide

(kenalog, orabase, kenalog-S, mycolog, aristocort, aristocort-A, aristoderm, neo-aristoderm, neo- aristocort) . See, e.g., Christophers, Enno; Schόpf,

Erwin; Kligman, Albert M.; Stoughton, Richard B . ;

Topical Corticosteroid Therapy; A Novel Approach to

Safer Drugs, Raven Press, pp. 3-4 (Table 1) . Additional suitable exemplary corticosteroids include temovate; diprolen,- psorcon; temovate; diprolene; cyclocort; diprosone; florone; halog; lidex; maxiflor,- topicort; aristocort A; diprosone; florone; maxiflor; valisone; cordran; kenalog; synalar; topicort LP; westcort; cordran; diprosone; kenalog; locold; synalar; valisone; westcort; aclovate; desowen; locorten; synalar; tridesilone,- valisone; hydrocortisone; dexamethasone; flumethalone,- prednisolone; and methylprednisolone . See, e.g.,

Christophers, Enno,- Schόpf, Erwin; Kligman, Albert M.;

Stoughton, Richard B.; Topical Corticosteroid Therapy;

A Novel Approach to Safer Drugs, Raven Press, p. 5 (Table 2) .

Additional suitable exemplary corticosteroids include diprolene and diprosone . See, e.g.,

Christophers, Enno; Schόpf, Erwin; Kligman, Albert M.;

Stoughton, Richard B.; Topical Corticosteroid Therapy; A Novel Approach to Safer Drugs, Raven Press, p. 5

(Table 3) .

Additional suitable exemplary corticosteroids include augmented betamethasone dipropionate

(diprolene) ; diflorasone diacetate (psorcon) ; clobetasol propionate (temovate) ; halobetasol propionate (ultravate) ; amcinonide (cyclocort) ; betamethasone dipropionate (diprolene, diprosone) ; diflorasone diacetate (florone) ; halcinonide (halog) ; fluocinonide (lidex) ; diflorasone diacetate (maxiflor) ; betamethasone dipropionate (maxivate) ; diflorasone diacetate (psorcom) ; desoximetasone

(topicort) ; (aristocort A) ; amcinonide (cyclocort) ; betamethasone dipropionate (diprosone) ; mometasone furoate (elocon) ; diflorasone diacetate (florone) ; halcinonide (halog) ; fluocinonide (lidex-E) ; diflorasone diacetate (maxiflor) ; betamethasone dipropionate (maxivate, psorion) ; betamethasone valerate (valisone) ; flurandrenolide (cordran) ; fluticasone propionate (cutivate) ; mometasone furoate (elocon) ; triamcinolone acetonide (kenalog) ; fluocinolone acetonide (synalar) ; hydrocortisone valerate (westcort) ; flurandrenolide (cordran) ; fluticasone propionate (cutivate) ; betamethasone dipropionate (diprosone) ; triamcinolone acetonide (kenalog) ; hydrocortisone butyrate (locoid) ; fluocinolone acetonide (synalar) ; betamethasone valerate (valisone) ; hydrocortisone valerate (westcort) ; alclometasone dipropionate (aclovate) ; triamcinolone acetonide (aristocort) ; desonide (desowen) ; flumethasone pivalate (locorten) ; fluocinolone acetonide (synalar) ; desonide (tridesilon) ; betamethasone valerate (valisone) ; hydrocortisone (eldecort, dexamethasone, flumethalone, hydrocortisone, methylprednisolone, or prednisolone); betamethasone; and dexamethasone.

Suitable symptomatic cold relievers include, e.g., wintergreen, menthol, thymol, camphor, oil of peppermint, eucalyptus oil, phenylephrine hydrochloride, pheniramine maleate, benzalkonium chloride, methyl salicylate, pseudoephedrine hydrochloride, oxymetazoline hydrochloride, xylometazoline hydrochloride, methazoline hydrochloride, epinephrine, spirits of turpentine, ephedra (ma huang) , coltsfoot (Tussilago farfara L.), ginger (Zingiber officinale) , and naphazoline hydrochloride .

Suitable topical acne drugs include, e.g., salicylic acid, resorcinol, resorcinol acetate, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, and pharmaceutically acceptable salts thereof.

In one specific embodiment of the disclosed subject matter, the medicament (e.g., analgesic, anesthetic, or antipruritic) includes one or more of camphor, menthol, benzocaine, butamben picrate, dibucaine, dibucaine hydrochloride, dimethisoquin hydrochloride, dyclonine hydrochloride, lidocaine, metacresol, lidocaine hydrochloride, pramoxine hydrochloride, tetracaine, tetracaine hydrochloride, benzyl alcohol, camphorated metacresol, juniper tar, phenol, phenolate sodium, resorcinol, diphenhydramine hydrochloride, tripelennamine hydrochloride, hydrocortisone, a corticosteroid, and hydrocortisone acetate .

In a specific embodiment of the disclosed subject matter, the cosmetic agent may include tourmaline,

Vitamin C, Vitamin E, Vitamin A, lactic acid, tartaric acid, citric acid, glycolic acid, malic acid, alpha- hydroxy octanoic acid, alpha-hydroxy caprylic acid, a mixed fruit acid, a sugar maye extract, salicylic acid, beta-hydroxybutanoic acid, tropic acid, trethomayic acid, a plant extract containing kinetin (6 furfurylaminopurine) , Vitamin C, a copper containing peptide, retin A, a cytokine, a Fibroblast Growth Factor, aminoguanidine, carnosine, or a combination thereof.

As used herein, an "analgesic" refers to a topically (i.e., externally) applied agent that relieves pain by altering perception of nociceptive stimuli without producing anesthesia or loss of consciousness; an "antipruritic" refers to a topically (i.e., externally) applied agent that prevents or relieves itching; and an "anesthetic" refers to a topically (i.e., externally) applied agent that may reversibly depress neuronal function, producing loss of ability to perceive pain and/or other sensations (see, Stedman's Medical Dictionary, 25th Ed., 111., 1990, p.65, p.77, and p.99). As used herein, a "cosmetic agent" refers to a substance suitable for topical administration (e.g., skin, hair, and/or nails) for purposes of beatifying a mammal (e.g., human) in accordance with cultural dictates. See, e.g., Stedman's Medical Dictionary, 25th edition, illustrated, p.362 (1991) .

As used herein, a "vasoconstrictor" refers to a substance or agent that promotes the constriction of blood vessels in hemorrhoidal tissue. Mosby's Medical, Nursing, & Allied Health Dictionary, Kenneth Anderson, 5th Ed., St. Louis, MO (1998). The vasoconstrictor is a substance that causes temporary constriction of blood vessels. 21 C. F. R. Chapter 1, Part 346 -- Anorectal Drug Products for Over-The- Counter Human Use .

As used herein, an "antibiotic agent" refers to a compound having activity against either Gram-positive or Gram-negative organisms (i.e., inhibits the growth or destroys the development of either Gram-positive or Gram-negative organisms). Stedman's Medical

Dictionary, Illustrated, (25th Ed.), Williams & Wilkins: Baltimore (1990) and Mosby's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis (1998) . As used herein, "antimicrobial agent" or

"preservative" refers to any substance which prevents bacterial growth, mold growth, fermentation, and/or decomposition. Concise Chemical and Technical Dictionary, 4th enlarged edition, Chemical Publishing Co., Inc., NY, NY p. 939 (1986).

Suitable anti -viral agents include, e.g., Echinacea (Echinacea angustifolia, E. pallida, E. purpurea) , Elderberry (Sambucus nigra) , Garlic (Allium sativum) , Lemon balm (Glycyrrhiza glabra) , Astragalus (Astragalus membranaceus) , eyebright (Euphrasia officinalis) , sage (salvia officinalis) , yarrow (Achillea millefolium) , nettles (Urtica dioica) , peppermint (menthe piperiya) , ephedra (Ephedra sinica) , marshmallow root (Althea officinalis) , mullein leaves or flowers (Verbascum spp.), plantain leaf (Plantago lanceolata, P. major), licorice root, thyme (Thymus vulgaris) , boneset (Eupatorium perfoliatum) , feverfew (Tanacetum parthenium) , catnip (Nepeta cataria) , yarrow (Achillea millefolium) , elder flower (Sambucus nigra, S. mayadenis) , ginger (Zingiber officinale), Ginko biloba, St. John's wort (Hypericum perforatum L.), and combinations thereof. Additional suitable anti-viral agents include, e.g., zinc, lysine, foscarnet, 3-deoxythmidin-2-ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, viracea2 , cytovene, famciclovir, valaciclovir, penciclovir, hexadecylosypropyl-cidofovir (HDP-CDV) , nonoxynol-9, docosanol (n-docosanol , 1-docosanol, or behenyl alcohol; which is a saturated 22-carbon straight-chain alcohol) , a pharmaceutically acceptable salts thereof, and combinations thereof.

Additional suitable anti-viral agents include, e.g., a hypochloride, a hypochloride generating compound, a peroxide, a peroxide generating compound, an organic halide, an organic halide generating compound, and combinations thereof.

Additional suitable medicaments include, e.g., levomenthol, Vitamin B_x, witch-hazel, iron powder, histamine dihydrochloride, beta-carotene, bamboo vinegar, glucosamine / chitin, methyl sulfonyl methane (MSM), clonidine, estradiol, tolnaftate, progesterone / northindrone acetate / norelgestromin, alprostadil, methylphenidate, rotigotine and oxybutynin.

As used herein, "treating" or "treat" includes (i) preventing a pathologic condition (e.g., respiratory infection) from occurring (e.g. prophylaxis) ; (ii) inhibiting the pathologic condition (e.g., respiratory infection) or arresting its development; and (iii) relieving the pathologic condition (e.g., respiratory infection), or symptoms related to the pathologic condition.

The adhesive patch described herein may be a topical patch, that may be topically applied to locally deliver one or more medicaments to the surface of the skin. Alternatively, the adhesive patch may be a transdermal patch, that may be topically applied to systemically deliver a medicament. Either way, the adhesive patch may be employed to treat a disease or disorder in a mammal. Suitable diseases or disorders include, e.g., acne, pain, inflammation, corns, canker sores, arthritis, headache, migraine, insect bites, smoking, the common cold, cold sores, fever, cracked skin, hemorrhoids, influenza, wrinkles, warts, obesity, toxin accumulation, sleep disorders, blisters, libido impairment, cough, itching, hypertension, postmenstrual syndrome, hypogonadism, fungal infections, depression, post-herpetic neuralgia, hormone deficiency, angina including angina pectoris, erectile dysfunction, symptoms associated with menopause, hypoestrogenism, vulvar and vaginal atrophy, postmenopausal osteoporosis, motion sickness, attention deficit hyperactivity disorder, fertility, neurological disorders including Parkinson's disease, and incontinence.

As used herein, "mammal" refers to a class of vertebrate animals of more than 15,000 species, including humans, distinguished by self -regulating body temperature, hair, and in the females, milk- producing mammae. Specifically, mammal may refer to a human, dog or cat. More specifically, mammal may refer to a human.

The amount of medicament 21 present in the therapeutic formulation 5 will typically follow FDA regulations, Federal Register, Vol. 48, No. 27, § 341 or complies with Handbook of Nonprescription Drugs, 10th Edition, 1993, p. 108. While the amount of medicament 21 present in the therapeutic formulation 5 may comply with FDA regulations (e.g., Federal Register, Vol. 48, No. 27, § 341), it is appreciated that those of skill in the art understand that the amount of medicament 21 present in the therapeutic formulation 5 may be higher than the amount permitted by the FDA. See, e.g., Handbook of Nonprescription Drugs, 10th Edition, 1993. This is because there may be a loss of concentration for the medicament 21 during the manufacturing, shipping or storage of the adhesive patch 1. As such, the FDA may allow for slightly more or slightly less (e.g., ±10%) medicament 21 to be present in the stability studies.

Aversive agent

As used herein, an "aversive agent" refers to any substance that is safe (non-toxic) when topically or orally administered, yet produces a relatively unpleasant taste upon oral administration. The relatively unpleasant taste may be, e.g., an extremely bitter taste. In a specific embodiment of the disclosed subject matter, the aversive agent 15 may be denatonium, or a suitable salt thereof.

As used herein, denatonium refers to N-benzyl-2- (2 , 6-dimethylphenylamino) -N, N-diethyl -2- oxoethanaminium. The compound is typically available as a benzoate or saccharide salt (anion) . Denatonium benzoate has a CAS Reg. No. of [3734-33-6] , and is structurally shown below.

Denatonium, usually available as denatonium benzoate (or under trade names such as Bitrex^® or Aversion^®) and as denatonium saccharide, is the most bitter compound known. It was discovered in 1958 during research on local anesthetics by Macfarlan Smith of Edinburgh, Scotland. Dilutions of as little as 10 ppm are unbearably bitter to most humans. Denatonium salts are usually colorless and odorless solids but are often traded as solutions.

Additional suitable aversive agents 15 include, e.g., berberine, bitter apple extracts, dihydrocapsaicin, heptanoyl guaiacylamide, isobutylamides, nonanoyl vanillylamide, phenols, quassin, quercetin, quinine hydrochloride, sucrose octaacetate, allspice, amino acids, benzoic benzylamine amide, bitter aloes, brucine sulfate, brucine, capsaicin analog, chlorosucrose derivatives, denatonium benzoate alkaloids, denatonium chloride, denatonium saccharide, eucalyptus oil, guaiacylamides, heptanoylisobutylamide, homovanillyl octylester, limonin, mace, menthol, methyl anthranilate, naringin, oil of bitter almonds, oil of nutmeg, peppermint oil, phenylthiocarbamide, quassia, quassin, quebracho, quinine, quinine sulfate, quinones, resiniferatoxin, spearmint oil, sucrose benzoate, sucrose derivatives, sucrose octaacetate, tinyatoxin and trichloro anisole. See, e.g., U.S. Patent Nos. 6,652,632 and 7,144,587; U.S. Published Patent Application Nos. 2003/075073 Al and 2003/124185 Al; and Published PCT Patent Application Nos. WO/0145506 Al; WO/03013476 Al; WO/03013479 Al; WO/03035783 Al; WO/9301712 Al; and WO/07022563 Al.

In one specific embodiment of the disclosed subject matter, the aversive agent is not a substance disclosed in U.S. Patent No. 7,011,843.

Any suitable aversive agent 15 may be employed, in any suitable amount, provided:

(1) the aversive agent 15 is safe (non-toxic) for oral and topical administrataion,-

(2) the aversive agent 15 has such a relatively unpleasant taste, that it effectively discourages an animal (e.g., human) from ingesting it;

(3) the aversive agent 15 has minimal or no therapeutic activity; (4) the aversive agent 15 will have minimal or no adverse affects upon the functional characteristics of the adhesive patch 1; and

(5) the aversive agent 15 remains stable in the formulation 5.

Typically, the amount of aversive agent 15 present in the formulation 5 will depend upon the specific compound or compounds employed as the aversive agent 15. Specifically, the aversive agent 15 may be present in about 0.0001 wt . % to about 1.0 wt . % of the formulation 5. More specifically, the aversive agent 15 may be present up to about 1.0 wt . % of the formulation 5, up to about 0.1 wt . % of the formulation 5, or up to about 0.01 wt . % of the formulation 5. The adhesive skin patch 1 includes an aversive agent 15 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the aversive agent 15 may be located on the entire surface of the front side 3 of the backing 2 or the aversive agent 15 may be located on a portion of the surface of the front side 3 of the backing 2. Specifically, the aversive agent 15 may be located on the entire surface of the front side 3 of the backing 2.

In addition to being located on the surface of the front side 3 of the backing 2, the aversive agent 15 may be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the aversive agent 15 may be partially embedded into the backing 2) . As shown in Figure 9, the aversive agent 15 may penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the aversive agent 15 may penetrate about one-tenth to about nine- tenths the thickness of the backing 2, or about one- fourth to about nine-tenths the thickness of the backing 2. As such, the aversive agent 15 may be partially embedded into the backing 2.

Specifically, the aversive agent 15 may be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the aversive agent 15 is partially embedded into the backing 2) . Alternatively, a portion of the front side 3 of the backing 2 may include the aversive agent 15 and other portions of the front side 3 of the backing 2 may include the pressure sensitive adhesive. For example, a central circular portion of the front side 3 of the backing 2 may include the aversive agent 15 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the aversive agent 15 may be in continuous contact with the skin surface of the patient. The aversive agent 15 may be manufactured (i.e., synthesized or partially synthesized) . Alternatively, the aversive agent 15 may be obtained from a plant or plant component (e.g., plant tissue). Suitable plant or plant components include, e.g., a herb, flower, fruit, seed, bark, stem, root, needle, bulb, berry, rhizome, rootstock, leaf, or a combination thereof.

Plant Tissue As used herein, "plant tissue" refers to the tissue of any organism of the plant kingdom, as opposed to one of the animal kingdom or of the kingdoms of Fungi, Protista, or Monera . The plant tissue may be any portion or portions of the plant (e.g., bark, roots, leaves, flowers, needles, bulbs, berries, rhizomes, rootstocks, stems, and seeds) , as well as the entire plant. The tissues of a plant ("plant tissue") generally fall into three main categories: dermal tissue, ground tissue, and vascular tissue. Dermal tissue refers to the "skin" layer of all plant organs and is responsible for environmental interaction (light passage, gas exchange, pathogen recognition and protection, color display, etc.) . Dermal tissue is composed of epidermal cells, closely packed cells that secrete a waxy cuticle that aids in the prevention of water loss. Ground tissue lies between dermal tissue and vascular tissue. The ground tissue comprises the bulk of the primary plant body. Parenchyma, collenchyma, and sclerenchyma cells are common in the ground tissue. In roots, the ground tissue may store sugars or starches to fuel the spring sap flow; in leaves, the ground tissue is the layer responsible for photosynthesis (the mesophyll) . Vascular tissue transports food, water, hormones and minerals within the plant. Vascular tissue includes xylem, phloem, parenchyma, and cambium cells.

As used herein, "bark" refers to the dry, dead outer covering of woody branches, stems and roots of plants that is very distinct and separable from the wood itself. It includes all tissue outside the cambium (growth layer between bark and wood) . As used here the terms "leaf" or "leaves" refer to those parts of a plant which grow along the sides of branches or stems or at the bases of plants. Most are green and contain chlorophyll, though they vary in their shapes and sizes. Leaves are the part of the plant that ordinarily performs photosynthesis (the process that converts sunlight and carbon dioxide into energy) .

As used herein, "needle" generally refers to a narrow stiff leaf, such as those of conifers (e.g., pine trees) .

As used herein, "root" refers to the part of a plant, normally underground, that absorbs nutrients and anchors the plant into the ground. As used herein, "bulb" refers to a spheroidal body growing from a plant either above or below the ground (usually below) , which is usually a bud, consisting of a cluster of partially developed leaves, and producing, as it grows, a stem above, and roots below, (e.g., the onion or tulip bulb) . A true bulb is a complete package containing next year's plant (flower) already forming inside. The contents of the bulb are often enclosed in protective, fleshy scales, which are held together by a small basal plate. The scales are modified leaves that contain enough nutrients to sustain the plant through dormancy and early growth. They may be loose and open like those of a lily, or tightly closed like those of a hyacinth. In many bulbs, a paper-thin tunic protects the scales (lilies don't have a tunic) . Roots will grow from the bulb's basal plate.

As used herein, "berry" refers to any small fruit that is pulpy or succulent throughout, having seeds loosely imbedded in the pulp, such as the currant, grape, or blueberry. Berry may be further defined as an indehiscent fruit derived from a single ovary and having the whole wall fleshy, such as the grape or tomato. Furthermore, berries come in various structures including simple, such as grape; blueberry, cranberry, or aggregate, such as blackberry; raspberry, strawberry mulberry.

As used herein, "rhizome" refers to a horizontal, usually underground stem that often sends out roots and shoots from its nodes (also called rootstalk or rootstock) .

As used herein, "rootstock" refers to a robust plant that provides the root system in grafting, also known as a stock. Scions and buds are grafted and budded to a rootstock or stock. Rootstock also refers to the elongated and often thick rhizomes of certain perennial herbaceous plants such as the Iris, Aspidistra and Solomon's Seal. As used herein, "stem" refers to the main

(usually aerial) axis (sometimes referred to as the trunk or stalk) of a tree, shrub, or plant. "Stem" also refers to the part of the plant that supports the leaves, flowers or fruits of a plant, such as the peduncle of a fruit or the pedicel of a flower.

As used herein, "seed" refers to a ripened ovule, consisting of an embryo with one or more integuments, or coverings, such as an apple seed, a currant seed, dill seed, or kola nut seed. By germination, most seeds produce a new plant. "Seed" also refers to any small seedlike fruit, though it may consist of a pericarp, or even a calyx, as well as the seed proper, such as a parsnip seed or thistle seed. The seed proper has an outer and an inner coat, and within these the kernel or nucleus. The kernel is either the embryo alone, or the embryo enclosed in the albumen, which is the material for the nourishment of the developing embryo. The scar on a seed, left where the stem parted from it, is called the hilum, and the closed orifice of the ovule, the micropyle .

Solvent When present, the solvent 13 may act as a carrier for, and specifically may dissolve, the formulation 5 or any component (s) thereof (e.g., medicament 21 and/or aversive agent 15) . Any suitable solvent 13 may be employed, provided the solvent 13 effectively dissolves the formulation 5 or any component (s) thereof, and the solvent 13 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.

The solvent 13 may include one or more organic compounds, one or more inorganic compounds, or mixtures thereof. Specifically, the solvent 13 will include one or more organic compounds, e.g., esters, terpenes, alcohols, ketones, aldehydes, fatty acids, partially or fully esterified fatty acids, wherein the structures are cyclic, non cylcic (e.g., alkyl) , alicyclic (i.e., a bridged ring compound), or aromatic, as well as organic compounds having combinations of these functional groups. Suitable exemplary solvents 13 are disclosed, e.g., in Aldrich Handbook of Fine Chemicals, 2000-2001 (Milwaukee, WI) . Specifically, the solvent 13 includes a polyhydric alcohol, organic hydrocarbon, water, or a combination thereof. The polyhydric alcohol may be erythritol, propylene glycol, ethylene glycol, triethylene glycol, or a combination thereof.

Erythritol is commercially available from Cragill (Minnetonka, Minnesota) . Additional suitable solvents 13 include, e.g., glycerin; triacetin,- diethylene glycol methyl ether; diethylene glycol methyl ether acetate; 1,3 -propane diol ; 2 -methyl -1 , 3 -propane diol; glycerol ricinoleate,- PEG-6 caprylic / capric glycerides; caprylic / capric triglycerides; propyleneglycol dicaprylate / dicaprate; glycerol monostearate ; glycerol monocaprylate; glycerol monolaurate; neopentyl alcohol; 1-hexademayol ; hydroxypropyl beta-cyclodextrin; vitamin E; vitamin E acetate; deoxycholic acid; taurodeoxycholic acid; 3- [ (3-cholamidopropyl) dimethylammonio] -1-propane- sulfonate; BigCHAP; cholic acid; cholesterol NF; propylene carbonate; lecithin; a medicinally acceptable salt thereof; or a combination thereof.

In a specific embodiment of the disclosed subject matter, the solvent 13 may be a volatile alcohol (e.g., ethanol) . In another specific embodiment of the disclosed subject matter, the solvent may be a volatile alcohol (e.g., ethanol), that partially or completely evaporates during the manufacturing process .

When present, the solvent 13 may be employed in any suitable amount, provided the amount of solvent 13 is effective to dissolve the formulation 5 or any component (s) thereof, and the effective amount of solvent 13 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about

1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. More specifically, the solvent 13 may be present in about 1.0 wt% to about 70.0 wt. %; in about 3.0 wt% to about 50.0 wt. %; or in about 5 wt . % to about 30 wt . % of the formulation 5. Typically, the amount of solvent 13 will depend on the compound or compounds employed as the solvent 13. For example, a polyhydric alcohol may be present up to about 70 wt .% of the formulation 5; or in about

20.0 wt .% to about 60.0 wt . % of the formulation 5; and water may be present in about 2.0 wt . % to about 50.0 wt .% of the formulation 5.

When present, the solvent 13 may be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the solvent 13 may be located on the entire surface of the front side 3 of the backing 2 or the solvent 13 may be located on a portion of the surface of the front side 3 of the backing 2.

Specifically, the solvent 13 may be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the solvent 13 may be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the solvent 13 may be partially embedded into the backing 2) . As shown in Figure 9, the solvent 13 may penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the solvent 13 may penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the solvent 13 may be partially embedded into the backing 2. Specifically, the solvent 13 may be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the solvent 13 is partially embedded into the backing 2) . Alternatively, a portion of the front side 3 of the backing 2 may include the solvent 13 and other portions of the front side 3 of the backing 2 may include any combination of the pressure sensitive adhesive 14 and aversive agent 15. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human) , the solvent 13 may be in continuous contact with the skin surface of the patient .

Pressure Sensitive Adhesive

The formulation 5 may further include a pressure sensitive adhesive. Any suitable pressure sensitive adhesive 14 may be employed, provided the pressure sensitive adhesive 14 provides the requisite adhesiveness to the adhesive skin patch 1 and the pressure sensitive adhesive 14 remains stable in the formulation 5.

Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.

It is appreciated that the suitable pressure sensitive adhesives 14 are known to those skilled in the art . Suitable pressure sensitive adhesives 14 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein. Specifically the pressure sensitive adhesive 14 is an acrylic ester copolymer.

Any suitable amount of pressure sensitive adhesive 14 may be employed, provided the amount of pressure sensitive adhesive 14 effectively provides the requisite adhesiveness to the adhesive skin patch 1 and the effective amount of the pressure sensitive adhesive 14 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The formulation 5 may include a pressure sensitive adhesive 14 in about 0.1 wt . % to about 50 wt . % , in about 0.5 wt . % to about 10.0 wt. %, or in about 1.0 wt . % to about 15.0 wt .% of the formulation 5.

Typically, the suitable amount of pressure sensitive adhesive 14 will depend upon the specific pressure sensitive adhesive 14 employed. For example, the pressure sensitive adhesive 14 may include one or more acrylic ester copolymers. Each of the one or more acrylic ester copolymers may be present up to about 20.0 wt .% of the formulation 5. Specifically, each of the acrylic ester copolymers may be present up to about 40.0 wt . % of the formulation 5, or up to about 30.0 wt .% of the formulation 5. More specifically, all of the one or more acrylic ester copolymers, when combined, may be present in about 3.0 wt . % to about 40.0 wt . % of the formulation 5, or in about 5.0 wt .% to about 30.0 wt . % of the formulation 5. As such, the total amount of acrylic ester copolymers may be about 3.0 wt . % to about 40.0 wt . % of the formulation 5, or about 5.0 wt . % to about 30.0 wt .% of the formulation 5.

Alternatively, the pressure sensitive adhesive 14 may include a hot melt pressure sensitive adhesive 14 or solvent based pressure sensitive adhesive 14 (e.g., polyacrylate, polyisobutylene, and polybutene) , rubber, silicone based pressure sensitive adhesives 14 (e.g., polydimethylsiloxane and resin mixtures), polystyrene-polybutadiene-polystyrene , polystyrene- polyisoprene-polystyrene, polystyrene-poly (ethylene- butylene) -polystyrene block polymers, or any combination thereof. In addition, the adhesive 14 may include a resin emulsion adhesive, wherein the resin emulsion adhesive may include vinyl acetate resin, acrylic ester copolymer, vinyl acetate/diocyl maleate copolymer, acrylic copolymer, or any combination thereof.

Other suitable pressure sensitive adhesives 14 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein.

The pressure sensitive adhesive 14 may be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the pressure sensitive adhesive 14 may be located on the entire surface of the front side 3 of the backing 2 or the pressure sensitive adhesive 14 may be located on a portion of the surface of the front side 3 of the backing 2. Specifically, the pressure sensitive adhesive 14 may be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the pressure sensitive adhesive 14 may be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 may be partially embedded into the backing 2) . As shown in Figure 9, the pressure sensitive adhesive 14 may penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the pressure sensitive adhesive 14 may penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the pressure sensitive adhesive 14 may be partially embedded into the backing 2.

Specifically, the pressure sensitive adhesive 14 may be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 is partially embedded into the backing 2) .

Alternatively, a portion of the front side 3 of the backing 2 may include the pressure sensitive adhesive 14 and other portions of the front side 3 of the backing 2 may include the aversive agent 15. The pressure sensitive adhesive 14, being partially embedded into the front side 3 of the backing 2, imparts strength and structure into the adhesive patch 1.

For example, when the pressure sensitive adhesive 14 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the pressure sensitive adhesives 14 may be in continuous contact with the skin surface of the patient.

Emulsifier

The formulation 5 or pressure sensitive adhesive 14 may optionally include a compound that emulsifies the formulation 5 or the pressure sensitive adhesive 14. One suitable compound that effectively emulsifies the formulation 5 or the pressure sensitive adhesive 14 is pectin. The emulsifier (e.g., pectin) may be present in any suitable amount, provided the suitable amount is effective to emulsify the formulation 5 or the pressure sensitive adhesive 14 and the emulsifier remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Specifically, the emulsifier (e.g., pectin) may be present up to about 30.0 wt .% of the formulation 5, in about 1.0 wt . % to about 20.0 wt .% of the formulation 5, or in about 2.0 wt .% to about 10.0 wt . % of the formulation 5.

Polymer The pressure sensitive adhesive 14 may optionally include one or more polymers 9. The polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5. Any suitable polymer 9 may be employed, provided the polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5, and the polymer 9 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.

Suitable polymers 9 include natural polymers and synthetic polymers. Specifically, the polymer 9 may include, e.g., karaya, a polyacrylamide, xanthum gum, guar gum, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, a derivative of algin, a polyacrylate, gelatin, polymaleic acid, polyacrylic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS, or a combination thereof. Other suitable polymers 9 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein. Specifically, the polymer 9 may include polyacrylamide, karaya, or a combination thereof.

Any suitable amount of polymer 9 may be employed, provided the amount of polymer 9 effectively provides structure and strength to the pressure sensitive adhesive 14 or to the formulation 5, and the effective amount of polymer 9 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Typically, the suitable amount of polymer 9 will depend upon the specific polymer 9 employed. Specifically, karaya may be employed as the polymer 9 up to about 60 wt . % of the formulation 5, in about 5.0 wt . % to about 45 wt . % of the formulation 5, or in about 8.0 wt . % to about 40 wt .% of the formulation 5; polyacrylamide may be employed as the polymer 9 up to about 40 wt . % of the formulation 5, in about 5.0 wt . % to about 35 wt . % of the formulation 5, or in about 8.0 wt . % to about 30 wt .% of the formulation 5; or both karaya and polyacrylamide may be employed as the polymer 9, wherein karaya is present in about 5.0 wt . % to about 35 wt .% of the formulation 5 and polyacrylamide is present in about 5.0 wt . % to about 30 wt . % of the formulation 5.

Humectant

The formulation 5 may optionally include one or more humectants 17 to provide a moistening effect to the pressure sensitive adhesive 14. The humectant 17 may optionally hydrate the polymer 9. Any suitable humectant 17 may be employed, provided the humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the humectant 17 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. One suitable humectant 17 is glycerin. Other suitable humectants 17 include polyhydric alcohols such as ethylene glycol, propylene glycol, triethylene glycol, tetraethylene glycol, sorbitol, and combinations thereof. Any suitable amount of humectant 17 may be employed, provided the amount of humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the amount of humectant 17 effectively remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Typically, the suitable amount of humectant 17 will depend upon the specific humectant 17 employed and the specific polymer 9 employed. For example, karaya, polyacrylamide, or a combination thereof may be employed as the polymer 9 and glycerin may be employed as the humectant 17, wherein the glycerin is present in about 25.0 wt . % to about 70.0 wt . % or in about 40.0 wt .% to about 55.0 wt . % of the formulation 5. Filler

The formulation 5 may optionally include one or more fillers 6. Any suitable filler 6 may be employed. Suitable fillers 6 include malto dextrin, dextrin, 70% sorbitol water, modified starches, depolymerized starches, and methylcellulose . As used herein, "malto dextrin" is a dextrose equivalent, wherein dextrose is D-glucose . Malto dextrin is commercially available as Amaizo Lodex 5 from Amerimay Maize-Products (Hammond, IN) . Any suitable amount of filler 6 may be employed in the formulation 5. The suitable amount of filler 6 may depend in part upon the specific filler present in the formulation 5. For example, malto dextrin may be present up to about 20.0 wt .% of the formulation 5, or in about 1.0 wt . % to about 10.0 wt .% of the formulation 5.

Skin Protectant or Skin Conditioner

The formulation 5 may optionally include a skin protectant 18 (i.e., topical moisturizer or skin conditioner) . Any suitable skin protectant 18 may be employed, provided the skin is effectively protected or moisturized and the skin protectant remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Additionally, it is preferable that the skin conditioner is medicinally acceptable for topical use in humans .

Suitable topical moisturizers 18 include, e.g. aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, aluminum hydroxide gel, cocoa butter, propylene glycol, ethylene glycol, triethylene glycol, hard fat, kaolin, mineral oil, petrolatum, topical starch, white petroleum, cod liver oil, shark liver oil, zinc oxide, or any combination thereof. Additional suitable topical moisturizers 18 are disclosed, e.g., in U.S. Patent Nos . 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; 4,274,420; 5,976,565; 5,536,263; and references cited therein.

As used herein, "aluminum hydroxide gel" refers to a suspension containing aluminum oxide (A12O3) , mainly in the form of a hydroxide. It is typically obtained by drying the product of interaction in aqueous solution of an aluminum salt with ammonium or sodium carbonate .

As used herein, "cocoa butter" refers to a fatty substance in cocoa beans; a thick oily solid obtained from cocoa beans and used in making chocolate, cosmetics, and suntan oil. Also known as threobroma oil, it lubricates and softens the skin.

As used herein, "topical starch" refers to cornstarch.

As used herein, "kaolin" refers to aluminum silicate; powdered and freed from gritty particles by elutriation. Kaolin refers to the name of the locality in China where the substance is found in abundance .

As used herein, "white petroleum" refers to a purified mixture of hydrocarbons obtained from petroleum. A bleached version of yellow soft paraffin, it is used as an emollient and as a base for ointments. It is odorless when rubbed into the skin and not readily absorbed.

As used herein, "mineral oil" refers to the heavy- liquid petrolatum; liquid paraffin or petroleum; a mixture of liquid hydrocarbons obtained from petroleum, and is typically used as a vehicle in medicinal preparations.

As used herein, "petrolatum" refers to petroleum jelly; a yellow soft paraffin; a yellowish mixture of the softer members of the paraffin or methane series of hydrocarbons, obtained from petroleum as an intermediate product in the distillation; typically used as a soothing application to burns and abrasions of the skin, and as a base for ointments. As used herein, "cod liver oil" refers to the partially destearinated fixed oil extracted from the fresh livers of Gadus morrhuae and other species of the family Gadidae, containing Vitamins A and D.

As used herein, "shark liver oil" refers to the oil extracted from the livers of sharks, mainly of the species Hypoprion brevirostris ; a rich source of Vitamins A and D.

As used herein, "zinc oxide" refers to ZnO, which is typically used as a protective ointment. As used herein, "calamine" is a pink powder of zinc oxide and a skin protectant containing about 98% zinc oxide and about 0.5% ferric oxide; "aloe" is the dried latex of leaves of Curaco Aloe (Aloe barbadenis Miller, Aloe vera Linne) or Cape Aloe (Aloe ferox Miller and hybrids) , of the family Liliacaea. Aloe is commercially available as Aloe Vera Gel from Terry Laboratories (Melbourne, FL) . Aloe Vera Gel is commercially available as Aloe Vera Gel 4OX (20.0 wt . % solution in water), Aloe Vera Gel IX (0.5 wt.% solution in water), Aloe Vera Gel 1OX (5.0 wt.% solution in water), or solid Aloe Vera. The solid Aloe Vera may be dissolved in a carrier, such as water, to the desired concentration. In addition, the commercially available forms of Aloe Vera are optionally available as decolorized Aloe Vera.

As used herein, "Vitamin E" is 3,4-dihydro- 2,5,7,8-tetramethyl-2- (4 , 8 , 12-trimethyltridecyl) -2H- 1- benzopyran-6-ol ; "Vitamin E acetate" is 3,4-dihydro- 2,5,7, 8-tetramethyl-2- (4,8, 12-trimethyltridecyl) -2H-1- benzopyran-6-ol acetate; "lanolin" is the fat-like secretion of the sebaceous glands of sheep (i.e., complex mixture of esters and polyesters of 33 high molecular weight alcohols and 36 fatty acids) which is deposited onto the wool fibers; "farnesol" is 3,7,11- trimethyl-2 , 6 , 10-dodecatrien-l-ol . Farnesol is commercially available from Amerimay Radiolabeled Chemicals (ARC) (St. Louis, MO), and "glycyrrhetinic acid" is a pentacyclic triterpenoid derivative of the beta-amyrin type and is shown below:

Any suitable amount of skin protectant 18 may be employed, provided the suitable amount of skin protectant 18 effectively protects or moisturizes the skin and the effective amount of skin protectant 18 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Additionally, it is preferable that the amount of skin conditioner employed is medicinally acceptable for topical use in humans . Specifically, the skin protectant 18 may be present up to about 20.0 wt.%, up to 10.0 wt . % , up to 5.0 wt.%, or up to 2.0 wt.% of the formulation 5. The suitable and effective amount of skin protectant 18 will depend in part upon the specific skin protectant 18 present in the formulation 5. For example, Aloe Vera Gel, 1OX may be present up to about 20.0 wt.% of the formulation 5, up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5. In addition, Vitamin E acetate may be present up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, up to about 3.0 wt.% of the formulation 5, up to about 2.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5. Specifically, the skin conditioner will be present in an amount that is consistent with any State or Federal regulations .

The skin protectant 18 may be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the skin protectant 18 may be located on the entire surface of the front side 3 of the backing 2 or the skin protectant 18 may be located on a portion of the surface of the front side 3 of the backing 2. Specifically, the skin protectant 18 may be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the skin protectant 18 may be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the skin protectant 18 may be partially embedded into the backing 2) . As shown in Figure 9, the skin protectant 18 may penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the skin protectant 18 may penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one- fourth to about nine-tenths the thickness of the backing 2. As such, the skin protectant 18 may be partially embedded into the backing 2. Specifically, the skin protectant 18 may be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the skin protectant 18 is partially embedded into the backing 2) . Alternatively, a portion of the front side 3 of the backing 2 may include the skin protectant 18 and other portions of the front side 3 of the backing 2 may include any combination of the solvent 13, pressure sensitive adhesive 14, and aversive agent 15. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the skin protectant 18 may be in continuous contact with the skin surface of the patient . Preservative

The formulation 5 may optionally include a preservative 7 that is useful for preventing bacterial growth, mold growth, fermentation, and/or decomposition. As used herein, "preservative" refers to any substance which prevents bacterial growth, mold growth, fermentation, and/or decomposition. Concise Chemical and Technical Dictionary, 4th enlarged edition, Chemical Publishing Co., Inc., NY, NY p. 939 (1986) . Any suitable preservative 7 may be employed, provided the preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition; and the preservative 7 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 2 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Suitable preservatives 7 include, e.g., quat-15, parabens, dichlorobenzyl alcohol, ethylene diamine tetreacetic acid, formaldehyde, gum benzoin, imidazolidinyl urea, phenyl -mercuric acetate, poly aminopropyl biguanide, proply gallate, sorbic acid, cresol, chloroacetamide sodium benzoate, chloromethyl - methylisothiazolinone, chloromethyl - methylisothiazolon, chloromethyl-methylisothiazolinone benzalkonium chloride, an octylisothiazolinone benzimidazol -compound, chloromethyl - methylisothiazolinone octylisothiazolinone, o- phenylphenol benzisothiazolinone, o-phenylphenol benzisothiazolinone, benzisothiazolinone, an aliphatic amine of 2-thiopyridineoxide, benzoic acid, editic acid, phenolic acid, benzyl alcohol, isopropyl alcohol, benzenethonium chloride, bronopol, cetrimide, chlorohexidine, chlorobutanol , chlorocresol , phenol, phenoxyethanol , phenyl ethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, proplyene glycol, sodium benzoate, sodium propionate, thimerosol, and medicinally acceptable salts thereof. Specifically, the preservative may be quat-15, which is commercially available from Dow Chemical (Midland Michigan) ; methyl paraben; ascorbic acid; or a combination thereof.

The preservative 7 may be employed in any suitable amount provided the amount of preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition and the effective amount of preservative 7 remains stable in the formulation 5. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The preservative 7 may be present up to about 99.9 wt. % of the formulation 5, up to about 20.0 wt . % of the formulation 5, up to 5.0 wt . % of the formulation 5, or up to 1.5 wt .% of the formulation 5. The amount of preservative 7 present in the formulation 5 will typically depend upon the specific compound or compounds employed as the preservative 7. For example, quat-15 may be employed in about 0.01 wt . % to about 1.5 wt .% of the formulation 5, in about 0.05 wt. % to about 0.15 wt . % of the formulation 5, or in about 0.08 wt .% to about 0.12 wt . % of the formulation 5. Fragrance

In one embodiment of the disclosed subject matter, the formulation 5 may include a fragrance 25. The fragrance 25 may be employed to impart a desirable scent or odor to the formulation 5, or may be employed as a solvent, to solubilize the medicament 21, aversive agent 15, or combination thereof. The fragrance 25 may be a floral scent, a fruit scent, a plant leaf scent, or any combination thereof. Specifically, suitable fragrances 25 include, e.g., grape fragrance, musk fragrance, light vanilla fragrance, Jergens lotion fragrance, Vaseline Intensive Care fragrance, Nivea Lotion fragrance, Ivory Soap fragrance, amaretto fragrance, blueberry fragrance, coffee fragrance, egg nog fragrance, peanut butter fragrance, rum cake fragrance, honey almond fragrance, ginger bread house fragrance, coffee cake & spice fragrance, raspberry rose fragrance, sassafras fragrance, strawberry fragrance, grapefruit pink fragrance, home sweet fragrance, jeweled citrus fragrance, lemon, mango fragrance, mulberry fragrance, orange flower fragrance, passion fruit fragrance, pikaki fragrance, freesia fragrance, china rain fragrance, coconut fragrance, apple fragrance, baked bread fragrance, cornucopia fragrance, lemon chiffon fragrance, peppermint twist fragrance, white cake fragrance, cherry pie fragrance, sugar plum fragrance, plum fragrance, romantic fragrance, sea fresh fragrance, tea fragrance, green floral fragrance, honeydew fragrance, kiwi fragrance, lilac fragrance, may bouquet fragrance, neutralizer fragrance, patchouli fragrance, peach fragrance, pine apple blossom fragrance, chocolate mint fragrance, frankincense fragrance, baked apple pie fragrance, cappuccino fragrance, cran-apple fragrance, maple syrup fragrance, buttered popcorn fragrance, sugar cookie fragrance, cotton maydy fragrance, cranberry cobbler fragrance, plumeria fragrance, rum fragrance, spring fever fragrance, watermelon fragrance, guava fragrance, honeysuckle fragrance, hyacinth fragrance, macadamia nut fragrance, melon fragrance, oakmoss fragrance, papaya fragrance, pear pineapple fragrance, blueberry fragrance, citrus-ginseng fragrance, garden dreams fragrance, banana creme pie fragrance, chocolate mint fragrance, cranberry fragrance, macadamia nut fragrance, pumpkin pie fragrance, chocolate German cake fragrance, banana nut bread fragrance, sweet potato pie fragrance, raspberry fragrance, sandalwood fragrance, spring flowers fragrance, ylang fragrance, heather fragrance, jasmine fragrance, lavender fragrance, magnolia fragrance, mountain air fragrance, orange essence fragrance, paradise fragrance, peony fragrance, alpine breeze fragrance, chamomile fragrance, clover fragrance, gardenia fragrance, and combinations thereof.

Essential Oil In one embodiment of the disclosed subject matter, the formulation 5 may include an essential oil 26. The essential oil 26 may be employed to impart a desirable scent or odor to the formulation 5, or may be employed as a solvent, to solubilize the medicament 21, aversive agent 15, or combination thereof.

Specifically, suitable essential oils 26 include, e.g., ajowan, sweet almond oil, allspice, aloe vera oil, ammi visnaga (khella) , amyris, angelica root, angelica seed, anise, anise seed, star anise, apricot kernel oil, absolute arnica, avocado oil, unrefined avocado oil, Copaiba balsam, balsam Peru genuine, balsam Peru oil, balsam peru liquid resin, balsam tolu, sweet french basil, basil, basil ct . methyl chavicol, lemon ct . citral basil, sweet ct . linalool basil, bay laurel, bay leaf, bay rum, bay leaf West Indies, bees wax, unrefined bees wax, benzoin absolute, benzoin resinoid, bergamot, mint bergamot, Italian bergamot oil, free bergaptene bergamot, birch, sweet birch, borage oil, boronia, butter, buchu leaf, cajeput, calamus, calendula oil, infused calendula oil, camellia oil, maynabis, caraway, caraway seed, cardamom, absolute carnation, carrot seed, high carotol carrot seed, carrot seed oil, cassia, cassis bud (black currant), castor oil, catnip, oil of catnip, cedarleaf, western red cedarleaf, cedarwood, Atlas cedarwood, Himalayan cedarwood, Virginia cedarwood, celery seed, chamomile, blue chamomile, German chamomile, Morocmay chamomile, Morocmay wild chamomile, Roman chamomile, champaca, cilantro, true cinnamon bark, cinnamon bark, cinnamon leaf, cinnamon cassia, cistus, citronella, Java citronella, ciste oil, artificial civet, clary sage, high sclareol clary sage, Clementine, Italian Clementine peel oil, clove, clove bud, clove leaf, cocoa, cocoa butter, unrefined cocoa butter, coconut oil, refined coconut oil, cognac, combava petitgrain, coriander, green coriander, cornmint, costus oil, cumin, cypress, davana oil, dill, dill weed, elemi, erigeron (fleabane) , eucalyptus citriodora, eucalyptus globulus, lemon eucalyptus, fennel, sweet fennel, fenugreek, fir, Mayada fir needle, Siberia fir needle, white fir needle, frankincense, India frankincense, Oman frankincense, galbanum oil, garlic, genet, geranium, geranium leaf, geranium rose, Bourbon geranium, Egyptian geranium, ginger, Cochin extra ginger, ginsing, Siberian ginsing, Korean ginsing, grapefruit, pink grapefruit, white grapefruit, grapeseed oil, hazelnut oil, helichrysum, helichrysum immortelle, Mad. helichrysum, Balkan helichrysum, Corsica helichrysum, France helichrysum, hemp oil, absolute honeysuckle, hyssop, hyssop decumbens, absolute immortelle, fragrant aster inula, Jamaimay gold, unrefined Jamaimay gold, jasmine, absolute jasmine, grandiflorum jasmine, sambac jasmine, jojoba oil, helio-carrot in jojoba, melissa in jojoba, absolute jonquille, juniper berry, Siberia juniper berry, Croatia juniper berry, lanolin, unrefined anhydrous lanolin, lantana camara, laurel nobilis, lavandin, abrialis lavandin, grosso lavandin, lavender, Oregon lavender, Bulgarian lavender, Russian lavender, high-altitude lavendar, wild-crafted lavender, lavendin, organic lavindin, lemon, lemongrass, lime, distilled lime, expressed lime, litsea, litsea cubeba, blue, pink and white lotus, macadamia oil, mace, green mandarin, red mandarin, yellow mandarin, manuka, absolute marigold, marigold flower, marjoram, Spanish marjoram, sweet marjoram (true) , massoia bark, melissa, codistilled melissa, "rectified" melissa, true melissa, absolute mimosa, mimosa, monarda, mugwort, musk seed, myrrh, myrtle, absolute narcissus, neroli (orange blossom), niaouli, nutmeg, extra nutmeg, oakmoss, absolute oak moss, olibanum, absolute opopanax, bitter orange, blood orange, sweet orange, wild West Indian orange, oregano, orris root, concrete orris, osmanthus, palm oil, refined palm oil, palmarosa, paprika, parsley seed, patchouli, India patchouli oil, Indonesia patchouli oil, peanut, peanut oil, pemay oil, pennyroyal, pepper, black pepper, super black pepper, peppermint, India peppermint, USA baby mint peppermint, pet perfume, petitgrain (orange leaves) , white pine, pine needle, evening primrose, ravensara anisata, true ravensara, ravensare, ravintsara, redberry, rosalina, rose, rose geranium, rose otto, Bulgarian rose, English rose, Turkish rose, rosehip seed oil, rosemary, rosemary anti -oxidant extract powder, rosemary verbenone, Morocco rosemary, Spain rosemary, rosewood, rosewood oil, rue, sage, white sage, sage dalmatian, sage officinalis, sage triloba, sandalwood, seabuckthorn berry, sesame oil, sesame seed oil, shea butter, unrefined shea butter, spikenard, green spikenard, spruce, St. John's wort, styrax resin, tagetes, tangerine, Dancy tangerine, tarragon, tea tree, Australia tea tree, thuja (cedar leaf), thyme, red thyme, thyme ct . linalool, thyme vulgaris, wild thyme, red thyme, mixed tocopherols, tolu balsam resin, absolute tuberose, tuberose, tumeric, valerian, vanilla, pure vanilla extract, vanilla bean, absolute vanilla bourbon, vegetable glycerin, absolute verbena, vetiver, violete leaves, vitex, organic Haiti vetiver, absolute violet leaf, walnut oil, wintergreen, natural wintergreen, wormwood, yarrow, ylang ylang, ylang ylang I, ylang ylang II, ylang ylang III, ylang ylang compound, ylang ylang complete, ylang ylang extra, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, and combinations thereof. Additional suitable essential oils 26 include, e.g., Satureja montana, carvacrol, thymol eugenol , australol, gaiacol, cinnamic aldehyde, geraniol, linalool, thujanol, myrcenol , terpineol , menthol and piperitol, geranial (citrals) , citronellal, cuminal , verbenone, thύjone, borneone (camphor), pinocamphone, cryptone, fenchone, menthone, piperitone and carvone, estragole, anethole, Phtalids (such as celery seed) , cineole, monoterpenol, an aversive agent derived from trees of the Myrteceae family; linalool oxide, linalool (Hissopus off. var . decumbens) , thymol: Trachyspermum ammi (Ajowan), thymus CT thymol; caravcrol : Origanum compactum (Oregano) Origanum heracleoticum (Greek Oregano) Corydothymus capitatus (Spanish Oregano) Satureja montana (winter or mountain savory), thymus CT carvacrol, Thymus serpyllum (wild thyme or mother-of-thyme); Eugenol: Eugenia caryophyllus (Clove tree) Cinnamomum verum - leaf (Ceylon Cinnamon) , ocimum gratissimum CT eugenol (hot or shrubby basil); gaiacol: guajacum officinalis

(Gaiac wood); linalool: Aniba rosaeodora (rosewood), coriandrum sativum (Coriander), thymus CT linalool, Lavandula reydovan; Geraniol: Cymbopogon martini (Palmarosa) , thymus CT geraniol; thujanol: Thymus CT thujanol, origanum majorana (Sweet marjoram or oregano); Borneol : Thyumus satureioides (Thym borneol- carvacrol type) , Inula graveolens (sweet inula) ; menthol: Mentha x piperita (peppermint), Mentha arvensis (field mint or cornmint) ; Citronnellol : Pelargonium asperum (geranium) ; terpinenelol4 :

Melaleuca alternifolia (tea tree) , origanum majorana (sweet marjoram or oregano); alpha terpineol: Ravensara aromatica (Ravensara) , Eucalyptus radiata (black or narrow-leaf peppermint eucalyptus) ; Cinnamaldehyde : Cinnamomum verum or zeylandicum (bark) (Ceylon cinnamon (bark) ) , Cinnamomum cassia (bark) (Chinese cinnamon (bark) , Cinnamomum loureirii (bark) (Vietnamese cinnamon bark) ; Cuminal : Cuminum cyminum (Cumin) , Eucalyptus polybractea CT cryptone (Blue mallee eucalyptus cryptone type); Phellandral: eucalyptus polybractea CT cryptone (Blue Mallee eucalyptus cryptone type); and combinations thereof.

Complexing Agent

In one embodiment of the disclosed subject matter, the formulation 5 may include an aversive agent 15 and/or medicament 21 that is not soluble and/or stable either without a solvent or with the specific solvent 13, in the amount employed. The use of a complexing agent may be employed to modulate (i.e., regulate) the solubility, stability, and/or the volatility of the aversive agent 15 and/or medicament 21 in the formulation 5. Any suitable complexing agent may be employed, provided the complexing agent effectively solubilizes and/or stabilizes the aversive agent 15 and/or and/or medicament 21, and the complexing agent remains stable in the formulation 5 over a prolonged period of time. Specifically, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.

In addition, any suitable amount of complexing agent may be employed, provided the amount of complexing agent effectively solubilizes and/or stabilizes the aversive agent 15 and/or and/or medicament 21, and the amount of complexing agent remains stable in the formulation 5 over a prolonged period of time. Suitable specific complexing agents include, e.g., cyclodextrins . As used herein, a "cyclodextrin" refers to a non-reducing cyclic oligosaccharide with at least 6 anhydroglucose units linked by alpha 1,4 bonds to form a ring. Cyclodextrins are typically produced by the action of the enzyme cyclodextrin glucosyltransferase [CGT-ase] on starch. The most common cyclodextrins include alpha, beta, and gamma cyclodextrins, which have six, seven, or eight, respectively, anhydroglucose units in the ring structure. All of the hydroxyl groups in cyclodextrins are oriented to the outside of the ring while the glucosidic oxygen and two rings of the non- exchangeable hydrogen atoms are directed towards the interior of the cavity. This combination gives cyclodextrins a hydrophobic inner cavity and a hydrophilic exterior. See, e.g., the Cerestar website (http://www.cerestar.com); the Betadexcyclodextrin website (http://www.betadexcyclodextrin.com); and M. L. Bender and M. Komiyama, Cyclodextrin Chemistry, Springer, Berlin, 1978.

Cyclodextrins are enzymatically-modified starches formed by the action of the enzyme cyclodextrin glucosyltransferase on starch. They are doughnut - shaped molecules, which may interact with organic molecules to form complexes. It is also possible for some organic molecules and some inorganic salts to associate with the hydroxyl groups of the cyclodextrin. Three cyclodextrins are typically formed, alpha, beta, and gamma cyclodextrin, which contain six, seven, or eight glucose molecules in the ring, respectively. The electron-dense glycosidic oxygen atoms are oriented inward and line the cavity. The hydroxyl groups are directed toward the outside of the ring. These hydrophilic groups interact with the water to give the cyclodextrins their aqueous solubility properties. The hydrogen and glycosidic oxygen atoms lining the cavity give the cyclodextrin molecule its hydrophobic character and its ability to interact with organic molecules to form complexes. Because of the free rotation of the C- 6 carbon, this end of the cyclodextrin cavity is narrower than the end with the C-2 and C-3 hydroxyls. Derivatives of cyclodextrin may be obtained, e.g., by replacing one or more hydroxyl groups with a suitable radical (i.e., pendant group). Suitable pendant groups include, e.g., sulfinyl; sulfonyl; phosphate; (Ci-Ci₂) alkyl optionally substituted with one or more (e.g., 1, 2, 3, or 4) hydroxy, carboxy, carbonyl , acyl , oxy, oxo; or a combination thereof. Suitable specific pendant groups include methyl, ethyl, hydroxypropyl , carboxymethyl , sulfate, phosphate, and an acrylate. For example, the specific pendant group may include (Ci-Ci₂) alkoxy optionally substituted with one or more hydroxy.

Specific suitable derivatives of cyclodextrin include, e.g., alpha-cyclodextrin sulfate, beta- cyclodextrin sulfate, gamma-cyclodextrin sulfate, alpha-hydroxypropyl cyclodextrin, beta-hydroxypropyl cyclodextrin, gamma-hydroxypropyl cyclodextrin, alpha- cyclodextrin phosphate, beta-cyclodextrin phosphate, and gamma-cyclodextrin phosphate. Cyclodextrins are starches that have been specially modified by the action of an enzyme to make a water-soluble ring-shaped molecule, capable of holding another, oil -like organic substance in its 'cavity'. Because of this unique property, cyclodextrins may be used to carry all kinds of active ingredients (e.g., drugs, fragrances, flavors, and vitamins) in a wide variety of formulations. Increased stability, water solubility, and controlled release are among the many application benefits. Specifically, cyclodextrins have the benefit of encapsulating a substance, thereby providing protection for the substance. This results in increased shelf-life and a reduced loss of degradation or decomposition. Cyclodextrins are themselves soluble in water, and may greatly increase the solubility of highly water insoluble substances. In addition, cyclodextrins may be used to control the release of a substance. Suitable cyclodextrins include alpha cyclodextrins 6 glucose units) , beta cyclodextrins (7 glucose units, and gamma cyclodextrins (8 glucose units) . Specifically, the cyclodextrin may be hydroxylpropyl beta cyclodextrin, hydroxylproplyl alpha cyclodextrin, or a combination thereof. In addition, the cyclodextrin may optionally be branched.

Suitable cyclodextrins, and derivatives thereof, may be found, e.g., at U.S. Patent No. 5,376,641; U.S. Patent No.5, 229, 370 ; U.S. Patent No.4 , 383 , 992 ; the Cerestar website (http://www.cerestar.com); the Betadexcyclodextrin website

(http://www.betadexcyclodextrin.com); French et al . , Archives in Biochem. and Biophysics, Volume III, (1965) 153-150; the carbomer website (http://www.carbomer.com) and references cited therein.

In one embodiment of the disclosed subject matter, an adhesive skin patch 1 is provided in which the formulation 5 does not include an aversive agent 15. In such an embodiment, the adhesive skin patch 1 may be manufactured, shipped, and stored without an aversive agent 15 and an aversive agent 15 may be introduced to the adhesive skin patch 1 at a later time .

The formulation 5 may secifically remain stable over the period of time typically experienced with the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years. The stability of the aversive agent 15, for example, is due in part to the formulation 5 including the aversive agent 15 in an adhesive formulation. The adhesive formulation may be a hydrogel that holds the aversive agent 15 in an available form while maintaining the necessary stability, pressure sensitive adhesion and effectiveness over a prolonged period of time, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years.

In suitable specific embodiments, the adhesive skin patch 1 may be sterile. In suitable specific embodiments, the adhesive skin patch 1 may be sterilized during the manufacturing process, such that the packaging materials sufficiently maintain the sterility of the adhesive skin patch 1 during the shipping and storage of the adhesive skin patch 1. The adhesive skin patch 1 may be sterilized employing any suitable and effective procedures. For example, the adhesive skin patch 1 may be sterilized by irradiation. Specifically, the adhesive skin patch 1 may be sterilized by terminal irradiation.

The adhesive skin patch 1 may have any suitable size and shape. In addition, the adhesive skin patch 1 may be cut, as desired, to provide an adhesive skin patch 1 of a desired size and shape. The adhesive skin patch 1 may be cut with any suitable cutting device such as a scissors, scalpel, or knife.

The adhesive skin patch 1 may have any suitable length. In one embodiment of the disclosed subject matter, the patch may be a self-wound roll 25 without a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. See, e.g., Figure 10. In such an embodiment, the adhesive skin patch 1 may have a length of about 12 inches to about 100 yards, about 10 feet to about 50 yards, or about 20 feet to about 20 yards. Additionally, in such an embodiment, the adhesive skin patch 1 may have a width of about 0.1 inch to about 5.0 inches, about 0.1 inch to about 1.0 inch, or about 0.1 inch to about 0.5 inch. In one embodiment of the disclosed subject matter, the adhesive skin patch 1 may be rectangular and may have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. In such an embodiment, the adhesive skin patch 1 may typically have a length of up to about 10 inches, up to about 6 inches, up to about 4 inches, or up to about 2 inches. The adhesive skin patch 1 may have any suitable width. Typically, the adhesive skin patch 1 will have a width of up to about 5 inches, up to about 2.5 inches, up to about 1 inch, or up to about 0.5 inch. Additionally, the adhesive skin patch

1 may have any suitable thickness. Typically, the adhesive skin patch 1 will have a thickness of about 0.10 mm to about 2.0 mm, about 0.15 mm to about 1.0 mm, or about 0.20 mm to about 0.75 mm.

In one specific embodiment of the disclosed subject matter, the adhesive skin patch 1 may be crescent, oval or circular in shape. The circular adhesive skin patch 1 may have a diameter of about 0.1 inch to about 10 inches. Specifically, the circular adhesive skin patch 1 may have a diameter of about 1.5 inches to about 5 inches. See, Fig. 7. In another specific embodiment of the disclosed subject matter, the adhesive skin patch 1 may be rectangular in shape. The rectangular adhesive skin patch 1 may have a length of about 1 inch to about 10 inches and a width of about 1 inch to about 10 inches. Specifically, the rectangular adhesive skin patch 1 may have a length of about 1 inch to about 2 inches and a width of about 0.1 inch to about 0.75 inch. See, Fig. 8.

In one embodiment of the disclosed subject matter, the adhesive skin patch 1 may have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. In such an embodiment, one or more adhesive skin patches 1 may be mounted on the release liner 10. For example, one adhesive skin patch 1 may have one release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. Alternatively, about 2 to about 100 or about

2 to about 20 adhesive skin patches 1 may be mounted on the release liner 10. The cost of having two or more patches 1 on a single release liner 10 is typically less expensive than skin patches 1 that are separately mounted on a single release liner 10. In addition, some consumers may prefer the ease and comfort of carrying a single patch assembly that includes a single release liner 10 and more than one (e.g., about 2 to about 20, or about 2 to about 10) adhesive patches 1 mounted on the single release liner 10.

The adhesive skin patch 1 may be applied to a skin surface of a patient. Alternatively, the adhesive skin patch 1 may be applied to an article of clothing of the patient, or any suitable object within the immediate vicinity (e.g., within about 10 feet) of the patient, such as a bed, couch or chair.

The adhesive patch 1 of the disclosed subject matter may be formulated or manufactured employing the above components. The adhesive patch 1 of the disclosed subject matter may be formulated or manufactured using any suitable technique. Specifically, the adhesive patch 1 may be formulated or manufactured as described herein or as described in U.S. Patent No. 5,536,263; U.S. Patent No. 5,741,510; and references cited therein; wherein the backing may be treated with a sizing agent 8 prior to the infusion of the formulation 5.

The invention may be illustrated by the following non-limiting examples.

Examples

Exemplary formulations 5 are provided in Example 1-8 below. Example 1 Example 5

component Percent component Percent

Glycerin 44 Glycerin 44 karaya 34 karaya 34 emulsion emulsion adhesive 7 adhesive 7 spirits of spirits of turpentine 4 turpentine 4 camphor 6 camphor 2 menthol 3 menthol 5 eucalyptus oil 1 eucalyptus oil 3 aloe vera 0.99 fragrance 0.98 denatonium denatonium benzoate 0.01 benzoate 0.02

100 100

Example 2 Example 6 component Percent component Percent

Glycerin 44 Glycerin 35 karaya 30 karaya 30 emulsion emulsion adhesive 7 adhesive 7 polyacrylamide 9.99 polyacrylamide 9.99 nicotine 4 fentanyl 8 propylene propylene glycol 5 glycol 10 denatoniunm quassin 0.01 chloride 0.01

100 100

Example 3 Example 7 component Percent component Percent

Glycerin 40 Glycerin 44 karaya 25 karaya 34 emulsion emulsion adhesive 7 adhesive 7 spirits of polyacrylamide 9.97 turpentine 2 propylene glycol 10 camphor 1.98 estrogen 3 menthol 4 ethanol 5 eucalyptus oil 2 denatonium cherry benzoate 0.03 fragrance 0.99 denatonium

100 benzoate 0.03 propylene glycol 4 100

Example 4 Example 8 component Percent component Percent

Glycerin 40 Glycerin 35 karaya 25 karaya 30 emulsion emulsion adhesive 7 adhesive 7 polyacrylamide 9.97 polyacrylamide 9.97 propylene glycol 10 fentanyl 8 propylene buprenorphine 3 glycol 10 sucrose ethanol 5 octaacetate 0.03 quassin 0.03 100

100

All publications, patents, and patent documents cited herein are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.

Claims

Claims

1. An adhesive patch that comprises a medicament and an aversive agent .

2. The adhesive patch of claim 1, that is a transdermal patch, suitable for systemically delivering a medicament.

3. The transdermal adhesive patch of claim 2, wherein the medicament comprises nicotine, estrogen, nitroglycerin, lidocaine or fentanyl .

4. The adhesive patch of claim 1, that is a topical patch, suitable for locally delivering a medicament to the surface of the skin.

5. The topical adhesive patch of claim 4, wherein the medicament comprises a topical analgesic, anti- pruritic agent, anti- inflammatory agent, anesthetic agent, keratolytic agent, rubrefacient agent, nonsteroidal anti-inflammatory drug (NSAID), vasodilator, antibiotic agent, anti -fungal agent, anti -viral agent, cosmetic agent, topical antitussive, topical acne drug or symptomatic cold reliever.

6. The adhesive patch of any one of claims 1-5, wherein the aversive agent comprises berberine, bitter apple extracts, dihydrocapsaicin, heptanoyl guaiacylamide, isobutylamides, nonanoyl vanillylamide, phenols, quassin, quercetin, quinine hydrochloride, sucrose octaacetate, allspice, amino acids, benzoic benzylamine amide, bitter aloes, brucine sulfate, brucine, capsaicin analog, chlorosucrose derivatives, denatonium benzoate alkaloids, denatonium chloride, denatonium saccharide, eucalyptus oil, guaiacylamides , heptanoylisobutylamide, homovanillyl octylester, limonin, mace, menthol, methyl anthranilate, naringin, oil of bitter almonds, oil of nutmeg, peppermint oil, phenylthiocarbamide, quassia, quassin, quebracho, quinine, quinine sulfate, quinones, resiniferatoxin, spearmint oil, sucrose benzoate, sucrose derivatives, sucrose octaacetate, tinyatoxin or trichloro anisole.

7. The adhesive patch of any one of claims 1-5, wherein the aversive agent comprises denatonium (N- benzyl-2- (2, 6-dimethylphenylamino) -N, N-diethyl -2- oxoethanaminium) , or a pharmaceutically acceptable salt thereof.

8. The adhesive patch of any one of claims 1-7, wherein the adhesive patch comprises : a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing; wherein the formulation comprises the aversive agent and the medicament .

9. The adhesive patch of claim 8, wherein the backing of the patch is porous.

10. The adhesive patch of claim 8, wherein the backing of the patch is non-porous.

11. The adhesive patch of claim 8, wherein the backing of the patch is vapor permeable.

12. The adhesive patch of any one of claims 8-11, wherein the formulation is positioned on the entire front side of the backing of the patch.

13. The adhesive patch of any one of claims 8-11, wherein the formulation is positioned on a portion of the front side of the backing of the patch.

14. The adhesive patch of any one of claims 8-13, wherein the formulation is partially embedded in the front side of the backing of the patch.

15. The adhesive patch of any one of claims 8-14, wherein the backing of the patch comprises a non-woven fabric .

16. The adhesive patch of any one of claims 8-14, wherein the backing of the patch comprises polycellulose fibers, polyester fibers, polyurethane fibers, polyolefin fibers, polyamide fibers, cotton fibers, copolyester fibers, films, or any mixture thereof .

17. The adhesive patch of any one of claims 8-14, wherein the backing of the patch comprises open cell foam.

18. The adhesive patch of claim 17, wherein the open cell foam comprises polyurethane, poly-vinyl chloride, polyethylene, or any combination thereof.

19. The adhesive patch of any one of claims 8-18, wherein upon contact with skin, the backing of the patch retains the formulation and the patch allows moisture from the skin to pass through the patch.

20. The adhesive patch of any one of claims 8-19, wherein the formulation further comprises an adhesive.

21. The adhesive patch of claim 20, wherein the adhesive is an acrylic ester copolymer, a water-based adhesive, a hot melt adhesive, a pressure sensitive adhesive, a solvent based pressure sensitive adhesive, a polyacrylate, a polyisobutylene, a polybutene, a rubber, a silicone based pressure sensitive adhesive, a polystyrene-polybutadiene-polystyrene block polymer, a polystyrene-polyisoprene-polystyrene block polymer, a polystyrene-poly (ethylene-butylene) -polystyrene block polymer, or any combination thereof.

22. The adhesive patch of claim 20, wherein the adhesive is an acrylic ester copolymer.

23. The adhesive patch of claim 22, wherein the acrylic ester copolymer is present in about 0.5 wt . % to about 18.0 wt . % of the formulation.

24. The adhesive patch of any one of claims 8-23, wherein the formulation further comprises a solvent.

25. The adhesive patch of claim 24, wherein the solvent comprises water, ethanol, triethylene glycol, ethylene glycol, glycerin, propylene glycol, triacetin, 1,3 -propane diol , 2 -methyl -1 , 3 -propane diol, glycerol ricinoleate, PEG- 6 caprylic / capric glycerides, caprylic / capric triglycerides , propyleneglycol dicaprylate / dicaprate , glycerol monostearate , glycerol monocaprylate , glycerol monolaurate , neopentyl alcohol, 1-hexademayol , hydroxypropyl beta-cyclodextrin, vitamin E, vitamin E acetate, deoxycholic acid, taurodeoxycholic acid, 3- [ (3 -cholamidopropyl) dimethylammonio] -1-propane-sulfonate, BigCHAP, cholic acid, cholesterol NF, propylene carbonate, lecithin, a pharmaceutically acceptable salt thereof, or a combination thereof.

26. The adhesive patch of claim 24, wherein the solvent comprises a (Ci-C₁₂) acyclic hydrocarbon, a (C₃-Ci₂) cyclic hydrocarbon, a (C₆-Ci₂) aryl hydrocarbon, a (C₆-Ci₂) heteroaryl hydrocarbon, or a (C₃-Ci₂) heterocyclic hydrocarbon; wherein any of the hydrocarbons optionally include one or more carbon-carbon double bonds and any of the hydrocarbons optionally include one or more carbon-carbon triple bonds; wherein any of the hydrocarbons optionally include one or more oxy (-0-) , carbonyl (C(=O)) , carboxylato (-C (=0) O-) , dioxy (-O-O-), dithio (-S-S-), imino (-NH-), methylene dioxy (-OCH₂O-), sulfinyl (-S0-), sulfonyl (-SO₂-), or thio (-S-); wherein any of the hydrocarbons are optionally substituted with one or more amino, hydroxyl , cyano, nitro, (Ci-C₁₂) alkoxy, halo, trifluoro, trifluoro (Ci- Ci₂)alkyl, NR¹R², or COOR¹; wherein R¹ and R² are each independently hydrogen, a (Ci-Ci₂) acyclic hydrocarbon or a (C₃-Ci₂) cyclic hydrocarbon.

27. The adhesive patch of claim 24, wherein the solvent is present in about 3.0 wt% to about 25.0 wt . % of the formulation.

28. The adhesive patch of any one of claims 8-27, wherein the formulation further comprises a polymer.

29. The adhesive patch of claim 28, wherein the polymer is karaya, a polyacrlyamide, xanthan gum, guar gum, a natural polymer, a synthetic polymer, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, derivatives of algin, a polyacrylate, polymaleic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS, or any combination thereof.

30. The adhesive patch of claim 28, wherein the polymer is karaya.

31. The adhesive patch of claim 30, wherein the karaya is present in about 13 wt . % to about 52 wt . % of the formulation.

32. The adhesive patch of claim 20, wherein the adhesive is positioned on the entire front side of the backing of the patch.

33. The adhesive patch of claim 20, wherein the adhesive is positioned on a portion of front side of the backing of the patch.

34. The adhesive patch of claim 20, wherein the adhesive is partially embedded in at least a portion of the backing of the patch.

35. The adhesive patch of any one of claims 8-34, wherein the formulation is positioned on the entire front side of the backing of the patch.

36. The adhesive patch of any one of claims 8-34, wherein the formulation is positioned on a portion of front side of the backing of the patch.

37. The adhesive patch of any one of claims 8-36, wherein the formulation is partially embedded in at least a portion of the backing of the patch.

38. The adhesive patch of any one of claims 8-37, wherein the formulation further comprises a fragrance.

39. The adhesive patch of claim 38, wherein the fragrance is a floral scent, a fruit scent, a plant leaf scent, or any combination thereof.

40. The adhesive patch of claim 38, wherein the fragrance comprises grape fragrance, musk fragrance, light vanilla fragrance, Jergens lotion fragrance, Vaseline Intensive Care fragrance, Nivea Lotion fragrance, Ivory Soap fragrance, amaretto fragrance, blueberry fragrance, coffee fragrance, egg nog fragrance, peanut butter fragrance, rum cake fragrance, honey almond fragrance, ginger bread house fragrance, coffee cake & spice fragrance, raspberry rose fragrance, sassafras fragrance, strawberry fragrance, grapefruit pink fragrance, home sweet fragrance, jeweled citrus fragrance, lemon, mango fragrance, mulberry fragrance, orange flower fragrance, passion fruit fragrance, pikaki fragrance, freesia fragrance, china rain fragrance, coconut fragrance, apple fragrance, baked bread fragrance, cornucopia fragrance, lemon chiffon fragrance, peppermint twist fragrance, white cake fragrance, cherry pie fragrance, sugar plum fragrance, plum fragrance, romantic fragrance, sea fresh fragrance, tea fragrance, green floral fragrance, honeydew fragrance, kiwi fragrance, lilac fragrance, may bouquet fragrance, neutralizer fragrance, patchouli fragrance, peach fragrance, pine apple blossom fragrance, chocolate mint fragrance, frankincense fragrance, baked apple pie fragrance, cappuccino fragrance, cran-apple fragrance, maple syrup fragrance, buttered popcorn fragrance, sugar cookie fragrance, cotton maydy fragrance, cranberry cobbler fragrance, plumeria fragrance, rum fragrance, spring fever fragrance, watermelon fragrance, guava fragrance, honeysuckle fragrance, hyacinth fragrance, macadamia nut fragrance, melon fragrance, oakmoss fragrance, papaya fragrance, pear pineapple fragrance, blueberry fragrance, citrus-ginseng fragrance, garden dreams fragrance, banana creme pie fragrance, chocolate mint fragrance, cranberry fragrance, macadamia nut fragrance, pumpkin pie fragrance, chocolate German cake fragrance, banana nut bread fragrance, sweet potato pie fragrance, raspberry- fragrance, sandalwood fragrance, spring flowers fragrance, ylang fragrance, heather fragrance, jasmine fragrance, lavender fragrance, magnolia fragrance, mountain air fragrance, orange essence fragrance, paradise fragrance, peony fragrance, alpine breeze fragrance, chamomile fragrance, clover fragrance, gardenia fragrance, or any combination thereof.

41. The adhesive patch of any one of claims 8-40, wherein the formulation further comprises an essential oil selected from ajowan, sweet almond oil, allspice, aloe vera oil, ammi visnaga (khella) , amyris, angelica root, angelica seed, anise, anise seed, star anise, apricot kernel oil, absolute arnica, avocado oil, unrefined avocado oil, Copaiba balsam, balsam Peru genuine, balsam Peru oil, balsam peru liquid resin, balsam tolu, sweet french basil, basil, basil ct . methyl chavicol, lemon ct . citral basil, sweet ct . linalool basil, bay laurel, bay leaf, bay rum, bay leaf West Indies, bees wax, unrefined bees wax, benzoin absolute, benzoin resinoid, bergamot , mint bergamot, Italian bergamot oil, free bergaptene bergamot, birch, sweet birch, borage oil, boronia, butter, buchu leaf, cajeput, calamus, calendula oil, infused calendula oil, camellia oil, maynabis, caraway, caraway seed, cardamom, absolute carnation, carrot seed, high carotol carrot seed, carrot seed oil, cassia, cassis bud (black currant), castor oil, catnip, oil of catnip, cedarleaf, western red cedarleaf, cedarwood, Atlas cedarwood, Himalayan cedarwood, Virginia cedarwood, celery seed, chamomile, blue chamomile, German chamomile, Morocmay chamomile, Morocmay wild chamomile, Roman chamomile, champaca, cilantro, true cinnamon bark, cinnamon bark, cinnamon leaf, cinnamon cassia, cistus, citronella, Java citronella, ciste oil, artificial civet, clary sage, high sclareol clary sage, Clementine, Italian Clementine peel oil, clove, clove bud, clove leaf, cocoa, cocoa butter, unrefined cocoa butter, coconut oil, refined coconut oil, cognac, combava petitgrain, coriander, green coriander, cornmint, costus oil, cumin, cypress, davana oil, dill, dill weed, elemi, erigeron (fleabane) , eucalyptus citriodora, eucalyptus globulus, lemon eucalyptus, fennel, sweet fennel, fenugreek, fir, Mayada fir needle, Siberia fir needle, white fir needle, frankincense, India frankincense, Oman frankincense, galbanum oil, garlic, genet, geranium, geranium leaf, geranium rose, Bourbon geranium, Egyptian geranium, ginger, Cochin extra ginger, ginsing, Siberian ginsing, Korean ginsing, grapefruit, pink grapefruit, white grapefruit, grapeseed oil, hazelnut oil, helichrysum, helichrysum immortelle, Mad. helichrysum, Balkan helichrysum, Corsica helichrysum, France helichrysum, hemp oil, absolute honeysuckle, hyssop, hyssop decumbens, absolute immortelle, fragrant aster inula, Jamaimay gold, unrefined Jamaimay gold, jasmine, absolute jasmine, grandiflorum jasmine, sambac jasmine, jojoba oil, helio-carrot in jojoba, melissa in jojoba, absolute jonquille, juniper berry, Siberia juniper berry, Croatia juniper berry, lanolin, unrefined anhydrous lanolin, lantana camara, laurel nobilis, lavandin, abrialis lavandin, grosso lavandin, lavender, Oregon lavender, Bulgarian lavender, Russian lavender, high-altitude lavendar, wild-crafted lavender, lavendin, organic lavindin, lemon, lemongrass, lime, distilled lime, expressed lime, litsea, litsea cubeba, blue, pink and white lotus, macadamia oil, mace, green mandarin, red mandarin, yellow mandarin, manuka, absolute marigold, marigold flower, marjoram, Spanish marjoram, sweet marjoram (true), massoia bark, melissa, codistilled melissa, "rectified" melissa, true melissa, absolute mimosa, mimosa, monarda, mugwort, musk seed, myrrh, myrtle, absolute narcissus, neroli (orange blossom), niaouli, nutmeg, extra nutmeg, oakmoss, absolute oak moss, olibanum, absolute opopanax, bitter orange, blood orange, sweet orange, wild West Indian orange, oregano, orris root, concrete orris, osmanthus, palm oil, refined palm oil, palmarosa, paprika, parsley seed, patchouli, India patchouli oil, Indonesia patchouli oil, peanut, peanut oil, pemay oil, pennyroyal, pepper, black pepper, super black pepper, peppermint, India peppermint, USA baby mint peppermint, pet perfume, petitgrain (orange leaves) , white pine, pine needle, evening primrose, ravensara anisata, true ravensara, ravensare, ravintsara, redberry, rosalina, rose, rose geranium, rose otto, Bulgarian rose, English rose, Turkish rose, rosehip seed oil, rosemary, rosemary anti -oxidant extract powder, rosemary verbenone, Morocco rosemary, Spain rosemary, rosewood, rosewood oil, rue, sage, white sage, sage dalmatian, sage officinalis, sage triloba, sandalwood, seabuckthorn berry, sesame oil, sesame seed oil, shea butter, unrefined shea butter, spikenard, green spikenard, spruce, St. John's wort, styrax resin, tagetes, tangerine, Dancy tangerine, tarragon, tea tree, Australia tea tree, thuja (cedar leaf), thyme, red thyme, thyme ct . linalool, thyme vulgaris, wild thyme, red thyme, mixed tocopherols, tolu balsam resin, absolute tuberose, tuberose, tumeric, valerian, vanilla, pure vanilla extract, vanilla bean, absolute vanilla bourbon, vegetable glycerin, absolute verbena, vetiver, violete leaves, vitex, organic Haiti vetiver, absolute violet leaf, walnut oil, wintergreen, natural wintergreen, wormwood, yarrow, ylang ylang, ylang ylang I, ylang ylang II, ylang ylang III, ylang ylang compound, ylang ylang complete, ylang ylang extra, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, and combinations thereof.

42. The adhesive patch of any one of claims 8-40, wherein the formulation further comprises an essential oil selected from basil (ocimum basilicum) , cardamom (elettaria cardamomum) , Roman chamomile {anthemis nobilis) , eucalyptus {eucalyptus radiate) , geranium (pelargonium x asperum) , MQV {melaleuca guinquenervia viridiflora) , neroli (citrus aurantium) , petitgrain

(citrus aurantium}, rosemary (rosemarinus officinalis camphor) , rosemary (rosemarinus officinalis verbenone) , or a combination thereof.

42. The adhesive patch of any one of claims 8-40, wherein the formulation further comprises an essential oil selected from Satureja montana, carvacrol, thymol eugenol , australol, gaiacol, cinnamic aldehyde, geraniol, linalool, thujanol, myrcenol, terpineol, menthol and piperitol, geranial (citrals) , citronellal, cuminal , verbenone, thujone, borneone (camphor) , pinocamphone, cryptone, fenchone, menthone, piperitone and carvone, estragole, anethole, Phtalids (such as celery seed), cineole, monoterpenol , an aversive agent derived from trees of the Myrteceae family; linalool oxide, linalool (Hissopus off. var . decumbens) , thymol: Trachyspermum awmi (Ajowan) , thymus CT thymol ; caravcrol : Origanum compaction (Oregano) Origanum heracleoticum (Greek Oregano) Corydothymus capitatus (Spanish Oregano) Satureja montana (winter or mountain savory) , thymus CT carvacrol , Thymus serpyllum (wild thyme or mother-of- thyme); Eugenol : Eugenia caryophyllus (Clove tree) Cinnamomum verum - leaf (Ceylon Cinnamon) , ocimum gratissimum CT eugenol (hot or shrubby basil); gaiacol : guajacum officinalis (Gaiac wood); linalool: Aniba rosaeodora (rosewood) , coriandrum sativum (Coriander), thymus CT linalool, Lavandula reydovan; Geraniol: Cymbopogon martini (Palmarosa) , thymus CT geraniol; thujanol: Thymus CT thujanol , origanum majorana (Sweet marjoram or oregano); Borneol : Thyumus satureioides (Thym borneol-carvacrol type) , Inula graveolens (sweet inula) ; menthol: Mentha x piperita (peppermint) , Mentha arvensis (field mint or cornmint) ; Citronnellol : Pelargonium asperum (geranium); terpinenelol4 : Melaleuca alternifolia (tea tree) , origanum majorana (sweet marjoram or oregano) ; alpha terpineol : Ravensara aromatica (Ravensara) ,

Eucalyptus radiata (black or narrow-leaf peppermint eucalyptus); Cinnamaldehyde : Cinnamomum verum or zeylandicum (bark) (Ceylon cinnamon (bark) ) , Cinnamomum cassia (bark) (Chinese cinnamon (bark) , Cinnamomum loureirii (bark) (Vietnamese cinnamon bark) ; Cuminal : Cuminum cyminum (Cumin) , Eucalyptus polybractea CT cryptone (Blue mallee eucalyptus cryptone type); Phellandral: eucalyptus polybractea CT cryptone (Blue Mallee eucalyptus cryptone type) ; or a combination thereof.

43. The adhesive patch of any one of claims 8-42, wherein at least a portion of the backing of the patch is treated with a sizing agent such that the portion of the backing that is treated with the sizing agent has a surface energy of about 20 dynes/cm² to about 65 dynes/cm².

44. The adhesive patch of claim 43, wherein the sizing agent is a fluorocarbon solution, a silicone- containing compound, or a combination thereof.

45. The adhesive patch of claim 44, wherein the silicone-containing compound is a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkene, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, a vinyl terminated polydialkylsiloxane, or a combination thereof.

44. The adhesive patch of claim 43, wherein the entire front side of the backing of the patch is treated with the sizing agent.

45. The adhesive patch of claim 43, wherein the sizing agent penetrates at least a portion of the underlying surface of the front side of the backing of the patch.

46. The adhesive patch of claim 43, wherein the sizing agent penetrates the entire underlying surface of the front side of the backing of the patch.

47. The .adhesive patch of claim 43, wherein the entire backing of the patch is treated with the sizing agent .

48. The adhesive patch of any one of claims 8-47, wherein the formulation further comprises a skin protectant .

49. The adhesive patch of claim 48, wherein the skin protectant is aloe, lanolin, glycerin, calamine, Vitamin E, Vitamin E acetate, Vitamin C, allantoin, aluminum hydroxide gel, bismuth subnitrate, boric acid, calamine, cocoa butter, dimethicone, glycerin, kaolin, live yeast cell derivative, petrolatum, pyridoxine hydrochloride, shark liver oil, sodium bicarbonate, sulfur, tannic acid, topical starch, trolamine, white petrolatum, zinc acetate, zinc carbonate zinc oxide, zinc sulfate, shea butter, or any combination thereof.

50. The adhesive patch of any one of claims 8-49, wherein the formulation further comprises a polyhydric alcohol.

51. The adhesive patch of claim 50, wherein the polyhydric alcohol is erythritol, ethylene glycol, propylene glycol, triethylene glycol, tetraethylene glycol, sorbitol, or any combination thereof.

52. The adhesive patch of claim 51, wherein the polyhydric alcohol is propylene glycol .

53. The adhesive patch of claim 51, wherein the polyhydric alcohol is present in about 0.5 wt% to about 25.0 wt . % of the formulation.

54. The adhesive patch of claim 51, wherein the polyhydric alcohol is present in about 0.5 wt% to about 5.0 wt .% of the formulation.

55. The adhesive patch of any one of claims 8-54, wherein the formulation further comprises water.

56. The adhesive patch of claim 55, wherein the water is present in about 5.0 wt . % to about 15.0 wt . % of the formulation.

57. The adhesive patch of any one of claims 1-56, wherein the medicament comprises an antibiotic agent.

58. The adhesive patch of claim 57, wherein the antibiotic agent is cilastatin, clavulanic acid, folinic acid, probenecid, pyridoxine, sulbactam, dapsone, ethambutol, isoniazid, pyrazinamide, rifampin, streptomycin, capreomycin, ethionamide, para aminosalicylic acid, cycloserine, ciprofloxacin, nalidixic acid, norfloxacin, ofloxacin, imipenam, meropenem, cilistatin, cefadroxil, cefazolin, cephalexin, cephalothin, cefaclor, cefamandole, cefonicid, cefoxitin, cefuroxine, cefoperazone, cefotaxime, ceftazidime, ceftazidime, ceftizoxime, ceftriaxone, moxalactam, cefepine, bacitracin, vancomycin, aztreonam, amoxicillin, clavulanic acid, benzathine, penicillin g, penicillin v, ampicillin, carbenicillin indamyl , carbenicillin, mezlocillin, piperacillin, ticarcillin, cloxacillin, dicloxacillin, floxacillin, methicillin, nafcillin, oxacillin, colistmethate, polymixin b, trimethoprim, co- trimoxazole, mafenide, sulfadiazine, sodium sulfacetamide, sulfacytine, sulfadiazine, sulfamethoxazole , sulfapyridine, sulfasalazine, sulfisoxazole, chloramphenicol, clindamycin, spectinomycin, azithromycin, clarithromycin, erythrmoycin, erythromycin estolate, spiramycin, chlortetracycline, demeclocycline, doxycycline, minocycline, oxytetracycline, amikacin, kanamycin, neomycin, streptomycin, tobramycin, nitrofurantoin, griseofulvin, potassium iodide, fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole, amphotericin b, nystatin, niclosamide, nifurtimox, piperazine, praziquantel, pyrantel pamoate, thiabendazole, amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine, pyrimethamine, quinidine gluconate, fansidar, diloxanide furoate, melarsoprol, nifurtimox, paromomycin, pentamidine, sodium stibogluconate, suramin, metronidazole, foscarnet, 3-deoxythmidin-2- ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, foscarnet, 3-deoxythmidin-2- ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, a pharmaceutically acceptable salt thereof, or any combination thereof.

59. The adhesive patch of any one of claims 1-58, wherein the antiviral agent is selected from the group of Echinacea {Echinacea angustifolia, E. pallida, E. purpurea) , Elderberry (Sambucus nigra) , Garlic {Allium sativum) , Lemon balm {Glycyrrhiza glabra) , Astragalus {Astragalus membranaceus) , eyebright {Euphrasia officinalis) , sage {salvia officinalis) , yarrow {Achillea millefolium) , nettles {Urtica dioica) , peppermint {menthe piperiya) , ephedra {Ephedra sinica) , marshmallow root {Althea officinalis) , mullein leaves or flowers {Verbascum spp.) , plantain leaf {Plantago lanceolata, P. major), licorice root, thyme {Thymus vulgaris) , boneset {Eupatorium perfollatum) , feverfew {Tanacetum parthenium) , catnip {Nepeta cataria) , yarrow {Achillea millefolium) , elder flower {Sambucus nigra, S. mayadenis) , ginger {Zingiber officinale) , Ginko biloba, St. John's wort {Hypericum perforatum L.) , and combinations thereof.

60. The adhesive patch of any one of claims 1-59, wherein the antiviral agent is selected from the group of zinc, lysine, foscarnet, 3-deoxythmidin-2 -ene, dideoxycytosine, dideoxyinosine, lamivudine, azidothymidine, indinavir, ritonavir, saquinavir, acyclovir, idoxuridine, ribavirin, vidarabine, amantidine, rinantidine, viracea, cytovene, famciclovir, valaciclovir, penciclovir, hexadecylosypropyl-cidofovir (HDP-CDV) , nonoxynol-9, docosanol (n-docosanol, 1-docosanol, or behenyl alcohol; which is a saturated 22 -carbon straight -chain alcohol), a pharmaceutically acceptable salt thereof, and combinations thereof.

61. The adhesive patch of any one of claims 1-60, wherein the antiviral agent is selected from the group of a hypochloride, a hypochloride generating compound, a peroxide, a peroxide generating compound, an organic halide, an organic halide generating compound, or a combination thereof.

62. The adhesive patch of any one of claims 1-61, wherein the formulation further comprises an antimicrobial agent or preservative.

63. The adhesive patch of claim 62, wherein the antimicrobial agent or preservative is quat-15, a paraben, dichlorobenzyl alcohol, ethylene diamine tetreacetic acid, formaldehyde, gum benzoin, imidazolidinyl urea, phenyl -mercuric acetate, poly aminopropyl biguanide, proply gallate, sorbic acid, cresol , chloroacetamide sodium benzoate, chloromethyl- methylisothiazolinone, chloromethyl- methylisothiazolon, chloromethyl-methylisothiazolinone benzalkonium chloride, an octylisothiazolinone benzimidazol-compound, chloromethyl- methylisothiazolinone octylisothiazolinone, o- phenylphenol benzisothiazolinone, o-phenylphenol benzisothiazolinone, benzisothiazolinone, an aliphatic amine of 2-thiopyridineoxide, benzoic acid, editic acid, phenolic acid, benzyl alcohol, isopropyl alcohol, benzenethonium chloride, bronopol , cetrimide, chlorohexidine, chlorobutanol , chlorocresol, phenol, phenoxyethanol , phenyl ethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, proplyene glycol, sodium benzoate, sodium propionate, thimerosol , a pharmaceutically acceptable salt thereof, or any combination thereof.

64. The adhesive patch of claim 63, wherein the antimicrobial agent or preservative is quat-15.

65. The adhesive patch of claim 63, wherein the quat- 15 is present in about 0.01 wt . % to about 0.1 wt . % of the formulation.

66. The adhesive patch of any one of claims 1-65, wherein the patch is individually wrapped.

67. The adhesive patch of any one of claims 1-65, wherein the patch further comprises a release liner that is mounted to the front side of the backing.

68. The adhesive patch of any one of claims 1-67, wherein the patch is sterile.

69. The adhesive patch of claim 68, wherein the patch is sterilized by irradiation.

70. The adhesive patch of claim 69, wherein the patch is sterilized by terminal irradiation.

71. The adhesive patch of any one of claims 1-70, wherein the patch further comprises packaging material .

72. The adhesive patch of any one of claims 1-65, wherein the patch releases the therapeutically effective amount of the medicament over a period of time of up to about 24 hours.

73. The adhesive patch of any one of claims 72, wherein the patch releases the therapeutically effective amount of the medicament over a period of time of up to about 12 hours.

74. A kit comprising:

(a) the patch of any one of claims 1-73; and

(b) packaging material .

75. The kit of claim 74 further comprising instructions for using the patch.