WO2011057363A1

WO2011057363A1 - Disposable device and uses thereof for skin and mucosal applications

Info

Publication number: WO2011057363A1
Application number: PCT/AU2010/001537
Authority: WO
Inventors: John Spurge
Original assignee: Dynamiclear Pty Ltd
Priority date: 2009-11-16
Filing date: 2010-11-16
Publication date: 2011-05-19

Abstract

The present invention relates generally to a disposable device for topical application of a liquid formulation to a skin and/or mucosal site in a subject.

Description

"Disposable device and uses thereof for skin and mucosal applications"

Cross-Reference to Related Applications

This application claims the benefit of priority from United States Patent Application No. 61/261,644 filed November 16, 2009, the entire content of which is incorporated herein by reference.

Technical Field

The present invention relates generally to a disposable device for topical application of a liquid formulation to a skin and/or mucosal site in a subject. The invention also relates to the disposable device including the liquid formulation, and uses thereof for treating skin and/or mucosal lesions.

Background Art

Topical application of liquid formulations to skin are useful for a variety of purposes including for example cosmetic applications, treating and/or preventing wrinkles, acne, and other skin or mucosal lesions including cuts and abrasions, or lesions associated with infections, such as Herpes Simplex viruses. However, the topical application of liquids to skin for any purpose including liquid cosmetic formulations, or liquid formulations for treating and/or preventing wrinkles, acne, and other skin or mucosal lesions can be messy and inconvenient. This is particularly relevant when it is necessary to saturate a skin or mucosal site with a liquid formulation. Methods of applying liquids to skin or mucosal surfaces have involved the use of a dropper to apply an amount directly to the lesion, which results in dripping, and wastage of the liquid formulation, as well as, the potential for contamination of the stock of the liquid formulation impacting subsequent applications. Applying the liquid formulation to an applicator, such as a cotton swab, also poses the same problems, in particular there is risk of contamination of the stock of the liquid. There remains a need for a disposable device for topical application of a liquid formulation to a skin and/or mucosal site in a subject, that is economical, easy to use, and avoids contamination of the liquid formulation.

Disposable devices useful for applying liquid formulations to treat skin or mucosal lesions associated with viral infections, e.g., Herpes Simplex virus, are particularly desirable. Herpes Simplex 1 (HSV1) or mouth herpes is commonly in the form of cold sores on and around the mouth. Herpes Simplex 2 (HSV2) or genital herpes is a much more intense strain commonly found on the genitals. However both types can be found on the mouth or genital areas. It is possible to be infected by both HSV1 and HSV2. Being infected by one particular strain does not make you immune to another.

Recurrent outbreaks of the Herpes virus generally follow a staged progression. The stages are easily identifiable and include prodrome, vesicles, ulceration, crust and healing. Prodrome is generally a short period of tingling, itching, numbness or burning with no visible sign of an outbreak. Vesicles are the formation of one or more fluid- filled blisters, often in a cluster and usually surrounded by sore, red skin: The ulceration stage is when the blisters open to form painful ulcers or open sores. At the edge of the sore, a soft or hard yellow crust begins to appear. Ulcers and painful, sore, red skin persist through this stage. At the crust stage, weeping sores or ulcers become completely covered by a crust or scab. No ulcers or blisters are present. The healing process is manifested by disappearance of the crust, swelling, pain and itching. Skin eruptions due to viral infection, especially Herpes viruses, generally have a normal infective course that lasts from 10 to 60 days depending on the exact causative species and anatomical location of the infection.

After the initial outbreak, the virus usually lies dormant in the skin or in nerve tissue (latent state) until something triggers another eruption or site infection. When the virus reactivates, it characteristically causes a sore at the site where it first entered the body. Often the trigger is unknown, but in some people overexposure to sunlight, fever, physical or emotional stress, hormonal changes such as pregnancy or menstruation, or certain foods and drugs seem to reactivate the virus. To date, there is neither a vaccine to prevent the Herpes infection, nor any way to eliminate the virus from the body. The fact that the herpes virus retreats into the nervous system makes it extremely difficult to eliminate completely:

Previous treatments for herpes virus infections have included the topical applications of 5% by weight of acyclovir (Zovirax®), oral administration of valacyclovir HCI (Valtrex®) and laser treatments such as Lectroject®. Each of these treatments is expensive to the patient and the effectiveness is quite slow and often painful. Side effects such as headache and nausea are not uncommon when using repeated applications of acyclovir, whilst the Lectroject® laser method of treating herpes increases the possibility of scar tissue formation.

Most herpes medications act to "suppress" the virus inside the body in order to reduce outbreaks. New pharmaceutical compositions have been described in the International Patent Application No. PCT/AU2006/00863 dated 30 June 2006, the corresponding accepted Australian Application No. 2006261580 and pending divisional Australian Application No. 2009217410 dated 21 September 2009 the contents of which are incorporated herein by reference in their entirety. The compositions work by substantially eliminating the virus on direct contact at the outbreak site which accelerates the recovery time of the viral outbreaks and reduces the inconvenience and embarrassment of the condition. The compositions can be conveniently administered in a single dose liquid formulation to each lesion at the first signs of an outbreak. Accordingly, there is also a need for a disposable device for topical application of a liquid formulation to treat or prevent skin and or mucosal lesions in a subject, and lesions associated with viral infections such as herpes, that is economical, easy to use, and avoids contamination of the liquid formulation.

Summary of Invention

The present invention provides a disposable device for topical application of a liquid formulation to a skin and/or mucosal site in a subject, said disposable device comprising:

an elongate member having a proximal end comprising an absorbent material; a receptacle for holding the liquid formulation, said receptacle having a top opening for receiving the absorbent material and a portion of the elongate member; and an applicator portion at a distal end of the elongate member,

wherein the absorbent material is configured to fit the receptacle such that the manual insertion of the absorbent material into the receptacle induces a wicking action that draws the liquid formulation through the elongate member to the applicator portion thereby delivering an amount of the liquid formulation to the applicator portion ready for use.

In the present context, the term "wicking action" shall be taken to include the flow or movement of liquid through thin tubes, and/or through porous media, and capillary action, capillarity, capillary motion.

By having the absorbent material configured to fit the receptacle, manual insertion of the absorbent material of the elongate member is easy, and the wicking action is rapid. Preferably, the amount of the liquid formulation delivered to the applicator portion is delivered within a time of about 1 sec to about 10 min after inserting the absorbent material into the receptacle comprising the liquid formulation during use. More preferably, the time is about 1 to 10 sec.

The disposable device according to any embodiment described herein delivers the liquid formulation to the applicator portion in an amount sufficient to topically apply to at least one skin or mucosal membrane site to be treated in the subject. In another example, the amount of the liquid formulation delivered to the applicator portion is sufficient to topically apply to several skin and/or mucosal sites. to be treated in the subject. In this example, it is contemplated that the amount of the liquid formulation that is delivered is sufficient to consecutively apply to one or more sites in a single use before disposal.

The receptacle may be of any shape or size that is convenient to hold, provided the absorbent material fits the receptacle upon manual insertion, for example, the receptacle may be a circular vial. In one example, the absorbent material contacts one or more side wall(s) of the receptacle during insertion of the absorbent material, and this contact provides friction that aids and/or induces the wicking action. In another example, the viscosity of the liquid formulation aids and/or induces the wicking action. In another example, the displacement of a volume of the liquid formulation during insertion of the absorbent material into the receptacle aids and or induces the wicking action. For example, the displacement of a volume of the liquid formulation during insertion of the absorbent material into the receptacle produces forces that and/or induces the wicking action.

Manual manipulation may be achieved by holding a region of the elongate member between the distal and proximal ends during use thereby avoiding touching of the absorbent material that makes contact with the liquid during use, and manual contact with the applicator portion is also avoided. In one example, the elongate member further comprises a handle or tab located between the proximal end comprising the absorbent material, and the applicator portion at the distal end, wherein the handle is suitable for grasping and inserting into the receptacle.

In one example, the elongate member comprises a conduit through which the liquid formulation is delivered to the applicator portion by the wicking action. In another example, the elongate member comprises a porous material attached to a solid support. In this example, the porous material is such that the liquid formulation is delivered to the applicator portion by a wicking action through the porous material. In another example, it may be desirable to control the time it takes for and/or the volume of the liquid formulation delivered to the applicator portion. This may be achieved by altering the substance of the conduit, or the porous matrix, or by including a porous matrix housed inside the conduit. The porous matrix may act to enhance or retard the wicking action. Any number of porous matrices, and or suitable materials for the manufacture of the conduit, e.g., a variety of plastics, polymers, or glass that are suitable for such a purpose will be known to a person skilled in the art.

The applicator portion may be an opening in the conduit at the distal end of the elongate portion. The applicator portion may also comprise an absorbent material at the distal end of the elongate member.

The invention further provides the disposable device according to any example hereof comprising the liquid formulation for applying to the skin and/or mucosal site in ' the subject, and may be further packaged ready for use. Those skilled in the art will readily appreciate that the device has numerous applications that require topically administering a liquid formulation to a skin and/or mucosal site in a subject, wherein it may be desirable to apply such a liquid formulation to one or more sites in a single use, and then discard the applicator and device for hygienic reasons. Such applications include cosmetic applications, treating and or preventing wrinkles, acne, and other skin or mucosal lesions including cuts and abrasions, or lesions associated with infections.

By "site" is meant that the skin or mucous membrane site appearing on any one or more body surface(s) such as the skin, hair follicle, nail cuticle, mucous membrane, anus, throat including oral mucosa, eyes including cornea, conjunctiva or eyelid, lips, ■ ears, or genitalia including vagina, labial tissue, penis, scrotum, etc.

The liquid formulation may be any suitable composition capable of being administered topically, subject to the proviso that it comprises at least some liquid to effect the wicking action, and has a viscosity to be capable of being drawn through the elongate member to the applicator portion during use. Accordingly, the liquid formulation may be a liquid emulsion, gel, aqueous solution, solvent solution, suspension, aqueous suspension, or solvent suspension. It will be apparent to the person skilled in the art that in the use of the device for treating and/or preventing wrinkles, acne, and other skin or mucosal lesions including cuts and abrasions, or lesions associated with infections, the liquid formulation may comprise any known agent, or compound in an amount sufficient for such purposes. A person skilled in the art would also be able to determine based on the amount of liquid delivered to the applicator portion, the concentration of the agent or compound required to treat and/or prevent wrinkles, acne and other skin or mucosal lesions including cuts and abrasions, or lesions associated with infections based on known components of liquid formulations known for that purpose. Such liquid formulations may be any available liquid formulation, e.g. as purchased from any commercially available source.

The disposable device has particular, but not necessarily exclusive, application for the topical treatment of skin and/mucosal membrane lesions in a subject. Accordingly, the invention also provides a disposable device according to any example hereof comprising a liquid formulation comprising an amount of copper as an active trace metal effective for the topical treatment of skin and/or mucosal membrane lesions in a subject. By "amount of copper" is meant a sufficient concentration of copper to ameliorate one or more visible symptoms of a skin lesion such as that associated with a cut, abrasion, wound, acne, infection by a bacterium, fungus or virus such as a Herpes Simplex Virus e.g., HSV-1 or HSV-2, Herpes Zoster Virus, Polio virus, Shingles- associated viruses, Varicella Zoster Virus, Chicken pox-associated viruses or Human Immunodeficiency Virus (HIV-1) or any serotype thereof capable of infecting a human or causing a skin lesion in another animal species. In one example, the copper is present in a trace amount, as an active trace metal.

By "topical treatment" is meant that the formulation is suitable for treatment of a skin or mucous membrane lesion appearing on any one or more body surface(s) such as the skin, hair follicle, nail cuticle, mucous membrane, anus, throat including oral mucosa, eyes including cornea, conjunctiva or eyelid, lips, ears, or genitalia including vagina, labial tissue, penis, scrotum, etc. Such treatment does not necessarily require administration by direct contact with that part of the body surface e.g., that part of the body surface having the lesion, however direct topical administration is clearly within the scope of the present invention.

By "lesion" is meant any localized abnormal structural change in a body part such as produced by wounding, infection, acne, or other injury involving a cut or break in the skin or mucosa. For example, a lesion in the present context includes any disruption to the skin or mucosa associated with infection of a subject by a bacterium, fungus or virus. For example, lesions associated with virus infection may be apparent on the face and/or mouth (e.g., orofacial herpes), genitalia (e.g., genital herpes), or hands (e.g., herpes whitlow), eye (e.g., herpes keratitis).

The liquid formulations comprising copper as provided with the disposable device of the present . invention will generally comprise a pharmaceutically acceptable copper salt wherein the transition metal cation has a charge of +2 or +3 such as a copper (II) complex or copper (III) complex, and the salt has low toxicity in humans. Examples of pharmaceutically acceptable copper salts are described e.g., Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing, Easton Pa. (1990) and include copper acetate, copper sulphate, copper chloride, copper salicylate, copper nitrate, copper (Il)-aspirinate, copper (II) salsalate, a mixed carboxylate copper (II) complex , and a caffeine, a copper (II) carboxylate-caffeine complex, and combinations thereof. A solvate of a copper salt may be employed. In one particular example, a formulation according to any example hereof comprises copper in the form of copper sulphate e.g., Cu(II)SO-) or a solvate thereof. In one example, the copper is provided as Cu(II)S0₄:7H₂0.

The liquid formulations as provided with the disposable device of the present invention may further comprise pharmaceutically acceptable carriers, excipients, and/or diluents. Pharmaceutically acceptable carriers, excipients and/or diluents utilized should be acceptable for human or veterinary applications. Such carriers, excipients and or diluents are well-known to those skilled in the art. Carriers and/or diluents suitable for use include any and all solvents, dispersion media, aqueous solutions, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. Except insofar as any conventional media or agent is incompatible with the active ingredient, use thereof in the composition is contemplated. Supplementary active ingredients can also be incorporated into the compositions.

The liquid formulations comprising copper as provided with the disposable device of the present invention may comprise copper ions or copper compounds. For example, irrespective of the anion employed, the copper ion may be present in the liquid formulation at a concentration in the range of about 1% (w/w) to about 5% (w/w), including about 2% (w/w) or about 3% (w/w) or about 4% (w/w) or about 5% (w/w) or 5.5% (w/w). Alternatively, or in addition, the copper compound is present in the range of between about 5% (w/w) of the formulation and about 9% (w/w) of the formulation, including about 7.0% (w/w) or about 7.1% (w/w) or about 7.2% (w/w) or about 7.3% (w/w) or about 7.4% (w/w) or about 7.5% (w/w) or about 7.6% (w/w) or about 7.7% (w/w) or about 7.8% (w/w) or about 7.9% (w/w) or about 8.0% (w/w) of the formulation. Concentrations of copper ions that are permissible when applied topically may be higher than those concentrations considered toxic when copper is : provided to isolated and cultured cells in vitro or by injection.

The invention further provides a disposable device according to any example hereof wherein a unit dose of the liquid formulation comprising copper ions or a copper compound is delivered to the applicator portion. The liquid formulations as provided with the disposable device of the present invention may also be in the form of an herbal formulation. In the present context, the term "herbal formulation" shall be taken to mean a formulation that does not comprise a synthetic compound as an active agent in the treatment of a lesion of the skin and/or mucosa. For example, a herbal formulation may comprise an active agent type derived from a plant or part thereof or a fungus or a part thereof e.g., from the root, stem, leaf, flower, fruit, or seed of a plant. A herbal formulation may comprise the active agent in a herbal base e.g., a plant-derived base comprising a liquid emulsion, gel, aqueous solution, solvent solution, suspension, aqueous suspension, or solvent suspension.

In another example, the present invention provides a disposable device comprising a topical formulation comprising an amount of copper e.g., as an active trace metal, in an aqueous herbal base effective for treatment of skin and mucosal membrane lesions in a subject.

By "topical formulation" is meant that the formulation is suitable for application direct to skin or a mucous membrane, such as directly on a lesion in the skin or mucous membrane. For example, a topical formulation is applied directly to one or more body surface(s) such as the skin, hair follicle, nail cuticle, mucous membrane, anus, throat including oral mucosa, eyes including cornea, conjunctiva or eyelid, lips, ears, or genitalia including vagina, labial tissue, penis, scrotum, etc. Application may comprise direct contact with that part of the body surface e.g., that part of the body surface having the lesion.

By "herbal base" is meant that the formulation base into which the active agent is introduced is derived substantially from a non-synthetic source such as a plant or part thereof or a fungus or a part thereof e.g., from the root, stem, leaf, flower, fruit, or seed of a plant. For example, the base may be liquid emulsion, gel, aqueous solution, solvent solution, suspension, aqueous suspension, or solvent suspension. In one particular example, liquid formulation may comprise an effective amount of a copper compound in an herbal base comprising one or more extracts selected from the group consisting of: Hypericum perforatum (St. John's wort) extract, Aloe barbadensis extract, Melaleuca alternifolia (tea tree) extract, Melissa officinalis (lemon balm) extract, Prunella vulgaris (selfheal) extract, and combinations thereof. It is to be understood that a herbal extract or herbal base may contribute to efficacy of copper in a formulation of the present invention.

In another example, the present invention provides a disposable device comprising a liquid formulation comprising a composition for the topical treatment of skin and mucosal membrane lesions in a subject, wherein the composition comprises an effective amount of a copper compound as described in any example hereof, and an herbal extract.

When present, a herbal extract, e.g., selected from the group consisting of: Hypericum perforatum (St. John's wort) extract, Aloe barbadensis extract, Melaleuca alternifolia (tea tree) .extract, Melissa officinalis (lemon balm) extract, Prunella vulgaris (selfheal) extract, and combinations thereof, is present at a concentration of about 0.05% (v/v) of an aqueous formulation to about 2% (v/v) of an aqueous formulation, including about 0.05% (v/v) of an aqueous formulation or about 0.1% (v/v) of an aqueous formulation or about 0.15% (v/v) of an aqueous formulation or about 0.2% (v/v) of an aqueous formulation or 0.5% (v/v) of an aqueous formulation or 1.0% (v/v) of an aqueous formulation or 1.5% (v/v) of an aqueous formulation or 2% (v/v) of an aqueous formulation. For example, a herbal extract such as that of Hypericum perforatum or Aloe barbadensis may be obtained or prepared by means of solvent (ethanol) extraction of a plant part e.g., flowers etc.

One or more skin protectants e.g., glycerin or sorbitol may also be included in the liquid formulation e.g., at a concentration of about 1% (w/w) to about 5% (w/w).

One or more preservatives, e.g., Germall Plus, Methyl Hydroxybenzoate or Propyl Hydroxybenzoyate, osmotic regulators, thickeners, flavors, fragrances, emollients, humectants, colorants, pigments and combinations thereof may also be included in the liquid formulation provided with the device of the present invention. The liquid formulation provided with the device according to any example hereof may further comprise citric acid, Vitamins such as Vitamin E or Vitamin A, caprylic triglyceride, or hydroxyelthylcellulose. The liquid formulation provided with the device according to any example hereof may further comprise sodium ascorbate e.g., at a concentration of about 3-10% (w/w) and/or hydrogen peroxide e.g., at a concentration of about 3-10% (w/w).

The disposable device of the present invention may be used to topically apply a liquid formulation without limitation to any subject susceptible to a lesion of the skin and/or mucosa, especially subjects that are at risk of virus infection or have a preexisting infection by one or more viruses. For example, the subject may be a sexually- active person, healthcare worker, or a subject having an immature or suppressed immune system e.g., a newborn, transplant recipient, HIV- 1 -infected subject or AIDS patient.

The liquid formulations provided with the disposable device of the present invention are effective in ameliorating one or more visible symptoms of a skin lesion or lesion in the mucosa e.g., associated with infection. For example, the liquid formulation will reduce duration and/or severity of a lesion and/or reduce pain and/or reduce inflammation and/or reduce itchiness and/or reduce virus shed. Alternatively, or in addition, a formulation of the present invention prevents or assists in preventing a lesion from increasing in size and/or decrease virus shed or spread during healing. Alternatively, or in addition, a formulation of the present invention prevents or reduces recurrence of a lesion or virus outbreak.

The disposable device of the present invention may be used to topically apply the liquid formulation at any stage during presentation of symptoms in a subject. For example, a formulation of the present invention provides a beneficial effect when applied early e.g., at first appearance of a lesion or with 24 hours or 48 hours or 72 hours of the first appearance of a lesion or before the lesion weeps. Alternatively, the formulation may be applied to an active lesion.

In one example, the present invention is performed as a stand-alone therapy. In another example, the present invention is performed as an adjunct therapy with other prophylactic or therapeutic treatment e.g., one or more of an antiviral agent, nonsteroidal anti-inflammatory drug (NSAID)j vaccine, dietary supplement, etc. including one or more of acyclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), penciclovir, docosanol, tromantadine, zilactin, lipactin, tea tree oil, cimetidine, probenecid, aspirin, lidocain, prilocaine, tetracaine, petroleum jelly, Herpevac, lysine, lactoferrin, vitamin C, vitamin A, vitamin E, and zinc.

In another example of the present invention, there is provided a method of treating skin and/or mucosal lesions in a subject comprising use of the disposable device according to any example hereof to topically apply a therapeutically effective amount of the liquid formulation to at least one skin or mucosal membrane lesion, said method comprising the steps of:

(a) manually inserting the absorbent material and a portion of the elongate member into the receptacle comprising the liquid formulation for a time sufficient to induce the wicking action and for delivery of an amount of the liquid formulation to the applicator portion to occur;

(b) contacting the at least one skin or mucosal membrane lesion with the applicator portion comprising the amount of the liquid formulation to thereby treat said skin or mucosal lesion.

In another example of the present invention, there is provided a method of preventing skin and/or mucosal lesions in a subject comprising use of the disposable device according to any example hereof to topically apply a therapeutically effective amount of the liquid formulation to at least one site on a subject at risk of developing a skin and/or mucosal membrane lesion at said site, said method comprising the steps of:

(b) contacting the at least one site at risk of developing a skin and/or mucosal membrane lesion with the applicator portion comprising the amount of the liquid formulation to thereby prevent said skin or mucosal lesion.

The therapeutic or prophylactic method described herein may further comprise applying to the lesion a therapeutically effective amount of a liquid formulation according to any example hereof e.g., for a time and under conditions sufficient to ameliorate one or more visible symptoms of a skin lesion or lesion in the mucosa e.g., associated with infection. For example, the amelioration of one or more symptoms may comprise a reduced duration and/or severity of a lesion and/or reduces pain and/or reduced inflammation ^'and/or reduced itchiness and/or reduced virus shed, and/or decrease in virus shed and/or decrease in virus spread. Alternatively, or in addition, a liquid formulation of the present invention is applied for a time and under conditions sufficient to prevent or reduce recurrence and or to prevent a lesion from increasing in size.

The therapeutic or prophylactic method of the present invention is particularly suited to the treatment and prevention of skin and/or mucosal lesions associated with a cut, abrasion, wound, acne, infection by a bacterium, fungus or virus, including one or more of Herpes Simplex Virus e.g., HSV-1 or HSV-2, Herpes Zoster Virus, Polio virus, Shingles-associated viruses, Varicella Zoster Virus, Chicken pox-associated viruses, Human Immunodeficiency Virus (HIV-1), or any serotype thereof capable of infecting a human or causing a skin lesion in another animal species. In a particular example, the present invention provides a method for the treatment and/or prevention of skin lesions associated with infection by a herpes virus e.g., HSV-1 and/or HSV-2 or any serotype thereof capable of infecting a human or causing a skin lesion in another animal species.

In the method according to any example hereof, the liquid formulation according to any example hereof may be applied with a disposable device of the invention once or more times during an outbreak, such as prior to virus shed or weeping of the lesion or to a visible and/or mature lesion. For example, a lesion may be applied to the mouth area of a subject suffering from a cold sore, or around the genitalia of a subject suffering from genital herpes.

The present invention also provides a kit comprising the disposable device according to any example hereof packaged with instructions for use.

Another example of the present invention provides for use of the disposable device, or kit according to any example hereof in the treatment or prevention of skin and/or mucosal lesions in a subject, wherein the skin and/or mucosal lesion is associated with a cut, abrasion, wound, acne, infection by a bacterium, fungus or virus, e.g., wherein the virus is selected from the group consisting of Herpes Simplex Virus e.g., HSV-1 or HSV-2, Herpes Zoster Virus, Polio virus, Shingles-associated viruses, Varicella Zoster Virus, Chicken pox-associated viruses, Human Immunodeficiency Virus (HIV-1), or any serotype thereof capable of infecting a human or causing a skin lesion in another animal species, especially HSV-1 and/or HSV-2 or any serotype thereof capable of infecting a human or causing a skin lesion in another animal species.

Throughout this specification including the claims, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a ^■ context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia before the priority date of the invention disclosed in this application.

The present invention is also described with reference to the following examples. It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific examples without departing from the spirit or scope of the invention as broadly described. The present examples are, therefore, to be considered in all respects as illustrative and not restrictive.

Brief Description of Drawings

Fig. 1 , Panel A is a schematic side view of an example of the disposable device according to the invention comprising a topical liquid formulation ready for use.

Fig. 1, Panel B is a schematic side view of the disposable device of Fig. 1, Panel A shown ready for use to treat or prevent skin and/or mucosal membrane lesions, wherein the absorbent material has been inserted into the receptacle and wi eking has occurred to deliver the amount of liquid formulation to the applicator portion.

Fig 2, Panel A is a schematic view showing the ease of manual manipulation of the disposable device shown in Fig 1, Panel B, demonstrating that contamination by manual handling of the applicator portion is avoided. Fig 2, Panel B is a schematic view showing the use of the disposable device of Fig. 2, Panel A to apply to treat a skin lesion on a subject.

Detailed Description of Exemplary Embodiments

Referring to Figures 1-2 of the drawings, reference numeral 10 generally designates an example of a disposable device for the topical application of a liquid formulation to a skin and/or mucosal site in a subject. Those skilled in the art will readily appreciate that the device has numerous applications that require topically administering a liquid formulation to a skin and/or mucosal site in a subject, wherein it may be desirable to apply such a liquid formulation to one or more sites in a single use, and then discard the applicator and device for hygienic reasons.

The disposable device 10 includes an elongate member 12 having a proximal end comprising an absorbent material 14 in the form of a first swab and an applicator portion 16 in the form of a second swab at the distal end of the elongate member 12. The elongate member 12 may be a double-tip swab, wherein both the absorbent material 14 and the applicator portion 16 may be made of cotton as shown in this example (Figure 1). The elongate member in this example has an annular cross-section defining a narrow tube or conduit 13 connecting the first and second swabs (14, 16). Other materials may be contemplated for both the absorbent material 14 and the applicator portion 16. The disposable device further includes a receptacle 18 in the form of a circular vial for holding the liquid formulation 20. The circular vial 18, has a top opening for 'receiving the first swab 14 and a portion of the elongate member 12. The first swab 14 is configured to fit the circular vial 18, wherein the first swab 14 contacts the sides of the circular vial 18, and wherein the first swab 14 fits snugly within the circular vial 18. The elongate member 12 may be manually held along any part or region of the narrow tube or conduit 13. The manual insertion of the absorbent material into the receptacle as shown in Figure I, Panel B, displaces a volume of the liquid formulation 20, wherein the volume displacement, e.g., by force, induces and/or aids a wickirtg action that draws the liquid formulation through the narrow tube or conduit 13 of the elongate member 12 to the second swab 16 thereby delivering an amount of the liquid formulation to the second swab 16 ready for use (Figure 1, Panel B). The receptaclel8 in this example further comprises a sealing member for the opening 22 i the form of a removable stopper lid, such that the disposable device may be provided packaged with the liquid formulation. Other sealing members include, but are not limited to screw caps, a removable film or membrane. The sealing member may also include a cap, e.g., a screw cap or stopper lid, in addition to removable film or membrane.

In this example, manual manipulation is achieved by holding a region of the elongate member 12, e.g., the narrow tube or conduit 13 between the distal and proximal ends during use thereby avoiding touching of the absorbent material that makes contact with the liquid during use, and manual contact with the applicator portion is also avoided. The first swab 14 is inserted into the receptacle 18, while also holding the outer part of the receptacle 18, which optionally includes a twisting action on either the receptacle 18 or the elongate member 12 by holding the narrow tube or conduit 13. As discussed supra, the insertion induces the wicking action to deliver an amount of liquid to the applicator portion 16, as shown in Figure 1, Panel B as shading in the applicator portion 16, e.g., the second swab. The device as shown ready for use in Figure 1, Panel B may then be further manipulated by holding the receptacle 18 thereby avoiding contamination of the liquid formulation to be applied to a desired skin or mucosal site, as shown in Figure 2.

The amount of liquid formulation that is rapidly delivered to the applicator portion is thus controlled without any mess, or unnecessary wastage. In this example, the amount of the liquid formulation delivered to the applicator portion is delivered within a time of about 1 sec to 10 sec after inserting the absorbent material into the receptacle comprising the liquid formulation during use.

As the device is economical to manufacture, it may then be disposed of after applying the liquid formulation to one or more sites in a single use. This provides the further advantage of being hygienic and avoids contamination with any stock source of liquid formulation, as the amount of liquid formulation provided with the device may also be disposed, accordingly the amount of the liquid formulation disposed is controlled, and loss due to contamination is minimized.

The disposable device has particular, but not necessarily exclusive, application for the topical treatment of skin and/mucosal membrane lesions in a subject. Examples of liquid formulations that may be used with the disposable device of the invention or supplied with the disposable device include liquid formulations comprising an amount of copper as an active trace metal effective for the topical treatment of skin and/or mucosal membrane lesions in a subject. For example, exemplary pharmaceutical compositions comprising copper for the topical treatment of skin and/or mucosal membrane lesions in a subject have been described in the International Patent Application No. PCT/AU2006/00863 dated 30 June 2006, the corresponding accepted Australian Application No. 2006261580 and pending divisional Australian Application No. 2009217410 dated 21 September 2009 the contents of which are incorporated herein by reference in their entirety. The compositions described therein work by substantially eliminating the virus on direct contact at the outbreak site which accelerates the recovery time of the viral outbreaks and reduces the inconvenience and embarrassment of the condition. The compositions can be conveniently administered in a single dose liquid formulation to each lesion at the first signs of an outbreak.

Previous topical medications have used high concentrations of copper sulphate, some as high as 10% by weight. High concentrations of copper have been found to cause blood poisoning which can be potentially fatal. In contrast, the pharmaceutical compositions contemplated for this purpose are used at a concentration of 5-9% by weight have antiviral effect in the treatment of skin lesions. Use of a lower concentration of copper results in the composition being safe, providing an effective dose to be used topically, even on open wounds. Prior art uses indicate that it is necessary to use high concentrations of copper sulphate to provide adequate anti-viral activity. It is also contemplated that copper when used in combination with 0.05 to 0.15% by weight of hypericum perforatum extract to provide a synergistic effect.

The present inventors have found that lower concentrations of a copper salt is significantly effective in the treatment of a lesion of the skin or mucosa, especially those caused by viral agents such as HSV-1 and/or HSV-2. More particularly, a composition comprising copper ions, such as in the form of copper sulphate pentahydrate. When combined in a herbal base e.g., Hypericum perforatum extract or Aloe barabensis extract the liquid formulations are effective in dramatically reducing the healing time of lesions due to infection by herpesviruses, stopping the normal progression of the viral outbreak from the stage at which the initial outbreak occurred, and also in reducing recurrence of lesions. Preferred liquid formulations contemplated for use with the disposable device of the present invention is a copper-based solution with copper as the active trace metal, preferably in an aqueous herbal base.

Whilst it is not intended that the present invention should be restricted in any way by a theoretical explanation of the mode of action of copper that may be included in the liquid formulations, it is believed that copper may exert an antiviral and healing effect by virtue of the composition being slightly acidic, which is corrosive to the virus. Accordingly, preferred compositions for use in the liquid formulations provided with the device possess an acid group and sulfur molecule to assists in penetration of the composition through the protective capsule of a virus such as herpes virus, thereby allowing for direct contact with the virus and subsequent destruction of the virus.

In one example, the liquid formulations provided with the disposable device of the present invention are those recognized in the pharmaceutical arts as being suitable for topical application and include, without intended limitation, liquid emulsion, gel, aqueous solution, solvent solution, suspension, aqueous suspension, or solvent suspension. The liquid formulations preferably include copper sulphate pentahydrate in from about 5 to 9, preferably 7.8% by weight or copper ion from about 1 to 5%, (equivalent to about 3 to 7% copper sulphate) , preferably 5% by weight.

Optionally, a skin protectant e.g., glycerin, is included e.g., from about 5% by weight, and a herbal extract is included from about 0.05 to 0.15%, preferably about 0.1 % by weight. In addition to the enhanced therapeutic effect, the preferred liquid formulation is also advantageous in that it is safe and has no known side-effects. The composition can also be safely used for veterinary purposes. A skin protectant forms a barrier over the skin surface to protect against irritation due to touching, rubbing etc. The skin protectant also provides a protective barrier over the lesion, preventing loss of the active ingredient to the action of saliva. In a preferred embodiment, the skin protectant is in the form of glycerin.

In addition to the foregoing ingredients, the liquid formulation as described in any example hereof may contain other ingredients such as are recognized by those skilled in the pharmaceutical industry as being typically present in such formulations. These include, without limitation, one or more preservatives, osmotic regulators, thickeners, flavours, fragrances, emollients, humectants, colorants, pigments and the like. It would be clear to the skilled addressee that the compounding of the compositions included in the liquid formulation will be carried out utilizing some or all of these ingredients depending on the area of application and intended use. For example, for a preparation intended for application in or around the mouth, it may be necessary to add flavours to mask the taste of the essential ingredients.

Although best long term results are achieved by applying the liquid formulations to a visible and mature lesion, patients have reported great success in preventing outbreaks by applying the composition in the early stages. This can include applying the composition topically to the affected area as the first sign of symptoms such as itching, tingling, redness or inflammation.

Example 1:

Exemplary copper liquid formulations of the invention in aqueous herbal base

An aqueous solution was prepared from formula 1 given below.

Formula 1

Components Typical Amount

Assay as copper sulphate pentahydrate (CUSO₄-SH2O) 7.80% w/w max (Assay equivalent copper sulphate anhydrous (CuS0₄) 5.0% w/w max Glycerin (Glycerol) 5.0% w/w max

Hypericum perforatum 0.1% v/v max Germall Plus (preservative) 0.3% v/v max Water Purified Balance

Formula 2

Components Typical Amount

Assay as copper sulphate 9% w/w max Glycerin (Glycerol) 5% w/w max Hypericum perforatum 0.15% v/v max Germall Plus (preservative) 0.3% v/v max Water Purified Balance

Formula 3

Components Typical Amount

Assay as copper sulphate 5% w/w max Glycerin (Glycerol) 1 % w/w max Hypericum perforatum 0.05% v/v max Germall Plus (preservative) 0.1 % v/v max Water Purified Balance

Formula 4

Components Typical Amount Assay as copper chloride 9% w/w max Glycerin (Glycerol) 3.0% w/w max Hypericum perforatum 0.2% v/v max Germall Plus (preservative) 0.2% v/v max Water Purified Balance

Formula 5

Components Typical Amount

Assay as copper chloride 9% w/w max Glycerin (Glycerol) 3.0% w/w max Hypericum perforatum 0.2% v/v max Germall Plus (preservative) 0.2% v/v max Water Purified Balance

Formula 6

Components Typical Amount

Assay as copper salicylate 9% w/w max Glycerin (Glycerol) 3.0% w/w max Hypericum perforatum 0.2% v/v max Germall Plus (preservative) 0.2% v/v max Water Purified Balance

Formula 7

Each solution was prepared by filling a suitable vessel with about 60% distilled water. Copper compound was added to water with continuous stirring. Mixing of a solution continued for 10 minutes or until the copper was fully dissolved. Glycerin was added to a solution and mixed for a few minutes. Hypericum perforatum was gradually added with continuous mixing. Each solution was then brought to final weight by the slow addition of the required amount of water with continuous blending for about 10 minutes. Preservative Germall Plus was added and a solution was then allowed to stand for 12 to 15 hours to stabilize. Each solution was then filtered to remove the sediment and packaged.

Example 2

Treatment of Herpes Simplex Patients with a copper liquid formulation of the invention

A solution prepared in Example 1 was tested for its effectiveness against Herpes virus. To determine efficacy of the liquid formulation in reducing the healing time of lesions associated with Herpes virus infection and/or reducing the recurrence of the lesions, 51 patients were observed.

Of the 51 patients treated with the composition, 34 suffered from mouth lesions associated with Herpes Simplex virus 1 infection, and 19 suffered from genital lesions associated with Herpes Simplex virus 2 infections, and 2 patients suffered from both mouth and genital lesions. Following topical application of the composition to the area of the viral -associated lesion, 38 of the 51 patients reported a dramatic reduction in the healing time of the lesion (with scab formation occurring within 24 hours) and 47 of the 51 patients reported a reduced recurrence of lesions. All patients reported a substantial reduction in pain and discomfort associated with the lesions following application of the liquid formulation.

Example 3

Safety, tolerabiliry and efficacy of the copper formulation in patients suffering from HSV-1 and/or HSV-2

A trial enrolled 150 herpes simplex patients (HSV 1 & HSV 2) having active lesions on external genitalia and skin, aged between 18 and 55 years.

Subjects were randomized into two groups (A and B). Subjects in Group A . topically applied a liquid formulation as defined in Example 1, transferring 2-3 drops of aqueous copper formulation (depending upon the affected area) to a wet cotton swab (enough to saturate it), e.g., the disposable device according to any example hereof is used wherein the applicator portion of the cotton swab is thoroughly saturated. The liquid formulation on the saturated cotton swab was then applied to the affected part only once at clinic. Subjects in Group B topically applied 0.5 - 1.5 grams of the comparator article (acyclovir 5% cream) twice daily (once in the morning and once at night) to cover affected areas for 7 days. Treatments were initiated on Day 1, pending the results of laboratory investigations. Patients in Group A presented for efficacy & safety assessments on Day 2, Day 3, Day 8 and Day 14. Group B patients presented on Day 3 and Day 8 for efficacy evaluation and on Day 14 for follow up. Patients also recorded their self-assessment of symptoms in a patient diary from Day 1 to Day 14.

Safety was evaluated by determining adverse event reports throughout the study.

Hematology and clinical chemistry labs, urinalysis, and physical exam of basic systems were obtained at initial screening and Day 14 (end of study) visits. The patient was withdrawn immediately from the study if the results show abnormal values in laboratory investigation reports.

Efficacy endpoint assessments determine time to achieve greater than about

50% crusting scabbing or healed ulcer. Cutaneous assessments are performed to determine disappearance of erythema, crust/scab formation in ulcers, disappearance of pain and disappearance of itching and burning sensation.

Cutaneous efficacy assessments are performed at each visit on Day 2, Day 3 and Day 8 in Group A and on Day 3 and Day 8 or until 100% crusting is observed in Group B.

Local cutaneous tolerability is evaluated with assessments of erythema, induration and stinging sensation on Day 1 , Day 2, Day 3 and Day 8 in Group A and on

ί

Day 3 and Day 8 in Group B or until 100% crusting is observed.

The foregoing case studies demonstrate the efficacy of copper formulations in an herbal base for the treatment of skin and mucosal membrane lesions associated with herpes virus infection.

Example 4: ' Exemplary liquid formulations comprising an amount of copper as an active trace metal for the topical treatment of skin and/or mucosal membrane lesions in a subject

An aqueous solution is prepared from formula given below.

Formula 8

Components Typical Amount

Assay as copper sulphate pentahydrate (CuS04-SH₂0) 7.80% w/w max (Assay equivalent copper sulphate anhydrous (CuS0₄) 5.0% w/w max Glycerin (Glycerol) 5.0% w/w max

Germall Plus (preservative) 0.3% v/v max Water Purified Balance

Formula 9

Components Typical Amount Assay as copper sulphate 9% w/w max Glycerin (Glycerol) 5% w/w max Germall Plus (preservative) 0.3% v/v max Water Purified Balance

Formula 10

Components Typical Amount

Assay as copper sulphate 5% w/w max Glycerin (Glycerol) 1 % w/w max Germall Plus (preservative) 0.1 % v/v max Water Purified Balance

Formula 11

Components Typical Amount

Assay as copper chloride 9% w/w max Glycerin (Glycerol) 3.0% w/w max

Germall Plus (preservative) 0.2% v/v max Water Purified Balance

Formula 12

Components Typical Amount

Assay as copper chloride 9% w/w max

Glycerin (Glycerol) 3.0% w/w max

Germall Plus (preservative) 0.2% v/v max

Water Purified Balance

Formula 13

Components Typical Amount

Assay as copper salicylate 9% w/w max Glycerin (Glycerol) 3.0% w/w max Germall Plus (preservative) 0.2% v/v max Water Purified Balance

Each solution is prepared by filling a suitable vessel with about 60% distilled water. Copper compound is added to water with continuous stirring. Mixing of a solution is continued for 10 minutes or until the copper is fully dissolved. Glycerin is added to a solution and mixed for a few minutes. One of more of the optional components listed below may also be added. Each solution is then brought to final weight by the slow addition of the required amount of water with continuous blending for about 10 minutes. Preservative Germall Plus, one or more other preservative listed below is added and a solution is then allowed to stand for 12 to 15 hours to stabilize. Each solution is then filtered to remove the sediment and packaged.

Each of the above solutions may optionally comprise any one of more of the following: sodium ascorbate at about 3-10% w/w;

hydrogen peroxide at about 3-10% w/w; Other optional constituents: osmotic regulators, thickeners, flavors, fragrances, emollients, humectants, colorants, pigments.

Other preservatives: Methyl Hydroxybenzoate, or Propyl Hydroxybenzoate.

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A disposable device for topical application of a liquid formulation to a skin and/or mucosal site in a subject, said disposable device comprising:

2. The disposable device of claim 1 , wherein the viscosity of the liquid formulation aids and/or induces the wicking action.

3. The disposable device of claim 1 or 2, wherein the absorbent material contacts one or more side wall(s) of the receptacle during insertion, wherein said contact aids and/or induces the wicking action.

4. The ^' disposable device according to any one of claims 1 to 3, wherein displacement of a volume of the liquid formulation during insertion of the absorbent material into the receptacle aids and/or induces the wicking action.

5. The disposable device according to any one of claims 1 to 4, wherein the amount of the liquid formulation delivered to the applicator portion is sufficient to topically apply to at least one skin or mucosal membrane site to be treated in the subject.

6. The disposable device according to any one of claims 1 to 5, wherein the amount of the liquid formulation delivered to the applicator portion is sufficient to topically apply to several skin and/or mucosal sites to be treated in the subject in a single use before disposal.

7. The disposable device according to any one of claims 1 to 6, wherein the amount of the liquid formulation delivered to the applicator portion is delivered within a time of about 1 sec to about 10 min after inserting the absorbent material into the receptacle comprising the liquid formulation during use.

8. The disposable device according to 7, wherein the time is about 1 to 10 sec.

9. The disposable device according to any one of claims 1 to 8, wherein the elongate member comprises a conduit through which the liquid formulation is delivered to the applicator portion.

10. The disposable device of claim 9, wherein the conduit comprises a porous matrix housed therein.

1 1. The disposable device according to claim 9 or 10, wherein the applicator portion is an opening at the distal end of the elongate portion.

12. The disposable device according to any one of claims 1 to 8, wherein the elongate member comprises a porous material attached to a solid support.

13. The disposable device according to any one of claims 1 to 11, wherein the elongate member is inserted by manually holding a region between the proximal and distal ends during use.

14. The disposable device according to any one of claims 1 to 13, wherein the applicator portion comprises an absorbent material attached to the distal end of the elongate member.

15. The disposable device according of claim 14, wherein the elongate member is a double-tip cotton swab with a hollow body.

16. The disposable device according to any one of claims 1 to 15, wherein the receptacle further comprises a sealing member for the opening.

17. The disposable device according claim 16, wherein the sealing member is a removable lid.

18. The disposable device according to any one of claims 1 to 17 comprising the liquid formulation for applying to the skin and/or mucosal site in the subject.

19. The disposable device according to claim 18, wherein the liquid formulation comprises an amount of copper as an active trace metal effective for the topical treatment of the skin and/or mucosal membrane lesions in the subject.

20. The disposable device according to claim 19, wherein the copper as an active trace metal is in the form of copper sulphate, copper chloride or copper salicylate.

21. The disposable device according to claim 19 or 20, wherein the copper as an active trace metal is at a copper ion concentration of about 1 to 5 % w/w.

22. The disposable device according to claim 21, wherein the copper ion concentration 5 % w/w.

23. The disposable device according to any one of claims 18 to 22, wherein the liquid formulation further comprises an herbal base.

24. The disposable device according to claim 20, wherein the base is an aqueous solution, liquid emulsion, or a gel comprising an amount of liquid.

25. The disposable device according to claim 18, wherein the liquid formulation comprises a composition for the topical treatment of the skin and/or mucosal membrane lesions in the subject, said composition comprises an effective amount of:

a copper compound;

and an herbal extract.

26. The disposable device according to claim 25, wherein the herbal extract is hypericum perforatum

27. The disposable device according to claim 25 or 26, wherein the copper compound is in the form of copper sulphate, copper chloride or copper salicylate.

28. The disposable device according to claim 27, wherein the copper compound is copper sulphate.

29. The disposable device according to claim 28, wherein the copper sulphate, is copper sulphate pentahydrate anhydrous.

30. The disposable device according to any one of claims 25 to 30, wherein the copper compound is at a concentration of about 5-9% (w/w).

31. The disposable device according to claim 28 or 29, wherein the copper sulphate is provided at a concentration of about 7.8% (w/w).

32. The disposable device according to any one of claims 25 to 31, wherein the copper compound provides a copper ion concentration of about 1-5% (w/w).

33. The disposable device according to any one of claims 25 to 32, wherein the hypericum perforatum extract is at a concentration of about 0.05 to 0.15% (v/v).

34. The disposable device according to any one of claims 18 to 33, wherein the liquid formulation further comprises a skin protectant.

35. The disposable device according to claim 34, wherein the skin protectant is at a concentration of about 1 to 5% (w/w).

36. The disposable device according to claim 35, wherein the skin protectant is glycerin.

37. The disposable device according to any one of claims 18 to 36, wherein the liquid formulation further comprises any one or more of a preservative, osmotic regulator, thickener, flavor, fragrance, emollient, humectant, colorant, or pigment.

38. The disposable device according to claim 37, wherein the preservative is Germall Plus.

39. The disposable device according to any one of claims 37 or 38, wherein the preservative is at a concentration of about 0.1 to about 0.3% (w/w).

40. The disposable device according to any one of claims 18 to 39, wherein the liquid formulation further comprises aloe vera at a concentration of about 1.0% (v/v).

41. The disposable device according to any one of claims 18 to 40, wherein the liquid formulation further comprises further comprising sodium ascorbate at a concentration of about 3-10% (w/w).

42. The disposable device according to any one of claims 18 to 41, wherein the liquid formulation further comprises hydrogen peroxide at a concentration of about 3- 10% (w/w).

5 43. A method of treating skin and/or mucosal lesions in a subject comprising use of the disposable device according to any one of claims 1 to. 42 to topically apply a therapeutically effective amount of the liquid formulation, to at least one skin or mucosal membrane lesion, said method comprising the steps of:

(a) manually inserting the absorbent material and a portion of the elongate 10 member into the receptacle comprising the liquid formulation for a time sufficient to induce the wicking action and for delivery of an amount of the liquid formulation to the applicator portion to occur;

(b) contacting the at least one skin or mucosal membrane lesion with the applicator portion comprising the amount of the liquid formulation to thereby treat said

15 skin or mucosal lesion.

44. A method of preventing skin and/or mucosal lesions in a subject comprising use of the disposable device according to any one of claims 1 to 42 to topically apply a therapeutically effective amount of the liquid formulation to at least one site on a 20 subject at risk of developing a skin and/or mucosal membrane lesion at said site, said method comprising the steps of:

(a) manually inserting the absorbent material and a portion of the elongate member into the receptacle comprising the liquid formulation for a time sufficient to induce the wicking action and for delivery of an amount of the liquid formulation to the

^ 25 applicator portion to occur;

30 45. The method of claim 42 or 43, wherein the skin lesion is associated with acne.

46. The method of claim 42 or 43, wherein the skin and/or mucosal lesion, is associated with a bacterial, fungal or^' viral infection.

47. The method of claim 46, wherein the viral infection is selected from the group consisting of Herpes Simplex virus, Herpes Zoster virus, Polio virus, Shingles- associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus.

48. The method of claim 47, wherein the viral infection is caused by Herpes Simplex virus.

49. A kit -comprising the disposable device according to any one of claims 1 to 42 packaged with instructions for use.

50. Use of the disposable device according to any one of claims 1 to 42, or the kit of claim 49 in the treatment or prophylaxis of skin and/or mucosal lesions in a subject.

51. The kit of claim 49, or the use of claim 50, wherein the skin lesion is associated with acne.

52. The kit of claim 49, or the use of claim 50, wherein the skin and or mucosal lesion is associated with a bacterial, fungal or viral infection.

53. The kit of claim 52, or the use of claim 50, wherein the viral infection is selected from the group consisting of Herpes Simplex virus, Herpes Zoster virus, Polio virus,

Shingles-associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus.

54. The kit of claim 53, or the use of claim 50, wherein the viral infection is caused by Herpes Simplex virus.