IE20190207A1 - Medical device for topical treatments - Google Patents

Abstract

The current invention concerns a medical device for the treatment of a fungicidal infection in a subject in need thereof, comprising: a medical container comprising a fungicidal medical composition, an applicator nozzle having an opening for applying said fungicidal medical composition to said subject, and an actuator mechanism for controlling said applicator nozzle, characterized, in that said medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem penetrates said penetrable seal of said medical container, thereby allowing a fluid communication between said medical container and said applicator nozzle.

Description

MEDICAL DEVICE FOR TOPICAL TREATMENTS TECHNICAL FIELD The present invention relates to a medical device for the treatment of dermatological disorders and a method for use thereof. The present invention more in particular relates to a medical applicator by which a fungicidal composition can be applied to dermatological disorders, such as, for example toenail onychomycosis.

BACKGROUND CN 103 764 219 discloses a medical applicator for the topical treatment of dermatological issues. A drawback of the above mentioned devices is the permeation of certain gases through the seals of bottles as well as the plastic of the bottle. Ethanol migrates through most plastics at the thicknesses used for blow moulding containers.

Manufacturers have devised methods to eliminate permeation such as packaging in glass ampoules or by employing plastics with gas barrier properties, such as polyethylene terephthalate (PET). PET greatly reduces permeation when a sufficient cross-section is provided in the package; however the current devices employ blow moulded containers in combination with conventional caps. The caps therefore be come the weakest part of these systems and oftentimes leak due to inconsistent sealing (PET/foil) or due to cap loosening.

Additionally, current container designs utilize conventional, single weld inner seals as a means of sealing the bottle contents. The size of the bottle cap and force with which it is tightened on the bottle therefore becomes critical to maintenance of the force needed to mechanically reinforce the foil over time. The loosening of the cap is a common failure and oftentimes results in leakage of the bottle contents —especially when the system is required to remain in storage for long periods prior to use. Such an applicator is discussed in the German patent application DE 102 O07 046 600 A1.

Some medical applicators use fibers, similar to brushes, to apply liquid medical solutions to a target area. These fibers, particularly after the applicator has been used, tend to entrap some liquid. This leads to stiff fibers that are knit together by com ponents from the medical solution. Additionally, particularly for onychomycosis, this can lead to transfer of a fungus from one nail to another as these fibres are hard to keep sterile.

Due to this, these applicators have a high upkeep requirement for proper use. Such applicators are discussed in the Chinese patent CN 206 492 102 U.

WO 2016/142305 discloses an applicator for topical application of an acidic liquid, the applicator comprising a container containing said acidic liquid, the container comprising an opening in fluid contact with a nib for a controlled release of the acidic liquid, wherein the nib comprises a plurality of fibers and an adhesive material adhering the fibers. A kit of parts for topical application of an acidic liquid is also disclosed, the kit of parts comprising a liquid release unit comprising a nib for a controlled release of the acidic liquid, and a container unit comprising a container configured to contain the acidic liquid, wherein the container unit further comprises a liquid release element for application of the acidic liquid to the nib, wherein the nib comprises a plurality of fibers and an adhesive material adhering the fibers. Such devices, however, do not provide sufficient or reliable closure of the applicator, thereby allowing at least partial loss of the acidic liquid through evaporation.

Therefore, it is desirable to overcome the disadvantages and drawbacks of the prior art with a medical skin applicator. It would be desirable if the skin applicator can be disposed in an inverted orientation during use, and ensure a liquid and/or gas tight closure of the applicator. It would be highly desirable if the medical skin applicator and its constituent parts are easily and efficiently manufactured and assembled.

SUMMARY OF THE INVENTION The present invention provides a medical device for the treatment of fungicidal infection according to the claims.

In a first aspect the present invention provides a medical device for the topical treatment of a disease in a subject in need thereof, comprising: — a medical container comprising a medical composition, — an applicator nozzle having an opening for applying said medical composition to said subject, and — an actuator mechanism for controlling said applicator nozzle.

More specifically, the present invention provides said medical device whereby medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle.

The penetrable seal is a good barrier for gasses and solvents. As a result, the low permeability of the medical container before use increases the shelf life of the medical device. Additionally, a nozzle applicator is used over a brush or fibre applicator. The smooth surface of a nozzle applicator is easier to clean and sterilize. Lastly the actuator mechanism allows for controlled application of medical doses of the fungicidal medical composition.

In the second aspect the present invention provides a kit comprising a medical device for the topical treatment of a disease in a subject in need thereof, comprising: - a medical container comprising a medical composition; - an applicator nozzle having an opening for applying said medical composition to said subject, an actuator mechanism for controlling said applicator nozzle, and a housing for a medical container.

More specifically, the present invention provides said kit, whereby said medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem penetrates pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle.

In the third aspect, the present invention provides a method for the treatment of fungicidal infection operating a medical device comprising the steps of: - Providing a medical device comprising a medical container holding a fungicidal medical composition, an applicator nozzle for applying said fungicidal medical composition and an actuator for controlling said application, actuating the actuator to facilitate fluid communication between the medical container and the applicator nozzle.

DESCRIPTION OF FIGURES Figure 1A shows a schematic overview of a possible embodiment of the medical device.

Figure 1B shows a schematic overview of a possible embodiment of the assembly of the medical device.

Figure 1C shows a possible embodiment of the actuation of the medical device.

Figure 1D shows a possible embodiment of the use of a possible embodiment of the medical device.

Figure 1E shows a schematic overview of a possible embodiment of the medical device after the penetrable seal has been pierced.

Figure 2A shows a longitudinal cross-sectional view of a possible embodiment of the housing according to the present invention.

Figure 2B shows a lateral cross-sectional view of a possible embodiment of the housing according to the present invention.

Figure 3 shows a possible embodiment of the medical container.

Figure 4A shows a cross-sectional view of a possible embodiment of the sealing ring according to the present invention.

Figure 4A shows a perspective of a possible embodiment of the sealing ring according to the present invention.

Figure 5A shows a detailed perspective of a possible embodiment of an actuating stem according to the present invention.

Figure 5B shows a cross-sectional view of a possible embodiment of an actuating stem according to the present invention.

Figure 6A shows a detailed cross sectional view of a possible embodiment of an applicator nozzle according to the present invention.

Figure 6B shows a perspective of a possible embodiment of an applicator nozzle according to the present invention.

Figure 7A shows a radial view of a possible embodiment of a cap according to the present invention.

Figure 7B shows an axial view of a possible embodiment of a cap according to the present invention.

Figure 8A shows a cross-sectional view of a possible embodiment of a nail file according to the present invention.

Figure 8B shows a cross-sectional view of a possible embodiment of a nail file according to the present invention.

Figure 9A shows a schematic overview of an alternative possible embodiment of the assembly of the medical device.

Figure 9B shows a perspective of an alternative possible embodiment of an actuating stem according to the present invention.

Figure 9C shows a perspective of an alternative possible embodiment of an actuating stem according to the present invention.

Figure 10A shows a schematic overview of a preferred embodiment of the medical device.

Figure 10B shows a schematic overview of a preferred embodiment of the assembly of the medical device.

Figure 10C shows a cross-sectional view of a preferred embodiment of the sealing ring according to the present invention.

Figure 10D shows a detailed perspective of a preferred embodiment of the actuating stem and spring according to a preferred embodiment of the medical device.

Figure 10F shows a cross-sectional view of a preferred embodiment of the actuating stem and spring according to a preferred embodiment of the medical device.

DETAILED DESCRIPTION OF THE INVENTION Unless othen/vise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

As used herein, the following terms have the following meanings: “A”, “an”, and “the” as used herein refers to both singular and plural referents unless the context clearly dictates othen/vise. By way of example, “a compartment” refers to one or more than one compartment.

“About” as used herein referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/-20% or less, preferably +/-10% or less, more preferably +/-5% or less, even more preferably +/-1% or less, and still more preferably +/-0.1% or less of and from the specified value, in so far such variations are appropriate to perform in the disclosed invention. However, it is to be understood that the value to which the modifier “about” refers is itself also specifically disclosed.

“Comprise”, “comprising”, and “comprises” and “comprised of” as used herein are synonymous with “include”, “including”, “includes”or “contain”, “containing”, “contains” and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.

The expression ‘% by weight”, ‘weight percent”, ‘%wt” or ‘wt%”, here and throughout the description unless othen/vise defined, refers to the relative weight of the respective component based on the overall weight of the formulation.

Spatially relative terms, such as "under", "below", "lower", "over", "upper" and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, elements described as "under" or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus, the exemplary term "under" can encompass both an orientation of over and under. The device may be othen/vise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms "upwardly", "downwardly", "vertical", "horizontal" and the like are used herein for the purpose of explanation only unless specifically indicated othe n/vise.

It will be understood that, although the terms first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present invention. The sequence of operations (or steps) is not limited to the order presented in the claims or figures unless specifically indicated othen/vise.

The term "sterile" refers to a surface and/or a device that is substantially free of foreign matter or undesired microorganisms. The "sterility" or "sterile" and derivatives thereof, refers to a medical grade sterility standard set, typically set by a regulatory agency. To achieve a desired sterility, the dose container or other component can be manufactured (filled and sealed) at a controlled clean-standard site, such as, for example, a "Class 100,000" site or better. The manufacturing/filling site can be a "Class 100 site" or other appropriately sterile and/or aseptic or clean room condition site to maintain a desired clean or sterility state until or during dispensing/use. Alternatively, the device can be packaged, then sterilized. The term "Class 100" means a facility that has less than 100 particles per cubic meter of clean room/space. The Class 100 standard may also refer to ISO Class 5. The term "Class 100,000" refers to a facility that has less than 100,000 particles per cubic meter of clean room/space. The clean room/space can maintain a positive-pressure environment. The positive-pressure environment is configured to operate so that, upon entrance into the space, air flows out of the clean room, limiting the possibility of contaminants entering the clean room. Equipment to provide the desired class, such as, for example, Class 100 status include, for example, Class 100 laminar flow workstations, Class 100 laminar flow exhausting hoods, HEPA-filters and the like. The term "sterile or clean'' extraction surface" refers to that part of the dose container that has or maintains a desired cleanliness and/or sterility. In some embodiments, to do so, the surface may be sealed or othen/vise protected from exposure to environmental conditions until and/or during use.

In some embodiments, the liquid medical can be any medical that is administered in liquid form; in one embodiment it is an aqueous medical composition, and in another embodiment it is a non-aqueous medical composition.

In a first aspect the present invention provides a medical device for the topical treatment of a disease in a subject in need thereof, comprising: a medical container comprising a medical composition, an applicator nozzle having an opening for applying said medical composition to said subject, and an actuator mechanism for controlling said applicator nozzle.

More specifically, the present invention provides said medical device whereby medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle.

The advantage of said penetrable seal, which is used to seal the medical container, is a high barrier and thus low permeability. This low permeability increases the shelf-life of the medical device, ensuring the medical device and composition work as intended.

The actuator mechanism comprises two positions. The first position will be called “closed”, the second will be called “open”. When the actuating mechanism is in the closed position, the actuating stem closes off the applicator nozzle. When the actuating mechanism is in the open position, the actuating stem allows fluid communication between the medical container and the applicator nozzle along the actuator stem. If the actuating stem is moved from the closed position to the open position while the penetrable seal is intact, the actuating stem will pierce said penetrable seal, due to which the seal becomes a penetrated seal. The penetrated seal does not seal off the medical container.

This will open the medical container, allowing fluid communication between the medical container and the applicator nozzle. Additionally, the actuator mechanism comprises two positions for the actuating stem. The “actuator mechanism” comprises the “actuating stem”, but can comprise additional elements.

The advantage of said mechanism is easier and cleaner application of the medical composition. Furthermore this preserves the medical composition in the medical container while the medical device is not in use.

The applicator, especially, may be arranged to deliver substantially the required dosage of the medical composition (on the topical location to be treated), avoiding an overdose (or insufficiency) of the medical composition that could lead to harming the skin instead of treating the skin. Hence, the present applicator, and also the herein proposed liquid release unit, allow a targeted application of the medical composition, thereby facilitation curing of e.g. a lesion, while substantially not affecting surrounding (healthy) tissue.

The present invention provides said medical device especially for application of a topical treatment, such as a treatment of a nail disorder, a skin disorder, a treatment of an oral health problem, a treatment of a topical problem at intimate areas, a skin removal (e.g. to remove a tattoo), etc. The invention also provides such medical composition as defined herein, especially for use in treatment of a topological lesion, such as in a medical treatment. Further, the invention also provides such medical composition per se, especially for use in treatment of a topological lesion, such as in a cosmetic treatment. The invention also provides such medical composition, especially for use in (acid) treatment of a skin disorder, such as in a treatment of superficial lesions, in particular skin lesions, mucous membrane lesions and/or nail lesions, viral warts, verrucae, water warts (molluscum contagiosum), corns and calluses, skin hyperpigmentation (such as age spots, solar lentigo, senial lentigo), acne, keratosis pilaris, actinic keratosis, ingrown toenails, onychomycosis, eyelid xanthelasma, psoriasis, fungal nail infections, epidermodysplasia veruciformis, a HPV (human papillomavirus) caused skin disorder, scars, wrinkles, and melasma. The invention also provides such medical composition liquid as defined herein, especially for use in (acid) treatment of topical oral health problems such as mouth ulcers (canker sores) and cold sores. The invention also provides such medical composition liquid as defined herein, especially for use in (acid) treatment of topical problems at intimate areas, at mucus membranes and tissue, such as hemorrhoids, genital warts. The invention also provides such medical composition as defined herein, especially for use in (acid) treatment for skin removal purposes such as a tattoo and/or a skin tag.

MEDICAL CONTAINER The medical container is preferably comprised of an acid resistant material. Good, alternative acid resistant materials for the medical container may be selected from the group consisting of acid resistant metals, chlorinated polyvinyl chloride (CPVC), (ECTFE), (enhanced PTFE), high-density poly ethylene (HDPE), polyether ether ketone (PEEK), polypropylene (PP), polysulfone (PSU), polyphenylene sulfide (PPS), polyvinyl chloride ethylene chlorotrifluoroethylene (enhanced) polytetrafluoroethylene, (especially type 1 (PVC, Type 1) or type 2 (PVC, Type 2)), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), Polyamide-imide (PAI), ultra-high molecular weight polyethylene (UHMW) and also coated (with an acid resistant material, especially an acid resistant polymer) metals like aluminium. Yet in a further embodiment, good materials for the container may independently be selected from the group consisting of high-density poly ethylene (HDPE), low-density poly ethylene (LDPE), polyamide (PA), polycarbonate (PC), polyethylene terephthalate (PET) (including e.g. polyethylene terephthalate glycol PETG), polymethylpentene (PMP), polyoxymethylene (POM), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polyvinyl chloride (especially rigid (PVC HART) and flexible (PVC WEICH), styrene (SAN), (ECTFE), chlorotrifluoroethylene propylene acrylonitrile ethylene ethylene (ETFE), (FEP), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), ethylene propylene chlorotrifluoroethylene fluorinated ethylene diene rubber (EPDM), fluorocarbon rubber (FPM), and acrylonitrile (nitrile) butadiene rubber (NBR). These materials are especially resistant against the acidity of an acidic liquid. It has been found that especially polypropylene (PP) and polyethylene terephthalate (PET) (such as e.g. polyethylene terephthalate glycol (PETG)), do have good acid resistance against the acids comprised in the acidic liquid according to the present invention whereas they also show different resistance for different acids. Yet, a most preferred acid resistant material is glass.

MEDICAL COMPOSITION In an embodiment of the invention, the medical composition comprises a film-forming polymer in an amount of 1 to 25 wt.%, relative to the total weight of said medical composition.

In a preferred embodiment, the medical composition comprises a film-forming polymer in an amount of 2 to 24 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 3 to 23 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 4 to 21 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of to 20 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 5 to 19 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 5 to 18 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 5 to 17 wt.%, more preferably the medical composition comprises a film-forming polymer in an amount of 5 to 16 wt.%, more preferably the medical composition comprises a film- forming polymer in an amount of 5 to 15 wt.%, most preferably the medical composition comprises a film-forming polymer in an amount of 6, 7, 8, 9, 10, 11, 12, 13, 14 wt.% or any amount there in between. Medical compositions comprising a film-forming polymer in amounts lower than 1 wt.% harden very slowly once applied as topical treatment to nails, or do not harden at all. Medical compositions comprising a film-forming polymer in an amount higher than 25 wt.% results in compositions which are too viscous.

This film-forming polymer is able to harden to a film after application. This is advantageous for topical treatment of infection in nails. This is also advantageous for the preservation of said medical composition, as the film-forming polymer has a self- sealing effect. This film-forming polymer may seal off insufficient closures when the actuator stem is in the first, closed position.

In a preferred embodiment, the film-forming polymer is based on acrylates, more preferably the film-forming polymer is a copolymer comprising at least one of methyl methacrylate and ethyl acrylate, more preferably the film-forming polymer is a copolymer comprising methyl acrylate and ethyl acrylate, more preferably the film- poly(ethyl trimethylammonioethyl methacrylate chloride). In a further preferred embodiment, the forming polymer is acrylate-co-methyl methacrylate-co- film forming polymer is a copolymer comprising ethyl acrylate monomer and methyl methacrylate monomer, wherein the ratio of the ethyl acrylate to the methyl methacrylate monomer is 1:4 to 2:1, more preferably about 1:2. Most preferably, the film forming poly(ethyl methacrylate-co- polymer is acrylate-co-methyl trimethylammonioethyl methacrylate chloride) 1:2:0.2. These polymers are known under CAS number 334341.

In a preferred embodiment, the medical composition comprises a solvent. In a further preferred embodiment, the medical composition comprises a mixture of solvents with varying volatility. In the most preferred embodiment, in combination with the poIy(ethyI acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride), the This combination is particularly suitable for providing a sufficiently liquid medical composition medical composition comprises ethanol, ethylacetate and butylacetate. which quickly forms a hard film suitable for treating infected nails. Suitable amounts of solvent are 25 to 85 wt.% solvents relative to the total weight of the medical composition, more preferably 30 to 85 wt.% solvents, more preferably 35% to 85% solvents, more preferably 40% to 85% solvents, more preferably 45% to 85% solvents, more preferably 50% to 85% solvents, more preferably 55% to 85% solvents, more preferably 60% to 85% solvents, more preferably 65% to 80% solvents, most preferably 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 wt.% of solvents relative to the total weight of the medical composition or any amount there in between.

Solvents allow for easier dosing of the biologically active agents. Volatile solvents allow the optimization of the viscosity as well as the hardening speed and properties of the film forming polymer. The combination of ethanol, ethylacetate and butylacetate is Due to the combination of volatilities, the rate at which the film forming polymer hardens once particularly well-suited for acrylate-based film-forming polymers. applied while retaining sufficient viscosity prior to application can be optimized.

In an embodiment, the medical composition may comprise a plasticizer. Suitable plasticizers include many commonly available commercial plasticizers, such as mono- and polycarboxylic acid esters, polymeric polyesters, polyalkyl ethers, and glycerol and glycol esters. In a further preferred embodiment, the medical composition comprises triacetin. Triacetin is also known as 1,2,3-triacetoxypropane. Suitable amounts of plasticizer are up to 5 wt.% relative to the total weight of the medical composition, preferably up to 4 wt.%, more preferably up to 3 wt.%. Preferably at least 0.5 wt.%, more preferably at least 1 wt.%, most preferably at least 1.5 wt.%.

Plasticizers are advantageous to optimize the glass-transition of the film-forming polymer as well as its mechanical properties and elongation. Furthermore, plasticizers affect the flow-rate of the medical composition and the rate at which the film-forrning polymer hardens. In an embodiment, said medical composition has a sufficiently low viscosity to ensure fluid communication between the medical container and the applicator nozzle. However, the viscosity needs to be high enough to prevent the medical composition to flow out of the medical device too quickly.

In a preferred embodiment of the invention, said medical composition is an antifungal composition. As examples of suitable antifungal agents mention may be made of, for example, polyenes, e.g., Natamycin, Nystatin; allylamines, e.g., Naftifine, Terbinafine; imidazoles, e.g., Bifonazole, Chlotrimazole, Econazole, Fenticonazole, Ketocanazole, Miconazole, Oxiconazole; triazoles, e.g., Fluconazole, ltraconazole, Terconazole; tolnaftate, ciclopirox, undecylenic acid, sulbentine, and morpholines, e.g., amorolfine, and the related morpholines disclosed in the U.S. Pat. No. 5,120,530. A preferred example of an antifungal composition is an amorolfine solution. In a particularly preferred embodiment, said fungicidal medical composition solution comprises Amorolfine, preferably between 1 and 20 wt.% Amorolfine, relative to the total weight of said fungicidal medical composition, more preferably between 2.5 and 10 wt.% Amorolfine, and most preferably about 3, 4, 5, 6 or 7 wt.% Amorolfine. Amorolfine is a known morpholine antifungal drug. Its effects in treating onychomycosis and other fungicidal infections is known. Advantageously it can be used with film-forrning polymers and is topically active in nails.

In a another preferred embodiment, said medical composition may be an acidic liquid for application to the nail or to the skin, especially applied to peel the skin or mucous membrane, especially the skin, by which the skin or mucous membrane may renew itself. The treatment liq uid will have an advantageous effect on the lesion to be treated; the medical composition, especially the acid(s) in the liquid, may have a peeling effect, the liq uid, especially the acid(s), may also provide an oxidation effect to the lesion. The medical composition may comprise different acidic liquids as one or more different liquids may be applied. Especially, the medical composition comprises one or more acids selected from acetic acid, trichloroacetic acid (TCA), formic acid (FA), and salicylic acid. The acidic liquid may (further) comprise one or more acids selected from acetic acid, hydrochloric acid (HCI), and nitric acid (HNO3). Especially, the medical composition, such as comprised by the medical device, may comprise one or more acids selected from the group consisting of trichloroacetic acid, salicylic acid, formic acid, glycolic acid, dichloroacetic acid, monochloroacetic acid, acetic acid, citric acid, ascorbic acid, boric acid, nitric acid, sulfuric acid, phosphoric acid, oxalic acid, lactic acid, hydrochloric acid.

In a specific embodiment, the medical composition has a pH less than 6, such as in the range of 2-6, preferably in the range of 3-5. In yet a further embodiment, the acidic liquid may especially comprises an acid at a concentration in the range of 0.5-10.0 wt.%, preferably 0.5-5.0 wt.%, more preferably 0.5-2.0 wt.%. The acidic liquid may also comprise two types of acids both at a concentration according to the above given ranges, such as a first acid at a concentration in the range of 0.2-8 wt.% and a second acid at a concentration in the range of 0.3-2.0 wt.%. In the most preferred embodiment, the medical composition comprises acetic acid.

The medical composition may optionally comprise one or more other ingredients, including one or more other active ingredients. The medical composition as described herein may comprise other ingredients commonly used in cosmetics and pharmaceutical products, such as one or more of a surfactant, a colorant, a nail penetrating compound, a skin restoring compound, a microenvironment controlling compound, and a perfume.

For instance, the medical composition may further include one or more excipients. An excipient is especially an inactive substance formulated alongside the active ingredient(s) of a product or medication, for the purpose of bulking-up formulations that contain such active ingredient(s). Excipients may for instance also be indicated as filler or diluent. Excipients may e.g. include one or more of binders, coatings, disintegrates, fillers, flavours, colorants, lubricants, glidants, sorbents, preservatives, sweeteners, etc.

The medical composition may further comprise e.g. comprise silk fibroin. Silk fibroin is a protein derived from hydrolysing of silk fibres, naturally secreted by silk work Bombyx mori. Silk fibroin has diverse applications in the biomedical field, which can be attributed to its high tensile strength, controllable biodegradability, non -cytotoxicity, Iow- antigenicity and non-inflammatory characteristics. The use of silk fibroin extract can aid the healing process during regeneration and repair of normal and functional nail tissue.

The medical composition may further (also) comprise pentylene glycol. Pentylene glycol is used as moisturizing agent. It is a colorless liquid, very low in odor, that is both water and oil-soluble. Due to its unique molecular properties, including a well separated charge distribution pattern, pentylene glycol performs its moisturizing activity much better than comparable chemicals, i.e. propylene glycol. The medical composition may further (also) comprise dimethyl isosorbide. Dimethyl isosorbide is a delivery enhancer which can place active ingredients where they are needed most and it is thus used as penetrating system forthe keratinous nail layer. Dimethyl isosorbide is a colorless liquid with excellent solvent properties. It enhances delivery of actives in the upper layers of the epidermis without promoting the product into the bloodstream. Moreover, dimethyl isosorbide improves stability of formulations, even those that are susceptible to hydrolysis and transesterification. The one or more of silk fibroin, pentylene glycol and dimethyl isosorbide may especially be applied in a medical composition for the treatment of nail fungus.

The medical composition may further e.g. comprise azone. Azone is a colorless to yellowish liquid comprising especially sodium hypochlorite as the active ingredient.

Azone has been used to enhance percutaneous absorption. Its ability to improve penetration makes it an attractive compound for incorporation into the medical composition. Additionally or alternatively, pyrrolidones amy be incorporated to enhance penetration. Also pyrrolidones show a high effect on hydrophilc diffusants and thus may function as a penetration enhancer in (human) skin.

The medical composition may further e.g. comprise a terpene. Terpenes are a large and diverse class of organic compounds, produced especially by a variety of plants.

Many terpenes are hydrocarbons, but oxygen-containing compounds such as alcohols, aldehydes or ketones (terpenoids) are also found. Their building block is the hydrocarbon isoprene, CH2=C(CH3)-CH=CH2. Terpene hydrocarbons therefore have molecular formulas (C5H8)n, they are classified according to the number of isoprene units. Plant oils, which contain terpenes, have shown increasing promise in vivo, inhibiting multiple species of bacteria. For example, cinnamon oil has shown broad- spectrum activity against Pseudomonas aeruginosa. Also olive leaf oil has shown beneficial properties, especial with respect to the micro-environment, having antimicrobial properties for some species as well as healing properties and supporting properties for other species. Cumene (isopropylbenzene) is a terpene that has been shown to comprise important anti-bacterial properties. Also Iimonene, carvone, and pinene have shown beneficial effects.

The medical composition may further e.g. comprise oxazolidones. The oxazolidinones are a class of antimicrobial agents which have a unique structure and good activity against gram-positive pathogenic bacteria. Oxazolidinones are a class of compounds containing 2-oxazolidine in the structure. Oxazolidinones represent a new class of synthetic antibacterial agents active against multiple-resistant gram-positive pathogens, including methicillin- resistant Staphylococcus aureus (MRSA), penicillin- resistant streptococci, and vancomycin- resistant enterococci. Hence, oxazolidones especially may be incorporated in the medical composition being able to contrail the microenvironment. The medical composition may further e.g. comprise urea (or carbamide). Urea is an organic compound with the chemical formula CO(NH2)2. Urea- containing creams are widely known and used as topical dermato logical products to promote rehydration of the skin. It further appears that urea can be indicated for psoriasis, xerosis, onychomycosis, ichthyosis, eczema, keratosis, keratoderma, corns and calluses. Its use in the e.g. the treatment and/or prevention of Athlete's foot may be intended as moisturizer agent for dry skin affected by athlete's foot. The medical composition may further e.g. comprise allantoin. Allantoin is a chemical compound with formula C4H5N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid. It is used for its moisturizing properties since it increases the water content of the extracellular matrix. It also enhances the desquamation of upper layers of dead skin cells, favouring a faster healing process of damaged skin. The medical composition may further e.g. comprise panthenol. Panthenol is the alcohol analogue of pantothenic acid (vitamin B5), and is thus a provitamin of B5. In organisms it is quickly oxidized to pantothenate. In e.g. the treatment (and/or prevention) of athIetes's foot, panthenol may be used as a humectant, emollient and moisturizer. The one or more of urea, allantoin, and panthenol may especially be applied in the medical composition for the treatment (and/or prevention) of Athlete's foot, such as in the applicator.

APPLICATOR NOZZLE AND ACTUATOR MECHANISM In a preferred embodiment of the invention, the actuator stem is biased towards the first position wherein the actuator stem closes off said opening of the applicator nozzle. The advantage is that moving the actuator stem to the open, unbiased position requires an action. This ensures that the medical composition is only released when desired. It also helps avoid leaks and spills. Lastly a bias towards the first, closed position reduces the chances for human error when closing the medical container. This improves the preservation of said medical composition.

In a further embodiment, the actuator mechanism comprises a spring for biasing said actuator stem in the first position. A spring is a cheap and reliable tool. They are well known, reliable and fit for use in medical applications.

In an embodiment, the penetrable seal is attached to a sealing ring, wherein said sealing ring is contacted with the medical container effectively sealing said medical container before first use. This allows for separate manufacture of the penetrable seal and the medical container. This also makes both the sealing ring and the medical container separate interchangeable parts. An empty medical container can be replaced with a new one without replacing the sealing ring, allowing the medical device to be refilled. Likewise, if the medical container is not yet empty but the treatment is halted, a sealing ring with penetrated seal can be replaced by a new sealing ring with penetrable seal for the long term preservation of the medical composition.

In an embodiment, the penetrable seal is preferably comprised of acid-resistant materials. Furthermore, the penetrable seal requires suitable permeability to prevent the loss of volatile substances from the medical composition. The penetrable seal also needs to be gas-tight upon being contacted with the medical container. In an embodiment, the penetrable seal is an extruded or co-extruded foil. In a more preferred embodiment, the penetrable seal comprises materials chosen from the list of high- density poly ethylene (HDPE), low-density poly ethylene (LDPE), polyamide (PA), polycarbonate (PC), polyethylene terephthalate (PET) (including e.g. polyethylene terephthalate glycol PETG), polymethylpentene (PMP), polyoxymethylene (POM), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polyvinyl chloride (especially rigid (PVC HART) and flexible (PVC WEICH), styrene acrylonitrile (SAN), ethylene chlorotrifluoroethylene (ECTFE), ethylene chlorotrifluoroethylene (ETFE), fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), ethylene propylene diene rubber (EPDM), fluorocarbon rubber (FPM), and acrylonitrile (nitrile) butadiene rubber (NBR) or acid resistant metals or alloys such as aluminium. In a more preferred embodiment, the penetrable seal comprises both a metal and polymers. The penetrable seal can further comprise lacquer layers. These can be both aesthetic and functional, as a lacquer can facilitate visual inspection of the penetrable seal prior to first use.

In a another embodiment, said actuator stem, when moved from the first, closed position to the second, open position displaces a volume of the medical composition equal to a single unit dose. This eases the use of the medical device. Accurate dosing is important for medical compositions, yet hard to do by a person not trained in the arts.

As such, a medical device that delivers single unit doses is easier to use. It also improves the treatment of infections as these treatments are often dose-sensitive.

In a preferred embodiment, said actuator stem comprises longitudinal channels to facilitate the flow of the medical composition along the actuator stem. This improves the fluid communication between the nozzle and the medical container. These longitudinal channels are synergistic with a medical composition comprising a film-forming polymer.

Broad channels ensure that the fluid communication is not blocked by small polymer films blocking off passages. Additionally these longitudinal channels lead to more regular fluid communication, which is required for the controlled release of the medical composition, for example for single unit doses.

The applicator allows the treatment of the topological disorder by local contact of the applicator on the nail or skin. This is safer and also more effective than applicators that need contact with a larger region than lesion or applicators that serve more than the lesion. The applicator may especially be configured to provide the medical composition to a local topical area of ranging from 0.01-4 cm2, such as 0.02-2.5 cmz, such as 0.1- 1.0 cm2, like 0.1-0.5 cmz, by means of a direct contact. Hence, in an embodiment, the applicator nozzle comprises a surface having a surface area or contact area in the range of 0.01 -4 cm2, preferably 0.1 -2.5 cm2.

In a further embodiment, the applicator comprises a grip part. Hence, in an embodiment, the applicator comprises an applicator nozzle comprising a surface having e.g. a surface or contact area in the range of 0.01-4 cmz, such as 0.1-2.5 cm2, and wherein the applicator comprises a grip part, wherein the physical topical application includes touching a topical area and keeping the applicator nozzle in physical contact with the topical area in the range of 0.2-5 seconds.

Assuming the applicator having a pen shape, the diameter over the length of the pen may be substantially round. Preferably, the applicator comprises a grip part. Such grip part may e.g. comprise a triangular cross-section, especially having rounded angles.

Hence, in yet an even more preferred embodiment, the applicator comprises different cross-sections, gradually changing from round to a grip part having a triangular cross- section (and optionally turning to a substantially round cross-section again). The applicator may include a closure. When defining the shape of the applicator, such closure may be included.

In a preferred embodiment, the actuator stem and/or spring are provided in a thermoplastic material. Metal springs can lead to corrosion, oxidation and other unwanted reactions of the medical composition. These negatively impact the shelf life of the composition. Even if the medical composition remains functional, small concentrations of metal ions and complexes can act as pigments and lead to discoloration of the medical composition as well as the film once applied.

The applicator nozzle, the actuator stem and/or said spring are preferably comprised of an acid resistant, polymer material. Good acid resistant polymer materials for the applicator nozzle, the actuator stem and/or said spring may be, independently, selected from the group consisting of chlorinated polyvinyl chloride (CPVC), ethylene chlorotrifluoroethylene (ECTFE), (enhanced) polytetrafluoroethylene, PTFE), polyether ether ketone (PEEK), polypropylene (PP), polysulfone (PSU), polyphenylene sulfide (PPS), polyvinyl chloride (enhanced high-density poly ethylene (HDPE), (especially type 1 (PVC, Type 1) or type 2 (PVC, Type 2)), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), Polyamide-imide (PAI), ultra-high molecular weight polyethylene (UHMW) and also coated (with an acid resistant material, especially an acid resistant polymer). Yet in a further embodiment, good materials for the applicator nozzle, the actuator stem and/or said spring may independently be selected from the group consisting of high-density poly ethylene (HDPE), low-density poly ethylene (LDPE), polyamide (PA), polycarbonate (PC), polyethylene terephthalate (PET) (including e.g. polyethylene terephthalate glycol PETG), polymethylpentene (PMP), polyoxymethylene (POM), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polyvinyl chloride (especially rigid (PVC HART) and flexible (PVC WEICH), styrene acrylonitrile (SAN), ethylene chlorotrifluoroethylene (ECTFE), ethylene chlorotrifluoroethylene (ETFE), fluorinated (FEP), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), ethylene propylene ethylene propylene diene rubber (EPDM), fluorocarbon rubber (FPM), and acrylonitrile (nitrile) butadiene rubber (NBR). These materials are especially resistant against the acidity of an acidic liquid.

In the most preferred embodiment, the applicator nozzle comprises polyoxymethylene (POM).

In a preferred embodiment, the the actuator stem and/or said spring are provided in polyoxymethylene (POM). POM is a relatively inert material which advantageously shows good resistance to adhesion, which prevents the formation of film on or along the actuator, while also showing good mechanical properties such as high strength, rigidity, high crystallinity, good fatigue resistance and is sufficiently impermeable. The combination of these characteristics makes POM particularly well suited for the parts of the assembly which come into contact with the medical composition.

In a further preferred embodiment, the actuator stem and/or said spring are provided according to figures 10D and 10F. This design for actuating spring is advantageous to use in combination with thermoplastic materials, including but not limited to POM.

Thermoplastic materials generally show fatigue under the effect of repeatedly applied loads, such as the repetitive actuation of the medical device. This makes compressing springs undesirable. The stem-spring designs according to figures 10D, 10F and also 9B minimize the effect of fatigue.

In a preferred embodiment, said medical device further comprises a nail file. This nail file can, but doesn’t need to be, attached to said medical device in any way. The advantage of the nail file is the comfort, for the client, to still be able to alter the application of the medical composition. In a more preferred embodiment, the medical container and actuator mechanism are contained within a housing. This housing can further comprise means of attachment for the nail file. In the most preferred embodiment of the present invention, the nail file can be slid into the housing. The ability to have a nail file easily carried along with the medical device allows the user to adjust the application of the medical composition, as well as using the nail file for regular purposes.

Additionally this can help mask the medical device as a nail kit, as patients often prefer discretion.

In a preferred embodiment, the medical device further comprises a removable cap for protecting the applicator nozzle. The cap can be placed over the nozzle preventing damage to the nozzle or the accidental actuation of the actuator mechanism. In a more preferred embodiment, the cap reduces the chances of leaks or droplets of medical composition escaping from the nozzle. This provides comfort and cleanliness to the end user, helps preserve the medical composition. When used with a medical composition comprising a film-forming polymer, it also reduces hardening of the medical composition in unwanted places, such as the nozzle interior or near the actuator mechanism.

In a further preferred embodiment, the cap comprises a leakage container. This leakage container seals the nozzle opening in particular. In a more preferred embodiment, this leakage container is impermeable to liquids. In the most preferred embodiment, the leakage container and its fit over the nozzle opening is hermetically sealed, and thus impermeable to liquids and gasses. This prevents the escape of volatiles such as solvent from the medical composition. This is advantageous for the shelf life of the medical composition. Furthermore, it prevents hardening of the medical composition in the nozzle interior.

In the second aspect the present invention provides a kit comprising a medical device for the topical treatment of a disease in a subject in need thereof, comprising: a medical container comprising a medical composition; an applicator nozzle having an opening for applying said medical composition to said subject, an actuator mechanism for controlling said applicator nozzle, and a housing for a medical container.

More specifically, the present invention provides said kit, whereby said medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem penetrates pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle.

This kit allows the medical device which it comprises to be refilled. The medical container is an exchangeable and interchangeable part. Some resistant fungal infections can take considerable time to treat, and may require the use of several medical containers worth of medical composition. For these users, a kit is advantageous. The design of larger medical devices to hold more of said medical composition according to the first aspect leads to bulky, indiscrete and unhandy medical devices. The kit according to the second aspect does not show these issues.

The third aspect of the present invention is a method for treatment of infection operating a medical device comprising the steps of : - Providing a medical device comprising a medical container holding a medical composition, an applicator nozzle for applying said medical composition and an actuating stem for controlling said application, - actuating the actuating stem to facilitate fluid communication between the medical container and the applicator nozzle.

Advantage of the method over vial and file application of medical compositions is easier, quicker and more accurate application. Additionally, the dosage control is improved when using an actuator mechanism which produces similar sized doses.

A preferred embodiment of said method for treatment of infection, wherein the medical device the medical container is sealed by a penetrable seal, which method further comprises : - Penetrating the penetrable seal with the actuator stem.

The advantage of this method a long shelf-life of the medical composition in the medical container before first use. This also allows the use of volatile, degrading, chemically reactive or othen/vise altering or changing constituents. An example of such a chemically reactive constituents are the film-forming polymers of a preferred embodiment of the first aspect.

The invention is further described by the following non -limiting examples which further illustrate the invention, and are not intended to, nor should they be interpreted to, limit the scope of the invention.

EXAMPLES It is supposed that the present invention is not restricted to any form of realization described previously and that some modifications can be added to the presented example of fabrication without reappraisal of the appended claims. For example, the present invention has been described referring to the topical treatment of infections, but it is clear that the invention can be applied to any topical medical composition.

These examples comprise preferred embodiments of the invention, and will be clarified through the figures.

EXAM PL E 1 Medical device The assembly of the medical device is shown in figure 1A. The medical device 1 comprises a medical container 3 which comprises a medical composition 11, suited for treating onychomycosis. The medical device comprises an applicator nozzle 6 and an actuator mechanism, which consists of an actuating stem 5 and a compression spring 9. The medical device further includes a housing 2 being tubular in shape with a distal end and a proximal end and a medical container sealed by a sealing ring 4 encased in the housing. The nozzle has a distal end, formed for the direct application of a fungicide to nails, and a proximal end. The medical device further includes a cap 7, which fits on the distal end of the nozzle. This seals the pharmaceutical composition from the housing. The nozzle, screwed on the medical container, is formed to be telescopically mounted onto the distal end of the housing.

Actuation mechanism The mechanism through which the medical device is actuated is shown in figures 1C and 1D. A new medical device which has not been used is shown in figure 1A. This shows a penetrable seal which is closed, without fluid in the actuator mechanism and near the nozzle. In this state the medical device has a long shelf-life.

During the first actuation, the stem pierces the penetrable seal 10. This allows fluid, being the medical composition 11, to flow along the channels in the actuating stem to the nozzle tip, through which it is applied topically. The device is actuated by applying a force on the nozzle tip, preferably by pressing the medical device down against a surface on which the medical composition is to be applied. When the force is released, the actuating stem will be returned to the closed position by the spring. The penetrable seal will remain open, leading to a continued fluid communication in the channels along the actuating stem. This is shown in figure 1E. The film-forming polymer will form a self- sealing film 12, particularly around the tip of the nozzle. This improves sealing and prevents leakage of the pharmaceutical composition.

Housing Figures 2A and 2B show a longitudinal and cross section of the housing. This housing keeps the medical device together and protects the other parts such as the medical container, which promotes child safety.

The housing is a half-open tubular shape. The distal opening 21 allows placement of medical containers and other parts inside the housing. The most outward edge near the opening is equipped with a track 23 for mounting the nozzle on the housing. The proximal, closed end has a convex closure 22. The side of the housing further comprises an indentation 25 fit to hold a nail file. This indentation is shaped to hold said nail file, with the edges of the indentation 26 preventing the file from moving laterally.

The indentation gives way to an opening 24 in the housing, through which the nail file can be slid. This way the nail file is mostly contained inside the housing, next to the medical container. This further limits the movement of the nail file. The indentation has a higher thickness near the opening in the form of a knob 27. This ensures the nail file cannot slide in and out of the housing without applying a minimum amount of force.

Medical container The medical container is shown on figure 3. It is an amber glass medicine bottle 31.

The medical container is open 33 and comprises a thread 32. This male thread 32 matches the female thread 65 of the nozzle, allowing the actuator mechanism, sealing ring and medical container to remain closed unless applying force once assembled.

The medical container comprises a medical composition 11 suitable for treating onychomycosis. The medical composition consists of 6.4 wt.% amorolfine hydrocholoride, 15 wt.% film-forming polymer, 1.2 wt.% triacetin, 5.5% butylacetate, 16.5% ethylacetate and 55.4% ethanol. The film-forming polymer is poly(ethyl acrylate- co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1:2:O.2.

Sealing ring A cross sectional view and a side view of the sealing ring are shown in figure 4A and 4B respectively. The sealing ring 4 is a cylindrical, plastic ring with a mostly uniform internal diameter D. and an almost uniform external diameter DE_ The sealing ring has a distal and a proximal end. The proximal end of the ring comprises a penetrable seal .

The plastic ring is formed by injection moulding of high density polyethylene. Injection moulding uses an entry point, a point where the polymer is injected into the die. The entry point 41 of the polymer is along edge of the ring, where it is flattened. This flattening of the ring simplifies the injection moulding. It is important that the entry point is not radial, as the radial flat surfaces of the ring are required to be smooth for functionality. As the entry point is typically not smooth, the entry point has to be axial.

This flattening leads to a smaller external diameter, DE_ The ring further comprises a small ridge 42 which improves the closure between the side of the ring and the inside of the nozzle. At the proximal end of the sealing ring, a penetrable foil is attached.

Additionally, the internal diameter near this penetrable foil Do is smaller than D._ The penetrable foil 10 comprises 3 layers: a 2k gold coloured lacquer, an aluminium layer and a polymer layer. The gold coloured lacquer weighs roughly 1.5 g/m2. The aluminium layer is comprised of soft, tempered aluminium and the layer is roughly 37}: thick. The polymer layer is a coextrusion coating which weighs 30g/m2. The total weight of the foil is 130 g/m2, with an average thickness of 68p. The foil has good mechanical properties, most notably very low permeability for a wide range of volatiles. Damage to the penetrable seal such as scratches are visible due to the contrast between the gold coloured lacquer and the aluminium and polymer layers.

Actuating stem A perspective of the stem is shown in figure 5A and a side view of the actuating stem is shown in figure 5B. The stem 5 is a narrow, longitudinal plastic element. It has a distal end, a centre and a proximal end, where the distal end goes through the distal opening of the nozzle.

The distal end of the stem has a distal tip 51 and a distal base 52. Both the distal tip and the distal base are tubular shapes. The distal tip has an external radius DA smaller than the internal radius of the distal opening of the nozzle. The distal base has an external radius DB larger than the internal radius of the distal opening of the nozzle.

When the distal base of the stem is pressed against the distal opening of the nozzle, no fluid can pass through, comprising the closed position of the actuating stem.

However, if the stem is pushed into the proximal direction, there is space for a fluid to flow past the stem through the nozzle, which is the open position of the actuating stem.

The centre of the stem has the largest external diameter. Rather than tubular, the centre and proximal ends of the stem consist of four equidistant wigs 54. Between these wigs are longitudinal channels 53, so the pharmaceutical fluid can flow past. At the distal side, the wigs have a central external diameter just larger than the diameter of the coil.

More proximally, the wigs have an external diameter smaller than the diameter of the coil. This allows the coil to fit around the distal end while the proximal end of the actuating stem deflects the coil when proximal pressure is applied. The coil will then provide a reactive pressure which biases the actuating stem towards the closed position.

The proximal end of the stem contains an indentation 55 in one of the wigs. This indentation is suited for relocating fluid, based on Archimedes’ law. The volume of the indentation is linked to the single dose of medical that is provided upon a single actuation of the actuating stem, due to the volume of liquid that is displaced. The proximal tip 56 of the stem is a flat surface. This flat surface is not perpendicular to the axis of the stem, but instead is angled to provide a sharp corner to piece the coil.

Nozzle A side view of the nozzle can be seen in figure 6A. A perspective of the nozzle is shown in figure 6B. The nozzle 6 is a tubular cone-like structure with a smooth surface. lt’s made of polyoxymethylene (POM) and has an opaque, white colour. The nozzle has a distal end, formed for the direct application of a fungicide to nails, and a proximal end.

The nozzle has a distal opening 61 for the application of a fungicidal medical composition and a proximal opening, for the attachment to the housing. The internal diameter at the distal end is considerably smaller than the internal diameter at the proximal end.

The nozzle has a base 62, which has an external diameter DK, which is about equal to the internal diameter of the housing. The nozzle further has a track 63, matching the key from the housing, consisting of a ridge 64 with an internal diameter equal to the external diameter of the key. This track and key mechanism ensures a good closure between the housing and the nozzle.

Inside the base of nozzle, near the proximal end, there is an internal thread 65 that matches the external thread 32 of the medical container. The sealing ring 4 is placed on the distal end of the medical container 3, with the foil sealing off the medical container. The coil is then placed on the distal end of the sealing ring, followed by the stem which is placed into the coil. The assembly of the stem, coil, sealing ring, and medical container can be placed into the nozzle, after which the medical container can be screwed in. This nozzle container assembly can then be telescopically mounted into the housing. The thread is characterized by DIN 168 standard GL18 with a pitch of 3mm.

From the distal end of the nozzle, it has a series of increasing internal diameters, so that the distal opening 61 has the smallest internal diameter DN, slightly larger than the external diameter DA from the distal tip of the actuating stem, but smaller than the external diameter DB of the actuating stem. The second internal diameter Dc is larger, bigger than external diameter DB of the actuating stem. The diameter then further increases to be able to hold the wigs of the actuating stem, and then even more so to hold the sealing ring. Additionally, the nozzle comprises a flat, tubular surface 67 on which the sealing ring rests when the nozzle container assembly is assembled.

The cap 7 is a rounded, knotted cone which looks transparent and dark blue. lt’s made by injection moulding of polymethylmethacrylate, PET, polyoxymethylene or a copolymer thereof. The cap has six planes of symmetry. The cap has a smooth exterior and interior surface. The exterior of the cap has two opposing grips 71, comprising concave indentations on the exterior of the cap. The interior of the cap has a leakage container 72, which is tubular shaped 73 with a sloped edge 75. When the cap is placed on the nozzle, the tip of the nozzle fits inside the sloped edge 75 of this leakage container, pushing the tubular shape outwards and ensuring a tight fit at the end of the slope 74. This prevents a leaking nozzle to leak into the rest of the cap. Additionally, the interior surface of the cap is reinforced by six ridges parallel to the axis of the cone, placed hexagonally.

Nail file The nail file 8 is drawn in figure 8A and 8B. In this example the nail file is cuboid, but this is not required for its function. It has rounded tips 81 to prevent accidental harm.

The side with the largest surface area of the cuboid is rough, to allow the filing of nails.

Both of the flat sides of the file have the same grit, and can both be used to file nails.

The narrow edge 82 is smooth. The external dimensions of the nail file are slightly smaller than the internal dimensions of the nail file holder 25 of the housing.

Spring The spring 9 is a compression spring. The compression spring is not drawn in detail.

Example 2 The second example corresponds to the assembly of a medical device according to figure 9A. This medical device comprises a housing 2’, a medical container 3, a spring- stem assembly 5’, a nozzle 6’ and a cap 7’. The housing 2’, the medical container 3, nozzle 6’, cap 7’ show different designs but are functionally identical to the medical device according to example 1.

Compared to example 1, example 2 has a spring-stem assembly 5’ which replaces the actuating stem 5, the separate spring 9 and the separate sealing ring 4. The spring- stem assembly 5’ comprises a fixation ring 4’ which functions similarly to the sealing ring 4. This fixation ring 4’ remains fixed on top of the medical container 3’ during use.

The penetrable seal 10’ is attached to the proximal side of the fixation ring 4’. A spring mechanism 9’ is attached to the distal side of the fixation ring 4’, to which the actuating stem is connected. The actuating stem comprises a distal base 52’ and a distal tip 51’, which fill the same function as in example 1. The penetrable seal needs to be pierced manually prior to first use. Alternatively a pin suitable for breaking the penetrable seal can be attached to the proximal side of the spring mechanism 9’ (not shown).

Advantageously, this assembly contains fewer parts and more importantly fewer small parts. This promotes safety and ease of assembly of the pen. Furthermore, the spring stem assembly can be produced in plastic or other materials. This means the medical composition does not come into contact with metal. This is required for some medical compositions to prevent oxidation or other unwanted reactions and improves shelf life and the stability of the medical composition.

Example 3 The third example corresponds to the assembly of a medical device according to figure 9A, entirely identical to example 2, with the exception of the spring stem assembly 5”.

The new spring stem assembly is shown in figure 9C.

This spring stem assembly again comprises a fixation ring 4”, to which a penetrable seal (not shown) is attached on the proximal side and a spring mechanism 9”is attached on the distal side. The actuating stem is attached to the spring mechanism 9” and comprises a distal tip 51”and a distal base 52”. The penetrable seal needs to be pierced manually prior to first use.

As for example 2, this assembly contains fewer parts. Furthermore, the spring mechanism 9” can be produced from various materials including sufficiently elastic plastics and metals. This allows the pen to be used in combination with medical compositions which are sensitive to materials.

Example 4 The third example corresponds to the assembly of a medical device according to figure 10A. The assembly is shown telescopically in figure 10B. This medical device comprises a housing 2, a medical container 3, a spring stem assembly 5”’, a sealing ring 4”’, a nozzle 6 and a cap 7 and a nail file 8. The housing 2, the medical container 3, nozzle 6, cap 7 and the nail file 8 shown are identical to example 1.

The spring-stem assembly 5”’ is similar to the actuating stem 5 from example 1, encompassing a distal tip 51”’, a distal base 52”’, longitudinal channels 53”’, four equidistant wigs 54”’, indentation 55”’ and proximal end 56”’. However, rather than being actuated by a separate spring 9, two wings 54”’ are provided with a spring mechanism 9”’. The spring-stem assembly 5”’ is preferably made of polyoxymethylene (POM) in order to provide sufficient elasticity and strength as well as good resistance against material fatigue.

The spring-stem assembly 5”’ is accompanied by a sealing ring 4”’. The sealing ring 4”’ is similar to the sealing ring 4 from example 1, encompassing the ring structure as well as the penetrable seal 10. However, rather than a largely uniform internal diameter D. and a smaller internal diameter Do close to the penetrable seal, the sealing ring 4”’ has a gradual transition between the distal internal diameter D. and the proximal internal diameter Do near the penetrable seal. This allows the spring mechanism 9”’, upon providing outwards pressure, to bias the spring-stem assembly towards the closed position.

Advantageously, the assembly requires fewer parts and the medical composition does not come into contact with metals. Furthermore, the penetrable seal can still be replaced by exchanging sealing rings. The design of the stem, particularly the longitudinal shape along with longitudinal channels 53”’ and indentation 55”’ allow for good dosage control.

Claims (2)

1. CLAIMS 1. A medical device for the topical treatment of a disease in a subject in need thereof, comprising: — a medical container comprising a medical composition, — an applicator nozzle having an opening for applying said medical composition to said subject, and — an actuator mechanism for controlling said applicator nozzle, characterized, in that said medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle. A medical device according to claim 1, wherein said medical composition comprises a film-forming polymer in an amount of 1 to 25 wt.%, relative to the total weight of said medical composition. A medical device according to any of the previous claims 1-2, wherein said actuator mechanism comprises a spring for biasing said actuator stem in said first position, preferably a thermoplastic spring. A medical device according to any of the previous claims 1-3, wherein said actuator stem, when moved from the first, closed position to the second, open position displaces a volume of the medical composition equal to a single unit dose of said medical composition. A medical device according to any of the previous claims 1-4, wherein said actuator stem is biased towards said first position wherein said actuator stem closes off said opening of said applicator nozzle. 35 10. 11. 12. 13.

2. A medical device according to any of the previous claims 1-5, wherein said penetrable seal comprises an aluminium layer. A medical device according to any of the previous claims 1-6, further comprising a sealing ring, which comprises said penetrable seal, suitable for sealing said medical container prior to first use. A medical device according to any of the previous claims 1-7, wherein said medical container is a glass container. A medical device according to any of the previous claims 1-8, wherein said medical composition is a fungicidal solution, preferably comprising amorolfine, more preferably between 1 and 20 wt.% amorolfine, relative to the total weight of said medical composition. A medical device according to any of the previous claims 1-9, wherein said actuator stem comprises longitudinal channels to facilitate the flow of the medical composition along the actuator stem. A medical device according to any of the previous claims 1-10, wherein said medical device further comprises a nail file. A medical device according to any of the previous claims 1-11, wherein said medical device further comprises a removable cap suited for protecting the applicator nozzle. Kit comprising medical device for the topical treatment of a disease in a subject in need thereof, comprising: — a medical container comprising a medical composition; — an applicator nozzle having an opening for applying said medical composition to said subject, an actuator mechanism for controlling said applicator nozzle, and a housing for a medical container, characterized, in that said medical container is sealed off with a penetrable seal; and in that said actuator mechanism comprises an actuating stem which is movable between (i) a first position wherein said actuator stem closes off said 14. 15. 3 opening of said applicator nozzle, and (ii) a second position wherein said applicator nozzle is in an open position and wherein said actuator stem pierces said penetrable seal of said medical container, thereby forming a passage for allowing a fluid communication between said medical container and said applicator nozzle. Method for treatment of infection disease operating a medical device comprising the steps of : — Providing a medical device comprising a medical container holding a fungicidal medical composition, an applicator nozzle for applying said fungicidal medical composition and an actuating stem for controlling said application, — actuating the actuating stem to facilitate fluid communication between the medical container and the applicator nozzle. Method for treatment of fungicidal infection according to claim 14, in which medical device the medical container is sealed by a penetrable seal, which method further comprises : — Penetrating the penetrable seal with the actuator stem. MACLACHLAN & DONALDSON Applicant’s Agents Unit 10, 4075 Kingswood Road Citywest Business Campus Dublin, D24 C56E