BE1026856A1 - MEDICAL DEVICE FOR TOPIC TREATMENTS - Google Patents

Abstract

The present invention relates to a medical device for the treatment of a fungal infection in an individual in need thereof, comprising: a medical container comprising an antifungal medical composition, an applicator nozzle with an opening for applying the antifungal medical composition to the individual, and an actuator mechanism for regulating the applicator nozzle, characterized in that the medical container is sealed with a pierceable seal; and that the actuator mechanism includes an actuator rod movable between (i) a first position in which the actuator rod closes the applicator nozzle opening and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod is the pierceable seal of the medical container pierces, allowing a fluid connection between the medical container and the applicator nozzle.

Description

MEDICAL DEVICE FOR TOPIC TREATMENTS

TECHNICAL AREA

The present invention relates to a medical device for the treatment of dermatological disorders and a method for its use. More particularly, the present invention relates to a medical applicator with which a fungicidal composition can be applied to dermatological disorders, such as, for example, onychomycosis of the toenail.

BACKGROUND

CN 103 764 219 describes a medical applicator for the topical treatment of dermatological problems. A drawback of the above devices is the penetration of certain gases through the seals of bottles, as well as the plastic of the bottle. Ethanol penetrates most plastics with the thicknesses used for blow molding containers.

Manufacturers have designed methods to eliminate penetration, such as packaging in glass ampoules or by using plastics with gas barrier properties, such as polyethylene terephthalate (PET). PET greatly reduces penetration when a sufficient cross section is provided in the package. However, current devices use blow molded containers in combination with conventional caps. The caps therefore become the weakest part of these systems and often leak due to inconsistent sealing (PET / film) or due to cap loosening.

In addition, current container designs utilize conventional single seal inner seals as a means of sealing the bottle contents. The size of the bottle cap and the force with which it is secured to the bottle therefore becomes critical for maintaining the force required to mechanically strengthen the film over time. Cap loosening is a common defect and often leads to leakage of the bottle contents - especially if the system has to be stored for a long time prior to use. Such an applicator is discussed in German patent application DE 102 007 046 600 A1.

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Some medical applicators use fibers, similar to brushes, to apply liquid medical solutions to a target area. These fibers tend to trap some liquid, especially after the applicator has been used. This leads to stiff fibers that are glued together by components of the medical solution. In addition, especially for onychomycosis, this can lead to the transfer of a fungus from one nail to another as it is difficult to keep these fibers sterile. As a result, these applicators have high maintenance requirements for proper use. Such applicators are discussed in Chinese patent CN 206 492 102 U.

WO 2016/142305 describes an applicator for topical application of an acidic liquid, the applicator comprising a container containing the acidic liquid, the container comprising an opening in fluid communication with a point for a controlled release of the acidic liquid, the tip being a multitude of fibers and an adhesive material which adheres the fibers. A kit of parts for topical application of an acidic liquid is also described, the kit of parts comprising a liquid dispensing unit comprising a controlled release point of the acidic liquid, as well as a container unit comprising a container configured to acidic liquid, the container unit further comprising a liquid dispensing element for applying the acidic liquid to the tip, the tip comprising a plurality of fibers and an adhesive material which adheres the fibers. However, such devices do not provide sufficient or reliable closure of the applicator, allowing at least partial loss of the acidic liquid by evaporation.

Therefore, it is desirable to overcome the drawbacks and drawbacks of the prior art with a medical skin applicator. It would be desirable if the skin applicator could be placed in an inverted orientation during use and to ensure a liquid and / or gastight closure of the applicator. It would be highly desirable if the medical skin applicator and its components are easily and efficiently manufactured and assembled.

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SUMMARY OF THE INVENTION

The present invention provides a medical device for treating a fungal infection according to the claims.

In a first aspect, the present invention provides a medical device for the topical treatment of a disease in an individual in need thereof, comprising:

a medical container comprising a medical composition, an applicator nozzle with an opening for applying the medical composition to the individual and an actuator mechanism for regulating the applicator nozzle.

More particularly, the present invention provides the medical device in which the medical container is sealed with a puncturable seal; and wherein the actuator mechanism includes an actuator rod movable between (i) a first position in which the actuator rod closes the applicator nozzle opening and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod is the pierceable seal of the medical container pierces to form a passageway to allow fluid communication between the medical container and the applicator nozzle.

The pierceable seal is a good barrier to gases and solvents. As a result, the low permeability of the medical container prior to use increases the shelf life of the medical device. In addition, a nozzle applicator is used instead of a brush or fiber applicator. The smooth surface of a nozzle applicator is easier to clean and sterilize. Finally, the actuator mechanism allows controlled application of medical doses of the antifungal medical composition.

In the second aspect, the present invention provides a kit comprising a medical device for the topical treatment of a disease in an individual in need thereof, comprising:

a medical container that includes a medical composition;

an applicator nozzle with an opening for applying the medical composition to the subject, an actuator mechanism for regulating the applicator nozzle and a housing for a medical container.

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More specifically, the present invention provides the kit, wherein the medical container is sealed with a pierceable seal; and wherein the actuator mechanism includes an actuator rod movable between (i) a first position in which the actuator rod closes the applicator nozzle opening and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod is the pierceable seal of the medical container pierces to form a passageway to allow fluid communication between the medical container and the applicator nozzle.

In the third aspect, the present invention provides a method of treating fungal infection using a medical device, comprising the steps of:

providing a medical device, comprising a medical container containing a fungicidal medical composition, an applicator nozzle for applying the fungicidal medical composition and an actuator for regulating application, actuating the actuator to fluidly connect the medical holder and applicator nozzle.

DESCRIPTION OF THE 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 activation of the medical device.

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

Figure IE shows a schematic overview of a possible embodiment of the medical device after the pierceable 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 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.

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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 view 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 actuator rod according to the present invention.

Figure 5B shows a cross-sectional view of a possible embodiment of an actuator rod 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 view 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 view of an alternative possible embodiment of an actuator rod according to the present invention.

Figure 9C shows a perspective view of an alternative possible embodiment of an actuator rod according to the present invention.

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

Figure 1OB shows a schematic overview of a preferred embodiment of the assembly of the medical device.

Figure IOC shows a cross-sectional view of a preferred embodiment of the sealing ring of the present invention.

Figure 1OD shows a detailed perspective of a preferred embodiment of the actuator rod and spring according to a preferred embodiment of the medical device.

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

DETAILED DESCRIPTION OF THE INVENTION

Unless otherwise defined, all terms used in the description of the invention, including technical and scientific terms, have the meaning generally understood by one skilled in the art to which this invention belongs. Definitions of terms are included by way of further explanation to better understand the teachings of the present invention.

As used herein, the following terms have the following meanings: "A," "the," and "it," as used herein, include both single and multiple referees, unless the context clearly states otherwise. For example, "a compartment" refers to one or more than one compartment.

By "about", as used herein when referring to a measurable value such as a parameter, an amount, a time period and the like, is meant to include variations of +/- 20% or less, preferably +/- 10% or less , more preferably +/- 5% or less, and even more preferably +/- 1% or less, and even more preferably +/- 0.1% or less, from and from said value, to the extent that such variations are suitable to perform in the described invention. However, it is to be understood that the value to which the "about" determination refers is itself specifically described.

"Include," "includes," "includes," and "consisting of," as used herein, are synonymous with "containing," "containing," or "contains," and are inclusive or undefined terms that describe the presence of what follows, e.g., component, and excludes the presence of additional, unlisted components, features, elements, members, steps known or described in the art.

Numeric ranges through endpoints include all numbers and fractions that fall within that range, as well as the listed endpoints.

The expression "% by weight", "weight percent" or "weight%" refers herein and throughout the description, unless otherwise defined, to relative weight

BE2018 / 5868 of the respective ingredient based on the total weight of the formulation.

Spatially relative terms, such as "bottom", "bottom", "top", "top", and the like, can be used herein for ease of description in describing the relationship of one element or feature to another element (s) or feature (s), as illustrated in the figures. It will be understood that the spatially relative terms are intended to include different orientations of the device in use, in addition to the orientation shown in the figures. For example, if the device in the figures is inverted, elements described as "below" other elements or features would be "above" the other elements or features. Therefore, the example term "bottom" can include both an upper and a lower orientation. The device may be oriented differently (rotated 90 degrees or rotated with different orientations) and the spatially relative descriptions used herein interpreted accordingly. Likewise, the terms "up", "down", "vertical", "horizontal" and the like are used herein for the purpose of explanation, unless specifically stated otherwise.

It will be appreciated that while the terms first, second, etc. may be used herein to describe various elements, constituents, regions, layers and / or portions, these elements, constituents, regions, layers and / or portions are not limited by these terms should be. These terms are used only to distinguish one element, component, area, layer, or portion from another area, layer, or portion. Thus, a first element, component, region, layer, or portion described herein may be called a second element, component, region, layer, or portion without departing from the teachings of the present invention. The sequence of actions (or steps) is not limited to the sequence described in the claims or figures, unless specifically stated otherwise.

The term "sterile" refers to a surface and / or device that is essentially free of foreign material or unwanted micro-organisms. "Sterility" or "sterile" and its derivatives refer to a range of standards of medical grade sterility, typically established by a regulatory agency. To achieve a desired sterility, the dose container or other part can be manufactured (filled and sealed) in a location of controlled purity,

BE2018 / 5868 such as a 'class 100.OOO' location or better. The manufacturing / filling location may be a 'class 100' location or other suitably sterile and / or aseptic location with cleanroom conditions to maintain a desired state of purity or sterility until or during delivery / use. Alternatively, the device can be packaged and then sterilized. The term 'class 100' means a facility that has less than 100 particles per cubic meter of cleanroom / space. The class 100 standard can also be called ISO class 5. The term 'class 100,000' refers to a facility that has less than 100,000 particles per cubic meter of cleanroom / space. The cleanroom / space can maintain an overpressure environment. The positive pressure environment is configured to operate to allow air to enter the cleanroom when entering the room, limiting the possibility of contaminants entering the cleanroom. Equipment for providing the desired class, such as, for example, class 100 status, includes class 100 laminar flow workstations, class 100 laminar flow fume hood, HEPA filters, and the like. The term "sterile or pure extraction surface" refers to that part of the dose container that has or maintains a desired purity and / or sterility. To do this, in some embodiments, the surface may be sealed or otherwise protected from exposure to ambient conditions until and / or during use.

In some embodiments, the liquid medicament can be any medicament 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 an individual in need thereof, comprising:

a medical container comprising a medical composition, an applicator nozzle with an opening for applying the medical composition to the individual and an actuator mechanism for regulating the applicator nozzle.

More particularly, the present invention provides the medical device in which the medical container is sealed with a puncturable seal; and wherein the actuator mechanism includes an actuator rod movable between

BE2018 / 5868 (i) a first position in which the actuator rod closes the opening of the applicator nozzle and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod pierces the pierceable seal of the medical container, thereby creating a passage shaped to allow fluid communication between the medical container and the applicator nozzle.

The advantage of the pierceable seal, which is used to seal the medical container, is a high barrier and therefore low permeability. This low permeability extends the shelf life of the medical device, ensuring that the medical device and composition function as intended.

The actuator mechanism has two positions. The first position will be called 'closed' and the second position will be called 'open'. When the actuator mechanism is in the closed position, the actuator rod closes the applicator nozzle. When the actuator mechanism is in the open position, the actuator rod allows fluid communication between the medical container and the applicator nozzle along the actuator rod. If the actuator rod is moved from the closed position to the open position while the pierceable seal is intact, the actuator rod will pierce the pierceable seal, making the seal a pierced seal. The pierced seal does not seal the medical container.

This will open the medical container, allowing fluid communication between the medical container and the applicator nozzle. In addition, the actuator mechanism includes two positions for the actuator rod. The "actuator mechanism" includes the "actuator rod", but may include additional elements.

The advantage of the mechanism is easier and cleaner application of the medical composition. In addition, it maintains the medical composition in the medical container while the medical device is not in use.

In particular, the applicator can be set to deliver essentially the required dosage of the medical composition (at the topical location to be treated), thereby avoiding overdose (or an insufficient amount) of the medical composition, which may result in damage to the the skin instead of treating the skin. Therefore, the present applicator, and also the

BE2018 / 5868 liquid release unit proposed herein, allows a targeted application of the medical composition, thereby facilitating the healing of, e.g., a lesion, while essentially not affecting the surrounding (healthy) tissue.

In particular, the present invention provides the medical device for the 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 on intimate parts, a skin removal (e.g., to have a tattoo to be removed), etc. The invention also provides such a medical composition as defined herein, particularly for use in treating a topological lesion, such as in medical treatment. Furthermore, the invention also provides such a medical composition per se, particularly for use in the treatment of a topological lesion, such as in a cosmetic treatment. The invention also provides such a medical composition, in particular for use in (acid) treatment of a skin disorder, such as in the treatment of superficial lesions, in particular skin lesions, mucous membrane lesions and / or nail lesions, viral warts, verrucae, water warts (molluscum contagiosum) , magpies and bunions, hyperpigmentation of the skin (such as age spots, liver spots, lentigo senilis), acne, keratosis pilaris, keratosis actinica, ingrown toenails, onychomycosis, xanthelasma of the eyelid, psoriasis, fungal infections of the nail, epidermodysplasplasplasis by HPV (human papillomavirus), scars, wrinkles, and melasma. The invention also provides such medical composition fluid as defined herein, particularly for use in the (acid) treatment of topical oral health problems such as mouth ulcers (mouth ulcers) and cold sores. The invention also provides such medical composition fluid as defined herein, in particular for use in (acid) treatment of topical problems on intimate parts, on mucous membranes and tissue, such as hemorrhoids, genital warts. The invention also provides such a medical composition as defined herein, in particular for use in (acid) skin removal treatment such as a tattoo and / or a fibroma.

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MEDICAL HOLDER

The medical container preferably consists of an acid-resistant material. Good alternative acid-resistant materials for the medical container can be selected from the group consisting of acid-resistant metals, chlorinated polyvinyl chloride (CPVC), ethylene chlorotrifluoroethylene (ECTFE), (reinforced) polytetrafluoroethylene, (reinforced PTFE), high density polyethylene (HDPE), polyether ether ketone (PEEK) , polypropylene (PP), polysulfone (PSU), polyphenylene sulfide (PPS), polyvinyl chloride (especially type 1 (PVC, type 1) or type 2 (PVC, type 2)), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyamide -imide (PAI), ultra high molecular weight (UHMW) polyethylene and also (with an acid resistant material, especially an acid resistant polymer) coated metals such as aluminum. In a further embodiment, good container materials can be independently selected from the group consisting of high density polyethylene (HDPE), low density polyethylene (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) N-butadiene rubber. against the acidity of an acidic liquid It has been found that in particular polypropylene (PP) and polyethylene terephthalate (PET) (such as, for example, polyethylene terephthalate talate glycol (PETG)) have good acid resistance to the acids in the acid liquid of the present invention, while also exhibiting different resistance to different acid. 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 at a level of 1 to 25% by weight relative to the total weight of the medical composition.

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In a preferred embodiment, the medical composition comprises a film-forming polymer at a level of 2 to 24% by weight, the medical composition more preferably comprises a film-forming polymer at a level of 3 to 23% by weight, the medical composition more preferably comprises a film-forming polymer in a content of 4 to 21% by weight, the medical composition more preferably comprises a film-forming polymer in a content of 5 to 20% by weight, the medical composition more preferably comprises a film-forming polymer in a content of 5 to 20% by weight. 19 wt%, the medical composition more preferably comprises a film-forming polymer at a level of 5 to 18 wt%, the medical composition more preferably includes a film-forming polymer at a level of 5 to 17 wt%, the medical more preferably a film-forming polymer composition at a level of 5 to 16 wt%, the medical composition more preferably comprises a film-forming polymer at a level of 5 to 15 wt% Most preferably, the medical composition comprises a film-forming polymer at a level of 6, 7, 8, 9, 10, 11, 12, 13, 14% by weight or any content in between. Medical compositions comprising a film-forming polymer at levels less than 1% by weight cure very slowly after being applied to nails as a topical treatment, or do not cure at all. Medical compositions comprising a film-forming polymer in an amount greater than 25% by weight lead to compositions that are too viscous.

This film-forming polymer is capable of curing into a film after application. This is beneficial for topical treatment of infection in nails. This is also beneficial for preserving the medical composition, since the film-forming polymer has a self-sealing effect. This film-forming polymer cannot seal enough closures when the actuator rod is in the first, closed position.

In a preferred embodiment, the film-forming polymer is based on acrylates, the film-forming polymer is more preferably a copolymer comprising at least one of methyl methacrylate and ethyl acrylate, the film-forming polymer is more preferably a copolymer comprising methyl methacrylate and ethyl acrylate, the film-forming polymer with more preferably poly (ethyl acrylate-co-methyl methacrylate-co-trimethyl ammonium ethyl methacrylate chloride). In a further preferred embodiment, the film-forming polymer is a copolymer containing ethyl acrylate monomer

BE2018 / 5868 includes methyl methacrylate monomer, the ratio of the ethyl acrylate to the methyl methacrylate monomer being 1: 4 to 2: 1, more preferably about 1: 2. Most preferably, the film-forming polymer is poly (ethyl acrylate-comethyl methacrylate-co-trimethyl ammonium ethyl methacrylate chloride) 1: 2: 0.2. These polymers are known under CAS number 33434-24-1.

In a preferred embodiment, the medical composition comprises a solvent. In a further preferred embodiment, the medical composition comprises a mixture of solvents of varying volatility. In the most preferred embodiment, in combination with poly (ethyl acrylate-comethyl methacrylate-co-trimethyl ammonium ethyl methacrylate chloride), the medical composition comprises ethanol, ethyl acetate and butyl acetate. This combination is particularly suitable for providing a sufficiently liquid medical composition that quickly forms a hard film suitable for treating infected nails. Suitable levels 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 wt% solvents, more preferably 40 to 85 wt% solvents, more preferably 45 to 85 wt% solvents, more preferably 50 to 85 wt% solvents, more preferably 55 to 85 wt% solvents, more preferably 60 to 85 wt% solvents, more preferably 65 to 85 wt% solvents, most preferably 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 wt% solvents relative to the total weight of the medical composition or any content in between.

Solvents allow easier dosing of the biologically active agents. Volatile solvents allow the optimization of the viscosity, as well as the cure speed and properties of the film-forming polymer. The combination of ethanol, ethyl acetate and butyl acetate is particularly suitable for acrylate-based film-forming polymers. Due to the combination of volatilities, the rate at which the film-forming polymer cures after application can be optimized while maintaining sufficient viscosity prior to application.

In one embodiment, the medical composition can include a plasticizer. Suitable plasticizers include many commonly available commercially available plasticizers such as mono- and polycarboxylic acid esters, polymeric

BE2018 / 5868 polyesters, polyalkyl ethers and glycerol and glycerol esters. In a further preferred embodiment, the medical composition comprises triacetin. Triacetin is also known as 1,2,3-triacetoxypropane. Suitable plasticizer levels are at most 5 wt% relative to the total weight of the medical composition, preferably at most 4 wt%, more preferably at most 3 wt%. Preferably at least 0.5 wt%, more preferably at least 1 wt%, most preferably at least 1.5 wt%.

Plasticizers are beneficial in optimizing 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-forming polymer cures. In one embodiment, the medical composition has a low enough viscosity to ensure fluid communication between the medical container and the applicator nozzle. However, the viscosity should be high enough to prevent the medical composition from flowing out of the medical device too quickly.

In a preferred embodiment of the invention, the medical composition is an anti-fungal composition. As examples of suitable antifungals, for example, polyenes, e.g., natamycin, nystatin; allylamines, e.g., naphthifine, terbinafine; imidazoles, e.g., bifonazole, chlotrimazole, econazole, fenticonazole, ketocanazole, miconazole, oxiconazole; triazoles, e.g., fluconazole, itraconazole, terconazole; tol naphthate, ciclopirox, undecylenic acid, sulbentine, and morpholines, e.g., amorolfine and the morpholines mentioned in U.S. Patent 5,120,530. A preferred example of an antifungal composition is an amorolfine solution. In a particularly preferred embodiment, the antifungal medical composition solution comprises amorolfine, preferably between 1 and 20 wt% amorolfine, relative to the total weight of the antifungal 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 anti-fungal drug of the morpholine type. Its effects in treating onychomycosis and other fungal infections are known. Advantageously, it can be used with film-forming polymers and is topically effective on nails.

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In another preferred embodiment, the medical composition may be an acidic liquid for application to the nail or skin, particularly applied for exfoliating the skin or mucous membrane, especially the skin, allowing the skin or mucous membrane to renew. The treatment fluid will have a beneficial effect on the lesion to be treated; the medical composition, especially the acid or acids in the liquid, can have a scaling effect, and the liquid, especially the acid or acids, can also provide an oxidation effect on the lesion. The medical composition can include different acidic liquids since one or more different liquids can be applied. In particular, the medical composition includes one or more acids selected from acetic acid, trichloroacetic acid (TCA), formic acid and salicylic acid. The acidic liquid may (further) comprise one or more acids selected from acetic acid, hydrochloric acid (HCl) and nitric acid (HNO3). In particular, the medical composition, as encompassed by the medical device, may include 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 can typically be an acid in a concentration in the range of 0.5-10 wt%, preferably 0.5-5.0 wt%, more preferably 0.5-2 .0 wt%. The acidic liquid may also include two types of acid, both in a concentration according to the above ranges, such as a first acid in a concentration in the range of 0.2-8 wt% and a second acid in 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 contain one or more other ingredients, including one or more other active ingredients. The medical composition as described herein may include other ingredients commonly used in cosmetics and pharmaceuticals, such as one or more of a surfactant, a dye, a nail-penetrating compound, a skin-repairing compound, a microenvironmental regulating compound and a fragrance. .

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The medical composition may further contain, for example, one or more excipients. In particular, an excipient is an inactive substance which is formulated together with the active ingredient or active ingredients of a product or drug to supplement formulations containing such active ingredients. Excipients can, for example, also be designated as fillers or diluents. Excipients can be, for example, one or more of binders, coatings, disintegrants, fillers, flavors, dyes, lubricants, flow aids, sorbents, preservatives, sweeteners, etc.

The medical composition may further include, for example, silk fibroin. Silk fibroin is a protein obtained by hydrolyzing silk fibers that are naturally secreted by the silkworm Bombyx mori. Silk fibroin has various biomedical applications due to its high tensile strength, regulatable biodegradability, non-cytotoxicity, low antigenicity and non-inflammatory properties. The use of silk fibroin extract can promote the healing process during regeneration and restoration of normal and functional nail tissue. The medical composition may further (also) comprise pentylene glycol. Pentylene glycol is used as a humectant. It is a colorless liquid with little odor that is soluble in both water and oil. Due to its unique molecular properties, including a well-separated charge distribution pattern, pentylene glycol exerts its wetting activity much better than comparable chemicals, such as propylene glycol. The medical composition may further (also) comprise dimethylisosorbide. Dimethylisosorbide is a delivery enhancer that can bring active ingredients where they are most needed and is therefore used as a penetration system for the keratinous nail layer. Dimethylisosorbide is a colorless liquid with excellent solvent properties. It enhances the release of active substances into the upper layers of the epidermis, without promoting the product getting into the blood. In addition, dimethyl isosorbide improves the stability of formulations, even those prone to hydrolysis and transesterification. The one or more of silk fibroin, pentylene glycol and dimethyl isosorbide can be used in particular in a medical composition for the treatment of nail fungus.

The medical composition may further include, for example, bleach. Bleach is a colorless to yellowish liquid containing mainly sodium hypochlorite as the active

BE2018 / 5868 component. Bleach is used to increase percutaneous absorption. Its ability to improve penetration makes it an attractive substance to include in the medical composition. In addition or alternatively, pyrrolidines can be included to improve penetration. Pyrrolidines also show a great effect on hydrophilic diffusers and can therefore act as penetration enhancers in (human) skin.

The medical composition may further comprise, for example, a terpene. Terpenes are a large and diverse class of organic compounds that are produced mainly by a variety of plants. Many terpenes are hydrocarbons, but oxygen-containing compounds such as alcohols, aldehydes or ketones (terpenoids) also occur. Its building block is the hydrocarbon isoprene, CH2 = C (CH3) -CH = CH2. Terpene hydrocarbons therefore have the molecular formula (CsHsjn and are classified according to the number of isoprene units. Vegetable oils containing terpenes have shown increasing promise in vivo for inhibiting multiple species of bacteria. For example, cinnamon oil has shown broad activity against Pseudomonas aeruginosa. Olive leaf oil has also shown beneficial properties, particularly with regard to the microenvironment, with antimicrobial properties for some species, as well as curative and supportive properties for others.Cumene (isopropylbenzene) is a terpene shown to contain important antibacterial properties. Limonene, carvone and pinene have also shown beneficial effects.

The medical composition may further include, for example, oxazolidinones. The oxazolidinones are a class of antimicrobial agents with 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 multidrug-resistant gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococci and vancomycin-resistant enterococci. Therefore, oxazolidinones in particular can be included in the medical composition because they can regulate the microenvironment. The medical composition may further comprise, e.g., urea (or carbamide). Urea is an organic compound with the chemical formula CO (NH2) 2. Urea-containing creams are well known and are used as a topical

BE2018 / 5868 dermatological products to promote skin rehydration. Furthermore, it appears that urea can be indicated for psoriasis, xerosis, onychomycosis, ichtyosis, eczema, keratosis, keratoderma, magpies and bunions. Its use in, for example, the treatment and / or prevention of athlete's foot may be intended as a moisturizing agent for dry skin affected by athlete's foot. The medical composition may further include, for example, allantoin. Allantoin is a chemical compound with the formula C4H6N4O3. It is also called 5-urea hydantoin or glyoxyldiureid. It is a diureid of glyoxylic acid. It is used for its moisturizing properties as it increases the water content of the extracellular matrix. It also increases the exfoliation of top layers of dead skin cells, which is beneficial for a faster healing process of damaged skin. The medical composition may further include, for example, panthenol. Panthenol is the alcohol analog of pantothenic acid (vitamin B5) and is therefore a provitamin of B5. In organisms, it is quickly oxidized to pantothenate. For example, in the treatment (and / or prevention) of athlete's foot, panthenol can be used as a humectant, emollient and moisturizer. The one or more of urea, allantoin and panthenol can be used in particular 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 rod is biased toward a first position in which the actuator rod closes the applicator nozzle opening. The advantage is that moving the actuator rod to the open, non-prestressed position requires an action. This ensures that the medical composition is delivered only if desired. It also helps to avoid leaks and spills. Finally, a bias towards the first, closed position reduces the risk of human error when closing the medical container. This improves the preservation of the medical composition.

In a further embodiment, the actuator mechanism includes a spring for biasing the actuator rod into the first position. A spring is a cheap and reliable tool. They are known, reliable and suitable for use in medical applications.

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In one embodiment, the pierceable seal is attached to a sealing ring, the sealing ring being in contact with the medical container and the medical container being effectively sealed prior to the first use. This allows separate fabrication of the pierceable 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 stopped, a pierced seal ring may be replaced with a new piercing seal ring for longer storage of the medical composition.

In one embodiment, the pierceable seal preferably consists of acid-resistant materials. Furthermore, the puncturable seal requires adequate permeability to prevent the loss of volatiles from the medical composition. The pierceable seal should also be gastight after it has been brought into contact with the medical container. In one embodiment, the pierceable seal is an extruded or coextruded film. In a more preferred embodiment, the puncturable seal comprises materials selected from the list of high density polyethylene (HDPE), low density polyethylene (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 acrylic nitrile (nitrile) butadiene rubber (NBR), or aluminum alloy or acid-resistant metals. more preferably, the pierceable seal comprises both a metal and polymers The pierceable seal can further include coatings tten. These can be both aesthetic and functional, as a lacquer can facilitate visual inspection of the pierceable seal prior to first use.

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In another embodiment, the actuator rod, when moved from the first, closed position to the second, open position, moves a volume of the medical composition equal to a single unit dose. This makes the use of the medical device easier. Accurate dosing is important for medical formulations, but difficult to do for a person not trained in the art. Therefore, a single dose unit medical device is easier to use. This also improves the treatment of infections, as these treatments are often dose sensitive.

In a preferred embodiment, the actuator rod includes longitudinal channels to facilitate the flow of the medical composition along the actuator rod. This improves the fluid connection between the nozzle and the medical container. These longitudinal channels are synergistic with a medical composition comprising a film-forming polymer. Wide channels ensure that the fluid connection is not blocked by small polymer films that block passageways. In addition, 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 topical disorder by local contact of the applicator on the nail or skin. This is safer and also more effective than applicators requiring contact with a larger area than the lesion or applicators serving more than the lesion. Specifically, the applicator can be configured to provide the medical composition in a local topical area in the range of 0.01-4 cm ² , such as 0.02-2.5 cm ² , such as 0.1-1.0 cm ² , such as 0.1-0.5 cm ² , by direct contact. Thus, in one embodiment, the applicator nozzle includes a surface with a surface or contact area in the range of 0.01-4 cm ² , preferably 0.1-2.5 cm ² .

In a further embodiment, the applicator comprises a handle part. Thus, in one embodiment, the applicator includes an applicator nozzle comprising a surface having, for example, a surface or contact area in the range of 0.01-4 cm ² , such as 0.1-2.5 cm ² , and the applicator comprising a grip member, wherein the physical topical application comprises touching a topical area and keeping the applicator nozzle in physical contact with the topical area in the range of 0.2-5 seconds.

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Assuming the applicator has a pen shape, the diameter along the length of the pen can be essentially round. Preferably, the applicator comprises a handle part. Such a handle part can for instance comprise a triangular cross section, in particular with rounded corners. Therefore, in an even more preferred embodiment, the applicator comprises different cross sections that gradually change from round to a grip part having a triangular cross section (and optionally changing again to a substantially round cross section). The applicator may include a closure. Such a closure may be included when defining the shape of the applicator.

In a preferred embodiment, the applicator rod 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 have an adverse effect on 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 after it has been applied.

The applicator nozzle, actuator rod and / or spring preferably consist of an acid-resistant polymer material. Good acid-resistant materials for the applicator nozzle, actuator rod and / or spring can be independently selected from the group consisting of chlorinated polyvinyl chloride (CPVC), ethylene chlorotrifluoroethylene (ECTFE), (reinforced) polytetrafluoroethylene, (reinforced PTFE), high density polyethylene (HDPE), polyetheretherone (PEEK), polypropylene (PP), polysulfone (PSU), polyphenylene sulfide (PPS), polyvinyl chloride (especially type 1 (PVC, type 1) or type 2 (PVC, type 2)), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE ), polyamide imide (PAI), ultra high molecular weight (UHMW) polyethylene and also coated (with an acid resistant material, especially an acid resistant polymer). In a further embodiment, good applicator nozzle materials, actuator rod and / or spring can be independently selected from the group consisting of high density polyethylene (HDPE), low density polyethylene (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),

BE2018 / 5868 ethylene chlorotrifluoroethylene (ECTFE), ethylene chlorotrifluoroethylene (ETFE), fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), ethylene propylene diene (EPDM) (fluorocarbon rubber), acrylonitrile rubber. These materials are particularly resistant to the acidity of an acidic liquid. In the most preferred embodiment, the applicator nozzle includes polyoxymethylene (POM).

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

In a further embodiment, the actuator rod and / or the spring of Figures 10D and 10F are provided. This actuator spring design is beneficial for use in conjunction with thermoplastic materials, including but not limited to POM. Thermoplastic materials generally exhibit fatigue under the influence of repeated loads, such as repeated actuation of the medical device. This makes compression springs undesirable. The rod spring designs of Figures 10D, 10F and also 9B minimize the effect of fatigue.

In a preferred embodiment, the medical device further comprises a nail file. This nail file can be attached in any way, but does not have to be attached, to the medical device. The advantage of the nail file is the ease for the client to be able to change 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 for attaching the nail file. In the most preferred embodiment of the present invention, the nail file can be slid into the housing. The ability to easily carry the nail file along with the medical device allows the user to adjust the application of the medical composition as well as to adjust the nail file

BE2018 / 5868 can be used for usual purposes. In addition, this can help mask the medical device as a nail set, 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 to prevent damage to the nozzle or accidental actuation of the actuator mechanism. In a more preferred embodiment, the cap reduces the chance of leaks or drops of medical composition escaping from the nozzle. This provides convenience and cleanliness to the end user and helps maintain the medical composition. When used with a medical composition that includes a film-forming polymer, it also reduces curing of the medical composition in unwanted areas, such as the interior of the nozzle or near the actuator mechanism.

In a further preferred embodiment, the cap comprises a leakage container. This leakage holder particularly seals the nozzle opening. In a more preferred embodiment, this leakage container is impermeable to liquids. In the most preferred embodiment, the leakage container and its pass over the nozzle opening is hermetically sealed and therefore impermeable to liquids and gases. This prevents the escape of volatile substances such as solvent from the medical composition. This is favorable for the shelf life of the medical composition. In addition, it prevents curing of the medical composition in the interior of the nozzle.

In the second aspect, the present invention provides a kit comprising a medical device for the topical treatment of a disease in an individual in need thereof, comprising:

a medical container that includes a medical composition;

an applicator nozzle with an opening for applying the medical composition to the subject, an actuator mechanism for regulating the applicator nozzle and a housing for a medical container.

More specifically, the present invention provides the kit, wherein the medical container is sealed with a pierceable seal; and wherein the actuator mechanism includes an actuator rod movable between (i) one

BE2018 / 5868 first position in which the actuator rod closes the opening of the applicator nozzle and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod pierces the pierceable seal of the medical container, thereby creating a passage for fluid communication between the medical container and applicator nozzle.

This kit allows the medical device included therein to be refillable. The medical holder is a replaceable and interchangeable part. Some resistant fungal infections require significant time treatment and may require the use of multiple medical containers of medical composition. A kit is beneficial for these users. The design of larger medical devices to contain more of the medical composition of the first aspect results in large, indiscrete and inconvenient medical devices. The second aspect kit does not present these issues.

The third aspect of the present invention is a method of treatment of infection using a medical device, comprising the steps of: providing a medical device comprising a medical container containing a medical composition, an applicator nozzle for applying the medical composition and actuator rod for controlling application, actuating the actuator rod to allow fluid communication between the medical container and the applicator nozzle.

The advantage of the method over vial and file application of medical compositions is easier, faster and more precise application. In addition, dosage control has been improved using an actuator mechanism that delivers doses of a similar size.

A preferred embodiment of the method of treatment of infection, wherein in the medical device the medical container is sealed with a pierceable seal, the method further comprising:

piercing the pierceable seal with the actuator rod.

The advantage of this method is a long shelf life of the medical composition in the medical container prior to the first use. This also allows the use of volatile, decomposing, chemically reactive or otherwise

BE2018 / 5868 changing or changing components possible. An example of such chemically reactive components is 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 which are not intended, nor are to be construed as limiting the scope of the invention.

EXAMPLES

It is believed that the present invention is not limited to any previously described form or embodiment and that some modifications to the described example of manufacture may be added without consideration of the appended claims. For example, the present invention has been described with reference to the topical treatment of infections, but it is clear that the invention can be applied to any topical medical composition.

These examples include preferred embodiments of the invention and will be elucidated with reference to the figures.

EXAMPLE 1

Medical device

The medical device assembly is shown in Figure 1A. The medical device 1 includes a medical container 3, which includes a medical composition 11 suitable for treating onychomycosis. The medical device includes an applicator nozzle 6 and an actuator mechanism consisting of an actuator rod 5 and a compression spring 9. The medical device further includes a housing 2 which is tubular with a distal end and a proximal end, and a medical container sealed by a sealing ring 4 enclosed by the housing. The nozzle has a distal end formed for the direct application of an antifungal agent to nails and a proximal end. The medical device further includes a cap 7 that fits the distal end of the nozzle. This makes the pharmaceutical composition

BE2018 / 5868 sealed from the housing. The nozzle, which is screwed to the medical container, is configured to be telescopically mounted on the distal end of the housing.

Activation mechanism

The mechanism by which the medical device is actuated is shown in Figures 1C and 1D. A new medical device that has not yet been used is shown in Figure 1A. This shows a pierceable seal that is closed, with no fluid in the actuator mechanism and near the nozzle. In this condition, the medical device has a long shelf life.

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

Housing

Figures 2A and 2B show a length and cross section of the housing. This housing holds the medical device together and protects the other parts such as the medical container, which is conducive to the safety of children.

The housing is a semi-open tube shape. The distal opening 21 allows placement of medical containers and other parts in the housing. The outer edge near the opening is provided with a track 23 for mounting the nozzle on the housing. The proximal closed end has a convex closure 22. The housing side further includes a recess 25 to contain a nail file.

BE2018 / 5868

This recess is shaped to contain the nail file, the edges of the recess 26 preventing the file from moving sideways. The recess merges into an opening 24 in the housing through which the nail file can be slid. In this way, the nail file is largely contained in the housing, next to the medical holder. This further limits the movement of the nail file. The recess has a greater thickness near the opening in the form of a bead 27. This prevents the nail file from slipping in and out of the housing without exerting a minimal amount of force.

Medical holder

The medical container is shown in Figure 3. It is an amber glass medicine bottle 31. The medical holder is open 33 and includes a screw thread 32. This male screw thread 32 fits the female screw thread 65 of the nozzle, allowing the actuator mechanism, sealing ring and medical holder to remain closed unless there is force is applied after assembly.

The medical container includes 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% butyl acetate, 16.5% ethyl acetate and 55.4% ethanol. The film-forming polymer is poly (ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1: 2: 0.2.

Sealing ring

Figures 4A and 4B show a cross-sectional view and a side view of the sealing ring, respectively. The sealing ring 4 is a cylindrical plastic ring with a largely uniform inner diameter Di and an almost uniform outer diameter De '. The sealing ring has a distai and a proximal end. The proximal end of the ring includes a pierceable seal 10.

The plastic ring is formed by injection molding of high-density polyethylene. Injection molding uses an entry point, a point where the polymer is injected into the mold. The polymer entry point 41 is along the edge of the ring where it is flattened.

BE2018 / 5868

This flattening of the ring simplifies injection molding. It is important that the entry point is not radial as the radial flat surfaces of the ring must be smooth for it to function. Since the entry point is usually not smooth, the entry point must be axial. This flattening results in a smaller outer diameter De. The ring further includes a small ridge 42 that improves the closure between the side of the ring and the inside of the nozzle. A pierceable film is attached to the proximal end of the sealing ring. In addition, the inner diameter near this pierceable foil Do is smaller than Di.

The pierceable film 10 comprises 3 layers: a 2k gold-colored lacquer, an aluminum layer and a polymer layer. The gold-colored lacquer weighs roughly 1.5 g / m ² . The aluminum layer consists of soft, tempered aluminum and the layer is roughly 37p thick. The polymer layer is a co-extrusion coating that weighs 30 g / m ² . The total weight of the film was 130 g / m ^2, with an average thickness of 68p. The film has good mechanical properties, in particular very low permeability for a wide range of volatiles. Damage to the puncturable seal, such as scratches, is visible due to the contrast between the gold-colored paint and the aluminum and polymer layers.

Actuator rod

Figure 5A shows a perspective view of the rod and Figure 5B shows a side view of the actuator rod. The rod 5 is a narrow, elongated plastic element. It has a distal end, a center and a proximal end, where the distal end passes through the distal opening of the nozzle.

The distal end of the rod has a distal tip 51 and a distal base 52. Both the distal tip and the distal base are tubular. The distal tip has an outer radius Da smaller than the inner radius of the nozzle distal opening. The distal base has an outer radius Db larger than the inner radius of the nozzle distal opening. When the distal base of the rod is pressed against the distal opening of the nozzle, no fluid can pass through. This is the closed position of the actuator rod. However, if the rod is pushed in the proximal direction, there is room for fluid to flow along the rod through the nozzle. This is the open position of the actuator rod.

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The center of the rod has the largest outer diameter. Rather than being tubular, the center and proximal ends of the rod consist of four equally spaced projections 54. Lengthways 53 are interposed between these projections so that the pharmaceutical fluid can flow past them. On the distal side, the protrusions have a central outer diameter just greater than the diameter of the coil. More proximally, the protrusions have an outer diameter smaller than the diameter of the coil. This allows the coil to fit around the distal end while the proximal end of the actuator rod deflects the coil when proximal pressure is applied. The coil then provides a reactive pressure that biases the actuator rod toward the closed position.

The proximal end of the rod includes a recess 55 in one of the protrusions. This recess is suitable for distributing fluid according to Archimedes' law. The volume of the recess is linked to the single dose of drug that is provided after a single actuation of the actuator rod, due to the volume of fluid displaced. The proximal tip 56 of the rod is a flat surface. This flat surface is not perpendicular to the axis of the rod, but is angled to provide an acute angle to pierce the film.

Nozzle

Figure 6A shows a side view of the nozzle. Figure 6B shows a perspective of the nozzle. The nozzle 6 is a tubular, conical structure with a smooth surface. It is made of polyoxymethylene (POM) and has an opaque white color. The nozzle has a distal end formed for the direct application of an antifungal agent 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 attachment to the housing. The inner diameter at the distal end is considerably smaller than the inner diameter at the proximal end.

The nozzle has a base 62, which has an outer diameter Dk approximately equal to the inner diameter of the housing. The nozzle further has a web 63 that fits the key of the housing, consisting of a ridge 64 with a

BE2018 / 5868 inner diameter equal to the outer diameter of the key. This track and wedge mechanism ensures a good seal between the housing and the nozzle.

In the base of the nozzle, near the proximal end, is an internal thread 65 that fits the external thread 32 of the medical container. The sealing ring 4 is placed at the distal end of the medical container 3, the foil sealing the medical container. The coil is then placed on the distal end of the sealing ring, followed by the rod placed in the coil. The rod, coil, seal ring and medical container assembly can be placed in the nozzle and the medical container screwed in. This nozzle holder assembly can then be telescopically mounted in the housing. The thread is characterized by DIN 168 standard GL18 with a pitch of 3 mm.

From the nozzle distal end, it has a range of increasing inner diameters, so that the distal opening 61 has the smallest inner diameter Dn, slightly larger than the outer diameter Da of the actuator rod distal tip, but smaller than the actuator rod outer diameter Db. The second outer diameter Dc is larger, greater than the outer diameter Db of the actuator rod. The diameter then increases further to include the protrusions of the actuator rod, and then even more to include the sealing ring. In addition, the nozzle includes a flat, tubular surface 67 on which the sealing ring rests when the nozzle holder assembly is assembled.

Cap

The cap 7 is a rounded, truncated cone that looks translucent and dark blue. It is made by injection molding of polymethyl methacrylate, PET, polyoxymethylene or a copolymer thereof. The cap has six planes of symmetry. The cap has a smooth outer and inner surface. The outside of the cap has two opposite handles 71, which include concave recesses on the outside of the cap. The inside of the cap has a leakage container 72, which is tubular 73 with a beveled edge 75. When the cap is placed on the nozzle, the tip of the nozzle fits into the beveled edge 75 of this leakage holder, pushing the tube shape outward and a tight fit at the end of the beveled edge 74

BE2018 / 5868 is insured. This prevents a leaking nozzle from leaking into the rest of the cap. In addition, the inner surface of the cap is reinforced with six ridges parallel to the axis of the cone, placed hexagonally.

Nail file

The nail file 8 is shown in Figures 8A and 8B. In this example, the nail file is cubic, but this is not required for its operation. It has rounded tips 81 to prevent accidental injury. The side with the largest area of the block is rough to allow filing of nails. Both flat sides of the file have the same roughness and can both be used to file nails. The narrow edge 82 is smooth. The outer dimensions of the nail file are slightly smaller than the inner dimensions of the nail file holder 25 of the housing.

feather

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

Example 2

The second example corresponds to the medical device assembly of Figure 9A. This medical device includes a housing 2 ', a medical container 3, a spring bar assembly 5', a nozzle 6 'and a cap 7'. The housing 2 ', the medical container 3, nozzle 6', cap 7 'have different designs, but are functionally identical to the medical device according to example 1.

Compared to Example 1, Example 2 has a spring rod assembly 5 'which replaces the actuator rod 5, the separate spring 9 and the separate sealing ring 4. The spring rod assembly 5 'includes a fixation ring 4' that functions similarly to the sealing ring 4. This fixation ring 4 'remains fixed on top of the medical container 3' during use. The pierceable seal 10 'is attached to the proximal side of the fixation ring 4'. A spring mechanism 9 'is attached to the distal end of the fixation ring 4' to which the actuator rod is connected. The actuator rod includes a distal base 52 'and a distal tip 51' performing the same function as in Example 1. The pierceable seal must be manually pierced prior to first use. As an alternative

BE2018 / 5868, a pin suitable for breaking the pierceable 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 is conducive to the safety and ease of assembly of the pen. Furthermore, the spring rod assembly can be produced in plastic or other materials. This means that the medical composition does not come into contact with metal. This is required for some medical formulations to prevent oxidation or other unwanted reactions and improves the shelf life and stability of the medical formulation.

Example 3

The third example corresponds to the medical device assembly of Figure 9A, completely identical to Example 2, except for the spring bar assembly 5. The new spring bar assembly is shown in Figure 9C.

This spring bar assembly again includes a fixation ring 4 to which a pierceable seal (not shown) is attached at the proximal side, and a spring mechanism 9 is attached at the distal side. The actuator rod is attached to the spring mechanism 9 and includes a distal tip 51 and a distal base 52. The pierceable seal must be manually pierced prior to first use.

As in 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 conjunction with medical compositions that are sensitive to materials.

Example 4

The third example corresponds to the medical device assembly of Figure 10A. This assembly is shown telescopically in Figure 10B. This medical device comprises a housing 2, a medical container 3, a spring bar assembly 5 ', a sealing ring 4', a nozzle 6 and a cap 7 and a

BE2018 / 5868 nail file 8. The housing 2, medical holder 3, nozzle 6, cap 7 and nail file 8 shown are identical to example 1.

The spring rod assembly 5 'is similar to the actuator rod 5 of Example 1, and includes a distal tip 51', a distal base 52 ', longitudinal channels 53', four equidistant projections 54 ', recess 55', and proximal end 56 ". However, instead of being actuated by a separate spring 9, two protrusions 54 'with a spring mechanism 9' are provided. The spring bar assembly 5 'is preferably made of polyoxymethylene (POM) to provide sufficient elasticity and strength, as well as good fatigue resistance.

The spring rod assembly 5 'is accompanied by a sealing ring 4'. The sealing ring 4 'is similar to the sealing ring 4 of Example 1, and includes the ring structure as well as the pierceable seal 10. However, instead of a largely uniform inner diameter Di and a smaller inner diameter Do near the pierceable seal, the sealing ring 4' has a gradual transition between the distal inner diameter Di and the proximal inner diameter Do near the pierceable seal. This allows the spring mechanism 9 'to bias the spring rod assembly toward the closed position after providing outward pressure.

Advantageously, the assembly requires fewer parts and the medical composition does not come into contact with metals. Furthermore, the pierceable seal can still be replaced by exchanging sealing rings. The design of the rod, especially the longitudinal shape together with the longitudinal channels 53 'and recess 55' allow good dosing control.

Claims (15)

CONCLUSIONS A medical device for the topical treatment of a disease in an individual in need thereof, comprising: a medical container comprising a medical composition, an applicator nozzle with an opening for applying the medical composition to the subject, and an actuator mechanism for regulating the applicator nozzle, characterized in that the medical container is sealed with a puncturable seal; and that the actuator mechanism includes an actuator rod movable between (i) a first position in which the actuator rod closes the applicator nozzle opening, and (ii) a second position in which the applicator nozzle is in an open position and wherein the actuator rod has the pierceable seal of pierces the medical container, thereby creating a passageway to allow fluid communication between the medical container and the applicator nozzle. A medical device according to claim 1, wherein the medical composition comprises a film-forming polymer in an amount of 1 to 25% by weight relative to the total weight of the medical composition. A medical device according to any of the preceding claims 1-2, wherein the actuator mechanism comprises a spring for biasing the actuator rod in the first position, preferably a thermoplastic spring. A medical device according to any one of the preceding claims 1-3, wherein the actuator rod, when moved from the first closed position to the second open position, a volume of the medical composition equal to a single unit dose of the medical composition moved. A medical device according to any one of the preceding claims 1-4, wherein the actuator rod is biased toward the first position with the actuator rod closing the applicator nozzle opening. A medical device according to any of the preceding claims 1-5, wherein the pierceable seal comprises an aluminum layer. BE2018 / 5868 A medical device according to any one of the preceding claims 1-6, further comprising a sealing ring comprising the pierceable seal suitable for sealing the medical container prior to the first use. A medical device according to any of the preceding claims 1-7, wherein the medical container is a glass container. A medical device according to any of the preceding claims 1-8, wherein the medical composition is a fungicidal solution, preferably comprising amorolfine, more preferably between 1 and 20 wt% amorolfine, relative to the total weight of the medical composition. A medical device according to any of the preceding claims 1-9, wherein the actuator rod includes longitudinal channels to facilitate the flow of the medical composition along the actuator rod. A medical device according to any of the preceding claims 1-10, wherein the medical device further comprises a nail file. A medical device according to any of the preceding claims 1-11, wherein the medical device further comprises a removable cap suitable for protecting the applicator nozzle. Kit comprising a medical device for the topical treatment of a disease in an individual in need thereof, comprising: a medical container that includes a medical composition; an applicator nozzle with an opening for applying the medical composition to the subject, an actuator mechanism for regulating the applicator nozzle, and a housing for a medical container, characterized in that the medical container is sealed with a pierceable seal; and in that the actuator mechanism includes an actuator rod movable between (i) a first position in which the actuator rod closes the applicator nozzle opening and (ii) a second position in which BE2018 / 5868 the applicator nozzle is in an open position and the actuator rod pierces the pierceable seal of the medical container, thereby creating a passageway to allow fluid communication between the medical container and the applicator nozzle. A method of treatment of infectious disease using 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 the fungicidal medical composition, and an actuator rod for regulating delivery, actuating the actuator rod to fluidly connect the medical container and facilitate the applicator nozzle. The method of treating a fungal infection according to claim 14, wherein in the medical device the medical container is sealed with a pierceable seal, the method further comprising: piercing the pierceable seal with the actuator rod.