WO2019103675A1

WO2019103675A1 - Applicator device for epicuteanous administration of medicaments

Info

Publication number: WO2019103675A1
Application number: PCT/SE2018/051123
Authority: WO
Inventors: Asko Päiviö
Original assignee: Innovation Skåne Ab
Priority date: 2017-11-24
Filing date: 2018-11-05
Publication date: 2019-05-31
Also published as: SE542450C2; SE1730325A1

Abstract

An applicator device for a medicament in paste, semi liquid or liquid form is disclosed. The applicator device comprises a sleeve with a distal end, configured for output of the medicament. The medicament can be confined in a lumen and pressurized to move towards the distal end. An annular flange is arranged at the distal end of the sleeve to form an applicator surface to be positioned towards the skin of a user for distribution of the medicament on the skin. A membrane is configured to be permeable to the medicament. The membrane is arranged across the lumen at the distal end and configured to be deflected from a plane in which the applicator surface of the annular flange extends when the medicament is subjected to a user induced pressure.

Description

APPLICATOR DEVICE FOR EPICUTEANOUS ADMINISTRATION OF

MEDICAMENTS

Technical Field

The present invention relates to an applicator device for epicutaneous administration of a medicament in paste, semi liquid or liquid form.

Background

A medicament in paste, semi liquid or liquid form, e.g. a cream, ointments, or liquid plaster, may be applied to the skin of a patient, i.e. administered epicutaneusly, to initiate transdermal administration of an active drug of the medicament to cause systemic exposure, or to cause a local effect, e.g.

alleviate local pain, improve wound healing or anaesthetize a skin area. Such a medicament is normally stored in a tube or a small cup. Typically, the user ejects the medicament from the tube, applies it on the skin and smears it over an area with a finger or hand. There are several disadvantages with this process. For example, the user, which may be a nurse or doctor, may suffer undesired exposure to active drugs. Furthermore, the medicament may be contaminated with micro-organisms by the contact with the person handling the medicament.

SE 15301 12-0 discloses a disposable container, comprising an open first end, provided with a closing cover, suitable for output of a medicine in paste or semi liquid form. An annular flange at the open first end is arranged to form an attach surface for a closing cover and to form an applicator for the distribution of the medicine to the skin of a user. The annular flange further comprises a part with a straight edge for manipulation of the medicine. Disadvantages of the device according to SE 15301 12-0 include, for example, an undesirable risk of scraping the skin of the patient with the outer peripheral edge of the annular flange, or with the inner edge constituting the transition between the open first end and the annular flange, during application of the medicine. Not only may the patient feel discomfort at such an event, e.g. when a sensitive burn wound in need of treatment is scraped. The risk of secondary infections is also increased due to the scraped skin. Hence, an improved applicator device for epicutaneous administration of medicaments would be advantageous, in particular allowing for avoiding more of the above-mentioned problems, including providing for safer handling and administration of epicutaneous medicaments.

Summary

Accordingly, examples of the present invention preferably seek to mitigate, alleviate or eliminate one or more deficiencies, disadvantages or issues in the art, such as the above-identified, singly or in any combination by providing an applicator device according to the appended patent claims.

According to a first aspect, an applicator device for a medicament in paste, semi liquid or liquid form is provided. The applicator device comprises a sleeve with a distal end, configured for output of the medicament, and a lumen, in which the medicament can be confined. In use and when the medicament is pressurized, it moves towards the distal end. The lumen extends in a

longitudinal direction between the distal end and an opposite proximal end. A membrane, comprising a resilient material and a porous structure having pores within a defined size interval and/or a plurality of apertures having a defined diameter, is configured to be permeable to the medicament is arranged across the lumen at the distal end and configured to be deflected distally from and relative a plane, when the medicament is subjected to a user induced pressure, i.e. the applicator device being set in a state of high internal pressure. In such a state of high internal pressure, the plane is extending perpendicular to the central axis of the applicator device and comprising a distal point, being the most distal point of the sleeve or any extension thereof. The membrane is in partial immediate connection to and located essentially proximally relative the plane, when the applicator device is in a state of low internal pressure, i.e. when not subjected to a user induced pressure or any other similar external force causing a corresponding induced pressure.

According to a second aspect, an applicator device is provided comprising an applicator device according to the first aspect, further comprising an annular flange arranged at the distal end of the sleeve. Such an angular flange may, for example, advantageously be used as an attachment surface of e.g. a removable sealing cover that protects the membrane and optionally the medicament from the environment upon storage.

According to a third aspect, an applicator device is provided comprising an applicator device according to the first aspect or the second aspect, wherein the lumen ends at a second surface at the proximal end, whereby the second surface and the sleeve forms a confined cavity being open towards the distal end. Such a confined cavity may, for example, advantageously be used for long term storage of medicaments therein, more advantageously when combined with e.g. a removable sealing cover that seals the distal end from the

environment.

According to a fourth aspect, an applicator device is provided comprising an applicator device according to the first aspect or the second aspect, wherein the proximal end is configured to be engaged with a dispensing end of a container configured to hold medicament. Advantageously, an applicator device according to this fourth aspect may, for example, be used in combination with containers, used currently for storage of medicaments, to provide the user with an improved way of application without having to discard presently available containers.

Further examples of the invention are defined in the dependent claims, wherein features for the second, third and fourth aspect of the disclosure is as for the first aspect mutatis mutandis.

Some examples of the disclosure provide for an applicator device wherein at least part of the sleeve adjacent the proximal end is flexible and/or tapers in a direction from the distal end to the proximal end. Such embodiments of the sleeve may advantageously, for example, provide the applicator device with features which make it user friendly and/or which enable increased access to the comprised medicament.

Some additional examples of the disclosure provide for an applicator device wherein the membrane is configured to be substantially impermeable to the medicament until a defined pressure is applied at a defined pressure threshold. Such a substantially impermeable membrane may advantageously prevent undesired leakage from the applicator device until a user controlled increased pressure triggers release of medicament therefrom.

It should be emphasized that the term“comprises/comprising” when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.

Brief Description of the Drawings

These and other aspects, features and advantages of which examples of the invention are capable of will be apparent and elucidated from the following description of examples of the present invention, reference being made to the accompanying drawings, in which;

Fig. 1 a is a schematic illustration of an applicator device 100, in a perspective view, showing an annular flange 104, a distal point 105 and a membrane 106, at the distal end 102, and a second surface 110 at the proximal end 109, connected to the distal end 102 via a sleeve 101 , according to examples of the disclosure;

Fig. 1 b is a schematic illustration of the applicator device of Fig. 1 a, in another perspective view, according to examples of the disclosure;

Fig. 2a is a view from the side of an applicator device 100 in a state of low internal pressure, showing a lumen 103, a confined cavity 1 1 1 , a plane 107, which plane 107 is extending perpendicular to the longitudinal direction 108 of the applicator device 100, and a membrane 106, which membrane 106 is in partial immediate connection to and located essentially proximally relative the plane 107, according to examples of the disclosure;

Fig. 2b is the applicator device 100 of Fig. 2a in a state of high internal pressure, wherein medicament in the inner space of the applicator device 100 is mediating this high internal pressure to force the membrane 106 to attain a convex configuration in partial immediate connection to and located essentially distally relative the plane 107, according to examples of the invention;

Fig. 3a is a view from the side of an applicator device 100, with an open proximal end 109 adapted for mechanical connection by aid of e.g. internal threads (not shown) of the inside surface 1 12 with a container 200 comprising medicament, according to examples of the invention;

Fig 3b is the applicator device 100 of Fig. 3a in mechanical sealed connection with a container 200, having an open dispensing end 201 and comprising medicament and being put in a state of high internal pressure by a user (not shown), whereby the high internal pressure of the combined internal volume leads to an outwards convex configuration of membrane 106 distally relative the plane 107, according to examples of the invention;

Fig. 4a is a view from the side of an applicator device 100 comprising a cutting element 113, with an open proximal end 109 adapted for mechanical connection by aid of e.g. internal threads (not shown) of the inside surface 1 12 with a container 200 comprising medicament, according to examples of the invention;

Fig 4b is the applicator device 100 of Fig. 4a in mechanical sealed connection with a container 200, having a dispensing end 201 which has been opened by penetration of the cutting element 1 13 through a previously protecting covering film (not shown) and comprising medicament and being put in a state of high internal pressure by a user (not shown), whereby the high internal pressure of the combined internal volume leads to an outwards convex configuration of membrane 106 distally relative the plane 107, according to examples of the invention;

Fig. 5 is the applicator device 100 and container 200 of Fig. 4b, comprising an additional sealing unit 1 14 which prevents medicament to leak out of the combined internal volume through any other exit but the membrane 106, according to examples of the invention;

Fig. 6a and 6b are illustrations of an applicator device 100 being mounted to a container 200, in which the distal end 102 is provided with a protective cover 6, which protective cover 6 is removably adhered to the distal surface of annular flange 104 whereby membrane 106 is protected from contact with the environment, according to examples of the invention;

Fig. 7a is a view from the side of an applicator device 100 in a state of low internal pressure, showing an annular flange 104 with a backwards bent configuration and a membrane 106, which membrane 106 is in partial immediate connection to and located essentially proximally relative the plane 107, according to examples of the disclosure;

Fig. 7b is the applicator device 100 of Fig. 7a in a state of high internal pressure, wherein medicament in the inner space of the applicator device 100 is mediating this high internal pressure to force the membrane 106 to attain a convex configuration with a curvature which is essentially in agreement and aligns smoothly with the curvature of the annular flange 104, according to examples of the invention; Fig. 8a is a view from the side of an applicator device 100 in a state of low internal pressure, showing a distal end 102 with a rounded-off peripheral edge, according to examples of the invention; and

Fig 8b is a view from the distal end 102 of the applicator device 100 of Fig. 8a, further provided with a protective cover 6, removably adhered to the rounded-off peripheral edge of the distal end 102, according to examples of the invention.

Detailed Description

Specific examples of the invention will now be described with reference to the accompanying drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the examples set forth herein; rather, these examples are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the examples illustrated in the accompanying drawings is not intended to be limiting of the invention. In the drawings, like numbers refer to like elements.

The applicator device 100 according to the invention essentially comprises a sleeve 101 with a lumen 103 and a distal end 102, provided with a membrane 106. Medicament in the form of e.g. a paste, semi liquid or liquid may be placed in the inner volume of the applicator device 100, preferably such that the entire or the major part of this volume comprises such medicament. The membrane

106 is essentially permeable to the form of medicament in the inner volume, when the same is subjected to a pressure which exceeds the external pressure. When the pressure in the inner volume is essentially equal to the external pressure, the medicament may essentially be prevented from passage through the membrane 106, by employment of an accordingly suitable adapted membrane 106. The inner volume may not, when the applicator device 100 is in use, be in connection with the external environment such that gas or liquid may be exchanged with the same by any other means than through the membrane 106. In a state of low internal pressure, i.e. a state in which the internal pressure of the inner volume is equal to or lower than the external pressure, the membrane 106 may attain a spatial configuration in which the major part of it is located immediately proximal relative a plane 107, which plane 107 is perpendicular to the extension of the applicator device 100 and comprising the most distal point of the sleeve 101 or any extension thereof. The applicator device 100 is adapted such its inner volume or the inner volume of a container 200 connected thereto, may be decreased by a user. For example, the sleeve 101 , a second surface 110 of the applicator device 100 or a container 200 connected thereto may be flexible, such as e.g. made of a flexible plastic or metallic material known in the art. Upon a user induced pressure on such a flexible part, a state of high internal pressure is attained, i.e. a state in which the internal pressure of the inner volume is higher than the external pressure. Such a pressure difference causes the membrane 106, which may be resilient, to bend outwards from the applicator device 100. Hence, it may deflect from the plane 107 such that it becomes a site of the most distal point of the applicator device 100. Preferably, the distal end 102 or any extension thereof, such as e.g. an annular flange 104, may be adapted by a suitable design and spatial configuration, as known in the art, such that the surface of the deflected membrane 107, in such a state of high internal pressure, becomes the most accessible and suitable part of the applicator device 100 for direct contact with the patient. Due to the permeable nature of the membrane 106 in combination with a state of high internal pressure, medicament is transferred from the inner volume through the membrane 106, whereby it becomes accessible on the outer surface of the membrane 106. In practice, the user, e.g. a nurse or the patient, may be provided with an applicator device 100 comprising medicament in its internal volume. After removal of an optional protective cover 6, the user may press a suitable flexible area of the applicator device 100, whereby the internal pressure is increased, causing the membrane 106 to deflect outwards and the medicament to become accessible on it outer surface. Typically, it may become obvious to the user by visual inspection, that the outer surface of the membrane 106 comprise medicament and its deflected nature may serve as further guidance for the following administration procedure. The outer surface of the membrane 106 and the medicament thereon may thereafter be applied to the area of administration, e.g. a wound, an area of infection or normal skin, while maintaining a high internal pressure in the inner volume of the applicator device 100. Medicament may thereby continuously leak out onto the outer surface of the membrane 106, to be transferred to the area of administration through a smearing action. Throughout this process, medicament confined in lumen 103 moves in a longitudinal direction 108 towards the distal end 102. According to one embodiment, the applicator device 100 may be provided with a second surface 1 10 at the proximal end 109. A confined cavity 1 1 1 is thereby defined by this second surface 1 10, the sleeve 101 and the inner area of the membrane 106. The volume of this confined cavity 1 1 1 may be adapted match the volume of one dose of medicament to be administered, whereby the applicator device 100, advantageously, may serve for one-time-use

administration of one dose of the medicament.

According to one embodiment, the proximal end 109 of the applicator device 100 may be configured, such as e.g. being provided with internal threads, to be engaged with a dispensing end 201 of a container 200 configured to hold medicament. Such a container 200 may be a standard tube with a standard dispensing end 201 , such as e.g. a threaded dispensing end 201 , currently used for normal storage of medicaments in the form of pastes or similar. The applicator device 100 may thus, advantageously, be employed for administration of medicaments contained in current standard tubes with a minimization of the risk of e.g. undesired exposure to the medicament.

According to one embodiment, the proximal end 109 of the applicator device 100 may be configured to puncture a sealing film, element or surface of a container 200 configured to hold medicament, when being engaged with the dispensing end 201 thereof. Current standard containers or tubes, used for storage of medicaments in the form of pastes or similar, are commonly provided with such a protective sealing film, element or surface for the enablement of long term storage. For example, the applicator device 100 may be provided with a cutting element 1 13 configured to puncture a sealing surface 202 of the dispensing end 201 when the proximal end 109 is engaged with the dispensing end 201 , such as e.g. when the dispensing end 201 is threaded onto or into the proximal end 109.

According to one embodiment, the applicator device 100 may comprise a sealing unit 1 14 arranged inside the sleeve 101. This may be configured for apposition against the dispensing end 201 when the proximal end 109 is engaged with the dispensing end 201.

According to one embodiment, the applicator device 100 may be provided with internal threads, for engagement with a threaded dispensing end 201 , a cutting element 113, for the puncturing of a sealing surface 202 of the dispensing end 201 and, optionally, with a sealing unit 114. Such a combination allows, advantageously, for employment the applicator device 100 in the administration of medicaments contained in a large subset of current standard tubes.

According to one embodiment, the proximal end 109 of the applicator device 100 may be configured to be engaged with a container 200 configured to hold medicament, by being force-fit to the dispensing end 201 of the same. For example, an inside surface 1 12 of at least part of the lumen 103 may be configured to be force-fit to the dispensing end 201 when the inside surface 1 12 is pushed towards the dispensing end 201.

According to one embodiment, the membrane 106 may be configured to be substantially impermeable to the medicament until a defined pressure is applied at a defined pressure threshold. The skilled person will provide a suitably configured membrane 106 on basis of the understanding that it should remain substantially impermeable under user imposed pressures that may be the result of the user holding or moving the applicator device 100 for purposes other than the desire to apply medicament onto the patient. The skilled person will furthermore readily understand which user applied force is a force that the user may conveniently apply when having a desire to apply medicament onto the patient, to configure the membrane 106 accordingly.

According to one embodiment, the membrane 106 may be resilient and comprise pores and/or apertures. Suitable materials for construction of such a membrane 106 are well known in the art and include, for example, medical rubber, resilient plastics or the like. The skilled person may be guided in the selection of material and design by the following desirable main properties: resilience to enable deflection from plane 107 at a high pressure state, pressure dependent permeability to enable throughput of medicament in a high pressure state and no or minor throughput in a low pressure state, medical grade quality to minimize the risk of undesired patient effects and inertness towards the medicament.

According to one embodiment, the applicator device 100 may be provided with a flexible annular flange 104. Such a flexible annular flange 104 may, advantageously, minimize the risk of undesired mechanical interaction with the patients skin during application of medicament, while simultaneously facilitate an even spread of the same.

The present invention has been described above with reference to specific examples. However, other examples than the above described are equally possible within the scope of the invention. The different features and steps of the invention may be combined in other combinations than those described. The scope of the invention is only limited by the appended patent claims.

More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.

Itemized list of embodiments

1A. According to one embodiment, an applicator device for a medicament in paste, semi liquid or liquid form is provided. The applicator device may comprise a sleeve with a distal end, configured for output of the medicament, and a lumen, in which the medicament can be confined. In use and when the medicament is pressurized, it may move towards the distal end. The lumen may extend in a longitudinal direction between the distal end and an opposite proximal end. A membrane may be configured to be permeable to the medicament and may be arranged across the lumen at the distal end and may be configured to be deflected from a plane, when the medicament is subjected to a user induced pressure. The plane may be extending perpendicular to the central axis of the applicator device and comprising a distal point, being the most distal point of the sleeve or any extension thereof.

1 B. An applicator device (100) for a medicament in paste, semi liquid or liquid form, comprising

a sleeve (101 ) comprising

a distal end (102) configured for output of the medicament, a lumen (103) in which the medicament can be confined, in use, and pressurized to move towards the distal end (102), wherein the lumen (103) extends in a longitudinal direction (108) between the distal end (102) and an opposite proximal end (109), and

a membrane (106) configured to be permeable to the medicament, wherein the membrane (106) is arranged across the lumen (103) at the distal end (102) and configured to be deflected from a plane (107), which plane (107) is extending perpendicular to the longitudinal direction (108) of the applicator device (100) and comprising a distal point (105), being the most distal point of the sleeve (101 ) or any extension thereof, when the medicament is subjected to a user induced pressure.

2. Applicator device according to claim 1 , further comprising an annular flange (104) arranged at the distal end (102) of the sleeve (101 ).

3. Applicator device according to any one of the preceding claims, wherein the lumen (103) ends at a second surface (1 10) at the proximal end (109), whereby the second surface (110) and the sleeve (101 ) forms a confined cavity (1 1 1 ) being open towards the distal end (102).

4. Applicator device according to any one of claims 1 to 2, wherein the proximal end (109) is configured to be engaged with a dispensing end (201 ) of a container (200) configured to hold medicament.

5. Applicator device according to claim 4, wherein the proximal end (109) is configured to be force-fit to the dispensing end (201 ).

6. Applicator device according to claim 5, wherein an inside surface (1 12) of at least part of the lumen (103) is configured to be force-fit to the dispensing end (201 ) when the inside surface (1 12) is pushed towards the dispensing end (201 ).

7. Applicator device according to according to any one of the preceding claims, wherein at least part of the sleeve (101 ) adjacent the proximal end (109) is flexible and/or tapers in a direction from the distal end (102) to the proximal end (109).

8. Applicator device according to claim 4, wherein the proximal end (109) comprises a locking mechanism, such as threads, for interlocking with the dispensing end (201 ).

9. Applicator device according to any one of claims 4 to 8, comprising a cutting element (1 13) configured to puncture a sealing surface (202) of the dispensing end (201 ) when the proximal end (109) is engaged with the dispensing end (201 ). 10. Applicator device according to claim 9, comprising a sealing unit (1 14) arranged inside the sleeve (101 ) and configured for apposition against the dispensing end (201 ) when the proximal end (109) is engaged with the dispensing end (201 ), whereby the sealing surface is fluidly sealed from the sleeve (101 ) when punctured.

11. Applicator device according to according to any one of the preceding claims, wherein the membrane (106) is configured to be substantially

impermeable to the medicament until a defined pressure is applied at a defined pressure threshold.

12. Applicator device according to according to any one of the preceding claims, wherein the membrane (106) comprises a resilient material. 13. Applicator device according to any one of the preceding claims, wherein the membrane (106) comprises a porous structure having pores within a defined size interval and/or comprises a plurality of apertures having a defined diameter. 14. Applicator device according to according to any one of the preceding claims, wherein the membrane (106) has a curvature being convex in a direction towards the skin when deflected from the plane (107).

15. Applicator device according to according to any one of claims 2 to 14, wherein the annular flange (104) is flexible.

Claims

1 . An applicator device (100) for a medicament in paste, semi liquid or liquid form, comprising

a sleeve (101 ) comprising

a membrane (106) configured to be permeable to the medicament, wherein

- the membrane (106) comprises a resilient material and a porous structure having pores within a defined size interval and/or a plurality of apertures having a defined diameter;

- the membrane (106) is arranged across the lumen (103) at the distal end (102) and configured to be deflected distally from and relative a plane (107), which plane (107) is extending perpendicular to the longitudinal direction (108) of the applicator device (100) and comprising a distal point (105), being the most distal point of the sleeve (101 ) or any extension thereof, when the medicament is subjected to a user induced pressure, i.e. the applicator device (100) being in a state of high internal pressure; and

- the membrane (106) is in partial immediate connection to and located essentially proximally relative the plane (107), when the applicator device (100) is in a state of low internal pressure

3. Applicator device according to claim 2, wherein the membrane (106) has a convex configuration with a curvature which is essentially in agreement and aligns smoothly with the curvature of the annular flange (104), when the applicator device (100) is in a state of high internal pressure.

4. Applicator device according to any one of the preceding claims, wherein the lumen (103) ends at a second surface (1 10) at the proximal end (109), whereby the second surface (110) and the sleeve (101 ) forms a confined cavity (1 1 1 ) being open towards the distal end (102).

5. Applicator device according to any one of claims 1 to 3, wherein the proximal end (109) is configured to be engaged with a dispensing end (201 ) of a container (200) configured to hold medicament.

6. Applicator device according to claim 5, wherein the proximal end (109) is configured to be force-fit to the dispensing end (201 ).

7. Applicator device according to claim 6, wherein an inside surface (1 12) of at least part of the lumen (103) is configured to be force-fit to the dispensing end (201 ) when the inside surface (1 12) is pushed towards the dispensing end (201 ).

8. Applicator device according to according to any one of the preceding claims, wherein at least part of the sleeve (101 ) adjacent the proximal end (109) is flexible and/or tapers in a direction from the distal end (102) to the proximal end (109).

9. Applicator device according to claim 5, wherein the proximal end (109) comprises a locking mechanism, such as threads, for interlocking with the dispensing end (201 ).

10. Applicator device according to any one of claims 5 to 9, comprising a cutting element (1 13) configured to puncture a sealing surface (202) of the dispensing end (201 ) when the proximal end (109) is engaged with the dispensing end (201 ).

11. Applicator device according to claim 10, comprising a sealing unit (1 14) arranged inside the sleeve (101 ) and configured for apposition against the dispensing end (201 ) when the proximal end (109) is engaged with the dispensing end (201 ), whereby the sealing surface is fluidly sealed from the sleeve (101 ) when punctured.

12. Applicator device according to according to any one of the preceding claims, wherein the membrane (106) is configured to be substantially impermeable to the medicament until a defined pressure is applied at a defined pressure threshold.

13. Applicator device according to according to any one of the preceding claims, wherein the membrane (106) has a curvature being convex in a direction towards the skin when deflected from the plane (107).

14. Applicator device according to according to any one of claims 2 to 13, wherein the annular flange (104) is flexible.