NL2016604B1 - Capsule holder for accommodating a capsule for including fluid for transportation across or into a biological barrier, capsule, assembly of a capsule holder and a capsule and device including a capsule holder. - Google Patents

Abstract

The present invention relates to a capsule holder (50) for accommodating a capsule (10) for comprising at least one dose of fluid for transportation across or into a biological barrier for use in intradermal drug delivery. The present invention also relates to a capsule (10) for cooperation with the capsule holder (50). The invention further relates to an assembly of the capsule holder (50) and the capsule (10). The invention furthermore relates to a device (100) for applying force to the capsule (1 0), which device comprises the capsule holder (50), wherein the device and the capsule holder are arranged for releasable attachment, which device comprises a displacement mechanism (112, 113, 114, 115, 118) for moving the capsule (10) in the capsule holder (50) towards the abutment surface (51) and for subsequently moving the protruding part with respect to the receiving part towards the abutment surface.

Description

CAPSULE HOLDER FOR ACCOMODATION A CAPSULE FOR COMPRISING FLUID FOR TRANSPORTATION ACROSS OR INTO A BIOLOGICAL BARRIER, CAPSULE, ASSEMBLY OR A CAPSULE HOLDER AND A CAPSULE AND DEVICE COMPRISING A CAPSULE HOLDER

The invention relates to a capsule holder according to claim 1 for a capsule for including at least one dose of fluid for transportation across or into a biological barrier. The invention further relates to a capsule according to claim 3 for cooperation with the capsule holder.

The international patent application WO 2013/043052 of the same applicant, a system for transporting fluid across or into a biological barrier.

The known system comprises a capsule that comprises a substrate from which two or more hollow micro needles project for penetrating the biological barrier; a reservoir for the fluid dose, which reservoir can be brought into fluid communication with the micro needles, where the fluid dose is transportable through the hollow micro needles across or into the biological barrier substantially all at a time, when force is applied to the capsule .

The known system further comprises a device provided with a displacement mechanism with a ram that after actuation ensures penetration the corneum stratum by the hollow micro needs at a sufficient rate until a controlled depth is reached as well as raising the pressure in the capsule for pressing the fluid through the hollow micro needles.

The housing of the known device holds the capsule.

The micro needle approach shows clear advantages about competing methods or transferring fluids through skin or other biological barriers. In contrast to hypodermic needles, micro needles reach into the dermis of the skin, where the immune system resides, and assure an intradermal drug delivery. Hypodermic needs are used for subcutaneous or intramuscular drug delivery, which is less effective. Due, when using hollow micro needles, a lesser amount of drug is needed compared to using hypodermic needs, for instance for a vaccine only 10-20% of the amount is needed. Furthermore, use of micro needles is relatively painful and drugs can be self-administered or administered by non-professionals. In addition, they overcome the molecular size limitations characteristic or conventional transdermal patches.

The known system provides a compact design with an elegant and simple operation. The system is patient friendly and allows for self-injection. It is thus suitable for daily use by any individual. It is also suitable for use in large groups, particularly in case of vaccination, and even in case of urgent calamities, for instance due to an outbreak or a lethal virus, such as SARS, Ebola, et cetera.

The known capsule is designed for use in the known device and comprises a substrate with an integrated reservoir having a dome shaped upper part that is deformable under force. Advantageously the know capsule is suitable for one time use only assuring optimal hygiene for users.

The invention has for its object to provide a capsule holder to allow quick and easy (re) placement of the capsule. A further object of the invention is to provide an improved capsule for cooperation with the capsule holder that can be used for an even wider range of applications. These objects are achieved by a capsule holder according to claim 1 and a capsule according to claim 3. The cooperating protruding and receiving parts of the capsule according to the invention enclose the reservoir and advantageously allow for an adjustable reservoir volume by predetermining the position of the protruding part with respect to the receiving part. Preferably the protruding part is arranged to be moved from a first position, the volume of the reservoir is at a maximum, to a second position, the volume of the reservoir is at a minimum. The adjustable reservoir volume is a major advantage over the known capsule as varying applications require varying amounts of fluid per dose. Furthermore, the reservoir shape ensures an even distribution of fluid over all micro needles. Both single reservoir and multiple reservoir form form part of the invention.

The capsule holder according to the invention allows for a suitable accommodation for the improved capsule according to the invention. The means for releasable attachment, respectively detachment, or the capsule holder for the device allow for a quick and reliable (re) placement of the capsule. Reuse of the remaining part of the device including the displacement mechanism, also referred to as the applicator, is made easy. The releasable attachment or the capsule holder allows for re-use or recycling or the capsule holder as well. Alternatively, a one-time use only or the capsule holder is possible. Thereby the hygiene for users is further optimized, as the abutment surface is brought into contact with a user's skin. The flat surface then automatically stretches the skin of the user facilitating penetration of the micro needles.

Preferably the capsule holder comprises a form-closed connection, such as a bayonet closure, for releasable attachment to the device for applying force to the capsule.

In a first preferred embodiment the capsule comprises biasing means for biasing the capsule in a direction away from the bottom of the capsule holder. Advantageously the biasing means keep the micro needles inside the housing prior to use. Furthermore, the biasing means ensure withdrawal of the micro needles into the capsule holder after use. Detached assembly of a capsule holder and a capsule has no protruding parts that could otherwise form a danger and is no longer suitable for use. In an elegant preferred embodiment the biasing means include arms that extend around the circumference or the capsule near the substrate. Preferably the arms are provided on the outer ends with feet to rest on the bottom of the capsule holder.

According to a second preferred embodiment the capsule is provided with spacers projecting outwardly from the receiving part to contact the housing of the capsule holder. In the assembled state the spacers define ventilation channels between the capsule and the capsule holder for air enclosed between the substrate and the bottom to escape when the capsule is moved. In a practical preferred embodiment the spacers are ribs extending generally in longitudinal direction over the outer surface of the receiving part.

In a combined embodiment of the first and second embodiment of the arms extend between and substantially transverse to adjacent spacers.

According to another preferred embodiment the capsule is made of plastic, preferably polyethylene (PE), except for the microneedles. Plastic, especially PE, is a suitable material for contact with most fluids.

According to a practical embodiment the protruding part is a plunger and the receiving part comprises a recess for the plunger. Preferably the receiving part is substantially cup-shaped. This embodiment allows for accurate measurement of the fluid dose and has a minimal amount or dead volume.

In a preferred multiple reservoir, the capsule comprises two or more sets of a receiving part and a protruding part, each set enclosing a separate reservoir for fluid. Advantageously each reservoir can be filled with a different fluid, contact between the different fluids is avoided. The capsule is now suitable for separate storage or the different components that make up so-called combination drugs and combination vaccines. As the different drug components or vaccine components are maintained separately in the capsule prior to the current intradermal delivery, the required extensive tests directed to the activity and shelf life of known combination drugs or vaccines, the different drug or vaccination components are mixed, can be successfully avoided. This does not only speed up the introduction of a newly developed drug or vaccine into the market, but also saves a huge amount of costs related to testing.

The present invention also relates to an assembly of a capsule holder according to the invention and a capsule according to the invention, the capsule is movable in the capsule holder from a starting position, the micro needles are inside the housing, to a position or use, the micro needles project out of the housing. The assembly can be sealed for storage.

In addition the present invention relates to a device for applying force to a capsule according to the invention, which device comprises a capsule holder according to the invention, the device and the capsule holder are arranged for releasable attachment, which device comprises a displacement mechanism for moving the capsule according to the invention in the capsule holder towards the abutment surface and for moving the protruding part with respect to the receiving part towards the abutment surface.

In a preferred embodiment of the device the displacement mechanism comprises a ram that is movable with respect to the ram. After actuation the sleeve hits a striking surface on the receiving part of the capsule to move the capsule from the starting position to the position of use. The ram hits a striking surface of the protruding part and proceeds in moving the protruding part with respect to the receiving part from the first to the second position.

The invention will now be elucidated in more detail below with reference to the drawings, in which:

Figure 1 shows a cross sectional view on a preferred embodiment or a device including an assembly or Figure 2A according to the invention;

Figure 2A shows a cross sectional view of an assembly or a first preferred embodiment of a capsule according to the invention and a capsule holder with the capsule in a starting position;

Figure 2B shows a cross sectional view of the assembly or Figure 2A with the capsule in a position of use;

Figure 2C shows a cross sectional view of the assembly or Figure 2A with the capsule in an end position;

Figure 3 shows a schematic view of the assembly or Figure 2A according to the invention;

Figure 4 shows a schematic view or a second preferred embodiment or a capsule according to the invention;

Figure 5 shows a schematic view of a third preferred embodiment or a capsule according to the invention; and

Figure 6 shows a schematic view of a third preferred embodiment or a capsule according to the invention.

Figure 1 shows a cross sectional view on a preferred embodiment or applicator 100 including the assembly or Figure 2A according to the invention.

Figure 2A shows a cross sectional view of an assembly or a capsule 10 according to the present invention in a preferred embodiment and a capsule holder 50. Figure 3 shows a schematic view of the assembly 10, 50. The capsule holder 50 is arranged to accommodate any capsule according to the invention. Further vary or such capsules are shown in figures 4, 5 and 6.

Capsule 10 comprises a substrate 11 from which two or more hollow micro needles 12 project. An example of a suitable type of hollow micro needles is described in the international patent application WO2014 / 077677 or the same applicant, which is incorporated by reference.

The capsule 10 comprises a receiving part 16 and a protruding part 13 to be received in the receiving part 16. The parts 13 and 16 cooperate and enclose a fluid reservoir 14 between two of their opposing or facing surfaces. The protruding part 13 is movable with respect to the receiving part 16. Preferably the protruding part 13 is movable with respect to the receiving part 16 from a first position to a second position, the volume of the reservoir 14 is larger in the first position than in the second position. The first and / or the second position can be set in dependence on the application and the corresponding dose or volume required.

The substrate 11 is comprised in the receiving part. The reservoir is in fluid communication with the micro needles 12 in the substrate 31. The hollow micro needles 12 are arranged for penetrating a biological barrier. A fluid dose present in the reservoir 14 can be transported through the hollow micro needles 12 across or into the biological barrier substantially all at a time when a force is exerted on the protruding part 13 in a direction towards the substrate 11. A plunger 13 forms the protruding part and the receiving part 16 comprises a recess 17 for receiving the plunger 13. The receiving part 16 is substantially cup-shaped, the substrate 11 forms the bottom of the cup and the walls of the cup define the recess 17.

Sealing means 15 are present between the receiving part 16 and the protruding part 13 to provide a fluid tight seal for the reservoir 14. The preferred embodiment shown sealing means 35 are formed by a sealing edge 15.

The capsule holder 50 comprises an outer bottom surface or abutment surface 51 for abutting the biological barrier. The abutment surface 51 is a substantially flat surface provided with micro opening 52 for the micro needles 12. The capsule holder comprises a housing 53 having a receiving space 54 for the capsule. Walls 55 extend upwards to define an opening to a passage 56 for the least part of the displacement mechanism, said passage 56 extending to the receiving space 54. The walls 55 are provided with means 59 for releasable attachment to the device 100. The capsule holder 50 preferably comprises part of a form-closed connection, such as bayonet closure 59, for releasable attachment to the applicator.

The capsule holder 50 is arranged for releasable attachment to a device or applicator, such as applicator 100 shown in figure 1. Applicator 100 comprises a displacement mechanism, such as a ram 112, for applying a force onto the capsule to move the capsule 10 in the capsule holder 50 towards the abutment surface 51.

The assembly further comprises biasing means 19 for biasing the capsule 10 in a direction away from the abutment surface 51. In the preferred embodiment shown the biasing means include a number of resilient arms 19 extending substantially in the circumferential direction of the capsule 10. The arms 19 are at the outer ends provided with feet 19A.

The applicator 100 and the capsule holder 50 are arranged for releasable attachment, preferably by a bayonet closure.

Applicator 100 is arranged for applying force to the capsule 10 and comprises a displacement mechanism for moving the capsule 10 in the capsule holder 50 towards the abutment surface 51 and for moving the protruding part 13 between the first and second position of use. A suitable applicator is described in the international patent application WO 2013/043052 or the same applicant, which is incorporated by reference.

Device or applicator 100 has a housing 111. The housing 111 is preferably a hand-held housing. The housing 111 is elongated and has a hollow inner space 111A.

In the housing a displacement mechanism is present that is arranged to push capsule 10 into the different positions, which are shown in figures 2A, 2B and 2C. The displacement mechanism comprises a ram 112 that is arranged movably in the hollow space 111A or the housing 111 in a direction that is substantially perpendicular to the abutment surface 51. The displacement mechanism further comprises pre-tensioning means for pre-tensioning the ram 112 in a starting position. This starting position is shown in figure 1. In the preferred embodiment shown the pre-tensioning means include a spring 113 and a drive 118 for eccentrically driving the ram 112. In the initial position of the displacement mechanism the eccentrical drive 118 is placed in an off center position. When the system is activated by the user drive 118 turns at least partly around thanks facilitating a controlled acceleration of the ram 112 by the pretensioning means towards the middle position and finally into the end position.

In Figure 2A the capsule is in a starting position. The volume of reservoir 14 is larger than in figure 2C. The capsule 10 rests with the feet 19A on the inner bottom surface of the capsule holder 50 while the micro needles 12 partly extend in the holes 52 the needle points remain inside the capsule holder 50.

In figure 2B the capsule is in a position of use. The capsule 10 has been moved into the capsule holder 50 against the force of the biasing arms 19 by the ram 112 of the applicator. The upper surface of the plunger 13 forms a striking surface 13S for the ram 112. Due to frictional forces the cup 16 will move together with the plunger 13.

The substrate 11 now contacts the inner bottom surface of the capsule holder 50 and the micro needles protrude out of the opening 52 in the abutment surface 51 for penetration of the biological barrier.

In figure 2C the ram is in an end position. The protruding part 13 has been moved into the receiving part 16 from the first to the second position by the ram 112. The reservoir volume 14 is much narrower than in figures 2A and 2B, preferably zero. The fluid has been pushed out of the reservoir 14 through the micro needles 12 into the biological barrier.

It is noted that figures 2A, 2B and 2C schematically show a ram 112 or the known applicator or WO 2013/043052.

In figure 1 an alternative preferred embodiment of the applicator is shown in which the ram 112 is provided with a sleeve 114 that is spring loaded by spring 115. In the initial position shown the ram 112 is retracted in the sleeve 114. When activating the system , the ram 112 and the sleeve 114 will move together, while the sleeve 114 hits the striking surface 16S of the receiving part 16 causing the capsule 10 to move to the position of figure 2B. When the substrate 11 contacts the inner bottom surface of the capsule holder 50 the sleeve 114 is stopped, while the ram 112 hits the striking surface 13S of the plunger 13 and subsequently moves on to the end position moving the plunger relative to the cup 16 towards the second position of figure 2C.

Figure 3 shows a schematic view of the assembly or Figure 2A according to the invention. The capsule 10 is provided with spacers 18 to create ventilation channels for air to escape from the receiving space 54 during movement of the capsule 10 in the capsule holder 50. In the preferred embodiment shown the spacers include mating ribs and grooves. Ribs 18 generally extend in longitudinal direction over the outer surface of the receiving part 16 and can be received in mating grooves on the inner surface of the capsule holder 50. The ribs 18 also serve for positioning the capsule 10 in its starting position in the capsule holder 50.

Figures 4, 5 and 6 each show a schematic view of a second, third and fourth preferred embodiment or a capsule according to the invention. In the second, third and fourth preferred embodiment the capsules 20, 30 and 40 each have multiple reservoirs.

Capsule 20 generally comprises the same parts as capsule 10. In figure 4, reference numerals or like parts are incremented by 10 with respect to figure 3.

Receiving part 26 is divided into two receiving compartments 26A, 26B having recesses 27A, 27B and protruding part 23 comprising two plungers 23A, 23B to be received by the recesses 27A, 27B respectively. Twenty, capsule 20 comprises two sets of cooperating parts 23A, 26A; 23B, 26B, each set of encloses and a separate reservoir for fluid.

Capsule 30 generally comprises the same parts as capsule 10. In figure 5, reference numerals or like parts are incremented by 20 with respect to figure 3.

Capsule 30 comprises three sets of cooperating parts, each set of encloses and a separate reservoir for fluid. Protruding part 33 comprises three plungers 33A, 33B, 33C and receiving part 36 is divided into three receiving compartments having recesses 37A, 37B, 37C (or which only the last two are shown) for receiving the plungers.

Capsule 40 generally comprises the same parts as capsule 10. In figure 6, reference numerals or like parts are incremented by 30 with respect to figure 3.

Capsule 40 consists of four sets of cooperating parts, each set of encloses and a separate reservoir for fluid. Protruding part 43 comprises four plungers 43A, 43B, 43C, 43D. Receiving part 46 is divided into four receiving compartments having recesses 47A, 47B, 47C, 47D (or which only the last two are shown) for receiving the plungers.

All parts of the capsule (with the exception of the micro needles) are preferably made of the same plastic material. A very suitable plastic is polyethylene (PE). A suitable coating may be used depending on the fluid to be transported.

Preferably the inner surface or the capsule holder is metallized to form a barrier against moisture and oxygen.

After use of the system, the capsule may be discarded and the pre-tensioning means can be reset to the initial position, in which the device 100 is ready for re-use. The resetting can be performed manually or automatically. The capsule holder may be discarded together with the capsule or be recycled.

It is noted that the pre-tensioning means of the applicator 100 preferably includes a spring 113. The necessary force to be delivered by the spring depends on the application. When the target area is reached by the micro needles lies in the epidermis or human skin a force or 150 - 500 Newton is expected to be sufficient.

Other suitable pre-tensioning means include electrical or electromechanical pre-tensioning means or pneumatical pre-tensioning means. Alternative drives for the ram include a linear actuator or a pneumatic actuator.

The capsule, capsule holder and device according to the invention are suitable for use with humans as well as animals. Examples of biological barriers include: skin, vessel walls, intestinal walls, the eye, etc.

Essentially any fluid can be delivered using the micro needle devices described. Typically, the fluid comprises an agent, which possesses therapeutic, prophylactic, or diagnostic properties in vivo, for example when administered to a human or an animal. Examples of suitable therapeutic and / or prophylactic active agents include proteins, such as hormones, antigens, such as vaccines, and growth factors; nucleic acids, such as antisense molecules; and narrower molecules, such as antibiotics, steroids, decongestants, neuroactive agents, anesthetics, and sedatives. Examples of suitable diagnostic agents include radioactive isotopes and radio opaque agents, metals, metal oxides, gases and labels including chromatographic, fluorescent or enzymatic labels.

The reservoir is suitable, leak-free storage or the agent composition before it is delivered. In the context of the present invention a capsule is meant to be an enclosure filled with a fluid dose, i.e. a predetermined amount or fluid to be transported substantially all at a time.

The reservoirs are separate and are each in fluid communication only with a limited number of the needles present in the corresponding substrate parts. All fluid doses present in the reservoirs can be transported through the hollow micro needles across or into the biological barrier substantially all at a time when a force is exerted on the striking surface of the protruding part in a direction towards the substrate. The number of reservoirs in the multiple reservoir can be designed for an envisaged application.

The invention is of course not limited to the described and shown preferred exponent. Especially all combinations or the preferred figures shown are included.

The invention generally relates to any edition falling within the scope of protection as defined in the claims and as seen in the light of the foregoing description and accompanying drawings.

Claims (16)

A capsule holder for accommodating a capsule for containing at least one dose of liquid for transport through or into a biological barrier, which capsule comprises a substrate from which protrude two or more hollow micronaids for penetrating the biological barrier and a reservoir for the fluid dose, which reservoir is adapted for fluid communication with the micro needles, wherein the fluid dose can be transported substantially completely in one go through the hollow micronaids through or into the biological barrier when force is exerted on the capsule, wherein the capsule further at least one receiving part comprising the substrate, and at least one protruding part to be received in the receiving part, in which the reservoir is enclosed between facing surfaces of the receiving part and the protruding part and the protruding part is arranged to be moved relative to it receiving part, wherein the capsule holder comprises a housing with a receiving space for the capsule, which housing has a bottom with openings for the micronaids, in which the outer surface of the bottom is substantially flat and forms a supporting surface which is intended to be supported against the biological barrier, in which the capsule holder is provided with means for releasably attaching to a device with a displacement mechanism for the capsule, wherein the housing has a passage for at least a part of the displacement mechanism, which passage extends into the receiving space. The capsule holder according to claim 1, wherein the capsule holder comprises a part of a form-locked connection, such as a bayonet closure, for releasably fastening to the device for moving the capsule. A capsule for cooperating with a capsule holder according to one or more of the preceding claims, for comprising at least one dose of liquid for transport through or in a biological barrier, which capsule comprises a substrate from which two or more hollow micronaids protrude for penetration of the biological barrier and a fluid dose reservoir, which reservoir is adapted for fluid communication with the micro needles, wherein the fluid dose can be substantially completely transported through the hollow micron sows in one go through or into the biological barrier when force is applied to the capsule, wherein the capsule further comprises at least one receiving part, which comprises the substrate, and at least one protruding part, which is to be received in the receiving part, wherein the reservoir is enclosed between facing surfaces of the receiving part and the protruding part and the protruding part are decorated to be moved relative to the receiving part. The capsule according to claim 3, wherein the capsule comprises biasing means for biasing the capsule in a direction away from the bottom of the capsule holder. The capsule as claimed in claim 4, wherein the biasing means comprise resilient arms extending around the circumference of the capsule near the substrate. The capsule according to claim 5, wherein the arms are provided at their ends with feet to rest on the bottom of the capsule holder. Capsule according to one or more of the preceding claims 3-6, wherein the capsule is provided with spacing elements which protrude outwards from the receiving part to make contact with the housing of the capsule holder. A capsule according to claim 7, wherein the spacer elements are ribs that extend substantially longitudinally over the outer surface of the receiving member. A capsule according to claim 7 or 8 referring to claim 5 or 6, wherein the arms extend between and substantially transversely of adjacent spacer elements. Capsule according to one or more of the preceding claims 3-9, wherein the capsule is made from plastic, preferably polyethylene, with the exception of the micronaids. The capsule according to one or more of the preceding claims 3-10, wherein the protruding part is a plunger. Capsule according to one or more of the preceding claims 3-11, wherein the receiving part is substantially cup-shaped. Capsule according to one or more of the preceding claims 3-12, wherein the capsule comprises two or more sets of a receiving part and a protruding part, wherein each set includes a separate liquid reservoir. An assembly of a capsule holder according to claim 1 or 2 and a capsule according to one or more of the preceding claims 3 to 13, wherein the capsule is movable in the capsule holder from a starting position, in which the micronaids are located in the housing, towards a position of use, in which the micro sowing protrudes from the housing. Device for exerting force on a capsule according to one or more of the preceding claims 3 to 13, which device comprises a capsule holder according to one or more of the preceding claims 1 or 2, wherein the device and the capsule holder are arranged for releasable attachment, which device comprises a displacement mechanism for moving the capsule in the capsule holder toward the support surface and then moving the projecting portion relative to the receiving portion toward the support surface. The device of claim 15, wherein the displacement mechanism comprises a ram with a sleeve movable relative to the ram.