LYOPHILISATE CONTAINER AND INFUSION KIT

Abstract

A lyophilisate container (39) comprising a compartment; a wall (3119, 3129) limiting the compartment; and a lyophilisate arranged inside the compartment. At least a portion of the wall (3119, 3129) is semipermeable allowing vapour permeation in one direction out of the compartment through the wall (3119, 3129) and preventing vapour permeation in an opposite direction into the compartment through the wall (3119, 3129).

Claims

1. A lyophilisate container comprising; a compartment; a wall limiting the compartment; and a lyophilisate arranged inside the compartment, wherein at least a portion of the wall is semipermeable allowing vapour permeation in one direction out of the compartment through the wall and preventing vapour permeation in an opposite direction into the compartment through the wall.

2. The lyophilisate container of claim 1, wherein the wall comprises a semipermeable membrane which is vapour permeable in the one direction and vapour tight in the opposite direction.

3. The lyophilisate container of claim 2, wherein the wall comprises a frame structure by means of which the semipermeable membrane is spanned.

4. The lyophilisate container of claim 1, comprising an outer encasing and an inner encasing positioned inside the outer encasing, wherein the wall is a portion of the inner encasing.

5. The lyophilisate container of claim 4, wherein the compartment is arranged in between the outer encasing and the inner encasing, and the at least a portion of the wall is oriented to allow vapour permeation in the one direction from the compartment to the inner encasing through the wall and to prevent vapour permeation in the opposite direction from the inner encasing to the compartment through the wall.

6. The lyophilisate container of claim 4, wherein the compartment is arranged in the inner encasing, and the at least a portion of the wall is oriented to allow vapour permeation in the one direction from the compartment to between the outer encasing and the inner encasing through the wall and to prevent vapour permeation in the opposite direction from between the outer encasing and the inner encasing to the compartment through the wall.

7. The lyophilisate container of claim 4, wherein the outer encasing or the inner encasing has a conical lateral area.

8. The lyophilisate container of claim 2, comprising a rigid body having a hole opening at one end side of the body and extending from the one end side of the body to the an other end side of the body, wherein the hole forms the compartment and the semipermeable membrane is attached to the body thereby closing the hole at the one end side of the body.

9. The lyophilisate container of claim 8, comprising a non-permeable foil having a high thermal conductivity, wherein the foil is attached to the body thereby closing the hole at the other end side of the body.

10. The lyophilisate container of claim 8, wherein the body has a conical lateral area.

11. The lyophilisate container of claim 1, being a pad-like structure, wherein the compartment is formed in between two sheets and at least one of the two sheets is the wall.

12. The lyophilisate container of claim 1, wherein the lyophilisate is a lyophilised drug formulation.

13. An infusion kit comprising a lyophilisate container according to claim 1, a lyophilised drug formulation positioned in the lyophilisate container and a flexible container having a first compartment filled with a reconstitution liquid and a port, in particular, the flexible container comprises a second compartment separated from the first compartment by a frangible seal and the lyophilisate container is arranged inside the second compartment of the flexible container, more particular, the lyophilisate container is embodied in the port of the flexible container.

14. The infusion kit of claim 13, wherein the port has a first mounting structure and the lyophilisate container has a corresponding second mounting structure such that the lyophilisate container is mountable to the body of the flexible container to expel the liquid through the lyophilisate container.

15. A method of preparing a lyophilisate container according to claim 1, comprising: positioning a moist substance inside a compartment of the lyophilisate container limited by a wall limiting the compartment, wherein at least a portion of the wall is semipermeable allowing vapour permeation in one direction out of the inside of the compartment through the wall and preventing vapour permeation in an opposite direction into the inside of the compartment through the wall; closing the compartment of the lyophilisate container; and lyophilising the moist substance in the compartment such that vapour permeates out of the inside of the compartment through the wall.

16. A method comprising the steps of: obtaining a lyophilisate container according to claim 1, reconstituting the lyophilisate of the lyophilisate container in a liquid inside the compartment of the lyophilisate container, and filtering the liquid solution comprising the reconstituted lyophilisate through the wall of the compartment.

17. The lyophilizate container of claim 12, wherein the lyophilizate is a highly potent drug formulation.

18. The lyophilizate container of claim 12, wherein the lyophilised drug formulation comprises a biological component.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0080] The lyophilisate container according to the invention, the kit according to the invention, the method of preparing a lyophilisate container according to the invention and the use according to the invention are described in more detail herein below by way of an exemplary embodiment and with reference to the attached drawings, in which:

[0081] FIG. 1 shows a perspective view of a first embodiment of a kit according to the invention having a first embodiment of a lyophilisate container according to the invention;

[0082] FIG. 2 shows a perspective view of a second embodiment of a kit according to the invention having a second embodiment of a lyophilisate container according to the invention;

[0083] FIG. 3 shows a perspective view of a third embodiment of a kit according to the invention having a third embodiment of a lyophilisate container according to the invention;

[0084] FIG. 4 shows a perspective view of a fourth embodiment of a kit according to the invention having a fourth embodiment of a lyophilisate container according to the invention;

[0085] FIG. 5 shows a perspective view of some components of a fifth embodiment of a kit according to the invention having a fifth embodiment of a lyophilisate container according to the invention;

[0086] FIG. 6 shows an exploded perspective view of some components of a sixth embodiment of a kit according to the invention having a sixth embodiment of a lyophilisate container according to the invention; and

[0087] FIG. 7 shows the kit of FIG. 6 while a lyophilisate is reconstituted and transferred from one compartment of a flexible container to another one.

DESCRIPTION OF EMBODIMENTS

[0088] In the following description certain terms are used for reasons of convenience and are not intended to limit the invention. The terms “right”, “left”, “up”, “down”, “under” and “above” refer to directions in the figures. The terminology comprises the explicitly mentioned terms as well as their derivations and terms with a similar meaning. Also, spatially relative terms, such as “beneath”, “below”, “lower”, “above”, “upper”, “proximal”, “distal”, and the like, may be used to describe one element's or feature's relationship to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions and orientations of the devices in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be “above” or “over” the other elements or features. Thus, the exemplary term “below” can encompass both positions and orientations of above and below. The devices may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly. Likewise, descriptions of movement along and around various axes include various special device positions and orientations.

[0089] To avoid repetition in the figures and the descriptions of the various aspects and illustrative embodiments, it should be understood that many features are common to many aspects and embodiments. Omission of an aspect from a description or figure does not imply that the aspect is missing from embodiments that incorporate that aspect. Instead, the aspect may have been omitted for clarity and to avoid prolix description. In this context, the following applies to the rest of this description: If, in order to clarify the drawings, a figure contains reference signs which are not explained in the directly associated part of the description, then it is referred to previous or following description sections. Further, for reason of lucidity, if in a drawing not all features of a part are provided with reference signs it is referred to other drawings showing the same part. Like numbers in two or more figures represent the same or similar elements.

[0090] FIG. 1 shows a first embodiment of a kit 1 according to the invention which includes a flexible container in the form of an infusion bag 2 and a lyophilisate container 3 according to the invention. The infusion bag 2 has a first compartment 21 housing a liquid diluent 24. Inside the first compartment 21 the lyophilisate container 3 is positioned, which houses a highly potent lyophilized drug formulation 34 as lyophilisate. In a front section, the flexible container 2 has an outlet compartment 25 separated from the first compartment by a frangible seal 22. The compartments 21, 25 are formed in two sheets of a flexible plastic material by providing firm seals along the edges and the frangible seal 22 in an appropriate manner. In particular, the first compartment 25 is formed by firm seals at the outer edges of the sheets and the frangible seal 22. The outlet compartment 25 is formed by a front firm seal and the frangible seal 22 at its back end. Centrally in the front firm seal a port 23 is mounted which is in fluid connection with the outlet compartment 25. The port 23 is embodied to be connected to a structure or device for intravenous administration.

[0091] The lyophilisate container 3 has an essentially cylindrical rigid body 31 through which an axial through-hole extends. At a bottom end, the through-hole is closed by a non-permeable or tight foil 33. At about the upper end of the through-hole, a semipermeable membrane 32 closes the through-hole. Thus, a compartment is formed inside the through-hole between the foil 33 and the membrane 32, in which the lyophilized drug substance is arranged.

[0092] In use of the infusion bag 2, a user manually opens the compartment of the lyophilisate container 3. This can, e.g., be done by pushing on the foil 31 until it breaks. Or, it can be done by squeezing the container 3 or flexible container 2 such that an increase in distance between membrane 32 and the foil 33 is achieved and the membrane 32 and foil 33 are peeled off the container 3. Then the diluent 24 streams into the compartment and dissolves the drug formulation 34 such that a drug solution is obtained. The dissolving of the drug formulation 34 can be assisted by the user shaking the infusion bag 1 in case that the drug substance is not prone to shaking movements. Then the user compresses the first compartment 21 such that the pressure inside the first compartment 21 rises. Caused by this pressure rise, the frangible seal 22 ruptures such that the first compartment 21 and the outlet compartment 25 form a common compartment. The infusion bag 1 is then hanged port 23 down on a support and an intravenous device is attached to the port 23. Thereby, the infusion bag 1 is changed to a single compartment infusion bag and can be applied as known in the art.

[0093] In FIG. 2 a second embodiment of a kit 10 according to the invention which includes a flexible container in the form of an infusion bag 20 and a lyophilisate container 30 according to the invention is shown. The infusion bag 20 has a first compartment 210 housing a liquid diluent 250, a second compartment 220 housing the lyophilisate container 30 in which a highly potent lyophilized drug formulation 350 as lyophilisate is positioned, and an outlet compartment 260 in a front section of the flexible container 20. The first compartment 210, the second compartment 220 and the outlet compartment 260 are separated from each other by frangible seals 230. The compartments 210, 220, 260 are formed in two sheets of a flexible plastic material by providing firm seals along their edges and the frangible seals 230 in an appropriate manner. Centrally in the front firm seal a port 240 is mounted which is in fluid connection with the outlet compartment 260. The port 240 is embodied to be connected to a structure or device for intravenous administration.

[0094] The lyophilisate container 30 has an essentially cylindrical rigid body 310 through which an axial through-hole extends. At a bottom end, the through-hole is closed by a non-permeable or tight foil 330. At a top end the through-hole is closed by a semipermeable membrane 320. Thus, a compartment is formed inside the through-hole between the foil 330 and the membrane 320, in which the lyophilized drug substance is arranged. Furthermore, a thorn 340 is positioned at the upper sheet inside the second compartment.

[0095] In use of the kit 10, a user manually opens the compartment of the lyophilisate container 30 by pressing the thorn 340 into the foil 310. Then the user manually compresses the first compartment 210 of the infusion bag 20 such that the frangible seal between the first and second compartments 210, 220 opens. The diluent 250 streams into the second compartment 220 and dissolves the drug formulation 350 inside the compartment of the lyophilisate container 30 such that a drug solution is obtained. The dissolving of the drug formulation 350 can be assisted by the user shaking the infusion bag 10 in case that the drug substance is not prone to shaking movements. Then the user compresses the second compartment 220 such that the right frangible seal 230 ruptures and the first compartment 210, the second compartment 220 and the outlet compartment 260 together form a common compartment. The infusion bag 10 is then hanged port 240 down on a support and an intravenous device is attached to the port 240. Thereby, the infusion bag 10 is changed to a single compartment infusion bag and can be applied as known in the art.

[0096] FIG. 3 shows a third embodiment of a kit 16 according to the invention which includes a flexible container in the form of an infusion bag 26 and a lyophilisate container 36 according to the invention. The infusion bag 26 has a first compartment 216 housing a liquid diluent 236. The first compartment 216 is generated by sealing two sheets of a flexible plastic material at their peripheral edges. In particular, firm seal seams are established along the edges.

[0097] In a front section of the flexible container 26 a lyophilisate container 36 is placed in a receiver plug 226, which is in fluid connection with the first compartment 216. The lyophilisate container 36 has a cylindrical shape and is dimensioned corresponding to the receiver plug 226. In particular, the lyophilisate container 36 is dimensioned to suit into the receiver plug 226. More specifically, it is inserted to a certain extent into the receiver plug 226 close to a separating barrier 246. At its bottom end it is closed by a non-permeable peelable foil 336. In between the foil 336 and a pointy tapered thorn 316 a lyophilisate compartment 246 is formed which houses a highly potent lyophilized drug formulation 326 as lyophilisate.

[0098] In use of the infusion bag 26, a user manually pushes the lyophilisate container 36 into the port 226. Thereby, the thorn 316 of the lyophilisate container 36 ruptures the membrane 246 such that the diluent flows into the compartment 326 of the lyophilisate container 36. Thereby, the drug formulation 326 is reconstituted and a drug solution is generated inside the infusion bag 26. After ensuring that the solution is completely mixed, the port 256 is connected to an intravenous device. Thereby, the infusion bag 26 can be applied as a known single compartment infusion bag.

[0099] In FIG. 4 a fourth embodiment of a kit 17 according to the invention which includes a flexible container in the form of an infusion bag 27 and a lyophilisate container 37 according to the invention is shown. The infusion bag 27 has a first compartment 217 housing a liquid diluent 237, a second compartment 227 with a receiver plug 257. The first compartment 217 and the second compartment 227 are separated from each other by a frangible seal 267. Otherwise, the compartments 217, 227 are formed in two sheets of a flexible plastic material by providing firm seals along the edges and the frangible seal 267 in an appropriate manner. Centrally, a port 247 is provided to the first compartment 217 which is in selective fluid connection with the first compartment 217. The port 247 is embodied to be connected to a structure or device for intravenous administration.

[0100] In use, the lyophilisate container 37 is plugged into the receiver plug 257 and opened towards the second compartment 227. By this insertion the lyophilisate container 37 and the compartment 227 create a through-hole that enables the connection of those two. Then, the user compresses the first compartment 217 such that the frangible seal 267 opens and one single common compartment is generated. Then the diluent is mixed with a drug formulation 317 initially located inside the lyophilisate container 37 such that a drug solution is generated inside the common compartment.

[0101] All seals involved in the embodiments of flexible containers described herein can be obtained by a process or step of attaching two or more elements or portions of a flexible sheet-like material such that a gas, a liquid or another fluid cannot pass the attached portions. In embodiments where the flexible sheet-like material is a foil and particularly a plastic foil, the sealing can be provided by applying a predefined temperature/energy and/or pressure at a particular location of the foil. Thereby, the foil can be coated with an adhesive which is thermo- and or pressure-activatable. Alternatively or additionally, the sealing can involve ultrasound-, high frequency- and or radio frequency welding. In order to generate firm seals and frangible seals the temperature/energy and/or pressure can be adjusted such that the aimed properties result.

[0102] FIG. 5 shows a fifth embodiment of a kit 18 according to the invention which includes a flexible container in the form of an infusion bag, a tube 28 and a pad 38 as a lyophilisate container according to the invention. The tube 28 has a lower collecting compartment 218 and an upper flushing portion 228. In the flushing portion 228 there is a receptacle slit 238. The pad 38 comprises an upper flexible sheet 318 and a lower flexible sheet 328 as wall which are attached to each other by peripheral seal seams along the edges. The lower flexible sheet 328 comprises a semipermeable membrane allowing vapour permeation out of the compartment. Between the sheets 318, 328 a compartment is formed in which a lyophilized drug formulation 338 is arranged as lyophilisate.

[0103] In use, the pad 38 is introduced into the slit 238 and the upper sheet 318 is pierced or stripped. Then a diluent is flushed from the flushing portion 228 through the pad 38 which dissolves the drug formulation 338. The solution is then filtered through the semipermeable membrane of the lower sheet 328 and gathered in the collecting compartment 218. As the need may, an additional pad having the same drug formulation can then be processed the same way to adjust a dosage of the drug formulation in the solution gathered in the collecting compartment 218 and/or an additional pad having another substance can be processed the same way to generate a combined drug formulation solution in the collecting compartment 218. The lower end of the tube 28 is provided with a connector or port to be coupled to an infusion bag or the like.

[0104] In FIG. 6 a sixth embodiment of a kit 19 according to the invention which includes a flexible container in the form of an infusion bag and a lyophilisate container 39 according to the invention is shown. The lyophilisate container 39 has a cylindrical inner encasing 319 and a cylindrical outer encasing 329. The inner encasing 319 consists of a frame structure 3119 by means of which a semipermeable membrane 3129 is spanned. Thereby, the semipermeable membrane 3129 covers the interior of the frame structure 3119. In particular, the frame structure 3119 is embodied with a flattened top ring, a flattened bottom ring and vertical bars extending between and connecting the rings. Furthermore, the bottom ring is equipped with a transparent and heat conducting foil such that a compartment is generated in the inner encasing 319 in which a lyophilized highly potent drug formulation 379 is positioned as lyophilisate and such that a visual control as well as an improved heat transfer can take place. By the positioning of the membrane 3119 the drug formulation 379 is only in contact with the membrane 3119 but not with the frame structure 3129. The top ring is open such that the interior of the inner encasing 319 is accessible top down. The semipermeable membrane 3129 is oriented such that vapour can escape from the inside of the inner encasing 319 but permeation of vapour to the inside of the inner encasing 319 is restricted or prevented.

[0105] The outer encasing 329 consists of a rigid cylinder having a bottom and an open upper end side. The inner encasing 319 is coaxially plugged into the outer encasing 329. The inner and outer encasings 319, 329 are dimensioned in a way that there is a free room or volume between the inner encasing 319 and the outer encasing 329.

[0106] The inner and outer encasings 319, 329 are coupled to each other by an outer lid 369. Further, there is an inner lid 339 provided to the inner encasing 319 that in its centre is connected to a top coupler 349. The top coupler is hollow and allows the transfer of substances into the inner encasing 319. At the bottom of the outer encasing 329 a bottom coupler 359 is provided.

[0107] In preparation of the lyophilisate container 39, the drug formulation 379 is lyophilized inside the inner encasing 319. Thereby, vapour escapes through the membrane 3129 and also possibly through the top coupler 349. More specifically, since the overall area of the membranes 3129 is comparably large and due to the close contact between the drug formulation 379 and a freeze drying shelve, an efficient lyophilisation can be achieved.

[0108] As shown in FIG. 7, in use, the lyophilisate container 39 is plugged to an infusion bag 29 as flexible container by means of the top coupler 349 and its bottom coupler 359. More specifically, the infusion bag 29 has a first compartment 219 filled with a diluent 239 and a second compartment 229. The diluent 239 is provided from the first compartment 219 via a first tube and the top coupler 349 into the inner encasing 319, where the drug formulation 379 is dissolved. The created drug solution 249 is then filtered through the membrane 3129 into the room between the inner encasing 319 and the outer encasing 329. From there it is provided through the bottom coupler 359 and a second tube 269 into the second compartment 229 of the infusion bag 29 where it is collected.

[0109] In an alternative use, multiple containers 39 are coupled in a sequence to the infusion bag. Thereby, the containers can be filled with the same drug formulation 379 to adjust the dosage within the drug solution or with a different drug formulation to be mixed with the drug formulation 329.

[0110] This description and the accompanying drawings that illustrate aspects and embodiments of the present invention should not be taken as limiting-the claims defining the protected invention. In other words, while the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. In some instances, well-known circuits, structures and techniques have not been shown in detail in order not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those of ordinary skill within the scope and spirit of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below. For example, whereas most examples described above are involving a drug formulation it is possible to operate the invention as well in non pharmaceutical applications such as in nutrition, chemical processes, analytical methods or similar.

[0111] The disclosure also covers all further features shown in the Figs. individually although they may not have been described in the afore or following description. Also, single alternatives of the embodiments described in the figures and the description and single alternatives of features thereof can be disclaimed from the subject matter of the invention or from disclosed subject matter. The disclosure comprises subject matter consisting of the features defined in the claims or the exemplary embodiments as well as subject matter comprising said features.

[0112] Furthermore, in the claims the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single unit or step may fulfil the functions of several features recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. The terms “essentially”, “about”, “approximately” and the like in connection with an attribute or a value particularly also define exactly the attribute or exactly the value, respectively. The term “about” in the context of a given numerate value or range refers to a value or range that is, e.g., within 20%, within 10%, within 5%, or within 2% of the given value or range. Components described as coupled or connected may be electrically or mechanically directly coupled, or they may be indirectly coupled via one or more intermediate components. Any reference signs in the claims should not be construed as limiting the scope.