MULTI CHAMBER SYRINGE UNIT AND METHOD OF PREPARING A MULTI CHAMBER SYRINGE

Abstract

A multi chamber syringe unit includes a longitudinal body with side wall, distal end side, proximal end side opposite to distal end side, an interior limited by side wall between distal end side and proximal end side and distal opening arranged in distal end side for providing a liquid out of the body. The syringe further includes a separating element arranged in the interior of the body such that distal chamber and proximal chamber are formed in the interior of the body, wherein the separating element seals the distal chamber from the proximal chamber. The syringe has a bypass arrangement provided in the side wall of distal chamber of the body. A first pharmaceutical liquid is arranged in distal chamber of the body and second pharmaceutical liquid in proximal chamber of the body. The multi chamber syringe unit allows for adequately administering plural pharmaceutical liquids by injection.

Claims

1.-15. (canceled)

16. A therapeutic method comprising: obtaining a multi chamber syringe unit, the multi chamber syringe unit including: a longitudinal body with a side wall, a distal end side, a proximal end side opposite to the distal end side, an interior limited by the side wall between the distal end side and the proximal end side and a distal opening arranged in the distal end side for providing a liquid out of the body, a separating element arranged in the interior of the body such that a distal chamber and a proximal chamber are formed in the interior of the body, wherein the separating element seals the distal chamber from the proximal chamber, a bypass arrangement provided in the side wall of the distal chamber of the body and located adjacent to the distal end side of the body, a first pharmaceutical liquid arranged in the distal chamber of the body, and a second pharmaceutical liquid arranged in the proximal chamber of the body, wherein the body and the separating element are arranged such that the distal chamber is essentially emptied when the separating element is moved to the bypass arrangement, wherein the first pharmaceutical liquid comprises an enzyme being hyaluronidase and the second pharmaceutical liquid comprises a therapeutic active ingredient, and wherein the first pharmaceutical liquid and the second pharmaceutical liquid are configured to form a gel together upon mixing; penetrating a needle of the multi chamber syringe unit into subcutaneous tissue; and activating the multi chamber syringe unit so as to firstly inject the first pharmaceutical liquid such that the hyaluronidase increases acceptance of the second pharmaceutical liquid in the subcutaneous tissue and secondly inject the second pharmaceutical liquid such that the first pharmaceutical liquid and the second pharmaceutical are subcutaneously mixed and together form a gel.

17. The therapeutic method of claim 16, wherein the therapeutic active ingredient comprises a protein.

18. The therapeutic method of claim 17, wherein the protein is an antibody.

19. The therapeutic method of claim 18, wherein the antibody is a monoclonal antibody.

20. The therapeutic method of claim 16, wherein the needle of the multi chamber syringe unit is connected to the distal opening of the distal end side of the body.

21. The therapeutic method of claim 16, wherein the first pharmaceutical liquid comprises an anesthetic.

22. The therapeutic method of claim 21, wherein the anesthetic is an amid based anesthetic.

23. The therapeutic method of claim 16, wherein the first pharmaceutical liquid and the second pharmaceutical liquid are configured to form the gel together upon mixing by the first pharmaceutical liquid comprising a first hydrogel and the second pharmaceutical liquid comprising a second hydrogel.

24. The therapeutic method of claim 16, wherein the multi chamber syringe unit comprises a rod and activating the multi chamber syringe unit comprises pressing the rod into the interior of the body.

25. The therapeutic method of claim 16, wherein the separating element is a middle plunger.

26. The therapeutic method of claim 16, wherein the multi chamber syringe unit comprises a closing element arranged in the interior of the body and closing the proximal chamber.

27. The therapeutic method of claim 26, wherein the closing element is an end plunger.

28. The therapeutic method of claim 26, wherein the multi chamber syringe unit comprises an activation rod connected to the closing element and activating the multi chamber syringe unit comprises pressing the rod into the interior of the body such that the closing element is distally moved.

29. The therapeutic method of claim 16, wherein the bypass arrangement comprises a longitudinal bulge provided in the side wall of the distal chamber of the body

30. A method of preparing a multi chamber syringe having a longitudinal body with a side wall, a distal end side, a proximal end side opposite to the distal end side, an interior limited by the side wall between the distal end side and the proximal end side, a distal opening arranged in the distal end side for providing a liquid out of the multi chamber syringe, and a bypass arrangement provided in the side wall of the distal chamber of the body and located adjacent to the distal end side of the body, comprising: sterilizing the multi chamber syringe; filling a first pharmaceutical liquid comprising an enzyme being hyaluronidase into the interior of the body adjacent to its distal end side; providing a separating element in the interior of the body of the multi chamber syringe such that a distal chamber and a proximal chamber are formed in the interior of the body, wherein the separating element seals the distal chamber from the proximal chamber; and filling a second pharmaceutical liquid comprising a therapeutic active ingredient into the proximal chamber of the interior of the body, wherein the first pharmaceutical liquid and the second pharmaceutical liquid are configured to form a gel together upon mixing.

31. The method of claim 30, further comprising providing a closing element in the interior of the body of the multi chamber syringe such that the proximal chamber is closed.

32. The method of claim 31, wherein the closing element is an end plunger.

33. The method of claim 30, wherein the multi chamber syringe is aligned with the distal end side of the body down during all steps of the method.

34. A prefilled multi chamber syringe unit configured to be used in the method of claim 16 comprising: a longitudinal body with a side wall, a distal end side, a proximal end side opposite to the distal end side, an interior limited by the side wall between the distal end side and the proximal end side and a distal opening arranged in the distal end side for providing a liquid out of the body; a separating element arranged in the interior of the body such that a distal chamber and a proximal chamber are formed in the interior of the body, wherein the separating element seals the distal chamber from the proximal chamber; a closing element arranged in the interior of the body and closing the proximal chamber; an activation rod with a finger rest, wherein the activation rod extends into the interior of the body and is connected to the closing element; a needle connected to the distal opening of the distal end side of the body; a bypass arrangement provided in the side wall of the distal chamber of the body and located adjacent to the distal end side of the body; a first pharmaceutical liquid arranged in the distal chamber of the body; and a second pharmaceutical liquid arranged in the proximal chamber of the body, wherein the body and the separating element are arranged such that the distal chamber is essentially emptied when the separating element is moved to the bypass arrangement, wherein the first pharmaceutical liquid comprises an enzyme being hyaluronidase and a first hydrogel, wherein the second pharmaceutical liquid comprises a therapeutic active ingredient and a second hydrogel, and wherein the first pharmaceutical liquid and the second pharmaceutical liquid are configured to form a gel together upon mixing.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The multi chamber syringe unit according to the invention, the preparation method according to the invention and the therapeutic method are described in more detail herein below by way of exemplary embodiments and with reference to the attached drawings, in which:

[0043] FIG. 1 shows a side view on a first embodiment of a double chamber syringe as a first embodiment of a multi chamber syringe unit during concomitant liquid provision in a first embodiment of a therapeutic method;

[0044] FIG. 2 shows a graph of the liquid provision of the therapeutic method of FIG. 1;

[0045] FIG. 3 shows a side view on a second embodiment of a double chamber syringe as a second embodiment of a multi chamber syringe unit during sequential liquid provision in a second embodiment of a therapeutic method;

[0046] FIG. 4 shows a graph of the liquid provision of the therapeutic method of FIG. 3;

[0047] FIG. 5 shows a side view on a third embodiment of a double chamber syringe as a third embodiment of a multi chamber syringe unit during preparation in a first embodiment of a preparation method according to the invention; and

[0048] FIG. 6 shows a side view on a fourth embodiment of a double chamber syringe as a fourth embodiment of a multi chamber syringe unit during preparation in a second embodiment of a preparation method according to the invention.

DETAILED DESCRIPTION

[0049] 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.

[0050] 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.

[0051] FIG. 1 shows a pre-filled double chamber syringe 1 as a first embodiment of a multi chamber syringe unit according to the invention. The syringe 1 has a longitudinal hollow glass body 2 with a tubular side wall 21 surrounding an interior of the body 2. At its one end in a longitudinal direction, in FIG. 1 this is the right end, the body 2 has a distal end side 23 which is equipped with a distal opening passing over in a needle connector 5. At its other opposite end in the longitudinal direction, in FIG. 1 this is the left end, the body 2 has a proximal end side 22 having a main opening.

[0052] Between the distal end side 23 and the proximal end side 22 the side wall 21 is equipped with a longitudinal bulge 26 as a bypass arrangement. In the interior of the body 2 a middle plunger 3 as a separation element and an end plunger 4 as a closing element are arranged. Between the middle plunger 3 and the distal end side 23 a distal chamber 24 is formed in the interior of the body 2. Similarly, between the middle plunger 3 and the end plunger 4 a proximal chamber 25 is formed in the interior of the body 2. In the distal chamber 24 of the body 2 a first pharmaceutical liquid 7 (in FIG. 1 and FIG. 2 also referred to as A) and in the proximal chamber 25 of the body 2 a second pharmaceutical liquid 8 (in FIG. 1 and FIG. 2 also referred to as B) are arranged.

[0053] The syringe 1 is further equipped with an activating rod 6 which extends through the main opening at the proximal end 22 into the interior of the body 2. The activating rod 6 at its left end side has a finger rest and at its right end side is connected to the end plunger 4.

[0054] As visualized in FIG. 1 the syringe 1 is operated by pushing the activating rod 6 from left to right into the interior of the body 2. Thereby, in situation i the operation is initiated by applying a force to the finger rest of the rod 6 which, e.g. can be done by a thumb of a hand. As shown in situation ii the pressure inside the proximal chamber 25 is increased by the force acting on the rod 6 and the middle plunger 3 is moved from left to right into the direction of the distal end side 23 of the body 2 until it lies adjacent to or at the bulge 26. In this position a bypass channel is formed besides the middle plunger 3 by the bulge 26. By further advancing the activating rod 6 as shown in situation iii, the second pharmaceutical liquid 8 bypasses the middle plunger 3 and is transferred from the proximal chamber 25 into the distal chamber 24 wherein the middle plunger 3 is not moving. There, as shown in situation iv, the first pharmaceutical liquid 8 is mixed with the second pharmaceutical liquid 7. By still further advancing the activating rod 6, as shown in situation v, the middle plunger 3 moves further to the right hand side and pushes the mixture of first and second pharmaceutical liquids 7, 8 through the needle connector 5 out of the syringe 1.

[0055] In use in a therapeutic application a needle mounted to the needle connector 5 penetrates a target tissue, e.g. subcutaneously, and the syringe is activated, e.g. by the patient, as described above. Thereby, as can be seen in FIG. 2, even though in situation i some first pharmaceutical liquid is purely provided the first and second pharmaceutical liquids 7, 8 are to a major extent injected concomitantly.

[0056] In FIG. 3 a pre-filled double chamber syringe 10 is shown as a second embodiment of a multi chamber syringe unit according to the invention. The syringe 10 has a longitudinal hollow glass body 20 with a tubular side wall 210 surrounding an interior of the body 20. At its one end in a longitudinal direction, in FIG. 3 this is the right end, the body 20 has a distal end side 230 which is equipped with a distal opening passing over in a needle connector 50. At its other opposite end in the longitudinal direction, in FIG. 3 this is the left end, the body 20 has a proximal end side 220 having a main opening.

[0057] Adjacent to the distal end side 230 the body 210 has a longitudinal bulge 260 as a bypass arrangement. In the interior of the body 20 a middle plunger 30 as a separation element and an end plunger 40 as a closing element are arranged. Between the middle plunger 30 and the distal end side 230 a distal chamber 240 is formed in the interior of the body 20. Similarly, between the middle plunger 30 and the end plunger 40 a proximal chamber 250 is formed in the interior of the body 20. In the distal chamber 240 of the body 20 a first pharmaceutical liquid 70 (in FIG. 3 and FIG. 4 also referred to as A) is arranged. In the proximal chamber 250 of the body 20 a second pharmaceutical liquid 80 (in FIG. 3 and FIG. 4 also referred to as B) is arranged.

[0058] The syringe 10 is further equipped with an activating rod 60 which extends through the main opening at the proximal end 220 into the interior of the body 20. The activating rod 60 at its left end side has a finger rest and at its right end side is connected to the end plunger 40.

[0059] As visualized in FIG. 3 the syringe 10 is operated by pushing the activating rod 60 from left to right into the interior of the body 20. Thereby, in situation i the operation is initiated by applying a force to the finger rest of the rod 60 which, e.g. can be done by a thumb of a hand. As shown in situation ii a pressure inside the proximal chamber 250 is increased and the middle plunger 30 is moved from left to right into the direction of the distal end side 230 of the body 20. During this movement of the middle plunger 30 the first pharmaceutical liquid 70 is provided through the needle connector 50 out of the distal chamber 240. As shown in situation iii the middle plunger 30 is further advanced to the right hand side and further first pharmaceutical substance 70 is dispensed. In situation iv the middle plunger 30 is moved as far to the right such that it lies adjacent to or at the bulge 260. In this position, a bypass channel is formed besides the middle plunger 30 by the bulge 260. The first pharmaceutical liquid 70 originally arranged in the distal chamber 240 of the body 20 is, to a large extent, already pushed out of the syringe 10 via the needle connector 50. The second pharmaceutical substance 80 starts to pass the middle plunger 30 via the bypass channel. By further advancing the activating rod 60, as shown in situation v the second pharmaceutical liquid 80 more and more bypasses the middle plunger 30 and is transferred from the proximal chamber 250 via the distal chamber 240 through the needle connector 50 out of the interior of the body 20.

[0060] In use, in a therapeutic application a needle mounted to the needle connector 50 penetrates a target tissue, e.g. subcutaneously, and the syringe 10 is activated, e.g. by the patient, as described above. Thereby, as shown in FIG. 4, the first and second pharmaceutical liquids 70, 80 are injected sequentially. In particular, since the bulge 260 is located close or adjacent to the distal end side 230 of the body 20 the distal chamber 240 is essentially emptied before the second pharmaceutical liquid 80 bypasses the middle plunger 30. Only in situation iv there is, for a comparably short time, a mixture of the first and second pharmaceutical liquids 70, 80 provided. However, it can efficiently be achieved that the first and second pharmaceutical liquids 70, 80 are administered one after the other.

[0061] FIG. 5 shows a first embodiment of a method of preparing a staked-in needle pre-filled double chamber syringe 19 as a multi chamber syringe (preparation method). The syringe 19 has a longitudinal glass body 29 with a side wall 219 surrounding an interior. The body 29 has a lower distal end side 239, an upper proximal end side 229 opposite to the distal end side 239 and a distal opening arranged in the distal end side 239 for providing liquids out of the syringe 19. The distal opening is equipped with a needle 59. Between the distal end side 239 and the proximal end side 229 a longitudinal bulge 269 is formed in the side wall 219 of the body 29.

[0062] As shown in FIG. 5, the preparation method comprises five steps A through E. In step A the syringe 19 is positioned distal or front side down and prepared by sterilization. In step B a first pharmaceutical liquid 79 is filled into the interior of the body 219 via the main opening at the proximal end side 229. It is located adjacent to the distal end side 239 of the body 219. In step C a middle plunger 39 as separation element is forced into the interior of the body 219 and forwarded until it is located above the bulge 269. Thereby, a distal chamber 249 containing the first pharmaceutical liquid is formed in the interior of the body 219.

[0063] In step D a second pharmaceutical liquid 89 is filled in the interior of the body 219 via the main opening at the proximal end side 229. The second pharmaceutical liquid 89 lies on top of the middle plunger 39. In step E an end plunger 49 as closing element is placed into the interior of the body 219 via its main opening at the proximal end side 229. Thereby, a closed proximal chamber 259 containing the second pharmaceutical liquid 89 is formed in the interior of the body 219.

[0064] In FIG. 6 a second embodiment of a method of preparing a pre-filled double chamber syringe 18 as a multi chamber syringe (preparation method) is shown. The syringe 18 has a longitudinal glass body 28 with a side wall 218 surrounding an interior. The body 28 has a lower distal end side 238, an upper proximal end side 228 opposite to the distal end side 238 and a distal opening arranged in the distal end side 238 for providing liquids out of the body 28. The distal opening is equipped with a needle connector 58. Between the distal end side 238 and the proximal end side 228 a longitudinal bulge 268 is formed in the side wall 218 of the body 28.

[0065] As shown in FIG. 6, the preparation method comprises seven steps A through G. In step A the syringe 18 is positioned distal or front side up and prepared by sterilization. In step B a middle plunger 38 as separation element is forced bottom-up into the interior of the body 218 and forwarded until it is located below the bulge 268. Thereby, a distal chamber 248 is formed in the interior of the body 218 and above the middle plunger 38. In step C a first pharmaceutical liquid 78 is filled top-down into the interior of the body 218 via the distal opening of the distal end side 238. It is located inside the distal chamber 248 of the body 28. In step D a sealing cap 68 is mounted to the distal end side 238 of the body such that the distal opening is closed.

[0066] In step E the syringe 18 is turned around such that the distal side 238 of the body 28 is down and the proximal end side 228 is up. In step F a second pharmaceutical liquid 88 is filled in the interior of the body 218 via the main opening at the proximal end side 228 of the body 28. The second pharmaceutical liquid 88 lies on top of the middle plunger 38. In step G an end plunger 48 as closing element is placed into the interior of the body 218 via its main opening at the proximal end side 228. Thereby, a closed proximal chamber 258 containing the second pharmaceutical liquid 88 is formed in the interior of the body 218.

[0067] 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.

[0068] 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.

[0069] 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.