Abstract:
Embodiments may include a method of delivering a drug. The method may include removing or releasing a structure from a patch-pump assembly. The patch-pump assembly may include a sealed prefilled drug-reservoir, a fluid passageway, a cannula-containing assembly, and a penetrator. The method may also include penetrating the sealed prefilled drug-reservoir containing the drug to establish fluid communication between the sealed prefilled drug-reservoir and a fluid passageway by removing or releasing the structure. The method may further include flowing the drug from the prefilled drug-reservoir to the fluid passageway. In addition, the method may include flowing the drug from the fluid passageway to a cannula-containing assembly. Furthermore, the method may include delivering the drug subcutaneously to a subject using the cannula-containing assembly.

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. patent application Ser. No. 14/384,152, filed Mar. 14, 2013, entitled “FLUID-CONNECTION MECHANISM FOR PATCH-PUMPS,” which is a 35 U.S.C. §371 U.S. National Stage Entry of PCT International Patent Application No. PCT/IL2013/050240 (WO 2013/140395) filed on Mar. 14, 2013, entitled “FLUID-CONNECTION MECHANISM FOR PATCH-PUMPS,” which claims priority to U.S. Provisional Application No. 61/612,436, filed on Mar. 19, 2012, entitled “FLUID-CONNECTION MECHANISM FOR PREFILLED PATCH-PUMPS,” each of which is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention is in the field of patch-pumps having a primary-container, said primary-container storing the drug to be delivered. In particular, the present invention addresses the creation of a fluid connection between said primary-container and a cannula assembly associated with said patch-pump. In some aspects, the present invention is particularly suitable for prefilled patch-pump application. 
       BACKGROUND OF THE INVENTION 
       [0003]    Infusion pumps are used for treating a number of disease states requiring subcutaneous delivery of a drug. As part of the current trend towards enhanced usability, some infusion pumps are now being produced as “patch-pumps”, meaning that the long tube between a remote pump and the infusion-set on the skin is eliminated. Instead, a device with a similar footprint to the infusion-set alone constitutes the entire pump, including the drug-reservoir and the actuator which drives the drug infusion. However, even though this transition to patch-pumps represents a miniaturization of the product, typically the filling process by which the patient fills the drug reservoir remains the same and is performed at the point-of-use. Other approaches for providing the drug in a patch-pump are (a) inserting a cartridge containing the drug into the patch-pump, and (b) having a pre-filled drug reservoir integrally contained within the patch-pump already during the pump manufacturing process; said drug-reservoir thereby constituting the primary-container for the drug. Whereas the act of inserting a cartridge-type reservoir into the patch-pump can open a liquid channel from the cartridge to the cannula assembly, for a drug-reservoir that is assembled within the patch-pump, an alternative means of creating this fluid connection is required. 
       OBJECTS OF THE INVENTION 
       [0004]    Thus the objective of the present invention is to enable a fluid connection to be created between an integral, optionally pre-filled drug-reservoir within a patch-pump and the cannula insertion assembly associated with said patch-pump. 
         [0005]    It is a further object of the invention to ensure that the pre-filled drug-reservoir remains sealed or that a sterile unit containing such drug reservoir be maintained as such, until directly before the activation of the patch-pump, such that the only materials that come in contact with the drug are the plastic and/or glass from which the reservoir is fabricated and one or more septa. 
         [0006]    It is a still further object of the invention to open said fluid connection while keeping the operation of said patch-pump as simple as possible and requiring a small number of activation-steps. 
       SUMMARY OF THE INVENTION 
       [0007]    The core element therefore of the present invention is a mechanism and method for exploiting one of the activation-steps required to initiate the operation of a patch-pump to create a fluid connection between the pre-filled drug reservoir assembly of said patch-pump and the cannula assembly associated with said patch-pump. 
         [0008]    The cannula assembly of a patch-pump may be associated with the patch-pump in a number of different ways: (a) fully integrated, in which case said cannula assembly is integrated within the housing of the patch-pump, as per the OmniPod product from Insulet Inc. (MA, USA); (b) external, in which case a short tube extends from the patch-pump to a small infusion set directly adjacent to (or sharing an adhesive pad with) the patch-pump; or (c) attached to, and preferably also detachable from, the housing of the patch-pump as per the preferred embodiment detailed below. 
         [0009]    The present invention describes the automatic opening of a liquid channel between a sealed pre-filled drug-reservoir and said cannula assembly as a result of one of the activation-steps undertaken when starting the patch-pump. Such steps typically include placing the patch-pump on the skin of the patient, removing a safety catch, or pressing a button which causes the cannula to be inserted or activates the actuator of said patch-pump. According to the present invention, the performance or one or more of these activation-steps will cause the automatic opening of a fluid channel between the pre-filled reservoir and the cannula assembly without a dedicated step being required for this purpose. Advantageously, this simplifies the use of the patch-pump while simultaneously ensuring that the pump cannot be activated in a state in which it is only later determined that the pre-filled reservoir remains sealed. 
         [0010]    In one embodiment, said opening of the fluid channel is performed automatically either on the step of removing a safety catch or cover, or a step of activating the cannula insertion. 
         [0011]    In some embodiments, this invention provides a selectively activatable patch-pump assembly, said patch-pump assembly comprising:
       a sealed prefilled drug-reservoir containing a drug to be delivered;   an associated conduit in connection therewith;   a selectively activatable penetrator which penetrates said sealed prefilled drug-reservoir and facilitates drug access to said conduit; and   a selectively activatable associated cannula-containing assembly for delivering a drug subcutaneously to a subject, in fluid connection with said conduit;
 
wherein a selective activation-step initiates penetration of said sealed prefilled drug-reservoir, drug access from said drug-reservoir to said conduit, drug access from said conduit to said cannula-containing assembly and delivery from said cannula-containing assembly, thereby being a selectively activatable patch-pump assembly.
       
 
         [0016]    According to this aspect, and as referred to herein the term “selectively activatable” is to be understood to refer to a requirement for an activation step, i.e., a specific action to be taken to produce the outcome. For example, and representing some embodiments, the term “selectively activatable patch-pump assembly” is to be understood to encompass an assembly whose delivery of the drug via known patch-pump mechanisms, is regulated such that an activation step is required or delivery from the patch pump is prevented. 
         [0017]    Similarly, the term “selectively activatable penetrator”, relates to a penetrator mechanism which penetrates a prefilled drug-reservoir and does so in a selective manner, thereby preventing spontaneous rupture of such reservoir. 
         [0018]    Similarly, the term “selectively activatable associated cannula-containing assembly”, relates to an assembly which provides for delivery of a drug subcutaneously to a subject, and does so in a selective manner, thereby preventing spontaneous subcutaneous puncture of the subject. 
         [0019]    It is to be understood that the invention provides a number of devices, which uniquely regulate coordinated activation steps for the selective penetration of a drug reservoir releasing such drug-containing contents into a proximal conduit, which conduit is selectively put into contact with an access port in a cannula-containing assembly, regulating delivery of such drug-containing contents subcutaneously to said subject. 
         [0020]    In some embodiments, the selectively activatable penetrator comprises a hypodermic needle. In other embodiments, the selectively activatable penetrator comprises any appropriate structure capable of penetrating the drug reservoir in a controllable manner. 
         [0021]    The sealed prefilled drug-reservoir containing a drug to be delivered is located proximally, and is associated with a conduit in connection therewith. It will be appreciated that the conduit may be of any suitable material, size and geometry to suit a particular device. 
         [0022]    The conduit, in turn, may contain, or at least partially include therewithin a selectively activatable penetrator which penetrates said sealed prefilled drug-reservoir and facilitates drug access to said conduit. In some embodiments, such conduit may contain a septum, which prevents access of the outside environment to said drug reservoir, thereby maintaining a sterile environment for said drug reservoir. 
         [0023]    In some embodiments, the selectively activatable penetrator is located within the conduit and is located minimally or partially within the septum, providing easier access to such drug reservoir upon activation thereof 
         [0024]    The selectively activatable associated cannula-containing assembly is located in fluid connection with the conduit. 
         [0025]    According to this aspect, and in some embodiments, the cannula-containing assembly provides for the delivery of the drug-containing substance liberated from the drug reservoir. In some embodiments, such cannula-containing assembly comprises a part capable of piercing the skin. In some embodiments, such cannula-containing assembly may resemble a venicath or similar structure, which provides for skin puncture to promote subcutaneous delivery. In some embodiments, such catheter-containing part may be flexible or rigid. 
         [0026]    A selective activation-step initiates penetration of said sealed prefilled drug-reservoir, drug access from said drug-reservoir to said conduit, drug access from said conduit to said cannula-containing assembly and delivery from the cannula-containing assembly. 
         [0027]    In some embodiments, the selectively activatable patch-pump assembly mechanism further comprises a safety catch or cover preventing the inadvertent activation of the patch-pump. 
         [0028]    According to this aspect, and in some embodiments, such safety catch may comprise a pin, or slot, or other structure, which locks or otherwise prevents the penetrating member from penetrating the drug reservoir, and or prevents the cannula-containing assembly from advancing within said patch pump assembly and initiating subcutaneous delivery. 
         [0029]    In some embodiments, removal or release of a safety catch or a cover, or a combination thereof, comprises the activation-step which initiates penetration of the sealed prefilled drug-reservoir and facilitates drug access to the conduit. 
         [0030]    In some embodiments, the selectively activatable patch-pump assembly further comprises a first spring-based mechanism, which propels the selectively activatable penetrator through the conduit and in some embodiments, through the septum, toward the sealed prefilled drug-reservoir, thereby facilitating penetration of the drug-reservoir. 
         [0031]    In some embodiments, the selectively activatable patch-pump assembly further comprises a second spring-based mechanism, which propels the cannula-containing assembly toward proximally located skin following drug access to the conduit. 
         [0032]    In some embodiments, the cannula-containing assembly comprises an access port, which access port is alignable with the conduit in a selective manner. In some embodiments, only activation, for example by depressing a button on a top or side of such device, results in controlled propelling of the cannula-containing assembly toward the skin of a wearer thereof, whereby an access port in such cannula-containing assembly is only aligned with the conduit when propelled sufficiently toward the skin of the subject. 
         [0033]    In some embodiments, the selectively activatable patch-pump assembly further comprises an actuator which compresses said prefilled drug-reservoir following penetration of said sealed prefilled drug-reservoir. 
         [0034]    Such actuator and arrangement may comprise any known means, and in some embodiments, specifically contemplates a drug delivery actuator such as that described in United States Patent Application Publication Number US 2009-0093772, fully incorporated by reference herein and United States Patent Application Publication Number US 2010-0022992, fully incorporated by reference herein. 
         [0035]    In some embodiments, the selectively activatable patch-pump assembly is a single unit. 
         [0036]    In some embodiments, the selectively activatable patch-pump assembly is comprised of operationally connectable units comprised of a drug reservoir-containing unit and a cannula-containing assembly. 
         [0037]    From a user-convenience perspective, the less number of activation-steps used the better. However, in order to minimize the chance of inadvertent activation, it is wise to also have a safety catch or cover. Thus, in the present invention, it is immaterial whether the activation-step which opens up the fluid channel between the prefilled-reservoir and the cannula assembly is the safety catch step or the cannula-insertion one. 
         [0038]    In a further embodiment, the cannula insertion also activates the actuator of the patch-pump, such that the number of activation-steps is reduced to the lowest practical minimum, thereby enhancing simplicity while improving patient compliance. 
         [0039]    In another embodiment of the approach in which removing the safety catch (or safety cover) opens said fluid channel, removal of said catch releases a spring-loaded hollow penetrating-member to penetrate through a septum of said drug-reservoir, said penetrating-member then serving as a fluid conduit towards the cannula assembly. In this way, the drug-reservoir remains sealed until just before use. 
         [0040]    In another embodiment, the conduit leads to a passageway which interfaces with the cannula assembly, such that when the cannula is inserted into the skin said passageway is then placed in fluid connection with said cannula. 
         [0041]    According to this aspect, the fluid connection from the prefilled drug-reservoir to the cannula is completed. Note that said cannula assembly may employ either a soft-cannula or a rigid-cannula. 
         [0042]    Some embodied contemplated devices are explained more fully below, in connection with the figures, but the same shall not be construed as limiting the invention. 
         [0043]    All publications, patents, and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of a conflict between the specification and an incorporated reference, the specification shall control. Where number ranges are given in this document, endpoints are included within the range. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges, optionally including or excluding either or both endpoints, in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. Where a percentage is recited in reference to a value that intrinsically has units that are whole numbers, any resulting fraction may be rounded to the nearest whole number. 
     
    
     
       FIGURES 
         [0044]      FIGS. 1 a  and 1 b    provide exploded and assembled isometric views of an embodied patch-pump incorporating the present invention, respectively; 
           [0045]      FIG. 2  provides an isometric cut-away view of the assembled patch-pump showing the prefilled-reservoir and the cannula assembly; 
           [0046]      FIGS. 3 a  and 3 b    show cross-sectional views of the patch-pump before and after removal of the safety cover; 
           [0047]      FIGS. 4 a  and 4 b    provide planar cut-away views showing the stages of the opening of the fluid channel as said safety cover is removed. 
           [0048]      FIGS. 5 a  and 5 b    show an embodied orientation and construction/arrangement of a fluid conduit system connecting the drug reservoir-containing element and cannula containing element. 
           [0049]      FIGS. 6 a , 6 b , 6 c , 6 d , 6 e  and 6 f    provide cut-away isometric views of an embodied patch-pump showing the stages of engagement of the elements for penetration of the drug-containing reservoir, activation of the cannula-containing assembly, and potential regulation of the same. 
           [0050]      FIGS. 7 a , 7 b , 7 c  and 7 d    depict an embodied patch pump of this invention in various cutaway views, to highlight certain elements of the device, and provide for ease of view of the same. 
           [0051]      FIG. 8  provides an embodied assembly comprised of operationally connectable units comprised of a drug reservoir-containing unit and a cannula-containing assembly, as opposed to the single unit, depicted in  FIGS. 1-6 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0052]    One embodiment of a patch-pump containing a mechanism of the present invention is shown in exploded form in  FIG. 1 a   , in which a cannula assembly  10 , associated with the patch-pump  12 , is attached to the housing of the patch-pump as per option c) above. Additionally, in this patch-pump, a safety cover  14  is employed to cover said cannula assembly  10 , preventing the inadvertent insertion of the cannula before it is required. 
         [0053]      FIG. 1 b    then shows said patch-pump in its assembled form, it being understood that said safety cover  14  is grasped and removed by the patient immediately prior to activation of the pump. 
         [0054]    As will be detailed in connection with the following figures, in this preferred embodiment, removal of this cover  14  initiates the creation of a fluid connection from the drug-reservoir to the cannula. 
         [0055]    Referring now to  FIG. 2 , this cut-away view shows certain component parts of the patch-pump mechanism and how they interact in order to enable the mechanism of the present invention to function in this described embodiment. 
         [0056]    According to this aspect, and in one embodiment, a drug is contained within a sealed prefilled drug-reservoir  20 , which is formed in the volume between a rigid reservoir wall  22  and a flexible reservoir wall  24 . The pump may further comprise an actuator  26 , which expands and by doing so moves the flexible wall  24  towards the rigid wall  22 ; thereby compressing the drug-reservoir  20  in order to expel the drug. The drug reservoir  20  further comprises a septum  28  at the end of a conduit  29  leading from the drug reservoir  20 , said septum  28  sealing said reservoir while allowing penetration thereof using a hollow penetrating member. 
         [0057]    Referring now to  FIG. 3 a   , this figure shows how, in this preferred embodiment, the safety cover  14  comprises an internal pin  30  which serves to restrain a first spring  32  in its compressed state.  FIG. 3 b    then shows how the removal of said safety cover  14  enables said spring  32  to expand until it hits a stop  34 . 
         [0058]    Referring now to  FIG. 4 a   , a planar view showing the spring  32  in its compressed state is shown, and then  FIG. 4 b    shows how the release of said spring  32  causes a penetrating-member  40  to pierce said septum  28 , emerging in said conduit  29 , thereby effecting a fluid connection between the interior of the drug-reservoir  20  and the fluid-passageway  42  leading to the cannula  44 . The prefilled drug-reservoir  20  is stationary relative to a central longitudinal axis defined by the assembly containing cannula  44  during penetration of the sealed prefilled drug reservoir  20  by the selectively activatable penetrator (penetrating member  40 ). 
         [0059]      FIG. 5A  shows an enlarged side perspective view of the device. The septum  28  and its piercing by the penetrating member  40  are seen in this view.  FIG. 5B  shows an exploded view of an embodiment of a fluid connection between the interior of the drug reservoir as it enters the fluid passageway  42  and its conveyance to the cannula  44 . 
         [0060]    Referring now to  FIGS. 6 a    through  6   f,  the details of how the drug from the fluid-passageway  42  flows through to the interior of the cannula  44  as the cannula is inserted into the body, are shown. In this embodiment, the type of cannula used permits an insertion-needle, which in turn, leads the cannula into its place and can be withdrawn. The steps of this process serve to create the above mentioned fluid connection, as follows. 
         [0061]      FIG. 6 a -6 b    shows the overall arrangement of the cannula insertion mechanism and its fluid connection to the drug reservoir, including an enlargement of the fluid connection, as shown in the inserts in  FIG. 6 a    and  FIG. 6 b   . In this aspect, the piercing of the septum  28  by the first penetrating member  40 , permits fluid exit from the drug reservoir  20  into the fluid passageway  42 . 
         [0062]      FIG. 6 c    shows the initial state of the cannula insertion mechanism in which both the insertion-needle  50  and cannula  44  are within the patch-pump. In this initial state, the flow from the passageway  42  (shown in  FIG. 6 b   ) is blocked by a plastic sleeve  52 , ensuring that none of the drug is lost until the cannula  44  has been inserted under the skin. Referring now to  FIG. 6 d   , the state in which the needle-insertion spring  56  has pressed the cannula-connector  54  down to the point where it comes in contact with the sleeve  52 . Note that at this point the tips of the needle  50  and cannula  44  start to emerge from the base of the patch-pump. Referring now to  FIG. 6 e   , the state in which the needle-insertion spring  56  has come to the end of its travel is shown. In this state, cannula-connector  54  has now moved down the sleeve  52  and taken its place. Also visible in this view is the hole  58  in the cannula-connector  54  which is now situated opposite the passageway  42 . The final stage in the cannula insertion is now shown in  FIG. 5 d   , in which the cannula-connector  54  has had the needle removed, leaving just the cannula  44  in place. In this state, the hole  58  in the cannula-connector  54  is aligned with the passageway  42  and thus enables flow of the drug from said passageway  42  through to the end of the cannula  44 ; thereby completing the liquid connection from the pre-filled drug-reservoir all the way to the subcutaneous layer. 
         [0063]      FIG. 7  depicts an embodied patch pump of this invention in various cutaway views, to highlight certain elements of the device, and provide for ease of view of the same.  FIG. 7 a    provides a side, cut-away view of the device, showing various elements of the drug insertion mechanism and drug reservoir element and connection between the same, prior to activation of the device.  FIG. 7 c    shows and side and partial top cut away view of the device in  FIG. 7 a   , emphasizing placement of the cannula  44  traversing the device in order to promote penetration of the skin proximally located beneath the device. The relative positioning of the drug reservoir  20 , septum  28  and first spring  32  are shown, as well. The conduit  42  in fluid connection with both the drug reservoir and cannula containing assembly is seen, as well.  FIGS. 7 b  and 7 d    provide line and filled in drawings of the connection between the drug reservoir and cannula containing assembly. 
         [0064]      FIG. 8  shows another embodied device of the invention. According to this aspect, the drug reservoir and associated elements  60  are attachable to the drug insertion mechanism  62 , in a manner facilitating fluid communication, as in the embodied device in  FIGS. 2-6 . In this aspect, multiple drug-containing reservoir elements  60  can be attached to the drug insertion means  62 . 
         [0065]    It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as set forth in the appended claims. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed in the scope of the claims. 
         [0066]    In the claims articles such as “a,” “an” and “the” mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” or “and/or” between members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention also includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. Furthermore, it is to be understood that the invention provides, in various embodiments, all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the listed claims is introduced into another claim dependent on the same base claim unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise. Where elements are presented as lists, e.g. in Markush group format or the like, it is to be understood that each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements, features, etc., certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements, features, etc. For purposes of simplicity those embodiments have not in every case been specifically set forth in haec verba herein. Certain claims are presented in dependent form for the sake of convenience, but Applicant reserves the right to rewrite any dependent claim in independent format to include the elements or limitations of the independent claim and any other claim(s) on which such claim depends, and such rewritten claim is to be considered equivalent in all respects to the dependent claim in whatever form it is in (either amended or unamended) prior to being rewritten in independent format.