Abstract:
An apparatus for connecting a compatibility liner with a source of perishable therapeutic is provided. In one exemplary system for connecting a reservoir of perishable therapeutic with a lumen, a hollow hub having a first end and a second end is provided. The first end of the hollow hub, which contains a bond port, is in fluid communication with the second end. The second end of the hollow hub may contain a docking groove that is sized to couple a reservoir to it. The system also includes an inner hypo-tube having a proximal tip and an inner lumen. This inner lumen is lined with a therapeutic compatible lining and is in fluid communication with the second end of the hub through the proximal tip of the inner hypo-tube. The inner lining and the proximal tip in this system are configured to shield therapeutic ejected from the reservoir from contacting materials that can diminish the integrity of the therapeutic.

Description:
FIELD OF THE INVENTION 
     The present invention relates to the transport of perishable therapeutics from a storage reservoir to a target site. More specifically the present invention relates to method and apparatus for effectively connecting a reservoir of perishable therapeutic to a lumen that is lined with a material compatible with the perishable therapeutic. 
     BACKGROUND OF THE INVENTION 
     The delivery of therapeutics to a target site in the body of a patient is a task that finds innumerable applications in the practice of modern medicine. In some application the therapeutic may be delivered through a needle and while in others the therapeutic may be delivered though a pump and catheter system. In either of these configuration, as with the many other plausible configurations, the objective is to deliver active therapeutic to a target site such that the therapeutic may cure the infirmities resident at the target site. For some perishable, sensitive or volatile therapeutic, such as certain viruses employed today, a compatibility issue can arise between the therapeutic and the channel or vessel that will transport the therapeutic from its storage vessel to its target site. When compatibility issues do arise between the therapeutic and its surroundings, the therapeutic may lose some or all of its effectiveness and may, upon its arrival at the target site, be partially or completely inert. In certain applications, the therapeutic may lose its effectiveness moments before it is delivered as it passes down and through the delivery lumen of the delivery device simply because the therapeutic has come in contact with a non-compatible material. 
     Therefore, the environment in which the therapeutic is stored as well as the environment in which the therapeutic must travel can and does affect the potency and effectiveness of certain perishable therapeutics. In order to avoid the risk of deterioration of the potency of perishable therapeutics it is, consequently, advantageous to minimize or eliminate the contact between non-compatible materials and the therapeutic during the delivery of the therapeutic to the target site. 
     SUMMARY OF THE INVENTION 
     The present invention includes the proper handling of perishable therapeutic. In one embodiment a system for connecting a reservoir of perishable therapeutic with a lumen is provided. This embodiment has a hollow hub having a first end and a second end. The first end of the hollow hub, which contains a bond port, is in fluid communication with the second end of the hollow hub. The second end of the hollow hub in this embodiment may contain a docking groove that is sized to couple a reservoir to it. This embodiment also includes an inner hypo-tube having a proximal tip and an inner lumen. The inner lumen may be lined with a perishable therapeutic compatible lining and may be in fluid communication with the second end of the hub through the proximal tip of the inner hypo-tube. The inner lining and the proximal tip may be configured to shield perishable therapeutic, ejected from the reservoir and present within the second end, from materials that are non-compatible with the therapeutic. 
     In a second embodiment a method for coupling a reservoir of perishable therapeutic to a lumen lined with a therapeutic compatible lining is provided. This method includes inserting the proximal end of a manifold hypo-tube into a first end of a hub, the hub also having a second end; placing the proximal end of an inner hypo-tube within the proximal end of the manifold hypo-tube and urging the proximal end of the inner hypo-tube through the proximal end of the manifold hypo-tube until the proximal end of the inner hypo-tube comes in contact with a stopping point in the hub. In this second embodiment the tip of the proximal end of the inner hypo-tube may be covered in a therapeutic compatible material and the inner surface of the inner hypo-tube may be covered with a therapeutic compatible lining. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a side sectional view of the proximal end of a concentric hypo-tube assembly employed in an embodiment of the present invention. 
     FIG. 2 is a cross-sectional view taken along line  2 — 2  of FIG.  1 . 
     FIG. 3 is a cross-sectional view taken along line  3 — 3  of FIG.  1 . 
     FIG. 4 is a side sectional view of the proximal end of a concentric hypo-tube assembly in accordance with an alternative embodiment of the present invention. 
     FIG. 5 is a side sectional view of the proximal end of a concentric hypo-tube assembly in accordance with another alternative embodiment of the present invention. 
     FIG. 6 is an enlarged sectional view of the proximal end of the concentric hypo-tube assembly as employed in the embodiment illustrated in FIG.  5 . 
    
    
     DETAILED DESCRIPTION 
     As described and used herein a “perishable therapeutic” includes a therapeutic whose efficiency can be diminished through the contact with specific non-compatible compounds or materials. These perishable therapeutics include adenoviral vectors; adeno-associated vectors; certain proteins including basic fibroblast growth factors; certain nucleic acids such as DNA plasmid; and, certain cells such as myoblasts, fibroblasts, and stem cells. Thus, regarding these examples, when these perishable therapeutics come in contact with stainless steel, for example, they lose some or all of their effectiveness as a therapeutic. This list of perishable therapeutics is not exhaustive but, instead, is meant to be exemplary of therapeutics that may lose some or all of their healing effectiveness once placed in proximity to a specific non-compatible material. 
     As described and used herein a “perishable therapeutic compatible lining” includes a lining that does not substantially retard the effectiveness of an otherwise perishable therapeutic. It may include a specific coating applied to a material as well as a separate material that is later adhered or placed adjacent to the underlying material that it lines. One primary purpose of this lining is to retard the degradation of therapeutic that comes in contact with it. While the lining may modify the effectiveness of the therapeutic it does so at a lesser rate than that of the material that it covers and would otherwise come in contact with the therapeutic. 
     As described and used herein “non-compatible” is an adjective used to describe materials that more than insubstantially affect the potency or effectiveness of a therapeutic. When quantified this may include materials that reduce a therapeutic&#39;s efficiency by approximately 10% through and including an entire 100% reduction in its effectiveness, thereby making the use of the therapeutic, after coming in contact with the non-compatible material, an inconsequential event. 
     FIG. 1 is a side sectional view of a concentric hypo-tube assembly  150  and hub  10  in accordance with one embodiment of the present invention. In FIG. 1 the hub  10  and the proximal end of the concentric hypo-tube assembly  150  are clearly evident. As can be seen the hub  10  may be shaped in the form of an hour-glass with a longer end  130  connected to a female luer connection  110  through a channel  145  having a stopping point  120 . The hub  10  in FIG. 1 contains a hub wall  11  which may be manufactured from a single material such as a polypropylene, a polycarbonate or any other material that is rigid and compatible with the perishable therapeutics that may be delivered by the hypo-tube assembly  150 . Alternatively, should this material not be compatible with the therapeutic it may be lined with a material that is. 
     As can be seen, the female luer connection  110  contains threads or grooves  12 , which are illustrated in FIG. 1 as angled dashed lines encircling the interior surface of the female luer connection  110 . These grooves  12  and the female luer connection  110  may be dimensioned so as to accept and secure a removable reservoir (which is not shown) containing perishable therapeutic. This perishable therapeutic may be injected down through the concentric hypo-tube assembly  150  to a target site within the body by depressing a syringe (not shown) integrated with the removable reservoir. As can be seen, a threaded reservoir containing the therapeutic may be readily attached to the female luer connection  110  by aligning and screwing the reservoir into the connection  110 . 
     As is evident the proximal end of a manifold hypo-tube  17  and the proximal end of an inner hypo-tube  18  are located within the longer end  130  of the hub  10 . The manifold hypo-tube  17  and the inner hypo-tube  18  may be designed for numerous medical applications. They may be designed to be part of an injection catheter used to inject perishable therapeutic into the heart or other dense tissue area of a patient. They may also be designed to be implanted in the body and used for long-term delivery of a therapeutic. When used for puncturing applications the hypo-tubes may be made from stainless steel or other suitably rigid materials. Conversely, when used in less stress-intensive applications the hypo-tubes may be made from less rigid materials such as plastic. 
     In this particular embodiment the manifold hypo-tube  17  is made from stainless steel and is attached to a spring mechanism of an injection catheter (not shown) which is used to inject a needle into the heart or cardiopulmonary sac of a patient. Once the needle is injected into the heart or cardiopulmonary sac the inner hypo-tube  18 , also stainless steel, would be used to carry therapeutic to the targeted site of the body. 
     In this embodiment the inner hypo-tube  18  contains a liner  104 , which may be made from polyether block-amide (one example of which is Pebax™ 5533) or any other material that is compatible with a perishable therapeutic that may contact the liner  104 . The proximal end of the inner hypo-tube  18  in this embodiment has a collar  19  adjacent to it. This collar  19  may be made from the same material as the liner or it may be made from another material as long as the second material is also compatible with the perishable therapeutic that may come in contact with it. The collar  19 , made from a therapeutically compatible material, may be sized to compressibly secure or press-fit itself to the stopping point  120  located within the channel  145  of the hub  10 . In this embodiment the liner  104  extends out of the inner hypo-tube and through the collar  19  to line the interior lumen of the collar. Therefore, when the inner hypo-tube is being manufactured the liner  104  may be protruding from the proximal end of the hypo-tube and may be covered by or threaded through the collar such that the liner  104  lines the interior lumen of the collar. 
     In this embodiment the inside diameter of the lumen in the inner hypo-tube  18  may be about 0.0130 inches and the outside diameter of the inner hypo-tube  18  may be about 0.0250 inches. The inside diameter of the liner  104  may be 0.0075 inches. Other sizes and dimensions are also possible. 
     The stopping point  120  of the hub  10  in this embodiment is sized such that it may snugly secure the collar  19  to the hub  10  after the collar  19  has been pushed or urged toward the stopping point  120 . In other words, the use of friction and the proper sizing of the dimensions between the stopping point  120  and the collar  19  create a mechanical adhesion or press-fit that couples the collar  19  to the hub  10  at the stopping point  120  and prevents over-wicking of adhesive  102 . 
     The hub wall  11  also contains a plurality of bond ports. In this figure a first bond port  14  is shown in the channel  145  of the hub  10  while a second bond port  15  is shown on the longer end  130  of the hub  10 . These bond ports may have a funnel-like configuration and may provide an access via from outside the hub to inside the hub to allow adhesive or other material to be injected from outside the hub  10  at different points along the hub  10 . 
     In FIG. 1 an adhesive  102  is shown after being injected into the hub  10  through the first bond port  14  and the second bond port  15  to secure the inner hypo-tube  18  and the manifold hypo-tube  17  to each other and to the hub  10 . As is evident the adhesive  102  surrounds the proximal end of the inner hypo-tube  18  as well as the proximal end of the manifold hypo-tube  17  but has not wicked past the stopping point  120  between the collar  19  and the hub  10 . In practice it is preferred that the amount of adhesive injected into the hub is controlled such that no adhesive wicks past the stopping point  120  and, consequently, risks coming in contact with therapeutic that may be injected down the lumen of the inner hypo-tube. The adhesive employed in this embodiment may be H.B. Fuller adhesive no. 3507 and Tra-con FDA2. 
     Other features of the hub  10  illustrated in FIG. 1 are the reinforcing nub  16  and the wing  13 . These two components extend from the tubular hourglass-designed hub  10  and allow the hub  10  to be grasped and rotated as required. For example, when a threaded reservoir of therapeutic needs to be screwed or coupled into the female luer connection  110  of the hub  10 , the wings  13  can be grasped by an operator and used to rotate the hub  10  to couple the hub  10  to the therapeutic reservoir (not shown). 
     In manufacturing the device illustrated in FIG. 1, a manufacturer may first gather the components to be assembled. These components would include the inner hypo-tube  18 , the manifold hypo-tube  17 , and the hub  10 . As a first step the manufacturer may insert the proximal or near end of the manifold hypo-tube  17  into the longer end  130  of the hub  10 . The proximal end of the manifold hypo-tube  17  may be completely inserted into the longer end  130  of the hub  10  until it touches an interior hub  10  wall or, alternatively, until it is located near an interior hub  10  wall. Whether or not the proximal end of the manifold hypo-tube touches an interior wall may be determined by the placement of the bond ports because adhesive injected through the bond ports may be obstructed from reaching the interior surfaces of the manifold hypo-tube if the placement of the manifold hypo-tube  17 , within the hub  10 , obstructs the bond ports. While the distance that the proximal end of the manifold hypo-tube  17  may be inserted into the hub  10  can vary, it is preferred that the proximal end of the manifold hypo-tube  17  does not touch an interior hub wall  11  so that adhesive injected into the second bond port  15  may flow both inside and outside of the manifold hypo-tube  17 . Should the manifold hypo-tube  17  come in contact with the hub wall, adhesive injected through the second bond port  15  may be deterred from traveling completely in and around the proximal end of the manifold hypo-tube  17 . Once the proximal end of the manifold hypo-tube  17  is inserted into the hub  10 , the proximal or near end of the inner hypo-tube  18 , may be placed within the manifold hypo-tube  17  and into the hub  10 . 
     As can be seen in FIG. 1 the proximal end of the inner hypo-tube has a collar  19  adjacent to its tip. This collar may be manufactured from the same material as the liner or any other material compatible with the perishable therapeutic that may be delivered by the device. The collar may be manufactured by extending the lining material, which lines the inner lumen of the inner hypo-tube  18 , 0.500 inches past the tip of the inner hypo-tube  18  and, then, by building or wrapping the collar material around the protruding lining material such that, upon completion, the collar is connected to the lumen material and contains an inner lumen of lining material seamlessly connected to the inner hypo-tube. Care should be taken when manufacturing the collar to avoid collapsing the lumen within the liner. Once the collar is manufactured, it should preferably be allowed to cure for 12 hours before it is trimmed. Care should also be taken here, as with the other portions of the assembly process, not to kink, force or otherwise twist the various components. In addition, an assembler should continually verify that no adhesive has entered or has otherwise come in contact with the lumen  101  of the liner  104 . 
     The inner hypo-tube  18  along with collar  19  may then be completely inserted into the hub  10  until the collar  19  comes in contact with the stopping point  120  located within the channel  145  of the hub  10 . Once the collar  19  reaches the stopping point  120 , an additional axial force may be placed on the inner hypo-tube  18  to further urge or press-fit the collar  19  into the stopping point  120 . The collar  19 , which may be made from Pebax™ 5533, may be soft and compressible so that it readily deforms under the additional axial load and securely contacts the stopping point  120  to provide a holding force to retain the collar  19  against the stopping point  120 . 
     After the hypo-tubes have been inserted and properly positioned within the longer end  130  of the hub  10  adhesive may be injected into the bond ports. Adhesive may first be injected into the first bond port  14  such that it surrounds the proximal end of the inner hypo-tube  18  and the collar  19  and the adhesive may then be injected into the second bond port to surround the proximal end of the manifold hypo-tube  17 . The adhesive injected in the first bond port may cement and lock the inner hypo-tube  18  to the hub  10  and the collar  19  to the tip of the inner hypo-tube  18 . It may also provide a bulwark for preventing the unwanted seepage of therapeutic past the collar  19  and down into the larger end  130  of the hub  10 . The adhesive may be manufactured by mixing the components by hand for a minimum of 2 minutes to ensure that there is a consistent color in the adhesive. It may then be delivered by placing it in a syringe for injection through the bond ports into the hub. 
     After adhesive is injected into the first bond port  14  it may be injected into the second bond port  15  to further secure the hypo-tubes to themselves and to the surrounding hub. Excessive adhesive should be removed from the surface of the hub. After the adhesive is allowed to cure, for preferably 12 hours, a 30× microscope may be used to verify a 1mm bond length between the inner hypo-tube  18  and the hub  10  and between the outer hypo-tube  17  and the hub  10 . 
     FIG. 2 is a cross-sectional view taken along line  2 — 2  of FIG. 1 that illustrates the liner  104 , the hub wall  11 , the liner lumen  101 , the manifold hypo-tube  17 , and the inner hypo-tube  18 . As can be seen, FIG. 2 illustrates that the longer end  130  of the hub  10  as well as the various lumens and hypo-tubes each have a circular cross-section and that they may be concentrically located about one another. While concentric circular cross-sections are shown in this embodiment other configurations and cross-sections may also be employed. For example, these cross-sections may also be hexagonal, square, and any other cross-section required by the specific application. Moreover, they may not be equally spaced about the same axis but may, instead, be located at different distances from a reference longitudinal axis. 
     In FIG. 2 the liner  104  is shown as not being in contact with the inner hypo-tube  18 , it is preferred, however, that the liner  104  should be in contact with the inner hypo-tube  18  so that the liner  104  may receive structural support from the inside surface of the inner hypo-tube  18  and so that the lumen may have the largest cross-sectional area possible. 
     FIG. 3 is a sectional view of a cross-section taken along line  3 — 3  of FIG.  1 . As can be seen, the wings  13  protrude outwardly from the hub wall  11  and are aligned 180 degrees from one another. As can also be seen, the collar  19  is in direct contact with the inner surface of the hub wall  11  as well as with the liner  104 . It is through this direct contact with the inner surface of the hub that adhesive injected into the hub at bond ports  14  and  15  is prevented from wicking past and into the female luer connection  110  side of the hub  10 . Liner lumen  101  is also evident in FIG.  3 . 
     FIG. 4 illustrates a sectional view of an alternative embodiment of the present invention. In FIG. 4 a hub  40  and hypo-tube assembly  420  are shown. The hub  40  has a female luer connection  400  having grooves  42  as well as reinforcing nubs  46 , wings  43 , a first bond port  44 , a second bond port  45 , a hub wall  41 , and a stopping point  410 . The hypo-tube assembly  420  includes a manifold hypo-tube  47 , an inner hypo-tube  48 , a liner  404 , a liner lumen  401 , and a collar  49  adjacent to the inner hypo-tube  48 . The collar  49  has a heat shrink material  405  placed at its end. This heat shrink material  405  may be made from Teflon™ while the collar may be made from a material that is compatible with a perishable therapeutic, and the hypo-tubes may be made from stainless steel. The hub wall  41  may be homogeneously manufactured from a plastic or other sufficiently rigid material. 
     As is evident, the proximal end of the inner hypo-tube  48  in this embodiment has been inserted into the hub  40 . However, rather than having a silo-shaped collar, as described in the first embodiment, the collar  49  in this embodiment has been covered or otherwise treated with a Teflon™ heat shrink which acts to constrict the outer diameter of the collar and provide a flush and snug fit between the collar  49  and the stopping point  410  of the hub  40 . 
     In order to secure the collar  49  to the hub  40 , heat should first be applied to the tip of the collar  49 , which contains the Teflon™ heat shrink. The tip of the collar  49  containing the heat shrink will then shrink or constrict under the forces of the heat shrink to a size that closely matches the dimensions of the stopping point  410  of the hub  40 . A close dimensional alignment between the tip of the collar  49  and the stopping point  410  will provide a good sealing engagement between the collar and the hub. A benefit of a good sealing engagement is that therapeutic threaded into the female luer connection  400  and injected into the liner lumen  401  will be prevented from passing the interface point between the collar  49  and the stopping point  410  and contacting materials that are not compatible with the therapeutic. To further secure the inner hypo-tube  48  to the stopping point  410 , and the other hypo-tube assembly  420  components to the interior of the hub  40 , an adhesive should be injected into the first bond port  44  and the second bond port  45  in this embodiment. 
     FIG. 5 illustrates a side sectional view of another alternative embodiment of the present invention. Rather than using the collars  19  and  49  described above, the embodiment illustrated in FIG. 5 uses a flared funnel-shaped liner end  506  to facilitate the clean contact and communication between therapeutic placed in the female luer connection  500  and the lumen  501  located within the inner hypo-tube  58 . 
     In FIG. 5 a hub  50  and hypo-tube assembly  530  are illustrated. This hub  50  along with the hypo-tube assembly  530  are shown in sectional view consistent with the illustrations provided in FIGS. 1 and 4 above. This hub  50  contains a hub wall  51 , the hub wall  51  having a first bond port  54 , a second bond port  55 , and a third bond port  59  wherein each bond port is conically shaped and provides a passage from the exterior of the hub  50  to the interior of the hub  50 . These bond ports provide access for adhesive to be injected into the hub during the assembly of the device. 
     Similar to the embodiments described above, the hub wall  51  contains reinforcing nubs  56  and wings  53 . These reinforcing nubs  56  and the wings  53  are used to help grasp and secure components to the female luer connection  500  of the hub  50 . This female luer connection  500  located at one end of the hub  50  is used to connect other components to the hub  50 . This female luer connection  500  contains grooves  52  resident within the inside walls of the female luer connection  500 . 
     Also evident in FIG. 5 are a liner  504 , a liner lumen  501 , an inner hypo-tube  58 , and a manifold hypo-tube  57 . In this embodiment, rather than having the collar touch the stopping point of the hub  50  as in the above embodiments, the proximal end of the inner hypo-tube  58  comes in contact with the stopping point  508  of the hub  50  and the liner  501  extends past the end of the inner hypo-tube  58  into the female luer connection  500  of the hub  50 . The liner  504  extending into the female luer connection  500  in this embodiment has a liner flared end  506  located at its most proximal end and a liner rim  507 . The liner flared end  506  and liner rim  507  extend into the female luer connection  500  and rest up against the hub wall  51 . In order to secure this distended liner section to a hub wall  11  adhesive.  502  may be injected behind the liner  504  through the third bond port  59  to secure the liner in place. However, when adhesive is injected into the connection it is preferred that the amount of adhesive is limited such that the adhesive does not wick past the liner rim  507  of the liner  504  and be placed at risk of contacting therapeutic that may be injected into the lumen  501 . 
     In use, when a source of therapeutic is secured or threaded into the female luer connection  500 , as the therapeutic is forced down into the lined lumen, the liner flared end  506  and the liner rim  507  may be pressed against the hub wall  51 , thereby contributing to a secure and tight contact point between the liner and the hub wall. 
     FIG. 6 is an enlarged view of the stopping point  508  of the hub  50  from FIG.  5 . As is clearly evident in this embodiment adhesive  502  has been injected and is securing the inner hypo-tube rim  508 , the liner  504  and the liner flared end  506 . As can also be seen, the adhesive  502 , while resident in, around, and between the inner hypo-tube, the hub, and the liner  504 , does not extend past the liner rim  507 . As mentioned above, it is preferable that the adhesive  502  does not extend past the liner rim  507  such that the potential contact between therapeutic and non-compatible materials such as the adhesive  502  may be minimized if not eliminated. 
     Target sites that may be treated by the various embodiments of the present invention include any mammalian tissue or organ, whether injected in vivo or ex vivo. Non-limiting examples include heart, lung, brain, liver, skeletal muscle, smooth muscle, kidney, bladder, intestines, stomach, pancreas, ovary, prostate, eye, tumors, cartilage and bone. 
     Therapeutics that may be employed in the various embodiments of the present invention include: adenoviral vectors; adeno-associated vectors; certain proteins including basic fibroblast growth factors; certain nucleic acids such as DNA plasmid; and, certain cells such as myoblasts, fibroblasts, and stem cells. 
     As will be understood by one of skill in the art, while various embodiments of the present invention have been presented, numerous other embodiments are also plausible. For example, rather than having the flared end of the liner protruding into the female luer connection of the hub the liner may instead wrap around and cover the inner hypo-tube rim which is then press-fit into the stopping point of the hub to form a fluid tight connection. Consequently, the disclosed embodiments are illustrative of the various ways in which the present invention may be practiced and other embodiments may be implemented by those skilled in the art without departing from the spirit and scope of the present invention.