Patent Publication Number: US-2016235562-A1

Title: Flexible stent with torque-absorbing connectors

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application is a divisional application of U.S. patent application Ser. No. 13/411,135 filed Mar. 2, 2012, which is a continuation application of U.S. patent application Ser. No. 11/973,707, filed on Oct. 9, 2007, now U.S. Pat. No. 8,128,679, which is a Continuation-in-Part application of U.S. patent application Ser. No. 11/805,584 filed on May 23, 2007, now U.S. Pat. No. 8,016,874, the entireties of which are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. The Field of the Invention 
     The present invention relates to a medical device. More particularly, the present invention relates to a flexible stent that provides elevated torque-absorbing properties. 
     2. The Relevant Technology 
     Atherosclerosis, sometimes called the hardening or clogging of the arteries, is an accumulation of cholesterol and fatty deposits, called plaque, on the inner walls of the arteries. Atherosclerosis causes a partial or total blockage of the arteries and, consequently, a reduced blood flow to the heart, legs, kidneys, or brain. 
     Traditionally, clogged arteries have been treated with surgical procedures that involve the removal of the diseased arterial tract. Angioplasty procedures, during which a stent is inserted in the diseased portion of the artery, have gained increased acceptance during the last two decades because of the reduced complexity of this procedure in comparison with other surgical procedures and because of the consequent reduction in risk and discomfort to the patient. 
     Referring first to  FIG. 1 , a stent  20  is a small tubular element that typically has a cylindrical structure  22  and that, once placed within a blocked vessel, acts as a scaffold that keeps the vessel open. Stent  20  may be implanted in a bodily vessel by disposing the stent over a balloon tipped catheter, by driving the stent to a target location in a vessel, and by subsequently inflating the balloon at the target location. 
     Alternatively, stent  20  may be caused to self-expand without the use of a balloon by manufacturing stent  20  from a shape memory material and by disposing stent  20  over a catheter in a contracted delivery configuration. Stent  20  is successively driven to a target location in a vessel, where a sheath covering stent  20  is withdrawn and stent  20  is allowed to self-expand. One type of self-expanding stent is produced from a superelastic material and is compressed inside the sheath into a contracted delivery configuration. When the stent is released from the sheath, the flexible material causes the stent to spring back to its original shape and size before compression. Another type of self-expanding stent is produced from a thermo-elastic shape-memory material that is formed into a desired size and shape and is then annealed at a temperature higher than a transition temperature. After cooling the stent to a temperature below the transition temperature, the stent becomes soft and can be reduced to a smaller size by crimping, so that it can be delivered to the target location, where the stent is warmed to a temperature above the transition temperature and returns to the preprogrammed size and shape. The present invention relates to both to balloon expandable stents and to self-expanding stents, as explained in greater detail in the following sections. 
     The stents in the prior art are formed as a metal mesh or, in general, as a web structure that provides some degree of flexibility. Certain types of anatomies require that stents with elevated degrees of flexibility be employed, for example, stents to be implanted in the carotid artery, because the bifurcated anatomy of the carotid artery and frequent movements of that part of the body require a stent that can adapt to such anatomy. The stent designs in the prior art typically increase flexibility by increasing cells size in the mesh or in the web structure. Therefore, whenever stent flexibility is increased in the stents in the prior art, scaffolding support is affected negatively due to the related reduction in web density. 
     A prior art stent is disclosed in U.S. Pat. No. 5,104,404, which teaches an articulated stent in which stent segments, formed by diamond-shaped cells disposed in ring form, are connected one to the other at some but not all of the tips of the diamond-shaped cells. This arrangement provides for a stent with a high degree of longitudinal flexibility, but also for limited support to the arterial walls at the junctions areas between the different stent segments. 
     With reference now to  FIG. 2 , other designs in the prior art have attempted to increase stent flexibility by forming the stent as a plurality of web rings  24  that are disposed longitudinally along tubular body  22  and that are coupled one to the other by flexible connectors  26 . Designs of this type are disclosed in U.S. patent application Ser. No. 10/743,857, U.S. Pat. Nos. 6,682,554 and 6,602,285, International Application PCT/EP99/06456, and German Patent Application Serial No. 19840645.2, the entireties of which are incorporated herein by reference. The function of flexible connectors  26  is to facilitate the bending of stent  20  by creating longitudinal segments softer than web rings  24 . At the same time, flexible connectors  26  transmit torque from one web ring  24  to adjacent web rings  24  when a bending force is applied to tubular body  22  or when a radial force is applied to tubular body  22 , for example, during deployment of stent  22  from the contracted delivery configuration to the expanded delivery configuration. Such a transmission of torque may cause different web rings  24  to rotate differentially upon application of a bending force or upon deployment of stent  20 . 
     One example of stent construction based on longitudinally alternating of web rings coupled by flexible connectors can be found in U.S. Pat. No. 6,190,403, which discloses a stent having a plurality of web rings disposed in longitudinal order. Each of the web rings is formed by longitudinally-oriented cells disposed circumferentially and is joined to a neighboring web ring by sinusoidal connectors that couple cell tips that are longitudinally aligned one with the other. The stent of the &#39;403 patent provides an elevated degree of scaffolding to the arterial walls, though its structure provides only for a limited degree of longitudinal flexibility due to the limited extent of longitudinal translation that is possible between web rings when a compressive force is applied. 
     Another example of stent construction based on longitudinally alternating web rings coupled by flexible connectors can be found in U.S. Pat. No. 6,451,049, which discloses a stent having a plurality of waveform rings coupled by longitudinal connectors that include a “U” bend. This construction also provides for an elevated degree of scaffolding of the vessel walls, but its flexibility is constrained by the limited ability to compress of the flexible segments. 
     In order to increase stent flexibility, stent designs have been introduced in which the flexible connectors between web rings do not have a longitudinal orientation but instead have a transverse orientation. Examples of such stent designs can be found in U.S. Pat. Nos. 5,980,552; 6,059,811; 6,508,834; and 6,589,276. The transverse orientation of the flexible connectors induce the web rings to rotate one in relation to the other upon the application of a bending or radial force to the stent, and in order to reduce torsional stress in the stent during bending and during expansion, the flexible connectors may have alternating directions. For example, the flexible connectors connecting two neighboring rings may be oriented in a direction opposite to the direction of the next set of flexible connectors. If the web rings are prevented from rotating, the torsional stress in the stent becomes absorbed by the flexible connectors and by the web rings, possibly causing the connectors to warp along their entire length. Additionally, this type of construction causes a foreshortening of the stent during expansion. 
     This problem is illustrated in greater detail in  FIGS. 3A-3B . A typical connector  28  couples first web ring  30  to second web ring  32  by connecting junction bend  34  on first ring  30  to junction bend  36  on second ring  32 . In order for stent  38  to provide an elevated degree of scaffolding to the vessel within which stent  38  is implanted, each junction bend  34  on web ring  30  is coupled to a junction bend  36  in web ring  32 , increasing stent density. The higher the density of stent  38 , however, the lower the flexibility, which may be increased by increasing the length of connector  28 . 
     When the length of connector  28  is increased, the bending capability and the flexibility of stent  38  is increased correspondingly because the moment applied by connector  28  to web rings  30  and  32  upon the application of a bending force on stent  34  is increased correspondingly. Unfortunately, long connectors disposed transversally on stent  38  can extend along a significant amount of the outer circumference of stent  38 . For example, if stent  38  has a diameter of 1.6 mm and if connector  28  is one mm long, connector  28  extends for approximately 72 degrees along the circumference of stent  38 . In turn, long connectors  28  will exert a significant amount of torque on junction bends  34  and  36 , and, consequently, on web rings  30  and  32 , and may warp along their entire length. In addition, long connectors  28  cause the size of stent cells to increase during expansion, therefore, long connectors cause a reduction in the scaffolding properties of stent  20 , or a reduction in the ability of stent  20  to effectively support the vessel, into which stent  20  is implanted. 
     By having long connectors  28  disposed in a direction essentially perpendicular to the longitudinal axis of stent  20 , connector  28  also tend to retain the bend radius of stent  20  during expansion and to cause a distortion of stent  20  in the expanded configuration. 
     Attempts have been made in the prior art to provide long connectors that extend along relatively limited portions of the circumference of stent  38  and that increase vessel support. For example, U.S. Pat. Nos. 5,449,373; 6,203,569; 6,740,114; 6,790,227; 6,942,689; 6,955,686; 6,998,060; 6,679,911; and 6,875,228 disclose stent constructions, in which the connectors have a variety of shapes in the form of the letters “M”, “N”, “W” or similar shapes, but which all include a plurality of segments oriented at certain angles with respect to the longitudinal axis of the stent. In particular, each of the prior art designs contains one or more central segments that are oriented at an angle with respect to the longitudinal axis of the stent, causing rotations in different degrees upon the application of a torsional force on the connector, for example due to a bending of the stent or during expansion. 
     Therefore, it would be desirable to provide a stent that generates an elevated degree of scaffolding to a bodily vessel while remaining highly flexible. 
     It would also be desirable to provide a stent, in which long connectors can be employed to increase stent flexibility and that can absorb torsional forces applied to the stent without warping along their entire lengths. 
     BRIEF SUMMARY OF THE INVENTION 
     A stent according to the present invention exhibits a highly flexible structure and elevated scaffolding properties, and at the same time is configured to absorb torque applied on the stent by bending or radial forces. 
     The stent according to the present invention is expandable from a contracted delivery configuration to an expanded deployed configuration and includes an essentially tubular body formed by a plurality of web rings disposed longitudinally. Each of the web rings is defined by a plurality of web elements that are disposed circumferentially and that, in the contracted delivery configuration, are substantially parallel to the longitudinal axis of the tubular body. Pairs of the web elements are sequentially adjoined at junction bends, and a junction bend in a first web ring is coupled to a junction bend in a neighboring web ring by one of the connectors. 
     Each of the connectors is formed by a plurality of segments disposed in a step-wise configuration. At least one of the connector segments is situated in a central position within the connector and is disposed with an orientation essentially parallel to the longitudinal axis of the stent. These connectors couple junction bends that are laterally offset one in relation to the other, making the connectors span diagonally along the profile of the tubular body. 
     The second segment may be rectilinear in shape and become twisted to acquire a helical curvature when a bending or expansion stress is applied to the stent. In one embodiment, the central element may be pre-deformed with a helical curvature in the contracted delivery configuration that becomes more accentuated during a bending or expansion of the stent. The central element may also be manufactured to have a cross-sectional area that is different from the cross-sectional areas of the end segments. 
     In one embodiment, each of the junction bends in the first web ring is connected to one junction bend in one neighboring web ring by one connector, so that each junction bend in one web ring is coupled to another junction bend in an adjacent web ring. 
     The stent of the present invention may be manufactured from a variety of materials, including metallic materials and plastic materials. When the stent is to be self-expanding, Nitinol or another shape memory material may be employed, while a balloon-expandable stent may be manufactured from stainless steel or other biocompatible metallic or plastic material. All or part of the stent (for example, the connector) may also be manufactured from a biodegradable material, for example, from a plastic absorbing material. In addition, the stent of the present invention may include a number of ancillary features known in the art, for example, may be coated with a bioactive agent or contain radio-opaque markers. 
     Methods of use of the stent according to the present invention are also provided. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       The drawings constitute a part of this specification and include exemplary embodiments of the invention, which may be embodied in various forms. It is to be understood that in some instances various aspects of the invention may be shown exaggerated or enlarged to facilitate an understanding of the invention. 
         FIG. 1  is a perspective view of an essentially tubular body of a stent. 
         FIG. 2  is a front view of a stent connector according to the prior art. 
         FIG. 3A  illustrates a configuration of stent connector according to the prior art, and 
         FIG. 3B  is a schematic top view of the essentially tubular body of a stent highlighting the span of the connector of  FIG. 3B  when disposed within the tubular body. 
         FIG. 4  is a perspective view of one embodiment of the present invention, showing the stent pattern in a detail view. 
         FIG. 5  is a detail view, illustrated as a flattened surface, of the web structure of a stent according to one embodiment of the present invention. 
         FIG. 5A  is a detail view, illustrated as a flattened surface, of the web structure of a stent according to an embodiment of the present invention. 
         FIG. 6  is a detail view of the web structure of  FIG. 5 . 
         FIG. 7  is a schematic plan view of a connector connecting two neighboring junction bends according to one embodiment of the present invention. 
         FIG. 8  is a perspective view of the connector of  FIG. 7 . 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION 
     The present invention relates to stent designs that can absorb an elevated degree of torque during expansion and after implantation in a patient while at the same time providing a highly flexible stent structure. One application of the present invention relates to closed cell stents, in particular, carotid stents, for which an elevated degree of lesion scaffolding and the capability of conforming to tortuous anatomies are key design features. 
     Detailed descriptions of embodiments of the invention are provided herein. It is to be understood, however, that the present invention may be embodied in various forms. Therefore, the specific details disclosed herein are not to be interpreted as limiting, but rather as a representative basis for teaching one skilled in the art how to employ the present invention in virtually any detailed system, structure, or manner. 
     Referring to  FIG. 4 , a stent  40  constructed according to the principles of the present invention includes an essentially tubular body  42  expandable from a contracted delivery configuration to an expanded deployed configuration. While body  42  is depicted in  FIG. 4  as essentially cylindrical in shape, body  42  may be provided with other shapes, for example, with a frustoconical shape or with the shape of a hyperboloid. 
     Body  42  is defined by a web structure  44 , shown in  FIG. 4  only in a detail view that relates to the contracted delivery configuration. Web structure  44  includes a plurality of web elements  46 , each formed by a plurality of crowns  48 . 
     Referring now to  FIG. 5 , each crown  48  includes a central member  50  having a first end member  52  and a second end member  54  extending respectively from the opposite ends of central member  50 . Central member  50 , first end member  52  and second end member  54  are each essentially linear in shape, and, in the contracted delivery configuration of stent  40 , central member  50  is disposed essentially parallel to the longitudinal axis of body  42  (see also  FIG. 4 ), while first and second members  52  and  54  extend from central member  50  at obtuse angles. Preferably, first and second members  52  and  54  extend from central member  50  at the same angle, but in other embodiments, first and second members  52  and  54  may extend from central member  50  at different angles. In still other embodiments, one or more of central member  50  and first and second members  52  and  54  may be non-rectilinear and have a curved shape. 
     Crowns  48  are nested one into the other in the contracted delivery configuration and are sequentially adjoined at one end by a junction bend  56  that exhibits an essentially arcuate shape. A series of crowns  48  is disposed circumferentially about the longitudinal axis of body  42  to form web rings  46 , which are joined one to the other by connectors  58 . As shown in  FIG. 5 , the crowns in one web ring may be disposed with an orientation that is opposite to the orientation of the crowns in a neighboring web ring. In the illustrated embodiment, two adjacent web rings are disposed with an orientation of crowns  48  that is 180 degrees different one from the other. 
     Stent  40  may be manufactured from a variety of biocompatible materials, including metal and plastic materials. For example but not by way of limitation, stent  40  may be manufactured from Nitinol or other shape memory material if a self-expanding configuration of stent  40  is desired, or from stainless steel if balloon expansion is foreseen. Alternatively, stent  40  may be manufactured from a plastic material that enables either a permanent stent placement or a temporary stent placement, for example, from a plastic absorbing material. 
     In some embodiments, crowns  48  and connectors  58  may be manufactured from a biodegradable material when it is expected that only temporary vessel support is required. In another embodiment, only connectors  58  may be manufactured from a biodegradable material, so that the scaffolding provided by stent  40  may change over time and connectors  58  will gradually dissolve in the fluid carried by the vessel (for example, blood), leaving web rings  46  intact and allowing web rings  46  to be disposed at specific angles in relation to each other, as required by the patient&#39;s anatomy or by the movements of the patient&#39;s body. 
     While  FIG. 5  illustrates that each junction bend  56  in one web ring is adjoined by connector  58  to a junction bend  60  in the adjacent web ring, only one out of a plurality of junction bends in one web ring (for example, one every three) may be adjoined to a junction bend in an adjacent web ring, providing stent  40  with larger open spaces between adjacent web rings  46 . An example of which is shown in  FIG. 5A . For example, the web ring  45   a  shown on the left is only connected to the web ring  45   b  in the middle by a single connector  58  (e.g. shown in black), such that the connector  58  is separated by at least seven junction bends  60 . In another example, the web ring  45   c  on the right is connected to the web ring  45   b  in the middle by two connectors  58 , such that the two connectors  58  are separated by three unadjoined junction bends  60 . Thus,  FIG. 5A  illustrates an embodiment of an endoprosthesis configured to transition from a contracted delivery configuration to an expanded deployed configuration. The endoprosthesis includes a plurality of longitudinally adjacent web rings  45   a - c  defining an essentially tubular web structure, each web ring  45   a - c  including a plurality of adjoined web elements  46 ,  48 . The endoprosthesis includes a plurality of junction bends  56 ,  60  adjoining pairs of the plurality of adjoined web elements  46 ,  48 , a first junction bend  56  in a first web ring  45   b  of the plurality of longitudinally adjacent web rings  45   a - c  is connected to a second junction bend  60  in an adjacent neighboring web ring  46   c  of the plurality of longitudinally adjacent web rings  45   a - c  by a first S-shaped connector  58   a , the second junction bend  60  being longitudinally offset from the first junction bend  56  and being circumferentially separated from the first junction bend  56 , a third junction bend  57  in the first web ring  45   b  of the plurality of longitudinally adjacent web rings  45   a - c  is connected to a fourth junction bend  61  in the adjacent neighboring web ring  45   c  of the plurality of longitudinally adjacent web rings  45   a - c  by a second S-shaped connector  58   b , the fourth junction bend  61  being longitudinally offset from the third junction bend  57  and being circumferentially separated from the third junction bend  57 , the first junction bend  56  being circumferentially separated from the third junction bend  57  by at least three unadjoined junction bends  59 , the first and second S-shaped connectors  58   a ,  58   b  having a plurality of segments disposed one in relation to the other in step-wise configuration, the plurality of segments being interconnected by connectors. While this more open design increases stent flexibility, the scaffolding properties of the stent are correspondingly decreased because of decreased stent density. 
     One aspect of the present invention is to provide an elevated degree of flexibility while retaining a closed cell structure, in which each junction bend  56  in one web ring  46  is coupled to a junction bend  60  in a neighboring web ring  46 . Therefore, stent  40  is well suited for delivery and implantation at sites that require elevated flexibility and elevated scaffolding, for example, in carotid arteries. At the same time, the step-wise configuration of connectors  58  enables the use of connectors  58  which are relatively long, increasing flexibility to suit tortuous anatomies and various body movements, but through which the torsion of one web ring  46  in relation to the other is decreased or eliminated, as explained in greater detail below. 
     It should be observed that each of connectors  58  does not adjoin two junction bends that are longitudinally aligned, but instead adjoin two junction bends  56  and  60  that are laterally offset one in relation to the other. This offset configuration is more advantageous than a configuration linking adjacent junction bends. More specifically, a configuration with connectors  58  linking junction bends  56  and  60  that are offset one from the other provides an elevated degree of flexibility to stent  40 , because in this configuration neighboring web rings have a greater ability to rotate one in relation to the other when stent  40  is deployed or becomes subjected to a bending stress. 
     Connectors  58  may join adjacent junction bends  56  and  60  at different points within the junction bends. For example, in the embodiment shown in  FIG. 5  and, in greater detail, in  FIG. 6 , connector  58  adjoins essentially the middle points of junction bends  56  and  60  by extending from essentially the middle point of junction bend  56  to essentially the middle point of junction bend  60 . In other embodiments, connector  58  may adjoin the lowest point in junction bend  56  with the highest point of junction bend  60 , or the highest point of junction bend  56  with the lowest point of junction bend  60 . It should be understood that in still other embodiments, connectors  58  may join junction bends  56  and  60  at a plurality of different points of the junction bends, and that some of the crowns  46  and connectors  58  are shown in  FIGS. 5 and 6  in darkened color only for illustrative purposes and not for indicating any particular structural or design differences from the neighboring crowns and connectors. 
     The structure and mode of operation of connector  58  is illustrated in greater detail in  FIGS. 6 and 7 . More particularly, connector  58  includes a first segment  62 , a second (middle) segment  64  and a third segment  66 , disposed one in relation to the other in a step-wise configuration. Within the structure of connector  58 , first segment  62  couples connector  58  with junction bend  56 , third connector  66  couples connector  58  with junction bend  60 , while second segment  64  couples first segment  62  with third segment  66 . Second segment  64  is arranged in a direction essentially parallel to the longitudinal axis of body  42 , while first segment  62  and third segment  66  are arranged at an angle A with respect to second segment  64 , for example, 110 degrees as shown in  FIG. 7 . In different embodiments, connector  58  may be composed of different numbers of segments, which may further be arranged at angles of varying amplitudes, for example, between 100 and 170 degrees. 
     Referring now to  FIGS. 7 and 8 , the configuration of connector  58  is such to absorb a torsional stress applied to body  42 , particularly during expansion of the stent from the contracted delivery configuration to the expanded deployed configuration. Such an ability to absorb torque is provided not only by the relative movements of first segment  62  and third segment  66 , by which the widths of angle A between second segment  64  and first segment  62 , and of angle B between second segment  64  and third segment  66 , may change as a consequence of torsional stress, but also by the twisting motion of second segment  64  to assume an essentially helical shape. By the twisting motion of second segment  64 , the torsional stress from, for example, first segment  62  is not entirely transmitted to third segment  66 , but is absorbed (entirely or partially) by the twisting motion of second segment  64 . 
     By disposing second segment  64  in a direction essentially parallel to the longitudinal axis of tubular body  42 , torque developing, for example, during deployment of the stent is absorbed at a much greater rate than in stent configurations having second segment  64  disposed at an angle in relation to the longitudinal axis of tubular body  42 . Therefore, the connector design of the present invention absorbs torque at a greater rate than, for example, designs where the connectors between the web rings have shapes reminiscent of the letters “N” or “W”, because the structure of connector  58  according to the present invention minimizes or eliminates the relative rotations of one web ring  46  in relation of a neighboring web ring  46 . At the same time, second segment  64  provides for a greater scaffolding of the vessel walls than connector designs in which no step-like pattern is present, in particular, than designs having no longitudinally disposed segments. By having second segment  64  disposed essentially parallel to the longitudinal axis of tubular body  42 , second segment  64  can become twisted, minimizing or eliminating the distortion problems in stents of the prior art that have long connectors, and improving surface contact of stent  40  with the vessel, within which stent  40  is disposed. 
       FIG. 8  illustrates in greater detail that second segment  64  has become deflected after the application of torsional stress on web structure  44 , for example, when web structure  44  is expanded during the deployment of stent  40  and the web rings on which junction bends  56  and  60  are situated tend to rotate one with respect to the other. During such absorption of torque, connecting area  68  between first segment  62  and second segment  64  may become tilted in a direction opposite to that of connecting area  70  between second segment  64  and third segment  66  when second segment  64  assumes a helical disposition. This phenomenon is particularly relevant when stent  40  is manufactured by producing its shape from a tube, for example through a laser cutting process, so that connectors  58  exhibit edges that are substantially square. In one embodiment of the invention, the twisting motion of second segment  64  towards a helical disposition may be facilitated by manufacturing connector  58  with connecting areas  68  and  70  disposed not one parallel to each other, but instead at an angle one with respect to the other. 
     Stent  40  may be disposed into a target vessel location, for example, in a location within a carotid artery, by inserting a guide wire into the artery, and by successively translating a catheter along the guide wire that carries the stent in a contracted condition. When the stent has reached the target location, as may be determined by tracking radio-opaque markers embedded in the stent, a balloon disposed on the catheter and within the stent is inflated, causing the stent to expand from the contracted condition to the deployed condition until contact with the vessel walls is achieved. Alternatively, if the stent is manufactured from a self-expanding material, after the target location has been reached, a sheath covering the stent is withdrawn, enabling the stent to self-expand until contact with the vessel walls is made and a support structure is created. 
     By providing a stent having a structure formed by web elements that are disposed in web rings and that are coupled by connectors in the manner described herein, so to form a closed cell structure, an improved support is provided to the vessel walls in comparison with open cell stents, and a highly flexible structure is achieved that provides an elevated degree of scaffolding support to the vessel walls even when the vessel is bent. 
     Stent  40  may include different features known in the art to provide certain beneficial properties. For example but not by way of limitation, stent  40  may be coated with a therapeutic coating that includes a bioactive agent, or may contain radiopaque markers, or may be coupled to a fabric that prevents the passage of emboli from the vessel wall into the blood stream. 
     It should be noted that, while the invention has been described in connection with the above described embodiments, it is not intended to limit the scope of the invention to the particular forms set forth, but on the contrary, it is intended to cover such alternatives, modifications, and equivalents as may be included within the scope of the invention. Accordingly, the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and the scope of the present invention is limited only by the appended claims.