Abstract:
A wearable, self-contained drug infusion device is disclosed that is capable of achieving the precise flow rate control needed for dose-critical drugs such as insulin. In preferred embodiments of the device, at least two flow channels are utilized in conjunction with a series of valves for providing a user with selectable, constant flow rate control. The device can be made with small dimensions so that it can be worn by the user with a minimum of discomfort and inconvenience. In addition, the simple mechanical nature of the device provides the user with close control over the flow rate, which is required for safe and effective delivery of insulin and other drugs. Also, the absence of electronic components allows the device to be manufactured inexpensively. The device is provided with a first channel that is long and narrow, functioning as a flow restrictor. The first channel is preferably provided in a serpentine pattern. A second channel is also provided that has a larger cross section so that flow is not restricted. A series of valves are used to force the flow of fluid through a selectable portion of the serpentine portion of the first channel before entering the remainder of the second channel and flowing to the delivery cannula. In one embodiment of the device, a needle port is provided in fluid communication with the delivery cannula for delivering bolus injections. In another embodiment, a bolus button is provided for delivering bolus injections. A flow restrictor is preferably included in the bolus button to limit the rate at which the bolus button refills.

Description:
[0001]    This application is a continuation of Ser. No. 09/931,102, filed Aug. 17, 2001, which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Serial No. 60/226,017, filed Aug. 18, 2000. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates generally to fluid delivery devices. In particular, it is concerned with a self-contained fluid delivery device that can be used to deliver a variety of medications at a selectable flow rate, and which may include a bolus port for intermittent immediate controlled delivery of additional doses of fluid.  
         BACKGROUND OF THE INVENTION  
         [0003]    Diabetes is a chronic disease that is caused by both hereditary and environmental factors. It is characterized by the body&#39;s inability to control glucose levels. Left untreated, it causes damage to the circulatory and nervous systems and results in organ failures, amputations, neuropathy, blindness and eventually death. It has been definitively shown that the cost of the complications related to diabetes significantly exceeds the cost of therapy. The Diabetes Control and Complications Trial (DCCT) was a ten-year study of 1400 patients to assess the benefits of close control of blood glucose levels. The study found that such close control provided 50% to 75% reductions in retinopathy, nephropathy, neuropathy and cardiovascular risk.  
           [0004]    There are roughly 17.5 million people with diabetes in the United States and Europe, and about 60 million more worldwide. Roughly 35% of these people use insulin to maintain close control of their glucose levels. Proper control of blood glucose levels through programmed insulin injection or infusion allows a high quality of life and a life expectancy of an additional 35 to 40 years from diagnosis.  
           [0005]    Currently, there are two principal modes of daily insulin therapy. The first mode includes syringes and insulin pens. These devices are simple to use and are relatively low in cost, but they require a needle stick at each injection, typically three to four times per day. The second is infusion pump therapy, which entails the purchase of an expensive pump that lasts for about three years. The initial cost of the pump is a high barrier to this type of therapy. From a user perspective, however, the overwhelming majority of patients who have used pumps prefer to remain with pumps for the rest of their lives. This is because infusion pumps, although more complex than syringes and pens, offer the advantages of continuous infusion of insulin, precision dosing and programmable delivery schedules. This results in closer glucose control and an improved feeling of wellness.  
           [0006]    The typical patient on intensive therapy injects insulin to provide a basal level and then takes supplemental boluses prior to meals during the day. Those on infusion pumps program their pumps to mimic this type of delivery schedule. There are several existing or anticipated means of insulin therapy that a patient might consider.  
           [0007]    The first are so-called oral agents that enhance the ability of the body to utilize insulin. Typical compounds include sulfonylureas, biguanides and thiazolidinediones. Oral agents are initially appropriate for Type 2 diabetics, whose bodies produce some insulin, although after a period of years these patients generally need to supplement with additional insulin. For Type 1 diabetics, the body does not produce insulin and these agents are not effective.  
           [0008]    Once the oral agents are no longer effective, insulin is injected using syringes or multi-dose insulin pens. The syringe is the least expensive means of delivery, but many patients are willing to pay a premium for the convenience of the insulin pen.  
           [0009]    A recent advance has been the development of extremely long-acting insulins. While regular insulins have a physiological onset in 10 minutes and peak activity in about 90 minutes, current long-acting insulins peak in roughly 8 hours. This type of insulin can be taken in the morning and can be accompanied by bolus delivery at meals. The alternative of simply taking all of one&#39;s insulin requirement in basal delivery is believed by many to be therapeutically unsound. Insulin resistance is theorized to build as a result of high concentrations of insulin in the bloodstream, and as a result ever increasing amounts of insulin are necessary to control blood glucose levels. Unfortunately, the basal plus bolus profile still results in the same high and undesirable frequency of injections, typically four per day. Long-acting insulin does provide good therapy for those patients whose bodies benefit from supplemental basal insulin, but this is a temporary condition and simply delays a more rigorous insulin injection regimen for six months to two years.  
           [0010]    As their interest in intensive therapy increases, users typically look to insulin pumps. However, in addition to their high cost (roughly 8 to 10 times the daily cost of syringe therapy) and limited lifetime, insulin pumps represent relatively old technology and are cumbersome to use. Also, from a lifestyle standpoint, the tubing (known as the “infusion set”) that links the pump with the delivery site on the user&#39;s abdomen is very inconvenient and the pumps are relatively heavy, making carrying the pump a bother.  
           [0011]    A new method of insulin delivery currently undergoing development is pulmonary delivery. The principal issue with pulmonary delivery is criticality of dose, as pulmonary delivery is relatively inefficient and difficult to quantify. As a result, it will be difficult to keep blood glucose levels in control with this delivery form, although it may prove very useful as a supplement for bolus delivery at mealtime. The inefficiency of delivery (currently about 10%) significantly drives up the cost of pulmonary therapy. The implications of chronic inhalation of insulin are also unknown.  
           [0012]    In summary, patients on oral agents eventually move to insulin, and existing pump therapy is very expensive. Interest in better therapy is on the rise, accounting for the observed growth in pump therapy and increased number of daily injections. What is needed to fully meet this increased interest is a form of insulin delivery that combines the best features of daily injection therapy (low cost and ease of use) with those of the insulin pump (continuous infusion, precision dosing and variable delivery rates), and that avoids the disadvantages of each. This will allow a greater number of patients to have access to improved insulin therapy at lower cost.  
           [0013]    Several attempts have been made to provide ambulatory or “wearable” drug infusion devices that are low in cost and convenient to use. Some of these devices are intended to be partially or entirely disposable. In theory, devices of this type can provide many of the advantages of an infusion pump without the attendant cost and inconvenience. Unfortunately, however, many of these devices cannot provide precise control over the flow rate of the drug at a low delivery cost, and are thus not compatible with dose-critical drugs such as insulin. In addition, devices that operate with fixed insulin flow rates may meet cost targets but still require bolus injections at mealtimes. Ultimately, therefore, these existing devices do not represent an optimal alternative to infusion pumps.  
         SUMMARY OF THE INVENTION  
         [0014]    The present invention substantially avoids the disadvantages and limitations of the prior art by providing a wearable, self-contained drug infusion device that is simple in construction but is capable of achieving the precise and variable flow rate control needed for dose-critical drugs such as insulin. The flow rate is selectable by the user to accommodate a wide range of individual metabolic rates. The device is significantly less expensive to manufacture than typical insulin pumps because electronic components are not necessary. Furthermore, the device is dependable because it can incorporate a purely mechanical process.  
           [0015]    In a preferred embodiment of the invention, the drug infusion device comprises a housing, a reservoir in the housing for containing a supply of fluid, and a cannula (needle) for delivering the fluid to a patient. The device further comprises first and second flow channels for delivering the fluid from the reservoir to the delivery cannula. The first flow channel is arranged in a serpentine pattern to increase its effective length. The cross section of the first channel (also referred to herein as the “serpentine channel”) is smaller than the cross section of the second channel. The second channel is further comprised of a plurality of nodes that are in fluid communication with the serpentine channel. The serpentine channel is divided into a number of sections, and each section is associated with a node in the second channel. The nodes can be selectively turned off to allow or prevent fluid from flowing through the node. Thus, when a node is open, fluid is able to pass through the second channel, which imparts less flow restriction due to its larger cross section and shorter length. By closing one or more nodes, fluid flowing from the reservoir to the needle is forced to travel through the portions of the serpentine channel associated with the closed nodes. Closing more nodes increases the effective length of the serpentine channel that the fluid must flow through. Thus, by closing more nodes, the effective length of the serpentine channel is increased, the flow restriction is increased, and the flow rate is decreased.  
           [0016]    In a preferred embodiment of the invention, a disc spring (also referred to as a Belleville spring) is included within the housing. When the device is activated, the Belleville spring engages and pressurizes the fluid reservoir, causing the fluid to flow out of the reservoir and toward the needle. The Belleville spring applies constant pressure on the reservoir, causing the flow rate to remain constant over time despite changes in the fluid volume in the reservoir.  
           [0017]    In another preferred embodiment, the first and second channels are formed in the housing, with one wall of the channels being formed by a flexible membrane that is fixedly attached to the housing. The nodes of the second flow channel are defined by indentations in the housing along the second flow channel. A flow rate selection device is movably attached to the housing, such that the flexible membrane is sandwiched between the housing and the flow rate selection device. The flow rate selection device is provided with detents which correspond in shape to the indentations in the housing. The flow rate selection device may be moved into alignment with the indentations so that a selected number of detents aligns with corresponding indentations. Because the shape of the detents matches the indentations, the detents push the flexible membrane into the indentations, preventing the flow of fluid through the nodes. Thus, the detent, membrane and indentation act like a valve at each node.  
           [0018]    In another preferred embodiment the device is provided with a bolus port for delivering a bolus injection of medicament. The port comprises an opening in the housing in communication with the proximal end of the delivery cannula. The opening is preferably sealed with an elastomeric septum so that a syringe may be used to deliver an additional dose of medicament through the port to the user immediately. When the bolus injection is completed and the syringe is removed, the septum reseals, preventing medicament from escaping through the bolus port and maintaining the hermetic seal around the device. The bolus port may also include a cone shaped guide for guiding the needle of the syringe to the membrane. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0019]    The various objects, advantages and novel features of the present invention will be more readily understood from the following detailed description when read in conjunction with the appended drawings, in which:  
         [0020]    [0020]FIG. 1 is a cross-sectional view of a first embodiment of a fully assembled drug infusion device in the pre-use configuration;  
         [0021]    [0021]FIG. 2 is a cross-sectional view of a first embodiment of the drug infusion device shown in FIG. 1, in the active use configuration;  
         [0022]    [0022]FIG. 3 is an exploded view of the infusion device shown in FIGS. 1 and 2;  
         [0023]    [0023]FIG. 4 is a perspective view of the drug infusion device of FIGS. 1 and 2 shown in the pre-use configuration;  
         [0024]    [0024]FIG. 5 is a perspective view of the drug infusion device of FIGS. 1 and 2 shown in the active use configuration.  
         [0025]    [0025]FIG. 6 is a detailed perspective view of flow channels and nodes used to regulate the flow rate in accordance with the present invention;  
         [0026]    [0026]FIG. 7 is a schematic illustrating the operation of nodes in a variety of positions;  
         [0027]    [0027]FIG. 8 is a cross-sectional view of a flow rate selection node in the open position;  
         [0028]    [0028]FIG. 9 is a cross-sectional view of a flow rate selection node in the closed position;  
         [0029]    [0029]FIG. 10 is a schematic of a fluid delivery device according to the present invention including a flow rate limited bolus button;  
         [0030]    [0030]FIG. 11 is a cross-sectional view of a second embodiment of a fully assembled drug infusion device in the pre-use configuration;  
         [0031]    [0031]FIG. 12 is a cross-sectional view of a second embodiment of the drug infusion device shown in FIG. 11, in the active use configuration;  
         [0032]    [0032]FIG. 13 is an exploded view of the infusion device shown in FIGS. 11 and 12; 
     
    
       [0033]    Throughout the drawings, like reference numerals will be understood to refer to like parts and components.  
       DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0034]    A fluid delivery device constructed in accordance with a first embodiment of the present invention is shown in FIGS.  1 - 5 . The device  10  may be used for the delivery of a liquid medication, preferably but not necessarily insulin, by continuous infusion into or through the skin of a patient. The device  10  is intended to be worn on the surface of the skin by the user, with a cannula (hollow needle) penetrating into the user&#39;s skin or transcutaneously through the skin into the subcutaneous tissue. The device  10  does not require any electronic components, and is intended to be simple and inexpensive to manufacture while providing a selectable constant flow rate of medicament to the patient. Although the present invention is not limited to specific dimensions, the device  10  preferably has an overall size (excluding the delivery cannula and the cannula shield  100 ) of about 50 millimeters in diameter and 12 millimeters in height. The delivery cannula may be rigid or flexible and may have any desired length, but a typical length is between 5 millimeters and 12 millimeters. The cannula shield  60  may be about 15 millimeters in height, making the total height of the device  15  about 27 millimeters. In lieu of a single delivery cannula, a plurality of microneedles may be used to deliver the liquid medication to the skin of the user. Since a typical microneedle length is only 0.5 millimeter, a device  10  constructed using microneedles may have a height dimension not much greater than 12 millimeters. The term “delivery cannula” as used herein will be understood to include not only a hollow needle of the type shown in the drawings, but also one or more microneedles or other structures that deliver liquid medications into or through the skin, whether by skin penetration or otherwise.  
         [0035]    FIGS.  1 - 5  show the assembly of a first embodiment of the device  10 . The housing of the device  10  is comprised of a top cover  12  and a bottom cover  14 . The bottom cover  14  has a flat surface adapted to be attached to the skin of a patient, and has an adhesive layer  16  on the outer surface  18  covered by a release liner  20 . The release liner  20  is removed to expose the adhesive layer  16 , so that the device  10  may be attached to the skin of the patient. The device  10  is held together by legs  22 ,  24  that extend upwardly from the bottom cover  14 , through openings  26 ,  28  in the top cover and engage threads  30  in a selector knob  32 .  
         [0036]    An annular flexible membrane  34  is attached to the inner surface of the top cover  12  to form a fluid reservoir  36 . The membrane  34  is sealed to the top cover  12  at the inner and outer diameter of the membrane  34 , forming a fillable space  36  between the membrane  34  and the inner surface of the top cover  12 . Heat sealing or any other sealing method suitable to create a fluid tight bond between the membrane  34  and the top cover  12  may be used.  
         [0037]    The bottom cover  14  has locator bosses  38  adapted to engage a Belleville spring  40 . The spring  40  remains unflexed until the device is put into use. Rotating the selector knob  32  causes the threads  30  to force the bottom cover  14  to move closer to the top cover  12 , as shown in FIG. 2. When the bottom cover  14  and top cover  12  are forced together, the Belleville spring comes into contact with the membrane  34  and flexes against the membrane  34 , causing the fluid within the reservoir  36  to become pressurized. Further details concerning the use of Belleville springs in a fluid reservoir can be found in commonly-assigned U.S. Pat. Nos. 5,957,895 and 6,074,369, both issued to Burton H. Sage and Robert I. Connelly, which are expressly incorporated herein by reference.  
         [0038]    The top cover  12  also has a protrusion  42  around a central opening  44  that is adapted to engage a hub  46 . The hub  46  retains a cannula  48  and snaps onto the top cover protrusion  42  so that the cannula  48  is in fluid communication with the central opening  44 .  
         [0039]    Before the device  10  may be used, the reservoir  36  must be filled with medicament. As shown in FIG. 3, a fill port  50  is provided. The port  50  comprises an opening  52  in the top cover  12 , a resealable membrane  54  covering the opening, and a cover  56  securing the membrane  54  in place. The resealable membrane  54  allows a syringe to be inserted into the reservoir  36  to fill the reservoir  36  with medicament, while sealing the fill port  50  when the syringe is removed, so that the medicament cannot escape through the fill port  50 . The selector knob  32  is provided with a slot  58  so that the fill port  50  is initially accessible. However, once the selector knob  32  is rotated, activating the device  10 , it cannot be rotated back to its original position. Thus, the fill port  50  may not be accessed after the device  10  has been activated. This feature guarantees that the device  10  may only be used once.  
         [0040]    In the device&#39;s initial configuration, the top cover  12  is separated from the bottom cover  14  as shown in FIGS. 1 and 4. In this position the spring  40  is not pressed against the membrane  34 , the cannula  48  is retracted so that it does not extend beyond the lower surface  18  of the bottom cover  14 , and the bottom end of the threads  30  engage the legs  22 ,  24  of the bottom cover  14 . A removable cover  60  is placed over the cannula  48  and hub  46  to protect and avoid unintentional contact with the cannula  48 .  
         [0041]    To use the device, the reservoir  36  is filled and the removable cover  60  is removed to expose the cannula  48 . Next, the release liner  20  is removed to expose the adhesive layer  16 , and the device  10  is attached to the patient&#39;s skin. Finally, the selector knob  32  is rotated. As the knob  32  is rotated through the first 180 degrees, the threads  30  force the legs  22 ,  24  further into the openings  26 ,  28 . As the legs  22 ,  24  are drawn into the openings  26 ,  28  the top cover  12  collapses down into the bottom cover  14 , as shown in FIGS. 2 and 5. Because the cannula  48  is fixedly attached to the top cover  12 , as the device  10  collapses the cannula  44  extends past the lower surface  18  of the bottom cover  14  and into the patient&#39;s skin. Next, the spring  40  comes into contact with the membrane  34  and flexes, imparting a precise pressure on the liquid medicament within the reservoir  36 . Finally, the selector knob  32  is rotated beyond 180 degrees to select the desired flow rate. The functionality of the selector knob  32  and the flow channels used to select the flow rate will be discussed in greater detail below.  
         [0042]    The only path by which liquid medicament may exit the reservoir  36  is through a port  62  formed into the top cover  12 . The port  62  allows liquid from the membrane reservoir  36  to flow to the top surface  64  of the top cover  12 . The port  62  is in fluid communication with flow channels  66  formed into the top surface  64  of the top cover  12  that lead eventually to the central opening  44  of the top cover  12  and the delivery cannula  48 .  
         [0043]    [0043]FIG. 6 shows a detailed view of the flow channels  66  formed into the surface  64  of the top cover  12 . The channels  66  have a very small cross section, the smallest being roughly 20 microns wide by 60 microns deep. One possible method of accurately producing channels of this size is the use of photolithography techniques to produce a metal negative of the channels and injection molding of plastic to form the top cover  12  with channels  66  formed into the surface  64 . However, the invention is not limited to any particular manufacturing technique, and those skilled in the art will recognize a variety of potential manufacturing methods. The flow channels  66  formed into the surface of the top cover  12  have an open side that is sealed with a flexible membrane  68  that forms one wall of the channels. The membrane  68  is preferably heat sealed to the top cover  12 , although it will be recognized that any suitable bonding method could be used. Because the channels  66  are very long with a small cross section, they act as a flow restrictor. The amount of pressure applied by the spring  36  together with the flow restriction caused by the flow channels  66  allows a precisely metered flow of medicament to the patient.  
         [0044]    Referring to the detailed view shown in FIG. 6, an initial flow channel  70  has a proximal end  72  and a distal end  74 . The proximal end  72  is in fluid communication with the reservoir port  62 , and the distal end  74  is in communication with two possible paths. The first path is a primary restrictor channel  76  and the second is a selector channel  78 . Both the primary restrictor channel  76  and the selector channel  78  have a proximal end that is in communication with the initial channel  70  and a distal end that is in communication with an exit channel  80 . While the primary restrictor  76  and selector  78  channels run generally parallel to each other, the primary restrictor channel  76 , due to its preferably serpentine pattern, is much longer than the selector channel  78 . The exit channel  80  leads to and is in fluid communication with the central opening  44  and also with the interior of the cannula  48 . The primary restrictor channel  76  is preferably formed into a series of closely packed 180 degree turns, making its effective length very long. Furthermore, the primary restrictor channel  76  is roughly 20 microns wide and 60 microns deep. Due to its long length and small cross section, the primary restrictor channel  76  acts as a flow restrictor.  
         [0045]    The selector channel  78  runs along the primary restrictor channel  76  in a relatively straight line, and is preferably larger in cross section than the primary restrictor channel  76 , thus not significantly restricting the flow of medicament. Along the selector channel  78  are a plurality of nodes  82  that are each in fluid communication with a different portion of the primary restrictor channel  76 . Each of the nodes  82  may be open or closed to allow or prevent fluid flow as will be described in greater detail later. As shown in FIG. 6, the selector knob  32  has a detent formed into its underside corresponding to each node  82 . A varying number of closed nodes can be selected by rotating the selector knob  32  so the appropriate number of detents  84  are lined up with nodes  82 , as illustrated in FIG. 7A- 1  through  7 C- 2 . A flexible membrane  86  is sandwiched between the top cover  12  and the selector knob  32 . The membrane  86  is sufficiently thin and flexible to allow the detents  84  to push the membrane  86  into the nodes  82 , closing off fluid flow through the node. The membrane  86  may consist of any suitable material, but a preferred material is polycarbonate having a thickness of about 2 to 3 mils.  
         [0046]    Each of the nodes  82  along the selector channel  78  work in conjunction with the selector knob  32  and the flexible membrane  86  to form a pinch valve, as shown in FIGS. 8 and 9. Each figure shows a cross section of a single node. Referring to FIG. 8, each of the nodes  82  are formed by an indentation  88  in the surface of the top cover  12  along the selector channel  78 . The bottom of the selector knob  32  has detents  84  shaped to correspond to the node indentations  88 . As shown in FIG. 8, when a detent  84  is not positioned directly over a node  82 , the valve remains open, and fluid is free to pass through the node  82 . As shown in FIG. 9, when a detent  84  is positioned over a node  82 , the detent  84  pushes the flexible membrane  86  into the node  82 , and closes the valve. Thus, fluid is not able to flow through the node.  
         [0047]    Referring back to FIG. 6, when fluid flows from the reservoir  36  toward the cannula  48  and reaches the distal end of the initial channel  74 , it can flow into either the primary restrictor channel  76  or the selector channel  78 . If all of the nodes  82  are open, almost all of the fluid will flow through the selector channel  78  to the exit channel  80  because there is much less flow restriction. However, if the first node  90  is closed, fluid is forced to flow through the portion of primary restrictor channel  76  between the first  90  and second  92  node. Because the serpentine portion imparts more restriction on the flow than the selector channel  78 , the total flow restriction is increased. If the remaining nodes  82  are left open, fluid will be able to avoid the remainder of the primary restrictor channel  76  by flowing into the selector channel  78  through the second node  92 . By turning the selector knob  32  further, more nodes  82  are closed. Closing additional nodes forces the fluid through additional sections of the primary restrictor channel  76 , increasing the flow restriction, and in turn lowering the flow rate. The maximum flow restriction (and minimum flow rate) is achieved when the selector knob  32  has been rotated so that all of the nodes  82  are closed and fluid is forced through the entire serpentine  76 .  
         [0048]    FIGS.  7 A- 1  through  7 C- 2  show schematically how the selector knob  32  can be turned to select different numbers of closed nodes. FIGS.  7 A- 1  and  7 A- 2  show the top cover  12  and selector knob  32  in a first position, such that none of the detents  84  are aligned with any of the node indentations  88 . In this position all of the nodes are open and the flow rate is maximized. FIGS.  7 B- 1  and  7 B- 2  show the top cover  12  and selector knob  32  in a second position. As shown, five of the detents  84  line up with five of the node indentations  88 . Thus, five nodes are closed, forcing fluid through the corresponding portions of primary restrictor channel  76 . Finally, FIGS.  7 C- 1  and  7 C- 2  show the top cover  12  and selector knob  32  in a third position, such that all of the detents  84  line up with a node indentation  88 . In this position, every node is closed, and fluid is forced through the entire primary restrictor channel  76 , minimizing the flow rate.  
         [0049]    The foregoing description describes the mechanism by which the device provides a basal flow rate of medicament to a patient. The following will describe how the device may also incorporate the ability to provide bolus injections. Bolus injections are particularly important with patients with diabetes, as they may need bolus injections of insulin with meals, for instance.  
         [0050]    In one embodiment, the device  10  is provided with a bolus port. Once the device  10  has been activated, and the cannula has been inserted into the patient, the bolus port may be accessed to inject additional quantities of medicament, as needed, through the same cannula, thereby avoiding the inconvenience of additional needle sticks. Referring to FIGS.  1 - 3 , the bolus port comprises an elastomeric septum  94  fixedly attached to the flexible membrane  86  over the central opening  44  in the top cover  12 . The septum is held in place by a port guide  96 . The port guide  96  is preferably a tall piece of plastic that is ultrasonically welded to the top cover  12 , trapping the septum  94  in place. The port guide  96  also has a cone shaped interior that helps to guide a needle down to the septum  94 . When a patient needs a bolus injection, they simply insert a syringe needle through the septum into the central opening  44  and inject. The additional dose is immediately carried into the body through the delivery cannula  48 . When the injection has been completed, the syringe may be removed, and the septum  94  seals behind it, maintaining a hermetic seal within the device  10 .  
         [0051]    In some applications, it may be important to limit the volume of medicament received through bolus injections. Once such application may be where the bolus injections are an opioid, although those skilled in the art will recognize that there are many such situations. The principles of the present invention may be applied to provide the device  10  with a bolus button. The bolus button allows the user to take bolus injections as needed, while limiting the amount of medicament delivered through the bolus button over a given time period. A schematic of a device  10  incorporating the bolus button is shown in FIG. 10.  
         [0052]    A bolus restrictor channel  98  is incorporated into the surface of the top cover  12  as the previously discussed flow channels were. The bolus restrictor channel  98  has a proximal end and a distal end. The proximal end is in fluid communication with the reservoir  36 , while the distal end is in fluid communication with a bolus button structure  100 . The flexible membrane  68  forms one wall of the bolus flow channel  98 . The bolus restrictor channel  98  preferably has a serpentine portion  102  to restrict the flow of medicament to the bolus button. The bolus restrictor channel  98  preferably incorporates a check valve  104  to prevent a reverse flow of medicament from the bolus button  100  back toward the reservoir  36 . A bolus exit channel  106  has a proximal end in communication with the bolus button  100  and a distal end in communication with the exit channel  80  and the central opening  44 . The bolus exit channel preferably incorporates a spring check valve  108  to prevent a backward flow of fluid from the exit channel  80  toward the bolus button  100 . The spring check valve  108  also exerts spring pressure so that fluid cannot flow from the bolus button toward the central opening  44  without overcoming the spring pressure. This prevents medicament from flowing into the patient through the bolus flow channel  98  until the bolus button  100  is depressed.  
         [0053]    The bolus button  100  is an indentation in the top cover  12  sealed with the flexible membrane  68 . Fluid flows into and fills the space created between the bolus button indentation and the flexible membrane. Once the bolus button  100  is filled, the fluid remains in the bolus button  100  and cannot flow out due to check valve  104  and spring check valve  108 .  
         [0054]    In order to inject a bolus, the user presses down on the membrane  68  of the bolus button  100  causing the fluid within the bolus button  100  to become pressurized. Once the pressure in the bolus button  100  overcomes the spring pressure of the spring check valve  108 , fluid exits the bolus button and flows out the bolus exit channel  106  toward the central opening  44  and the cannula  48 . As the bolus button  100  empties, the flexible membrane  68  deforms into the bolus button indentation.  
         [0055]    Once the bolus button  100  is empty, fluid will begin to flow into it from the reservoir  36 . However, the rate at which the bolus button  100  refills is limited by the bolus restrictor channel  98 . Thus, the maximum rate at which the user can take bolus injections is governed by the amount of restriction in the serpentine portion  102 . Even if a patient continuously pushed the bolus button  100 , they would only receive as much medicament with each push as would have flowed into the bolus button  100  since the previous push.  
         [0056]    In another preferred embodiment, the cavity which defines the bolus button volume is provided with an adjustable plug. The plug is a threaded member that can be adjusted in or out of a threaded hole within the bolus button indentation in order to adjust the volume of the bolus button  100 . Other means of altering the volume of the bolus cavity may be provided and are within the scope of the invention.  
         [0057]    FIGS.  11 - 13  illustrate a second embodiment  210  of the present invention. Referring to FIGS.  11 - 13  for the assembly of the second embodiment of the device, the two major components of the product are the top cover  212  and the collapsible bottom cover  214  which comes in contact with the skin of the user. The needle  216  for delivering the medicament is retained into the top cover  212  by an adhesive connection such as ultra-violet cured epoxy. Also on the inside surface  218  of the top cover the bladder membrane  220 , in an annulus shape, is heat sealed to the surface  218  at both its inner diameter and outer diameter such that the medicament could be contained between it and the inside of the top cover  212 . The assembly is held together by permanent connection of the bottom cover  214  to the top cover  212 . A selector knob  222  is retained onto the top cover  212  by welded connection of the hub  252  to the top surface of the top cover  212  such that the selector knob  222  is free to rotate. Finally, a disc spring  226  is retained at its inner diameter to the bottom cover  214  onto a standing locator ring  228 . The spring  226  is unstressed from the date of manufacture, and is not stressed until time of use of the product by the user.  
         [0058]    As the product is shipped to the user (FIG. 11), the bottom cover  214  is domed outward so as to extend just beyond the height of the needle  216  hubbed into the top cover  212  as shown. To use the device, the user would first select the desired flow rate using the selector knob  222  on the top of the unit. As the selector knob  222  is rotated, it will give an audible and tactile click as it passes through each flow rate, and the rate at any given position can be read through the port  230  on the selector knob (see FIG. 13). Once the rate is selected, the user would then fill the unit using a simple filling device with a sharp needle with the proper amount of medicament through the fill port  232  which is comprised of (see FIG. 12) an elastomeric fill port septum  234  which is secured to the top cover  212  at the port location  232  by means of a septum cap  236 . Since the unit is intended to be worn for a  24  hour period, regardless of flow rate, a different volume of medicament would need to be inserted into the unit for each flow rate selected. Therefore, a feature of the present invention would comprise a physical stop for the filling device plunger which is at a different depth for each flow rate selected using the selector knob  222  in the previous step. Referring again to FIG. 11, after filling the unit, the user would remove the shield  238 , exposing the still hidden needle  216  under the unit. Then the user would peel off the release liner  240  from the adhesive carrier  242  on the bottom cover  214  (note that the adhesive carrier  242  is only adhered to the bottom cover  214  in the area shown by the adhesive layer  244  while the carrier  242  is adhered to the skin of the user over its entire area.) The unit would then be adhered to the skin of the patient at a suitable location such as on the abdomen.  
         [0059]    To activate the unit, the user would then press firmly down on the unit so as to cause the thin outer perimeter  246  of the bottom cover  214  to collapse inward and allow the bottom cover  214  to fold into the recess in the top cover  212 . As the bottom cover  214  collapses into the top cover  212  the needle  216 , which is attached to the top cover  212 , will by virtue of this attachment, travel downward through the opening in the bottom cover  214  and into the skin of the user. Note in FIG. 12 how the needle  216  protrudes beyond the bottom surface of the bottom cover  214 . Then, as the bottom cover  214  collapses into the top cover  212  the spring  226  is forced into contact with the bladder  220  containing the medicament. This spring force causes the disc spring  226  to deflect downward into its zero spring-rate range and therefore imparts a precise pressure upon the medicament in the bladder  220  which would initiate the flow of the medicament into the skin. Finally, as the bottom cover  214  collapses inward the inner ring of the bottom cover  214  contacts the locking ring  248  and forces it upward through holes in the top cover  212  and into the teeth  250  of the inner diameter of the selector knob  222 . This locks the selector knob  222  into place such that the flow rate cannot be either inadvertently or intentionally moved to another setting after initiation of flow.  
         [0060]    To remove the product, the user simply pull upward on the unit, away from the skin, until the collapsed bottom cover  214  pops back out to its domed position as in FIG. 11 and the unit will then be in a safe position, and the needle will be retracted from the skin. At this point the user can simply peel the device from the skin, replace the shield  238  over the needle  216  if desired, and discard. It should also be noted that after activation of the unit, the selector knob cannot be rotated, even after retracting the needle. If the lock ring  248  forces the selector knob  222  to rotate slightly upon activation then the fill port  232  will be occluded such that the unit cannot then be refilled thereby forcing the product to be single-use.  
         [0061]    Finally, referring to FIGS.  11 - 13 , the second embodiment also includes a bolus port on the top of the unit to enable the user to immediately inject a measured quantity of medicament directly into the skin through the unit&#39;s needle  216 . This allows the user to take a quick dose of medication without having to resort to an additional needle stick. The bolus port is incorporated into the hub  252  retaining the selector knob  222  to the top of the top cover  212 . The port is ultrasonically welded to the top surface of the top cover  212  thereby trapping the elastomeric septum  254  between the membrane seal  68  and the bolus port. In this manner, the septum  254  acts as a self-sealing needle port, connecting directly to the node immediately upstream of the needle  216 . The bolus port can be used at any time during which the unit is adhered to the body and the needle is set into the skin.  
         [0062]    Although the present invention has been described in reference to certain preferred embodiments thereof, it will be understood that the invention is not limited to the details of these embodiments. Various substitutions and modifications have been described in the course of the foregoing description, and other substitutions and modifications will occur to those of ordinary skill in the art. All such substitutions and modifications are intended to fall within the scope of the invention as defined in the appended claims.