Abstract:
A system and method for delivering drug solutions to a user, the system having a housing with a drug reservoir therein. The system also includes an activation assembly having a delivery needle and an activation device for activating delivery. The system further includes a pump, associated with the drug reservoir and a flow restrictor. When activated, the pump moves the drug out of the drug reservoir through the delivery needle and into the skin of the user. The pump may be in the form of a spring.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    The present invention relates to the administration of a drug solution and, more particularly, to the delivery of a viscous drug solution into a mammal.  
           [0002]    Various devices have been developed for the delivery of medications into living organisms, including syringes in which a liquid is delivered from a chamber using pressure asserted by a manual plunger through a needle inserted under the skin.  
           [0003]    However, certain drug solutions, in their deliverable state are highly viscous. Furthermore, the drug volumes frequently exceed 1 milliliter (ml), a volume that could be effectively absorbed by the subcutanceous tissue upon injection. These include certain drugs delivered subcutaneously to enhance fertility, treat cancer, rheumatoid arthritis and multiple sclerosis, allergies, and other conditions. For example, one such cited compound has a viscosity of about 50 cp (centapoise). The delivery of these types of drugs presents certain challenges as delivery of such solutions by means of a typical syringe is inappropriate and may be ineffective. Highly viscous drugs are more difficult to deliver because they require more pressure to deliver using standard technology and also need a longer period of time to absorb into the system of the patient. Highly viscous drugs are difficult to inject by hand because it requires more pressure on the syringe plunger to move drug out of the syringe body through the needle and into the user. The patient may be unable to provide such pressure for an extended period of time, which results in a incomplete dosage, or the patient may move the needle when applying the additional pressure during delivery resulting in unnecessary infliction of pain to the patient.  
           [0004]    In addition to highly vicous drugs, it should be mentioned that high dosage volumes of low viscous formulations, such as water, also do not get absorbed if injected using existing technology. An injection of a high volume dosage using existing technology, such as a standard syringe, will result in intolerable pain to the patient. This is due to the body&#39;s inability to quickly absorb such a volume of drug in a short period of time. Thus, it is necessary for high volume doses to be delivered at a rate at which the body can absorb the drug solution. As a result, the delivery time needs to be longer. Using standard technology, the injection of a high volume dosage would likely result in movement of the needle during delivery which inflicts unneeded pain on the patient and may result in an incomplete delivery.  
           [0005]    Other drug delivery devices have been designed to delivery drug solution. These include applicants&#39; own inventions disclosed and described in U.S. Pat. Nos. 5,527,288; 5,997,501; 5,848,991; 5,814,020; and 5,858,001; as well as U.S. patent application Ser. Nos. 09/072,875; and 09/439,879. These inventions are directed to various drug delivery systems. However, such devices and methods are not appropriate for delivering viscous drug solutions as they require considerable more energy to move the drug out of the drug reservoir and into the user. Moreover, the present invention requires considerable time for delivery due to the user&#39;s inability to quickly absorb the drug solution into his/her system. The combination of increased power requirements combined with increased delivery time for injection would make modification of the aforementioned inventions impracticable and ineffective.  
           [0006]    Thus, there is a need for a drug delivery device for the delivery of viscous drug solutions.  
           [0007]    There is a further need for a drug delivery device for the delivery of viscous drug solutions that effectively delivers the appropriate volume of drug to the user in a manner that enables the drug solution to become properly absorbed into the user&#39;s system during delivery without inflicting any unnecessary pain.  
           [0008]    There is yet a further need for a drug delivery device for the delivery of high volume dosage of drug solution capable of delivering the volume at a rate at which the body can absorb the drug so that the dosage is effective and pain during delivery to the patient is minimized.  
         SUMMARY OF THE INVENTION  
         [0009]    The present invention relates to systems and methods for delivering drug solutions to a user over an extended period of time. The system includes a housing and a drug reservoir housed in the housing. The system also includes an activation assembly having a delivery needle for insertion into the skin of a user, and an activation device for activating liquid communication between the drug reservoir and delivery needle and for activating the insertion of the delivery needle into the skin. The system also includes a movable channel that effects liquid communication between the drug reservoir and the delivery needle upon activation. A flow restrictor is in communication with the moveable channel to restrict the flow of drug therethrough. The system further includes a pump for moving drug out of the drug reservoir, through the delivery needle and into the user when activated.  
           [0010]    In a preferred embodiment, the pump is a spring, biased against the drug reservoir. When activated, the spring forces drug out of the drug reservoir through the flow restrictor and needle and into the user.  
           [0011]    In a preferred embodiment, the flow restrictor is a length of tubing. The preferred range of diameter of tubing is from 0.5 to 0.05 mm and the preferred length of tubing can go up to about 10 cm. In a preferred embodiment, the delivery rate of drug using the system has been tested to achieve flow rates of between 2 and 3 ml/hour.  
           [0012]    In a preferred embodiment, the activation device is a knob. When the knob is rotated, it results in liquid communication between the drug reservoir and delivery needle, and when it is subsequently depressed, it results in movement of the delivery needle into the skin to active delivery.  
           [0013]    The system also includes the ability to move the delivery needle from a first storage position, to a second delivery position to a third locked position. This enables the system to be safely stored prior to activation and to prevent reuse or contamination or harm to the user or health care worker upon completion of use of the system.  
           [0014]    The system may also include a layer of adhesive on the housing that contacts the skin during delivery. The adhesive acts to secure the housing, and more particularly the needle, during delivery.  
           [0015]    The foregoing and other objects, features, and advantages of the drug delivery systems and methods will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]    [0016]FIG. 1 is a front cross-sectional view of the preferred embodiment of the drug delivery system of the present invention prior to use;  
         [0017]    [0017]FIG. 1A is a top sectional view of the embodiment of FIG. 1;  
         [0018]    [0018]FIG. 1B is a side sectional view of the of the embodiment of FIG. 1;  
         [0019]    [0019]FIG. 1C is a side view of an alternative embodiment of FIG. 1 having an adhesive layer;  
         [0020]    [0020]FIG. 1D is a front view of the embodiment of FIG. 1C;  
         [0021]    [0021]FIG. 2 is a front cross-sectional view of the preferred embodiment of the drug delivery system of FIG. 1 initiating use;  
         [0022]    [0022]FIG. 2A is a top sectional view of the embodiment of FIG. 2;  
         [0023]    [0023]FIG. 2B is a side sectional view of the of the embodiment of FIG. 2;  
         [0024]    [0024]FIG. 3 is a front cross-sectional view of the preferred embodiment of the drug delivery system of the present invention during delivery of the drug solution;  
         [0025]    [0025]FIG. 3A is a front cross-sectional view of the preferred embodiment of the drug delivery system of the present invention at the end of delivery of the drug solution;  
         [0026]    [0026]FIG. 3B is a top sectional view of the embodiment of FIG. 3A;  
         [0027]    [0027]FIG. 3C is a side sectional view of the of the embodiment of FIG. 3B;  
         [0028]    [0028]FIG. 4 is a front cross-sectional view of the preferred embodiment of the drug delivery system of the present invention after use;  
         [0029]    [0029]FIG. 4A is a top sectional view of the embodiment of FIG. 4;  
         [0030]    [0030]FIG. 4B is a side sectional view of the embodiment of FIG. 4;  
         [0031]    [0031]FIG. 4C is a front cross-sectional view of the preferred embodiment of the drug delivery system of the present invention in its final and locked position;  
         [0032]    [0032]FIG. 4D is a side sectional view of the embodiment of FIG. 4C;  
         [0033]    [0033]FIG. 4E is a top sectional view of the embodiment of FIG. 4C;  
         [0034]    [0034]FIG. 5 is a perspective view of the drug reservoir and needle assembly prior to use;  
         [0035]    [0035]FIG. 6 is a second perspective view of the embodiment of FIG. 5;  
         [0036]    [0036]FIG. 7 is a perspective view of the drug reservoir and needle assembly initiating use;  
         [0037]    [0037]FIG. 8 is second perspective view of the embodiment of FIG. 7;  
         [0038]    [0038]FIG. 9 is a perspective view of the drug reservoir and needle assembly during drug delivery;  
         [0039]    [0039]FIG. 10 is second perspective view of the embodiment of FIG. 9;  
         [0040]    [0040]FIG. 11 is a perspective view of the drug reservoir and needle assembly after use;  
         [0041]    [0041]FIG. 11A is a second perspective view of the embodiment of FIG. 11;  
         [0042]    [0042]FIG. 12 is a perspective view of the drug reservoir and needle assembly during in its final and locked position;  
         [0043]    [0043]FIG. 14 is a second perspective view of the embodiment of FIG. 13;  
         [0044]    [0044]FIG. 15 is a perspective view of the embodiment of FIG. 1;  
         [0045]    [0045]FIG. 16 is a schematic view of the set up for experiments using the present invention;  
         [0046]    [0046]FIG. 17 is a table illustrating the results of an experiment using a 40 mm tube length with a 0.05 mm diameter at a starting pressure of about 950 mbar;  
         [0047]    [0047]FIG. 18 is a table illustrating the results of an experiment using a 140 mm tube length with a 0.05 mm diameter at a starting pressure of about 1000 mbar;  
         [0048]    [0048]FIG. 19 is a table illustrating the results of an experiment using a 70 mm tube length with a 0.05 mm diameter at a starting pressure of about 950 mbar;  
         [0049]    [0049]FIG. 20 is a table illustrating the results of an experiment using a 70 mm tube length with a 0.05 mm diameter at a starting pressure of about 675 mbar; FIG. 21 is a table illustrating the results of an experiment using a 70 mm tube length with a 0.2 mm diameter at a starting pressure of about 400 mbar;  
         [0050]    [0050]FIG. 22 is a table illustrating the results of an experiment using a 140 mm tube length with a 0.2 mm diameter at a starting pressure of about 650 mbar;  
         [0051]    [0051]FIG. 23 is a table illustrating the results of an experiment using a 70 mm tube length with a 0.05 mm diameter at a starting pressure of about 900 mbar; and  
         [0052]    [0052]FIG. 24 is a table illustrating the results of an experiment using a 70 mm tube length with a 0.05 mm diameter at a starting pressure of about 650 mbar. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0053]    Referring now in more detail to the drawing, which illustrates the general structure and function of preferred embodiments of the invention, a preferred embodiment or device  5  includes a housing  10 , as shown in FIGS.  1 A-C. The housing  10  also includes a drug cartridge  11  which is inserted through an opening  12  in the housing. The cartridge  11  has a neck  13  which is held in place by a conical depression  14  in the housing  10  when the cartridge is fully inserted into the device  5 . The cartridge  11  further includes a rubber plunger  15 . When the cartridge  11  is inserted into the opening  12  in the housing  10 , the plunger  15  is pierced by an internal needle  16 . The internal needle  16  is held within a cylinder  17 . The cylinder  17  is held within a recess  18  within the housing. The cylinder  17  is pre-loaded by means of spring  19  placed along the outer axis  17 A of the cylinder. The spring  19  is held within a portion of the length of the recess  18  by cylinder lip  20  and recessed step  21 . At the bottom end  17 B of the cylinder  17  is a central opening  40  through which the needle  16  projects.  
         [0054]    The needle  16  is connected to a length of tubing  22 . The tubing acts as a flow restrictor and limits the flow rate of the drug solution as it travels through the length of tubing. The cylinder  17  has an angled base for matingly fitting with a latch  23 . The latch has a head  24  for engagement with a portion of an injector knob  25 . As can be seen from the top view, FIG. 1(A), the knob  25  has an outer face  26  and a central axis  27  which is fixed to a delivery needle  28  which is spring loaded within the housing  10  by means of an injection coil spring  29 .  
         [0055]    The housing may include an adhesive layer  60  which is applied to the surface of the housing  10  that is in contact with the user&#39;s skin during delivery, as shown in FIGS. 1C and 1D. The adhesive layer  60  is protected prior to use by a removable liner  62 , typically made of paper or plastic. The liner  62  has a tab  64  protruding from one portion of the housing  10  to ease in grabbing and removing the liner  62 .  
         [0056]    To use the device, the cartridge  11  is inserted into the opening  12  within the housing  10 . The cartridge  11  is depressed into the opening  12  until the neck of the cartridge is flush against the outer surface of the housing  10 , as shown in FIG. 1A. As the cartridge  11  is depressed, the needle  16  is pressed against the plunger  15  and penetrates through the plunger to establish liquid communication with the drug solution in the cartridge. At this point, the drug is ready for injection into the user.  
         [0057]    Prior to use, the user peels off the removable liner  62  from the adhesive layer  60  to expose the adhesive. The user places the housing  10  against the skin at the injection site so that the adhesive  60  is in contact with the skin and secures the housing thereto. Then, the user depresses the knob  25  so that the face of the knob  26  becomes flush with the housing  10  as shown in FIG. 2. The depression of the knob  25  causes the latch head  24  to move from a first angled recess  35  in the knob axis to a second recess  30 . This movement causes the head  24  to clear the mating engagement of the protuberance on the head  31  with the mating recess in the shaft  27  of the knob  25  as shown in FIG. 2(B). As the protuberance on the latch head  31  clears the knob shaft recess  35 , the angled base of the cylinder  17  causes the latch  23  to move in a lateral direction to the right as indicated by the arrow in FIG. 2. This results in a clearance of the latch  23  from the cylinder base  17 B which enables the cylinder  17  to travel upward under the force of the spring  19 . As the cylinder  17  moves upward it causes the drug within the cartridge  11  to move out of the cartridge through the tubing  22  and into the delivery needle  28 , as shown in detail in FIG. 3A. Concurrently, depression of the knob  25  also causes the delivery needle  28  to move out of the housing  10  and into the skin of the user. The latch head  23  is received into the second recess  30  during use. The angled slope  37  of the first recess  35  allows it to move into the second recess  30  and the vertical surface  38  within the housing prevents the delivery needle  28  from retracting back into the housing  10  during use.  
         [0058]    Once the delivery is complete, the stopper  15  will end its travel along the length of the cartridge  11  and rest on the cartridge lip  13 . At that time, the user will be able to view the end of delivery indication through a slot  39  within the housing as shown in FIG. 15. The user would then turn the knob  25  counter-clockwise as indicated by the arrow in FIG. 4. Because the delivery needle  28  is spring loaded to retract, the turning of the knob enables the latch head  24  to move out of the second recess  30  and into an appropriately sized slot  33  in the knob shaft as shown in side view FIG. 4(B). Upon completion of the turning, the latch head rests within the slot  33  on the knob shaft  27  as shown in FIG. 4(F). Once the latch  23  moves into this position, the knob  25  cannot be depressed and the delivery needle  28  cannot extend out of the housing  10  thereby preventing reuse or any potential harm or injury to the user or healthcare provider.  
         [0059]    In an effort to determine appropriate flow rate for highly viscous drugs, applicants have completed a number of experiments using various sizes of tubing. The experiments were conducted using a fixed volume of water  50  forced through a length of tubing  52  by means of a spring  54 , as shown in FIG. 16. The pressure was measured using a pressure transducer  56 . The results of the experiments are set forth in FIGS. 17 through 22. The sizes of the tubing varied in diameter from 0.05 mm to 0.2 mm. The length of tubing used in the experiments was 40 mm, 70 mm and 140 mm.  
         [0060]    The tubing material is TFL special sub-lite wall tubing manufactured by Zeus. As can be seen from FIGS.  17 - 24 , the delivery rate of drug achieved in the tests was up to 3 ml/hr.  
         [0061]    It should be noted that while the experimental tests indicate certain delivery rates, pressure settings and tube dimensions, these parameters may be altered to attain a desired delivery rate or to accommodate a particular drug having a particular viscosity. Moreover, while viscosity of drugs used with the present invention are around 50 cp, the viscosity can be up to 150 cp depending upon the drug&#39;s ability to remain in liquid form and not crystalize.  
         [0062]    In addition, the volume of drug for delivery can vary depending upon the force applied to move it through the system. In the experiments, the volume of solution ranged from about 2 to 3 milliliters. However, the volume of drug may be altered depending upon the geometry of the flow path and the force used to move drug out of the reservoir.  
         [0063]    The system may also include a layer of adhesive applied to the underside of the housing that contacts the skin during delivery. The adhesive is secured to the housing by means of glue or other compound and is covered with a removable liner such as paper. During use, the user removes the liner from the bottom of the housing and applies the housing to the injection site in preparation for delivery. The adhesive secures the housing in position, so that the needle does not move during delivery. Because the delivery time is longer than a standard injection, movement of the needle is to be avoided. Otherwise, any movement of the needle while in the skin can cause the user uneccessary pain and discomfort.  
         [0064]    It is further appreciated that the present invention may be used to deliver a number of drugs. The term “drug” used herein includes but is not limited to peptides or proteins (and mimetic thereof), antigens, vaccines, hormones, analgesics, anti-migraine agents, anti-coagulant agents, medications directed to the treatment of diseases and conditions of the central nervous system, narcotic antagonists, immunosuppressants, agents used in the treatment of AIDS, chelating agents, antianginal agents, chemotherapy agents, sedatives, anti-neoplastics, prostaglandins, antidiuretic agents and DNA or DNA/RNA molecules to support gene therapy.  
         [0065]    Typical drugs include peptides, proteins or hormones (or any mimetic or analogues or any thereof) such as insulin, calcitonin, calcitonin gene regulating protein, atrial natriuretic protein, colony stimulating factor, betaseron, erythropoietin (EPO), interferons such as α, β or γ interferon, somatropin, somatotropin, somastostatin, insulin-like growth factor (somatomedins), luteinizing hormone releasing hormone (LHRH), tissue plasminogen activator (TPA), growth hormone releasing hormone (GHRH), oxytocin, estradiol, growth hormones, leuprolide acetate, factor VIII, interleukins such as interleukin-2, and analogues or antagonists thereof, such as IL-1ra; analgesics such as fentanyl, sufentanil, butorphanol, buprenorphine, levorphanol, morphine, hydromorphone, hydrocodone, oxymorphone, methadone, lidocaine, bupivacaine, diclofenac, naproxen, paverin, and analogues thereof; anti-migraine agents such as sumatriptan, ergot alkaloids, and analogues thereof; anticoagulant agents such as heparin, hirudin, and analogues thereof, anti-emetic agents such as scopolamine, ondansetron, domperidone, metoclopramide, and analogues thereof; cardiovacular agents, anti-hypertensive agents and vasodilators such as diltiazem, clonidine, nifedipine, verapamil, isosorbide-5-monotritate, organic nitrates, agents used in treatment of heart disorders, and analogues thereof; sedatives such as benzodiazepines, phenothiazines, and analogues thereof; chelating agents such as defroxanune, and analogues thereof; antidiuretic agents such as desmopressin, vasopressin, and analogues thereof; anti-anginal agents such as fluorouracil, bleomycin, and analogues thereof; anti-neoplastics such as fluorouracil, bleomycin, and analogues thereof; prostaglandins and analogues thereof; and chemotherapy agents such as vincristine, and analogues thereof, treatments for attention deficit disorder, methylphenidate, fluvoxamine, bisoprolol, tacrolimus, sacrolimus and cyclosporin.  
         [0066]    While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.