Abstract:
An ophthalmic drug delivery device having two actuation assemblies for dispensing incompatible dosage forms and facilitating the prevention of dosage form reflux.

Description:
[0001]     This application is a continuation of PCT/US2005/045459 filed Dec. 15, 2005 entitled “Device for Ophthalmic Drug Delivery,” which claims priority from U.S. Provisional Application No. 60/638,775 filed Dec. 22, 2004. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention generally pertains to a device for ophthalmic drug delivery. More particularly, but not by way of limitation, the present invention pertains to such a device for posterior segment ophthalmic drug delivery.  
       DESCRIPTION OF THE RELATED ART  
       [0003]     Several diseases and conditions of the posterior segment of the eye threaten vision. Age related macular degeneration (ARMD), choroidal neovascularization (CNV), retinopathies (e.g., diabetic retinopathy, vitreoretinopathy), retinitis (e.g., cytomegalovirus (CMV) retinitis), uveitis, macular edema, glaucoma, and neuropathies are several examples.  
         [0004]     ARMD is the leading cause of blindness in the elderly of developed countries. ARMD attacks the center of vision and blurs it, making reading, driving, and other detailed tasks difficult or impossible. About 200,000 new cases of ARMD occur each year in the United States alone. Current estimates reveal that approximately forty percent of the population over age 75, and approximately twenty percent of the population over age 60, suffer from some degree of macular degeneration. “Wet” ARMD is the type of ARMD that most often causes blindness. In wet ARMD, newly formed choroidal blood vessels (CNV) leak fluid and cause progressive damage to the retina.  
         [0005]     In the particular case of CNV in ARMD, three main methods of treatment are currently being developed, (a) photocoagulation, (b) photodynamic therapy, and (c) the use of angiogenesis inhibitors. Photocoagulation is the most common treatment modality for CNV. However, photocoagulation can be harmful to the retina and is impractical when the CNV is near the fovea. Furthermore, over time, photocoagulation often results in recurrent CNV. Photodynamic therapy is a relatively new technology. The long-term efficacy of photodynamic therapy to treat ARMD is still largely unknown. Oral or parenteral (non-ocular) administration of anti-angiogenic compounds is also being tested as a systemic treatment for ARMD. However, due to drug-specific metabolic restrictions, systemic administration usually provides sub-therapeutic drug levels to the eye. Therefore, to achieve effective intraocular drug concentrations, either an unacceptably high dose or repetitive conventional doses are required.  
         [0006]     Various needles and cannulae have been used to deliver drugs to the back of the eye, external to the globe. Examples of such needles and cannulae are disclosed in U.S. Pat. No. 6,413,245 and the references cited therein. U.S. Pat. No. 6,413,245 discloses preferred cannulae for sub-Tenon, juxtascleral delivery of a drug depot to the posterior segment of a human eye and is incorporated herein by reference. These preferred cannulae have a distal portion with a radius of curvature substantially equal to the radius of curvature of the globe of the human eye. When these cannulae are used to create such a drug depot, drug reflux may sometimes occur during or immediately after administration.  
         [0007]     A need remains in the field of ophthalmology for improved devices for the administration of an ophthalmic drug, especially to the posterior segment of the eye. Improved devices are also needed to minimize or prevent drug reflux as described above, and to facilitate drug depot placement. These improved devices should be safe for the patient, should be easy for the physician to use, and should improve the efficacy of drug administration.  
       SUMMARY OF THE INVENTION  
       [0008]     The present invention is an ophthalmic drug delivery device including a body having a plunger chamber, a first actuation chamber, and a second actuation chamber. A plunger assembly having a first sealing member is slidably disposed within the plunger chamber. The device includes a first actuation assembly having a first contact member disposed in the plunger chamber, a second sealing member slidably disposed in the first actuation chamber, and a spring member disposed between the first sealing member and the first contact member. The device also includes a second actuation assembly having a second contact member disposed in the plunger chamber and a third sealing member slidably disposed in the second actuation chamber. A cannula is fluidly coupled to the first actuation chamber and the second actuation chamber. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]     For a more complete understanding of the present invention, and for further objects and advantages thereof, reference is made to the following description taken in conjunction with the accompanying drawings in which:  
         [0010]      FIG. 1  is a front, sectional, schematic view of a drug delivery device according to a preferred embodiment of the present invention with the plunger assembly in a fully undepressed position;  
         [0011]      FIG. 2  is a fragmentary, front, sectional, schematic view of the device of  FIG. 1  with the plunger assembly in a partially depressed position;  
         [0012]      FIG. 3  is a fragmentary, front, sectional, schematic view of the device of  FIG. 1  with the plunger assembly in a fully depressed position; and  
         [0013]      FIG. 4  is a front, sectional, schematic view of a drug delivery device according to a second preferred embodiment of the present invention with the plunger assembly in a fully undepressed position. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0014]     The preferred embodiments of the present invention and their advantages are best understood by referring to  FIGS. 1-4  of the drawings, like numerals being used for like and corresponding parts of the various drawings.  
         [0015]     As shown in  FIG. 1 , drug delivery device  10  preferably includes a body  11  having a plunger chamber  12 , an actuation chamber  14 , and an actuation chamber  16 ; a plunger assembly  18  having a handle  20  and a sealing member  22 ; an actuation assembly  24  having a contact member  26  and a sealing member  28 ; an actuation assembly  30  having a spring member  32 , a contact member  34 , and a sealing member  36 ; and a cannula  38  fluidly coupled to both actuation chamber  14  and actuation chamber  16 . Device  10  is preferably sized so as to comfortably fit within a physician&#39;s hand.  
         [0016]     Sealing member  22  is in slidable, fluid tight engagement with the interior surface of plunger chamber  12 . Spring member  32  is preferably coupled to sealing member  22  on a first end and contact member  36  on a second end. Sealing member  28  is in slidable, fluid tight engagement with the interior surface of actuation chamber  14 . Sealing member  36  is in slidable, fluid tight engagement with the interior surface of actuation chamber  16 . Cannula  38  may be any conventional blunt-tip cannula or sharp-tip needle suitable for ophthalmic drug delivery. Preferred cannulae for cannula  38  for use in sub-Tenon, juxtascleral delivery of a drug depot to the posterior segment of a human eye are disclosed in U.S. Pat. No. 6,413,245.  
         [0017]     A dosage form  40  is disposed within actuation chamber  16  between sealing member  36  and cannula  38 . A dosage form  42  is disposed within actuation chamber  14  between sealing member  28  and cannula  38 . Device  10  is preferably packaged with dosage forms  40  and  42  preloaded. Alternatively, dosage forms  40  and  42  may be loaded by the user prior to administration.  
         [0018]     Dosage forms  40  and  42  may be any dosage form containing a drug or pharmaceutically active agent. Dosage forms  40  and  42  may be in liquid, semi-solid, or solid form. For example, dosage forms  40  and  42  may be a solution, a suspension, an emulsion, an ointment, a gel forming solution, a gel, a bioerodable polymer, a non-bioerodable polymer, or a powder. Preferably, dosage forms  40  and  42  include any ophthalmically acceptable pharmaceutically active agent. Examples of pharmaceutically active agents suitable for dosage forms  40  and  42  are disclosed in U.S. Pat. No. 6,416,777, which is incorporated herein by reference. One preferred pharmaceutically active agent is angiostatic steroids for the prevention or treatment of diseases or conditions of the posterior segment of the eye, including, without limitation, ARMD, CNV, retinopathies, retinitis, uveitis, macular edema, and glaucoma. Such angiostatic steroids are more fully disclosed in U.S. Pat. Nos. 5,679,666 and 5,770,592, which are incorporated herein by reference. Preferred ones of such angiostatic steroids include 4,9(11)-Pregnadien-17α,21-diol-3,20-dione and 4,9(11)-Pregnadien-17α,21-diol-3,20-dione-21-acetate. In addition, dosage forms  40  and  42  may include a combination of a glucocorticoid and an angiostatic steroid as pharmaceutically active agents. For this combination, preferred glucocorticoids include dexamethasone, fluoromethalone, medrysone, betamethasone, triamcinolone, triamcinolone acetonide, prednisone, prednisolone, hydrocortisone, rimexolone, and pharmaceuitcally acceptable salts thereof, and preferred angiostatic steroids include 4,9(11)-Pregnadien-17α,21-diol-3,20-dione and 4,9(11)-Pregnadien-17α,21-diol-3,20-dione-21-acetate. Dosage forms  40  and  42  may also comprise conventional non-active excipients to enhance the stability, solubility, penetrability, or other properties of the active agent.  
         [0019]     Device  10  is especially suitable for the delivery of a dosage form  40  and a dosage form  42  that exhibit some kind of mutual incompatibility and are best kept separate until just before delivery. In addition, dosage form  40  may include one of the ophthalmically acceptable pharmaceutically active agents suitable for localized delivery to the posterior segment of the eye mentioned hereinabove, and dosage form  42  may include a biocompatible polymer for preventing drug reflux during sub-Tenon, juxtascleral delivery of a drug depot to the posterior segment of the eye. A preferred polymer is a biocompatible, bioerodable polymer.  
         [0020]     The following describes a preferred procedure by which a physician may use drug delivery device  10  for sub-Tenon, juxtascleral delivery of a drug depot to the posterior segment of an eye. Preferred cannulae for cannula  38  for such drug delivery are disclosed in U.S. Pat. No. 6,413,245. In the superior temporal quadrant of the eye, the physician uses fine scissors to create a small incision in the conjuctiva and Tenon&#39;s capsule to bare sclera at a point about 8 mm to about 9 mm posterior to the limbus. Cannula  38  of device  10  is then inserted through the incision. The distal tip of cannula  38  is advanced along the curvature of the sclera until the tip is located in the desired position. The physician then slowly depresses head  21  of handle  20  so that sealing member  22  of plunger assembly  18  cooperates with spring member  32  and contact member  34  of actuation assembly  30  to slide sealing member  36  toward cannula  38 . As sealing member  36  is moved toward cannula  38 , dosage form  40 , which contains an appropriate pharmaceutically active agent, is slowly dispensed from cannula  38  to create a drug depot on the outer surface of the sclera below the Tenon&#39;s capsule. When sealing member  36  reaches the position shown in  FIG. 2 , spring member  32  is partially compressed, substantially all of dosage form  40  has been dispensed from cannula  38 , and all of dosage form  42  remains in actuation chamber  14 . The spring force of spring member  32  may be optimized for different volumes, forms, viscosities, and delivery rates of dosage form  40 . As the physician continues to slowly depress head  21  of handle  20 , sealing member  22  then cooperates with contact member  26  of actuation assembly  24  to slide sealing member  28  toward cannula  38 . As sealing member  28  is moved toward cannula  38 , dosage form  42 , which contains a biocompatible, bioerodable polymer, is slowly dispensed from cannula  38  to seal the sub-Tenons space anterior to the drug depot and prevent reflux of dosage form  40 . When sealing member  28  reaches the position shown in  FIG. 3 , spring member  32  is fully compressed, and substantially all of dosage form  42  has been dispensed from cannula  38 . The physician slowly withdraws cannula  38  from the incision. The physician then applies an antibiotic ointment, and optionally applies a pressure patch to the incision.  
         [0021]     As shown in  FIG. 4 , drug delivery device  10   a  has a substantially identical structure to device  10  with the exception that actuation chambers  14  and  16  are formed adjacent to one another instead of with a space therebetween like in device  10 . The operation of device  10   a  is substantially identical to the operation of device  10 .  
         [0022]     From the above, it may be appreciated that the present invention provides an improved device for the administration of an ophthalmic drug, especially to the posterior segment of the eye. The device of the present invention also minimizes or prevents drug reflux during ophthalmic drug delivery. The device is safe for the patient, easy for the physician to use, and improves the efficacy of drug administration.  
         [0023]     The present invention is illustrated herein by example, and various modifications may be made by a person of ordinary skill in the art. For example, although the use of the device of the present invention is described above in connection with sub-Tenon, juxtascleral delivery of a drug depot to the posterior segment, it can also be utilized in connection with other ophthalmic or non-ophthalmic drug delivery. As another example, handle  20  may be replaced with an automated assembly for displacing sealing member  22 , if desired.