Patent Publication Number: US-2007112316-A1

Title: Cochlear drug delivery system and method

Description:
This continuation application claims the benefit of U.S. patent application Ser. No. 10/389,251 filed on Mar. 14, 2003, and also U.S. Provisional Patent Application No. 60/364,431, filed Mar. 15, 2002, each of which are incorporated by reference in their entirety herein. 
    
    
     BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      The present invention relates generally to treatment of target disease areas of the body, including inner ear disorders, such as Meniere&#39;s disease, tinnitus, and hearing loss. More particularly, the present invention relates to a method and apparatus for administering medication to the disease target area, such as the middle ear and/or inner ear (or cochlea).  
      2. Related Art  
      Various situations or medical conditions of the inner ear require the administration of drugs or like medicines to the middle ear. Such medical conditions or inner ear disorders can include sudden neurosensory hearing loss, Meniere&#39;s disease, and tinnitus. These conditions affect up to 40 million persons in the United States, and are the cause of significant loss of productivity and quality of life. Costs to the U.S. military related to treatment of sudden neurosensory hearing loss are estimated at 1.5 billion dollars per year.  
      For example, Meniere&#39;s disease, also known as idiopathic endolymphatic hydrops, is classified as an inner ear disorder. Meniere&#39;s disease is characterized by episodic rotational vertigo (spinning sensation or dizziness), hearing loss, tinnitus (ringing, buzzing or roaring in the ears), and a sensation of pressure or fullness in the ear. The vertigo of Meniere&#39;s disease occurs in attacks of a spinning sensation, and is accompanied by dysequilibrium (an off-balance sensation), nausea, and vomiting. The vertigo lasts from 20 minutes to 2 hours (or more), during which the person is unable to perform normal activities.  
      Sudden neurosensory hearing loss, Meniere&#39;s disease, and tinnitus usually may be treated medically or surgically. Various medications may be taken in conjunction with a low salt diet. Such medications include urea, glycerol, isosorbide, diuretics (dyazide), acetazolamide (Diamox), steroids (prednisone or dexamethasone), antibiotics (gentamycin), calcium channel blockers (Fluanarizine or Cinnarzine), niacin, betahistine (Serc), or anesthetics.  
      One disadvantage with medications is that they are often administered orally or intravenously, each of which results in a systemic administration of the medication. Systemic administration of medication is problematic in some applications in that the medication is distributed throughout much of the patient&#39;s body. By distributing the medication throughout the patient&#39;s body, concentrations of the medication vary in different parts of the body. For instance, the concentration of the medication may be low in one area of the body but relatively high in other areas.  
      It is generally advantageous to treat a diseased portion of the body with a therapeutic concentration of the medication being administered, that is, a concentration high enough to effectively treat the condition but not so high as to reach a toxic level. However, it is often the case that systemic administration of medication is problematic in that the desired therapeutic level of medication is delivered to the diseased portion of the body that is being treated, but higher than therapeutic levels are delivered to other parts of the body. This can lead to the serious and undesirable result of systemic toxicity.  
      Surgical procedures used to treat these conditions include endolymphatic shunt, insertion of a Tympanostomy tube, sacculotomy, cochleosacculotomy, endolymphatic sac surgery, chemical labyrinthectomy with antibiotics, surgical labyrinthectomy, and vestibular nerve section surgery. The endolymphatic shunt procedure drains excess fluids from the inner ear. An incision is made behind the ear, through the mastoid, and a tube is inserted.  
      Insertion of a Tympanostomy tube is a minor procedure in which a tiny tube is inserted and maintained in a hole through the eardrum. Sacculotomy and cochleosacculotomy are also relatively minor procedures which involve perforation of the saccule through the stapes footplate (sacculotomy), or through the round window, via the basilar membrane (cochleosacculotomy).  
      Endolymphatic sac surgery includes: endolymphatic sac decompression, in which bone overlying the endolymphatic sac is drilled away to make a larger cavity for the sac; endolymph-subarachnoid shunt, which involves placing a tube between the endolymphatic sac and the cranium; endolymph-mastoid shunt, which involves placing a tube between the endolymphatic sac and the mastoid cavity; and endolymphatic sac ablation, which completely destroys the endolymphatic sac.  
      Chemical labyrinthectomy destroys the vestibular system, or vestibular hair cells, using certain antibiotics. Surgical labyrinthectomy is the surgical destruction of either a portion or the entire labyrinth. Finally, vestibular nerve section surgery cuts the nerve from the vestibular apparatus.  
      One disadvantage with surgical treatment is the expense and invasiveness of surgery. In addition, many of the surgical procedures used for treating these disorders are considered controversial.  
     SUMMARY OF THE INVENTION  
      It has been recognized that it would be advantageous to develop a system and method for treating diseased target areas of the body, including inner and/or middle ear disorders, such as sudden neurosensory hearing loss, Meniere&#39;s disease, and tinnitus. In addition, it would be advantageous to develop such a system and method for delivering drugs directly to the middle ear and cochlea and to diseased target areas in the head and neck area. In addition, it would be advantageous to develop such a system and method that is convenient, unobtrusive, and inexpensive.  
      The present invention provides a drug administration system configured to administer a drug to a user&#39;s ear, and includes a housing, sized and shaped to substantially fit behind the user&#39;s ear to pump the drug in controlled amounts to the user&#39;s middle ear. A drug reservoir can also be included and can be disposed in the housing and can include a drug configured to treat an inner ear condition. A catheter can be operatively coupled to the drug reservoir and can be sized and shaped to extend from the drug administration unit and into the user&#39;s middle ear.  
      In accordance with another aspect of the invention, the invention provides a drug administration system configured to administer a drug to a diseased target area of a user&#39;s body. The system can include a housing, sized and shaped to substantially fit behind the user&#39;s ear to pump the drug in controlled amounts to the diseased target area of the user&#39;s body. A drug reservoir can be disposed in the housing and can include a drug configured to treat the diseased target area. A catheter can be operatively coupled to the drug reservoir and can be sized and shaped to extend from the drug administration unit and into the user&#39;s body. The catheter can include a section at least partially disposed adjacent the diseased target area.  
      In accordance with another aspect of the invention, the invention provides a method for administering a drug to a user&#39;s ear, the method including the steps of: a) disposing a drug administration unit behind the user&#39;s ear, the drug administration unit including a drug reservoir containing a drug configured to treat an inner ear condition, and a catheter operatively coupled to the drug reservoir; b) disposing the catheter inside the user&#39;s ear; and c) dispensing the drug from the drug reservoir, through the catheter, and into the user&#39;s ear.  
      In accordance with another aspect of the invention, the invention provides a method for administering a drug to a diseased target area of a user&#39;s body, the method including the steps of: a) disposing a drug administration unit behind the user&#39;s ear, the drug administration unit including a drug reservoir containing a drug configured to treat the diseased target area, and a catheter operatively coupled to the drug reservoir; b) disposing at least a section of the catheter adjacent the diseased target area; and c) dispensing the drug from the drug reservoir, through the catheter, and to the diseased target area.  
      Additional features and advantages of the invention will be apparent from the detailed description which follows, taken in conjunction with the accompanying drawings, which together illustrate, by way of example, features of the invention. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a schematic view of an embodiment of a drug delivery system in accordance with the present invention;  
       FIG. 2  is a schematic view of the drug delivery system of the present invention;  
       FIG. 3  is a side view of an embodiment of a drug administration unit in accordance with the present invention disposed behind a user&#39;s ear;  
       FIG. 4  is a side view of another embodiment of a drug administration unit in accordance with the present invention disposed behind a user&#39;s ear;  
       FIG. 5  is a cross-sectional view of a user&#39;s ear with a catheter in accordance with an embodiment of the drug delivery system; and  
       FIG. 6  is a cross-sectional view of a user&#39;s ear with another catheter in accordance with an embodiment of the present invention. 
    
    
     DETAILED DESCRIPTION  
      Reference will now be made to the exemplary embodiments illustrated in the drawings, and specific language will be used herein to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Alterations and further modifications of the inventive features illustrated herein, and additional applications of the principles of the inventions as illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, are to be considered within the scope of the invention.  
      As illustrated in  FIGS. 1 and 2 , a drug administration system, indicated generally at  10 , in accordance with the present invention is shown for administering a drug to a user&#39;s middle or inner ear, or the user&#39;s cochlea. The system  10  includes a drug administration unit  14 , and a catheter  16  operatively or fluidly coupled to the drug administration unit  14  and extending to the user&#39;s middle ear. The system  10  also can include a separate programmer  18  and a database  22 . Although the system and method of the present invention are described and illustrated with particular reference to treating Meniere&#39;s disease, it is of course understood that the system and method can be applied to other diseases or treatments. The drug administration unit  14  can be configured to pump any drug or medicament desired.  
      The drug administration unit  14  pumps a drug from a drug reservoir  30  to the user. The drug can be pumped by a pump  34  through the catheter  16  which can have a proximal end operatively or fluidly coupled to the pump  34 . The catheter  16  can have a distal end inserted through the user&#39;s ear canal and ear drum, as discussed in greater detail below. Alternatively, the catheter can be inserted through the skin behind the outer ear and navigated into the middle ear. The drug can include gentamycin, steroids, gene vectors, apoptotic agents, regenerative agents, and the like.  
      The drug administration unit  14  also can include a controller  54  coupled to the driver or motor  46  to control the motor, and thus the pump  34 . The controller  54  also can be electrically coupled to the power source  50 . The controller  54  can include control electronics or circuitry, such as a microprocessor, and memory to store operating instructions and/or performance information, as is known in the art. A driver or motor  46  can be connected to drive the pump  34 . A power source  50 , such as a battery, can be connected to power the motor  46 , and thus the pump  34 .  
      Alternatively, the drug administration unit  10  can include a pressure reservoir  56  operatively coupled to the drug reservoir  30  to drive or expel the drug out of the drug reservoir  30 . For example, the pressure reservoir  56  can include a gas or fluid under pressure, and can bear against the drug reservoir  30 , such as through a diaphragm. Alternatively, the drug reservoir itself can be pressurized, in which case a dosing valve can be disposed between the pressurized reservoir and the catheter. Of course, a dosing valve can also be utilized in those embodiments that do not include a pressurized reservoir.  
      The motor  46  and pressure reservoir  30  are examples of a means for pumping, forcing, dispelling and/or dispensing the drug from the drug reservoir. It is of course understood that other means can be used, including for example, mechanical springs exerting a force against the drug reservoir, an electric motor, a spring wound motor, a chemical reaction source creating a pressure, etc.  
      In addition, the drug administration unit  10  can include a control valve  58  operatively coupled to the drug reservoir  30 , the pump  34 , or the catheter  16 . The control valve  58  can control the rate of drug delivery. The controller  54  can be operatively coupled to the control valve  58  to control the valve, and thus the delivery of the drug.  
      The drug administration unit  14  can include a housing  62  which houses the reservoir  30 , the pump  34 , the motor  46  (or pressure reservoir  56 ), the power source  50 , the controller  54  and the control valve  58 . In one aspect, the drug administration unit  14  or the housing  62  is sized to be relatively small, and thus can be inconspicuous.  
      Referring to  FIGS. 3 and 5 , the housing  62  can be shaped, sized, and configured to substantially fit behind the user&#39;s ear  64 . Thus, the housing  62  can be substantially un-noticeable behind the user&#39;s ear  64 , or can be concealed behind the user&#39;s ear. The housing  62 , or drug administration unit  14 , can have a teardrop shape, or lima bean shape, as shown, to conform to the contours of the user&#39;s ear, and help conceal the housing  62  behind the user&#39;s ear  64 . In one aspect, a majority of the housing  62  is hidden by the user&#39;s ear  64 . An inconspicuous housing  62  or drug administration unit  14  can have a distinct advantage over larger, more conspicuous drug pumps, especially for younger users who are particularly concerned with appearance and being accepted by peers.  
      The drug administration unit  14  advantageously can be directly attached to the user&#39;s ear  64  or head. Referring to  FIGS. 1 and 3 , the drug administration unit  14  has an arcuate earpiece  66  extending from the housing  62  and which is sized and shaped to extend over the user&#39;s ear  64 , or over an attachment between the user&#39;s ear and the user&#39;s head, to secure the drug administration unit  14  behind the user&#39;s ear  64 . The earpiece  66  may be a separate member attached to the housing  62 , or may be formed integrally with the housing  62 . Alternatively, an adhesive pad  67  ( FIG. 5 ) can be disposed on the housing  62  to adhere the housing  62  to the user&#39;s skin behind the ear. An earpiece or an adhesive pad are examples of attachment means for attaching the housing  62  or drug administration unit  14  behind the user&#39;s ear  64 . It is of course understood that any means for attaching may be used, including for example, a ring fitting around the user&#39;s ear, a portion of the user&#39;s eye glasses, etc.  
      As indicated above, the catheter  16  is operatively or fluidly coupled to the drug administration unit  14 . A first or proximal end of the catheter  16  can be operatively or fluidly coupled to the pump  34  or drug reservoir  30 , while a second or distal end can be disposed in the user&#39;s middle ear. The catheter  16  can be coupled to the housing  62  opposite the ear piece  66 , and sized and shaped to extend under the user&#39;s ear  64  (such as between the ear lobe and head) and into the ear  64 , as shown in  FIGS. 3 and 5 . Referring to  FIG. 5 , the catheter  16  can be sized and shaped to extend through the user&#39;s ear canal  68  and ear drum  70 , and into the user&#39;s middle ear  72 .  
      Thus, in one embodiment, the catheter  70  has a length less than approximately 10 cm. However, in alternative embodiments the catheter can be of any length. For instance, the present invention can be used to deliver medication to target areas other than the ear near which the system is disposed. Such target areas can include head, neck, eyes, nose, throat, the contralateral ear, etc. Of course, utilizing the system for treatment of various diseased target areas may require a variety of catheter lengths to adequately reach the target area while the drug delivery system is held relatively motionless behind the user&#39;s ear. The system can be advantageously used in these applications to provide the patient with mobility while remaining substantially concealed behind the ear. In this embodiment, the patient is provided with a greater level of mobility than conventional methods and relative movement between features of the drug delivery system is reduced to a minimum.  
      In one aspect, a distal end  74  of the catheter  16  is configured to be disposed in the middle ear  72 , adjacent the circular window  76  of the cannula  78 . Thus, the catheter  16  may deliver the drug to the cannula  78 . Alternatively, the distal end  74  of the catheter  16  may be configured to deliver a drug to other locations in the middle ear  72  or inner ear  80 . In addition, in one embodiment the drug administration unit can be implanted under the patient&#39;s skin.  
      In addition, referring to  FIG. 6 , a catheter  16   b  can be configured to circulate the drug to maintain a constant concentration of the drug at the distal end  74 , and thus at the circular window  76 . The catheter  16   b  may form a loop with a distal end of the loop disposed at the round window. Thus, the catheter  16   b  can include two hollows or lumens, one for delivery and one for return. In the embodiment just described, the catheter includes a “closed loop” catheter which includes means for circulating the drug between the catheter and various components of the drug delivery system. In addition, the catheter can also include any type of catheter known in the art. Thus, as used herein, the term “closed loop” shall be understood to include systems that provide for circulation of the drug being delivered between the catheter and various components of the drug delivery system. A conventional catheter can also be used, wherein the catheter may terminate in a membrane which serves to deliver the medication at a controlled rate, but does not include a path for otherwise returning or circulating the medication.  
      The drug reservoir  30  can be sized to contain approximately a one-month supply of the drug. In addition, the entire drug administration unit  14  can be designed to be disposable after the drug supply is depleted, or after about a month. It is anticipated that the entire drug administration unit  14  and catheter  16  can be removed and disposed.  
      Alternatively, the pump  34  and reservoir  30  can be removably disposed in the drug administration unit  14  or housing  62 , and can be removed and disposed after use. Similarly, the catheter  16  also can be removed and disposed. A new reservoir  30 , pump  34 , and catheter  16  can then be disposed in the drug administration unit  14 . Thus, any component that has fluid contact with the user&#39;s body can be disposed of after use. The motor  46 , power source  50 , controller  54 , and/or housing  62  can be reusable. Thus, the reservoir  30  and pump  34  are disposable for health reasons, while the motor  46 , power source, and controller  54  can be reusable for cost effectiveness. Similarly, the pressure reservoir  56  can be removably disposed in the housing  62 , and can be replaceable as required.  
      As indicated above, the drug administration unit  14  and housing  62  can be small and inconspicuous. Thus, the pump  34  itself can be relatively small. For example, the pump  34  may have a stroke volume of 1 μl (microliter). In addition, the pump  34  should be accurate (1% to 5%) and reliable. In one embodiment, the pump  34  can have a dose range of 1-100 1 μl/hr, while in other embodiments, the dose range can be above or below this range.  
      The pump  34  can be a micromotor-driven, micropiston pump, as described in U.S. Pat. Nos. 5,944,495; 5,941,533; 5,931,647; 5,799,690; 5,710,401; 5,647,575; 5,632,606; 5,618,163; 5,603,354; and 5,556,263, which are herein incorporated by reference.  
      The programmer or control unit  18  advantageously can be physically separate from the drug administration unit  14 , thus further reducing the size of the drug administration unit  14 . The programmer  18  can control, or provide the operating instructions, to the drug administration unit  14 , or controller  54  thereof. Thus, although physically separated, the programmer  18  and drug administration unit  14  can be operatively coupled, or can be in communication, as described in greater detail below.  
      The programmer  18  can include a manual input device  90 , such as a keypad, to receive manual instructions from a user. The programmer  18  also can include a visual display  92  to display information. In one aspect, the programmer  18  can include a programmer controller  94  for calculating or determining a drug dose, and appropriate operating instructions for the drug administration unit  14  to achieve the calculated dose. Memory  96  can be connected to the programmer controller  94  to store the operating instructions for the drug administration unit  14 , and any performance information from the drug administration unit  14 . A power source  98 , such as a battery, can be connected to the programmer controller  94 .  
      The programmer  18  can be controlled with a variety of control units. For instance, the control unit may be comprised of a PDA or similar device which provides integration and communication between the programmer and various components of the drug administration unit. Utilizing a PDA or similar device can enable the programmer to be controlled by the user, and can be tailored to various levels of user sophistication. Of course, any suitable programmer can be used with the present invention. In addition, the PDA itself can be used as a programmer.  
      As indicated above, the programmer  18  and drug administration unit  14  can be operatively coupled, or can be in communication, so that operating instructions determined by the programmer  18 , or programmer controller  94 , can be communicated or transferred to the drug administration unit  14 , or controller  54 . Thus, the programmer  18  and drug administration unit  14  can include communication devices  100  and  102 , respectively, configured to transmit and/or receive information. The programmer  18  and drug administration unit  14  can be electrically coupled by an electronic cable  104 , which is removably connected to respective data ports  106  and  108 . Thus, the operating instructions from the programmer controller  94  can be transmitted by the cable  104  to the controller  54 . Alternatively, the programmer  18  and drug administration unit  14  can communicate wirelessly, or utilize wireless communications. For example, the communication devices  100  and  102  can be wireless, or can include transmitter/receivers for transmitting and/or receiving radio frequencies (RF), acoustic waves, or infrared (IR), indicated by  110 . In addition, performance information from the drug administration unit  14  can also be transmitted to the programmer  18 .  
      The cable  104  or transmitter/receivers are examples of means for operatively coupling the programmer  18  and the drug administration unit  14  or controller  54 , and for transferring instructions from the programmer to the controller, or to and from the controller  94  or memory  96  of the programmer and the controller  54  or memory of the drug administration unit. In addition, performance information can be transferred from the drug administration unit  14  to the programmer  18 . It is of course understood that any means for transferring may be utilized, including for example, any type of electromagnetic radiation, vibrations, magnetism, etc.  
      As indicated above, the separate programmer  18  allows certain components, such as the input device  90 , display  92 , programmer controller  94 , etc., to be physically separated from the drug administration unit  14  so that the drug administration unit  14  can be as small as possible, and thus easy to conceal. In addition, the separate programmer  18  allows important operating or control components, such as the input device  90 , to be removed from the drug administration unit  14  to prevent tampering, such as may happen with a younger user.  
      The programmer  18  also includes a housing  112  which houses the input device  90 , display  92 , programmer controller  94 , power supply  98 , memory  96 , and communication device  100 . The input device  90  can include one or more push-type buttons for receiving input or instructions in response to prompts on the display  92 . Alternatively, the display  92  and input device  90  may be integrated to form touch-screen-type display and input.  
      In one aspect, the programmer  18 , or memory  96 , stores or records the dose information, such as time and date, and drug dose. Furthermore, a record of several entries of drug dose for different dates and times preferably are recorded. These records may then be downloaded to a database  22 , such as in a computer, for further analysis by the user, doctor, or healthcare professional. As described above, the records in the memory  96  may be transferred over an electric cable  120 , or RF or IR transmission, indicated by  122 . Thus, the records can be sent via phone-line or remotely. The records allow the doctor or healthcare professional determine whether adjustments need to be made in the drug doses, etc.  
      Referring to  FIG. 4 , another drug administration unit  130  is shown which is similar in many respects to that described above. The unit  130  includes an arcuate earpiece  132  for securing the unit  130  to the user&#39;s ear  64 . A catheter  134  extends along the earpiece  132  and into the user&#39;s ear  64 . The catheter  134  can be partially disposed within the earpiece  132 , or can be disposed externally of the earpiece  132 . In addition, the catheter  134  can have a rigid portion which itself forms the earpiece  132 .  
      Referring again to  FIG. 1 , the drug administration unit  14  can have a manual input device, such as buttons  140 , to act as emergency override controls. Thus, the buttons  140  can be electrically coupled to the motor controller  54  and/or power source  50  to stop operation of the motor  46 , and thus the pump  34 .  
      A method for using the above-described system, and for administering a drug to a user&#39;s ear, includes disposing the drug administration unit behind the user&#39;s ear, and disposing the catheter inside the user&#39;s ear. For example, an arcuate earpiece can be disposed over the user&#39;s ear, and a distal end of the catheter can be disposed through the user&#39;s eardrum. The drug can be dispensed from the drug reservoir, through the catheter, and into the user&#39;s ear. The drug can be dispensed by pumping the drug from the drug reservoir with a pump disposed in the housing and operatively coupled to the drug reservoir. Alternatively, the drug can be dispensed by forcing the drug from the drug reservoir with a pressure reservoir disposed in the housing and operatively coupled to the drug reservoir.  
      Operating instructions can be provided to the drug administration unit from a programmer that can be physically separate from the drug administration unit. The drug can be controlled with a control valve operatively coupled between the drug reservoir and the catheter. Drug delivery information can be obtained from the drug administration unit, and stored in a database.  
      It is to be understood that the above-referenced arrangements are illustrative of the application for the principles of the present invention. Numerous modifications and alternative arrangements can be devised without departing from the spirit and scope of the present invention while the present invention has been shown in the drawings and described above in connection with the exemplary embodiments(s) of the invention. It will be apparent to those of ordinary skill in the art that numerous modifications can be made without departing from the principles and concepts of the invention as set forth in the claims.