Abstract:
A delivery system includes a housing along with a tip connected to one end of the housing. A first cannula extending from the tip is provided for inserting a rod implant into tissue. A second cannula, concentrically disposed within the first cannula, is utilized to force the rod implant from the first cannula and for ejecting a fluid behind the inserted rod implant in the tissue.

Description:
[0001]    The present invention relates to methods and apparatus for delivering solid or semi-solid materials into the eye. Specifically, the present invention relates to a drug delivery system and methods that can be used to introduce implants containing therapeutic or active agents, including bioerodible implants, into various locations within the eye, including into the vitreous of the eye. 
         [0002]    A primary difficulty in treating diseases of the eye is the inability to introduce drugs or therapeutic agents into the eye and maintain these drugs or agents at a therapeutically effective concentration in the eye for the necessary duration. Systemic administration may not be an ideal solution because, often, unacceptably high levels of systemic dosing is needed to achieve effective intraocular concentrations, with the increased incidence of unacceptable side effects of the drugs. Simple ocular instillation or application is not an acceptable alternative in many cases because the drug may be quickly washed out by tear-action or is otherwise depleted from within the eye into the general circulation. Suprachoroidal injections of drug solutions have also been performed, but again the drug availability is short-lived. Such methods make it difficult to maintain therapeutic levels of drug for adequate time periods. 
         [0003]    Efforts to address this problem have lead to the development of drug delivery devices, or implants, which can be implanted into the eye such that a controlled amount of desired drug can be released constantly over a period of several days, or weeks, or even months. Many such devices have been previously reported. See, for example, U.S. Pat. No. 4,853,224, which discloses biocompatible implants for introduction into an anterior segment or posterior segment of an eye for the treatment of an ocular condition. U.S. Pat. No. 5,164,188 discloses a method of treating an ocular condition by introduction of a biodegradable implant comprising drugs of interest into the suprachoroidal space or pars plana of the eye. See also U.S. Pat. Nos. 5,824,072, 5,476,511, 4,997,652, 4,959,217, 4,668,506, and 4,144,317. Other method includes anchoring a plug or tack containing a drug into the sclera of the eye (see, e.g. U.S. Pat. No. 5,466,233). 
         [0004]    Various sites exist in the eye for implantation of a drug delivery device or implant, such as the vitreous of the eye, anterior or posterior chambers of the eye, or other areas of the eye including intraretinal, subretinal, intrachoroidal, suprachoroidal, intrascleral, episcleral, subconjuctival, intracorneal or epicorneal spaces. Wherever the desired location of implantation, typical methods of implantation all require relatively invasive surgical procedures, pose a risk of excessive trauma to the eye, and require excessive handling of the implant. For example, in a typical method for placement in the vitreous, an incision is made through the sclera, and the implant is inserted into and deposited at the desired location in the vitreous, using forceps or other like manual grasping device. Once deposited, the forceps (or grasping device) is removed, and the incision is sutured closed. Alternatively, an incision can be made through the sclera, a trocar can be advanced through the incision and then the implant can be delivered through the trocar. Similar methods can be employed to deliver implants to other locations, e.g., implantation in the anterior chamber of the eye through an incision in the cornea. 
         [0005]    The drawbacks of such techniques for implant delivery are many-fold. Extensive handling of the implant is necessary in these techniques, creating a risk that the implant will be damaged in the process. Many such implants are polymer-based and are relatively fragile. If portions of such plants are damaged and broken-off, the effective therapeutic dose delivered by the implant once placed will be significantly altered. In addition, it becomes inherently difficult using these methods to achieve reproducible placement from patient to patient. Also of import is that fact that all such techniques require an incision or puncture in the eye large enough to require suturing. Thus, such techniques are typically performed in a surgical setting. 
         [0006]    U.S. Pat. No. 6,899,717 provides for an ergonomically designed apparatus in which a simple manual depression of an actuator produces proportional movement of a linkage that causes an implant or micro-implant (Drug Delivery System, DDS) to be ejected through an applicator cannula and disposed at the desired location in the eye. Small gauge cannulas are provided for self-sealing methods of delivery. 
         [0007]    However, it has been found that a DDS deposited at a desired location in the vitreous does not remain at the desired location but may track back with the applicator cannula during withdrawal of the cannula. It has been concluded that the viscous property of the vitreous humor appears to be the cause of the attraction between the DDS and the application cannula. 
         [0008]    The present invention overcomes this problem with two mechanisms. 
         [0009]    The first mechanism provides a stylet that pushes the DDS out from a needle into the vitreous and the second mechanism provides for the injection of a viscous material from the same stylet. The viscous material plugs up the channel of the needle in the vitreous and accordingly prevents the DDS from tracking back with the applicator cannula during withdrawal. 
       SUMMARY OF THE INVENTION 
       [0010]    An embodiment of delivery system for intraocular (such as intravitreal) administration of one or more solid or semi-solid implants to the eye of a patient in accordance with the present invention may include a housing with a tip connected to one end of the housing along with a first cannula extending from the tip for inserting a rod implant into tissue. 
         [0011]    A second cannula may be concentrically disposed within said first cannula for forcing said rod implant out of the first cannula and for ejecting a fluid behind the insertion rod implant in said tissue. 
         [0012]    A rod implant may also be part of the present invention along with a fluid which may be a viscous material or have a viscous inducing component such as for example a polymeric high molecular weight hyaluronic acid, carbomers, polyacrylic acid, cellulosic derivatives, polycarbophil, polyvinylpyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, derivatives thereof and mixtures thereof. 
         [0013]    A first piston may be provided and slidably disposed within the housing along with a first plunger fixed to the first piston and also slidably disposed within the housing for ejecting the rod implant, disposed in the first cannula lumen, from the first cannula lumen by movement of the first plunger and first piston toward the tip. 
         [0014]    A second cannula may be provided which extends from the first piston and is concentrically disposed within the first cannula and extendable through the first cannula lumen for forcing the rod implant out of the first cannula lumen as the first plunger is moved toward the tip. 
         [0015]    A second piston may be provided and slidably disposed within the first plunger and a chamber is defined between the first piston and second piston within the first plunger. The second cannula is in fluid communication with the chamber and a second plunger, fixed to the second piston, is provided for ejecting the fluid, disposed in the chamber, through the second cannula by movement of the second plunger and the second piston toward the tip. 
         [0016]    Preferably, the first cannula has an angulated end for facilitating penetration of tissue and the second cannula has a blunt end to facilitate engagement with the implant rod. The fluid comprises a viscous material for stabilizing the ejected rod implant. 
         [0017]    A method in accordance with the present invention for implanting a drug delivery system rod into the vitreous of an eye generally includes disposing a drug delivery system rod into the vitreous of an eye and stabilizing a position of the rod in the vitreous by a viscous material. More particularly, the rod may be implanted through a first cannula lumen and the viscous material is ejected into the vitreous proximate the rod by a second cannula. 
         [0018]    The method further includes using a second cannula to push the rod out of the first cannula lumen and such action is performed before ejecting the viscous material proximate the rod which may not only stabilize the rod within the viscous but also further push the rod into the vitreous. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0019]    The advantages and features of the present invention will be better understood by the following detailed description when considered in connection with the accompanying drawings, in which: 
           [0020]      FIG. 1  is a perspective view of an applicator in accordance with the present invention generally showing a housing, a tip connected to one end of the housing, first and second pistons, first and second cannulas, and first and second plungers; 
           [0021]      FIG. 2  is a cross sectional view of the applicator shown in  FIG. 1 ; 
           [0022]      FIG. 3  is an enlarged cross sectional view of the applicator tip and cannulas illustrated in  FIGS. 1 and 2 ; 
           [0023]      FIG. 4  is a cross sectional view illustrating the use of the applicator in injecting a rod implant into tissue; and 
           [0024]      FIG. 5  is a view similar to  FIG. 4  illustrating the stabilization of the rod within the tissue by a viscous material. 
       
    
    
     DETAILED DESCRIPTION 
       [0025]    With reference to  FIGS. 1-5 , there is shown a syringe needle stylet drug delivery system intravitreal implant applicator  10  in accordance with the present invention which generally includes a housing  14  which may be formed from any suitable material and is preferably transparent in order to visualize the position of a first piston  16  and plunger  18  therein. A tip  22  is connected to one end  24  of the housing  14  by means of threads  28 , or the like, (See  FIG. 2 ) and a first cannula  30  extends from the tip  22  which includes a lumen  32  therethrough, as most clearly seen in  FIG. 3 . Preferably, the first cannula  30  is angulated for facilitating a penetration of vitreous  34  illustrated in  FIGS. 4 and 5 . 
         [0026]    With continued reference to  FIG. 3 , a rod implant  38 , disposed within the first lumen  32 , is ejected therefrom by a second cannula  42  which extends through the first cannula lumen  32  and forces the rod implant  38  out of the first cannula lumen  32  as the first piston  16  and plunger  18  is moved toward the tip  22 . This is illustrated in  FIG. 4  by the arrows  46 . Suitable rod implants and method of manufacturing same is set forth in U.S. patent application Ser. No. 11/859,627, filed Sep. 21, 2007 and entitled “Steroid Containing Drug Delivery Systems”. This patent is to be incorporated herein in its entirety by this specific reference thereto. 
         [0027]    Providing the second cannula  42  with a blunt end  50  facilitates ejection of the rod  38 . The rod  38  and may be an intravitreal drug delivery system (DDS) such as Posurdex and the Brimonidine. A housing handle  56  and a first plunger handle  58  facilitate the manual movement of the first plunger  18  and the first piston  16  for ejecting the DDS rod  38  through the first cannula  30 . 
         [0028]    A second piston  64  is disposed within the first plunger  18  and interconnected to a second plunger  66  and handle  68 . Initially defined between the first piston  16  and second piston  64  is a chamber  74  for containing any biocompatible viscous material, such as, for example, Healon. 
         [0029]    Alternatively, the fluid may include any suitable viscosity inducing component such as, for example, but are not limited to, a polymeric high molecular weight hyaluronic acid, carbomers, polyacrylic acid, cellulosic derivatives, polycarbophil, polyvinylpyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, derivatives thereof and mixtures thereof. 
         [0030]    The viscosity-inducing component may be a polymeric hyaluronate component, for example, a metal hyaluronate component, preferably selected from alkali metal hyaluronates, alkaline earth metal hyaluronates and mixtures thereof, and still more preferably selected from sodium hyaluronates, and mixtures thereof. Such components are described and set forth in U.S. Ser. No. 11/859,621 hereinabove referenced and incorporated herein. 
         [0031]    In addition, the delivery of an active agent or implant described in U.S. Ser. Nos. 10/966,764, 11/741,366, 11/039,192, 11/116,698, 11/695,527; 60/939,659 and 11/742,350 which are to be incorporated herein in their entirety by this specific reference thereto. 
         [0032]    As illustrated, the second cannula  42  is in fluid communication with the chamber  74  for enabling ejection of the fluid, or viscous material,  78  through the second cannula  42  by movement of the second plunger  66  and second piston  64  toward the tip  22  as illustrated by the arrow  84 . 
         [0033]    As shown in  FIG. 5  the viscous material  78 , forced from the second cannula  42  behind the rod  38 , both stabilizes the rod  38  and prevents movement thereof as the applicator  10  with cannulas  30  and  42  are withdrawn from the vitreous  34 . In addition, the viscous material  78  may further force the rod  38  into the viscous  34  to a desired location. 
         [0034]      FIGS. 4 and 5  further illustrate a method of implanting a drug delivery system rod into the vitreous of an eye in accordance with the present invention. This method generally includes disposing a drug delivery system rod into the vitreous of an eye and stabilizing a position of the rod in the vitreous by a viscous material. The rod is implanted through a first cannula lumen  32  through the use of the second cannula  42  for pushing the rod  38  out of the first cannula lumen  32 . 
         [0035]    As illustrated in  FIG. 5 , the viscous material  78  is injected into the vitreous  34  proximate the rod  38  via the second cannula  42 . Further pushing of the rod  38  in the vitreous  34  may be accomplished by continued movement of the second piston  64  and second plunger to force more of the viscous material  78  behind the rod  38 . After injecting of the viscous material  78  the applicator  10  is removed from the viscous  34 . 
         [0036]    Although there has been hereinabove described a specific drug delivery system and methods in accordance with the present invention for the purpose of illustrating the manner in which the invention may be used to advantage, it should be appreciated that the invention is not limited thereto. That is, the present invention may suitably comprise, consist of, or consist essentially of the recited elements. Further, the invention illustratively disclosed herein suitably may be practiced in the absence of any element which is not specifically disclosed herein. Accordingly, any and all modifications, variations or equivalent arrangements which may occur to those skilled in the art, should be considered to be within the scope of the present invention as defined in the appended claims.