Patent Document

BACKGROUND OF THE INVENTION  
         [0001]    The present invention relates to a device and method for delivering a drug directly to an interior portion of a mammalian body. More particularly, the present invention relates to an improved drug injection device and method which is operable to effectively and easily inject a sustained release drug implant into thin tissues, such as the sclera of an eye, for example.  
           [0002]    Over the years, various drugs have been developed to assist in the treatment of a wide variety of ailments and diseases. However, in many instances such drugs are not capable of being administered either orally or intravenously without the risk of various detrimental side effects.  
           [0003]    CMV retinitis is a disease that is characterized by inflammation of the retina caused by infection with cytomegalovirus. CMV retinitis is one of the most common causes of sight-threatening infections among people with HIV. The symptoms include loss of visual acuity, blind spots, and the loss of peripheral vision. Left untreated, CMV retinitis can lead to blindness.  
           [0004]    Intravenous ganciclovir (GCV) is effective in the treatment of CMV retinitis in AIDS patients, but bone marrow toxicity limits its usefulness. Continuous maintenance GCV therapy is necessary to prevent progression or recrudescence of the disease, but despite maintenance therapy a significant number of patients experience a relapse during treatment. Additionally, there are other risks and problems associated with systemic GCV administration.  
           [0005]    Intravitreal GCV injections administered once or twice weekly have resulted in temporary remission of CMV retinitis in AIDS patients. Intravitreal GCV injections may provide a higher intraocular drug concentration than systemic therapy and reduce the incidence of neutropenia. However, current treatment of CMV retinitis in AIDS patients is clearly suboptimal. Ganciclovir is virustatic and thus disease inhibition requires maintenance drug administration.  
           [0006]    A more detailed explanation of the use of intravenous GCV and intravitreal injections of GCV can be found in U.S. Pat. No. 5,902,598, herein incorporated in its entirety by reference. A discussion of the difficulties associated with the systemic therapy of cyclosporine A in the treatment of uveitis can be found in U.S. Pat. Nos. 5,773,019 and 6,001,386, herein incorporated in their entirety by reference.  
           [0007]    Accordingly, there exists a strong need for the elimination of the undesirable physiological problems associated with GCV treatment of CMV retinitis, while maintaining the advantageous properties of this treatment. Although delivering the drug locally with injections may minimize the systemic toxicity of GCV, repeated injection is not a practical mode of administration.  
           [0008]    Due to the risks that certain drugs impose, researchers have developed systems for administering such drugs to aid in the treatment of these ailments and diseases. A general discussion of drug delivery control systems is provided in Controlled Drug Delivery (Part I), Xue Shen Wu, Ph.D. pp32, 33, 44-46, 63, 66, and 67 (Technomic Publishing Co. Inc., 1996), the entire contents of which are incorporated herein by reference. The systems have been designed largely to reduce and to control the release rate of incorporated drugs. However, these systems failed to achieve many of the advantages solved by later devices.  
           [0009]    For example, U.S. Pat. No. 4,014,335 to Arnold, relates to various ocular inserts that act as a deposit or drug reservoir for slowly releasing a drug into the tear film for prolonged periods of time. These inserts are fabricated as a three-layer laminate of flexible polymeric materials that are biologically inert, non-allergenic, and insoluble in tear fluid. To initiate the therapeutic programs of these devices, the ocular inserts are placed in the cul-de-sac between the sclera of the eyeball and the eyelid for administering the drug to the eye. Multiple layer laminate systems can present a challenge to reproducibly manufacture and are more difficult to produce by large-scale or commercial manufacturing procedures.  
           [0010]    The device of U.S. Pat. No. 3,416,530 is manufactured with a plurality of capillary openings that communicate between the exterior of the device and the interior chamber generally defined from a polymeric membrane. While the capillary openings in this construction are effective for releasing certain drugs to the eye, they add considerable complexity to the manufacture of the device because it is difficult to control the size of these openings in commercial manufacturing using various polymers.  
           [0011]    U.S. Pat. No. 3,618,604 describes a device that does not involve such capillary openings, but instead provides for the release of the drug by diffusion through a polymeric membrane. The device, as disclosed in a preferred embodiment, comprises a sealed container with the drug contained in an interior chamber. Nonetheless, as described in U.S. Pat. No. 4,014,335, certain problems have been identified with such devices such as the difficult task of sealing the margins of the membrane to form the container. In addition, stresses and strains introduced into the membrane walls from deformation during manufacturing of those devices may cause the reservoir to rupture and leak.  
           [0012]    U.S. Pat. No. 6,001,386 to Ashton, et al relates to an implantable sustained release drug implant with an inner core containing an effective amount of a low solubility agent covered by a non-bioerodible polymer coating layer that is permeable to the low solubility agent disclosed.  
           [0013]    The above described systems and devices are intended to provide sustained release of drugs effective in treating patients at a desired local or systemic level for obtaining certain physiological or pharmacological effects. However, there are many problems associated with their use, including the fact that it is often difficult to inject the drug implant into the eye which must then be secured in place, for example, via a “suture tab” connected to the drug implant. Injection devices prior to the present invention have not met with great success in being able to quickly deliver the drug implant to its intended target location. For example, maintaining close tolerances between the injector and drug implant, as well as creating sufficient lubricity in the injector cannula to allow a smooth passage of the drug implant therethrough, are a few of the many consistent problems in these prior injector designs.  
           [0014]    There thus remains a need for an improved injection device for delivering a drug implant adapted for sustained release of a drug to a patient to obtain a desired local or systemic physiological or pharmacological effect.  
         SUMMARY OF THE INVENTION  
         [0015]    The present invention addresses the problems associated with prior art injection devices by providing an injection device having an injection needle having a lateral opening formed in the outer surface thereof adjacent the distal, pointed end of the needle. The opening is configured to accept and releasably hold a drug implant therein. The drug implant may be in any of a variety of forms, for example, round, cylindrical, rectangular, square, etc., having a sustained release drug contained within a protective sheath which is designed for slow release of the drug at the implant site, some examples of which may be seen in copending application numbers ______ which are commonly assigned to applicant herein, the entire references of which are incorporated herein by reference.  
           [0016]    With the drug implant releasably secured in the lateral opening of the needle, the distal end of the needle is advanced through the tissue (e.g., intravitreal) until it reaches the target site in the organism (e.g., adjacent the retina of a human eye). Various release mechanisms are disclosed herein for releasing the drug implant from the needle opening at the implant site. Once the drug implant is released from the needle, the needle may be withdrawn from the organism. It will thus be appreciated that the drug implant does not travel through a cannula with the present invention. Subsequent steps for securing the drug implant in place, if needed, may be carried out in any known surgical manner (e.g., using sutures). 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0017]    [0017]FIG. 1 is a fragmentary, perspective view of the inventive needle with a drug implant shown in spaced relation to the opening in the needle;  
         [0018]    [0018]FIG. 2 is a side elevational view of FIG. 1;  
         [0019]    [0019]FIG. 3 is the view of FIG. 2 showing the drug implant positioned within the needle opening and a movable covering;  
         [0020]    [0020]FIG. 4 is the view of FIG. 3 showing the covering in place over the drug implant and needle opening;  
         [0021]    [0021]FIG. 5 is a cross-sectional view showing a first embodiment of a securing and release mechanism for the drug implant;  
         [0022]    [0022]FIG. 6 is a cross-sectional view of a second embodiment showing a friction-fit between the drug implant and needle opening;  
         [0023]    [0023]FIG. 7 is a cross-sectional view thereof as taken generally along the line  7 - 7  of FIG. 6;  
         [0024]    [0024]FIG. 8 is a fragmentary, cross-sectional view of a third embodiment of a securing and release mechanism for the drug implant;  
         [0025]    [0025]FIG. 9 is the view of FIG. 8 showing the securing and release mechanism in the secured position;  
         [0026]    [0026]FIG. 10 is a fourth embodiment of a securing and release mechanism for the drug implant;  
         [0027]    [0027]FIG. 11 is the view of FIG. 10 showing the releasing movement of the mechanism;  
         [0028]    [0028]FIG. 12 is a fifth embodiment of a securing and release mechanism for the drug implant showing the mechanism in the secured position; and  
         [0029]    [0029]FIG. 13 is the view of FIG. 12 showing the mechanism in the release position. 
     
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0030]    Referring now to the drawing, there is seen in a distal end of a needle  10  having a pointed, distal end  10   a  for directing into the tissue of a target surgical site of a mammalian organism, for example a human eye. The opposite, proximal end of the needle may be of any desired configuration for manual or machine manipulation of needle  10  consistent with the intended uses of needle  10  set forth herein (not shown).  
         [0031]    Needle  10  may be made of any suitable material for injection within a mammalian organism, some examples of which include titanium, stainless steel, ceramic, and polymer. The diameter of needle  10  is sized to enable direct injection of needle  10  within the delicate tissues of a human eye.  
         [0032]    A drug implant is indicated by reference numeral  12  and is illustrated herein in the shape of a cylinder having an outer diameter less than the diameter of needle  10  adjacent distal end  10   a  thereof, although the drug implant may be of other shapes as desired. Drug implant  12  is a slow-release implant capable of controlled release of a drug to the implant site. Needle  10  is the vehicle for delivering implant  12  to the implant site.  
         [0033]    More particularly, needle  10  is seen to include a lateral opening  14  therein adjacent distal end  10   a  thereof. Opening  14  serves to releasably hold drug implant  12  therein until the distal end  10   a  of needle  10  reaches the implant site in the organism, at which time drug implant  12  is released from opening  14 . Once drug implant  12  is released at the implant site, needle  10  may be withdrawn from the organism and either sterilized for subsequent use or discarded in single-use designs of needle  10 .  
         [0034]    Opening  14  may be of any desired configuration, but is preferably configured to match the shape of the drug implant  12  releasably held therein. As seen in FIGS. 3 and 4, a protective cover  16  may be provided in coaxial, sliding engagement with needle  10 . Covering  16  is selectively movable along the shaft of needle  10  from the open position seen in FIG. 3 to the closed position seen in FIG. 4 wherein drug implant  12  is prevented from falling free of opening  14  until the target site is reached, at which time covering  16  may be moved in the opposite direction to the open position. An extensible rod (not shown) may be attached to covering  16  to selectively move it between the open and closed positions.  
         [0035]    Attention is now turned to FIG. 5 which shows a first embodiment of an implant release mechanism. In this embodiment; a center bore  18  is provided as an axial extension of opening  14  wherein a spring  20  may be positioned to apply a biasing force against drug implant  12  such that implant  12  is forcibly held between the spring and the distal end wall  14   a  of opening  14 . A longitudinally extending rod  22  may be attached to the distal end  20   a  of spring  20  whereby rod  22  may be retracted in a direction opposite distal needle end  10   a  to release the biasing force of spring  20 , thereby allowing release of implant  12  from needle  10  at the implant site.  
         [0036]    [0036]FIG. 6 shown a second embodiment wherein drug implant  12  is engaged in opening  14  by friction-fit at opposite ends  12   a,   12   b  thereof. As seen in the cross-section view of FIG. 7, drug implant  12  which is cylindrical in this embodiment, is engaged in opening  14  by the three planar walls  14   b,    14   c,  and  14   d  of opening  14  frictionally engaging the cylindrical side wall  12 ′ thereof. Although no release mechanism is shown in FIGS.  6  or  7 , any of the release mechanisms described herein may be used in combination with any of the securing mechanisms described herein which will be detailed more fully below.  
         [0037]    [0037]FIGS. 8 and 9 show another embodiment of a securing and release mechanism for implant  12 . To load the implant  12  in opening  14 , longitudinally extending rod  24  is retracted to the position shown in FIG. 8 whereby a clearance  14 ′ is provided in opening  14  to allow easy insertion of implant  12  therein. Once implant  12  is inserted into opening  14 , rod  24  may be moved in the opposite direction toward distal end  10   a  until the distal end of the rod  24   a  engages the proximal end  12   a  of the implant  12 . Rod  24  and the axial bore  10   b  in which rod  24  extends may be provided with latch  26  and slot  28 , respectively, such that rod  14  may be locked into the engaged position seen in FIG. 9 until the implant site is reached, at which time latch  26  may be disengaged from slot  28  (e.g., by rotating rod  24 ). A manually operable push-tab  30  may be attached to rod  24  and lie exteriorly of needle  10  to allow easy one-touch manipulation of rod  24 .  
         [0038]    Referring to FIGS. 10 and 11, a release mechanism is shown comprising a shaft  32  reciprocally mounted in axial bore  10   e  formed in needle  10 . Shaft  32  includes an angled distal end  32   a  which may be moved to the secured position wherein end  32   a  is in just-touching relation to the proximal end of implant  12  as seen in FIG. 10. To release implant  12  at the implant site, shaft  32  is moved further toward distal end  10   a  whereupon the leading tip of end  32   a  wedges beneath implant  12  causing implant  12  to dislodge from opening  14  as seen in FIG. 11.  
         [0039]    In yet a further embodiment of implant release mechanism, the rod  24  of the embodiment of FIGS. 8 and 9 is used in combination with a spring  34  located within opening  14 . In the load/release position shown in FIG. 13, spring  34  is unbiased and rod  24  is retracted. In this position, implant  12  may be inserted into opening  14  and pressed against spring  34  to put spring  34  in tension. In the fully inserted position of implant  12  seen in FIG. 12, spring  34  is fully tensioned and applying an outward biasing force against implant  12 . While the implant and spring are held in this position (e.g., by pressing with a finger), rod  24  is extended until end  24   a  thereof is engaged against the proximal end  12   a  of implant  12 . Rod  24  may be locked in place as explained above with regard to FIGS. 8 and 9, at which time implant  12  is held tightly within opening  14  since the force of end  24   a  against implant  12  is stronger than the biasing force of spring  24 . Once needle  10  has been injected within the organism and end  10   a  thereof is at the implant site, the user releases and retracts rod  24  to the position seen in FIG. 13, at which time the force against implant end  12   a  is removed and the biasing force of spring  34  takes over to force implant  12  from opening  14 . Needle  10  may then be retracted from the implant site, leaving implant  12  in place.  
         [0040]    It will thus be appreciated that the present invention provides an improved injection device for delivering slow-release drug implants to the inside body of an organism. Since the drug implant is both held and released at the distal end of the needle, there is no need for a cannula delivery of the implant which obviates that many problems associated therewith as explained in the Background section hereof.

Technology Category: 1