U.S. patent application number 12/121062 was filed with the patent office on 2009-02-05 for juxtascleral drug delivery and ocular implant system.
Invention is credited to Karl Cazzini.
Application Number | 20090036827 12/121062 |
Document ID | / |
Family ID | 40338817 |
Filed Date | 2009-02-05 |
United States Patent
Application |
20090036827 |
Kind Code |
A1 |
Cazzini; Karl |
February 5, 2009 |
Juxtascleral Drug Delivery and Ocular Implant System
Abstract
Ophthalmic drug delivery devices useful for delivery of
pharmaceutically active agents to the posterior segment of the eye
are disclosed.
Inventors: |
Cazzini; Karl; (Lindenhurst,
IL) |
Correspondence
Address: |
ALCON
IP LEGAL, TB4-8, 6201 SOUTH FREEWAY
FORT WORTH
TX
76134
US
|
Family ID: |
40338817 |
Appl. No.: |
12/121062 |
Filed: |
May 15, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60953054 |
Jul 31, 2007 |
|
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Current U.S.
Class: |
604/60 ; 424/427;
604/200; 604/294 |
Current CPC
Class: |
A61F 9/0017
20130101 |
Class at
Publication: |
604/60 ; 424/427;
604/200; 604/294 |
International
Class: |
A61F 9/00 20060101
A61F009/00; A61F 2/14 20060101 A61F002/14; A61M 31/00 20060101
A61M031/00; A61M 37/00 20060101 A61M037/00 |
Claims
1. An ophthalmic drug delivery device, comprising: an injector
housing; a capsule containing pharmaceutically agent disposed
within said injector housing; a delivery cannula coupled to a
distal surface of said injector housing; an injector cannula
slidably disposed within said delivery cannula and said injector
housing, said injector cannula having a first tip for penetrating
said capsule, and a second tip for dispensing said pharmaceutically
active agent; an extension assembly for extending said injector
cannula from said delivery cannula; and a compression assembly for
compressing said capsule and allowing delivery of said
pharmaceutically active agent.
2. The drug delivery device of claim 1 wherein said extension
assembly comprises: a first plunger shaft slidably disposed in said
injector housing; a positioning member coupled to said first
plunger shaft and disposed within said injector housing; and an
injector cannula guide coupled to said injector cannula and
disposed within said injector housing beneath said positioning
member; whereby depression of said first plunger shaft displaces
said positioning member said injector cannula guide to extend said
injector cannula from said delivery cannula.
3. The drug delivery device of claim 2 wherein said compression
assembly comprises: a compression member coupled to said first
plunger shaft; and a locking mechanism for removably coupling said
first plunger shaft and said positioning member.
4. The drug delivery device of claim 2 wherein said compression
assembly comprises: a second plunger shaft slidably disposed within
said first plunger shaft; and a compression member coupled to said
second plunger shaft.
5. The drug delivery device of claim 1 wherein said injector
cannula is made from a superelastic material.
6. The drug delivery device of claim 1 wherein said injector
housing may be opened so as to enable placement of said
capsule.
7. The drug delivery device of claim 1 wherein said capsule is
disposed within said injector housing, and said injector housing is
sealed.
8. An ophthalmic drug delivery device, comprising: an injector
housing; a delivery cannula coupled to a distal surface of said
injector housing; an injector cannula slidably disposed within said
delivery cannula and said injector housing, said injector cannula
having a first opening proximate a distal tip; a mandrel slidably
disposed within said injector cannula; an extension assembly for
extending said injector cannula from said delivery cannula; and a
drug eluting implant disposed within said injector cannula.
9. The drug delivery device of claim 8 wherein said extension
assembly comprises: a first plunger shaft slidably disposed in said
injector housing; a positioning member coupled to said first
plunger shaft and disposed within said injector housing; and an
injector cannula guide coupled to said injector cannula and
disposed within said injector housing beneath said positioning
member; whereby depression of said first plunger shaft displaces
said positioning member said injector cannula guide to extend said
injector cannula from said delivery cannula.
10. The ophthalmic drug delivery device of claim 9 further
comprising a delivery assembly having a second plunger shaft
slidably disposed within said first plunger shaft, whereby
depressing said second plunger displaces said mandrel and said
implant along an interior of said injection cannula.
11. The ophthalmic drug delivery device of claim 8 wherein said
implant comprises a strip wound around said mandrel.
Description
[0001] This application claims the priority of U.S. Provisional
Patent Application 60/953,054 filed Jul. 31, 2007.
FIELD OF THE INVENTION
[0002] The present invention generally pertains to instruments for
localized delivery of pharmaceutically active agents to body
tissue. More particularly, but not by way of limitation, the
present invention pertains to instruments for localized delivery of
pharmaceutically active agents to the posterior segment of the
eye.
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] Age related macular degeneration (ARMD) is the leading cause
of blindness in the elderly. 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 (choroidal neovascularization (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)
the use of angiogenesis inhibitors, and (c) photodynamic therapy.
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. 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. Periocular injections of these compounds often result in
the drug being quickly washed out and depleted from the eye, via
periocular vasculature and soft tissue, into the general
circulation. Repetitive intraocular injections may result in
severe, often blinding, complications such as retinal detachment
and endophthalmitis. Photodynamic therapy is a new technology for
which the long-term efficacy is still largely unknown.
[0006] In order to prevent complications related to the
above-described treatments and to provide better ocular treatment,
researchers have suggested various implants aimed at localizing
delivery of anti-angiogenic compounds to the eye. U.S. Pat. No.
5,824,072 to Wong discloses a non-biodegradable polymeric implant
with a pharmaceutically active agent disposed therein. The
pharmaceutically active agent diffuses through the polymer body of
the implant into the target tissue. The pharmaceutically active
agent may include drugs for the treatment of macular degeneration
and diabetic retinopathy. The implant is placed substantially
within the tear fluid upon the outer surface of the eye over an
avascular region, and may be anchored in the conjunctiva or sclera;
episclerally or intrasclerally over an avascular region;
substantially within the suprachoroidial space over an avascular
region such as the pars plana or a surgically induced avascular
region; or in direct communication with the vitreous.
[0007] U.S. Pat. No. 5,476,511 to Gwon et al. discloses a polymer
implant for placement under the conjunctiva of the eye. The implant
may be used to deliver neovascular inhibitors for the treatment of
ARMD and drugs for the treatment of retinopathies, and retinitis.
The pharmaceutically active agent diffuses through the polymer body
of the implant.
[0008] U.S. Pat. No. 5,773,019 to Ashton et al. discloses a
non-bioerodable polymer implant for delivery of certain drugs
including angiostatic steroids and drugs such as cyclosporine for
the treatment of uveitis. Once again, the pharmaceutically active
agent diffuses through the polymer body of the implant.
[0009] All of the above-described implants require careful design
and manufacture to permit controlled diffusion of the
pharmaceutically active agent through a polymer body (i.e., matrix
devices) or polymer membrane (i.e., reservoir devices) to the
desired site of therapy. Drug release from these devices depends on
the porosity and diffusion characteristics of the matrix or
membrane, respectively. These parameters must be tailored for each
drug moiety to be used with these devices. Consequently, these
requirements generally increase the complexity and cost of such
implants.
[0010] U.S. Pat. No. 5,824,073 to Peyman discloses an indentor for
positioning in the eye. The indentor has a raised portion that is
used to indent or apply pressure to the sclera over the macular
area of the eye. This patent discloses that such pressure decreases
choroidal congestion and blood flow through the subretinal
neovascular membrane, which, in turn, decreases bleeding and
subretinal fluid accumulation.
[0011] Therefore, a need exists for an ophthalmic drug delivery
device for the creation of a posterior juxtascleral depot
containing a pharmaceutically active agent. The device should be
capable of safe, effective, rate-controlled, localized delivery of
a wide variety of pharmaceutically active agents. The procedure for
using such a device should be safe, simple, quick, and capable of
being performed in an outpatient setting. Ideally, such a device
should be easy and economical to manufacture. Such a device is
especially needed for localized delivery of pharmaceutically active
agents to the posterior segment of the eye to combat ARMD, CNV,
retinopathies, retinitis, uveitis, macular edema, glaucoma, and
neuropathies.
SUMMARY OF THE INVENTION
[0012] In one aspect, the present invention is an ophthalmic drug
delivery device having an injector housing, a capsule containing a
pharmaceutically agent disposed within the injector housing, a
delivery cannula coupled to a distal surface of the injector
housing, an injector cannula slidably disposed within the delivery
cannula and the injector housing, an extension assembly for
extending the injector cannula from the delivery cannula, and a
compression assembly. The injector cannula has a first tip for
penetrating the capsule, and a second tip for dispensing the
pharmaceutically active agent. The compression assembly compresses
the capsule and allows delivery of the pharmaceutically active
agent.
[0013] In another aspect, the present invention is an ophthalmic
drug delivery device having an injector housing; a delivery cannula
coupled to a distal surface of said injector housing; an injector
cannula slidably disposed within said delivery cannula and said
injector housing, said injector cannula having a first opening
proximate a distal tip; a mandrel slidably disposed within said
injector cannula; an extension assembly for extending said injector
cannula from said delivery cannula; and a drug eluting implant
disposed within said injector cannula.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] 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:
[0015] FIG. 1 is a side sectional view schematically illustrating
the human eye and a posterior juxtascleral depot in the posterior
segment of the eye according to the present invention;
[0016] FIG. 2 is detailed cross-sectional view of the eye of FIG. 1
along line 2-2;
[0017] FIG. 3 is a schematic view of the drug delivery device of
the present invention showing the injector cannula in the fully
retracted position;
[0018] FIG. 4 is a schematic view of the device of FIG. 3 showing
the injector cannula in the fully deployed position;
[0019] FIG. 5 is a schematic view of the device of FIG. 3 showing
the plunger shaft unlocked from the positioning member;
[0020] FIG. 6 is a schematic view of an alternative embodiment of
the drug delivery device of the present invention;
[0021] FIG. 7 is a schematic view of a second alternative
embodiment of the drug delivery device of the present invention;
and
[0022] FIGS. 8-10 are enlarged, fragmentary, schematic views of an
alternate embodiment of the implant of the device of FIG. 7.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] The preferred embodiments of the present invention and their
advantages are best understood by referring to FIGS. 1-10 of the
drawings, like numerals being used for like and corresponding parts
of the various drawings.
[0024] FIGS. 1-2 illustrate various portions of the human eye
important to a complete understanding of the present invention.
Referring first to FIG. 1, a human eye 90 is schematically
illustrated. Eye 90 has a cornea 92, a lens 93, vitreous 95, a
sclera 100, a choroid 99, a retina 97, and an optic nerve 96. Eye
90 is generally divided into an anterior segment 89 and a posterior
segment 88. Anterior segment 89 of eye 90 generally includes the
portions of eye 90 anterior of ora serata 11. Posterior segment 88
of eye 90 generally includes the portions of eye 90 posterior of
ora serata 11. Retina 97 is physically attached to choroid 99 in a
circumferential manner proximate pars plana 13. Retina 97 has a
macula 98 located slightly lateral to optic disk 19. As is well
known in the ophthalmic art, macula 98 is comprised primarily of
retinal cones and is the region of maximum visual acuity in retina
97. At the center of macula 98 is a fovea 117. A Tenon's capsule or
Tenon's membrane 101 is disposed on sclera 100. A conjunctiva 94
covers a short area of the globe of eye 90 posterior to limbus 115
(the bulbar conjunctiva) and folds up (the upper cul-de-sac) or
down (the lower cul-de-sac) to cover the inner areas of upper
eyelid 78 and lower eyelid 79, respectively. The bulbar conjunctiva
94 is disposed on top of Tenon's capsule 101.
[0025] As is shown in FIGS. 1 and 2, and as is described in greater
detail hereinbelow, a posterior juxtascleral drug depot 150
containing a pharmaceutically active agent is preferably disposed
directly on the outer surface of sclera 100, below Tenon's capsule
101 for treatment of posterior segment ophthalmic diseases or
conditions. Depot 150 may be used in humans or animals.
[0026] FIG. 3 illustrates the preferred embodiment of a device 200
for the creation of posterior juxtascleral depot 150. An injector
housing 2 encloses a positioning member 5 surrounding a compression
member 7. Injector cannula guide 9 is affixed to an injector
cannula 4, which is free to slide inside a delivery cannula 3. As
shown in FIG. 4, a sealed polymer capsule 22 containing a
predetermined dose of a fluidized pharmaceutical preparation is
loaded into capsule space 10, by opening injector housing 2 along
line 20. Alternatively, capsule 22 could be prepackaged inside a
sealed injector housing 2 within the capsule space 10. The surgeon
makes a small incision in conjunctiva 94, presents delivery cannula
3 to the conjunctival incision, and advances injector cannula 4
into the space between Tenons capsule 101 and sclera 100, by slowly
depressing plunger shaft 1, as shown in FIG. 4. Plunger shaft 1 is
locked and engaged with slots 24 located in the positioning member
5, by means of a locking member 6, such as to prevent drug capsule
22 from being ruptured during advancement of injector cannula 4.
Visible reference markings 11 may be placed on the outside of the
plunger shaft 1, thereby alerting the surgeon as to the precise
position of injector tip 4a. Alternatively, a light guide (not
shown) may be used to deliver light to the blunt injector tip 4a,
enabling the position of tip 4a to be determined by trans-scleral
illumination. Once injector cannula 4 is in the desired drug
delivery position, the surgeon rotates plunger shaft 1 ninety
degrees to disengage locking member 6 from slots 24 within
positioning member 5. As shown in FIG. 5, further depression of
plunger shaft I allows compression member 7 to impale drug capsule
22 on penetrating tip 8 of injector cannula 4. Still further
depression of plunger shaft 1 allows compression member 7 to
compress capsule 22, thereby forcing the fluidized drug to flow
through injector cannula 4, and exit injector tip 4a at the desired
injection site.
[0027] Injector cannula 4 is preferably made from a superelastic
Nitinol tube, which has been preformed by means well known to those
skilled in the art, to retain and follow the profile of the outer
globe of sclera 100 during advancement to and retreat from the
posterior juxtascleral injection site. This mechanism guarantees a
safe and efficacious means for delivering a posterior juxtascleral
depot to posterior segment 88.
[0028] FIG. 6 illustrates an alternative embodiment of device 200.
In this embodiment, depression of plunger 32 extends injector
cannula 4 to the desired location for making the drug depot. The
drug is delivered by depressing plunger 34, which punctures drug
containing capsule 22, and directs it to the injection site. In a
refinement of this embodiment, a protective sheath (not shown) may
be placed over injector cannula 4 to protect surrounding tissues
during deployment of the injector cannula 4. This sheath could be
illuminated to provide a trans-scleral illumination of the distal
tip 4a of injector cannula 4.
[0029] FIG. 7 illustrates a further embodiment of device 200 in
which the device has been modified to deliver a drug eluting
polymer implant 52. Such a drug-eluting implant could be fabricated
from a biocompatible and bio-erodable carrier matrix such as
poly-DL-lactide-co-glycolide (PLG). Other suitable carrier
materials are well known to those skilled in the art. FIGS. 8-10
depict an alternate embodiment of this concept, illustrating how a
biodegradable/bio-erodable ocular strip implant 52 is deployed
using the methods described for a juxtascleral injection. In this
case, strip 52 encapsulates the pharmaceutical preparation
prescribed. Drug-eluting strip 52 is wound onto flexible delivery
mandrel 54 and guided to the end of injector cannula 4. Once in
position, drug eluting strip 52 may be unfurled by a mechanism
which rotates delivery mandrel 54, causing strip 52 to unroll and
exit through delivery aperture 56. In so doing, drug-eluting strip
52 may be deployed flat, within the confines of the sub-Tenons
space, and assume its drug delivery function.
[0030] From the above, it may be appreciated that the present
invention provides improved devices and methods for safe,
effective, rate-controlled, localized delivery of a variety of
pharmaceutically active agents to the eye, and particularly to the
posterior segment of the eye to combat ARMD, CNV, retinopathies,
retinitis, uveitis, macular edema, glaucoma, and neuropathies.
[0031] It is believed that the operation and construction of the
present invention will be apparent from the foregoing description.
While the apparatus and methods shown or described above have been
characterized as being preferred, various changes and modifications
may be made therein without departing from the spirit and scope of
the invention as defined in the following claims.
* * * * *