U.S. patent application number 10/697423 was filed with the patent office on 2004-07-08 for ophthalmic drug delivery device.
Invention is credited to Yaacobi, Yoseph.
Application Number | 20040131655 10/697423 |
Document ID | / |
Family ID | 26857116 |
Filed Date | 2004-07-08 |
United States Patent
Application |
20040131655 |
Kind Code |
A1 |
Yaacobi, Yoseph |
July 8, 2004 |
Ophthalmic drug delivery device
Abstract
The present invention is directed to a drug delivery device for
a human eye. The human eye has a sclera, an inferior oblique
muscle, and a macula. The device of the present invention includes
a pharmaceutically active agent, and a geometry that facilitates
the implantation of the device on an outer surface of the sclera,
beneath the inferior oblique muscle, and with the pharmaceutically
active agent disposed above the macula. Methods of delivery a
pharmaceutically active agent to the posterior segment of the human
eye are also disclosed.
Inventors: |
Yaacobi, Yoseph; (Fort
Worth, TX) |
Correspondence
Address: |
ALCON RESEARCH, LTD.
R&D COUNSEL, Q-148
6201 SOUTH FREEWAY
FORT WORTH
TX
76134-2099
US
|
Family ID: |
26857116 |
Appl. No.: |
10/697423 |
Filed: |
October 30, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10697423 |
Oct 30, 2003 |
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10187006 |
Jul 1, 2002 |
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6669950 |
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10187006 |
Jul 1, 2002 |
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09664790 |
Sep 19, 2000 |
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6416777 |
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60160673 |
Oct 21, 1999 |
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Current U.S.
Class: |
424/427 |
Current CPC
Class: |
A61F 9/0017 20130101;
A61F 9/00781 20130101; A61K 9/0051 20130101 |
Class at
Publication: |
424/427 |
International
Class: |
A61F 002/00 |
Claims
What is claimed is:
1. An ophthalmic drug delivery device, comprising: a body having a
scleral surface for placement proximate a sclera and a well having
an opening to said scleral surface; and an inner core disposed in
said well comprising a pharmaceutically active agent, wherein said
pharmaceutically active agent comprises nepafenac.
2. An ophthalmic drug delivery device, comprising: a body having a
scleral surface for placement proximate a sclera and a well having
an opening to said scleral surface; and an inner core disposed in
said well comprising a pharmaceutically active agent, wherein said
pharmaceutically active agent comprises a cyclooxygenase
inhibitor.
3. The ophthalmic drug delivery device of claim 2 wherein said
pharmaceutically active agent is a Cox I inhibitor.
4. The ophthalmic drug delivery device of claim 2 wherein said
pharmaceutically active agent is a Cox II inhibitor.
Description
[0001] This application is a divisional of U.S. application Ser.
No. 10/187,006, filed Jul. 1, 2002, which is a continuation of U.S.
application Ser. No. 09/664,790, filed Sep. 19, 2000, now U.S. Pat.
No. 6,416,777, which claims priority from U.S. Provisional
Application No. 60/160,673, filed Oct. 21, 1999.
FIELD OF THE INVENTION
[0002] The present invention generally pertains to biocompatible
implants for localized delivery of pharmaceutically active agents
to body tissue. More particularly, but not by way of limitation,
the present invention pertains to biocompatible implants 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 in the biocompatible implant field
for a surgically implantable ophthalmic drug delivery device
capable of safe, effective, rate-controlled, localized delivery of
a wide variety of pharmaceutically active agents. The surgical
procedure for implanting 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. Furthermore, because of its versatility and capability
to deliver a wide variety of pharmaceutically active agents, such
an implant should be capable of use in ophthalmic clinical studies
to deliver various agents that create a specific physical condition
in a patient. Such an ophthalmic drug delivery 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] The present invention is directed to a drug delivery device
for a human eye. The human eye has a sclera, an inferior oblique
muscle, and a macula. The device of the present invention includes
a pharmaceutically active agent, and a geometry that facilitates
the implantation of the device on an outer surface of the sclera,
beneath the inferior oblique muscle, and with the pharmaceutically
active agent disposed above the macula. Because of its unique
geometry, the device is especially useful 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] 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:
[0014] FIG. 1 is a side sectional view schematically illustrating
the human eye and an ophthalmic drug delivery device implanted in
the posterior segment of the eye according to the present
invention;
[0015] FIG. 2 is detailed cross-sectional view of the eye of FIG. 1
along line 2-2;
[0016] FIG. 3 is a three dimensional schematic representation of
the human eye in situ;
[0017] FIG. 4 shows the eye of FIG. 3 after partial removal of the
lateral rectus muscle;
[0018] FIG. 5 is a schematic representation of the anterior view of
a human eye;
[0019] FIG. 6 is a schematic representation of the posterior view
of a human eye;
[0020] FIG. 7 is a perspective, orbital view of an ophthalmic drug
delivery device for the right human eye according to a first
preferred embodiment of the present invention;
[0021] FIG. 8 is a perspective, orbital view of the ophthalmic drug
delivery device of FIGS. 7 and 9 including a ramp for mating with
the inferior oblique muscle;
[0022] FIG. 9 is a perspective, scleral view of the ophthalmic drug
delivery device of FIG. 7;
[0023] FIG. 10 is a perspective view of an oval shaped drug core or
tablet for use with the ophthalmic drug delivery devices of the
present invention;
[0024] FIG. 11 is a perspective view of two, mating half-oval
shaped drug cores or tablets for use with the ophthalmic drug
delivery devices of the present invention;
[0025] FIG. 12 is a perspective, orbital view of the ophthalmic
drug delivery device of FIGS. 7 and 9 for the left human eye;
[0026] FIG. 13 is a perspective, orbital view of the ophthalmic
drug delivery device of FIGS. 12 and 14 including a ramp for mating
with the inferior oblique muscle;
[0027] FIG. 14 is a perspective, scleral view of the ophthalmic
drug delivery device of FIGS. 7 and 9 for the left human eye;
[0028] FIG. 15 is a perspective, orbital view of the ophthalmic
drug delivery of FIGS. 7 and 9 including a tapered longitudinal
part of the device;
[0029] FIG. 16 is a perspective, orbital view of a shortened
version of the ophthalmic drug delivery device of FIGS. 7 and
9;
[0030] FIG. 17 is a perspective, orbital view of the ophthalmic
drug delivery device of FIG. 16 including a ramp for mating with
the inferior oblique muscle;
[0031] FIG. 18 is a perspective, orbital view of an ophthalmic drug
delivery device for the right human eye according to a second
preferred embodiment of the present invention;
[0032] FIG. 19 is a perspective, orbital view of the ophthalmic
drug delivery device of FIG. 18 including a ramp for mating with
the inferior oblique muscle;
[0033] FIG. 20 is a perspective, orbital view of an ophthalmic drug
delivery device for the right human eye according to a third
preferred embodiment of the present invention; and
[0034] FIG. 21 is a perspective, orbital view of the ophthalmic
drug delivery device of FIG. 20 including a ramp for mating with
the inferior oblique muscle.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0035] The preferred embodiments of the present invention and their
advantages are best understood by referring to FIGS. 1 through 21
of the drawings, like numerals being used for like and
corresponding parts of the various drawings.
[0036] FIGS. 1 through 6 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, posteriorly to
optic disk 19. 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. 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. Conjunctiva 94 is disposed on
top of Tenon's capsule 101.
[0037] As is shown in FIGS. 1 and 2, and as is described in greater
detail hereinbelow, device 50 is preferably disposed directly on
the outer surface of sclera 100, below Tenon's capsule 101 for
treatment of most posterior segment diseases or conditions. In
addition, for treatment of ARMD and CNV in humans, device 50 is
preferably disposed directly on the outer surface of sclera 100,
below Tenon's capsule 101, with an inner core of device 50
proximate macula 98.
[0038] FIG. 3 illustrates a left human eye 90 within its orbit 112.
As can be seen from FIG. 3, inferior oblique muscle 107 runs under
lateral rectus muscle 105. The insertion line 107a of inferior
oblique muscle 107 into sclera 100 is located just above the
superior border of lateral rectus muscle 105. Of course, the
position of the inferior oblique muscle in a right human eye 90 is
a mirror image to its position on left human eye 90 of FIG. 3.
Cornea 92, conjunctiva 94, superior rectus muscle 103, inferior
rectus muscle 104, superior oblique muscle 106, and limbus 115 are
also shown in FIG. 3.
[0039] FIG. 4 similarly shows a left human eye 90 within its orbit
112. However, a portion of lateral rectus muscle 105 is not shown
in FIG. 4 to allow visibility of the portion of sclera 100 and
optic nerve 96 usually hidden by the muscle. In FIG. 4, an
insertion line 107b of inferior oblique muscle 107 into sclera 100
is lower than insertion line 107a of FIG. 3, indicating the
representative physiological variability of the insertion line of
the inferior oblique muscle in the human eye.
[0040] FIG. 5 schematically illustrates an anterior view of human
eye 90 with its four recti muscles, the superior rectus muscle 103,
the medial rectus muscle 108, the inferior rectus muscle 104, and
the lateral rectus muscle 105. FIG. 5 also shows the relationship
between the limbus, represented in FIG. 5 by circumferential line
115, and the insertion lines of the recti muscles, represented in
FIG. 5 by circumferential lines 113.
[0041] The posterior view of human eye 90 is schematically
illustrated in FIG. 6. FIG. 6 shows the locations of the superior
rectus muscle 103, the lateral rectus muscle 105, the inferior
rectus muscle 104, the medial rectus muscle 108, the superior
oblique muscle 106, the inferior oblique muscle 107 and its
insertion line 107a, the optic nerve 96, the cilliary vessels 109,
the sclera 100, the scleral area 110 above macula 98, the long
cilliary arteries 111, and the vortex veins 114.
[0042] FIGS. 7 and 9 schematically illustrate an ophthalmic drug
delivery device 50 for the right human eye according to a first
preferred embodiment of the present invention. Device 50 may be
used in any case where localized delivery of a pharmaceutically
active agent to the eye is required. Device 50 is particularly
useful for localized delivery of pharmaceutically active agents to
the posterior segment of the eye. A preferred use for device 50 is
the delivery of pharmaceutically active agents to the retina
proximate the macula for treating ARMD, choroidial
neovascularization (CNV), retinopathies, retinitis, uveitis,
macular edema, glaucoma, and neuropathies.
[0043] Device 50 generally includes a body 21 having a convex,
dome-shaped, orbital surface 12 and a concave, dome-shaped, scleral
surface 14. Scleral surface 14 is designed with a radius of
curvature that facilitates direct contact with sclera 100. Most
preferably, scleral surface 14 is designed with a radius of
curvature equal to the radius of curvature 91 of an average human
eye 90. (See FIG. 1) Orbital surface 12 is preferably designed with
a radius of curvature that facilitates implantation under Tenon's
capsule 101. When viewed from the top, body 21 preferably has a
generally "F-shaped" geometry with a longitudinal part 15, a
transversal part 18, and a knee 32 therebetween. Longitudinal part
15 and transversal part 18 are preferably joined at knee 32 to form
an angle of about ninety degrees. Longitudinal part 15 has a
proximal end 25, a rounded edge 24, a stopper 36, and a notch 42.
As is described in more detail hereinbelow, notch 42 is designed to
accommodate the origin of inferior oblique muscle 107. Stopper 36
defines the lower portion of notch 42 and is preferably slightly
elevated from the remainder of the generally convex orbital surface
12. As is described in greater detail hereinbelow, stopper 36 is
designed to prevent excessive advancement of device 50 toward optic
nerve 96 through contact on the anterior border of inferior oblique
muscle 107. Transversal part 18 has a distal end 58, a rounded edge
28, and a well or cavity 20 having an opening 64 to scleral surface
14. Well 20 and opening 64 preferably have a generally oval shape.
As is explained in more detail hereinbelow, transversal part 18
allows cavity 20 to be placed more directly over the area of sclera
100 overlying macula 98.
[0044] An inner core 81, which is shown in FIG. 10, is preferably
disposed in well 20. As shown in FIG. 10, inner core 81 is
preferably a tablet comprising one or more pharmaceutically active
agents. Tablet 81 preferably has a generally oval body 46 with a
concave, dome-shaped, scleral surface 85 and a convex, dome-shaped,
orbital surface 86. Body 46 also preferably has a peripheral bevel
87 disposed thereon. Alternatively, as shown in FIG. 11, the inner
core may comprise mating, half-oval tablets 82a and 82b. Tablet 82a
preferably has a body 47 identical to one half of body 46 of tablet
81. Tablet 82b preferably has a body 48 equal to the opposite half
of body 46 of tablet 81. Still further in the alternative, inner
core 81, or inner cores 82a and 82b, may comprise a conventional
hydrogel, gel, paste, or other semi-solid dosage form having one or
more pharmaceutically active agents disposed therein.
[0045] Returning to FIG. 9, a retaining member 62 is preferably
disposed proximate opening 64. Retaining member 62 prevents inner
core 81 from falling out of well 20. When inner core 81 is a
tablet, retaining member 62 is preferably a continuous rim or lip
disposed circumferentially around opening 64 that is designed to
accommodate bevel 87 of tablet 81. Alternatively, retaining member
62 may comprise one or more members that extend from body 21 into
opening 64.
[0046] Although not shown in FIGS. 9 through 11, inner core 81 may
alternatively comprise a suspension, solution, powder, or
combination thereof containing one or more pharmaceutically active
agents. In this embodiment, scleral surface 14 is formed without
opening 64, and the suspension, solution, powder, or combination
thereof diffuses through a relatively thin extension of scleral
surface 14 or other membrane below inner core 81. Still further in
the alternative, device 50 may be formed without well 20 or inner
core 81, and the pharmaceutically active agent(s) in the form of a
suspension, solution, powder, or combination thereof may be
dispersed throughout body 21 of device 50. In this embodiment, the
pharmaceutically active agent diffuses through body 21 into the
target tissue.
[0047] The geometry and dimensions of device 50 maximize
communication between the pharmaceutically active agent of inner
core 81 and the tissue underlying scleral surface 14. Scleral
surface 14 preferably physically contacts the outer surface of
sclera 100. Alternatively, scleral surface 14 may be disposed
proximate the outer surface of sclera 100. By way of example,
device 50 may be disposed in the periocular tissues just above the
outer surface of sclera 100 or intra-lamellarly within sclera
100.
[0048] Body 21 preferably comprises a biocompatible,
non-bioerodable material. Body 21 more preferably comprises a
biocompatible, non-bioerodable polymeric composition. Said
polymeric composition may be a homopolymer, a copolymer, straight,
branched, cross-linked, or a blend. Examples of polymers suitable
for use in said polymeric composition include silicone, polyvinyl
alcohol, ethylene vinyl acetate, polylactic acid, nylon,
polypropylene, polycarbonate, cellulose, cellulose acetate,
polyglycolic acid, polylactic-glycolic acid, cellulose esters,
polyethersulfone, acrylics, their derivatives, and combinations
thereof. Examples of suitable soft acrylics are more fully
disclosed in U.S. Pat. No. 5,403,901, which is incorporated herein
in its entirety by reference. Said polymeric composition most
preferably comprises silicone. Of course, said polymeric
composition may also comprise other conventional materials that
affect its physical properties, including, but not limited to,
porosity, tortuosity, permeability, rigidity, hardness, and
smoothness. Exemplary materials affecting certain ones of these
physical properties include conventional plasticizers, fillers, and
lubricants. Said polymeric composition may comprise other
conventional materials that affect its chemical properties,
including, but not limited to, toxicity, hydrophobicity, and body
21 - inner core 81 interaction. Body 21 is preferably impermeable
to the pharmaceutically active agent of inner core 81. When body 21
is made from a generally elastic polymeric composition, the shape
of well 20 may be made slightly smaller than the shape of inner
core 81. This frictional fit secures inner core 81 within well 20.
In this embodiment, body 21 may be formed with or without retaining
member 62, and inner core 81 may be formed with or without bevel
87, if desired.
[0049] Inner core 81 may comprise any ophthalmically acceptable
pharmaceutically active agents suitable for localized delivery.
Examples of pharmaceutically active agents suitable for inner core
81 are anti-infectives, including, without limitation, antibiotics,
antivirals, and antifungals; antiallergenics and mast cell
stabilizers; steroidal and non-steroidal anti-inflammatory agents;
cyclooxygenase inhibitors, including, without limitation, Cox I and
Cox II inhibitors; combinations of anti-infective and
anti-inflammatory agents; anti-glaucoma agents, including, without
limitation, adrenergics, .beta.-adrenergic blocking agents,
.alpha.-adrenergic agonists, parasypathomimetic agents,
cholinesterase inhibitors, carbonic anhydrase inhibitors, and
prostaglandins; combinations of anti-glaucoma agents; antioxidants;
nutritional supplements; drugs for the treatment of cystoid macular
edema including, without limitation, non-steroidal
anti-inflammatory agents; drugs for the treatment of ARMD,
including, without limitation, angiogenesis inhibitors and
nutritional supplements; drugs for the treatment of herpetic
infections and CMV ocular infections; drugs for the treatment of
proliferative vitreoretinopathy including, without limitation,
antimetabolites and fibrinolytics; wound modulating agents,
including, without limitation, growth factors; antimetabolites;
neuroprotective drugs, including, without limitation, eliprodil;
and angiostatic steroids for the 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 in their entirety by reference. Preferred ones
of such angiostatic steroids include
4,9(11)-Pregnadien-17.alpha.,21-diol-3,20-dione and
4,9(11)-Pregnadien-17.alpha.,21-diol-3,20-dione-21-acetate. A
preferred non-steroidal anti-inflammatory for the treatment of
cystoid macular edema is nepafenac. Inner core 81 may also comprise
conventional non-active excipients to enhance the stability,
solubility, penetrability, or other properties of the active agent
or the drug core.
[0050] If inner core 81 is a tablet, it may further comprise
conventional excipients necessary for tableting, such as fillers
and lubricants. Such tablets may be produced using conventional
tableting methods. The pharmaceutically active agent is preferably
distributed evenly throughout the tablet. In addition to
conventional tablets, inner core 81 may comprise a special tablet
that bioerodes at a controlled rate, releasing the pharmaceutically
active agent. By way of example, such bioerosion may occur through
hydrolosis or enzymatic cleavage. If inner core 81 is a hydrogel or
other gel, such gels may bioerode at a controlled rate, releasing
the pharmaceutically active agent. Alternatively, such gels may be
non-bioerodable but allow diffusion of the pharmaceutically active
agent.
[0051] Device 50 may be made by conventional polymer processing
methods, including, but not limited to, injection molding,
extrusion molding, transfer molding, and compression molding.
Preferably, device 50 is formed using conventional injection
molding techniques. Inner core 81 is preferably disposed in well 20
after the formation of body 21 of device 50. Retaining member 62 is
preferably resilient enough to allow bevel 87 of inner core 81 to
be inserted through opening 64 and then to return to its original
position.
[0052] Device 50 is preferably surgically placed directly on the
outer surface of sclera 100 below Tenon's capsule 101 with well 20
and inner core 81 directly over the area of sclera 100 above macula
98 using the following preferred technique that is capable of being
performed in an outpatient setting. The surgeon first performs an 8
mm peritomy in one of the quadrants of eye 90. Preferably, the
surgeon performs the peritomy in the infra-temporal quadrant, about
3 mm posterior to limbus 115 of eye 90. Once this incision is made,
the surgeon performs a blunt dissection to separate Tenon's capsule
101 from sclera 100. Using scissors and blunt dissection, an
antero-posterior tunnel is formed along the outer surface of sclera
100 and below inferior oblique muscle 107, preferably following the
inferior border of lateral rectus muscle 105. The inferior oblique
muscle 107 is then engaged with a Jamison muscle hook. The tip of
the hook is then advanced just posterior to the inferior oblique
muscle to form a portion of the tunnel that will accommodate
transversal part 18 of device 50. Once the tunnel is formed, the
surgeon uses Nuggett forceps to hold transversal part 18 of device
50 with scleral surface 14 facing sciera 100 and distal end 58 of
transversal part 18 away from the surgeon. The surgeon then
introduces device 50, distal end 58 first, into the tunnel at the
level of the peritomy. Once in the tunnel, the surgeon advances
device 50 along the tunnel toward inferior oblique muscle 107 until
stopper 36 contacts the anterior border of muscle 107. At the level
of the visualized inferior oblique muscle 107, the surgeon rotates
device 50 underneath muscle 107 so that transversal portion 18 of
device 50 enters the portion of the tunnel just posterior to
inferior oblique muscle 107. When the surgeon feels that knee 32
cannot advance any further, the surgeon slightly moves device 50 in
an antero-posterior direction to allow for the accommodation of
inferior oblique muscle 107 within notch 42 between transversal
part 18 and stopper 36. Due to the notch 42 and the location of
well 20 near distal end 58 of transversal part 18, inner core 81 is
positioned directly over the portion of sclera 100 above macula 98.
Proximal end 25 of longitudinal part 15 may then be sutured to
sclera 100. The surgeon then closes the peritomy by suturing
Tenon's capsule 101 and conjunctiva 94 to sclera 100. After
closing, the surgeon places a strip of antibiotic ointment on the
surgical wound. All sutures are preferably 7-0 Vicryl sutures. For
the treatment of ARMD and CNV, the pharmaceutically active agent of
inner core 81 is preferably one of the angiostatic steroids
disclosed in U.S. Pat. Nos. 5,679,666 and 5,770,592.
[0053] The geometry of body 21 of device 50, including the concave
nature of scleral surface 14; the shape and locations of
transversal portion 18, well 20, opening 64, inner core 81, and
retaining member 62; and the shape and locations of notch 42 and
stopper 36, all facilitate the delivery of a pharmaceutically
effective amount of the pharmaceutically active agent from inner
core 81 through sclera 100, choroid 99, and into retina 97, and
more particularly into macula 98. The absence of a polymer layer or
membrane between inner core 20 and sclera 100 also greatly enhances
and simplifies the delivery of an active agent to retina 97.
[0054] It is believed that device 50 can be used to deliver a
pharmaceutically effective amount of a pharmaceutically active
agent to retina 97 for many years, depending on the particular
physicochemical properties of the pharmaceutically active agent
employed. Important physicochemical properties include
hydrophobicity, solubility, dissolution rate, diffusion
coefficient, partitioning coefficient, and tissue affinity. After
inner core 20 no longer contains active agent, the surgeon may
easily remove device 50. In addition, the "pre-formed" tunnel
facilitates the replacement of an old device 50 with a new device
50.
[0055] FIG. 8 illustrates an ophthalmic drug delivery device 60, a
slight modification of ophthalmic drug delivery device 50 that is
useful for certain implantations of the present invention. As shown
in FIG. 8, device 60 has a geometry substantially similar to device
50 of FIGS. 7 and 9, with the exception that a ramp 45 has been
added to orbital surface 12 of body 21 proximate notch 42. Ramp 45
is a slanted surface that preferably travels from scleral surface
14, on a first end, to orbital surface 12 on a second end.
Alternatively, ramp 45 may travel from a location within edge 24 of
longitudinal part 15, on a first end, to orbital surface 12 on a
second end. Ramp 45 facilitates the accommodation of inferior
oblique muscle 107 within notch 42 between transversal part 18 and
stopper 36 when device 60 is implanted within eye 90, as described
hereinabove in connection with device 50. Device 60 may be made
using techniques substantially similar to device 50.
[0056] FIGS. 12 and 14 schematically illustrates an ophthalmic drug
delivery device 70 for the left human eye. The geometry of device
70 is a mirror image of the geometry of device 50 for the right
human eye as described hereinabove in connection with FIGS. 7 and
9. The use of device 70 is substantially identical to the use of
device 50, and device 70 may be made using techniques substantially
similar to device 50.
[0057] FIG. 13 illustrates an ophthalmic drug delivery device 75
for the left human eye, a slight modification of ophthalmic drug
delivery device 70 that is useful for certain implantations of the
present invention. The geometry and use of device 75 of FIG. 13 is
substantially similar to the geometry and use of device 60 of FIG.
8, except that device 75 is a mirror image of device 60.
[0058] FIG. 15 schematically illustrates an ophthalmic drug
delivery device 30, a slight modification of ophthalmic drug
delivery device 50 that is useful for certain implantations of the
present invention. As shown in FIG. 15, device 30 has a geometry
substantially similar to device 50 of FIGS. 7 and 9, with the
exception that longitudinal part 15 has a tapered thickness, when
viewed from edge 24, preferably beginning at a location 33 and
continuing to proximal end 25. This portion of longitudinal part 15
is disposed anteriorly within eye 90 and may be visible to others.
Therefore, due to this tapered thickness, device 30 may be more
comfortable or cosmetically acceptable to the patient. The use of
device 30 of FIG. 15 is substantially similar to the use of device
50, and device 30 may be made using techniques substantially
similar to device 50.
[0059] FIGS. 16 schematically illustrates an ophthalmic drug
delivery device 40, a slight modification of ophthalmic drug
delivery device 50 that is useful for certain implantations of the
present invention. As shown in FIG. 16, device 40 has a geometry
substantially similar to device 50 of FIGS. 7 and 9, with the
exception that a length of longitudinal part 15 in device 40 has
been shortened relative to device 50. Similar to device 30, this
shortening of longitudinal part 15 may result in device 40 being
more comfortable or cosmetically acceptable to the patient. The use
of device 40 of FIG. 16 is substantially similar to the use of
device 50, and device 40 may be made using techniques substantially
similar to device 50.
[0060] FIG. 17 illustrates an ophthalmic drug delivery device 80, a
slight modification of ophthalmic drug delivery device 40 that is
useful for certain implantations of the present invention. As shown
in FIG. 17, device 80 has a geometry substantially similar to
device 40 of FIG. 16, with the exception that a ramp 45 has been
added to orbital surface 12 of body 21 proximate notch 42. Ramp 45
is a slanted surface that preferably travels from scleral surface
14, on a first end, to orbital surface 12 on a second end.
Alternatively, ramp 45 may travel from a point within edge 24 of
longitudinal part 15, on a first end, to orbital surface 12 on a
second end. Ramp 45 facilitates the accommodation of inferior
oblique muscle 107 within notch 42 between transversal part 18 and
stopper 36 when device 80 is implanted within eye 90, as described
hereinabove in connection with device 50. Device 80 may be made
using techniques substantially similar to device 50.
[0061] FIG. 18 schematically illustrates an ophthalmic drug
delivery device 65 for the right human eye according a second
preferred embodiment of the present invention. Device 65 may be
used in any case where localized delivery of a pharmaceutically
active agent to the eye is required. Device 65 is particularly
useful for localized delivery of active agents to the posterior
segment of the eye. A preferred use for device 65 is the delivery
of pharmaceutically active agents to the retina proximate the
macula for treating ARMD, choroidial neovascularization (CNV),
retinopathies, retinitis, uveitis, macular edema, glaucoma, and
neuropathies.
[0062] Device 65 generally includes a body 29 having a convex,
dome-shaped, orbital surface 12 and a concave, dome-shaped, scleral
surface 14 (not shown). Scleral surface 14 is designed with a
radius of curvature that facilitates direct contact with sclera
100. Most preferably, scleral surface 14 is designed with a radius
of curvature equal to the radius of curvature 91 of an average
human eye 90. Orbital surface 12 is preferably designed with a
radius of curvature that facilitates implantation under Tenon's
capsule 101. When viewed from the top, body 21 preferably has a
generally "C-shaped" geometry with a longitudinal part 17, a
transversal part 18, and a knee 32 therebetween. Longitudinal part
17 and transversal part 18 are preferably joined at knee 32 to form
an angle of about ninety degrees. Longitudinal part 17 has a
proximal end 25 and a rounded edge 24. A stopper 37 forms the
"lower" part of the C-shaped geometry and is preferably slightly
elevated from the remainder of the generally convex orbital surface
12. A notch 42 is located in longitudinal part 17 and is defined by
transversal part 18 and stopper 37. Similar to notch 42 of device
50 of FIGS. 7 and 9, notch 42 of device 65 is designed to
accommodate the origin of inferior oblique muscle 107. Similar to
stopper 36 of device 50, stopper 37 is designed to prevent
excessive advancement of device 65 toward optic nerve 96 through
contact on the anterior border of inferior oblique muscle 107.
Transversal part 18 has a distal end 58, a rounded edge 28, and a
well or cavity 20 having an opening 64 (not shown) to scleral
surface 14 (not shown) for holding an inner core similar to those
described above in connection with FIGS. 10 and 11. Well 20 and
opening 64 preferably have a generally oval shape.
[0063] The use of device 65 is substantially similar to the use of
device 50 as described hereinabove. Device 65 may be made using
techniques substantially similar to device 50.
[0064] FIG. 19 illustrates an ophthalmic drug delivery device 67, a
slight modification of ophthalmic drug delivery device 65 that is
useful for certain implantations of the present invention. As shown
in FIG. 19, device 67 has a geometry substantially similar to
device 65 of FIG. 19, with the exception that a ramp 45 has been
added to orbital surface 12 of body 29 proximate notch 42. Ramp 45
is a slanted surface that preferably travels from scleral surface
14, on a first end, to orbital surface 12 on a second end.
Alternatively, ramp 45 may travel from a point within edge 24 of
longitudinal part 17, on a first end, to orbital surface 12 on a
second end. Ramp 45 facilitates the accommodation of inferior
oblique muscle 107 within notch 42 between transversal part 18 and
stopper 37 when device 67 is implanted within eye 90, as described
hereinabove in connection with device 50. Device 67 may be made
using techniques substantially similar to device 50.
[0065] FIG. 20 schematically illustrates an ophthalmic drug
delivery device 52 for the right human eye according a third
preferred embodiment of the present invention. Device 52 may be
used in any case where localized delivery of a pharmaceutically
active agent to the eye is required. Device 52 is particularly
useful for localized delivery of active agents to the posterior
segment of the eye. A preferred use for device 52 is the delivery
of pharmaceutically active agents to the retina proximate the
macula for treating ARMD, choroidial neovascularization (CNV),
retinopathies, retinitis, uveitis, macular edema, glaucoma, and
neuropathies.
[0066] Device 52 generally includes a body 39 having a convex,
dome-shaped, orbital surface 12 and a concave, dome-shaped scleral
surface 14 (not shown). Scleral surface 14 is designed with a
radius of curvature that facilitates direct contact with sclera
100. Most preferably, scleral surface 14 is designed with a radius
of curvature equal to the radius of curvature 91 of an average
human eye 90. Orbital surface 12 is preferably designed with a
radius of curvature that facilitates implantation under Tenon's
capsule 101. When viewed from the top, body 39 preferably has a
generally "L-shaped" geometry with a longitudinal part 15, a
transversal part 18, and a knee 32 therebetween. Longitudinal part
15 and transversal part 18 are preferably joined at knee 32 to form
an angle of about ninety degrees. Similar to notch 42 of device 50
of FIGS. 7 and 9, longitudinal part 15 and transversal part 18 of
device 52 form a region 43 designed to accommodate the origin of
inferior oblique muscle 107. Longitudinal part 15 has a proximal
end 25 and a rounded edge 24. Transversal part 18 has a distal end
58, a rounded edge 28, and a well or cavity 20 having an opening 64
(not shown) to scleral surface 14 for holding an inner core similar
to those described above in connection with FIGS. 10 and 11. Well
20 and opening 64 preferably have a generally oval shape.
[0067] The use of device 52 is substantially similar is
substantially similar to the use of device 50 as described
hereinabove. Device 52 may be made using techniques substantially
similar to device 50.
[0068] FIG. 21 illustrates an ophthalmic drug delivery device 54, a
slight modification of ophthalmic drug delivery device 52 that is
useful for certain implantations of the present invention. As shown
in FIG. 21, device 54 has a geometry substantially similar to
device 52 of FIG. 20, with the exception that a ramp 45 has been
added to orbital surface 12 of body 29 proximate region 43. Ramp 45
is a slanted surface that preferably travels from scleral surface
14, on a first end, to orbital surface 12 on a second end.
Alternatively, ramp 45 may travel from a point within edge 24 of
longitudinal part 15, on a first end, to orbital surface 12 on a
second end. Ramp 45 facilitates the accommodation of inferior
oblique muscle 107 within region 43 when device 54 is implanted
within eye 90, as described hereinabove in connection with device
50. Device 54 may be made using techniques substantially similar to
device 50.
[0069] 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. The
surgical procedure for implanting such devices is safe, simple,
quick, and capable of being performed in an outpatient setting.
Such devices are easy and economical to manufacture. Furthermore,
because of their capability to deliver a wide variety of
pharmaceutically active agents, such devices are useful in clinical
studies to deliver various ophthalmic agents that create a specific
physical condition in a patient.
[0070] 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 present invention is described
hereinabove with reference to an ophthalmic drug delivery device
having a generally "F-shaped", "C-shaped", or "L-shaped" geometry
when viewed from the top, other geometries may be used, especially
if they facilitate the placement of the device under the inferior
oblique muscle and the location of pharmaceutically active agent
over the macula when the device is implanted on the outer surface
of the sclera and below the Tenon's capsule of the human eye.
[0071] 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.
* * * * *