WO2003009774A2 - Ophthalmic drug delivery device - Google Patents

Ophthalmic drug delivery device Download PDF

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Publication number
WO2003009774A2
WO2003009774A2 PCT/US2002/023048 US0223048W WO03009774A2 WO 2003009774 A2 WO2003009774 A2 WO 2003009774A2 US 0223048 W US0223048 W US 0223048W WO 03009774 A2 WO03009774 A2 WO 03009774A2
Authority
WO
WIPO (PCT)
Prior art keywords
drug delivery
sclera
eye
pharmaceutically active
delivery device
Prior art date
Application number
PCT/US2002/023048
Other languages
French (fr)
Other versions
WO2003009774A3 (en
Inventor
Yoseph Yaacobi
Original Assignee
Alcon, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to EP02750196A priority Critical patent/EP1409065B1/en
Priority to BR0210494-6A priority patent/BR0210494A/en
Priority to MXPA03011609A priority patent/MXPA03011609A/en
Priority to PL368207A priority patent/PL204644B1/en
Priority to JP2003515170A priority patent/JP4261343B2/en
Priority to AU2002319596A priority patent/AU2002319596B2/en
Application filed by Alcon, Inc. filed Critical Alcon, Inc.
Priority to CA002447802A priority patent/CA2447802C/en
Priority to DK02750196T priority patent/DK1409065T3/en
Priority to DE60217679T priority patent/DE60217679T2/en
Publication of WO2003009774A2 publication Critical patent/WO2003009774A2/en
Publication of WO2003009774A3 publication Critical patent/WO2003009774A3/en
Priority to US10/706,105 priority patent/US7094226B2/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts

Definitions

  • the present invention generally pertains to biocompatible implants for delivery of pharmaceutically active agents to the eye. More particularly, but not by way of limitation,
  • the present invention pertains to biocompatible implants for delivery of pharmaceutically active agents to the posterior segment of the eye.
  • Age related macular degeneration (ARMD), choroidal neovascularization (CNV),
  • retinopathies e.g., diabetic retinopathy, vitreoretinopathy
  • retinitis e.g., cytomegalovirus
  • CMV CMV retinitis
  • Age related macular degeneration is the leading cause of blindness in the
  • CNV choroidal neovascularization
  • Photodynamic therapy is a new
  • the pharmaceutically active agent diffuses tlirough the polymer body of
  • the pharmaceutically active agent may include drugs
  • the implant is placed
  • 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
  • U.S. Patent No. 5,476,511 to Gwon et al. discloses a polymer implant for
  • the implant may be used to deliver
  • neovascular inhibitors for the treatment of ARMD and drugs for the treatment of
  • the pharmaceutically active agent diffuses through the
  • implant for delivery of certain drugs including angiostatic steroids and drugs such as
  • the indentor has a raised portion that is used to indent or apply pressure to the sclera
  • U.S. Patent Nos. 5,725,493 and 5,830,173 both disclose non-bioerodable implants that have a drug containing reservoir located outside the globe of the eye and a drug
  • surgically implantable ophthalmic drug delivery device capable of safe, effective, rate- controlled, delivery of a wide variety of pharmaceutically active agents.
  • such a device should be easy and
  • One aspect of the present invention is an ophthalmic drug delivery device having a
  • the injection port first end and a second end, an injection port, a reservoir, and a sleeve.
  • a needle of a syringe is for sealingly engaging a needle of a syringe, which is for providing a fluid comprising a
  • the reservoir is disposed within the device, is fluidly
  • the sleeve is for engaging the device proximate overlapping
  • portions of the first end and the second end for forming a generally ring-shaped three-
  • FIG. 1 is a side sectional view schematically illustrating the human eye
  • FIG. 2 is a partially dissected, three dimensional schematic representation of the human eye
  • FIG. 3 is a perspective view of an ophthalmic drug delivery device according to a
  • FIG. 4 is a perspective view of the ophthalmic drug delivery device of FIG. 3
  • FIGS. 1-4 of the drawings like numerals being used for like
  • FIGS. 1-4 schematically illustrate an ophthalmic drug delivery device 10
  • Device 10 may be used in
  • a preferred use for device 10 is the delivery of pharmaceutically active agents to the
  • ARMD choroidial neovascularization
  • CNV choroidial neovascularization
  • retinopathies retinitis
  • Eye 52 has a
  • An anterior segment 66 of eye 52 generally includes the portions of eye 52 anterior of a line
  • a posterior segment 68 of eye 52 generally includes the portions of eye 52 posterior of line 67.
  • Retina 62 is physically attached to choroid 60 in a circumferential manner
  • Retina 62 has a macula 72 located slightly lateral to its optic
  • macula 72 is comprised primarily of
  • Tenon's membrane 74 is disposed on sclera 58.
  • a conjunctiva 76 covers a short area
  • Conjunctiva 76 is disposed on top of Tenon's
  • Eye 52 also has an equator 21. As shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are
  • device 10 is preferably disposed directly on the outer surface of sclera 58, below Tenon's
  • Device 10 is
  • FIGS. 3 and 4 schematically illustrate device 10 in greater detail.
  • a body 12 preferably includes a body 12 having a generally ring-shaped three-dimensional geometry
  • body 12 in its assembled state shown in FIGS. 3 and 4. In its unassembled stated, body 12
  • a sleeve 26 encircles overlapping ends 28 and 30 of body 12 to maintain the ring-shaped three-dimensional
  • Body 12 has a scleral surface 14, an orbital surface 16, an anterior side 18, and a
  • Body 12 also has a reservoir 22 located in its interior. Reservoir 22 preferably runs the entire length of body 80, and preferably has a plurality of openings 25
  • reservoir 22 may also have one or
  • openings 25 have a generally rectangular cross-section, but any number of materials that can be used for openings 25.
  • cross-section can be used for these openings.
  • Body 12 preferably further has an injection port 24. At least a portion of injection
  • port 24 is preferably made of a fluid impervious material that can be penetrated by a
  • a preferred material is silicone
  • injection port 24 is preferably colored or marked by raised protuberances. Injection port 24 preferably extends from anterior side 18 of body 12. Reservoir 22 extends into injection port 24.
  • the remainder of body 12 preferably comprises a biocompatible, non-bioerodable
  • Body 12 more preferably comprises a biocompatible, non-bioerodable
  • polymeric composition may be a homopolymer, a
  • copolymer straight, branched, cross-linked, or a blend.
  • polyglycolic acid polylactic-glycolic acid, cellulose esters, polyethersulfone, acrylics,
  • polymeric composition most preferably comprises silicone.
  • polymeric composition may also comprise other conventional materials that affect its physical properties, including, but not limited to, porosity, tortuosity, permeability,
  • polymeric composition may comprise other conventional materials that affect its chemical properties, including, but not limited to, toxicity and hydrophobicity.
  • a conventional syringe 100 and needle 102 may be used to measure the length of a patient's body.
  • Fluid 104 may comprise a solution, a
  • fluid 104 is a suspension with or without microparticles formed from bioerodable polymers.
  • Fluid 104 includes one or more ophthalmically acceptable pharmaceutically active agents, and may also include conventional non-active incipients. Examples of pharmaceutically active agents suitable for fluid 104 are anti-infectives,
  • antiallergenic agents including, without limitation, antibiotics, antivirals, and antifungals; antiallergenic agents
  • cyclooxygenase inhibitors including, without limitation, Cox I and Cox II inhibitors
  • glaucoma agents including, without limitation, adrenergics, -adrenergic blocking agents,
  • anhydrase inhibitors and prostaglandins; combinations of anti-glaucoma agents;
  • drugs for the treatment of ARMD including, without limitation, angiogenesis inhibitors and nutritional
  • drugs for the treatment of herpetic infections and CMV ocular infections drugs for the treatment of proliferative vitreoretinopathy including, without limitation,
  • wound modulating agents including, without limitation, growth factors; antimetabolites; neuroprotective drugs, including, without limitation,
  • eliprodil eliprodil
  • angiostatic steroids for the treatment of diseases or conditions of posterior
  • segment 26 including, without limitation, ARMD, CNV, retinopathies, retinitis, uveitis,
  • Preferred ones of such angiostatic steroids include
  • dione-21 -acetate dione-21 -acetate.
  • preferred angiostatic steroids are preferably formulated as a
  • macular edema is nepafenac.
  • the conventional non-active excipients may include, but are not limited to, ingredients to enhance the stability, solubility, penetrability, or other properties of fluid 104.
  • hydrolytic enzymes such as proteases, esterases, hyaluronidases, and collegenases may be utilized to enhance the penetration of the
  • Body 12 is preferably impermeable to fluid
  • Device 10 may be made by conventional polymer processing methods, including,
  • device 10 is formed using conventional injection molding
  • Device 10 is preferably surgically placed directly on the outer surface of sclera 58
  • surgeon first performs a 360 degree peritomy about 3 mm posterior to limbs 77 of eye 52. The surgeon then performs a blunt dissection
  • Injection port 24 is preferably
  • needle 102 to inject fluid 104 into reservoir 22.
  • the surgeon preferably moves lower
  • injection port 24 may be easily visualized beneath the Tenon's capsule and any combination thereof.
  • Port 24 reseals automatically upon removal of the
  • Fluid 104 is disposed throughout reservoir 22, and is in communication with
  • sclera 58 via openings 25, or any other openings from reservoir 22.
  • device 10 can be used to deliver a pharmaceutically effective
  • properties include hydrophobicity, solubility, dissolution rate, diffusion coefficient, and
  • device 10 may be used to deliver both a localized distribution of drug primarily proximate macula 72, or to deliver drug to substantially the entire retina, depending upon the particular fluid 104 and its .
  • reservoir 22 no longer contains any fluid 104, a surgeon may refill reservoir 22 as described hereinabove.
  • posterior side 20 of body 12 may also include a sharp surface or
  • device 10 minimizes the risk of penetrating the
  • the devices of the present invention are
  • agents to the posterior segment of the eye to combat diseases such as ARMD, CNV,
  • retinopathies retinitis, uveitis, macular edema, and glaucoma.
  • implanting the devices is safe, simple, quick, and capable of being performed in an
  • the devices are easy and economical to manufacture. Furthermore,

Abstract

An ophthalmic drug delivery device (10) having a first end and a second end (Figure 3), an injection port (24), a reservoir, (22), and a sleeve (26) is disclosed. The injection port is for sealingly engaging a needle (102) of a syringe (100), which is for providing a fluid (104) comprising a pharmaceutically active agent. The reservoir is disposed within the device, is flui dly coupled to the injection port, and has an opening (25) for communicating the fluid to an outer surface of a sclera (58) of an eye (52). The sleeve is for engaging the device proximate overlapping portions of the first end and the second end for forming a generally ring-shaped three-dimensional geometry upon implantation of the device on the outer surface of the sclera. The device is useful for the treatment of a disease of the posterior segment (68) of the eye.

Description

OPHTHALMIC DRUG DELIVERY DEVICE
This application is related to U.S. Patent Application Serial No. 09/660,000 filed
September 12, 2000 entitled "Drug Delivery Device", now U.S. Patent No. 6,413,540,
and U.S. Patent Application Serial No. 09/664,790, filed September 19, 2000 entitled
"Ophthalmic Drug Delivery Device", now U.S. Patent No. 6,416,777, both of which are
incorporated herein in their entirety by this reference.
Field of the Invention
The present invention generally pertains to biocompatible implants for delivery of pharmaceutically active agents to the eye. More particularly, but not by way of limitation,
the present invention pertains to biocompatible implants for delivery of pharmaceutically active agents to the posterior segment of the eye.
Description of the Related Art
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.
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.
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 sub-Tenon's capsule injections of these compounds carry the potential risk of penetrating the globe and the severe, often blinding, complications of
retinal detachment and endophthalmitis. In addition, it is difficult to perform such
injections in a reproduceable manner, and each injection may result in a different
distribution of drug along the scleral surface. Furthermore, many attempts to inject drug
below the Tenon's capsule actually result in injections into the Tenon's capsule itself or
the surrounding tissue, which is not desirable. Repetitive intraocular injections may also result in retinal detachment and endophthalmitis. Photodynamic therapy is a new
technology for which the long-term efficacy is still largely unknown.
In order to prevent complications related to the above-described treatments and to provide better ocular treatment, researchers have suggested various implants aimed at
delivery of anti-angiogenic compounds to the eye. U.S. Patent No. 5,824,072 to Wong
discloses a non-biodegradable polymeric implant with a pharmaceutically active agent
disposed therein. The pharmaceutically active agent diffuses tlirough 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. U.S. Patent 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.
U.S. Patent 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.
All of the above-described implants require careful design and manufacture to
permit controlled diffusion of the pharmaceutically active agent through a polymer body or polymer membrane 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.
U.S. Patent 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.
U.S. Patent Nos. 5,725,493 and 5,830,173 both disclose non-bioerodable implants that have a drug containing reservoir located outside the globe of the eye and a drug
delivery tube running from the reservoir and into the vitreous cavity at the pars plana. Despite the above-described ophthalmic implants, a need still exists for a
surgically implantable ophthalmic drug delivery device capable of safe, effective, rate- controlled, 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. Ideally, such an ophthalmic drug delivery device
would be capable of localized delivery of pharmaceutically active agents to a specific
portion of the retina, as well as pan-retinal delivery of pharmaceutically active agents. Summary of the Invention
One aspect of the present invention is an ophthalmic drug delivery device having a
first end and a second end, an injection port, a reservoir, and a sleeve. The injection port
is for sealingly engaging a needle of a syringe, which is for providing a fluid comprising a
pharmaceutically active agent. The reservoir is disposed within the device, is fluidly
coupled to the injection port, and has an opening for communicating the fluid to an outer
surface of a sclera of an eye. The sleeve is for engaging the device proximate overlapping
portions of the first end and the second end for forming a generally ring-shaped three-
dimensional geometry upon implantation of the device on the outer surface of the sclera.
Brief Description of the Drawings
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:
FIG. 1 is a side sectional view schematically illustrating the human eye;
FIG. 2 is a partially dissected, three dimensional schematic representation of the human eye;
FIG. 3 is a perspective view of an ophthalmic drug delivery device according to a
preferred embodiment of the present invention; and
FIG. 4 is a perspective view of the ophthalmic drug delivery device of FIG. 3
showing a preferred method of operation. Detailed Description of the Preferred Embodiments
The preferred embodiments of the present invention and their advantages are best
understood by referring to FIGS. 1-4 of the drawings, like numerals being used for like
and corresponding parts of the various drawings.
FIGS. 1-4 schematically illustrate an ophthalmic drug delivery device 10
according to a preferred embodiment of the present invention. Device 10 may be used in
any case where delivery of a pharmaceutically active agent to the eye is required. Device
10 is particularly useful for delivery of active agents to the posterior segment of the eye.
A preferred use for device 10 is the delivery of pharmaceutically active agents to the
retina for treating ARMD, choroidial neovascularization (CNV), retinopathies, retinitis,
uveitis, macular edema, and glaucoma.
Referring to FIGS. 1-2, a human eye 52 is schematically illustrated. Eye 52 has a
cornea 54, a lens 56, a sclera 58, a choroid 60, a retina 62, and an optic nerve 64. An anterior segment 66 of eye 52 generally includes the portions of eye 52 anterior of a line
67. A posterior segment 68 of eye 52 generally includes the portions of eye 52 posterior of line 67. Retina 62 is physically attached to choroid 60 in a circumferential manner
proximate pars plana 70. Retina 62 has a macula 72 located slightly lateral to its optic
disk 19. As is well known in the ophthalmic art, macula 72 is comprised primarily of
retinal cones and is the region of maximum visual acuity in retina 62. A Tenon's capsule
or Tenon's membrane 74 is disposed on sclera 58. A conjunctiva 76 covers a short area
of the globe of eye 52 posterior to limbus 77 (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 76 is disposed on top of Tenon's
capsule 74. Eye 52 also has an equator 21. As shown in FIG. 2, superior rectus muscle 80, inferior rectus muscle 82, lateral rectus muscle, 84, and medial rectus muscle 86 are
attached to sclera 58.
As is shown in FIGS. 1 and 2, and as is described in greater detail hereinbelow,
device 10 is preferably disposed directly on the outer surface of sclera 58, below Tenon's
capsule 74 for treatment of most posterior segment diseases or conditions. Device 10 is
most preferably disposed directly on the outer surface of sclera 58, below Tenon's capsule
74, proximate equator 21.
FIGS. 3 and 4 schematically illustrate device 10 in greater detail. Device 10
preferably includes a body 12 having a generally ring-shaped three-dimensional geometry
in its assembled state shown in FIGS. 3 and 4. In its unassembled stated, body 12
preferably has a generally rectangular three-dimensional geometry. A sleeve 26 encircles overlapping ends 28 and 30 of body 12 to maintain the ring-shaped three-dimensional
geometry.
Body 12 has a scleral surface 14, an orbital surface 16, an anterior side 18, and a
posterior side 20. Body 12 also has a reservoir 22 located in its interior. Reservoir 22 preferably runs the entire length of body 80, and preferably has a plurality of openings 25
to posterior side 20. Although not shown in FIGS. 3-4, reservoir 22 may also have one or
more openings to scleral surface 14, anterior side 18, or orbital surface 16 of body 12. As
shown in FIGS. 3-4, openings 25 have a generally rectangular cross-section, but any
cross-section can be used for these openings.
Body 12 preferably further has an injection port 24. At least a portion of injection
port 24 is preferably made of a fluid impervious material that can be penetrated by a
needle and that reseals itself upon removal of the needle. A preferred material is silicone
rubber. In addition, injection port 24 is preferably colored or marked by raised protuberances. Injection port 24 preferably extends from anterior side 18 of body 12. Reservoir 22 extends into injection port 24.
The remainder of body 12 preferably comprises a biocompatible, non-bioerodable
material. Body 12 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. Patent 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 and hydrophobicity.
As shown in FIG. 4, a conventional syringe 100 and needle 102 may be used to
impart a fluid 104 (indicated by arrows) containing a pharmaceutically active agent or
agents into reservoir 22 via injection port 24. Fluid 104 may comprise a solution, a
suspension, an emulsion, an ointment, a gel forming solution, a gel, a bioerodable
polymer, a non-bioerodable polymer, microparticles, or combinations thereof. Most
preferably, fluid 104 is a suspension with or without microparticles formed from bioerodable polymers. Fluid 104 includes one or more ophthalmically acceptable pharmaceutically active agents, and may also include conventional non-active incipients. Examples of pharmaceutically active agents suitable for fluid 104 are anti-infectives,
including, without limitation, antibiotics, antivirals, and antifungals; antiallergenic agents
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; decongestants; anti-
glaucoma agents, including, without limitation, adrenergics, -adrenergic blocking agents,
α-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 posterior
segment 26, including, without limitation, ARMD, CNV, retinopathies, retinitis, uveitis,
macular edema, and glaucoma. Such angiostatic steroids are more fully disclosed in U.S.
Patent Nos. 5,679,666 and 5,770,592. Preferred ones of such angiostatic steroids include
4,9(1 l)-Pregnadien-17α,21-diol-3,20-dione and 4,9(1 l)-Pregnadien-17α,21-diol-3,20-
dione-21 -acetate. These preferred angiostatic steroids are preferably formulated as a
suspension. A preferred non-steroidal anti-inflammatory for the treatment of cystoid
macular edema is nepafenac. The conventional non-active excipients may include, but are not limited to, ingredients to enhance the stability, solubility, penetrability, or other properties of fluid 104. In particular, hydrolytic enzymes such as proteases, esterases, hyaluronidases, and collegenases may be utilized to enhance the penetration of the
pharmaceutically active agents through natural and newly formed connective tissue that
may encapsulate device 10 after implantation. Body 12 is preferably impermeable to fluid
104.
Device 10 may be made by conventional polymer processing methods, including,
but not limited to, injection molding, extrusion molding, transfer molding, and
compression molding. Preferably, device 10 is formed using conventional injection
molding techniques. Device 10 is preferably surgically placed directly on the outer surface of sclera 58
below Tenon's capsule 74 using a simple surgical technique that is capable of being
performed in an outpatient setting. The surgeon first performs a 360 degree peritomy about 3 mm posterior to limbs 77 of eye 52. The surgeon then performs a blunt dissection
to separate Tenon's capsule 74 from sclera 58 up to a point slightly posterior of equator 21. As shown best in FIG. 2, the surgeon then positions device 10 on the outer surface of
sclera 58 below superior rectus muscle 80, medial rectus muscle 86, inferior rectus muscle
82, and lateral rectus muscle 84 generally near equator 21. Injection port 24 is preferably
located in the infra-temporal quadrant of eye 52 between inferior rectus muscle 82 and
lateral rectus muscle 84. The surgeon tightens device 10 around sclera 58 and fixes
overlapping ends 28 and 30 of body 12 with sleeve 26. The surgeon then moves Tenon's
capsule 74 back to its original position and sutures it in place. After closing, the surgeon
places antibiotic ointment on the surgical wound.
Once device 10 is located in the desired position, the surgeon uses syringe 100 and
needle 102 to inject fluid 104 into reservoir 22. The surgeon preferably moves lower
eyelid 79 downward and instructs the patient to look upward so as to expose injection port 24. Injection port 24 may be easily visualized beneath the Tenon's capsule and any
connective tissue encapsulating device 10 due to its color or raised protuberances. The
surgeon sticks needle 102 into injection port 24, injects fluid 104 into reservoir 22, and
removes needle 102 from the port 24. Port 24 reseals automatically upon removal of the
needle. Fluid 104 is disposed throughout reservoir 22, and is in communication with
sclera 58 via openings 25, or any other openings from reservoir 22.
It is believed that device 10 can be used to deliver a pharmaceutically effective
amount of a pharmaceutically active agent through sclera 58 and choroid 60 into retina 62
for many years, depending on the particular physicochemical properties of the particular
fluid 104 and its pharmaceutically active agent employed. Important physicochemical
properties include hydrophobicity, solubility, dissolution rate, diffusion coefficient, and
tissue affinity. In addition, it is believed that device 10 may be used to deliver both a localized distribution of drug primarily proximate macula 72, or to deliver drug to substantially the entire retina, depending upon the particular fluid 104 and its .
pharmaceutically active agents and incipients. After reservoir 22 no longer contains any fluid 104, a surgeon may refill reservoir 22 as described hereinabove. Although not
shown in FIGS. 1-4, posterior side 20 of body 12 may also include a sharp surface or
edge. During refilling of reservoir 22, the surgeon may move device 10 slightly
posteriorly so that such sharp surface or edge pierces any connective tissue that may
encapsulate device 10 after implantation. Piercing this connective tissue facilitates proper
distribution of fluid 104 via openings 25. In addition, unlike repetitive sub-Tenon's
capsule injections of drug formulations, device 10 minimizes the risk of penetrating the
globe of the eye, always results in fluid 212 being distributed below the Tenon's capsule
74 on the outer surface of sclera 58, and results in a reproduceable distribution of fluid
212 on a desired portion of the outer surface of the sclera 58. From the above, it may be appreciated that the present invention provides
improved devices and methods for safe, effective, rate-controlled delivery of a variety of
pharmaceutically active agents to the eye. The devices of the present invention are
especially useful for localized and/or pan-retinal delivery of pharmaceutically active
agents to the posterior segment of the eye to combat diseases such as ARMD, CNV,
retinopathies, retinitis, uveitis, macular edema, and glaucoma. The surgical procedure for
implanting the devices is safe, simple, quick, and capable of being performed in an
outpatient setting. The 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 agents that create a specific
physical condition in a patient or animal subject.
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.

Claims

What is claimed is:
1. An ophthalmic drug delivery device, comprising:
a first end and a second end;
an injection port for sealingly engaging a needle of a syringe, said syringe for
providing a fluid comprising a pharmaceutically active agent;
a reservoir disposed within said device, fluidly coupled to said injection port, and
having an opening for communicating said fluid to an outer surface of a sclera of an eye;
and
a sleeve for engaging said device proximate overlapping portions of said first end
and said second end for forming a generally ring-shaped three-dimensional geometry
upon implantation of said device on said outer surface of said sclera.
2. The ophthalmic drug delivery device of claim 1 further comprising an
anterior side, and wherein said injection port is disposed on said anterior side.
3. The ophthalmic drug delivery device of claim 1 further comprising a
posterior side, and wherein said posterior side comprises a sharp exterior surface for
piercing connective tissue that may encapsulate said device upon implantation on said outer surface of said sclera.
4. The ophthalmic drug delivery device of claim 1 wherein said reservoir
comprises a plurality of said openings for communicating said fluid to said outer surface of said sclera.
5. The ophthalmic drug delivery device of claim 1 wherein said device
delivers said pharmaceutically active agent through said sclera and a choroid into a retina
of said eye.
6. The ophthalmic drug delivery device of claim 5 wherein said device
delivers said pharmaceutically active agent to substantially all of said retina.
7. The ophthalmic drug delivery device of claim 5 wherein said device
delivers said pharmaceutically active agent to a portion of said retina proximate said
device.
PCT/US2002/023048 2001-07-23 2002-07-22 Ophthalmic drug delivery device WO2003009774A2 (en)

Priority Applications (10)

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BR0210494-6A BR0210494A (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
MXPA03011609A MXPA03011609A (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device.
PL368207A PL204644B1 (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
JP2003515170A JP4261343B2 (en) 2001-07-23 2002-07-22 Ophthalmic drug administration device
AU2002319596A AU2002319596B2 (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
EP02750196A EP1409065B1 (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
CA002447802A CA2447802C (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
DK02750196T DK1409065T3 (en) 2001-07-23 2002-07-22 Ophthalmic drug delivery device
DE60217679T DE60217679T2 (en) 2001-07-23 2002-07-22 DEVICE FOR RELEASING AN OPHTHALMIC MEDICINAL PRODUCT
US10/706,105 US7094226B2 (en) 2001-07-23 2003-11-12 Ophthalmic drug delivery device

Applications Claiming Priority (2)

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US30728401P 2001-07-23 2001-07-23
US60/307,284 2001-07-23

Related Child Applications (1)

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EP (1) EP1409065B1 (en)
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EP1409065A2 (en) 2004-04-21
ES2278936T3 (en) 2007-08-16
EP1409065A4 (en) 2006-01-11
DK1409065T3 (en) 2007-05-21
CN1525872A (en) 2004-09-01
CA2447802C (en) 2009-09-29
ZA200308993B (en) 2004-11-19
AU2002319596B2 (en) 2006-04-27
PL368207A1 (en) 2005-03-21
US7094226B2 (en) 2006-08-22
CN1203814C (en) 2005-06-01
WO2003009774A3 (en) 2003-08-21
JP2005521433A (en) 2005-07-21
JP4261343B2 (en) 2009-04-30
US20040106906A1 (en) 2004-06-03
MXPA03011609A (en) 2004-07-01
PT1409065E (en) 2007-03-30
DE60217679D1 (en) 2007-03-08
EP1409065B1 (en) 2007-01-17
CA2447802A1 (en) 2003-02-06
BR0210494A (en) 2004-06-22
DE60217679T2 (en) 2007-10-25
PL204644B1 (en) 2010-01-29

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