U.S. patent application number 12/998652 was filed with the patent office on 2011-09-22 for biocompatible biodegradable intraocular implant system.
This patent application is currently assigned to InSight Innovations, LLC. Invention is credited to Kevin H. Cuevas.
Application Number | 20110230963 12/998652 |
Document ID | / |
Family ID | 42198717 |
Filed Date | 2011-09-22 |
United States Patent
Application |
20110230963 |
Kind Code |
A1 |
Cuevas; Kevin H. |
September 22, 2011 |
BIOCOMPATIBLE BIODEGRADABLE INTRAOCULAR IMPLANT SYSTEM
Abstract
Generally, an intraocular implant and methods for treating an
ocular condition. As to certain embodiments, an intraocular
biocompatible biodegradable implant (11) which can provide a
biocompatible biodegradable material in the form of a flexible
membrane (12) containing an active agent (24) which implanted
between an intraocular lens (8) and the surface of the posterior
capsule (5) of the eye (1)(4) inhibits migration of residual lens
epithelial cells after cataract surgery by providing structural or
pharmaceutical barriers to reduce posterior capsule (5)
opacification of the eye (1)(4).
Inventors: |
Cuevas; Kevin H.; (Denver,
CO) |
Assignee: |
InSight Innovations, LLC
|
Family ID: |
42198717 |
Appl. No.: |
12/998652 |
Filed: |
November 19, 2009 |
PCT Filed: |
November 19, 2009 |
PCT NO: |
PCT/US2009/006195 |
371 Date: |
May 13, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61199674 |
Nov 20, 2008 |
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61270567 |
Jul 10, 2009 |
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Current U.S.
Class: |
623/6.56 |
Current CPC
Class: |
A61F 2/15 20150401; A61L
2300/416 20130101; A61L 27/54 20130101; A61F 2/14 20130101; A61L
2300/61 20130101; A61L 2430/16 20130101; A61L 27/58 20130101; A61F
9/0017 20130101; A61F 2/1602 20130101; A61L 2300/604 20130101; A61F
2210/0004 20130101; A61F 2230/0065 20130101; A61F 2002/009
20130101; A61K 9/0051 20130101 |
Class at
Publication: |
623/6.56 |
International
Class: |
A61F 2/16 20060101
A61F002/16 |
Claims
1. An intraocular implant, comprising: a) a biocompatible
substantially planar circular flexible membrane configured to
implant in a localized region inside an eye, wherein the localized
region is selected from the group consisting of: i) between the
lens and the surface of the posterior capsule; ii) between the lens
and the surface of the iris; and iii) overlying the iris
intraocular implant; b) an aperture element which communicates
between opposed sides of said membrane to provide a passage
opening, said passage opening configured to intraocularly align
with a visual axis of said eye, thereby providing a line of sight
which passes through said passage opening.
2. The intraocular implant of claim 1, wherein said aperture
element defines a generally circular passage opening.
3. The intraocular implant of claim 2, wherein said generally
circular passage opening has a diameter in the range of about 1.5
millimeter to about 9 millimeters.
4. The intraocular implant of claim 1, wherein said biocompatible
flexible membrane is generated from a polymeric material selected
from the group consisting of: polyurethane, polyisobutylene,
ethylene-alpha-olefin copolymer, acrylic polymers, acrylic
copolymers, vinyl halide polymer, vinyl halide copolymer, polyvinyl
esters, polyvinylidene chloride, polyacrylonitrile, polyvinyl
ketones, polyvinyl aromatic, polystyrene, ethylene-methyl
methacrylate copolymers, acrylonitrile-styrene copolymers, ABS
resins, ethylene-vinyl acetate copolymers, polyamides, Nylon 66,
polycaprolactone, alkyd resins, polycarbonates, polyoxyethylenes,
polyimides, polyesters, epoxy resins, rayon-triacetate, and
cellophane.
5. The intraocular implant of claim 1, wherein said membrane
comprises a biodegradable membrane.
6. The intraocular implant of claim 5, wherein said membrane is
generated from a polymeric material selected from the group
consisting of: polylactide polymers (PLA), copolymers of lactic and
glycolic acids (PLGA), polylactic acid-polyethylene oxide
copolymers, poly(.epsilon.-caprolactone-co-L-lactic acid (PCL-LA),
glycine/PLA copolymers, PLA copolymers involving polyethylene
oxides (PEO), acetylated polyvinyl alcohol (PVA)/polycaprolactone
copolymers, hydroxybutyrate-hydroxyvalerate copolymers, polyesters
of aspartic acid and aliphatic diols, poly(alkylene
tartrates)/polyurethane copolymers, polyglutamates, biodegradable
nonpeptidic polyamides, amino acid polymers, polyanhydride drug
carriers such as, but not limited to, poly(sebacic acid) (PSA),
aliphatic-aromatic homopolymers, poly(anhydride-co-imides),
poly(phosphoesters), poly(phosphazenes), poly(iminocarbonate),
crosslinked poly(ortho ester), hydroxylated polyester-urethanes,
hydrogels, and methylcellulose.
7. The intraocular implant of claim 5, further comprising at least
one active agent dispersed in said membrane releasable in
sufficient amounts to treat an ocular condition.
8. The intraocular implant of claim 7, wherein said at least one
active agent is selected from the group consisting of: antibiotic
agents, antibacterial agents, antiviral agents, antiglaucoma
agents, antiallergenic agents, antiinflammatory agents,
antiproliferative agents, immune system modifying agents,
anticancer agents, antisense agents, antimytotic agents, myotic
agents, ace inhibitors, endogenous cytokines, basement membrane
influencing agents, endothelial cell growth agents, epithelial cell
growth agents, adrenergic agonists, adrenergic blockers,
cholinergic agonists, cholinergic blockers, aldose reductase
inhibitors, analgesics, anesthetics, antiallergics,
antihypertensives, pressors, antibacterials, antivirals,
antifungals, antiprotozoals, anti-infectives, antitumor agents,
antimetabolites, daunomycin, antiangiogenic agents, tyrosine kinase
inhibitors, aminoglycosides, gentamicin, kanamycin, neomycin,
vancomycin, amphenicols, chloramphenicol, cephalosporins, cefazolin
HCl, penicillins, ampicillin, penicillin, carbenicillin, oxycillin,
methicillin, lincosamides, lincomycin, polypeptide antibiotics,
polymixin, bacitracin, tetracycline, minocycline, doxycycline,
quinolones, ciprofloxain, moxifloxacin, gatifloxacin, levofloxacin,
sulfonamides, chloramine T, sulfones, sulfanilic acid, acyclovir,
gancyclovir, vidarabine, azidothymidine, dideoxyinosine,
dideoxycytosine, dexamethasone, epinephrine, isoflurphate,
adriamycin, bleomycin, mitomycin, ara-C, actinomycin D, scopolamin,
analgesics, codeine, morphine, keterolac, naproxen, anesthetics,
lidocaine, beta.-adrenergic blocker, beta.-adrenergic agonist,
ephidrine, epinephrine, aldose reductase inhibitor, epalrestat,
ponalrestat, sorbinil, tolrestat, cromolyn, beclomethasone,
dexamethasone, flunisolide, colchicine, anihelminthic agents,
ivermectin, suramin sodium, antiamebic agents, chloroquine,
chlortetracycline, antifungal agents, amphotericin,
antiangiogenesis compounds, anecortave acetate, retinoids,
tazarotene, brimonidine alphagan, Alphagan P, acetozolamide,
bimatoprost, lumigan, timolol, mebefunolol, memantine, alpha-2
adrenergic receptor agonists, 2-methoxyestradiol, antineoplastic
agents, vinblastine, vincristine, alpha interferon, beta
interferon, gamma interferon, antimetabolites, folic acid analogs,
purine analogs, pyrimidine analogs, immunosuppressant agents,
azathiprine, cyclosporine, mizoribine, miotic agents, carbachol,
mydriatic agents, atropine, protease inhibitors, aprotinin,
camostat, gabexate, vasodilators, bradykinin, epidermal growth
factor, basic fibroblast growth factor, nerve growth factors,
steroidal anti-inflammatory agents, 21-acetoxypregnenolone,
alclometasone, algestone, amcinonide, beclomethasone,
betamethasone, budesonide, chloroprednisone, clobetasol,
clobetasone, clocortolone, cloprednol, corticosterone, cortisone,
cortivazol, deflazacort, desonide, desoximetasone, dexamethasone,
diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort,
flucloronide, flumethasone, flunisolide, fluocinolone acetonide,
fluocinonide, fluocortin butyl, fluocortolone, fluorometholone,
fluperolone acetate, fluprednidene acetate, fluprednisolone,
flurandrenolide, fluticasone propionate, formocortal, halcinonide,
halobetasol propionate, halometasone, halopredone acetate,
hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone,
medrysone, meprednisone, methylprednisolone, mometasone furoate,
paramethasone, prednicarbate, prednisolone, prednisolone
25-diethylamino-acetate, prednisolone sodium phosphate, prednisone,
prednival, prednylidene, rimexolone, tixocortol, triamcinolone,
triamcinolone acetonide, triamcinolone benetonide, triamcinolone
hexacetonide, vascular endothelial growth factor inhibitors,
bevacizumab, ranibisumab, pegatanib, transforming growth factor
inhibitors, and fibroblast growth factor inhibitors.
9. The intraocular implant of any one of claim 1, 5 or 7, further
comprising an amount of non-active agent dispersed in said
membrane.
10. The intraocular implant of claim 9, wherein said amount of
non-active agent is selected from the group consisting of: sodium
bisulfite, sodium bisulfate, sodium thiosulfate, benzalkonium
chloride, chlorobutanol, thimerosal, phenylmercuric acetate,
phenylmercuric nitrate, methylparaben, polyvinyl alcohol and
phenylethyl alcohol, sodium carbonate, sodium borate, sodium
phosphate, sodium acetate, sodium bicarbonate, sodium chloride and
potassium chloride.
11. The intraocular implant of claim 5, wherein said membrane
comprises a first membrane layer coupled to a second membrane
layer.
12. The intraocular implant of claim 11, wherein said first
membrane layer and said second membrane layer comprise different
polymeric materials.
13. The intraocular implant of claim 12, wherein said first
membrane layer biodegrades at a different rate than said second
membrane layer.
14. The intraocular implant of claim 13, wherein at least one of
said first membrane layer and said second membrane layer include an
active agent.
15. The intraocular implant of claim 14, wherein said first
membrane layer and said second membrane layer each contain said
active agent, and wherein said active agent contained in said first
membrane layer is different than said active agent contained in
said second membrane layer.
16. The intraocular implant of claim 5, wherein said membrane
comprises a first annular zone and a second annular zone.
17. The intraocular implant of claim 16, wherein said first annular
zone biodegrades at a different rate than said second annular
zone.
18. The intraocular implant of claim 17, wherein at least one of
said first annular zone and said second annular zone contain an
active agent.
19. The intraocular implant of claim 18, wherein said first annular
zone and said second annular zone each contain an active agent, and
wherein said active agent contained in said first annular zone is
different than said active agent contained in said second annular
zone.
20. The intraocular implant of claim 5, further comprising an outer
boundary of said membrane which defines a generally circular
area.
21. The intraocular implant of claim 20, further comprising a
plurality of radial slit elements each originating at said aperture
element extending radially outward toward said outer boundary.
22. The intraocular implant of claim 20, further comprising a
plurality of radial slit elements each originating at said outer
boundary extending radially inward toward said aperture
element.
23. The intraocular implant of claim 20, further comprising a
plurality of radial capillaries which communicate between said
outer boundary and said aperture element, said plurality of radial
capillaries configured to allow fluid within said eye to circulate
between said first side of said intraocular implant and a surface
of said localized region inside said eye.
24. The intraocular implant of claim 20, further comprising a
plurality of outer boundary recess elements which periodically
interrupt the outer boundary.
25. The intraocular implant of claim 5, further comprising a
plurality of corrugate elements disposed in generally linear
parallel relation to provide undulations in said biodegradable
biocompatible flexible membrane, said plurality of corrugate
elements configured to allow fluid within said eye to circulate
between said first side of said intraocular implant and said
surface of said posterior capsule of said eye.
26. The intraocular implant of claim 5, further comprising a
plurality of perforation elements which communicate between opposed
sides of said membrane.
27. The intraocular implant of claim 5, further comprising a
patterned surface element coupled to said membrane, said pattern
surface element configured to reduce travel of said intraocular
implant within said localized region of said eye.
28-30. (canceled)
31. The intraocular implant of claim 5, further comprising an
amount of alkylphosphocholine dispersed in said membrane releasable
in amounts sufficient to provide a concentration of
alkylphosphocholine in said localized region in a range of about
0.5 mM to about 1.5 mM for about five days.
32. The intraocular implant of claim 5, further comprising an
amount of mitomycin-C dispersed in said membrane releasable in
amounts sufficient to provide a concentration of mitomycin-C in
said localized region of about 0.04 mg/mL for a period of about
five days.
33-68. (canceled)
Description
[0001] This application is the United States National Stage of
International Patent Cooperation Treaty Patent Application No.
PCT/US2009/006195, filed Nov. 19, 2009, which claims the benefit of
U.S. Provisional Patent Application No. 61/270,567, filed Jul. 10,
2009 and claims the benefit of U.S. Provisional Patent Application
No. 61/199,674, filed Nov. 20, 2008, each hereby incorporated by
reference herein.
I. TECHNICAL FIELD
[0002] Generally, an invention comprising an intraocular implant
and methods for treating an ocular condition. In particular, an
embodiment of an intraocular biocompatible biodegradable implant
including a biocompatible biodegradable material and an active
agent which implanted between an intraocular lens and the surface
of the posterior capsule of the eye inhibits migration of residual
lens epithelial cells after cataract surgery by providing
structural or pharmaceutical barriers to reduce posterior capsule
opacification of the eye.
II. BACKGROUND
[0003] Visually impairing cataract is the leading cause of
preventable blindness in the world. Presently, the only known
treatment for cataract is the surgical removal of the opacified
lens of the affected eye and replacement with an artificial
intraocular lens ("IOL"). Technological advances in cataract
surgery with IOL implantation have made cataract surgery among the
most effective surgical procedures.
[0004] Now referring primarily to FIGS. 1 and 2, which show a top
view and a cross section view of a phakic eye (1). The most common
technique of cataract surgery may be extracapsular cataract
extraction ("ECCE") which involves the creation of an incision (42)
near the outer edge of the cornea (2) and a circular opening
(44)(shown in FIGS. 3 and 4) in the anterior lens capsule (43)(also
herein referred to as the "anterior capsule") through which the
opacified lens (3) can be removed from the lens capsule (45)(also
referred to as the "capsular bag"). Now referring primarily to
FIGS. 3 and 4 which show a top view and a cross section view of a
psuedophakic eye (4), the lens capsule (43) anchored to the ciliary
body (6) through the zonular fibers (7) can be left substantially
intact. The IOL (8) can then be placed within the lens capsule (43)
through the circular opening (44) in the anterior capsule (43). The
IOL (8) can be acted on by zonular forces exerted on the outer
circumference of the lens capsule (45) which establishes the
location of the IOL (8) within the lens capsule (45). The intact
posterior capsule (5) acts as a barrier to the vitreous humor (9)
within the posterior segment of the eye.
[0005] The most frequent complication to ECCE and other methods of
cataract surgery can be opacification of the posterior capsule (5).
Posterior capsule opacification ("PCO") results from the migration
of residual lens epithelial cells ("LEC") between the IOL (8) and
the surface of the posterior capsule (5) subsequent to cataract
surgery. The residual LECs once located between the IOL (8) and the
surface of the posterior capsule (5) can proliferate leading to
clouding of the normally clear posterior capsule (5). Clouding of
the posterior capsule (5) can decrease visual acuity if the
opacification occurs within the visual axis (21).
[0006] Visually significant PCO requires an additional surgery to
clear the visual axis of the eye. Presently, the most widely
utilized procedure to clear the visual axis of PCO may be
Neodymium: Yttrium-Aluminum-Garnet ("Nd:YAG") laser capsulotomy.
However, there may be substantial problems with this procedure such
as IOL damage, postoperative intraocular pressure spikes, vitreous
floaters, cystoid macular edema, retinal detachment, and IOL
subluxation, or the like. Additionally, pediatric patients can be
difficult to treat and a delay in treatment can lead to
irreversible amblyopia. Many underdeveloped countries do not have
access to a Nd:YAG laser and the cost can be prohibitive.
[0007] Prevention or inhibition of PCO fall into two broad
categories: mechanical and pharmacological. Mechanical mechanisms
to inhibit PCO have primarily focused on configuration of the IOL
(8). Configuring the IOL to include a sharp posterior edge may
provide a structural barrier to the migration of residual LECs
between the IOL and the surface of the posterior capsule (5).
Cleary et al., Effect of Square-edged Intraocular Lenses on
Neodymium: YAG Laser Capsulotomy Rates in the United States, J.
Cataract & Refractive Surgery, Vol. 13, p. 1899 (November
2007). However, while introduction of square edged IOLs appears to
have reduced incidence of PCO, a review of Medicare claims data
from 1993 to 2003 evidences that the number of laser capsulotomies
performed in the United States to treat PCO in recipients of square
edged IOL remains substantial.
[0008] Pharmacological mechanisms have been proposed as a way to
inhibit or prevent PCO. The effect of topical treatment with
nonsteroidal anti-inflammatory drugs ("NSAIDs") such as diclofenac
and indomethacin after phacoemulsification do not appear to inhibit
PCO. Inan et al., Effect of Diclofenac on Prevention of Posterior
Capsule Opacification in Human Eyes, Can J Ophthalmol, 41; 624-629
(2006). Additionally, the majority of pharmacological agents tested
in vitro for inhibition of migration and proliferation of LECs are
antimetabolites and antimitotics which have not been used
clinically because of their toxic side effects. Inan U U, Ozturk F,
Kaynak S, et al. Prevention of Posterior Capsule Opacification by
Intraoperative Single-dose Pharmacologic Agents, J Cataract Refract
Surg, 27:1079-87 (2001); Inan U U, Ozturk F, Kaynak S. Ilker S S,
Ozer E, Guler, Prevention of Posterior Capsule Opacification by
Retinoic Acid and Mitomycin, Graefes Arch Clin Exp Ophthalmol 239:
693-7 (2001); Cortina P, Gomez-Lechon M J, Navea A, Menezo J L,
Terencio M C, Diaz-Llopis, M, Diclofenac Sodium and Cyclosporine A
Inhibit Human Lens Epithelial Cell Proliferation in Culture,
Graefes Arch Clin Exp Ophthalmol 235: 180-5 (1997); Ismail M M,
Alio J L, Ruiz Moreno J M, Prevention of Secondary Cataract by
Antimitotic Drugs: Experimental Study, Ophthalmic Res, 28:64-9
(1996); Emery J., Capsular Opacification After Cataract Surgery,
Curr Opin Ophthalmol 9:60-5 (1998); Hartmann C, Wiedemann P, Gothe
K, Weller M, Heimann K, Prevention of Secondary Cataract by
Intracapsular Administration of the Antibiotic Daunomycin,
Ophthalmologie, 4:102-6 (1990).
[0009] Also, available is a sealed capsule irrigation device which
functions to allow selective irrigation of the lens capsule with
LEC inhibiting pharmacologic agents. Maloof A J, Neilson G,
Milverton E J, Pandy S K, Selective and specific targeting of lens
epithelial cells during cataract surgery using sealed-capsule
irrigation, J Cataract Refract Surg, 29:1566-68 (2003). It is not
clear, however, that use of the device can be reduced to routine
practice. Problems relating to incomplete seal of the lens capsule
(45) resulting in leakage of potentially toxic chemicals into the
anterior chamber (46) of the eye, rupture of the lens capsule (45)
during manipulation of the irrigation device, difficulty in
assessing kill of LECs within the lens capsule and an increase in
the duration of routine cataract surgery limit the usefulness of
the irrigation device.
[0010] Another prominent problem with routine cataract surgery and
other surgical procedures such as retinal surgery, cornea
transplant surgery, glaucoma surgery, or the like, can be
postoperative administration of antibiotics to prevent
endophthalmitis. Topical antibiotic and anti-inflammatory eye drops
represent the mainstay of drug delivery for intraocular surgery.
However, there has yet to be a prospective randomized study showing
that topical antibiotics prevent endophthalmitis. Also, because the
human cornea acts as a natural barrier to biologic and chemical
insults, intraocular bioavailability usually requires frequent
dosing regimens for each medication. Topical drops can be difficult
for young and elderly patients and the drop schedule can be
cumbersome and confusing particularly when following surgery each
eye is on a different drop schedule. These difficulties can result
in non-compliance with serious consequences such as
endophthalmitis, glaucoma, and cystoid macular edema. Recent
prospective studies supporting the use of intracameral antibiotic
injections for prophylaxis of endophthalmitis have stirred debate
regarding the risks associated with this method of antibiotic
prophylaxis including the short duration of protective effect
(possibly less than 24 hours), the introduction of potentially
contaminated substances in the anterior chamber, endothelial cell
toxicity, toxic anterior segment syndrome, dilutional and
osmolarity errors during mixing, and the like. Also, the systemic
administration of drugs for treatment of localized ocular
conditions may not be preferred because of the inefficiency
associated with indirect delivery of the drugs to a target
organ.
[0011] Recognizing these disadvantages of conventional delivery of
antibiotics and other drugs to the eye, external ocular inserts
were developed utilizing biologically inert materials to act as a
reservoir for slow release of the drug. These external ocular
inserts may be placed within the upper and lower conjunctival
fornix of the eye to achieve a uniform sustained rate of release of
drug in therapeutically effective amounts. However, patients can be
intolerant of these devices due to difficulty in insertion and
removal and mild to moderate conjunctival irritation during use
which may explain why external ocular inserts have not been widely
accepted in clinical practice.
III. DISCLOSURE OF INVENTION
[0012] Accordingly, a broad object of the invention can be to
provide a biocompatible intraocular implant and methods of
treatment of an ocular condition by implantation of the
biocompatible intraocular implant inside the eye with embodiments
which can be intraocularly implanted in the posterior capsule of
the eye to provide mechanical or pharmaceutical barriers or both to
interrupt progression of the ocular condition, the ciliary sulcus
between the iris and the lens, or in the anterior chamber
overlaying the iris.
[0013] Another broad object of the invention can be to provide a
biocompatible intraocular implant locatable between the surface of
the posterior capsule of the eye and an implanted IOL to provide a
mechanical barrier for treatment of an ocular condition.
[0014] Another broad object of the invention can be to provide a
biocompatible biodegradable intraocular implant locatable between
the surface of the posterior capsule of the eye and an implanted
IOL to provide a biodegradable mechanical barrier for treatment of
an ocular condition.
[0015] Another broad object of the invention can be to provide a
biocompatible biodegradable intraocular implant locatable between
the surface of the posterior capsule of the eye and an implanted
IOL which combines a biocompatible biodegradable material which
continually, or substantially continually, releases a
therapeutically effective amount of an active agent to treat an
ocular condition.
[0016] Another broad object of the invention can be to provide a
biocompatible biodegradable intraocular implant locatable between
the surface of the posterior capsule of the eye and an implanted
IOL during cataract surgery which by structural or pharmaceutical
barriers inhibits migration of residual lens epithelial cells to
the surface of the posterior capsule.
[0017] Another broad object of the invention can be to provide a
biocompatible biodegradable intraocular implant locatable between
the surface of the posterior capsule of the eye and an implanted
IOL during cataract surgery which by structural or pharmaceutical
barriers inhibits proliferation of residual lens epithelial cells
to the surface of the posterior capsule as a prophylaxis of
PCO.
[0018] Another broad object of the invention can be to provide a
biocompatible or biocompatible biodegradable intraocular implant
locatable anterior to the natural crystalline lens or an implanted
IOL within the ciliary sulcus for administration of one or more
active agents.
[0019] Another broad object of the invention can be to provide a
biocompatible or biocompatible biodegradable intraocular implant
locatable in the anterior chamber overlaying the iris.
[0020] Naturally, further objects of the invention are disclosed
throughout other areas of the specification, drawings, photographs,
and claims.
IV. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is a top view of the phakic eye with the natural lens
intact.
[0022] FIG. 2 is a cross section 2-2 of the phakic eye with the
natural lens intact.
[0023] FIG. 3 is a top view of the pseudophakic eye having the
natural lens replaced with an IOL.
[0024] FIG. 4 is a cross section 3-3 of the psuedophakic eye having
the natural lens replaced with an IOL.
[0025] FIG. 5 is a front view of a particular embodiment of the
inventive intraocular implant of generally circular
configuration.
[0026] FIG. 6 is a front view of a particular embodiment of the
inventive intraocular implant further providing patterned surface
elements.
[0027] FIG. 7 is a perspective view of particular embodiment of the
inventive intraocular implant shown in FIG. 5.
[0028] FIG. 8 is a front view of a particular embodiment of the
inventive intraocular implant which further provides radial slit
elements originating at the outer boundary.
[0029] FIG. 9 is a front view of a particular embodiment of the
inventive intraocular implant which further provides radial slit
elements originating at the aperture element.
[0030] FIG. 10 is a front view of a particular embodiment of the
inventive intraocular implant which further provides perforation
elements.
[0031] FIG. 11 is a front view of a particular embodiment of the
inventive intraocular implant which further provides two more
flexible membrane zones.
[0032] FIG. 12 is a front view of a particular embodiment of the
inventive intraocular implant which further provides one or more
recess elements.
[0033] FIG. 13 is a front view of a particular embodiment of the
inventive intraocular implant which includes both radial slit
element originating from the aperture element and recess elements
which periodically interrupt the outer boundary.
[0034] FIG. 14 is a perspective view of a plurality of an
embodiment of the inventive intraocular implant which can be
stacked front to back.
[0035] FIG. 15 is a perspective view of an embodiment of the
inventive intraocular implant which further provides radial
capillary elements.
[0036] FIG. 16 is a perspective view of an embodiment of the
inventive intraocular implant which further provides corrugate
elements.
[0037] FIG. 17 shows an embodiment of the intraocular implant held
by forceps for implantation into an eye having the natural lens
removed.
[0038] FIG. 18 is top view of the pseudophakic eye having the
natural lens removed allowing an embodiment of the intraocular
implant to be positioned on the surface the posterior capsule
through an opening made in the anterior capsule.
[0039] FIG. 19 is a cross section view of the psuedophakic eye
having the natural lens removed allowing an embodiment of the
intraocular implant to be positioned on the surface the posterior
capsule through an incision made in the anterior capsule.
[0040] FIG. 20 is a cross section view of the psuedophakic eye
having the intraocular implant positioned between the surface the
posterior capsule and the implanted IOL.
[0041] FIG. 21 is a cross section view of the phakic eye having the
intraocular implant positioned between the iris and the natural
crystalline lens of the eye.
[0042] FIG. 22 is front view of an embodiment of the intraocular
implant affixed to a sterile card prior to implantation.
[0043] FIG. 23 is a side view of an embodiment of the intraocular
implant affixed to a sterile card prior to implantation.
V. MODE(S) FOR CARRYING OUT THE INVENTION
[0044] Generally, the invention comprises an intraocular implant
and methods for treating an ocular condition. In particular, an
embodiment of a biocompatible biodegradable intraocular implant
including a biocompatible material or a biocompatible biodegradable
material and an active agent which implanted between an IOL and the
surface of the posterior capsule of the eye inhibits migration of
residual LECs after cataract surgery by providing structural or
pharmaceutical barriers to reduce posterior capsule opacification
of the eye.
DEFINITIONS
[0045] "A" or "an" entity refers to one or more of that entity; for
example, "a polymer" refers to one or more of those compositions or
at least one composition. As such, the terms "a" or "an", "one or
more" and "at least one" can be used interchangeably herein.
Furthermore, the language "selected from the group consisting of"
refers to one or more of the elements in the list that follows,
including combinations of two or more of the elements.
[0046] "About" for the purposes of the present invention means that
ranges may be expressed as from "about" one particular value to
"about" another particular value. When such a range is expressed,
another embodiment includes from the one particular value to the
other particular value. Similarly, when values are expressed as
approximations, by use of the antecedent "about," it will be
understood that the particular value forms another embodiment. In
the context of such a numerical value or range "about" means plus
or minus 10% of the numerical value or range recited or
claimed.
[0047] "Active agent" for the purposes of this invention means any
substance used to treat an ocular condition.
[0048] "Biocompatible" for the purposes of this invention means the
ability of any material to perform the intended function of an
embodiment of the invention without eliciting any undesirable local
or systemic effects on the recipient and can include
non-biodegradable materials such as: polyurethanes,
polyisobutylene, ethylene-alpha-olefin copolymers, acrylic polymers
and copolymers, vinyl halide polymers and copolymers, polyvinyl
esters, polyvinylidene chloride, polyacrylonitrile, polyvinyl
ketones, polyvinyl aromatics such as polystyrene, copolymers of
vinyl monomers and olefins such as ethylene-methyl methacrylate
copolymers, acrylonitrile-styrene copolymers, ABS resins,
ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and
polycaprolactone, alkyd resins, polycarbonates, polyoxyethylenes,
polyimides, polyesters, epoxy resins, rayon-triacetate, cellophane,
or the like, or biodegradable materials, as herein described.
[0049] "Biodegradable" for the purposes of this invention means the
ability of any biocompatible material to breakdown within the
physiological environment of the eye by one or more physical,
chemical, or cellular processes at a rate consistent with providing
structural or pharmaceutical barriers (or both) at a therapeutic
level controllable by selection of a polymer or mixture of polymers
(also referred to as polymeric materials), including, but not
limited to: polylactide polymers (PLA), copolymers of lactic and
glycolic acids (PLGA), polylactic acid-polyethylene oxide
copolymers, poly(.epsilon.-caprolactone-co-L-lactic acid (PCL-LA),
glycine/PLA copolymers, PLA copolymers involving polyethylene
oxides (PEO), acetylated polyvinyl alcohol (PVA)/polycaprolactone
copolymers, hydroxybutyrate-hydroxyvalerate copolymers, polyesters
such as, but not limited to, aspartic acid and different aliphatic
diols, poly(alkylene tartrates) and their copolymers with
polyurethanes, polyglutamates with various ester contents and with
chemically or enzymatically degradable bonds, other biodegradable
nonpeptidic polyamides, amino acid polymers, polyanhydride drug
carriers such as, but not limited to, poly(sebacic acid) (PSA),
aliphatic-aromatic homopolymers, and poly(anhydride-co-imides),
poly(phosphoesters) by matrix or pendant delivery systems,
poly(phosphazenes), poly(iminocarbonate), crosslinked poly(ortho
ester), hydroxylated polyester-urethanes, or the like. Hydrogels
such as methylcellulose which act to release drug through polymer
swelling are specifically excluded from the term.
[0050] "Intraocular" for the purposes of this invention means
inside the eyeball (also referred to as an "eye") and without
limitation to the forgoing the anterior chamber, the ciliary
sulcus, and posterior capsule of the eye; however, specifically
excluding the external surface of the eye or intracorneal or
intrasclera regions of the eye.
[0051] "Localized Region" for the purposes of this invention means
substantially within a localized tissue region of the eye
therapeutically affected (whether structurally or pharmaceutically)
by implantation of embodiments of an intraocular implant.
[0052] "Ocular condition" for the purposes of this invention means
a disease, ailment or condition which affects or involves the eye
or any one of the parts or regions of the eye, such as PCO. The eye
includes the eyeball and the tissues and fluids which constitute
the eyeball, the periocular muscles (such as the oblique and rectus
muscles) and the portion of the optic nerve which is within or
adjacent to the eyeball.
[0053] "Posterior ocular condition" for the purposes of this
invention means a disease, ailment or condition which affects or
involves a posterior ocular region or site such as the choroid or
sclera (in a position posterior to a plane through the posterior
wall of the lens capsule), vitreous, vitreous chamber, retina,
optic nerve (i.e. the optic disc), and blood vessels and nerve
which vascularize or innervate a posterior ocular region or
site.
[0054] "Suitable for implantation" for the purposes of this
invention means with regard to embodiments of the intraocular
implant dimensions which allow insertion or implantation without
causing excessive tissue damage.
[0055] "Therapeutic level" for the purposes of this invention means
an amount or a concentration of an active agent that has been
locally delivered to an ocular region that is appropriate to
reduce, inhibit, or prevent a symptom of an ocular condition.
[0056] Now generally referring to FIGS. 5-13, particular
embodiments of the inventive intraocular implant (11) can provide a
biocompatible flexible membrane or a biocompatible biodegradable
flexible membrane (also generally referred to as a "flexible
membrane" (12)) having an outer boundary (13) configured to allow
the intraocular implant (11) to locate in the concavity of the
posterior capsule (5) of the psuedophakic eye (4), or other
localized region inside the eye such as the ciliary sulcus or
anterior chamber (46) depending on the application. As a
non-limiting example, the intraocular implant (11) can be located
in the posterior capsule (5) for the purpose of isolating the
surface of the posterior capsule (5) from migration of residual
LECs after cataract surgery, or reducing or preventing the
migration of residual LECs between the surface of an IOL (8)
implanted in the lens capsule (45) and the surface of the posterior
capsule (5).
[0057] Intraocular implants (11) suitable for implantation can
provide a flexible membrane (12) having an outer boundary (13)
which as a non-limiting example defines a circular area having a
diameter in a range of about 9 millimeters ("mm") and about 15 mm
depending on the recipient; however, the invention is not so
limited, and the outer boundary (13) can define a substantially
circular, ovoid, or other configuration of the outer boundary (13)
suitable for implantation into the concavity of the posterior
capsule (5) of the psuedophakic eye (4), or other localized region
inside the eye.
[0058] Now referring primarily to FIG. 8, particular embodiments of
the flexible membrane (12) can further include one or more radial
slit elements (14) cut through the thickness of the flexible
membrane with the radial slit elements (14) originating at the
outer boundary (13) cut a distance radially toward the center of
the flexible membrane (12). The one or more radial slit elements
(14) can have sufficient length and width to allow the flexible
membrane (12) to conform to a greater extent with the concavity of
the posterior capsule (5) of the psuedophakic eye (4) or other
localized region inside the eye. As one non-limiting example, the
radial slit elements (14) can provide an opening in the flexible
membrane (12) having a greater slit width (15) at the outer
boundary (13) of the flexible membrane (12) than proximate the
center of the flexible membrane (12). As a non-limiting example,
the flexible membrane (12) when received by the concavity of the
posterior capsule (5) can deform to reduce the slit width (15) at
the outer boundary (13) of the flexible membrane (12).
[0059] Now referring primarily to FIGS. 12 and 13, particular
embodiments of the flexible membrane can further provide one or
more recess elements (16) located along the outer boundary (13) of
the flexible membrane (12). The outer boundary (13) of the flexible
membrane (12) can be interrupted once or periodically to provide
one or more of the recess elements (16) which can be configured,
for example, as semicircular notches, triangular notches, indents,
or the like which can function to allow added flexure to more
readily locate the flexible membrane in the posterior capsule of
the eye (or other localized region), as above described, or can
function to reduce sequestration of peripheral cortical material
during the final irrigation and aspiration steps in cataract
surgery.
[0060] With respect to the particular embodiments of the
intraocular implant shown in FIGS. 5-13 and specifically referring
to FIG. 7 as a non-limiting example, the flexible membrane (12) can
have a thickness (17) disposed between a front surface (18) and a
back surface (19)(also referred to as "a first side" and "a second
side" or "opposed sides"). As to particular embodiments of the
intraocular implant (11), the front surface (18) and the back
surface (19) can be disposed in substantially parallel opposed
relation, providing a relatively uniform thickness of the
intraocular implant (11) in a range of about 5 microns (".mu.m")
and about 100 .mu.m. However, certain embodiments of the
intraocular implant (11) can provide a flexible membrane (12)
thinner proximate the center and thicker proximate the outer
boundary (13) or can provide a flexible membrane thicker proximate
the center and thinner at the edges depending upon the application.
As one non-limiting example, the thickness (17) of the flexible
membrane (12) may be thinner in the center to align with the visual
axis of the psuedophakic eye (4) to increase visual acuity or
promote directional biodegradation of the intraocular implant (11)
from the center toward the outer boundary (13).
[0061] Now referring primarily to FIG. 6, particular embodiments of
the intraocular implant (11), can provide patterned surface
elements (20) which can engage the surface of the posterior capsule
(5) to reduce travel of the intraocular implant (11) or maintain
the alignment of the center of the intraocular implant (11) with
the visual axis of the eye (21)(see also FIG. 21). The patterned
surface elements (20) can provide an irregular or uniform pattern,
texture, or roughness sufficient to fix or reduce travel of the
intraocular implant (11) in the posterior capsule (5). As to
certain embodiments of the intraocular implant (11) the patterned
surface elements (20) can also provide pockets which function to
provide a localized space to deliver or sequester an amount of an
active agent (24). The patterned surface elements can be variously
configured to deliver or sequester an active agent (24) depending
on the application. The pattern surface elements (20) can be one
piece with the flexible membrane (12) or can be applied to the
flexible membrane (12) as a pattern surface element layer.
[0062] Now referring primarily to FIG. 10, certain embodiments of
the flexible membrane (12) can further include one or more
perforation elements (22) which provide a corresponding one or more
perforation openings (23) which communicate between the front
surface (18) and the back surface (19) of the flexible membrane
(12) for the purpose of increasing rate of biodegradation of the
flexible membrane (12) or control release rate of an active agent
(24). The active agent (24)(shown for example in FIGS. 9, 10 and 13
as a stipple pattern) is not intended to be limited to those
particular embodiments of the intraocular implant (11) or limit the
active agent (24) to any particular composition, particle size, or
amount.
[0063] Now referring primarily to FIG. 14, certain embodiments of
the flexible membrane (12) can further provide two or more flexible
membrane layers (25). The two or more membrane layers (25) can take
the form of a first flexible membrane layer (26) and a second
flexible membrane layer (27) or additional flexible membrane layers
(28) extruded as a single piece, coupled together as one unit, or
stacked front to back (whether single piece, coupled or stacked the
term "coupled" may be used to refer to the association of a
plurality of flexible membrane layers). Each of the first flexible
membrane layer (26) and the second flexible membrane layer (27) or
additional flexible layers (28) can be generated from the same or
different biocompatible biodegradable materials. As a non-limiting
example, in an embodiment of the invention for the treatment of
PCO, the first flexible membrane layer (26) can be made of a
biocompatible biodegradable material which can have the back
surface (19) disposed adjacent the surface of the posterior capsule
(5) to provide both a structural barrier to the migration of LECs
to the surface of the posterior capsule but to further function as
a pharmaceutical barrier which inhibits proliferation or kills LECs
by the substantially continuous release of an active agent (24)
such as alkylphosphocholine at a rate which provides a therapeutic
level, such as a localized concentration of about 1.0 millimolar
("mM") for a period of at least five days to inhibit or prevent
PCO. The front surface (18) of the first flexible membrane layer
(26) can be coupled adjacent the back surface (19) of the second
flexible membrane layer (27) (for example by melt co-extrusion)
produced from the same or different biocompatible biodegradable
material and the front surface (18) of the second flexible membrane
layer (27) can be disposed toward an IOL (8) implanted into the
posterior capsule (5) to provide a structural barrier to migration
of LECs toward the surface of the posterior capsule and can further
function as a pharmaceutical barrier which inhibits proliferation
or kills LECs by the substantially continuous release of the same
active agent (24) (such as an alkylphosphocholine) or a different
active agent (24) such as mitomycin-C at a therapeutic level, such
as a localized concentration of about 0.04 mg/mL, for a period of
at least about five days to inhibit or prevent PCO. Thus, by
configuring the layers in different combinations the rate of
release of various active agents can be adjusted depending on the
application.
[0064] Now referring primarily to FIG. 11, two or more flexible
membrane zones (29) can be established with each flexible membrane
zone (29) generated from a particular flexible membrane material.
As to certain embodiments, the two or more flexible membrane zones
(29) can be established as concentric regions with a first annular
zone (30) surrounded by a second annular zone (31). The first
annular zone (30) can be of different biocompatible or
biocompatible biodegradable material then the second annular zone
(31). For example, the first annular zone (30) can provide a
biocompatible biodegradable material selected for a greater rate of
biodegradation or active agent (24) release (or both) relative to
the second annular zone (31) which can provide a biocompatible
biodegradable material selected for a lesser rate of biodegradation
or active agent (24) release (or both). In that configuration of
the inventive intraocular implant (11), the prominent function of
the first annular zone (30) can be to provide a pharmaceutical
barrier or treatment of an ocular disorder, while the prominent
function of the second annular zone (31) can be to provide a
structural barrier or treatment of an ocular disorder. In
particular embodiments of the inventive intraocular implant for the
inhibition of PCO, the first annular zone can be made of the
biocompatible biodegradable material poly(lactide-co-glycolide)
having an active agent (24) such as alkylphosphocholine dispersed
substantially uniformly through out which can provide a
pharmaceutical barrier to the proliferation of LECs on the surface
of the posterior capsule (5) to inhibit or prevent PCO by release
of a therapeutic level of alkylphosphocholine of about 1.0 mM for a
period of at least about five days. The first annular zone (30) can
substantially biodegrade in the entirety in a period of about five
days to about ten days. The second annular zone can be made of the
same biocompatible biodegradable material having the same or
different active agent (24) dispersed substantially uniformly
throughout to provide both a structural barrier to inhibit
migration of LECs toward to the surface of the posterior capsule
and can provide a pharmaceutical barrier by release of the same or
different active agent (24) such as alkylphosphocholine at a
therapeutic level or provide a localized concentration of about 1.0
mM for a period of at least twenty days to inhibit or prevent
PCO.
[0065] Again referring generally to FIGS. 5-16, particular
embodiments of the inventive intraocular implant (11) can further
include an aperture element (32) having a passage opening (33)
sufficiently large to align with the visual axis of the eye (21) to
provide a line of sight which passes through the intraocular
implant (11) or the first annular zone (30) or the second annular
zone (31).
[0066] While the aperture element (32) shown in FIGS. 5-14 define a
substantially circular passage opening having a diameter in the
range of about 1.5 mm and about 9 mm depending upon the application
and the recipient; the invention is not so limited and certain
embodiments of the inventive intraocular implant (11) can provide
an aperture element (32) which defines an oval, square, triangle,
or other configuration of passage opening (33) sufficient to
provide a line of sight which passes through the intraocular
implant (11). As to those embodiments of the invention which are
utilized with an intraocular optical implant, such as an IOL as
further described herein, the passage opening (33) can be
dimensioned in relation to the intraocular optical implant to avoid
reduction in the field of vision provided by the intraocular
optical implant or to avoid a reduction in clarity of vision within
visual field. Alternately, in those embodiments of the invention in
which the passage opening (33) has insufficient dimension to avoid
overlaying all or part of the visual field afforded by the
intraocular optical implant, embodiments of the intraocular implant
(11) can be further configured to provide an optical element of
sufficient clarity so as not to substantially effect vision within
the visual field afforded by an intraocular implant (11).
[0067] Now referring specifically to FIGS. 9, 13, and 14, the
aperture element (33) can further include one or more radial slit
elements (14) each originating at the aperture element (33) and
terminating at a distance from the outer boundary (13) of the
flexible membrane (12). The one or more radial slit elements (14)
can have sufficient length and width to allow the flexible membrane
(12) to conform to a greater extent with the concavity of the
posterior capsule (5)(or other localized region) of the eye and
with respect to embodiments of the intraocular implant (11) which
are biodegradable can function to promote directional
biodegradation of the intraocular implant proximate the aperture
element toward the outer boundary (13). Again, the radial slit
elements (14) can provide one or more interruptions in the aperture
element (32) which can be of lesser or greater width or length to
control the rate at which the flexible membrane (12) biodegrades
within the posterior capsule (5) of the eye.
[0068] Now referring primarily to FIGS. 15 and 16, particular
embodiments of the intraocular implant (11) can further provide
radial capillaries (34) which communicate between the outer
boundary (13) and the aperture element (32) of the flexible
membrane (12) configured to allow or facilitate circulation of the
fluid within the eye, for example, between the flexible membrane
(12) and the posterior capsule (5) of the eye. Similarly, as shown
by FIG. 16, particular embodiments of the intraocular implant (11)
can further provide one or more corrugate elements (35) which can
be disposed in substantially linear parallel relation to generate
undulations in the flexible membrane (12) sufficient when the
flexible membrane (12) locates against the surface of the posterior
capsule (5)(or surface of a localized region) to provide channels
(36) in which the fluids of the eye can circulate.
[0069] Referring in general to FIGS. 5-16, embodiments of the
intraocular implant can further include an active agent (24)(shown
as stipple pattern in FIGS. 9, 10, and 13 although the invention is
not so limited) mixed with or dispersed in the biodegradable
polymer of the flexible membrane (12). The composition of the
biodegradable polymers of the flexible membrane (12) of the
intraocular implant (11) can be varied to provide a continuous or
substantially continuous release of a therapeutic level of a
particular active agent (24) or a particular mixture of active
agents (24) effective for the ocular condition being treated.
Active agents (24) that can be used include, but are not limited to
(either alone or in combination): ace-inhibitors, endogenous
cytokines, agents that influence the basement membrane, agents that
influence the growth of endothelial or epithelial cells, adrenergic
agonists or blockers, cholinergic agonists or blockers, aldose
reductase inhibitors, analgesics, anesthetics, antiallergics,
anti-inflammatory agents, antihypertensives, pressors,
antibacterials, antivirals, antifungals, antiprotozoals,
anti-infectives, antitumor agents, antimetabolites such as
daunomycin, antiangiogenic agents, tyrosine kinase inhibitors,
antibiotics such as aminoglycosides such as gentamicin, kanamycin,
neomycin, and vancomycin; amphenicols such as chloramphenicol;
cephalosporins, such as cefazolin HCl; penicillins such as
ampicillin, penicillin, carbenicillin, oxycillin, methicillin;
lincosamides such as lincomycin; polypeptide antibiotics such as
polymixin and bacitracin; tetracyclines such as tetracycline,
minocycline, and doxycycline; quinolones such as ciprofloxacin,
moxifloxacin, gatifloxacin, and levofloxacin; sulfonamides such as
chloramine T; sulfones such as sulfanilic acid; anti-viral drugs
such as acyclovir, gancyclovir, vidarabine, azidothymidine,
dideoxyinosine, dideoxycytosine; epinephrine; isoflurphate;
adriamycin; bleomycin; mitomycin; ara-C; actinomycin D;
scopolamine; and the like, analgesics, such as codeine, morphine,
ketorolac, naproxen, an anesthetic, lidocaine; beta.-adrenergic
blocker or beta.-adrenergic agonist such as ephedrine, and
epinephrine; aldose reductase inhibitor such as epalrestat,
ponalrestat, sorbinil, tolrestat; antiallergic such as cromolyn,
beclomethasone, dexamethasone, and flunisolide; colchicine,
anihelminthic agents such as ivermectin and suramin sodium;
antiamebic agents such as chloroquine and chlortetracycline; and
antifungal agents such as amphotericin; anti-angiogenesis compounds
such as anecortave acetate; retinoids such as Tazarotene,
anti-glaucoma agents such as brimonidine (Alphagan and Alphagan P),
acetozolamide, bimatoprost (Lumigan), timolol, mebefunolol;
memantine; alpha-2 adrenergic receptor agonists;
2-methoxyestradiol; anti-neoplastics such as vinblastine,
vincristine, interferons; alpha, beta and gamma., antimetabolites
such as folic acid analogs, purine analogs, and pyrimidine analogs;
immunosuppressants such as azathyprine, cyclosporine and
mizoribine; miotic agents, such as carbachol, mydriatic agents such
as atropine, etc., protease inhibitors such as aprotinin, camostat,
gabexate, vasodilators such as bradykinin, epidermal growth factor,
basic fibroblast growth factor, nerve growth factors, steroidal
anti-inflammatory agents such as 21-acetoxypregnenolone,
alclometasone, algestone, amcinonide, beclomethasone,
betamethasone, budesonide, chloroprednisone, clobetasol,
clobetasone, clocortolone, cloprednol, corticosterone, cortisone,
cortivazol, deflazacort, desonide, desoximetasone, dexamethasone,
diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort,
flucloronide, flumethasone, flunisolide, fluocinolone acetonide,
fluocinonide, fluocortin butyl, fluocortolone, fluorometholone,
fluperolone acetate, fluprednidene acetate, fluprednisolone,
flurandrenolide, fluticasone propionate, formocortal, halcinonide,
halobetasol propionate, halometasone, halopredone acetate,
hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone,
medrysone, meprednisone, methylprednisolone, mometasone furoate,
paramethasone, prednicarbate, prednisolone, prednisolone
25-diethylamino-acetate, prednisolone sodium phosphate, prednisone,
prednival, prednylidene, rimexolone, tixocortol, triamcinolone,
triamcinolone acetonide, triamcinolone benetonide, triamcinolone
hexacetonide; vascular endothelial growth factor inhibitors such as
bevacizumab, ranibisumab, pegatanib; transforming growth factor
inhibitors; fibroblast growth factor inhibitors, and any of their
derivatives.
[0070] As to particular embodiments of the inventive intraocular
implant the active agent (24) can be dispersed throughout the
biocompatible biodegradable polymer of the flexible membrane (12)
by mixing the active agent (24) into the melted biodegradable
polymer and then solidifying the resulting biodegradable polymer by
cooling, having the active agent (24) substantially uniformly
dispersed throughout. The biodegradable polymer or mixture of
biodegradable polymers can be selected to have a melting point that
is below the temperature at which the active agent (24) becomes
reactive or degrades. Alternatively, the active agent (24) can be
dispersed throughout the biodegradable polymer by solvent casting,
in which the biodegradable polymer is dissolved in a solvent, and
the active agent (24) dissolved or dispersed in the solution. The
solvent is then evaporated, leaving the active agent (24) in the
polymeric matrix of the biodegradable material. Solvent casting
requires that the biodegradable polymer be soluble in organic
solvents. Alternatively, the biodegradable intraocular implant (11)
can be placed in a solvent having a concentration of the active
agent (24) dissolved and in which the biodegradable intraocular
implant swells. Swelling of the biodegradable intraocular implant
draws in an amount of the active agent (24). The solvent can then
be evaporated leaving the active agent (24) within the flexible
membrane (12) of the biodegradable intraocular implant (12). As to
each method of dispersing the active agent (24) through out the
biodegradable polymer of the flexible membrane (12), therapeutic
levels of active agent (24) can be included in biocompatible
biodegradable polymer to treat a particular ocular condition. The
biodegradable polymer usually comprises at least about 10, at least
about 20, at least about 30, at least about 40, at least about 50,
at least about 60, at least about 70, at least about 80, or at
least about 90 weight percent of the implant with the balance of
the weight being the active agent (24) or other non-active agents
(37) dispersed in the biocompatible biodegradable polymer (shown as
open stipples in FIGS. 9 and 13; however, the non-active agents are
not limited to these particular embodiments of the flexible
membrane (12)).
[0071] Other non-active agents (37) may be included in the
biocompatible biodegradable polymer formulation for a variety of
purposes. For example, buffering agents and preservatives may be
employed. Preservatives which may be used include, but are not
limited to, sodium bisulfite, sodium bisulfate, sodium thiosulfate,
benzalkonium chloride, chlorobutanol, thimerosal, phenylmercuric
acetate, phenylmercuric nitrate, methylparaben, polyvinyl alcohol
and phenylethyl alcohol. Examples of buffering agents that may be
employed include, but are not limited to, sodium carbonate, sodium
borate, sodium phosphate, sodium acetate, sodium bicarbonate, and
the like, as approved by the FDA for the desired route of
administration. Electrolytes such as sodium chloride and potassium
chloride may also be included in the formulation.
[0072] A non-limiting example of producing biodegradable
embodiments the inventive intraocular implant for treating an
ocular condition such as PCO can be made by mixing an active agent
(24) and biodegradable polymer to form an active agent polymer
material. The active agent polymer material can be extruded or
molded to form embodiments of the biocompatible biodegradable
intraocular implant (11) or flexible membrane (12) having active
agent release characteristics at a therapeutic level. As but one
non-limiting example, the intraocular implant (11) can
substantially continuously release active agent (24) to provide a
localized concentration of alkylphosphocholine at therapeutic
levels of about 0.5 mM to 1.5 mM for at least 5 days or release
mitomycin-C to provide a localized concentration of 0.04 mg/mL, or
both, for a period of at least about five days to inhibit or
prevent PCO. It is to be understood that this specific example of
providing an embodiment of an intraocular implant (11) for the
inhibition or prevention of PCO, is not intended to be limiting,
and embodiments of the intraocular implant (11) can be utilized to
treat a wide range of ocular conditions including posterior ocular
conditions or anterior chamber conditions of the eye.
[0073] Embodiments of the biocompatible flexible membrane (12) or
the biocompatible biodegradable flexible membrane (12) can be made
by a variety of methods, and while not particularly limited,
examples of molding methods which can be used to form a film or
sheet includes T-die molding, inflation molding, calender molding,
heat press molding, spin cast molding, injection molding, cast
molding, or the like.
[0074] The inventive intraocular implant (11) of a biodegradable
polymer of the invention can be molded in thinner thickness in
order to increase biodegradability, but its thickness can be freely
adjusted to satisfy strength, flexibility and release of active
agent(s) (24) to achieve therapeutically effective levels localized
to the site of implantation of the intraocular implant. Thickness
of the flexible membrane can be in the range of about 5 .mu.m to
about 300 .mu.m, or about 10 .mu.m to 100 .mu.m. Elastic modulus of
the flexible can generally be 1,200 MPa or less, more preferably
600 MPa or less. Tensile strength can fall in the range of about 10
MPa to 100 MPa, more preferably in a range of 15 MPa to 70 MPa,
further more preferably in a range of 20 MPa to 50 MPa.
[0075] Again referring primarily to FIGS. 1-4, as above described
the most common surgical technique of cataract surgery may be ECCE
(although use of the inventive intraocular implant (11) is not
limited to cataract surgery or to any particular technique of
cataract surgery) which involves the creation of a circular opening
(44) in the anterior lens capsule (43) through which the opacified
lens (3) can be removed. The remaining portion of the lens capsule
(45), anchored to the ciliary body (6) through the zonular fibers
(7) can be left intact. The IOL (8) can then be placed within the
lens capsule (43). The IOL (8) can be acted on by zonular forces
exerted on the outer circumference of the lens capsule (45) which
establishes the location of the IOL (8) within the lens capsule
(45). The intact posterior capsule (5) acts as a barrier to the
vitreous humor (9).
[0076] Now referring primarily to FIGS. 17-19, following cataract
extraction and cortex removal by ECCE or other surgical procedures
to treat other ocular conditions, embodiments of the biocompatible
or biocompatible biodegradable intraocular implant (11) can be held
in forceps (38) as shown for example in FIG. 17. Embodiments of the
intraocular implant (11) may also be removably fixed to the surface
of a small card (41) from which it can be lifted with the forceps
(38) prior to insertion into the eye as shown for example in FIGS.
22 and 23. The intraocular implant (11) can be folded upon itself
to reduce the apparent dimension for passage through the corneal or
scleral incision (42) as well as circular opening (44) in the
anterior lens capsule (43) surrounded by the pupil (39) of the iris
(40), as shown in FIGS. 17-19.
[0077] Now referring specifically to FIG. 19, which provides an
example of a non-limiting method, the intraocular implant (11) can
be positioned within localized region of the lens capsule (45)
having a front surface (18)(or first side) proximate the surface of
the posterior capsule (5). The passage opening (33), of embodiments
of the intraocular implant (11) which provide an aperture element
(32), can be aligned with the visual axis of the eye (21) to
provide a line of sight which passes through the passage opening
(33) of the intraocular implant (11)(or the first annular zone or
the second annular zone of the intraocular implant). The IOL (8)
can then be located inside the lens capsule (45) by conventional
methods to overlay the intraocular implant (11) placed in the
cavity of the posterior capsule (5).
[0078] As a non-limiting example, FIG. 20 shows the IOL (8)
overlying the intraocular implant (11) with the passage opening
(33) of the aperture element (32) centered underneath the IOL (8).
If centration of the intraocular implant (11) is not adequate, it
can be readily manipulated into position with a Sinskey Hook or
similar instrument. Once implanted into the eye, particular
embodiments of the biocompatible biodegradable intraocular implant
(12) can biodegrade as above described with normal turnover of the
fluid of the eye.
[0079] Now referring primarily to FIG. 21, in those surgical
procedures in which the natural crystalline lens (3) is not removed
such as retinal surgery, cornea transplant surgery, glaucoma
surgery, or the like, or in cataract surgery in which the
intraocular implant (11) is not located posterior the IOL (8) (for
example, due to posterior capsule tear), the intraocular implant
(12) can be placed anterior to the natural lens (3) or the IOL (8)
within the ciliary sulcus.
[0080] Now referring primarily to FIGS. 22 and 23, the invention
can further include a intraocular implant packaging substrate (41)
on which embodiments of the inventive intraocular implant (11) can
be releasably fixed. The intraocular implant (11) can be removed by
manipulation with forceps (38) for use in various applications as
above described.
[0081] As can be easily understood from the foregoing, the basic
concepts of the present invention may be embodied in a variety of
ways. The invention involves numerous and varied embodiments of an
intraocular implant (11) which as to particular embodiments can be
used but is not limited to control of migration of residual lens
epithelial cells between the posterior surface of an IOL (8) and
the surface of the posterior capsule (5) of the eye to reduce
opacification of the posterior capsule (5).
[0082] As such, the particular embodiments or elements of the
invention disclosed by the description or shown in the figures or
tables accompanying this application including the best mode are
not intended to be limiting, but rather exemplary of the numerous
and varied embodiments generically encompassed by the invention or
equivalents encompassed with respect to any particular element
thereof. In addition, the specific description of a single
embodiment or element of the invention may not explicitly describe
all embodiments or elements possible; many alternatives are
implicitly disclosed by the description and figures.
[0083] It should be understood that each element of an apparatus or
each step of a method may be described by an apparatus term or
method term. Such terms can be substituted where desired to make
explicit the implicitly broad coverage to which this invention is
entitled. As but one example, it should be understood that all
steps of a method may be disclosed as an action, a means for taking
that action, or as an element which causes that action. Similarly,
each element of an apparatus may be disclosed as the physical
element or the action which that physical element facilitates. As
but one example, the disclosure of "an implant" should be
understood to encompass disclosure of the act of
"implanting"--whether explicitly discussed or not--and, conversely,
were there effectively disclosure of the act of "implanting", such
a disclosure should be understood to encompass disclosure of "an
implant" and even a "means for implanting." Such alternative terms
for each element or step are to be understood to be explicitly
included in the description.
[0084] In addition, as to each term used it should be understood
that unless its utilization in this application is inconsistent
with such interpretation, common dictionary definitions should be
understood to included in the description for each term as
contained in the Random House Webster's Unabridged Dictionary,
second edition, each definition hereby incorporated by
reference.
[0085] Thus, the applicant(s) should be understood to claim at
least: i) each of the intraocular implants herein disclosed and
described, ii) the related methods disclosed and described, iii)
similar, equivalent, and even implicit variations of each of these
devices and methods, iv) those alternative embodiments which
accomplish each of the functions shown, disclosed, or described, v)
those alternative designs and methods which accomplish each of the
functions shown as are implicit to accomplish that which is
disclosed and described, vi) each feature, component, and step
shown as separate and independent inventions, vii) the applications
enhanced by the various systems or components disclosed, viii) the
resulting products produced by such systems or components, ix)
methods and apparatuses substantially as described hereinbefore and
with reference to any of the accompanying examples, x) the various
combinations and permutations of each of the previous elements
disclosed.
[0086] The background section of this patent application provides a
statement of the field of endeavor to which the invention pertains.
This section may also incorporate or contain paraphrasing of
certain United States patents, patent applications, publications,
or subject matter of the claimed invention useful in relating
information, problems, or concerns about the state of technology to
which the invention is drawn toward. It is not intended that any
United States patent, patent application, publication, statement or
other information cited or incorporated herein be interpreted,
construed or deemed to be admitted as prior art with respect to the
invention.
[0087] The claims set forth in this specification, if any, are
hereby incorporated by reference as part of this description of the
invention, and the applicant expressly reserves the right to use
all of or a portion of such incorporated content of such claims as
additional description to support any of or all of the claims or
any element or component thereof, and the applicant further
expressly reserves the right to move any portion of or all of the
incorporated content of such claims or any element or component
thereof from the description into the claims or vice-versa as
necessary to define the matter for which protection is sought by
this application or by any subsequent application or continuation,
division, or continuation-in-part application thereof, or to obtain
any benefit of, reduction in fees pursuant to, or to comply with
the patent laws, rules, or regulations of any country or treaty,
and such content incorporated by reference shall survive during the
entire pendency of this application including any subsequent
continuation, division, or continuation-in-part application thereof
or any reissue or extension thereon.
[0088] The claims set forth in this specification, if any, are
further intended to describe the metes and bounds of a limited
number of the preferred embodiments of the invention and are not to
be construed as the broadest embodiment of the invention or a
complete listing of embodiments of the invention that may be
claimed. The applicant does not waive any right to develop further
claims based upon the description set forth above as a part of any
continuation, division, or continuation-in-part, or similar
application.
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