U.S. patent application number 11/457628 was filed with the patent office on 2006-11-02 for sustained release ophthalmological device and method of making and using the same.
Invention is credited to Eric M. Dobrusin, Michael E. Snyder.
Application Number | 20060246112 11/457628 |
Document ID | / |
Family ID | 27617576 |
Filed Date | 2006-11-02 |
United States Patent
Application |
20060246112 |
Kind Code |
A1 |
Snyder; Michael E. ; et
al. |
November 2, 2006 |
SUSTAINED RELEASE OPHTHALMOLOGICAL DEVICE AND METHOD OF MAKING AND
USING THE SAME
Abstract
An ophthalmological implant including a layer of pharmaceutical
agent and an overlying layer of a bioerodible material, a
biodegradable material a bioavailable material or a mixture
thereof.
Inventors: |
Snyder; Michael E.;
(Montgomery, OH) ; Dobrusin; Eric M.; (Bloomfield
Hills, MI) |
Correspondence
Address: |
DOBRUSIN & THENNISCH PC
29 W LAWRENCE ST
SUITE 210
PONTIAC
MI
48326
US
|
Family ID: |
27617576 |
Appl. No.: |
11/457628 |
Filed: |
July 14, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10346671 |
Jan 17, 2003 |
7090888 |
|
|
11457628 |
Jul 14, 2006 |
|
|
|
60349465 |
Jan 18, 2002 |
|
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60397698 |
Jul 22, 2002 |
|
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Current U.S.
Class: |
424/427 |
Current CPC
Class: |
A61F 9/0017 20130101;
Y10S 623/901 20130101; A61F 2/147 20130101; A61F 2250/0068
20130101; A61F 2210/0004 20130101; A61F 2250/0067 20130101; A61F
2/1694 20130101; A61F 2002/1683 20130101 |
Class at
Publication: |
424/427 |
International
Class: |
A61F 2/00 20060101
A61F002/00 |
Claims
1) An ophthalmological implant comprising: a. a filament configured
for insertion into an eye; b. a first layer including a
pharmaceutical agent; c. a second layer overlying the first layer
and including a material selected from a bioerodible material, a
biodegradable material, a bioavailable material or a mixture
thereof.
2) An endocapsular tension ring comprising: a. a filament
configured for insertion into an eye as an endocapsular tension
ring; b. a first layer including a pharmaceutical agent; c. a
second layer of variable thickness overlying the first layer and
including a material selected from a bioerodible material, a
biodegradable material a bioavailable material or a mixture
thereof, the second layer being dimensioned for prolonged release
of the pharmaceutical agent from the ring as the second layer
degrades.
3) A method for making an endocapsular tension ring comprising the
steps of: a. providing a filament configured for insertion into an
eye as an endocapsular tension ring; b. attaching a first layer
including a pharmaceutical agent to the filament; c. attaching a
second layer of variable thickness over the first layer, the second
layer including a material selected from a bioerodible material a
biodegradable material a bioavailable material or a mixture
thereof, and the second layer being dimensioned for prolonged
release of the pharmaceutical agent from the filament as the second
layer degrades.
4) The implant of claim 1, wherein the first and second layer
selectively coats a portion of the filament.
5) The implant of claim 4, wherein the selective coating of the
filament is selected from continuously, intermittently, uniformly,
non-unifomrly, or a combination thereof.
6) The implant of claim 1, wherein the filament has a substantially
uniformed thickness along its length.
7) The implant of claim 1, wherein the filament includes an
arc-shaped "J-loop", arc-shaped "C-loop", a complete
circumferential support member, a partial circumferential support
member, a plate (e.g., a plate haptic configuration), a radial
support member, a pararadial support member, a tangential support
member, a circumferential support member, or a combination
thereof.
8) The implant of claim 1, wherein the surface of the filament
comprises a structure configured to receive the first layer
selected from a well, divot, pore, groove, other types of crevices,
or a combination thereof.
9) The implant of claim 1 wherein the pharmaceutical agent is
selected from an antimicrobials, an antithrombotic, an antiseptic
an antifungal, a chelating, an anticoagulant, antibiotic, an
anti-inflammatory, a steroid, an antiglaucomatous or a combination
thereof.
10) The implant of claim 1, wherein over a major portion of its
length, the outer surface of the tension ring, having the first and
second layer, is selected from a smooth surface an irregular
surface, a stepped surface, a tapered surface, a surface having no
slope or a combination thereof.
11) The endocapsular tension ring of claim 2, wherein the first and
second layer selectively coats a portion of the filament.
12) The endocapsular tension ring of claim 11, wherein the
selective coating of the filament is selected from continuously,
intermittently, uniformly, non-unifomrly, or a combination
thereof.
13) The endocapsular tension ring of claim 2, wherein the filament
has a substantially uniformed thickness along its length.
14) The endocapsular tension ring of claim 2, wherein the filament
has a non-uniform thickness.
15) The endocapsular tension ring of claim 2, wherein the surface
of the filament comprises one or more features configured to
receive the first layer selected from a well, divot, pore, groove,
other types of crevasses, or a combination thereof.
16) The endocapsular tension ring of claim 2, wherein the
pharmaceutical agent is selected from an antimicrobials, an
antithrombotic, an antiseptic, an antifungal, a chelating, an
anticoagulant, antibiotic, an anti-inflammatory, a steroid, an
antiglaucomatous or a combination thereof.
17) The endocapsular tension ring of claim 2, wherein over a major
portion of its length, the outer surface of the tension ring is
selected from a smooth surface an irregular surface, a stepped
surface, a tapered surface, a surface having no slope or a
combination thereof.
18) The endocapsular tension ring of claim 3, wherein the
pharmaceutical agent is selected from 5-fluorouracil (5-FU),
cyclosporine A (CsA), vancomycin, ganciclovir, fluocinolone
acetonide, dexamethasone, daunorubicin, indomethacin, timolol,
mitomycin-C, or mixtures thereof.
19) The endocapsular tension ring of claim 3, wherein over a major
portion of its length, the outer surface of the tension ring is
selected from a smooth surface an irregular surface, a stepped
surface, a tapered surface, a surface having no slope or a
combination thereof.
20) The endocapsular tension ring of claim 19, wherein over a major
portion of its length, the outer surface of the tension ring is
selected from a smooth surface an irregular surface, a stepped
surface, a tapered surface, a surface having no slope or a
combination thereof.
Description
CLAIM OF BENEFIT OF FILING DATE
[0001] The present application claims the benefit of the filing
date of U.S. Provisional Application Ser. Nos. 60/349,465, filed
Jan. 18, 2002, and 60/397,698, filed Jul. 22, 2002, the contents of
which are hereby incorporated by reference for all purposes.
TECHNICAL FIELD
[0002] The present invention relates to ophthalmologic implants and
more particularly to implants that incorporate a sustained release
pharmaceutical agent, such as a steroid, an antibiotic, an
anti-inflammatory agent, antiglaucomatous, or a combination
thereof,
BACKGROUND OF THE INVENTION
[0003] Currently available delivery systems for intraocular
therapeutics are generally limited to 1) drops, which carry issues
of expense, inconvenience, patient noncompliance (by overuse,
underuse, or inappropriate frequency of use) as well as difficulty
for delivery of the medications by certain patients (especially
those with arthritic conditions who cannot manipulate the vials
properly); 2) injections; and 3) bulky intravitreal implants placed
within the vitreous cavity of the eye, requiring incisions in the
eye and delicate manipulations of the vitreous gel.
[0004] There is a need to provide an efficient technique and device
for introducing a pharmaceutical agent into the eye, particularly
for sustained release following a surgical procedure. In another
aspect, there is a need to provide an effective and convenient
mechanism to deliver antibiotics, anti-inflammatory,
antiglaucomatous, or other pharmaceuticals to the intraocular
environment for therapeutic and prophylactic purposes, particularly
following cataract or clear lens removal surgeries.
[0005] In yet another aspect, there is a need for an implant having
applied thereto one or a plurality of sustained release
pharmaceutical agents in a manner such that over time the active
ingredient of the pharmaceutical agent (or agents) becomes
bioavailable within an eye.
[0006] The following items may be relevant to the present invention
and are hereby incorporated by reference herein for all purposes:
U.S. Pat. Nos. 4,853,224; 5,273,751; 5,375,611; 5,401,880;
5,569,463; 5,616,122; 5,624,704; 5,843,184; 5,876,438; 5,902,283;
6,162,487; and 6,322,592.
SUMMARY OF THE INVENTION
[0007] The present invention provides an improved ophthalmologic
implant (e.g., an endocapsular tension ring, an intraocular lens,
or the like) that has attached thereto a pharmaceutical agent in a
sustained release medium for implantation into a human eye. The
implant may be fabricated in any of a number of different ways, but
in a highly preferred embodiment, it includes a plurality of
layers, at least one of which degrades, erodes or otherwise
diminishes by becoming bioavailable over time to release an
underlying layer including a pharmaceutical agent.
[0008] In one preferred embodiment, a pharmaceutical agent is
dispersed in sustained release medium material that is coated over
a surface of an implant, impregnated into a space within the
implant or combination thereof.
[0009] In certain other preferred embodiments, the needs of the art
are met by providing an improved ophthalmologic implant (e.g., an
endocapsular tension ring an intraocular lens or the like)
comprising: [0010] a) a filament or other implant member configured
for insertion into an eye; [0011] b) a first layer including a
pharmaceutical agent; [0012] c) a second layer overlying the first
layer and including a bio-compatible sustained release medium
material selected from an a bioerodible material a biodegradable
material, a bioavailable material or a mixture thereof.
[0013] Among such particularly preferred embodiments, the present
invention more specifically contemplates an ophthalmologic implant
comprising: [0014] a) a filament configured for insertion into an
eye; [0015] b) a first layer including a pharmaceutical agent;
[0016] c) a second layer of variable thickness overlying the first
layer and including a sustained release medium material selected
from a bioerodible material, a biodegradable material, a
bioavailable material or a mixture thereof the second layer being
dimensioned for prolonged release of the pharmaceutical agent from
the ring as the second becomes smaller.
[0017] In another alternative preferred aspect, the present
invention contemplates a method for making an ophthalmologic
implant comprising the steps of: [0018] a) providing a filament
configured for insertion into an eye as an ophthalmologic implant
selected from an endocapsular tension ring or an intraocular lens;
[0019] b) attaching a first layer including a pharmaceutical agent
to the filament; and [0020] c) attaching a second layer of variable
thickness over the first layer, the second layer including a
sustained release medium material selected from a bioerodible
material, a biodegradable material, a bioavailable material or a
mixture thereof, and the second layer being dimensioned for
prolonged release of the pharmaceutical agent from the filament as
the second layer becomes smaller.
[0021] The present invention contemplates not only methods of
making ophthalmologic implants, but methods of implanting the
implants into an eye (e.g., a human, a dog eye, horse eye or the
like), therapies that employ the use of such an implant in an eye,
as well as the implants themselves. The present invention affords
numerous advantages including the elimination of a need or an
implant recipient to receive prolonged post-operative therapy with
topically applied pharmaceutical agents. In turn, this will help
reduce post-operative prescription drug costs, and associated
health care needs.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 illustrates a plan view of a general configuration of
an intraocular lens.
[0023] FIGS. 2-4 illustrate plan views of various endocapsular
tension ring devices that may be treated in accordance with the
present invention.
[0024] FIGS. 5-13 illustrate views showing how a sustained release
medium may be employed on an implant.
[0025] FIGS. 14-28 illustrate longitudinal cross-sectional views of
various alternative structures in accordance with the present
invention.
DETAILED DESCRIPTION OF THE INVENTION
[0026] In general, the ophthalmologic implants of the present
invention will include at least one member, such as a filament,
particularly one that is made of a biocompatible material that
supports a pharmaceutical agent, and more preferably a
pharmaceutical agent that is carried by a sustained release medium
material, such as one selected from a bioerodible material, a
biodegradable material, a bioavailable material or a mixture
thereof.
[0027] The pharmaceutical agent herein may be a single agent, an
admixture of agents, or multiple agents applied in simultaneous or
serial coatings or layers. The pharmaceutical agent preferably is
selected from an antibiotic, an anti-inflammatory, an
antiglaucomatous, a steroid, or a combination thereof. By way of
illustration (but without limitation to the employment of other
unlisted agents), specific examples of pharmaceutical agents
include 5-fluorouracil (5-FU), cyclosporine A (CsA), vancomycin,
ganciclovir, fluocinolone acetonide, dexamethasone, daunorubicin,
indomethacin, timolol, mitomycin-C, or mixtures thereof.
[0028] The pharmaceutical agent is preferably attached to an
implant by applying a mixture that includes the pharmaceutical
agent and a sustained release medium for functioning as a carrier
or supports a barrier layer, or a combination thereof, Thus, the
mixture may include a dispersion that includes a matrix and a
pharmaceutical agent therein. It may alternatively or additional
comprise layers, such a layer of a suitably carried pharmaceutical
agent and a barrier layer over it.
[0029] Existing commercially available implants may be employed, or
custom designed ones may be employed. In either case, the structure
of the implant may be varied as desired for accommodating the
pharmaceutical agent, such as by modifying the structure for
increasing available surface area per unit volume. For example, in
another preferred embodiment, a component of an implant (e.g., the
filament) has wells, divots, pores, grooves, or other crevices for
containing the pharmaceutical agent on one or more sides of the
filament. The wells, divots, pores, grooves, or other crevices may
vary in size, depth, or number along the length of the filament so
as to correspond to a desired dosing regimen of the agent(s) over
time, A variety of axial cross-sectional or longitudinal
configurations could achieve similar results, including but not
limited to spiraling, rifling, fluting, stippling, or dimpling. The
surface of the implant may also be treated such as by surface
roughening (e.g., mechanically, chemically or a combination
thereof), a primer or other coating, or a combination thereof. The
surface of the implant might be crosslinked with a pharmaceutical
compound or moiety, or a polymer or oligomer containing the
same.
[0030] In one embodiment, it is contemplated that the
pharmaceutical agent is supported or carried by a porous structure.
Such a structure may be made by producing a mixture that includes
at least one porogenic agent, compacting or shaping the mixture to
its desired form, and heating or otherwise treating (e.g., by
solvent) the product obtained in such a way that the porogen is
removed. At least one pharmaceutical agent may be incorporated in
the pores where the porogenic agent used to be.
[0031] In another embodiment, the pharmaceutical agent may be
applied in a first state and reacted or otherwise transformed to
form a second state. For instance, an implant may be dipped in a
pharmaceutical agent and then irradiated, heated or otherwise
treated.
[0032] When the implants are coated, in accordance with any of the
processing steps herein, they may be coated by a suitable coating
technique, including (by way of example, without limitation,
spraying, dipping, swabbing, brushing, rolling, curtain coating,
doctor blading, vapor deposition or combinations thereof.
[0033] In yet another embodiment, it is also possible to place an
implant in a mold and overmold the implant with a material
including a pharmaceutical agent.
[0034] The implants, sustained release medium, a pharmaceutical
agent, or a combination thereof may also include a suitable
polymeric agent for increasing tack, for enhancing penetration or
both. An example of a suitable additional agent is disclosed in
U.S. Pat. No. 6,162,487, hereby incorporated by reference.
[0035] A highly preferred embodiment of the present invention is to
employ an antibiotic as a pharmaceutical agent. However, the
present invention is not limited to antibiotics. Thus,
pharmaceutical agents for use in accordance with the present
invention may be selected from antimicrobials, antithrombotic
agents, antiseptics, antibiotics, anti-fungal agents, steroids,
chelating agents, anticoagulants, or combinations thereof. Other
pharmaceutical compounds may also be employed.
[0036] It may be the case that a pharmaceutical agent is coated
onto an implant or is delivered to a matrix material in combination
with an art-disclosed pharmaceutically acceptable carrier that may
be the same as or different from the sustained release medium. Such
carrier preferably is relatively inert relative to the
pharmaceutical agent, and also is generally bio-compatible.
Accordingly, it will be appreciated that the sustained release
medium herein, any carrier, a pharmaceutical agent, or combination
thereof may be solid, semi-solid, liquid, gel, amorphous solid,
crystalline solid, freeze-dried, spray-dried, supercooled, or
provided in any other suitable form.
[0037] It will be appreciated that the present invention is
suitable for use or in connection with a number of different
ophthalmologic implants, including but not limited to an
endocapsular tension ring or an intraocular lens. It should be
appreciated that any structure associated with the implant (e.g. a
haptic, an endocapsular component or otherwise) may be varied as
desired. For example, a suitable implant structure that is
configured to be held within a capsular bag of an eye can be coated
in accordance with the present invention, and may include an
arc-shaped "J-loop", arc-shaped "C-loop", a complete
circumferential support member, a partial circumferential support
member, a plate (e.g., a plate haptic configuration), a radial
support member, a pararadial support member, a tangential support
member, a circumferential support member, or a combination
thereof.
[0038] The gross shape of the implant is such so as to be readily
placed within an eye. By way of example, an endocapsular tension
ring is configured so as to be positioned within the fornix of the
capsular bag, as is typical with the known standard endocapsular
tension rings. The implants may be made of any suitable material,
e.g., a plastic material such as poly(methylmethacrylate) or other
acrylic, preferably for affording some flexibility with the gross
structure of the implant. Among the many alternative configurations
of the present invention, examples of combinations contemplated by
the invention include: [0039] 1) A member with a hollow core in
which a pharmaceutical agent, sustained release pharmaceutical
agent or medicinal material is impregnated into the cores pores or
crevices on a surface of the member, or coated pharmaceutical agent
could be pre-loaded (either by manufacture or postmanufacturing
preparation) or placed intraoperatively. The aqueous material of
the eye could percolate or flow through the cavity via openings at
either ends, channels, grooves, fenestrations, or other openings
between the central core and the outer wall. [0040] 2) A ring with
a solid or hollow composition with one or more elements, grooves,
or other modifications of the ring which affix or allow the
fixation of a pharmaceutical agent, sustained release
pharmaceutical agent or material impregnated with a pharmaceutical
agent, whether in the form of a filament, aggregate, film, or other
geometric or non-geometric configuration; or [0041] 3) A ring
composed of pharmaceutical agent, sustained release pharmaceutical
agent or biodegradable material impregnated pharmaceutical
agent.
[0042] A ring as described above could be designed for fixation
within the ciliary sulcus or pars plana of the eye either by
passive means or suture fixation to the eye.
[0043] Turning in detail to a highly preferred embodiment of the
present invention, a method is employed pursuant to which a
pharmaceutical agent is applied to an implant and thereafter, the
implant with the pharmaceutical agent thereon is coated
continuously, intermittently, uniformly, non-uniformly, entirely or
partially with a non-toxic, sustained release medium material,
which would allow for sustained release of the pharmaceutical
agent. A preferred common characteristic for the sustained release
medium material (which may be a polymer, a starch or other suitable
material), will diminish over time by contact with or exposure to
enzymes, hydrolysis, surrounding tissue fluids, cells, or the
like.
[0044] In a highly preferred embodiment, the sustained release
medium material is provided as a barrier layer, such as one having
a varying (e.g., tapering continuously, step-wise or a combination
thereof) thickness along the length of the filament so that the
pharmaceutical agent at different positions along the length of the
ring would be released at different times, depending on the
thickness of the layer at a particular point along the length of
the implant. The thickness may vary in a tapering thickness from
one end of the ring to the other, a sinusoidal thickness along the
ring length, or in a step-wise variation in thickness. In such a
stepwise variant, then length of each step may determine the dosing
interval, while the thickness of the layer coating at any given
step would determine when that aloquot of pharmaceutical agent
would be released.
[0045] In another highly preferred embodiment, the pharmaceutical
agent(s) may exist within an admixture of the sustained release
medium material, perhaps in the form of liposomes or some other
mechanism of micropackaging of the pharmaceutical agent(s). One or
more admixtures containing one, two, or more pharmaceutical agents
could be applied to the ring, either varying along the length or
with serial, overlapping coatings, so as to vary the agent(s) and
doses of the agent(s) per unit time over time.
[0046] In one embodiment, the ring filament is first coated over
some or all of its outer surface with a pharmaceutical agent and
then the bioerodable (or as discussed above a biodegradable or
bioabsorbable material) is applied in a varying thickness over the
pharmaceutical agent.
[0047] To illustrate, in one highly preferred embodiment, an
implant member would be placed on a suitable surface, e.g., a
substantially planar surface, and one or more pharmaceutically
active agents would be sprayed, swabbed, brushed, vaporized, dipped
or otherwise coated continuously, intermittently, uniformly or
non-uniformly, entirely or partially onto the exposed surface of
the filament and allowed to dry, polymerize, crystallize, or
otherwise adhere or attach. The implant could be turned over,
exposing the previously downfacing, protected surface. Another
application of the same or other pharmaceutical agent(s) or
admixture of agents would be similarly applied to the now upward,
exposed surface and similarly allowed to dry, polymerize,
crystallize, or otherwise adhere or attach. The filament could then
be weighted at an end or otherwise drawn into a straight, hollow
tube, effectually straightening out the ring-shaped native
configuration of the filament. The sustained release medium
material could then be applied in a uniform, tapered, or stepwise
tapered fashion by either serial dipping, at varying locations
along the length of the straightened complex, immersion with a
varying time of immersion for varying portions along the length of
the implant within a fluidic medium including the sustained release
medium as to predicatably vary the thickness of the sustained
release medium along the length of the implant. Alternatively, the
tube could act as a mask so that the sustained release medium could
be applied in varying thicknesses by varying the amount of the
length of the implant exposed for varying duration of time while by
being sprayed, swabbed, brushed, vaporized, sputtered, dipped or
otherwise coated.
[0048] An another highly preferred embodiment, the implant could be
coated, as described above, or otherwise, with one or more layers
of one or more admixtures of a degradeable layer, such as a layer
that includes a bioerodable agent and/or a pharmaceutical agent(s).
For example, one or more initial coats of a sustained release
medium may include pharmaceutical agent(s) with or without steroid,
properties, while one or more subsequent outer coats of another
admixture might include pharmaceutical agents with or without
steroid antimicrobial properties. This type of configuration would
have the effect of delivering antimicrobial and anti-inflammatory
agents first, then eliminating the antimicrobial agent from the
sustained release admixture once the window of vulnerability of
infection has passed. As to certain pharmaceutical agents, one
skilled in the art should recognize that there may be little risk
to allowing a continued non-toxic dose release of antimicrobial
agent to occur during the entire duration of planned time of
release of the other pharmaceutical agent. In such a setting a
single admixture applied either in one or more coats might
suffice.
[0049] A practitioner skilled in the art will also recognize the
potential benefits of adding other or additional pharmaceutical
agents, depending on the nature of the recipient eye's other
coexisting disease(s) and future as yet unknown applications of
pharmaceutical agents which, may include other anti-infective,
anti-ocular hypertensive anti-inflammatory, anti-angiogenesis,
anti-proliferative, anti-neoplastic, growth factors, stimulatory
agents or, even vectors for introduction of gene therapy or gene
modulating agents.
[0050] It will also be appreciated that some or all of the polymer
coating may include a dispersion of a pharmaceutical agent. It is
also possible using the invention described herein to design a
therapy where two or more different pharmaceutic agents are
incorporated in the sustained release medium material, the
pharmaceutic agent layer or both. The quantities of each may be
variable along the length of the filament. Thus it is possible that
a first agent is incorporated for release over a first time period
(e.g., during the first about 1 to about 8 days following implant)
and a second or additional agent is incorporated for release over a
different time period (e.g. during the about 1 to about 30 days
following implant, or commencing after a certain period of time,
such as after about 7 days).
[0051] By way of example, in one preferred embodiment of the
invention, designed for following routine anterior segment eye
surgery, the pharmaceutical agent delivery might occur along a
schedule as follows: [0052] 1) Antimicrobial agent: Released to
achieve a; least microbiocidal levels in the eye fluids for at
least 4-7 days at a non-toxic level to the native intraocular
tissues. [0053] 2) Steroid agent: Released at gradually taper
dosage over approximately 28-40 days [0054] 3) Non-steroidal
anti-inflammatory drug (NSAID) Released at gradually taper dosage
over approximately 28-40 days,
[0055] Other agents may be desired in some cases or as newer
pharmaceuticals become available.
[0056] The particular bio-compatible material for use as a
sustained release medium may be selected as desired. Such material
may be provided for securing onto an ophthalmologic implant in a
form selected from a liquid, a powder, a gel, or a mixture thereof.
Solid materials may be crystalline, amorphous, or a mixture
thereof, either in their as provided state or in an intermediate or
final state. The material may include or consist essentially of a
small molecule, an oligomer, a polymer (organic, biological or a
combination thereof), or combinations thereof. Preferably the
material is of one or more pH levels that are compatible with an
eye.
[0057] The specific material may vary. Examples of materials that
may be employed for providing a sustained release include, without
limitation, caprolactones (e.g., a
polyactide-coglycolide-co-aprolactone (PGLC) polymer),
multivesicular liposomes (e.g., with unilamellar vesicles,
mutilamellar vesicles, neosomes, closely packed non-concentric
vesicles (such as DEPOFOAM.TM.), or combinations thereof), salts
(e.g., an ammonium salt of
1-0-hexadecylpropanediol-3-phospho-ganiclovir (HDP-P-GCV)),
poly(lactic acid), poly (glycolic acid), copolymers of lactic and
glycolic acids, poly (DL-lactide-co-glycolide) (PLGA) or blends of
PLGA of different molecular weights, poly (orthoester), acrylic
polymers, methacrylic polymers, poly (hydroxyethylmethacrylate),
polysulfone or mixtures thereof. The present invention contemplates
that the material employed may be one that is not listed herein and
the omission from the above list should not be construed as
limiting of the scope of the invention.
[0058] It is contemplated that a suitable material for delivering a
pharmaceutical agent might include a material that releases the
agent over time through or as a result of diffusion, chemical
reaction, ion exchange, degradation or combination thereof.
[0059] The materials may comprise microspheres, microparticles,
other vesicles capillaries combinations thereof, or other
forms,
[0060] The amount of material, the method of application to an
implant or both are selected so that any pharmaceutic that is
carried with or by the material can be released continuously, in
spaced intervals, or a combination thereof, over a predetermined
period of time of at least one minute, at least an hour, at least a
day, at least a week, at least a month, at least a year or longer.
The bio-compatible material may be a pharmaceutical agent itself,
or it may function as a support or carrier for the pharmaceutical
agent.
[0061] The present invention may be used for delivery of any of a
number of different applications. In one preferred embodiment, a
method is contemplated pursuant to which a crystalline lens of the
eye is removed (e.g., either by cataract surgery, clear lens
removal surgery, or otherwise), and an implant (e.g., a tension
ring) is placed into the fornix of the capsular bag, such as by use
of an injector mechanism or by direct placement. The implant can
stay within the capsular bag permanently without need for removal,
and may share the contents of the capsular bag with an intraocular
lens, an artificial iris prosthesis, or another intraocular
prosthesis designed for intracapsular positioning.
[0062] For example, one method of the present invention
contemplates including a step of placing of a suture length or
other filament, carrying an ocular antihypertensive medication, in
the subconjunctival space of a patient having glaucoma. Another
method contemplates including a step of placing of a suture length
or other filament, carrying cyclosporin or another agent in the
subconjunctival space of an eye for treating dry eye. The present
invention also contemplates applying an antibiotic or wound healing
pharmaceutical agent to a suture for inserting anywhere in the
body.
[0063] In yet another method, a ring carrying an antiglaucomatous
medication is implanted within an eye.
[0064] In yet another method, such as in an instance when a
capsular bag has been damaged and an implant can not be readily
placed within the fornix, it is possible that a step is employed in
which a passive fixation, suture fixation, or both, of the implant
is performed within the ciliary sulcus of the eye.
[0065] The medicinal materials of the present invention may also be
included on other surgical supplies for use in an eye, such as
sutures or surgical instruments.
[0066] The implants of the present invention may be permanent or
temporary. Accordingly, the methods herein also contemplate
performing a subsequent removal, replacement, or both, of an
implant. While it is typical that many of the implants herein will
be employed for a single use and then disposed of, it is also
possible that implants may be removed and re-used (including a
possible step of re-treating the implant for adding more
pharmaceutical agent. Removal and replacement of on implant on a
periodic basis is thus contemplated, either at regular intervals of
similar amounts of time or at different amounts of time.
[0067] Turning now to examples of different structural embodiments,
reference is made to the drawings, Various other embodiments will
be apparent as well from a review of the drawings, which are not
intended as limiting. For example, in some drawings, it is
illustrated that the outer layer is generally tapered. It need not
be, but can be of constant cross section. For example, there can be
different thicknesses of barrier layer, pharmaceutic agent layer,
the implant or a combination thereof over discrete locations along
the implant. Further, the respective consecutive doses need not be
adjacent to one another but can be staggered over the length of the
filament. The corners of the coatings that correspond to the
respective doses that are depicted in the drawings herein may also
be smooth curves. The implant may also be structured as a helical
or with threads for varying its surface topography.
[0068] FIG. 1 shows an intraocular fens (IOL) 10 that may be
treated in accordance with the present invention. The SOL 10
includes a lens portion 12 and one or more haptics 14. Examples of
various other IOL configurations can be gleaned from U.S. Pat. No.
6,352,542 and the art cited therein, hereby expressly incorporated
by reference.
[0069] FIGS. 2-4 illustrate examples of a first endocapsular
tension ring 18, a second endocapsular tension ring 20, and a third
endocapsular tension ring 24, all including positioning holes at
their ends. From FIG. 3, it is seen that there may be included a
radially centrally extending portion 22 to help facilitate possible
ring exchange when repeated or prolonged closing is desired. FIG. 4
includes a centrally extending end portion 26 that may be open or
openable, so as to define an internal cavity into which additional
doses of a pharmaceutical agent may be introduced subsequently.
[0070] Additional alternative implant structures, without
limitation, are shown in FIGS. 5 and 6, where there are depicted
examples of plate haptic IOLs 28 and 36. More specifically, the IOL
28 of FIG. 5 includes a lens 34 and opposing plate end portions
having perforations 30 and 32 therein. The perforations may be the
same or different size and the same or different number on either
side of the lens 34 for permitting access to a pharmaceutical
agent.
[0071] FIG. 6 shows a variation of FIG. 5, in which one (or
optionally both) of the plate portions has a channel or is
otherwise adapted for receiving a pharmaceutical agent.
[0072] It will be realized that the embodiments of FIGS. 1-6 may be
adapted in any suitable manner and may include any suitable
structure for supporting a pharmaceutical agent, including those
discussed herein.
[0073] By way of example, with reference to FIGS. 7-13, there are
shown various structural alternatives for securing a pharmaceutical
agent (e.g., supported pharmaceutical agent) to an implant.
[0074] For example, in FIG. 7, a sectional view of FIG. 5, the
pharmaceutical agent may be provided as a filament, ribbon, film,
cord, or other member 44 that is woven through perforations 30 of a
plate portion 42 of a haptic, such as the haptic of FIG. 5.
[0075] In FIG. 8, there is seen an approach where a plate portion
46 has a cavity for receiving a pharmaceutical agent 48. The plate
portion is such that perforations 32 from one or more sides of the
plate portion allow transport of the pharmaceutical agent through
the plate portion.
[0076] It will be appreciated that the approaches of FIGS. 7 and 8
may be used in combination in a single implant, as in FIG. 5, or
they may be used individually.
[0077] Turning to FIG. 9, there is shown a possible approach to
carrying a pharmaceutical agent on an external portion of a plate
haptic, such as the type of FIG. 6. In this embodiment, an aperture
50 may be defined in the plate portion 52 onto which a filament,
ribbon, film, cord, or other member may be inserted, coated, bonded
or otherwise attached or affixed.
[0078] The embodiment of FIG. 9 likewise may be used alone or in
combination with one or both of the embodiments of FIGS. 7 and
8.
[0079] Turning now to FIGS. 10-13, there are shown alternative
approaches for treating a thin member, such as a haptic (e.g., wire
or plate) an endocapsular tension ring or other structure for
carrying a pharmaceutical agent.
[0080] In FIG. 10, showing a view in cross-section, member 56
includes passages 58 in communication with a central passage into
which a pharmaceutical agent 60 may be introduced.
[0081] In FIG. 11, a member 62 includes opposing spaced ends 64 and
66 and an opening for receiving a pharmaceutical agent 68. The
agent 68 is released through an opening 70 defined by the ends 64
and 66, which may be a hole, a channel or otherwise.
[0082] In FIG. 12, there is seen an approach wherein an implant is
laminated to include a member 72 having a layer 74 with a
pharmaceutical agent attached thereto.
[0083] FIG. 13 shows yet another alternative, pursuant to which a
member 76 is coated over at least a portion, if not substantially
the entirety of its outer surface with a layer 78 including a
pharmaceutical agent.
[0084] The embodiments illustrated in FIGS. 7-13 are not intended
as limited to the employment of a pharmaceutical agent dispersed or
otherwise carried in a matrix of a suitable pharmaceutical carrier.
As the discussion of FIGS. 14-28 will demonstrate, and as discussed
herein, other layers or combinations are possible.
[0085] For example, the various embodiments of FIGS. 14-28,
illustrate the concepts discussed herein of employing a barrier
layer that will diminish over time for exposing a thereby releasing
pharmaceutical agent. The barrier layer may be smooth, or irregular
(e.g., stepped, jagged, or otherwise) over some or all of its outer
surface, inner surface or combination thereof. Preferably, the
barrier layer overlies a layer of pharmaceutical agent, which in
turn is disposed on or within an implant member, that effectively
is a core of the device. The layer of pharmaceutical agent likewise
may be smooth or irregular over some or all of its outer or inner
surface, as may be the underlying implant member itself.
[0086] FIG. 14 illustrates a device 78 that has a variable
sectional thickness stepped barrier layer 80, over an implant
member 82, with a region 84 in which pharmaceutical agent is
located.
[0087] FIG. 15 shows a structure that has a region of
pharmaceutical agent 86 generally beneath variable sectional
thickness stepped barrier layer 88. The region 86 varies in
thickness along the length and as a result of a notched or
corrugated structure of an implant member 90 outer surface.
[0088] FIG. 16 shows an implant member 92 with overlying region 94
of pharmaceutical agent a variable sectional thickness stepped
barrier layer 96. The member 92 further includes axially spaced
flanged 98 for dividing the region 94 into subregions. The presence
of subregions here, as in other embodiments disclosed (e.g., FIG.
15) is that a plurality of different pharmaceutical agents may be
carried, each in a different subregion. Further, it is possible to
delay the start of another dose by requiring the barrier layer to
become eliminated.
[0089] FIGS. 17 and 18 illustrate an alternative to FIG. 16 in
which the subregions are further defined shaped wells. From a side
view, as seen in FIG. 17, a barrier layer 100 may overlie
pharmaceutical agent subregions 102 defined by a predetermined
structure of an implant member 104. The top view of FIG. 18
illustrates an example of an implant member surface 106 that has
walls 108 for defining a well 110. Each well may carry the same or
a different pharmaceutical agent.
[0090] Structures for the implant members, shown in FIG. 17, may
alternatively employ ribs along the length, such as axially spaced
circumferential or partially circumferential ribs.
[0091] FIGS. 19 and 20 illustrate yet another alternative
embodiment in which subregions are defined. As seen from a side
view in FIG. 19, a barer layer 112 overlies subregions 114 with a
pharmaceutical agent, carried over an implant member 116. In the
embodiment of FIG. 20, there is shown an option for further
controlling dosing by providing beneath a barrier layer 118, an
implant member 120 having first wells 122 and second wells 124. The
first wells 122 may extend over a different length of the implant
member 120, so that after a period of time only the pharmaceutical
agent of the first wells is released.
[0092] The embodiments of FIGS. 21 and 22 illustrate yet another
alternative employing a pharmaceutical agent region 126, a barrier
layer 128 and implant member 130. In this aspect, at least first
well 132, second well 134 and third well 136 are staggered in
partially overlapping relation to each other where the second well
spans at least the length between the first well 132 and third well
136, for helping to assure more continuous and less episodic
release of the pharmaceutical agent.
[0093] The embodiments of FIGS. 23 and 24 show yet another
alternative embodiment, in which well sizes are varied for
receiving different volumes of pharmaceutical agent. Thus a barrier
layer 138 over a pharmaceutical agent region 140 can be configured
on an implant member 142 so that (as seen from the top view of FIG.
24), a wall 144 defines first, second and optionally third wells
146, 148 and 150.
[0094] Instead of varying the length of the well, it is also
possible to vary its height. Moreover, as appreciated, the barrier
layer of each of the embodiments shown need not be stepped or
irregular, but may be smooth and continuous of constant thickness
sloping thickness.
[0095] To illustrate, FIG. 25 shows an embodiment that has a smooth
sloping barrier layer 152. As seen in FIG. 26, a suitable pattern
154 of wells for the pharmaceutical agent may be employed if
desired such as described previously. The pattern may be selected
as desired.
[0096] FIG. 27 illustrates yet another alternative in which an
implant member 156 is generally smooth over its outer surface.
Pharmaceutical agent is applied to define raised regions 158 over
which a barrier layer 160 is applied. The thickness of the barrier
layer may vary along the length 20 that as the thickness diminishes
over time only certain regions 158 will become exposed. Thus it is
possible that there can be simultaneous exposures of pharmaceutical
agent along substantial portions of, if not the entirety of the
length of the implant.
[0097] FIG. 28 illustrates another strategy for helping to
facilitate simultaneous exposure along the length of an implant as
in FIG. 27, a layer of pharmaceutical agent 164 on an implant
member 166 (e.g., having a contoured surface 168 which though
possibly irregular is illustrated as smooth, substantially free of
a slope).
[0098] While a preferred method and device herein contemplates an
opthalmological implant placed in an eye following cataract
surgery, other applications are also possible. For example, one
approach may be to provide an implantable tube that has a
biodegradeable or bio-erodable material on the inside of the tube.
Over time the tube inner diameter will gradually increase. In this
manner, such a tube can be placed in a passageway between the globe
and the subconjunctival space outside the scleral wall of the eye
during a glaucoma surgery, for helping to regulate pressure by way
of the gradually changing tube inner diameter.
[0099] The present invention also finds utility in other biomedical
implant applications, For example, it is possible to employ the
techniques herein for preparing a coated stent having a sustained
release pharmaceutical agent on it, on a suture material, on a
surgical instrument, a breathing tube, an othopedic pin, a syringe
needle, an intravenous needle, or otherwise.
[0100] It is also contemplated that a post of body piercing jewelry
article can be coated with a sustained release composition that
releases on anti-inflammatory, an antibiotic, steroid, or other
pharmaceutical agent. A like approach may be taken for treating
animal tagging devices prior to tagging an animal (e.g., a
livestock tag). In this manner, infection or other adverse
reactions can be treated when making an initial piercing.
[0101] It will be readily appreciated that for preparing devices
other than opthalmological implants, the methods herein described
can be adapted readily by selecting suitably desired materials and
agents, and by substituting the implant members described herein
with the desired article to be coated (e.g., a stent, an earring
post, livestock tag post, etc.).
[0102] In addition, while a feature of the present invention may
have been described in the context of only one of the illustrated
embodiments, such feature may be combined with one or more other
features of other embodiments, for any given application. It will
also be appreciated from the above that the fabrication of the
unique structures herein and the operation thereof also constitute
methods in accordance with the present invention.
[0103] It is understood that the above description is intended to
be illustrative and not restrictive. Many embodiments as well as
many applications besides the examples provided will be apparent to
those of skill in the art upon reading the above description. The
scope of the invention should, therefore, be determined not with
reference to the above description, but should instead be
determined with reference to the appended claims, along with the
full scope of equivalents to which such claims are entitled. The
disclosures of all articles and references, including patent
applications and publications, are incorporated by reference for
all purposes.
* * * * *