U.S. patent application number 12/985758 was filed with the patent office on 2011-05-26 for ophthalmic drug delivery system and method.
Invention is credited to Gholam A. Peyman.
Application Number | 20110125090 12/985758 |
Document ID | / |
Family ID | 44062607 |
Filed Date | 2011-05-26 |
United States Patent
Application |
20110125090 |
Kind Code |
A1 |
Peyman; Gholam A. |
May 26, 2011 |
OPHTHALMIC DRUG DELIVERY SYSTEM AND METHOD
Abstract
An ocular device comprising a biodegradable, and absorbable body
configured in a shape for implanting directly exterior and anterior
to a crystalline lens capsule in a patient's eye shaped in a C
configuration or a ring configuration to stably lay on zonules or
the anterior lens capsule or an intraocular lens (IOL) between an
iris and an outer surface of the lens capsule, or in the choroid
shaped in straight rod configuration or in a snake-shaped
semicircle configuration to follow the inside curvature of the
sclera and readily position inside the suprachoroidal space, or
under the retina shaped in a rod configuration or a semicircle
configuration the device comprising a deformable material such that
the device is folded upon implantation, the device optionally
containing an ocular therapeutic agent released upon implanting in
the patient's eye.
Inventors: |
Peyman; Gholam A.; (Sun
City, AZ) |
Family ID: |
44062607 |
Appl. No.: |
12/985758 |
Filed: |
January 6, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12611682 |
Nov 3, 2009 |
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12985758 |
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61114143 |
Nov 13, 2008 |
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Current U.S.
Class: |
604/93.01 |
Current CPC
Class: |
A61K 38/13 20130101;
A61K 9/0051 20130101; A61F 9/0017 20130101; A61K 31/436 20130101;
A61P 27/02 20180101; A61K 31/365 20130101 |
Class at
Publication: |
604/93.01 |
International
Class: |
A61F 9/00 20060101
A61F009/00 |
Claims
1. An ocular device comprising a biodegradable, and absorbable body
configured in a shape for implanting directly exterior and anterior
to a crystalline lens capsule in a patient's eye shaped in a C
configuration or a ring configuration to stably lay on zonules or
the anterior lens capsule or an intraocular lens (IOL) between an
iris and an outer surface of the lens capsule, or in the choroid
shaped in straight rod configuration or in a snake-shaped
semicircle configuration to follow the inside curvature of the
sclera and readily position inside the suprachoroidal space, or
under the retina shaped in a rod configuration or a semicircle
configuration the device comprising a deformable material such that
the device is folded upon implantation, the device optionally
containing an ocular therapeutic agent released upon implanting in
the patient's eye.
2. The device of claim 1 sized between 8 mm diameter and 18 mm
diameter, inclusive.
3. A method of treating a patient by administering the device of
claim 1 and intravitreally injecting the ocular therapeutic
agent.
4. The device of claim 1 containing a liquid medium in which an
agent is suspended.
5. The device of claim 1 containing a therapeutic agent in the
device.
Description
[0001] This application is a CIP of U.S. application Ser. No.
12/611,682 filed Nov. 3, 2009, which claims priority from U.S.
Application No. 61/114,143 filed Nov. 13, 2008, the contents of
which are expressly incorporated by reference herein in its
entirety.
BRIEF DESCRIPTION OF THE DRAWING
[0002] The FIGURE shows a embodiments of the device.
[0003] Known methods of drug delivery to the eye have drawbacks, as
the following illustrations demonstrate. Topical drug deliver must
be repeated many times on a daily basis because of low or slow
penetration. Compliance is also a problem. Subconjunctival drug
delivery can be painful and has slow drug penetration. Intravitreal
drug delivery has a short duration, typically of 2 to 30 days, so
additional intervention and/or repeated injections are needed. The
possibility of potential infections and retinal injury are also
problems. Scleral implants and trans-scleral implants have not been
attempted or tested. The implanted devices usually are made of
polymers; there is usually slow intraocular penetration when
polymers are injected into the eye. The vitreous usually requires
additional intervention with attendant potential complications,
such as infection, retinal injury, etc.
[0004] Method of intraocular delivery of various therapeutic agents
and methods are disclosed in Peyman et al., Retina, The Journal of
Retinal and Vitreous Diseases 29 (2009) 875-912, which is expressly
incorporated by reference in its entirety.
[0005] The disclosed system and method uses the capsular bag,
obtained during or after cataract extraction, as a polymeric slow
release drug delivery system and method. It is used for drug
delivery and for simultaneous support for the lens capsule.
[0006] The inventive system is used during or after intra-ocular
surgery for cataract extraction in the same session. After an
opening in the anterior chamber is made, a circular area of the
anterior capsule is removed to extract the lens cortex and
nucleus.
[0007] In one embodiment, the system and method is used
post-surgically to prevent or to treat inflammation. After surgery,
most if not all eyes have some inflammation for which treatment is
administered. For example, all patients who have diabetic
retinopathy have post-surgical ocular inflammation. All patients
who have a previous history of uveitis have more excessive
inflammation.
[0008] In one embodiment, the device is a capsular ring of any size
configured in a shape for implanting outside the crystalline lens.
Thus, the device is not dependent on removal of the crystalline
lens. In this embodiment, the device is intraocular but is
extralens, it is external to the lens. It is supported in the eye
by the lens zonules or ciliary body.
[0009] In one embodiment, the device is a capsular ring of any size
configured in a shape for implanting over the lens capsule having
an intraocular lens. In this embodiment, where the eye contains an
intraocular lens, the device is configured for implanting between
the iris and the outer part of the lens capsule.
[0010] It is important that the device shape fits its position,
that is, its location, inside the eye. The length of the device
fits a large space inside the eye, and provides a longer duration
of agent release over a wider area inside the eye than known
devices.
[0011] In one embodiment, the device is configured for implanting
anterior to the lens. In this embodiment, the device is configured
either C-shaped or ring shaped to lay on the zonules or the
anterior lens capsule or the intraocular lens (IOL). Any other
device shape would not be stable in this position, that is, this
location.
[0012] In one embodiment, the device is configured for implanting
in the choroid. In this embodiment, the device is configured either
as a rod or as a snake-shaped semicircle. In these configurations,
the device follows the inside curvature of the sclera and can
readily snake inside the suprachoroidal space. Any other device
shape would be difficult to configure in the suprachoroidal space,
and could penetrate the choroid and the retina resulting in serious
complications. Any other device shape may not sufficiently large to
cover a relatively large area.
[0013] In one embodiment, the device is configured for implanting
under the retina, that is, for subretinal implantation. In this
embodiment, the device is configured either as a rod or as a
semicircle, following the curvature of the retina and the
subretinal space. Although a circular device may be implanted under
the retina, implanting would be difficult. A circular device would
not follow the retinal curvature and would bulge the retina.
[0014] In all embodiments the device is biodegradable, also termed
bioadsorbable; no foreign body remains in the eye after the device
is absorbed.
[0015] The FIGURE shows various embodiments of the device. The
device is rod shaped and may be straight, curved, C-shaped, closed
loop, Its length ranges from 1 mm to 60 mm inclusive. In one
embodiment, its length ranges from 15 mm to 600 mm inclusive. Its
diameter ranges from 30 micrometers to 3 millimeters inclusive and
is round, flat, bead-shaped, etc. The device is made of
biodegradable polymers that contain and release agent contained
within the device and/or within the polymers. In one embodiment the
device is solid. In one embodiment the device is not-solid. In
either embodiment, the device may be sized to be between 8 mm
diameter and 18 mm diameter, inclusive.
[0016] The device is shaped as a rod, tube, open loop, or closed
loop. In embodiments where the device is a rod, the device can be a
solid rod or a hollow tube with closed ends. The device is folded
for easy implanting through an incision that is as small as 1 mm.
The nanlded over the lens capsule in the posterior chamber. For
implanting, a viscoelastic substance is also implanted for
lubrication and ease of implantation, as known to one skilled in
the art. Once the device is it in place, the device is
unfolded.
[0017] For a suprachoroidal implantation application, the device is
shaped as a rod, tube or open loop. It is not shaped as a closed
loop. The device is implanted under the sclera over the ciliary
body or the choroid of the eye through a small incision, preferably
in the sclera at the plars plana area 1 mm to 4 mm behind the
limbus of the cornea/sclera junction, or anywhere else in the
sclera. The incision reaches the ciliary body/choroid. The space
between the ciliary body/choroid and the sclera is called
suprachoroidal space. The device which has a semicircular or
straight rod configuration is threaded in the suprachoroidal space
in any desired direction toward any meridian. The resilient
structure of the device assists in moving it in this space to the
desired length. Because of its round tip, it cannot penetrate the
choroidal vessels but follows the suprachoroida space when pushed
against the resilient sclera. Its location can also be verified by
indirect ophthalmoscopy. After the implantation, the scleral
incision is closed with a suture.
[0018] For a subretinal implantation application, the device is
shaped as a rod, tube, or semicircle. The device is implanted
through a pars plana vitrectomy through the sclera. A subretinal
bleb is created using a balanced saline solution at the desired
retinal location, e.g., in the superior retina. Using forceps, the
device is inserted gently into the subretinal space where it
remains until it is adsorbed. It is known that material injected
under the retina, with time, diffuses from that location into the
subretinal space under the macula and exerts a therapeutic
effect.
[0019] Implantation methods are known to one skilled in the art.
Implantation may use forceps. Implantation may use an injector.
[0020] In one embodiment, the device contains agents that are
neuronal cell protective and/or neuronal cell proliferative. The
agents can be on the device, in the device, both on and in the
device, and/or administered with the device by, e.g., simultaneous
or substantially simultaneous injection upon implantation. Such
devices are used for implanting in patients with glaucoma,
neurodegenerative diseases including dry or wet forms of age
related macular degeneration (ARMD), retinitis pigmentosa where the
retinal cells and retinal pigment epithelial cells die by aging and
genetic/inflammatory predisposition, and diabetic retinopathy.
[0021] One non-limiting example of such an agent is rho kinase
(ROCK). ROCK plays an important role in cell proliferation, cell
differentiation and cell survival/death. Blockade of ROCK promotes
axonal regeneration and neuron survival in vivo and in vitro,
thereby exhibiting potential clinical applications in spinal cord
damage and stroke. ROCK inhibitors attenuated increases in
pulmonary arterial pressures in response to intravenous injections
of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium
nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased
pulmonary and systemic arterial pressures and vascular resistances
in monocrotaline-treated rats.
[0022] Its use to prevent and/or treat in degenerative retinal
diseases such as ARMD, retinitis pigmentosa, and glaucoma has not
been reported and thus is new. ARMD can have an inflammatory
component, contributing to cell death and apoptosis. Oxidative and
ischemic injury in ARMD and diabetic retinopathy also contributes
to ROCK activation. Because ROCK plays an important role in these
processes, inhibiting ROCK can prevent neuronal cell death.
[0023] In one embodiment, ROCK inhibitors are injected directly
into the eye, e.g., in the vitreous cavity, under the retina, under
the choroid, etc. Methods and formulations are disclosed in the
following references, each of which is expressly incorporated by
reference in its entirety: Peyman et al. Retina 7 (1987) 227;
Khoobehi et al., Ophthalmic Surg. 22 (1991) 175; Berger etl al.,
Investigative Ophthamology & Visual Science, 37 (1996) 2318;
Berger etl al., Investigative Ophthamology & Visual Science, 35
(1994) 1923. In one embodiment, ROCK inhibitors are injected in a
polymeric formulation to provide a slow release system. In this
embodiment, the polymeric material is made from any biodegradable
polymer as known to one skilled in the art. Examples of suitable
materials include, but are not limited to, polymers and/or
co-polymers (poly)lactic acid (PLA), (poly)glycolic acid (PGA),
lactic acid, (poly)caprolactone, collagen, etc. These can be
injected or implanted in a shape and location as described above.
In one embodiment, ROCK inhibitors are administered in a slow
release system.
[0024] In one embodiment, ROCK inhibitors are administered with one
or more other agents that inhibit inflammatory processes, inhibit
angiogenesis, and/or inhibit fibrosis. Such agents include, but are
not limited to, vascular endothelial growth factor (VEGF)
inhibitors, platelet-derived growth factor (PDGF) inhibitors, and
integrin inhibitors. In one embodiment, ROCK inhibitors are
administered in a non-slow release form, and VEGF, PDGF, and/or
integrin inhibitors are administered in a slow release form. In one
embodiment ROCK inhibitors are administered in a slow release form,
and VEGF, PDGF, and/or integrin inhibitors are administered in a
non-slow release form. In one embodiment, ROCK inhibitors and VEGF,
PDGF, and/or integrin inhibitors are administered in a dual,
triple, or quadruple slow release form.
[0025] Examples of ROCK inhibitors include, but are not limited to,
the following agents: fasudil hydrochloride (inhibitor of cyclic
nucleotide dependent- and rho kinases); GSK 429286 (a selective
ROCK inhibitors); H 1152 dihydrochloride (a selective ROCK
inhibitor); glycyl-H 1152 dihydrochloride (a more selective analog
of H 1152 dihydrochloride); HA 1100 hydrochloride (a
cell-permeable, selective ROCK inhibitor); SR 3677 hydrochloride (a
potent, selective ROCK inhibitor); Y 39983 dihydrochloride (a
selective ROCK inhibitor); and Y 27632 dihydrochloride a selective
p160 ROCK inhibitor). VEGF inhibitors include, but are not limited
to, Avastin, Lucentes, etc. PDGF inhibitors include, but are not
limited to, Sunitinib. Integrin inhibitors are known to one skilled
in the art.
[0026] The concentration of ROCK inhibitor is administered so that
its concentration upon release ranges from less than 1 micromol to
1 millimole. In one embodiment, the concentration of agent is
administered so that its concentration upon release ranges from 1
micromole/day to 100 micromol day. Such concentrations are
effective and are non-toxic.
[0027] The agents may be in any biocompatible formation as known to
one skilled in the art. The agents may be formulated as
microspheres, microcapsules, liposomes, nanospheres, nanoparticles,
etc. as known to one skilled in the art.
[0028] The general configuration of the device is new. The device
is implanted by any of three different methods in various parts of
the eye. In one method, the device is configured for implanting
over the lens capsule and between the iris and the lens in the
posterior chamber. In one method, the device is configured for
implanting in the suprachoroidal space; in this embodiment, agent
contained in and/or on or with the device is delivered to the
choroid and retina. In one method, the device is configured for
implanting in the subretinal space; in this embodiment, agent
contained in and/or on or with the device is delivered to the
sensory retina.
[0029] In an intralens device, the device may be of any shape. The
following embodiments are illustrative only and are not limiting.
In one embodiment, the device is ring shaped. In one embodiment,
the device is shaped as an open ring (e.g., doughnut or tire
shape). In one embodiment, the device is shaped as a rod, which may
be straight or curved. In one embodiment, the device is shaped as a
semicircle. In one embodiment, the device contains one ring. In one
embodiment, the device contains at least two concentric rings. In
one embodiment, the device is shaped as an oval. In one embodiment,
the device is C shaped. In one embodiment, the device is shaped as
triangle. In one embodiment, the device is shaped as a quadratic.
In one embodiment, the device is spring-shaped. In one embodiment,
the device is shaped in a zigzag configuration. A tube structure
permits delivery of agent that must be in a liquid medium, such
agents include agents for gene modification or stem cells.
[0030] In one embodiment, the size of the device ranges from 1 mm
in diameter up to about 34 mm in diameter. In one embodiment, the
size of the device ranges from 1 mm in diameter up to about 20 mm
in diameter. In one embodiment, the thickness of the device may
range from about 50 .mu.m to about 3000 .mu.m. In one embodiment,
the thickness of the device may range from about 10 .mu.m to about
3000 .mu.m. In one embodiment, the device is made from a polymeric
material that is absorbable. In one embodiment, the device is made
from a polymeric material that is nonabsorbable, e.g., polylactic
acid polyglycolic acid, silicone, acrylic, polycaprolactone, etc.
In one embodiment, the device is made as microspheres.
[0031] The device is positioned in the lens capsule, e.g., after
cataract extraction prior to or after IOL implantation. In one
embodiment, it is positioned inside the lens capsule after cataract
extraction and acts as a polymeric capsular expander keeping the
capsular bag open for intraocular lens (IOL) implantation). In one
embodiment, the device is positioned on the haptics of the IOL. In
one embodiment, the device is located inside the capsule or under
the iris supported by the lens zonules, or it can be sufficiently
large to lie in the ciliary sulcus, or ciliary body, or hanging
from the zonules in a C-shaped configuration.
[0032] For implantation, after removing the lens cortex and nucleus
inside the capsule through a capsulotomy, the inventive device is
implanted before or after an IOL is implanted. The inventive device
is flexible, deformable, and re-moldable. In one embodiment, the
inventive device is implanted through a incision one mm or less
using an injector, forceps, etc. The incision may be made in the
cornea for cataract removal. In one embodiment, the inventive
device is implanted in an eye without cataract extraction. In this
embodiment the inventive device may be implanted under the iris,
e.g., after traumatic anterior segment injury, and lies over the
crystalline lens, IOL, and zonules. Implantation may be facilitated
by using a visco-elastic material such as healon, methyl cellulose,
etc.
[0033] Retino-choroidal diseases are aggravated after cataract
surgery. Retino-choroidal diseases include, but are not limited to,
diabetes, existing prior inflammations such as uveitis, vascular
occlusion, wet age related macular degeneration, etc. Patients with
these diseases are candidates for the inventive drug delivery
system and method. Other indications are prophylactic therapy prior
to development of retinal complications, such as inflammation (CME)
and infection, and therapy for an existing disease. Other
indications are conditions in which any intraocular drug delivery
to treat aging processes if cataract surgery is contemplated or
after IOL implantation. In latter situation, the inventive device
can be implanted in the capsule or over the IOL under the iris
Other indications are post-surgical inflammations, post-surgical
infections such as after cataract extraction, and any intraocular
delivery.
[0034] In one embodiment, medication can be coated on a surface and
eluted from the surface of the inventive device for delivery, using
methods known in the art (e.g., drug-coated stents). In one
embodiment, medication can be incorporated in the polymeric
material using methods known to one skilled in the art. The
following medications can be delivered, alone or in combinations,
to treat eyes using the inventive system and method: steroids,
non-steroidal anti-inflammatory drugs (NSAIDS), antibiotics,
anti-fungals, antioxidants, macrolides including but not limited to
cyclosporine, tacrolimis, rapamycin, mycophenolic acid and their
analogs, etc. For example, voclosporin (FIG.) is a next generation
calcineurin inhibitor, an immunosuppressive compound, developed for
the treatment of uveitis, an inflammation of the uvea, the
treatment of psoriasis, and for the prevention of organ rejection
in renal transplant patients. It can be used with other
immunomodulatores, etanercept, infliximab, adalimumab, etc. Other
examples include: antibodies (e.g., anti-vascular endothelial
growth factor), immunomodulators, antiproliferative agents, gene
delivery agents (e.g., to treat damaged neuronal tissue),
neuroprotective agents, anti-glaucoma agents (e.g., to treat or
prevent increases in intraocular pressure, etc.). In one
embodiment, combinations of agents may be provided in a single
device or in multiple devices.
[0035] The duration of delivery is manipulated so that the agent(s)
is released at a quantity needed to achieve therapeutic effect for
each agent, if more than one agent is administered, as long as
necessary. Duration may be a single dose, may be one day, may be
daily for up to 12 months or longer, may be several times a day. In
embodiments using a polymer, reimplantation is possible through a
small incision once the polymer is absorbed.
[0036] Other variations or embodiments will be apparent to a person
of ordinary skill in the art from the above description. Thus, the
foregoing embodiments are not to be construed as limiting the scope
of the claimed invention.
* * * * *