U.S. patent application number 12/575573 was filed with the patent office on 2010-01-28 for implantable drug delivery system.
Invention is credited to Theron Robert Rodstrom.
Application Number | 20100022945 12/575573 |
Document ID | / |
Family ID | 28041734 |
Filed Date | 2010-01-28 |
United States Patent
Application |
20100022945 |
Kind Code |
A1 |
Rodstrom; Theron Robert |
January 28, 2010 |
IMPLANTABLE DRUG DELIVERY SYSTEM
Abstract
An implantable medicament delivery device includes a core body
which further includes a single basin or multiple smaller basins
for containing a drug or a medicament. Each basin is covered by a
screen. The implantable drug delivery device is placed within the
body of an animal, and the drug is allowed to diffuse through the
holes in the screen to provide treatment of a disease or
condition.
Inventors: |
Rodstrom; Theron Robert;
(Cranfills Gap, TX) |
Correspondence
Address: |
ALCON
IP LEGAL, TB4-8, 6201 SOUTH FREEWAY
FORT WORTH
TX
76134
US
|
Family ID: |
28041734 |
Appl. No.: |
12/575573 |
Filed: |
October 8, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10385791 |
Mar 11, 2003 |
7621907 |
|
|
12575573 |
|
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|
|
60363150 |
Mar 11, 2002 |
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Current U.S.
Class: |
604/22 ;
29/428 |
Current CPC
Class: |
A61K 9/0051 20130101;
A61F 9/0017 20130101; Y10T 29/49826 20150115 |
Class at
Publication: |
604/22 ;
29/428 |
International
Class: |
A61F 9/007 20060101
A61F009/007; B23P 11/00 20060101 B23P011/00 |
Claims
1. A method of making implantable drug delivery platform comprising
the steps of: a) forming a basin containment portion around a
basin, said basin being constructed and arranged to contain the
drug; b) affixing a first screen to said basin containment portion
to cover said basin.
2. The method as defined in claim 1 further including the step of
placing a second screen on the opposite side of said basin.
3. The method as defined in claim 2 wherein said second screen is
affixed to said basin containment portion.
4. The method as defined in claim 1 wherein said basin containment
portion is substantially planar.
5. The method as defined in claim 1 wherein said first screen is
formed to be substantially planar.
6. The method as defined in claim 2 wherein said second screen is
formed to be substantially planar.
7. The method as defined in claim 1 wherein the combination of said
basin containment portion and said screen are formed to encircle an
internal body part.
8. The method as defined in claim 1 wherein the step of forming
said screen is further defined by forming the number and size of
the holes in said screen depending on one or more factors selected
from a group including medicament solubility, medicament
dissolution rate, and medicament concentration.
9. The method as defined in claim 1 further including the step of
dividing said basin into at least two smaller basins.
10. The method as defined in claim 9 further including the step of
forming the size and number of the holes in said screen covering
said smaller basins.
11. A method of treating a disease within the eye of an animal,
said method comprising the steps of: making an incision in the
sclera; inserting a drug delivery device through said incision,
said drug delivery device including: a basin containment portion
including a basin constructed and arranged to contain the drug; a
screen constructed and arranged to cover said basin and be affixed
to said basin containment portion.
12. The method as defined in claim 11 the opposite sides of said
basin is formed as a screen.
13. The method as defined in claim 11 wherein said basin passes
through said basin containment portion and on the bottom of said
basin is a second screen, said second screen being constructed and
arranged to cover the basin and be affixed to said basin
containment portion.
14. The method as defined in claim 11 wherein said basin
containment portion is substantially planar.
15. The method as defined in claim 11 wherein said screen is
substantially planar.
16. The method as defined in claim 13 wherein said second screen is
substantially planar.
17. The method as defined in claim 11 wherein the size of the holes
in said screen is dependent on one or more factors selected from a
group including medicament solubility, medicament dissolution rate,
and medicament concentration.
18. The method as defined in claim 13 wherein the number and size
of the holes in said second screen is dependent on one or more
factors selected from a group including medicament solubility,
medicament dissolution rate, and medicament concentration.
19. The method as defined in claim 11 wherein said well in said
basin containment portion is divided into at least two smaller
basins.
20. The method as defined in claim 17 wherein the size and number
of the holes in said screen covering said smaller basins are
different.
Description
[0001] This application is a continuation of patent application
Ser. No. 10/385,791, filed Mar. 11, 2003, which claims priority
from U.S. Provisional Patent Application, Ser. No. 60/363,150 filed
Mar. 11, 2002.
FIELD
[0002] The present invention pertains to a drug delivery system;
more particularly, the present invention pertains to an implantable
small drug delivery device for use with human beings or other
animals.
BACKGROUND
[0003] There are many conditions or diseases which occur within the
body of a human being or an animal which respond effectively to
treatment by the use of one or more medicaments. For many such
conditions and diseases the medicament is taken orally. Once
swallowed, the medicament eventually migrates to the location of
the condition or disease by passing through the gastrointestinal
system. In still other instances, medicament is delivered to the
location of the condition or disease through the bloodstream.
Specifically, the medicament is injected by a syringe into a muscle
or soft tissue and then carried by the flow of blood. In still
other situations, generally in a health care facility, an IV drip
may be used to place the medicament directly into a blood vessel.
In yet other situations, some type of surgical intervention is used
to physically place a particular medicament within the body at or
near the location of a condition or disease.
[0004] It has been found that by use of the techniques developed
for the creation of integrated circuits, small drug delivery
devices can be manufactured which may be used to both contain and
then deliver medicament to the site of a condition or disease
within the human body. Examples of such small drug implantation
devices are disclosed in the following U.S. patents: U.S. Pat. No.
5,770,076; U.S. Pat. No. 5,797,898; U.S. Pat. No. 5,985,328; U.S.
Pat. No. 6,123,861, and U.S. Pat. No. 6,331,313. Many of these
small drug implantation devices are highly complex and,
accordingly, both difficult and expensive to manufacture. Thus,
there remains a need in the art for a simple, low cost,
easy-to-manufacture implantable small drug delivery device that can
be adapted for implantation within the body of a human being or
other animal to deliver medicament to a wide variety of
locations.
SUMMARY
[0005] The simple, low cost, easy-to-manufacture implantable drug
delivery system of the present invention enables the implantation
of a mechanism within the body to deliver medicament to a wide
variety of locations. The disclosed system includes at least one
basin, well, or open space. The basin, well, or open space is
enframed, enclosed, encased, or formed in a core body. The basin,
well, or open space within the core body or basin encasement
portion is of sufficient size to contain the desired amount of a
medicament needed for prolonged internal treatment of a chronic
condition or disease. Typical of such chronic conditions or
diseases are those that are known to occur within the eye.
[0006] Covering the basin, well, or open space, which is surrounded
by the core body, at either the top, or the bottom, or both, is a
screen. The screen is used to control the release or movement of a
drug or a medicament from a tablet, a powder, or a slurry placed in
the basin, well, or open space into the body of a human or an
animal. The number, size, location, and arrangement of the holes in
the screen or screens is a function of the solubility of the
medicament contained in the basin, well, or open space, the
dissolution rate of the medicament, the concentration of the
medicament, and the form of the medicament--be it a tablet, a
powder, a slurry, or a combination thereof.
[0007] Once one or more medicaments have been placed into the
basin, well, or opening, and the basin, well, or opening is covered
with a screen, the entire combination of the drug or medicament,
the core body in which the basin is formed, and the screen is
implanted within the body. For example, for conditions or diseases
occurring within the eye, one technique is to insert the disclosed
drug delivery system into the eye through the sclera portion. Once
the disclosed drug device has been properly positioned at its
desired location, it may be affixed in place using a variety of
methods, to include passing sutures through a hole formed in the
core body.
[0008] Dispersion of the medicament out of the basin, well, or open
space occurs when fluid from within the body moves through the
perforations in the screen into the basin. This flow of fluid
through the screen initiates the dissolution of the medicament
within the basin. The dissolved medicament will then slowly diffuse
outwardly through the holes in the screen to provide continuing
treatment of the condition or disease as long as a quantity of
medicament remains within the basin of the disclosed drug delivery
device.
DESCRIPTION OF THE DRAWING FIGURES
[0009] A better understanding of the implantable drug delivery
system of the present invention may be had by reference to the
drawing figures, wherein:
[0010] FIG. 1 is a side elevational view of an embodiment of the
invention inserted into a human eye;
[0011] FIG. 2A is an exploded perspective view of the preferred
embodiment;
[0012] FIG. 2B is a perspective view of a core body similar to that
shown in FIG. 2A;
[0013] FIG. 2C is a perspective view of a screen similar to that
shown in FIG. 2A;
[0014] FIG. 2D is a magnified planar view of a portion of a screen
such as shown in FIG. 2C;
[0015] FIG. 3 is an exploded perspective view of a first alternate
embodiment;
[0016] FIGS. 4A and 4B are perspective views of a second and third
alternate embodiment of the disclosed drug delivery system;
[0017] FIG. 5 is a side elevational view of the drug delivery
system attached to a support piece;
[0018] FIG. 6A is a perspective view of the drug delivery system
including a sharpened edge or scalpel nose portion;
[0019] FIG. 6B is an exploded view of the embodiment shown in FIG.
6A;
[0020] FIG. 6C is a perspective view of the drug delivery system
including a sharpened edge similar to that shown in FIG. 6A;
[0021] FIG. 6D is an exploded view of the embodiment shown in FIG.
6C;
[0022] FIG. 7 is a perspective view of an alternate embodiment of
the core body of the drug delivery system of the present invention
further including a channel for the resupply of medicament to the
basin;
[0023] FIG. 7A is an alternate embodiment of the core body of the
drug delivery system shown in FIG. 7, including a flanged portion;
and
[0024] FIG. 8 is a perspective view of yet another alternate
embodiment of the drug delivery system including multiple smaller
basins;
[0025] FIG. 9 is a perspective view of a drug delivery system
having a three compartment basin including internal passageways for
medicament migration between compartments;
[0026] FIG. 10 is a perspective view of a drug delivery system
including two smaller basins within a larger basin;
[0027] FIG. 11 is a perspective view of an alternate embodiment of
the drug delivery system shown in FIG. 10;
[0028] FIG. 12 is a perspective view of a drug delivery system
having a single basin;
[0029] FIG. 13 is a perspective view of a first alternate
embodiment of the drug delivery system shown in FIG. 12;
[0030] FIG. 14 is a perspective view of a second alternate
embodiment of the drug delivery system shown in FIG. 12;
[0031] FIG. 15 is a perspective view of a third alternate
embodiment of the drug delivery system shown in FIG. 12;
[0032] FIG. 16 is a perspective view of a fourth alternate
embodiment of the drug delivery system shown in FIG. 12;
[0033] FIG. 17 is a perspective view of a fifth alternate
embodiment of the drug delivery system shown in FIG. 12;
[0034] FIG. 18 is a perspective view of a sixth alternate
embodiment of the drug delivery system shown in FIG. 12;
[0035] FIG. 19 is a perspective view of a seventh alternate
embodiment of the drug delivery system shown in FIG. 12;
[0036] FIG. 20 is a perspective view of an eighth alternate
embodiment of the drug delivery system shown in FIG. 12;
[0037] FIG. 21 is a perspective view of a first alternate
embodiment of the drug delivery system shown in FIG. 10;
[0038] FIG. 22 is a perspective view of a second alternate
embodiment of the drug delivery system shown in FIG. 10;
[0039] FIG. 23 is a graph of drug concentration over time in an in
vitro study using betaxolol HCl tablets; and;
[0040] FIG. 24 is a graphic of drug concentration over time in an
in vitro study using nepafenac tablets.
DESCRIPTION OF THE EMBODIMENTS
[0041] In the following description of the preferred and alternate
embodiments, reference numbers are used to facilitate the
description of the disclosed invention. Throughout this
description, the same numbers in the units and tens places refer to
the same portion of each embodiment. The numbers in the hundreds
and thousands places are used to designate an alternate
embodiment.
[0042] As may be seen in FIG. 1, the present invention is a small
implantable drug delivery system 10 shown being used for the
treatment of condition or diseases affecting an inner portion of an
eye. Such diseases include but are not limited to ARMD (age related
macular degeneration), PDR (proliferative diabetic retinopathy),
neovascular glaucoma, ischemic and iatrogenic retinopathy,
posterior ocular inflammation and retinal edema.
[0043] While the preferred embodiment of the present invention is
described herein according to its use for treatment of inner eye
diseases, it will be understood by those of ordinary skill in the
art that the present invention may be used at any location in the
body of an animal suitable for the treatment of a disease or
condition with medicament contained in a small drug delivery
device.
[0044] In addition to treatment of the diseases of the eye, a drug
delivery device according to the present invention could be
positioned adjacent to the prostate gland in men for the treatment
of prostate cancer or benign prostate hyperplasia. By using the
disclosed device, the negative side effects normally associated
with the treatment of prostate cancer, such as hot flashes, vocal
changes, or breast enlargement could be significantly reduced or
even eliminated. In addition, those of ordinary skill in the art
will understand that the amount of a drug or medicament needed for
treatment of a disease or condition could be significantly reduced,
thus reducing patient cost. Patient compliance with a treatment
regimen would improve as the need for frequent drug administration
would effectively be eliminated. Pharmacist workload and exposure
to hazardous or toxic pharmaceuticals would be reduced. The
opportunity for drug-drug or drug-food interaction would be
effectively avoided. And the opportunity to provide drug
combination therapy would be increased.
[0045] Similar advantages could also be obtained if the disclosed
device instead included a contraceptive implanted within a female.
Still other potential applications include the treatment of vaginal
fungal infections with an anti-fungal medicament.
[0046] Victims of Parkinson's disease would also be candidates for
implantation of the disclosed drug delivery device within the brain
to slowly release medicament for reduction of tremors. Patients
with ulcerative colitis or a variety of different
gastroenterological diseases may also be able to obtain relief by
implantation of the disclosed device in their GI tract.
[0047] As may be seen in FIG. 2A, the drug delivery system 10
includes a basin 14. The basin is formed in a basin containment,
enframement, or encasement portion 12. For simplification of
description, the basin containment, enframement, or encasement
portion is called the core body 12. In the preferred embodiment,
the core body 12 is formed from a substantially planar rigid piece
of material. The basin 14 in FIG. 2A is shown with a top 16 and a
bottom 18. The top 16 of the basin 14 intersects the upper face 20
of the core body 12. In the preferred embodiment, the bottom 18 of
the basin 14 intersects the lower face 22 of the core body 12. The
illustrated basin 14 is effectively a hole which passes through the
core body 12. If the top 16 is larger than the bottom 18, the basin
14 may have tapered walls 17.
[0048] A still better understanding of the construction of the core
body 12 may be had by reference to FIG. 2B. Therein, the core body
12 is shown having an arcuate modified race-track outer perimeter.
The basin 14 contained therein passes completely therethrough from
the upper face 20 to the lower face 22 and has a perimeter roughly
parallel to the outer perimeter of the core body. For a better
appreciation of the small size of the disclosed drug delivery
system, the length of the core body 12 is about 9.5 mm and the
width is about 5.3 mm.
[0049] The basin 14 may be located at the center of the core body
12 as shown in FIG. 2B or closer to one end of the core body 12.
The size of the basin 14 is sufficient to hold a variety of
different medicaments. Such medicaments may include those that are
directly or indirectly a neuro-protectant, an anti-oxidant, an
anti-apoptotic agent, a soluble growth factor agonist or
antagonist, an anti-proliferative agent, an anti-angiogenic agent,
an anti-edematous agent, a vascular targeting agent, an
anti-inflammatory, or an antibiotic, whether they be small organic
molecules or biologics, such as proteins, ribozymes, antibodies,
antibody fragments, aptameters, or oligonucleotides. More
specifically, suitable medicaments include, but are not limited to,
signal transduction inhibitors, protein kinase antagonists,
tyrosine kinase antagonists, VEGF receptor antagonists, integrin
antagonists, matrix metalloproteinase inhibitors, glucocorticoids,
NSAIDS, COX-1 and/or -2 inhibitors, and angiostatic steroids. Each
of these medicaments may be in the form of either a powder, a
slurry, or a tablet. The amount of such medicament should be
sufficient to provide enough treatment of the disease for which the
medicament is prescribed for a predetermined time period, depending
on the type and severity of the disease. If desired, a variety of
different additives may be added to the medicament to increase its
effectiveness. For example, an additive with water affinity, such
as an excipient humectant, may be added to the medicament for the
purpose of attracting water molecules to the area where the device
is inserted into the eye to initiate or to aid dissolution of the
medicament or transport of the medicament out of the basin 14.
[0050] To minimize the formation of small bubbles within the basin
14, it is preferable that the size and shape of the basin 14 and
the size and shape of the medicament placed in the basin 14 should
be substantially the same to minimize the amount of free air.
[0051] As shown in FIG. 2C, a first screen 24 is formed to be
attached to the upper face 20 of the core body 12 to cover the top
16 of the basin 14. Optionally, a second screen 26 is attached to
the lower face 22 of the core body 12 to cover the bottom 18 of the
basin 14. In the preferred embodiment, the screen 24 is as shown in
FIG. 2C. Specifically, the screen 24 has an arcuate modified race
track perimeter 36 which is roughly parallel to the perimeter of
the basin 14 and the perimeter of the core body 12. That portion 23
of the screen in which the holes 28 are formed may be of equal
thickness with the perimeter 25 or a different thickness depending
on the construction of the device 10.
[0052] As may be seen in FIG. 2D, the screen 24 or screens 24, 26
are formed to contain a plurality of holes 28. The number, size,
location, and arrangement of the holes 28 in the screen 24 or
screens 24, 26 is a function of a variety of factors to include the
solubility of the drug which is placed in the basin 14, the
dissolution rate of the drug which is placed in the basin 14, and
the concentration of the drug which is placed in the basin 14.
Typically, the size of the holes 28 will be anywhere from
substantially about 0.2 microns to substantially about 100 microns.
However, because of the versatility of the disclosed invention in
other applications still different hole sizes may be used. While it
is understood that a generally uniform distribution of the holes 28
over the surface of the screen 24 or screens 24, 26 enables maximum
dissolution of the medicament, other non-uniform distribution of
holes 28 are also possible as explained below. Additionally, those
of ordinary skill in the art will understand that when the drug
delivery system of the present invention is used within the eye,
the holes must be small enough to block the passage of any
undissolved particles of medicament which might interfere with
vision.
[0053] A suitable thickness for each screen will be from about 0.05
mm to 0.5 mm, and a suitable thickness of the core body 12 will be
from about 0.5 mm to about 3.0 mm, preferably about 1.0 mm to about
2.0 mm, depending on the amount of medicament that is intended to
be administered at the target implantation site.
[0054] When either metallic or non-metallic materials are used to
fabricate the disclosed drug delivery device, the screen 24 or
screens 24, 26 may be affixed to the core body 12 using a variety
of different adhesives, to include silicon rubber, cyano acrylates,
or commonly available bio-compatible room temperature adhesives,
thermal adhesives, epoxies, or ultraviolet light cured adhesives.
In the preferred embodiment, the screen 24 or screens 24, 26, like
the core body 12, are also formed to be substantially planar.
[0055] A variety of different materials may be used to fabricate
the core body 12 and the screens 24, 26. Such materials may be
selected from a variety of different bio-compatible materials to
include silicon, glass, ruby, sapphire, diamond, or ceramic. If
desired, a bio-compatible metal may be used to form the core body
12 and the screens 24, 26. Such bio-compatible metals include gold,
silver, platinum, stainless steel, tungsten, and titanium. When a
bio-compatible metal is used, the screen 24 or screens 24, 26 may
be welded to the core body 12 using a variety of different
techniques, to include laser welding, thermo-electro bonding, as
previously indicated, or the glues and adhesives described
above.
[0056] Those of ordinary skill in the art will understand that the
effectiveness of the disclosed drug delivery platform is determined
by the delivery of the appropriate number of molecules of
medicament during a predetermined period of time. Accordingly, the
sum total of the area of the holes 28 in the screen or screens must
enable the desired delivery rate of medicament from the basin 14.
Generally, this is referred to as hole density. For the purposes of
this disclosure, hole density is the total area of the holes
divided by the total surface area of the device, even that area not
covered by a screen.
[0057] The number of holes, their size, their location, and their
general appearance on the surface of a screen forms a hole pattern.
This hole pattern will be adjusted to assure that required amount
of medicament is delivered at the needed flow rate. When multiple
basins are formed in the core body, multiple hole patterns in the
screens may be used to control the flow of medicament. For example,
a hole pattern having holes concentrated at one end of a basin will
initially cause a fast flow of medicament. But, as the medicament
is used up, the medicament will have a longer path to travel before
exiting the basin 14; accordingly, the release rate of medicament
out of the drug delivery basin 14 will drop off over time.
[0058] In an alternate embodiment 110 shown in FIG. 3, the bottom
118 of the basin 114 may itself be formed as a screen, thus
obviating the need for the use and attachment of a second screen 26
as shown in FIG. 2A. In other applications, as shown in FIG. 3, it
is also possible for the basin 114 to have a solid bottom. When the
basin 114 has a solid bottom, only a single screen 124 is used on
the top 116 of the basin 114.
[0059] While the preferred embodiment shows a modified racetrack
perimeter 36 with the basin 14 closer to the distal end 15 and a
suture hole 30 placed at the proximal end 13, it will be understood
by those of ordinary skill in the art that numerous other designs
of the implantable drug delivery platform are possible without
departing from the scope of the present invention. For example, the
drug delivery platform may be formed with multiple suture holes 30
or with straight sides such as the triangle shape 310 as shown in
FIG. 4A. Alternatively, a square shape, a circular shape, a paddle
shape, or any other convenient shape which may be inserted through
a small incision in the eye or located in a portion of the body
where the medicament is determined to be most effective may be
used.
[0060] Because of the adaptability of the disclosed invention to
being configured in a variety of different shapes, particularly if
the core body and screen(s) are formed of a bio-compatible metal,
the disclosed device may be formed as a ring or in a cylinder 380,
as shown in FIG. 4B. When configured in this manner, the device may
be crimped around a tendon, a ligament, a muscle fiber, a blood
vessel, a nerve bundle, or any other part of the body which would
respond to local administration of a medicament. Similarly, such
cylinder 380 could also be placed within a tubular conduit within
the body and either expanded or sutured to affix its position.
[0061] If desired, different types of medicaments may be placed in
different core bodies having different shapes or different colors.
The use of different medicaments in different shaped or colored
core bodies will reduce confusion of medications by enabling
surgeons to distinguish between medicaments by the shape or color
of the device in which the medicament is contained.
[0062] In certain situations it may be necessary to orient the drug
delivery device in a particular position with regard to the
condition or disease being treated. In such situation, the drug
delivery device 410 may be attached to a support piece 432 as shown
in FIG. 5 to enable a desired orientation of the core body 412.
[0063] In still another embodiment of the drug delivery platform
510 as shown in FIGS. 6A and 6B, the core body 512, the upper
screen 524, and a lower plate 525 may be fabricated to form a
sharpened edge 534. While a thin planar embodiment as shown in
FIGS. 2A, 3, and 4A may be suitable for insertion into the vitreous
body of the eye, other applications may require penetration of soft
tissue. When the core body 512 is formed such that a portion of the
perimeter edge 536 of the core body 512 is formed to include a
sharpened edge 534, the core body 512 itself may be used to make an
initial incision or enlarge an incision through which the drug
delivery device 510 is placed. In this embodiment, the leading edge
of the upper screen 524 is that portion of the sharpened edge which
is used to make initial contact for creating an opening through
which the drug delivery platform may be inserted.
[0064] In yet another alternate embodiment 610, as shown in FIGS.
6C and 6D, the sharpened edge may be placed on the portion on the
edge of a solid piece 625 located under the basin 614.
[0065] While sufficient medicament can be placed within the basin
of the core body to treat the condition or disease for a minimal or
prolonged period of time, it may be necessary to actually replace
the medicament if the condition or disease is particularly
persistent. While the entire device may be replaced, it has been
found that when the device is used inside a patient for a prolonged
period of time, such as a year or more, the basin 714 within the
core body 712 may be refilled by the use of a passageway 738
running from the perimeter edge 736 of the core body 712 into the
basin 714 as shown in FIG. 7. Because of the small size of the core
body 712, it may not be possible to drill a passageway from the
perimeter edge 736 to the basin 714. In such cases, it may be
necessary to form the core body 712 from two mating pieces 712A,
712B, each mating piece including a partial channel. These two
partial channels come together either horizontally or vertically to
form a small hole 738 from the perimeter edge 736 to the basin 714
when the mating pieces 712A and 712B are placed one on top of the
other.
[0066] In still another embodiment 810, the end of the passageway
838 may be attached to a flange 840. The flange 840 facilitates
location of the opening for the refilling of the basin 814 with a
medicament by the use of a syringe (not shown). In addition, the
use of a flange 840 may prevent or reduce contamination. The flange
840 may be located on the side of the core body 812 or a short
distance away and connected by a small tube 842. The passage way
838 may be formed as a tortuous path as shown in FIG. 7A.
[0067] In complex situations, it may be necessary to place multiple
medicaments near the site of the condition or disease. In such
cases multiple basins may be formed within the core body 943, 945.
As shown in FIG. 8, the core body 912 includes at least a smaller
proximal basin 943 and a smaller distal basin 945. Because of the
different medications, it may be necessary to cover the proximal
943 and distal 945 basins with a screen, including a different
number and different size of holes over each of the proximal 943
and distal 945 smaller basins.
[0068] Still other embodiments of the disclosed drug delivery
platform appear in FIGS. 9 through 23, as described below.
[0069] In FIG. 9 is shown an embodiment of the drug delivery device
1010 which includes a proximal basin 1043, a middle basin 1045, and
a distal basin 1047. The proximal basin 1043 is separated from the
middle basin 1045 by use of a first partition 1041, and the middle
basin 1045 is separated from the distal basin 1047 by use of a
second partition 1049. If required, the transport or movement of
medicament between the various smaller basins may be facilitated by
passages 1048 formed in the partitions 1041, 1049. It is also to be
noted that the pattern of the holes in both the first screen 1024
on the upper face 1020 of the core body 1012 and the second screen
on the lower face 1024 of the core body 1012 is shaped for control
of the release of medicament. Specifically, a U-shaped pattern 1050
is included at the distal end 1015 and an arcuate pattern 1052 is
included at the proximal end 1013. This embodiment is particularly
useful when it is necessary to place three medicaments, M1, M2, and
M3 within the body of an animal. Alternatively, the partitions 1041
and 1049 may be solid or impermeable to keep the medicaments M1,
M2, and M3 separate.
[0070] FIG. 10 illustrates an embodiment 1110 for the dissipation
of two medicaments, M1 and M2 within the body. Accordingly, the
core body 1112 is divided into a proximal smaller basin 1143 and a
distal smaller basin 1147 using a solid or impermeable partition
1141 therebetween. Release of the medication M2 is controlled by a
U-shaped pattern of screen holes 1150 in both the upper screen 1124
and in the lower screen 1126 over the distal partition 1147. Over
the proximal basin 1143 is located a trapezoidal pattern of screen
holes 1154 for controlling the release of the medicament M1.
[0071] In FIG. 11, another two-compartmented implantable drug
delivery platform 1210 is shown. Note that there is a first pattern
of screen holes 1256 which covers the entire distal basin 1247 and
a second pattern of screen holes 1258 which covers the entire
proximal basin 1243 which hold medicaments M2 and M1
respectively.
[0072] In FIG. 12 is shown an embodiment 1310 with a single basin
1314 for holding a medicament M. The single basin 1314 is formed by
the joining together of the two core body pieces, 1312A and 1312B.
Each of the pieces 1312A, 1312B includes a full pattern of screen
holes 1360 to cover the basin 1314 formed between the two portions
1312A, 1312B of the core body.
[0073] In FIG. 13 is shown yet another embodiment 1410 including a
single basin 1414. In this embodiment 1410, the core body 1412
includes a lower screen 1426 covered by an upper screen 1424. Note
that the upper screen 1424 fully covers the core body 1412 and is
configured with a full pattern of screen holes 1460 to cover the
entire basin 1414.
[0074] In FIG. 14 is shown yet another single basin embodiment
1510. In this embodiment, the upper screen 1524 has a perimeter
1536 which fits inside the inside perimeter of the basin 1514
formed in the core body 1512.
[0075] In FIG. 15 is shown yet another embodiment 1610 with a
single well 1614. In this embodiment 1610, the upper screen 1634
includes a downwardly depending flange 1662 which is constructed
and arranged to be press fit within the perimeter of the basin 1614
formed within the core body 1612. Alternatively, as shown in FIG.
18, the flange may be placed on the core body 1612 to extend
upwardly to engage a recessed portion in a screen 1624.
[0076] In FIG. 16 is shown yet another embodiment 1710 having a
single basin 1714. The single basin 1714 is formed in a core body
1712 which further fits within a core body holder 1712C. The core
body holder 1712C includes an open portion 1712C.1 therein which
will securely hold the core body 1712. Covering the basin 1714
within the core body 1712 is an upper screen 1724. The bottom
portion of the core body 1712 is formed to be a screen.
[0077] In FIG. 17 is shown an embodiment 1810 similar to the
embodiment 1710 shown in FIG. 16. However, rather than the core
body holder 1812D having a contiguous perimeter, the core body
holder 1812D is formed to have two prongs forming an open space
1812D.1 therebetween. The open space 1812D.1 is constructed and
arranged to receive the core body 1812. A groove 1864 captures the
two prongs of core body holder 1812D. Once again, the core body
1812 is covered with a screen 1824 and the bottom of the core body
1812 is formed as a screen.
[0078] In FIG. 18 the disclosed embodiment 1910 includes a core
body 1912 which has an upwardly extending flange 1966 which fits
into the upper screen 1924 so that the upper screen 1924 may be
positioned on the core body 1912 over the basin 1914.
[0079] In FIG. 19 is shown an embodiment 2010 including a
substantially hollow core body 2012. Resting on the bottom face
2022 of the substantially hollow core body 2012 is a lower screen
2026, and on the top face 2020 of the core body is an upper screen
2026.
[0080] In FIG. 20 is shown an embodiment 2110 including a proximal
smaller basin 2143 and a distal smaller basin 2147. The partition
2141 dividing the proximal smaller basin 2143 from the distal
smaller basin 2147 has passages 2148 formed therein for the
movement of medicament therethrough. Release of the medicaments M1,
M2 is controlled by the arcuate pattern of holes 2152 formed in
both the upper screen 2124 and the lower screen 2126.
Alternatively, the partition 2141 may run along the long axis of
the basin 2114 to form side-by-side smaller basins.
[0081] In FIG. 21 is still yet another embodiment 2210 including a
proximal smaller basin 2243 and a distal smaller basin 2247. A
partition 2241 divides the proximal basin 2243 from the distal
basin 2247 in the core body 2212. Both the upper screen 2224 and
the lower screen 2226 contain a U-shaped pattern of holes 2250 at
the distal end 2215 and a full pattern of holes 2260 at the
proximal end 2213.
[0082] In FIG. 22 is shown an oblong thickened embodiment 2310
which includes circular screens 2324, 2326 to be placed on the
upper face 2320 and lower face 2322 of the core body 2312.
EXAMPLES
[0083] Devices similar to those depicted in FIG. 15 were implanted
into eight New Zealand White rabbits. The screen was attached to
the core body using a silicone adhesive. The contralateral eye was
used as a control. One rabbit was taken out of the study at two
days. Three animals were tested at one month, and the remaining
four rabbits were tested at three months. Hiso-pathological
observations were conducted at both one month and three months. At
one month, three of the animals exhibited a small number of
inflammatory cells in the vitreous. One animal of these three also
exhibited minimal inflammation in ora serrata. The final animal had
minimally swollen lens fibers. Toxicology observations for this
group were unremarkable. Toxicology observations for all of the
animals in the three-month sampling were unremarkable.
[0084] In an in vitro study, betaxolol HCl, a relatively high water
soluble substance, was tableted with 10% microcrystalline cellulose
and 0.40% magnesium stearate with a total weight of 22 mg. The
betaxolol HCl tablet was inserted into the basin of a drug delivery
devices similar to the embodiment depicted in FIG. 15. The devices
utilized one 8 micron 1% porosity screen on one side of the basin.
The ratio of the area of all holes to the area of the screen was
about 0.18%. The ratio of the area of all holes to the area of all
surfaces on the drug delivery device was about 0.02%. Loaded drug
delivery devices according to the present invention were placed in
a 4 mL HPLC vial with phosphate/saline buffer and then stirred
using a small stir bar. The vials were periodically sampled and
analyzed for drug concentration by HPLC. As shown in FIG. 24 a plot
of drug concentrates over time demonstrates the release
profiles.
[0085] In a second in vitro study, another second drug formulation
using a substance with a relatively low water solubility, nepafenac
in tablet form, was also studied in a device similar to the
embodiment depicted in FIG. 15. These tablets also contained 10%
microcrystalline cellulose and 0.40% magnesium stearate. One tablet
was placed in a two-sided 14 micron 25% porosity device. The ratio
of the area of all holes to the area of the screen was about 45%.
The ratio of the area of all holes to the area of all surfaces on
the drug delivery device was about 0.48%. A second tablet was
placed in a two-sided 14 micron 1% device. The ratio of the area of
all holes to the area of the screen was about 0.18%. The ratio of
the area of all holes to the area of all surfaces on the drug
deliver device was about 0.02%. The drug release studies were
performed as described above. As shown in FIG. 25, plot "A" shows
the release profile from the two-sided 14 micron 25% porosity
device. Plot "B" is the release profile from the two-sided 14
micron 1% porosity device. A third experiment was performed by
replacing the phosphate/saline buffer from the two-sided 14 micron
1% porosity device and reinitiating the experiment. This experiment
is demonstrated by plot "C."
Operation
[0086] Once a medical condition or disease within the body is
identified and located, a physician will determine whether or not
such condition or medication may be treated with a medicament
placed in close proximity to site of the condition or disease. If
the decision is made to treat the condition or disease with a
medicament placed close to the condition or disease, it then
becomes necessary to actually place the medicament near the
condition or disease. In other applications, it may be necessary to
treat a condition or disease from a short distance. Such short
distance treatment may require sustained levels of medicament flow
from the drug delivery device.
[0087] In the embodiment 10 shown in FIG. 1, the condition or
disease is contained within the eye of a patient. For example, a
surgeon may insert an implantable device into the vitreous chamber
of a patient by making a small incision in the sclera. The drug
delivery platform 10 is then inserted through the incision and held
in place by threading a suture through the suture hole 30 in the
core body 12 and attaching the other portion of the suture to the
eye. The orientation of the platform is such that the implanted
platform remains out of the path of light rays from the lens to the
retina.
[0088] To prevent coating of the implanted devices with cells which
can block the movement of medicament from the basin through the
holes in the screen, an anti-proliferative coating may be used on
both the screen and core body. Similarly, materials such as silicon
may form chips so as to prevent chipping the screen, and the core
body may be coated with a substance to prevent chipping.
[0089] As previously mentioned, while the preferred embodiment is
shown for the purpose of inserting medicament to treat a condition
or disease within the inner eye, those of ordinary skill in the art
will understand that the disclosed implantable drug delivery
platform 10 may be used at any location within the body of an
animal where a condition or disease is best treated with an
implanted medicament.
[0090] The present invention, having now been disclosed according
to its preferred and alternate embodiments, will now be understood
by those of ordinary skill in the art. Those of ordinary skill in
the art will understand that numerous other embodiments of the
present invention may also be embodied by the foregoing disclosure.
Such other embodiments shall be included within the scope and
meaning of the appended claims.
* * * * *