U.S. patent application number 13/500884 was filed with the patent office on 2014-08-21 for manufacturing method for shape memory polymer intraocular devices.
This patent application is currently assigned to THE REGENTS OF THE UNIVERSITY OF COLORADO. The applicant listed for this patent is Malik Y. Kahook, Naresh Mandava, Bryan Rech, Robin Shandas. Invention is credited to Malik Y. Kahook, Naresh Mandava, Bryan Rech, Robin Shandas.
Application Number | 20140232025 13/500884 |
Document ID | / |
Family ID | 46798785 |
Filed Date | 2014-08-21 |
United States Patent
Application |
20140232025 |
Kind Code |
A1 |
Kahook; Malik Y. ; et
al. |
August 21, 2014 |
MANUFACTURING METHOD FOR SHAPE MEMORY POLYMER INTRAOCULAR
DEVICES
Abstract
A shape memory polymer (SMP) intraocular lens may have a
refractive index above 1.45, a Tg between 10.degree. C. and
60.degree. C., inclusive, de minimis or an absence of glistening,
and substantially 100% transmissivity of light in the visible
spectrum. The intraocular lens is then rolled at a temperature
above Tg of the SMP material. The intraocular device is radially
compressed within a die to a diameter of less than or equal to 1.8
mm while maintaining the temperature above Tg. The compressed
intraocular lens device may be inserted through an incision less
than 2 mm wide in a cornea or sclera or other anatomical structure.
The lens can be inserted into the capsular bag, the ciliary sulcus,
or other cavity through the incision. The SMP can substantially
achieve refractive index values of greater than or equal to
1.45.
Inventors: |
Kahook; Malik Y.; (Denver,
CO) ; Mandava; Naresh; (Denver, CO) ; Shandas;
Robin; (Boulder, CO) ; Rech; Bryan; (Boulder,
CO) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Kahook; Malik Y.
Mandava; Naresh
Shandas; Robin
Rech; Bryan |
Denver
Denver
Boulder
Boulder |
CO
CO
CO
CO |
US
US
US
US |
|
|
Assignee: |
THE REGENTS OF THE UNIVERSITY OF
COLORADO
Denver
CO
|
Family ID: |
46798785 |
Appl. No.: |
13/500884 |
Filed: |
March 7, 2012 |
PCT Filed: |
March 7, 2012 |
PCT NO: |
PCT/US12/28150 |
371 Date: |
April 6, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61449865 |
Mar 7, 2011 |
|
|
|
61474696 |
Apr 12, 2011 |
|
|
|
Current U.S.
Class: |
264/1.1 |
Current CPC
Class: |
C08F 220/302 20200201;
B29L 2011/0016 20130101; C08F 220/1804 20200201; C08F 220/1804
20200201; A61F 2210/0023 20130101; A61L 2430/16 20130101; A61L
2400/16 20130101; A61F 2210/0014 20130101; B29C 61/003 20130101;
A61L 27/16 20130101; A61F 2/142 20130101; C08F 220/1804 20200201;
C08F 222/1063 20200201; C08F 222/1063 20200201; A61L 27/16
20130101; C08F 222/1063 20200201; A61L 27/50 20130101; C08F
220/1804 20200201; A61F 2/14 20130101; C08F 220/302 20200201; B29C
69/025 20130101; A61F 2/16 20130101; A61L 27/16 20130101; C08F
222/1063 20200201; C08L 33/08 20130101; C08F 222/1063 20200201;
C08L 33/10 20130101; C08F 226/02 20130101; C08F 222/1063 20200201;
C08F 226/02 20130101; A61F 2210/0019 20130101; B29D 11/023
20130101; B29C 61/06 20130101; A61F 2002/16905 20150401 |
Class at
Publication: |
264/1.1 |
International
Class: |
B29D 11/02 20060101
B29D011/02 |
Claims
1. A method of manufacturing an intraocular device comprising
providing a shape memory polymer (SMP) material with a Tg; forming
the SMP material in a permanent intraocular device form;
mechanically compressing the intraocular device at a temperature
above Tg to deform the intraocular device into a smaller volume;
and cooling the deformed intraocular device while still in
compression to a temperature below Tg to thereby create a stable
deformed intraocular device with a delivery profile allowing for
insertion through an incision of 2 mm or less.
2. The method of claim 1, wherein the forming operation further
comprises cast molding the SMP material into the permanent
intraocular device form.
3. The method of claim 2 further comprising oversizing a mold by
0.1-20% of a desired final size of the permanent intraocular device
form to account for volume shrinkage that may occur during a
polymerization process of the SMP material in the cast molding
operation.
4. The method of claim 1 wherein the forming operation further
comprises liquid injection molding the SMP material into the
permanent intraocular device form.
5. The method of claim 4 further comprising utilizing ultra-high
pressures during the liquid injection molding operation to minimize
volume shrinkage during polymerization.
6. The method of claim 1, wherein the forming operation further
comprises cryolathing the SMP material into the permanent
intraocular device form.
7. The method of claim 1, wherein the delivery profile of the
deformed intraocular device is configured to fit within an incision
less than or equal to 1.8 mm wide.
8. The method of claim 1 further comprising rolling the intraocular
device at a temperature above Tg of the SMP material; cooling the
rolled intraocular device while still in a rolled form to a
temperature below Tg to thereby create a stable rolled intraocular
device; and mechanically compressing the intraocular device to a
diameter of less than or equal to 1.8 mm.
9. The method of claim 1 further comprising rolling the intraocular
device at a temperature above Tg of the SMP material; and radially
compressing the intraocular device within a die to a diameter of
less than or equal to 1.8 mm while maintaining the temperature
above Tg.
10. The method of claim 1 further comprising packaging the deformed
intraocular device for storage at or above room temperature.
11. The method of claim 1, wherein the intraocular device is an
intraocular lens.
12. The method of claim 1, wherein the intraocular device is an
intracorneal implant.
13. The method of claim 1, wherein the SMP material comprises a
tert-butyl acrylate (tBA) monomer and a bisphenol A propoxylate
diacrylate (BPA-P) diacrylate cross-inking polymer.
14. The method of claim 1, wherein the SMP material comprises a
tert-butyl acrylate (tBA) monomer and a poly(ethylene glycol)
dimethacrylate cross-inking polymer with a molecular weight
substantially between 500 and 2000, inclusive, and with a
crosslinking percentage substantially between 10 wt % to 50 wt %,
inclusive.
15. The method of claim 1, wherein the SMP material comprises a
tert-butyl acrylate (tBA) monomer and poly(ethylene glycol)
diacrylate crosslinking polymer with a molecular weight
substantially between 500 and 2000, inclusive, and with a
crosslinking percentage substantially between 10 wt % to 50 wt %,
inclusive.
16. The method of claim 1, wherein the SMP material comprises a
tert-butyl acrylate monomer, an isobutyl acrylate monomer, a butyl
acrylate monomer, and a poly(ethylene glycol) dimethacrylate and/or
a poly(ethylene glycol) diacrylate cross-linking monomer with a
molecular weight substantially between 500 and 2000, inclusive.
17. The method of claim 16, wherein the Tg of the SMP material is
between 10 C and 60 C.
18. The method of claim 1, wherein the Tg of the SMP material is
greater than or equal to human body temperature.
19. The method of claim 1, wherein the intraocular device once
implanted and reformed exhibits greater than 98 percent shape
recovery from the deformed intraocular device to upon reaction to
an external stimulus.
20. The method of claim 19 wherein the external stimulus is heat
above Tg.
21. The method of claim 20, wherein Tg is substantially equal to
37.degree. C.
22. The method of claim 19, wherein the external stimulus is
ultraviolet radiation.
23. The method of claim 19, wherein the reaction to the external
stimulus is delayed for up to 600 seconds.
24. The method of claim 19, wherein the reaction initiates within 3
to 25 seconds.
25. The method of claim 1, wherein the SMP material comprises a
color additive.
26. (canceled)
27. (canceled)
28. (canceled)
29. (canceled)
30. (canceled)
31. (canceled)
32. (canceled)
33. (canceled)
34. (canceled)
35. (canceled)
36. (canceled)
37. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority pursuant to
35 U.S.C. .sctn.119(e) of U.S. provisional application No.
61/449,865 filed 7 Mar. 2011 entitled "Shape memory polymer
intraocular lenses" and U.S. provisional application No. 61/474,696
filed 12 Apr. 2011 entitled "Shape memory polymer intraocular
lenses," which are hereby incorporated herein by reference in their
entirety.
TECHNICAL FIELD
[0002] The technology described herein relates to artificial
intraocular lenses.
BACKGROUND
[0003] The human eye functions to provide vision by transmitting
light through a clear outer portion called the cornea, and focusing
the image by way of a crystalline lens onto a retina. The quality
of the focused image depends on many factors including the size and
shape of the eye, and the transparency of the cornea and the
lens.
[0004] When age or disease causes the lens to become less
transparent, vision deteriorates because of the diminished light
which can be transmitted to the retina. This deficiency in the lens
of the eye is medically known as a cataract. An accepted treatment
for this condition is surgical removal of the lens and replacement
of the lens function by an artificial intraocular lens (IOL).
[0005] Intraocular lenses are employed as replacements for the
crystalline lens after either extracapsular or intracapsular
surgery for the removal of a cataract. In the United States, the
majority of cataractous lenses are removed by a surgical technique
called phacoemulsification. During this procedure, an opening is
made in the anterior capsule and a thin phacoemulsification cutting
tip is inserted into the diseased lens and vibrated ultrasonically.
The vibrating cutting tip liquefies or emulsifies the lens so that
the lens may be aspirated out of the eye. The diseased lens, once
removed, is replaced by an artificial lens.
[0006] Intraocular lenses are generally of two types, those that
are placed in the anterior chamber, i.e., between the iris and the
cornea, and those that are placed in the posterior chamber, i.e.,
behind the iris. Both types of lenses are conventionally employed
with the choice between an anterior chamber and a posterior chamber
lens being partly dictated by requirements of the patient and
partly dictated by the preferences of the physician inserting the
lens. A third type of lens, known as iris-fixated lenses because
they are secured to the iris periphery, can be thought of as being
within one of the two types above, in that their optic portion is
in either the anterior or posterior chamber.
[0007] Intraocular lenses normally consist of an optic with at
least one and preferably two or more haptics that extend generally
radially from the optic and contain distal portions that normally
seat in the scleral spur for an anterior chamber lens and either in
the ciliary sulcus or within the lens capsule for a posterior
chamber lens. The optic normally comprises a circular transparent
optical lens. The haptic in most lenses is a flexible fiber or
filament having a proximate end affixed to the lens and having a
distal end extending radially away from the periphery of the lens
to form a seating foot. Several haptic designs are currently in
use, for example, a pair of C-shaped loops in which both ends of
each loop are connected to the lens, and, for example, J-shaped
loops in which only one end of the loop is affixed to the lens.
[0008] Haptics are usually radially resilient and extend outwardly
from the periphery of the lens and gently, but elastically, engage
appropriate circumferential eye structures adjacent the iris or
within the capsular bag. This resiliency is due to the conventional
elastic properties of the materials of the haptic. The result is a
haptic which when compressed and released will uncontrollably
spring back immediately. This property makes the process of
implantation and final positioning of the lens difficult since the
haptics must be constrained during implantation. Also, once
situated, the flexibility of the conventional haptic material makes
the lens susceptible to decentration from being pushed by vitreous
pressure from behind the lens or shifting due to pressure from
adjacent ocular tissue. Also, the forces generated by the elastic
recoil of the haptic release may damage the delicate local
tissue.
[0009] The optimum position for a posterior chamber lens is in the
capsular bag. This is an extremely difficult maneuver for the
surgeon to accomplish. When a posterior chamber lens is employed it
must be placed through the small pupillary opening, and the final
haptic position is hidden behind the iris and not visible to the
surgeon. It is therefore highly desirable to keep the overall
dimensions of the posterior chamber lens as small as possible
during implantation, letting it expand when it is finally situated
where the surgeon intends, usually in the capsular bag. A small
device is easier to manipulate in the eye, reduces the chance of
the haptics coming in contact with the corneal endothelial tissue,
and allows the surgeon ease of insertion, as he must often insert a
lens with a 14 mm overall dimension through a pupil of 5 to 8 mm
diameter. A smaller lens also reduces the lens/iris contact and can
better guarantee that the intraocular lens and its haptics will be
in the capsular bag.
[0010] In recent years intraocular lenses with and without haptics
having relatively soft body portions have been provided such that
the body portion could be folded generally across the diameter
thereof for insertion into a smaller opening during implantation of
the lens. Lenses formed of liquid or hydrogel constrained within a
sheath have been designed which allow the lens body to be folded
before insertion and then subsequently filled when in position.
Unfortunately, the soft materials used for the bodies of these
lenses lack the restorative strength sometimes required to return
to their original shape.
[0011] Further, these lens types are typically deployed using
either an elastic release mechanism, wherein mechanical energy
stored by bending the elastic material is released when the
mechanical constraint is removed, or through water uptake, also
known as hydration, wherein the lens gradually absorbs water
through an osmotic diffusion process. Both processes are difficult
to control. In the former case, the elastic recoil may damage local
tissue or may move the lens away from the center. In the latter
case, the ultimate shape of the lens may become distorted if the
expanding lens comes into contact with surrounding tissue. Further,
hydrating materials are known to possess poor shape recovery
properties.
[0012] In the natural lens, bifocality of distance and near vision
is provided by a mechanism known as accommodation. The natural
lens, early in life, is soft and contained within the capsular bag.
The bag is suspended from the ciliary muscle by the zonules.
Relaxation of the ciliary muscle tightens the zonules, and
stretches the capsular bag. As a result, the natural lens tends to
flatten. Tightening of the ciliary muscle relaxes the tension on
the zonules, allowing the capsular bag and the natural lens to
assume a more rounded shape. In this way, the natural lens can be
focused alternatively on near and far objects. As the lens ages, it
also becomes harder and is less able to change shape in reaction to
the tightening of the ciliary muscle. This makes it harder for the
lens to focus on near objects--a medical condition known as
presbyopia. Presbyopia affects nearly all adults over the age of 45
or 50.
[0013] Typically, when a cataract or other disease requires the
removal of the natural lens and replacement with an artificial IOL,
the IOL is a monofocal lens, requiring that the patient use a pair
of spectacles or contact lenses for near vision. Some bifocal IOLs
have been created, but are not been widely accepted. Some IOL
designs are single optic lenses having flexible haptics that allow
the optic to move forward and backward in reaction to movement of
the ciliary muscle. However, the amount of movement of the optic in
these single-lens systems may be insufficient to allow for a useful
range of accommodation. In addition, the eye must be medicated for
one to two weeks to decrease eye movement in order for capsular
fibrosis to entrap the lens that thereby provide for a rigid
association between the lens and the capsular bag. Further, the
commercial models of these lenses are made from a hydrogel or
silicone material. Such materials are not resistive to the
formation of posterior capsule opacification ("PCO"). The treatment
for PCO is a capsulotomy using a Nd: YAG laser that vaporizes a
portion of the posterior capsule. Such destruction of the posterior
capsule may destroy the mechanism of accommodation of these
lenses.
[0014] Known accommodative lenses also lack extended depth of focus
in addition to having poor accommodation performance. Such known
lenses further require precise lens sizing for proper function over
a range of capsular bag sizes and lack long-term capsular fixation
and stability. Further, as current lens replacement surgeries move
towards smaller incision size, IOLs in general require the ability
to be delivered through such small incisions.
[0015] Dual-optic lenses leverage the ability of the ciliary
body-zonule complex to change the shape of the capsular bag. This
allows the inter-lens distance to change, thereby allowing a change
in refractive error. These dual-optic lenses can be large secondary
to the optical hardware needed to create this optical system and
requires larger corneal incisions to insert into the eye.
[0016] Intracorneal lenses are designed to treat refractive error
or presbyopia. Intracorneal lenses include corneal implants and
lenses, which are inserted through a small incision in the cornea
created by a blade or a laser. The pocket formed by the incision in
the cornea is used to position the implant to change the shape of
the cornea. In the case of a lens implant, the pocket is used to
position the refractive lens in the optically effective location.
Some lenses create a pinhole-type effect to treat presbyopia. As
current intraocorneal lenses move towards smaller incision size,
devices in general require the ability to be delivered through such
small incisions. Laser technology such as the femtosecond laser has
enhanced the ability to create these smaller corneal wounds and
pockets for implantation.
[0017] Phakic intraocular lenses are implanted either in the
anterior chamber supported by the angle structures or in the
posterior sulcus immediately posterior to the iris and anterior to
the native lens. The lens is implanted through a minimally invasive
wound at the limbus and inserted into or through the anterior
chamber. The lenses are used to treat refractive error and have the
risk of causing trauma to the lens and/or angle structures. Smaller
incisions require folding the lens and then lens deployment in the
eye, which increases the risk of damage to intraocular
structures.
[0018] The information included in this Background section of the
specification, including any references cited herein and any
description or discussion thereof, is included for technical
reference purposes only and is not to be regarded subject matter by
which the scope of the invention as defined in the claims is to be
bound.
SUMMARY
[0019] Shape-memory polymers (SMP) are a class of smart materials
that can be tailored to have significant mechanical property
changes in response to a given stimulus. The ability to recover
from large deformations and adapt to differing environmental
conditions greatly facilitates use of SMP devices in minimally
invasive surgery. Current shape memory polymer formulations can be
created to have independently programmed modulus and glass
transition temperatures (Tg). The ability to precisely control
mechanical properties of SMP along with the transparent nature of
the material, a refractive index in ranges very similar to the
range of a human lens (1.386-1.406 and greater), and proven
biocompatibility allows for the creation of unique solutions for
treatment of various ophthalmic diseases. Therefore, there are many
aspects of a hydrophobic, acrylate-based, SMP intraocular lens
which are appealing in view of other lens options.
[0020] One clear advantage of the SMP systems disclosed herein is
the dramatic capability to vary mechanical properties by changing
material properties such as cross-linked weight percentage,
fractions of each component co-monomer, and other ingredient
properties. This provides the capability to design the required
mechanical properties for the specific application into the
material. For example, varying Tg for particular SMP formulations
affects resultant rubbery modulus. Additional property changes can
be incorporated, for example, by varying the weight percentage of
the co-monomers forming the SMP. The SMP material qualities may
also be leveraged to change the radius of curvature of the anterior
and posterior surfaces of particular IOL designs with heat, UV
light, or other processes to change the central and/or paracentral
power of the particular lens.
[0021] A variety of intraocular lenses may be formed of a shape
memory polymer with high degrees of "shape certainty" or
"shape-fixity" (i.e., the accuracy of the recovered shape after
transition from the deformed shape back to the permanent shape).
The lenses are deformed and compressed into a compact preoperative
shape that allows for implantation through a small incision, gently
unfurl and expand into guaranteed post-operative shapes (permanent
shapes), and provide an integrated haptic for a stable and
nontraumatic apposition to ciliary sulcus, capsular bag, or
anterior chamber angle structures. The SMP lenses may be deformed
and compressed to sizes smaller than currently known and available
for implantation through an incision size under 2 mm, which is
currently the lower limit.
[0022] In one exemplary implementation, a method of manufacturing
an intraocular device includes providing a shape memory polymer
(SMP) material with a Tg, forming the SMP material in a permanent
intraocular device form, mechanically compressing the intraocular
device at a temperature above Tg to deform the intraocular device
into a smaller volume; and cooling the deformed intraocular device
while still in compression to a temperature below Tg to thereby
create a stable deformed intraocular device with a delivery profile
allowing for insertion through an incision of 2 mm or less. In one
embodiment, the intraocular device may be rolled at a temperature
above Tg of the SMP material. The rolled intraocular device may
then be cooled while still in a rolled form to a temperature below
Tg to thereby create a stable rolled intraocular device. The
intraocular device may then be mechanically compressed to a
diameter of less than 1.8 mm. In another embodiment, the
intraocular device may be rolled at a temperature above Tg of the
SMP material. The intraocular device may then be radially
compressed within a die to a diameter of less than 1.8 mm while
maintaining the temperature above Tg.
[0023] In another exemplary implementation, a shape memory polymer
(SMP) intraocular lens may have a refractive index above 1.45, a Tg
between 15.degree. C. and 40.degree. C., inclusive, de minimis or
an absence of glistening, and substantially 100% transmissivity of
light in the visible spectrum. In one embodiment, the SMP
intraocular lens may be formed of a combination of 50 weight
percent tBA, 28 weight percent isobutyl acrylate, and 22 weight
percent PEGDMA 1000. In another embodiment, the SMP intraocular
lens may be formed of a combination of 22 weight percent tBA and 78
weight percent PEGDMA 1000. In a further embodiment, the SMP
intraocular lens may be formed of a combination of 65 weight
percent tBA, 13 weight percent butyl acrylate, and 22 weight
percent PEGDMA 1000.
[0024] In a further exemplary implementation, a method of
implanting an intraocular lens device includes making an incision
in a cornea or sclera less than 2 mm wide. In one embodiment, an
intraocular lens is into the capsular bag through the incision. In
another embodiment, an intraocular lens is inserted into the
ciliary sulcus through the incision. In another embodiment, a
method of implanting an intraocular lens device includes making an
incision into a cornea less than 2 mm wide to access the anterior
chamber. An intraocular lens is then inserted into the anterior
chamber through the incision. In a further embodiment, a method of
implanting an intracorneal implant device includes making an
incision into a cornea less than 2 mm wide to create a tunnel in
the cornea. An intracorneal implant device is then inserted into
the anterior chamber through the incision.
[0025] This Summary is provided to introduce a selection of
concepts in a simplified form that are further described below in
the Detailed Description. This Summary is not intended to identify
key features or essential features of the claimed subject matter,
nor is it intended to be used to limit the scope of the claimed
subject matter. A more extensive presentation of features, details,
utilities, and advantages of the present invention as defined in
the claims is provided in the following written description of
various embodiments of the invention and illustrated in the
accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] FIG. 1 is a graph depicting the storage modulus vs.
temperature attributes for several exemplary SMP formulations.
[0027] FIG. 2 is a graph depicting the UV blocking properties and
optical clarity of the exemplary SMP formulations of FIG. 9 as a
percentage of transmission over a range of wavelengths in the UV
and visible spectrum.
[0028] FIG. 3 is a graph depicting the storage modulus vs.
temperature attributes for several exemplary SMP formulations.
[0029] FIG. 4 is a graph depicting the UV blocking properties and
optical clarity of the exemplary SMP formulations of FIG. 11 as a
percentage of transmission over a range of wavelengths in the UV
and visible spectrum.
[0030] FIG. 5 is a graph depicting the compression properties of
the exemplary SMP formulations of FIG. 11.
[0031] FIG. 6 is a graph depicting the tensile properties of an
exemplary SMP formulation at two different rates of strain.
[0032] FIG. 7 is an optical profilometry image of a sample SMP IOL
lens surface showing average surface roughness.
[0033] FIG. 8A is an isometric view of an exemplary shape memory
polymer (SMP) intraocular lens (IOL) with placement haptics in a
permanent or deployed configuration.
[0034] FIG. 8B is a top plan view of the SMP IOL of FIG. 1A.
[0035] FIG. 8C is a front elevation view of the SMP IOL of FIG.
1A
[0036] FIG. 8D is a side elevation view of the SMP IOL of FIG.
1A.
[0037] FIG. 9A is a top plan view of an exemplary SMP IOL placed on
a rolling die with a channel for rolling the SMP IOL.
[0038] FIG. 9B is a front elevation view of the rolling die of FIG.
2A with the SMP IOL folded into the channel under compression by a
wire running axially down the channel.
[0039] FIG. 10A is a schematic front elevation view of the rolling
die of FIG. 2A with the edges of the SMP IOL folded over and the
rolling die cooled below Tg.
[0040] FIG. 10B is a schematic elevation view of the SMP IOL
removed from the rolling die and maintaining a deformed, rolled
configuration.
[0041] FIG. 11 is a schematic diagram of the rolled SMP IOL placed
in a fabric sock.
[0042] FIG. 12A is a top plan view, in cross section of the SMP IOL
within the fabric sock being pulled through a tube of decreasing
diameter formed in a compression die heated above Tg.
[0043] FIG. 12B is a is a top plan view, in cross section of the
SMP IOL within the fabric sock compressed within the smallest
diameter section of the tube while the compression die is cooled
below Tg.
[0044] FIG. 13 is a schematic elevation view of the SMP IOL removed
from the compression die and sock maintaining a deformed, rolled,
extended, and radially compressed configuration.
[0045] FIG. 14A is a schematic top plan view of a folding and
compression tool used to fold a SMP IOL in conjunction with a
temperature-regulated compression system.
[0046] FIG. 14B is a schematic side elevation view in cross section
of the tool of FIG. 7A used in conjunction with a
temperature-regulated compression tool.
[0047] FIG. 14C is a schematic side elevation view in cross section
of the folding and compression tool in a compressed position with
the temperature-regulated compression tool.
DETAILED DESCRIPTION
[0048] Known acrylic lens materials are unable to be compressed
significantly to achieve desired functionality. While various
methodologies are known to fold or roll acrylic IOLs, these merely
address the need to reduce the form factor of a deployed shape for
the purposes of minimizing the required incision size for
implantation. The actual volume displaced by these lenses remains
constant so there is a limit on the minimum size that such IOLs can
reach. Further, the ability to fold or roll these IOLs is limited
by the ability of the material to resist strain caused by the
stress of folding and return to a desired shape and provide the
necessary optical qualities after implantation. Further, there is
little control over the speed and force with which deployment of a
lens occurs once it is implanted, which often causes trauma to
tissues which engage haptics of the IOL.
[0049] In contrast, the SMP IOLs disclosed herein are actually more
deformable (in some cases greater than 65% compression and greater
than 250% tensile strain) and thus the volume displaced by such
devices can actually be reduced for implantation. This allows for
implantation through reduced incision sizes (sub 2 mm and even sub
1.8 mm) and thus reduced trauma to the human eye. Several other
benefits are also achievable by using SMP IOLs. It is notable that
the refractive index of many of the formulations
(n.sub.0.apprxeq.1.464) is relatively high (higher than the
refractive index of human lens tissue) and thus allows for the
possibility of reducing the thickness of the lens and therefore of
the size of the delivery profile. The refractive index of SMP IOLs
can further be modified by formulation of the SMP material. The
formulations of the SMP materials can also be adjusted to slow or
time delay the shape recovery process in order to reduce trauma to
tissue in the implant location and to allow the surgeon adequate
time for manipulation and placement of the IOL in the proper
location. With some SMP formulations, post implant modification is
possible, e.g., to change the curvature of the optic or the index
of refraction. This may be realized through application of
non-intrusive heating of the SMP IOL, or portions thereof,
post-implant via laser or ultrasound. Such heating may be applied
to particular sections of the SMP IOL which have different
cross-link weight percentages of material (and thus different Tg in
those areas) to allow activation of a secondary or tertiary shape
change, which may be used to effect changes to the refractive
index, the curvature of the optic, or the expansion of the haptics.
For example, the configuration of the haptic-optic junction may be
changed to modify the vault of the optic by heating the junction.
Such secondary or tertiary shape changes may also be used to
promote interaction with the lens capsule, vitreous, zonules and
surrounding tissues to help in accommodation. In addition, the
baseline positioning of the two optics in a dual optic
accommodative intraocular lens system can be changed even after
implantation.
[0050] Further, some SMP IOL formulations may be impregnated with
various drugs that may be eluted from the SMP IOL once implanted in
vivo to assist with the healing process of the optical tissue
traumatized during implantation or to deliver therapeutic
medications to treat other ocular diseases. The medication or
active ingredient (e.g., a biologic agent) may be integrated into
the SMP IOL as part of the polymerization process, within a
swelling agent (e.g., as a chemical or physical hydrogel polymer
structure), or as a biodegradeable, drug-eluting polymer portion of
the final SMP IOL device. Exemplary drugs that may be impregnated
in the SMP IOL may include antibiotics, anti-inflammatories,
anti-histamines, anti-allergy, biologic agents (e.g., anti-VEGF
agents, siRNAs, etc), and glaucoma medications (i.e., medications
to decrease eye pressure, which include, but are not limited to,
prostaglandins, parasympathetic/sympathetic-based medications,
alpha agonists, beta blockers, carbonic anhydrase inhibitors, Rho
Kinase inhibitors, adenosine agonists, endothelin agonists and
antagonists, etc). Other agents that may be linked to an SMP IOL
include viral vectors and cell-based therapeutics.
[0051] Shape Memory Polymer Materials
[0052] SMP materials have significant capacity to change shape or
otherwise activate with a mechanical force in response to an
external stimulus. The stimulus may be light, heat, chemical, or
other types of energy or stimuli. The thermomechanical response of
SMP materials may be controlled through formulation to predict and
optimize shape-memory properties. Shape memory polymer devices may
be designed and optimized to a high degree of tailorability that
are capable of adapting and responding to particular biomedical
applications and patient physiology.
[0053] A polymer may be considered a SMP if the original shape of
the polymer can be deformed and remain stable in the deformed state
until acted upon by an external stimulus, and then the original
shape can be recovered by exposing the material to the appropriate
stimulus. In one implementation, the stimulus may be heat. The
original shape may be set by molding, extruding, stamping, or other
typical polymer processing process. In addition, a disc, rod, or
other configuration of the material may be formed by the above
processes and then shaped into a final shape with cryolathing,
which is a process involving freezing of the material followed by
laser and/or mechanical cutting of the material into a final shape.
The temporary shape may be set by thermo-mechanical deformation.
Heating the deformed SMP material above a shape deformation
recovery temperature results in recovery of the original shape,
even if the original molded shape of the polymer is altered
mechanically at a lower temperature than the deformation recovery
temperature. SMP materials disclosed for use in the applications
herein have the ability to recover large deformation upon heating
and in appropriate formulations with greater than 99% accuracy of
the original shape.
[0054] In one implementation using heat stimulus, a polymer
transition temperature may be tailored to provide for a deformation
recovery temperature, at body temperature, about 37.degree. C.;
i.e., the glass transition temperature, Tg, of the polymer is
designed to be about 37.degree. C. The distinct advantage of this
approach is the utilization of the thermal energy of the human body
to naturally activate the SMP material. For some applications, the
mechanical properties (e.g., stiffness) of the material are
strongly dependent on Tg. Thus, it may be difficult to design an
extremely stiff device when Tg is close to the body temperature due
to the compliant nature of the polymer. Another consideration in
medical applications is that the required storage temperature of a
shape memory polymer with Tg about 37.degree. C. will typically be
below room temperature requiring "cold" storage before deployment.
In higher temperature transportation or storage environments, the
folded shape may be retained through the use of a constraining
device which does not allow the device to deploy into its initially
molded shape.
[0055] In an alternative implementation, the recovery temperature
is higher than the body temperature, i.e., Tg>37.degree. C. The
advantage of this implementation is that the storage temperature
can be equal to room temperature facilitating easy storage of the
device and avoiding unwanted deployments before use. the folded
shape may be retained through the use of a constraining device
which does not allow the device to deploy into its initially molded
shape. However, local heating of the material upon deployment may
be needed to induce recovery of the SMP material. Local damage to
some tissues in the human body may occur at temperatures
approximately 5 degrees above the body temperature through a
variety of mechanisms including apoptosis and protein denaturing.
Local heating bursts may be used to minimize exposure to elevated
temperatures and circumvent tissue damage. The use of one method
over the other is a design decision that depends on the targeted
body system and other device design constraints such as required
in-vivo mechanical properties.
[0056] A SMP material or network may include dissolving materials
which may include part of the network or may be included in the
formulation of the network before the network is polymerized (e.g.,
as an aggregate, mixed into the formulation). Dissolving materials
may include materials that disperse over time, even if the material
or part of the material does not actually dissolve or enter into a
solution with a solvent. In other words, a dissolving material as
used herein may be any material that may be broken down by an
anticipated external environment of the polymer. In one embodiment,
a dissolving material is a drug which elutes out of a SMP network.
A dissolving material may be attached by chemical or physical bonds
to the polymer network and may become disassociated with the
polymer network over time.
[0057] Dissolving materials, through their dissolution over time,
may be used for many purposes. For example, the dissolution of a
material may affect a dissolution or break-up of a biomedical
device over time. Alternatively, the dissolution of a material may
elute a drug, achieving a pharmacological purpose. Medications or
drugs can be infused into SMP devices to aid in healing (e.g.,
anti-inflammatory), avoid complications (e.g., anti-thrombotic), or
to combat potential infection (e.g., antibiotic). Medications may
be added by injection into the liquid polymer before curing.
Medications may also be added to SMP devices post-polymerization
using various surface modification or coating techniques, for
example, plasma deposition.
[0058] In certain embodiments, the SMP polymer segments can be
natural or synthetic, although synthetic polymers are preferred.
The polymer segments may be non-biodegradable. Non-biodegradable
polymers used for medical applications preferably do not include
aromatic groups, other than those present in naturally occurring
amino acids. The SMP utilized in the IOLs disclosed herein may be
nonbiodegradable. In some implementations, it may be desirable to
use biodegradable polymers in the SMP IOLs, for example, when
temporary sterilization is desired or additional functionality is
necessary.
[0059] The polymers are selected based on the desired glass
transition temperature(s) (if at least one segment is amorphous) or
the melting point(s) (if at least one segment is crystalline),
which in turn is based on the desired application, taking into
consideration the environment of use. Representative natural
polymer blocks or polymers include proteins such as zein, modified
zein, casein, gelatin, gluten, serum albumin, and collagen, and
polysaccharides such as alginate, celluloses, dextrans, pullulane,
and polyhyaluronic acid, as well as chitin,
poly(3-hydroxyalkanoate), especially poly(.beta.-hydroxybutyrate),
poly(3-hydroxyoctanoate), and poly(3-hydroxyfatty acids).
Representative natural biodegradable polymer blocks or polymers
include polysaccharides such as alginate, dextran, cellulose,
collagen, and chemical derivatives thereof (substitutions,
additions of chemical groups, for example, alkyl, alkylene,
hydroxylations, oxidations, and other modifications routinely made
by those skilled in the art), and proteins such as albumin, zein,
and copolymers and blends thereof, alone or in combination with
synthetic polymers.
[0060] Representative synthetic polymer blocks or polymers include
polyphosphazenes, poly(vinyl alcohols), polyamides, polyester
amides, poly(amino acid)s, synthetic poly(amino acids),
polyanhydrides, polycarbonates, polyacrylates, polyalkylenes,
polyacrylamides, polyalkylene glycols, polyalkylene oxides,
polyalkylene terephthalates, polyortho esters, polyvinyl ethers,
polyvinyl esters, polyvinyl halides, polyvinyl pyrrolidone,
polyesters, polylactides, polyglycolides, polysiloxanes,
polyurethanes and copolymers thereof. Examples of suitable
polyacrylates include poly(methyl methacrylate), poly(ethyl
methacrylate), poly(butyl methacrylate), poly(isobutyl
methacrylate), poly(ethylene glycol dimethacrylate) (PEGDMA),
diethylene glycol dimethacrylate (DEGDMA), poly(ethylene glycol)
diacrylate (PEGDA), poly(hexyl methacrylate), poly(isodecyl
methacrylate), poly(lauryl methacrylate), poly(phenyl
methacrylate), poly(ethyl acrylate), poly(methyl acrylate),
poly(isopropyl acrylate), butyl acrylate, poly(butyl acrylate),
poly (tert-butyl acrylate), poly(isobutyl acrylate), poly(isobornyl
acrylate) and poly(octadecyl acrylate).
[0061] Synthetically modified natural polymers include cellulose
derivatives such as alkyl celluloses, hydroxyalkyl celluloses,
cellulose ethers, cellulose esters, nitrocelluloses, and chitosan.
Examples of suitable cellulose derivatives include methyl
cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl
methyl cellulose, hydroxybutyl methyl cellulose, cellulose acetate,
cellulose propionate, cellulose acetate butyrate, cellulose acetate
phthalate, carboxymethyl cellulose, cellulose triacetate, and
cellulose sulfate sodium salt. These are collectively referred to
herein as "celluloses."
[0062] Representative synthetic degradable polymer segments include
polyhydroxy acids, such as polylactides, polyglycolides and
copolymers thereof poly(ethylene terephthalate); polyanhydrides,
poly(hydroxybutyric acid); poly(hydroxyvaleric acid);
poly[lactide-co-(.epsilon.-caprolactone)];
poly[glycolide-co-(.epsilon.-caprolactone)]; polycarbonates,
poly(pseudo amino acids); poly(amino acids);
poly(hydroxyalkanoate)s; polyanhydrides; polyortho esters; and
blends and copolymers thereof. Polymers containing labile bonds,
such as polyanhydrides and polyesters, are well known for their
hydrolytic reactivity. The hydrolytic degradation rates of these
polymer segments can generally be altered by simple changes in the
polymer backbone and their sequence structure.
[0063] Examples of non-biodegradable synthetic polymer segments
include ethylene vinyl acetate, poly(meth)acrylic acid, polyamides,
polyethylene, polypropylene, polystyrene, polyvinyl chloride,
polyvinylphenol, and copolymers and mixtures thereof. The polymers
can be obtained from commercial sources such as Sigma Chemical Co.,
St. Louis, Mo.; Polysciences, Warrenton, Pa.; Aldrich Chemical Co.,
Milwaukee, Wis.; Fluka, Ronkonkoma, N.Y.; and BioRad, Richmond,
Calif. Alternately, the polymers can be synthesized from monomers
obtained from commercial sources, using standard techniques.
[0064] In some implementations, thiol-vinyl and thiol-yne polymer
compounds as disclosed in international application no.
PCT/US2009/041359 entitled "Thiol-vinyl and thiol-yne systems for
shape memory polymers" filed 22 Apr. 2009, which is hereby
incorporated by reference herein in its entirety, may be used to
form IOLs. In other implementations, polymer formulations may
undergo a two-stage curing process in which a second, photo-induced
polymerization of still unreacted functional groups is undertaken
after an initial cure stage. Such a dual cure system for
manufacturing SMP materials is described in U.S. provisional patent
application No. 61/410,192 entitled "Dual-cure polymer systems"
filed 10 Nov. 2010, which is hereby incorporated by reference
herein in its entirety.
[0065] Tailoring of specific SMP formulations allows IOLs to be
created to meet specific design requirements and to be manufactured
using scalable liquid injection manufacturing techniques. SMP
formulations were developed to optimize the following properties:
[0066] Shape fixity of >98.5%; [0067] Recovery rates of between
0.25 seconds to 600 seconds, including clinically desirable rates
of between 3 and 25 seconds, inclusive; [0068] Minimum device
deformations of at least 40% in any dimension during the
manufacturing process, and preferentially of 100-200%; [0069]
Rubbery modulus of 250 kPa to 20,000 kPa; [0070] Tailoring of Tg
for folding, compression, and injection; [0071] Glistening-free (an
industry term describing optical imperfections possible in polymer
formulations for intraocular lenses); [0072] UV blocking
capabilities; [0073] Coloration of blue, yellow, red, and green, or
combinations thereof; [0074] Cycle times for liquid injection
manufacturing of 30 seconds to 20 minutes; [0075] Ability to
tolerate high temperature mold-based manufacturing, e.g.,
temperatures of as much as 400 degrees; [0076] Capability to
tolerate high-pressure mold-based manufacturing, specifically
pressures of as much as 50 Mpa; [0077] Ability to flow through
extremely narrow channels (<100 microns diameter) during the
mold-based manufacturing process (i.e., low viscosity at
manufacturing temperatures); and [0078] Volume shrinkage to
permanent shape of 3%-15% or less after thermal curing in the
mold-based manufacturing process. Some exemplary SMP formulations
and their measured properties are reported in Table A below. In one
formulation, tert-butyl acrylate (tBA) is combined with
poly(ethylene glycol) dimethacrylate (PEGDMA) 1000 as a
cross-linker. The weight percentages of each may be varied to
design an SMP with particular desired material properties.
TABLE-US-00001 [0078] TABLE A Max Rubbery Tensile Tg Modulus Strain
Compressive Glistening Formulation (.degree. C.) (MPa) RI (%)
Strain (%) Properties tBA (78%): 40 2.5 1.465 >250 >65
Glistening PEGDMA 1000 Free (22%) tBA (65%): 25 2.5 1.475 >125
>65 Glistening nBA (13%): Free PEGDMA 1000 (22%) tBA (50%): 17
2.5 1.468 >100 >65 Glistening isobutyl Free acrylate (28%):
PEGDMA 1000 (22%)
[0079] As one example of the optimization, recovery time is
controlled by the relationship of the glass transition temperature
(Tg) of the SMP material used to the environmental temperature (Te)
in which an SMP device is deployed. A Tg<Te deploys more slowly
than a Tg=Te, and a Tg>Te deploys at the fastest rate. Tg of the
material may be controlled from -35.degree. C. up to 114.degree. C.
allowing a wide range of control over the deployment rate into the
body. Desirable ranges for Tg in IOL devices may be between
10.degree. C. and 60.degree. C., and even more desirably between
15.degree. C. and 45.degree. C. Devices have been created that
deploy in less than a second all the way up to several minutes to
fully deploy.
[0080] In order to deliver the IOLs through the smallest possible
incision, the mechanical properties of the SMP devices may be
developed to achieve high levels of recoverable strain. In tension,
up to 180% strain can be achieved for 10% cross-linked systems and
up to 60% strain can be achieved in 40% cross-linked systems. In
compression 80% or more strain can be achieved with the above
percentage cross-link. The desired levels of strain in tension and
compression are determined by the level of deformation required to
fit the SMP IOL into the delivery system. Formulations with lower
amounts of cross-linking can undergo higher levels of deformation
without failure. Current IOLs utilize 5%-40% cross-linking to
achieve the material properties for the desired level of
recoverable strain.
[0081] Manufacturing of SMP IOLs may be achieved through either
thermal initiation or photo-initiation or a combination of the two
processes. For thermal initiation, both peroxides and azo
initiators have been utilized. 2,2-dimethoxy-2-phenylacetophenone
(DMPA) may be used for photo-initiation. Formulations vary in
quantity from 0.01% by weight to 1% by weight of initiator. These
are varied to optimize cycle time during the manufacturing process
and still maintain desired thermomechanical properties.
[0082] Colorant can also be added to the formulations. SMP
materials with SPECTRAFLO (trademark of Ferro) liquid colors have
been created. Formulations with 0.1% to 2% by weight have been
created, which allows various colors to be added yet maintain
desired thermomechanical properties.
[0083] The ability to change refractive index has also been
investigated through changes to the SMP formulation. Table B below
provides data on the refractive index of the different components
used in several exemplary formulations.
TABLE-US-00002 TABLE B Refractive Chemical Name Index @ 36.degree.
C. Functionality tert-Butyl Acrylate (tBA) 1.4031 Monomer
Poly(ethylene glycol) 1.4609 Cross-linker dimethacrylate (PEGDMA)
550 Poly(ethylene glycol) 1.460 Cross-linker dimethacrylate
(PEGDMA) 1000 Polycarbonate (PC) 1.4635 Cross-linker Diacrylate 610
KIFDA 542 (King Industries, 1.475 Cross-linker Inc., Norwalk, CT)
Bisphenol A propoxylate 1.515 Cross-linker diacrylate (BPA-P)
Diacrylate Poly(ethylene glycol) 1.467 Cross-linker diacrylate
(PEGDA) 575 Poly(ethylene glycol) 1.47 Cross-linker diacrylate
(PEGDA) 700
While certain molecular weights of the cross-linkers are presented
with measured refractive indexes in Table B, other molecular
weights can be uses in varying formulations. For example,
poly(ethylene glycol) diacrylate (PEGDA), poly(ethylene glycol)
diacrylate (PEGDA) may be used with good result in various
molecular weights of between 500 and 2000.
[0084] SMP samples listed in Table C below were created and the
refractive indices were measured. Cross-linking of 20% for the
noted cross-linker polymer was used. The results show only slight
changes to the refractive index values based on the formulations
created. Increasing the content of the cross-linker in the
formulations may be used to change the refractive index values
more. In addition other formulations may be prepared with
poly(carbonate) diacrylate, KIFDA-542 diacrylate (available from
King Industries, Inc., Norwalk, Conn.), and bisphenol-A propoxylate
diacrylate that have a greater effect on changing the refractive
index.
TABLE-US-00003 TABLE C Tg Glistening Formulation (.degree. C.) RI
Evaluation tBA (80%):PEG DM A 550 (20%) 52 1.465 glistens tBA
(64%):nBA (24%):PEGDMA 550 (12%) 32 glistens tBA (78%):PEGDMA 1000
(22%) 40 1.465 does not glisten tBA (60%):nBA (20%):PEGDMA 550
(20%) 30 glistens tBA (56%):nBA (14%):PEGDMA 550 (30%) 32 glistens
tBA (80%):PC-DA (20%) 59 1.463 glistens tBA (78%):SR601 (22%) 71
1.48 does not glisten tBA (78%):SR602 (22%) 52 1.478 does not
glisten tBA (78%):CD9038 (22%) 41 1.468 does not glisten tBA
(65%):nBA (13%):PEGDMA 1000 (22%) 25 1.475 does not glisten tBA
(78%):PEGDMA 1000 (22%):BTA (.5%) 40 1.465 does not glisten tBA
(78%):PEGDMA 1000 (22%):BTA (1%) 40 1.465 does not glisten
isobutylA (78%):PEGDMA 1000 (22%) -13.5 nBA (78%):PEGDMA 1000 (22%)
-27.5 tBA (50%):isobutylA (28%):PEGDMA 1000 17.5 1.468 does not
(22%) glisten HPPA (78%):PEGDMA 1000 (22%) 23 1.542 does not
glisten HPMAEP (78%):PEGDMA 1000 (22%) 34 1.536 does not glisten
tBA (60%):PEGDMA 1000 (40%) 18 does not glisten tBA (76%):isobutylA
(14%):PEGDMA 1000 43 (10%) tBA (85%):PEGDMA 1000 (15%) 48
[0085] The ability to change light transmission properties through
the SMP materials has been investigated.
2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate
(BTA) was added to the SMP IOL formulation of as an ultraviolet
(UV) wavelength blocker as indicated in the table above. Two
formulations with 0.5% UV blocker and 1% UV blocker were created
and then analyzed for UV through visible wavelength transmission
and dynamic mechanical analysis. FIG. 1 is a graph showing the
storage modulus and the tan delta (the ratio of the storage modulus
to the loss modulus) of the following three material formulations
over a range of temperatures from 0 to 100.degree. C.:
[0086] SMP106: 78% tBA and 22% PEGDMA 1000 with no UV blocker;
[0087] SMP122: SMP106 with 0.5 weight % BTA functionalized UV
blocker added; and
[0088] SMP123: SMP106 with 1.0 weight % BTA functionalized UV
blocker added.
The upper curve is the storage modulus and the lower curve is the
tan delta. As is apparent, the addition of the small amounts of BTA
as a UV blocker has little if any effect on the modulus of the SMP
materials and the Tg (the peak of the tan delta curve) is constant
for all three formulations.
[0089] FIG. 2 shows the effect of the addition of the BTA UV
blocker on the SMP materials of FIG. 1. As is apparent, the
addition of the UV blocker has negligible effect on light
transmission in the visible wavelengths, but sharply attenuates
wavelengths below about 380 nm, which is the upper end of the UV
spectrum.
[0090] FIG. 3 is a graph showing the storage modulus and the tan
delta of two additional SMP formulations over a range of
temperatures from -20 to 100.degree. C. in comparison to SMP
106:
[0091] SMP119: 65 wt % tBA, 13 wt % butyl acrylate, 22 wt % PEGDMA
1000; and
[0092] SMP126: 50 wt % tBA, 28 wt % isobutyl acrylate, 22 wt %
PEGDMA 1000.
The upper curve is the storage modulus and the lower curve is the
tan delta. The difference in formulas provide different Tg for use
in different environments and for different applications in which
it may be useful to have a lower transition temperature. SMP119 has
a Tg of about 25.degree. C. and SMP126 has a Tg of about 17.degree.
C. However, even with the differences in Tg, the storage moduli of
the SMP119 and SMP126 formulations compare favorably to the SMP106
material. FIG. 4 also indicates that the light transmission
properties of SMP119 and SMP126 compare favorably to the SMP106
formula.
[0093] FIG. 5 is a graph depicting stress-strain data curves for
SMP106, SMP119, and SMP126 for the materials under compression. As
is apparent, the SMP119 and SMP126 formulas exhibit significantly
less stress under a compressive strain of 65% compared to the
SMP106 formula. This allows these materials to be more easily
deformed at lower temperatures, such as room temperature. FIG. 6 is
another stress-strain curve for SMP106 for two separate rates of
elongation under tension, i.e., for rates of 10 mm/min and 20
mm/min. As shown in the graph, SMP106 performs quite well under
tension and withstood up to and over 250% strain at both rates.
[0094] The post deployment shape should be highly controlled to
maximize the optical characteristics of the device. The higher the
shape fixity, defined as the percent change in recovered shape
compared to the original molded shape, the higher the
reproducibility and confidence that the deployed IOL will function
as intended. The SMP materials disclosed herein provide extremely
high shape fixity (>95-99%). This is in large part because the
SMP materials deploy using a non-elastic, non-melt shape recovery
process (i.e., it is not a phase change using fluid properties).
Further, the SMP materials are not a hydrogel or other type of
hydrating material. The SMP materials transform from one
highly-reproducible, non-changing, non-creeping, non-deforming,
storage shape, to another highly-reproducible, non-changing,
non-creeping, non-deforming, secondary (permanent) shape.
[0095] The SMP materials have a pre-programmed shape;
post-deployment the SMP devices release internal stored energy to
move to the programmed shape, which may or may not be adaptive to
the local tissue. The local tissue does not play a part in shaping
the form of the SMP devices. The SMP devices return to their
"permanent" shape as originally formed when molded, before being
deformed for smaller profile delivery. The speed of full deployment
from the deformed state to the glass (permanent) state can be
varied over a wide range from less than a second to over 600
seconds depending upon the SMP formulation.
[0096] Additionally, because of the high Tg (i.e., at or above body
temperature) of the SMP formulations, the processes of packaging,
shipping, storing, and ultimately implanting SMP devices does not
require refrigerated storage or ice or an otherwise low-temperature
operating environment. Thus, a significant advantage of the SMP
materials described herein is that they can be stored in the stored
shape for extended periods of time, they can be packaged in
constrained forms within a customized delivery system, and they can
be deployed without need for prior refrigeration or other
temperature changes. For example, during shipping of a device, the
environmental effect of cycling of temperatures and inadvertent
deployment of a device can be eliminating by constraining the
device in a delivery system or packaging system.
[0097] A variety of intraocular lens types can be made of SMP
materials according to the formulations described above with
selected material properties to meet the needs of the particular
lens type or design. Several of these lens options are described
below
[0098] Intraocular Lenses
[0099] SMP intraocluar lenses are designed to be inserted through
significantly smaller incisions than other currently commercially
available foldable lens technologies. An exemplary SMP intraocular
lens 100 is depicted in FIGS. 1 and 2 and will be discussed in
greater detail herein below. In addition the lens shape is highly
conserved (i.e., there is high shape fixity>98%) after
deployment in the eye. An intracapsular bag lens may have a shape
that creates contact with the anterior capsular leaflet as well as
the capsule just posterior to the equator allowing for a decrease
in posterior capsule opacity formation. A ciliary sulcus lens may
have a vault which allows it to avoid trauma to the iris. An
anterior chamber lens may have an appropriate vault to decrease the
risk of pupillary block and decrease the risk of trauma to the
anterior chamber angle support structures.
[0100] There are many advantages to SMP technology when applied to
intraocular lenses. First, the intraocular lens is compressible and
deformable. This ability to compress the material and configure it
in a small platform allows for smaller incision sizes for delivery.
Such SMP lenses, which fit through smaller incisions, offer
significant benefit. For example, with cataract surgery there is
less astigmatism, quicker recovery, and less trauma to the eye with
smaller incisions. Also, with laser technology and improved
ultrasound technology, cataract surgery can be performed with
smaller incisions; the limiting factor with present options is the
larger incision size needed for the replacement lens.
[0101] A second advantage to the shape memory polymer technology in
intraocular lens is that deployment of the lens uses
thermomechanical recovery rather than an elastic recovery process.
The formulation can be modified to change the time or speed of
deployment of the lens. This can vary depending upon the location
of needed deployment. For example, deployment near delicate
structures, such as in the capsular bag or near the corneal
endothelium, may require slower, surgeon-tailored deployment to
avoid damage to these structures. This modification of deployment
speed is not possible with other currently available lens
technologies. Also the modulus of the SMP material can be modified
to optimize the softness of lens material to minimize trauma to eye
structures. For each of the lens types described above, the SMP
material properties allow for a slow, tailored deployment, which
results in less trauma to the areas with which the lens optic or
haptics come in contact.
[0102] A third advantage is the ability to easily modify the
refractive index of the lens. The refractive index can he changed
through modifications of SMP formulation. In addition, the surface
curvature of the lens, which is important in designing optical
power, can be modified through the liquid injection molding process
or post molding with cutting such as with a laser. Further, the
curvature of lens as well as the refractive index of the lens can
be modified post implantation with heat, UV, or laser light
modification.
[0103] A fourth advantage is that the surface characteristics and
implantation of SMP lenses may decrease inflammation and cellular
opacification. As an example, FIG. 7 is an optical profilometry
image of a sample SMP lens surface showing average surface
roughness of 16 nanometers. This low roughness measure minimizes
optical artifacts such as spectral filtering and maximizes optical
clarity of the lens. In FIG. 7 the darker areas surrounded by the
circles are areas toward the higher end of the measured roughness
on the right-hand scale (i.e., toward the 203 nm measurement) while
the other dark areas in the image are toward the lower end of
measured roughness (i.e., toward the -186 nm measurement). For
example, an intracapsular SMP IOL will have contact with the
capsular bag to decrease the movement of the lens, but the
smoothness of the surface retards the migration of epithelial cells
and subsequent formation of posterior capsular opacification.
[0104] Since the SMP lens is materially robust, the lenses may be
also modified with surface polishing as well as other known
mechanisms to reduce the proliferation of cells on the surface of
intraocular lenses. In addition the slow deployment of an SMP lens
can minimize cellular opacification. There is a tension between the
size of the IOL and the collection of epithelial cells on the lens
due to the tight fit within the capsular bag. For example, an
intracapsular lens will have contact with the capsular bag in a
fashion to decrease the migrations of the lens, but the contact
with epithelial cells can lead to subsequent formation of posterior
capsular opacification, especially if the fit is tight and the
material is unable to pass around the lens. This problem is
compounded if during deployment, the capsular bag is impacted and
damaged, which generates increased cell production in response to
the trauma. Configurations of standard intraocular lenses to
decrease this common complication of cataract surgery and lens
placement are well known. However, with SMP lenses, the size and
apposition of the implanted SMP lens to the capsular bag can be
increased over current lenses because of the compressibility and
deformability of the SMP lens material and the slow deployment that
allows a tight fit while minimizing trauma. The ability to polish
the surface further mitigates this problem.
[0105] Dual Optic Lenses
[0106] Larger lenses such as dual optic lenses and other
accommodative intraocular lenses may be used to treat refractive
error and presbyopia simultaneously. Dual optic lenses are
generally constructed with a primary intraocular lens having an
optic with a primary optical power and refractive index, and a
secondary intraocular lens having an optic with a secondary optical
power and possibly a different refractive index. The secondary
optic is typically attached to and spaced apart from the primary
optic by material struts or similar structures about the periphery
of the lenses. The two lenses to act synergistically to allow for
both near and distance vision depending on the relationship (e.g.,
separation distance) between the two optics as well as the
geometric association between the two optics which also may (or may
not) be adjustable in each individual patient post
implantation.
[0107] These dual optic lenses often require larger than
conventional incisions for entry into the eye. These larger
platform lenses may be made with SMP materials, which are highly
compressible and deformable allowing for smaller incisions sizes,
and thus can improve surgical outcomes for the reasons stated
above. In addition, if formed using SMP materials, these larger
lenses can be deployed more slowly allowing the surgeon to position
the lens in such a fashion as to avoid inadvertent trauma to
important eye structures and careful apposition to structures in
the target location. This decreases the trauma risk that these
larger platform lenses could cause in the eye. In addition, these
lenses are quite complex and require high precision optics
capabilities, which are conserved because of the high shape fixity
of the SMP materials.
[0108] Other accommodative lenses strive to replicate the functions
of the normal human lens. Mechanisms of accommodation are thought
to be secondary to ciliary body contraction and zonular deformation
of the lens capsule and a change in lens shape as well as an
anterior-posterior movement of the lens complex. With SMP
materials, a lens may be created which has close apposition to the
lens capsule in multiple areas so that there is an ability to
replicate the actions of the native lens. In fact, an SMP lens may
be made which expands in the intracapsular space, fills either the
whole space or a larger area of the space, and responds to the
ciliary body-zonule actions. In addition, an SMP lens can be
inserted through a smaller anterior capsular opening, which may
help preserve the responsiveness of the lens to the native
accommodative process. The local dimensions, thickness in
particular, of the SMP lens may be modified post implantation
(which may affect local stiffness) if a change in shape is needed
to replicate the accommodation process by adding SMP material into
the IOL that is of different cross-link density and therefore
different activation temperature (Tg) and/or different modulus.
[0109] Phakic Intraocular Lenses
[0110] A phakic intraocular lens is a lens which is placed in the
anterior chamber through a corneal incision. As with the other
intraocular lenses discussed above, an SMP phakic lens may be
compressed for implantation through a much smaller incision than
presently available lenses. A SMP phakic lens may also be designed
to deploy slowly so there is little to no corneal endothelial or
native lens trauma. The tailored surgeon-controlled deployment
allows for positioning of the haptics against the anterior chamber
structures without damaging the trabecular meshwork or iris. The
force placed on the angle structures by the haptics is consistent
and more reproducible than with a conventional lens, which deploys
by elastic recovery. A SMP phakic lens may also be designed to
deploy in the anterior chamber for placement behind the iris plane
during deployment. With current phakic IOL technology, if placed
behind the iris, there is a known higher incidence of cataract
formation. This incidence can be reduced or eliminated with slow
tailored deployment and positioning of an SMP lens.
[0111] Intracorneal Implants
[0112] Intracorneal implant devices have not achieved great success
in the national and international markets due to several
limitations which include: (a) difficulty with implantation; (b)
requirement for large incisions in the cornea to accommodate
current devices; (c) inability to correct "refractive surprises"
without returning to the procedure or operating room; and (d)
limitation in geometrical configurations of current devices due to
inherent material properties. In contrast, SMP intracorneal
implants may be designed to leverage the benefits of the
compressibility and deformability of SMP materials. A laser or
blade is used to make an intracorneal incision, tunnel, and pocket
to deliver the intracorneal implant. One of the current challenges
is the severe trauma often seen to the corneal tissues during
insertion of these devices. A "tight fit" is needed as well as an
adequate intracorneal passageway to advance the intracorneal
implant. The intracorneal implants are designed to be small enough
to atraumatically be passed through a corneal incision and into the
desired pocket. Then, the thermomechanical deployment and
decompression of the implant occurs allowing for a secure
positioning of the implant.
[0113] Extrusion and displacement of the intracorneal implants may
be decreased with the SMP technology as well as decreasing
infection rates because of the minimization of corneal trauma as
well as the presence of a smaller incision, tunnel, and pocket.
Advantages of using SMP materials for intracorneal implants
compared to traditional devices may include the ability to implant
devices through minimally invasive approaches (e.g., through
incisions created by femtosecond lasers) with subsequent shape
change achieving larger device diameters for refractive correction.
Another advantage is the ability to change the shape and size of
SMP intracorneal implant devices post implantation in the cornea,
for example, if a "refractive surprise" occurs or if further
changes in refractive correction are needed. This can be achieved
by constructing the intracorneal implants with different material
formulas in different areas to provide differing Tg and refractive
index values for each of the areas as described above with respect
to SMP IOLs. A further advantage is the ability to implant the
devices in a more "rubbery" state, thus causing less trauma to the
stromal tissue of the cornea.
[0114] Shape Memory Polymer Intraocular Compression and
Packaging
[0115] FIGS. 8A-13 depict exemplary steps in a process to deform a
SMP IOL into a compressed shape for packaging and implantation, at
which point the SMP IOL will deploy and expand to return to its
permanent shape with an extremely high degree of shape fixity.
FIGS. 8A and 8D depict an exemplary, generic SMP intraocular lens
100. The SMP IOL 100 has a center optic 102 and haptics 104
extending symmetrically from opposing sides of the optic 102. Each
of the haptics 104 may be formed in sections including a shoulder
106 connected with the optic 102, an arm 108, and a terminal end
110. Upon deployment, the haptics 104 unfurl from their rolled and
compressed conditions to press the terminal ends 110 against the
tissue forming the cavity of implantation to secure the optic in an
appropriate position.
[0116] The SMP IOL is formed by injection molding one of the
formulations described above. In an exemplary implementation, an
80-20 (tBA-PEGDMA 550) combination is used to create a 6 mm
diameter optic 102 with extending haptics 104. The tBA-PEGDMA 550
mixture has extremely low viscosity when heated in the mold and is
thus able to easily flow through and fill the mold to form the very
small diameter haptics 104. In another exemplary implementation, a
combination of tBA (78%) and PEGDMA 1000 (22%), with or without a
UV blocker BTA (0.5-1.0%) (e.g., SMP106, SMP122, and SMP123,
respectively) may be used to create the optic 100. These formulas
similarly have extremely low viscosities. In a cast process
molding, the mold may be oversized by 0.1-20% to account for a
5-20% volume shrinkage that typically occurs for these polymer
chemistries during the polymerization process. In a liquid
injection molding process, ultra-high pressures (e.g.,
>500-40,000 psi) may be utilized to minimize volume shrinkage as
much as possible during polymerization. In addition, the
combination of injection molding with pre-polymization techniques
may be implemented to further minimize volume shrinkage during the
polymerization process.
[0117] In one implementation, the cure temperature and de-molding
temperature may be the same to avoid thermal cycling.
Alternatively, the mold may be cooled to an optimal de-mold
temperature where the material exhibits the greatest robustness,
typically somewhere slightly (e.g., 8.degree. C.) below Tg. Once
released from the mold, the SMP IOL 100 is in its permanent form.
However, for implantation, it is desirable to reduce the size and
form factor of the SMP IOL 100 such that it can be implanted
through a smaller incision.
[0118] FIGS. 9A and 9B schematically depict a first step in the
deformation process for the SMP IOL 202 to package the SMP IOL 202
into a deformed shape for storage and ultimately implantation. A
rolling die 204 defining a longitudinal channel 206 therein may be
used to initially roll the SMP IOL 202. The SMP IOL 202 is placed
over the channel oriented with the haptics extending across the
channel as well. A tension wire 208 is placed parallel to and
directly above the channel 206 over the SMP IOL 202 while the ends
of the tension wire 208 are position coaxially with the
longitudinal center of the channel 206. The rolling die 204 and SMP
IOL 202 are then heated to approximately Tg. The tension on the
wire 208 is increased, drawing the entire length of the tension
wire 208 into the channel 206 the tension wire is coaxial with the
longitudinal center of the channel. The tension wire 208 thereby
pushes the SMP IOL 202 within the channel 206, folding the SMP IOL
202 in half around the tension wire 208 and deforming the SMP IOL
202 into a U-shape 202' as shown in FIG. 9B. A first side of the
U-shaped SMP IOL 202' (labeled "b" in FIG. 2B) is folded over the
wire 208 in the channel 206. Then a second side of the U-shaped SMP
IOL 202' (labeled "c" in FIG. 9B) is folded over the first side
about the wire 208. The tension wire 208 can then be removed. In
one exemplary embodiment, the channel may be 1.8 mm wide by 2.0 mm
deep resulting in an SMP IOL 202' that has maximum diametrical
dimensions of 1.8 mm by 2.0 mm.
[0119] As depicted in FIG. 10A, the rolled SMP IOL 302 is next
cooled below Tg while remaining within the channel 306 in the
rolling die 304. The cooling of the SMP IOL 302 while in the die
channel locks the SMP IOL 302 in the rolled configuration. The SMP
IOL 302 can then be removed from the channel 306 in the rolling die
304 and will maintain its rolled shape as shown in FIG. 10B.
[0120] The rolled SMP IOL 402 is next placed within a fabric sheath
or sock 404 as shown in FIG. 11 for transmission of the rolled SMP
IOL 402 through a compression die. The fabric sock 404 may be
closed at one end and open at an opposite end and sized to fit
snugly around the rolled SMP IOL 402. The fabric sock 404 may be
significantly longer than the length of the rolled SMP IOL 402 in
order to assist in pulling the SMP IOL 402 through a compression
die. In an exemplary implementation, the fabric sock 404 may be
made of a silk fabric.
[0121] FIGS. 12A and 12B depict the SMP IOL 402 in the fabric sock
404 being pulled through a compression die 502. The compression die
502 defines a borehole 508 extending laterally therethrough from an
entrance side 504 to and exit side 506. The borehole 508 in the
compression die 502 may be divided into several sections of varying
diameter. An entrance section 510 opening up to the entrance side
504 may be of a constant diameter of slightly larger than the
diameter of the rolled SMP IOL 402 such that the SMP IOL 402 can be
easily inserted into the borehole 508 of the compression die 502. A
middle section 512 of the borehole 508 tapers in diameter from the
diameter of the entrance section 510 to a smaller diameter that
transitions into and is congruent with a diameter of an exit
section 514 that opens the exit side 506. Continuing with the
exemplary embodiment described above wherein the maximum diameter
of the rolled SMP IOL 402 is 2.0 mm, the diameter w of the entrance
section 510 may be formed as 2.0 mm or slightly greater. The middle
section 512 may then transition from 2.0 mm to 1.5 mm in diameter,
and the diameter w' of the exit section may be a constant 1.5 mm in
diameter.
[0122] As shown in FIGS. 12A and 12B, the open end of the fabric
sock 404 is placed within the borehole 508 from the entrance side
504 and is long enough to extend the length of the borehole 508 and
extend out of the exit side 506. The open end of the fabric sock
404 may then be grasped to pull the rolled SMP IOL 402 within the
fabric sock 404 into the entrance section 510 of the borehole 508.
The compression die 502 is heated to a temperature greater than Tg
for the SMP formulation used until the SMP IOL 402 reaches a
temperature greater than Tg and is softened. The fabric sock 404 is
then pulled through the borehole 508 whereby the rolled SMP IOL 402
is likewise pulled through the middle section 512 and radially
compressed. The compressed SMP IOL 402' is then left in the reduced
diameter exit section 514 while the compression die and the
compressed SMP IOL 402 therein are cooled to a temperature below
Tg, thereby locking the compressed SMP IOL 402' in the compressed
state. Once the compressed SMP IOL 402' has been cooled below Tg,
it can be removed from the compression die 502 and the fabric sock
404 and will remain in the compressed shape with a maximum diameter
of w' for packaging, storage, and ultimately implantation as
indicated in FIG. 13.
[0123] In an exemplary experiment, an SMP IOL with a 6 mm diameter
optic was rolled and compressed to a final diameter, w', of 1.5 mm.
The compressed SMP IOL was loaded into a 15 gauge hypodermic tube.
The compressed SMP IOL in the tube was then introduced into a
heated water bath at body temperature. A rod was inserted within
the hypodermic tube to push the IOL out the end of the tube and
deliver it into the water bath. Once in the water bath, the SMP IOL
expanded and unfurled to return to its original form with a 6 mm
diameter optic with >98% accuracy in size and form.
[0124] Another exemplary implementation of a device and method for
folding the IOL is depicted schematically in FIGS. 14A-14C. FIG.
14A depicts a first step in the deformation process for an SMP IOL
702 to package the SMP IOL 702 into a deformed shape for storage
and ultimately implantation. A rolling die 710 is formed with a
pair of parallel walls 704 extending above a top surface of the die
710 to define a longitudinal channel 706 therein. The base of the
channel 706 may be arcuate or semicircular in cross section in
order to aid in the folding and achieve a relatively cylindrical
SMP IOL 702 in the final compressed form. The SMP IOL 702 is placed
on the walls 704 over the channel 706 and oriented with the haptics
extending across the channel 706 as well. The rolling die 710 and
SMP IOL 702 are then heated to approximately Tg. The lateral edges
of the SMP IOL 702 may then be folded over within the channel 706
between the walls 704 to form a rolled shape similar to the
configuration of the IOL 302 in FIG. 10B. In one implementation,
the IOL 702 may be folded by hand using a tweezers or forceps. In
another implementation, a tension wire as described with respect to
FIGS. 9A and 9B may be used to depress the IOL 702 into the channel
706. In one exemplary embodiment, the channel 706 may be 1.8 mm
wide by 2.0 mm deep resulting in an SMP IOL 702 that has maximum
diametrical dimensions of 1.8 mm by 2.0 mm.
[0125] FIG. 14B depicts a second component of the deformation
device, a second compression die 720 that works in cooperation with
the roll die 710 to further compress the IOL 702. A pair of
parallel channels 728 are formed within a top surface of the
compression die 720 that are complementary to or slightly larger in
size (i.e., length, width, and depth) than the size of the walls
704 (i.e., length, width, and height) of the rolling die 710. A
recessed wall 724 is thus formed within the top surface of the
compression die 720 that separates and defines the channels 728.
The recessed wall 724 may thus be of a complementary width to or
slightly smaller in width than the channel 706 on the rolling die
710. The top surface of the recessed wall 724 may further define a
shallow trough 726 with a curved or semi-circular cross section.
The compression die 720 may further be formed with one or more
fluid channels 722 with inlet and outlet fittings in order to
maintain the compression die 720 at or above the Tg of the SMP IOL
702.
[0126] Once the SMP IOL 702 is rolled in the channel 706 of the
rolling die 710, the rolling die 710 is inverted and placed on top
of the compression die 720. The walls 704 of the rolling die 710
fit within the channels 728 of the compression die 720. The
recessed wall 724 of the compression die 720 extends into the
channel 706 of the rolling die 710 and the trough 726 contacts the
SMP IOL 702 within the channel 706. The rolling die 710 and the
compression die 720 are then pressed together and the SMP IOL 702
is further compressed in size when measured in cross-sectional
diameter (however, the SMP IOL may increase in axial length
slightly when under radial compression between the rolling die 710
and the compression die 720.
[0127] As shown in FIG. 14 C, since the depth of the parallel
channels 728 within the compression die 720 is slightly larger than
the height of the parallel walls 704 on the rolling die 710, the
top surface of the rolling die 710 and the top surface of the
compression die 720 reach an interface and halt the compression of
the SMP IOL 702. The depth of the trough 726 and the depth of the
channel 706 are chosen to define a separation distance between the
base of the channel 706 and the base of the trough 726 that
corresponds to a desired final diameter of the compressed SMP IOL
702. In an exemplary experiment, an SMP IOL with a 6 mm diameter
optic was compressed using this method to a final diameter of 1.6
mm. The compressed SMP IOL can then be loaded into an injection
tool for ab interno delivery.
[0128] In another exemplary implementation, an SMP IOL folded by
this technique may be loaded into a lens injector for implantation.
In an exemplary IOL placement, a small incision may be made at the
corneal limbus with a blade or laser and the tip of the injector
may be inserted into the anterior chamber. Because of the slow
deployment of the SMP IOL, the surgeon can place the haptics and
the optic in the correct location during lens deployment to avoid
extensive manipulation of the SMP IOL after full deployment. In
addition, cataract extraction and lens implantation can be
performed with a smaller anterior capsular opening--as small as
less than 1.8 mm in diameter. A smaller capsular opening with less
disruption of the anterior capsule will increase the accommodative
ability of the implanted lens as the physiology of accommodation is
less disrupted.
In one exemplary implementation, the injector tip may be placed
through the cornea incision, across the anterior chamber, into the
small anterior capsular opening. The lens may be injected directly
into the capsular bag and slowly deploy without significant trauma
to the lens capsule. This is not possible with rapid deployment of
known expanding lenses which often leads to capsular tears.
Similarly a sulcus SMP IOL will be supported in the ciliary sulcus
with gentle pressure and apposition of the haptics to the ciliary
sulcus structures. Further, an anterior chamber SMP IOL will be
supported by the anterior chamber angle structures with gentle
pressure and apposition of the haptics to the anterior chamber
angle structures. The slow, gradual deployment of an SMP IOL will
significantly reduce the trauma to these tissue structures as
compared to the rapid, elastic deployment of present IOL
materials.
[0129] All directional references (e.g., proximal, distal, upper,
lower, upward, downward, left, right, lateral, longitudinal, front,
back, top, bottom, above, below, vertical, horizontal, radial,
axial, clockwise, and counterclockwise) are only used for
identification purposes to aid the reader's understanding of the
present invention, and do not create limitations, particularly as
to the position, orientation, or use of the invention. Connection
references (e.g., attached, coupled, connected, and joined) are to
be construed broadly and may include intermediate members between a
collection of elements and relative movement between elements
unless otherwise indicated. As such, connection references do not
necessarily infer that two elements are directly connected and in
fixed relation to each other. The exemplary drawings are for
purposes of illustration only and the dimensions, positions, order
and relative sizes reflected in the drawings attached hereto may
vary.
[0130] The above specification, examples and data provide a
complete description of the structure and use of exemplary
embodiments of the invention as defined in the claims. Although
various embodiments of the claimed invention have been described
above with a certain degree of particularity, or with reference to
one or more individual embodiments, those skilled in the art could
make numerous alterations to the disclosed embodiments without
departing from the spirit or scope of the claimed invention. Other
embodiments are therefore contemplated. It is intended that all
matter contained in the above description and shown in the
accompanying drawings shall be interpreted as illustrative only of
particular embodiments and not limiting. Changes in detail or
structure may be made without departing from the basic elements of
the invention as defined in the following claims.
* * * * *