U.S. patent application number 11/613356 was filed with the patent office on 2008-06-26 for packaging solutions.
This patent application is currently assigned to BAUSCH & LOMB INCORPORATED. Invention is credited to Daniel J. Hook, Joseph C. Salamone, Erning Xia.
Application Number | 20080148689 11/613356 |
Document ID | / |
Family ID | 39186115 |
Filed Date | 2008-06-26 |
United States Patent
Application |
20080148689 |
Kind Code |
A1 |
Xia; Erning ; et
al. |
June 26, 2008 |
PACKAGING SOLUTIONS
Abstract
The present invention is directed to new and improved packaging
systems for storing ophthalmic devices such as contact lenses and
to methods for packaging such ophthalmic devices with aqueous
packaging solutions to improve the comfort of the lens during wear.
In particular, the present invention is directed to a packaging
system for storing an ophthalmic device in an aqueous packaging
solution comprising an anionic polymer and a non-ionic polyol. Such
solutions can be retained on the surface of an unused lens for
extended periods of time, resulting in surface modification that
persists in the eye, which may provide significant improvement in
the wetting properties of fresh contact lenses used for the first
time and, moreover, even several hours after lens insertion,
preventing dryness and improving lubricity.
Inventors: |
Xia; Erning; (Penfield,
NY) ; Hook; Daniel J.; (Fairport, NY) ;
Salamone; Joseph C.; (Boca Raton, FL) |
Correspondence
Address: |
Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester
NY
14604-2701
US
|
Assignee: |
BAUSCH & LOMB
INCORPORATED
Rochester
NY
|
Family ID: |
39186115 |
Appl. No.: |
11/613356 |
Filed: |
December 20, 2006 |
Current U.S.
Class: |
53/431 ; 206/5.1;
53/425; 53/440 |
Current CPC
Class: |
A45C 11/005 20130101;
B65B 25/008 20130101; A61L 12/14 20130101; A61L 12/08 20130101;
A61L 12/147 20130101 |
Class at
Publication: |
53/431 ; 53/425;
53/440; 206/5.1 |
International
Class: |
B65B 55/22 20060101
B65B055/22; B65B 55/12 20060101 B65B055/12; B65B 55/14 20060101
B65B055/14; B65D 85/00 20060101 B65D085/00 |
Claims
1. A method of preparing a package comprising a storable, sterile
ophthalmic device, the method comprising: (a) immersing an
ophthalmic device in an aqueous packaging solution comprising an
anionic polymer and a non-ionic polyol, wherein the aqueous
packaging solution has an osmolality of at least about 200 mOsm/kg
and a pH in the range of about 6 to about 9; (b) packaging the
solution and the device in a manner preventing contamination of the
device by microorganisms; and (c) sterilizing the packaged solution
and device.
2. The method of claim 1, wherein the ophthalmic device is a
contact lens.
3. The method of claim 1, wherein the ophthalmic device comprises a
polymerization product of a monomeric mixture comprising one or
more silicone-containing monomers.
4. The method of claim 1, wherein the anionic polymer possesses a
Mark-Houwink Constant of greater than 0.6.
5. The method of claim 1, wherein the anionic polymer possesses a
Mark-Houwink Constant of greater than about 1.
6. The method of claim 1, wherein the anionic polymer possesses a
Mark-Houwink Constant of greater than about 1.6.
7. The method of claim 1, wherein the anionic polymer in the
aqueous packaging solution is a carboxy-containing
polysaccharide.
8. The method of claim 7, wherein the carboxy-containing
polysaccharide is selected from the group consisting of a
carboxy-containing cellulose, hyaluronate, chondroitin sulfate,
guar, alginate, pectin, xanthan and mixtures thereof.
9. The method of claim 7, wherein the carboxy-containing
polysaccharide is a carboxymethylcellulose.
10. The method of claim 1, wherein the anionic polymer in the
aqueous packaging solution is a carboxy-containing vinyl
polymer.
11. The method of claim 10, where the carboxy-containing vinyl
polymer is selected from the group consisting of a carbomer,
polymer of acrylic acid and/or methacrylic acid and mixtures
thereof.
12. The method of claim 1, wherein the anionic polymer in the
aqueous packaging solution is an anionic polypeptide.
13. The method of claim 12, wherein the anionic polypeptide is
selected from the group consisting of a poly(glutamic acid),
poly(aspartic acid) and mixtures thereof.
14. The method of claim 1, wherein the anionic polymer has a degree
of substitution value of about 0.5 to about 1.5.
15. The method of claim 1, wherein the concentration of the anionic
polymer in the aqueous packaging solution is about 0.01 to about
10% w/w.
16. The method of claim 1, wherein the non-ionic polyol is selected
from the group consisting of glycerin, ethylene glycol,
poly(ethylene glycol), propylene glycol, monosaccarides,
disaccharides, oligopolysaccharides or polysaccharides and mixtures
thereof.
17. The method of claim 1, wherein the anionic polymer is a
carboxymethylcellulose and the non-ionic polyol is glycerin.
18. The method of claim 1, wherein the solution further comprises a
buffering agent.
19. The method of claim 1, wherein the aqueous packaging solution
coats the ophthalmic device more uniformly than that of a similar
aqueous packaging solution in which the non-ionic polyol is not
present in the aqueous packaging solution.
20. The method of claim 1, further comprising hermetically sealing
the ophthalmic device and the aqueous packaging solution in the
package.
21. The method of claim 20, wherein heat sterilization is performed
subsequent to sealing of the package.
22. The method of claim 1, wherein the aqueous packaging solution
does not contain an effective disinfecting amount of a disinfecting
agent.
23. The method of claim 1, wherein the aqueous packaging solution
does not contain a germicide compound.
24. A packaging system for the storage of an ophthalmic device
comprising a sealed container containing one or more unused
ophthalmic devices immersed in an aqueous packaging solution
comprising an anionic polymer and a non-ionic polyol, wherein the
aqueous packaging solution has an osmolality of at least about 200
mOsm/kg, a pH of about 6 to about 9 and is heat sterilized.
25. The packaging system of claim 24, wherein the ophthalmic device
is a contact lens.
26. The packaging system of claim 24, wherein the ophthalmic device
comprises a polymerization product of a monomeric mixture
comprising one or more silicone-containing monomers.
27. The packaging system of claim 24, wherein the anionic polymer
possesses a Mark-Houwink Constant of greater than 0.6.
28. The packaging system of claim 24, wherein the anionic polymer
possesses a Mark-Houwink Constant of greater than about 1.
29. The packaging system of claim 24, wherein the anionic polymer
possesses a Mark-Houwink Constant of greater than about 1.6.
30. The packaging system of claim 24, wherein the anionic polymer
in the aqueous packaging solution is a carboxy-containing
polysaccharide.
31. The packaging system of claim 30, wherein the
carboxy-containing polysaccharide is selected from the group
consisting of a carboxy-containing cellulose, hyaluronate,
chondroitin sulfate, carboxy-containing guar, alginate, pectin,
xanthan and mixtures thereof.
32. The packaging system of claim 30, wherein the
carboxy-containing polysaccharide is a carboxymethylcellulose.
33. The packaging system of claim 24, wherein the anionic polymer
has a degree of substitution value of about 0.5 to about 1.5.
34. The packaging system of claim 24, wherein the concentration of
the anionic polymer in the aqueous packaging solution is about 0.01
to about 10% w/w.
35. The packaging system of claim 24, wherein the non-ionic polyol
is selected from the group consisting of glycerin, ethylene glycol,
poly(ethylene glycol), propylene glycol, monosaccarides,
disaccharides, oligopolysaccharides or polysaccharides and mixtures
thereof.
36. The packaging system of claim 24, wherein the anionic polymer
is a carboxymethylcellulose and the non-ionic polyol is
glycerin.
37. The packaging system of claim 24, wherein the aqueous packaging
solution further comprises a buffering agent.
38. The packaging system of claim 24, wherein the aqueous packaging
solution coats the ophthalmic device more uniformly than that of a
similar aqueous packaging solution in which the non-ionic polyol is
not present in the solution.
39. The packaging system of claim 24, wherein package is heat
sterilized subsequent to sealing of the package.
40. The packaging system of claim 24, wherein the solution does not
contain an effective disinfecting amount of a disinfecting
agent.
41. The packaging system of claim 24, wherein the aqueous packaging
solution does not contain a germicide compound.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Technical Field
[0002] The present invention generally relates to packaging
solutions for ophthalmic devices such as contact lenses.
[0003] 2. Description of Related Art
[0004] Blister-packs and glass vials are typically used to
individually package each soft contact lens for sale to a customer.
Saline or deionized water is commonly used to store the lens in the
blister-packs, as mentioned in various patents related to the
packaging or manufacturing of contact lenses. Because lens material
may tend to stick to itself and to the lens package, packaging
solutions for blister-packs have sometimes been formulated to
reduce or eliminate lens folding and sticking. For this reason,
poly(vinyl alcohol) (PVA) has been used in contact lens packaging
solutions.
[0005] It has been stated that if a lens is thoroughly cleaned
before insertion, lacrimal fluid can adequately wet the lens.
Furthermore, the difficulties of adding a surfactant to a packaging
solution, including the possibility of lowering shelf-life and/or
adverse reactions during heat sterilization, have further limited
the use of surfactants in a packaging solution for the purpose of
providing any possible or marginal effect on lens comfort. It is
only after a lens has been worn, when proteins or other deposits
have formed on the surface of the lens, that surfactants have been
used in standard lens-care solutions.
[0006] It is highly desirable that contact lens be as comfortable
as possible for wearers. Manufacturers of contact lenses are
continually working to improve the comfort of the lenses.
Nevertheless, many people who wear contact lenses still experience
dryness or eye irritation throughout the day and particularly
towards the end of the day. An insufficiently wetted lens at any
point in time will cause significant discomfort to the lens wearer.
Although wetting drops can be used as needed to alleviate such
discomfort, it would certainly be desirable if such discomfort did
not arise in the first place.
[0007] U.S. Pat. No. 5,882,687 discloses a package containing a
contact lens suitable for immediate use which comprises (a) a
solution comprising a soluble polyanionic component and having a
viscosity of less than 50 cps at 25.degree. C., an osmolality of at
least about 200 mOsm/kg and a pH in the range of about 6 to about
9; (b) at least one contact lens, and (c) a container for holding
the solution and contact lens sufficient to preserve the sterility
of the solution and contact lens, wherein the solution contains no
additional disinfectant component. However, a polyanion such as
carboxymethylcellulose alone can possess a shape of a sphere or
random coil and has a Mark-Houwink Constant (.alpha.) of 0 when in
the shape of a sphere and 0.5 to 0.8 when in the shape of a random
coil. This type of polyanion may not coat uniformly a surface of a
contact lens, resulting in the lens being relatively uncomfortable
during use.
[0008] Accordingly, it would be desirable to provide an improved
packaging system for ophthalmic devices such as an ophthalmic lens
that the lens would be comfortable to wear in actual use and allow
for extended wear of the lens without irritation or other adverse
effects to the cornea.
SUMMARY OF THE INVENTION
[0009] In accordance with one embodiment of the present invention,
a method of preparing a package comprising a storable, sterile
ophthalmic device is provided comprising:
[0010] (a) immersing an ophthalmic device in an aqueous packaging
solution comprising an anionic polymer and a non-ionic polyol,
wherein the aqueous packaging solution has an osmolality of at
least about 200 mOsm/kg and a pH in the range of about 6 to about
9;
[0011] (b) packaging the solution and the device in a manner
preventing contamination of the device by microorganisms; and
[0012] (c) sterilizing the packaged solution and device.
[0013] In accordance with a second embodiment of the present
invention, a method for packaging and storing a contact lens is
provided comprising, prior to delivery of the contact lens to the
customer-wearer, immersing the contact lens in an aqueous packaging
solution inside a package and heat sterilizing the solution,
wherein the aqueous packaging solution comprises an anionic polymer
and a non-ionic polyol, wherein the aqueous packaging solution has
an osmolality of at least about 200 mOsm/kg and a pH of about 6 to
about 9.
[0014] In accordance with a third embodiment of the present
invention, a packaging system for the storage of an ophthalmic
device is provided comprising a sealed container containing one or
more unused ophthalmic devices immersed in an aqueous packaging
solution comprising an anionic polymer and a non-ionic polyol,
wherein the aqueous packaging solution has an osmolality of at
least about 200 mOsm/kg, a pH of about 6 to about 9 and is heat
sterilized.
[0015] In accordance with a fourth embodiment of the present
invention, a packaging system for the storage of an ophthalmic
device is provided comprising:
[0016] (a) an aqueous packaging solution comprising an anionic
polymer and a non-ionic polyol, wherein the aqueous packaging
solution has an osmolality of at least about 200 mOsm/kg and a pH
in the range of about 6 to about 9;
[0017] (b) at least one ophthalmic device; and
[0018] (c) a container for holding the solution and ophthalmic
device sufficient to preserve the sterility of the solution and
ophthalmic device, wherein the solution does not contain an
effective disinfecting amount of a disinfecting agent.
[0019] By combining a non-ionic polyol with an anionic polymer such
as an anionic carboxymethylcellulose to form an aqueous packaging
solution, a more uniform coating of the anionic polymer may be
obtained. It is believed that the Mark-Houwink Constant (.alpha.)
of the anionic polymer increases to a level resulting in a coating
that is more uniform over the lens, and hydrogen bonding of the
anionic polymer is more effective. Thus, the lens will be more
comfortable to wear in actual use and may allow for the extended
wear of the lens without irritation or other adverse effects to the
cornea.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] The present invention provides a packaging system for the
storage of ophthalmic devices intended for direct contact with body
tissue or body fluid. As used herein, the term "ophthalmic device"
refers to devices that reside in or on the eye. These lenses can
provide optical correction, wound care, drug delivery, diagnostic
functionality or cosmetic enhancement or effect or a combination of
these properties. Representative examples of such devices include,
but are not limited to, soft contact lenses, e.g., a soft, hydrogel
lens; soft, non-hydrogel lens and the like, hard contact lenses,
e.g., a hard, gas permeable lens material and the like, intraocular
lenses, overlay lenses, ocular inserts, optical inserts and the
like. As is understood by one skilled in the art, a lens is
considered to be "soft" if it can be folded back upon itself
without breaking. Any material known to produce an ophthalmic
device including a contact lens can be used herein. It is
particularly useful to employ biocompatible materials herein
including both soft and rigid materials commonly used for
ophthalmic lenses, including contact lenses. The preferred
substrates are hydrogel materials, including silicone hydrogel
materials and non-silicone hydrogel materials.
[0021] A wide variety of materials can be used herein. Hydrogels in
general are a well-known class of materials that comprise hydrated,
crosslinked polymeric systems containing water in an equilibrium
state. Hydrogel contact lens materials are made from at least one
hydrophilic monomer, such as 2-hydroxethyl methacrylate (HEMA),
N-vinylpyrrolidone (NVP) or N,N-dimethylacrylamide (DMA). Hydrogels
generally have a water content greater than about 15 weight percent
and more commonly between about 20 to about 80 weight percent.
[0022] One class of hydrogels is silicone hydrogels. These
materials are usually prepared by polymerizing a mixture containing
at least one silicone-containing monomer and at least one
hydrophilic monomer. Typically, either the silicone-containing
monomer or the hydrophilic monomer functions as a crosslinking
agent (a crosslinker being defined as a monomer having multiple
polymerizable functionalities) or a separate crosslinker may be
employed. Applicable silicone-containing monomeric units for use in
the formation of silicone hydrogels are well known in the art and
numerous examples are provided in U.S. Pat. Nos. 4,136,250;
4,153,641; 4,740,533; 5,034,461; 5,070,215; 5,260,000; 5,310,779;
and 5,358,995.
[0023] Representative examples of applicable silicon-containing
monomeric units include bulky siloxanyl monomers represented by the
structure of Formula I:
##STR00001##
wherein X denotes --O-- or --NR--; each R.sup.1 independently
denotes hydrogen or methyl; each R.sup.2 independently denotes a
lower alkyl radical, phenyl radical or a group represented by
##STR00002##
wherein each R.sup.2' independently denotes a lower alkyl or phenyl
radical; and h is 1 to 10.
[0024] Examples of bulky monomers are
3-methacryloyloxypropyltris(trimethyl-siloxy)silane or
tris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred
to as TRIS and tris(trimethylsiloxy)silylpropyl vinyl carbamate,
sometimes referred to as TRIS-VC and the like.
[0025] Such bulky monomers may be copolymerized with a silicone
macromonomer, such as a poly(organosiloxane) capped with an
unsaturated group at two or more ends of the molecule. U.S. Pat.
No. 4,153,641 discloses, for example, various unsaturated groups
such as acryloyloxy or methacryloyloxy groups.
[0026] Another class of representative silicone-containing monomers
includes, but is not limited to, silicone-containing vinyl
carbonate or vinyl carbamate monomers such as, for example,
1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;
3-(trimethylsilyl)propyl vinyl carbonate;
3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;
t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl
vinyl carbonate; trimethylsilylmethyl vinyl carbonate and the like
and mixtures thereof.
[0027] Another class of silicon-containing monomers includes
polyurethane-polysiloxane macromonomers (also sometimes referred to
as prepolymers), which may have hard-soft-hard blocks like
traditional urethane elastomers. They may be end-capped with a
hydrophilic monomer such as 2-hydroxyethyl methacrylate (HEMA).
Examples of such silicone urethanes are disclosed in a variety or
publications, including PCT Published Application No. WO 96/31792
discloses examples of such monomers, which disclosure is hereby
incorporated by reference in its entirety. Representative examples
of silicone urethane monomers are represented by Formulae II and
III:
E(*D*A*D*G).sub.a*D*A*D*E'; or (II)
E(*D*G*D*A).sub.a*D*A*D*E'; or (III)
wherein:
[0028] D independently denotes an alkyl diradical, an alkyl
cycloalkyl diradical, a cycloalkyl diradical, an aryl diradical or
an alkylaryl diradical having 6 to about 30 carbon atoms;
[0029] G independently denotes an alkyl diradical, a cycloalkyl
diradical, an alkyl cycloalkyl diradical, an aryl diradical or an
alkylaryl diradical having 1 to about 40 carbon atoms and which may
contain ether, thio or amine linkages in the main chain;
[0030] * denotes a urethane or ureido linkage;
[0031] a is at least 1;
[0032] A independently denotes a divalent polymeric radical of
Formula IV:
##STR00003##
wherein each R.sup.s independently denotes an alkyl or
fluoro-substituted alkyl group having 1 to about 10 carbon atoms
which may contain ether linkages between the carbon atoms; m' is at
least 1; and p is a number that provides a moiety weight of about
400 to about 10,000;
[0033] each of E and E' independently denotes a polymerizable
unsaturated organic radical represented by Formula V:
##STR00004##
wherein: R.sup.3 is hydrogen or methyl;
R.sup.4 is hydrogen, an alkyl radical having 1 to 6 carbon atoms,
or a --O--Y--R.sup.6 radical wherein Y is --O--, --S-- or
--NH--;
R.sup.5 is a divalent alkylene radical having 1 to about 10 carbon
atoms;
R.sup.6 is a alkyl radical having 1 to about 12 carbon atoms;
X denotes O-- or --OCO--;
Z denotes --O-- or --NH--;
Ar denotes an aromatic radical having about 6 to about 30 carbon
atoms;
[0034] w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.
[0035] A preferred silicone-containing urethane monomer is
represented by
##STR00005##
wherein m is at least 1 and is preferably 3 or 4, a is at least 1
and preferably is 1, p is a number which provides a moiety weight
of about 400 to about 10,000 and is preferably at least about 30,
R.sup.7 is a diradical of a diisocyanate after removal of the
isocyanate group, such as the diradical of isophorone diisocyanate,
and each E'' is a group represented by:
##STR00006##
[0036] In another embodiment of the present invention, a silicone
hydrogel material comprises (in bulk, that is, in the monomer
mixture that is copolymerized) about to about 50 percent, and
preferably about 10 to about 25, by weight of one or more silicone
macromonomers, about 5 to about 75 percent, and preferably about 30
to about 60 percent, by weight of one or more polysiloxanylalkyl
(meth)acrylic monomers, and about 10 to about 50 percent, and
preferably about 20 to about 40 percent, by weight of a hydrophilic
monomer. In general, the silicone macromonomer is a
poly(organosiloxane) capped with an unsaturated group at two or
more ends of the molecule. In addition to the end groups in the
above structural formulas, U.S. Pat. No. 4,153,641 discloses
additional unsaturated groups, including acryloyloxy or
methacryloyloxy groups. Fumarate-containing materials such as those
disclosed in U.S. Pat. Nos. 5,310,779; 5,449,729 and 5,512,205 are
also useful substrates in accordance with the invention.
Preferably, the silane macromonomer is a silicon-containing vinyl
carbonate or vinyl carbamate or a polyurethane-polysiloxane having
one or more hard-soft-hard blocks and end-capped with a hydrophilic
monomer.
[0037] Suitable hydrophilic monomers include amides such as
N,N-dimethylacrylamide and N,N-dimethylmethacrylamide, cyclic
lactams such as N-vinyl-2-pyrrolidone and poly(alkene glycols)
functionalized with polymerizable groups. Examples of useful
functionalized poly(alkene glycols) include poly(diethylene
glycols) of varying chain length containing monomethacrylate or
dimethacrylate end caps. In a preferred embodiment, the poly(alkene
glycol) polymer contains at least two alkene glycol monomeric
units. Still further examples are the hydrophilic vinyl carbonate
or vinyl carbamate monomers disclosed in U.S. Pat. No. 5,070,215,
and the hydrophilic oxazolone monomers disclosed in U.S. Pat. No.
4,910,277. Other suitable hydrophilic monomers will be apparent to
one skilled in the art.
[0038] In one embodiment, the lens can be a Group II and Group IV
lens having a water content greater than about 50% by weight, and
preferably about 55% to about 80% water, although the invention is
applicable for any type of soft hydrogel contact lens.
Representative contact lens materials include, but are not limited
to materials known by the following USAN and the USAP Dictionary of
Drug Names: bufilcon A, etafilcon A, methafilcon A, ocufilcon C,
perfilcon A, phemfilcon A, vifilcon A, hilafilcon A, hilafilcon B,
balafilcon A, methafilcon B, ocufilcon D, methafilcon A, etafilcon
A lidofilcon A or B, and alphafilcon A.
[0039] The above materials are merely exemplary, and other
materials for use as substrates that can benefit by being packaged
in the aqueous packaging solution according to the present
invention and have been disclosed in various publications and are
being continuously developed for use in ophthalmic devices such as
contact lenses and other medical devices can also be used. For
example, an ophthalmic device for use herein can be a cationic
ophthalmic lens such as a cationic contact lens or the ophthalmic
device can be fluorinated silicone-containing monomers. Such
monomers have been used in the formation of fluorosilicone
hydrogels to reduce the accumulation of deposits on contact lenses
made therefrom, as disclosed in, for example, U.S. Pat. Nos.
4,954,587; 5,010,141 and 5,079,319. The use of silicone-containing
monomers having certain fluorinated side groups, i.e.,
--(CF.sub.2)--H, have been found to improve compatibility between
the hydrophilic and silicone-containing monomeric units. See, e.g.,
U.S. Pat. Nos. 5,321,108 and 5,387,662.
[0040] In another embodiment, the present invention is also
directed to a contact lens for extended-wear or specialty uses,
such as for relatively thick lenses. Extended lenses are lenses
capable of being worn overnight, preferably capable of being worn
for at least one week, most preferably capable of wear for a
continuous period of one week to one month. By "capable" is meant
lenses approved by one or more governmental regulatory authorities
for such consumer use, for example, the U.S. Food & Drug
Administration (USFDA) in the U.S. or its equivalent in other
countries.
[0041] Extended-wear lenses require relatively high oxygen
permeability. The oxygen-permeability is the rate at which oxygen
will pass through a material. The oxygen-permeability Dk of a lens
material does not depend on lens thickness. Oxygen permeability is
measured in terms of barrers which have the following units of
measurement:
[0042] On the other hand, the oxygen transmissibility of a lens, as
used herein, is the rate at which oxygen will pass through a
specific lens. Oxygen transmissibility, Dk/t, is conventionally
expressed in units of barrers/mm, where t is the average thickness
of the material (in units of mm) over the area being measured. For
example, a lens having a Dk of about 90 barrers
(oxygen-permeability barrers) and a thickness of about 90 microns
(about 0.090 mm) would have a Dk/t or about 100 barrers/mm (oxygen
transmissibility barrers/mm).
[0043] Ophthalmic devices such as contact lenses for application of
the present invention can be manufactured employing various
conventional techniques, to yield a shaped article having the
desired posterior and anterior lens surfaces. Spincasting methods
are disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545; preferred
static casting methods are disclosed in U.S. Pat. Nos. 4,113,224
and 4,197,266. Curing of the monomeric mixture is often followed by
a machining operation in order to provide a contact lens having a
desired final configuration. As an example, U.S. Pat. No. 4,555,732
discloses a process in which an excess of a monomeric mixture is
cured by spincasting in a mold to form a shaped article having an
anterior lens surface and a relatively large thickness. The
posterior surface of the cured spincast article is subsequently
lathe cut to provide a contact lens having the desired thickness
and posterior lens surface. Further machining operations may follow
the lathe cutting of the lens surface, for example, edge-finishing
operations.
[0044] After producing a lens having the desired final shape, it is
desirable to remove residual solvent from the lens before
edge-finishing operations. This is because, typically, an organic
diluent is included in the initial monomeric mixture in order to
minimize phase separation of polymerized products produced by
polymerization of the monomeric mixture and to lower the glass
transition temperature of the reacting polymeric mixture, which
allows for a more efficient curing process and ultimately results
in a more uniformly polymerized product. Sufficient uniformity of
the initial monomeric mixture and the polymerized product are of
particular concern for silicone hydrogels, primarily due to the
inclusion of silicone-containing monomers which may tend to
separate from the hydrophilic comonomer. Suitable organic diluents
include, for example, monohydric alcohols such as C.sub.6-C.sub.10
straight-chained aliphatic monohydric alcohols, e.g., n-hexanol and
n-nonanol; diols such as ethylene glycol; polyols such as glycerin;
ethers such as diethylene glycol monoethyl ether; ketones such as
methyl ethyl ketone; esters such as methyl enanthate; and
hydrocarbons such as toluene. Preferably, the organic diluent is
sufficiently volatile to facilitate its removal from a cured
article by evaporation at or near ambient pressure. Generally, the
diluent is included at about 5 to about 60 percent by weight of the
monomeric mixture, with about 10 to about 50 percent by weight
being especially preferred.
[0045] The cured lens is then subjected to solvent removal, which
can be accomplished by evaporation at or near ambient pressure or
under vacuum. An elevated temperature can be employed to shorten
the time necessary to evaporate the diluent. The time, temperature
and pressure conditions for the solvent removal step will vary
depending on such factors as the volatility of the diluent and the
specific monomeric components, as can be readily determined by one
skilled in the art. According to a preferred embodiment, the
temperature employed in the removal step is preferably at least
about 50.degree. C., for example, about 60.degree. C. to about
80.degree. C. A series of heating cycles in a linear oven under
inert gas or vacuum may be used to optimize the efficiency of the
solvent removal. The cured article after the diluent removal step
should contain no more than twenty percent by weight of diluent,
preferably no more than about 5 percent by weight or less.
[0046] Following removal of the organic diluent, the lens can then
be subjected to mold release and optional machining operations. The
machining step includes, for example, buffing or polishing a lens
edge and/or surface. Generally, such machining processes may be
performed before or after the article is released from a mold part.
Preferably, the lens is dry released from the mold by employing
vacuum tweezers to lift the lens from the mold, after which the
lens is transferred by means of mechanical tweezers to a second set
of vacuum tweezers and placed against a rotating surface to smooth
the surface or edges. The lens may then be turned over in order to
machine the other side of the lens
[0047] Next, the ophthalmic device will be immersed in an aqueous
packaging solution containing at least an anionic polymer and a
non-ionic polyol and stored in a packaging system according to the
present invention. Generally, a packaging system for the storage of
an ophthalmic device according to the present invention includes at
least a sealed container containing one or more unused ophthalmic
devices immersed in an aqueous packaging solution. Preferably, the
sealed container is a hermetically sealed blister-pack, in which a
concave well containing a contact lens is covered by a metal or
plastic sheet adapted for peeling in order to open the
blister-pack. The sealed container may be any suitable generally
inert packaging material providing a reasonable degree of
protection to the lens, preferably a plastic material such as
polyalkylene, PVC, polyamide, and the like.
[0048] Any suitable anionic polymer may be employed in accordance
with the present invention provided that it functions as described
herein and has no substantial detrimental effect on the ophthalmic
device such as a contact lens being stored or on the wearer of the
lens. The anionic polymer is preferably ophthalmically acceptable
at the concentrations used. The anionic polymer can include two (2)
or more anionic (or negative) charges, preferably three (3) or more
anionic (or negative) charges and most preferably ten (10) or more
anionic (or negative) charges. As one skilled in the art will
readily appreciate, the anionic polymer can include multiple
charges in the same unit of the polymer or can include one or more
charges on different repeating units in the polymer. Particularly
useful anionic polymers are those which are water soluble, for
example, soluble at the concentrations used in the presently useful
liquid aqueous media, such as a liquid aqueous medium containing
the anionic polymer. Particularly useful anionic polymers are those
which are not eliminated during terminal sterilization of the
packaged lenses.
[0049] In one embodiment, a class of anionic polymers includes one
or more polymeric materials having multiple anionic charges. In one
embodiment, an anionic polymer is an anionic polysaccharide.
Representative examples of suitable anionic polymers for use herein
include, but are not limited to, hyaluronic acid or a derivative
thereof and/or salts thereof; carboxymethylcelluloses;
carboxymethylhydroxyethylcelluloses; carboxymethylstarch;
carboxymethylhydroxyethylstarch; hydrolyzed polyacrylamides;
hydrolyzed polyacrylonitriles; heparin; heparin sulfate,
homopolymers and copolymers of one or more acrylic and methacrylic
acids, acrylates and methacrylates; alginic acid or a derivative
thereof and/or salts thereof; vinylsulfonic acid or a derivative
thereof and/or salts thereof; polymers of amino acids such as
polymers of aspartic acid, glutamic acid and the like or a
derivative thereof and/or salts thereof; p-styrenesulfonic acid and
the like or a derivative thereof and/or salts thereof;
2-methacryloyloxyethylsulfonic acids or a derivative thereof and/or
salts thereof; 3-methacryloyloxy-2-hydroxypropylsulfonic acids or a
derivative thereof and/or salts thereof;
2-acrylamido-2-methylpropanesulfonic acids or a derivative thereof
and/or salts thereof; allylsulfonic acid or a derivative thereof
and/or salts thereof; and the like and mixtures thereof. In one
embodiment, an anionic polymer is an anionic polysaccharide. In
another embodiment, an anionic polymer includes one or more of
poly(acrylic acid), poly(methacrylic acid), polysaccharides,
alginic acid, pectinic acid, carboxymethylcellulose, hyaluronic
acid, heparin, heparin sulfate, carboxymethylchitosan,
carboxymethylstarch, carboxymethyldextran, chondroitin sulfate,
carboxymethylguar, any salts thereof, and mixtures thereof. The
above list is intended for illustrative purposes only and not to
limit the scope of the present invention. Such polymers are known
to those of skill in the art.
[0050] In another embodiment, an anionic polymer includes one or
more cellulose derivative, anionic polymers derived from acrylic
acid (e.g., polymers derived from acrylic acid, acrylates and the
like and mixtures thereof), anionic polymers derived from
methacrylic acid (e.g., polymers derived from methacrylic acid,
methacrylates, and the like and mixtures thereof), anionic polymers
derived from alginic acid (e.g., polymers derived from alginic
acid, alginates, and the like and mixtures thereof), anionic
polymers derived from amino acids (e.g., polymers derived from
amino acids, amino acid salts, and the like and mixtures thereof)
and mixtures thereof. Particularly useful anionic polymers for use
herein include cellulose polymers such as
carboxymethylcelluloses.
[0051] The anionic polymer for use herein can have a Mark-Houwink
Constant greater than 0.6, preferably greater than about 1 and more
preferably greater than about 1.6. In one embodiment, the anionic
polymer can have a Mark-Houwink Constant between about 1 to about
1.4. The Mark-Houwink constant (.alpha.) is calculated using the
technique disclosed in Introduction to Physical Polymer Science,
Third Edition, L. H. Sperling, Wiley-Interscience, A John Wiley
& Sons, Inc., Publication, New York, 2001. Interpretation of
the Mark-Houwink constant for CMC is illustrated below in Table
1:
TABLE-US-00001 TABLE 1 Values of the Mark-Houwink Constants
(.alpha.) Mark-Houwink Constants (.alpha.) Interpretation 0 Spheres
0.5 0.8 Random coils 1.0 Stiff coils 2.0 Rods
[0052] A Mark-Houwink Constant of zero is indicative of a spherical
polymeric structure. A Mark-Houwink Constant between 0.5 and 0.8
indicates a physical configuration described as random coils. A
Mark-Houwink Constant above 0.8 indicates a structure that is more
ordered than random approaching a stiff coil. A Mark-Houwink
Constant of about 1.0 is a stiff coil and a Mark-Houwink Constant
of 2.0 represents a rod-like structure.
[0053] In one embodiment, the carboxy-containing polymer is an
anionic carboxy-containing polysaccharide. Suitable polysaccharides
of the present invention include carboxy-containing polysaccharides
such as, for example, a carboxy-containing cellulose, hyaluronate,
chondroitin sulfate, algin, pectin and xanthan. The anionic polymer
could also be derived from carboxy-containing vinyl polymers, such
as carbomers, poly(acrylic acid and poly(methacrylic acid), and
derivatives thereof, or from anionic polypeptides, such as
poly(glutamic acid) and poly(aspartic acid), and derivatives
thereof.
[0054] In one embodiment, the average molecular weight of an
anionic carboxy-containing polymer is a minimum of about 90 kDa and
a maximum of about 700 kDa. Generally, the average molecular weight
of the anionic carboxy-containing polymer is a minimum of about 150
kDa, preferably a minimum of about 200 kDa, and more preferably a
minimum of about 250. The average molecular weight of the anionic
carboxy-containing polymer is a maximum of about 650 kDa,
preferably a maximum of about 600 kDa, more preferably a maximum of
about 550 kDa and most preferably a maximum of about 500 kDa.
[0055] The amount of the anionic polymer present in the aqueous
packaging solution is that amount effective to improve the surface
properties of the ophthalmic device when combined with a non-ionic
polyol. Preferably, the anionic polymer is present in the packaging
solution of the invention in an amount of at least about 0.01% w/v.
The specific amount of such anionic polymers used can vary widely
depending on a number of factors, for example, the specific anionic
polymer and non-ionic polyol being employed. Generally, the
concentration of the anionic polymer is from about 0.01 to about
10% w/w and preferably from about 0.5 to about 1.5% w/w.
[0056] It is likewise preferable that the anionic polymer have a
degree of substitution value that is a minimum of about 0.5 and a
maximum of about 1.5. Preferably, the anionic polymer can have a
degree of substitution value that is a minimum of about 0.9 to a
maximum of about 1.1.
[0057] In one embodiment, the non-ionic polyol for use herein can
be a non-ionic polyol containing 2 to about 12 carbon atoms and
preferably 2 to 4 carbon atoms and from 2 to 6 hydroxyl groups.
Representative examples of such non-ionic polyols include glycerin,
ethylene glycol, poly(ethylene glycol), propylene glycol, sorbitol,
mannitol, monosaccharides, disaccharides, and neutral
oligo-polysaccharides, such as from methylcellulose,
hydroxypropylmethylcellulose, guar, hydroxypropylguar, and
oligomers of poly(vinyl alcohol) and derivatives thereof, and the
like and mixtures thereof. In one embodiment, a non-ionic polyol
can be glycerin, ethylene glycol, propylene glycol, sorbitol,
mannitol, monosaccharides and mixtures thereof. In another
embodiment, the non-ionic polyol can be disaccharides,
oligosaccharides, poly(ethylene glycol) and mixtures thereof. In a
preferred embodiment, the non-ionic polyol is glycerin.
[0058] The amount of non-ionic polyol present in the aqueous
packaging solution will generally be an amount sufficient to
increase the Mark-Houwink Constant of the anionic polymer in the
solution such that a relatively more uniform coating can be formed
on the surface of the device when packaged in a solution according
to the present invention. In general, the concentration of the
non-ionic polyol in the solution will ordinarily range from about
0.01 to about 10% w/w and preferably from about 0.5 to about 3%
w/w.
[0059] The aqueous packaging solutions according to the present
invention are physiologically compatible. Specifically, the
solution must be "ophthalmically safe" for use with a lens such as
a contact lens, meaning that a contact lens treated with the
solution is generally suitable and safe for direct placement on the
eye without rinsing, that is, the solution is safe and comfortable
for daily contact with the eye via a contact lens that has been
wetted with the solution. An ophthalmically safe solution has a
tonicity and pH that is compatible with the eye and includes
materials, and amounts thereof, that are non-cytotoxic according to
ISO standards and U.S. Food & Drug Administration (FDA)
regulations. The solution should be sterile in that the absence of
microbial contaminants in the product prior to release must be
statistically demonstrated to the degree necessary for such
products. The liquid media useful in the present invention are
selected to have no substantial detrimental effect on the lens
being treated or cared for and to allow or even facilitate the
present lens treatment or treatments. The liquid media are
preferably aqueous-based. A particularly useful aqueous liquid
medium is that derived from saline, for example, a conventional
saline solution or a conventional buffered saline solution.
[0060] The pH of the present aqueous packaging solutions should be
maintained within the range of about 6.0 to about 9, and preferably
about 6.5 to about 7.8. Suitable buffers may be added, such as
boric acid, sodium borate, potassium citrate, citric acid, sodium
bicarbonate, tris(hydroxymethyl)aminomethane, and various mixed
phosphate buffers, e.g., combinations of Na.sub.2HPO.sub.4,
NaH.sub.2PO.sub.4 and KH.sub.2PO.sub.4, and the like and mixtures
thereof. Generally, buffers will be used in amounts ranging from
about 0.05 to about 2.5% by weight, and preferably from about 0.1
to about 1.5% by weight of the solution.
[0061] Typically, the aqueous packaging solutions of the present
invention are also adjusted with tonicity agents, to approximate
the osmotic pressure of normal lacrimal fluids. The solutions are
made substantially isotonic with physiological saline used alone or
in combination, otherwise if simply blended with sterile water and
made hypotonic or made hypertonic the lenses will lose their
desirable optical parameters. Correspondingly, excess saline may
result in the formation of a hypertonic solution which will cause
stinging and eye irritation.
[0062] Examples of suitable tonicity adjusting agents include, but
are not limited to, sodium and potassium chloride, dextrose,
glycerin, calcium and magnesium chloride and the like and mixtures
thereof. These agents are typically used individually in amounts
ranging from about 0.01 to about 2.5% w/v and preferably from about
0.2 to about 1.5% w/v. Generally, a 0.9% solution of sodium
chloride is equivalent in osmolality to a 3 percent of glycerol
solution or a 5 percent solution of monosaccharide, so the amount
of a specific agent will vary depending on the agent used.
Preferably, the tonicity agent will be employed in an amount to
provide a final osmotic value of at least about 200 mOsm/kg,
preferably from about 200 to about 400 mOsm/kg, and more preferably
from about 250 to about 350 mOsm/kg.
[0063] If desired, one or more additional components can be
included in the aqueous packaging solutions. Such additional
component or components are chosen to impart or provide at least
one beneficial or desired property to the packaging solution. Such
additional components may be selected from components which are
conventionally used in one or more ophthalmic device care
compositions. Examples of such additional components include
cleaning agents, wetting agents, nutrient agents, sequestering
agents, viscosity builders, contact lens conditioning agents,
antioxidants, and the like and mixtures thereof. These additional
components may each be included in the packaging solutions in an
amount effective to impart or provide the beneficial or desired
property to the packaging solutions. For example, such additional
components may be included in the packaging solutions in amounts
similar to the amounts of such components used in other, e.g.,
conventional, contact lens care products.
[0064] Useful sequestering agents include, but are not limited to,
disodium ethylenediaminetetraacetic acid (EDTA), alkali metal
hexametaphosphate, citric acid, sodium citrate and the like and
mixtures thereof.
[0065] Useful viscosity builders include, but are not limited to,
hydroxyethylcellulose, methylcellulose,
hydroxypropylmethylcellulose, poly(N-vinylpyrrolidone), guar,
hydroxyethylguar, hydroxypropylguar, poly(vinyl alcohol) and the
like and mixtures thereof.
[0066] Useful antioxidants include, but are not limited to, sodium
metabisulfite, sodium thiosulfate, N-acetylcysteine, butylated
hydroxyanisole, butylated hydroxytoluene and the like and mixtures
thereof.
[0067] The method of packaging and storing an ophthalmic device
such as a contact lens according to the present invention includes
at least packaging an ophthalmic device immersed in the aqueous
packaging solution described above. The method may include
immersing the ophthalmic device in an aqueous solution prior to
delivery to the customer/wearer, directly following manufacture of
the device. Alternately, the packaging and storing in the solution
of the present invention may occur at an intermediate point before
delivery to the ultimate customer (wearer) but following
manufacture and transportation of the lens in a dry state, wherein
the dry lens is hydrated by immersing the lens in the aqueous
packaging solution. Consequently, a package for delivery to a
customer may include a sealed container containing one or more
unused contact lenses immersed in an aqueous packaging solution
according to the present invention.
[0068] In one embodiment, the steps leading to the present
ophthalmic lens packaging system includes (1) molding an ophthalmic
lens in a mold comprising a posterior and anterior mold portion,
(2) removing the lens from the mold and hydrating the lens, (3)
introducing the aqueous packaging solution with the anionic polymer
and non-ionic polyol into the container with the lens supported
therein, and (4) sealing the container. Preferably, the method also
includes the step of sterilizing the contents of the container.
Sterilization may take place prior to, or most conveniently after,
sealing of the container and may be effected by any suitable method
known in the art, e.g., by autoclaving of the sealed container and
its contents at temperatures of about 120.degree. C. or higher.
[0069] The following examples are provided to enable one skilled in
the art to practice the invention and are merely illustrative of
the invention. The examples should not be read as limiting the
scope of the invention as defined in the claims.
EXAMPLE 1
[0070] A clean hilafilcon A lens, which is a copolymer composed
mainly of HEMA and NVP, was soaked in a lens packaging solution
within the scope of the present invention overnight and autoclaved
for 30 minutes at 121.degree. C. The ingredients and amounts of the
solution are set forth in Table 2. The carboxymethylcellulose was a
medium viscosity (MV) grade (viscosity no greater than 30 cp). The
XPS results for the lens are set forth below in Table 4.
TABLE-US-00002 TABLE 2 Ingredients % w/w Sodium borate 0.215 Boric
acid 1.000 Ethylenediaminetetraacetic 0.050 acid (EDTA)
Carboxymethylcellulose 1.000 (MV) Glycerin 1.000 pH = 7.16
Osmolality = 347 mOsm/kg
COMPARATIVE EXAMPLE A
[0071] A clean hilafilcon A lens as used in Example 1 was soaked in
a lens packaging solution outside the scope of the invention
overnight and autoclaved for 30 minutes at 121.degree. C. The
ingredients and amounts of the solution are set forth in Table 3.
The XPS results for the lens are set forth below in Table 4.
TABLE-US-00003 TABLE 3 Ingredients % w/w Sodium borate 0.215 Boric
acid 1.000 EDTA 0.050 Carboxymethylcellulose 1.000 (MV) pH = 7.49
Osmolality = 237 mOsm/kg
Testing
[0072] Sample specimens prepared in Example 1 and Comparative
Example A were analyzed for its atomic concentration by XPS and
compared to a clean hilafilcon A lens rich in HEMA and NVP content
which was not soaked in a packaging solution and autoclaved. The
X-ray Photoelectron Spectrometer (XPS) utilized in this study was a
Physical Electronics [PHI] Model 5600. This instrument utilized an
aluminum anode operated at 300 watts, 15 kV and 27 milliamps. The
excitation source was monochromatized utilizing a torodial lens
system. The 7 mm filament was utilized for the polymer analysis due
to the reduced sample damage and ease of photoionization
neutralization. The base pressure of this instrument was
2.0.times.10.sup.-10 torr while the pressure during operation was
1.0.times.10.sup.-9 torr. This instrument made use of a
hemispherical energy analyzer. The practical measure of sampling
depth for this instrument at a sampling angle of 45.degree. and
with respect to carbon was approximately 74 angstroms. All elements
were charge corrected to the CH.sub.x peak of carbon to a binding
energy of 285.0 electron volts (eV).
[0073] Each of the specimens was analyzed utilizing a low
resolution survey spectra [0-1100 eV] to identify the elements
present on the sample surface. The high resolution spectra were
performed on those elements detected from the low resolution scans.
The elemental composition was determined from the high resolution
spectra. The atomic composition was calculated from the areas under
the photoelectron peaks after sensitizing those areas with the
instrumental transmission function and atomic cross sections for
the orbital of interest. Since XPS does not detect the presence of
hydrogen or helium, these elements will not be included in any
calculation of atomic percentages. It is also noted that atomic
percentages may vary if a different instrument design, i.e.,
transmission function, is utilized, so that for purposes of exact
reproducibility the atomic percentage numbers in the application
refer to the specified instrument design, as will be understood by
the skilled artisan.
[0074] The low resolution XPS survey spectra taken at a takeoff
angle of 45.degree. for the untreated lens' surfaces contained
peaks for carbon, nitrogen, oxygen, boron and sodium. The analysis
of the lens' material begins with the examination of the unmodified
matrix (control). Table 4 below contains the XPS data for the
samples. This data reflects the atomic composition over the top 74
angstroms (relative to carbon 1 s electrons). The percentages
reflect all elements except hydrogen and helium.
TABLE-US-00004 TABLE 4 Atomic Concentration Carbon Nitrogen Oxygen
Boron Sodium Cleaned Product 74.6 4.1 21.3 0.0 0.0 Comp. Ex. A 72.9
3.7 22.3 1.1 0.0 Ex. 1 70.2 1.8 25.7 1.4 0.9
[0075] As can be seen from Table 4, the amount of nitrogen in the
lens soaked in a packaging solution containing both an anionic
polymer and a non-ionic polyol of the present invention is
substantially reduced when compared to a lens soaked in a packaging
solution containing only an anionic polymer. The substantial
reduction in the amount of nitrogen present on the lens indicates
that the surface of the lens has been covered with the components
of the packaging solution, thereby providing a more uniform coating
thereon.
[0076] It will be understood that various modifications may be made
to the embodiments disclosed herein. Therefore the above
description should not be construed as limiting, but merely as
exemplifications of preferred embodiments. For example, the
functions described above and implemented as the best mode for
operating the present invention are for illustration purposes only.
Other arrangements and methods may be implemented by those skilled
in the art without departing from the scope and spirit of this
invention. Moreover, those skilled in the art will envision other
modifications within the scope and spirit of the features and
advantages appended hereto.
* * * * *