U.S. patent application number 14/719341 was filed with the patent office on 2015-12-24 for protection of contact lenses from microbial contamination caused by handling.
This patent application is currently assigned to CooperVision International Holding Company, LP. The applicant listed for this patent is CooperVision International Holding Company, LP. Invention is credited to Kathleen Khong, Andrew Luk, Inna Maltseva, Carol Ann Morris.
Application Number | 20150366311 14/719341 |
Document ID | / |
Family ID | 53539735 |
Filed Date | 2015-12-24 |
United States Patent
Application |
20150366311 |
Kind Code |
A1 |
Maltseva; Inna ; et
al. |
December 24, 2015 |
Protection of Contact Lenses from Microbial Contamination Caused by
Handling
Abstract
A sealed contact lens package contains a sterile, unworn contact
lens and a contact lens packaging solution comprising epsilon
polylysine (.epsilon.PLL). The .epsilon.PLL protects the contact
lens from microbial contamination caused by handling the lens when
it is removed from its package.
Inventors: |
Maltseva; Inna; (San
Francisco, CA) ; Morris; Carol Ann; (Pleasanton,
CA) ; Khong; Kathleen; (Milpitas, CA) ; Luk;
Andrew; (Pleasanton, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CooperVision International Holding Company, LP |
St. Michael |
|
BB |
|
|
Assignee: |
CooperVision International Holding
Company, LP
St. Michael
BB
|
Family ID: |
53539735 |
Appl. No.: |
14/719341 |
Filed: |
May 22, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62014348 |
Jun 19, 2014 |
|
|
|
Current U.S.
Class: |
206/205 ;
53/472 |
Current CPC
Class: |
B65D 81/22 20130101;
A45C 11/005 20130101; C11D 3/3719 20130101; C11D 3/0078 20130101;
B65B 25/008 20130101 |
International
Class: |
A45C 11/00 20060101
A45C011/00; B65B 25/00 20060101 B65B025/00; B65D 81/22 20060101
B65D081/22 |
Claims
1. A sealed contact lens package comprising a sterile, unworn
contact lens and a contact lens packaging solution comprising
epsilon polylysine (.epsilon.PLL), wherein the unworn contact lens
exhibits reduced contamination from at least one microbe, wherein
said reduced contamination is determined by a test where
Pseudomonas aeruginosa (PA) introduced to the lens during removal
from the contact lens packaging solution compared to a control
contact lens packaged in an identical contact lens packaging
solution but without said .epsilon.PLL, and wherein the unworn
contact less results in less than a two log kill of PA compared to
the control contact lens when tested after 24 hours incubation with
10.sup.4 CFU PA using an in vitro bioactivity assay.
2. The package of claim 1, wherein the contact lens is a silicone
hydrogel contact lens.
3. The package of claim 1, wherein the contact lens is a non-ionic
contact lens.
4. The package of claim 1, wherein the contact lens is a daily
disposable contact lens.
5. The package of claim 1, wherein the sealed contact lens package
comprises a plastic base member that comprises a cavity and a
flange region extending outwardly around the cavity, and a
removable foil attached to the flange region.
6. The package of claim 1, wherein the packaging solution comprises
between 5 ppm and 500 ppm .epsilon.PLL.
7. A sealed contact lens package comprising: a) a plastic base
member comprising a cavity which retains a sterile, unworn contact
lens and a contact lens packaging solution comprising epsilon
polylysine (.epsilon.PLL); and b) a resealable cover that forms a
liquid-tight seal with the plastic base member, wherein the unworn
contact lens exhibits reduced contamination from at least one
microbe, wherein said reduced contamination is determined by a test
where Pseudomonas aeruginosa (PA) introduced to the lens during
removal from the contact lens packaging solution compared to a
control contact lens packaged in an identical contact lens
packaging solution but without said .epsilon.PLL.
8. The package of claim 7, wherein the contact lens is a silicone
hydrogel contact lens.
9. The package of claim 7, wherein the contact lens is an ionic
contact lens.
10. The package of claim 7, wherein the contact lens is a daily
wear contact lens.
11. The package of claim 7, wherein the plastic base member
comprises a plurality of threads for engagement with a compatible
set of threads on the resealable cover.
12. The package of claim 7, wherein the packaging solution
comprises between 5 ppm and 500 ppm .epsilon.PLL.
13. The package of claim 1, wherein the at least one microbe is
Pseudomonas aeruginosa.
14. The package of claim 1, wherein the at least one microbe is
Staphylococcus aureus.
15. The package of claim 1, wherein the at least one microbe is a
microbe found in microbial keratitis.
16. A method of manufacturing the sealed contact lens package, said
method comprising: placing an unworn contact lens and a contact
lens packaging solution comprising .epsilon.PLL in a receptacle
configured to receive a contact lens and sealing the receptacle
with a cover to provide a sealed contact lens package, wherein the
unworn contact lens exhibits reduced contamination from at least
one microbe, wherein said reduced contamination is determined by a
test where Pseudomonas aeruginosa (PA) introduced to the lens
during removal from the contact lens packaging solution compared to
a control contact lens packaged in an identical contact lens
packaging solution but without said .epsilon.PLL, and wherein the
unworn contact less results in less than a two log kill of PA
compared to the control contact lens when tested after 24 hours
incubation with 10.sup.4 CFU PA using an in vitro bioactivity assay
and/or wherein the contact lens package comprises a resealable
cover.
17. The method of claim 16, further comprising sterilizing the
unworn contact lens by autoclaving the sealed contact lens package.
Description
[0001] This application claims the benefit under 35 U.S.C.
.sctn.119(e) of prior U.S. Provisional Patent Application No.
62/014,348, filed Jun. 19, 2014, which is incorporated in its
entirety by reference herein.
FIELD
[0002] The field of the invention is contact lenses packages.
BACKGROUND
[0003] Microbial contamination of contact lenses is a serious
public health concern due to its implications in ocular
infiltrates, infections and microbial keratitis. Studies have
demonstrated that lens handling greatly increases the incidence of
microbial contamination of lenses (see e.g. Szczotka-Flynn et al.,
Eye Contact Lens (2010) 36(2):116-29). Daily disposable contact
lens wearers can be particularly at risk for contamination due to
the non-compliant storage of contact lenses after use in their
original packaging solution and subsequent reuse (Boost et al.,
Optom Vis Sci (2011) 88(12:1409-13).
[0004] .epsilon.-polylysine is a homopolymer of about 25-35
residues of L-lysine in which the epsilon-amino and carboxyl groups
of L-Lysine are linked. It is a naturally-occurring polymer
produced by Streptomyces species. It has broad-spectrum
antimicrobial activity and has been widely used as a food
preservative in Japan and as an additive in a variety of consumer
products. The use of .epsilon.-polylysine in contact lens care
solutions has been described (see e.g. U.S. Pat. No. 6,187,264, and
U.S. Pat. Publ. No. 2005/0074467). Antimicrobial hydrogels made
from epsilon-poly-L-lysine-graft-methacrylamide have been reported
(Zhou et al., Biomaterials 32 (2011) 2704-2712).
[0005] Other background publications include co-pending U.S. patent
application Ser. No. 14/109,976, U.S. Pat. Publ. No. 2012/0074352,
U.S. Pat. Publ. No. 2011/0071091, U.S. Pat. Publ. No. 2005/0074467,
U.S. Pat. Publ. No. 2004/0135967, U.S. Pat. No. 4,168,112, U.S.
Pat. No. 7,282,214, U.S. Pat. No. 7,402,318, EP Pat. No. 1328303B1,
and PCT Publ. No. WO94/13774.
SUMMARY
[0006] The invention provides a sealed contact lens package
comprising a sterile, unworn contact lens and a contact lens
packaging solution, said contact lens packaging solution comprising
epsilon polylysine (.epsilon.PLL), wherein the unworn contact lens
exhibits reduced contamination from at least one microbe, wherein
said reduced contamination is determined by a test where
Pseudomonas aeruginosa (PA) introduced to the lens during removal
from the contact lens packaging solution compared to a control
contact lens packaged in an identical contact lens packaging
solution but without said .epsilon.PLL. In one aspect of the
invention, in the test, the unworn contact less results in less
than a two log kill of PA compared to the control contact lens when
tested after 24 hours incubation with 104 CFU PA using an in vitro
bioactivity assay. In another aspect of the invention, the contact
lens package comprises (a) a plastic base member comprising a
cavity which retains a sterile, unworn contact lens and a contact
lens packaging solution comprising epsilon polylysine
(.epsilon.PLL); and (b) a resealable cover that forms a
liquid-tight seal with the plastic base member.
DETAILED DESCRIPTION
[0007] We demonstrate that the initial removal of contact lenses
from their original sterile packaging can result in significant
microbial contamination of the lenses, even when handled
immediately after hand washing. We have found that the addition of
epsilon polylysine (.epsilon.PLL) to the contact lens packaging
solution can reduce or completely eliminate such lens-handling
contamination. Disclosed herein is a sealed contact lens package
comprising a sterile, unworn contact lens and a contact lens
packaging solution comprising epsilon polylysine (.epsilon.PLL) in
an amount effective to reduce or completely eliminate microbial
contamination introduced to the lens during its removal from the
package. As used herein, "unworn" means that the contact lens has
never been placed on an eye, and "sealed" means having a
water-tight seal.
[0008] With the present invention, a sealed contact lens package
comprising a sterile, unworn contact lens and a contact lens
packaging solution comprising epsilon polylysine (.epsilon.PLL) are
provided. The unworn contact lens exhibits reduced contamination
from at least one microbe. The reduced contamination can be
determined by a test where Pseudomonas aeruginosa (PA) introduced
to the lens during removal from the contact lens packaging solution
compared to a control contact lens packaged in an identical contact
lens packaging solution but without said .epsilon.PLL. In the
present invention, at least one microbe can comprise, consists of,
consists essentially of, or include Pseudomonas aeruginosa and/or
Staphylococcus aureus, and/or the at least one microbe is a
microbe(s) found in microbial keratitis and/or at least one microbe
causing at least in part or entirely ocular infiltrates and/or
infections.
[0009] The contact lens sealed in the contact lens package of the
present disclosure may be made from any contact lens material,
including but not limited to conventional hydrogels and silicone
hydrogels. As used herein, a "conventional hydrogel" refers to a
material formed from polymerization of one or more hydrophilic
monomers such as 2-hydroxyethyl methacrylate (HEMA) or vinyl
alcohol, optionally in combination with other monomers, and
contains no siloxane (i.e. a molecule comprising at least one Si--O
group). Examples of conventional hydrogels include etafilcon A,
nelfilcon A, ocufilcon B, ocufilcon D, omafilcon A, omafilcon D and
polymacon. Silicone hydrogel materials are typically formed from
polymerization of one or more monomers or prepolymers comprising at
least one Si--O group with one or more hydrophilic monomers.
Examples of silicone hydrogels include balafilcon A, comfilcon A,
enfilcon A, somofilcon A, narafilcon A, narafilcon B, lotrafilcon
A, stenfilcon A, and senofilcon A. In a specific example, the
sealed contact lens package comprises a sterile, unworn silicone
hydrogel contact lens. In a specific example, the silicone hydrogel
contact lens is non-ionic, meaning it that it contains no anionic
groups that bind to the cationic amine groups present in the
.epsilon.PLL via ionic interaction. In a further specific example,
the silicone hydrogel contact lens is made from a material selected
from comfilcon A or stenfilcon A. In another example, the sealed
contact lens package comprises an unworn conventional hydrogel
contact lens made from a material selected from ocufilcon B,
ocufilcon D, or omafilcon A.
[0010] The contact lens sealed in the contact lens package of the
present disclosure may be of any lens wear modality. Lens wear
modality refers to the how many days and nights in a row the lens
can be worn without removal. In one example, the contact lens
sealed in the contact lens package of the present disclosure is a
daily disposable lens. Daily disposable lenses are indicated for
single use, up to about 12 or 16 hours of continuous wear, and
should be discarded after the single use. In another example, the
contact lens sealed in the contact lens package of the present
disclosure is a daily wear lens. Daily wear lenses are worn during
the waking hours, typically up to about 12 to 16 hours, and are
removed before sleep. Daily wear lenses are typically stored in a
contact lens case containing a contact lens care solution for
cleaning and disinfecting the lens during the hours of non-use.
Daily wear lenses are typically discarded after a maximum of 30
days wear. In yet another example, the contact lens is an extended
wear lens. Extended wear lenses are typically worn continuously for
up to 6, 14 or 30 consecutive days and nights.
[0011] The packaging solution sealed within the contact lens
package of the present disclosure may be any contact-lens
compatible solution comprising an effective amount of .epsilon.PLL.
In one example, the packaging solution comprises, consists, or
consists essentially, of an aqueous solution of a buffer, and/or a
tonicity agent, and .epsilon.PLL. In another example, the packaging
solution contains additional agents such as one or more additional
antimicrobial agents, and/or a comfort agent, and/or a hydrophilic
polymer, and/or a surfactant and/or other additive that prevents
the lens from sticking to the package. The packaging solution can
have a pH in the range of about 6.8 or 7.0 up to about 7.8 or 8.0.
In one example, the packaging solution comprises phosphate buffer
or borate buffer. In another example, the packaging solution
comprises a tonicity agent selected from sodium chloride or
sorbitol in an amount to maintain osmolality in the range of about
200 to 400 mOsm/kg, and typically from about 270 mOsm/kg up to
about 310 mOsm/kg. Throughout this disclosure a reference to
"examples", "an example", "one example", or similar phrase, is
intended to introduce a feature or features of the contact lens
package, unworn contact lens, or packaging solution, as the case
may be (depending on context) that can be combined with any
combination of previously-described or subsequently-described
examples (i.e. features), unless a particular combination of
features is mutually exclusive, or if context indicates
otherwise.
[0012] An effective amount of .epsilon.PLL is an amount that
reduces microbial contamination introduced to the lens during its
removal from the contact lens package (e.g., as compared to no
.epsilon.PLL present). The ability of .epsilon.PLL to reduce
microbial contamination introduced to a lens during its removal
from a package can be demonstrated using methodology substantially
as described in Example 1 or Example 2 below. Example 1
demonstrates that microbial contamination of contact lenses caused
by normal, non-pathogenic skin flora can be significantly reduced
by inclusion of .epsilon.PLL in the contact lens packaging
solution. Example 2 demonstrates that microbial contamination of
contact lenses caused by Pseudomonas aeruginosa (PA), one of the
most common pathogens implicated in microbial keratitis, can also
be significantly reduced by inclusion of .epsilon.PLL in the
contact lens packaging solution. In a specific example, the unworn
contact lens exhibits reduced contamination from PA introduced to
the lens during removal from the packaging solution compared to a
control contact lens in the same packaging comprising a contact
lens packaging solution without .epsilon.PLL but otherwise
identical, as determined using a lens handling assay as described
or substantially as described in Example 2. In various examples,
the packaging solution comprises .epsilon.PLL in amounts of at
least 5 ppm, 10 ppm, 25 ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm, 250
ppm, or 500 ppm. In specific examples, the packaging solution
comprises 10-50 ppm .epsilon.PLL, 25-75 ppm .epsilon.PLL, 50-150
ppm .epsilon.PLL, or 100-500 ppm .epsilon.PLL. The concentration of
.epsilon.PLL in a packaging solution is determined prior to its
contact with the unworn contact lens.
[0013] .epsilon.PLL is commercially available typically as a
homopolymer ranging from about 25 to about 35 lysine (LYS) residues
(CAS no. 28211-04-3). All fractions of the naturally-occurring
homopolymer of .epsilon.PLL may be used. Alternatively, a select
fraction of the .epsilon.PLL may be used (e.g. a homopolymer of
30-35 LYS residues) with the remaining fractions removed and not
used in this option. As an alternative to naturally-occurring
.epsilon.PLL, the .epsilon.PLL used in the packaging solution may
be obtained from synthetic peptide methods.
[0014] In some examples the amount of .epsilon.PLL included in the
contact lens packaging solution results in less than a two log kill
of PA compared to a control contact lens when tested after 24 hours
incubation with 10.sup.4 CFU (colony-forming units) PA as
determined using an in vitro bioactivity assay substantially as
described in Example 4 below. In such example the contact lens
package remains effective against microbial contamination
introduced from initial handling of the lens during its removal
from its original packaging, and thus is particularly suitable for
a daily disposable contact lens.
[0015] We demonstrate in Example 2 below that once the unworn
contact lens is removed from the contact lens package the remaining
packaging solution when covered up by the original blister foil can
resist microbial contamination when left at ambient temperature for
up to 16 hours. Thus, the contact lens package described herein can
provide protection against microbial contamination that might arise
from a non-compliant daily lens wearer who stores a worn lens
overnight in its original package and remaining packaging solution
for a second day of wear. Thus, in one example, the contact lens
package comprises a plastic base member comprising a cavity
configured to retain the contact lens and packaging solution and a
flange region extending outwardly around the cavity. A removable
foil is attached to the flange region to provide a sealed contact
lens package. Such contact lens packages, which are commonly
referred to as "blister packs", are well-known in the art (see e.g.
U.S. Pat. No. 7,426,993). In other examples, the contact lens
package comprises a contact lens indicated for daily wear for at
least 2 days, wherein the package is configured to allow resealing
after its initial opening for subsequent replacement of the lens
for overnight storage after it has been worn. For example, the
contact lens package may comprise a plastic base member comprising
a cavity configured to retain the contact lens and packaging
solution and a resealable cover. As used herein, a "resealable
cover" is one that is configured to form a liquid-tight or
spill-proof seal with the base member after the contact lens
package is opened. For example, the plastic base member may
comprise a plurality of threads for engagement with a compatible
set of threads on a cap which serves as the resealable cover. Such
configurations are commonly used in contact lens care cases (see
e.g. U.S. Pat. No. 3,977,517). Thus an advantage of the contact
lens package disclosed herein is that it can serve a dual purpose,
i.e. both as a contact lens package for a sterile, unworn contact
lens and as a subsequent contact lens carrying case for a worn
lens.
[0016] It will be appreciated that conventional manufacturing
methods can be used to manufacture the sealed contact lens package
of any of the above examples. Thus, in one aspect of the present
disclosure is a method of manufacturing a contact lens package
including the step of placing an unworn contact lens and a contact
lens packaging solution comprising .epsilon.PLL in a receptacle,
placing a cover on the receptacle, and sealing the cover on the
receptacle. Generally, the receptacle is configured to receive a
single contact lens and an amount of packaging solution sufficient
to completely cover the contact lens, typically about 0.5-1.5 ml.
The receptacle may be made from any suitable material, such as
glass or plastic. In one example, the receptacle comprises a
plastic base member comprising a cavity configured to retain the
contact lens and packaging solution and a flange region extending
outwardly around the cavity, and the cover comprises a removable
foil attached to the flange region to provide the sealed contact
lens package. The removable foil may be sealed by any conventional
means such as heat sealing or gluing. In another example, the
receptacle is in the form of a plastic base member comprising a
plurality of threads and the cover comprises a plastic cap member
comprising a compatible set of thread for engagement with the
threads of the base member thereby providing a resealable cover. It
will be appreciated that other types of packaging can also be used
to provide a resealable package. For example the contact lens
package may comprise a plastic cover comprising features that
engage with compatible features of the receptacle to form an
interference fit. The method of manufacturing the sealed contact
lens package may further comprise sterilizing the unworn contact
lens by autoclaving the sealed contact lens package.
[0017] The details of the contact lens or lenses, components of the
solution, formulations, and all of the various other details as
described U.S. patent application Ser. No. 14/109,976, filed Dec.
18, 2013 and entitled "Antimicrobial Ophthalmic Devices" are
incorporated in their entirety by reference herein and form a part
of the present application.
[0018] The following Examples illustrate certain aspects and
advantages of the present invention, which should be understood not
to be limited thereby.
Example 1
Contamination of Commercial Contact Lenses after Handling with
Washed Hands
[0019] Commercially available balafilcon A contact lenses in their
original blister packaging were used in this lens-handling study.
Five individuals washed their hands with soap and water and dried
their hands using paper towels. The foil cover of each blister was
opened aseptically with a gloved hand by the investigator. Each
individual removed and gently rubbed the lens for approximately 5
seconds using the same hand used to turn off the faucet. Each
rubbed lens was then placed into an individual sterile 2 mL
microcentrifuge (Eppendorf.TM.) tube with 1 mL PBS-T and capped. As
used herein, PBS refers phosphate buffered saline of 0.78 wt. %
NaCl, 0.05 wt. % sodium phosphate monobasic, and 0.36 wt. % sodium
phosphate dibasic at pH 7.5. PBS-T refers to PBS with 0.05%
Polysorbate 80.
[0020] To extract any bacteria from the handled lenses, the tubes
were sonicated for 3 cycles of 30 seconds each with 10 seconds
vortexing in between. After the final sonication the tubes were
vortexed for 10 minutes at 1000 rpm using a multi-tube vortexer.
The entire volume of extract from each tube was plated onto a blood
agar plate, allowed to dry in a biochemical hood, and incubated at
37.degree. C. for 48-72 hours. Bacteria were counted and reported
as CFU/lens. Each bacterium with a distinct phenotype was
identified using a Biotyper.
[0021] Detectable levels of contamination from common skin bacteria
(Staphylococcus epidermidis and Staphylococcus warneri) were found
on all five balafilcon A contact lenses. The range of contamination
was from 115-6500 CFU/lens. No lens was sterile. Although the
identified bacteria are not commonly found in microbial keratitis,
they can cause disease in immune-compromised patients.
[0022] To determine whether .epsilon.PLL in a contact lens
packaging solution would be protective immediately against microbes
deposited during lens removal from a blister package, the above
lens-handling study was repeated using ocufilcon D, comfilcon A,
and omafilcon A contact lenses that had been individually packaged
in a contact lens blister package containing a packaging solution
of either PBS or PBS with 500 ppm .epsilon.PLL, sealed with a foil
cover, and autoclaved. All three lenses demonstrated a significant
reduction in bioburden when .epsilon.PLL was present in the
packaging solution, with the following average log kill: ocufilcon
D--2.4, comfilcon A--1.4, and omafilcon A--2.2.
[0023] Finally, we repeated the above lens-handling study to
compare the contamination level of an ocufilcon D contact lens
removed from a sealed autoclaved package containing PBS packaging
solution with or without 500 ppm .epsilon.PLL. We also determined
the level of microbial contamination of ocufilcon D contact lenses
that were removed from their sealed autoclaved packages containing
PBS packaging solution. The lenses were removed from their packages
aseptically using sterile forceps and placed into a well of a
24-well plate containing 1 ml of Optifree.TM. or AQuify.TM. brand
contact lens solutions. Lenses exposed to ClearCare.TM. brand
contact lens solutions were placed into the manufacturer-provided
lens holder. After an overnight soak, the lenses (5 for each lens
solution) were removed from the care solution using the above
hand-washing, handling protocol and extracted as described above.
As expected, the ClearCare.TM. contact lens solution, which does
not contain any antimicrobial agents, did not provide protection
against handling contamination. However, surprisingly, neither
Optifree.TM. nor AQuify.TM. brand contact lens care solutions, both
of which contain active antimicrobial agents, had any significant
effect on bioburden. Only the solution containing PLL in the
blister resulted in a statistically significant reduction in
bacterial count (p=0.00002). The results are shown in Table 1.
TABLE-US-00001 TABLE 1 Subject # Solution 1 2 3 4 5 Ave StDev P
value PBS Log 2.3 2.8 2.4 3.0 2.8 2.7 0.27 PBS + CFU/ 1.1 0.7 0 0.3
0.8 0.6 0.39 0.00002 500 ppm Lens .epsilon.PLL Optifree .TM. 2.3
2.6 1.1 2.2 2.1 2.1 0.51 0.070 AQuify .TM. 2.4 2.7 2.9 3.0 3.3 2.9
0.30 0.348 ClearCare .TM. 0.5 2.5 2.3 2.8 .35 2.3 1.00 0.528
[0024] These experiments indicate that handling is a significant
source of microbial contamination of conventional hydrogel and
silicone hydrogel contact lenses. .epsilon.PLL is protective
against environmentally-derived bacteria deposited on the lens by
lens handling. The carryover of .epsilon.PLL from a packaging
solution significantly reduced bioburden delivered by handling.
Example 2
Lens Handling Assay--Contamination of Contact Lenses from Pathogens
Common in Microbial Keratitis
[0025] The bacterial adherence onto the surface of comfilcon A
lenses removed from autoclaved blister packages containing a
packaging solution of PBS with or without .epsilon.PLL (10, 25,
100, or 500 ppm) was evaluated using a modification of methods
described by Nomachi et al., Eye & Contact Lens (2013)
39:234-238. Briefly, the bacterial adherence onto the surface of
comfilcon A contact lenses was evaluated using stock solutions of
Pseudomona aeruginosa (PA) and Staphylococcus aureus (SA) prepared
substantially as described in Example 3 below. Sterile surgical
plastic gloves were put on both hands aseptically. After the seal
of the comfilcon A package was opened, the thumb and index finger
of a hand gloved were dipped into the bacterial suspension
(approximately 10.sup.3 CFU/ml in PBS) and used to remove a lens
from a package. Four lenses of each type of packaging solution were
tested. Each lens was placed into a microcentrifuge tube with 1 mL
PBS-T, sonicated for 1.5 minute and vortexed for 10 minutes at 1000
rpm. The entire volume of the extract was plated onto a culture
dish with tryptic soy agar (TSA) and grown at 37.degree. C. for 2
days in an incubator.
[0026] Table 2 below shows the average CFU/Lens (n=4) on contact
lenses removed from the different packaging solutions.
TABLE-US-00002 TABLE 2 0 ppm 10 ppm 25 ppm 100 ppm 500 ppm Organism
.epsilon.PLL .epsilon.PLL .epsilon.PLL .epsilon.PLL .epsilon.PLL PA
54 42 16 1 0 SA 43 37 35 21 7
[0027] After removal of the contact lenses by finger and thumb
contaminated with PA, as described above, the blister package and
remaining packaging solution were left covered with the original
blister foil at ambient temperature. After 16 hours, the entire
volume of remaining packaging solution (.about.1 mL) was plated
onto a culture dish with TSA and left in an incubator at 37.degree.
C. for 2 days to grow. The packaging solution without any added ePL
had an average of 331 CFU/Lens. None of the ePL-containing
packaging solutions exhibited microbial growth, i.e. all had 0
CFU/Lens.
Example 3
Preparation of Bacterial Suspensions
[0028] Cultures were prepared from growing a single colony of each
of the bacterial species shown in Table 3 below in 50 mL.
trypticase soy broth (TSB) overnight at 37.degree. C. on a rotary
shaker. 1 mL of each culture was centrifuged, and the bacterial
pellet resuspended in 1.0 mL of the diluent shown in Table 3. For
each bacterial species, a suspension of approximately 10.sup.8
CFU/mL was prepared by diluting the bacterial suspension to achieve
the optical density indicated in Table 3. Each suspension is
further diluted for use in the handling assay described in Example
2 or the in vitro bioactivity assay described in Example 4.
TABLE-US-00003 TABLE 3 Species Strain OD.sub.660 Media Diluent PA
ATCC 99027 ~0.1 0.01% TSB in PBS-T SA ATCC 13880 ~0.3 10.0% TSB in
PBS-T
Example 4
In Vitro Bioactivity Assay
[0029] A contact lens is removed from its packaging and rinsed in
2.5 ml sterile PBS for a few seconds to remove residual packaging
solution. The rinsed lens is then transferred to an individual well
of a 24-well plate containing 1.0 mL of 10.sup.4 CFU PA. The plate
is incubated at 37.degree. C. with gentle shaking for 24 hours. The
lens is removed from its well and transferred to a well of a
12-well plate containing 2.5 mL of sterile PBS. The plate is gently
swirled for about 30 seconds. This step is repeated once for each
lens.
[0030] Each washed lens is placed in a microcentrifuge tube
containing 1 mL of Dey-Engley (DE) neutralizing broth and adhered
bacteria are removed by a combination of sonication for about 2
minutes and vortexing for about 10 minutes. Serial dilutions are
made for each recovered cell suspension using DE neutralizing broth
and suitable dilutions are plated onto TSA. Plates are incubated
overnight at 37.degree. C. and CFUs are counted.
[0031] The CFU for each plate is multiplied by the dilution factor
(DF) as well as the plating dilution factor (PDF). The total CFUs
recovered for a given sample are then converted to the log 10. To
calculate the log kill of a contact lens packaged in a packaging
solution comprising .epsilon.PLL (i.e. the "test lens"), the log of
CFU/lens of the test lens is subtracted from that of a control
lens, which is identical to the test lens and packaged in an
identical package and contact lens packaging solution except that
the packaging solution lacks the .epsilon.PLL. For example, if the
mean log 10 value of an antimicrobial lens is 1.05 and the mean log
10 value of an otherwise identical control lens lacking the active
antimicrobial agent is 5.52, the log kill is 5.52-1.05=4.47.
[0032] Although the disclosure herein refers to certain illustrated
examples, it is to be understood that these examples are presented
by way of example and not by way of limitation. The intent of the
foregoing detailed description, although discussing exemplary
examples, is to be construed to cover all modifications,
alternatives, and equivalents of the examples as may fall within
the spirit and scope of the invention as defined by the additional
disclosure.
[0033] A number of publications and patents have been cited
hereinabove. Each of the cited publications and patents are hereby
incorporated by reference in their entireties.
[0034] The present invention includes the following
aspects/embodiments/features in any order and/or in any
combination:
1. A sealed contact lens package comprising a sterile, unworn
contact lens and a contact lens packaging solution comprising
epsilon polylysine (.epsilon.PLL), wherein the unworn contact lens
exhibits reduced contamination from Pseudomonas aeruginosa (PA)
introduced to the lens during removal from the contact lens
packaging solution compared to a control contact lens packaged in a
substantially identical contact lens packaging solution without
.epsilon.PLL. 2. A sealed contact lens package comprising a
sterile, unworn contact lens and a contact lens packaging solution
comprising epsilon polylysine (.epsilon.PLL), wherein the unworn
contact lens exhibits reduced contamination from at least one
microbe, wherein said reduced contamination is determined by a test
where Pseudomonas aeruginosa (PA) introduced to the lens during
removal from the contact lens packaging solution compared to a
control contact lens packaged in an identical contact lens
packaging solution but without said .epsilon.PLL. 3. The package of
any preceding or following embodiment/feature/aspect wherein, in
the test, the unworn contact less results in less than a two log
kill of PA compared to the control contact lens when tested after
24 hours incubation with 10.sup.4 CFU PA using an in vitro
bioactivity assay. 4. The package of any preceding or following
embodiment/feature/aspect, wherein, in the test, the unworn contact
less results in less than a one log kill of PA (but more than a
zero log kill) compared to the control contact lens when tested
after 24 hours incubation with 10.sup.4 CFU PA using an in vitro
bioactivity assay. 5. The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens is a silicone
hydrogel contact lens. 6. The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens is a non-ionic
contact lens. 7. The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens is an ionic
contact lens. 8. The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens is a daily
disposable contact lens. 9. The package of any preceding or
following embodiment/feature/aspect, wherein the contact lens is a
daily wear contact lens. 10. The package of any preceding or
following embodiment/feature/aspect, wherein the packaging solution
comprises between 5 ppm and 500 ppm .epsilon.PLL. 11. The package
of any preceding or following embodiment/feature/aspect, wherein
the packaging solution comprises between 5 ppm and 50 ppm
.epsilon.PLL. 12. The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens package further
comprises (a) a plastic base member comprising i) a cavity which
retains the unworn contact lens and the contact lens packaging
solution, and ii) a flange region extending outwardly around the
cavity; and (b) a removable foil attached to the flange region. 13.
The package of any preceding or following
embodiment/feature/aspect, wherein the contact lens package further
comprises (a) a plastic base member comprising a cavity which
retains the unworn contact lens and the contact lens packaging
solution; and (b) a resealable cover that forms a liquid-tight seal
with the plastic base member. 14. The package of any preceding or
following embodiment/feature/aspect, wherein the plastic base
member comprises a plurality of threads for engagement with a
compatible set of threads on the resealable cover. 15. The package
of any preceding or following embodiment/feature/aspect, wherein
the at least one microbe is Pseudomonas aeruginosa. 16. The package
of any preceding or following embodiment/feature/aspect, wherein
the at least one microbe is Staphylococcus aureus. 17. The package
of any preceding or following embodiment/feature/aspect, wherein
the at least one microbe is a microbe found in microbial keratitis.
18. A method of manufacturing the sealed contact lens package, said
method comprising placing an unworn contact lens and a contact lens
packaging solution comprising .epsilon.PLL in a receptacle
configured to receive a contact lens and sealing the receptacle
with a cover to provide a sealed contact lens package, wherein the
unworn contact lens exhibits reduced contamination from Pseudomonas
aeruginosa (PA) introduced to the lens during removal from the
contact lens packaging solution compared to a control contact lens
packaged in a substantially identical contact lens packaging
solution without .epsilon.PLL, and wherein the unworn contact less
results in less than a two log kill of PA compared to the control
contact lens when tested after 24 hours incubation with 10.sup.4
CFU PA using an in vitro bioactivity assay. 19. A method of
manufacturing the sealed contact lens package, said method
comprising placing an unworn contact lens and a contact lens
packaging solution comprising .epsilon.PLL in a receptacle
configured to receive a contact lens and sealing the receptacle
with a cover to provide a sealed contact lens package, wherein the
unworn contact lens exhibits reduced contamination from at least
one microbe, wherein said reduced contamination is determined by a
test where Pseudomonas aeruginosa (PA) introduced to the lens
during removal from the contact lens packaging solution compared to
a control contact lens packaged in an identical contact lens
packaging solution but without said .epsilon.PLL, and wherein the
unworn contact less results in less than a two log kill of PA
compared to the control contact lens when tested after 24 hours
incubation with 10.sup.4 CFU PA using an in vitro bioactivity
assay. 20. The method of any preceding or following
embodiment/feature/aspect, wherein the contact lens package is any
one embodiments described above (e.g., 1 through 17.) 21. The
method of any preceding or following embodiment/feature/aspect
further comprising sterilizing the unworn contact lens by
autoclaving the sealed contact lens package. 22. A method of
manufacturing the sealed contact lens package, said method
comprising placing an unworn contact lens and a contact lens
packaging solution comprising .epsilon.PLL in a receptacle
configured to receive a contact lens and sealing the receptacle
with a cover to provide a sealed contact lens package, wherein the
unworn contact lens exhibits reduced contamination from Pseudomonas
aeruginosa (PA) introduced to the lens during removal from the
contact lens packaging solution compared to a control contact lens
packaged in a substantially identical contact lens packaging
solution without .epsilon.PLL, and wherein the contact lens package
comprises a resealable cover. 23. A method of manufacturing the
sealed contact lens package, said method comprising placing an
unworn contact lens and a contact lens packaging solution
comprising .epsilon.PLL in a receptacle configured to receive a
contact lens and sealing the receptacle with a cover to provide a
sealed contact lens package, wherein the unworn contact lens
exhibits reduced contamination from at least one microbe, wherein
said reduced contamination is determined by a test where
Pseudomonas aeruginosa (PA) introduced to the lens during removal
from the contact lens packaging solution compared to a control
contact lens packaged in an identical contact lens packaging
solution but without said .epsilon.PLL, and wherein the contact
lens package comprises a resealable cover. 24. The method of any
preceding or following embodiment/feature/aspect, wherein the
contact lens package is any one of 1 through 17. 25. The method of
any preceding or following embodiment/feature/aspect, further
comprising sterilizing the unworn contact lens by autoclaving the
sealed contact lens package.
[0035] The present invention can include any combination of these
various features or embodiments above and/or below as set forth in
sentences and/or paragraphs. Any combination of disclosed features
herein is considered part of the present invention and no
limitation is intended with respect to combinable features.
[0036] Applicants specifically incorporate the entire contents of
all cited references in this disclosure. Further, when an amount,
concentration, or other value or parameter is given as either a
range, preferred range, or a list of upper preferable values and
lower preferable values, this is to be understood as specifically
disclosing all ranges formed from any pair of any upper range limit
or preferred value and any lower range limit or preferred value,
regardless of whether ranges are separately disclosed. Where a
range of numerical values is recited herein, unless otherwise
stated, the range is intended to include the endpoints thereof, and
all integers and fractions within the range. It is not intended
that the scope of the invention be limited to the specific values
recited when defining a range.
[0037] Other embodiments of the present invention will be apparent
to those skilled in the art from consideration of the present
specification and practice of the present invention disclosed
herein. It is intended that the present specification and examples
be considered as exemplary only with a true scope and spirit of the
invention being indicated by the following claims and equivalents
thereof.
* * * * *