U.S. patent application number 11/923685 was filed with the patent office on 2008-05-01 for acidic processes to prepare antimicrobial contact lenses.
Invention is credited to Nayiby Alvarez-Carrigan, Frank Neely, Osman Rathore, David Turner, Kent Young.
Application Number | 20080102095 11/923685 |
Document ID | / |
Family ID | 39345003 |
Filed Date | 2008-05-01 |
United States Patent
Application |
20080102095 |
Kind Code |
A1 |
Young; Kent ; et
al. |
May 1, 2008 |
ACIDIC PROCESSES TO PREPARE ANTIMICROBIAL CONTACT LENSES
Abstract
This invention relates to antimicrobial lenses containing metals
and methods for their production.
Inventors: |
Young; Kent; (Jacksonville,
FL) ; Rathore; Osman; (Jacksonville, FL) ;
Alvarez-Carrigan; Nayiby; (St. Augustine, FL) ;
Turner; David; (Jacksonville, FL) ; Neely; Frank;
(Jacksonville, FL) |
Correspondence
Address: |
PHILIP S. JOHNSON;JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
39345003 |
Appl. No.: |
11/923685 |
Filed: |
October 25, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60863583 |
Oct 31, 2006 |
|
|
|
Current U.S.
Class: |
424/409 ;
424/618 |
Current CPC
Class: |
A61L 12/088 20130101;
A01N 59/16 20130101; A61P 27/02 20180101; G02B 1/043 20130101; A01N
25/08 20130101 |
Class at
Publication: |
424/409 ;
424/618 |
International
Class: |
A01N 25/34 20060101
A01N025/34; A01N 59/16 20060101 A01N059/16 |
Claims
1. A method of preparing an antimicrobial lens comprising a metal
salt, wherein said method comprising the steps of (a) treating a
cured lens, a solution comprising, consisting essentially of, or
consisting of a salt precursor and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0;
and (b) treating the lens of step (a) with a solution comprising,
consisting essentially of, or consisting of a metal agent and an
effective amount of an acidic substance, wherein the pH of said
solution is less than about 7.0.
2. The method of claim 1 wherein the acidic substance is selected
from the group consisting of acetic acid, hydrochloric acid, and
sulfuric acid.
3. The method of claim 1 wherein the acidic substance is acetic
acid.
4. The method of claim 1 wherein the effective amount of the acidic
substance is about 0.01% to about 10%.
5. The method of claim 1 wherein the effective amount of the acidic
substance is about 0.5%.
6. The method of claim 1 wherein the effective amount of the acidic
substance is about 0.05%.
7. The method of claim 1 wherein the ph of the solution of steps
(a) and (b) is about 2 to about 5.
8. The method of claim 1 wherein the ph of the solution of steps
(a) and (b) is about 2 to about 4.
9. The method of claim 1 wherein the pH of the solution of steps
(a) and (b) is about 3 to about 4.
10. The method of claim 1 wherein the salt precursor is selected
from the group consisting of tetra-alkyl ammonium lactate,
tetra-alkyl ammonium sulfate, tetra-alkyl ammonium chloride,
tetra-alkyl ammonium, bromide, tetra-alkyl ammonium iodide, sodium
chloride, sodium iodide, sodium bromide, lithium chloride, lithium
sulfide, sodium sulfide, potassium sulfide, and sodium tetrachloro
argentate.
11. The method of claim 1 wherein the salt precursor is selected
from the group consisting of sodium chloride, sodium iodide, sodium
bromide, lithium chloride, lithium sulfide, sodium sulfide,
potassium sulfide, and sodium tetrachloro argentite.
12. The method of claim 1 wherein the salt precursor is sodium
iodide.
13. The method of claim 1 wherein the metal agent is selected from
the group consisting of silver iodide, silver chloride, and silver
bromide.
14. The method of claim 1 wherein the salt precursor is selected
from the group consisting of silver nitrate, silver triflate, and
silver acetate.
15. The method of claim 1 wherein the salt precursor is silver
acetate.
16. A method of preparing an antimicrobial lens comprising a metal
salt, wherein said method comprising the steps of (a) treating a
cured lens, a solution comprising, consisting essentially of, or
consisting of a metal agent and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0;
and (b) treating the lens of step (a) with a solution comprising,
consisting essentially of, or consisting of a salt precursor and an
effective amount of an acidic substance, wherein the pH of said
solution is less than about 7.0.
17. An antimicrobial lens comprising a metal salt, prepared by a
method comprising the steps of (a) treating a cured lens, a
solution comprising a salt precursor and an effective amount of an
acidic substance, wherein the pH of said solution is less than
about 7.0; and (b) treating the lens of step (a) with a solution
comprising a metal agent and an effective amount of an acidic
substance, wherein the pH of said solution is less than about
7.0.
18. The antimicrobial lens of claim 17 wherein the metal salt is
silver iodide, the salt precursor is sodium nitrate, the metal
agent is silver nitrate and the pH of the solutions of steps (a)
and (b) is about 3-4.
19. An antimicrobial lens comprising a metal salt, prepared by a
method comprising the steps of (a) treating a cured lens, a
solution comprising a metal agent and an effective amount of an
acidic substance, wherein the pH of said solution is less than
about 7.0; and (b) treating the lens of step (a) with a solution
comprising, consisting essentially of, or consisting of a salt
precursor and an effective amount of an acidic substance, wherein
the pH of said solution is less than about 7.0.
20. The antimicrobial lens of claim 19 wherein the metal salt is
silver iodide, the salt precursor is sodium nitrate, the metal
agent is silver nitrate and the pH of the solutions of steps (a)
and (b) is about 3-4.
Description
RELATED APPLICATION
[0001] This application is a non-provisional filing of a
provisional application, U.S. Ser. No. 60/863,583, filed on Oct.
31, 2006.
FIELD OF THE INVENTION
[0002] This invention relates to methods of preparing antimicrobial
lenses
BACKGROUND OF THE INVENTION
[0003] Contact lenses have been used commercially to improve vision
since the 1950s. The first contact lenses were made of hard
materials. They were used by a patient during waking hours and
removed for cleaning. Current developments in the field gave rise
to soft contact lenses, which may be worn continuously, for several
days or more without removal for cleaning. Although many patients
favor these lenses due to their increased comfort, these lenses can
cause some adverse reactions to the user. The extended use of the
lenses can encourage the buildup of bacteria or other microbes,
particularly, Pseudomonas aeruginosa, on the surfaces of soft
contact lenses. The build-up of bacteria and other microbes can
cause adverse side effects such as contact lens acute red eye and
the like. Although the problem of bacteria and other microbes is
most often associated with the extended use of soft contact lenses,
the build-up of bacteria and other microbes occurs for users of
hard contact lens wearers as well.
[0004] Others have taught that the addition of antibacterial agents
such as metal salts to contact lenses can inhibit the growth of
bacteria or other microbes. See, US 2004/0150788, which is hereby
incorporated by reference in its entirety. In order produce
manufacturing quantities of contact lenses containing antibacterial
agents, processes to prepare these lenses must give consistent
results. When some of the processes disclosed in US 2004-0150788
are used with different contact lens formulations, the contact
lenses that are produced have variable amounts of antibacterial
agents contained therein. Since the amount of antibacterial agent
in every lens must be consistent from lot to lot, it is desirable
to find process to prepare contact lenses containing antibacterial
agents that produce a consistent product. This need is met by the
following invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIG. 1 Silver content vs Sodium Iodide concentration in a
neutral process.
[0006] FIG. 2. Silver content vs Sodium Iodide in an acidified
process.
DETAILED DESCRIPTION OF THE INVENTION
[0007] This invention includes a method of preparing an
antimicrobial lens comprising, consisting essentially of, or
consisting of a metal salt, wherein said method comprising the
steps of [0008] (a) treating a cured lens, a solution comprising,
consisting essentially of, or consisting of a salt precursor and an
effective amount of an acidic substance, wherein the pH of said
solution is less than about 7.0; and [0009] (b) treating the lens
of step (a) with a solution comprising, consisting essentially of,
or consisting of a metal agent and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0.
As used herein, the term, "antimicrobial lens" means a lens that
exhibits one or more of the following properties, the inhibition of
the adhesion of bacteria or other microbes to the lenses, the
inhibition of the growth of bacteria or other microbes on lenses,
and the killing of bacteria or other microbes on the surface of
lenses or in an area surrounding the lenses. For purposes of this
invention, adhesion of bacteria or other microbes to lenses, the
growth of bacteria or other microbes on lenses and the presence of
bacteria or other microbes on the surface of lenses are
collectively referred to as "microbial colonization." Preferably,
the lenses of the invention exhibit a reduction of viable bacteria
or other microbe of at least about 0.25 log, more preferably at
least about 0.5 log, most preferably at least about 1.0 log
L>90% inhibition). Such bacteria or other microbes include but
are not limited to those organisms found in the eye, particularly
Pseudomonas aeruginosa, Acanthamoeba species, Staphylococcus.
aureus, Escherichia. coli, Staphylococcus epidermidis, and Serratia
marcesens.
[0010] As used herein, the term "acidic substance" refers to a
composition may be added to a solution to reduce the pH of said
solution to a pH of less than 7. Examples of acidic substances
include but are not limited to acetic acid, sulfuric acid, and
hydrochloric acid. The preferred acidic substance is acetic acid.
The term "effective amount" refers to the concentration of the
acidic substance required to reduce the pH of the solution to less
than 7. It is preferable that the effective amount reduce the pH of
the solution to less, than about 5, more preferably to less than
about 4, most preferably less than about 3.6. The preferred acidic
substance, acetic acid, is present in a concentration of about
0.01% to about 10% (weight percent, based on the total weight of
the solution), more preferably about 0.5%, most preferably about
0.05%. The acidic substance in step (a) and step (b) may be the
same or different. It is preferred that the acidic substance of
steps (a) and (b) are the same.
[0011] As use herein, the term "metal salt" means any molecule
having the general formula [M].sub.a [X].sub.b wherein X contains
any negatively charged ion, a is >1, b is >1 and M is any
positively charged metal selected from, but not limited to, the
following Al.sup.+3, Co.sup.+2, Co.sup.+3, Ca.sup.+2, Mg.sup.+2,
Ni.sup.+2, Ti.sup.+2, Ti.sup.+3, Ti.sup.+4, V.sup.+2, V.sup.+3,
V.sup.+5, Sr.sup.+2, Fe.sup.+2, Fe.sup.+3, Ag.sup.+1, Ag.sup.+2,
Au.sup.+2, Au.sup.+3, Au.sup.+1, Pd.sup.+2, Pd.sup.+4, Pt.sup.+2,
Pt.sup.+4 Cu.sup.+1 Cu.sup.+2, Mn.sup.+2, Mn.sup.+3, Mn.sup.+4,
Zn.sup.+2, and the like. Examples of X include but are not limited
to CO.sub.3.sup.-2, NO.sub.3.sup.-1, PO.sub.4.sup.-3, Cl.sup.-1,
I.sup.-1, Br.sup.-1, S.sup.-2, O.sup.-2 and the like. Further X
includes negatively charged ions containing CO.sub.3.sup.-2
NO.sub.3.sup.-1, PO.sub.4.sup.-3, Cl.sup.-1, I.sup.-1, Br.sup.-1,
S.sup.-2, O.sup.-2, and the like, such as
C.sub.1-5alkylCO.sub.2.sup.-1. As used herein the term metal salts
does not include zeolites, disclosed in WO03/011351. This patent
application is hereby incorporated by reference in its entirety.
The preferred a is 1, 2, or 3. The preferred b is 1, 2, or 3. The
preferred metals ions are Mg.sup.+2, Zn.sup.+2, Cu.sup.+1,
Cu.sup.+2, Au.sup.+2, Au.sup.+3, Au.sup.+1, Pd.sup.+2, Pd.sup.+4,
Pt.sup.+2, Pt.sup.+4, Ag.sup.+2, and Ag.sup.+1. The particularly
preferred metal ion is Ag.sup.+1. Examples of suitable metal salts
include but are not limited to manganese sulfide, zinc oxide, zinc
sulfide, copper sulfide, and copper phosphate. Examples of silver
salts include but are not limited to silver nitrate, silver
sulfate, silver iodate, silver carbonate, silver phosphate, silver
sulfide, silver chloride, silver bromide, silver iodide, and silver
oxide. The preferred silver salts are silver iodide, silver
chloride, and silver bromide.
[0012] The amount of metal in the lenses is measured based upon the
total weight of the lenses. When the metal is silver, the preferred
amount of silver is about 0.00001 weight percent (0.1 ppm) to about
10.0 weight percent, preferably about 0.0001 weight percent (1 ppm)
to about 1.0 weight percent, most preferably about 0.001 weight
percent (10 ppm) to about 0.1 weight percent, based on the dry
weight of the lens. With respect to adding metal salts, the
molecular weight of the metal salts determines the conversion of
weight percent of metal ion to metal salt. The preferred amount of
silver salt is about 0.00003 weight percent (0.3 ppm) to about 30.0
weight percent, preferably about 0.0003 weight percent (3 ppm) to
about 3.0 weight percent, most preferably about 0.003 weight
percent (30 ppm) to about 0.3 weight percent, based on the dry
weight of the lens.
[0013] The term "salt precursor" refers to any compound or
composition (including aqueous solutions) that contains a cation
that may be substituted with metal ions. The concentration of salt
precursor in its solution is between about 0.00001 to about 10.0
weight percent, (0.1-100,000 ppm) more preferably about 0.0001 to
about 1.0 weight percent, (1-10,000 ppm) most preferably about
0.001 to about 0.1 weight percent (10-1000 ppm) based upon the
total weight of the solution. Examples of salt precursors include
but are not limited to inorganic molecules such as sodium chloride,
sodium iodide, sodium bromide, sodium sulfide, lithium chloride,
lithium iodide, lithium bromide, lithium sulfide, potassium
bromide, potassium chloride, potassium sulfide, potassium iodide,
rubidium iodide, rubidium bromide, rubidium chloride, rubidium
sulfide, caesium iodide, caesium bromide, caesium chloride, caesium
sulfide, francium iodide, francium bromide, francium chloride,
francium sulfide, sodium tetrachloro argentite, and the like.
Examples of organic molecules include but are not limited to
tetra-alkyl ammonium lactate, tetra-alkyl ammonium sulfate,
quaternary ammonium halides, such as tetra-alkyl ammonium chloride,
bromide or iodide. The preferred salt precursor is selected from
the group consisting of sodium chloride, sodium iodide, sodium
bromide, lithium chloride, lithium sulfide, sodium sulfide,
potassium sulfide, potassium iodide, and sodium tetrachloro
argentite and the particularly preferred salt precursor is sodium
iodide.
[0014] The term "metal agent" refers to any composition (including
aqueous solutions) containing metal ions. Examples of such
compositions include but are not limited to aqueous or organic
solutions of silver nitrate, silver triflate, or silver acetate,
silver tetrafluoroborate, silver sulfate, zinc acetate, zinc
sulfate, copper acetate, and copper sulfate, where the
concentration of metal agent in solution is about 1 .mu.g/mL or
greater. The preferred metal agent is aqueous silver nitrate, where
the concentration of silver nitrate is the solution is about
greater than or equal to 0.0001 to about 2 weight percent, more
preferably about greater than 0.001 to about 0.01 weight percent
based on the total weight of the solution.
[0015] The term "solution" refers to an aqueous substance such as
deionized water, saline solutions, borate or buffered saline
solution, or organic substance such as C1-C24 alcohols, cyclic
amides, acyclic amides, ethers and acids.
[0016] The term "treating" refers to any method of contacting
solutions of the metal agent and the acidic substance or, the salt
precursor and the acidic substance, with the lens, where the
preferred method is immersing the lens in a solution of containing
either the metal agent and the acidic substance or the salt
precursor and the acidic substance. Treating can include heating
the lens in these solutions, but it preferred that treating is
carried out at ambient temperatures. The time of treating is
preferably about 1 minute to 24 hours, most preferably about 3
minute to about 30 minutes
[0017] As used herein, the term "lens" refers to an ophthalmic
device that resides in or on the eye. These devices can provide
optical correction, wound care, drug delivery, diagnostic
functionality, cosmetic enhancement or effect or a combination of
these properties. The term lens includes but is not limited to soft
contact lenses, hard contact lenses, intraocular lenses, overlay
lenses, ocular inserts, and optical inserts. Soft contact lenses
are made from silicone elastomers or hydrogels, which include but
are not limited to silicone hydrogels, and fluorohydrogels.
[0018] For example the term lens includes but is not limited to
those made from the soft contact lens formulations described in
U.S. Pat. No. 5,710,302, WO 9421698, EP 406161, JP 2000016905, U.S.
Pat. No. 5,998,498, U.S. patent application Ser. No. 09/532,943,
U.S. Pat. No. 6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat. No.
5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811, and
U.S. Pat. No. 5,965,631. Examples of soft contact lenses
formulations include but are not limited to the formulations of
etafilcon A, balafilcon A, bufilcon A, deltafilcon A, droxifilcon
A, phemfilcon A, ocufilicon A, perfilcon A, ocufilcon B, ocufilcon
C, ocufilcon D, ocufilcon E, metafilcon A, B, vifilcon A focofilcon
A, tetrafilcon B, and silicone hydrogels, as prepared in U.S. Pat.
No. 5,998,498, U.S. Ser. No. 09/532,943, a continuation-in-part of
U.S. patent application Ser. No. 09/532,943, filed on Aug. 30,
2000, WO03/22321, U.S. Pat. No. 6,087,415, U.S. Pat. No. 5,760,100,
U.S. Pat. No. 5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No.
5,849,811, and U.S. Pat. No. 5,965,631. These patents as well as
all other patent disclosed in this paragraph are hereby
incorporated by reference in their entirety.
[0019] Lenses of the invention may be made from silicone hydrogel
components. A silicone-containing component is one that contains at
least one [--Si--O--Si] group, in a monomer, macromer or
prepolymer. Preferably, the Si and attached O are present in the
silicone-containing component in an amount greater than 20 weight
percent, and more preferably greater than 30 weight percent of the
total molecular weight of the silicone-containing component. Useful
silicone-containing components preferably comprise polymerizable
functional groups such as acrylate, methacrylate, acrylamide,
methacrylamide, N-vinyl lactam, N-vinylamide, and styryl functional
groups. Examples of silicone components which may be included in
the silicone hydrogel formulations include, but are not limited to
silicone macromers, prepolymers and monomers. Examples of silicone
macromers include, without limitation, polydimethylsiloxane
methacrylated with pendant hydrophilic groups as described in U.S.
Pat. Nos. 4,259,467; 4,260,725 and 4,261,875; polydimethylsiloxane
macromers with polymerizable functional group(s) described in U.S.
Pat. Nos. 4,136,250; 4,153,641; 4,189,546; 4,182,822; 4,343,927;
4,254,248; 4,355,147; 4,276,402; 4,327,203; 4,341,889; 4,486,577;
4,605,712; 4,543,398; 4,661,575; 4,703,097; 4,837,289; 4,954,586;
4,954,587; 5,346,946; 5,358,995; 5,387,632; 5,451,617; 5,486,579;
5,962,548; 5,981,615; 5,981,675; and 6,039,913; polysiloxane
macromers incorporating hydrophilic monomers such as those
described in U.S. Pat. Nos. 5,010,141; 5,057,578; 5,314,960;
5,371,147 and 5,336,797; macromers comprising polydimethylsiloxane
blocks and polyether blocks such as those described in U.S. Pat.
Nos. 4,871,785 and 5,034,461, combinations thereof and the like.
All of the patents cited herein are hereby incorporated in their
entireties by reference.
[0020] The silicone and/or fluorine containing macromers described
in U.S. Pat. Nos. 5,760,100; 5,776,999; 5,789,461; 5,807,944;
5,965,631 and 5,958,440 may also be used. Suitable silicone
monomers include tris(trimethylsiloxy)silylpropyl methacrylate,
hydroxyl functional silicone containing monomers, such as
3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane
and those disclosed in WO03/22321, and mPDMS containing or the
siloxane monomers described in U.S. Pat. Nos. 4,120,570, 4,139,692,
4,463,149, 4,450,264, 4,525,563; 5,998,498; 3,808,178; 4,139,513;
5,070,215; 5,710,302; 5,714,557 and 5,908,906.
[0021] Additional suitable siloxane containing monomers include,
amide analogs of TRIS described in U.S. Pat. No. 4,711,943,
vinylcarbamate or carbonate analogs described in U.S. Pat. No.
5,070,215, and monomers contained in U.S. Pat. No. 6,020,445,
monomethacryloxypropyl terminated polydimethylsiloxanes,
polydimethylsiloxanes,
3-methacryloxypropylbis(trimethylsiloxy)methylsilane,
methacryloxypropylpentamethyl disiloxane and combinations
thereof.
[0022] In addition to soft contact lens formulations, hard contact
lenses may be used. Examples of hard contact lens formulations are
made from polymers that include but are not limited to polymers of
poly(methyl)methacrylate, silicon acrylates, silicone acrylates,
fluoroacrylates, fluoroethers, polyacetylenes, and polyimides,
where the preparation of representative examples may be found in JP
200010055, JP 6123860 and U.S. Pat. No. 4,330,383. Intraocular
lenses of the invention can be formed using known materials. For
example, the lenses may be made from a rigid material including,
without limitation, polymethyl methacrylate, polystyrene,
polycarbonate, or the like, and combinations thereof. Additionally,
flexible materials may be used including, without limitation,
hydrogels, silicone materials, acrylic materials, fluorocarbon
materials and the like, or combinations thereof. Typical
intraocular lenses are described in WO 0026698, WO 0022460, WO
9929750, WO 9927978, WO 0022459, and JP 2000107277. U.S. Pat. Nos.
4,301,012; 4,872,876; 4,863,464; 4,725,277; 4,731,079. All of the
references mentioned in this application are hereby incorporated by
reference in their entirety.
[0023] Preferably, the lenses of the invention are optically clear,
with optical clarity comparable to lenses such as lenses made from
etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon,
acquafilcon A, balafilcon A, and lotrafilcon A. The most preferred
lens formulations are those used to prepare ionic lenses. Monomers
that are useful in the preparation of such lenses include
methacrylic acid and the like. Examples of the most preferred lens
formulations include those used to prepare etafilcon A, balafilcon
A, bufilcon A, deltafilcon A, droxifilcon A, phemfilcon A,
ocufilicon A, perfilcon A, ocufilcon B, ocufilcon C, ocufilcon D,
ocufilcon E, metafilcon A, B, vifilcon A focofilcon A, and
tetrafilcon B
[0024] Many of the lens formulations cited above may allow a user
to insert the lenses for a continuous period of time ranging from
one day to thirty days. It is known that the longer a lens is on
the eye, the greater the chance that bacteria and other microbes
will build up on the surface of those lenses. Therefore there is a
need to develop lenses that release antimicrobial agents such as
silver, over an extended period of time.
[0025] The term "cured" refers to any of a number of methods used
to react a mixture of lens components (ie, momoner, prepolymers,
macromers and the like) to form lenses. Lenses can be cured by
light or heat. The preferred method of curing is with radiation,
preferably UV or visible light, and most preferably with visible
light. The lens formulations of the present invention can be formed
by any of the methods know to those skilled in the art, such as
shaking or stirring, and used to form polymeric articles or devices
by known methods.
[0026] For example, the antimicrobial lenses of the invention may
be prepared by mixing reactive components and any diluent(s) with a
polymerization initiator and curing by appropriate conditions to
form a product that can be subsequently formed into the appropriate
shape by lathing, cutting and the like. Alternatively, the reaction
mixture may be placed in a mold and subsequently cured into the
appropriate article.
[0027] Various processes are known for processing the lens
formulation in the production of contact lenses, including
spincasting and static casting. Spincasting methods are disclosed
in U.S. Pat. Nos. 3,408,429 and 3,660,545, and static casting
methods are disclosed in U.S. Pat. Nos. 4,113,224 and 4,197,266.
The preferred method for producing antimicrobial lenses of this
invention is by molding. In the case of hydrogel lenses, for this
method, the lens formulation is placed in a mold having the
approximate shape of the final desired lens, and the lens
formulation is subjected to conditions whereby the components
polymerize, to produce a hardened disc that is subjected to a
number of different processing steps including treating the
polymerized lens with liquids (such as water, inorganic salts, or
organic solutions) to swell, or otherwise equilibrate this lens
prior to enclosing the lens in its final packaging. This method is
further described in U.S. Pat. Nos. 4,495,313; 4,680,336;
4,889,664; and 5,039,459, incorporated herein by reference.
Polymerized lenses that have not been swelled or otherwise
equilibrated are considered cured lenses for purposes of this
invention.
[0028] Further, the invention includes a method of preparing an
antimicrobial lens comprising, consisting essentially of, or
consisting of a metal salt, wherein the method comprises, consists
essentially of, or consists of the steps of [0029] (a) treating a
cured lens, a solution comprising, consisting essentially of, or
consisting of a metal agent and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0;
and [0030] (b) treating the lens of step (a) with a solution
comprising, consisting essentially of, or consisting of a salt
precursor and an effective amount of an acidic substance, wherein
the pH of said solution is less than about 7.0. The terms
antimicrobial lens, metal salt, salt precursor, metal agent,
effective amount and treating all have their aforementioned
meanings and preferred ranges.
[0031] Still further the invention includes an antimicrobial lens
comprising, consisting essentially of, or consisting of a metal
salt, prepared by a method comprising the steps of [0032] (a)
treating a cured lens, a solution comprising, consisting
essentially of, or consisting of a salt precursor and an effective
amount of an acidic substance, wherein the pH of said solution is
less than about 7.0; and [0033] (b) treating the lens of step (a)
with a solution comprising, consisting essentially of, or
consisting of a metal agent and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0.
The terms antimicrobial lens, metal salt, salt precursor, metal
agent, effective amount and treating all have their aforementioned
meanings and preferred ranges.
[0034] Yet still further, the invention includes an antimicrobial
lens comprising, consisting essentially of, or consisting of a
metal salt, prepared by a method comprising the steps of [0035] (a)
treating a cured lens, a solution comprising, consisting
essentially of, or consisting of a metal agent and an effective
amount of an acidic substance, wherein the pH of said solution is
less than about 7.0; and [0036] (b) treating the lens of step (a)
with a solution comprising, consisting essentially of, or
consisting of a salt precursor and an effective amount of an acidic
substance, wherein the pH of said solution is less than about 7.0.
The terms antimicrobial lens, metal salt, salt precursor, metal
agent, effective amount and treating all have their aforementioned
meanings and preferred ranges.
[0037] In order to illustrate the invention the following examples
are included. These examples do not limit the invention. They are
meant only to suggest a method of practicing the invention. Those
knowledgeable in contact lenses as well as other specialties may
find other methods of practicing the invention. However, those
methods are deemed to be within the scope of this invention.
EXAMPLES
The following abbreviations were used in the examples
Blue HEMA=the reaction product of reactive blue number 4 and HEMA,
as described in Example 4 or U.S. Pat. No. 5,944,853
CGI 819=bis(2,4,6-trimethylbenzoyl)phenylphosphineoxide
DI water=deionized water
DMA=N,N-dimethylacrylamide
HEMA=hydroxyethyl methacrylate
MAA=methacrylic acid;
mPDMS=mono-methacryloxypropyl terminated polydimethylsiloxane (MW
800-1000)
acPDMS=bis-3-acryloxy-2-hydroxypropyloxypropyl
polydimethylsiloxane
Norbloc=2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole
ppm=parts per million micrograms of sample per gram of dry lens
PVP=polyvinylpyrrolidinone (360,000 or 2,500)
Simma 2=3-methacryloxy-2-hydroxypropyloxy)propylbis
(trimethylsiloxy)methylsilane
TAA=t-amyl alcohol
Sodium Sulfate Packing Solution (SSPS)
SSPS contains the following in deionized H.sub.2O:
1.40 weight % sodium sulfate
0.185 weight % sodium borate [1330-43-4], Mallinckrodt
0.926 weight % boric acid [10043-35-3], Mallinckrodt
0.005 weight % methylcellulose
Preparation Lens Type A
[0038] A hydrogel blend was made from the following monomer mix
(all amounts were calculated as weight percent: 30.00% SIMM 2,
28.0% mPDMS, 5.0% acPDMS, 19.0% DMA, 7.15% HEMA, 1.60% MM, 7.00%
PVP 360,000, 2.0% Norbloc, 1.0% CGI 819 and 0.02% Blue HEMA, 60
weight percent of the preceding component mixture was further
diluted with diluent, 40 weight percent of 72.5:27.5 TAA: PVP
2,500, to form the final monomer mix. The blend placed in a two
part contact lens mold and was cured using the following sequential
conditions a) room temperature for 30 seconds using a visible light
that emits 1 mW/sq cm, b)75.degree. C. 120 seconds, c) 75.degree.
C. 120 seconds 1.8 mW/sq/cm, and d) 75.degree. C. 240 seconds 6.0
mW/sq cm. The cured lenses are removed from the molds and hydrated
with Di.
Example 1
Preparation of Antimicrobial Lenses from Cured Lenses without an
Acidic Substance
[0039] Cured and hydrated lenses of Type A are placed in a jar with
sodium iodide solution in deionized water (500-700 ppm), containing
50 ppm of methylcellulose (.about.3 mL solution per lens,) and
rolled on a jar roller overnight. The lenses were transferred from
the jar to a blister pack where the excess sodium iodide solution
was removed. A solution (800 .mu.L, 150 ppm) of silver nitrate in
deionized water, containing the appropriate dispersion agent, was
added to the blister for two to five minutes. The silver nitrate
solution was removed, and the lenses were placed in a jar
containing deionized water and rolled on a jar roller for
approximately thirty minutes. The deionized water was replaced with
borate buffered sodium sulfate solution containing 50 ppm
methylcellulose water (SSPS), and allowed to roll on the jar roller
for an additional 30 minutes. The solution was then replaced with
fresh SSPS.
[0040] The lenses were then transferred to new blisters and dosed
with 950 .mu.L of SSPS. The blisters were sealed and autoclaved at
125.degree. C. for 18 minutes and analyzed for silver content using
the method described below. The results are presented in FIG. 1.
This data shows that increasing the concentration of sodium iodide,
unexpectedly reduces the amount of silver iodide deposited into the
lens.
[0041] Silver content of the lenses after lens autoclaving was
determined by Instrumental Neutron Activation Analysis "INAA". INAA
is a qualitative and quantitative elemental analysis method based
on the artificial induction of specific radionuclides by
irradiation with neutrons in a nuclear reactor. Irradiation of the
sample is followed by the quantitative measurement of the
characteristic gamma rays emitted by the decaying radionuclides.
The gamma rays detected at a particular energy are indicative of a
particular radionuclide's presence, allowing for a high degree of
specificity. Becker, D. A.; Greenberg, R. R.; Stone, S. F. J.
Radioanal. Nucl. Chem. 1992, 160(1), 41-53; Becker, D. A.;
Anderson, D. L.; Lindstrom, R. M.; Greenberg, R. R.; Garrity, K.
M.; Mackey, E. A. J. Radioanal. Nucl. Chem. 1994, 179(1), 149-54.
The INAA procedure used to quantify silver content in contact lens
material uses the following two nuclear reactions: [0042] 1. In the
activation reaction, .sup.110Ag is produced from stable .sup.109Ag
(isotopic abundance=48.16%) after capture of a radioactive neutron
produced in a nuclear reactor. [0043] 2. In the decay reaction,
.sup.110Ag (.tau..sup.1/2=24.6 seconds) decays primarily by
negatron emission proportional to initial concentration with an
energy characteristic to this radio-nuclide (657.8 keV). The
gamma-ray emission specific to the decay of .sup.110Ag from
irradiated. standards and samples are measured by gamma-ray
spectroscopy, a well-established pulse-height analysis technique,
yielding a measure of the concentration of the analyte.
Example 2
Preparation of Antimicrobial Lenses from Cured Lenses with an
Acidic Substance
[0044] The procedure of Example 1 was repeated with one exception,
0.05% weight percent of Acetic Acid in deionized water was added to
the sodium iodide solution and the silver nitrate solution. The
lenses were analyzed for silver content and the data is presented
in FIG. 2. This data shows that the acidified process gives the
expected increase in the amount of silver iodide deposited in the
lens as the amount of sodium nitrate is increased.
* * * * *