Title: METHOD OF MAKING OCULAR DEVICES
BACKGROUND OF THE INVENTION
The present invention generally relates to an improved method of making
biomedical ocular devices from a monomer mixture containing hydrophilic and
hydrophobic components. By filtering the monomer mixture, the hydrophilic and
hydrophobic components are finely dispersed within the mixture. Additionally, the
presence of microbubbles is decreased. This method is useful in preparing contact
lenses, intraocular lenses and ocular devices such as corneal rings, for example.
Biomedical ocular devices are made from a variety of materials. In general, there
are three classes of materials which are used to prepare contact lenses, intraocular lenses,
or ocular devices: hydrogels, non-hydrophilic soft materials, and rigid gas permeable
materials.
A common type of material for use as a soft contact lens is a hydrogel (see for
example, U.S. Pat. No. 3,220,960 to Drahoslav and Wichterle). Hydrogels constitute
crosslinked polymeric systems that can absorb and retain water in an equilibrium state.
Hydrogels generally have a water content greater than about 5 weight percent and more
commonly between about 10 to about 80 weight percent.
A particular group of hydrogel materials include those containing silicone
monomers. Polymeric silicone materials are generally hydrophobic and have been used
in a variety of biomedical applications, including contact lenses and intraocular lenses.
Silicone-containing monomers in contact lenses are desired to increase the oxygen
permeability or DK value. Such materials are usually prepared by polymerizing a
mixture containing at least one silicone-containing monomer and at least one hydrophilic
monomer.
Hydrophobic materials, including silicone-containing monomers, have poor
compatibility with hydrophilic monomers. Poor compatibility may result in phase
separation where the components of the mixture may actually separate out upon standing
or not be uniformly dispersed throughout the solution. In extreme cases, aggregation of
the components may result in separate layers. Poor compatibility of the components may
result in opaque materials upon curing. This can be particularly problematic when
preparing monomer mixtures to be used to make contact lenses since it is necessary that
the contact lens be optically clear.
Diluents have typically been used to overcome this incompatibility. A diluent is
defined as a substance which is substantially nonreactive with the components in the
monomer mixture. Diluents may be aqueous or organic in nature.
In addition to a uniformly dispersed mixture, the monomer mixture must be free
of contaminants and microbubbles to ensure the formation of a transparent lens upon
curing. The monomer mixture may need to be filtered to remove any contaminants from
the initial monomers. The presence of contaminants will affect the transparency of the
cured lens, resulting in poor optical quality for the wearer. U.S. Patent No. 5,789,464 to
Muller discloses purifying prepolymers by precipitation with acetone, dialysis or
ultrafiltration, with ultrafiltration being especially preferred. Continuously purifying the
solution by ultrafiltration results in a selected degree of purity, which can be as high as
desired. Pure prepolymers or comonomers result in monomer mixtures free of
contaminants resulting in good quality of optical lenses.
Dissolved gases may cause microbubbles in the resultant cured product which
may also affect the optical quality and transparency of the cured lens. The dissolved
gases are oxygen and nitrogen from the air and may interfere with polymerization.
Microbubbles may form in the monomer liquid upon standing or as the monomer
mixture progresses through a manufacturing line toward a casting machine.
The monomer mixture may be subjected to a vacuum to remove any dissolved
gases in the monomer mixture. Unfortunately, vacuum may also evaporate volatile
components from the monomer mixture. U.S. Pats. Nos. 5,435,943 (Adams et al);
5,656,208 (Martin et al); 5,753,150 (Martin et al) and 5,804,107 (Martin et al) disclose
filtering and degassing the monomer mixture. In these patents, the monomer mixture is
placed in a drum and drawn by the action of a pump. The monomer passes through a
filter in order to remove extraneous particulate contaminates that may be present in the
monomer. The monomer then proceeds through a separate degassing unit. The
degassing unit consists of a monomer in a gas permeable line, which is surrounded by a
chamber. Contained within the gas permeable line is a static flow mixer which causes a
turbulent flow and the boundary layer to be broken up. The chamber is maintained at a
subatmospheric pressure. Under such conditions, the gases within the monomer mixture
are removed. The process of first filtering the monomer mixture and then degassing
involves multiple stages.
Non-homogeneous dispersement of monomer components and dissolved gases
result in poor optical quality of cured contact lenses, intraocular devices, and ocular
devices including corneal rings. The present invention provides for a simple method
which improves the optical quality of such lenses and devices.
SUMMARY OF THE INVENTION
The present invention is an improved method for producing biomedical ocular
devices including contact lenses, intraocular lenses and devices such as corneal rings.
The biomedical ocular devices are made from a monomer mixture comprised of a
hydrophilic monomer and a hydrophobic monomer. By filtering the monomer mixture
through an in-line filter prior to casting, the hydrophilic and hydrophobic monomers are
finely dispersed. Additionally, the dissolved gases are broken down, thereby reducing
the formation of undesirably large bubbles in the finished biomedical ocular device. The
filtration leads to a more homogeneous mixture thereby improving the optical clarity of
the finished biomedical ocular device.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a simplified flow chart showing the various components of an apparatus to filter
monomer mixture used in molding contact lenses;
FIG. 2 is a light microscopic photograph taken under lOX-magnification showing a
contact lens cast without dispersion of the monomer mixture; and
FIG. 3 is a light microscopic photograph taken under lOX-magnification showing a
contact lens cast with dispersion of the monomer mixture.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention is an improved method for producing biomedical ocular
devices, in particular contact lenses, intraocular lenses and devices such as corneal rings.
The biomedical ocular device is made from a monomer mixture comprising a hydrophilic
monomer and a hydrophobic monomer, wherein the improvement comprises filtering the
monomer mixture with an in-line filter. Filtering the monomer mixture prior to casting
the lens leads to a fine dispersion or distribution of the components. The biomedical
ocular devices produced by this method have improved cosmetic yield and optical
clarity.
Any known biomedical ocular device composition containing dissimilar materials
may be used with this invention. Preferred compositions have both hydrophilic and
hydrophobic monomers. Especially preferred are silicone hydrogels.
Silicone hydrogels are prepared by polymerizing a mixture containing at least one
silicone-containing monomer and at least one hydrophilic monomer. The silicone-
containing monomer may function as a crosslinking agent (a crosslinker being defined as
a monomer having multiple polymerizable functionalities) or a separate crosslinker may
be employed.
An early example of a silicone-containing contact lens material is disclosed in
U.S. Patent No. 4,153,641 (Deichert et al assigned to Bausch & Lomb Incorporated).
Lenses are made from poly(organosiloxane) monomers which are α,ω terminally bonded
through a divalent hydrocarbon group to a polymerized activated unsaturated group.
Various hydrophobic silicone-containing prepolymers such as 1,3-
bis(methacryloxyalkyl)-polysiloxanes were copolymerized with known hydrophilic
monomers such as 2-hydroxy ethyl methacrylate (HEM A).
U.S. Patent No. 5,358,995 (Lai et al) describes a silicone hydrogel which is
comprised of an acrylic ester-capped polysiloxane prepolymer, polymerized with a bulky
polysiloxanylalkyl (meth)acrylate monomer, and at least one hydrophilic monomer. Lai
et al is assigned to Bausch & Lomb Incorporated and the entire disclosure is incorporated
herein by reference. The acrylic ester-capped polysiloxane prepolymer, commonly
known as M2DX consists of two acrylic ester end groups and "x" number of repeating
dimethylsiloxane units. The preferred bulky polysiloxanylalkyl (meth)acrylate
monomers are TRIS-type (methacryloxypropyl tris(trimethylsiloxy)silane) with the
hydrophilic monomers being either acrylic- or vinyl-containing.
The silicone-containing monomers may be copolymerized with a wide variety of
hydrophilic monomers to produce silicone hydrogel lenses. Preferred hydrophilic
monomers may be either acrylic- or vinyl-containing. The term "vinyl-type or "vinyl-
containing" monomers refers to monomers containing the vinyl grouping (CH2=CHR)
and are generally reactive. Such hydrophilic vinyl-containing monomers are known to
polymerize easily. Acrylic-containing monomers are those monomers containing the
acrylic group (CH2=CRCOX) wherein R=H or CH3 and X=O or NH, which are known to
polymerize readily.
Suitable hydrophilic monomers include: unsaturated carboxylic acids, such as
methacrylic and acrylic acids; acrylic substituted alcohols, such as 2-
hydroxyethylmethacrylate and 2-hydroxethylacrylate; vinyl lactams, such as N-vinyl
pyrrolidone; and acrylamides, such as methacrylamide and N,N-dimethylacrylamide. A
further example is the hydrophilic oxazolone monomers disclosed in U.S. Pat. No.
4,910,277 (Bambury et al). Other suitable hydrophilic monomers will be apparent to one
skilled in the art.
Other examples of silicone-containing monomer mixtures which may be used
with this invention include the following: vinyl carbonate and vinyl carbamate monomer
mixtures as disclosed in U.S. Pat. Nos. 5,070,215 and 5,610,252 (Bambury et al);
fluorosilicone monomer mixtures as disclosed in U.S. Pat. Nos. 5,321,108; 5,387,662
and 5,539,016 (Kunzler et al); fumarate monomer mixtures as disclosed in U.S. Pat. Nos.
5,374,662; 5,420,324 and 5,496,871 (Lai et al) and urethane monomer mixtures as
disclosed in U.S. Pat. Nos. 5,451,651; 5,648,515; 5,639,908 and 5,594,085 (Lai et al), all
of which are commonly assigned to assignee herein Bausch & Lomb Incorporated, and
the entire disclosures of which are incorporated herein by reference.
Examples of non-silicone hydrophobic materials include alkyl acrylates and
methacrylates.
The reaction mixture may additionally comprise a diluent. As previously stated,
diluents are substantially nonreactive with the monomers in the monomeric mixture.
The diluent is generally removed after polymerization.
Water may be used as a diluent, or alternately, an organic diluent may be
employed, including: monohydric alcohols, with C6-CI0 straight-chained aliphatic
monohydric alcohols, such as n-hexanol and n-nonanol, being especially preferred; diols,
such as ethylene glycol; polyols, such as glycerin; ethers, such as dipropylene glycol and
diethylene glycol monobutyl ether; ketone, such as methyl ethyl ketone; esters, such as
methyl enanthate, ethylene carbonate and glyceryl triacetate; and hydrocarbons. Other
suitable diluents will be apparent to a person of ordinary skill in the art. Preferred
diluents include 3,7-dimethyl-3-octanol, methyl enanthate, hexanol and nonanol.
The monomer mix of the present invention may include additional constituents
such as UN-absorbing agents, initiators, crosslinking agents, internal wetting agents,
hydrophilic monomeric units, toughening agents, or colorants such as those known in the
contact lens art.
Conventional curing methods such as UV polymerization, thermal
polymerization, or combinations thereof, can be used to cast these ethylenically
unsaturated compounds. Representative free radical thermal polymerization initiators
can be organic peroxides and are usually present in the concentration of about 0.01 to 1
percent by weight of the total monomer mixture. Representative UV initiators are known
in the field such as, benzoin methyl ether, benzoin ethyl ether, 1164, 2273, 1116, 2959,
3331 (EM Industries) and Irgacure 651 and 184 (Ciba-Geigy). In the preferred
embodiment, Darocur 1173 is the UV initiator.
The monomer mixture may include a tinting agent, defined as an agent that, when
incorporated in the final lens, imparts some degree of color to the lens. Conventional
tinting agents are known in the art, including non-polymerizable agents, or polymerizable
agents that include an activated unsaturated group that is reactive with the lens-forming
monomers. One preferred example of this latter class is the compound 1 ,4-bis(4-(2-
methacryloxyethyl)phenylamino)anthraquinone, a blue visibility-tinting agent disclosed
in U.S. Patent No. 4,997,897 (Melpolder).
The monomer mixture may also include a UN-absorbing agent, defined as an
agent that reduces light in the general region of 200 to 400 nm. Representative
polymerizable UN absorbing materials for contact lens applications are described in U.S.
Patent Νos. 4,304,895 (Loshaek), 4,528,311 (Beard et al), 4,716,234 (Dunks et al),
4,719,248 (Bambury et al), 3,159,646 (Milionis et al) and 3,761,272 (Manneus et al).
Examples of UN-absorbing compounds include the benzotriazoles and benzophenones.
Silicone hydrogels of this invention are typically formed by polymerizing a
monomer mixture comprising: about 10 to about 90 weight percent of a silicone-
containing monomer, preferably 20 to 70 weight percent of a silicone-containing
monomer, more preferably 40 to 70 weight percent; about 5 to about 70 weight percent
of a hydrophilic monomer, preferably 10 to 50 weight percent of a hydrophilic monomer,
more preferably 20 to 40 weight percent of a hydrophilic monomer; and about 5 to about
50 weight percent of a diluent, preferably 5 to 40 weight percent of a diluent, more
preferably 5 to 30 weight percent of a diluent.
Various techniques for molding hydrogel polymer mixtures into contact lenses
are known in the art, including spin casting and cast molding. Spin casting processes are
disclosed in U.S. Pat. Nos. 3,408,429 and 3,496,254. U.S. Patent No. 4,555,732
discloses a process in which the lens is initially cured by spincasting. The lens is
subsequently lathe cut to provide a contact lens having the desired thickness and lens
surface.
Another method of forming and curing a lens is cast molding. Cast molding
involves charging a quantity of polymerizable monomeric mixture to a mold assembly,
and curing the monomeric mixture while retained in the mold assembly to form a lens,
for example, by free radical polymerization of the monomeric mixture. The mold
assembly defines a mold cavity for casting the lens, including an anterior mold for
defining the anterior lens surface and a posterior mold for defining the posterior lens
surface. U.S. Patent No. 5,271,875 describes a static cast molding method that permits
molding of a finished lens in a mold cavity defined by a posterior mold and an anterior
mold.
Examples of techniques to cure the lens material include heat, microwave
radiation, infrared radiation, electron beam radiation, gamma radiation, ultraviolet (UN)
radiation, and the like; combinations of such techniques may be used.
Regardless of which method is used to cast the lens, it is important that casting
conditions be maintained as to minimize any adverse affects on the monomer mixture.
Besides contact lenses and intraocular lenses, another application for this
invention is the manufacture of ocular devices such as intrastromal corneal rings. These
devices are flexible rings which are inserted beneath the surface of the cornea to elevate
the edge of the cornea. This results in the front of the eye being flattened, decreasing
nearsightedness.
Additionally, another application may include the manufacture of an ocular
device which may be used as an ophthalmic drug delivery vehicle. This may be in the
form similar to that of a shield worn on the eye or an insert placed in the ocular region.
Inserts can also be used to deliver lubricants and other medicaments to the ocular area.
A simplified flow chart for processing a monomer mixture is shown in FIG. 1.
In particular, FIG. 1 shows the various components of an apparatus used to finely
disperse the monomer mixture components used in molding contact lenses.
As illustrated in FIG.l, apparatus 10 contains container 20, line 36, switching
valve 40, pump 50, line 66, filter 70 and injection needle 80.
Typically, monomer mixture is provided in container 20 having cap 22. Line 36
includes end 34 which extends to the bottom of container 20. Opposite end 38 of line 36
extends into a side of switching valve 40.
Pump 50 is connected to switching valve 40. Pump 50 may be a syringe or any
other mechanism such that pump 50 is able to create a vacuum and pull liquid from
container 20 into line 36 and thereby into switching valve 40. Switching valve 40 is
open to line 36 when pump 50 draws liquid from container 20 but is closed to injection
line 66. Pump 50 is preferably a small volume syringe (i.e., 250 μL) and able to
accurately dispense microliter aliquots of liquid. Once pump 50 has finished the drawing
of liquid from container 20, switching valve 40 will close so that pump 50 can push the
liquid into filter 70.
Filter 70 is a filter having a small pore size, preferably 0.22 μm pore size. The
diameter and filter membrane area may be any appropriate size. Preferred is a
replaceable or disposable filter membrane that is 13 mm in diameter and has a 0.8 cm2
filter area. The filter membrane may be any inert material commonly used to filter
organic solvents. A preferred filter membrane material is polytetrafluoroethylene
(PTFE), which is a stable polymer inert to most chemicals. Filter 70 is connected to line
66. Connector 75 joins line 66 to injection needle 80. Injection needle 80 leads to a lens
casting machine (not shown) where the filtered monomer mixture will be placed into a
contact lens mold and cured to form a contact lens. The amount of monomer mixture
used to make a contact lens is small, approximately 40 μL per lens. Due to the small
amount of liquid dispensed, the pressure of the overall system is low. The pressure
exerted through the injection line by the syringe pump is dissipated when the monomer is
dispensed.
FIG. 2 depicts a 10X magnification of cured contact lens examined under a light
microscope. The monomer mixture used to cast this lens was prepared without n
dispersion of the monomer mixture. There appear numerous "spots", some of which are
dark and some which are light circles ringed in dark perimeters. These spots represent
microbubbles trapped within the dimensions of the lens matrix.
FIG. 3 depicts a 10X magnification of cured contact lens. The monomer mixture
prior to curing has been filtered through a 0.22 μm filter in accordance with the present
invention. There are fewer "spots" in this figure than in FIG. 2. This indicates that the
monomer mixture has been dispersed, i.e., the presence of microbubbles has been
decreased and are not visible under this magnification. FIG. 3 shows a lens which has
better optical clarity than the lens in FIG. 2.
As stated previously, by filtering the monomer mixture through a filter just prior
to casting, the hydrophilic and hydrophobic components are finely dispersed. Any
dissolved gases contained within the monomer mixture are broken up and finely
dispersed throughout the mixture. Cured contact lenses thus produced have few
instances of cosmetic defects. Intraocular lenses and ocular devices such as corneal rings
would also have improved optical clarity and few instances of cosmetic defects.
COMPARATIVE EXAMPLE 1
Monomer mixture was prepared by combining 55 parts by weight TRIS-VC
(tris(trimethylsiloxy)silylpropyl methacrylate), 30 parts by weight NVP (N-vinyl
pyrrolidone), 15 parts by weight V2D25 (a silicone-containing vinyl carbonate), 15 parts
by weight 1-nonanol, 1 parts by weight Vinal Acid (N-vinyloxycarbonyl alanine), 0.5
parts by weight Darocur 1173 and 150 ppm by weight tint. Each component was
individually weighed and added sequentially to a glass container. The solution was
mixed for at least 1-2 hours and filtered through a 5 μm PTFE filter. The resulting
solution was visually transparent. Lenses were cast and cured under the presence of UV
light. Lenses were released from the molds, hydrated and examined for particle defects.
TABLE 1
EXAMPLES 2-7
Monomer mixture was prepared as in Example 1. Prior to casting, the mixture
was passed through a 0.22 μm PTFE in-line filter and immediately cast.
TABLE 2
By using a 0.22 μm in-line filter, the cosmetic yield (particle defects) increased
significantly as compared to Example 1, thus also significantly reducing the number of
defective lenses which would otherwise be discarded.
While the above serves to illustrate preferred embodiments, it is understood that
the invention is not limited thereto, and modifications and variations would be evident to
a person of ordinary skill in the art.