WO2004094075A1 - Antimicrobial coatings for ophthalmic devices - Google Patents
Antimicrobial coatings for ophthalmic devices Download PDFInfo
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- WO2004094075A1 WO2004094075A1 PCT/US2004/011513 US2004011513W WO2004094075A1 WO 2004094075 A1 WO2004094075 A1 WO 2004094075A1 US 2004011513 W US2004011513 W US 2004011513W WO 2004094075 A1 WO2004094075 A1 WO 2004094075A1
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- copolymers
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/10—Optical coatings produced by application to, or surface treatment of, optical elements
- G02B1/18—Coatings for keeping optical surfaces clean, e.g. hydrophobic or photo-catalytic films
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
- A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
- A01N41/04—Sulfonic acids; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
- A61L12/14—Organic compounds not covered by groups A61L12/10 or A61L12/12
Definitions
- the present invention relates to antimicrobial, including antibacterial, coatings for ophthalmic devices, preferably polymer coatings for contact lenses.
- Prolonged use of contact lenses may allow for increased proliferation and accumulation of bacteria or other microbes, such as, but not limited to, Pseudomonas aeruginosa, Acanthamoeba species, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, and Serratia marcesens, on the surfaces of the contact lenses.
- bacteria or other microbes such as, but not limited to, Pseudomonas aeruginosa, Acanthamoeba species, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, and Serratia marcesens, on the surfaces of the contact lenses.
- This accumulation can cause side effects such as contact lens acute red eye.
- Other adverse effects associated with microbial growth and attachment may include, but are not limited to, contact lens associated red eye, infiltrative keratitis, and microbial keratitis.
- the present invention prevents strong attachment of microbes to the ophthalmic devices thereby allowing the consumer's natural defenses to remove a substantial amount of the microbes from the ocular environment before adverse effects occur.
- the proliferation of attached bacteria or other microbes is reduced.
- the present invention reduces the adhering bacteria or other microbes and reduces their proliferation rate on ophthalmic devices and therefore make the ophthalmic devices safer for humans, especially for contact lens wear.
- this invention includes a method of preventing microbial attachment on ophthalmic devices, preferably contact lenses, by attaching a polymer to one or more surfaces of an ophthalmic device, wherein said polymer has a molar ratio of greater than about 2 carboxylate groups to about 1 sulfonate groups. Further, this invention includes a method of preventing microbial growth on ophthalmic devices, preferably contact lenses, by attaching a polymer to one or more surfaces of an ophthalmic device wherein said polymer has a molar ratio of great than about 2 carboxylate groups to about 1 sulfonate group) and placing the ophthalmic device on a cornea.
- Figure 1 is a plot of the non-mediated P. aeruginosa adhesion (expressed as the percentages of adhered bacteria per lens) on unfunctionalized and functionalized lenses.
- Figure 2 is a plot of the plasma mediated P. aeruginosa adliesion (expressed as the percentages of adhered bacteria per lens) on unfunctionalized and functionalized lenses.
- Figure 3 is a plot of the plasma mediated P. aeruginosa adhesion (expressed as the percentages of adhered bacteria per lens) on functionalized lenses as a function of MA/SS ratio.
- Figure 4 is a plot of reduction of plasma mediated P. aeruginosa adhesion on functionalized lenses compared to unfunctionalized lenses.
- Figure 5 is a plot of the non-mediated S. aureus adhesion (expressed as the percentages of adhered bacteria per lens) on unfunctionalized and functionalized lenses characterized by the MA/SS ratio.
- Figure 6 is a plot of the plasma mediated S. aureus adhesion on (expressed as the percentages of adhered bacteria per lens) on functionalized lenses compared to unfunctionalized lenses.
- Figure 7 is a plot of S. aureus adhesion (expressed as the percentages of adhered bacteria per lens) on functionalized lenses as a function of MA/SS ratio.
- Figure 8 is a plot of reduction of plasma mediated S. aureus adhesion on functionalized lenses compared to unfunctionalized lenses.
- Figure 9 is a plot of the bacteriophobic effect of lenses coated with random biospecific acrylic tercopolymers with ratio MA/SS of 3.2 ("J&J lenses") with either P. aeruginosa or S. aureus.
- Figure 10 is a plot of tear-like-mediated bacterial adhesion of P. aeruginosa and S. aureus on functionalized lenses at various MA/SS ratios.
- Figure 11 is a plot of bacterial proliferation of P. aeruginosa on the lenses in the presence of synthetic media or synthetic tear fluid over time.
- Figure 12 is a plot of bacterial proliferation of S. aureus on the lenses in the presence of synthetic media or synthetic tear fluid over time.
- Random biospecific polymer has substituents with suitable chemical groups or random copolymerizations of suitable monomers, which contain arrangements of chemical functions which mimic natural biospecific sites.
- a good background article is Jozefowicz and Jozefonvicz, Randomness and Biospecificity: random copolymers are capable of biospecific molecular recognition in living systems, Biomaterials, 18 (1997) 1633-1644 (incorporated herein by reference).
- Mediated means at least one ophthalmic device surface has interacted with at least one naturally occurring protein(s) in plasma or tear fluid or tear-like fluid which resulted in a change in the bacterial or other microbial adhesion and proliferation on the ophthalmic device.
- Bacteria and other microbes colonize a surface by either a mediated or a non- mediated mechanism.
- the non-mediated attachment is weak and the microbes are easily removed, generally do not proliferate and are considered a less serious problem than in a mediated attachment.
- the mediated mechanism utilizes adhesive proteins such as, but not limited to f ⁇ bronectin, to form a strong attachment to a surface.
- Adhesive proteins generally have several binding sites for various molecules. The nature (both density and type of charge) of the surface charge may control which protein binding sites interact with the surface and thereby may control the sites available for bacterial or microbial adherence.
- binding sites required for mediated bacterial or other microbial adhesion and proliferation are used to bind the protein to the surface then bacterial or other microbial adhesion and proliferation can be reduced.
- Binding for the polymer includes but is not limited to chemical bonds, or entanglements (interpenetrating network).
- a polymer comprises neutral groups and ionic groups.
- the ionic groups include but are not limited to carboxylate groups and sulfonate groups, which are attached to the surface of an ophthalmic device, preferably a silicone hydrogel contact lens.
- "Preventing microbial attachment,” as used herein, means reducing the amount of microbes which attach to the ophthalmic device, preferably by at least 50%, more preferably about 90% (as compared to microbes attached to ophthalmic devices which do not contain the neutral and ionic groups disclosed herein) and/or inhibiting the ability of microbes to attach to the ophthalmic device.
- Preventing microbial growth means reducing the growth rate at which microbes grow on an ophthalmic device, preferably by at least 50% (as compared to microbes growing on the surfaces of the ophthalmic device which do not contain the neutral and ionic groups disclosed herein) and/or inhibiting the ability of microbes to attach to the ophthalmic device, and/or killing microbes on the surface of the ophthalmic devices or in an area surrounding the ophthalmic device.
- Bacteriophobic properties of an ophthalmic device as used herein means that the device is able to prevent microbial attachment on the device.
- Bacteriostatic properties of an ophthalmic device as used herein means that the device is able to prevent microbial growth on the device.
- optical devices mean contact lenses that reside in or on the eye, such as soft contact lenses, hard contact lenses, overlay lenses, ocular lenses and ophthalmic lenses.
- the contact lenses preferably comprise one or more of the following: poly(methyl)methacrylate polymer, poly(hydroxyethyl)methacrylate polymer, polyacrylic acid polymer, silicone acrylate polymer, fluoroacrylate pqlymer, fluoroether polymer, polyacetylene polymer, polyimide polymer, hydrogels, silicone materials, acrylic materials, fluorocarbon materials, mixtures and copolymers of any of the foregoing, etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon, acquaf ⁇ lcon A, balafilcon A, lotrafilcon A, lotrafilcon B, and silicone hydrogels.
- the lenses may alternatively comprise or consist of random biospecific polymers.
- Merobes mean bacteria and other microbes, including but nor limited to, microbes found in or on the eye or tear fluid, particularly Pseudomonas aeruginosa, Acanthamoeba species, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Serratia marcesens and combinations thereof.
- a "synthetic tear fluid,” as used herein, means any fluid that has protein composition and ionic strength properties similar to human tears, including but not limited to a solution of 5% blood plasma supplemented with Lysozyme at 4.5g/L and Lactoferrin at 1.7g/L.
- Polymer means a polymer having one or more carboxylate groups and one or more sulfonate groups, such as methacrylic acid copolymers, methyl methacrylate copolymers, sodium styrenesulfonate copolymers, methyl methacrylate-methacrylic acid-sodium styrene sulfonate random copolymers or combinations thereof.
- the molar ratio of carboxylate groups to sulfonate groups is preferably greater than about 2, more preferably about 2 to about 4.
- Patent Application Publication No. US2002/0068804 Al all of which are herein incorporated by reference, teach polymers and the methods of making said polymers, which may be effective in the present invention.
- Polymers may be prepared by free radical polymerization, condensation polymerization and other methods known to those skilled in the art.
- One embodiment of a polymer is a water-insoluble polymer, containing carboxylate and sulfonate groups, obtained by free radical copolymerization of one or more aliphatically unsaturated monomers containing carboxylate groups, or the correspondingly functionalized derivatives of the monomers, as a first component with one or more aliphatically unsaturated monomers containing sulfonate groups, or the correspondingly functionalized derivatives of the monomers, as a second component and a third component which comprises an aliphatically unsaturated monomer, the correspondingly functionalized derivatives being converted into carboxylate and sulfonate groups after the copolymerization.
- a polymer is a water-insoluble polymer obtainable by free- radical polymerization of (a) at least one monomer of the general formula R-A a , in which R is an aliphatically unsaturated organic radical with the valence "a", A is a carboxyl group, carboxylate group, sulfuric acid group, sulfonic acid group, phosphoric acid group, phosphonic acid group, phosphorous acid group, phenolic hydroxyl group or a salt of one of the groups, and a is 1, 2 or 3, with the proviso that, if the monomer of the formula contains a carboxyl group or a carboxylate group, either (1) this monomer contains at least one further radical A having a different one of the definitions specified for A, or (2) at least one additional monomer of the formula is also used in which A has a different one of the definitions specified for A; and (b) at least one other aliphatically unsaturated monomer.
- R is an aliphatically unsaturated organic radical
- polymer also includes macromer, which is a precursor to a polymer, and which can be incorporated into the lens of the invention.
- the polymers used in the invention are biospecific polymers, i.e. polymers capable of biospecific molecular recognition. It is known in the art that random attachment of functional groups to certain polymers results in biospecificity. It is also known that the level of biological activity varies with the composition of the copolymer, such that there may be a maximum in activity at some intermediate composition between maximum and zero content of the functional groups. In the present invention, it is preferable for the polymer to have random substitution of several substrates, e.g. carboxylate and sulfonate groups.
- Monomers which are suitable for preparing the polymers, include but are not limited to, acrylic acid, methacrylic acid, 4-vinylsalicylic acid, itaconic acid, vinylacetic acid, cinnamic acid, 4-vinylbenzoic acid, 2-vinylbenzoic acid, sorbic acid, caffeic acid, maleic acid, methylmaleic acid, dimethylmaleic acid, dihydroxymaleic acid, isocrotonic acid, fumaric acid, methylfurnaric acid, allylacetic acid and the alkali metal salts, specially the sodium salts, of these acids, vinylsulfonic acid, allylsulfonic acid, methallylsulfonic acid, 4-styrenesulfonic acid, 2-styrenesulfonic acid, vinyltoluene-sulfonic acid, 2-acrylamido-2-methyl-l- propanesulfonic acid (AMPS), 4-carboxy styrenesulfonic acid and the alkal
- An embodiment of the present invention is a method for preventing microbial adhesion and growth comprising attaching a polymer to a surface of an ophthalmic device, wherein said polymer has carboxylate and sulfonate groups.
- the molar ratio of the carboxylate groups to sulfonate groups is preferably greater than about 2, more preferably about 2 to about 4.
- the polymer is attached to at least the surface of the ophthalmic device which contacts the cornea or the surface of the ophthalmic device which contacts the interior of the eyelid during conventional use of the ophthalmic device. More preferably, the polymer is attached to the surface of the ophthalmic device which contacts the cornea and the surface which contacts the interior of the eyelid during conventional use. Most preferably, the polymer is attached to all of the surfaces of the ophthalmic device.
- the ophthalmic device with the attached polymer may be placed in a fluid, such as tears, storage fluid, such as the fluid used to store contact lenses during shipment, before use and between uses by the consumer or the fluid used to clean and/or disinfect the contact lenses between uses by the consumer.
- a fluid such as tears
- storage fluid such as the fluid used to store contact lenses during shipment
- a synthetic tear fluid may be used to mimic these fluid examples in in vitro testing.
- the polymer is attached to the surface of an ophthalmic device, including but not limited to a contact lens, by methods known to those skilled in the art including but not limited to surface grafting, plasma polymerization, mold transfer coating or tampo printing.
- an ophthalmic device including but not limited to a contact lens
- adhesive proteins such as fibronectin
- the ophthalmic device is preferably a contact lens, preferably comprising poly(methyl)methacrylate polymer, silicon acrylate polymer, fluoroacrylate polymer, fluoroether polymer, polyacetylene polymer, polyimide polymer, hydrogels, silicone materials, acrylic materials, fluorocarbon materials, etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon, acquafilcon A, balaf ⁇ lcon A, lotrafilcon A, lotrafilcon B, silicone hydrogels, or combinations thereof.
- a contact lens preferably comprising poly(methyl)methacrylate polymer, silicon acrylate polymer, fluoroacrylate polymer, fluoroether polymer, polyacetylene polymer, polyimide polymer, hydrogels, silicone materials, acrylic materials, fluorocarbon materials, etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon,
- the binding of the adhesive protein may result in substantially reducing microbial (including but not limited to bacterial) adhesion to the device, preferably about 90% reduction takes place as compared to a device without the polymer.
- the microbes may include but are not limited to Pseudomonas aeruginosa, Acanthamoeba species, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermis, Serratia marcesens, or combinations thereof.
- the polymer includes but is not limited to methyl methacrylate copolymers, methacrylic acid copolymers, sodium styrenesulfonate copolymers, methyl methacrylate-methacrylic acid-sodium styrene sulfonate random copolymers or combinations thereof.
- the molar ratio of carboxylate group to sulfonate group is about 2 to about 4, preferably greater than about 2.
- MMA Methylmethacrylate
- MA methacrylic acid
- SS Sodium styrene sulfonate
- MMA (6.0 ml, 56.1 mmol), MMA (1.27 ml, 15 mmol), and SS (0.854 g, 3.74 mmol) were charged into the reaction vessel, and DMSO (35 ml) was then added.
- a solution of ATBN (2,2'-Azobisisobutyronitrile, CAS # 78-67-1) in DMSO (dimethyl sulfoxide) (5.5 mg/ml) was prepared separately, and 1.0 ml of this was introduced into the reaction vessel.
- the set-up was purged of oxygen by using liquid N 2 freeze-pump-thaw method (repeated three times). The reaction was then heated to 75 °C, and allowed to proceed for 16 to 18 hours under nitrogen.
- MMA and MA were distilled prior to use.
- SS contained 9.96% w/w H 2 O, which was accounted for in the stoichiometric calculations.
- the polymer was pulverized in a commercial blender and 5.8 grams were further purified by stirring in 200 ml of deionized water at 60C, followed by filtration and further washing with deionized water (2 x 50 ml), and drying in vacuo (5 mbar) at 65°C for 6.5 hours to yield 5.2g of a white powder.
- a polymer from Example 2 was dissolved into a 70:30 ethanol: ethyl lactate solvent solution to make 1.5% (w/v) solution of polymer.
- the solution was used to coat Zeonor 1060R (trademark) lens molds via spin coating according to the following procedure.
- the 1.5% polymer from Example 2 coating solution was applied to the Zeonor front curve mold surface by dispensing approximately 3 ⁇ l of the solution into the center of a mold spinning at approximately 7500 rpm and thereafter spun for 8 seconds. > During the last 2 seconds of spinning the excess coating near the edge of the mold . was cleared using a pressurized air jet nozzle ( ⁇ 15 psi).
- the back curve mold is coated similarly using the 1.5% polymer solution from Example 2 is used for the coating and the coating is applied to the mold spinning at 6000 rpm for 2 seconds followed by 6 seconds of spinning at 7500 rpm. Again, a pressurized air jet is used to remove excess coating near the edge of the mold for the last two seconds of spin time.
- MMA and MA were distilled prior to use.
- SS was determined to contain 9.74% w/w H 2 O, which was accounted for in the stoichiometric calculations.
- the polymer was filtered, and dried in vacuo at 65°C. The dried polymer was ground to a fine powder.
- One gram of the polymer was soaked in 50 ml of isopropanol, filtered, then washed twice with 30 ml isopropanol and once with 50 ml of hexane and dried in vacuo at 65°C to yield the "IPA-washed fraction.”
- One gram of the polymer was stirred into 50 ml of deionized water at 60C, cooled to room temperature, filtered, and washed twice with 30 ml of deionized water and dried in vacuo at 65°C to obtain the "water- washed fraction.”
- Example 4A the water-washed fraction had a significantly higher MMA content as compared to the IPA-washed fraction. Without being limited to mechanism, this suggests that water removed the more ionic chains in the sample. Washing the polymer with water did not change the MA/SS ratio significantly as compared to the IPA-washed fraction.
- Example 4 and 4B with the polymer with an intermediate to high overall MMA content, water washing did not significantly impact the composition or the MA/SS ratio of the polymer. Since the biospecific interactions of polymer chains are derived from the random functional group distribution, any purification technique that systemically alters the composition of the polymer (e.g. removal of highly ionic chains) will skew the distribution. It is preferable to preserve the original statistical distribution obtained during polymerization for MMA/MA/SS copolymers, and in order to do so, total (theoretical) ionic content of less than or equal to 25% on molar basis is preferred.
- the compositions in Table 1 labeled (actual) were determined from 1H NMR spectra, as indicated in Example 5-14.
- compositions in Table 2 labeled were determined from 1H NMR spectra (270 MHz), acquired in deuterated DMSO.
- the peaks used to calculate the relative ratios were the aromatic protons of the SS residues ( ⁇ 6.8-7.6 ppm), the methyl ester protons from MMA ( ⁇ 3.5 ppm), and the combined peak ( ⁇ 0.2-2.2 ppm) from the ⁇ -methyl protons of MMA/MA and the ⁇ -methylene protons of MMA/MA/SS.
- the polymers were purified, prior to 1H NMR analysis, by washing with deionized water. Two grams of the polymer was stirred into 60-70 ml of deionized water at 50 to 60°C, cooled to room temperature, filtered, and washed twice with 30 ml of deionized water and dried in vacuo at 65°C. The 1H NMR spectra did not show any evidence of residual monomers.
- Silicone hydrogels were coated using the method in Example 2 with random biospecific polymers (P,Q,R,S) with a ratio of COO-/SO3- ranging between 0 and 5. Table 3
- PBS with Ca++ and Mg++ was finally added to the bacterial pellet to obtain suitable bacterial dilutions (10 -10 cfu/ml) determined from the standard curve corresponding to the absorbency versus cfu and the suspensions were mixed with a vortex mixer.
- Bacterial solutions were diluted in order to obtain 30 to 300 colonies spread on the agar plates.
- the lenses were aseptically transferred into cell culture boxes and washed five times in 2 ml of Phosphate-buffered saline ("PBS"). The lenses were then incubated for 1 hour at room temperature under stirring with synthetic tear fluid.
- the synthetic tear fluid is human plasma diluted at 5% in PBS supplemented with Lysozyme (4.7 g/1) and lactoferrin (1.7 g/1). After the incubation periods, lenses were washed three times with PBS and were then transferred to new cell culture boxes. The bacterial adhesion is reported as % adhesion of the bacteria in suspension which are adhered to the lens.
- phosphate-buffered saline PBS
- the lenses were then incubated with 1 ml of two concentrations of the radio-labeled bacteria for 1 hour at 30°C or at 37°C (respectively for the bacteria strains) under stirring. After five washings of the lenses with PBS, the lenses were transferred to counting vials, 10 ml of scintillation fluid was added, the solutions were mixed with a vortex mixer and the radioactivity incorporated by the adhered bacteria was measured with a B-counter. The bacterial adhesion is reported as the adhesion percentages of the bacteria in suspension, which are adhered to the lens.
- Synthetic tear fluid coated lenses were first incubated for 1 hour with suspended bacteria. The unbound bacteria were removed by washing the lenses 5 times in buffer. The lenses were then transferred to new tubings containing 1 ml of the selected media. They were then incubated at 37°C under stirring for various periods of time ranging between 0 and 5 hours. At the end of the incubation, both the number of surface-bound organisms and the number bacteria in suspension (Br) were determined.
- the number of surface-bound bacteria (Bs) was determined by detaching the organisms from the surface according to the following scheme. Washing the lenses in PBS, and incubating the lenses in 1 ml of a solution of trypsin for 5 min. at 37°C under smooth stirring. Then, the solutions is vortex mixed and sonicated for 3 minutes, followed by 3 washings of the lenses in PBS. The pool of the washings are spun at 3500 rpm for 15 minutes. The bacterial pellet is resuspended in PBS and counted for cfu after suitable dilutions on agar gel.
- plasma mediated P. aeruginosa adhesion is measured on control lenses (unfunctionalized lenses) and lenses coated with the tercopolymers (functionalized lenses); in this case, the lenses were characterized by the MA/SS ratio.
- the mediated bacterial adhesion is from 4 to 6 time greater than the non- mediated adhesion.
- Figure 4 shows the variation of the I ratio as a function of MA/SS ratio in the copolymers. Inhibition of the bacterial adhesion reached as high as 50% for MA/SS ratios of 2.29 and 3.45. When MA/SS ratio is 0 (and the copolymer has only MMA and SS monomers), the inhibition of the bacterial adhesion is significantly lower (20%) as compared to 50%.
- poly-Hema lenses made as is known in the art is significantly lower than on uncoated silicone hydrogel lenses as is shown in Figure 5.
- the non-mediated adhesion values on copolymers with MA/SS ratio of 0 and on MA/SS ratio of 4.44 are between the adhesion values for the controls.
- the mediated bacterial adhesion is from 5 to 10 times higher on the nonfunctionalized lenses and from 2 to 5 times higher on functionalized lenses compared to the non-mediated bacterial adhesion as seen in Figure 6.
- Adhesion of S. aureus on poly HEMA coated control lenses is 0.93+-0.28%/lens and 1.5+- 0.48%/lens on nonfunctionalized lenses.
- Functionalized lens with (MA, SS, MMA) the mediated adhesion of S. aureus is significantly lower than that observed in the nonfunctionalized.
- MA, SS and MMA are all present in the tercopolymer.
- Figure 7 shows that functionalized lenses have low adhesion values for MA/SS ratio equal to 2.29, 3.45 and 4.44.
- the inhibition of the mediated bacterial adhesion is evidence by the comparison between bacterial adhesion on functionalized lenses and nonfunctionalized lenses and is calculated by the I formula described above.
- lenses coated with MMA, MA and SS copolymers show bacteriophobic properties when the lenses are exposed to synthetic tear fluid with regard to the mediated adhesion of P. aeruginosa and S. aureus.
- the maximum of the bacteriophobic effect for both strains is observed for the lenses coated with the tercopolymer MA/SS 2.29 and 3.45.
- P. aeruginosa is significantly lower than that observed in the case of the controls especially for the ratio 2.29 and 4.44. Bacteriophobic effect
- the functionalized lenses have a long time lag (> 2 hours) which is then followed by an exponential proliferation.
- the number of bacteria adhered to the functionalized lenses is about 35 times lower (for P. aeruginosa) and 8 times lower (for S. aureus) as compared to the control lenses.
- ⁇ log Log N5-LogN0 (log cfu/lens or Log cfu/mL in the case of control) with NO : bacterial concentration introduced initially (with 0 Hours of the proliferation)
- N5 bacterial concentration obtained after 5 hours of proliferation.
- Nn2 the number of the bacteria at the moment t2
- T the time necessary to increase the population number from Nnl to Nn2
- N5 control/NO control with, NO lenses the number of the total proliferation on lenses after 0 hours of the incubation time
- N5 lenses the number of the total proliferation on lenses after 5 hours of the incubation time
- NO control the number of the total proliferation in suspension after 0 hours of the incubation time
- N5 control the number of the total proliferation in suspension after 5 hours of the incubation time
- Lenses incubated in the presence of synthetic tear fluid as a proliferation medium show that after 5 hours, the number of bacteria generated by the proliferation of the adhered bacteria as compared to the control in suspension is about 40 times in P. aeruginosa and 10 times in S. aureus.
- the functionalized lenses have approximately the same microbial growth as seen in the ocular environment without contact lenses and have a decreased microbial growth compared to that seen with contact lenses in having adhered microbes, including, but not limited to bacteria.
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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JP2006510036A JP2006523866A (en) | 2003-04-16 | 2004-04-14 | Antibacterial coating for ophthalmic devices |
EP04759857A EP1628781A4 (en) | 2003-04-16 | 2004-04-14 | Antimicrobial coatings for ophthalmic devices |
CA002522521A CA2522521A1 (en) | 2003-04-16 | 2004-04-14 | Antimicrobial coatings for ophthalmic devices |
BRPI0409582-0A BRPI0409582A (en) | 2003-04-16 | 2004-04-14 | antimicrobial coatings for ophthalmic devices |
AU2004232942A AU2004232942A1 (en) | 2003-04-16 | 2004-04-14 | Antimicrobial coatings for ophthalmic devices |
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US10/414,880 | 2003-04-16 | ||
US10/414,880 US20040208983A1 (en) | 2003-04-16 | 2003-04-16 | Antimicrobial coatings for ophthalmic devices |
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WO2004094075A1 true WO2004094075A1 (en) | 2004-11-04 |
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WO2004110593A1 (en) * | 2003-06-12 | 2004-12-23 | Matsushita Electric Industrial Co., Ltd. | Air cleaner, functional filter and method of manufacturing the filter, air cleaning filter, and air cleaner device |
US7572468B1 (en) * | 2004-12-28 | 2009-08-11 | The United States Of America As Represented By The Secretary Of Agriculture | Extraction of carotenoids from plant material |
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- 2004-04-14 CA CA002522521A patent/CA2522521A1/en not_active Abandoned
- 2004-04-14 KR KR1020057019485A patent/KR20060033710A/en not_active Application Discontinuation
- 2004-04-14 WO PCT/US2004/011513 patent/WO2004094075A1/en active Application Filing
- 2004-04-14 AU AU2004232942A patent/AU2004232942A1/en not_active Abandoned
- 2004-04-14 CN CNA200480016837XA patent/CN1898032A/en active Pending
- 2004-04-14 EP EP04759857A patent/EP1628781A4/en not_active Withdrawn
- 2004-04-14 JP JP2006510036A patent/JP2006523866A/en not_active Abandoned
- 2004-04-14 BR BRPI0409582-0A patent/BRPI0409582A/en not_active IP Right Cessation
- 2004-04-15 TW TW093110441A patent/TW200507886A/en unknown
- 2004-04-16 AR ARP040101296A patent/AR043874A1/en unknown
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EP1050314A1 (en) * | 1999-05-07 | 2000-11-08 | Healthshield Technologies L.L.C. | Antimicrobial contact lens |
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Also Published As
Publication number | Publication date |
---|---|
JP2006523866A (en) | 2006-10-19 |
US20040208983A1 (en) | 2004-10-21 |
KR20060033710A (en) | 2006-04-19 |
EP1628781A4 (en) | 2008-09-17 |
CN1898032A (en) | 2007-01-17 |
AR043874A1 (en) | 2005-08-17 |
AU2004232942A1 (en) | 2004-11-04 |
BRPI0409582A (en) | 2006-04-18 |
CA2522521A1 (en) | 2004-11-04 |
TW200507886A (en) | 2005-03-01 |
EP1628781A1 (en) | 2006-03-01 |
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